Textbook of oral pathology [2 ed.] 9789350901717, 9350901714

Table of contents :
Front Cover
Preliminary Pages
Chapter-01 Microscope
Chapter-02 Tissue Processing Methods
Chapter-03 Histological Staining Methods
Chapter-04 Diagnostic Pathology
Chapter-05 Advanced Diagnostic techniques
Chapter-06 Healing of Wound
Chapter-07 Hyperplasia, Hamartoma and Neoplasm
Chapter-08 Teeth Anomalies
Chapter-09 Craniofacial Anomalies
Chapter-10 Dental Caries
Chapter-11 Benign Tumors
Chapter-12 Premalignant Lesions and Conditions
Chapter-13 Malignant Tumors
Chapter-14 Odontogenic Tumors
Chapter-15 Cyst of Orofacial Region
Chapter-16 Periodontal Pathology
Chapter-17 Salivary Gland Pathology
Chapter-18 Bacterial Infection
Chapter-19 Fungal or Myocotic Infection
Chapter-20 Viral Infection
Chapter-21 Acquired Immunodeficiency Syndrome
Chapter-22 Odontogenic Infection and Pulp Pathology
Chapter-23 Bone Disease Manifested in Jaw
Chapter-24 Diseases of Lip
Chapter-25 Tongue Disorders
Chapter-26 Temporomandibular Joint Pathology
Chapter-27 Chemical and Physical Injuries
Chapter-28 Blood Pathology
Chapter-29 Skin Disorders
Chapter-30 Allergic and Immunologic Diseases of Oral Cavity
Chapter-31 Endocrine Disorders
Chapter-32 Nutrition and Oral Cavity
Chapter-33 Neuromuscular Disorders and Orofacial Pain
Chapter-34 Forensic Odontology
Chapter-35 Syndromes of the Orofacial Region
Appendix I Differential Diagnosis of Most Common Lesions of Oral Cavity
Appendix II Glossary
Appendix III Normal Values of Various Laboratory Parameters
Appendix IV Classification Systems of Odontogenic Tumor
Appendix V Histology Diagrams of Oral Tissues
Answers Key of MCQs
Index

Citation preview

S E C O N D

l D I T I O N

Textbook of

ORAL

PATHOLOGY ft '

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Editors

ANIL GOVINDRAO GIIOM SHUBHANGI MHASKE ( lEDHE)

JAYPEE

Textbook of

ORAL PATHOLOGY

Textbook of

ORAL PATHOLOGY Second Edition

Editors Anil Govindrao Ghom

Shubhangi Mhaske ( Jedhe )

MDS ( Oral Medicine and Radiology )

MDS (Oral Pathology )

Professor and Head Department of Oral Medicine and Radiology Chhattisgarh Dental College and Research Center Sundra, Rajnandgaon, Chhattisgarh , India

Professor and Head Department of Oral Pathology People’s Dental Academy Bhopal, Madhya Pradesh, India

Forewords Manisha Sanjay Tijare Jagdish V Tupkari

JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD New Delhi •London •Philadelphia •Panama

®

Jaypee Brothers Medical Publishers (P) Ltd.

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Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2013, Jaypee Brothers Medical Publishers All rights reserved. No part of this book may be reproduced in any form or by any means without the prior permission of the publisher. Inquiries for bulk sales may be solicited at: [email protected] This book has been published in good faith that the contents provided by the contributors contained herein are original, and is intended for educational purposes only. While every effort is made to ensure accuracy of information, the publisher and the editors specifically disclaim any damage, liability, or loss incurred, directly or indirectly, from the use or application of any of the contents of this work. If not specifically stated, all figures and tables are courtesy of the editors. Where appropriate, the readers should consult with a specialist or contact the manufacturer of the drug or device. Textbook of Oral Pathology First Edition: 2009 Second Edition: 2013 ISBN 978-93-5090-171-7 Printed at

Contributors Amol Gadbail  MDS (Oral Pathology)

Lecturer Department of Oral Pathology and Microbiology Sharad Pawar Dental College Sawangi, Wardha, Maharashtra, India

Monal Yuwanati  MDS (Oral Pathology)

Assistant Professor Department of Oral Pathology and Microbiology People’s College of Dental Academy Bhopal, Madhya Pradesh, India

Anil Govindrao Ghom

Pradnya Lele 

MDS (Oral Medicine and Radiology)

MDS (Oral Pathology)

Professor and Head Department of Oral Medicine and Radiology Chhattisgarh Dental College and Research Institute Sundra, Rajnandgaon, Chhattisgarh, India

Lecturer Department of Oral Pathology and Microbiology Government Dental College and Hospital, Mumbai, Maharashtra, India

Aparna Thombre 

MDS (Oral Medicine and Radiology)

Pranoti Pradhan

MDS (Oral Pathology)

Professor Department of Oral Medicine and Radiology Maitri Dental College and Research Centre, Durg, Chhattisgarh, India

Ashok Mhaske 

MDS (Oral Medicine and Radiology)

Reader Department of Oral Pathology and Microbiology VSPM Dental College and Research Institute, Nagpur, Maharashtra, India

Rashmi Ekka MS (General Surgery)

Vice Dean, Professor and Head Department of Surgery People’s College of Medical Sciences and Research Centre Bhopal, Madhya Pradesh, India

Avadhoot Avadhani MDS (Oral Pathology)

Faculty of Dentistry Sir John Walsh Research Institute University of Otago Dunedin, New Zealand

Lecturer Department of Oral Medicine and Radiology Chhattisgarh Dental College and Research Institute Sundra, Rajnandgaon, Chhattisgarh, India

Sangamesh Halawar MDS (Oral Pathology)

Reader Department of Oral Pathology Vasantdada Patil Dental College and Hospital Kavalapur, Sangli, Maharashtra, India

Textbook of Oral Pathology

vi

Satish Chhugani

Shubhangi Mhaske (Jedhe)

MDS (Oral Medicine and Radiology)

MDS (Oral Pathology)

Postgraduate Student Department of Oral Medicine and Radiology Chhattisgarh Dental College and Research Institute Sundra, Rajnandgaon, Chhattisgarh, India

Savita Ghom MDS (Oral Medicine and Radiology)

Lecturer Department of Oral Medicine and Radiology Chhattisgarh Dental College and Research Institute Sundra, Rajnandgaon, Chhattisgarh, India

Professor and Head Department of Oral Pathology People’s Dental Academy, Bhopal, Madhya Pradesh, India

Smruti Nanda  BDS Lecturer Department of Oral Medicine and Radiology Chhattisgarh Dental College and Research Institute Sundra, Rajnandgaon, Chhattisgarh, India

Seema Vaidya

Vivek Thombre 

MDS (Oral Medicine and Radiology)

MDS (Periodontology)

Lecturer Department of Oral Medicine and Radiology Chhattisgarh Dental College and Research Institute Sundra, Rajnandgaon, Chhattisgarh, India

Reader Department of Periodontology Chhattisgarh Dental College and Research Institute Sundra, Rajnandgaon, Chhattisgarh, India

Foreword to the Second Edition It is at once a great privilege and pleasure to write a foreword for the invaluable compilation of 2nd edition of Textbook of Oral Pathology by Dr Anil Govindrao Ghom and Dr Shubhangi Mhaske (Jedhe). The authors have taken extraordinary pains and care in putting together meticulously the data collected over many years. This has resulted in production of superb new edition. The excellent features of this edition are that the authors covered all the topics according to new syllabus of almost all universities. Special attraction, which I found in the book, is the multiple choice questions at the end of each chapter and the points to remember. An attempt has been made in the book, to simplify and make it easy to remember the subject. The book will help the undergraduate and postgraduate students to get a bird’s eye view of the entire topics. I would like to congratulate the efforts of editors for designing 2nd edition of Textbook of Oral Pathology. I am sure that the book will rapidly find a place in most progressive libraries the world over.

Manisha Sanjay Tijare  MDS (Oral Pathology)

Professor and Head Department of Oral Pathology and Microbiology People’s College of Dental Sciences and Research Centre Bhopal, Madhya Pradesh, India Dean, Faculty of Dentistry Barkatullah University, Bhopal, Madhya Pradesh, India PhD Guide Barkatullah University, Bhopal, Madhya Pradesh, India Executive Committee Member Indian Association of Oral and Maxillofacial Pathologists (IAOMP)

Foreword to the First Edition It gives me immense pleasure to write a few words about the Textbook of Oral Pathology. This book is the outcome of combined efforts of Dr Anil Govindrao Ghom, Professor of Oral Medicine and Radiology and Dr (Mrs) Shubhangi Mhaske (Jedhe), Associate Professor of Oral Pathology and Microbiology. I know Dr Shubhangi as undergraduate as well as postgraduate student. I feel her sincerity coupled with hard work and humanly approach toward the patients during her postgraduate studies contributed in making the textbook. My heartiest congratulations to Professor (Dr) Anil Govindrao Ghom and Dr (Mrs) Shubhangi Mhaske (Jedhe) for their great endeavor in bringing out the book. The book contains six sections which are divided into 37 chapters related to oral lesions/diseases inclusive of basic topics of oral pathology. The topics like microscopy, stains and routine as well as special investigations are noteworthy. The lots of updated information in the book will be helpful to undergraduates, postgraduates and also for practising dental fraternity. The total of over 600 clinical photographs, microphotographs and line diagrams incorporated in the book are definitely useful for in-depth understanding of the subject. The textbooks available on these subjects are many, but only a few ones cover both the subjects: oral medicine and radiology as well as oral pathology. Contribution of Indian authors toward the books in dentistry is less as compared to the foreign authors. Therefore, Mrs Mhaske (Jedhe) deserves a word of appreciation for her sincere and painstaking efforts. The book is an excellent contribution to a scientific literature in Indian scenario and thereby facilitating our students to understand various diseases.

With regards and best wishes

Jagdish V Tupkari

Professor and Head Department of Oral Pathology and Microbiology Government Dental College and Hospital Mumbai, Maharashtra, India

Preface to the Second Edition I may not have gone where I intended to go, but I think I have ended up where I needed to be. ― Douglas Adams In the study of oral and dental sciences, oral pathology is the subject that concentrates on the mechanisms of the disease process and the morphologic changes in tissue that it causes. Everyday, there are new additions to the knowledge of the subject and we have to keep pace with it to update our students about it. That is the reason, we are here with the 2nd edition of Textbook of Oral Pathology. In our first edition, there is a lot of feedback which has come to improve the quality of the book. We tried to incorporate all the feedback in the book. As due to new Dental Council of India (DCI) guidelines, multiple choice questions (MCQs) are part and parcel of examination pattern of the Bachelor of Dental Surgery (BDS) curriculum. We have incorporated MCQs at the end of every chapter so that students can practice it and have some insight into what type MCQs can be there in the examination. Also, we have included ‘points to remember’ in every disease so that with respect to time, students can revise it fast. There are also many new additions of photographs—clinical, histopathological as well as radiological in this edition. In spite of an essential sincere efforts, elements of human error or shortcomings are likely; the readers are welcome to point out all such mistakes and render valuable suggestions for further improvements and shall be greatly acknowledged.

Anil Govindrao Ghom Shubhangi Mhaske (Jedhe)

Preface to the First Edition In the study of oral and dental sciences, oral pathology is the subject that concentrates on the morphologic changes in oral tissues which cause diseases and the mechanisms of the disease process. Most recently published works on the subject are the product of eminent authorities with multiple authorship with current research advances. ‘Why another book in oral pathology’? This question can probably be answered by the phrase, Nothing can be changed by changing the face But many things can be changed by facing the change. The purpose of the book is mainly to provide the undergraduate and postgraduate students, an easy way of reference for covering a broad-spectrum of oral pathology in lucid and simple language. In support of all the composite works, it can be stated that the progress of oral and maxillofacial pathology in its many varied specialties coming up has made the subject too vast to be covered adequately by a single author. Also, a balance between the advances and the basic essentials is need of the hour. With this balanced perspective and from the viewpoint of the graduate and postgraduate students under training, the authors have endeavored to compile the oral and maxillofacial pathology with respect to the related essential clinical oral medicine and radiology. The book gives an extensive coverage and emphasizes on detailed description, adequate well-labeled illustrations, flow charts, recent developments and molecular aspects. Aside from oral pathology in general, the initial phase of the book includes the basics of the embryology, anatomy and pathology. The study of microscope, tissue processing, diagnostic tests and advanced techniques are also included. The photomicrographs and the clinical photographs in the book signify the adage: “A picture is worth a thousand words”; as the reader is encouraged to study the details and to clarify the confusion of the topics. In spite of sincere efforts, elements of human error or shortcomings are likely; the readers are welcome to point out all such mistakes and render valuable suggestions for further improvements and shall be greatly acknowledged.

Anil Govindrao Ghom Shubhangi Mhaske (Jedhe)

Acknowledgments This book could not have been written without the encouragement and motivation of my teachers and students. I would also like to express my gratitude for my contributors Drs Sangamesh Halawar, Pranoti Pradhan, Monal Yuwanati, Pradnya Lele, Aparna Thombre, Avadhoot Avadhani, Vivek Thombre, Amol Gadbail, Rashmi Ekka, Seema Vaidya, Smruti Nanda, Savita Ghom, Satish Chhugani, without whose help and cooperation writing the book would have been an uphill task. I would like to acknowledge the efforts of my Postgraduate students Satish, Manjari, Mansi and Bharani. I am also thankful to Drs Swati Arora and Varun Rastogi, Senior Lecturers, Department of Oral and Maxillofacial Pathology, Kalka Dental College, Meerut, Uttar Pradesh, India, for their contribution of different classification systems of odontogenic tumors. Last but not least, my dear wife, “As fish is without water, so is me without my wife Savita.” Her contribution to my life is beyond what I can express in words. I am also thankful to my daughter Milini and son Sanvil for their love and affection. Finally, I am indebted to the almighty for presenting me with such wonderful opportunities and people in this life.

Anil Govindrao Ghom I dedicate my work to my caring devoted mother, Late Mrs Sulochana Jedhe to whom I owe special idiosyncratic gratitude throughout my life. I express my profound thankfulness to my enthusiastic, dynamic and empathetic husband Dr Ashok Mhaske (Vice Dean, Professor and Head, Department of Surgery, People’s College of Medical Sciences and Research Centre); my compassionate son Sumedh; benevolent father Shri Shrikant Jedhe (Retd), Additional Registrar, Cooperative Societies, Maharashtra Government; munificent parents-in-laws Anna and Aai (Shri NS Mhaske and Mrs Rukhmini Mhaske); knit family ties Niket, Samir (Engineer), Sharayu Tayade (Engineer), Shirin, Dr Mandakini, Dr Maya and Advocate Dharmanand. I extend my indebted thankfulness to all who contributed especially my colleagues, relatives, friends, and dear students. Each one provided extremely and distinctly valuable support for the completion of this work. My special thanks to Honorable Suresh Vijaywargiya, Chairman, People’s Group, Bhopal; Ms Megha Vijaywargiya, Director (Human Resource), People’s Group, Bhopal, Madhya Pradesh, India, for the inestimable support and my colossal inspiration; Dr Jagdish V Tupkari, Professor and Head, Department of Oral Pathology and Microbiology, Government Dental College and Hospital, Mumbai, Maharashtra, India; Dr Suresh Barpande, Dean, Government Dental College and Hospital, Aurangabad; Dr Vinay Hazare, Dean, Government Dental College and Hospital, Nagpur, Maharashtra, India; Dr MK Gupta, Dean, People’s Dental Academy, Bhopal, Madhya Pradesh, India; Dr Alka Kale, Dean, KLE Institute of Dental Sciences, Belgaum, Karnataka, India; Dr PV Wanjari and Dr Sangeeta Wanjari, Professor and Head, Department of Oral Pathology, Modern Dental College, Indore, Madhya Pradesh, India.

Shubhangi Mhaske (Jedhe)

Contents 1. MICROSCOPE

1

Shubhangi Mhaske (Jedhe )

Definition of Microscope 1 ; History of Microscope 1 ; Simple Microscope 3; Compound Microscope 3; Parts of Microscope 3; Image Formation in Microscope 10 ; Specialized Microscopy Techniques 11 ; Maintenance of Laboratory Microscope 19

2. TISSUE PROCESSING METHODS

22

Shubhangi Mhaske ( Jedhe ) , Avadhoot Avadhani Introduction and Terminology 22 ; Gross Examination 22; Preparation of Tissue Specimen for Histological Staining 23; Routine Method for Histological Study 25; Study ofHard Tissues 30 ; Frozen Sections 32; Staining of Cut Sections 32; Mounting 33; Artifacts in Histological Sections 33

3. HISTOLOGICAL STAINING METHODS

36

Shubhangi Mhaske ( Jedhe ) , Amol Gadbail

Chemistry of Stains 36 ; Classification of Stains 37 ; Theories of Staining 38 ; Vital Staining 39 ; Factors Affecting Staining 39 ; Staining Procedure 40 ; Hematoxylin and Eosin Stains 40 ; Special Stains 42 ; Gordon and Sweets ' Methodfor Reticulin Fibers 43

4. DIAGNOSTIC PATHOLOGY

47

Shubhangi Mhaske ( Jedhe ) , Pradnya Lele

Biopsy 47; Types of Biopsy Procedures 48 ; Exfoliative Cytology 51 ; Oral Mucosal Brush Biopsy 54 ; Liquid Based Cytology 55 ; Fine Needle Aspiration Cytology 55 ; Frozen Section Biopsy 56

5. ADVANCED DIAGNOSTIC TECHNIQUES

57

Shubhangi Mhaske (Jedhe ) , Monal Yuwanati

Hi stoche mi cal Techniques 57 ; Fixation in Histochemistry 57 ; Enzyme Histochemistry 58 ; Immunohistochemical Methods 58 ; Immunofluorescent Techniques 59 ; Flow Cytometry 61 ; Polymerase Chain Reaction 61 ; Hybridization Methods 62; Laser Captures Microdissection 63; Proteomics 63; Cytogenetics 64

6. HEALING OF WOUND Shubhangi Mhaske ( Jedhe )

Factors Affecting the Wound Healing 68; Cascade of Wound Healing 72; Healing of Biopsy Wounds 74 ; Healing of Extraction Wounds 74; Healing of

68

Textbook of Oral Pathology

Fractures 75; Healing of Osseointegrated Implants 76 ; Healing of Pulp 76 ; Cementum 77 ; Dentin 77; Enamel 77; Skin Healing and Oral Mucosal Wound Healing 77 ; A Clinical Approach to Optimizing Wound Healing 79

7. HYPERPLASIA , HAMARTOMA AND NEOPLASM

82

Shubhangi Mhaske ( Jedhe )

Dysplasia 82; Neoplasm 85 ; Carcinogenesis Metastasis 92 ;

Metaplasia 82; Hyperplasia 82; Hamartoma 83; Choriostoma 84 ; Carcinogenesis 87; Chemical Carcinogenesis 87 ; Physical 88 ; Hormonal Carcinogenesis 89 ; Biologic Carcinogenesis 89 ; Grading and Staging of Tumors 93

8. TEETH ANOMALIES

97

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) , Savita Ghom Disorders of Development of Teeth 97 ; Scale of Human Tooth Development 98 ; Disorders of Size of Teeth 98 ; Disturbances in Shape of Teeth 99 ; Disorders of Number of Teeth 109 ; Structure of Teeth 111

9. CRANIOFACIAL ANOMALIES

111

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Developmental Anomalies of Jaws 128 ;

Developmental Disorders of Oral Mucosa 138

10. DENTAL CARIES

144

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Theories of Cariogenesis 145 ; Secondary Contributing Factors in Dental Caries 150 ; Classification 152; Smooth Surface Caries 153 ; Pit and Fissure Caries 156 ; Root Caries 158 ; Recurrent Caries 160 ; Chemical Measures of Caries Control 164

11. BENIGN TUMORS

167

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Characteristics of Benign Tumor 168 ; Classification of Benign Tumor 168 ; Epithelial Origin 168 ; Fibrous Connective Tissue 178 ; Cartilage 184 ; Adipose Tissue 186 ; Bone 189; Vascular Tissue 196 ; Neural Tissue 203; Muscle 211 ; Giant Cell Lesion 213

12. PREMALIGNANT LESIONS AND CONDITIONS Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Concept of Precancer 219 ; Terminology and Definitions 219 ; Leukoplakia 220 ; Erythroplakia 229 ; Carcinoma in situ 231 ; Oral Lesion Associated with use of Tobacco 233; Lichen Planus 235; Oral Submucous Fibrosis 243 ; Dyskeratosis Congenita 249 ; Lupus Erythematosus 250

219

Contents

13. MALIGNANT TUMORS

255

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) , Ashok Mhaske

Classification 256 ; Etiology and Risk Factors for Oral Cancer 256 ; Risk Factors 258 ; Epithelial Tumors 258 ; Metastatic Carcinoma 266 ; Basal Cell Carcinoma 267; Adenosquamous Carcinoma 269 ; Basaloid Squamous Carcinoma 269 ; Sinonasal Undifferentiated Carcinoma 270 ; Verrucous Carcinoma 271 ; Transitional Cell Carcinoma 273; Malignant Melanoma 273; Spindle Cell Carcinoma 277; Adenoid Squamous Cell Carcinoma 277 ; Nasopharyngeal Carcinoma 278 ; Merkel Cell Carcinoma 279 ; Fibrous Connective Tissue 279 ; Malignant Fibrous Histiocytoma 282; Synovial Sarcoma 282; Adipose Tissue 283; Cartilage 284 ; Mesenchymal Chondrosarcoma 287; Bone 287; Ewing 's Sarcoma 289 ; Vascular 291 ; Neural Tissue 292; Muscle 294

14. ODONTOGENIC TUMORS

299

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Classification of Odontogenic Tumors 299 ; Development of Tooth 301 ; Stages of Tooth Development 301 ; Ameloblastoma 303; Variant of Ameloblastoma 313; Squamous Odontogenic Tumor 317 ; Calcifying Epithelial Odontogenic Tumor 318 ; Adenomatoid Odontogenic Tumor or Cyst 321 ; Mixed Odontogenic Tumors 325 ; Continuum Concept (Cahn and Blum) 325; Ameloblastic Fibroma 326 ; Ameloblastic Fibrodentinoma 328 ; Ameloblastic Fibro-odontoma 328 ; Odontoma 329 ; Odontoameloblastoma 331 ; Odontogenic Fibroma 332; Granular Cell Odontogenic Tumor 333; Odontogenic Myxoma 333; Malignant Tumors 335

15. CYST OF OROFACIAL REGION Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Classification 343; Theories of Cyst Enlargement 343; Dentigerous Cyst 345; Eruption Cyst 349 ; Odontogenic Keratocyst 350 ; Primordial Cyst 355 ; Gingival Cyst of Newborn 355 ; Gingival Cyst of Adult 356 ; Lateral Periodontal Cyst 357; Glandular Odontogenic Cyst 358 ; Calcifying Epithelial Odontogenic Cyst 359 ; Inflammatory Radicular Cyst 361 ; Residual Cyst 364 ; Inflammatory Collateral Cyst 365 ; Paradental Cyst 365; Mandibular Buccal Infected Cyst 366 ; Suppurating Cyst 366 ; Healing Cyst 366 ; Nonodontogenic Cysts 366 ; Median Palatine Cyst 368 ; Nasoalveolar Cyst 369 ; Median Mandibular Cyst 370 ; Globulomaxillary Cyst 370 ; Nonepithelial Cysts 370 ; Aneurysmal Bone Cyst 371 ; Cysts of the Maxillary Sinus 372; Antral Pseudocyst 374 ; Retention Cyst 374 ; Soft Tissue Cyst 374 ; Branchial Cleft Cyst 376 ; Oral Lymphoepithelial Cyst 376 ; Thyroglossal Duct Cyst 377; Anterior Median Lingual Cyst 377 ; Oral Cyst with Gastric or Intestinal Epithelium 377 ; Cystic Hygroma 377; Follicular Cysts of the Skin 378 ; Nasopharyngeal Cyst 378 ; Thymic Cyst 378 ; Cysts of Salivary Glands 378 ; Parasitic Cyst 378 ; Cysticercosis Cellulose 379 ; Syndromes Associated with Odontogenic Cysts 380 ; Treatment of Cysts 381

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Textbook of Oral Pathology

16. PERIODONTAL PATHOLOGY

386

Vivek Thombre , Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Fibromatosis Gingiva 386 ; Retrocuspid Papilla 388 ; Gingival Inflammation or Gingivitis 388 ; Necrotizing Ulcerative Gingivitis 391 ; Desquamative Gingivitis 392 ; Plasma Cell Gingivitis 393; Granulomatous Gingivitis 394 ; Gingival Abscess 394 ; Pericoronal Abscess 395; Chronic Inflammatory Enlargement 396 ; Gingival Enlargement due to Drugs 397 ; Pregnancy Tumor 398 ; Granuloma Pyogenicum 399 ; Periodontal Pockets 401 ; Adult Periodontitis 402; Rapidly Progressive Periodontitis 402 ; Aggressive Periodontitis/Juvenile Periodontitis 403; Papillon-Lefevre Syndrome 405 ; Haim-Munk Syndrome 406

17. SALIVARY GLAND PATHOLOGY

409

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe )

Classification of Salivary Gland Disorders 410 ; Development of Salivary Gland 410 ; Major Salivary Glands 411 ; Aberrancy 412 ; Aplasia and Hypoplasia 412; Hyperplasia of Salivary Gland 413 ; Atresia 413; Accessory Duct 414 ; Diverticuli 414 ; Sialorrhea 414 ; Xerostomia 414 ; Sialolithiasis 415; Strictures and Stenosis 417 ; Mucocele (Mucous Extravasation Phenomenon) 417; Salivary Duct Cyst or Mucus Retention Cyst 419 ; Ranula 419 ; Sialosis (Sialadenosis) 420 ; Allergic Sialadenitis 421 ; Mumps 421 ; Cytomegalovirus Inclusion Disease 422 ; Bacterial Sialadenitis 422; Sjogren s Syndrome 424 ; Mikulicz s Disease or Benign Lymphoepithelial Lesion 427; Uveoparotid Fever 428 ; Tumors of Salivary Glands 428 ; Histogenesis 428 ; Theories of Salivary Gland Tumor Histogenesis 429; General Features of Salivary Gland Tumors 429 ; Clinical Staging of Salivary Gland Tumors 429 ; Pleomorphic Adenoma 430 ; Basal Cell Adenoma 433; Canalicular Adenoma 434 ; Warthin 's Tumor 435 ; Oncocytoma 437; Myoepithelioma 438 ; Ductal Papillomas 438 ; Mucoepidermoid Carcinoma 440 ; Central Mucoepidermoid Carcinoma 444 ; Acinic Cell Adenocarcinoma 444 ; Adenoid Cystic Carcinoma 445 ; Polymorphous Low Grade Adenocarcinoma 447 ; Malignant Mixed Tumor 448 ; Connective Tissue Tumors 449 ; Necrotizing Sialometaplasia 450

18. BACTERIAL INFECTION

453

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Impetigo 453; Erysipelas 454 ; Syphilis 455 ; Gonorrhea 460 ; Leprosy (Hansen Disease ) 462; Tuberculosis 465; Actinomycosis 468 ; Noma 471 ; Scarlet Fever 472; Diphtheria 473 ; Tularemia 474 ; Rhinoscleroma 474 ; Granuloma Inguinale 475; Oral Manifestations 475 ; Streptococcal Tonsillitis and Pharyngitis 476 ; Tonsillar Concretion and Tonsillolithiasis 476 ; Lymphogranuloma Venereum 476 ; Myiasis 477 ; Cat Scratch Disease 478 ; Pyostomatitis Vegetans 479 ; Sinusitis 479

19. FUNGAL OR MYOCOTIC INFECTION Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Candidiasis 484 ; Oral Candidiasis 486 ; Chronic Mucocutaneous Candidiasis 491 ; Forms ofCandidiasis 491 ; Histoplasmosis 492; Blastomycosis 493; Mucormycosis 495;

484

Contents

Cryptococcosis 496 ; Coccidioidomycosis 497; Geotrichosis 498 ; Sporotrichosis 498 ; Rhinosporidiosis 499 ; Aspergillosis 500 ; Paracoccidioidomycosis 501 ; Toxoplasmosis 502; Leishmaniasis 502; Trichinosis 503

20. VIRAL INFECTION

505

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe )

Human Herpes Virus 505 ; Herpes Simplex Infection 505 ; Measles 509 ; Varicella Zoster Infection 510 ; Herpes Zoster 512; James Ramsey Hunt Syndrome 514 ; Rubella 514 ; Enteroviruses 514 ; Foot and Mouth Disease 516 ; Condyloma Acuminatum 517 ; Verruca Vulgaris 518 ; Focal Epithelial Hyperplasia 518 ; Molluscum Contagiosum Infection 519 ; Cytomegalovirus Infection 520 ; Infectious Mononucleosis 521

21. ACQUIRED IMMUNODEFICIENCY SYNDROME

524

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe )

Classification 525 ; AIDS Related Complex 526 ; Prevalence 526 ; Characteristic of HIV Virus 527; Clinical Features 527 ; Oral Manifestations 528 ; Uncommon Oral Manifestation of HIV 534 ; Diagnostic Tests 536 ; Screening Test for AIDS 536 ; Management 537 ; Prevention 538

22. ODONTOGENIC INFECTION AND PULP PATHOLOGY

540

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) , Seema Vaidya Effect of Infection on Host 541 ; Pathophysiology of Infection 541 ; Pulp 542; Classification of Pulpitis 542; Pulpitis 542; Pulp Degeneration 545 ; Pulp Calcifications 546 ; Necrosis of Pulp 548 ; Cracked Tooth Syndrome 549 ; Periapical Abscess 549 ; Periodontal Abscess 551 ; Acute Exacerbation of a Chronic Lesion 552; Periapical Granuloma 553; Osteomyelitis 555; Acute Suppurative Osteomyelitis 557 ; Chronic Suppurative Osteomyelitis 559 ; Infantile Osteomyelitis 560 ; Synovitis, Acne , Pustulosis, Hyperostosis and Osteomyelitis Syndrome 562; Chronic Recurrent Multifocal Osteomyelitis 563; Cellulitis 565; Ludwig 's Angina 566 ; Fatal Complications of Oral Infection 568 ; Oral Foci of Infections 571 ; Dry Socket 573

23. BONE DISEASE MANIFESTED IN JAW

576

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) , Pranoti Pradhan Fibro-osseous Lesions 576 ; Classification 576 ; Fibrous Dysplasia 577 ; Cherubism 580 ; Central Giant Cell Granuloma 582; Paget 's Disease 584 ; Familial Gigantiform Cementoma 587 ; Ossifying Fibroma, Cementifying Fibroma and Cemento-ossifying Fibroma 588 ; Juvenile Ossifying Fibroma 590 ; Osteoporosis 591 ; Infantile Cortical Hyperostosis 593; Osteopetrosis 594 ; Osteogenesis Imperfecta 596; Pierre Robin Syndrome 597 ; Marfan 's Syndrome 597 ; Down 's Syndrome 598 ; Achondroplasia 599; Osteosclerosis 600 ; Massive Osteolysis 600 ; Gardner ' s Syndrome 601

24. DISEASES OF LIP Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Classification of Lip Disorders 604 ; Anatomy 604 ; Developmental Disturbance of Lip 605 ; Cheilitis 610 ; Etiology 610 ; Miscellaneous 617

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Textbook of Oral Pathology

25. TONGUE DISORDERS

619

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Embryology of Tongue 619 ; Anatomy of Tongue 620 ; Papillae 620 ; Muscle 621 ; Arterial Supply 621 ; Venous Drainage 621 ; Nerve Supply 621 ; Lymphatic Drainage 622; Functions of Tongue 622 ; Classification of Tongue Disorders 623; Aglossia and Microglossia 623; Macroglossia 624 ; Ankyloglossia 625 ; Cleft Tongue 626 ; Ankyloglossum Superius Syndrome 626 ; Lingual Varicosities 627; Lingual Thyroid Nodule 627; Variations in Tongue Movement 628 ; Patent Thyroglossal Duct Cyst 628 ; Lingual Polyp 629 ; Lingual Cyst 629 ; Fissured Tongue 629 ; Median Rhomboid Glossitis 630 ; Benign Migratory Glossitis 631 ; Hairy Tongue 633; Crenated Tongue 634 ; Foliate Papillitis 634 ; Leukokeratosis Nicotina Glossi 634 ; Depapillation of the Tongue 635; Dysgeusia and Hypogeusia 637; Dyskinesia 638 ; Paralysis of Tongue 638 ; Squamous Cell Carcinoma 639 ; Pigmentation of Tongue 640

26. TEMPOROMANDIBULAR JOINT PATHOLOGY

643

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Coronoid Hyperplasia 643; Condylar Hyperplasia 643; Condylar Hypoplasia 644 ; Bifid Condyle 645; Osteoarthritis 645 ; Rheumatoid Arthritis 646 ; Ankylosis 648 ; Subluxation (Hypermobility) 650 ; Gout 651 ; Synovial Chondromatosis 652; Temporomandibular Joint Dysfunction 652

27. CHEMICAL AND PHYSICAL INJURIES

655

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) LineaAlba 655 ; Habitual Cheek or Lip Biting 656 ; Traumatic Ulcer 657 ; Electrical and Thermal Burns 658 ; Anesthetic Necrosis 659 ; Chemical Burns 659 ; Smoker Melanosis 661 ; Drug Induced Discoloration of Oral Mucosa 661 ; Outright Lesion 662; Traumatic Sequestration 662; Methamphetamine Abuse Lesion 663; Submucosal Hemorrhage 663; Oral Lesion as Complication to AntiNeoplastic Therapy (Non-Infectious) 664 ; Cervicofacial Emphysema 665; Myospherulosis 666 ; Attrition 666 ; Abrasion 668 ; Erosion 669 ; Abfraction 670 ; Dentinal Sclerosis 671 ; Secondary and Tertiary Dentin 671 ; Resorption of Teeth 672; Hypercementosis 675; Cementicles 676 ; Bruxism 676 ; Traumatic Lesion Due Sexual Habit 678 ; Oral Piercing and other Body Modification 679 ; Fracture of Teeth 680 ; Amalgam Tattoo 681 ; Bismuthism 681 ; Plumbism 682; Mercurialism 683; Argyria 684 ; Arsenism 685 Auric Stomatitis 685 ; Inflammatory Fibrous Hyperplasia 685; Inflammatory Papillary Hyperplasia 686 ; Epulis Granulomatosum 687 ; Nodular Fasciitis 688 ; Uremic Stomatitis 688 ; Traumatic Keratosis 689 ; Bisphosphonates Associated Osteonecrosis 689

28. BLOOD PATHOLOGY Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe )

Disease of Lymph Tissue 693 ; Disease of Red Blood Cells 694 ; White Blood Cell Disorders 705; Disease of Platelet 708 ; Disease due to Clotting Defect 710 ; Dysfibrinogenemia 713 ; Macroglobulinemia 714 ; Malignancy Involving

693

Contents

Blood Tissue 714 ; Primary Reticular Cell Sarcoma 717 ; Mycosis Fungoides 718 ; Burkitt ’s Lymphoma 718 ; Chronic Myeloid Leukemia 723; Chronic Lymphatic Leukemia 724 ; Multiple Myeloma 725 ; Plasmacytoma 727 ; Extranodal NK/T-Cell Lymphoma 728

29. SKIN DISORDERS

731

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Erythema Multiforme 731 ; Pemphigus 734 ; Paraneoplastic Pemphigus 737 ; Bullous Pemphigoid 737 ; Benign Mucous Membrane Pemphigoid 738 ; Familial Benign Chronic Pemphigus 740 ; Dermatitis Herpetiformis 742; Pityriasis Rosea 743; Incontinentia Pigmenti 743; Acanthosis Nigricans 744 ; Ehlers Danlos Syndrome 745 ; Psoriasis 746 ; Pachyonychia Congenita 747 ; Porokeratosis 748 ; Keratosis Follicularis 749 ; Warty Dyskeratoma 750 ; Seborrheic Keratosis 750 ; Hereditary Mucoepithelial Dysplasia 751 ; Pseudoxanthoma Elasticum 751 ; Hyalinosis Cutis Et Mucosa Oris 752; White Sponge Nevus 753; Hereditary Benign Intraepithelial Dyskeratosis 754 ; Hereditary Hemorrhagic Telangiectasia 754 ; Peutz-Jeghers Syndrome 755; Ephelis 755 ; Actinic Lentigo 756 ; Lentigo Simplex 756 ; Sebaceous Hyperplasia 756 ; Xeroderma Pigmentosum 757 ; Tuberous Sclerosis 757 ; Ectodermal Dysplasia 758 ; Cow den Syndrome 760 ; Graft versus Host Resistance 760 ; Crest Syndrome 761 ; Scleroderma 761 ; Kawasaki Disease 763

30. ALLERGIC AND IMMUNOLOGIC DISEASES OF ORAL CAVITY

766

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Introduction/Overview 766 ; Hypersensitivity Reaction 766 ; Wegner ’ s Granulomatosis 767; Sarcoidosis 769 ; Drug Allergy 770 ; Allergic Contact Stomatitis 771 ; Secondary Vaccinia 772; Angioedema 773; Aphthous Stomatitis (Recurrent Aphthous Ulcers (RAUs) or Canker Sores) 774 ; Behqet ’s Syndrome 776 ; Transient Lingual Papillitis 777 ; Perioral Dermatitis 778 ; Reiter ’ s Syndrome 778 ; Lichenoid Contact Stomatitis/Lichenoid Tissue Reaction 779 ; Chronic Ulcerative Stomatitis 781 ; Crohn ’s Disease 782

31. ENDOCRINE DISORDERS

784

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Anatomy and Physiology 784 ; Diseases of Pituitary Gland 785; Progeria 788 ; Hyperthyroidism 788 ; Hypothyroidism 790 ; Hyperparathyroidism 791 ; Hypoparathyroidism 793 ; Pseudohypoparathyroidism 793; Diabetes Mellitus 794 ; Addison 's Disease 796 ; Adrenogenital Syndrome 797 ; Melasma 797 ; Cushing ’s Syndrome 797

32. NUTRITION AND ORAL CAVITY Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Disturbances in Protein Metabolism 800 ; Disturbances in Lipid Metabolism 804 ; Disturbances in Carbohydrate Metabolism 807 ; Disturbances in Mineral Metabolism 809 ; Miscellaneous Disorders 811 ; Fat Soluble Vitamins 821 ; Disorders of Bilirubin 825

800

Textbook of Oral Pathology

33. NEUROMUSCULAR DISORDERS AND OROFACIAL PAIN

830

Anil Govindrao Ghom , Shubhangi Mhaske ( Jedhe ) Muscle Disorders 830 ;

Neuromuscular Disorders 834 ;

Facial Pain 839

34. FORENSIC ODONTOLOGY

849

Anil Govindrao Ghom , Savita Ghom Record Management 849 ; Identification 850 ; Dental Evaluation 850 ; Personal Recognition 853; Fingerprinting 853 ; Physical Anthropologic Examination of Bones and Teeth 853 ; Postmortem Serology and DNA Profiling 854 ; Bite Marks 854 ; Human Abuse 858 ; Dentist as Expert Witness 859

35. SYNDROMES OF THE OROFACIAL REGION

860

Shubhangi Mhaske ( Jedhe )

Syndromes Associated with Craniofacial Anomalies of Genetic Origin 862; Syndromes Associated with Skin and Pigmentation 868 ; Broad Groups of Pigmentary Disorders 871 ; Syndromes Associated with Salivary and Lacrimal Glands 872; Syndromes Affecting Teeth 873 ; Syndromes Associated with Lips and Cheek 875; Syndromes Associated with Tongue 876 ; Syndromes Associated with Gingiva 877 ; Syndromes Associated with Nerves 878 ; Syndromes Associated with Blood 880 ; Syndromes Associated with Vascular Malformations 882; Syndromes Associated with Immunodeficiency 882 ; Syndromes Associated with Hormonal Disturbances 883; Syndromes with Benign Oral Neoplastic or Hamartomatous Components 884

889

APPENDICES Appendix I: Differential Diagnosis of Most Common Lesions of Oral Cavity 890 Aparna Thombre Appendix II: Glossary Rashmi Ekka

938

Appendix III: Normal Values of Various Laboratory Parameters 951 Smruti Nanda Appendix IV: Classification Systems of Odontogenic Tumor 953 Satish Chhugani Appendix V: Histology Diagrams of Oral Tissues 978 Sangamesh Halawar

ANSWERS KEY OF MCQS Index

1003 1005

Microscope

Shubhangi Mhaske (Jedhe)

A

Chapter Outline 3 3 3 3 3

Definition History of microscopy Simple microscope Compound microscope Parts of microscope • Light source • Lens • Illumination in microscope • Condensers • Object mechanical stage • Objectives • Nosepiece

The light microscope, now 400 years old , is the standard instrument for the examination of histological preparations . The word microscope is derived from two Greek words micro meaning small and scope meaning to view . Thus, it is an instrument which enables us to view small objects . It magnifies (enlarges) the image of that small object and thus makes it possible to be seen by the viewer.

DEFINITION OF MICROSCOPE An optical instrument that uses a lens or a combination of lenses to produce magnified images of small objects, especially of objects too small to be seen by the unaided eye .

• Mechanical tube • Eyepieces 3 Micrometry 3 Image formation in microscope 3 Specialized microscopy techniques • Stereomicroscope

• • • • • •

Dark field microscope Phase contrast microscope Polarized microscopy Fluorescence microscopy Confocal microscope Electron microscope 3 Maintenance of microscope

HISTORY OF MICROSCOPE ( FIGS 1.1 AND 1.2 ) The early pioneers in the history of the microscope are Digges of England and Hans and Zachcharias Janssen (1590 ) of Holland , Robert Hooke (1665 ), John Marshal (1700 ), Martin Frobenius Ledermuller (1768 ), Louis Jablot (1755 ), Meyen (1747). But it was Antony van Leeuwenhoek who was the first to make and use a real microscope (Table 1.1). Early microscopes were simple microscopes but with advance of science compound microscopes were built .

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Figure 1.1 Antony van Leeuwenhoek microscope

Figure 1.2 Robert Hooke microscope

Table 1.1 Contributors in history of microscope

Year

Inventor/Scientist

Contribution

Circa 1000AD

Unknown

Reading stone, A glass sphere that magnified when laid on top of reading material

Circa 1284

Salvino D’Armate (Italy)

Inventing the first wearable eye glasses

1590

Watchmakers Hans and Zachcharias Janssen (Holland)

Multiple lenses placed in a tube magnified object kept in front

1665

Physicist Robert Hooke (England)

Looked at a sliver of cork through a microscope lens and noticed some “pores” or “cells” in it

1674

Antony van Leeuwenhoek (Father of Microscopy)

Built a simple microscope with only one lens to examine blood, yeast, insects and many other tiny objects

1830

Joseph Jackson Lister

Reduction of spherical aberration or the “chromatic effect” by lens combinations without blurring the image for compound microscope

1872

Ernst Abbe

“Abbe Sine Condition” formula for the maximum resolution in microscopes

1903

Richard Zsigmondy

Developed the ultramicroscope

1932

Frits Zernike

Phase-contrast microscope

1931

Ernst Ruska

Electron microscope

1981

Gerd Binnig and Heinrich Rohrer

Scanning tunneling microscope

Microscope

SIMPLE MICROSCOPE A simple microscope consists of a single lens or a magnifying glass.

3

Principle: A lens of short focal length is used to produce an enlarged image of an illuminated object at a short distance; the lens fixed in a frame is adjustable to view the object. The shorter the focal length, the larger the magnified image.

COMPOUND MICROSCOPE (FIGS 1.3A AND B) A compound microscope consists of two or more lenses. Principle: If a lens of short focal length is used to produce an enlarged image of an illuminated object at a short distance, then another lens can be so fixed that it would produce a further enlargement of that image.

PARTS OF MICROSCOPE Microscope Part: • • • • • • • • •

Light source Lens Illumination in microscope Condensers Object mechanical stage Objectives Nosepiece Mechanical tube Eyepieces.

Light Source The light microscope uses natural daylight or artificial visible light. (The resolution of light microscope is limited by wavelength of its light source). A progression of light sources has developed from oil lamps to the low voltage electric lights of today. In histopathology laboratories microscopes with three different types of light sources are found, the conventional light microscope using natural or artificial visible light, the fluorescence microscope using ultraviolet light, and electron microscope using a beam of electrons. Light microscope: Uses a visible light of 400 to 800 nm wavelengths to illuminate an object up to 0.2 mm made visible with perfect optics given in a microscope. In light microscope two different types of illuminations are used.

A

B Figures 1.3A and B The first compound microscope

Fluorescent microscope: Uses ultraviolet light with a shorter wavelength below 400 mm which a light microscope cannot. It can demonstrate, with the help of fluorochrome dyes. High pressure mercury lamp, halogen lamps are used generate ultraviolet light. Light source used in fluorescent microscope is different, i.e. in modern microscope high intensity illumination systems are used. They should to be used with specialized filters for protection of eyes. Electron microscope: This technique of microscopy is different from light microscopy as it uses a stream of electrons in a magnetic field. This stream of electrons has a very short wavelength (a 50 KV electron beam produces light of 0.0055 nm) This is one hundred thousandth that of the visible light.

Illumination In light microscope two different types of illuminations are used (Figs 1.4A and B) Critical illumination: When the object and light source from the substage condenser is in the same plane it is called as the critical illumination, as commonly used in simple equipments, but this produces uneven illumination of the object though modern filament lamps are used. Kohler illumination: This is used for specialized type of microscopy where an image of the light source is focused by the lamp collector or field lens in the focal plane of the condenser. The image of the field or lamp diaphragm is

Textbook of Oral Pathology

∙

Negative: It is concave shaped and diverge rays and forms virtual image.

Condensers

4

A

B Figures 1.4A and B Critical and Kohler illumination

Light from the lamp is directed into the first major optical component—the sub stage condenser-either directly or from a mirror or prism. The main purpose of the condenser is to focus or concentrate the available light into the plane of the object, i.e. the condenser collects the maximum possible light reflected by the mirror or the inbuilt light source and condenses or converges it to a very small area at the position of the specimen. Condensers used for routine microscopy should have the same numerical aperture. The ideal condenser should form a true image of the light source. It is practically useful to have a condenser with a top lens that can be swung out of the path of light, thus filling the whole field with light when very low power objective are used (Fig. 1.6). Three types of condensers are used. Abbe condenser: Named after Ernst Abbe. It is simplest and least expensive type. Because of its simplicity and good light gathering capacity, it is used with most microscopes unless specified otherwise; it has an NA of 0.25. It consists of two lens elements (Figs 1.7A to C). Abbe condenser is not corrected for spherical and chromatic aberration but serves well for general observation. Some types of Abbe condensers are “variable focus condensers” in which the upper lens element is fixed and lower lens is focusable. When the lower element is raised to it is to position it is

Figure 1.5 Types of lenses used in optical components of

microscope

focused in the object plane and the aperture diaphragm is in turn focused at the back focal plane of the objective and can be examined with the eyepiece removed.

Lens It is named lenses because shaped like the seeds of lentil. Piece of glass or other transparent material, usually circular, having two surface ground or polished in a specific form in order that light ray passing through it either converges or diverges. There are two types of lens which are used. They are (Fig. 1.5): ∙

Positive: It can be convex shaped and converges rays of light forming real image

Figure 1.6 Parts of condenser

Microscope

5

A

B

C

Figures 1.7A to C Types of condensers used in modern microscopes. (A) Aplantic condenser; (B) Achromatic condenser;

(C) Achromat/aplanat condenser

similar to the above condenser. But when its position is lowered, light is focused in between the elements, thus the light can emerge as a large diameter parallel bundle. For 10x the field area is larger. To illuminate this large area the top lens element is removed to achieve the illumination of entire field. For medium and high magnification the top lens element of the variable focus condenser remains in place. Aplanatic condensers: These types of condensers are optically corrected for spherical aberration. These are not available form all microscope manufacturers, but are of better quality than Abbe condensers (Figs 1.7A to C). The achromatic condensers: These are corrected for both spherical and chromatic aberrations. It has NA of 1.40. Because of its high degree of correction, it is recommended for research microscopy and for color photomicrography where the highest degree of perfection in the image is desired (Figs 1.7A to C).

Object Stage A rigid platform above the condenser which supports the glass slide is object stage. This object stage has an aperture in the center through which the light can pass to illuminate the specimen on the glass slide (Fig. 1.8). The stage holds the slide firmly and allows the slide movements with a mechanical vertical and horizontal adjustment screws. The mechanical stage is graduated with Vernier scales and the x and y movements assist the operator to return to an exact desired location in the specimen. Traveling range in most of the microscopes is 76 mm(X) 30 mm(Y).

Figure 1.8 Parts of mechanical stage

Objectives Performance of a microscope is dependent wholly on the quality of the optics—the objectives. The main task of objective is to collect maximum light possible from the object, unite it and form a high quality magnified image some distance above. Every objective has a fixed working distance, focal length, magnification and numerical aperture (NA) (Fig. 1.9). The working distance is the distance between an object in focus and the front of the lens system. The focal length is the distance from the center of a simple lens to the point at which parallel rays of light are brought to a sharp focus; in the compound lens it is the distance between an object in focus and a point approximately halfway between the component lenses.

Textbook of Oral Pathology Table 1.2 Color codes used for objectives

Objective color codes

6

Figure 1.9 Specifications mentioned on objectives

Magnification

Color code

4x

Red

10x

Yellow

40x

Light blue

100x

White

Numerical aperture depends primarily on the extreme range of the divergent rays that can be made to admit into the lens (angular aperture) and secondarily on the refractive index of the medium between the object and the objective. The relation between numerical aperture, angular aperture and refractive index is NA = Refractive index × sine angular aperture

Magnification It is product of magnification values of eyepiece and objective in a standard microscope. Magnification in a standard microscope with tube length of 160 mm is calculated using the formula: Magnification =

Tube length Focal length of objective

For microscopes with tube length other than 160 mm: Magnification =

Tubelength × eyepiece magnification Focal length of the objective

Magnification for low power objective with focal length 16 mm and standard tube length of 160 mm is: Magnification = 160/16 = 10

Color Codes Microscope manufacturers label their objectives with color codes to help in rapid identification of the magnification. In addition to color coding other information is also embossed on the objective (Table 1.2).

Numerical Aperture The ability of the lens to distinguish fine structural adjacent details in a specimen is known as the resolving power. This ability is expressed in terms of numerical aperture, as NA, as it is usually called.

The numerical aperture for any objective is always imprinted on its mount. A 10x achromatic objective usually has a numerical aperture of 0.25 and a 20x achromat will usually have a numerical aperture of 0.50; apochromatic objectives have higher numerical apertures than achromats (Fig. 1.9 ).

Resolution It is the smallest distance between two dots or lines that can be seen as separate entities. It depends on the wavelength of light and the NA of the lens. As the NA of the objective increases, the resolving power increases. It is calculated as: ∙ ∙ ∙

R = λ/2NA R = 0.61λ/NA R = 1.22λ/[NA (obj) + NA (cond)] λ = Wave length NA = Numerical aperture

Types of Objectives (Figs 1.10A to C) In most modern microscopes objectives are usually made up more than one lens. This series of lenses is used to overcome certain limitations in the lenses, i.e. Optical aberrations: Aberration is the failure of a lens to produce exact point to point correspondence between an object and its image. Every lens system has an aberration to a greater or lesser extent. To improve the image quality, the lenses are designed by combining different lens shapes

Microscope

7

A A

B

C

Figures 1.10A to C Design and arrangement of lens system

in objectives

and glass materials. It is possible to construct compound lenses of different glass elements to correct this fault. An achromat lens is corrected for two colors, blue and red, producing a secondary spectrum of yellow/green. This secondary spectrum can be reduced by adding fluorite to objective. Such a lens is called as fluorite lens. Fluorite lenses need to be corrected for yellow green, which is done by adding more lens components. Such type of lens is apochromat which is most expensive. Chromatic aberration: White light is composed of all the spectral colors on passing through a simple lens, each wavelength will be refracted to a different extent, with blue being brought to a shorter focus than red. This defect of lens is ‘chromatic aberration’ and results in an unsharp image with colored fringes (Figs 1.11A and B). The objective can be both ‘apochromat’ and ‘achromat’ types to correct these optical aberrations. Spherical aberration: It is caused when light rays entering a curved lens at its periphery which are refracted more than those rays entering the center of the lens and are not brought to a common focus (Fig. 1.12). Different types of objectives are as followes: Achromatic: Corrected for two colors red and blue. It is the most widely used for routine purposes. Fluorite: Green light is brought to a shorter focus and violet light to a longer focus. Apochromat: All colors are brought into same focus. It is fully corrected for three colors. By the design of the lens and use of fluorite, the formation of a secondary spectrum is almost completely eliminated and all colors are brought to the same focus. These lenses are used especially for photomicrography and for screening cytological smears.

B Figures 1.11A and B Chromatic aberrations and its

correction

Figure 1.12 Spherical aberration

Plan-achromat: Although histological sections are flat the image produced by the microscope is not flat. It is saucer shaped; it is not possible to focus the whole of the field sharply at any one time. This aberration is corrected using flat-field objectives also called plan-achromat lenses.

Nosepiece In most modern microscopes up to six objectives are mounted on resolving nosepiece. For rapid change of all objectives they should be at focus and they should focus the same central area of the section when brought into the position. Such nosepieces are known as ‘par-focal’ and ‘par-central’.

Mechanical Tube Light from the objective is received into the bottom of the microscope body-tube. From there it travels to the eyepiece

Textbook of Oral Pathology

8

in a tube called mechanical tube. The distance from objective to eyepiece is called “mechanical tube length” and it is defined as “the distance from the nosepiece opening, where the objective is mounted, to the top edge of the observation tubes where the eyepieces (oculars) are inserted”. In standard microscopes this is 160 mm, while in few special purpose microscopes it is 170 mm. In most microscopes tube length cannot be altered. Such microscopes are called as finite length microscope. In these microscopes if additional filters such as polarizer, analyzer fluorescent filters are used, tube length becomes more than 160 mm and aberrations will be introduced in the image formed. To overcome this limitation, most of the modern microscopes use infinity corrected optics where image is projected to the infinity. In this system, tube length can be altered without affecting the quality of the image. Infinitycorrected systems have the advantage of being easier to design and also make possible the insertion of less costly accessories in the “parallel” light path. This advanced new optical system allows microscopes to support complex optical component clusters in the optical pathway between the objective and the lens tube. This is especially useful for techniques such as confocal, polarized, DIC, and fluorescence microscopy where specialized lens systems must be employed for optimum results.

A

B

Figures 1.13A and B Position of field lens and eye lens in

Ramsden and Huygenian eyepieces

Eyepieces The purpose of an eyepiece in a compound microscope is to enlarge the primary image formed by the objective, and to render it visible as a virtual image in the microscope and also to correct some of the defects of the objective. Huygenian eyepieces are the simplest form of eyepiece in common use; they are cheap, but they are not corrected for chromatic difference of magnification. Although, Huygenian eyepieces can be used with lowpower achromats, they give under-corrected curvature of field and lateral colors with intermediate and higher power objectives. The other main kind of eyepiece is the positive eyepiece with a diaphragm below its lenses, commonly known as the Ramsden eyepiece. These eyepieces are corrected for chromatic aberration of magnification (Figs 1.13A and B).

Different Types of Eyepieces Compensating eyepieces are compound lenses with a chromatic difference of magnification which is equal and opposite to that of high-power objectives. They

Figure 1.14 Compensating eyepieces are required in

binocular microscopes

are essential for use with apochromatic objectives, but they also improve the performance of most highpower achromatic objectives. Eyepieces for binocular microscopes must be accurately paired, with equal centration, magnification, and field in order to reduce eye strain. Interocular distance should be accurately adjusted, and the microscopist should sit at the correct height for the eyepieces to come to the exact height of the observer’s eyes (Fig. 1.14). Eyepieces, generally, are produced with different magnifying powers, ranging from about 4x to 25x. The most common in use are those with a magnifying power of 10x or 15x.

Microscope

Pointer eyepieces: A fine pointer could be incorporated in the eyepiece in order to enable us to point out a certain portion of the specimen. Such types of eyepieces are called as pointer eyepieces (Figs 1.15A and B).

9

Multihead demonstration eyepieces: Some types of eyepieces are such that 4 to 5 people can view the same portion of an object at a time. This type is called ‘double demonstration eyepieces’ (Fig. 1.16).

Micrometry The most common method of making such measurements is the use of ocular micrometer and stage micrometer. We can make measurements in compound microscopes only in the range of 0.2 to 25 mm. We cannot measure dimensions smaller than 0.2 mm because it is less than the resolving power of a compound microscope. Likewise, measurement

A

Figure 1.16 Multihead viewing microscope

Figure 1.17 Ocular micrometer/Graduated reticle

B Figures 1.15A and B Pointer eyepieces are helpful in

locating area of interest

above 25 mm is also not practical because it will be above the average field diameter of a wide field eyepiece. Larger objects can, however, be measured with a stereomicroscope. The ocular micrometer (OM) (Fig. 1.17) is a glass disk with a diameter of 1 cm. It is engraved with an arbitrary scale of 100 divisions or less. It is also referred to as a reticle, reticule or graticule. Since it is fitted into the eyepiece of the compound microscope it is more appropriate to call it an ocular micrometer. This is the scale that is used for all measurements. Since the scale is arbitrary, is to be calibrated (standardize) using a known standard scale, the stage micrometer (SM). A stage micrometer is a standard microscope slide having a scale of defined length. Usually, the scale is 1 mm (1000 mm) divided into 100 divisions, so that one

Textbook of Oral Pathology

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stage micrometer division = 10 mm. Such a microlevel scale is made by methods such as photographic process, physical engraving or electro-deposition of a metallic film directly onto the glass surface. A protective cover glass slip is usually mounted on the scale. The scale may be encircled by a black line during use for easy location and focusing under the microscope. The calibration of the ocular micrometer refers to determination of the distance of one division in terms of the absolute distance of a stage micrometer. A simple Vernier principle is used for this purpose. How many of OM divisions are equal to how many of the SM divisions under a particular microscope–eyepiece–objective combination is found out. Suppose, it is found that 2 OM divisions are equal to 1 SM division which means that 2 OM divisions have a value equivalent to the absolute distance of 1 SM division, i.e. 10 mm. This is given by 1 OM division = 10 mm/2 = 5 mm. This value is often known as micrometer value or calibration factor. Once this value has been determined, the dimension of any specimen can be calculated by multiplying the number of OM divisions spanned by the specimen with the calibration factor. It must be remembered that a calibration factor only applies to a specific microscope– eyepiece–objective combination (Fig. 1.18).

IMAGE FORMATION IN MICROSCOPE Real image: The real image in a microscope is formed by the objective lens. The image is formed at a greater magnification, and is inverted. This is when the object is moved nearer the lens. Virtual image: If the object is placed still nearer the lens within the principal focus, the image is formed on the same side as the object, is enlarged, the right way up, and cannot be projected onto the screen. This is the virtual image. The eyepiece in a microscope forms the virtual image of the real image projected by the objective. The microscopy utilizes transmitted and reflected light for image formation. Transmitted light is light which passes through the object or specimen from source below and image is create in eyepiece after passing through the objective. Whereas when light reflects from a smooth surface, the incoming light is referred to as an incident light and the light that is bounced away from the surface is termed the reflected light. Reflection of light occurs when the light come upon an object surface that does not absorb the light and bounces the light away from the

Figure 1.18 OM (Ocular micrometer) (eyepiece scale) is

coincided with the SM (Stage micrometer)

surface. The reflection of visible light is a property of the behavior of light that is fundamental in the function of majority of today microscopes. Light is often reflected by one or more plane or flat mirrors within the microscope to direct the light path through lenses that form the virtual images which is visible in the eyepieces. Other optical components in the microscope, such as prisms, filters, and lens coatings, also carry out their functions in forming the image with a crucial dependence on the phenomenon of light reflection. A transmitted light microscope will typically be of little use to anyone wanting to examine the structure of biological specimen. As a result, the reflected light microscope has been developed for these purposes. Reflected light microscopy is often referred to as incident light, epi-illumination, or metallurgical microscopy (Mostly used in Metallurgy studies), and is the method of choice for fluorescence and for imaging specimens that remain opaque (Fig. 1.19). In reflected light microscopy, the pathway for reflected light begins with illuminating rays originating in the lamp housing for reflected light. This light next passes through the collector lens and into the vertical illuminator where it is controlled by the aperture and field diaphragms. After passing through the vertical illuminator, the light is

Microscope

Specialized Microscopy Techniques: • • • • • • •

Stereomicroscope Dark field microscope Phase contrast microscope Polarized microscopy Fluorescence microscopy Confocal microscope Electron microscope.

SPECIALIZED MICROSCOPY TECHNIQUES Stereomicroscopy (Figs 1.21A and B) Figure 1.19 Image formation in reflected light microscope

It is optical microscope designed for low magnification observation or a sample using incident light illumination rather than transillumination. It uses two separate optical paths with two objectives and two eyepieces to provide slightly different viewing angles to the left and right eyes. Stereomicroscopy overlaps macro photography for recording and examining solid samples with complex surface topography where a three-dimensional view is essential for analyzing the detail. The stereo microscope is often used to study the surfaces of solid specimens or to carry out close work such as grossing of specimen, etc.

Dark Field Microscopy

Figure 1.20 Image formation in light microscopes

then reflected by a beamsplitter through the objective to illuminate the specimen. Light reflected from the surface of the specimen re-enters the objective and passes into the binocular head where it is directed either to the eyepieces or to a port for photomicrography (Fig. 1.20). The principal focus or focal point is the single point where the parallel rays of light entering the lens are brought together by refraction. The focal point is the point where the clear image of an object is formed. Focal length is the distance between the optical center of the lens and the principal focus.

Dark field microscopy is an optical microscopy illumination technique used to enhance the contrast in unstained samples. It works on the principle of illuminating the sample with light that will not be collected by the objective lens, so not form part of the image. This produces the classic appearance of a dark, almost black, background with bright objects on it. For the dark field method, the cone of light normally illuminating the specimen should not enter the microscope objective, only light that is scattered or reflected by the specimen is seen by the objective. This is achieved in the conventional microscope by use of dark field diaphragm stops or a special dark field substage condenser like Abbe, paraboloid or cardioid condensers. A dark field stop is inserting the stop below the condenser. The light rays from the condenser pass outside the objective and thus form a hollow cone. Now any object with a refractive index different from the surrounding medium, placed within this hollow cone, will only reflect light into the objective and thus the object will appear ‘bright’ against the dark background. The condensers used for this type of microscopy are (Figs 1.22A to C).

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A

B

Figures 1.21A and B Stereomicroscope with two objectives and binocular eyepieces. Two light sources reflect light from above

the specimen and beneath the object stage for surface topography and viewing low magnification of sections respectively

A

B

C

Figures 1.22A to C Condenser used for dark field microscopy. (A) Cardioid condenser; (B) Abbe condenser;

(C) Paraboloid condenser

Types of Condenser Used in Dark Field Microscopy • Abbec ondenser: Used within low power objective • Paraboloid condenser: High power oil immersion objective • Cardioid condenser: More refined and corrected for aberrations than the paraboloid condenser. It is used with oil immersion objective. Two lenses, the objective and eyepiece, are responsible for the formation of the image. The object or specimen is illuminated by the light passing through the condenser

which forms the true image of the light source at the specimen plane. The illuminated specimen is magnified by the objective to produce a real, inverted image. A magnified upright virtual image of this real, inverted image is produced by the eyepiece which will be seen by the observer’s eyes. Dark field microscope is used to demonstrate spirochetes trypanosomes, parasites, and other microorganisms in body fluids and cell suspensions, also in flow cell techniques and autoradiographic grain counting. When observed under dark field microscope, these organism appear bright in dark background.

Microscope

Phase Contrast Microscopy (Figs 1.23 and 1.24) Phase contrast microscopy, first described in 1934 by Dutch physicist Frits Zernike, is a contrast-enhancing optical technique which is utilized to produce highcontrast images of transparent specimens, such as living cells (usually in culture), microorganisms, thin tissue slices, lithographic patterns, fibers, latex dispersions, glass fragments, and subcellular particles (including nuclei and other organelles). One of the major advantages of phase contrast microscopy is that living cells can be examined in their natural state without previously being killed, fixed, and stained. As a result, the dynamics of ongoing biological

processes can be observed and recorded in high contrast with sharp clarity of minute specimen detail. Phase contrast microscopy is widely employed in diagnosis of tumor cells and the growth, dynamics, and behavior of a wide variety of living cells in culture. Brightfield microscope can be converted into phase contrast by two specialized accessories. A specially designed annular diaphragm, which is matched in diameter and optically conjugates to an internal phase plate residing in the objective rear focal plane, is placed in the condenser front focal plane. The phase contrast microscope is probably the most outstanding contribution to microscopy in recent years. It can be used to produce excellent contrast effects, with a wide variety of otherwise transparent specimens. Since it permits visualization of interior details in cell structures, it has a definite advantage over the dark field microscope. Probably its widest application is in the field of tissue culture, where it permits one to examine and photograph living, growing cell. Phase contrast microscope is standard biological microscope and is equiped with modified objective and condensers. ∙ ∙

Figure 1.23 Phase contrast objective

Condensers: Condenser has a series of annular diaphragm made of opaque glass with a clear narrow ring, to produce a controlled, hollow cone of light. Objective: It requires a different size of annulus an image of which is formed by the condenser in the basic focal plane of the objective as a bright ring of light. The Objective has a phase shifting plate or positive phase plate which is a clear glass disk with a circular trough etched in it to half the depth of disk. The trough also contains a neutral density light absorbing material to reduce the brightness of the direct rays which could otherwise obscure the contrast obtained.

The light passing through the trough has a phase difference of 1/4 of wavelength (Figs 1.25A and B).

Principles of Phase Contrast Microscope

Figure 1.24 Phase plate of phase contrast microscope

showing different objectives

The basis of phase contrast microscope is the exaggeration of minute differences in the refractive indices by advancing or retarding light waves, thus converting them into difference of amplitude, which are seen as variation in brightness. Thus if two unstained structures of almost the same refractive index are examined by ordinary illumination it will be found that they are indistinguishable from each other.

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Figure 1.26 Different types of polarizing filters for polarizing

A

microscope

structure of living cell due to difference in the refractive index of the components of the cell and is of great value in cytology, hematology and microbiology (Figs 1.25A and B).

Polarized Light Microscopy (Fig. 1.26) B

Applications

Birefringence is a property, which is shown by crystalline structures, amyloid deposits, proteins, pigments and lipids. When such substances are viewed in a microscope with polarized filters, they may appear bright or even colored against a dark background. In this type of microscope is used two ‘polarizers’ made up of Nicole Prisms are used. One is placed beneath the substage condenser and is held in a rotatable graduated mount, and can be removed from the light path when not required. The other called ‘analyzer’ is placed between objective and eyepiece and is also graduated for measurements to be taken. When a birefringent substance is rotated between two polarizers, which are crossed, the image appears and disappears alternately at each 45° of rotation. In a complete revolution of 360° the image appears four times. Only, the polarizer is used, and if no rotating stage is available, the polarizer itself can be rotated. Changes in intensity and color are seen during rotation. The color changes in a rotation of 90°, and back to its original color in the next 90°. This is due to differential absorption of light, depending upon the vibration direction of two rays in a birefringent substance.

Phase contrast microscope is valuable in examination of wet mounts and hanging drop preparations. It can reveal cellular

Principle of polarized microscopy: A ray of light consists of electromagnetic waves vibrating in all directions at right

Figures 1.25A and B Image formation and photomicrograph

in phase contrast microscope

For each transparent or translucent particle in the object, two rays result from an incident light, The direct, or undiffracted ray comes through the angular diaphragm, passes through the object and is focused on the phase shifting ring which either retards or advances the ray 1/4th wavelength with respect to the secondary. The second ray of the incident beam is modified by being scattered and diffracted in passing around the margin of the object. This ray does not pass through the phase shifting ring but traverses the other areas of the transparent disk, and the wavelength is neither advanced nor retarded. Thus there is an optical difference of 1/4th wavelength, which causes a phase difference with the asynchronous waves producing reinforced darkness or brightness at certain points. Thus ‘phase contrast’ is made visible to the observer’s eye with the help of ‘phase shifting plate’, which enhances the optical effect of the difference.

Microscope

angles to the path of the ray of light itself. In polarized light the waves are made to vibrate in one plane only. This is achieved by the rotating Nicole prisms, i.e. polarizer and analyzers, which is interrupted in the beam of light. The specimen are labeled into two categories isotropic or anisotropic.

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Isotropic (Singly refractive): The substance which are not illuminated by the change in direction of the beam or 90° rotation of the analyzer, the rays transmitted by the lower prism will not pass through the upper, the field is now dark and the position is called crossed Nicole Anisotropic (Birefringent or doubly refractive): These substances are seen as positive after the changes in direction of the beam of light, i.e. 90° rotation of analyzer, the objects are seen as bright against a dark background. Collagen fibers, bone matrix, striated muscle, cholesterol, Zenker fixed RBC, pigments such as formalin pigment, crystal such as talc and vegetable, fibers like cotton and linen are anisotropic”.

Figure 1.27 Polarized microscopy can be applied to see

enamel hypoplasia and dental caries

Applications: The polarizing microscope can be a useful means of identification of tissue components and of exogenous an endogenous crystal specially when combined with special staining techniques and with histochemistry” With this—“ The polarizing microscope can be a useful in identification of exogenous an endogenous tissue components and crystal. It is more effective when combined with special staining techniques and histochemistry” (Fig. 1.27).

Fluorescence Microscopy (Figs 1.28 to 1.30) Objects invisible by ultraviolet light may become brilliantly luminous if coated with a fluorescent substance, like fluorchromes. Fluorchromes are the dyes which absorb radiation (e.g. Ultraviolet light) and become excited; these excited molecules are then capable of emitting radiation of longer wavelength and which disappear almost immediately after withdrawal of the exciting radiation. This is called ‘fluorescence’. Thus fluorescence is the property of some substances, which illuminated by light of certain wavelength causes them to emit the rays of different and longer one. In fluorescence microscopy a fluorescent specimen is illuminated with invisible ‘ultraviolet light’ (UV light has wavelength below 400), the light rays of longer wavelength within the spectrum of visible light are given off and those are seen as various colors of on dark

Figure 1.28 Fluorescent microscope principle showing filters,

arc lamp and the image formed

background. A completely dark room is desirable. Brilliant fluorescence depends upon maximum contrast and is reduced if there is background light in the room. The equipment consists of: Light source: Halogen lamps which give off sufficient blue light (9400–500 nm). Ultraviolet lamps need to be warmed up before use and have short life. Filters: Two filters are place, each in between condenser and source (Exciter filter); other is placed between the objective and eyepiece (Barrier filter).

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Figure 1.29 Fluorescent microscope path of light

– Exciter filter: The exciter filter is made up of heat filter (heat absorbing filter), red stop filter (this filter removes red light) and wavelength selection (this is main exciter filter that allows only the desired wavelength to pass). – Barrier filter: Light on passing through these filters illuminates the specimen, the objective collects both exciting and fluorescent wavelengths. The former is removed by barrier filter to prevent short wavelength light from damaging the retina of the eye. Condensers: Dark ground condensers which do not allow direct light into the objective, and in addition to a dark contrasting background to the fluorescence are used. Routine bright field condensers are able to illuminate the object using all the available energy but they also direct the rays beyond the object into the objective. This is hazardous to the eyes of the observer. Objectives: For fluorescence microscopy objectives with high numerical apertures are preferred. The intensity increases with increase in the numerical apertures. Hence apochromat are generally preferred. Eyepiece: The eyepiece with lower magnification is desirable as fluorescence is inversely proportional to the square of the eyepiece magnification.

Figure 1.30 Epithelial cells in fluorescent microscopy

exhibiting tonofilaments

Applications: Fluorescent techniques have become recently widely used in research and fluorchrome dye methods are routinely employed for the demonstration of tissue components, bacteria, fungi, heavy metal in sections and for the identification of malignant cell in exfoliative cytology (Fig. 1.29).

Microscope

Fluorescent microscopy is the bases for immunofluorescence techniques for the demonstration of antigens and antibodies in tissues and sera. Fluorochrome dyes which are used routinely are Thioflavin T (amyloid) acridine orange (Malignant cells, mucin and fungi) Auramine-Rhodamine (Acid fast bacilli).

Confocal Microscope (Figs 1.31A and B) Confocal (“having the same focus”) microscopy is one of the most significant advances in microscopy. The principle of confocal imaging was patented by Marvin Minsky. With this technique it is possible to control depth of field, elimination, reduction of background illumination, to collect

A

serial optical sections from thick specimens and create 3-D image of the the specimen using microcomputers. In conventional fluorescence entire specimen is illuminated by the light from xenon or mercury bulbs, and light from all areas of the specimen enter the objective and image is obtained. In confocal microscope only a pinpoint area is illuminated and light from this area enters objective and passes through a pinhole filter to eliminate out of focus light. As only a small area is focused very bright light is needed. This is provided by the laser system. Coherent light emitted by the laser system passes through a pinhole aperture that is situated in a conjugate plane (confocal) with a scanning point on the specimen and a second pinhole aperture positioned in front of the detector (a photomultiplier tube). As the laser is reflected by a dichromatic mirror and scanned across the specimen in a defined focal plane, secondary fluorescence emitted from points on the specimen (in the same focal plane) pass back through the dichromatic mirror and are focused as a confocal point at the detector pinhole aperture. The significant amount of fluorescence emission that occurs at points above and below the objective focal plane is not confocal with the pinhole termed. Out-of-focus light rays and is eliminated. Refocusing the objective in a confocal microscope shifts the excitation and emission points on a specimen to a new plane that becomes confocal with the pinhole apertures of the light source and detector. In this way entire specimen is covered point by point using a scanner, images of individual points are acquired, processed, analyzed and image is displayed. Applications: The broad range of applications available to laser scanning confocal microscopy includes a wide variety of studies in neuroanatomy and neurophysiology, stem cell research as well as morphological studies of a wide spectrum of cells and tissues. In addition, the growing use of new fluorescent proteins is rapidly expanding the number of original research reports coupling these useful tools to modern microscopic investigations.

Electron Microscope

B Figures 1.31A and B Confocal microscope and its image

formation

The electron microscope has gained its fundamental superiority over the light microscope is because of its high resolving power to produce extreme fine details. In light microscopy highest resolution that is possible theoretically is half of the wavelength of light. Thus limit of resolution of light microscopy is 0.2 microns (Fig. 1.32). With use of ultraviolet rays this can be improved to 0.1 microns. But

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Figure 1.32 Image formation in electron microscopes and

A

light microscopes

intracellular components, certain bacteria and most of the viruses are smaller than this and cannot be visualized. So attempts were made to use other types of radiation. In 1933 Ernst Ruska and Max Knoll succeeded in this by building electron microscope. In electron microscope it is possible to enlarge the image 250,000 times or more. This image can be photographed for permanent record and it enlarged 4 to 6 time without undue loss of details, thus giving pictures in the range of two million times as large as the object. Greater resolving power (0.2 nm) makes it possible to obtain images of protein molecular viruses, unstained flagella, internal structure of cell, etc. Two types of electron microscope are used: 1. The transmission electron microscope (TEM) 2. The scanning electron microscope (SEM).

Transmission Electron Microscope The transmission electron microscope is similar to the light microscope in that it uses lenses to form magnified image. Both have condenser lenses to concentrate the incident beam upon the specimen. This beam passes through the specimen to the objective (magnetic) then to the projector lens and forms an enlarged image onto a fluorescent screen. Difference lies in the radiation used and type of lenses. In electron microscope beam of electron is used instead of visible light, and electromagnetic lenses are used in place of glass lenses (Figs 1.32 to 1.34).

B Figures 1.33A and B Transmission electron microscope

Electron gun: It generates beam of electrons. It is made of anode and tungsten filament, housed in a wehnelt shield. Filament generates electrons by thermionic emission. Between tungsten filament and anode high voltage difference is maintained so that electrons that are emitted from filament are accelerated towards object. Electron lenses: These electrons pass through a set of electron lenses. These are made up of electromagnetic coils or solenoids. When energized these generate a magnetic field that forces electrons to a focus. Current and voltage in these coils can be varied to change the focus of electron beam.

Microscope

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Figure 1.34 TEM of cartilage cells

Figure 1.36 SEM image of blood filled artery

MAINTENANCE OF LABORATORY MICROSCOPE Like every precision mechanical instrument, microscopes will last longer and provide better performance if cleaned and lubricated at regular intervals. The actual work involved is simple and not time-consuming. After long use of the instrument, overhauling, cleaning and lubricating are required. Major defects come from forced movement especially when dried grease or fixed dirt on the movable parts causes wearing out the teeth of the gears. This occurs commonly between fine adjustment and coarse adjustment gears. Figure 1.35 Tooth enamel crack (SEM)

Image formation: Focused electrons pass through object. These electrons are directed to the viewing screen or image recording unit.

Scanning Electron Microscope The scanning electron microscope provides a topographic view of the surface contours of the specimen. For this it uses an incident electron beam and the reflected electrons produce the image which is three dimensional. As it mimics our own natural perception, the image is instantly appreciated (Figs 1.35 and 1.36).

Optical Maintenance After long use of microscope, lenses become covered by fixed dust, dirt and film. Under the worst conditions, such as high humidity, fungi may grow on the inner lens surfaces. This microbial growth may erode the lens surfaces. Such lenses cannot be cleaned routinely and should be returned to the manufacturer. Optical glasses are generally softer than window glasses so gentle touch is required while cleaning such glasses. Lenses are cemented with adhesive materials. The lenses may become loose, if there is prolonged use of solvent materials are used for cleaning as these dissolve the adhesive cement. So xylene should not be used. Petroleum spirit is recommended by some manufacturers. The recommended

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agent to clean the lenses is xylol. Commercially available detergent based glass cleaning agents may be used. Alcohol and acetone should be avoided as they may seep into the mount and dissolve the cements.

Cleaning of Eyepiece If eyepieces are observed under good light, dirt and film that may be present on the outer surfaces of lens can be seen readily. Dirt on the inner lens surface may be seen by looking through the field lens. Following steps should be followed for cleaning: ∙ Loosen dirt with camel-hair brush, and blow it off with blower. ∙ If oil or other grease film remains, distilled water should be sprayed and wiped off with lens paper or clean lintfree cloth. ∙ If the film persists lens cleaning solution should be applied and wiped off promptly. ∙ Circular motion should be applied for cleaning and polishing. ∙ The necessity of cleaning inner surfaces may be determined by focusing the microscope on a specimen and rotating the eyepiece, if dirt spots rotate, cleaning is required. Unscrew lower and upper lens elements and clean as described for outer surfaces.

Objectives Objectives should be taken apart from nosepiece for cleaning. Exposed front surfaces of all objectives cleaned. Because the back lens usually located in the deep position

though narrow hole, only skilled repairman or the manufacturer can clean it. Usually, lens surfaces of the objectives are smaller than eyepieces, for checking dirt or crack on the surface is recommended to use a magnifying glass.

Condenser For the Abbe condenser, take apart iris diaphragm unit from condenser, clean the top lens from surface and back surface of the field lens.

BIBLIOGRAPHY 1. Clyde Walter Mason, Émile Monnin Chamotl. Handbook of chemical microscopy, Wiley. 1983;4(1). 2. From cells to proteins. Imaging Nature across dimensions; Valtere Evangelista (Ed). Springer; 2004. 3. http://www.leica-microsystems.com/products/lightmicroscopes/ 4. http://www.microscopesmanufacturer.com/ 5. http://www.olympusmicro.com/primer/techniques/ fluorescence/fluorhome.html 6. http://www.olympusmicro.com/primer/techniques/index. html 7. http://www.sciencephoto.com/media/467645/view 8. http://www.sciencephoto.com/media/85586/view 9. John Bankroft, Marilyn Gamble; Theory and Practice of histological techniques; Churchil Livingstone; 2008. 10. Molecular biology of the cell: Reference edition, Bruce Alberts, (Eds) Garland Science Publishers. 2008:5(1). 11. Simon Henry Gage. The Microscope and Histology. BiblioBazaar; 2010.

MULTIPLE CHOICE QUESTIONS 1. Who discovered microscope: a. Galileo b. Ruska c. Leeuwenhoek d. Janssen

3. Range of wavelength used in fluorescent microscope is: a. 600–800 nm b. Below 400 nm c. Below 600 nm d. 400–800 nm

2. Range of wavelength used in light microscope is: a. 400–800 nm b. 200–400 nm c. 800–1000 nm d. 40–80 nm

4. The numerical aperture (NA) of Abbe condenser is: a. 2.5 b. 0.25 c. 25 d. 0.10

Microscope 5. Traveling range in most of the microscope is: a. 26 mm (X) 30 mm (Y) b. 30 mm (X) 76 mm (Y) c. 96 mm (X) 30 mm (Y) d. 76 mm (X) 30 mm (Y) 6. Most expensive lens is: a. Apochromat b. Achromat c. Fluorite d. Plan-achromat 7. The numerical aperture (NA) of achromatic condenser is: a. 2.5 b. 0.25 c. 25 d. 1.40

8. Length of a mechanical tube in a standard microscope is: a. 100 mm b. 120 mm c. 160 mm d. 200 mm 9. Most simple and common form of eyepiece is: a. Huygenian b. Compensating c. Pointer d. None 10. Widely used method for diagnosis of tumor cells is: a. Polarized light microscopy b. Fluorescence microscopy c. Phase contrast microscopy d. Confocal microscopy

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Tissue Processing Methods

Shubhangi Mhaske (Jedhe ), Avadhoot Avadhani A

Chapter Outline O O O O

Introduction and terminology

O Microwave tissue processing/ microwave stimulate tissue

Gross examination Tissue preparation

O Study of hard tissues

processing

• Ground section • Hard tissue microtome/Saw microtome • Decalcification methods for hard tissue

Tissue processing • Fixation • Dehydration • Clearing • Paraffin infiltration • Embedding

O O O 3

• Sectioning with microtome • Picking the section

INTRODUCTION AND TERMINOLOGY Histology: This is the microscopic examination or study of tissues . Histopathologv: This refers to the microscopic examination of tissue to study the manifestations of the disease . Specifically, it refers to the examination of a biopsy of surgical specimen or autopsy by a pathologist, after the specimen has been processed and histological sections are made onto glass slides .

Histotechnique: This refers to the procedure of preparing the tissue for histological study. Specimen accessioning: This tissue specimens received in the surgical pathology laboratory^ are accompanied by a request form or a requisition form that lists the patient’s

Frozen sections Staining of cut sections Mounting Artifacts in histological sections

details with a brief clinical history and provisional diagnosis (Fig . 2.1) . It also describes the surgical details with date and time of procedure performed . The specimens are placed in fixative containers or jars immediately after biopsy. The specimens are accessioned by giving them a unique number that will identify each specimen for each patient. Each laboratory has its own way of biopsy specimen labeling giving the tissue the unique accession number. Bar codes and Quick response codes (QRC) are also being practiced in some modem pathology laboratories ( Fig . 2.2 ) . The Bar code on the request form is read by the department computer generating the complete information of the patient.

GROSS EXAMINATION Tissues removed from the body for diagnosis arrive in the Pathology department and are examined and grossed by

https: //t.me / LibraryE

Tissue Processing Methods

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Figure 2.2 Bar codes and quick response code add ease of

access of data in computer records

Figure 2.1 Biopsy request form

a pathologist, resident pathologist, pathology assistant or technician. Large variety of specimens are received in the Oral and Maxillofacial Pathology laboratory ranging from Jaw resections, large and small tumor masses, cysts, or small incisional biopsies of large lesional tissues. Smaller biopsies are difficult to describe from their anatomical source or site unless described thoroughly in request card. Gross examination consists of describing the specimen for size, color, shape, number, etc. and the time at which tissue was received (Fig. 2.3). After grossing, the tissue is placed in tissue cassettes for further treatment by serial processing steps (Figs 2.4 and 2.5).

PREPARATION OF TISSUE SPECIMEN FOR HISTOLOGICAL STAINING Tissues from the body whether biopsies or tissues from autopsy are processed in a series of chemical reagents to

Figure 2.3 The biopsy specimen received in the laboratory

with details of Registration number, date and time of biopsy removal, nature of biopsy and other specimen details

render it firm and soft enough to be able to cut into thin sections by special knives. The tissue has to be fixed, following which it must be processed into a form in which it can be made into thin microscopic sections. The usual way this is done is with paraffin. Tissues embedded in paraffin, which is similar

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A

B Figures 2.4A and B Tissue processing/carrying cassettes

A

B

Figures 2.5A and B The tissue is placed with a small label of biopsy number in this tissue cassette after careful desired grossing

Tissue Processing Methods

in density to tissue, can be sectioned at anywhere from 3 to 10 microns, usually 6 to 8 microns routinely. The technique of getting fixed tissue into paraffin is called tissue processing. Though the term tissue processing is used after the tissue fixation, but the entire procedure of histotechnique can be enlisted as the main steps in this process are (Flow chart 2.1): Steps in Processing • Obtaining the specimen • Fixation • Dehydration • Clearing • Embedding • Cutting.

ROUTINE METHOD FOR HISTOLOGICAL STUDY Fixation Fixation in simple terms is strengthening and prevention of tissue decomposition. Fresh tissue is placed in a preservative. The agent used for fixation of tissue is called as fixative. Flow chart 2.1 Steps in processing

Aim of fixation: The aim of fixation is to preserve the tissues permanently in are life-like a state as possible. Fixation should be carried out as soon as possible after removal of the tissues (in the case of surgical pathology) or soon after death (with autopsy) to prevent autolysis. Purpose of fixation: Its main aim is to prevent or arrest autolysis, and bacterial decomposition and putrefaction. Another role of fixation is to coagulate the tissue so as to avoid or prevent loss of diffusible substances, to make the tissue strong enough to withstand the tissue processing treatment with reagents and wax embedding and to prepare the tissue for differential staining methods with reagents and dyes. Effects of fixation: There is coagulation of proteins and other coagulable constituents. The loss of the cellular components is prevented. The refractive index of tissues is altered in varying degree. Fixation has a marked effect on staining and it facilitates the action of dyes. Removal of fixative: The fixative should be removed by overnight washing. The tissue cassette is placed in a trough and is kept under running water overnight with a small stream of water directed onto the specimen cassette. Requisites of Fixation • T he tissue ideally be grossed or cut into 0.5 cm thickness for better penetration of the fixative. • The volume of the fixative used must be 20 times that of the specimen. • The time or length of fixation depends on the size of the specimen.

Factors Affecting Fixation Size of tissue: Smaller tissue samples are fixed in short duration but larger specimens require minimum 24 hours. Type of tissue: Soft tissues are penetrated faster by the fixative solutions than hard tissue. Duration: Most fixatives penetrate the depth of 1mm in one hour. So it also relates with size of specimen. Temperature: The diffusion of molecules of fixatives increases with increase in temperature. Concentration of fixative: Concentrations above 10 percent of the neutral buffered formalin (NBF) increases the chances of hardening and shrinkage. Buffer: Osmolality of buffers also affects the fixation. Hypertonic and hypotonic solutions may lead to shrinkage of tissue.

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Ionic composition: Various ions (Na+, K+, Ca2+, and Mg+) can affect the cellular structure. 26

Common Fixatives • 1 0 percent neutral buffered formalin (NBF) • Zenker’s fluid (mercuric chloride, and potassium dichromate solution) • Lugol’s solution (potassium iodide and iodine solution) • Bouin’s fluid (picric acid and formaldehyde solution) • Carnoy’s solution (absolute alcohol and chloroform).

Dehydration Since paraffin wax is immiscible with water, the water in the specimen must be removed before the infiltration with wax. This process is usually carried out by submerging specimens in an ethanol of increasing concentration. Ascending grades of alcohol starting from 70 percent, 80 percent, 90 percent, 95 percent and then absolute alcohol (two changes) are used to dehydrate the specimen. The tissue cassette is placed in each of the solutions for minimum 1 hour. Ethanol is miscible with water in all proportions so that the water in the specimen is replaced by the alcohol. Increasing concentrations of alcohol are to avoid excessive distortion of the tissue (Fig. 2.6).

Clearing After the tissue fixation is now essentially water-free, still it is not possible to infiltrate it with wax because wax and ethanol are largely immiscible.

Therefore, it is essential to use an intermediate solvent that is fully miscible with both ethanol and paraffin wax. This solvent will displace the ethanol in the tissue, and then this in turn will be displaced by molten paraffin wax. This stage in the process is called clearing and the reagent used is called a clearing agent. It is called “clearing” because this procedure imparts an optical clarity or transparency to the tissue due to their relatively high refractive index. Another important role of the clearing agent is to remove a substantial amount of fat from the tissue, which otherwise presents a barrier to wax infiltration. A popular clearing agent is xylene and multiple changes are required to completely displace ethanol.

Wax Infiltration In this procedure the tissue is infiltrated with a suitable histological wax preferably the paraffin wax-based histological waxes due to its physical characteristics. A typical wax is liquid at 60°C and can be infiltrated into tissue at this temperature then allowed to cool to 20°C where it solidifies to a consistency that allows sections to be consistently cut. These waxes are mixtures of purified paraffin wax and various additives that may include resins such as styrene or polyethylene. These waxes have very particular physical properties which allow tissues infiltrated with the wax to be sectioned at a thickness down to at least 3 to 4 mm, to form ribbons as the sections are cut on the microtome, and to retain sufficient elasticity to flatten fully during flotation on a warm water bath (Fig 2.7).

Embedding

Figure 2.6 Manual processing of tissue involves dehydration of

the tissue with increasing grades of alcohol and clearing with two changes of xylene. The tissue is kept for almost one hour in each jar

Once the specimen, is thoroughly infiltrated with wax, it should be embedded into block which can be clamped into a microtome for section cutting. This can be carried out either manually or using embedding machines. In embedding machine the embedding procedure is carried out using an embedding center where a mould is filled with molten wax and the specimen placed into it. The specimen orientation is very important at this step as it will determine the “plane of section”. A cassette is placed on top of the mould, topped up with more wax and the whole thing is placed on a cold plate to solidify. When this is completed the block with its attached cassette can be removed from the mould and is ready for microtomy (Figs 2.8A to D).

Tissue Processing Methods

Sectioning with Microtome When the tissues have been embedded, they must be cut into sections that can be placed on a slide. This is done with a microtome. The microtome is a equipment that holds a knife with a mechanism for advancing a paraffin block. The most important necessities for proper sectioning are a very sharp knife. Knives are either of the standard thick metal variety or thin disposable variety (like a disposable razor blade). Microtome has a mechanism for advancing the block across the knife. Usually this distance can be set, for most paraffin embedded tissues at 6 to 8 microns (Figs 2.9 and 2.10). Figure 2.7 Tissue is kept in melted paraffin for 2 hours for

complete infiltration of wax. This equipment is called paraffin wax bath

A

B

C

D

Picking the Sections Once sections are cut, they are floated on a warm water bath that helps to remove wrinkles. Then they are picked up on a glass microscopic slide.

Figures 2.8A to D Preparation of the tissue paraffin wax blocks requires two L molds and tissue embedding blocks. Care

should be taken that tissue infiltrated in paraffin is placed at the base properly oriented for section cutting

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The glass slides are then placed in a warm oven for about 15 minutes to help the section adhere to the egg albumin coated slide (Fig. 2.11). 28

MICROWAVE TISSUE PROCESSING/ MICROWAVE-STIMULATED PROCESSING

Figure 2.9 Section cutting or tissue sectioning is done on the

microtome

Figure 2.10 The desired thickness in microns approx 5 μ

(arrow) is adjusted and the sections are cut by rotating the wheel

Rapid manual microwave-stimulated paraffin wax processing of small batches of tissues gives excellent results, which are comparable to tissues processed by longer automated non-microwave methods. Processing is undertaken in a dedicated microwave oven, which is fitted with precise temperature control and timer, and an interlocked fume extraction system to preclude accidental solvent vapor ignition (Fig. 2.12). Agitation is provided by an air-nitrogen system. Domestic microwave ovens with a temperature probe and timer accurate in seconds are suitable for tissue processing. Toxic and flammable solvent vapors generated during processing cannot always be adequately vented from these ovens and may present an ignition hazard if the

Figure 2.11 After cutting the sections are spread on a hot

water bath and picked up on glue coated slides

Tissue Processing Methods

containers of about 200 mL capacity are ideal for processing batches of up to 14 cassettes per container.

Fixation

Figure 2.12 Microwave tissue processing

electrical system is unprotected. Ovens should therefore be used within a fume cupboard to minimize this problem. Calibration of domestic ovens is essential for optimum results and the accuracy of the temperature probe, duration of cycle time, and net power levels at various settings must be determined before the oven is used to process tissues. Hints for Microwave Processing • • • • • •

• •

issue blocks should be as thin as possible T Process blocks of similar thickness together Length and width are not important Reagent volumes should be at least 50 times that of specimen volume The temperature probe should be placed centrally in processing baths Use a dummy load to check heat generation should reagents boil on minimum settings—an equal volume of reagent irradiated together with the primary load effectively halves the energy received by the primary load. Pre-heat paraffin wax baths in a conventional oven. An increase in the number of cassettes or fluid volumes will require a concomitant increase in power and or time to achieve the correct processing temperature.

For rapid processing, tissues are fixed by microwave irradiation, or in 95 percent ethanol (600 mL)-polyethylene glycol PEG 400 (45 mL) 102 from which specimens can be transferred directly to dehydrant. Formaldehyde-fixed tissues must be rinsed in running tap water for 5 minutes before microwave processing and an extra dehydration change incorporated into the schedule. Processing times for formaldehyde-fixed tissues need to be increased above those provided for coagulant-fixed tissues. Picric acid fixed tissues should not be microwave processed as there is an explosion risk even in well washed tissues.

Principle Microwave exposure is used to dehydrate, clear and impregnate tissue samples. Fixation of tissue samples is achieved prior to processing in the microwave oven. Processing schedules are developed using tissue thickness as a determining factor. Dehydration is accomplished using ethyl alcohol. Isopropanol is substituted for xylene as a clearing agent. The isopropanol is boiled out of the tissue during the impregnation process by heating paraffin above the boiling point of isopropanol. Equipment and Reagent Used Equipment • Rotator • Commercial microwave operating at approximately 600 Watt • Paraffin pot. Temperature set at 84°C. This instrument is used to recycle paraffin • Paraffin pot. Temperature set at 60°C. Reagent • Ethyl alcohol • Isopropanol • Paraffin.

Procedure Equipment Tissues are processed in conventional plastic cassettes, including those with (provided the metal lids lie below the fluid). Transparent glass or solvent-resistant plastic

Microwave Biopsy (1 mm Thick) Procedure (Process Time 45 Minutes Including Fixation) Tissue samples are placed in plastic prelabeled cassettes and allowed a fixation time of 30 minutes for fresh tissue (Most

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samples are fixed adequately upon receipt). Fresh samples should be placed on a rotomixer agitator to enhance fixation. Rinse cassettes with water to eliminate the possibility of a salt precipitation when the cassettes are placed in the ethyl alcohol. Place cassettes into the teflon processing rack. Around 20 cassettes will fit in 1 rack leaving the top level empty to allow for evaporation. Around 80 cassettes can be processed at a time using 4 racks and 4 plastic processing containers. If you are processing less than 8 cassettes you should place at least 8 empty cassettes in the bottom of the rack. This will regulate the temperature and ensure proper processing. Place processing rack in plastic container and fill with 100 percent ethyl alcohol to rinse off water. Discard alcohol and fill with 400 mL of fresh 100 percent ethyl alcohol. Place the plastic container in the microwave oven and place the temperature probe centrally into the container. Make sure the probe does not touch the cassettes. When starting the microwave follow these steps: ∙ Depress the power switch and observe that after a brief period, during which the vent system comes up to speed, the stop switch indicator extinguishes. ∙ Depress the lamp switch and observe that the chamber light is illuminated. ∙ The turntable is not used therefore the switch should not be depressed. ∙ The airflow bubblier is not used therefore the switch should not be depressed. ∙ Set the timer select pushbutton to the minute’s selection. ∙ Set the time-at temperature mode using the timer mode select switch. ∙ Set the time pause position (out) of a timer/door button.

Microwave at a Temperature of 67˚C for 5 Minutes Take the plastic container and processing rack from the microwave and remove the rack from the container draining the rack on a paper towel. Dump the ethyl alcohol. Place the processing rack back into the plastic container and fill with isopropyl alcohol. Place the plastic container in the microwave. Add the temperature probe centrally into the bath and microwave at a temperature of 74°C for 3 minutes. Remove the plastic container and rack from the microwave. Place the processing rack into an empty container and fill with paraffin that is at a temperature setting of 60°C. Agitate the rack so that the excess Isopropanol will mix with the paraffin. Pour this paraffin

into a paraffin pot that is at a temperature of 84°C. Refill the container with fresh paraffin that is 60°C. Place the container in the microwave. Add the temperature probe centrally into the bath and microwave at a temperature of 65°C for 2 minutes. Open the microwave door and agitate the rack several times to ensure temperature consistency. Adjust the temperature setting to 80°C for 5 minutes. Remove the container from the microwave and dump paraffin into the paraffin pot that is set at a temperature of 84°C. Remove the processing rack from the plastic container and place cassettes at embedding center. Place processing rack into xylene to remove excess paraffin. Both plastic containers can be reused for the next run.

STUDY OF HARD TISSUES Hard mineralized tissues are extremely firm and very difficult to prepare histological sections. The teeth and bone are studied histologically by following methods: Types of Hard • G round section • Hard tissue microtomy • Decalcification with chemical agents and thereafter regular tissue processing and staining. In procedure of decalcification inorganic or mineral composition is lost and organic structure remains. For example, enamel is completely lost in decalcification and what remain is dentin, pulp and cementum in tooth.

Ground Section Calcified tissue like teeth and bone may be ground to a thin section. Equipment for Making Ground Section • L aboratory lathe • Coarse and fine abrasive lathe wheel with water directed onto wheel • Wooden block 1 × 1 inches in size • Adhesive tape • Camel hair brush • Mounting medium • Microscope slide and cover glass.

Tissue Processing Methods

Procedure for Ground Section The specimen is cut in mesiodistal or buccolingual plane into half by means of carborundum wheel if a longitudinal section is to be prepared. For the cross, section the tooth is cut half in horizontal direction. The wooden block is wrapped with adhesive tape, sticky side directed outwards towards the tooth specimen. First coarse abrasive wheel of the lathe is used and then a fine abrasive wheel up to 1 mm thickness of the tooth or bone. The hard tissue or tooth is ground on an abrasive stone manually on an Arkansas stone (Fig. 2.13). When the desired thickness is achieved, the section is carefully lifted by camel hair brush and mounted on the slide (Fig. 2.14).

Hard Tissue Microtome/Saw Microtome (Fig. 2.15) Slices of very hard materials such as resin embedded undecalcified bone or teeth can be prepared without destroying the morphology of the specimens for the use in light microscopy section thicknesses of approximately 30 microns can be achieved under optimal conditions. With the saw microtome, slices of about 100 to 500 microns thickness are prepared and finished to a thickness of about 20-30 microns for the transmission light microscope.

Decalcification Methods for Hard Tissue (Fig. 2.16) The ground section can demonstrate the inorganic or calcified portion. For the study of organic component and structure, it is required that the hard tissue be made soft enough to render it to be cut by knife into thin sections and then stain it. The steps for decalcification and staining of the hard tissue includes.

Decalcification

Figure 2.13 The tooth is slowly abraded in one direction keeping

The decalcification is done by immersing the tooth or bone in acid of specific concentration until the specimen becomes soft. The decalcifying agents are nitric acid 5 percent, formic acid 10 percent, EDTA. The nitric acid decalcifies the tooth fast than any other reagent, i.e. approximately within a week. The disadvantage of HNO3 method is that the tissue integrity may not be preserved intact.

the tooth parallel to the arkansas stone immersed in water

Figure 2.14 Ground sections mounted on slides

Figure 2.15 Saw microtome-Specimens are embedded in

resin after fixation (Courtesy: Lieca)

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Figure 2.16 The decalcifying solution is changed till the teeth

become soft enough for further processing and cutting

Formic acid and EDTA are slow decalcifies but give better results. The tissue is checked by piercing with needle or a X-ray is taken for remains of calcified material. The tissue is washed in running water for 24 hours to remove the acid completely. For fixation, it is then immersed in neutralized and 10 percent buffered formalin to which excess CaCO3 is added. The procedure after fixation is same as for other soft tissue specimens.

Figure 2.17 Cryostat for frozen sections

FROZEN SECTIONS At times during performance of surgical procedures, it is necessary to get a rapid diagnosis of a pathologic process. The surgeon may want to know if the margins of his resection for a malignant neoplasm are clear before closing, or an unexpected disease process may be found and require diagnosis to decide what to do next, or it may be necessary to determine if the appropriate tissue has been obtained for further workup of a disease process. This is accomplished through use of a frozen section. The piece(s) of tissue to be studied are snap frozen in a cold liquid or cold environment (–20 to –70° Celsius) (Fig. 2.17). Freezing makes the tissue solid enough to section with a microtome.

STAINING OF CUT SECTIONS Frozen sections are performed with an instrument called a cryostat (Fig. 2.17). The cryostat is just a refrigerated box containing a microtome. The temperature inside the

Figure 2.18 The tissue section on the slide needs to be deparaffinized in xylene before the actual staining procedure starts

cryostat is about –20 to –30° Celsius. The tissue sections are cut and picked up on a glass slide. The sections are then ready for staining. The embedding process must be reversed in order to get the paraffin wax out of the tissue and allow water soluble dyes to penetrate the sections. Therefore, before any staining to be done, the slides are “deparaffinized” by running them through xylenes (or substitutes) to alcohols to water (Fig. 2.18). There are no stains that can be done on tissues containing paraffin. The staining process makes use of a variety of dyes that have been chosen for their ability to stain various cellular components of tissue. The routine stain is that of hematoxylin and eosin (H and E) (Fig. 2.19). Other

Tissue Processing Methods

to remove the water, then through clearing agents to a point at which a permanent resinous substance beneath the glass cover slip, or a plastic film, can be placed over the section. 33

ARTIFACTS IN HISTOLOGICAL SECTIONS

Figure 2.19 Hematoxylin and eosin stained slides

A number of artifacts that appear in stained slides may result from improper fixation, from the type of fixative, from poor dehydration, incomplete paraffin infiltration, improper reagents, and poor microtome sectioning. Tissues that are insufficiently dehydrated prior to clearing and infiltration with paraffin wax will be hard to section on the microtome, with tearing artifacts and holes in the sections. In humid climates, tissue processing cycles should allow sufficient time for dehydration and final ethanol dehydrant solution should be at 100 percent concentration. Though alcohols such as ethanol make excellent fixatives for cytologic smears, they tend to make tissue sections brittle, resulting in microtome sectioning artifacts with chattering and a “venetian blind” appearance. Bubbles under the cover slip may form when the mounting media is too thin, and as it dries air is sucked in under the cover slip. Contamination of clearing agents or cover slipping media may also produce a bubbled appearance under the microscope.

BIBLIOGRAPHY Figure 2.20 Slide storing cabinet with slide trays that can

hold atleast 100 slides

stains are referred to as “special stains” because they are employed in specific situations according to the diagnostic need.

MOUNTING (FIG. 2.20) The stained section on the slide must be covered with a thin piece plastic or glass to protect the tissue from being scratched, to provide better optical quality for viewing under the microscope, and to preserve the tissue section for years to come. The stained slide must go through the reverse process that it went through from paraffin section to water. The stained slide is taken through a series of alcohol solutions

1. Artifacts in Histological and Cytological Preparations. http:// www.leica-microsystems.com/pathologyleaders/artifactsin-histological-and-cytological-preparations/. Accessed on 30-06-12. 2. Baird IL, Willian B, Bockman OT. Technique of decalcification suited to electron microscopy of tissues closely associated with bonnet. Anat Rec. 1067;159:281-90. 3. Boon ME, Kok LP. Microwave Cookbook of Pathology: The art of microscopic visualization, 2nd Edn. Rev Leiden. Leyden: Coulomb Press; 1998. 4. Clayden EC. A discussion on the preparation of bone sections by the paraffin wax-method with special reference to the control of decalcification. J Med Lab Technol. 70:10323. 5. Clearly SF. Survey of microwave and radiofrequency biological effects and mechanisms. DWE publication. FDA. 1978;75:1-33. 6. Comanescu M, Annaratone L, D’Armento G, Cardos G, Sapino A, Bussolati G. Critical steps in tissue processing

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in histopathology. Recent Pat DNA Gene Seq. 2012;6(1): 22-32. 7. Cooke, Colour Atlas of Anatomical Pathology, 3rd Ed. J. 8. Cunningham CD, Schulte BA, Bianchi LM, Weber PC, Schmiedt BN. Microwave decalcification of human temporal bones. Laryngoscope. 2001;777:278-82. 9. DC Allen, RI Cameron. Histopathology. Specimens: Clinical, Pathological and Laboratory Aspects, Springer; 2004.p.518. 10. Diana Weedman Molavi. The Practice of Surgical Pathology: A Beginner’s Guide to the Diagnostic Process, 1st Edn. Springer; 2008;344. 11. Engelbreth-Holm J, Plum CM. A rapid and easy method of decalcification. J Pathol Bacteriol. 1951;65:751-3. 12. Geoffrey Rolls. An Introduction to Specimen Processing. Leica Biosystems, Wetzlar, Germany 26. May 2011. http://www.leica-microsystems.com/pathologyleaders/anintroduction-to-specimen-processing/. Accessed on 30-06-12. 13. Hornbeck C, Emmanual J, Bloebaum RD. A comparative study of three paraffin media for preparing large decalcified bone sections. J Histotechnol. 1986:9:227-9. 14. http://www.leica-microsystems.com/biosystems/products/ total-histology/tissue-processing/. Accessed on 30-06-2012. 15. Iza KB. Dimenstein, Grossing Technology in Surgical Pathology http://www.grossing-technology.com. Accessed on 30-06-2012. 16. Lillie RD, Laskey A, Greco J, Jacquier Burtner H, Jones P. Decalcification of bone in relation to staining and phosphatases techniques. Am J Clin Pathol. 1951;21:711-22.

17. Ng K PL, Ng, L. Microwave-stimulated decalcification of compact bones. Eur J Morphol. 1992;50:150-5. 18. Quick Reference Handbook for Surgical Pathologists, 1st Edn. Springer; 2011.p.201. 19. Rode SM, Faria MR, Monteiro MP. Using microwaves goes the decalcification of mineralized tissues of rat mandibles. Rev Odontol Univ Sao Paulo. 1996;70:15-8. 20. Roncaroli E, Mussa B, Bussolati G. Microwave oven for improved tissue fixation and decalcification. Pathologica. 1991;55:307-10. 21. Susan C, Lester MD. Manual of Surgical Pathology 2nd Edn.). 2005.p.384. 22. The Washington Manual of Surgical Pathology. Peter A Humphrey, Louis P Dehner, John D Pfeifer L W and W 2008.p.816. 23. Vongsavan N, Matthews B, Harrison GK. Decalcification of teeth in the microwave oven. Histochem J. 1990;22:31180. 24. Werner Martin, Chott Andreas, Fabiano Alfredo, Battifora Hector. Effect of Formalin Tissue Fixation and Processing on Immunohistochemistry American Journal of Surgical Pathology. 2000;24(7):pp.1016-9. 25. Westra. Surgical Pathology Dissection: An Illustrated Guide. WH Westra, RH Hruban, TH Phelps, C Isacson, 2nd Edn. 2003.p.280. 26. Winsor L. Tissue processing. In Woods A and Ellis R eds. Laboratory histopathology. New York: Churchill Livingstone, 1994;4.2-1–4.2-39.

MULTIPLE CHOICE QUESTIONS





5. Glass microscope slide is coated with: a. Alcohols b. Nitric acid c. Paraffin d. Egg albumin

1. Which one of the following is NOT a decalcifying agent: a. Nitric acid 5% b. EDTA c. Ethyl alcohol d. Formic acid 10%

6. Lugol’s solution is: a. Potassium iodide, iodine solution b. Mercuric chloride, potassium dichromate c. Absolute alcohol, chloroform d. Picric acid, formaldehyde

2. Most common fixative agent is: a. Xylene b. 10% Neutral formalin c. Chloroform d. EDTA 3. Carnoy solution contains: a. Mercuric chloride, potassium dichromate b. Absolute alcohol, chloroform c. Potassium iodide, iodine solution d. Picric acid, formaldehyde



4. Dehydration of specimen is done by: a. Alcohols b. Chloroform c. Acids d. Distill water

7. Embedding is usually done with: a. Paraffin b. Chloroform c. Both d. None

8. Paraffin wax bath is used for: a. Infiltration b. Dehydration c. Clearing d. Sectioning

Tissue Processing Methods



9. Potassium chloride and potassium dichromate solution is: a. Lugol’s solution b. Zenker’s solution c. Carnoy’s solution d. Bouin’s fluid 10. Melting point of paraffin is: a. 20 degree centigrade b. c. 100 degree centigrade d.

30 degree centigrade 60 degree centigrade

11. Disposable blades used in microtomy are coated with: a. Acetone b. Polytetrafluoroethylene c. Stainless steel d. Carbon 12. Universal size of slides used in microtomy: a. 35 × 25 mm b. 76 × 25 mm c. 30 × 40 mm d. 40 × 50 mm 13. Temperature required to prevent splitting and cracking of the section: a. 100°C for 1 hour b. 150°C for 30 minutes c. 37°C for 24 hours d. 200°C for 8 hours 14. Cryostates were introduced in: a. 1959 b. 1954 c. 1969 d. 1988

15. Poly-L-lysine coating is: a. 0.05% PLL aqueous c. 0.01% PLL aqueous

b. d.

0.03% PLL aqueous 0.02% PLL aqueous

16. The minimum thickness up to which a tissue should be dissected: a. 3–4 mm b. 1–2 mm c. 7–8 mm d. 5–6 mm 17. Cryostates were introduced in: a. 1959 b. 1954 c. 1969 d. 1988 18. Which gas is given of while chloroform is heated: a. Laughing gas b. Ethylene gas c. Phosgene gas d. Hydrogen sulfide 19. Stages of tissue processing are a. Embedding, clearing, infiltrating, dehydration b. Clearing, dehydration, embedding, infiltrating c. Infiltrating, clearing, dehydration, embedding d. Dehydration, clearing, infiltrating, embedding 20. Dehydration reagents are mainly: a. Hydrophobic b. Hydrophilic c. Both d. None.

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Histological Staining Methods

Shubhangi Mhaske (Jedhe ), Amol Gadbail A

Chapter Outline O Chemistry of stains O Classification of stains O Theories of staining

O O O O O

• Chemical theory • Physical theory Vital staining Factors affecting staining Staining procedure Hematoxylin and eosin stain Special stains • PAS (Periodic acid Schiff method) • Trichrome stains

INTRODUCTION Antoniy van Leeuwenhoek discovered microscope (1719) and started a new era in biological sciences . Robert Hook demonstrated that cell is basic unit of life . In following years description of cell and its constituents was given. All these observations were made without any aid except use of microscope . Under microscope, tissues and their constituents are usually transparent and colorless and cannot be easily distinguished from each other. In order to make different structures easily identifiable two different techniques were developed . Altering contrast and resolution : Contrast and resolu tion can be altered using microscopes such as phase contrast, polarizing and electron microscope. Contrast

Masson trichrome van Gieson 's method

Gordon and sweets ' method for reticulin fibers Mallory' s phosphotungstic acid hematoxylin (PTAH) for

muscle striations Oil red O stain Congo red

Sudan black B Prussian blue (Perl 's Prussian blue reaction) Safranin O

Toluidine stains Giemsa stain

can be altered by the use of silver or gold impregnation techniques also . Alteration of color: Alteration of color is achieved by using some chemical that binds to some structural component of a cell and imparting a color to it, which can be easily identified . This is very cost effective, specific and sensitive technique that can be used in day today practice of histology .

CHEMISTRY OF STAINS Stain is any substance which when added to living cells or to fixed structures or structural components makes them clearly visible or detectable . A staining agent is composed of two components, chromogen and auxochrome .

Histological Staining Methods

Chromogen: Property of color to a substance comes from the chromogen group. Most important chromogen groups are azo, nitro, nitroso, quinoid and ethylene groups act as chromogen. These groups do not have the ability to bind to the tissues. Auxochrome: This ability of binding to the tissues comes from auxochrome group, which contains ionizable groups that bind to tissues. Sulfates, carboxyls and hydroxyls groups form auxochrome, e.g. picric acid. It contains nitro and hydroxy groups. Nitro group is chromogen as it imparts yellow color. Hydroxy group helps picric acid to bind to the tissues thus acts as auxochrome. If hydroxy radicals are removed although the resulting compound has yellow color it cannot bind to the tissues, so it is not a true staining agent. Similarly if nitro groups are removed from picric acid it loses its color although it can bind to the tissues, again not a true staining agent. Thus both chromogen and auxochrome are necessary for calling a compound staining agent.

CLASSIFICATION OF STAINS (TABLES 3.1 TO 3.4) Table 3.1 First—based on the source

Natural • Hematoxylin • Carmine Synthetic or artificial • Nitroso – Naphthol green • Nitro – Picric acid • Azo – Congo red – Orange G – Sudan III and IV – Bismark brown – Methyl orange

• Xanthene – Eosin – Rose Bengal – Rhodamine B – Erythrosin – Phenolphthalein – Pyronin Y – Anthra quinone – Alizarin red • Thiazole – Tital yellow • Quinolin – Pinacyanol • Phthalocyanine – Alcian blue

Table 3.2 Second—based on tissue component of stains

Protein

Ninhydrin Schiff’s method, Millon reaction, diazotization-coupling method for Tyrosine, performic acid-alcian blue method for sulfide and disulfide bonds, DMB­nitrite method modified Sakaguchi method for arginine.

Nucleic acid

DNA

Feulgen reaction, naphthoic acid hydrazine­Feulgen method

RNA

Methyl green pyronine method

DNA and RNA

Gallocyanin­chrome alum, acridine orange

Glycogen

PAS, Best’s Carmine, Hexamine silver method

Mucins

PAS, alcian blue, alcian blue­PAS technique, Dialyzed Iron­Prussian blue technique, Hale’s Technique, Azure A, Toluidine blue, Southgate’s mucicarmine

Routine

Oil red O, Sudan black B, bromine-acetone Sudan black, Nile blue sulfate

Free fatty acid

Copper rubeanic acid method

Cholesterol

Perchloric acid-naphthoquinone (PAN)

Proteoglycerides

Gold hexamine method, Filipino method, UV­Schiff method osmium tetraoxide method

Triglycerides

Calcium lipase method

Carbohydrate

Lipids

Connective tissue

Masson trichrome, van Gieson’s method.

Bone

Trichrome stains, PAS, Schmorl’s picrothionin method, silver staining, von Kossa method, solochrome cyanine method

Neural

Silver impregnation, Bielschowsky’s silver stain, PTAH method, Cajal’s method

Amyloid

Highman’s congored, Sirius red, Toluidine blue, crystal violet, Thioflavin T

Mast cell granules

Toluidine blue, azure A, PAS, alcian blue­safranine

Keratine, keratohyalin

Performic acid alcian blue method, Lendrum’s Phloxin-tartazine method, Ayub-Schlar method

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Textbook of Oral Pathology Table 3.3 Based on pH

Acidic

Basic

Eosin, erythrosine, fluorescein, picric acid, alizarin, acid fuchsin, bismarck brown

Hematoxylin, acridine red, aniline blue, azure, basic fuchsin, crystal violet, malachite green, safranine

38

Table 3.4 Example of different stain

Type of stain

Examples

Reaction of stain:

Acidic—Eosin stain Basic—Hematoxylin stain Neutral—Leishman stain

Physical stain

Stain dissolve in tissue without any chemical reaction such as: SUDAN III for fatty tissues

Vital stain

Staining living tissue inside the body—Trypan blue stain

Supra-vital stain:

Staining living tissues outside the body—Brilliant cresyl blue

Metachromatic stain

Staining the tissues with a color different from the original color of stain ­ Toluidine blue staining for mast cells

Polychromatic stain

Staining the tissues with multiple colors in spite of using a single stain ­ Giemsa stain for blood

Orthochromatic stain:

Staining the tissues with the same color of the stain, such as H & E

Histochemical stain

Staining the different chemical components of the cell

Immuno-histo-chemical stain:

Localization and staining specific proteins by the antigen antibody reaction

THEORIES OF STAINING Much of the discussion pertaining to the theory of staining took place during 1920 to 1930. It was related to the doubt whether staining is chemical or physical. Thus there are two theories, chemical and physical.

Chemical Theory Certain parts of cell are acidic and others basic and few are neutral. Similarly staining agents are also acidic, basic or neutral. Thus it is natural to expect that acidic stains form chemical bonds with basic tissue components and basic stains combine with acidic tissue components, e.g. cytoplasm of most of cells is acidic so it combines with basic stain eosin. Nucleus is acidic as it contains DNA and RNA stains with basic stain hematoxylin. Chemical theory explains the specificity of staining. But it cannot explain certain facts such as absence of

new products, which is one of properties of chemical reactions. Also a chemical reaction is continuous until one of the reactants is exhausted. This is rarely observed in staining.

Physical Theory According to physical theory one of the three physical factors are responsible for staining. Physical penetration of dyes: Most of the tissue components are more or less porous. In these pores staining agents penetrate because of simple physical forces such as capillarity and osmosis. Adsorption of stains: Staining agents are adsorbed onto the surface of tissue by physical forces such as van Der Waal’s forces. Absorption of stains: Absorption is a process by which one substance takes another substance into it. Tissues take

Histological Staining Methods

up staining agent in solution form and retain it in the same form even it dried completely. Any or all of these factors may be responsible for staining. Physical theory does not explain the specificity of staining and differential staining. Now it is believed that reactions involved in staining lies in the borderland between the chemistry and physics, where it is impossible to say that a given product is purely physical or purely chemical. Various mechanisms such as electrostatic bonding, hydrogen bonding, van Der Waal’s forces, covalent bonding, hydrophobic bonding and dye aggregation are involved in staining.

VITAL STAINING It is the method of demonstrating living cells. It is of two types: supravital staining and infravital staining. Supravital staining is done for live tissue, where cells retain vitality after staining. Infravital staining is done to cells that are removed from the body and cells loose their vitality after application of the stain, e.g. alizarin red is supravital staining used to demonstrate developing bone. Toluidine blue is supravital staining that is used to demonstrate precancerous lesions in the oral cavity. India ink preparation is infravital staining method used to demonstrate macrophages. Direct staining: Dyes such as eosin stain tissues perfectly when in alcoholic or aqueous solutions. This is known as direct staining (Fig. 3.1). Indirect staining: Stains such as hematoxylin require additional substance known as mordant before satisfactorily binding to the tissue. This is known as indirect staining (Fig. 3.2).

Figure 3.1 Direct staining

Progressive staining: Different component of tissues are stained in sequence, so that at the end of correct time differential staining is achieved, e.g. eosin. Regressive staining: In this technique tissue is first over stained so that all parts of tissue take up the stain and then excess stain is removed from unwanted parts of tissue by a process known as differentiation. Hematoxylin is differentiated using acid alcohol or prolonged water wash. Staining by selective solubility: Certain substances have ability to dissolve in particular tissue components, such as lipids. Such substances are known as lysochromes. Usually lysochromes are alcoholic solutions that preferentially dissolve in lipids than in alcohol. This results in staining of lipids, e.g. Sudan Dyes. Staining by chemical production of colored substance: Some staining procedures use pale or colorless solution, which react with tissue components to produce colored substances, e.g. Feulgen reaction. In feulgen reaction straw colored or colorless solution of leuco basic fuchsin is used. It is converted into purple colored substance in presence of aldehyde group in tissues. Metallic impregnation: Some metallic substances can be reduced by tissues into opaque, usually black deposits. Certain intestinal cells contain melanin and phenolic substances which reduce ammoniacal silver nitrate into silver and appear black such cells are called argentaffin cells. Certain cells do not reduce ammoniacal silver nitrate directly but do so when extraneous reducer is added. Such cells are known as argyrophil cells. Metallic impregnation techniques are used to demonstrate reticulin, nerve fibers, spirochetes and fungi. Metachromatic staining: Certain tissue substances combine with stains to produce a color that is different from the original color produced in the rest of the tissue. This is known as metachromasia and substance that produces metachromatic staining is known as chromotrope, e.g. Toluidine blue: original color of this dye is blue. But in tissue components such as cartilage, mucins, mast cell granules and amyloid it takes red color. Other metachromatic stains are azure A and B, methyl violet and safranine.

FACTORS AFFECTING STAINING Figure 3.2 Indirect staining

Fixation: Fixation has profound effects of staining. Different fixative retains different tissue components to

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differencing degrees. Well­retained tissue substances are stained well. For example, aldehyde retain proteins well but do not retain lipids. Alcohols are poor fixatives but retain lipids well.

Deparaffinization: Hematoxylin and eosin stains are usually aqueous solutions, not miscible with paraffin. To stain tissues, paraffin must be removed from the tissues first. This is usually done by two changes of xylene.

Temperature: Usually staining is done at room temperature. But temperature of staining solution can be changed. It has two effects: 1. It increases diffusion of the dye molecules. 2. It allows greater reactivity between dye and tissue.

Hydration: Xylene is also hydrophobic. This is removed by an agent that is both miscible with water and xylene. The ideal candidate for this is alcohol. Xylene from tissues is removed by increasing decreasing concentrations of alcohol in water.

pH: Staining depends on pH as it controls the ionization of both tissues and stains which is prerequisite for staining.

Nuclear staining: It is done by dipping the slide in hematoxylin solution.

Presence of impurities: Impurities present in any stain sample have influence on dye solubility and they have real effect on the intensity of staining. An impurity may alter the pH, it may alter the dissociation of dye or tissue or it may act as mordant. In some cases impurities are necessary to assure proper staining, pure stain may be detrimental to staining. For example, if Rose Bengal is used with distilled water poor results are obtained. If tap water is used instead of distilled water excellent results are obtained.

Differentiation: In regressive staining excess hematoxylin in tissues is removed usually by one percent acid alcohol (1% HCl in 70% alcohol). Differentiation is also brought by prolonged water wash. In progressive staining this step is omitted.

Ripening of staining solution: Some staining solutions are effective only after exposure to air, light or warmth for weeks or months or exposure to chemical oxidizers. Hematoxylin when freshly prepared is useless as a nuclear stain. It becomes active after some weeks of storage. This is because natural hematoxylene is not a dye but when oxidized it forms hematin which is a good stain. Hematoxylene can be oxidized naturally by sunlight which takes months or by chemical oxidizers such potassium permanganate or mercuric oxide instantaneously. Steps of Staining Procedure • • • • • • •

Deparaffinization Hydration Nuclear staining Differentiation Bluing Counterstaining Dehydration.

STAINING PROCEDURE After making paraffin sections of the tissue block routine staining of hematoxylin and eosin and if required, special staining is done. Most of the principals of staining hold good for most of the stains with minor modifications. A section usually goes through seven steps during staining.

Bluing: Nuclear staining results in red colored nucleus. This is converted into bluish black color by weak alkali solutions such as lithium carbonate, ammonia water or tap water. Counterstaining: This is done by keeping slides in eosin solution. Dehydration: After staining slide is mounted using DPX. DPX is hydrophobic. So water from the tissues should be removed first. This is done by increasing concentration of alcohol. Later alcohol is removed by the changes of xylene. Any remaining water is removed by warming on the slide warmer.

HEMATOXYLIN AND EOSIN STAINS (FIG. 3.3) The most popular, time tested routinely used stain in histology and histopathology methods is hematoxylin and eosin, commonly called as HE. Their popularity is because of the simplicity of staining method and stain preparation, good contrast, long lasting staining which is beneficial for preserving slides. It mainly stains nucleus with good intranuclear detail. Similarly, eosin stains cytoplasm and most of connective tissue fibers in varying degrees of pink color.

Hematoxylin It is most successfully used natural staining agent. It is extracted from Haematoxylin campechianum, which is cultivated in West India. It is extracted from the wood using hot water and precipitated by urea from aqueous solution.

Histological Staining Methods

Classification of Hematoxylin Based on Mordants • Alum: Ehrlich’s, Delafield’s, Mayer’s, Harris, Cole’s, Carazzi’s and Gill’s • Iron: Weigert’s, Heidenhain’s, Loyez’s, Verhoeff’s • Tungsten: Phosphotungstic acid hematoxylin (PTAH) • Molybdenum: Phosphomolybdic acid hematoxylin • L ead: For demonstration of endocrine cells of GIT • C hromate: Weigert-pal’s technique • H ematoxylin without mordant: For demonstration of minerals like iron and copper. Alum hematoxylin: Alum hematoxylin are most com­ monly used hematoxylin solutions. Mordant used is either Figure 3.3 Hematoxylin and eosin stain potash alum (aluminum potassium sulfate) or ammonium alum (aluminum ammonium sulfate). These stains can be Natural hematoxylin is not a stain as it does bind to the used either progressively or regressively. These initially tissues. On oxidation it forms hematin. This hematin binds give red color to nucleus. This color is converted into blue­ to the tissue and gives color. Hematoxylin can be oxidized black color when section is washed in a weak alkali solution. This is called as bluing. Alkaline solutions such as saturated to hematin by two methods. solution of lithium carbonate, 0.5 percent ammonia in distilled 1. Natural oxidation water, Scott’s tap water substitute or tap water can be used 2. Chemical oxidation. for bluing. Alum hematoxylin are sensitive to acidic solutions Natural oxidation: Exposure to sunlight, heat or prolonged used in few staining techniques such as trichrome staining. So storage in light can oxidize hematoxylin to hematin. This in connective tissue stains alum hematoxylin cannot be used. process takes a very long time as long as 3 to 4 months. But Iron hematoxylin: Ferric chloride and ferric ammonium once the solution is ripened in this way it can be stored for sulfate are used as mordants in iron hematoxylin. These longer time. And it becomes better with passage of time. salts are strong oxidizers. So they are not mixed with Ehrlich and Delafield’s hematoxylin solutions are prepared hematoxylin; they are either used before or after application in this manner. of hematoxylin solution, to prevent over oxidation. In Chemical oxidation: Oxidation of hematoxylin to hematin Weigert’s hematoxylin, mordant is applied after keeping can be achieved rapidly by the use of chemical oxidizers slide in hematoxylin solution (postmordanting). In such as sodium idodate (Mayer’s Harris, Gill’s), potassium Heidenhain’s hematoxylin it is applied before putting the idodate (Carazzi’s) mercuric oxide (Harris) iodine solution slide in hematoxylin solution (premordanting). Mordant (Cole’s hematoxylin) or potassium permanganate (PTAH). solution is also used for differentiation. Iron hematoxylin Chemically oxidized has a very short life as chemicals can be used to demonstrate wide variety of tissue in addition continue is to oxidize hematoxylin continuously. Once all to nucleus. Using Heidenhain’s hematoxylin mitochondria, is converted to hematin further oxidation of hematin into a muscle fibers and myelin can be demonstrated. Verhoeff’s colorless compound occurs which is unsuitable for staining. hematoxylin is used to demonstrate elastic fibers. Iron hematoxylins are technique sensitive, time consuming Use of mordant: Hematoxylin is a anionic substance and have short lifespan. Differentiation stage requires which does not have good affinity to tissue. To increase microscopic control for accuracy. affinity various mordants are used. Mordants form a complex with hematoxylin forming a positive charge Phosphotungstic acid hematoxylin: It is used to which binds to negatively charged tissue components like demonstrate myelin sheath. Here phosphotungstic acid nuclear chromatin. Based on mordants hematoxylin can be acts as a mordant. If Phosphomolybdic acid is used in classified into various types. Only major three like alum, place of phosphotungstic acid, as a mordant, it can be used to demonstrate collagen, coarse reticulin fibers and iron and tungsten described below.

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42

argentaffin cell granules. Lead salts are used as mordants in demonstration of granules of endocrine cells of GIT. Chromate is used as mordant in Weigert­pal technique to demonstrate myelin. In this technique tissues are treated with dichromate solution before embedding. Later sections are dipped in hematoxylin to get brilliant staining of myelin. In few techniques minerals present in tissues act as mordants. In this way iron and copper present in tissues can be demonstrated with hematoxylin without any mordant.

Eosin Eosin is a Xanthene dye. It is available in various forms such as eosin Y: eosin yellow, water soluble eosin s: ethyl eosin, alcohol soluble eosin B: bluish eosin. Of this eosin Y is more popular and is widely used. Eosin is most suitable and popular stain used with hematoxylin. This is because it gives good contrast with hematoxylin. It stains cytoplasm of different cells differently in varying shades of pink and red. Similarly it can stain different types of connective tissue fibers and matrices differently. In addition to routine staining it is used in pap stain along with azure. It is usually used in concentration of 0.5 to 1 percent aqueous solution. To increase staining capacity and to get sharp and crisp staining little acetic acid is added to this solution.

cartilage, fungi and Russell bodies. All these structures can be demonstrated by PAS reaction (Fig. 3.4).

Trichrome Stains (Fig. 3.5) Popularly called as connective tissue stains, trichrome stains are used in differential demonstration of connective tissue components such as collagen, muscle, fibrin, etc. In this technique two or more acidic dyes of different molecular weight and contrasting color are used in the staining. How exactly differential staining observed in trichrome stains is not understood. But various tissue factors and molecular weight of the dyes are thought to be responsible for this. Due to fixation tissues form networks. These

SPECIAL STAINS When there is need to identify stain special structures use of H & E stain is limited. In such cases staining agents that can identify structure of interest are employed. There are numerous special stains that are available, but only a handful are employed regularly. PAS and trichromes are most commonly employed in identifying glycogen and collagen fibers respectively.

Figure 3.4 PAS stain showing positive magenta color for

mucin

PAS (Periodic Acid Schiff Method) This is a technique for the demonstration of carbohydrates in tissue sections. When basic fuschin is reduced using HCl it form Schiff’s base. This is a colorless compound which regains its color once it comes in contact with oxidizing groups in tissue sections it again gains its color. In this technique periodic acid applied to expose oxidizing groups of glycogen molecule. Later tissue is flooded with Schiff’s base. Glycogen molecules are stained into a bright pink or magenta color. Glycogen is present in many substances such as basement membrane, mucins,

Figure 3.5 Trichrome stain showing more than one color

Histological Staining Methods

networks create pores of different sizes in different structures. In RBC’s very dense network with small pores is produced. In muscles pores of intermediates size are produced. As collagen is loose tissue it produces least dense network and pores or large size. Dyes of different molecular weight occupy these pores. Thus dye of least molecular weight occupies smallest pore and larger pores are occupied by large dye molecules.

43

Masson Trichrome (Fig. 3.6) In this method with a small molecule size dye acid fuchsin/ ponceau is used first and this stains all tissue elements in the section. This stain is selectively removed from unwanted areas by differentiating with phosphomolybdic acid, which also acts as a mordant for the next step of the procedure. A Figure 3.7 van Gieson’s stain showing collagen stained red dye of large molecular size, light green is then applied to the section. Nucleus is stained by hematoxylin. Thus nuclei saturated solution of picric acid and acid fuschin. The and elastic fibers are stained blue to black, cytoplasm, mixture of the two acid dyes in acid solution competes for muscle and acidophilic granules are stained red; collagen, available linkages. reticulin, basement membranes, osteoid and basophilic Acid fuchsin being a larger molecular size is restricted granules are stained green. to more permeable collagen fibers whereas the diffusible picric acid penetrates the compact muscle, cytoplasm and van Gieson’s Method (Fig. 3.7) red cells. These results in blue/black nuclei, red collagen The van Gieson Technique is a trichrome stain for the and other tissues such as muscle, elastin, reticulin, basement demonstration of connective tissue. It is suitable for membrane, and fibrin take yellow color. showing coarse collagen fibers, but not recommended for fine collagen fibers or muscle collagen comparisons. In GORDON AND SWEETS’ METHOD this technique nucleus is stained first using hematoxylin. Then slides are kept in van Gieson solution which contains FOR RETICULIN FIBERS (FIG. 3.8) This method is used for reticulin fibers. Reticulin fibers are fine delicate fibers, which are normally found connected to stronger and coarser collagen fibers. They make up the bulk of the supporting framework of the liver, spleen and lymph nodes. The basic principle in this stain is silver from silver oxides is selectively deposited on the reticulin fibers, which appear black after conversion to reduced silver, by the reducing agent (formalin). Gold chloride is used as a toner to give a clearer background and unreduced silver is removed by treatment with sodium thiosulphate.

Mallory’s Phosphotungstic Acid Hematoxylin (PTAH) for Muscle Striations (Fig. 3.9) Figure 3.6 Masson’s trichrome stain showing green collagen

fibers and red muscle fibers

The PTAH stain demonstrates many tissue structures, particularly fibrin, muscle striations, cilia and glial fibers, plus many CNS structures.

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Figure 3.8 Gordon and Sweet stain for reticulin fiber

Figure 3.10 Oil red O staining

Figure 3.9 PTAH stain

Figure 3.11 Congo red stain of amyloid

The mechanism by which two­color staining is achieved from a mixture of hematin and phosphotungstic acid is obscure. The blue color was due to metachromatic like staining effect.

Oil Red O Stain (Fig. 3.10) The purpose of oil red stain is to demonstrate fat or lipids in fresh tissue sections. Fat occurring in an abnormal place, such as fatty emboli that may develop after either a bone fracture or an injury that crushes a fatty body area. Tumors arising from fat cells (liposarcomas) can be differentiated from other types of tumors. Staining with oil­soluble dyes is based on the greater solubility of the dye in the lipoid substances than in the usual hydroalcoholic dye solvents.

Congo Red Amyloid is homogeneous and eosinophilic; the deposits are extracellular and may become sufficiently large enough to cause damage to surrounding tissues. When stained with the Congo red stain the amyloid will birefringe an apple green color under the polarizing microscope (Fig. 3.11).

Sudan Black B (Fig. 3.12) This stain is used for lipofuscin pigments. Lipofuscins, the wear-and-tear pigment, and is the accumulation of liposome’s, which have absorbed the worn-out, indigestible parts of the cell and known as residual bodies. It is a yellow brown pigment, and will stain after being processed in paraffin.

Histological Staining Methods

Prussian Blue (Perl’s Prussian Blue Reaction) Prussian blue histology stain is used to stain iron (ferric iron and ferritin). This method is considered by many to be the first classical histochemical reaction. The reaction occurs with the treatment of sections in acid solutions of ferrocyanides. Any ferric ion (+3) in the tissue is combined with the ferrocyanides and results in the formation of a bright blue pigment called Prussian blue or ferric ferrocyanides (Fig. 3.13). It demonstrates ferric iron in tissue sections.

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Figure 3.14 Safranin O stain showing orange color

Figure 3.12 Sudan black B stain for triglyceride

Figure 3.15 Toluidine blue stain

Safranin O This histology stain will stain mucin, cartilage and mast cells granules on formalin-fixed, paraffin-embedded tissue sections, and may be used for frozen sections as well. It stains them orange/red (Fig. 3.14). Safranin O is sometimes used as a counterstain. The cartilage and mucin will be stained orange to red, and the nuclei will be stained black. The background is stained green.

Toluidine Stains (Fig. 3.15)

Figure 3.13 Persian stain for iron detection

Mast cells are found in the connective tissue and their cytoplasm contains granules (metachromatic) composed of heparin and histamine.

Textbook of Oral Pathology

Giemsa Stain (Fig. 3.16) This is a histology stain for peripheral blood smears and bone marrow. It is also used to visualize parasites and malaria. This is a Romanowski type stain. Methylene blue and eosin are used. Erythrocytes stain pink/red. Platelets and leukocytes stain blue. Giemsa’s stain is a member of the Romanowski group of stains, which are defined as being the black precipitate formed from the addition of aqueous solutions of methylene blue and eosin, dissolved in methanol.

46

BIBLIOGRAPHY Figure 3.16 Giemsa stain showing parasites

Toluidine blue should stain mast cells red­purple and the background blue. Metachromasia, tissue elements staining a different color from the dye solution, is due to the pH, dye concentration and temperature of the basic dye. Blue or violet dyes will show a red color shift, and red dyes will show a yellow color shift with metachromatic tissue elements.

1. Bancroft JD, Gamble M. Theory and Practice of Histological Techniques, 6th edn. London: Churchill Livingstone, 2008. 2. Brown RW. Histologic Preparations: Common Problems and Their Solutions. Northfield, IL: College of American Pathologists, 2009. 3. Horobin RW, Bancroft JD. Troubleshooting Histology Stains. New York, Edinburgh: Churchill Livingstone, 1998. 4. Kiernan JA. Histological and Histochemical Methods: Theory and Practice, 4th edn. Bloxham, UK: scion, 2008. 5. Michael H Ross, Wojciech Pawlina. Histology: A Text and Atlas. Hagerstwon, MD: Lippincott Williams and Wilkins, 2006. ISBN 0-7817-5056-3.

MULTIPLE CHOICE QUESTIONS



1. Staining agent composed of: a. Chromogen group b. c. Both d.

6. Stains with acidic pH is: a. Picric acid c. Hematoxylin

Auxochrome group None of the above

2. Which one belongs to the chromogen group: a. Sulfates b. Carboxyl c. Hydroxyl d. Azo



3. Which one belongs to the auxochrome group: a. Azo b. Carboxyl c. Nitro d. Nitroso



4. Which one is the natural source of stains: a. Hematoxylin b. Picric acid c. Eosin d. Quinolin 5. Stains with acidic pH is: a. Hematoxylin c. Safranine

b. d.

Eosin Basic fuchsin

b. d.

Erythrosine Alizarin

7. Mordant used in which staining technique: a. Indirect staining b. Direct staining c. Progressive staining d. Regressive staining

8. Hematoxylin mainly stains: a. Cytoplasm b. c. Muscle fiber d.

Nucleus Connective tissue

9. Carbohydrate in tissue can be demonstrated by: a. Trichrome stains b. Iron hematoxylin c. PAS d. Eosin 10. Popularly used eosin is: a. Eosin Y c. Eosin B

b. d.

Eosin S Eosin Z.

Diagnostic Pathology

Shubhangi Mhaske (Jedhe), Pradnya Lele A

Chapter Outline 3 Biopsy 3 Types of biopsy 3 Incisional biopsy 3 Excisional biopsy 3 Punch biopsy

3 3 3 3 3

Exfoliative cytology Oral mucosal brush biopsy Liquid based cytology Fine needle aspiration cytology Frozen section biopsy

INTRODUCTION

Indications

There are various important investigations which are required for the diagnosis and treatment plan of various disorders related to the oral cavity. Laboratory studies are an extension of physical examination in which tissue; blood, urine or other specimens are obtained from patients and are subjected to histological, bio-examination, microbiological or immunological examination. Information obtained from these investigations help in identifying the nature of the disease .

Alteration from normal : When after careful clinical examination, any alteration from normal is seen and it is not possible to identify the condition clinically, a histopathological investigation is necessary.

Autopsy: It is the histopathological study of the tissues removed after the death of an individual . Biopsy: It is the study of tissues removed from a living being to confirm the diagnosis through histopathological study.

BIOPSY It is a process of surgically removing tissue from a patient for histopathological examination. It provides valuable information in determining the prognosis and type of the treatment required .

Evaluation of histological nature: It is also indicated to evaluate the exact histological nature of any soft tissue or intra-osseous lesion . Screening of abnormal tissue : To screen abnormal tissues removed from oral cavity including granuloma and cyst.

Confirmation of diagnosis : It is also done to confirm the existence and nature of directly apparent malignancy so that the treatment can be undertaken immediately . Evaluation of nonneoplastic lesion : It is also done for diagnostic tests for evaluation of nonneoplastic lesions such as mucosal nodules, papilloma, erosive lichen planus, erythema multiforme, lupus erythematous pemphigus, pemphigoid and desquamative gingivitis .

Textbook of Oral Pathology

Contraindication 48

Inflammatory lesion: Biopsy is not usually indicated in acute infalmmatory lesion. Site near the vital structure: One should be very careful while performing biopsy of the lesion adjacent to vital structure. Angiomatous lesion: Unless it is needed you shouldn’t go for the biopsy of angiomatous lesion. Biopsy should not be delayed when following features are present: Rapid increase in size of the lesion that cannot be explained by inflammation, edema and opening of new vascular channels. Absence of any recognized irritant, particularly when the lesion is chronically ulcerated or bleeds spontaneously. Presence of firm regional lymph nodes, especially when they seem to be fixed to surrounding tissues. Destruction of roots and loosening of teeth with evidence of rapid expansion of the jaw History of malignancy elsewhere in the body, previous history of oral cancer and radiation therapy. Application of Biopsy in Dentistry • • • • • •

Diagnosis of pathologic lesions Determining neoplastic and non-neoplastic lesions Therapeutic assessment Grading of tumor Diagnosis of metastatic lesions Evaluation of recurrence.

Complication of Biopsy • • • •

Hemorrhage Infection Poor biopsy wound healing Spread to adjacent organs and reaction to local anesthesia.

Ideal Requirement of Biopsy Tissue Less traumatized: The tissue taken for biopsy should have minimal trauma. Adequate representative tissue: It must include the most suitable representative pathologic region of a lesion for a pathologist to interpret. To facilitate treatment: Biopsy sample should help to facilitate to prescribed treatment and assess its efficacy.

Normal adjacent tissue: To compare and strengthen the diagnosis normal adjacent tissue should be included.

Handling Biopsy Tissue Biopsy should reach to histopathologist without any damage. During biopsy the grasping area of forceps should be away from the site to be removed.

Submission of Specimen Information: The submission of specimen should be accompanied by the date of biopsy, name, age and sex of the patient, the area from where biopsy specimen is taken and brief description of clinical appearance of lesion and associated symptoms, along with tentative clinical diagnosis. Iodine containing surface antiseptics should be avoided since they have a tendency to stain certain tissue cells permanently. Includes normal tissue: The biopsy specimen should not only include some of the lesion but also the adjacent clinically normal tissue. The portion of the biopsy specimen to be used for routine histological study should be placed at once in a suitable fixing solution—usually 10 percent neutral buffered formalin and sent to the pathology laboratory. Teeth specimen: For the histologic examination of teeth, the apex of tooth should be clipped with a pair of pliers or a small hole should be drilled into the radicular pulp with dental bur to allow penetration of the fixative. The excellent preservation of cellular detail required is obtained by following methods: ∙ Cutting the specimen into tiny blocks before fixation. ∙ Use of special fixatives that preserve cellular detail with minimum disruption from rapid dehydration or osmotic shock. ∙ Post fixation and processing of tissues in the laboratory after the initial period of prefixation. As soon as possible after the surgical procedure.

TYPES OF BIOPSY PROCEDURES (TABLE 4.1) Incisional Biopsy Incisional biopsy can be performed by removing a wedge shaped specimen of the pathological tissue along with surrounding normal zone.

Diagnostic Pathology Table 4.1 Types of biopsy

Commonly used

Less commonly used

• Aspiration

• Bite

• Curettage

• Brush

• Excisional

• Cone

• Incisional

• Core

• Fine needle

• Endoscopic

• Punch

• Irrigation

• Scrape

• Pressure

• Trephine

• Shave

available in market. The different sizes are color coded to help quickly identify the correct size (Figs 4.1A and B).

Procedure In this technique, a sharpened hollow tube; several millimeters in diameter is rotated until underlying bone or

• Sponge

Indications Large lesion: If the lesion is large and diffuse and extends deeply into the surrounding tissue so that total removal cannot be obtained easily with local anesthesia, an incisional biopsy is indicated. Management point of view: Lesions in which diagnosis will determine whether the treatment should be conservative or radical.

Procedure Site selection: Carefully observe and palpate the lesion so that a decision can be made regarding the appropriate site that will produce a more representative specimen. It is best to select the site away from an area of necrosis, and areas of intense inflammation which may make interpretation difficult.

A

Infiltration of local anesthesia: The tissue around the specimen is infiltrate with 2 percent local anesthetic solution. Make a incision: With a scalpel, make an elliptical incision encompassing the selected area of the lesion. The incisional lines must be deep enough to include underlying connective tissue to the level of muscle or bone. Suturing: Suture is inserted through the end; upward tension is applied while tissue sample is dissected out.

Punch Biopsy With this technique the surgical defect that is produced is small and does not require suturing. Nowadays disposable, punch tools with a sharp seamless blade covered with a safety cap for protection are

B Figures 4.1A and B Disposable punch biopsy kit with different

sizes and color codes (Courtesy: Healthlink Biopsy company tools)

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muscle is reached. The tissue is then removed in the same manner as in incisional or excisional biopsy. 50

Excisional Biopsy Total excision of a small lesion for microscopic examination is called as ‘excisional biopsy’. It is a therapeutic as well as a diagnostic procedure. Normal tissue on the margins of the lesion should be included.

Indications It is indicated when the lesion is relatively small and less than 1 cm in diameter, sessile or pedunculated and well circumscribed (Figs 4.2A and B). Tissues which are freely movable and located above the mucosa or just beneath the surface.

A

It is the preferred treatment if, the size of lesion is such that it may be removed along with the margins of normal tissue and wound can be closed primarily.

Contraindication Larger lesions than 2 to 4 cm—more cases are to be operated with proper surgical planning and anesthesia Vascular lesions—e.g. hemangioma Tumors adherent to important vital structures or major blood vessels.

Procedure Anesthetize the lesion with 2 percent local anesthetic containing vasoconstrictor. Care is taken not to inject directly into the lesion that is to be removed. With the scalpel make an elliptical incision on either side of the base of the lesion so that incision line intersected. The blade should be at an angle of 45° towards the center of the lesion. Outward tension is placed on the lesion by means of suture or with the help of tissue forceps attached at the edge of specimen. Care must be taken not to crush the specimen. The specimen is now gently dissected out with either a scalpel or a pair of surgical scissors. The tissue must immediately be submerged in 10 percent formalin solution. Surgical site is closed with either silk or absorbable sutures placed approximately 5 mm apart. Care of sending large excisional tumor mass/cyst biopsy specimens for histopathology. The specimen should be immediately immersed in 10 percent neutral buffered formalin for fixation (Figs 4.3A and B). The volume of the fixative should be enough to fix the specimen. It is said that the volume of the fixative solution should be 20 times more than the size of the biopsy mass.

Mounting of the Specimen

B Figures 4.2A and B Smaller lesions of approximately 2 to 4 cm can be excised under local anesthesia with normal adjacent skin or mucosa

Making of a good museum specimen involves meticulous planning at the time of biopsy, grossing and careful handling thereafter. Oral lesions vary widely in their gross presentations, color, texture, pattern of growth and are relatively smaller and more fragile. The specimen is tied or mounted onto a glass plate or glass or with the help of suture thread or fine nylon wires (Figs 4.3A and B). Then it is carefully placed or immersed into a transparent jar of acrylic or preferably glass filled with 10 to 20 percent formalin (Figs 4.4A and B).

Diagnostic Pathology

51

A

B

Figures 4.3A and B Biopsy specimen should be immerzed in 10 percent neutral buffered formalin immediately after

removal to fix or preserve in a lifelike state

A

B Figures 4.4A and B Nowadays PET bottles acrylic is also

used for ease of mounting the specimen

The size of the jar is selected as per the suitable display of the specimen. The jar is sealed airtight with adhesive. Labeling should be properly done so as to demonstrate the structures and pathology.

EXFOLIATIVE CYTOLOGY Exfoliative cytology is a technique in which exfoliated cells assessed for pathological change. The cells examined are either manually scraped (mechanical exfoliation) or they are the cells which are spontaneously exfoliated.

Exfoliative cytology is an attractive option for early diagnosis of oral cancer including atypias and squamous cell carcinomas. It is a useful tool for detection, monitoring of initial alterations and establishment of adequate treatment. Recent advances in exfoliative cytology such as development of cytomorphometric method, DNA content determination, detection of tumor markers has contributed to renewed interest in this field. In this, the surface of the lesion is either wiped with some sponge material or scraped to make a smear. The appreciation of the fact that some cancer cells are so typical that they can be recognized individually has allowed the development of this diagnostic technique, which is developed by Dr George Papanicolaou who, is also known as the ‘father of cytology’ and the technique is called as PAP smear. Use of cytology in orofacial area was done in the year 1949 by Morrison.

Principle of PAP smear Individual cells can often be diagnosed as such microscopically by their large size, their pleomorphism, increased nucleo-cytoplasmic ratio, hyperchromatism and prominence of nuclei and their abnormal mitosis. Cancer cells exfoliate more easily than normal cells most likely because their cohesiveness is lowered as a result of either decrease in number of tight junctions.

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Indication, Advantage and Disadvantage of Exfoliative Cytology

malignant and for which, the dentist is unable to obtain permission for a biopsy.

Indication • Patient refusal for biopsy • Follow up • Debilitated patient • Aid in the diagnosis • Rapid evaluation • Patient who received radiotherapy • Vesicular lesion Advantages • Blood less procedure • Minimum discomfort • No anesthesia • Check against false negative biopsy • Recurrent carcinoma • Screening test • No complication • Rapid diagnosis • No delayed wound • Healing • Cost effective Disadvantages • Firm tumors • Inadequate sampling • Poor cellularity.

Patient who received radiotherapy: For sequential laboratory evaluation of an area of the mucosa that has previously been treated by radiation or by excisional biopsies to remove malignancy.

Indications Compromize situation: It is done as a compromize, when the patient refuses for biopsy. Follow up: As a means of follow-up for recurrence in patients who had radiation therapy for the lesion that was superficial or adjacent to bone, periodic recall of high-risk patient.

Vesicular lesion: For evaluation of vesicular lesions where facilities for rapid evaluation of Tzanck smears are not available.

Advantages Blood less procedure: It is quick, simple, painless, bloodless and an inexpensive procedure. Minimum discomfort: It causes minimum discomfort to the patient and is easily performed. No anesthesia: No anesthesia is required. Check against false negative biopsy: It helps to check against false negative biopsy. Recurrent carcinoma: It is especially helpful in a followup detection of recurrent carcinoma. Screening test: It is valuable for screening lesions whose gross appearance is such that biopsy is not warranted. No complication: It is a safe procedure as complications are rare. Rapid diagnosis: It enables a rapid diagnosis and is economical. No delayed wound healing: Less risk of delayed wound healing and infection. Cost effective: Cost of cytological investigation is less as compared to others.

Debilitated patient: In place of biopsy, when dealing with extremely debilitated patients posing problems to determine a suitable biopsy site.

Others advantage: 100 percent accuracy in lymph node aspiration from metastatic carcinoma, melanoma, Hodgkin’s and Non-Hodgkin’s lymphoma.

Aid in the diagnosis: As an aid to the diagnosis of some dermatological diseases such as Pemphigus, white sponge nevus, oral malignant and premalignant lesions.

Disadvantages

Rapid evaluation: For rapid evaluation of an oral lesion that on clinical grounds, is thought to be malignant or pre-

∙ ∙

Firm tumors: Firm tumors may prevent a proper cytodiagnosis due to paucity of cells in the aspirate. Inadequate sampling: Oral cytology can give false negative findings due to inadequate sampling.

Diagnostic Pathology

∙

Poor cellularity: Some specimens cannot be assessed ∙ due to poor cellularity. Instruments Used • G lass microscopic slide, lead pencil, cement spatula or wax carver. • Wooden tongue depressor, tooth pick, canister of cytospray. • 95 percent isopropyl alcohol or ethyl alcohol.

Procedure You should always use two slides for each site to be sampled.

∙ ∙

Class III (indeterminate): This is a stage in between that of class II and IV and separates noncancer cells from cancer cells displaying wider atypia that may be suggestive of cancer but they are not clear-cut and may represent precancerous lesion or carcinoma in situ and a biopsy is recommended in such cases. Class IV (suggestive of cancer): Few cells with malignant characteristic or many cells with borderline features. Biopsy is mandatory in such cases. Class V (positive of cancer): Cells that are obviously malignant. Biopsy is mandatory in such cases (Figs 4.5 and 4.6).

Patient data: With lead pencil print the patient’s name, date when the slide is prepared and the site of the lesion on frosted end of glass microscopic slide. The instrument selected to remove the superficial cell must have a square edge with a contour sufficient to scrape off the superficial layer of cells. When the lesion is very small, the edge of tooth pick is effective. Clearing the surface: Clear the surface of oral lesions of debris and mucus. While the tissue is stretched, the squared edge of the collection instrument is positioned at the back of the lesion and is firmly held and brought forward and pressure applied until visible material is collected. Vigorous scraping of the entire surface of the lesion several times is done with a metal cement spatula or a moistened tongue blade. Collected material is then quickly spread evenly over the microscopic slide. Fix it in commercial preparation such as spraycyte, 95 percent alcohol or equal part of alcohol and ether, immediately before it dries. Then allow it to stand for thirty minutes so that it air dried. Repeat the procedure and prepare a second smear.

Figure 4.5 Class V cytology showing cellular and nuclear

pleomorphism with increased mitosis. PAP stain (x 400)

Reporting/Interpretation It is reported by a cytologist as follows into one of the following five classes: ∙ Class I (normal): It indicates that only normal cells are observed ∙ Class II (atypical): Presence of minor atypia but no evidence of malignant changes

Figure 4.6 Keratinizing and nonkeratinizing epithelial cells

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ORAL MUCOSAL BRUSH BIOPSY 54

The most recent development in oral biopsy technique is the oral mucosal brush biopsy. It was introduced in 1999. This technique utilizes a disposable brush to collect a transepithelial sampling of cells. This brush has got 2 cutting surfaces i.e. flat end and circular border (Figs 4.7 and 4.8). Specimen obtained brushing on the site and smeared on clean labelled glass slide (Figs 4.9 and 4.10). The sample is screened by an neurally networked computer that is programmed to detect cytologic changes associated with premalignancy and squamous cell carcinoma.

Figure 4.7 Oral CDx brush for mucosal brush biopsy

Figure 4.9 Technique of CDx brush biopsy

Figure 4.8 Circular brush can generate deeper cells for

Figure 4.10 Brush is rolled onto the slide to shed

analysis

or the plating of the cells

Diagnostic Pathology

The specimen is reviewed by a pathologist for final diagnosis. This technique is ideal for determining the need for scalpel biopsy in benign-appearing oral mucosal leukoplakias.

55

LIQUID BASED CYTOLOGY Correspond to a sampling where cells are put in a suspension in a conservative liquid. Sample taken in the same manner with the help of cytobrush and immediately rinsed in bottle containing a fixative and is transported. After centrifugation, sediments that are obtained spread onto the slide followed by staining with PAP staining (Figs 4.11 and 4.12).

Figure 4.13 Aspirate expressed carefully onto slide

and spread evenly before fixation

Advantages of Liquid Cytology • • • •

Produces homogenous smears Decreases debris Has a long storage life Samples used for immunohistochemistry, HPV testing, DNA ploidy analysis, micronuclei count, etc.

FINE NEEDLE ASPIRATION CYTOLOGY

Figure 4.11 Cells are put in suspension before placing

onto slide in steps 1, 2 and 3

It is the microscopic examination of an aspirate obtained by inserting a fine needle into the lesion. It is a painless and a safe procedure for rapid diagnosis. First discovered by Kun in 1847 and reintroduced in 1930 by Martin and Ellis.

Indications FNAC of salivary glands is a useful procedure for evaluation of salivary gland tumors. It is indicated in lesions in which open biopsy require extensive procedures. It is also used for examination of enlarged clinically suspicious lymph nodes. It is used to check against recurrence or local extension. Detection of metastatic squamous cell carcinoma within cervical nodes can also be done by FNAC.

Procedure Insert needle into lesion: Position the needle within the target tissue.

Figure 4.12 Liquid cytology and PAP stain

Apply full suction: Plunger is pulled to apply negative pressure. Redirect needle within target, Apply suction until small amount of aspirate appears in hub of the needle.

Textbook of Oral Pathology

FROZEN SECTION BIOPSY

Obtain greater field: Needle is moved back and forth within the target tissue to obtain a greater field. 56

Release negative pressure: Negative pressure is then released while the needle remains within the target tissue. Blowing of aspirate on slide: Needle is withdrawn and then the defumed air drawn in the syringe and the aspirate is blown onto the slide (Fig. 4.13). Fixing: Fixing is done in 95 percent alcohol for 1 hour for PAP stain and a little prolonged for HE stain.

It is performed in order to get an immediate histological report of a lesion. It is done to determine whether a lesion is malignant or not. It is also used to evaluate the margins of an excised cancer, to ascertain that the entire lesion is removed at the time of surgery. The tissue is obtained from lesion and it is kept in deep freeze and then frozen tissue is sectioned and stained to get a prompt diagnosis. In this type of biopsy, the slides cannot be preserved for future reference.

Steps in FNAC • • • • • •

BIBLIOGRAPHY

Insert needle into lesion Apply full suction Obtain greater field Release negative pressure Blowing of aspirate on slide Fixing.

1. John Bankroft. Theory and practice of histological techniques; Churchill Livingstone; 6th edn. 2. Natarajan S, Ranjan J, Boaz K. Museum mounting techniques: Revisited econo-mode. Indian J Pathol Microbiol. 2012;55:260-1.

MULTIPLE CHOICE QUESTIONS

1. Biopsy is contraindicated in: a. Pappiloma b. c. Angiomatous lesions d.



2. Biopsy is used for: a. Diagnosis of pathological lesions b. Grading of tumor for diagnosis c. Diagnosis of metastatic lesions d. All of the above 3. Karnovsky’s fixative is: a. 4% Formaldehyde c. 10% Acetic acid

b. d.

Erythema multiforme Erosive LP



5. Incisional biopsy is indicated when the lesion is: a. Small and diffuse b. Small and localized c. Large d. Large and diffuse extends deeply into surrounding tissues

6. To determine the nature of fluid the procedure is: a. Excisional biopsy b. Incisional biopsy c. Aspiration biopsy d. Intraosseous biopsy 7. Which of the following procedure is rarely performed in oral cavity: a. Punch biopsy b. Excisional biopsy c. Incisional biopsy d. Aspiration biopsy 8. Slides cannot be preserved for future in: a. Oral mucosal brush biopsy b. Punch biopsy c. Frozen section biopsy d. Incisional biopsy

10% Formalin None

4. Excisional biopsy is indicated when a lesion is: a. Less than 2 cm in diameter b. Less than 1 cm in diameter c. More than 2 cm in diameter d. More than 5 cm in diameter





9. Father of cytology is: a. C. Gram b. Edward Jenner c. Morrison d. Dr George Papanicolaou

10. Test which determines the number of colonies of bacteria is: a. Snyder test b. Lactobacillus count test c. Albans test d. Dewar test

Advanced Diagnostic Techniques Shubhangi Mhaske (Jedhe), Monal Yuwanati A

Chapter Outline O O O O O O O O O

Histochemical techniques Fixation in histochemistry Enzyme histochemistry Immunohistochemical methods Immunofluorescent techniques Flow cytometry Polymerase chain reaction ( PCR) Hybridization methods Laser captures microdissection

As knowledge of pathology expanded, it was found that hematoxylin and eosin staining alone is not adequate to identify various structures present within tissues . A need for procedures that can identify special structures was felt . This led to identification of various special dyes and various techniques that can identify one or few components that are difficult to identify by routine H&E staining . Such techniques involved identifying definite chemical groups, so they were called as histochemical techniques . Advances in immunology led to replacement of these chemicals and dyes with antibodies . This improvement led to increased sensitivity and specificity in identifying various tissue components . Advances in genetics brought about a revolution in field of pathology and microbiology . Now because of use of various DNA /RNA based techniques, it is now possible to identify pathology at gene level . Also very rapid identification of microorganisms is possible .

O Proteomics O Cytogenetics • Karyotyping

• • • • •

Chromosomal banding Karyotype analysis Chromosome ideograms/karyogram Alterations in chromosome number Number and size of bands

HISTOCHEMICAL TECHNIQUES Histochemistry is study of the chemical composition of tissues by means of specific staining reactions. It involves identification of various enzymes and other chemical substances in relation to tissues or organelles within a cell . To study the distribution of these chemical substances it is essential to preserve these carefully. Certain fixatives cause alteration in chemical structure, making identification of these substances difficult . Thus fixation is one of important aspect during histochemistry .

FIXATION IN HISTOCHEMISTRY For identification and localization of chemical substances tissue must be preserved in a such way that it causes minimal changes the reactivity of the cytoplasmic and extracellular macromolecules, for example enzymes, proteins, carbohydrates, lipids and nucleic acids . This is

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accomplished by using optimum osmotic conditions, cold temperatures, controlled pH of the fixing solutions, and the minimum possible exposure to the fixative. Formaldehyde is widely used fixative. It is ideal for fixing proteins and enzymes. It causes cross linking of proteins without affecting their reactivity. But it is a poor preservation of lipids. But it is used to fix lipids especially phospholipids by adding calcium which prevents dissolution of phospholipids. For histochemical techniques neutral buffered formaldehyde is used as cold solution. Formal calcium is also used. Other substances used are gluteraldehyde and acrolein. For study of glycogen, glycoprotein, proteoglycans and nucleic acids mixtures of many chemicals are used as fixatives. For example Rossmans fluid is used for visualization of glycogen, glycoprotein, and proteoglycans, Conroy’s solution is used as fixative for nucleic acids. Certain tissue groups are highly labile and sensitive. Such chemicals cannot be fixed by use of fixative. They are visualized from fresh frozen sections, where tissue is rapidly frozen by used of liquid nitrogen immediately after removal from the body. Other techniques are freeze drying and freeze substitution. Various techniques involved in identifying different chemicals and structures are given in the chapter Theory and practice of staining.

ENZYME HISTOCHEMISTRY It involves identifying and locating enzymes within the cell. The technique involves series of chemicals to get insoluble colored reaction product. By this technique various enzymes have been identified (Table 5.1).

IMMUNOHISTOCHEMICAL METHODS Immunohistochemistry is the localization of antigens in tissue sections by the use of antibodies labeled with fluorescent dye, enzyme or radioactive isotope or colloidal gold. Albert H Coons 1941 was the first to label antibodies with a fluorescent dye, and use it to identify antigens in tissue sections. With the expansion and development of immunohistochemistry technique, enzyme labels have been introduced such as peroxidase and alkaline phosphatases. Colloidal gold label has also been discovered and used to identify immunohistochemical reactions at both light and electron microscopy level. Other labels include radioactive elements, and the immunoreactions can be visualized by

Table 5.1 Techniques in enzyme histochemistry

Enzymes

Technique

Alkaline phosphatases

Gomori Calcium method, Azo dye coupling method, Naphthol AS-BI method

Acid phosphatases

Gomori lead method, Azo dye coupling method, Naphthol AS-BI method

ATP

Metal precipitation method

Esterase

a Naphthyl acetate method, Indoxyl acetate method

Cytochrome oxidase

Seligman’s technique

β-glucuronidase

Naphthol AS-BI method

G6PD

Lead method

autoradiography. Since immuno-histochemistry involves specific antigen-antibody reaction, it has apparent advantage over traditionally used special and enzyme staining techniques that identify only a limited number of proteins, enzymes and tissue structures. Therefore, immunohistochemistry has become a crucial technique and widely used in many medical research laboratories as well as clinical diagnostics.

Principle The basic principle of this technique is isolation of tissue antigen that is needed to be localized in tissue. Using this pure protein, antibodies are formed. Such antibodies are labeled with enzymes. These labeled antibodies are used to cleave a suitable substrate that produces a insoluble colored precipitate in the tissues. Animals such as mouse, guinea pig, sheep or rabbit are used to develop antibodies. Such antibodies contain different types of antibodies derived from different clones of plasma cell. Such antibodies are called polyclonal antibodies. They are highly sensitive but specificity is low. To increase specificity monoclonal antibodies are used. They are manufactured by a special process known as hybridoma technique. Here plasma cells producing specific antibody are fused with malignant cells obtained from myeloma, a neoplasm of B-lymphocytes. Monoclonal antibodies are highly specific. Various enzymes are used for labeling of the antibodies. More commonly used are alkaline phosphatases and horse radish peroxidase. These enzymes produce color

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when substrate is applied. Different enzymes use different substrates. Alkaline phosphatase enzyme uses Fast Red and New Fuchsin. On the other hand horse radish peroxidase uses Diamino Benzidine and AEC as substrate. Types • Direct method • Indirect method.

Types (Fig. 5.1) There are numerous immunohistochemistry methods that may be used to localize antigens. Direct method: It is also called as single step method. Here labeled antibody is directly applied to tissues. Later addition of substrate causes formation of colored precipitate. Indirect method: This is two step methods where two antibodies are applied. First, primary antibody is applied which reacts with protein of interest. This is followed by a second antibody which is “antibody of primary antibody”. This secondary antibody is labeled with enzyme, which on application of substrate produces colored precipitate. There are numerous other methods available for immunohistochemistry which vary in specificity and sensitivity. They are labeled antibody method, enzyme bridge method, PAP method, APAAP method, immune complex method, avidine biotine Method, streptavidine biotine method, and avidin-biotine-peroxidase complex method, LSAB method, polymeric methods and CSA method.

adjunct to H & E diagnosis in a majority of equivocal tumor cases, through the establishment of a definitive diagnosis or through confirmation of H & E section impression. It is used to establish origin of a tumor. For this various markers are used. Tumor markers of patient course and outcome: Certain proteins and enzymes are indicators of prognosis and response to therapy. Such molecules are used to determine the course and outcome of the therapy (Table 5.2). Other applications: Immunohistochemistry is used to identify bacteria and viruses in odontogenic tumors and other lesions. It is used to identify human papilloma virus in ameloblastoma. Similarly it has been used to identify various genes that contribute to tumorigenesis, growth and spread of tumors.

IMMUNOFLUORESCENT TECHNIQUES Immunofluorescent techniques are similar to immunohistochemistry. Here instead of enzymes antibodies are labeled with a fluorescent dye-fluorescence. There are two Table 5.2 Various markers used in oral pathology

Tissue

Markers

Epithelium

Keratins

General mesenchymal marker Vimentin, desmin, GFAP Muscle markers

Desmin, actins, myoglobin, myogenin

Applications of Immunohistochemistry

Neural markers

Diagnostically challenging oral malignant neoplasm: Immunohistochemistry has been shown to be an effective

S-100, GFAP, neurofilaments, and CD57

Endothelial markers

CD31, CD34, and factor VIII–related antigen

Melanocytic markers

HMB45, MART-1 (Melan-A), and S-100 protein

Lymphoid markers

κ and l, CD3, CD15, CD20, CD30, CD45, CD68, CD79a, ALK-1, and TdT

Neuroendocrine markers

Synaptophysin and chromogranin

Ewing’s tumor marker

CD99

Figure 5.1 Direct and indirect immunohistochemistry

Metastatic tumor markers

CK7, CK20, villin

Salivary gland tumor markers

S-100 protein and actins

Odontogenic tumor markers

Shethilin, enamelin, ameloblastin

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techniques in immunofluorescence, i.e. direct and indirect technique. 60

Direct immunofluorescence technique: In this technique antigens are detected in the tissues of patients. Here labeled antibodies are directly applied to the tissues. If antigen of interest is present in the tissues it will show fluorescence when viewed under fluorescent microscope (Fig. 5.2). Indirect immunofluorescence technique: This is a method of detecting antibodies in plasma. In this technique (Fig. 5.2) direct immunofluorescence method plasma containing primary antibodies is applied to suitable substrate. Over this secondary antibody labeled with fluorescein is applied and slide is observed under fluorescent microscope for fluorescence (Fig. 5.3). Applications: Direct immunofluorescence has more application in dentistry than indirect technique. Direct technique has application in diagnosis of various vesiculobullous lesions (Table 5.3). It is used in diagnosis of lichen planus, lupus erythematosus, pemphigus vulgaris, and mucous membrane pemphigoid. Anti-human IgG, IgA, IgM, complement component (C3), and fibrinogen are used to diagnose these lesions. These are used on fresh frozen sections or tissues fixed with Michael’s solution. Based on location and appearance of immunofluorescence these lesions are diagnosed (Fig. 5.3).

Figure 5.3 Indirect immunofluorescence technique

Table 5.3 Immunofluorescence appearance of various vesiculobullous lesions

Pemphigus vulgaris: It shows interepithelial distribution of anti-IgG immunofluorescence (some C3 deposition is also noted). It takes a net like distribution pattern.

Lesion

Serum component

Appearance

IgG

Net like ditribution

Mucous membrane pemphigoid: It shows a linear pattern of immunofluorescence at the basement membrane. All three antibodies, i.e. anti-IgG, anti-IgA, and anti-C3 antibodies are deposited at the basement membrane.

Pemphigus vulgaris Mucous membrane pemphigoid

IgG, IgA, C3

Linear distribution along basement membrane

Lichen planus

IgG, IgA, C3

Shaggy or fibrillar pattern

Lupus erythematosus

C3, IgM, IgA, and IgG

Coarse granular deposition

Figure 5.2 Direct immunofluorescence technique

Lichen planus: Lichen planus (LP) shows a characteristic pattern of fibrinogen deposition outlining the basement zone and extending irregularly into the superficial lamina propria, described as a “shaggy” or “fibrillar” pattern. Another finding typical of but less frequently observed in lichen planus is the presence of IgM-, IgA-, IgG-, or C3positive “cytoid,” “colloid,” or “apoptotic” bodies, located in the epithelium and superficial connective tissue.

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Lupus erythematosus: DIF reactions in specimens of oral mucosal lupus erythematosus (LE) exhibit coarse granular deposits of C3, IgM, IgA, and IgG in the basement zone.

FLOW CYTOMETRY Flow cytometry is the process in which measurements are made while cells in a liquid suspension are forced to flow one at a time through a measuring device. It is a technique for counting, examining and sorting cells suspended in a stream of fluid. It allows simultaneous analysis of the physical and/or chemical characteristics of single cells flowing through an optical and/or electronic detection apparatus (Fig. 5.4). A beam of laser light is directed onto a stream of fluid containing suspension of cells. A number of detectors are aimed at the point where the stream passes through the light beam; one in line with the light beam and several perpendicular to it. Each cell passing through the beam scatters the light in some way. This scattered light is picked up by the detectors, and analyzed by using computers. By detecting variations in the brightness at each detector it is then possible to extrapolate various types of information about the physical and chemical structure of each individual cell. To aid in detection cells are usually stained immunocytochemically or by immunofluorescent stains.

The main limitation of flow cytometry is need for single cell suspension. This is not a problem for samples such as blood and other body fluids. It is difficult to employ this technique for solid tumors. But now various techniques have been developed to overcome this difficulty. Application of Flow Cytometry in Pathology • It is used to support a diagnosis of malignancy when the morphological changes are equivocal. • It can be used to classify tumors of borderline malignancy. • It provides prognostic information independent of stage and grade of the tumor. • It helps to identify tumor relapse. • It helps to detect tissue of region of a tumor. Tissue from paraffin embedded tissue can also be used for flow cytometry. The section is dewaxed hydrated by passing through xylene and graded alcohols. Then tissue is minced with sharp scissors in a watch glass. Following this tissue is digested using 0.5 percent pepsin and a liquid suspension is prepared. This releases the DNA which is stained using appropriate agent and then fed into the flow cytometer.

POLYMERASE CHAIN REACTION Polymerase chain reaction (PCR) is the enzymatic amplification of a specific DNA sequence in vitro to obtain large number of DNA copies. This technique amplifies DNA without involving any live organism, so it can be repeated any number of times. As it is a in vitro procedure it can be subjected to different modifications. Polymerase chain reaction (PCR) is used to amplify specific regions of a DNA strand. Following steps are followed in PCR (Fig. 5.5). Denaturation: The DNA which needs to be amplified is isolated. It is added to reaction mixture which contains nucleotides, primer, which closely resembles gene of interest, and polymerase enzyme in a micropipette and heated to high temperature of 90 to 95°C. At this temperature two strands of DNA separate. Application: Once primary attaches to the DNA polymerase starts synthesizing the DNA for nucleotides present in the reaction mixture.

Figure 5.4 Parts of a flow cytometer

Annealing: Temperature lowered to 50 to 60°C. At this temperature primer attaches to gene of interest. In this way two DNA chains are formed at the end of one cycle. In next

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RT-PCR: The RT-PCR (Reverse transcription-PCR) is a method used to amplify, isolate or identify a known sequence from RNA. In this technique DNA is synthesized first from RNA using the enzyme reverse transcriptase. This DNA acts as an template for further amplification.

62

Application of PCR in Dentistry Microbial identification: The use of PCR has revolutionized the diagnosis and study of infectious diseases and malignancies associated with microorganisms. PCR is used to identify bacteria and viruses in infections. It has been used to study microorganisms causing periodontal, endodontic infections and to identify microorganisms of dental caries. Human genetics: PCR plays an important role in the identification of chromosomal disorders and hereditary diseases, including cystic fibrosis, Gaucher’s disease, alpha-1-antitrypsin deficiency, hemophilia, and sickle cell anemia. PCR can also be used to analyze fetal DNA for aneuploidy the presence of extra chromosomes or the absence of chromosomes, trisomy 21, Turner’s syndrome, Klinefelter’s syndrome, and for sex determination. Forensic odontology: PCR is used for identification of mutilated or decomposed human tissues, for sex determination, and for disputed paternity cases. Figure 5.5 Steps involved in PCR

step these two DNA chains act as template for next cycle. By the end of next cycle 2X2 DNA are formed. In next step 4X2 DNA chains are formed. This process continuous exponentially. This whole step is repeated many number of times to amplify the DNA. The reaction is terminated after sufficient number of DNA fragments is formed. The DNA amplified is separated by electrophoresis and analyzed.

Modifications of PCR Hot-start PCR: This is a technique that reduces nonspecific amplification during the initial set-up stages of the PCR. Multiplex-PCR: The use of multiple, unique primer sets within a single PCR reaction. Nested PCR: Nested PCR increases the specificity of DNA amplification, by reducing background due to nonspecific amplification of DNA. Quantitative PCR: This is used to measure the quantity of a PCR product.

Tumor biology: PCR is used to identify various cancer associated genes.

HYBRIDIZATION METHODS Hybridization refers to pairing of complimentary copies of DNA. As pairing between two DNA fragments is very specific, one copy can be used to detect other copy. This detector copy is known as a probe. It is labeled with either fluorescent material or radioactive isotopes. Southern blot: This is a detection method for DNA. The DNA under question is digested using enzymes to produce small fragments. These fragments are separated by electrophoresis on agar gel. Once these fragments are separated they are blotted on to a paper by placing the paper on agar gel. Once the DAN fragments are separated and blotted probe is applied. After washing it may be observed under UV light. If it shows positive reaction it means that it contains DNA under investigation. Northern blotting: It is similar to southern blotting. The only difference is in this technique instead of DNA, RNA is detected. The procedure is similar to Southern blotting.

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Western blotting: Western blotting is not a DNA/RNA blotting method. It a method used to separated proteins. It is also similar to southern blotting. In situ hybridization: It is a method of identifying DNA and RNA in tissue samples. It is similar to southern blotting method. Here a probe containing complementary copy of DNA/RNA under investigation is prepared. The probe is either labeled with radioactive isotope or fluorescent dyes. In latter case it is called as fluorescent in situ hybridization (FISH). The labeled probe is placed on tissue and allowed to hybridis. This is detected by observation under fluorescent microscope or by exposing X-ray film in case of radioactive labeled probes. ISH has wide applications in dentistry. It is used to detect various viruses in the tissues. Similarly it is used to identify various genes involved in tumor biology (Fig. 5.6).

LASER CAPTURES MICRODISSECTION Tissue obtained by biopsy contains mixture of different cell populations. In such case it becomes difficult to obtain homogeneous population of cells for further study. In a new technique it is possible to isolate and obtain a homogeneous population of cells using infrared laser light. In this technique a plastic sheet is placed on the slide. The area of interest is identified and it is radiated with laser light. This caused plastic film in that area to melt and adhere to tissue. The adherent tissue can be lifted and further processed. Thus in this technique it is possible to obtain specific area of tissue and homogeneous population of cell without distorting the structure and contents. This method is fast,

Figure 5.6 In situ hybridization

precise, and adaptable to a wide range of tissues and molecules to be studied. Both the tissue left behind and the tissue retrieved can be identified, and the morphology of both is excellent. Large numbers of well-characterized cells can be obtained within a few minutes. The applications of microdissection in pathology increasing. It is used to obtaining pure cell populations from fresh, frozen, or fixed tissues and cytology samples for DNA molecular genetic analysis; gene expression studies involving mRNA such as RT-PCR (Fig. 5.7).

PROTEOMICS It is also called as microarray technology. Here it is possible to simultaneously analyze tens of thousands of genes in single step. The main applications of this technology are study of gene expression analysis, genotyping for detection of point mutations, single nucleotide pleomorphism, etc. Conceptually, DNA microarray technology is similar to the

Figure 5.7 Laser capture microdissection

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underlying principles of Northern and Southern blotting. Here first step is preparation of probes. Probes are labeled genomic DNA, cDNA and oligonucleotides produced from tumor mRNA by a process of reverse transcription. These probes are attached or “printed” on a solid phase or a “chip”. The tumor to be tested is applied on this chip. Complementary DNA hybridizes with the corresponding probes. This hybridization results in varying green/red and yellow fluorescent emissions. These emissions are then scanned by a argon laser reader and a scanning confocal microscope. This is analyzed by computer for quantification of intensity of thousands of different genes on the array. This is compared with normal tissues. Thus in recent times diagnostic pathology has witnessed a range new technologies to help in diagnosis, prognosis, and treatment of the diseases. Some of these methods are based on antigen and antibody reactions, some are based on DNA hybridization, and some are based on laser technology.

There are 22 pairs of chromosomes which match up exactly. The karyotyping procedure is time consuming and technically demanding, when done manually. Nowadays karyotyping has become fully automatic due to software (e.g. LeicaTM, Metasystems TM and CytovisionTM) are utilized. Cytogenetic analyzes are almost always based on examination of chromosomes fixed during mitotic metaphase. Centromere position and arm ratios can assist in identifying specific pairs of chromosomes, but inevitably several or many pairs of chromosomes appear identical by these criteria. The ability to identify specific chromosomes with certainty was revolutionized by the discovery that certain dyes would produce reproducible patterns of bands when used to stain chromosomes.

CYTOGENETICS

Q banding: Chromosomes are stained with a fluorescent dye such as quinacrine.

Cytogenetics is the study of normal and abnormal chromosomes. This includes examination of chromosome structure, learning and describing the relationships between chromosome structure and phenotype, and in quest of the causes of chromosomal abnormalities. In the simplest case, examination of chromosomes and characterization of an individual’s karyotype for detection of acquired or genetic chromosomal abnormalities, such as translocations, deletions, monosomies or trisomies, etc. The karyotyping procedure is one of the most important steps in conventional cytogenetic analysis. The karyogram is an image representation of stained human chromosomes with the widely used Giemsa Stain metaphase spread (G-banding) in which homologous chromosomes are paired in 23 classes, arranged in order of decreasing size.

Karyotyping The karyotyping is a set of procedures, in the scope of the cytogenetics, which produces a visual representation of the 46 chromosomes, paired and arranged in decreasing order of size, observed during the metaphase step of the cellular division (meiosis). These chromosomes are then arranged systematically for comparison. The chromosomes pairs are numbered from largest to smallest.

Chromosomal Banding Chromosome banding has since become a standard and indispensable tool for cytogenetic analysis and several banding techniques have been developed:

G banding: Produced by staining with Giemsa after digesting the chromosomes with trypsin. C banding: Chromosomes are treated with acid and base, then stained with Giemsa stain. Each of these techniques produces a pattern of dark and light (or fluorescent versus non-fluorescent) bands along the length of the chromosomes. Importantly, each chromosome displays a unique banding pattern, analogous to a bar code, which allows it to be reliably differentiated from other chromosomes of the same size and centromeric position.

Number and Size of Bands Idealized diagrams (ideograms) of G-banded chromosomes are published as standard reference points for chromosome banding. The G-bands are usually portrayed in black and the R-bands in white. Bands are numbered consecutively away from the centromere on both the short (p) and long (q) arms. The total number of bands or ‘resolution’ in the human karyotype depends on state of chromosomes and stage of mitosis. Karyotypes are arranged with the short arm of the chromosome on top, and the long arm on the bottom. In

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addition, the differently stained regions and sub-regions are given numerical designations from proximal to distal on the chromosome arms. Chromosomes can be Classified by the Position of Their Centromere • Metacentric: If its two arms are equal in length. • Submetacentric: If arms’ lengths are unequal. • Acrocentric: If the p arm is so short that is hard to observe, but still present.

Alterations in Chromosome Number Aneuploidy: Abnormal chromosome number. Trisomy: Cell has one extra chromosome. Monosomic: Cell has one missing chromosome. Nondisjunction: It occurs when either homologue fail to separate during anaphase I of meiosis, or sister chromatids fail to separate during anaphase II. Translocation: It is the result of chromosomal breakage but the broken segment transfers itself to a broken segment of another chromosome. There are both balanced and unbalanced translocations. Deletion: Deletion occurs when a chromosome breaks and a portion of the chromosome is lost. Inversion: A section of the chromosome is inverted (reversed) on the same chromosome.

Karyotype Analysis Obtain chromosome: Obtain a set of chromosomes. Matching: Match the chromosomes with their homologous mate. It should be very systematic. The number one chromosome is the largest. Its corresponding mate should be of the same size, with the same banding pattern, and have the same centromere location. Determining the karyotype abnormalities: Determine the karyotype abnormality using the chromosome analysis key that is below (Fig. 1). Identify abnormality: Identify abnormality using as standard reference points for chromosome banding for the disorder.

Chromosome Ideograms/Karyogram A consistent numbering system is essential for mapping chromosomes. In Paris 1971 a mapping system known as

the International System for Cytogenetic Nomenclature (ISCN) was established. The rules of the ISCN numbering system ∙ Numbering of a chromosome begins at its centromere. ∙ Chromosomes are assigned a long arm and a short arm, based on the position of their centromere. The shorter arm of the chromosome is known as the p, or peptite arm, from the French word for small. The longer arm is known as the q. Chromosomal regions that are present on the short arm will begin with the designation p, while regions on the long arm will begin with q. ∙ By convention, the p arm of the chromosome is always shown at the top in a karyotype. ∙ Each arm of the chromosome is divided into regions. The numbers assigned to each region gets larger as the distance from the centromere to the telomere increases. Regions are identified by specific morphological features that are consistently found on a chromosome, such as the presence of a prominent Giemsa-staining band. The regions are named p1, p2, etc. on the short arm and q1, q2, etc. on the long arm. ∙ Depending on the resolution of the staining procedure, it may also be possible to detect additional bands within each region, which are designated by adding a digit to the number of the region, increasing in value as the distance from the centromere increases. Groups of Chromosomes • G roup A: Chromosomes 1–3 are largest with median centromere • G roup B: Chromosomes 4–5 are large with submedian centromere • G roup C: Chromosomes 6–12 are medium sized with submedian centromere • G roup D: Chromosomes 13–15 are medium sized with acrocentric centromere • Group E: Chromosomes 16–18 are short with median or submedian centromere • Group F: Chromosomes 19–20 are short with median centromere • Group G: Chromosomes 21–22 are very short with acrocentric centromere • Chromosome X is similar to group C • Chromosome Y is similar to group G. Chromosomes are arranged into seven groups based on size and centromere location. The centromeres can be found in the middle of the chromosome (median), near one

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Figure 5.8 Classification of chromosomes for karyotyping

end (acrocentric), or in between these first two (submedian) (Fig. 5.8). Cytogenetic approaches enable researchers to precisely identify the chromosomal location of any gene and examine cells from any type of tissue, especially tumor cells. Identify cells that have lost or gained a specific chromosome, undergone a translocation event involving a specific set of chromosomes, or lost or gained a copy of a given gene or genes. Determine whether specific regions of chromosomes have been lost or gained without ever looking at the chromosomes under a microscope.

5.

6.

7.

BIBLIOGRAPHY 1. Espina V, Wulfkuhle JD, Calvert VS, VanMeter A, Zhou W, Coukos G, Geho DH, Petricoin EF 3rd, Liotta LA. Lasercapture microdissection. Nat Protoc. 2006;1(2):586-603. 2. Fend F, Raffeld M. Laser capture microdissection in pathology. J Clin Pathol. 2000;53(9):666-72. 3. George J Netto, Rana D Saad, Peter A Dysert. Diagnostic molecular pathology: current techniques and clinical applications, part I. Proc (Bayl Univ Med Cent). 2003;16(4):379-83. 4. Hannon-Fletcher M. Cytopathology, in Advanced Techniques in Diagnostic Cellular Pathology. In: Hannon-

8.

9.

10.

Fletcher M, Maxwell P (Eds), John Wiley & Sons, Ltd, Chichester, UK, 2009. doi: 10.1002/9780470745069.ch2 Jordan RC, Daniels TE, Greenspan JS, Regezi JA. Advanced diagnostic methods in oral and maxillofacial pathology. Part I: molecular methods. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92(6):650-69. Jordan RC, Daniels TE, Greenspan JS, Regezi JA. Advanced diagnostic methods in oral and maxillofacial pathology. Part II: immunohistochemical and immunofluorescent methods. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;93(1):56-74. Nederlof PM, van der Flier S, Wiegant J, Raap AK, Tanke HJ, Ploem JS, van der Ploeg M. Multiple fluorescence in situ hybridization. Cytometry, 1990;11:126-31. doi: 10.1002/ cyto.990110115. O’Grady A, O’ Loughlin J, Magee H. Tissue in Situ Hybridization, in Advanced Techniques in Diagnostic Cellular Pathology. In: Hannon-Fletcher M, Maxwell P (Eds), John Wiley & Sons, Ltd, Chichester, UK, 2009. doi: 10.1002/9780470745069.ch6 Poletti E, Grisan E, Ruggeri A. Automatic classification of chromosomes in Q-band images. Proc. 29th Annual International Conference of IEEE-EMBS, IEEE, New York; 2008. pp. 1911-4. Strachan T, Read AP. Human molecular genetics. Bios Scientific Publishers, Oxford, UK, 1996.

Advanced Diagnostic Techniques

MULTIPLE CHOICE QUESTIONS 1. Who was the first to label antibodies with a fluorescent dye: a. Albert Coons b. Morrison c. Alban d. Flemming 2. Which one of the following is a marker for epithelium: a. Desmin b. Keratin c. CD99 d. CK7 3. Which one of the following is NOT a muscle marker: a. Desmin b. Actin c. Myoglobin d. Enamelin 4. CD3, CD15, CD20 are the examples of: a. Epithelium markers b. Neural markers c. Lymphoid markers d. Endothelial markers 5. S-100 protein is: a. Salivary gland marker b. Melanocytic marker c. Ewing’s tumor marker d. None

6. Immunofluorescence appearance of lichen planus is: a. Net like b. Shaggy or fibrillar type c. Coarse granular d. Linear 7. Southern blot method is used to detect: a. RNA b. DNA c. Both RNA and DNA d. Proteins 8. Method employed for identifying ATP enzymes are: a. Gomori calcium method b. Seligman’s technique c. Metal precipitation method d. All 9. Odontogenic tumor marker is: a. Shethilin b. CK20 c. Villin d. ALK-1 10. Coarse granular deposition immunofluorescence appearance seen in: a. Pemphigus b. Lichen planus c. Candidiasis d. Lupus erythematous

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Healing of Wound

Shubhangi Mhaske (Jedhe) A

Chapter Outline O O O O O O

General factors affecting healing Cascade of wound healing Healing of biopsy wound Healing of tooth extraction wound Healing of bone fracture Healing of pulp

INTRODUCTION Oral wounds are relatively common mucosal wounds; healing in these tissues can reflect the susceptibility of other mucosal tissue to repair and infection . Wound repair is a well orchestrated and highly coordinated process that includes a series of overlapping phases : inflammation, cell proliferation, matrix deposition, and tissue remodeling . This involves a complex, dynamic series of events including : clotting, inflammation, granulation tissue formation , epithelialization, neovascularization, collagen synthesis, and wound contraction. The knowledge of the physiology of the normal wound healing process through the phases of hemostasis, inflammation, granulation and maturation provides a framework for an understanding of the basic principles of wound healing . Wound healing is the physiologic response to tissue trauma. It is related to tissue reconstitution which is the process by which the body replenishes cells that are being lost by normal physiologic events . In both processes similar

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Healing cementum Healing of dentin Healing of enamel Difference between skin healing and mucosal wound healing O Clinical approach to optimizing wound healing O O O O

events occur in varying degrees . The same basic molecular mechanisms governing growth and differentiation are active to a different extent . Without these being properly in place, even old wounds may be become subject to “reopening ”.

FACTORS AFFECTING THE WOUND HEALING There are many factors that can affect wound healing which interfere with one or more phases in this process, thus causing improper or impaired tissue repair. These multiple factors can lead to impaired wound healing . Factors may be considered in one of two categories depending on their source .

Extrinsic factors: Impinge on the patient from the external environment.

Intrinsic factors : Directly affect the performance of bodily functions through the patient 's own physiology or condition .

Healing of Wound

In general terms, the factors that influence repair can be categorized into local and systemic. Local factors are those that directly influence the characteristics of the wound itself, while systemic factors are the overall health or disease state of the individual that affect his or her ability to heal (Table 6.1). Many of these factors are related, and the systemic factors act through the local effects affecting wound healing.

Local Factors Location of Wound Wound in an area which has a good vascular bed heals more rapidly than wounds in an area which is relatively avascular. Immobilization is important in healing of a fracture. If the wound is in an area that is subjected to constant movement and so the formation of new connective tissue is disrupted (in the corner of mouth) thus delaying the healing process.

Poor Circulation and Oxygenation It has been shown in numerous clinical studies that typical wound partial pressures of oxygen are markedly reduced and may be the rate limiting process in wound repair. Oxygen is essential for maintaining cellular integrity, function, and repair when tissues are injured. Oxygen not only plays an important role in energy metabolism, but also is very important in polymorphonuclear cell function, neovascularization, fibroblast proliferation, and collagen deposition. Though in cases of acute hypoxia, healing will occur as long as other factors such as nutrients, blood flow, and immune function remain adequate, to allow

regeneration of capillaries and restoration of nutrient delivery. Thus, other factors collaterally play a role in situations where oxygen delivery is impaired and chronic nonhealing wounds may develop.

Dressings and Local Infection Wound infection delays collagen synthesis and causes granulation tissue to become more fragile and prone to bleeding. Wound Infection also delays healing as microorganisms compete for oxygen and nutrients with macrophages and fibroblasts. The use of dressings, which adhere to the wound bed, and the inappropriate usage of antiseptics can all lead to the hindrance of wound healing.

Foreign Bodies Foreign bodies in the wound may be due to the presence of grit, parts of old dressings, suture material, staples, etc. These set­up an inflammatory response, which may increase the length of the inflammatory phase. Presence of foreign body also hampers the process of response of cellular events, mesh formation and collagen integrity subsequently leading to delayed healing.

Wound Temperature This will inevitably slow down the healing process. The optimum temperature for cellular activity and division is 37°C and with a drop of 1°C it will take up to three hours for mitotic cell division to restart. Frequent dressing changes, application of cold solution and leaving the wound exposed can decrease the local temperature.

Table 6.1 Local and systemic factor affecting the wound healing

Local factors

Systemic factors

Social factors

• Location of wound • Poor circulation and oxygenation • Dressings and local infection • Foreign bodies • Wound temperature • Saliva (in case of oral wounds) • Mechanical stress • Desiccation or dryness of wound

• Nutritional status • Age and gender • Smoking and alcohol drinking • Drugs • Vascular and oxygen supply • Surgical techniques • Stress • Obesity • Infection • Diseases • Sex hormones • Immunocompromised conditions, cancer, radiation therapy, AIDS

• Poverty • Lifestyle • Housing • Cultural beliefs

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Saliva (in Case of Oral Wounds)

Desiccation or Dryness of Wound

Besides prevention of wound infections through the above antimicrobial effects, saliva plays other roles in the healing of oral wounds as well. Salivary EGF speeds up the healing process by its angiogenetic and cell proliferating effects. EGF promotes re-epithelialization of oral mucosa. In addition to EGF in saliva, many other growth factors including insulin-like growth factor (IGF), transforming growth factor (TGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), insulin like growth factors and nerve growth factor (NGF) produced at the wound also contribute to the healing process. Insulin-like growth factor (IGF-1), an isoform of IGF, stimulates chemotaxis of endothelial cells and proliferation of keratinocytes and fibroblasts, which promote re­ epithelialization and extension of wound. Transforming growth factor -beta1, an isoform of TGFbeta, promotes chemotaxis of monocytes, macrophages, neutrophils, lymphocytes, keratinocytes and fibroblasts, and production of growth factors from those cells. These accelerate vascularization, deposition of extra­ cellular matrices and inhibition of degradation of extra­ cellular matrices. Furthermore, saliva contains several blood clotting factors (IXa, VIII, XI) at a level comparable to plasma, and saliva can replace platelets in the thrombin generation. This property of saliva is highly important in the oral wound healing because, although saliva dilutes blood­ clotting factors of blood origin, blood­clotting can be initiated. A relatively high amount of salivary kallikrein is suggested to play a role in vasodilatation around mucosal injuries to facilitate healing and defense of the injured area. Hence, any condition which affect the salivary secretion any delay the wound healing.

Dry wounds do not heal well due to the formation of eschar which slows down the migration of cells in the epidermis. This is because migrating cells are forced deep into the dermis beneath the scab and healthy tissue becomes devitalized. In turn healing is delayed due to the enlargement of the wound. This is more in case of skin/cutaneous wound. Therefore the patient must not become dehydrated.

Mechanical Stress

Drugs

Mechanical stress can disturb the growth of granulation tissue which is an essential part of wound healing particularly in the process of healing by secondary intension. This is because mechanical stress interrupts the proliferation of new capillary growth. These new capillaries carry the oxygen that is needed for epithelialization and without the capillaries the wound will be unable to heal up due to the hypoxic conditions.

There are a variety of drugs that can impair the healing process. Medication can have a delaying effect on healing as well as an accelerating effect depending on the nature of the drug. Steroids are used as anti-inflammatory and immunosuppressant which will reduce the body’s response to damage, delaying the healing process. For example, Corticosteroids and nonsteroidal inflammatory drugs reduce the normal inflammatory response and by

Systemic Factors Nutritional Status Wound healing requires an adequate supply of macro and micronutrients. Deficiencies can result in poor wound healing, reduced tensile strength, wound dehiscence, and increased vulnerability to infection and poor quality scars.

Age In advancing age, many processes slow down. The inflammatory response is reduced; therefore the risk of infection is increased. Collagen metabolism is reduced with the resulting scar being more fragile and there is less support for blood vessels thus making them more prone to damage. It is more likely that other medical problem, which are common in the elderly, slow down the healing process more than age itself.

Smoking and Alcohol Drinking Smoking and alcohol abuse which leads to damage of the Liver and digestive system which can indirectly lead to delayed wound healing. Smoking can also affect epithelialization rates and cause problems with scarring. The pathophysiological effects are multidimensional, including arteriolar vasoconstriction, cellular hypoxia, demineralisation of bone, and delayed revascularization.

Healing of Wound

suppressing the synthesis of fibroblasts and collagen and slowing down epithelialization. Antibiotics can enhance wound healing as they kill infective agents allowing healing to proceed. For example Aspirin and anticoagulants may cause excessive bleeding with the potential of a hematoma if not given in the correct dosage. Immunosuppressive drugs reduce leukocyte activity which reduces the inflammatory response and increases the risk of infection. Cytotoxic drugs interfere with cell proliferation including cells needed for wound healing.

Vascular and Oxygen Supply A good blood supply is needed for wounds to heal. Taking excessive quantities of caffeine (coffee, cola drinks, or chocolate) or a high nicotine intake (smoking) can lead to vasoconstriction and lead to reduced tissue perfusion of the wound area. Shock, hypoxia, diseases such as anemia and chronic obstructive airways disease, or an impaired arterial blood supply may cause a reduced supply of oxygen getting to the wound. Although angiogenesis is stimulated by hypoxia, an adequate oxygen supply is required by the wound. Without it collagen synthesis and epithelialization are impaired.

Surgical Techniques If tissue is handled roughly during surgery, it may become devitalized and provide a focus for infection. A hematoma may form if hemostasis is not achieved which can cause tissue damage by exerting pressure at the wound edges and is also a perfect environment for bacteria to grow. If sutures or staples are put in too tightly then tissue will become damaged with a poor cosmetic result.

Stress Stress can be caused by a variety of things such as hypoxia, hypothermia, pain, and psychological issues. Irrespective of the cause, the overall effect is the stimulation of the sympathetic nervous system which leads to increase in levels of nor­adrenaline causing vasoconstriction and a diminished perfusion to the wound. Glucocorticoid has inhibitory effect on fibroblast activity, collagen synthesis and granulation tissue formation which results in delay in wound healing.

Obesity Wound dehiscence and wound infection is increased in an obese person due to a decrease in perfusion to the wound.

Infection Healing is delayed as bacteria compete with macrophages and fibroblasts for oxygen within the wound. There can be further tissue damage from this inflammatory response and abscesses may be formed. As the wound returns to the inflammatory phase, healing is slowed down.

Diseases Various diseases have an influence on the healing process such as: ∙ Diabetes: There is a high­risk of infection in diabetic patients. High blood glucose levels will encourage invading microorganisms to multiply and hyperglycemia has a damaging effect on phagocytosis. Both of these will increase the risk of infection. ∙ Malignancy: Patients may have chemotherapy or radio­ therapy. Radiotherapy can produce local skin damage and slows down healing. It has a fibrosing effect on local blood vessels as well as reducing the amount of fibroblasts and endothelial cells (Cutting, 1994). ∙ Respiratory disease (e.g. chronic obstructive airways disease): The amount of oxygen to the wound bed is diminished so causing a hypoxic state.

Social Factors Poverty The black report found that people who were living in poverty were more likely to become ill than those that were fairly affluent. Poverty can lead to a poor nutritional intake, which is important for wound healing. It can also affect the patient’s ability to afford to have sufficient heating during cold weather, so causing peripheral vasoconstriction and a decreased blood supply to the wound.

Lifestyle and Habits The lifestyle of the patient can influence wound healing, especially if the person smokes, drinks excessive amounts of alcohol or abuses drugs.

Housekeeping Poor housekeeping can mean a lack of cleanliness, thereby increasing the risk of wound infection.

Cultural Beliefs These may have an influence on diet, e.g. fasting or which dressings can be used as some contain porcine or bovine within them. Some patients may also have objections to being ‘cared for’ by members of the opposite sex.

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Textbook of Oral Pathology Table 6.2 General and cellular events in wound healing

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General events

Factors or cellular events

• Rapid hemostasis • Inflammation • Mesenchymal cell differentiation, proliferation, and migration to the wound site • Appropriate angiogenesis • Re-epithelialization • Proper synthesis and desired alteration of collagen to provide strength to the healing tissue

• Coordinated cell activation • Cell division • Chemotaxis • Migration • Differentiation of many cell types

CASCADE OF WOUND HEALING Wound healing can be described as a complex and dynamic cascade of events initiated by injury. The initial or primitive response to injury is essential occurs in phases and can be called as an innate host immune response for the restoration of tissue integrity. The events of each phase should happen in a precise and regulated manner. Delayed wound healing occurs if there are interruptions, aberrancies, or prolongation in the process. These phases and their biophysiological functions must occur in the proper sequence, at a specific time, and continue for a specific duration at an optimal intensity (Table 6.2). All the cellular events are mediated by locally released growth factors and cytokines, which may act in an autocrine or paracrine manner. Research work on acute wounds in an animal model shows that wounds heal in four phases. It is believed that chronic wounds must also go through the same basic phases. Phases of Wound Healing • Hemostasis • Inflammation • Proliferation or granulation • Remodeling or maturation.

Hemostasis The first action the body takes immediately after wounding is to control bleeding as damaged blood vessels must be sealed. Hemostasis serves as the initiating step and foundation for the healing process. Inflammation results in vasodilatation and increased vascular permeability. The blood vessels themselves constrict in response to injury but this spasm ultimately relaxes. The platelet is the cell which acts as the important utility worker sealing off the damaged blood vessels. The platelets secrete

vasoconstrictive substances to aid in this process but their prime role is to form a stable clot sealing the damaged vessel. The injured blood vessel vasoconstricts, and the endothelium and nearby platelets activate the intrinsic part of the coagulation cascade. Under the influence of ADP (adenosine diphosphate) leaking from damaged tissues the platelets aggregate and adhere to the exposed collagen. They also secrete factors which interact with and stimulate the intrinsic clotting cascade through the production of thrombin, which in turn initiates the formation of fibrin from fibrinogen. The fibrin mesh strengthens the platelet aggregate into a stable hemostatic plug. The clot that forms is made of collagen, platelets, thrombin, and fibronectin, and these factors release cytokines and growth factors that initiate the inflammatory response. Finally platelets also secrete cytokines such as platelet-derived growth factor (PDGF), which is recognized as one of the first factors secreted in initiating subsequent steps. The fibrin clot also serves as a scaffold for invading cells, such as neutrophils, monocytes, fibroblasts and endothelial cells. The clot also serves to concentrate the elaborated cytokines and growth factors in wound healing. Hemostasis occurs within minutes of the initial injury unless there are underlying clotting disorders such as deficiency of Factor XIII (the fibrin­stabilizing factor) is associated with impaired wound healing secondary to decreased chemotaxis or decreased adhesion of cells in the inflammatory area. Hemostasis → Blood vessels constrict → Platelets → Secrete vasoconstrictive substance → ADP influence aggregation of platelets → Intrinsic cascade → Thrombin secretion → Fibrinogen stimulates → Fibrin formation → Fibrin mesh entangles platelets to form hemostatic plug.

Healing of Wound

Epithelial cells located on the skin edge begin proliferating and sending out projections to re­establish a Clinically inflammation is the second stage of wound protective barrier against fluid losses and further bacterial healing add marked as erythema, swelling and warmth invasion. often associated with pain. This stage usually lasts up to 4 The stimulus for epithelial proliferation and chemotaxis days post injury. is EGF and TGF-beta produced by activated platelets and In wound healing, it is important to clean up the debris. macrophages (fibroblasts do not appear to synthesize TGFNeutrophils arrive via the blood and migrate into the beta). Epithelialization begins shortly after wounding and is tissue spaces of the wound within the first 24 hours. The first stimulated by inflammatory cytokines (IL-1 and TNFneutrophils phagocytize debris and microorganisms and beta) up regulate KGF gene expression in fibroblasts). provide the first line of defense against infection. They are In turn, fibroblasts synthesize and secrete keratinocyte aided by local mast cells. growth factor (KGF)-1, KGF-2, and IL-6, which simulate As fibrin is broken down as part of this clean-up neighbouring keratinocytes to migrate in the wound the degradation products attract the next cell involved. area, proliferate, and differentiate in the epidermis. Also Monocytes also migrate into the wound after about 24 there is marked increase in new blood vessel formation hours. Once in the tissues, these cells also phagocytose called angiogenesis. This serves purpose of providing the bacteria and dead tissue, this causes them to grow and they nutrition to the cells which help in wound healing. become large cells called macrophages. Fibroblasts and endothelial cells are the predominant Macrophages provide a second line of defense. They cells proliferating during this phase. Endothelial cells located also secrete a variety of chemotactic and growth factors at intact small capillaries are attracted by VEGF (secreted such as fibroblast growth factor (FGF), epidermal growth predominantly by keratinocytes on the wound edge, but also factor (EGF), transforming growth factor beta (TGF-beta) by macrophages, fibroblasts, platelets, and other endothelial and interleukin-1 (IL-1) there by coordinating much of the cells) to begin forming new capillary tubes. healing process. Fibroblasts travel into the wound site from the An activated macrophage is important for the transition surrounding tissue, become activated and commence into the proliferative phase. These locally acting chemicals producing collagen, and proliferate. PDGF and EGF are the stimulate the regrowth of epithelium, new capillaries and main signals to fibroblasts and are derived from platelets the migration of fibroblasts. and macrophages. PDGF expression by fibroblasts is At least 20 different growth factors are involved in amplified by autocrine and paracrine signaling. normal wound healing. In the absence of monocytes, there Fibroblasts already located in the wound site (termed are no growth factors to stimulate mitosis in adjacent “wound fibroblasts”) begin synthesizing collagen and healthy tissues. This means that regeneration of damaged transform into myofibroblasts for wound contraction tissues cannot occur. (induced by macrophage- secreted TGF-beta 1).

Inflammation

Proliferation or Granulation

To replenish the damage part is prime importance for successful healing of wound. This is achieved by the cell induction, proliferation and migration. This leads to granulation tissue formation as well as epithelialization. The granulation stage starts approximately four days after wounding and usually lasts until day 21 in acute wounds depending on the size of the wound. It is characterized clinically by the presence of pebbled red tissue in the wound base and involves replacement of dermal tissues and sometimes subdermal tissues in deeper wounds as well as contraction of the wound. Epithelialization begins shortly after wounding and is first stimulated by inflammatory cytokines (IL-1 and TNFalpha up regulate KGF gene expression in fibroblasts).

Remodeling or Maturation The main feature of this phase is the deposition of collagen in an organized and well­mannered network. Once the basic structure of the house is completed interior finishing may begin. So too in wound repair the healing process involves remodeling the dermal tissues to produce greater tensile strength. The principle cell involved in this process is the fibroblast. Early in wound healing, the matrix is thin and allows fibroblasts, neutrophils, lymphocytes, and macrophages to easily maneuver through it. Initially, the matrix is composed mainly of fibrin and fibronectin (arising from the efforts for hemostasis and by macrophages).

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Glycosaminoglycans, proteo-glycans, and other proteins (such as secreted protein acidic rich in cysteine, or SPARC) are synthesized next by the fibroblasts. As the matrix becomes denser with thicker, stronger collagen fibrils, it becomes stiff and less resistant. The fibroblasts are capable of “adaptive response” to the changing mechanical loading on the matrix as it matures. The remodeling of the accommodating matrix depends on the cell migration throughout the matrix and proteolysis of the matrix proteins.

When the edges of the wound are brought together into contact and held in place by sutures, the blood clots, and in a matter of hours, numerous leukocytes are mobilized in the area. Connective tissue cells in immediate vicinity undergo transformation into fibroblasts which in turn undergo mitotic division. New fibroblasts begin to migrate into and across the line of incision. These cells form thin, delicate collagen fibrils which intertwine and coalesce in a general direction parallel to the surface of the wound. Endothelial cells of capillaries begin to proliferate and small capillary buds grow out and across the wound. These buds eventually form new capillaries which fill with blood and a rich network of young capillaries and capillary loops are formed.

Keloid: In case of defect in extracellular matrix formation (from diet or disease), then the wound’s strength is greatly compromised. In contrast, presence of excessive collagen synthesis, a hypertrophic scar or keloid can result. The final phase of wound healing involves wound contraction and the remodeling of the ECM produced by fibroblasts during the proliferative phase. The fibronectin produced in the formation of granulation tissue diminishes over time as the matrix is remodelled. This process involves the induction of MMPs 1­3, enzymes which are each involved in the catabolism of different ECM components. These enzymes are controlled by natural tissue inhibitors of matrix metalloproteinase (TIMPS), and the balance between MMP and TIMP expression is crucial for normal matrix remodeling. Remodeling can take up to 2 years after wounding. During wound contraction phenotypic changes to the fibroblasts populating the wound occur, with a switch for a pro­fibrotic myofibroblasts phenotype, characterized by an increase in expression of a­smooth muscle actin. The attachment of these cells to each other and the surrounding matrix then facilitates wound contraction, with the myofibroblasts contracting pseudopodia attached to the ECM. This remodeling of the ECM in the skin leads to scar formation. However, some marked differences in the oral mucosa wound healing may be due to intrinsic characteristics of the tissue.

It occurs when there is a loss of tissue and the edges of the wound cannot be approximated like in the palate or on the alveolar mucosa. The material which fills the defect in secondary healing is called granulation tissue. After the removal of the lesion, blood clots and the repair process begins. It is basically identical with the healing by primary intention except that the fibroblasts and capillaries have a greater distance to migrate, more granulation tissue must form and healing is slower. Cellular proliferation begins around the periphery of the wound and fibroblasts and endothelial cells grow into the clot along the fibrin strands. In addition, polymorphonuclear leukocytes, mononuclear phagocytes and later the lymphocytes migrate into the granulation tissue from the adjacent vessels and tissues. Large numbers of leukocytes also accumulate on the surface of the wound. As granulation tissue matures, it becomes more fibrous through condensation of collagen bundles and the surface of the lesion becomes epithelialized. Lesions become somewhat avascular.

HEALING OF BIOPSY WOUNDS

HEALING OF EXTRACTION WOUNDS

Biopsy: It is the removal of tissue for the purpose of microscopic examination and diagnosis.

The healing of extraction wound does not differ from the healing of other wounds of the body except as it is modified by the peculiar anatomic situation which exists after the removal of tooth.

Primary Healing Healing by primary intention or healing by first intention is that type of healing which occurs after excision of a piece of tissue with close apposition of the edges of the wound.

Secondary Healing

Immediate Reaction Following an Extraction After the removal of a tooth, blood which fills the socket coagulates, red blood cells get entrapped in the fibrin

Healing of Wound

meshwork and the ends of blood vessels in the periodontal ligament are sealed off. Hours after the tooth extraction, if blood clot is dislodged, healing may be greatly affected and may be extremely painful. However, if the healing is normal, within 24 to 48 hours, there is vasodilation and engorgement of blood vessels in the remnants of periodontal ligament and there is mobilization of leukocytes to the immediate area around the clot. Surface of the blood clot is covered by a thick layer of fibrin. It is important to recognize that the collapse of unsupported gingival tissue into the opening of fresh extraction wound is of great aid in maintaining the clot in position.

First Week Wound Proliferation of fibroblasts from connective tissue into the remnants of periodontal ligament is evident and these fibroblasts begin to grow into the clot around the periphery. The clot is gradually replaced by granulation tissue. Epithelium at the periphery of the wound exhibits evidence of proliferation seen in the form of mild mitotic activity. Crest of the alveolar bone, which marks up the margin or neck of the socket exhibits beginning of osteoclastic activity. Endothelial proliferation signals the beginning of capillary growth. During this period, blood clot begins to undergo organization by in­growth of fibroblasts and occasionally by small capillaries from the residual periodontal ligament. An extremely thick layer of leukocytes gathers over the surface of the clot and the edges of the wound continue to exhibit epithelial proliferation.

Third Week Wound Original clot appears almost completely organized by maturation of granulation tissue. Very young trabeculae of osteoid or uncalcified bone are forming around the entire periphery of the wound from the socket wall. Early bone is formed by osteoblasts derived from pluripotential cells of the original periodontal ligament which assume osteogenic function. Original cortical bone of alveolar socket undergoes remodeling so that it no longer consists of such a dense layer. Crests of alveolar bone have been rounded off by osteoclastic resorption. By this time, surface of the wound may have become completely epithelialized.

Fourth Week Wound There is continuous deposition and remodeling, resorption of the bone filling the alveolar socket. Due to this, crest of the alveolar bone undergoes considerable amount of osteoclastic resorption during the healing process and because of this, bone filling the socket does not extend beyond alveolar bone crest. It is obvious that crest of the healing socket does not extend above the alveolar crest.

Radiographic Changes in Healing Sockets

A tooth having been removed and after variable and unspecified length of time, there is gradual loss of density of the lamina dura and at the same time bone develops at the base and sides of the socket. By the time that the socket is filled with bone, all traces of lamina dura is gone. Later the new bone consolidates and comes to resemble the adjacent bone. Most healed socket reveal slight or marked cortical bone formation at the surface of Second Week Wound the alveolar process. Following the removal of teeth, the During the second week, after extraction of the tooth, the alveolar margins undergo some resorption. The surface blood clot is becoming organized by fibroblasts growing usually becomes flat or slightly curved but smooth. into the clot and forming fibrin meshwork. At this stage, new delicate capillaries have penetrated to the center of the clot. Remnants of periodontal ligament HEALING OF FRACTURES have been gradually undergoing degeneration. Walls of the bony socket appear slightly frayed. In some cases, Immediate Effect of a Fracture trabeculae of osteoid can be seen extending outward from After fracture, Haversian vessels of the bone are torn at the walls of the alveolus. the fracture site so are the vessels of periosteum and Epithelial proliferation over the surface of the wound marrow cavity that happen to cross the fracture line. Due is extensive. Margins of the alveolar socket exhibits to disruption of vessels, there is considerable extravasation prominent osteoclastic resorption and fragments of necrotic of blood in that area, but at the same time, there is loss of bone are seen in the process of resorption or sequestration. circulation and lack of local blood supply. The bone cells

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or osteocytes of Haversian system die due to tearing of vessels at the fractured site. Concomitant with the disruption of blood supply and the tearing of the blood vessels, there is death of bone marrow adjacent to the fracture line. The blood clot formation, play an important role in healing of the fracture, which later on is replaced by granulation tissue followed by its subsequent replacement by bone.

Callus Formation It is a structure which unites the fractured ends of bone and is composed of varying amounts of fibrous tissue, cartilage and bone. There are two types of callus: 1. External callus: It consists of new tissue which forms around the outside of the two fragments of bone. 2. Internal callus: It consists of new tissue arising from the marrow cavity. Periosteum is an important structure in callus formation and ultimate healing of fracture. Cells of periosteum torn at the fracture line usually die, but peripheral to the area is found a flurry of cellular activity within hours of injury. Outer or fibrous layer of periosteum is relatively inert and actually lifted away from the surface of bone by proliferation of cells in osteogenic or inner layer of periosteum which assumes features of osteoblasts which in turn begins the formation of small amount of new bone at some distances from the fractured site. There is continuous proliferation of these osteogenic cells forming a collar of callus around or over the surface of fracture. New bone which begins to form in the external callus usually consists of irregular trabeculae laid down at right angles to the surface. This differentiation of cells into osteoblasts and subsequent formation of bone occurs in the deepest part of the callus collar. In the rapidly growing area of collar, varying number cells of the osteogenic layer differentiate into chondroblasts rather than osteoblasts and actually form cartilage. This cartilage fuses with bone and then begins to calcify by endochondroal bone formation. The calcified cartilage is gradually resorbed and replaced by bone. Internal callus forms from endosteum of Haversian canals and undifferentiated cells of bone marrow. Shortly after the fracture, endosteum begins to proliferate within a week to form new bone, which gradually unite and establish the continuity of bone. After this, both external and internal callus remodel to form indistinguishable bone.

HEALING OF OSSEOINTEGRATED IMPLANTS Implants are of three types, i.e. endodontic, endo­osseous and subperiosteal. Osseointegration is the term used for healing of bone around an endo­osseous implant. This results in an intimate interface between the bone and the implant. The healing process in the initial phases is same as of the healing of the extraction wound. Osteogenesis and remodeling are the prime features seen during the process. For successful osseointegration, it is required that the implant should be totally free of any small amount of load or movement. Healing process consist initially of deposition of the granulation tissue and woven bone. Complete healing requires a period of several months together. The process is completed with the deposition of cancellous or compact bone around the implant. Currently the implants used for support the restorative or rehabilitative oral procedures are biocompatible. Biocompatible implants serve as a normal interface of the connective tissue and the implant as is with the dentogingival junction. Peri­implant disease is the term used for the pathologic changes seen around the implant. It involves periimplant mucositis peri­implantitis. The inflammation is seemed more at the coronal aspect; the apical osseointegration is maintained under favorable conditions.

HEALING OF PULP Dental pulp regeneration is difficult task as it is enclosed in dentin without the collateral blood supply except through the apical foramen. With the advent of the concept of tissue engineering and discovery of stem cells regeneration of dental pulp have been a long quest. Moony and Rutherford were the pioneers in the regeneration of the pulp. The regeneration can be cell based pulp/dentin tissue regeneration or non­cell­based regeneration. Dental pulp stem cells (DPSCs), Stem cells from human exfoliated deciduous teeth (SHED), Stem cells for apical papilla (SCAP) are potentially suitable cell source for dentin – pulp regeneration. These stem cells can differentiate into specific tissue cells and can be used further for the other tissue defects after in vitro culture and characterization. Healing in pulp consists of initial response in form of acute pulpitis or pulpal

Healing of Wound

inflammation consisting of vasodilatation and capillary proliferation. This response is reversible or irreversible based on the nature of the stimulus. (Refer chapter Pulp and periapical diseases). The degree of inflammation, the time of irritation and infection, and the location of the exposure must be regarded as decisive factors for the healing of the inflamed pulp. The origins of newly differentiated odontoblasts and ability of precursor cells in the pulp to differentiate, particularly under the influence of bone morphogenic protein, a cytokine responsible for the differentiation of osteoblasts is main factor which will determine the healing or repair of pulp. In majority of case, the pulp is not uniformly affected by deep carious lesions. After a week new collagen is formed against the necrotic zone and the beginnings of a calcifying front. Odontoblast­like cells orientate against the calcifying front and develop cellular extension around which bone­like tissue is deposited after 4 weeks. After 12 weeks, a hard tissue barrier with tubules is formed.

CEMENTUM Cementum is considered to be avascular dental tissue. Then too it has the capacity to repair to a limited extent by the formation of cellular intrinsic fiber cementum. Cementum resorption may be by local or systemic factors. It is not considered to be a continuous process. There is alteration of the resorption and the repair process. Cementum repair requires presence of viable connective tissue. Cementum repair can occur in both vital and nonvital teeth. The cells for cemental repair are gained from the undifferentiated mesenchymal cells present in the periodontal ligament. The recruitment of the cementoblasts occurs after the stimulation by the various growth factors like the BMP­2, BMP-3, PDGF, IGF-1, TGF-beta, etc. The proteins like the bone sialoprotein (BSP), osteopontin (OPN), etc. are also involved in the differentiation of cementoblast progenitor cells to cementoblast. Repair and the regeneration of cementum is important as the principal fibers of the periodontal ligament are embedded into the cementum at one end. This prevents the tooth from being extruded and thus increases its stay in the oral cavity.

dentin. The dentin has less and irregularly arranged tubules. There can be a demarcation in the normal dentin. Also the continuity is lost between the normal and tertiary dentin. This reparative dentin is formed by odontoblasts and sub­ odontoblasts. Types of Tertiary/Reparative Dentin • • •

Reactionary dentin: – Formed by damaged existing odontoblasts Reparative dentin: – Formed by odontoblast-like cells Sclerotic dentin: – Transparent dentin – Due to advancing caries and attrition – Octocalcium phosphate crystals and some derived from saliva.

ENAMEL Although it was said earlier that repair or regeneration of enamel is not possible as the cell responsible for enamel formation during the tooth development, ameloblasts are not present lifelong. They are lost once the complete enamel formation occurs. But, now­a­days, various studies regarding the regeneration of enamel are being carried out. There can be remineralization of the subsurface of the enamel depending on the supply of calcium and phosphate ions from saliva. The use of fluoride is also done in remineralization of enamel. The enamel treated with fluoride becomes more resistant than the normal to further demineralization. Studies have been going on the use of nano hydroxyapatite crystals (20–40 nm) for repair of enamel.

SKIN HEALING AND ORAL MUCOSAL WOUND HEALING Although cutaneous and mucosal wound healing proceed through the same stages of hemostasis, inflammation, proliferation, and remodeling, mucosal wounds demonst­ rate accelerated healing compared to cutaneous wounds. Mucosal wounds also generally heal with minimal scar formation, and hypertrophic scars are rare in the oral cavity.

DENTIN

Healing Response in Skin

Reparative dentin is the tertiary dentin which is the dentin formed due to caries, attrition, cavity preparation and microleakage. This can be in the form of tubular or atubular

The damaged epidermis is regenerated by two mechanisms: 1. Involves the activation of epidermal keratinocytes in the wound margin.

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2. Involves the proliferation, simultaneously with this keratinocyte activation, of hair follicle cells, their migration into the skin, and their transformation to epidermal keratinocytes. Phospholipids of the cellular membrane are essential for both the cellular function and morphological maintenance. Fatty acids, the major component of these phospholipids, are key factors in the regulation of cell proliferation and differentiation. Among the fatty acids known to constitute the cell membrane, palmitic acid (16:0) is a basic unit in the membranes of all human cells. Once the epidermis is damaged, then rapid cell proliferation becomes necessary, and the abundant palmitic acid (16:0) stored in hair follicle cells is used for wound epithelialization, i.e. wound healing in a dynamic environment.

Healing Response in Oral Mucosa The oral mucosa shows earlier wound healing than does the skin, because “early wound healing” of the oral mucosa has been studied in terms of the “moisture environment in the oral cavity” but not from other aspects. The oral mucosal epithelium (both the basal and suprabasal layers) demonstrated a significantly higher percent composition of palmitic acid (16:0) than did the epidermis, but with no difference in its distribution between the two layers. There is a much higher energy metabolism in the oral mucosa than in the skin. The skin is significantly more dependent on essential fatty acids than the oral mucosa, thus suggesting that the skin is more susceptible than the oral mucosa to wound healing failure attributed to malnutrition. Lower neutrophil, macrophage, and T­cell infiltrations were consistently observed in the intra­oral injury site. One possibility is that within the oral cavity, saliva provides many necessary growth factors, making macrophage function less critical. Saliva containing abundant amounts of cytokines, growth factors, and protease inhibitors—is the primary factor that accounts for rapid oral wound healing. At sites of injury, the epithelium is a rich source of both pro­inflammatory mediators, such as IL-1, and TNF-a, as well as growth factors, such as vascular endothelial growth factor (VEGF). The rapid healing and the absence of scars in oral mucosa are most directly related to intrinsic characteristics of the tissue and not to environmental factors such as temperature, salivary flow, the absence of a hemostatic plug, or microflora.

Notably, the mucosal epithelium differs from skin in that it lacks a stratum corneum and does not need to serve functionally as a barrier to water loss. Furthermore, mucosal healing occurs in a fully hydrated environment. In the skin, migrating keratinocytes at the wound edge express high levels of VEGF, suggesting that keratinocyte derived VEGF stimulates angiogenesis during wound healing. Keratinocytes are also capable of modulating fibroblast behavior, including collagen synthesis, through the production and release of soluble factors. Keratinocytes from skin and oral mucosa respond differently to equivalent IL­1b stimulation. Keratinocytes from skin and mucosa maintain differential regulatory pathways that lead to differential responsiveness at sites of injury. This fundamental difference in intrinsic genetic response to wounding between skin and mucosa, which makes mucosal wounds heal faster and with less inflammation and scar formation. Excessive scarring such as hypertrophic scars and keloid scars have not been reported in the oral mucosa. Scalds to the oral mucosa do not result in contractures unlike scalding to the skin. It was hypothesized that secretory leukocyte protease inhibitor (SLPI; a cationic serine protease inhibitor with antimicrobial and anti-inflammatory properties) found in large quantities in the saliva may have a role in mediating scarless healing in the oral mucosa. Various reasons have been suggested for minimal scarring in the oral cavity, including distinct fibroblast phenotype, the presence of bacteria that stimulate wound healing and the moist environment and growth factors present in saliva. Oral mucosal wounds also demonstrate a more highly regulated angiogenic response and have a differential expression of key profibrotic growth factors compared with skin, resulting in less scarring than in skin wounds. Great differences have been observed in wound healing between the oral mucosa and the skin. Oral mucosa wound repair is characterized by rapid re­epithelialization as well as enhanced wound repopulation and matrix reorganization in vitro. Oral mucosal wounds were shown to contain significantly lower levels of macrophages, neutrophils and T­cells when compared with dermal wounds Research had demonstrated that oral fibroblasts are phenotypically distinct, and are capable of achieving a higher number of cumulative population doublings in vitro when compared to patient matched skin fibroblasts.

Healing of Wound Table 6.3 Systemic and local aspects

Systemic aspects

Local aspects

• Optimize nutritional status ­ Consult with dietician - Ensure adequate protein and caloric intake, trace metals, vitamins • Examine psychosocial status ­ Depression inhibits compliance and wound healing ­ Pain control is extremely important • Optimize biochemical status - Acid base balance - Endocrinologic status, blood sugars, hypothyroidism ­ Correct renal failure, liver failure • Optimize perfusion and oxygenation ­ Cardiac status ­ Pulmonary status - Anemia - Vascular bypass surgery if required • Correct spasticity and other physical factors contributing to abnormal mobility • Examine and reduce all medications

• Optimize wound environment by ­ Thorough wound debridement - Eliminate foreign bodies, dead space and necrotic tissue - Elimination of infection systemic/topical antimicrobials Ph active agents ­ Decreased edema ­ Off­load pressure ­ Provide moist wound environment

Oral mucosal fibroblasts (OMFs) were shown to produce increased levels of epithelial mitogens keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF), produce lower levels of α-smooth muscle actin, all factors implicated in fibrotic wound healing. Oral mucosal fibroblasts have also been shown to exhibit greater proliferation in the presence of basic fibroblast growth factor (beta-FGF) in vitro. OMF have increased ability to remodel ECM and contract a wound by use of fibroblast populated collagen lattices. The matrix metalloproteinase activity of OMFs has also been shown to be superior to dermal fibroblasts, with increased levels of MMP­2 with a decreased production/ activation of TIMPs.

A CLINICAL APPROACH TO OPTIMIZING WOUND HEALING (TABLE 6.3) The multitude of factors affecting wound healing should be examined for every individual. In general, to provide for optimal wound healing one should strive to eliminate underlying causative and/or contributory factors and stimulate positive physiologic factors required for the healing process.

BIBLIOGRAPHY 1. Ahn C, Mulligan P, Salcido RS. Smoking—the bane of wound healing: biomedical interventions and social influences. Adv Skin Wound Care. 2008;21:227-38. 2. Anaya DA, Dellinger EP. The obese surgical patient: a susceptible host for infection. Surg Infect (Larchmt). 2006;7:473-80. 3. Arnold M, Barbul A. Nutrition and wound healing. Plast Reconstr Surg. 2006;117(7 Suppl):42S-58S. 4. Balaji SM. Tobacco smoking and surgical healing of oral tissues: a review. Indian J Dent Res. 2008;19:344-8. 5. Bishop A. Role of oxygen in wound healing. J Wound Care 2008;17:399-402. 6. Bjarnsholt T, Kirketerp­Moller K, Jensen P, Kit M, Krogfelt K, Phipps R, et al. Why chronic wounds won’t heal: a novel hypothesis. Wound Repair Regen. 2008;1:2-10. 7. Boyapati L, Wang HL. The role of stress in periodontal disease and wound healing. Periodontol. 2000,2007;44:195210. 8. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest. 2007;117:121922. 9. Broughton G, 2nd, Janis JE, Attinger CE. The basic science of wound healing (retraction of Witte M, Barbul A. In: Surg Clin North Am 1997;77:509-28). Plast Reconstr Surg. 2006;117(7 Suppl):12S-34S.

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10. Burgess C. Topical vitamins. J Drugs Dermatol. 2008; 7(7 Suppl):s2-s6. 11. Calabro P, Yeh ET. Obesity, inflammation, and vascular disease: the role of the adipose tissue as an endocrine organ. Subcell Biochem. 2007;42:63-91. 12. Campos AC, Groth AK, Branco AB. Assessment and nutritional aspects of wound healing. Curr Opin Clin Nutr Metab Care. 2008;11:281-8. 13. Cha J, Falanga V. Stem cells in cutaneous wound healing. Clin Dermatol. 2007;25:73-8. 14. Chan LK, Withey S, Butler PE. Smoking and wound healing problems in reduction mammaplasty: is the introduction of urine nicotine testing justified? Ann Plast Surg. 2006;56:111-5. 15. Choudhry MA, Chaudry IH. Alcohol intoxication and postburn complications. Front Biosci. 2006;11:998-1005. 16. da Costa MA, Campos AC, Coelho JC, de Barros AM, Matsumoto HM. Oral glutamine and the healing of colonic anastomoses in rats. JPEN J Parenter Enteral Nutr. 2003;27:182-5. 17. Davis SC, Ricotti C, Cazzaniga A, Welsh E, Eaglstein WH, Mertz PM. Microscopic and physiologic evidence for biofilm­associated wound colonization in vivo. Wound Repair Regen. 2008;16:23-9. 18. de Mello VD, Kolehmainen M, Schwab U, Mager U, Laaksonen DE, Pulkkinen L, et al. Effect of weight loss on cytokine messenger RNA expression in peripheral blood mononuclear cells of obese subjects with the metabolic syndrome. Metabolism. 2008;57:192-9. 19. Dong Y-L, Fleming RYD, Yan TZ, Herndon DN, Waymack JP. Effect of ibuprofen on the inflammatory response to surgical wounds. J Trauma. 1993;35:340-3. 20. Dvivedi S, Tiwari SM, Sharma A. Effect of ibuprofen and diclofenac sodium on experimental wound healing. Indian J Exp Biol. 1997;35:1243-5. 21. Edwards R, Harding KG. Bacteria and wound healing. Curr Opin Infect Dis. 2004;17:91-6. 22. Emery CF, Kiecolt-Glaser JK, Glaser R, Malarkey WB, Frid DJ. Exercise accelerates wound healing among healthy older adults: a preliminary investigation. J Gerontol Med Sci. 2005;60(A):1432-6.

23. Fitzgerald DJ, Radek KA, Chaar M, Faunce DE, DiPietro LA, Kovacs EJ. Effects of acute ethanol exposure on the early inflammatory response after excisional injury. Alcohol Clin Exp Res. 2007;31:317-23. 24. Fontana L, Eagon JC, Colonna M, Klein S. Impaired mononuclear cell immune function in extreme obesity is corrected by weight loss. Rejuvenation Res. 2007;10:41-6. 25. Franz MG, Steed DL, Robson MC. Optimizing healing of the acute wound by minimizing complications. Curr Probl Surg. 2007;44:691-763. 26. Galiano RD, Tepper OM, Pelo CR, Bhatt KA, Callaghan M, Bastidas N, et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol. 2004;164:1935-47. 27. Galkowska H, Olszewski WL, Wojewodzka U, Rosinski G, Karnafel W. Neurogenic factors in the impaired healing of diabetic foot ulcers. J Surg Res. 2006;134:252-8. 28. Gallagher KA, Liu ZJ, Xiao M, Chen H, Goldstein LJ, Buerk DG, et al. Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J Clin Invest. 2007;117:1249-59. 29. Gawronska-Kozak B, Bogacki M, Rim JS, Monroe WT, Manuel JA. Scarless skin repair in immunodeficient mice. Wound Repair Regen. 2006;14:265-76. 30. Gentilello LM, Cobean RA, Walker AP, Moore EE, Wertz MJ, Dellinger EP. Acute ethanol intoxication increases the risk of infection following penetrating abdominal trauma. J Trauma. 1993;34:669­74. 31. Gilliver SC, Ashworth JJ, Ashcroft GS. The hormonal regulation of cutaneous wound healing. Clin Dermatol. 2007;25:56-62. 32. Glaser R, Kiecolt-Glaser JK. Stress-induced immune dysfunction: implications for health. Nat Rev Immunol. 2005;5:243-51. 33. Godbout JP, Glaser R. Stress-induced immune dysregulation: implications for wound healing, infectious disease and cancer. J Neuroimmune Pharmacol. 2006;1:421-7. 34. Gogia PP. Physiology of wound healing. In: Clinical wound management. Gogia PP, editor, editor. Thorofare, NJ: Slack Incorporated, 1995. pp. 8-12.

Healing of Wound

MULTIPLE CHOICE QUESTIONS 1. Salivary EGF speeds up healing process by: a. Angiogenetic effect b. Cell proliferation c. Re­epithelialization d. All of the above

8. Radiographic changes of a healing socket involves: a. Loss of lamina dura b. Sharper image of lamina dura c. Both a and b d. None of the above

2. Following are the phases of wound healing except: a. Hemostasis b. Inflammation c. Loss of function d. Granulation

9. Primary factor that accounts for rapid oral wound healing: a. Saliva b. Blood c. Fibrin d. All of the above

3. Deficiency of following factor is associated with impaired wound healing: a. Factor II b. Factor IV c. Factor XIII d. Factor XII

10. Factor which delay healing is: a. Proteins b. Anemia c. Low radiation dose d. Vitamins

4. Initially, during maturation the matrix is composed of: a. Fibrin b. Fibronectin c. Both a and b d. None of the above

11. Hormones which delay wound healing is: a. Growth hormone b. Thyroid hormones c. ACTH d. None

5. After wounding, remodeling can take up to: a. 5 years b. 2 years c. 6 months d. 8 weeks

12. In healing of extraction of wounds, osteoid or uncalcified bones are form during: a. 1st week b. 2nd week c. 3rd week d. 4th week

6. The material which fills the defect in secondary healing is called as: a. Scar tissue b. Eschar c. Granulation tissue d. Fibronectin 7. The following, are correct, except: a. I week wound–proliferation of fibroblasts b. II week wound–fibrin meshwork c. III week wound–maturation of granulation tissue d. IV week wound–maturation of granulation tissue

13. In healing of extraction of wounds, complete surface epithelialization occurs during: a. 1st week b. 2nd week c. 3rd week d. 4th week 14. Wound contraction occurs in healing wound of skin due to presence of: a. Actin and myosin b. Fibroblasts c. Cytokine d. Glycosaminoglycans

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Hyperplasia, Hamartoma and Neoplasm Shubhangi Mhaske (Jedhe) A

Chapter Outline O O O O O O O

Dysplasia Metaplasia Hyperplasia Hamartoma

Choriostoma Neoplasm Carcinogenesis

DYSPLASIA This word is originated from ancient Greek word dys -, difficulty + plasia, formation. It is a loss in the uniformity of the cells, as well as a loss in the architectural orientation. Dysplasia is usually referred to change seen in the epithelium , e . g . epithelial dysplasia in premalignant and malignant lesions .

METAPLASIA (Greek: change in form)

Metaplasia is defined as a reversible change of one type of mature epithelial or mesenchymal cells, usually

O O O O O O O

Type of carcinogenesis Chemical carcinogens Physical carcinogens ( radiation) Hormonal carcinogens Biologic carcinogens ( virus) Metastasis Tumor grading

in response to abnormal stimuli, and often reverts back to normal after removal of the stimulus .

HYPERPLASIA (From ancient Greek huper, “ over ” plasis, ‘ [ formation” ) Hyperplasia represents overgrowth of normal mature tissues with a limited cellular proliferation or it is an increase in the number of parenchymal cells resulting in enlargement of the organ or tissue . Hyperplasia can be :

Physiologic hyperplasia: It occurs due to hormonal changes as in pregnancy. Pathologic hyperplasia: It may occur as inflammatory, non-inflammatory growth .

Hyperplasia, Hamartoma and Neoplasm

Characteristic Features of Hyperplasia • It does not have autonomous growth. • It ceases growth at some point like hamartoma. • Clinically hyperplasia may be seen as an overgrowth, or mass, or tumorous swelling. • Histologically, it is increased cellularity by virtue of their proliferation. It makes them resemble neoplastic proliferations, difference being absence of dysplastic features. • Hyperplasias are usually reactive lesions. • They are initiated by an identifiable stimulus, e.g. irritation of mucosa—fibrous hyperplasia (Fig. 7.1). • The process or growth stops when stimulus is removed. • Inflammatory lesions may be initiated and controlled by same stimulus repeatedly, e.g. peripheral giant cell granuloma, pulp polyp (chronic hyperplastic pulpitis). • The process or growth stops but the size of the lesion does not usually regress on its own.

HAMARTOMA Hamartoma is an overgrowth or abnormal proliferation of mature cells and tissues or structures native to that part.

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Figure 7.1 Localized fibrous hyperplasia due to irritation

of removable prosthesis

They are dysmorphic proliferation of tissue often with one element predominating. These tissues do not have inherent capacity for continuous growth but they nearly parallel the growth of host. Because of this property the distinction between hamartoma and benign tumors is often subjective as most benign tumors of infancy and childhood are actually developmental hamartoma (Table 7.1).

Table 7.1 Classification of hamartoma

Odontogenic hamartoma

Nonodontogenic hamartoma

Unknown or doubtful origin

Those involving teeth: • Dens invaginatus • Dens evaginatus • Talon’s cusp • Those not involving teeth (as these lesions do not have uncoordinated uncontrolled growth they can be called hamartoma than neoplasm) • Enameloma • Odontoma (complex and compound) • Gigantiform cementoma • Dental lamina cyst of the newborn

Epithelial origin • Epstein pearls and Bohn’s nodules • Oral and labial melanotic macule • Pigmented cellular nevus Vascular origin • Hemangioma • Lymphangioma • Glomus tumor Osseous origin • Torus palatinus • Torus mandibularis Adipose tissue • Lipoblastomatosis Neural tissue • Neurofibromatosis

• Granular cell myoblastoma • Congenital epulis of the newborn • Melanotic neuroectodermal tumor of infancy • Fibromatosis gingivae

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Characteristic Features of Hamartoma

Grading of Teratoma (Gonzalez-Crussi)

• G rowth of hamartoma ceases with general body growth. • They do not infiltrate into surrounding tissue. • In bone they are treated by enucleation. If they are present in soft tissue they are removed by pericapsular incision.

• • • •

0 or mature (benign) 1 or immature: Probably benign 2 or immature, possible malignant 3 or frankly malignant—additional cancer staging applies.

Cystic teratomas usually are grade 0 and, conversely, grade 0 teratomas usually are cystic. Grade 0, 1 and 2 pure CHORIOSTOMA teratomas have the potential to become malignant (grade Choriostoma are tumor like proliferation of tissue not native 3), and malignant grade 3 pure teratomas have the potential to the site. Histologically it is normal tissue found at abnormal to metastasize. A teratoma can be pure and not malignant site. They are similar to hamartoma with basic difference is yet highly aggressive. that proliferating tissue is not usual or native to the site. Growing teratoma syndrome, is referred when chemoHeterotrophic gastrointestinal cyst: It may occur therapy the malignant elements are eliminated of a mixed in tongue or floor of the mouth of infants and contains tumor, leaving pure teratoma which has potential to grow gastrointestinal glandular structures. Rarely bone and very rapidly. cartilage may be found in the tongue, known as osseous Malignant transformation: A teratoma with malignant choriostoma and cartilagnous choriostoma respectively. transformation (TMT) is a very rare form of teratoma that Lingual thyroid nodule: Presence of thyroid tissue in the may contain elements of somatic (nongerm cell) malignant tumors such as carcinoma, sarcoma or leukemia. posterior part of tongue. Fordyce’s granules: It is ectopic sebaceous glands in the oral cavity. Presence of salivary gland within lymph nodes.

Teratomas of Tongue

Teratoma in a few cases, has been found within the body of the tongue, but occasionally has been attached Teratoma to the base of the tongue by a pedicle or to the side of Teratomas are thought to be present at birth (congenital), the tongue. They may be so large as to fill the mouth but small ones are often not discovered until much later completely. in life. A teratoma is an encapsulated tumor with tissue There does not appear to be any sex predilection. or organ components resembling normal derivatives of Although teratomas are thought to arise in the all three germ layers. The tissues of a teratoma, although developing blastomere, some cells being displaced or normal in themselves, may be quite different from separated; it is possible that normal muscle-forming surrounding tissues and may be highly disparate. cells migrating from the occipital myotomes have been Teratomas have been reported to contain hair, teeth, accompanied by neuroectodermal and other cells. In a bone and very rarely, more complex organs such as eyes, few examples, a second teratoma has been found in the torso, and hands, feet or other limbs. proximate area. Classification of Teratoma • S olid teratoma contains only tissue (perhaps including more complex structure). • Cystic teratoma contains only pockets of fluid or semifluid such as cerebrospinal fluid, sebum or fat. • Mixed teratoma contain both solid and cystic parts.

Histopathology Most often immature neuroectodermal tissue present; however, cartilage, bone, skin, or cystlike structures lined by stratified squamous epithelium, pseudostratified ciliated columnar epithelium, intestinal epithelium, muscle, and nerve have been found.

Hyperplasia, Hamartoma and Neoplasm

Lab Findings

Normal Cell Cycle (Fig. 7.2)

Elevated carcinoembryonic antigen and alpha-fetoprotein levels have been found. In some cases urinary vanillylmandelic acid and dopamine levels have also been increased.

All renewing cells go through a series of events known as cell cycle. After mitosis (M phase), cells spend a variable period of resting (G1 phase).

Management There is excellent prognosis following surgical excision. In spite of the rule (regarding ovarian teratomas) that the greater the immaturity and amount of neuroepithelium, the poorer the prognosis, there is evidence reported that lingual teratomas are not malignant.

NEOPLASM Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia (new growth in Greek) is the abnormal proliferation of cells. Before the progression to neoplasia, cells often show an abnormal pattern of growth, such as metaplasia or dysplasia. However, they do not always progress to neoplasia. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the stimuli.

Definition

Etiology of Oral Cancer • • • • • • • • • •

Hereditary predisposition Racial and geographic factors Environmental and cultural factors Age Sex Acquired preneoplastic conditions Tobacco and related products/smoking Diet Chronic inflammation Hormonal factors.

Etiology of Oral Cancer The etiology of oral cancer in man is unknown. However, several pre-existing conditions/factors have been found with such frequency in patients with cancer that they may be considered. There are various risk factors associated with oral cancer which are described in Table 7.2.

Hereditary Predisposition

The risk of developing cancer in relatives of a known “It is an abnormal mass of tissue, growth of which exceeds cancer patient is 3 times higher than control population. and is uncoordinated with that of normal tissue and persists Genetic cancers comprise not greater than 5 percent of all in the same excessive manner after cessation of the stimuli which evoked the change”.

Nomenclature Neoplasms may be benign, pre-malignant (carcinoma in situ) or malignant (cancer). Benign tumors are designated by attaching oma to cell of the origin. Tumor from fibrous tissue is called as fibroma. Malignant tumors arising from mesenchymal tissues are known as sarcomas, like osteosarcoma. Malignant tumors of epithelial origin are called carcinoma, like adenocarcinoma and squamous cell carcinoma. Metastatic cancer occurs when cancerous cells spread into other surrounding tissues, or enter the circulatory system and travel to other parts of the body, producing new tumors.

Figure 7.2 Normal cell cycle

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• Tobacco use • Alcohol use • Dietary factors, including insufficient fruit and vegetable intake • Overweight and obesity • Physical inactivity • Chronic infections from Helicobacter pylori, hepatitis B virus (HBV), hepatitis C virus (HCV) and some types of human papilloma virus (HPV) • Environment and occupational risks including ionizing and non-ionizing radiation.

cancers, e.g. retinoblastoma, familial polyposis coli, cancer of breast, etc.

Racial and Geographic Factors Cancers are largely due to the influence of environment and geographic differences affecting the whole population such as climate, water, diet, habit. For example: Black Africans commonly have cancers of skin, penis, cervix, and liver. Europeans and Americans commonly develop malignancies of lung, breast, and colon. Carcinoma of stomach is five times higher in Japanese than in Americans. Nasopharyngeal cancer is common in South East Asians.

Environmental and Cultural Factors The environment contains number of carcinogens which produce its effect directly or indirectly. For example: Cigarette smoking is the etiology of cancer of oral cavity, pharynx, larynx, esophagus, lung, pancreas and urinary bladder. Alcohol causes cancer of esophagus and liver. Alcohol and tobacco together accelerate the risk of developing cancer of upper aerodigestive tract. Betel nut chewing causes cancer of cheek and tongue. Industrial and environmental materials are carcinogenic. This includes exposure to substances like arsenic, asbestos, benzene, and naphthylamine. Overweight individuals, deficiency of vitamin A, people consuming foods rich in animal fats and low in fiber content have more risk of developing cancers like colon cancer.

Age Generally it occurs in older individual past fifth decade of life but there is variation in age groups. For example, acute leukemia occurs in children, neuroblastoma in infancy.

Sex Certain malignancies are more common in men such as basal cell carcinoma. Similarly, female are also prone to specific malignancies such as breast cancer or cervical cancers.

Acquired Preneoplastic Conditions These may be inflammatory, hyperplastic conditions or may be certain benign tumors. For example, chronic atrophic glossitis, leukoplakia of oral cavity, vulva and penis, cirrhosis of liver, chronic irritation and multiple neurofibromas.

Tobacco and Related Products/Smoking Tobacco consumption and smoking contribute to cancer (cancer, heart disease, and cerebrovascular disease). Tobacco is a cause of cancer of the lung, mouth, pharynx, larynx, esophagus, bladder, pancreas, stomach, kidney, uterine cervix, and myeloid leukemia. Tobacco and smoke contain a wide variety of mutagens and substances that are carcinogenic to human.

Diet Excessive consumption of alcoholic beverages is associated with cancers of the breast, oral cavity (primarily in smokers), and liver.

Hormonal Factors Endogenous reproductive hormones play a large role in cancer, including that of the breast, prostate, ovary, and endometrium.

Chronic Inflammation Chronic inflammation results in the release of oxidative mutagens from white cells and other sentinel cells of the immune system, which combat bacteria, parasites, and viruses by destroying them with potent, mutagenic oxidizing agents. These oxidants protect humans from immediate death from infection but they also cause oxidative damage to DNA, chronic killing of cells with compensatory cell division, and mutation; thus, they contribute to cancer.

Hyperplasia, Hamartoma and Neoplasm

CARCINOGENESIS

∙

Carcinogenesis or oncogenesis or tumorigenesis means induction of tumors; agents which can induce tumors are called carcinogens.

The Hallmarks of Cancer The hallmarks of cancer encompass six biological capabilities acquired during the multistep development of human tumors. The hallmarks represent an organizing code for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks is genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Types of Carcinogens • • • •

Chemical carcinogens Physical carcinogens (radiation) Hormonal carcinogens Biologic carcinogens (virus).

CHEMICAL CARCINOGENESIS Chemical carcinogens are divided into two broad groups:

Initiators of Carcinogenesis Direct-acting carcinogens: These require no metabolic conversion to become carcinogens. ∙ Alkylating agents: It includes various chemotherapeutic drugs that have successfully cured, controlled or delayed recurrence of certain types of cancers only to later evoke a second form of cancer usually leukemia. Various agents used are cyclophosphamide, chlorambucil, busulfan, melphalan, nitrosourea, β-propiolactone and epoxides. This tragic consequence is called as “Pyrrhic victory” which becomes less of a victory when their initial use has been converted to cause later on second form of cancer. ∙ Acylating agents: Substances like acetyl imidazole. Indirect-acting carcinogens or procarcinogens: These are chemical substances requiring metabolic activation for becoming potent initial carcinogens.

∙

∙

∙

Polycyclic aromatic hydrocarbons (in tobacco, smoke, animal foods, industrial oil, and atmospheric pollutants). Important chemical compounds included are benzanthracene, benzpyrene, methylcholan threne. They may cause lung cancer, skin cancer, cancer of oral cavity, and sarcoma. Aromatic amines and azo dyes: These are βnaphthylamine, benzidine, azo dyes used for coloring foods, and acetyl aminofluorene. They may cause bladder cancer and hepatocellular carcinoma. Naturally occurring products: Aflatoxin, actinomycin-D, mitomycin-C, safrole, and betel nut. They can cause hepatocellular carcinoma. Miscellaneous: Nitroso compounds, vinyl chloride monomer, asbestos, arsenical compounds, metals like nickel, lead, chromium, and insecticides, fungicides can cause gastric carcinoma, hemangiosarcoma of liver, bronchogenic carcinoma, epidermal hyperplasia, basal cell carcinoma, and lung cancer. Carcinogenesis Chemical carcinogenesis • Initiators of carcinogenesis – Direct-acting carcinogens - Alkylating agents - Acylating agents – Indirect-acting carcinogens or procarcinogens - Polycyclic aromatic hydrocarbons - Aromatic amines and azo dyes - Naturally occurring products - Nitroso compounds • Promoters of carcinogenesis – Phorbol, phenols, drugs like phenobarbital Physical carcinogenesis • Radiation carcinogenesis • Nonradiation physical carcinogenesis like mechani cal injury or implants of inert materials Hormonal carcinogenesis • Estrogen • Contraceptive hormones • Anabolic steroids • Hormone dependent tumors Biologic carcinogenesis • RNA oncogenic viruses • DNA oncogenic viruses.

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further clonal proliferation of the initiated cell. Sometimes two or more initiators are the chemical, oncogenic virus Certain chemical substances lacking the intrinsic or radiant energy may act in concert to induce malignant carcinogenic potential but helping the initiated cell to transformation referred to as co-carcinogens. proliferate further are called promoter of carcinogenesis. For example, phorbol, phenols, drugs like phenobarbital, PHYSICAL CARCINOGENESIS and artificial sweeteners likes saccharine. It is divided into two groups:

Promoters of Carcinogenesis

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Mechanism of Action and Stage of Chemical Carcinogen

Radiation Carcinogenesis

The great majority of chemical carcinogens are mutagens. They bind directly to DNA and RNA or cytoplasmic proteins to specific sites within molecule inducing miscoding error during transcription and replication. The carcinogenicity of chemical agents is dose dependent and multiple traditional doses have same oncogenecity as a single comparative dose. The carcinogenicity of chemical agents can be significantly enhanced by the subsequent administration of promotors. To be effective the promotor must follow the initiator. The phenomenon of cellular transformation by chemical carcinogenesis is a progressive process involving two different stages. They are initiation and promotion.

Radiation whenever in the form of UV light from sunlight, UV lamp, welder’s arc, or ionizing radiation like X-ray, α, β and γ ray, radioactive isotopes, protons and neutrons are established carcinogens. Most frequent radiation induced cancers are leukemia, cancer of thyroid, skin, breast, lung, and salivary gland. Therapeutic irradiation can also induce carcinogenesis. Radiant energy has potential of producing mutation and even killing the cells. It can affect carcinogenesis by the following facts: Few tumors appear only after long latent period during which successive generation of clones are developed. The radiation initiation is generally irreversible, but at a low dosage level is amenable to repair. The effect of radiation depends upon a number of factors Initiation such as type of radiation, dose, length of interval between In this initiator, interacts with DNA of target cell to induce the doses, capability of cells to repair in intervals and mutation that is more or less irreversible to transform it various host factors such as age, individual susceptibility, immune competence, hormonal influence and type of cell into initiated cell: irradiated. Metabolic activation: Only indirect acting carcinogen or The ultimate mechanism of radiation may directly alter pro-carcinogens require metabolic activation, chiefly by the cellular DNA and it may dislodge ions from water and mixed oxidizes of cytochrome P 450 system located in other molecules of cell and result in the formation of highly microsomal compounds of the endoplasmic reticulum or reactive free radicals that may bring about the damage. in the nucleus. Radiation mutation may render cell vulnerable to other Reactive electrophiles: They are electron deficient carcinogenic influence, i.e. acting as cocarcinogen, inhibition protons, which bind to electron rich portions of other of cell division and inactivation of enzymes, and radiation molecules of cell such as DNA, RNA or other proteins. might cause cell killing; permitting survivors to proliferate Target molecules: The primary target is DNA, producing and thereby become vulnerable to oncogenic influence. mutagenesis. Nonradiation Carcinogenesis Initiated cell: The unrepaired damage produced in the DNA of the cell becomes permanent only if the altered cell undergoes at least one cycle of proliferation.

Promotion It does not damage the DNA but enhances the effect of directacting carcinogen or procarcinogens. The ultimate effect

Mechanical injury to tissues such as from stones in the gallbladder, stones in the urinary tract, and healed scars following burns or trauma have been suggested as causes of increased risk of the carcinoma. Implants of inert materials such as plastic, glass, etc. in prostheses and foreign bodies like metal foils observed to cause tumor development in experimental animals.

Hyperplasia, Hamartoma and Neoplasm

HORMONAL CARCINOGENESIS Carcinoma is most likely to develop in organs and tissues which undergo proliferation under influence of excessive hormonal stimulation. Hormone sensitive tissues developing tumors are breast, endometrium, myometrium, vagina, thyroid, liver, prostate, and testis.

Estrogen In experimental animals: Induction of breast cancer in mice by administration of high doses of estrogen. Other cancers which can be induced in mice by estrogens are squamous cell carcinoma of cervix, connective tissue tumor of myometrium, tumor of kidney in hamsters, and benign and malignant tumors of liver in rats. In humans: Women receiving estrogen therapy and women with estrogen secreting granulosa cell tumor of the ovary have increased risk of developing endometrial carcinoma. Adenocarcinoma of the vagina is seen with increased frequency in adolescent daughter of mother who had received estrogen therapy during pregnancy.

and in certain types of cancers in humans. The association of oncogenic virus with neoplasia was observed by an Italian physician Sanarelli in 1889 who noted association between myxomatosis of rabbit with poxvirus. Oncogenic viruses fall into two broad groups, i.e. those containing ribonucleic acid are termed as RNA oncogenic viruses and those containing deoxyribonucleic acid are termed as DNA oncogenic viruses. Types of Virus Causing Cancer RNA oncogenic viruses • Acute transforming viruses (Rous sarcoma virus) • Slow transforming tumor viruses (mammary tumor virus MMTV) • Human T-cell lymphotropic viruses (HTLV) DNA oncogenic viruses • Papovavirus group • Adenoviruses • Poxvirus • Hepadnaviruses • Herpes virus.

Contraceptive Hormones

RNA Oncogenic Viruses

Increased risk of developing breast cancer, benign tumors of the liver and few patients have developed hepatocellular carcinoma.

These are retroviruses, i.e. they contain the enzyme reverse transcriptase, which is required for reverse transcription of viral RNA to synthesize viral DNA strands. Based on their activity to transplant target cells into neoplastic cells, they all are divided into three subgroups: 1. Acute transforming viruses: It includes Rous sarcoma virus in chickens, leukemia-sarcoma viruses of avian, feline, bovine and primate. 2. Slow transforming tumor viruses: Mouse mammary tumor virus (MMTV) that causes breast cancer in daughter mice. 3. Human T-cell lymphotropic viruses (HTLV): It can cause adult T-cell leukemia-lymphoma syndrome and AIDS.

Anabolic Steroids Consumption of anabolic steroids by athletes to increase the muscle mass also increases the risk of developing benign and malignant tumors of the liver.

Hormone Dependent Tumors It has been shown in experimental animals that induction of hyperfunction of adenohypophysis is associated with increased risk of developing neoplasia of the target organs following preceding functional hyperplasia.

BIOLOGIC CARCINOGENESIS

Mechanism of RNA Viral Oncogenesis

The epidemiological studies on different types of cancer indicate the involvement of transmissible biologic agents in their development, chiefly viruses. It has been estimated that about 20 percent of all cancers worldwide are virus associated cancers. Therefore biological carcinogenesis is largely viral oncogenesis. A large number of viruses have been proved to be oncogenic in wide variety of animals

Reverse transcriptase acts as a template to synthesize a single strand of matching viral DNA. Single strand of viral DNA is then copied by DNA dependent DNA synthetase to form another strand of complementary DNA resulting in double stranded viral DNA or provirus. The provirus is then integrated into the DNA of the host cell genome and may transform the cell into a neoplastic cell.

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Virus replication begins after integration of provirus into host cell genome. Integration results in transcription of proviral genes or progenes into messenger RNA which then forms components of the virus particle, i.e. virion core proteins from gag gene, enveloped glycoprotein from env gene and reverse transcriptase from pol gene. The three components of virus particles are then assembled at the plasma membrane of host cells and virus particles released by budding off from plasma membrane, thus completing the process of replication.

DNA Oncogenic Viruses

development in humans. Free radicals scavenging vitamins C and E have been shown to protect against cancer development in animal models.

Biology of Tumor Growth The life cycle of malignant tumors can be divided into four phases.

Induction of Malignant Changes in the Target Cell (Transformation) Large number of carcinogen agents induces neoplastic transformation of cells in vivo and in experimental animals. All etiologic factors ultimately affect the function of two sets of genes, one is proto-oncogenes or oncogenes and another one is anti-oncogenes or cancer suppressor genes. The majority of carcinogens are mutagenes which bind the DNA directly or indirectly by undergoing enzymatic activation, inducing miscoding errors during transcription and replication. Oncogenes may code for growth promoting factors and as a result the tumor cells produce large amount of growth factors to which, only they can respond. Oncogenes may encode a defective receptor that sends stimulating signals to the cells, even in the absence of growth factors. Thus cancer is a genetic disease that results when multiple mutations accumulate in the DNA of a cell and specific chromosomal abnormalities predispose to cancer.

They are divided into four groups: 1. Papovavirus group: Human papilloma virus, polyoma virus, SV-40 (simian vacuolating) virus. Herpes virus: Epstein-Barr virus, human herpesvirus, cytomegalovirus, lucke’s frog virus, Marek’s disease virus. 2. Adenoviruses: It can cause upper respiratory infections and pharyngitis. In man, they are not known to be involved in tumors but in hamsters they may induce sarcomas. 3. Poxvirus: In rabbits it can cause myxomatosis and in humans it can cause molluscum contagiosum and may induce squamous cell papilloma. 4. Hepadnaviruses: Hepatitis B virus is a member of this family and it can cause acute hepatitis and is responsible for carrier state which can result in some cases to Growth of Transformed Cells (Kinetics of chronic hepatitis progressing to hepatic cirrhosis and Tumor Cell Growth) onto hepatocellular carcinoma. The monoclonal cancer cell (10 mm in diameter) has to undergo about 30 population doublings to produce 109 Mechanism of DNA Viral Oncogenesis cells weighing approximately 1 gm, which is the smallest Replication: The virus may replicate in the host cell with clinical detectable mass. To produce a tumor of 1012 consequent lysis of infected cell and release of virions. cells, weighing 1 kg approximately, which is usually the Integration: The viral DNA may integrate into the host maximum size compatible with life, the tumor cells have cell DNA. This results in neoplastic transformation of the to undergo 10 further population doublings. So by the time the tumor is clinically detectable, it has already completed host cell. a major portion of its life cycle. In tumor cells, there is an Oxidative Mechanism of Carcinogenesis imbalance between cell production and cell loss, therefore Active oxygen species and other free radicals are known the tumor grows progressively. The rate of tumor growth to be mutagenic. Further these agents have emerged as depends upon the growth fraction and the degree of mediators of the other phenotypic and genotypic changes imbalance between cell production and cell loss. that lead to form mutation to neoplasia. Free radical production is ubiquitous in all respiring Mechanism of Local Invasion and organism and is enhanced by many disease states, by Distant Metastases carcinogen exposure and under conditions of stress. There are three routes through which metastases of tumor Free radicals may, therefore, contribute widely to cancer cells occur, i.e. local invasion, via blood vessels and via

Hyperplasia, Hamartoma and Neoplasm

lymphatics. The local invasion takes the path of least resistance and the tumor cells invade the surrounding tissue spaces. In case of oral malignancies distant metastasis is mainly via lymphatics, either by lymphatic permeation or by lymphatic embolism. It spreads through blood vessels and if this occurs, the tumor cells invade the lumen of blood vessels, the tumor emboli form, which are fragmented and the tumor cells are lodged into distant tissues. Theories of Carcinogenesis • • • • • •

Epigenetic theory Genetic theory Virus theory Immune surveillance theory Monoclonal hypothesis Multistep theory.

Theories of Carcinogenesis Epigenetic Theory According to this theory, the carcinogenic agents act on the activators or suppressors of genes and not on the genes themselves and result in the abnormal expression of genes.

Genetic Theory This is the most popular theory which suggests that cells become neoeplastic because of alteration in the DNA. It is suggested that the secret of cancer lies within the normal cells themselves in the form of proto-oncogenes (c-oncs). The mutated cells transmit their characters to the next progeny of cells. Expression of mutated gene or point mutation leads production of various growth factors or they disrupt underlying normal regulatory control. The qualitative and quantitative changes in the expression of genome may be brought about by carcinogenic influence, i.e. chemicals, viruses, radiation or spontaneous random mutations.

perform the function of suppressing cell proliferation, thus allowing them to proliferate. According to genetic regulatory mechanism theory, primary change in the cell consists of a modification of repressor molecule which controls the functions of the gene. The repressor molecules are either RNA or protein. The modification of repressor molecules removes their orderly inhibitory control, which is responsible for normal morphogenesis and differentiation, and unearths the cell genetic potentiality for unrestricted growth. This concept of loss of growth control is described as ‘feedback deletion’.

Virus Theory Viruses participate at some stage in the development of cancer. The concept of mode of action of virus has taken many forms. Virus is present as a parasite in all tumor cells and it is transmitted from cell to cell and stimulates extreme hyperplasia without affecting the genome cell. It acts as a biologic carcinogen on some cellular constituents to release or activate neoplastic potentialities normally present in cells. Carcinogens of all kinds ultimately act by creating some new auto-synthesizing cytoplasmic constituents, probably an autocatalytic protein, which can excite the cell to unlimited growth.

Immune Surveillance Theory

It suggests that an immune-competent host mounts an attack on developing tumor cells so as to destroy them while an immune incompetent host fails to do so. According to original immunological theory, normal cells contain specific self-marker (identity proteins) which is recognized by the normal growth regulating mechanism. These proteins serve as receptor for chemical carcinogens (hapten) and the resulting complex is self-replicating. The complex (complex antigen) triggers off an immune response and the antibody (free or cell bound) combines Oncogenes: Oncogenes are the transforming genes with the self-marker carcinogen complex and eliminates it. present in many tumor cells. Closely related genes are The new race of cells produced is with self-markers deleted detected on normal animal and human cells and are called and goes unrecognized by growth regulatory mechanism. ‘proto-oncogenes’ or ‘cellular oncogenes’, abbreviated as The high incidence of cancer in AIDS patients is in support of this theory. c-oncs. Cellular oncogenes of the host cells can transcribe its copies in the viral genome of acute transforming oncogenic retroviruses called as viral oncogenes or v-oncs. An alternate mechanism is by anti-oncogenes in which there is inactivation or deletion of genes that normally

Monoclonal Hypothesis Currently, there is strong evidence on studies of human and experimental animals that most cancers arise from single clone of transformed cell. The best documentation

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of monoclonal origin of cancer cells comes from the study of G6PD in women who are heterozygous for its two isoenzymes A, and B. It is observed that all tumor cells in benign uterine tumor (leiomyoma) contain either A or B genotypes of G6PD, i.e. the tumor cells are derived from a single progenitor cell.

Multistep Theory According to this theory, carcinogenesis is a multistep process which is substantiated by in vitro changes in experimental animals as well as in vivo changes in human cancers. In chemical carcinogenesis, there are two essential features, i.e. initiation and promotion. Many tumors arise from combination of activation or growth promoting oncogenes and inactivation of growth suppressing antioncogenes. In some cancers, there is initial dysplastic change that may progress into carcinoma in situ and then into invasive carcinoma.

METASTASIS Metastasis is defined as spread of tumor by invasion in such a way that discontinuous secondary tumor mass/masses are formed at the site of lodgment. This metastasis is the transfer of the disease from one organ or part to another not directly connected with it. If malignant cells do not metastasize, the surgical removal of primary neoplasm would completely cure the patient. Metastasis is fundamentally an embolic process. The invasiveness of malignant cells involves motility, which requires changes of shape and adhesiveness and ability to degrade the matrix in order to penetrate it. Thus, a definition of the behavior of the metastatic tumor cells is the tendency to cross the tissue compartment/boundary and intermix with other cell types. The metastatic process can be divided into several sequential steps although these steps are interconnected. Factors which control metastasis are proteolysis, cell adhesion, tumor angiogenesis, cell mediated immunity and genetic factor.

Steps of Metastasis

the basement membrane and invasion of connective tissue (carcinoma) → Entering the wall of blood and lymphatic vessels → Survival of malignant cells in the blood stream → Emergence of the malignant cells from the blood vessels in the form of the emboli and lodgment in other tissues → Survival in the compatible tissue environment and induction of growth factor to stimulate new vessel formation to obtain nutrition → Multiplication of neoplastic cells and growth to form secondary neoplasm at the new site. Each of these steps is probably controlled by different molecular mechanism and this may explain the differences in the behavior with reference to tumor metastasis. Neoplastic cells within a single tumor might differ in their ability to metastasize. A subpopulation of cells pre-exists within the heterogeneous primary tumor. The relative size of this subpopulation in the primary tumor may vary with time between the neoplasms.

Routes of Metastasis Lymphatics: Particularly for carcinoma and lymphosarcoma. For example, mouth to neck nodes and breast to axillary nodes. Blood stream: Particularly veins from gut via portal circulation to liver, from systemic sites through right heart to lung, from left heart to any systemic sites. Cavities: Along epithelium lined cavities, for example, respiratory tract, gut, urogenital tract, etc. Others: Transcelomic spread, cerebrospinal fluid, tissue planes and through nerve sheath.

Pattern of Metastatic Spread Mechanistic theory: The capillary bed of the first organ which encounters viable neoplastic cells is the preferred site of metastasis. Seed and soil hypothesis: It suggests that availability of fertile environment (the soil) in which compatible tumor cells (the seed) can grow is important. Ewing suggested that varying pattern of metastasis is due to fact that different tumor cells thrive in certain biological sites (soils) but not in the other sites.

Cell interaction: Interaction between cell surface The breaking of loose neoplastic cells from the parent protein of malignant cells and organ specific protein, e.g. tumor → Invasion of the matrix (sarcoma), penetration of fibronectin receptor.

Hyperplasia, Hamartoma and Neoplasm

GRADING AND STAGING OF TUMORS

CIN Grading Depending on Thickness of Squamous Epithelium Involved by Dysplastic Cells

Grading

• Mild • Moderate • Severe.

The grading features are those indicative of proliferation and differentiation. It is defined as macroscopic and microscopic degree of differentiation of tumor. Grading depends mainly on two histologic features, the degree of anaplasia and the rate of growth. Different types of grading systems are as follows: Broder’s Classification System • G rade I (Well differentiated, i.e. less than 25 percent anaplastic cells): It is characterized by the presence of relatively mature cell with little nuclear aberration and with the presence of keratin pearls and individual cell keratinization. • Grade II (Moderately differentiated, i.e. 25 to 50 percent anaplastic cells): It is characterized by the presence of tumor cell exhibiting a wide range of differentiation, keratinization is occasionally present, and nuclear aberrations are moderately abundant. Usually the invasion is poorly delineated from the stroma. • Grade III (Moderately differentiated, i.e. 50 to 75 percent anaplastic cells): It is characterized by disorderly and poorly differentiated cells with no tendency towards keratinization, nuclear aberrations are abundant. • Grade IV (Poorly differentiated, i.e. more than 75 percent anaplastic cells): In it cells are so poorly differentiated that they cannot be identified as epithelial origin on the basis of histology alone, nuclear aberrations are abundant and no keratinization is found.

CIN Grading Alternative classification for grading of dysplasia and carcinoma in situ together is cervical intraepithelial neoplasia (CIN).

Staging It is the extent of spread of tumor within patients. It is assessed by clinical examination (size and extent of primary lesion), investigations, pathological examination, degree of infiltration of primary lesion, presence or absence of metastasis to regional lymph nodes, presence and absence of distant metastasis, involvement of contralateral or ipsilateral node and whether nodes are fixed or not.

Objectives ∙ ∙ ∙ ∙ ∙

To aid clinician in the planning of treatment. To give some indication of prognosis. To assist in evaluation of the result of treatment. To facilitate the exchange of information between treatment centers. To contribute to the continuing investigations of human cancer.

TNM Staging (Table 7.3) It is universally accepted system which is developed by UICC (Union International Control of Cancer). AJC (American Joint Committee) It divides all cancers into stage 0 to 4, and takes into account all three previous TNM systems. • Stage 0: Tis N0 M0 • Stage 1: T1 N0 M0 • Stage 2: T2 N0 M0 • Stage 3: T3 N0 M0, T1 N1 M0, T2 N1 M0 and T3 N1 M0 • Stage 4A: T4 N0 M0, T4 N1 M0, any T N2 M0 • Stage 4B: Any T N3 M0 • Stage 4C: Any T, any N, M1 Dukes ABC Staging It is used in cancers of bowel:

CIN Grading • • •

CIN I: It represent less than one-third involvement of the thickness of the epithelium. CIN II: In it there is one-third to two-thirds involvement. CIN III: It is full thickness or equivalent to carcinoma in situ.

• Stage A: When tumor is confined to submucosa and muscle and cure rate is 100 percent. • Stage B: Tumor penetrates the entire thickness of bowel wall into pericolic or perirectal tissues and cure rate is 70 percent. • Stage C: It is characterized by lymph node metastasis and reduces the cure rate to 30 percent.

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Primary tumor (T)

Regional lymph nodes (N)

Distant metastasis (M)

Local extent is major factor contributing to prognosis. • Tx: Primary tumor cannot be assessed. • T0: No evidence of primary tumor. • Tis: Carcinoma in situ. • T1: Tumor 2 cm or less in diameter. • T2: Tumor 2-4 cm in diameter. • T3: Tumor more than 4 cm in greatest diameter. • T4: Tumor of any size in which tumor invades adjacent structure (e.g. cortical bone, inferior alveolar nerve, floor of mouth, skin of face, etc.).

• Nx: Regional lymph node cannot be assessed. • N0: No regional lymph node metastasis. • N1: Metastasis in single ipsilateral lymph node less than 3 cm in diameter. – N1a: Nodes considered not to contain tumor growth. – N1b: Nodes considered to contain growth. • N2: Single lymph node, no more than 6 cm in greatest dimension, of bilateral/ contra-lateral lymph node, none more than 6 cm. – N2a: Single ipsilateral lymph node more than 3 cm but less than 6 cm. – N2b: Multiple ipsilateral lymph nodes less than 6 cm. – N2c: Bilateral or contralateral lymph node less than 6 cm in greatest dimension. • N3: Metastasis in lymph node more than 6 cm and it is fixed. – N3a: Ipsilateral nodes at least one greater than 6 cm. – N3b: Bilateral nodes greater than 6 cm. – N3c: Contralateral nodes at least one greater than 6 cm.

• Mx: Distant metastasis cannot be assessed. • M0: No distant metastasis. • M1: Distant metastasis. Category M1 may be further specified according to the notation. – Pulmonary—PUL – Osseous—OSS – Hepatic—HEP – Brain—BRA – Lymph nodes—LYM – Bone marrow—MAR – Pleura—PLE – Peritoneum—PER – Skin—SKI – Other—OTH

Hyperplasia, Hamartoma and Neoplasm Table 7.4 STNMP staging

S—site of primary tumor

Size of tumor—it is denoted by T

Regional nodes were grouped as

Metastasis

Pathology of lesion

• • • • • • •

• T1 - Less than 2 cm in diameter. • T2 - Between 2 cm and 4 cm in diameter. • T3 - Between 4 cm and 6 cm in diameter and extending beyond the primary region and extending through adjacent periosteum. • T4 - Greater than 6 cm in diameter and extending to involve adjacent structures

• N0 - No palpable nodes. • N1 - Equifocal node enlargement. • N2 - Clinically palpable homolateral regional nodes, not fixed • N3 - Same as N2 but fixed • N4 - Clinically palpable contralateral or bilateral nodes, not fixed. • N5 - Same as N4 but fixed

• M0 - No distant metastasis • M1 - Clinical evidence of distant metastasis without definite histological or radiographic conformation. • M2 - Proven evidence of metastases beyond regional nodes

• P0 - Hyperkeratotic lesion showing atypia. • P1 - Carcinoma in situ. • P2 - Basal cell carcinoma. • P3 - Verrucous carcinoma. • Well differentiated squamous cell carcinoma. • Moderately differentiated squamous cell carcinoma. • Poorly differentiated squamous cell carcinoma.

S1 - Lip and skin. S2 - Lip mucosa. S3 - Tongue. S4 - Cheek. S5 - Palate. S6 - Floor of mouth. S7 - Alveolar process. • S8 - Antrum. • S9 - Central carcinoma of bone.

STNMP Staging System (Table 7.4) Nowaday in the TNM staging site and pathology of lesion is added. This is described in Table 7.4.

BIBLIOGRAPHY

1. Ashley JV, Shafer AD. Teratoma of the tongue in a newborn. Cleve Clin Q. 1983;50:34. 2. Grier EA, MacNerland RH. Benign teratoma of the tongue. Ill Med J. 1967;132:43. 3. Kjeld P. Focal epithelial hyperplasia, 1st edn. Chrono Press; 2012. 4. Kumar V, Abbas A, Mitchel R. Robbins and Cotran Pathologic Basis of Disease, 8th edn. Elesevier India Pvt. Ltd; 2009. 5. Lalwani AK, Engel TL. Teratoma of the tongue: a case report and review of the literature. Int J Pediatr Otorhinolaryngol. 1992;24:261.

6. Mahour GH, Landing BH, Wooley MM. Teratomas in children: clinicopathologic studies in 133 children. Z Kinderchir. 1978;23:365. 7. Rodin AE, Singula P. Teratoma of the tongue at birth. Pediatr Pathol. 1985;3:291. 8. Shafer, Levy H. A Textbook of Oral Pathology, 4th edn. WB Saunder’ s company; Philadelphia. 9. Sperber G. Craniofacial development; BC Decker Inc; Canada; 2001. 10. Stevenson R, Hall J. Human malformations and elated anomalies, 2nd edn. Oxford University Press; 2006. 11. Toll A. Intravascular papillary endothelial hyperplasia; Ceed publishing; 2012. 12. Uchida K, Urata H, Suzuki H. Teratoma of the tongue in neonates: report of a case and review of the literature. Pediatr Surg Int. 1998;14:79.

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MULTIPLE CHOICE QUESTIONS 1. Loss in uniformity and architectural orientation is called as: a. Dysplasia b. Metaplasia c. Hyperplasia d. Hamartoma

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2. Pulp polyp is an example of: a. Hamartoma b. c. Hyperplasia d.





Dysplasia Metaplasia

3. Fordyces granules comes under: a. Choriostoma b. Odontogenic hamartoma c. Nonodontogenic hamartoma d. Teratoma



7. Following are the DNA oncogenic virus except: a. HTLV b b. Hepadna virus c c. Herpes d d. Adeno virus



8. All are the theories of carcinogenesis except: a. Genetic theory b. Epigenetic theory c. Virus theory d. Mechanistic theory

4. DNA synthesis is absent in which phase: a. M phase b. G 2 phase c. S phase d. G 1 phase 5. Chlorambucil, cyclophosphamide, nitrosourea are the examples of: a. Physical carcinogens b. Chemical carcinogens c. Biologic carcinogens d. Hormonal carcinogens

6. Malignant tumors of epithelial origin are called as: a. Fibromas b. Sarcomas c. Carcinomas d. Odontogenic hamartoma





9. Grading of the tumors mainly depends on two histologic features: a. The degree of anaplasia b. The rate or growth c. Both d. None of the above 10. Universally accepted grading system for tumors is: a. TNM staging b. STNMP staging c. Dukes ABC system d. AJC system

Teeth Anomalies

Anil Govindrao Ghom , Shubhangi Mhaske (Jedhe), Savita Ghom A

Chapter Outline

• • • • • • • •

O Scale of human tooth development • Disorders of size of teeth

• Microdontia

o Macrodontia Disturbances in shape of teeth

• • • •

Gemination Twining

•

Concrescence

• • • • • • • •

Talon' s cusp Di laceration Dens in dente

Fusion

Globodontia

• Shovel shaped incisors • Moon' s molar

• Hutchinson' s incisor • Carabelli' s cusp • Mulberry molar

o Disorders of number of teeth or

Environmental enamel hypoplasia Mottled enamel or dental fluorosis Molar incisor hypominerlization Amelogenesis imperfecta Dentinogenesis imperfecta Dentin dysplasia

• Regional odontodysplasia • Fibrous dysplasia of dentin • Dentin hypocalcification O Anomalies associated with eruption of the teeth • Eruption of teeth • Theories of tooth eruption • Pre- deciduous dentition • Delayed eruption • Embedded and impacted teeth • Ankylosis or submerged teeth • Transposition • Eruption sequestrum • Ectopic eruption • Premature exfoliation • Postpermanent dentition

Dens evaginatus Taurodontism Supernumerary roots Ectopic enamel

• Anodontia

Supernumerary teeth Structure of teeth

hypodontia

DISORDERS OF DEVELOPMENT OF TEETH Developmental disorders or anomalies are either prenatal or postnatal in origin, which can be inherited or acquired . Their recognition and evaluation require a thorough knowledge

of the normal chronology of the human dentition and of the normal development and structure of the teeth. These disorders may be due to abnormalities in the differentiation of the dental lamina and the tooth germs, causing anomalies in the number, size , and form of teeth (abnormalities of morphodifferentiation) or to abnormalities in the formation

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of the dental hard tissues resulting in disturbances in tooth structure (abnormalities of histodifferentiation). Abnormality in morphodifferentiation occur in early stage  while in histodifferentiation it occur in later stage; in some disorders both stages of differentiation are abnormal.

SCALE OF HUMAN TOOTH DEVELOPMENT ∙ ∙ ∙ ∙ ∙ ∙

6 weeks (40–42 days): Rupture of buccopharyngeal membrane. 42–48 days: Dental lamina formation. 55–56 days: Bud stagedeciduous incisor, canine and molar. 14th week: Bell stage for deciduous bud for permanent. 18th week: Dentin and functional ameloblast. 32nd week: Dentin and functional ameloblasts of permanent 1st molar.

The developmental disturbances of teeth can be classified under broad category as (Table 8.1) ∙ Disorders of size of teeth ∙ Disorders of shape of teeth ∙ Disorders of number of teeth ∙ Disorders of structure of teeth ∙ Disorders of eruption of teeth.

Table 8.1 Classification of anomalies of teeth

S. No.

Disorder affecting teeth

Subtypes

1.

Size

•  Microdontia •  Macrodontia

2.

Shape

•  •  •  •  •  •  •  •  •  •  • 

3.

Number

•  Anodontia •  Supernumerary teeth

4.

Structure

A. Enamel    i.  Amelogenesis imperfecta   ii.  Enamel hypoplasia B. Dentin i. Dentinogenesis imperfect ii. Dentin dysplasia C. Both enamel and dentin i. Regional odontodysplasia D. Cementum

5.

Eruption

•  •  •  •  •  •  •  • 

DISORDERS OF SIZE OF TEETH The size of both the teeth as well as the jaws is influenced by genetic and environmental factors. Studies of twins have shown that for the teeth, at least, genetic factors plays a major role this variation. The anomalies of teeth due to disturbance in size are microdontia and macrodontia.

Microdontia It refers to teeth that are smaller than normal. There are three types of microdontia. ∙ True generalized: All the teeth are smaller than normal.  It occurs in pituitary dwarfism, Down’s syndrome and congenital heart disease. ∙ Relative generalized: The teeth are or slightly smaller than normal teeth; but the jaws are larger than the normal which simulate the microdontia. It is hereditary. It often exhibits spacing between the teeth. ∙ Localized: It involves only single tooth. It occurs with congenital heart diseases, Down’s syndrome and  progeria (Hutchison’s–Gilford syndrome characterized  by dwarfism and premature senility).

Gemination Twining Fusion Concrescence  Talon’s cusp Dilaceration Dens evaginatus Dens invaginatus Taurodontism Supernumerary roots Miscellaneous

Premature eruption  Delayed eruption  Embedded and impacted teeth  Ankylosis or submerged teeth  Transposition  Eruption sequestrum  Ectopic eruption  Premature exfoliation

Clinical Features Localized microdontia Most commonly affected teeth are maxillary lateral incisors and 3rd molars (Fig. 8.1). Supernumerary teeth are frequently smaller than normal. One of the common form of localized microdontia is peg shaped laterals in which the mesial and distal sides converges or taper incisally, forming peg shaped or cone shaped crown. In case of molar, they may also undergo a change in shape from five to four cusps in case of mandibular molar and from four to three cusps in upper molars.

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Figure 8.1 Microdontia of 3rd molar showing small size

Figure 8.2 Macrodontia of 2nd molar showing more cusp of

the tooth

Management Crown and bridge work is required for esthetic rehabilitation of teeth. Points to Remember Teeth  smaller  than  normal,  occurs  with  Down’s  syndrome, dwarfism, congenital heart disease, true generalized, relative generalized, localized, peg shaped laterals.

Macrodontia It is also called megadontia. These are the teeth which are larger than normal. It is of three types: 1. True generalized: All the teeth are larger than normal.  It is commonly associated with pituitary gigantism. 2. Relative generalized: Teeth are normal or slightly larger than normal, but present in a smaller jaw. 3. Localized: One or more large teeth exist in relation to an otherwise normal dentition and body size.

Causes

In many cases tooth with macrodontia show more cusps (Fig. 8.2).

Management If necessary orthodontic treatment is done. If impacted, extraction is indicated. Points to Remember Teeth are larger than normal, associated with pituitary gigantism, facial hemihypertrophy, angioma of face, true generalized, localized, relative generalized.

DISTURBANCES IN SHAPE OF TEETH Disturbances in tooth form may involve the crown, the root, or both. The most frequent variations of the crowns of teeth affect maxillary permanent lateral incisors, which may be peg-shaped or show an accentuated cingulum-either variation sometimes being associated with an invagination. Premolars  or  molars  with  an  increased  or  decreased  number of cusps are also frequently seen. Variations in the number, course, form, and size of roots are particularly common.

It is occasionally seen in facial hemihypertrophy, in which half of the teeth in unilateral distribution are affected. Angioma of face, pituitary gigantism and genetic component.  Gemination

Clinical Features Teeth are larger than normal. There is crowding, which may result in malocclusion. Due to lack of space impaction of teeth is common. It should not be confused with fusion.

It refers to the process whereby, single tooth germ invaginates resulting in incomplete formation of two teeth that may appear as bifid crown on single root. It occurs during the proliferation stage of the growth cycle of tooth.

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Etiology

Management

Hereditary and familial tendency is present. It results from the splitting of a tooth germ during development or from the fusion of a normal tooth bud with a developing supernumerary tooth (Fig. 8.3).

Affected tooth structure should be removed and crown may  be restored and reshaped. Reduction of mesiodistal width with periodic disking. Final jacket crown preparation.

Clinical Features

Points to Remember

Males and females are equally affected.

Hereditary and familial tendency, bifid crown or single root, results from splitting of tooth germ, commonly affected permanent maxillary incisors, deciduous mandibular incisors, pulpal infection, malocclusion, and periodontal pathosis.

Location: The commonly affected teeth are deciduous mandibular incisors and permanent maxillary incisors. Bifid crown: It appears clinically as bifid crown on single root. It does not increase or decrease the number of teeth present. There are common pulp canals and either single or partially divided pulp chambers.

Twining It indicates cleavage of tooth germ which results in formation of supernumerary teeth that is mirror image or near image of tooth from which it has developed.

Crown is wider than normal with shallow groove extending from incisal edge to cervical region. Enamel or dentin of crown of geminated teeth may be  Fusion hypoplastic or hypocalcified. Invagination of crown occurs It is also called ‘synodontia’. It represents the embryonic with complete and incomplete division. union of normally separated tooth germs. It represents Complication: Areas of hypoplasia and invagination lines  junction at the level of dentin between juxtaposed normal or areas of coronal separation represent caries susceptible tooth germs. area, which may lead to pulpal infection. It may also cause malocclusion and periodontal pathosis.

Etiology It is transmitted as autosomal dominant trait with reduced penetration.  Physical  force  or  pressure  generated  during  development causes contact of tooth germs. Two separate developing tooth germs being initially close together; as they grow and expand; they contact with each other and the germs fuse to varying degrees (Fig. 8.4). Classification of Fusion •  C   omplete: If fusion takes place before calcification begins, the two teeth may be completely united to form a single large tooth. •   Incomplete: If contact of teeth occurs later, i.e. when the portion of crown has completed its formation; then there is union of root only.

Clinical Features

Figure 8.3 Gemination is a macrodont formed when there is

partial division of tooth germ

Location: It is seen more commonly in anterior teeth. It is more common in deciduous dentition than in permanent dentition. It may occur between a normal tooth and a supernumerary tooth such as mesiodens or distomolar.

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Figure 8.6 Fusion of molar teeth

Management Figure 8.4 Fusion is a process in which two adjacent tooth

germ fuse to form a macrodont

Morphology of teeth should be determined radiographically for  endodontic  treatment.  After  endodontic  treatment,  tooth may be reshaped with a restoration that will mimic independent crown. Points to Remember Synodontia, tooth is almost twice in size, spacing, periodontal conditions, dental caries, endodontic treatment.

Concrescence It is a form of fusion that occurs after the root and other major parts involved in teeth are formed or when the roots of two or more teeth are united by cementum, below the cementoenamel junction. It is also called ‘false gemination.

Etiology Figure 8.5 Fusion of crown (cusps)

Tooth is almost twice in size than normal, with or without bifid crown. Tooth may have separate or fused root canals (Figs 8.5 and 8.6). Sign: Clinically there may be spacing and periodontal  problems (Fig. 8.3). Dental caries is common in fused teeth. It may result in reduced number of teeth in the jaws. When deciduous teeth fuse, the corresponding permanent teeth may be absent.

It may occur due to traumatic injury, overcrowding of the teeth with resorption and interdental bone loss, distal inclination of crown of molar, space restriction during development, excessive occlusal trauma and local infection after development. Classification Concrescence •  T   rue concrescence: If roots are bound during development. •   Acquired concrescence: If the condition occurs after development.

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Clinical Features

Talon’s Cusp

Location: It is common in maxillary 2nd and 3rd molar area. Either primary or secondary teeth are affected. Usually  involved two teeth, roots are fused by cementum (Figs 8.7 and 8.8). Teeth may fail to erupt or incompletely erupt. There may be malocclusion or the teeth may be impacted.

It projects lingually from cingulum area of maxillary and mandibular teeth or it is an anomalous hyperplasia of cingulum on the lingual of maxillary and mandibular incisors, resulting in the formation of supernumerary cusp.

Management Dentist must be careful while doing extraction. Points to Remember Traumatic injury, roots are fused by cementum, careful while extraction.

Pathogenesis A  focal proliferation of tissue during development and exuberant development of the fourth lobe (cingulum) leads to development of talon cusp.

Clinical Features (Fig. 8.5) It may be found in both sexes and common in both dentitions. It resembles like an eagle’s talon. It blends smoothly with the erupted tooth, except that there is deep developmental groove where the cusp blends with sloping lingual tooth surface (Figs 8.9 and 8.10). It is composed of normal enamel, dentin and contains a form of pulp tissue. Cusp may or may not contain pulp  horn and is usually T shaped. Patients face problems with  esthetic and there is high incidence of caries. In some cases occlusal interference may be there. It may be associated with Rubinstein-Taybi syndrome.

Management Removal of cusp followed by endodontic therapy should be carried out. Points to Remember Figure 8.7 Concrescence is fusion between two teeth by means

of cementum (Courtesy: Dr Alka Kale, Dean and Prof Head Oral Pathology, KLES’s Institute of Dental Sciences, Belgaum)

Focal proliferation of tissue during development of forth lobe, eagle’s talon, Rubinstein Taybi syndrome.

Dilaceration It refers to angulations or sharp bends or curve in the roots or crowns of the teeth.

Etiology Mechanical trauma to calcified portion of partially formed teeth results in dilaceration. The portion formed after trauma is in different direction causing the dilaceration. Developmental defect and obstacle to the normal direction of growth can cause dilacerations.

Clinical Features Figure 8.8 Fused roots due to concrescence

Location: It is most commonly found in maxillary incisors.

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Figure 8.9 Talon’s cusp (Courtesy: Dr Alka Kale, Prof and Head, Oral Pathology, KLES’s Institute of Dental Sciences, Belgaum)

Figure 8.11 Dilacerations seen in incisors and molars

Figure 8.10 Talon’s cusp is seen on permanent maxillary

Figure 8.12 Dilacerations at the crown of the teeth

lateral

Curve or bending occurs anywhere along the length of tooth, sometimes at cervical portion or midway along the root or even just at the apex of root. Sometimes, angles are so acute that a tooth does not erupt. If the defect is in the crown of an erupted tooth, the angular distortion will be recognized (Figs 8.11 to 8.13).

Management There is difficulty at the time of extraction. Dilacerated crown has to be restored with crown to improve esthetics and function and to preclude dental caries and periodontal disease.

Points to Remember Angulations  or  sharp  bends,  mechanical  trauma,  curve  or bending, angular distortion, dilacerated crown.

Dens in Dente It is also called dens invaginatus or dilated composite odontome or gestant odontome. Infolding of the outer surface of the tooth into its interior surface occurs. It is a developmental variation which is thought to arise as a result of an invagination in the surface of crown before calcification.

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A

B Figures 8.13A and B Curved root seen in dilacerations

Etiology There is relative retardation in growth of a portion of the enamel organ, with the result that this part remains stationary and the remainder grows around it. Another  view  is  that  invagination  is  due  to  active  proliferation of an area of enamel organ which then grows into dental papilla, as a sort of adenoma. Study shows that there is presence of extravascular fluid in the soft tissue that fills the potential invagination cavity of the tooth, before it erupts, suggesting that there is increased venous pressure within the invagination. It could be due to pressure on the blood vessels as they pass through the entrance channel of the invagination cavity where enamel is forming concentrically and centripetally, thus tending to progressively narrow the entrance. Expansion  of  the  invagination  could  then  result  from  the increased venous pressure and transudation (Fig. 8.14). It can occur due to infection of the deciduous predecessor or trauma. Pressure on the growing teeth can  also cause invagination. Types of Dens in Dente •  Coronal dens invaginatus  •  Radicular dens invaginatus.

Classification Coronal dens invaginatus: It is anomalous infolding of enamel organ into dental papilla. It results in fold of hard tissue within the tooth, characterized by enamel lining the fold and covering the dentin peripheral to it (Fig. 8.9).

Figure 8.14 Pathogenesis of dense invaginatus

Radicular dens invaginatus: It is a result of invagination of Hertwig’s epithelial root sheath resulting in accentuation of  normal longitudinal root grooves. It is lined by cementum. Root sheath may bud off and form a invagination, that results in a circumscribed cementum defect in root.

Clinical Features Coronal dens invaginatus Location: Commonly affected tooth is permanent maxillary  lateral and central incisor. The mandibular incisor or cuspid is the next most commonly affected tooth. Age and sex predilection: It is diagnosed in children or in adolescents. It is more common in females. This condition is frequently bilateral. In mild type form there is a deep pit in cingulum (Fig. 8.15). In moderate type pocket of enamel is formed within tooth, with dentin at periphery. Opening to the surface is constricted or remains open. Food debris may become packed in this area with resultant caries and infection of pulp. In severe type it may exhibit an invagination extending nearly to the apex of the root. The crown may or may not be enlarged in size. The shape of crown may be conical or it may be of irregular shape. In some cases there appears to be a grossly magnified cingulum rising to the level of the incisive edge of the tooth, but lacking the normal contour of a cingulum

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Figure 8.15 Severity of dens invaginatus

Figure 8.17 Radicular dens invaginatus

chamber by a thin wall and opens in oral environment through very narrow constriction (Fig. 8.17).

Radiological Features The affected tooth demonstrates an enlargement of root. Opening is situated along the lateral aspect of the root.

Histopathological Features

Figure 8.16 Coronal dens invaginatus (Courtesy: Dr Alka Kale, Prof and Head, Oral Pathology, KLES’s Institute of Dental Sciences, Belgaum, Karnataka, India)

The lining consists of enamel and at the opening of the between the two cusps this is continuous with the enamel that covers the exterior of the tooth. In invagination of severe type, pulp cavity is grossly encroached upon and may be represented by a mere slit in the dentine on each side of the invagination cavity. Enamel  lining is defective owing to poor mineralization and may be totally absent in the area.

Management Tooth should be restored prophylactically.

(Fig. 8.16). The labial face of the tooth is often bulbous. Some teeth with these abnormalities are so misshapen as to defy verbal description. Radicular dens invaginatus (Fig. 8.17) Location: It is more is common in 1st mandibular premolar, upper  lateral  incisor  and  second  molar.  Abnormality  is  usually unilateral. It occurs most frequently at the site of an anatomical defect of the root. It is also said to be an incomplete attempt of bifurcation of roots. ∙ Crown is small, short and conical with a small orifice. ∙ Lingual marginal ridge is prominent. Invagination presents as cavity that is separated from the pulp

Points to Remember Mild type, moderate type, severe type, constricted opening to the surface, conical crown, grossly magnified cingulum, crown is small, short, prominent lingual marginal ridge, enlargement of root, lining consists of enamel, mere slit in the dentine.

Dens Evaginatus It is also called Leong’s premolar, evaginated odontome or occlusal enamel pearl. Dens evaginatus is a developmental condition that appears clinically as an accessory cusp or

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globules of enamel on occlusal surface, between buccal and lingual cusps of premolar. 106

Points to Remember Leong’s premolar, evagination of an area of inner enamel  epithelium, tubercle of enamel, polyp like protuberance, incomplete eruption radiologically tuberculated appearance.

Pathogenesis

It is caused by proliferation and evagination of an area of inner enamel epithelium during tooth development process. After this there is also proliferation of odontogenic  Taurodontism mesenchyme into dental organ also occurs. It is described in 1913 by Sir Arthur Keith. In this, crown Clinical and Radiological Features of tooth is enlarged at the expense of root. The shape of taurodont teeth resembles that of molar Location: It occurs on premolar and molar teeth and usually teeth of cud chewing animal, i.e. tauro-bull dont-tooth. occurs unilaterally or bilaterally. It develops in persons of It is characterized by anatomical crown of normal shape Mongoloid ancestry. It consists of all three dental tissues, and size, an elongated and short roots, it exhibits enlarged i.e. enamel, dentine and cementum. It appears as a tubercle of enamel on occlusal surface of pulp chambers. the affected tooth. Polyp like protuberance in central groove, on lingual Etiology ridge of buccal cusp is seen. It is hereditary in origin and usually caused by genetically determined  trait.  Failure  of  Hertwig’s  epithelial  root  Other features: There may be incomplete eruption. Pulp  sheath to invaginate at proper horizontal level and exposure and subsequent infection may occur, following mutation resulting from odontoblastic deficiency during occlusal  wear  or  fracture.  Pulpal  extension  is  seen  in  the  dentinogenesis of the root can leads to taurodontism. pulp of patient. Radiological features: Occlusal tuberculated appearance (Fig. 8.18).

surface

exhibits

Shaw’s Types of Taurodontism (Fig. 8.19) ∙

Management If tubercle is a cause of occlusal interference, it should be removed under aseptic conditions.

∙ ∙

Figure 8.18 Dens evaginatus showing tuberculated

appearance

Hypotaurodont—in this condition bi or trifurcation extents near the cervical area of the root. This is mild form. Mesotaurodont—in this bi or trifurcation occur at the middle area of the root. Hypertaurodont—in this condition bi or trifurcation occur at the apices of the root.

Figure 8.19 Types of taurodontism (redraw image)

Teeth Anomalies

Clinical and Radiological Features (Fig. 8.20) Age: It is common in early aged men but has gradually decreased in incidence over last 3 million years. Location: It may affect either deciduous or permanent dentition and teeth involved are invariably molars. It may be unilateral or bilateral, or may exhibit any combination of quadrant involvement. Involved teeth tend to be of rectangular shape rather than the normal tapering towards root. It may associate with certain dermatological condition like epidermolysis bullosa, otodental dysplasia and dyskeratosis congenita. Syndromes which are associated with this disease are Klinefelter syndrome and Trichodento-osseous syndrome (Table 8.2).

Radiological features: There is increase apico-occlusal height with bifurcation close to apex of tooth.

Management No specific treatment is necessary. Points to Remember Hereditary, failure of Hertwig’s epithelial root sheath to  invaginate, Klinefelter’s syndrome, Trichodento-osseous syndrome, rectangular shape teeth.

Supernumerary Roots It is the development of increase number of root on the tooth.

Clinical Features Location: Teeth that are normally single rooted exhibit two roots. Both, maxillary and mandibular molars particularly 3rd molars are affected showing supernumerary roots (Fig. 8.21). They develop as slender outgrowths at the center of furcation area of molar teeth.

Management It assumes significance only during exodontia as these roots may be broken off during extraction. Points to Remember 3rd molars, slender outgrowths, center of furcation area. Figure 8.20 Taurodontism showing enlarged root trunk.

Radiograph showing enlarged pulp chamber (Courtesy: Dr Alka Kale, Prof and Head, Oral Pathology, KLES’s Institute of Dental Sciences, Belgaum) Table 8.2 Syndrome associated with taurodontism

Autosomal dominant conditions

Chromosomal and other conditions

•  Apert syndrome •  Axenfled-Rieger •  Basal cell nevus •  Ecodermal dysplasia •  Otodental dysplasia •  Trichodento-osseous Autosomal recessive conditions •  Ackerman

•  Klinefleter syndrome •  Down syndrome •  Dyschomdrosteosis X-linked conditions •  Dyskeratosis congenital •  Fragile X •  Orofaciodigital , type I Figure 8.21 Supernumerary root in the teeth

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Ectopic Enamel 108

These are presence of enamel at location which is not normal. Types •  Enamel pearls •  Cervical enamel extension.

Types Enamel pearls: Pearls or droplets are described as small  buttons or nodules of enamel, usually about 1 mm or 2 mm in diameter, that form on the root, or at bifurcation or trifurcation of multirooted teeth. It arises from local activity of  remnants  of  Hertwig’s  epithelium  before  it  reduces  to  rests of Malassez.

Figure 8.22 Enamel pearl in the cervical area

Cervical enamel extension: Represent the dipping of enamel from the cementoenamel junction towards the bifurcation of molar teeth. This is triangular extension of coronal enamel with apex directed towards the bifurcation of the tooth.

Clinical and Radiological Features Location: It is common in trifurcation of maxillary molars, followed by bifurcation of mandibular molars. Those found on maxillary molars are on, usually, mesial or distal aspect in contrast to those on mandibular molars, which are most often on buccal or lingual aspect. Rarely, small pulpal extensions may reach into center of nodule and thereby constitute additional hazard. Rarely, tiny nodule may be sufficiently close to gingival margin to become involved in the periodontal problems. Radiographic features: It appear as well-defined radiopaque nodules along the root’s surface (Fig. 8.22). 

Histopathological Features Overgrowth may be simply a cap of enamel over dentin and replacing cementum in that area.

Management If it is causing periodontal problems, mass can be removed. Points to Remember Enamel pearls, cervical enamel extension, small pulpal  extensions, radiopaque nodules, periodontal problems.

Figure 8.23 Mulberry molar with spherical aggregate

Globodontia It is common in crown of premolar and molar teeth. Teeth have a round globular clover leaf appearance. It is characteristic of otodental syndrome in which there is also deafness. Other anomalies associated with it are fusion of molar and premolar teeth and double pulp chamber (Fig. 8.3).

Mulberry Molar It is a characteristic syphilitic lesion of posterior teeth in which hyperplastic enamel develops with spherical aggregates or globules on the surface of dentin (Fig. 8.23).

Teeth Anomalies

Moon’s Molar First molar is commonly involved. It is syphilitic lesion of posterior teeth. Cusp of teeth shows exaggerated rounded  or nodular shapes. It is often grossly distorted, usually narrower mesiodistally with loss of angulation of occlusal edge, which may give cusp a squarish appearance.

Hutchinson’s Incisor

Classification •      •  • 

True –  Total (oligodontia)  –  Partial (hypodontia) False  Pseudo

Clinical Features

It  commonly  affected  the  anterior  teeth.  Center  of  the  It is higher in women and most probably in Mongoloid, than whites. Absence may be unilateral or bilateral. incisal edge shows typical notching. In true total anodontia all teeth are missing and it An affected tooth is screwdriver shaped, with tapering marginal ridges converging towards the incisor edge. Teeth involves both deciduous and permanent dentition. In true partial anodontia there is absence of one or may show barrel shaped outline. more  teeth.  Commonly  missing  are  3rd  molar,  maxillary  lateral incisor, maxillary or mandibular 2nd premolar (Fig. Carabelli’s Cusp 8.24). It is accessory lingual cusp located on the mesiopalatal False anodontia results due to extraction of teeth. cusp of maxillary second deciduous molars and 1st, 2nd Pseudoanodontia refers to multiple unerupted teeth. and 3rd permanent molars. It may be unilateral or bilateral, Hypodontia is usually associated with microdontia, with marked deviation in size. reduce alveolar development, increases freeway space and retained primary teeth. Shovel Shaped Incisors It is morphologically an anomaly of the crowns of incisor teeth. It is more common in the maxillary arch. The shovel shape is manifested by the prominence of the mesial and distal marginal ridges which enclose a central fossa on the lingual surface of incisor teeth. It has frequently a short root.

Management Patient  can  be  managed  by  orthodontic  treatment  and  by  restoration or prosthesis.

DISORDERS OF NUMBER OF TEETH It includes, anodontia, ectodermal dysplasia and supernumerary teeth.

Anodontia or Hypodontia It is congenital absence of teeth.

Etiology Hereditary ectodermal dysplasia, cleidocranial dysplasia, craniofacial dysostosis, cleft lip, and cleft palate can cause anodontia. Genetic  factors,  evolutionary  trend  towards  few  teeth  also lead to anodontia. In some cases X-ray radiation can  be causative factors.

Figure 8.24 Patient showing missing teeth in partial

anodontia

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Points to Remember Hypodontia 110

•  More common in permanent than primary dentition •  May be associated with mutations in developmental  control genes •  Absence of primary teeth associated with absence of  permanent successors •  May be associated with other developmental abnormalities. Severe hypodontia/anodontia •  Rare  •  Associated  most  frequently  with  hypohidrotic  ectodermal dysplasia (HED) •  HED usually X-linked recessive.

Supernumerary Teeth It is also called hyperdontia.

Etiology A  supernumerary  tooth  develops  from  3rd  tooth  bud  arising from dental lamina near the permanent tooth bud or possibly from splitting of the permanent bud itself. It is inherited as an autosomal dominant trait, if associated with syndromes. It is inherited as an autosomal recessive trait when associated with only supernumerary teeth. Types of Supernumerary Teeth •  Supplemental supernumerary teeth: These teeth duplicate the typical anatomy of posterior and anterior teeth. •  Rudimentary supernumerary teeth: These are dysmorphic and can assume conical forms.   –  Conical – small peg shaped    –   Tuberculate – barrel shaped anterior with more  than one cusp   –  Molariform – small premolar like or molar like.

Figure 8.25 Extracted mesiodens

Distomolar: It is found in molar region frequently located distal to 3rd molar. Generally, these teeth are smaller than  normal 2nd and 3rd molar. General crown morphology is  highly abnormal. Paramolar: It is supernumerary molar, usually small and rudimentary and is situated buccally or lingually to one of the maxillary molars or inter-proximally between 1st, 2nd and 3rd maxillary molars. Peridens: Supernumerary teeth that erupt ectopically, either buccally or lingually to the normal arch are referred as peridens.

Clinical Features Sex predilection: Males are affected more than females. Male to female ratio is 2:1. Location: It may occur in both dentitions, but frequently found in permanent dentition and more often in mandible. It may be erupted or impacted and occurs in 1 percent of the population.

Most common supernumerary teeth are as follows:

Supernumerary teeth occurs most often with cleft palate Supernumerary teeth which occur in the bicuspid region, most frequently in the lower jaw, are commonly well formed and resemble the normal teeth.

Mesiodens: It is located at or near the midline in the incisal region of maxilla between central incisors. It may occur singly or paired, erupted or impacted or even inverted. It is a small tooth with cone shaped crown and short root. It may cause retarded eruption, displacement or resorption of adjacent root. It frequently causes improper alignment (Fig. 8.25).

Shape: Their form is normal or conical or can be just arranged as masses of dental tissue. Supernumerary teeth frequently prevent permanent teeth from erupting or cause them to erupt in an abnormal direction or site, even without being any contact between them (Fig. 8.26). In some cases fusion of supernumerary teeth can occur with normal teeth (Fig. 8.27).

Teeth Anomalies Table 8.3 Syndrome with globodontia or supernumerary cusps as component

Figure 8.26 Supernumerary teeth in upper anterior region

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Syndrome

Prominent features

Otodental dysplasia

Sensorineural hearing loss, anamolies, missing premolars

Cartilage hair – hypoplasia

Short-limbed dwarfism due to skeletal dysplasia, sparse hair, dental anomalies (supernumerary cusps), lymphopenia, anemia, neutropenia

dental

Rothmund-thomson Atrophy,  pigmentation,  telangiectasia,  juvenile cataract, saddle nose, congenital bone defect, disturbances of hair growth, hypogonadism, dental anomalies, soft tissue contractures, proportionate short stature, anemia, osteogenic sarcoma

STRUCTURE OF TEETH The disturbances during odontogenesis or development of tooth germ cause defects in the hard tissues of teeth. These can be discussed under following headings, enamel, dentin and both enamel and dentin.

Environmental Enamel Hypoplasia It is an incomplete or defective formation of organic enamel matrix. Local and systemic factors that interfere with the normal matrix formation can cause enamel surface defects and irregularities. Figure 8.27 Fusion of supernumerary tooth with permanent

Classification of Enamel Hypoplasia

Syndrome: It is associated with cleidocranial dysplasia, orofacial  digital  syndrome  and  Gardner’s  syndrome  (Table 8.3).

•  M   ild: There may be only few small grooves, pits and fissures on enamel surface. •  Moderate:  Enamel  exhibits  rows  of  deep  pits  arranged horizontally across the surface. •   Severe: Considerable  portion  of  enamel  may  be  absent.

Management

Causes of Environmental Hypoplasia

molar tooth

It depends on potential effect on normal dentition, their position, number and complications that may result from surgical removal. If required, they should be extracted. Points to Remember More common in maxilla than mandible, occasionally associated with other developmental defects more common in females than males.

•  •  •  •  •  •  •  • 

Hypoplasia due to nutritional deficiency  Hypoplasia due to exanthematous disease  Hypoplasia due to congenital syphilis  Hypoplasia due to hypocalcemia  Hypoplasia due to birth injury  Hypoplasia due to local infection or trauma  Hypoplasia due to tetracycline  Hypoplasia due to chronic lead poisoning.

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Clinical Features

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occlusal surface and occlusal third of the tooth appears to be arranged in agglomerate mass of globule, rather than in well Hypoplasia due to nutritional deficiency: It occur due formed cusp. The crown is narrower on occlusal surface, to deficiency of vitamin A, C, D, calcium and phosphorus.  than at the cervical margin (Figs 8.29A and B).  Two-thirds of this occurs during infancy period or early childhood. Frequently involved are those teeth which Hypoplasia due to hypocalcemia: Tetany induced by are formed within the first year of after birth. Vitamin D decreased level of calcium in the blood, which is as low deficiency causes rickettsial phenomenon, resulting from as 6 to 8 mg/mL. As calcium is required for normal tooth  lack of proper calcification of enamel matrix. Horizontal formation, there is defective formation of the enamel. pitting occurs in rows, on the teeth undergoing matrix Enamel hypoplasia in it is usually of ‘pitting’ variety. formation at the time of dietary deficiency or during course Hypoplasia due to birth injury–in prenatal type marked of febrile episode. Pitting characteristically picks up stain  enamel hypoplasia affects incisal 2/3rds of enamel on and discoloration occurs (Fig. 8.28). maxillary primary incisors. It is due to gastrointestinal Hypoplasia due to exanthematous disease: It include tract disturbances or metabolic disorders in the fetal life, measles, chickenpox and scarlet fever. There is temporary probably during 2nd and 3rd trimester of pregnancy. In elevation of body temperature. Temperature may remain neonatal type a wide band or line of enamel affects the elevated for prolonged period of time and under these circumstances, ameloblasts may be adversely affected. Hypoplasia due to congenital syphilis: It involves maxillary and mandibular permanent incisors and 1st molars. Incisors affected are called Hutchinson incisors and molar are called mulberry molar’s (Moon molar, Fournier’s  molar). Hutchinson’s incisors are upper central incisor is screw driver shaped. Mesial and distal surfaces of crown are tapering and converging towards incisal edge of the tooth, rather than towards cervix. In addition, incisal edge is also notched. The cause behind this is the absence of the central tubercle or calcification center. In mulberry molars crown of 1st molar in congenital syphilis is irregular. Enamel of the  A

B Figure 8.28 Hypoplasia occur due to nutritional deficiency

presented as horizontal pitting

Figures 8.29A and B Hypoplasia occur affecting the anterior

teeth

Teeth Anomalies

primary teeth of children associated with premature birth or low birth weight. In traumatic birth, it may affect the process of amelogenesis.

called mottled enamel. It is due to disturbance in tooth formation caused by excessive intake of fluoride, during the formative period of dentition.

Hypoplasia due to local infection or trauma: Most commonly affected teeth are permanent maxillary incisor or maxillary or mandibular premolar. Localized type of hypoplasia caused by local infection or trauma is called turner’s hypoplasia and that tooth is called as turner’s tooth. There may be any degree of hypoplasia, ranging from mild brownish discoloration of enamel to severe pitting and irregularity of the crown. If deciduous teeth become carious during the period when the crown of succeeding permanent tooth is formed, bacterial infection involving periapical tissues may occur and this may disturb the ameloblastic layer of permanent tooth bud, resulting in hypoplastic crown. When deciduous teeth have been driven into alveolus and have disturbed the permanent tooth bud and if this permanent tooth bud is still being formed, the resulting injury may be manifested as yellowish or brownish stains or pigmentation of enamel, usually on labial surface or as true hypoplastic pitting defect. Hypoplastic defect may contain cementum, which may be stained yellowish brown.

Pathogenesis

Hypoplasia associated with tetracycline ingestion: It may be incorporated in calcifying enamel matrix by formation of  a  tetracycline  calcium  orthophosphate  complex.  After  teeth eruption and exposure to sunlight, discoloration may result, ranging from light yellow to brown. Varying degree of hypocalcification may also exist. Tetracycline should not be administered during pregnancy and until the child become 8-year-old.

Formative stage: Disturbance of ameloblasts during the formative stage of tooth development and higher level of fluorides interfere with the calcification process of matrix. Matrix formation stage: There is diminished matrix production, change of matrix composition and change in ion transport mechanism. Maturation stage: In maturation phase, there is diminished withdrawal of protein and water.

Clinical Features Dental fluorosis in primary dentition is less severe as compared to permanent dentition. It frequently becomes stained as unsightly yellow to brown color, which is caused by coloring agents from food, medicine and by disintegration of the increase protein contain in the hypomineralized parts of the enamel. Sometimes, white patches in enamel may become striated, pitted and mottled. The range of severity and appearances changes: ∙ Questionable change: It is characterized by occasional white flecking or spotting of enamel. ∙ Mild changes: It is manifested by white opaque areas involving more of the tooth surface. ∙ Moderate and severe:  Changes  showing  pitting  and  brownish staining of the surface and sometimes even corroded appearance. Teeth which are moderately or severely affected may show tendency for wear or even fracture of enamel (Fig. 8.30).

Hypoplasia associated with chronic lead poisoning: It is more common in children with low economic status. Fetus of lead poisoned mother can be affected because lead readily crosses the placenta during pregnancy. Pitting type  Clinical Classification for Fluorosis (TF) of hypoplasia is more common in cases of lead poisoning. ∙ Score 0: The normal translucency of the glossy creamywhite enamel remains after wiping and drying of the Management surface. The hypoplastic teeth are more susceptible to dental caries ∙ Score 1: Thin white opaque lines are seen running than the normal teeth. The restoration is usually confined across the tooth surface. The lines correspond to the to area of involvement. Chrome steel crown is given in position of perikymata. In some cases snow-capping of case of severe hypoplasia. Eight percent stannous fluoride  cusps may also be seen. has been found to decrease the sensitivity of teeth which ∙ Score 2: The opaque whites flecks are more pronounced may be due to exposed dentin. and frequently merge to form small cloudy areas scattered over the whole surface. Mottled Enamel or Dental Fluorosis ∙ Score 3: Merging of the white lines occurs and cloudy Drinking  water  that  contains  in  excess  of  1  PPM  (part  areas of opacity occur to spread into many parts of the per million) fluoride can affect the ameloblasts during surface. In between the cloudy area, white lines can the tooth formation stage and can cause the clinical entity also be seen.

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placed on the affected teeth. The patient was instructed not to rinse or eat for 30 minutes. 114

Points to Remember Questionable changes, mild changes, moderate, severe changes, clinical classification for fluorosis, hypomineralized with an irregular prism pattern, bleaching with 30 percent H2O2, calcium sucrose phosphate gel.

Molar Incisor Hypomineralization

Figure 8.30 Hypoplasia occur due to fluoride toxicity showing

corroded appearance

∙ ∙ ∙ ∙ ∙ ∙

Score 4: The entire surface exhibits a marked opacity or appears chalky white. Score 5: The entire surface is opaque and there are round pits that are less than 2 mm in diameter. Score 6: The small pits may frequently be seem merging in the opaque enamel to form bands that are less than 2 mm in vertical height. Score 7: There is loss of the outermost enamel in irregular areas and less than half of surface is involved. Score 8: The loss of the outermost enamel involves more than half of the enamel. The remaining intact enamel is opaque. Score 9: The loss of the major part of outer enamel results in change of the anatomic shape of the surface. A cervical rim of opaque enamel is often noted. 

Histopathological Features Enamel  of  these  teeth  has  been  described  as  hypomineralized with an irregular prism pattern and with scalloped or  arcading  pattern  of  enamel.  DE  junction  is  more  pronounced than in normal teeth.

Management Bleaching with 30 percent H2O2 (hydrogen peroxide): This technique is enhanced by micro-abrasion or grinding of the surface layer. Calcium sucrose phosphate gel: Treatment involves cleaning the affected teeth with pumice and glycerin, rinsing with water and applying 37 percent phosphoric acid for 1 or 2 minutes. The treatment is repeated followed by application of 2 percent sodium fluoride for 4 minute. Finally, a thick layer of 40 percent calcium sucrose gel is

There is enamel defect of one ore more permanent molar and incisor. The enamel may be white, yellow, brown with sharp demarcation between defective and surrounding normal enamel. Enamel is soft and porous like discolored chalk or Old Dutch cheese (cheese molar). The enamel of affected molar is fragile, can chip easily. Enamel molar sensitive to cold, warm, mechanical trauma.

Amelogenesis Imperfecta It is also called hereditary enamel dysplasia, hereditary brown enamel and hereditary brown opalescent teeth. It represents group of hereditary defects of enamel associated with any other generalized defect. It is an ectodermal disease in which mesodermal component is normal. Classification Hypoplastic type: There is defective formation of enamel matrix. •  Autosomal dominant   –  Pitted    –  Local    –  Smooth    –  Rough  •  Autosomal recessive    –  Local    –  Enamel agenesis  •  X-linked dominant  Hypocalcification type: There is defective mineralization of formed matrix. •  Autosomal dominant  •  Autosomal recessive  Hypomaturation type: In this enamel crystal lattice remains immature. •  X-linked recessive  •  Autosomal recessive – pigmented  •  Snow-capped teeth autosomal dominant  Hypomaturation/hypoplastic with taurodontism.

Teeth Anomalies

Classification

vary from opaque white to translucent brown. Some of the enamel may be missing on newly erupted teeth, especially Classification  depends  upon  the  stage  of  at  which  the  on the incisal and occlusal surface and may be chalky disease occurs. This classification was given by Witkop. in interproximal areas. Delay in eruption occurs with According to this classification, there are mainly four  resorption of teeth in the alveolus. type of amelogenesis imperfecta exists. Rough: Both primary and secondary teeth are affected. Clinical Features Enamel  is  hard  with  rough  granular  surface  that  may  be  chipped from underlying dentine, rather than abrade away as Hypoplastic type (Fig. 8.31) It includes localized portions of enamel that do not reach seen with smooth type. Enamel is 1/4th to 1/8th in thickness.  Teeth are white to yellow-white when newly erupted. Teeth normal thickness during development. do not meet at contact points but retain normal tooth outline Autosomal dominant than the smooth type of imperfecta. May have thicker enamel Pitted: Both the dentitions are affected. It appears as at cervical areas. There is also anterior open bite present. thin enamel on teeth that do not contact with each other Autosomal recessive type mesiodistally. Pinpoint to pinhead pits randomly distributed  Teeth which are erupted have distinct yellow color like of over  the  surface.  Enamel  on  newly  erupted  teeth  is  hard  normal dentition. Surface is rough and granular, resembling with normal yellow white color. Staining of teeth occurs ground glass. after exposure to oral environment, giving teeth a black Enamel agenesis: Nearly complete lack of enamel appearance. formation. Teeth are widely spaced and do not meet each Local: Teeth in both the dentitions are affected. Horizontal other at contact point. Patient may have anterior open bite. rows of depressions or one large hypoplastic area with Numerous teeth are missing in the dentition and represent hypocalcification adjacent to and below the hypoplastic radiographically as unerupted teeth undergoing resorption. area is found. Defects are most prominent on buccal surfaces of the teeth, involving middle 3rd of enamel. Hypocalcified (Fig. 8.32) Incisal or occlusal surfaces of the teeth are usually not The enamel is so soft that it can be removed by a prophylaxis instrument. involved. Smooth:  Enamel  is  thin,  hard  and  glossy  with  smooth  Autosomal dominant surface. Enamel is 1/4th to 1/8th of its normal thickness.  Enamel is of normal thickness, although occasional areas  On newly erupted teeth they have yellow color, but may of hypoplasia are seen on middle 3rd of labial surface.

Figure 8.31 Amelogenesis imperfecta showing exposed

dentin and yellow enamel

Figure 8.32 Amelogenesis imperfecta (hypocalcification type)

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The enamel is so soft that it may be lost soon after eruption, leaving crown composed of only dentin. Enamel  has  cheesy consistency and can be scraped from dentin with an instrument or penetrated easily by dental explorer. Newly erupted teeth are covered with dull lusterless opaque, white, and honey colored or yellowish orange or brown enamel. Exposed dentin may be hypersensitive.  Anterior  open  bite may be present. Patients with this condition are prone  to form calculus rapidly. Hypomaturation type (Fig. 8.33) The enamel can be pierced by an explorer point under firm pressure and can be lost by chipping away from the underlying, normal appearing dentin. Autosomal dominant It is more commonly found in males both primary and permanent dentitions are affected permanent teeth are mottled yellow white in color, but gradually may be darkened  with  absorption  of  stains.  Primary  teeth  of  affected males have ground glass opaque white appearance. Patient  occasionally  shows  slight  yellow  cast  to  enamel  surface. Teeth meet at contact points and have normal contour. Enamel approaches normal thickness, but it may  be thinner. Point of explorer can be forced into enamel.  Autosomal recessive pigmented Both primary and permanent dentitions are affected. Enamel  has  milky to shiny, agar brown color on newly erupted teeth. It may become more deeply stained on contact with exogenous agents.

Teeth are of normal thickness and tend to chip away, especially  around  restoration.  Patient  tends  to  form  large  amount of calculus which may contain pigment forming agents. Teeth may be seen undergoing resorption within alveolus. Snow capped teeth Location: Maxillary teeth are affected more commonly than mandibular one. Both primary and secondary dentitions are affected. Appearance: In this condition varying amount of enamel on incisal or occlusal aspect of crown is present and has opaque white appearances. Opacity may be solid or flecked and may involve enamel surface. Junctional line of opaque white and translucent enamel is sharp. Pattern of defect on teeth anterior to the posterior teeth  resemble that which would be obtained when dipped into white paints. Hypomaturation type/hypoplastic with taurodontism/ amelogenesis imperfecta with taurodontism In this type there is enamel hypoplasia with hypomaturation is seen. Both deciduous and permanent dentition is involved. Hypomaturation-hypoplastic pattern: In this predominant  defect  is  hypomaturation.  Enamel  appears  as  yellow-white to yellow brown color. Radiologically enamel and dentin have same density. Hypoplastic-hypomaturation type:  Primary  defect  is  enamel hypoplasia with thin enamel. Amelogenesis imperfecta with taurodontism: In this taurodontism is associated with amelogenesis imperfecta. This is seen in Tricho-Dento-Osseous syndrome.

Histopathological Features Hypoplastic type: There are disturbances in differentiation or viability of ameloblasts in hypoplastic type. Hypocalcification type: In hypocalcification, there is defect in matrix structure and mineral deposition. Hypomaturation type: In hypomaturation type there is alteration in enamel rods and rod sheath structure.

Management Figure 8.33 Brownish discoloration of teeth in amelogenesis

imperfecta (hypomaturation type)

Cosmetic improvement should be done with the help of crown and veneer placement.

Teeth Anomalies

Points to Remember •  •  • 

Hypoplastic type:  Pitted,  local,  smooth,  rough,  enamel agenesis disturbances in differentiation or viability of ameloblasts. Hypocalcified:  Enamel  is  so  soft,  cheesy  consistency hypersensitive exposed dentin defect in matrix. Hypomaturation type:  Affected  permanent  teeth  are mottled yellow white in color, pigmented, snow capped teeth, dipped into white paints alteration in enamel rods.

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Dentinogenesis Imperfecta There are various names for dentinogenesis imperfecta like hereditary opalescent dentin and odontogenesis imperfecta or capdepont’s teeth. Affected  teeth  are  of  tulip shape (broad crown with constriction are the cervical area). Classification •  •  • 

Shield type I: Dentinogenesis imperfecta always occurs with osteogenesis imperfecta. Shield type II: It is also called hereditary opalescent dentin. It does not occur in association with osteogenesis imperfecta. Shield type III: It is also called ‘Brandywine type’.  It has got shell teeth appearances and multiple pulp exposure.

Clinical Features (Fig. 8.34) Shield type I: It segregates as an autosomal dominant trait with variable expressivity. Features of this condition are multiple bone fractures, hyperextensible joints, blue sclera and progressive deafness. Deciduous teeth are more severely affected than permanent teeth. Color of teeth may  vary from brownish violet to yellowish brown.  Amber  translucency of both primary and permanent dentition may be seen. Enamel may be lost and dentin undergoes  rapid  attrition.  Usual  scalloping  of  dentinoenamel  junction is absent. The teeth are shorter than normal often markedly, in respect to the roots and crowns. In the incisor region the crowns tend to more nearly square, but the mesial and distal borders are sometimes curve. The bicuspids and molars are flatter than normal and the normal circumferential curves are accentuated so that the teeth shows bulbous appearance. The neck of teeth

Figure 8.34 Bluish type of discoloration seen in case of

dentinogenesis imperfecta

suddenly narrows down. The appearance of crowns may be described as ‘dumpy’. Shield type II: It is inherited as an autosomal dominant trait. Both dentitions are affected. Other clinical features are same, except they are somewhat of severe form and it is not associated with osteogenesis imperfecta. Shield type III: It is also inherited as an autosomal dominant trait. Both the dentitions are affected. Opalescent color, bell shaped crown and multiple pulp exposure. It has got shell teeth appearance, i.e. normal thickness of enamel with thin dentin in association with enlarged pulp. Radiographic features: Teeth have bullous crown, cervical constriction, thin roots and early obliteration of root canals and pulp chambers.

Histopathology Features Enamel  is  normal  and  dentin  is  composed  of  irregular dentinal tubules, with large areas of uncalcified matrix. Cellular inclusions like odontoblasts are common with obliteration of pulp chamber. Odontoblasts degenerate rapidly, becoming entrapped in the matrix. Tubules are larger in diameter and less numerous than normal, in a given volume of dentin. Atypical odontoblast cells occur at the surface of pulp.

Management Cast metal crown in posteriors and jacket crown in anterior can be given.

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Points to Remember 118

Capdepont’s  teeth,  tulip  shape  teeth,  multiple  bone  fractures, hyperextensible joints, blue sclera, brownish violet to yellowish brown teeth, dumpy appearance of crowns, opalescent color, bell shaped crown shell teeth appearance, radiographically bullous crown, cervical constriction, thin roots, irregular dentinal tubules, with large areas of uncalcified matrix, cellular inclusions like odontoblasts, atypical odontoblast.

Dentin Dysplasia It is a rare disturbance of dentin formation, characterized by normal but atypical dentin formation, with abnormal pulp morphology. Hereditary and autosomal dominant trait can lead to dentin dysplasia. Classification According to shield (clinical): •  Shield type I—dentin dysplasia •  Shield type II—anomalous dysplasia.  According to witkop (radiological): •  Radicular dentin dysplasia  •  Coronal dentin dysplasia.

Clinical Features (Fig. 8.35) Shield type I: It is also called rootless teeth, non-opalescent and opalescent dentin and radicular dentin dysplasia. Permanent and primary teeth are of normal size, shape and  consistency. Affected teeth are occasionally slightly amber  and translucent. There is malalignment and malpositioning due to extreme mobility. Minor trauma may result in exfoliation. Shield type II: Significant differences in color in both the dentitions. Primary teeth with yellow, brown, bluish, grayamber translucent appearances. Permanent teeth of normal  color. Obliteration of pulp chamber does not occur before eruption.

Figure 8.35 Pulp is absent in case of dentin dysplasia

dentinal tubule formation appears to be blocked so that new dentin forms around obstacle and takes the characteristic appearance described as lava flowing around boulder. Electron studies (Sauk) shows this pattern results due from  repetitive attempts to form root structure. Shield type II: Deciduous teeth exhibit defective dentin and permanent teeth show relatively normal dentin. In radicular portion dentin is amorphous and atubular and in coronal portion dentin is relatively normal. In permanent teeth pulp contain multiple pulp stones or denticles.

Management Prosthetic replacement  should  be  done  for  esthetic  point  of view. Endodontic therapy: It is difficult in type I dentin dysplasia as there is no pulp canal is seen. In case of periapical radiolucency it can be treated with retrograde filling. Points to Remember Rootless teeth, malalignment, malpositioning, yellow brown, bluish, gray-amber primary teeth and normal color permanent teeth, no pulp, thistle tube shaped or flame shaped, lava flowing around boulder, dentin is amorphous atubular, multiple pulp stones or denticles.

Radiological features: There is no pulp or very little pulp is present in the deciduous teeth. There is also presence of periapical radiolucency without any cause. In case of dentin dysplasia type there is thistle tube shaped or flame shaped pulp is seen.

It is also called odontogenic dysplasia or ghost teeth. It is a localized arrest in tooth development.

Histopathological Features

Clinical Features

Regional Odontodysplasia

Shield type I: Coronal dentin is normal apically there are  Location: Deciduous and permanent teeth are involved. areas of tubular dentin which obliterates the pulp. Normal Maxillary arch involved more than mandibular. Most

Teeth Anomalies

frequently affected are permanent central incisor, lateral incisor and cuspid. Single tooth or several teeth in one quadrant are affected. 119

Appearance: Affected teeth are small and mottled brown  (Fig. 8.36). Shape is irregular with evidence of defective mineralization. Affected teeth are susceptible to caries, local infection and  prone to fracture. There is either delay or total failure of eruption. All the elements of  tooth are hypocalcified and  hypoplastic. Radiological features: There is thin enamel and dentin which surround the large radiolucent pulp. This will results in pale wispy image of tooth and, hence, it is called ghost teeth (Fig. 8.37).

Histopathological Features There is marked reduction in amount of dentin with widening of predentin layer. Large areas of interglobular dentin and irregular tubular pattern of dentin is also evident. Reduced enamel epithelium of unerupted teeth shows irregular calcified bodies which is called enameloid conglomerates. Scattered area of odontogenic epithelium with patterns of intramural calcification is present.

Management Extraction of teeth followed by prosthetic appliances should be done.

Figure 8.37 Ghost teeth appearance seen in regional

odontodysplasia

In some cases endodontic treatment on nonvital teeth yield good results. Points to Remember Odontogenic dysplasia, ghost teeth, small and mottled brown teeth, irregular shape, local infection, thin enamel and dentin, interglobular dentin, irregular tubular pattern of dentin, enameloid conglomerates, scattered area of odontogenic epithelium.

Fibrous Dysplasia of Dentin This is autosomal dominant disease in which teeth are normal clinically. Radiologically there are radiodense products occupying pulp chamber and canals. There is also presence of small foci of radiolucency in the pulp. There is no decrease in length of root in contrast to dentin dysplasia.

Dentin Hypocalcification

Figure 8.36 Mottled brown discoloration of tooth in regional

odontodysplasia

In this condition normal dentin is calcified by deposition of calcium salts in the organic matrix in the form of globules, which increases in size by further peripheral deposition of salts, until all the globules are finally united into a homogenous structure. Etiological factors responsible for are same as that of environmental hypocalcification of enamel. In dentinal hypocalcification, there is failure union of many of these globules, leaving interglobular areas of uncalcified matrix.

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There is no alteration in their clinical appearance. It is easily detected in both, ground section and decalcified histological matrix. 120

Points to Remember Deposition of calcium salts, interglobular area of uncalcified matrix.

ANOMALIES ASSOCIATED WITH ERUPTION OF THE TEETH (TABLE 8.4) Eruption of Teeth The axial or occlusal movement of tooth from its developmental position within the jaw to its functional position in the occlusal plane is known as eruption of teeth. There are three types of movements: 1. Pre-eruptive: When deciduous tooth germ first differentiates, there is good deal of space between them. But due to their rapid growth, this available space is utilized and developing teeth become crowded together, especially in incisor and canine region. This crowding is relieved by growth in length of infant jaws, which provides room for second deciduous molars to drift  backward  and  anterior  teeth  to  drift  forward.  At  the same time, the tooth germ also moves outward as jaw  increases  in  width  and  height.  Permanent  teeth  with deciduous predecessors also undergo complete movement before they reach the position from which they will erupt. As  their  deciduous  predecessors  erupt,  they  move  to a more apical position and occupy their own bony crypt.  Premolars  begin  their  development  lingual  to  their predecessors at the level of occlusal surface and in same bony crypt. They are situated beneath the Table 8.4 Eruption disturbances

Anomalies affecting eruption of teeth •  •  •  •  •  •  •  •  • 

Premature eruption/predecidious dentition  Delayed eruption  Embedded and impacted teeth  Ankylosis or submerged teeth  Transposition  Eruption sequestrum  Ectopic eruption  Premature exfoliation  Postpermanent dentition 

divergent roots of deciduous molars. The permanent molars which do not have predecessors also move from the site of their initial differentiation. 2. Eruptive: There is axial or occlusal movement of tooth from its developmental position within the jaw to its final functional position in the occlusal plane. It is important to recognize that jaw growth is normally occurring while most teeth are erupting, so that movement in plane other than axial is superimposed on eruptive movement. 3. Posteruptive: These movements are those that maintain the position of the erupted tooth while the jaw continued to grow and compensates for proximal and occlusal wear.

Theories of Tooth Eruption Bone Remodeling It is supposes that selective deposition and resorption of bone brings eruption. In experiments, where tooth germ is removed and the follicle is left in position the eruptive pathway still forms in bone. Thus this indicates the dental follicle and not bone as major determinant in tooth eruption.

Root Growth Root formation is also unlikely to be the cause of tooth eruption; as the onset of root formation is not synchronous with onset of axial tooth movement. It causes overall increase in length of tooth that must be accompanied by root growing in the bone of jaw by an increase in jaw length or by crown moving occlusally. But it is not accepted. For example, if erupting tooth is prevented from erupting by pinning it to the bone, root growth continues and is surrounded by resorption of bone at base of socket. Thus although it can produce force, root growth cannot be translated into eruptive tooth movement unless there is some structure at the base of tooth, capable of withstanding this force. But no such structure is exists. Advocates  of  the  root  growth  theory  postulated  the  existence of a ligament, the cushion–hammock ligament, straddling the base of the socket from one bony wall to the other like a sling. But the structure described as the cushionhammock ligament is the pulp delineating membrane that runs across the apex of the tooth and has no bony insertion. So it cannot act as a fixed base.

Vascular Pressure It states that there is a higher pressure system either within or around the base of tooth. It is known that teeth move in synchrony with arterial pulsation, so local

Teeth Anomalies

volume changes can produce limited tooth movement. Whether such pressure is prime for movement of teeth is debatable because surgical excision of the root and, therefore, the local vasculature does not prevent tooth eruption.

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Periodontal Ligament Traction There is good deal of evidence that eruptive force resides in the dental follicle-periodontal ligament complex. As long  as periodontal tissue is available tooth movement occurs. Tissue culture experiments have shown that ligament fibroblast is able to contract a collagen-gel which in turn brings about movement of a disk of root tissue attached to that gel. Thus there is no doubt that periodontal ligament fibroblasts have the ability to contract and transmit a contractile force to the extracellular environment and in particular to the collagen fiber bundles in vitro. The entire morphological features exist in vivo to permit similar movement. In summary, eruptive movement is brought about by a combination of events involving a force initiated by the fibroblasts. This force is transmitted to the extracellular compartment via fibronexuses and to collagen fiber bundles; which aligned in an appropriate inclination brought about by root formation, bring about tooth movement. These fiber bundles must have the ability to remodel for eruption to continue and interference with this ability affects the eruptive process. The removal of bone to create the eruptive pathway is also dictated by the tissue surrounding the tooth.

Predeciduous Dentition It is also called congenital teeth, fetal deciduous teeth, dentition proceox and natal and neonatal teeth. The teeth erupted in the oral cavity at the time of birth are called natal teeth and those teeth erupting prematurely in 1st 30 days of life are called neonatal teeth (Fig. 8.38).

Etiology There is familial pattern is seen. Secretion of several endocrine organs like thyroid, adrenals and gonads may alter the eruption rate of teeth. Endocrinal disturbances and adrenogenital syndrome can also cause premature eruption. Eruption  accelerated  by  febrile incident or hormonal stimulation.

Figure 8.38 Neonatal teeth in lowers anterior

Classification •  Mature: They are fully developed in shape and comparable in morphology to the primary teeth. Prognosis is relatively good.  •  Immature: Their structure and development is incomplete. Poor prognosis of teeth. 

Clinical Features Location:  Usually  only  one  or  two  teeth  erupt  early  and  most often deciduous and mandibular central incisors. Appearance: They are often well-formed and normal in all aspects, except they may be mobile. Natal teeth: There is premature eruption of teeth or teeth like structures that are present at birth. They are hyper mobile because of their limited root development. Within relatively short time, premature erupted tooth will become stabilized and other teeth of the arch are erupted. Teeth may be conical or may be normal in size and shape and opaque yellow-brownish in color. Teeth appear to be attached to a small mass of soft tissue. Some teeth are so much mobile that there is danger of displacement and possible aspiration and in this case, removal is indicated. Sharp incisal edges of tooth may cause laceration of lingual surface of tongue or may interfere with nursing. It may associate with syndromes like Ellis-Van Creveld syndrome and cleft palate. Neonatal teeth: They are teeth or teeth like structures that erupt prematurely during neonatal period, from birth to 30 days.

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Riga Fede disease: It is a complication from natal and neonatal teeth. There is ulceration of the ventral surface of the tongue caused by the sharp incisal edges. It leads to interference with proper suckling and feeding and thus the neonate is at risk of nutritional deficiency.

Histopathological Features Most of the crowns of natal and neonatal teeth are covered with hypoplastic enamel with varying degrees of severity. Absence of root formation, ample vascularized pulp, irregular dentin formation and lack of cementum formation are characteristic features.

Embedded and Impacted Teeth Embedded teeth are those which are unerupted, usually because of lack of eruptive force. Impacted teeth are those prevented from erupting by some physical barrier in eruption path.

Etiology

Lack of space due to crowding of dental arch and premature loss of deciduous teeth with subsequent partial closure of the spaces they occupied. Rotation of tooth bud results in teeth which are aimed at wrong direction because their axis is not parallel to normal Management eruption path. Extraction of the teeth can be done if it is causing Some systemic disease like osteopetrosis, ectodermal inconvenience during suckling, interference with breast dysplasia, cleidocranial dysostosis, rickets and cretinism feeding and causing traumatic injury. Extraction should be  can be associated with impactions. done after 10 days of life. The other option that may be used is rounding of the Clinical Features sharp angle of incisal edges of teeth. If not necessary, tooth Location: Most commonly affected teeth are maxillary and should not be removed. mandibular third molars and maxillary cuspids, followed Points to Remember Congenital teeth, dentition proceox, hyper mobile teeth,  teeth  may  be  conical,  possible  aspiration,  Ellis-Van  Creveld  syndrome,  Riga  Fede  disease,  ulceration  of  the ventral surface of the tongue, hypoplastic enamel, absence of root formation, irregular dentin formation.

Delayed Eruption Etiology Systemic disease like rickets, cretinism and cleidocranial dysplasia and local factors like fibromatosis gingiva in which dense connective tissue does not permit the eruption of teeth.

Clinical Features Individual permanent teeth are observed to be delayed in eruption. There may be partially impacted permanent teeth. There is deviation in the eruption path of teeth. Patients may suffer from pseudoanodontia.

Management Extract the primary teeth and use space maintainers until  the permanent tooth erupts.

by the premolars and supernumerary teeth. Teeth may be impacted distally, mesially, horizontally, etc. (Figs 8.39 and 8.40). Dentigerous cyst may be associated with impacted teeth and may cause displacement and destruction of bone. Periodontal pocket formation and subsequent infections may occur. Because of location, impacted tooth may cause resorption of roots of adjacent teeth. There may be periodic pain and trismus when infection occurs around the partially impacted teeth. Referred pain from impacted teeth is also been described.

Management It depends upon the tooth involved. In some cases, like in maxillary cuspids, orthodontic treatment with surgical exposure can be done to bring the tooth in normal occlusion. Surgical removal can be done. Points to Remember Commonly affected maxillary mandibular third molars,  dentigerous cyst, periodontal pocket formation, resorption of roots of adjacent teeth, referred pain.

Teeth Anomalies

abnormal pressure from the tongue can lead to ankylosis of tooth. Absence of periodontal ligament may also lead to ankylosis of teeth. It occurs when partial root resorption is followed by repair; with either cementum or bone that unite the tooth root with alveolar bone. Ankylosis does occur after traumatic injury particularly occlusal trauma. It may follow root canal therapy, if the apical periodontal ligament is irritated or seriously damaged.

Clinical Features Figure 8.39 Inverted impacted canine

Figure 8.40 Mesioangular impacted of mandibular right and

left third molar (Courtesy: Dr Parate)

Ankylosis or Submerged Teeth Submerged teeth are deciduous teeth that have undergone variable degree of root resorption and then have become ankylosed to bone.

Location: Most commonly affected are mandibular deciduous second molars, followed by anterior teeth. Exfoliation and subsequent replacement by permanent  teeth  is  prevented  due  to  ankylosis.  Patient  who  has  one  or two ankylosed teeth is more likely to have other teeth ankylosed. Gradual loss of occlusal plane as the tooth is submerged below the level of occlusion. Teeth affected lack mobility even after root resorption. On percussion it produces characteristic solid muffled sound in contrast to dull, cushioned sound of normal teeth on percussion. There may be development of malocclusion, local periodontal disturbances and dental caries occurs. There is considerable difficulty while doing extraction of the teeth, sometimes necessitating surgical removal. Radiological features: There is absence of periodontal ligament space (Fig. 8.41).

Histopathological Features There is an area of root resorption which has been repaired by a calcified material, bone or cementum which is continuous with the alveolar bone. The periodontal ligament is completely obliterated in the area of ankylosis.

Management

Ankylosis of the teeth should be considered as interruption in  rhythm  of  eruption.  Unerupted  permanent  teeth  may  Keep tooth under observation. If required, surgical excision  is carried out. become ankylosed by enostosis of enamel. Many terms like infraocclusion, secondary retention, Points to Remember reimpaction and reinclusion are also used for this. Disturbance in local metabolism, absence of periodontal Etiology ligament, gradual loss of occlusal plane, solid muffled sound, malocclusion, local periodontal disturbances, There is disturbance in local metabolism, injury, chemical calcified material, bone or cementum. and thermal irritation, local failure of bone growth and

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Management These teeth can be prosthetically altered to improve function and esthetics.

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Eruption Sequestrum Etiology As  the  molar  teeth  erupt  through  bone,  they  will  occasionally separate small osseous fragments of bone like corkscrew. If bony spicule is large or eruption is fast, complete resorption cannot occur.

Clinical Features Figure 8.41 Ankylosis showing absence of periodontal

ligament space

Appearance: It is a tiny irregular spicule of nonviable bone overlying the crown of an erupting permanent molar. Spicule directly overlies the central occlusal fossa, but is contained within the soft tissues. Sign:  As  the  tooth  continues  to  erupt,  the  cusps  emerge  and the fragments of bone completely sequestrate through mucosa and are lost. Symptoms:  Child  may  complain  of  slight  soreness  produced by compression of soft tissues over the spicule, by the movement of the spicule in the soft tissue crypt during mastication and following eruption through mucosa. For few days, fragment of bone may be seen lying on crest of ridge in a tiny depression which can be easily removed.

Management Removal of spicule should be done, if it is needed. Points to Remember Figure 8.42 Transposition of canine with premolar

Transposition Tooth may be found occupying an unusual position in relation to other teeth, in the dental arch, i.e. two teeth apparently exchanging their position.

Clinical Features (Fig. 8.42) Teeth often exchange their positions. Permanent canine is most often involved, with its position interchanged with lateral incisor. Second premolar is infrequently found between first and second molar. Transposition of central and lateral incisor is rare. Transposition does not occur in primary dentition.

Separate small osseous fragments of bone like corkscrew, spicule of nonviable bone, fragments of bone sequestrate, slight soreness.

Ectopic Eruption If the tooth is larger than the normal mean size of all maxillary primary and permanent teeth and smaller maxilla or posterior positioning of maxilla in relation to the cranial base can lead to ectopic eruption. Some local factors like abnormal angulation and delayed calcification also lead to ectopic eruption.

Clinical Features It  occurs  most  frequently  in  boys  than  girls.  Eruption  of  permanent 1st molar into roots of primary 2nd molar may

Teeth Anomalies

cause destruction of distal root of maxillary 2nd molar. It may become hopelessly locked and produce premature exfoliation.

Management You should looped brass wires in contact area.

Premature Exfoliation It is seen in Papillon lefevre syndrome, familial juvenile periodontitis, familial fibrous dysplasia, hypophosphatasia, cyclic neutropenia, histiocytosis and acrodynia. There is widespread loss of supporting alveolar bone. There is also loosening, migration of the teeth. In some cases there is also spontaneous loss of teeth. There is no treatment, except to correct the etiological factors.

Postpermanent Dentition Person who have all the permanent teeth extracted and yet  have subsequently erupted teeth, particularly after insertion of complete denture come in this category. They possibly develop from bud of dental lamina beyond the permanent tooth germs.

BIBLIOGRAPHY 1.  Ansari  G,  Reid  JS.  Dentinal  dysplasia  type  I:  review  of  the  literature  and  report  of  a  family.  ASDC  J  Dent  Child.  1997;64:429-34.

2.  Antunes  NL,  Gorlick  R,  Callaja  E,  Lis  E.  Numb  chin  syndrome  in  Ewing  sarcoma.  J  Pediatr  Hematol  Oncol.  2000;22:521-3. 3.  August M, Magennis P, Dewitt D. Osteogenic sarcoma of  the jaws: factors influencing prognosis. Int J Oral Maxillofac Surg. 1997;26:198-204. 4.  Ayers KM, Colquhoun AN. Leukaemia in children. Part I:  Orofacial complications and side-effects of treatment. N Z Dent J. 2000;96:60-5. 5.  Bartlett  DW,  Evans  DF,  Smith  BG.  The  relationship  between gastroesophageal reflux disease and dental erosion. J Oral Rehabil. 1996;23:289-97. 6.  Bennett JH, Thomas G, Evans AW, Speight PM. Osteosarcoma  of the jaws: a 30-year retrospective review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90:323-32. 7.  Brenneise CV, Conway KR. Dentin dysplasia, type II: report  of 2 new families and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87:752-5. 8.  Cunha  RF,  Boer  FA,  Torriani  DD,  Frossard  WT.  Natal  and  neonatal  teeth:  review  of  the  literature.  Pediatr  Dent.  2001;23:158-62. 9.  de  Alava  E,  Pardo  J.  Ewing  tumor:  tumor  biology  and  clinical applications. Int J Surg Pathol. 2001;9:7-17. 10.  Gorsky  M,  Epstein  JB.  Craniofacial  osseous  and  chondromatous sarcomas in British Columbia—a review of  34 cases. Oral Oncol. 2000;36:27-31. 11.  Kelleher M, Bishop K. The etiology and clinical appearance  of tooth wear. Eur J Prosthodont Restor Dent. 1997;5:157-60. 12.  Kowalski  LP,  Bagietto  R,  Lara  JR,  et  al.  Prognostic  significance of the distribution of neck node metastasis from oral carcinoma. Head Neck. 2000;22:207-14. 13.  Kurisu K, Tabata MJ. Human genes for dental anomalies.  Oral Dis. 1997;3:223-8.

MULTIPLE CHOICE QUESTIONS 4. Dilacerations most commonly found in: a. Mandibular incisiors b. Mandibular canine c. Maxillary incisiors d. Maxillary canine

1. In microdontia, most commonly affected teeth are: a. Mandibular central incisior b. Maxillary lateral incisior c. Mandibular first molar d. Mandibular lateral incisior    

2. ‘Syndontia’ refers to:   a.  Fusion     c.  Twining  

     

3. Talon’s cusp is associated with:   a.  Down’s syndrome    b.  Hunter’s syndrome    c.  Eagle’s syndrome  d. Rubinstein-Taybi syndrome

b.  d. 

Gemination  Concrescence

   

5. Taurodontism is associated with:   a.  Klinefelter’s syndrome  b. Rubinstein-Taybi syndrome   c.  Down’s syndrome    d.  Turner’s syndrome

 

6. Mulberry molar commonly involves: a. First molars b. Second molars   c.  Canines   d.  First premolars

 

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7. Screwdriver shape, typical notching is the feature of: a. Mulberry molar   b.  Hutchinson’s molar  c. Dens evaginatus   d.  Fournier’s molar

   

8. Tooth located between central incisors of maxilla is called:   a.  Paramolar   b.  Distomolar    c.  Mesiodens  d.  Peridens

 

126

     

9. Multiple unerupted supernumerary teeth seen in:   a.  Eagle’s syndrome  b. First arch syndrome   c.  Gorham’s syndrome    d.  Gardner’s syndrome

10. Drinking water that contains in excess of 1 PPM fluoride results in:     a.  Enamel dysplasia  b. Dentin dysplasia c. Dental fluorosis d. Dentin hypocalcification 11. Which one of the following is also refers as “stress lesion”:     a.  Attrition   b.  Abfraction      c.  Abrasion  d.  Erosion 12. ‘Exostosis of roots’ refers to: a. Hypercementosis b.     c.  Cementicles   d. 

Internal resorption Dentinal sclerosis

Craniofacial Anomalies

Anil Govindrao Ghom , Shubhangi Mhaske (Jedhe) A

Chapter Outline 3 Agnathia 3 Agenesis 3 Micrognathia 3 Macrognathia

3 3 3 3 3 3

Facial hemihypertrophy Facial hemiatrophy Segmental odontomaxillary dysplasia Cleidocranial dysplasia Craniofacial dysostosis Mandibulofacial dysostosis

Congenital : Present at or before birth but not necessarily inherited, i . e. transmitted through the genes . Hereditary: They are apparent at birth but some may not become evident for years . The cell consists of cytoplasm and nucleus. Nucleus of each somatic cell contains 23 pairs of chromosome out of which one is the pair of sex chromosome; rest 22 pairs of chromosomes are called as autosomes . Chromosome is a nuclear structure composed of DNA, which contains units of hereditary gene. Gene is a portion of DNA coded for the synthesis of specific protein or polypeptide chain. Gene is determinants of hereditary characteristics . Locus is the site occupied by the gene on chromosome . An allele is number of alternative form that gene may take.

3 3 3 3 3 3 3 3 3 3

Focal osteoporosis bone marrow defect Chondroectodermal dysplasia Arhinencephaly Apert's syndrome Stafne defect Labial and oral melanotic macule Fordyce granule Leukoedema Caliber persistent artery Lateral soft tissue fistulas

If both the allele at a given locus are identical to pair, it is called as homozygous and if the allele are different it is called as heterozygous . A gene showing trait in heterozygous is considered as dominant . Genes are transmitted from one generation to other in a generally predictive way .

Autosomal dominant inheritance: Every affected person has at least one affected parent . Males and females are both affected likely . There is no skipping of generation. Affected person typically transmit trait to their offsprings. Autosomal recessive inheritance: Appear only in the siblings . One-fourth siblings are affected . Males and females are equally likely to be affected .

X -linked dominant : Since females have twice as many X-chromosomes, they exhibit a higher frequency of trait .

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Affected female will transmit the gene to one-half of her offsprings. 128

X-linked recessive: Incidence of the trait is much higher in males than in females. Affected man can transmit it to his daughters who are carriers. Trait cannot be transmitted from father to son.

DEVELOPMENTAL ANOMALIES OF JAWS Agnathia It is also called hypognathous. It is a extremely rare congenital defect characterized by absence of maxilla or mandible. If mandible is absent, the upper part of the face may be normal and the skin of the lower part will be continuous with the suprasternal integument. The hyoid bone is sometimes absent, despite the presence of a rudimentary tongue. In the place of buccal orifice, there may be a vertical slit. In case of unilateral absence of mandibular ramus, it is not unusual for ear to be deformed or absent. There may be absence of ears, absent or hypoplastic tongue, cleft palate, dysplastic ears, hypertelorism, microstomia, narrow auditory canal with palpebral fissures slanting down.

Agenesis The failure of development of some part of mandible or maxilla is termed as agenesis. Mandible is most commonly affected than maxilla the condyle, entire mandible on one side and ramus reveal the abnormality. In maxilla, one maxillary process or even premaxilla are usually imperfect. The most common developmental defect in mandible is the absence of condyle, in which there is no articular fossa and the eminentia articularis is either absent or rudimentary. Majority of the patients have their chin deviating towards the affected side. The ramus is small and usually coronoid process is absent, with the result that the anteroposterior diameter of ramus is reduced.

Micrognathia It means small jaws as compared to normal size. In this case either maxilla or mandible may be affected. There are two types of micrognathia.

Types • Apparent micrognathia: This is not due to abnormality of small jaw, in terms of size but rather to an abnormal positioning or abnormal relation of one jaw to another, which produces illusion of micrognathia. • True micrognathia: It is due to small jaw. It is again classified as: – Congenital: It is present since birth – Acquired: It is acquired later in the life.

Etiology Congenital: In congenital type, etiology is usually unknown. In many instances it is associated with other congenital abnormalities, particularly congenital heart disease and Pierre robin syndrome (cleft palate, micrognathia, glossoptosis). Acquired: Acquired type is postnatal type and result from disturbances in the area of TM joint (ankylosis). Mouth breathing can be a predisposing factor for maxillary micrognathia. Agenesis of condyle also results in true mandibular micrognathia which may occur due to ankylosis of TMJ. Posterior positioning of mandible with regard to skull or to a steep mandibular angle result in an apparent retrusion of the jaw.

Clinical Features Micrognathia of maxilla is due to deficiency of premaxillary area and patient with this deformity appears to have the middle third of face retracted. True mandibular micrognathia is uncommon and patient appears clinically to have severe retrusion of chin, steep mandibular angle and deficient chin button. Micrognathia is one cause of abnormal alignment of teeth. This can be seen by observing the occlusion of teeth. Often, there will not be enough room for the teeth to grow. If the upper jaw is short, then, occlusion may also be abnormal. In true micrognathia, the jaw is small enough to interfere with feeding of the infant and may require special nipples in order to feed adequately. There may be difficulty in respiration. Due to the small size of the arch, the jaw is not able to accommodate the tongue, which is forced back into the oropharynx, blocking the air passage. Syndromes associated with micrognathia: Pierre Robin syndrome, Hallerman-Streiff syndrome, trisomy 13, trisomy

Craniofacial Anomalies

18, Turner’s syndrome, Treacher-Collins syndrome and Marfan’s syndrome.

Management

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Surgery or orthodontic appliances may be recommended. If upper jaw is short, then it can be corrected with surgical orthodontic treatment by properly aligning the teeth and then moving surgically and elongating the short maxilla, in order for three to four millimeters of the upper central incisors to show when an individual is smiling.

Macrognathia It refers to the condition in which jaw size is larger than the normal. It is also called as megagnathia. Figure 9.1 Macrognathia

Etiology It is cause by Pituitary gigantism, Paget’s disease of bone, acromegaly and in some form of fibrous dysplasia.

Clinical Features Mandibular protrusion or proganthism is common occurrence, which is due to disparity in the size of maxilla to mandible and posterior positioning of maxilla in relation to the cranium. Mandible is larger than normal which results in increased mandibular body length (Fig. 9.1). Points to Remember Deficiency of premaxillary area, steep mandibular angle, deficient chin button, abnormal alignment of teeth, blocking the air passage, Pierre Robin syndrome, Hallerman-Streiff syndrome, surgery or orthodontic appliances. Gummy smile: In certain patients with congenital abnormalities, there may be elongation of maxilla. There is much “show” when the patient smiles, so that there is a so-called “gummy” smile. This is due to the upper jaw being too long. Size of ramus is large, which forms less steep angle with body of mandible. There is excessive condylar growth and anterior positioning of the glenoid fossa, which may also result in mandibular prognathism. There is prominent chin button.

Management Resection of portion of mandible should be done to decrease the length, followed by orthodontic treatment.

Points to Remember Megagnathia, mandibular protrusion, size of ramus is large, gummy smile, resection of portion of mandible.

Facial Hemihypertrophy It is also called as Friedreich’s disease, hemihyperplasia. It may involve entire half of the body, one or both limbs, face, head and associated structures.

Etiology Hormonal imbalance, incomplete twinning, chromosomal abnormalities, localized alteration of intrauterine development, lymphatic abnormalities, vascular abnormalities and neurogenic abnormalities can leads to facial hemihypertrophy. Types • Complex hemihyperplasia: One entire side of body is enlarged • Simple hemihyperplasia: Enlargement is limited to single limb • Hemifacial hyperplasia: It is confined to one side of face.

Clinical Features Age and sex distribution: Females are affected more than males. It has vague onset, usually in childhood, adolescence or early adult life.

Textbook of Oral Pathology Buccal mucosa frequently appears velvety and may hang in soft pendulous folds on affected side.

Histopathological Features

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Epithelium is increase in size. Connective tissue also show hyperplasia.

Management After patient growth is ceased, cosmetic repair by soft tissue debulking, face lifts can be performed. Points to Remember

Figure 9.2 Facial hemihypertrophy showing enlargement of

one side of face

Location: It may occur alone or in generalized hemihypertrophy. It involves the eyelids, cheeks, lips, facial bones, tongue, ears and tonsils (Fig 9.2). Symptoms: Occasionally, poorly localized, vague, painful sensation in muscles affected. Enlargement of one half of the head present since birth. Enlarged side grows at a rate proportional to uninvolved side. It is associated with other abnormalities like mental deficiency, skin abnormalities and compensatory scoliosis. Hemifacial hypertrophy may be accompanied by hemimegalencephaly, which is characterized by hypertrophy of one cerebral hemisphere with ipsilateral ventricular dilatation. Pigmentation and hemangioma may occur on skin. There is progressive asymmetry due to enlargement of soft tissues, including the lips, ear and tongue. Syndrome associated: Syndromes associated with facial hemihypertrophy are Proteus syndrome, Maffucci’s syndrome, Ollier syndrome and Klippel-Trenaunay-Weber syndrome.

Oral Manifestations Size of crown, root may enlarge. Rate of development of permanent teeth on the affected side is more rapid and erupt before their counterparts on the uninvolved side. Primary teeth shed early. Bone of maxilla or mandible is also enlarged. Unilateral macroglossia of tongue: Tongue is commonly involved and bizarre patterns of enlargement of papilla, in addition to unilateral enlargement of tongue.

Friedreich’s sensation in hemangioma, epithelium is lifts.

disease, poorly localized, vague, painful muscles, mental deficiency, pigmentation, Proteus syndrome, macroglossia of tongue, increase in size, soft tissue debulking, face

Facial Hemiatrophy It is also called as Parry-Romberg syndrome, Romberg hemifacial atrophy, hemifacial microstomia and progressive facial hemiatrophy. Parry-Romberg syndrome is a rare disorder characterized by slowly progressive wasting (atrophy) of the soft tissues of half of the face (hemifacial atrophy).

Etiology Atrophic malfunction of cervical sympathetic nervous system, trauma, infection, peripheral trigeminal neuralgia, localized scleroderma and hereditary factors also cause Parry-Romberg syndrome. Recently, it has been observed Borrelia species. Infection (lyme disease) can also cause facial hemiatrophy. In most cases, Parry-Romberg syndrome appears to occur randomly for unknown reasons (sporadically).

Clinical Features Onset: Onset noted in 1st or 2nd decades of life as a white line furrow or mark on one side of face or eyebrow near midline. In rare cases, the disorder is apparent at birth. Location: In most cases, progressive tissue wasting is limited to one-half of the face, usually the left side. Progress: In most affected individuals, hemifacial atrophy typically progresses over approximately three to five years and then ceases. Affected areas may demonstrate shrinkage and atrophy of tissues beneath the skin (subcutaneous

Craniofacial Anomalies

tissue), in the layer of fat under the skin (subcutaneous fat) and in underlying cartilage, muscle and bone. en coup de sabre (strike of sword): Sharp line of demarcation resembling a scar between normal and abnormal near midline of forehead known as linear scleroderma. Skin: In addition, the skin overlying the affected areas may become darkly pigmented (hyperpigmentation) with, in some cases, certain areas of white (depigmented) patches (vitiligo).There may be hollowing of cheek and eyes may appear depressed in the orbits. Neurological manifestation: This may include severe headache that lasts for extended periods of time and may be accompanied by visual abnormalities, nausea and vomiting (migraine). There is also facial pain due to trigeminal neuralgia. There are periods of uncontrolled electrical disturbances in brain (seizures) that usually are characterized by rapid spasms of a muscle group that spread to adjacent muscles (contralateral Jacksonian epilepsy). Hair: There is graying (blanching) of hair as well as abnormal bald patches on the scalp with loss of eyelashes and the middle (median) portion of eyebrows (alopecia). Base of skull: There is underdevelopment of the base of skull in some cases whose face is affected. Malar bones: When the malar bone is small, the side of the face is flat but an absent malar bone produces a depression inferior to the orbit. Face: The soft tissue of face are small and thinner than normal. Ear: Aplasia or hypoplasia of external ear. The ear canal is missing.

Oral Manifestations Lip and tongue: Many individuals also experience atrophy of half of the upper lip and tongue. Teeth: Delayed eruption or wasting of the roots of certain teeth on the affected side. Jaws: In individuals with the disorder, initial facial changes usually involve the tissues above the upper jaw (maxilla) or between the nose and the upper corner of the lip (nasolabial fold) and progress to involve the angle of mouth, the areas around the eye, brow, ear and/or the neck.

Malocclusion: There is reduced growth of jaws and eruption of teeth is retarded. There is also malocclusion on the affected side.

Histopathological Features There is atrophy of epidermis with perivascular infiltrate of lymphocytes and monocytes. Degenerative changes in vascular endothelium.

Management Orthodontic treatment, plastic surgery and hearing aids are recommended. Points to Remember Parry-Romberg syndrome, lyme disease, tissue wasting one-half of the face, shrinkage and atrophy of tissues beneath the skin, en coup de sabre (strike of sword), hyperpigmentation, vitiligo, seizures, contralateral Jacksonian epilepsy, loss of eyelashes, soft tissue of face are small, aplasia or hypoplasia of external ear, atrophy of half of the upper lip, delayed eruption, malocclusion, atrophy of epidermis with perivascular infiltrate of lymphocytes.

Segmental Odontomaxillary Dysplasia It is also called hemimaxillofacial dysplasia. It can be confused with craniofacial fibrous dysplasia or hemifacial hyperplasia.

Clinical and Radiological Features It is discovered in childhood. Sign: There is painless unilateral enlargement of the maxillary bone. There may be fibrous hyperplasia of overlying gingival soft tissue. Primary teeth in the affected area may be hypoplastic showing enamel defect. Radiographic features: There is vertically oriented thickened trabecular which results in granular appearance. The maxillary sinus is smaller on affected side.

Histopathological Features Gingival soft tissue may show fibrosis. Affected bone consists of irregular trabeculae with woven appearance. There are also presences of resting and reversal lines.

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Management 132

Orthodontic therapy and orthognathic surgery can be performed in this case. Points to Remember Hemimaxillofacial dysplasia, fibrous hyperplasia, hypoplastic primary teeth, vertically oriented thickened trabecular, irregular trabeculae with woven appearance.

Cleidocranial Dysplasia It is also called as cleidocranial dysostosis, Marie and sainton disease, craniocleido-dysostosis. Hereditary and when inherited, it appear as a true dominant Mendelian characteristic incomplete penetration of genetic trait.

Lacrimal and zygomatic bone are also underdeveloped. Sagittal suture is characteristically sunken, giving skull a flat appearance.

Oral Manifestations Maxilla and paranasal sinus are underdeveloped, resulting in maxillary micrognathia. Maxilla is underdeveloped and smaller than normal, in relation to mandible. Unerupted teeth: Prolonged retention of primary dentition and delayed eruption of permanent dentition. Numerous unerupted teeth are found which are most prevalent in the mandibular premolar and incisor area (Figs 9.4 and 9.5).

Clinical Features The disease affects men and women with equal frequency. Location: It primarily affects skull, clavicle and dentition. There may be complete absence of clavicle and patients have unusual mobility. They are being able to bring their shoulders forward until they meet in midline (Fig. 9.3). The head is brachycephalic (reduced anterior-posterior dimension but increased skull width) or wide and short. Nasal bridge is depressed with a broad base. In skull the fontanels often remain open or at least exhibit delayed closing and for this reason, tend to be rather large. Open skull suture and multiple wormian bones are present and there is occasional stunting of long bone.

Figure 9.4 Patient showing unerupted teeth

Figure 9.3 Patient showing unusual mobility of shoulder in

Figure 9.5 Over retained deciduous teeth in cleidocranial

cleidocranial dysplasia

dysplasia

Craniofacial Anomalies

There is paucity and complete absence of cementum, crowding and disorganization of developing permanent dentin and presence of supernumerary teeth usually in anterior region. High and narrow arched palate and cleft palate may be common. Roots of teeth are often some what short and thinner than the normal. Maxilla is small and mandible is usually normal in size, which gives the appearance of prognathism. The crown may be pitted as a result of enamel hypoplasia.

Radiological Features PA chest view will show absence of clavicle (Fig. 9.6). Radiograph shows suture and fontanels having delayed closure or sometime they remain open throughout the life. Wormian bone can also be seen (Fig. 9.7).

Mandible show coarse trabeculation with areas of increased density.

Histopathological Features Microscopic study of unerupted teeth shows that is lack secondary cementum. Some author stated that insufficient alveolar bone resorption also lead to impaired tooth eruption.

Management Full mouth extraction with denture construction, autotransplantation of selected impacted teeth followed by prosthetic restoration should be done. Points to Remember Marie and sainton disease, absence of clavicle, brachycephalic, nasal bridge is depressed, flat appearance of skull, maxillary micrognathia, unerupted teeth, paucity and complete absence of cementum, high narrow arched palate, enamel hypoplasia, mandible show coarse trabeculation, and lack secondary cementum.

Craniofacial Dysostosis It is also called as Crouzon’s disease or syndrome. In some instances, Crouzon syndrome is inherited as an autosomal dominant trait. In other cases, affected individuals have no family history of disease. The disorder is characterized by distinctive malformations of the skull and facial (craniofacial) region. Figure 9.6 Cleidocranial dysplasia showing clavicle

deficiency appreciated in radiograph

Figure 9.7 Open sutures of skull in cleidocranial dysplasia

Clinical Features Age: Crouzon’s syndrome is a rare genetic disorder that may be evident at birth (congenital) or during infancy. In most infants with Crouzon syndrome, the fibrous joints between certain bones of the skull (cranial sutures) close prematurely (craniosynostosis). The premature closing results in brachycephaly (short head), scaphocephaly (boat shaped head) and trigonocephaly (triangle shaped head). In addition, facial abnormalities typically include unusual bulging or protrusion of the eyeballs (proptosis) due to shallow eye cavities. Outward deviation of one of the eyes (divergent strabismus or exotropia); widely spaced eyes (ocular hypertelorism). Exophthalmos (protrusion of eyes) with divergent strabismus and optic neuritis and choked disks, resulting frequently in blindness are also present. Bulging of frontal bone in midline, over the nose and downward sloping of back of head (Fig. 9.8).

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Unilateral or bilateral cross-bite is evident with open bite and crowding in mandibular teeth. Shovel shaped maxillary incisors, cleft lip and palate are also evident. The antrum is small and underdeveloped. The mandible is large as compared to maxilla, so there is prognathism.

134

Management Maxillofacial surgery for correction of facial deformities should be done. Points to Remember

Figure 9.8 Patient is having Crouzon’s syndrome. Note

parrot beak and bulging of frontal bone in midline

Craniosynostosis, brachycephaly (short head), scaphocephaly (boat shaped head) and trigono cephaly (triangle shaped head), proptosis, divergent strabismus or exotropia, ocular hypertelorism, protrusion of eyes, bulging of frontal bone in midline, triangular frontal defect, maxillary hypoplasia, parrot beak, highly arch palate, unilateral or bilateral cross-bite, shovel shaped maxillary incisors cleft lip.

Mandibulofacial Dysostosis It is also called Treacher Collin syndrome and ‘Franceschetti syndrome. It is often inherited as autosomal dominant trait. It results from retardation or failure of differentiation of maxillary mesoderm at and after the 50 mm stage of the embryo.

Clinical Features

Figure 9.9 High arch with cross bite in patient with Crouzon’s

syndrome

There is protuberant frontal region with an anteriorposterior ridge overhanging the frontal eminence and often passing to the root of nose (triangular frontal defect).

Oral Manifestations Maxillary hypoplasia with shortened anteroposterior dimension of maxillary arch is present. Dental arch width is reduced and this gives an appearance of highly arch palate (Fig. 9.9). In some cases, facial angle is exaggerated and the patient nose is prominent and pointed, resembling parrot beak.

There is underdevelopment of zygomatic bone, resulting in midfacial deformities. Craniofacial malformations associated with Treacher Collins syndrome include underdeveloped (hypoplastic) or absent cheek (malar) bone. There is downward inclination of palpebral fissure. There is deficiency of eyelashes. In some cases, eyes assume corresponding slant. A notching (colobomas) from the outer third of lower eyelids, There is varying degree of visual impairment in some cases. Affected infants may also have underdeveloped (hypoplastic) and/or malformed (dysplastic) ears (pinnae) with blind ending or absent external ear canals (microtia), resulting in hearing impairment (conductive hearing loss). There is absence of external auditory canal resulting in partial or complete deafness of patients (Fig. 9.10). The normal prominence of cheek is either missing or reduced depending upon the presence or absence of malar bone. There is usually hypoplasia of malar bone.

Craniofacial Anomalies

An incompletely developed, abnormally small lower jaw and macrostomia (an unusually large mouth) can also occur. There is presence of high arch palate with cleft palate, abnormal position and malocclusion of teeth with anterior open bite.

Radiographic Features It demonstrated hypoplasia of condyle and coronoid process with prominent antegonial notching.

Management Cosmetic improvement and surgical interventions to improve osseous and ear defect is done. Figure 9.10 Ear deformity seen in case of Treacher Collins

syndrome

Points to Remember Treacher Collin syndrome, underdevelopment of zygomatic bone, hypoplastic or absent cheek bone, deficiency of eyelashes, colobomas, malformed ears, hypoplasia of malar bone, lower anterior teeth stand away, bird face appearance, macrostomia, hypoplasia of condyle.

Focal Osteoporosis Bone Marrow Defect They are derived from bone marrow hyperplasia of persisting embryonic marrow remnants and site of abnormal healing following extraction, trauma and local inflammation.

Clinical and Radiological Features Sex predilection: It is more common in females than males. Figure 9.11 Bird fish appearance seen in Treacher Collins

syndrome

Other features are secondary mental deficiency, blind fistulae between the angle of ears and the angle of mouth. Associated features: Anal atresia/stenosis, congenital cardiac anomaly, rectovaginal fistula and tracheoesophageal fistula.

Oral Manifestations There is underdevelopment of mandible with steep mandibular angle. Due to this, lower anterior teeth stand away from upper teeth, when the mouth is closed. Bird face appearance: Facial appearance sometimes resembles fish or bird (Fig. 9.11).

Location: It is common in molar, premolar region in mandible. Radiographic features: It is incidentally found on radiograph. It appear as radiolucent, circumscribed area from several millimeter to centimeter in diameter (Fig. 9.12).

Histopathological Features Bone marrow contain cellular hemopoietic component which may show variable fatty components. In some cases lymphoid aggregates may be present.

Management There is no specific treatment for it after diagnosis is confirmed.

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Figure 9.12 Focal osteoporotic bone defect showing

Figure 9.13 Chondroectodermal dysplasia showing extra

finger

radiolucent circumscribed area

It is also called as Ellis-van-Creveld disease.

irregular in position. The teeth are affected, with eruption occurring at birth or shortly thereafter. The deciduous molars present a crenate occlusal surface. The permanent dentition is more likely to be defective than the deciduous one. Eruption is delayed. The lip deformity often referred to as a partial hairlip results from an abnormally short upper lip, which may also be sunken secondary to hypoplasia of maxilla.

Clinical Features

Management

It is congenital and the patient present evidence of chondrodysplasia, ectodermal dysplasia, polydactylism and congenital morbus cordis. Post-axial polydactyly in the hands, i.e. an extra finger lateral to the normal fifth finger, is a consistent finding (Fig. 9.13). Polydactyly in the feet is a rare finding. Bone dysplasia is characterized by acromesomelia, i.e. relative shortening of the distal (acromelic) and middle (mesomelic) segments. It may interfere with the ability to make a tight fist. There may be a deformity of the knees that frequently progress and causes a significant malalignment. The nails of the fingers and toes are dysplastic. The hairs tend to be fine and sparse. Congenital heart defects may include hypoplasia of aorta, atrial and ventricular septal defects and a single atrium. There is dwarfism, i.e. the long bones being short and the trunk of normal length.

No treatment is necessary. Dental care of patient should be done.

Points to Remember Persisting embryonic marrow remnants, radiolucent, circumscribed area, cellular hemopoietic component, lymphoid aggregates.

Chondroectodermal Dysplasia

Oral Manifestations Teeth: Teeth are deficient in number; those which do develop are small, rudimentary, conical, spaced and

Points to Remember Ellis-van-Creveld disease, chondrodysplasia, ectodermal dysplasia, polydactylism, congenital morbus cordis, post-axial polydactyly, bone dysplasia, congenital heart defects, dwarfism, teeth is deficient, partial hairlip.

Arhinencephaly It is a developmental abnormality of the skull and face in which there is absence or deficiency of the olfactory portion of brain. Absence of the vertical and cribriform plates of ethmoid and of crista galli result in the orbits being more closely set, a condition known as hypotelorism. There is depression of nose and absence of the bridge because of lack of nasal bones and nasal septum. There is wide cleft in the central portion of the lip, where the philtrum is absent and with failure of development of

Craniofacial Anomalies

any part of the premaxilla, the cleft is continuous through the palate. In some cases an associated deformity of the frontal portion of skull presents an angular appearance resembling the prow of a boat presumably due to premature fusion of metopic sutures.

Management Surgical management: Cosmetic and functional defect is treated by interdisciplinary approach using multiple surgical procedures. Craniotomy: It is performed in first year of life to treat craniosynostosis.

Points to Remember Hypotelorism, wide cleft, depression of nose, failure of development of premaxilla, prow of a boat’ appearance.

Apert’s Syndrome It is also called as acrocephalosyndactly. Acrocephalosyndactyly is believed to be transmitted by an autosomal dominant gene occurring sporadically in about 1–20,00,000 of the general population. It is characterized by craniosynostosis.

Clinical Features Craniosynostosis: It can produce acrobrachycephaly (tower skull), kleeblattschadel deformity (cloverleaf skull). Skull often presents a horizontal supraorbital grove. Premature closure of the sutures occur and the often and anterior fontanelle is open due to late closure. The occiput is flattened and tall appearance to the forehead is seen. Ocular lesion: There is ocular proptosis, hypertelorism and downward slanting of palpebral fissure. Patient may be having visual loss which can occur due to chronic exposure of the unprotected eye, increased intracranial pressure and compression of optic nerve. Limb defect: Features of hand and feet include syndactylism. Osseous or cutaneous fusion of fingers is usually present.

Oral Manifestations Oral features include a high palatal vault and the presence of posterior palatal and uvular clefts. Dental malocclusion is consistent. Other oral features include mandibular proganthism, malocclusion and retarded eruption. Trapezoid lip: This appearance occur when lips are relaxed and result due to midface hypoplasia and mouth breathing.

Points to Remember Acrocephalosyndactyly, craniosynostosis, ocular proptosis, hypertelorism, syndactylism, cutaneous fusion of fingers, high palatal vault, uvular clefts, dental malocclusion, trapezoid lip, craniotomy.

Stafne Defect It is also called as Stafne bone cyst, lingual mandibular salivary gland depression, latent bone cyst, static bone cyst and lingual cortical mandibular defect. It is discovered in 1942 by Stafne. This represents focal concavity of the cortical bone on the lingual surface of the mandible.

Clinical Features Age: It is commonly noticed in middle aged and older adults. Location: It is most commonly seen in posterior mandible in the location of salivary gland. In some cases this can be seen in anterior region where sublingual gland is present. Rarely parotid gland can cause depression in the area of ramus of the mandible. Sign and symptoms: It is asymptomatic and remain stable in size so bears a name static bone cavity. Radiological features: There is radiolucent defect below the mandibular canal in the posterior mandible between molar teeth and angle of the mandible. Lesion is welldefined with sclerotic border (Fig. 9.14).

Histopathological Features In the defect normal submandibular gland tissue can be seen. In some cases no tissue can be found assuming that gland has displaced at the time of biopsy.

Management No treatment is necessary as it is asymptomatic and does not increase in size.

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Figure 9.14 Stafne’s bone cyst presented as radiolucency

below the mandibular canal and surrounded by well corticated border

Figure 9.15 Multiple melanotic macule present on lower lip

Histopathological Features Points to Remember Stafne bone cyst, posterior mandible, asymptomatic, radiolucent defect below the mandibular canal, normal submandibular gland tissue.

DEVELOPMENTAL DISORDERS OF ORAL MUCOSA Labial and Oral Melanotic Macule It is also called as focal melanosis or solitary labial Lentigo. It represents an increase in synthesis of melanin pigments by basal cell layer melanocytes without increase in the number of melanocytes. It is the most common pigmentation to occur in oral cavity of light skinned individuals. It is not depended on sun exposure.

Clinical Features Age and sex distribution: Mean age is 41 to 45 years. Equal occurrence in both sexes. Location: It is attributed to actinic exposure and therefore occurs on vermilion border of the lower lip. Sometimes it can also occur on gingiva, palate and buccal mucosa. Appearance: It present as small, flat macule which may be single or multiple. Color of pigmentation is brown or brown black. Sign: Solitary lesion is less than 1 cm in diameter and constant in size. Lesions are oval or irregular in outline. It is an asymptomatic condition (Fig. 9.15).

Increase amount of melanin in basal cell layer. Also there is melanin in lamina propria. Increase number of clear cells and dendritic cells are also found. Melanophagocytosis can also be seen. Normal stratified squamous epithelium is seen in this case. There is presence of melanin incontinence (deposits in subepithelial stroma) in macrophages or melanophages. The melanin can be distinguished from iron deposits by the loss of brown color after bleaching.

Management Excision biopsy, electrocautery, laser ablation or cryosurgery can be done. Points to Remember Focal melanosis, actinic exposure, small, flat macule, lesion is less than 1 cm, increase melanin pigmentation in basal cell layer, clear cells, dendritic, melanin incontinence.

Fordyce Granule A Fordyce granule is a developmental anomaly characterized by heterotrophic collection of sebaceous glands at various sites in oral cavity which is covered with intact mucosa.

Pathogenesis It has been postulated that the occurrence of sebaceous glands in the mouth may result from the inclusion in the

Craniofacial Anomalies

Histopathological Features It consists of submucosal cluster of sebaceous acini and communicated with the oral epithelium by the way of duct (Figs 9.17 and 9.18). In some cases all are grouped around one or more duct which opens on the surface of mucosa. These ducts may show keratin plugging. They are identical with those seen with normal sebaceous gland on the skin except for the absence of hair follicles.

Figure 9.16 Fordyce granules seen on buccal mucosa

oral cavity of the ectoderm having some of the potentialities of the skin in the course of development of the maxillary and mandibular processes during embryonic life.

Clinical Features Age and sex distribution: It is seen in any age group with somewhat more prevalent in males as compared to females. Location: It is most commonly found bilaterally in symmetrical pattern on mucosa of the cheek, opposite to the molar teeth. It is also found on inner surface of lips, in retromolar area lateral to anterior faucial pillar and occasionally on the tongue, gingiva, frenum and palate. Appearance: They appear as small yellow spots, either discretely separated or forming relatively large plaques often projecting slightly above the surface of tissue (Fig. 9.16). The granules may be isolated or they may occur in confluent sheets. Sometime they may occur in clusters and may form plaque like lesions. On the tongue it appears as dome shaped nodules varying in size from a few millimeters to 2 cm in diameter on the midline dorsum of the tongue. They are more yellow than white. It increases rapidly in number at puberty and continues to increase through the adult life. They are neither ectopic nor adenomas and usually are submucosal. They are sharply delineated and with smooth surface which is not ulcerated. They have got slightly cheesy consistency.

Figure 9.17 Sebaceous gland showing pilosebaceous tract (Courtesy: Dr Sangamesh Halawar, Reader, Deptt of Oral Pathology, VPDC and H. Kavalapur, Sangli, Maharashtra)

Figure 9.18 Fordyce’s granule

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If it causes disfigurement then surgical removal can be done. Points to Remember Heterotrophic collection of sebaceous glands, bilaterally in symmetrical pattern on mucosa of the cheek, small yellow spots, on tongue dome shaped nodules, more yellow than white, cheesy consistency, submucosal cluster of sebaceous acini, keratin plugging.

Leukoedema It is an abnormality of the buccal mucosa, which clinically resembles early leukoplakia. It has got prevalence in blacks due to presence of background pigmentation that makes edematous changes noticeable. It is seen more commonly in a person who is useing tobacco. It may be related to poor oral hygiene.

Clinical Features Age and sex distribution: It is common in age group of 15 to 35 year with prevalence in black. Male predilection in the ratio of 2:1. Location: The most common sites of involvement are buccal mucosa and lip. The lesion is bilateral. Appearance: Buccal mucosa retains the normal softness and flexibility but exhibits grayish white, slightly folded opalescent appearance that is described as epithelium covered with diffuse edematous film or velvetlike veil (Fig. 9.19). Mother of pearl appearance: In some cases, lesion is diffuse and shows a filmy, mother of pearl appearance, often with delicate overlapping curtain like mucosal folds. In this disease desquamation may occur which may leave surface of the lesion eroded. It can be eliminated by the stretching and scraping of mucosa but re-establishes itself almost immediately.

Histopathological Features There is increase in thickness of epithelium, broad rete pegs and intracellular edema of spinous layer. Cells at the surface are flattened and may retain pyknotic nuclei that contain glycogen. The characteristic edematous cells appear extremely large and pale, and they present a reticular pattern.

Figure 9.19 Leukoedema affecting buccal mucosa

Management No treatment is necessary as it has not got any premalignant potential. Points to Remember Common sites are buccal mucosa and lip, velvetlike veil appearance, Mother of pearl appearance, eliminated by the stretching and scraping of mucosa, thickness of epithelium, broad rete pegs, intracellular edema of spinous layer, pyknotic nuclei.

Caliber Persistent Artery It is vascular anomalies where main arterial branch reached the superficial surface without reduction in size.

Clinical Features Age and sex distribution: It is more commonly seen in older individuals without any sex predilection. Location: It is most commonly seen on lip mucosa with some lesions have bilateral or involving both lip. Appearance: It appears as linear, arcuate or papular elevation. This can be of black to bluish in color. Sign: Stretching of lip can cause artery inconspicuous. There is presence of vertical pulsation or pulsatile lip nodules. In some cases there is ulceration of overlying mucosa.

Histopathological Features There is thick wall artery located close to surface.

Craniofacial Anomalies

Management No treatment is necessary for this. Sometime if biopsy is performed for mistaken diagnosis, there is brisk bleeding from the lesion.

6.

Points to Remember

7.

Lip mucosa, linear, arcuate or papular elevation, stretching of lip can cause artery inconspicuous, thick wall artery.

8.

Lateral Soft Tissue Fistulas It can occur due to defect in development of second branchial arch. It is very rare anomaly.

9.

Clinical Features Location: They are bilaterally seen on anterior tonsillar pillar. Sometime they can also be seen on posterior pillar. Appearance: There is perforation ranging from few mm to 1 cm in diameter. Sign and symptoms: It is asymptomatic and some cases may be associated with absence or hypoplasia of palatine tonsil, hearing loss and preauricular fistulas.

10. 11.

12.

Management

13.

No treatment is necessary for this as the lesion is asymptomatic.

14.

Points to Remember Anterior tonsillar pillar, perforation, hearing loss and preauricular fistulas.

15.

BIBLIOGRAPHY

16.

1. Alves-Pereira D, Berini-Aytés L, Gay-Escoda C. Ellis-van Creveld syndrome. Case report and literature review. Med Oral Patol Oral Cir Bucal. 2009;14(7):E340-3. Review. 2. Becktor KB, Reibel J, Vedel B, Kjaer I. Segmental odontomaxillary dysplasia: clinical, radiological and histological aspect of four cases. Oral Dis. 2002;8:10610. 3. Belludi A, Belludi S, Bhardwaj A, Dilliwal S. Crouzon syndrome—a case report. Gen Dent. 2012;60(3):e162-5. 4. Bowden CM Jr, Kohn MW. Mandibular deformity associated with unilateral absence of the condyle. J Oral Surg. 1973;31:469-72. 5. Braun-Falco O, Plewig G, Wolff HH, et al. Diseases of connective tissue, in Braun-Falco, Plewig G, Wolff HH et al,

17.

18.

19.

20.

(Eds): Dermatology, 2nd edn. New York, Springer-Verlag Berlin Heidilberg; 2000.pp.773-74. Bufalino A, Paranaíba LM, Gouvêa AF, Gueiros LA. Cleidocranial dysplasia: oral features and genetic analysis of 11 patients Oral Dis. 2012;18(2):184-90. doi: 10.1111/ j.1601-0825. 2011.01862.x. Epub 2011 Oct 24. Burglen L, Soupre V, Diner PA, Gonzales M, Vazquez MP. Oto-mandibular dysplasias: genetics and nomenclature of syndromes. Ann Chir Plast Esthet. 2001;46:400-9. Cleidocranial Dysplasia. Mendoza-Londono R, Lee B. Editors In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, (Eds). SourceGeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-. 2006 [updated 2009 Jun 25]. CN, Shakuntala BS, Mathew S, Krishnamurthy NH, Yumkham R. Cleidocranial dysplasia presenting with retained deciduous teeth in a 15-year-old girl: a case report. J Med Case Rep. 2012;6(1):25. Demendi C, Németh M, Langmár Z. Orv Hetil. Congenital disorders. Holoprosencephalia. 2011;152(52):2105-8. Danforth RA, Melrose RJ, Abrams AM, Handlers JP. Segmental odontomaxillary dysplasia: Report of eight cases and comparison with hemimaxillofacial dysplasia. Oral Surg Oral Med Oral Pathol. 1990;70:81-5. Golan I, Baumert U, Hrala BP, Müssig D. Dentomaxillofacial variability of cleidocranial dysplasia: clinicoradiological presentation and systematic review. Dervis E, Dervis E. Progressive facial hemiatrophy with linear scleroderma. Ped Dermatol. 2005;22(5):436-9. Diego Mauricio Bravo-Calderón, Denise Tostes Oliveira, Wagner Humberto Martins dos Santos. Bilateral osteoporotic bone marrow defects of the mandible: a case report Head and Face Medicine. 2012;8:22. Drake DL. Segmental odontomaxillary dysplasia: an unusual orthodontic challenge. Am J Orthod Dentofacial Orthop. 2003;123:84-6. De Felice C, Parrini S, Chitano G, Gentile M, Dipaola L, Latini G. Fordyce granules and hereditary non-polyposis colorectal cancer syndrome. Gut. 2005;54(9):1279-82. Epub 2005. Olivier JH. Fordyce granules on the prolabial and oral mucous membranes of a selected population. SADJ. 2006;61(2):072-4. Fordyce spots. A little regarded finding in the area of lip pigmentation and mouth mucosa]. Dreher A, Grevers G. Laryngorhinootologie. 1995;74(6):390-2. Gekas J, Li B, Kamnasaran D. Current perspectives on the etiology of agnathia-otocephaly. Eur J Med Genet. 2010;53(6):358-66. Epub 2010 Sep 16. Gillessen-Kaesbach G. Familial holoprosencephaly: further example of autosomal recessive inheritance. Birth Defects Orig Artic Ser. 1996;30:251–9.

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21. Goldschmidt B, Lopes CA, Moura M, Fasano DM, Andrade MC, Cysne LB, Gonçalves MB, Bravin JS, Kugelmeier T, Viana CF, Silva FA, Marinho AM. Agnathia and associated malformations in a male rhesus monkey. J Med Primatol. 2008;37(4):173-6. 22. Gordy FM, Crews KM, O Carroll MK. Focal osteoporotic bone marrow defect in the anterior maxilla. Oral Surg Oral Med Oral Pathol. 1993;76(4):537-42. 23. Grabb WC. The first and second arch syndrome. Plast Reconstr Surg. 1965;36:485-508. 24. Coletă E, Siminel M, Gheonea M. Holoprosencephaly sequence. Rom J Morphol Embryol. 2011;52(2):725-8. 25. Hwang KS, Ding DC, Chang YK, Chen WH, Chu TY. Otocephaly. J Chin Med Assoc. 2007;70(7):298-301. 26. Kauvar EF, Solomon BD, Curry CJ, van Essen AJ, Janssen N, Dutra A, Roessler E, Muenke M. Holoprosencephaly and agnathia spectrum: Presentation of two new patients and review of the literature. Am J Med Genet C Semin Med Genet. 2010;154C(1):158-69. 27. KCP Santos, MEP Dutra, C Costa, CA Lascala, CE Lascala, JX de Oliveira. CASE REPORT Aplasia of the mandibular condyle. Dentomaxillofac Radiol. 2007:36:420-2. 28. Khandelwal R, Agrawal P, Majumdar MR. BMJ Case Rep. 2012;8:2012. Dentomaxillofac Radiol. 2003;32(6):347-54. 29. Krogstad O. Aplasia of the mandibular condyle. Eur J Orthod. 1997;19:483-9. 30. Mankin HJ, Jupiter J, Trahan CA. Hand and foot abnormalities associated with genetic diseases. Hand (N Y). 2011;6(1):18-26. Epub 2010 26. 31. Masood SA, Sangster G, Chen E, Tice H, Julian KC, Lewis D, Ibrahim H. Agnathia-otocephaly. J La State Med Soc. 2008;160(6):325-7. 32. Mata Zubillaga D, Lapeña López de Armentia S. Cleidocranial dysostosis. A review of 11 cases in five generations]. An Pediatr (Barc). 2008;69(2):162-6. 33. Minett CP, Daley TD. Hemimaxillofacial dysplasia (segmental odontomaxillary dysplasia): case study with 11 years of follow-up from primary to adult dentition. J Oral Maxillofac Surg. 2012;70(5):1183-91. Epub 2011 Jul 20. 34. Muenke M, Beachy PA. Holoprosencephaly. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B, (Eds). The Metabolic and Molecular Bases of Inherited Disease. 8 ed. New York, NY: McGraw-Hill; 2001:6203-30. 35. Neville BW, Damm DD, Allen CM, Bouquot JE. Developmental defects of the oral and maxillofacial region. In: Oral and maxillofacial pathology (2nd edn). Philadelphia, PA: WB Saunders; 2002.pp.17-18. 36. Packota GV, Pharoah MJ, Petrikowski CG. Radiographic features of segmental odontomaxillary dysplasia: a study of 12 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82:577-84.

37. Pandey S, Pai KM, Nayak AG, Vineetha R. Unilateral segmental odontomaxillary hypoplasia: an unusual case report. Imaging Sci Dent. 2011;41(1):39-42. Epub. 2011 Mar 26. 38. Poswillo D. The pathogenesis of the first and second branchial arch syndrome. Oral Surg Oral Med Oral Pathol 1973;35:302-28. 39. Powler JR, Glassman S. Agenesis of the mandibular condyles. Oral Surg. 1954;7:133-9. 40. Proffit WR. The etiology of orthodontic problems. In: Proffit WR, Fields HW Jr, Sarver DM (Eds). Contemporary Orthodontics. 4th edn. St Louis: CV Mosby; 2006.pp.11344. 41. Prusack N, Pringle G, Scotti V, Chen SY. Segmental odontomaxillary dysplasia: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90:483-8. 42. Rudnik-Schöneborn S, Zerres K, Graul-Neumann L, Wiegand S, Mellerowicz H, Hehr U. Two Adult Patients with Ellis-van Creveld Syndrome Extending the Clinical Spectrum. Mol Syndromol. 2011;1(6):301-6. Epub 2011 Sep 14. 43. Schmotzer CL, Shehata BM. Two cases of agnathia (otocephaly): with review of the role of fibroblast growth factor (FGF8) and bone morphogenetic protein (BMP4) in patterning of the first branchial arch. Pediatr Dev Pathol. 2008;11(4):321-4. Epub 2008 Jan 3. 44. Segal N, Puterman M. Cleidocranial dysplasia—review with an emphasis on otological and audiological manifestations. Int J Pediatr Otorhinolaryngol. 2007;71(4):523-6. Epub 2007 Jan 18. 45. Sencimen M, Delilbasi C, Gulses A, Okcu KM, Gunhan O, Varol A. Focal osteoporotic hematopoietic bone marrow defect formation around a dental implant: a case report. Int J Oral Maxillofac Implants. 2011;26(1):e1-4. 46. Shah B, Ashok L, Sujatha GP. Ellis-van Creveld syndrome: a case report. J Indian Soc Pedod Prev Dent. 2008;26 (Suppl 1):S19-22 47. Shen Z, Zou CC, Yang RW, Zhao ZY. Cleidocranial dysplasia: report of 3 cases and literature review. Clin Pediatr (Phila). 2009;48(2):194-8. Epub 2008 Oct 2. Review. 48. Smith DW. Recognizable patterns of human malformation. 3rd edn. Philadelphia: WB Saunders; 1982.pp.497-500. 49. Sommer A, Gambichler T, Bacharach-Buhles M, von Rothenburg T, Altmeyer P, Kreuter A. Clinical and serological characteristics of progressive facial hemiatrophy: acase series of 12 patients, J Am Acad Dermatol. 2006;54(2):227-33. 50. Stavropoulos D, Bartzela T, Tarnow P, Mohlin B, Kahnberg KE, Hagberg C. Dental agenesis patterns in Crouzon syndrome. Swed Dent J. 2011;35(4):195-201. 51. Taysi K, Marsh JL, Wise DM. Familial hemifacial microsomia. Cleft Palate J. 1983;20:47-53.

Craniofacial Anomalies 52. Totori-Donati, Paolo, Rossi, Andrea, Biancheri, Roberta. “Brain Malformations”. In: Totori-Donati, Paolo, Rossi, Andrea, Raybaud, C (Eds). Pediatric Neuroradiology: Brain, Head, Neck and Spine. 1. Springer; 2005.pp. 92-95. ISBN 3-540-41077-5. 53. Tu JH, Eisen AZ. Scleroderma In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, Fitzpatrick TB (Eds). Dermatology in general medicine, 5th edn. McGrawHill; 1999.pp.2023-33.

54. Vinay C, Reddy RS, Uloopi KS, Sekhar RC. Clinical manifestations of Ellis-van Creveld syndrome. J Indian Soc Pedod Prev Dent. 2009;27(4):256-9. 55. Whitt JC, Rokos JW, Dunlap CL, Barker BF. Segmental odontomaxillary dysplasia: report of a series of 5 cases with long-term follow-up. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(2): e29-47. Review. 56. Wilson GN. Craniofacial defects in the Goldenhar syndrome. Am J Med Genet. 1983;14:435-43.

MULTIPLE CHOICE QUESTIONS 1. ‘Friedreich’s disease’ is: a. Facial hemihypertrophy b. Macrognathia c. Genesis d. Micrognathia

6. ‘Parrot beak’ appearance of nose seen in: a. Franceschetti syndrome b. Parry-Romberg syndrome c. Marie Sainton disease d. Crouzon’s disease

2. Following are associated with micrognathia except: a. Pierre-Robin syndrome b. Turner’s syndrome c. Marfan’s syndrome d. Costen’s syndrome

7. Chondroectodermal dysplasia is also known as: a. Ellis-van Crevald disease b. Treacher Collins syndrome c. Crouzon’s disease d. None

3. ‘Hypognathus’ means: a. Micrognathia b. Macrognathia c. Agnathia d. Facial hemiatrophy

8. In oral melanotic macule there is: a. Decrease in synthesis of melanin pigments b. An increase in synthesis of melanin pigments c. An increase in the number of melanocyte d. Decrease in the number of melanocyte

4. ‘Parry Romberg’ syndrome refers to: a. Macrognathia b. Facial hemiatrophy c. Micrognathia d. Agnathia

9. Deficiency of eyelashes seen in the following except: a. Crouzon’s disease b. Treacher Collins syndrome c. Mandibulofacial dysostosis d. Franceschetti syndrome

5. Complete absence of clavicle seen in: a. Mandibulofacial dysostosis b. Arhinencephaly c. Craniofacial dysostosis d. Cleidocranial dysplasia

10. Keratin plugging seen in: a. Focal epithelial hyperplasia b. Fordyce’s granule c. Oral melanotic macule d. Crouzon’s disease

143

Dental Caries

Anil Govindrao Ghom , Shubhangi Mhaske (Jedhe) A

Chapter Outline 3 Definition 3 Theories of cariogenesis

• The legend of worm • Chemical theory • Humoral theory

3 3 3 3 3 3

• Vital theory • Miller' s acidogenic/ chemoparasitic theory • Proteolysis theory • Proteolysis chelation theory • Sucrose chelation theory • Autoimmune theory Secondary contributing factors in dental caries Classification Smooth surface caries Pit and fissure caries Root caries Recurrent caries

3 3 3 3 3

Nursing bottle caries Rampant caries

Arrested caries Pre- eruptive caries Caries activity tests

• • • • • •

Lactobacillus count test Snyder test Alban' s test Streptococcus mutans level in saliva Buffer capacity test Fosdick calcium dissolution test

• Dewar test • Swab test • Reductase test 3 Control of dental caries 3 Chemical measures of caries control

INTRODUCTION

DEFINITION

Dental caries is a complex, continuous, dynamic biological process of tooth decay with multifactorial etiology. The process of dental decay comprises of periods of progres sion alternating with periods of arrest and repair of affected dental tissues . The word caries derived from Latin meaning rot’ or decay .

Dental caries is defined as a progressive irreversible microbial disease affecting the hard parts of tooth exposed to the oral environment, resulting in demineralization of the inorganic constituents and dissolution of the organic constituent, thereby leading to a cavity formation .

4

Dental Caries

THEORIES OF CARIOGENESIS

Chemical Theory

These are the current concepts of caries pathogenesis. These are based on sound experimental evidences. Among these Miller’s acidogenic theory is most accepted one.

Parmly (1819) proposed that an unidentified chemical agent was responsible for caries. He stated that caries began on enamel surface where food putrefied and acquired sufficient dissolving power to produce the disease chemically.

History/Old Theories Exogenous theories • The legend of worm • Chemical theory • Parasitic or septic theory Endogenous theories • Humoral theory • Vital theory. Theories of Etiopathogenesis • • • •

Miller’s acidogenic theory Proteolytic theory Proteolysis-chelation theory Sucrose chelation theory.

The Legend of Worm In ancient Sumerian text, it is stated that dental caries is caused by a worm that drank the blood of the teeth and fed on the roots of jaws. This is known as the legend of worms. It was obtained from the Mesopotamian area which dates to about 5000 BC. This theory is supported in the ancient literature of India, China, Finland, Scotland and the writing of Homer (Fig. 10.1).

Humoral Theory According to this ancient theory the four humors of the body are blood, phlegm, black bile and yellow bile and any change in the relative proportion of these elements causes disease. Similarly, dental caries is caused by the change in these humors. According to Greek physician and philosopher Gallen, Dental caries is produced by the internal action of acid and corroding humors. Hippocrates, the father of medicine, while favoring the concept of humoral pathology also referred to the accumulated debris around teeth and to their corroding action. He also stated that the stagnation of food and juices was the cause of the decay.

Vital Theory The theory stated in 18th century says that tooth decay originated like bone gangrene, from within the tooth itself.

Miller’s Acidogenic/Chemoparasitic Theory WD Miller proposed this theory in 1890. He based his theory on observations of following investigators: ∙ Pasteur discovered that microorganisms can transform sugars into lactic acid. ∙ Emil Magitot demonstrated that fermentation of sugars can cause dissolution of tooth mineral in vitro. ∙ Underwod and Miles stated that caries is absolutely dependent on the presence of organisms that create an acid which removes the lime salt. WD Miller’s chemoparasitic theory states, “Dental decay is a chemoparasitic process consisting of two stages, the decalcification of enamel, which results in its total destruction and the decalcification of dentin as a preliminary stage, followed by dissolution of the softened residue.” The chemoparasitic theory can be better described with the role of the following factors together causing decay: Factors Responsible for Chemoparasitic Theory

Figure 10.1 Legend of worm theory

• • • •

Role of carbohydrates Role of microorganisms Role of acids Role of dental plaque.

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Role of Carbohydrate

∙

Various food substances can directly or indirectly affect dental caries. Food substances act as substrates for microorganisms of dental plaque, which form acids, thereby causing dental caries. Other substances may affect microflora in negative way thus protecting the tooth from caries. Among these carbohydrates is main cause of dental caries. There is considerable increase in caries incidence after exposure of modern civilization to refined foods. This is mainly because these substances contain more amounts of sticky carbohydrates.

Route of administration: Glucose or sucrose administered intravenously or by gastric tube do not contribute to decay as they are unavailable for microbial breakdown, thus oral intake of sticky carbohydrates are found to be the cause behind the dental decay.

Cariogenicity of Carbohydrate Varies with • • • • •

Frequency of ingestion Physical form Chemical composition Route of administration Presence of other food constituents.

Frequency of ingestion: More is the frequency of ingestion; more is the chance of dental caries. The risk of caries incidence increases greatly if carbohydrates are taken repeatedly in between two major meals. It provides an almost constant supply of carbohydrate to the plaque bacteria for fermentation and subsequent production of acids. Physical form: Sticky, solid carbohydrates are more cariogenic than in any other forms. Sugars that are easily cleared are less damaging than soft retentive ones. Chemical composition: Cariogenicity among carbohydrates also varies. ∙ The carbohydrates in the form of glucose, sucrose and fructose, etc. rapidly diffuse into the plaque due to their low molecular weight and therefore make themselves easily available for fermentation by plaque bacteria. ∙ Polysaccharides are less fermented by plaque bacteria than the monosaccharides and disaccharides. ∙ Sucrose is utilized by Streptococcus mutans to synthesize an extracellular insoluble polysaccharide (dextran) with the help of glucosyl transferase enzyme. Dextran helps the plaque to adhere firmly onto the tooth surface and helps a direct contact between the acids liberated by microorganisms and the tooth, thus causing demineralization. Thus, sucrose is most potent cariogenic substance.

Other polysaccharides synthesized by the cariogenic bacteria are glucan (from glucose) and levan (from fructose). Glucan and levan are weakly adhering substances so are less cariogenic.

Presence of other food constituents: Refined pure carbohydrates are more caries producing than crude carbohydrates complexes with other food elements capable of reducing enamel solubility.

Role of Microorganisms (Fig. 10.2) It is generally agreed that dental caries is caused by acid resulting from action of microorganisms on carbohydrates. Microbiology of Dental Caries (Table 10.1). Animal studies with sophisticated experiments and sterile conditions have confirmed the essential role of microorganisms in the initiation and progression of dental caries. The absolute requirement of the microorganisms which are said to be inducing dental caries, specifically bacteria that can produce acids, particularly lactic acid, from the substrate of host’s diet and can tolerate very low pH ( 2 cm diameter Lack of intense pain Aggressive behavior Typically in the vertebrae or major bones of the lower extremity Often affects the spongiosa of the bone Absence of neural axons upon staining

composed of osteoid and newly formed trabeculae within highly vascularized osteogenic connective tissue. From this core osteoblasts differentiate towards surface. Formation of definite trabeculae, with rimming of active osteoblasts occurs. Osteoclasts and foci of bone resorption are also usually evident.

Management Medical management: NSAIDs like salicylates relives the pain. Surgical management: Open surgical curettage and CT guided percutaneous radio‐frequency (RF) ablation, laser, ethanol, or thermocoagulation therapy. Points to Remember Unknown etiology, elevated prostaglandin E2 levels in nidus responsible for bone pain and vasodilatation, tumor infarction may be involved during cases of spontaneous regression, cortical osteoid osteomas are often associated with nonaggressive periosteal reactions, OOs and osteoblastomas are histologically similar but differ in size, pain intensity, location, aggressiveness, and neural staining patterns. OOs are classified by their relative position to the bone: cortical, cancellous, intraarticular, and subperiosteal.

Osteochondroma

Figure 11.44 Osteoid osteoma showing central nidus around

which bony trabeculae enclosing marrow spaces are formed: CN–Central nidus; T–Trabeculae; MS–Marrow space

Radiographic Features There is well-defined radiolucent nidus with surrounding zone of sclerosis. Central nidus is typically < 1.5 cm in diameter. Angiography shows highly vascular central nidus, intense circumscribed blush that develops during the early arterial phase and persists into venous phase is diagnostic.

Histopathological Features Osteoid osteoma consists of bony trabeculae that are formed around a central core (Fig. 11.44). The core is

Osteochondroma or solitary osteocartilaginous exostosis is characterized by a cartilage-capped, osseous projection protruding from the surface of affected bone. It is considered the most common tumor of skeletal bones. These tumors are considered to be developmental lesions rather than true neoplasms and are often referred to as an osteocartilaginous exostosis (or simply exostosis). It is most likely to represent a choristoma, rather than a neoplasm. There is intermingling of two lesions resulting in the term osteochondroma. They are very common and account for 10 to 15 percent of all bone tumors and 20 to 50 percent of all benign bone tumors. It may be of central and peripheral types or solitary and multiple types.

Etiology Several theories have been suggested to explain the pathogenesis of osteochondroma. Few of them are explained as follows: Osteochondromas are most likely caused by either a congenital defect or trauma of the perichondrium.

Benign Tumors

According to Keith et al, this tumor resulted from defects in the periosteal cuff and herniation of the epiphyseal plate cartilage during fetal growth and development. Lichtenstein theorized the periosteum has the potential to develop osteoblasts and chondroblasts. According to Virchow’s physeal theory, a portion of the physeal cartilage becomes separated from the parent tissue then rotates 90� and grows in a direction transverse to the long axis of the bone.

Hereditary multiple exostoses (HME); (Familial osteochondromatosis diaphyseal aclasis): It is an autosomal dominant condition that can lead to both sessile and pedunculated lesions. The lesions may occur on different bones or on the same bone, and symptoms present in the first decade of life. The risk of malignant transformation to chondrosarcoma in hereditary multiple osteochondromatosis is unknown, but may be 25 to 30 percent compared to approximately 1 percent for a solitary osteochondroma.

Clinical Features

Complications: It includes fracture, vascular compromise, neurologic sequelae, bursa formation, and malignant transformation.

Age and sex distribution: The mean age at diagnosis is usually 40 years. Lesions grow even after patient attains skeletal maturity. Females are more prone for the lesion. Location: It is relatively uncommon in the jaws. When jaws are affected, it occurs in coronoid process followed by the condyle, symphysis and other sites occasionally. The lesion is usually discovered incidentally on radiographic examination or on palpation of a protruding mass in the affected area. In case of condylar osteochondroma, malocclusion in the form of a lateral open bite on the contralateral side and progressive facial asymmetry is seen. Pain may precede or accompany facial asymmetry. Signs and symptoms: Clinically, osteochondroma present with pain due to mechanical irritation or a painless mass. Other signs and symptoms of TM joint dysfunction which may be present are swelling, pain, clicking, malocclusion, facial asymmetry and posterior apertognathia. On gross examination, an osteochondroma is an irregular bony mass with a bluish gray cap of cartilage. Opaque yellow cartilage has calcification within the matrix. The base of the lesion has a rim of cortical bone and central cancellous bone. The risk of malignant degeneration increases as the number and size of the osteochondroma increases. In general, a sessile lesion is more likely to degenerate into sarcoma than an exostosis. Peripheral osteochondroma: Tongue is the most common site of involvement in the oral cavity. On the tongue, it appears as a pedunculated swelling of about 1 to 2 cms in the posterior part of the dorsum of tongue, near the foramen cecum. It has broad base. Variants of osteochondroma include subungual exostosis, dysplasia epiphyseal is hemimelica, turret exostosis, traction exostosis, bizarre parosteal osteochondromatous proliferation, and florid reactive periostitis. They are usually sporadic, but can be part of:

Radiographic Features It usually appears smooth, regular surface and projection of the cortex in continuity with the underlying bone. Irregular calcifications are often seen. CT scan or MRI images demonstrate continuity of marrow space into lesion. The diagnosis of osteochondroma is based on clinical and radiographic findings.

Histopathological Features (Fig. 11.45) This tumor consists of three layers, i.e. outer perichondrium, cartilage and innermost layer of bone. Perichondrium is continuous with the periosteal layer of bone in which this tumor develops. Beneath this layer chondrocytes are clustered. This arrangement gives appearance of a growth plate. Chondrocytes form cartilage that undergoes ossification. Bone may contain normal bone marrow.

Figure 11.45 Osteochondroma showing outer perichondrium, middle cartilage layer and innermost bone layer

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The criteria of osteochondroma includes the presence of clusters of chondrocytes in the cartilaginous cap, arranged in parallel, oblong, lacunar spaces, similar to those of normal epiphyseal cartilage. The histological distinction between osteochondroma and chondrosarcoma can be difficult, however, lack of high cellularity, pleomorphism, and plump cells with large or double nuclei favor a benign lesion.

Torus Palatinus It is also called as ‘palatine torus’. It is a slowly growing flat based bony protuberance or excrescence which occurs in the midline of the hard palate. It has been stated that functional stress and genetic factors are important for its origin. Types ∙

Histopathology Outer layer:

Fibrous perichondrium that is continuous with periosteum of underlying bone

∙

Middle layer:

Cartilaginous cap < 2 cm thick. Superficial chondrocytes are clustered, deeper chondrocytes resemble a growth plate

∙

Deeper layer:

Endochondral ossification and transition to cancellous bone with inter trabecular red or fatty marrow

Hyperplasias

Osteochondroma

•  B   one shape preserved •    Smooth, regular outline •    Symmetrical proportionate enlargement •    Increased opacification •    Normal marrow trabeculation •    Enlargement of ipsilateral mandible

•  E  xophytic bulbous or globular dome shaped sessile or pedunculated out growth over the cortical surface •    May have irregular outline •    Cortex and marrow continue into lesion •    Rest of jaw bone normal

Management It consists of surgical removal. Points to Remember Choristoma, periosteal cuff, herniation of the epiphyseal plate cartilage, physeal theory, condylar osteochondroma, pain due to mechanical irritation, peripheral osteochondroma, hereditary multiple exostoses (HME); Familial osteochondromatosis diaphyseal aclasis, irregular calcifications, outer perichondrium, cartilage and innermost layer of bone layer, chondrocytes are clustered.

∙

Flat torus: It has broad base and extend symmetrically on both side of raphe Spindle torus: It is midline ridge along the palatine raphe Nodular torus: Multiple protuberance with individual base Lobular torus: Lobulated mass from single base.

Clinical Features Age and sex distribution: It occurs in about 20 percent of the population. Females are affected twice more commonly than males. Development is initiated in young adults, before 30 years. Location: It occurs in the midline of the palate and may extend to involve the palatal process of the palatine bone. Appearance: The growth may be slow or there may be a period of rather rapid growth which ceases altogether before the patient has advanced into adult life. It may be variable in size and shape and be described as flat, spindle shaped, nodular or mushroom like (Fig. 11.46). Sign and symptoms: It is covered with normal mucosa, which appears pale and occasionally ulcerated, when traumatized. There is a nodular irregularity around some of the masses of new bone, formed on one side of the midline.

Histopathological Features It is usually composed of compact bone or cancellous bone surrounded by a capsule of compact bone. An inner core of cancellous bone may be present in the larger specimens.

Management As it is benign it is usually not treated, except in some cases where patient requires a complete denture and tori is causing more undercuts and problems for fitting of complete denture. In these cases surgical removal of tori can be done.

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Figure 11.46 Torus palatinus presenting as a hard bony lobulated growth with a smooth overlying mucosal surface

Figure 11.47 Mandibular tori present on lingual side in the

region of molar

Points to Remember

Points to Remember

Palatine torus, flat, spindle shaped, nodular or mushroom like, composed of compact bone or cancellous bone.

Mandibular tori growth on the lingual surface of the mandible, above the mylohyoid line.

Torus Mandibularis

Exostosis

It is also called as ‘mandibular tori’. It is an exostosis or outgrowth of bone found on the lingual surface of the mandible. They consist primarily of compact bone.

It is also called as ‘hyperostoses’. They are small regions of osseous hyperplasia of cortical bone and occasionally, cancellous bone, on the surface of the alveolar process.

Causes Genetic and environmental factors are responsible for its formation. Masticatory stress is reported as an essential factor underlying the formation.

Clinical Features Age: It occurs in 8 percent of the population. It is usually discovered in middle aged adults. Location: It may occur singly, multiply; unilaterally, but is usually bilateral in premolar region. Sign: There is growth on the lingual surface of the mandible, above the mylohyoid line, usually opposite to the bicuspid teeth. Their sizes are variable ranging from an outgrowth that is just palpable to one that contacts a torus on the opposite side (Fig. 11.47).

Management It does not require any treatment. Removal may be necessary, if a mandibular denture is planned.

Clinical Features Location: They are less common than mandibular and palatal tori. It may develop on the palatal surface of maxillary alveolar process, at the border between the attached gingiva and vestibular mucosa, in canine or molar area. They seldom attain large size and may be solitary or multiple. Their shape may be nodular, pedunculated or flat protuberance on the surface of bone. They are bony hard on palpation. Buccal exostosis: It is bilateral row of bony hard nodule along the facial aspect of maxillary or mandibular alveolar ridge. Palatal tubercle: It is bony protuberance seen at lingual aspect of maxillary tuberosity. Reactive subpontic exostosis: It is also called as subpontic osseous proliferation, subpontic osseous hyperplasia— these develop beneath pontic of posterior bridge.

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Management They do not required any treatment. 196

Points to Remember Hyperostosis, palatal surface of maxillary alveolar process, nodular, pedunculated or flat protuberance, buccal exostosis, palatal tubercle, reactive subpontic exostosis.

VASCULAR TISSUE Hemangioma It is also called as ‘vascular nevi. It is a benign tumor which occurs most commonly in vertebrae and skull. It is characterized by endothelial proliferation of blood vessels. It is often congenital in origin. It is composed of seemingly disorganized vessels that are filled with blood and is connected to the main vascular system. Initially hemangioma has been thought to be developmental vascular malformation. Nowadays hemangioma is the term used for tumors with endothelial cell proliferation. For structural anomalies of blood vessel without endothelial proliferation is term as vascular malformation. Vascular malformations are described later in this chapter. Under the heading of hemangioma, we will describe hemangioma of infancy and central hemangioma.

Location: Mandible to maxilla ratio is 2:1. Fifty percent cases are found in mandible, mostly in the body and ramus area. Sign: There is nontender expansion of jaws and the swelling is bony hard in consistency. Symptoms: Pain is present in many cases and is probably throbbing in nature. Compressible swelling, which may pulsate and bruit may be detected on auscultation. There is anesthesia of skin supplied by mental nerve. Bleeding from gingiva around the neck of affected teeth can occur. Pumping tooth syndrome is present, i.e. it demonstrates pumping action, i.e. if the tooth is depressed into the socket, it will rebound into its original position within few minutes. Teeth in affected area may be loosened and may migrate. Aspiration of the lesion produces blood. Radiological features: Lesion shows honeycomb appearance (small loculations) or soap bubble appearance (large loculations). Large lesion can cause cortical expansion and in some cases ‘sunburst appearance’, can be seen. Hemangioma of infancy (Figs 11.48 and 11.49) Age and sex distribution: It is more commonly seen in children in first decade of life. More seen in female than in males in the ratio of 3:1.

Types ∙ ∙ ∙

Superficial hemangioma: Usually consists of raised, reddish to purple tumor with a distinct margin. Deep subcutaneous hemangioma: Often have a deep bluish hue with normal overlying skin, making diagnosis more difficult. Central: It occurs in the bone.

Clinical and Radiological Features Central The lesion originates either from the periosteum and resorbs the underlying bone or it occurs within the bone as an anomaly of blood vessels in the marrow spaces. Age and sex distribution: It is rarely discovered in the jaws. Most cases are found at birth or arise at early age. Female to male ratio is 2:1.

Figure 11.48 Vascular malformation seen along the

distribution of trigeminal nerve

Benign Tumors

Figure 11.49 Hemangioma of tongue

dome-shaped with normal or blue surface coloration, they seldom blanch. After 6 to 10 months tumors slows down and color changes from red to dull-purple hue. Tumor resolves by the age of 9 years. In some individual permanent change like atrophy, scarring, wrinkling or telangiectasia can occur. Compressibility test is positive continued pressure and squeezing will drive the blood out of the lesion and the swelling crumbles. As soon as the pressure removed, the swelling reappears with refilling. In cases of hemangioma affecting the tongue, there may be loss of mobility of the tongue. It may affect a part of tongue or the entire tongue. PHACE(S) syndrome: Many cases of hemangioma are associated with PHACE (S) syndrome which consist of posterior fossa brain anomalies, hemangioma, arterial anomalies, cardiac defect and coarctation of aorta, eye anomalies and sternal cleft or supraumbilical raphe.

Histopathological Features (Figs 11.51 and 11.52) In it, many small capillaries lined by a single layer of endothelial cells supported by connective tissue stroma are seen. It is comprised of numerous interwining capillarysized vessels, lined by endothelium with relatively flat or plump nuclei; depending on the duration of the lesion. Those with plump endothelial nuclei are younger and often demonstrate mitotic activity. There is endothelial proliferation occurs in this lesion.

Figure 11.50 Strawberry angioma of lip showing irregular

margin and ulceration

Location: It is most commonly seen in head and neck region. The most common site of occurrence are the lips, tongue, buccal mucosa and palate. Strawberry hemangioma (Fig. 11.50): Superficial tumors of the skin appear raised and bosselated with bright red color lesion. They are firm on palpation. Subcutaneous tissues as well as skin are often involved. Swelling is compressible. It slightly protrudes from the skin surface as a sessile hemisphere. It is irregular and there may be small areas of ulceration with scabs. The more superficial ones are often lobulated and will blanch under finger pressure. Deeper lesions tend to be

Figure 11.51 Blood vessels (BV) of capillary hemangioma tend to be small and of irregular shape. They are lined by plump endothelial cells (EC)

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Clinical Features Location: They are more common on face along the distribution of trigeminal nerve (Figs 11.48 and 11.49).

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Port-wine stain: It is capillary, rather than cavernous variety which is usually more bluish. These reddish macular vascular malformations are called as port- wine stain. It generally starts at birth and darkens as the child grows, but it does not really grow. It is common on the face and at the shoulders, neck and buttock. The port wine stain is generally smooth, but could be slightly raised. It is seldom over 5 mm in diameter. It is deep purple-red in color, which may become paler in later life. Color blanches readily on pressure (Fig. 11.53). Figure 11.52 Large dilated cavernous blood spaces

containing blood

As the lesion resolves vascular spaces become less prominent and replaced by fibrous connective tissue.

Management As most of the lesion undergo spontaneous remission, they do not required any treatment for the disease. Systemic corticosteroid: It will reduce the size of lesion. Other drug which can be used are IV vincristine, interferon. Points to Remember

Salmon patch: It is present since birth and usually disappears before the first birthday. It is seen over the forehead, occiput or anywhere in the midline of the body. Venous malformation: They are blue and easily compressible. They are presented as small isolated ecstasies to complex growth which involve multiple tissues. Secondary thrombosis and phlebolith can occur. It appears as a flat or raised lesion of mucosa. Mass may vary in size and may become larger on physical activity or standing, but may reduce in size once the patient is flat on the examining table. Sometimes lesion may increase in size, which can burry the teeth and cause serious deformity and disfigurement. The texture of mucosa may be more or less unchanged, showing an increased vascularity on

Central: Pain is present, compressible swelling, anesthesia of skin supplied by mental nerve, pumping tooth syndrome, aspiration of the lesion produces blood, radiologically honeycomb and soap bubble appearance. Hemangioma of infancy: Strawberry hemangioma, atrophy, scarring, wrinkling or telangiectasia, compressibility test is positive, PHACE(S) syndrome, bosselated with bright red color lesion. Histopathologically single layer of endothelial cells flat or plump nuclei, numerous intertwining capillarysized vessels, plump endothelial nuclei, systemic corticosteroid, vincristine, interferon.

Vascular Malformation In contrast to hemangioma vascular malformation are present at birth and persist throughout the life.

Figure 11.53 Port-wine stain is deep red in color

Benign Tumors

the surface; but in some cases, appearance in pebbly. The mucosal hemangioma is typically a soft, moderately well circumscribed lesion. if associated with large vessels. Arteriovenous malformation: It also called as ‘arteriovenous shunt’ or ‘arteriovenous malformation’. These are high flow lesion result from arterial and venous communication. Palpable thrill or bruit is noticeable. Overlying skin warm to touch. The tumor more often is traumatized and bleeds profusely. It also undergoes ulceration with secondary infection. Types of Arteriovenous Malformation ∙ ∙ ∙

Cirsoid aneurysm: It is a tortuous mass of small arteries and veins linking a larger artery and vein. Varicose aneurysm: It consists of endothelium lined sac connecting an artery and a vein. Aneurysm varix: It is a direct connection between artery and vein.

Histopathological Features Vascular malformation does not show endothelial proliferation. In capillary malformation there is central feeder vessel with radiating, lobular extensions. The lumina are typically small, perhaps to the point of masking the vascular nature of the lesion (Fig. 11.54). In cavernous type there are large dilated blood sinuses which have thin walls each showing endothelial lining. The sinusoidal spaces are usually filled with blood.

When lesion vascular channels are considerably enlarged, the term cavernous hemangioma has traditionally been applied. This differs from capillary hemangioma in that it is less well circumscribed, is larger and is usually deeper in submucosal tissues. Sclerosing hemangiomas: Sluggish blood flow may result in organized or dystrophically calcified thrombi within the dilated vessels. Such hemangiomas are called as sclerosing hemangiomas. The vessels may be arranged in a haphazard or a somewhat lobular pattern and there may be areas with fibrosis of the background stroma. Chronic inflammatory cells may be scattered in multiple foci. Walls are occasionally thickened as a result of adventitial fibrosis and inflammatory cells may be scattered throughout the stroma. In long standing cases thrombus formation may take place, followed by calcification. Such hemangiomas are called as phleboliths.

Management It usually regresses by itself during adolescent period. Laser surgery, cryosurgery by dry ice can also be effective. Sclerosing technique: Intralesional injections of sclerosing chemicals, such as 3 percent sodium morrhuate are effective. Injection of boiling water or hypertonic saline may also be given. Flashlamp pulsed dye laser: It is effective in treatment of port-wine stain. Points to Remember Port-wine stain, Salmon patch, arteriovenous malformation, arteriovenous shunt or arteriovenous malformation, central feeder vessel with radiating, lobular extensions, sclerosing hemangioma, dystrophically calcified thrombi, chronic inflammatory cells, phleboliths, adenventitial fibrosis and inflammatory, sclerosing technique, flashlamp pulsed dye laser.

Struge-Weber Syndrome

Figure 11.54 Capillary hemangioma

It is also called as Struge-Weber angiomatosis or encephalotrigeminal angiomatosis. It is characteristic by hamartomatous vascular proliferation involving tissue and brain. It is causes by persistence vascular plexus around the cephalic portion of the neural tube. It is postulated to be a developmental defect of certain ectodermal and mesodermal elements closely approximated

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Clinical and Radiological Features Port-wine stain or nevus flammeus: A facial port-wine stain in the distribution of the first branch of the trigeminal nerve is present. The port-wine stain is present at birth and is unilateral, but may cross the midline and also involve mucosae. Some patients also have bilateral facial lesions, involvement of the trunk or extremities. Leptomeningeal angiomatosis: There is homolateral leptomeningeal angiomatosis, usually over the posterior parietal and occipital lobes of the cerebral cortex. This angiomatosis can cause convulsive disorder of grand mal type. Characteristic S-shaped intracranial calcifications are found in the leptomeninges within the first few months of life, on CT scans and on X-rays after the age of 2 years. They increase in density until the end of second decade when 50 to 60 percent of patients show this on radiography. Ocular manifestation: Patients with additional involvement of in the distribution of the second branch of the trigeminal nerve have a high-risk of ocular complications like glaucoma, episclera, choroid and retina.

Lymphangioma It is a benign hamartomatous proliferation of lymphatic vascular tissue. It is a hamartoma, rather than a neoplasm. In it abnormal vessels are filled with clear protein rich fluid containing lymph rather than blood. Types ∙ ∙ ∙ ∙

Superficial: It presents as a circumscribed lesion, which appears as small blisters and slightly elevated skin patches. Lymphangioma simplex (capillary lymphangioma): It consists of small capillary sized vessels. Cavernous lymphangioma: It composed of larger dilated lymphatic vessels. Cystic lymphangioma: They are large, cystic, and translucent and may be seen in the neck, mediastinum or axilla. These are called as cystic hygroma.

Clinical Features Age: They may be present at birth with majority becoming clinically evident early in life, but with a small number not being manifested for a number of years.

Histopathological Features

Location: It may occur alone or in association with hemangioma or other anomalous blood vessels. It occurs in dorsal and lateral borders of tongue, lips, gingiva and buccal mucosa.

There is excessive number of dilated blood vessels in middle and deep dermis. There is vascular dilatation in gingival lesion.

Appearance: Usually the disfigurement is noticed by the child parents. Occasionally, the vesicles may be rubbed with clothes, get infected and become painful.

Management

Signs: They are soft masses that dissect along the tissue planes and turn out to be more extensive than anticipated. The surface of the lesion may be smooth or nodular. Color ranging from normal mucosal pink to bluish and may be quite translucent. They are liable to trauma. Due to this, lesions are subjected to periodic attacks of inflammation which cause the swelling to become larger and tender for the time being. Aspiration yields lymph that is high in lipid. If the tongue is affected, enlargement may occur and the term ‘macroglossia’ is applied. On the tongue, it is characterized by irregular nodularity of the surface of the tongue with gray and pink, grapelike projection. They are often elevated and nodular in appearance and may have the

Oral features: The gingiva exhibits slight vascular hyperplasia.

Port-wine stain is managed by newer Flashlamp pulsed dye lasers. Care should be taken while performing surgical procedure in affected area. Points to Remember Struge-Weber angiomatosis, port-wine stain or nevus flammeus, leptomeningeal angiomatosis, gingiva exhibits slight vascular hyperplasia, high-risk of ocular complications like glaucoma, episclera, choroid and retina, excessive number of dilated blood vessels, newer flashlamp pulsed dye lasers.

Benign Tumors

same color as the surrounding mucosa. Lip involvement and its deformity is called as macrocheilia. Cystic hygroma is the term used for large lymphangiomas spreading into and distending the neck, are called as cystic hygroma.

Histopathological Features (Figs 11.55 and 11.56) Capillary types are composed of proliferation of thin walled endothelium-lined channels, primarily devoid of erythrocytes.

Cavernous type is characterized by presence of dilated sinusoidal endothelium lined vascular channels, devoid of erythrocytes. Occasional channels may be filled with blood and it is called as hemangio-lymphangioma.

Management Treatment is generally not indicated for small lesions. Surgical removal of the bulk of the lesion can be done. Partial or complete spontaneous involution is occasionally noted. Points to Remember Benign hamartomatous proliferation of lymphatic vascular tissue, disfigurement, surface smooth or nodular, macroglossia, irregular nodularity, cystic hygroma, macrocheilia, proliferation of thin walled endothelium-lined channels, dilated sinusoidal endothelium, hemangio-lymphangioma.

Glomus Tumor

Figure 11.55 Lymphangioma showing lymph channels with this wall consisting of thin endothelial lining. Channels contain lymph

It is also called as ‘glomangioma’. It is a rare neoplasm derived from glomus cells. They are thought to be closely related to hemangiopericytoma. The glomus is arteriovenous anastomosis that controls the blood supply and temperature of the skin and certain deeper tissues. These functions appear to be mediated in some way by the rich nerve supply and by certain epithelioid cells that ensheath the arteriole of the glomus. The epithelial cells are thought to be comparable to pericytes.

Clinical Features Location: The tumor probably arises from these specialized glomus cells and occurs most frequently under the nails and on the body surface especially in head and neck area. In the oral cavity the lesion is usually located on the dorsum of the tongue, lip, palate, buccal mucosa and tongue. Age: The tumor usually occurs in the 5th decade. Size: They are small lesions, rarely exceeding a cm in diameter. Symptoms: They often give rise to attacks of very severe pain and are exquisitely tender. Pain is stabbing in nature. Signs: The color varies from deep red to purple or blue.

Histopathological Features Figure 11.56 Lymphangiomas high power

It consists of glomus cells and these may reproduce to some extent, the structure of the normal glomus (Fig. 11.57).

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Histopathological Features It shows tightly packed cells which surrounds endothelial line vascular channels. Arrangement of cells is haphazard with round to ovoid nuclei. The blood vessels show irregular branching which results in ‘staghorn’ and ‘anterlike’ appearance. Dense reticulin network also surrounds the vessels (Fig. 11.58).

202

Points to Remember Derived from pericytes cells, slow growing, painless mass, nasal obstruction and epistaxis, tightly packed cells, round to ovoid nuclei, staghorn’ and ‘anterlike’ appearance. Figure 11.57 Glomus cells (G) of glomus tumor

In some cases, glomus cell may be arranged around the blood vessels in a manner suggesting hemangiopericytoma or the blood vessels may be so prominent as to resemble cavernous hemangioma.

Management It is a benign tumor and removal effects cure. Points to Remember Glomangioma, arteriovenous anastomosis, pericytes, attacks of very severe pain, color varies from deep red to purple or blue, glomus cells arranged around the blood vessels.

Hemangiopericytoma It is rare tumor derived from pericytes cells with processes which encircles endothelial cells of capillaries.

Clinical Features Age: Adults are more commonly affected. Location: It is most common seen in lower extremities with some cases also occurs in head and neck region. Intraorally it is seen in buccal mucosa. Appearance: It is slow growing, painless mass. In some cases of superficial region there may be vascular pigmentation. Symptoms: In nasal cavity it may occur result in symptoms of nasal obstruction and epistaxis.

Figure 11.58 Hemangiopericytoma showing staghorn pattern

Benign Tumors

Nasopharyngeal Angiofibroma

NEURAL TISSUE

It is rare vascular and fibrous tumor like lesion that occurs only in nasopharynx. It is locally destructive behavior. This tumor expands medially via sphenopalatine foramen. It can also extent to maxillary sinus, middle cranial fossa and oral cavity.

Neuroma

Clinical Features

Pathogenesis

Age and sex distribution: It occurs exclusively in males in age group of 2nd decade.

Nerve damage may result from fracture, dissection, removal of cyst, nerve avulsion for neuralgia or even extraction of teeth. It is an overgrowth of severed nerve, attempting to regenerate when the scar tissue or misalignment of a fractured nutrient canal blocks the distal end. Proliferating nerve forms unorganized collection of nerve fibers, composed of varying proportion of axons, perineural connective tissue and Schwann cells.

Symptoms: Nasal obstruction and epistaxis are common symptoms. Radiological features: Anterior bowing of posterior wall of maxillary sinus is characteristic features of this disease.

Histopathological Features It consist of dense fibrous connective tissue that contain numerous dilates, thin walled blood vessels (Fig. 11.59). Vascular components are more prominence at periphery than at the center.

Management Surgical excision should be done. Points to Remember Nasal obstruction, epistaxis anterior bowing of posterior wall of maxillary sinus, numerous dilates, thin walled blood vessels.

It is also called as amputation neuroma or traumatic neuroma. It is not a true neoplasm, but an exuberant attempt at repair of a damaged nerve trunk.

Clinical Features Location: It is typically occurs near the mental foramen, on the alveolar ridge in edentulous areas or on the lips and tongue. Age and sex distribution: It is seen middle age adults and more commonly seen in the women. Appearance: It appears as a small nodule or swelling of the mucosa. Symptoms: Due to the pressure applied by enlargement of the tangled mass in its bony cavity, severe pain may be experience. It may have reflex neuralgia with pain referred to the eye, face and head. It is a slow growing reactive hyperplasia that seldom becomes large, rarely in excess of 1 cm in diameter.

Histopathological Features It shows mass of irregular and interlacing neurofibrils and Schwann cells, situated in connective tissue stroma of either scanty or plentiful proportion (Fig. 11.60). The proliferating nerve fibers themselves may occur either in small discrete bundles or spread diffusely throughout the tissue. Mild chronic inflammatory cell infiltrate can also be present.

Management Figure 11.59 Dilated blood vessels present in fibrous stroma

in case of nasopharyngeal angiofibroma

Simple excision of nodule along with proximal portion of the involved nerve.

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Signs: It usually occurs singly and jaw expansion (Fig. 11.61) may lead to perforation. The mass is firm on palpation. It is nonproductive to aspiration. 204

Histopathological Features (Figs 11.62 and 11.63) Schwannoma is proliferation of Schwann cells. The tumor is well encapsulated with epineurium making the capsule. It is composed of two types of tissues: Antoni type A and Antoni type B. Antoni type A: This pattern is distinctive and well organized. It is made up of cells with elongated or spindle

Figure 11.60 Traumatic neuroma showing neurofibrils and

Schwann cells

Points to Remember Amputation neuroma, unorganized collection of nerve fibers, small nodule or swelling, severe pain, reflex neuralgia, irregular and interlacing neurofibrils and Schwann cells, mild chronic inflammatory cell infiltrate.

Neurilemmoma It is also called as Schwannoma, perineural fibroblastoma, neurinoma and lemmoma. It is of neuroectodermal origin, arising from Schwann cells that make the inner layer covering the peripheral nerves.

Figure 11.61 Jaw expansion seen in neurilemmoma

Clinical Features Age and sex distribution: It occurs at any age, from very young to very old, with equal frequency in both the sexes. Location: The tumor usually occurs in the subcutaneous tissue, but internal organs such as stomach may be affected. Intraorally, mandible is the most commonly affected site for central lesion. Other sites which can be involved in these tumors are palate, floor of mouth and buccal mucosa. It is a slowly growing lesion and is usually of long duration at the time of presentation. Symptoms: Usual complain is lump in jaw, in case of central tumor and single circumscribed nodule, in case of soft tissue lesions. Paresthesia may be associated, which occurs anterior to the tumor. Pain is localized to the tumor site.

Figure 11.62 Neurilemmoma showing Antoni type A cells

surrounding verocay body

Benign Tumors

of view multiple endocrine neoplasia syndromes (MEN) 2b type is important which is discussed below.

Types ∙ ∙ ∙

MEN 1: Benign tumor of pancreatic islet, adrenal cortex, parathyroid gland and pituitary gland MEN 2A (Sipple syndrome): There is development of adrenal pheochromocytomas and medullary thyroid carcinoma MEN 2B: It have mucosal neuroma which involve oral mucous membrane.

Clinical Features Figure 11.63 Antoni A area is composed of spindle shaped

Schwann cells arranged in interlacing fascicles. There is characteristic nuclear palisading in between two compact rows of well aligned nuclei; the cell processes form eosinophilic acellular areas verocay bodies. Mitotic figures also may be present

Oral neuroma: The neuroma is most common on the lips, tongue and buccal mucosa. They produce Bumpy Lips since the neuroma present at birth or may develop later appear as small elevated sessile nodules on the vermilion producing puffy lips. On the tongue they are commonly present on the anterior third. Bilateral neuroma can occur commissural mucosa. Pheochromocytomas of adrenal gland: These are bilateral and multifocal. The tumor cells secrete catecholamine which results in profuse sweating, intractable diarrhea, headache, flushing, heart palpitation and severe hypertension. Medullary carcinoma of thyroid gland also occur which arise from the parafollicular cells.

shaped nuclei, which are aligned to form a characteristic palisading pattern, while intercellular fibers are arranged in parallel fashion between rows of nuclei. When such clusters of palisaded cells occur around eosinophilic substance they create verocay body. The eosinophilic material substance is made up of cytoplasmic processes of Schwann cells and duplicated basement membrane.

Histopathological and Laboratory Features

Antoni type B: It does not exhibit this characteristic palisading, but rather a disorderedly arrangement of cells and fibers, with vacuolated areas.

Neuroma is characterized by marked hyperplasia of nerve bundles with prominent thickening of perineurium is also seen.

Management

Laboratory finding: Serum or urinary level of calcitonin are elevated in patient who is having thyroid gland medullary carcinoma.

Surgical excision is the treatment of choice. Points to Remember

Management

Schwannoma, slowly growing lesion, lump in jaw, paresthesia, jaw expansion, perforation, Antoni type A, Antoni type B, intercellular fibers are arranged in parallel, verocay body.

Prophylactic removal of thyroid gland should be done as there are chances of medullary carcinoma.

Multiple Endocrine Neoplasia Syndromes (MEN Syndrome) This is a group of syndromes characterized by tumors of various endocrine organs occurring in association with a variety of other pathologic features. In oral physician point

Points to Remember Oral neuroma, bumpy lips, puffy lips, pheochromocytomas of adrenal gland, medullary carcinoma of thyroid gland, marked hyperplasia of nerve bundles with prominent thickening of perineurium, level of calcitonin are elevated, prophylactic removal of thyroid glands.

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Paraganglioma 206

Types of Paraganglioma

It is inherited as a simple autosomal dominant trait with variable penetrance. It arises from the connective tissue sheath of Schwann cells and axons. There are three sites of origin: within the inferior dental canal, in the substance of the bone and beneath the periosteum. Solitary lesions are termed as neurofibroma. Neurofibroma can be part of neurofibromatosis which is having multiple lesions.

Carotid body tumor: These are located in carotid body.

Clinical Features

Jugulotympanic paraganglioma: These are present in temporal bone and middle ear.

Age and sex distribution: It occurs at any age but is found more in younger group with no sex predilection.

Clinical and Radiographic Features

Location: Most commonly affected sites are trunk, face and extremities.

It is also called as carotid body tumor, chemodectoma, glomus jugulare tumor, glomus tympanicum tumor. Paraganglia are specialized tissue of neural crest origin which are associated with autonomic nerves and ganglia throughout the body.

Age and sex distribution: It is seen in middle age adults with no sex predilection. Location: The head and neck area is common site for this tumor. Carotid body tumor: It is seen at bifurcation of internal and external carotid artery. It is slow growing painless mass below the angle of jaw in neck region. Angiography will demonstrate characteristic vascular lesion. Jugulotympanic paraganglioma: In these symptoms includes dizziness, tinnitus, hearing loss and cranial nerve palsies.

Appearance: It may appear as numerous sessile or pedunculated, elevated smooth surfaced nodules of variable size, which are scattered over the skin surface (Fig. 11.64). Solitary lesion: They are soft, painless lesion varying in size from small nodules to larger masses. Elephantiasis neuromatosa: In other forms, there are deeper, more diffuse lesions which are often of greater proportion than superficial nodules and are sometimes referred to as elephantiasis neuromatosa. In some cases, loose overgrowth of thickened, pigmented skin may hang in folds.

Histopathological Features It is characterized by round or polygonal epitheloid cells that are organized in nest or Zellballen. The Zellballen are large and irregular in shaped. The tumor is vascular and surrounded by thin fibrous capsule.

Management It includes surgery, radiation therapy depending on extent of tumor. Points to Remember Carotid body tumor, seen at bifurcation of internal and external carotid artery, Jugulotympanic paraganglioma, dizziness, tinnitus, polygonal epitheloid, nest or Zellballen.

Neurofibroma or Neurofibromatosis It is also called, von Recklinghausen’s disease of skin or fibroma Molluscum.

Figure 11.64 Neurofibromatosis of left side of face involving

orbital region

Benign Tumors

The plexiform variant of neurofibromatosis feels like a bag of worms. Café au lait spots: In addition majority of the patients exhibit asymmetric areas of cutaneous pigmentation, often described as cafe au lait spots.

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Crowe’s sign: Axillary freckling present in neurofibromatosis is called Crowe’s sign. Lisch bodies: These are translucent brown pigmented spots on the iris.

Oral Manifestations Location: It may occur in mandibular canal, buccal mucosa and alveolar ridge, and below the periosteum. The central lesion may have multiple lesions, occurring in both jaws simultaneously, expanding and filling the maxillary sinus. Solitary central lesion may infrequently be associated with brown spots on skin.

Figure 11.65 Herringbone (H) pattern seen in neurofibromas

Appearance: There are discrete, nonulcerated nodules, which tend to be of the same color as the normal mucosa. Symptoms: It may produce pain or paresthesia, if associated with mandibular nerve. Sign: It may expand and perforate the cortex, producing a swelling that is either hard or firm on palpation. Macroglossia may be there due to diffuse involvement of the tongue.

Radiological Features In some cases it is well demarcated or poorly demarcated unilocular or multilocular radiolucency. There is also enlargement of mandibular foramina, mandibular canal and increase in dimension of coronoid notch.

Histopathological Features (Figs 11.65 and 11.66) Neurofibroma is proliferation of fibroblasts surrounding the neurites as well as of neurites themselves. It is composed of proliferation of delicate spindle cells with thin wavy or serpentine nuclei intermingled with neurites in an irregular pattern as well as delicate interwining connective tissue fibrils. Fibers give rise to herringbone or storiform pattern. It consists of collagenous tissue and nerve fibers, the later running throughout the lesion. Mast cells are typically found in this lesion.

Figure 11.66 Neurofibroma (high power)

Cellular and myxoid patterns predominate. Melanocytes are sometimes found in addition to mast cells. Plexiform neuromas: Some of the lesions may consist of masses of convoluted nerves the individual axons of which are surrounded by thickened perineurium. Lesion of this type is called as plexiform neuromas.

Management Solitary lesion may be surgically excised. Facial lesion of neurofibromatosis should be removed with the help of carbon dioxide laser and dermabrasion. It has got high potential for malignant change.

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Points to Remember 208

von Recklinghausen’s disease of skin, numerous sessile or pedunculated, elevated smooth surfaced nodules, elephantiasis neuromatosa, bag of worms, Café au lait spots, Crowe’s sign, Lisch bodies, unilocular or multilocular radiolucency, enlargement of mandibular foramina, mandibular canal, proliferation of fibroblasts, thin wavy or serpentine nuclei intermingled with neuritis, herring bone or storiform pattern, mast cells, melanocyte, plexiform neuromas, carbon dioxide laser and dermabrasion.

Ganglioneuroma It is same like neuroblastoma, but in it, differentiated cells are numerous. It grows less rapidly than the neuroblastoma and when fully differentiated, it is depicts benign characteristic. The fully differentiated ganglioneuroma is composed of cells that are very much like the normal cells. Numerous nerve fibers and well differentiated nerve bundles are present.

Congenital Granular Cell Tumor It is also celled as congenital epulis’, congenital epulis of newborn’. Congenital granular cell tumor (CGCT) is an uncommon congenital tumor. It is a benign gingival soft tissue lesion of unknown etiology. The original first description of the lesion was dated in 1871 by Neumann. It is also termed as congenital granular cell epulis of newborn.

Location: The CGCT shows very peculiar site predilection for the maxillary anterior alveolar ridge though cases have been reported in mandibular anterior region. The ratio of occurrence of CGCT in maxillary/ mandibular jaw is 3:1. Canine-incisor region is most frequently affected. Size: The size of the mass varies from a few millimeters to nine centimeter in diameter. Appearance: Clinically congenital granular cell tumor may mimic oral teratoma-epignathus and melanotic neuroectodermal tumor of infancy, as well as other possible diagnoses, such as fibroma, lipoma, leiomyoma, rhabdomyoma, rhabdomyosarcoma, peripheral giant cell granuloma, pyogenic granuloma, neurofibroma, myxoma, hemangioma, lymphangioma, and alveolar lymphangioma. The large lesions are of therapeutic concern as they interfere with feeding and respiration of the infant. Signs and symptoms: Patient complains of smooth swelling. The swelling appears as a pink-to-red polypoid mass on the alveolar ridge which is usually round or oval, showing irregular lobulation. Base is usually pedunculated, but it may be sessile. Usually size is 2 cm or less, although lesions as large as 7.5 cm have been reported. Larger lesion may be large enough to protrude from the mouth (Figs 11.67 and 11.68).

Histogenesis The histogenesis of the Neumann’s tumor/congenital granular cell tumor has long been debatable as various authors suggested different source of origin of the tumor. The proposed source of origin includes undifferentiated mesenchymal cell, odontogenic epithelial, pericytic, and fibroblastic, histiocytes, nerve-related, smooth muscle, and primitive mesenchymal cells.

Clinical Features Age and sex distribution: It presents at birth as a congenital epulis, i.e. fibrous mass arising from the gingival mucosa of the maxilla or mandible. There is a female preponderance of 8:1 perhaps indicating a hormonal component in its development.

Figure 11.67 A fibrous mass arising from the anterior

alveolar/gingival mucosa of the maxilla

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Figure 11.68 Specimen of congenital granular cell tumor

Figure 11.69 Congenital granular cell tumor showing uniform distribution of polygonal granular cells arranged in sheets

Histopathological Features (Figs 11.69 to 11.72) Histologically, CGCT shows uniform distribution of large ovoid cells with fine granular eosinophilic cytoplasm and this cell may show arrangement as ribbons nest or as pattern less diffuse sheets as seen in our case. The cells have ill defined cell outlines and intercellular bridges. Electron microscopic examination of the granular cells of CGCT shows heterogeneous electron-dense granules, lysosomes, and cytoplasmic lipid droplets. The CGCT and granular cell/myoblastoma tumor have similar microscopic features. However, the latter is less vascular and is typically covered by hyperplastic squamous cell epithelium. In older tumors, these cells may become elongated and separated by fibrous connective tissue. Immunohistochemical analysis shows the tumor cells to be negative for S–100 proteins.

Management The large lesions are of therapeutic concern as they interfere with feeding and respiration of the infant. The recommended treatment is surgical excision under local or general anesthesia, although spontaneous regression. Recurrence or malignant change is rare. Points to Remember Congenital epulis, mimic oral teratoma-epignathus, interfere with feeding, pink-to-red polypoid mass, pedunculated, sessile, uniform distribution of large ovoid cells, fine granular eosinophilic cytoplasm, heterogeneous electrondense granules, lysosomes, cytoplasmic lipid droplets.

Figure 11.70 Congenital granular cell tumor showing granular

cells with indistinct cell outlines and eosinophilic granular cytoplasm

Melanotic Neuroectodermal Tumor of Infancy The tumor is of neural crest origin. In the past, it is been thought to be arise from odontogenic epithelium and retina. Due to this fact these tumors are called as pigmented ameloblastoma, melanoameloblastoma, melanotic ameloblastoma, retinal anlage tumor, and melanotic progonoma. But this origin is now proven that is not present so all above term should be discarded and it should be called as melanotic neuroectodermal tumor of infancy.

Clinical and Radiological Features Age and sex distribution: It occurs in infants under the age of six months, with equal sex distribution.

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A

NSE - Positive

Figure 11.72 Congenital epulis of newborn showing

fibroblasts

B

CD 68 -Negative Figures 11.71A and B Immunohistochemical study of CGCT shows positivity for neuron specific enolase (NSE) and negative for CD 68 marker

Location: Maxilla is more commonly affected than mandible. It is more common in anterior region. Sign: The tumor forms a mass that expands the bone without pain and tenderness. It has rapidly growing, nonulcerated, darkly pigmented lesions. The color of lesion can be blue or black. Radiological features: The tumor destroyed underlying bone causing displacement of developing teeth.

Histopathological Features (Fig. 11.73) It consists of both pigmented and nonpigmented cells.

Figure 11.73 Melanotic tumor of infancy

Pigmented cells are cubical or rather flattened and have large, pale nuclei. The cytoplasm contains melanin in the form of minute rod shaped particles, often aggregated into large masses that obscure all the internal cellular details. These pigmented cells are arranged in solid groups or form a lining of the small cleft like spaces. Unpigmented cells are small, round well stained nucleus that nearly fills the cell body. They occur in groups, often within the spaces lined by the pigmented cells. The central portion of the alveolar spaces contain many neuroblast like cells which show little cytoplasm and exhibit a round deeply staining nucleus.

Benign Tumors

Laboratory finding: There is high urinary level of vanillylmandelic acid (VMA).

Management

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Conservative surgical excision or simple curettage can be done. Points to Remember Pigmented ameloblastoma, expands the bone without pain, destroyed underlying bone, pigmented cells are cubical, unpigmented cells are small, round, high urinary level of vanillylmandelic acid.

MUSCLE Leiomyoma

Figure 11.74 Leiomyoma

It is a benign tumor derived from smooth muscle and is found in a variety of anatomic sites like skin and subcutaneous tissues.

Types ∙ ∙ ∙

Solid leiomyomas Vascular leiomyomas (angiomyomas) Epitheloid leiomyomas.

Clinical Features Age and sex distribution: It occurs in middle decades of life. Males are affected more commonly than females. Location: It usually occurs in uterus. It is uncommon in oral cavity due to general absence of smooth muscles except in blood vessel walls and circumvallate papillae of tongue. The smooth muscle of the arrectores pilorum may be a source of cheek tumor. In oral cavity, it can occur in lip, tongue, palate and cheek. Appearance: It is a slow growing, painless lesion, which is superficial and often pedunculated. Symptoms: The patient may complain of sore throat or tumor in the throat. In some cases, there may be pain. Signs: In most of the cases, the lesion is small. It does not ulcerate and resembles the normal mucosa in color and texture.

Histopathological Features (Figs 11.74 and 11.75) It is composed of interlacing bundles of smooth muscle fibers, interspersed by varying amounts of fibrous connective tissue.

Figure 11.75 Leiomyoma showing fiber bundles with blunt

ended nucleus (cigar-shaped nucleus)

The muscle nuclei are typically spindle shaped with blunt ends. The bundles of fibers appear to form whorls because of their fascicular arrangement in varying planes. There may be palisading arrangement of the nuclei. Angioleiomyoma: In some cases, origin from the blood vessels is obvious since the vessels are enlarged with thick muscular walls and around the tumor muscle fibers are dispersed in a circular manner. It is called as angioleiomyoma or angiomyoma. Rarely, angiomyoma may contain adipose tissue, then it is called as angiomyolipoma. Epitheloid leiomyoma composed of epitheloid cells rather than spindle cells.

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Management It is treated by conservative surgical excision of the tumor. 212

Points to Remember Slow growing, painless lesion, sore throat, interlacing bundles of smooth muscle fibers, muscle nuclei, spindle shaped, fascicular arrangement in varying planes, angioleiomyoma, epitheloid leiomyoma.

Rhabdomyoma It is a benign tumor of striated muscle origin. Term was introduced by Zenker. Rare but have predilection for head and neck region.

Types ∙ ∙

Adults rhabdomyomas Fetal rhabdomyomas.

Clinical Features Age and sex distribution: Adult type most commonly occurs in 5th decade of life with male to female ratio of 2:1. Fetal types usually occur in young children. Location: It mostly occurs in the head and neck regions. The most common sites of occurrence, intraorally, are the floor of the mouth, tongue, soft palate, buccal mucosa and lower lip. Symptoms: It is painless and slowly growing. Laryngeal and pharyngeal lesion may lead to airway obstruction. Appearance: It presents as a well circumscribed tumor mass which may have a known duration of months or even several years.

Histopathological Features (Fig. 11.76) The nucleus is vesicular and cells with several nuclei are sometimes seen. Based on histological features, there are two types seen, i.e. adults and fetal. In adult type, the tumor is composed of large, round cells that have granular, eosinophilic cytoplasm and show irregular cross striations. The cytoplasm is rich in glycogen and glycoprotein. This type also demonstrates peripheral vacuolization which results in spider web appearance. In fetal type is characterized by immature skeletal muscles in varying stages of development and undifferentiated mesenchymal cells.

Figure 11.76 Rhabdomyoma showing deeply eosinophilic polygonal cells with small peripherally placed nuclei and few intracellular vacuoles

Management It is excised conservatively usually enucleating with ease. Points to Remember Striated muscle origin, painless, well circumscribed tumor mass nucleus is vesicular, spider web appearance.

Granular Cell Tumor It is also called myoblastic myoma, granular cell myoblastoma and granular cell schwannoma. Initially it is thought to be derived from striated muscles. So this is called as granular cell myoblastoma. But, these tumors may be found in areas like breast and skin, where the striated muscles are absent. In neural theory it is proposed that these tumors are derived from the connective tissue of nerves and hence was called as granular cell neural fibroma. It is also believed to be originated from Schwann cells so it is called as granular cell schwannoma. Some authors state that it is derived from stem cells with a leiomyofibrillogenic capacity, which may be some type of specialized smooth muscle cells peculiar to certain tissue, that are found in characteristic sites of the tumor.

Benign Tumors

Clinical Features

Management

Age and sex distribution: It can occur at any age and females are affected more commonly than males.

Conservative surgical excision is recommended.

Location: Most common site of occurrence is dorsum of tongue followed by skin, lips, breast, subcutaneous tissue, vocal cord and floor of mouth. Appearance: Lesion which is found on tongue is usually single firm, submucosal nodule within the substance of the tongue itself. Signs: The size of the tumor varies from a few millimeters to centimeters. Lesion is not ulcerated and may have normal covering or may exhibit some clinical leukoplakia.

Histopathological Features (Fig. 11.77) The lesion is composed of two types of cells granular cells and satellite cells. It is made up of strands and fascicles of cells which are large, 20 to 40 microns in diameter and show an extremely granular eosinophilic cytoplasm, interspersed with a collagenous stroma and covered with hyperplastic lingual mucosa. The large granular cells are called as Abrikossoff myocytes. These granules may be fine or in some instance may be very coarse. In some cases, the tumor cells have been found to be arranged in concentric whorls around myelinated nerve fibers.

Points to Remember Myoblastic myoma, firm, submucosal nodule, granular cells, satellite cells, granular eosinophilic cytoplasm, Abrikossoff myocytes, consesvative surgical excision.

GIANT CELL LESION It is applied for the lesions, containing giant cells. Giant cells are large multinucleated cells of different origins. It is chiefly a tumor of long bones, occurring at the epiphyseal end involving the adjacent metaphysis. It is an extremely uncommon tumor of head and neck and creates a lot of confusion with respect to diagnosis. It exhibits variable clinical and histopathological features ranging from benign to malignant. Foreign body giant cells, Langhan’s giant cells, Touton giant cells, tumor giant cells, are various types of giant cells apart from the miscellaneous types of giant cells such as Reed Sternberg cells of Hodgkin’s lymphoma.

Origin of Giant Cells Different theories are given to describe the origin of giant cells in these lesions: Giant cells might be derived from the proliferating giant cells associated with the resorption of deciduous tooth roots. But for this association of the lesion in transition period, i.e. from of deciduous to permanent tooth should be there: but such association is found in only few cases. Another theory states that it originated from the endothelial cells of capillaries. To support this theory: there is a common occurrence of giant cells in vascular channels, suggesting that they arise from endothelial cells. Sapp found that giant cells, ultrastructurally, contain a sufficient number of features in common with osteoclasts. This concludes that they represent a slightly modified form of the cells.

Giant Cell Tumors It is debatable that true giant cell tumor occur in the jaw. Giant cell tumor usually found in long tubular bone.

Clinical Features Figure 11.77 Granular cell myoblastoma showing abundant

cytoplasm

Age: It is most frequently seen in 3rd and 4th decades, it is unusual in patients less than 20 years.

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Location: The commonest sites for giant cell tumor are the lower end of the femur, upper end of the tibia and lower end of the radius. In the oral cavity, it is rare and if found it is in jaw. Signs and symptoms: The principle symptoms are swelling of the bone accompanied in some cases by pain. The swelling may be tender and egg shell crackling can be elicited in large tumors.

Histopathological Features The tumor forms a maroon or reddish brown fleshy mass that replaces the spongiosa of the bone. It consists of numerous giant cells lying in cellular matrix composed of spindle-shaped cells and scanty collagen. The giant cells are large with numerous vesicular nuclei situated towards the center of the cells leaving a clear area of cytoplasm around the periphery (Fig. 11.78). The cytoplasm is granular and vacuoles are often present. There is even distribution of giant cells throughout the lesion.

Management The usual method of treatment is curettage, but this is followed by a high recurrence rate.

Common Giant Cell Lesions of the Oral Cavity (Ipe Varghese et al) Microbial lesions: Tuberculosis, leprosy, Actinomycosis, sarcoidosis. Tumor and tumor-like lesions: Central giant cell granuloma, peripheral giant cell granuloma, giant cell fibroma, giant cell tumor, osteosarcoma, rhabdomyosarcoma, Hodgkin’s lymphoma. Cystic lesions: Traumatic bone cyst, aneurysmal bone cyst. Metabolic lesions: Hyperparathyroidism. Osteodystrophic lesions: Noonan-like multiple giant cell lesion syndrome. Miscellaneous lesions: Cherubism, Paget’s disease, fibrous dysplasia.

Peripheral Giant Cell Granuloma It is also called as peripheral giant cell reparative granuloma, giant cell epulis, osteoclastoma and peripheral giant cell tumor. It is five times more common as compared to central giant cell granuloma. It seems to originate from either periodontal ligament or mucoperiosteum.

Points to Remember

Etiology

Egg shell crackling, a maroon or reddish brown fleshy mass, numerous giant cells.

It is an unusual response of tissue to injury. The trauma may be caused by tooth extraction and dental irritation. It can occur in chronic infections. It may appear under the stimulus of increased circulating parathormone, i.e. primary and secondary hyperparathyroidism.

Clinical Features (Figs 11.79 to 11.81) Age and sex distribution: It is most often seen over 20 years of age, with an average of 45 years. Females are affected twice as common as males. It is predominant in white persons. Location: It occurs on gingiva and alveolar mucosa, most frequently anterior to molars. It is common in mandible than maxilla.

Figure 11.78 Giant cell tumor showing many giant cell

dispersed in cellular background

Appearance: In early stage, it appears as discoloration and slight swelling of the buccal aspect of the gingiva. Later the lesion increase in size and becomes rounded and very often pedunculated.

Benign Tumors

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Figure 11.79 Peripheral giant cell granuloma showing growth

in hour-glass manner

Figure 11.81 Peripheral giant cell (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Lesions with much fibrous tissue are paler. It may feel from soft to hard. The lesions vary in size from 0.5 cm to 1.5 cm in diameter. It is vascular or hemorrhagic and sometimes ulceration is also present. There may be tenderness on palpation. In edentulous patients, it may present as a vascular, ovoid or fusiform swelling of the crest of the ridge, seldom over 1 to 2 cm in diameter or there may be granular mass of tissue which seems to be growing from the tissue covering the slope of the ridge. Radiographic features: There is cupping resorption of bone seen on the radiograph.

Histopathological Features (Figs 11.82 and 11.83) Figure 11.80 Peripheral giant cell granuloma showing a

dumb-bell/hour-glass shaped growth joining buccal and lingual interdental papillae of maxillary molars

Sometimes, it grows in an hour-glass manner, with the waist of the lesion between two teeth and the globular extremities presenting buccally and lingually. Signs: The color of the lesion is usually dark red or maroon color. If sufficient amount of hemosiderin exists near the periphery, the lesion is bluish; otherwise it is red and or pink.

Multinucleated giant cells and young connective tissue spindle shaped cells are scattered throughout the granulation tissue in delicate reticular and fibrillar connective tissue stroma. Giant cells are usually more numerous and may be large. The matrix consists of spindle shaped cells with oval nuclei, similar to those if the giant cells. Capillaries are numerous around the periphery of the lesions and giant cells, sometimes, may be found in it. Extravagated erythrocytes and varying amounts of hemosiderin are also present. The overlying epithelium

Textbook of Oral Pathology

is normal, but sometimes it may shows acanthosis and ulceration.

Management

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Excision with borders of normal tissue with entire base of the lesion and elimination of chronic irritant should be done to avoid recurrence. Points to Remember

Figure 11.82 Peripheral giant cell granuloma showing covering epithelium, a subepithelial normal connective tissue zone and lesional tissue showing giant cells

Hour-glass manner, dark red or maroon color, vascular, ovoid or fusiform swelling, cupping resorption of bone, multinucleated giant cells and young connective tissue spindle shaped cells, capillaries are numerous, extravagated erythrocytes, varying amounts of hemosiderin, excision with borders of normal tissue.

BIBLIOGRAPHY

A

B Figures 11.83A and B Peripheral giant cell granuloma (Courtesy:

Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

1. Campanacci M. Bone and Soft Tissue Tumors. Springer Verlag, Wien; New York; 1999.pp.391-414. 2. Dalambiras S, Boutsioukis C, Loannis DMD. Peripheral osteoma of the maxilla: Report of an unusual case. Oral Surgery, Oral Medicine, Oral Pathology, and Endodontology. 2005;100(1):E19-E24. 3. Ethunandan M, Mellor TK. Hemangiomas and vascular malformation of the maxillofacial region: review: Br J Oral Maxillofac Surg. 2006;44:263-72. 4. Fonseca, Marciani, Turvey. Oral and maxillofacial surgery. 2nd edn, 2008;604-5. 5. Frassica FJ, Waltrip RL, Sponseller PD et al. Clinicopathologic features and treatment of osteoid osteoma and osteoblastoma in children and adolescents. Orthop Clin North Am. 1996;27:559-74. 6. Gitelis S. et al. Benign Bone Tumors, Instructional Course Lectures 1993,45:426-46. Huvos, Andrew, Bone Tumors: Diagnosis, Treatment and Prognosis. WB Saunders Co, 1991. 7. Giudici MA, et al. Cartilaginous Bone Tumors, Radiologic Clinics of North America. 1993;31(2):237-59, Bullough, Peter. Orthopaedic Pathology (3rd), London. Times Mirror International Publishers T Limited, 1997. 8. Golding JSR. The natural history of osteoid osteoma: A report of twenty cases. J Bone Joint Surg. 1954;36-B:218-29. 9. Head and Neck Surgical Pathology. Lippincott Williams and Wilkins; 2000.p.736. 10. Makley JT, Dunn MJ. Prostaglandin synthesis by osteoid osteoma. Lancet. 1982;2:42, Letter. 11. Mayur Chaudhary, Meena Kulkarni: Osteoid osteoma of mandible, JOMFP. 2007:11(2);52-5. 12. Orzincolo C, Ceruti S, Cardona P et al. Diagnostic imaging of osteoid osteoma. Radiol Med. 1995;92:351-7.

Benign Tumors 13. Rana RS, Wu JS, Eisenberg RL. “Periosteal Reaction.” Amer Jou of Roen. 2009;193(4): W259-272. 14. Ribas Mde O, Martins WD, de Sousa MH, Zanferrari FL, Lanzoni T. Osteochondroma of the mandibular condyle: literature review and report of a case. J Contemp Dent Pract. 2007; 8(4):52-9.

15. R Rajendran, B.Shivapathasundaram. Shafer’s Textbook of Oral Pathology, 6th Edn, 2009;150-1. 16. Saito T, Utsunomiya T, Furutani M, Yamamoto H. Osteochondroma of the mandibular condyle: a case report and review of the literature. J Oral Sci. 2001; 43(4):293-7.

MULTIPLE CHOICE QUESTIONS 1. Which one of the following tumor is of epithelial origin: a. Fibroma b. Lipoma c. Papilloma d. Osteoma

11. Antoni type A and Antoni type B tissue seen in: a. Neuroma b. Glomus tumor c. Neurilemmoma d. Neurofibroma

2. Mark the odd one from the following: a. Papilloma b. Keratoacanthoma c. Nevus d. Myxoma

12. “ Café-au-lait” spots seen in: a. Ganglioneuroma b. c. Rhabdomyoma d.

3. ‘Self healing carcinoma’ refers to: a. Verruciform xanthoma b. Keratoacanthoma c. Nevus d. Fibroma

13. Multinucleated giant cells and young spindle shaped cells seen in: a. Peripheral giant cell granuloma b. Pyogenic granuloma c. Teratoma d. Pregnancy tumor

4. Multiple papillomas are associated with: a. Cowden’s syndrome b. Ramsay hunt syndrome c. Proteus syndrome d. Nager’s syndrome 5. Foam cells are seen in: a. Keratoacanthoma c. Adenoma

b. d.

14. Staphylococcus or streptococci involved in: a. Pyogenic granuloma b. Teratoma c. Both d. None

Verruciform xanthoma Both

15. Dysphagia seen in: a. Torus palatines c. Torus mandibularis

6. ‘Self healing carcinoma’ refers to: a. Verruciform xanthoma b. Myxoma c. Keratoacanthoma d. Nevus

Osteoid osteoma Nevus

9. ‘Pumping tooth syndrome’ is present is: a. Osteochondroma b. Hemangioma c. Lymphangioma d. Neuroma 10. Strawberry angioma and Salmon’s patch are types of: a. Cavernous hemangioma b. Arterial hemangioma c. Central hemangioma d. Capillary hemangioma

Osteochondroma None

17. Rhabdomyoma is a tumor originating from: a. Nerve tissue b. Smooth muscle c. Striated muscle d. Vascular endothelium

b. d.

b. d.

16. Reed Sternberg cells are characteristically seen in: a. Alpha thalassemia b. Glandular fever c. Hansans disease d. Hodgkins disease

7. ‘Whorl and cartwheel’ pattern of fibroblasts seen in: a. Giant cell fibroma b. Fibrous epulis c. Chondroma d. Fibrous histiocytoma 8. ‘Slip sign’ seen in: a. Lipoma c. Fibroma

Fibroma Neurofibroma

18. Abtropfing affect is seen in: a. Junctional nevus b. c. Apthous ulcer d.

Pemphigus Erythema multiforme

19. Satellite lesion with locally invasive property is seen in: a. Chronic hypertrophic candidiasis b. Leukoplakia c. Dental ulcers d. Hemangioma 20. Oral hairy leukoplakia is seen in which of the following conditions: a. AIDS b. Hepatitis B c. Smokers keratitis d. Candidiasis

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218

21. Acanthosis with intraepithelial vacuolation and hyperkeratosis is seen in: a. Hairy tongue b. Hyperplastic candidiasis c. Speckeled leukoplakia d. Desquamative gingivitis 22. Which of the following is not a features of torus mandibularis: a. Common in mongoloid b. Present on the lingual surface of mandible below the mylohyoid line c. Usually bilateral d. May or may not associated with torus palatinus 23. Hemangiopericytoma resembles: a. Hemangioma b. Glomous tumor c. Ewings tumor d. Plasmacytoma 24. Which of the following epithelial changes commonly signify precancerous condition: a. Dyskeratosis b. Hyperkeratosis c. Parakeratosis d. Acanthosis 25. A patient has filmy white opalescence bilaterally on buccal mucosa, the lesion fades on stretching. The most likely diagnosis is: a. White sponge nevus b. Leukoplakia c. Lichen planus d. Leukoedema 26. Papillomatous tongue is observed in: a. Lymphangioma b. Hyalinia cutus et mucosa syndrome c. Fetal face syndrome d. Tuberous sclerosis

27. Storiform pattern of fibrous tissue is seen in: a. Fibrosarcoma b. Malignant fibrous histiocytoma c. Neurofibroma d. Ameloblastic Fibroma 28. Which of the following shows pseudo epitheliomatous hyperplasia: a. Sq cell carcinoma b. Basal cell carcinoma c. Verrucous carcinoma d. Granular cell myoblastoma 29. White rough pedunculated lesion on palate is most likely: a. Pleomorphic adenoma b. Papilloma c. Nevus d. Fibroma 30. Which of the following is a connective tissue tumor: a. Lipoma b. Melanoma c. Carcinoma d. Papilloma 31. Etiology of neurofibromatosis is: a. Genetic b. Viral c. Injury d. Endocrine 32. Hodgkin disease is considered to be: a. Follicular reticulosis b. Inflammatory disease c. Chronic granulomatous disease d. A malignant neoplasm 33. Presence of verocay bodies and having predilection for occurrence in the tongue are seen in: a. Granular cell myoblastoma b. Neurilemmoma c. Neurofibroma d. Metaplasia

12

Premalignant Lesions and Conditions Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline        Â

Concept of precancer Terminology and Definitions Field cancerization Leukoplakia Erythroplakia Carcinoma in situ Bowen’s disease Smoker’s palate or stomatitis nicotina

CONCEPT OF PRECANCER The concept of a two-step process of cancer development in the oral mucosa, i.e. the initial presence of a precursor (premalignant, precancerous) lesion subsequently developing into cancer, is well-established. It is applied to that altered state of tissue which often, but not always, has high potential to undergo malignant transformation. Some benign lesions or conditions, for varying length of time, also generally precede oral cancer. Interestingly, these lesions or conditions share the same etiological factors with oral cancer, particularly the use of tobacco and exhibit same site and habit relationship. Many of them show high potential to become cancer and are therefore termed as precancerous. It is especially important to remember that a premalignancy is not guaranteed to eventually transform into cancer, as is often but erroneously believed. Many precancers, in

      Â

Snuff dipper lesion Cigarette smoker’s lip lesion Lichen planus Erosive lichen planus Oral submucous fibrosis Dyskeratosis congenita Lupus erythematosus

fact, do so only in a small proportion of cases, forcing the clinician to make some very real choices relative to the management of such lesions. Individuals with oral precancer run 69 times greater risk of developing oral cancer as compared to tobacco users who do not have precancer.

TERMINOLOGY AND DEFINITIONS Terminology and definitions currently used in the field of oral precancer are still debated. The use of the terms ‘oral precancer’ and ‘oral premalignancy’ is bit confusing and poses few difficulties, since this terminology signifies an invariable development of carcinoma from precursor diseases. Several researchers have tried to come to consensus over internationally accepted terminologies and definitions since many decades. The World Health Organization (WHO) has accepted the latest international proposed terminology and definitions,

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subdividing oral precancer into precancerous lesions and precancerous conditions. 220

Oral Precancer is Distinguished by WHO Precancerous lesion: It is defined as a morphologically altered tissue in which cancer is more likely to occur, than its apparently normal counter parts. For example, Leukoplakia, erythroplakia, mucosal changes associated with smoking habits, carcinoma in situ, Bowen disease, and actinic keratosis, cheilitis and elastosis. Precancerous condition: It is defined as a generalized state or condition associated with significantly increased risk for cancer development. For example, oral submucous fibrosis (OSMF), syphilis, sideropenic dysplasia, oral lichen planus, dyskeratosis congenita and lupus erythematosus (Table 12.1).

Field Cancerization The concept of field cancerization also should be understood with precancerous lesions and conditions. Slaughter et al in 1953 postulated the concept of field cancerization. It was hypothesized that the entire epithelial surface of the upper aerodigestive tract has an increased risk for the development of (pre)malignant lesions because of multiple genetic abnormalities in the whole tissue region. It is described as the histologically altered epithelium surrounding tumor samples taken from the upper aerodigestive tract. It is considered to be the result of exposure to carcinogens that caused multiple genetic abnormalities in the whole tissue region and due to widespread migration of transformed cells through the whole aerodigestive tract. Two types of migration might be involved in the concept of this last theory: ∙ ∙

Migration of tumor cells by, for example, saliva (micrometastases); or Intraepithelial migration of the progeny of the initially transformed cells. However, many researchers have

Table 12.1 Premalignant lesions and conditions (WHO 1978)

Precancerous lesions

Precancerous conditions

Leukoplakia

Submucous fibrosis

Erythroplakia

Actinic keratosis

Palatal lesions in reverse smokers

Lichen planus Discoid lupus erythromatosus

since attempted to use recent molecular techniques to elucidate the mechanism that underlies the clinical phenomenon of field cancerization.

LEUKOPLAKIA The term leukoplakia originates from two Greek wordsleuko, i.e. white and plakia, i.e. patch. It is defined as any white patch on mucosa, which cannot be rubbed or scraped off and which cannot be attributed to any other diagnosable disease. It may also be defined as a keratotic white lesion of oral mucosa that cannot be characterized clinically or histopathologically as any other disease entity. Different definition of leukoplakia is described in Table 12.2.

Classification It is desirable to record separately the various forms of leukoplakia and for this purpose, the following subdivisions are recommended.

Table 12.2 Definition of leukoplakia

A white patch or plaque that cannot be characterized clinically or pathologically as any other disease

WHO 1978

Whitish patch or plaque that cannot be characterized, clinically or pathologically, as any other disease and which is not associated with any other physical or chemical causative agent except the use of tobacco

First International Conference on oral leukoplakia. Malmo, Sweden, 1984

A predominantly white lesion of the oral mucosa that cannot be characterized as any other definable disease

International Symposium, Uppsala, Sweden,1996

A predominantly white lesion of the oral mucosa that cannot be characterized as any other definable disease

International Symposium, Uppsala, Sweden

A predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion

WHO (1997)

Not defined-no distinction is made from other white patches

WHO (2005)

Premalignant Lesions and Conditions

Clinical Classification (WHO 1980) ∙

∙

Flow chart 12.1 Etiopathogenesis of leukoplakia

Homogeneous: Lesions that are uniformly white – Smooth – Furrowed( fissured) – Ulcerated Nonhomogeneous: Lesions in which part of the lesion is white and rest appears reddened. – Nodular – speckled.

221

According to Banoczy ∙

∙

∙

Leukoplakia simplex: A uniform raised plaque formation, varying in size, with regular edges. It corresponds to homogeneous type of leukoplakia. Leukoplakia erosiva: A lesion with slightly raised, rounded, red and/or whitish excrescence, that may be described as granules or nodules

Leukoplakia verrucosa: It is characterized by verrucous proliferation raised above the mucosal surface. Points to Remember WHO (1998) described subdivisions of leukoplakia as: • Thin, smooth leukoplakia (preleukoplakia older terminology): Translucent thin gray soft flat plaques usually with sharply demarcated borders. • Thick, fissured leukoplakia: Two-thirds of white plaques has distinctly white appearance (from thickening of keratin layer), fissured and are leathery to palpation. • Granular, verruciform leukoplakia: Lesions have surface irregularities of nodular or granular nature with verrucous appearance. • Erythroleukoplakia: Lesion showing intermixed red and white areas, because the epithelial cells are so immature that they no longer are able to produce keratin. Etiology Tobacco, alcohol, chronic irritation, candidiasis, electromagnetic reaction or galvanism, syphilis, nutritional deficiency, condition causing xerostomia, hormones, drugs, virus, idiopathic or cryptogenic leukoplakia.

Etiopathogenesis (Flow chart 12.1) Local Factors Tobacco: It refers to dried leaves of nicotina tobaccum. Tobacco is used widely in two forms. It can be used in

smokeless tobacco like chewable tobacco and oral use of snuff or it can be used as smoking tobacco such as cigar, cigarette, bidi and pipe. When tobacco is chewed, various materials leach out of it, such as tobacco tars and resins. These are the extracts of tobacco, containing various chemical constituents such as Nitroso-no-rnicotine, nicotine, pyridine, picoline and collidin. All these chemical constituents as well as the alkaline pH of snuff (8.2 to 9.3) act as local irritants and are related to the alterations of mucosa. Smokeless tobacco is believed to result in chemical damage that produces sublethal cell injury within the deeper layers of oral epithelium. This in turn, induces concomitant epithelial hyperplasia. Smoking tobacco is harmful as this smoke contains polycyclic hydrocarbons, beta-naphthylamine, nitrosamines, carbon monoxide, nicotine, etc. which act as source of irritation. The heat produced by smoking tobacco also plays a major role. Exposure to heat results in alteration of tissue. The initial signs of heat-induced alteration of tissue are increased reddening and stippling of mucosal surface. As the use of irritant continues with the exposure to heat, minute white and red striations are formed and the tissue surface may appear slightly swollen. The striations may be caused by increased capillary proliferation and keratin formation.

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With continued irritation, the lesion precipitates with circumscribed configuration. 222

Alcohol: The prevalence of leukoplakia is higher among the regular and occasional drinkers than the non-drinkers. It causes irritation and burning sensation of oral mucosa, when applied locally. Alcohol facilitates the entry of carcinogen into exposed cells and thus alters the oral epithelium and its metabolism. But most alcohol consumers use tobacco in some form or the other. Sanguinarine: Persons who used toothpaste or mouth rinse containing herbal extract sanguinarine, develop leukoplakia. This type of leukoplakia sanguinaria associated with keratosis. Chronic irritation: Continuous trauma or local irritation in the oral cavity is suspected as a causative agent for leukoplakia. The source of irritation or trauma may be any, viz. malocclusion, ill-fitting dentures, sharp broken teeth, hot spicy food, root piece, etc. The usual site to such irritation is the buccal mucosa and less often the alveolar ridge. Chronic irritation must be intense enough to induce surface epithelium to produce and retain keratin. Leukoplakia is a protective reaction of the traumatized mucosa against chronic irritation. Mechanical factor in combination with other thermal and chemical factors, account for the etiology of more than 40 percent cases of leukoplakia. Candidiasis: The presence of Candida albicans has been reported very frequently in association with leukoplakia, more commonly with nodular type. Candidal leukoplakia may be associated with other local factors, such as tobacco smoking, denture wearing or occlusal friction. Tobacco smoking may result in candidal colonization because of increased keratinization, reduced salivary immunoglobulin-A concentration or depressed polymorphonuclear leukocyte function. Electromagnetic reaction or galvanism: Galvanism is the generation of current due to difference in the electrical potential of two dissimilar metals. Galvanic current may arise in mouth between dissimilar, opposing or adjacent metallic restorations. Patient’s complaint may range from a mere metallic taste to persistent pain, due to chronic inflammation of adjacent oral mucosa to even neuralgic pain. These mucosal changes may promote malignant transformation of leukoplakia.

Regional and Systemic Factors Syphilis: It is regarded as a predisposing factor for the development of leukoplakia. White patches are often seen on tongue in tertiary syphilis. Spirochete, the causative agent for syphilis has predilection for the actively mobile tissues of tongue. These tissues are heavily involved during secondary stage of syphilis which leads to diffuse vasculitis and progresses to obliterative endarteritis, eventually resulting in a circulatory deficiency to the lingual papillae. This causes atrophy of filiform and fungiform papillae and results in bald, smooth lingual surface. Shrinkage of the lingual musculature may also occur resulting in a wrinkled surface. With the protective papillae missing, the dorsum of tongue is left extremely susceptible to oral irritation and leukoplakia frequently develops on it. Leukoplakic involvement may be minor or severe and it may be diffuse or localized. In many cases, leukoplakia is of dysplastic variety. Carcinoma of tongue frequently develops in such cases of leutic glossitis. Nutritional deficiency: Deficiency of vitamin A is known to produce metaplasia and keratinization of certain epithelial structures. Hence, it may be causative factor for leukoplakia. Patients with leukoplakia show lower serum levels of vitamin A. Vitamin B complex deficiency has also been suggested as a predisposing factor. It might be related to alteration in the oxidation pattern of the epithelium, making it more susceptible to irritation. In some cases of sideropenic anemia leukoplakia can occur. Condition causing xerostomia: Salivary gland diseases, anticholinergic drugs and radiation can cause some cases of leukoplakia. Hormones: It is difficult to demonstrate significance of male and female sex hormone deficiency and endocrine dysfunction in the etiology of leukoplakia. Drugs: Some drugs like anticholinergic, antimetabolic and systemically administered alcohol may predispose for the leukoplakia. Virus: Two types of viruses have been linked with leukoplakia, viz. herpes simplex virus (HSV) and human papilloma virus (HPV). A specific increase in cell-mediated immunity to HSV was observed in dysplastic leukoplakia. HPV associated antigen has also been demonstrated in cases of leukoplakia. These viruses are believed to induce

Premalignant Lesions and Conditions

mucosal changes by altering the DNA and chromosomal structure of the cells and by inducing proliferation of such altered cells. Idiopathic or cryptogenic leukoplakia: In a small proportion of cases, no underlying cause has been found. Such lesions are termed as idiopathic (cryptogenic) leukoplakia. These lesions have higher potential for malignant transformation.

Clinical Features Sex and age distribution: It occurs more commonly in older age group, i.e. 35 to 45 years and above. Males are affected more frequently than females, due to direct consequence of tobacco habit. Prevalence in India is 0.2 to 4.9 percent. Location: It can occur anywhere on the oral mucosa. Buccal mucosa and commissures are more commonly involved. The lesion is regarded as commissural, if it extends posteriorly from labial commissure over a distance of about 2 cm, in triangular shape and as buccal, if it involves the central zone of buccal mucosa in the molar region and along the occlusal line. In males commissural involvement occurs more frequently than buccal one with the latter’s being the commoner site in females (Fig. 12.1). Lip lesions are more common in men and tongue lesions are more common in women. The involvement of various sites depends upon the type of tobacco habit. Sublingual keratosis refers to leukoplakia occurring in floor of mouth and ventral surface of tongue.

Figure 12.1 Commissural leukoplakia

Appearance: The extent of involvement may vary from small, well-localized, irregular patches to diffused lesions involving considerable portion of oral mucosa. Multiple patches of leukoplakia may vary from nonpalpable, faintly translucent, white area to thick fissured papillomatous indurated lesion areas of involvement are not uncommon (Fig. 12.2). The surface of the lesion is often finely wrinkled or shriveled in appearance and may feel rough on palpation. Lesion may be white or yellowish white, but with heavy use of tobacco may assume brownish color. Ebbing tide type: Some leukoplakias that occur in the floor of the mouth are referred to as ebbing tide type, since they appear similar to the undulations left on the sand by the ebbing tide. It occurs due to loose binding and consequent movement of the mucosa in the floor of mouth. Symptoms: Some patients may report a feeling of increased thickness of mucosa. Those with ulcerated and nodular type may complain of burning sensation. Enlarged cervical lymph nodes may signal occurrence of metastasis. Sometimes the leukoplakic changes may be reversed by merely removing the source of irritation. Pre-leukoplakia: A different entity termed as preleukoplakia has been distinguished. It is a low grade or very mild reaction of the mucosa appearing as grayish white but not completely white lesion with slight lobular pattern and indistinct borders blending with the adjacent normal mucosa.

Figure 12.2 Leukoplakia on right side of buccal mucosa

showing homogeneous pattern

223

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Sharp’s Staging 224

• S tage I: Earliest lesion—nonpalpable, faintly translucent, white discoloration. • Stage II: Localized or diffuse, slightly elevated plaque of irregular outline. It is opaque white and may have fine granular texture. • Stage III: Thickened white lesion showing induration and fissuring.

Clinical Types Homogeneous: It is also called leukoplakia simplex. It accounts for 84 percent of cases. It is usually, localized lesions of extensive white patches present a relatively consistent pattern throughout. However, sometimes the surface lesion may be described as corrugated, with pattern of fine lines, or wrinkled or papillomatous surface. It is characterized by raised plaque formation consisting of single or group of plaques varying in size with irregular edges. They are usually white in color but may be yellowish white or yellow. Leukoplakia seen amongst clay pipe smokers and betel quid chewers are generally of homogeneous type. They have no red component (Figs 12.3 and 12.4). Ulcerated leukoplakia: It occurs in 13 percent of cases. It is characterized by red area, which at times exhibit yellowish areas of fibrin, giving the appearance of ulceration. White patches are present at the periphery of the lesion. It is seen exclusively at commissures and anterior part of buccal mucosa. Sometimes, it manifests as ulceration

Figure 12.3 Homogeneous leukoplakia seen on right buccal

mucosa

Figure 12.4 Homogeneous leukoplakia (Courtesy: Dr Aparna

Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

with minimum keratinization. Sometimes, it is associated with pigmentation of varying intensity, usually on the periphery of the lesion. Heat produced during smoking also contributes to the occurrence of pigmentation. Nodular leukoplakia: It is also called ‘leukoplakia erosiva’ or ‘speckled leukoplakia’. A mixed red white lesion is seen in which small keratotic nodules are scattered over an atrophic patch of oral mucosa. Nodules may be pinhead sized or even larger. It has got a high malignant potential. Verrucous leukoplakia: It is also called leukoplakia verrucosa. It is characterized by verrucous proliferation above the mucosal surface. The most common sites are buccal mucosa, alveolar mucosa, and tongue, floor of mouth, gingiva and lips. The disease is most commonly seen in elderly women and is usually detected several years after its occurrence due to its slow growing nature. It is seen in 6th and 7th decades of life. It is seen on alveolar mucosa and cheek. It is a white lesion with a broken up surface due to multiple papillary projections that may be heavily keratinized. They may be accompanied by homogeneous leukoplakia on other oral mucosal surfaces. It begins as a simple solitary hyperkeratosis, but tends to become multifocal over varying period of time. It is slow growing, persistent and irreversible. In the course of time erythematous component may develop in the lesion. Later, it becomes exophytic and wart-like and transforms into a lesion that is clinically and microscopically identical to verrucous carcinoma or squamous cell carcinoma.

Premalignant Lesions and Conditions

Oral florid papillomatosis: Extensive lesions of verrucous leukoplakia are called ‘oral florid papillomatosis’. 225

Points to Remember Leuko (white) and plakia (patch), commissural type is triangular in shape, sublingual keratosis, nonpalpable, faintly translucent, white area to thick fissured papillomatous indurated lesion, ebbing tide type, feeling of increased thickness of mucosa, pre-leukoplakia, homogeneous has localized lesions of extensive white patches present a relatively consistent pattern throughout, ulcerated leukoplakia, nodular leukoplakia, verrucous leukoplakia, verrucous proliferation above the mucosal surface, oral florid papillomatosis.

Staging of Leukoplakia (OLP Staging) A clinical staging system for oral leukoplakia (OL system) on the lines of TNM staging was recommended by WHO (2005) taking into account the size (L) and the histopathological features (P) of the lesion.

Figure 12.5 Frictional keratosis (Courtesy: Dr Sangamesh

Halawar, Reader, Department of Oral Pathology, CDCRI, Rajnandgao, Chhattisgarh, India)

Staging of Leukoplakia • • • •

• • • •

Lx: Size not specified L1: Single or multiple lesions together 4 cm – Px: Epithelial dysplasia not specified – P0: No epithelial dysplasia – P1: Mild-to-moderate dysplasia – P3: Severe epithelial dysplasia Stage I: L1P0 Stage II: L2P0 Stage III: L3P0 or L1/L2 P1 Stage IV: L3P1 or any LP2.

Figure 12.6 Leukoplakia showing acanthosis of stratum

spinosum

Histopathological Features (Figs 12.5 to 12.8)

Surface Changes

It should be understood that leukoplakia is purely a clinical terminology and histopathologically it is reported as epithelial dysplasia. WHO in 2005 proposed four grades of epithelial dysplasia based on architectural disturbances and cytological atypia. ∙ Squamous hyperplasia – benign lesion ∙ Mild dysplasia – better prognosis ∙ Moderate dysplasia ∙ Severe dysplasia.

Keratosis: There occurs keratinization of mucosal epithelium that is normally non-keratinized or there is an increase in the keratin layer in the areas that are normally keratinized. Hyperorthokeratinization/hyperkeratinization: There is abnormal increase in thickness of orthokeratin layer or stratum corneum over the surface. Hyperparakeratinization: Superficial epithelial cells are flat and acidophilic with pyknotic nuclei. There is increased

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226

A Figure 12.7 Leukoplakia showing 1-hyperorthokeratosis, 2-acanthosis, 3-juxta epithelial inflammatory cells, 4-broad blunt rete pegs (Courtesy: Reader, Department of Oral Pathology, VPDC and H, Karalapur, Sangli, Maharashtra, India)

thickness of parakeratin layer, exceeding the normal thickness.

Epithelial Changes Vacuolar degeneration: Cytoplasmic structure is indistinct and the nuclei are pushed to the cell periphery. Vacuolar degeneration may occur in the stratum spinosum or stratum germinatum. B

Acanthosis: An increase in the number of cells of stratum spinosum (spinous layer or prickle cell layer) leading to the abnormal thickening of the layer. Basal cell hyperplasia: An increase in the number of cells in the basal layer of epithelium. Intraepithelial edema: There can be intracellular edema (hydropic degeneration) which consists of swollen, rounded epithelial cells with a honeycomb like cytoplasm, but with the same staining affinity for the nucleus or intercellular edema (spongiosis) which consists of dilation of intercellular spaces and disruption of intercellular junctions due to accumulation of fluid between the epithelial cells.

Dysplastic Changes All leukoplakias do not lead to malignancy. Only a few of them do so. There are various features which indicate

Figures 12.8A and B Leukoplakia (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

probability of leukoplakia progressing to malignancy which are called as dysplastic features and lesions which show such features are said to be having epithelial dysplasia. Epithelial dysplasia is reported in 3 percent of snuff induced leukoplakias and 16 percent of smoking habitrelated to leukoplakia. Nodular leukoplakia shows higher frequency of epithelial dysplasia as compared to others. It is usually graded into mild, moderate and severe categories, depending upon the degree and extent of involvement of the epithelium. Histological diagnosis is established, if two or more of the following signs are present.

Premalignant Lesions and Conditions

Microscopic Features Associated with Oral Epithelial Dysplasia Architectural (tissue) changes: • Loss of polarity • Abnormal orientation of epithelial cells • Basal cell hyperplasia • Increased cellular density • Bulbous drop-shaped rete pegs • Disordered maturation from basal to squamous cells • Abnormal stratification of the epithelium • Dyskeratosis Cellular changes: • Abnormal variation in nuclear size (anisonucleosis) • Abnormal variation in cell size (anisocytosis) • Increased nuclear/cytoplasmic ratio • Enlarged nuclei and cells • Hyperchromatic nuclei • Increased mitotic figures • Abnormal mitotic figures (abnormal in shape or location) • Nuclear and cellular pleomorphism • Increased number and size of nucleoli.

Cytological Features of Dysplasia Loss of polarity and abnormal orientation of epithelial cells: Basal epithelial cells are usually cuboidal or short columnar. They are arranged perpendicular to basement membrane. In dysplastic lesions this arrangement is changed. Cells become haphazardly arranged on the basement membrane. Basal cell hyperplasia: Basal cells are most active cells that have capacity to divide. As in dysplasia there is increased mitosis the basal cells divide to form a large number of basaloid cells. Increased cellular density: Because of increased mitosis there is increase in the cell density in the epithelium Bulbous drop-shaped rete pegs: As basal cell proliferation induces the change in basal part of rete pegs and they appear very broad. This gives rete peg bulbous shape of drop shape. Disordered maturation from basal to squamous cells: Epithelial cells gradually mature as they move towards the surface. As they move they differentiate or mature to start forming keratin and depositing it. This process is called as

maturation. In dysplasia this process is hampered. Cells fail to mature and retain their basal cell appearance leading to immature morphology sometimes. Abnormal stratification of the epithelium: As maturation is affected, different layers of the epithelium are not clearly demarcated. The cells are not defined in strata and appear almost similar to each other. Dyskeratosis: Keratinization is a process where epithelial cells mature to accumulate keratin proteins. This process is always prominent in the stratum corneum or uppermost layer of the epithelium. In dysplasia, epithelium shows dyskeratosis where this process is abnormal and it may start from the lower level itself. So in such lesion keratinized epithelial cells may be found in prickle cell layer where they are usually not present. This is called as individual cell keratinization. Sometimes, a group of flattened epithelial cells form tight concentric rings leading to formation of keratin pearl may be seen.

Cellular Changes Abnormal variation in nuclear size (anisonucleosis): In dysplasia, there is profound changes in the nucleus. These include variation in nuclear size and shape. Nucleus becomes enlarged with prominent nucleoli. All these changes indicate that nucleus is very active. Abnormal variation in cell size (anisocytosis): Cytoplasm also shows great variation is size and shape. Few cells become very big gaining giant proportions. Increased nuclear/cytoplasmic ratio: Normal nuclear/ cytoplasmic ratio is in the range of 1:4 to 1:6. In malignancy and premalignant lesions, this ratio is altered as there is increase in size of nucleus and cytoplasm. Nucleus and cytoplasm become almost equal in volume. Abnormal mitotic figures (abnormal in shape or location): In addition to increased mitosis, there is formation of abnormal mitosis leading to formation enlarged tripolar or tetrapolar mitotic figures. Sometimes nucleus divides without division of cytoplasm (poikilocarynosis). Normally, mitosis is limited to basal cells. But in dysplasia even upper layers show mitotic figures.

Connective Tissue Changes Chronic inflammatory cell infiltration is seen in connective tissue of leukoplakia in 50 percent cases. Sub mucosal, homogeneous, eosinophilic material is usually seen in

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connective tissue. Also, there is replacement of degenerated elastic fibers by a hyaline fibrous tissue. This is known as hyaline degeneration. It is seen in 10 percent of cases. 228

Grading of Dysplasia There are various schemes for grading dysplasia. These are WHO system, Ljubljana system Smith and Pindborg system of photographic standards, etc.

WHO Dysplasia System • Hyperplasia with increased number of cells: This may be in the spinous layer (acanthosis) or in the basal and parabasal cell layer (basal cell hyperplasia). The architecture of the epithelium is preserved, and there is no cellular atypia. • Dysplasia with three grades: 1. Mild dysplasia: Architectural disturbance is limited to the lower-third of the epithelium, accompanied by cytological atypia. 2. Moderate dysplasia: Architectural disturbance extends into the middle-third of the epithelium, accompanied by an upgraded degree of cytological atypia. 3. Severe dysplasia: Architectural disturbance is greater than two-thirds of the epithelium with associated cytological atypia or architectural disturbance in the middle-third of the epithelium with sufficient cytological atypia to upgrade from moderate-to-severe dysplasia. • Carcinoma in situ: Full or almost full thickness of the epithelium shows architectural disturbance, accompanied by pronounced cytological atypia. Atypical mitotic figures and abnormal superficial mitoses are present.

Ljubljana Classification System Simple hyperplasia: A benign hyperplastic process with retention of the normal pattern of the epithelium which is thickened because of an increased prickle cell layer. The cellular components of the basal and parabasal region of the epithelium (one to three layers) remain unchanged. There is no cellular atypia. Abnormal hyperplasia: Basal and parabasal cells are augmented to a degree which constitutes up to onehalf of the total epithelial thickness. It is important that stratification is fully retained. Occasionally, more than this proportion of the epithelium may be involved by the

hyperplastic cells without significant atypical nuclear changes. Nuclei in the cells of the augmented basal and parabasal layers may be moderately enlarged but still maintain a uniform distribution of nuclear chromatin. Occasional typical mitosis may be found in or near the basal layer. Small numbers of epithelial cells, less than 5 percent, are dyskeratotic. Atypical hyperplasia (risky epithelium): Epithelium demonstrates a recognizable alteration of epithelial cells towards malignancy, but not to such a degree as is seen in carcinomatous cells. Stratification is still preserved in the general epithelial structure. The nuclei are enlarged and the nuclear contour may be irregular with marked variations in staining intensity. The nuclear/cytoplasmic ratio is increased. Mitotic figures are increased but not numerous, and they are found within the two-thirds of the epithelium above the basement membrane. They are rarely, if ever, abnormal. Dyskeratotic cells are frequent. Civatte bodies (apoptotic cells) may be present. Carcinoma in situ: This shows the features of carcinoma without invasion. Stratification of the epithelium as a whole is lost. Marked cellular alterations of the type found in atypical hyperplasia are present to a considerably greater degree. Many mitotic figures present throughout the epithelium, including its upper one-third and abnormal mitoses are frequently found.

Malignant Potential The term malignant transformation is used to denote development of oral cancer from pre-existing leukoplakia (Table 12.3). Malignant transformation occurs in 0.3 percent to 10 percent of cases. It is higher in women (6%) than men (3.9%), due to involvement of endogenous factors. Leukoplakia associated with chewing habit of tobacco shows higher rate of transformation as compared to others. In buccal mucosa and commissural region 1.8 percent malignant transformation occurs. In lip and tongue region 16 percent to 38.8 percent malignant transformation occurs. Nodular dysplasia has got higher risk of malignant transformation than other clinical types. Idiopathic leukoplakia and candidaassociated leukoplakia also come under high risk (Table 12.4). If the following features are present, there is a high risk of malignant transformation: ∙ Persistence of lesion for several years ∙ Female patient ∙ Lesion situated on the margins, base of tongue and floor of mouth

Premalignant Lesions and Conditions Table 12.3 WHO (2005) classification for prognosis

Phases of leukoplakic lesions based on malignant risk and prognosis • Phase I: Thin, smooth leukoplakia – better prognosis • Phase II: Thick, fissured leukoplakia • Phase III: Proliferative verrucous leukoplakia (PVL) – higher malignant transformation rate • Phase IV: Erythroleukoplakia – poor prognosis

Table 12.4 Malignant transformation potential of various lesions

∙ ∙

Disease

Malignant potential

Proliferative verrucous leukoplakia

++++++

Erythroplakia

++++++

Nicotine palatinus in reverse smokers

+++++

Oral submucous fibrosis

+++

Speckled, granular (non-homogeneous) leukoplakia

+++

Actinic cheilitis

+++

Smooth, thick (homogeneous) leukoplakia

++

Smokeless tobacco keratosis

+

Lichen planus

+

Erosive lesions Combination of above factors.

Management Elimination of etiological factor: Various etiological factors like smoking, sharp, broken down teeth should be stopped or removed. You should also exchange faulty metal restorations and metal bridge and elimination of other etiological factors like syphilis, alcohol, etc. Vitamin therapy: It has a protective effect on the epithelium. Daily requirement is 4000 IU. It is given orally, parentally or topically in a therapeutic dose of 75000300000 IU for 3 months. Vitamin A may be used topically after painting the lesion with podophyllin solution (it inhibit mitosis). Vitamin A + Vitamin E: This therapy is given to inhibit metabolic degradation. 13-cis-retinoic acid: It is a synthetic analog of vitamin A; usually given in high doses of 1.5 to 2 mg/kg body

weight for 3 months. If relapse occurs then low doses of 13-cis-retinoic acid 0.5 mg/kg body weight are given for 9 months. It may be given with β carotene (this drug may produce a variety of toxic effects which include facial erythema, dryness, peeling of skin, conjunctivitis and hypertriglyceridemia). Antioxidant therapy: Considerable data shows that β-carotene supplementation can be beneficial for treatment of oral leukoplakia. Vitamin A palmitate: Short-term treatment with vitamin A palmitate along with aromatic retinoid of all trans -B-A vitamin acid plus B-cis-B-A vitamin acid may show healing and improvement. Nystatin therapy: It is given in candidal leukoplakia. 500000 IU twice daily plus 20 percent borax glycerol or 1 percent gentian violet or mouth rinses with chlorogen solution. Vitamin B complex: It is given as supplement in cases of commissural and lingual lesion. Antimycotic preparation: The antimycotic preparation canesten and pimafucin have also been effective. Panthenol: Panthenol lingual tablet and oral spray may be used against glossitis and glossodynia, in case of tongue lesion. Estrogen: In some cases, administration of estrogen can be helpful. Surgical management: To give proper treatment microscopic examination is necessary for which biopsy is taken. The most meaningful sites for taking biopsy specimen are the areas that display greater surface irregularities such as cracks and fissures and those associated with erythematous areas. We can go for conventional surgery or cryosurgery or fulguration or LASER.

ERYTHROPLAKIA It is also called erythroplasia of Queyrat. Erythroplakia is a persistent velvety red patch. Reddish color results from absence of surface keratin layer and due to presence of connective tissue papillae containing enlarged capillaries projected close to the surface. The first mention of a non-hemorrhagic red patch of an upper aerodigestive tract site was in a vocal cord lesion reported in 1852.

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The first truly descriptive paper of erythroplakia, however, was a 1911 report by Queyrat, of a red macule on the glans penis of a syphilitic patient. It was Queyrat who coined the term erythroplasia. About the same time, Rubin used the term incipient carcinoma to describe the microscopic features of erythroplakia, most common histopathological diagnosis as carcinoma in situ, based on his experience with lesions of uterine cervix.

Definition It is term used for chronic red mucosal macule which cannot be given any other specific diagnostic name and cannot be attributed to traumatic, vascular or inflammatory causes. Classification ∙ ∙ ∙

Homogeneous Erythroplakia interspersed with patches of leukoplakia Speckled or granular.

Etiology It can be idiopathic. Alcohol and smoking can be causative factor for erythroplakia. A secondary infection or superinfection with candidiasis may be associated with dysplastic oral mucosal cells. Candida albicans has often been demonstrated in erythroleukoplakia lesions and the red component of these lesions (often the white component as well) diminishes or disappears after antifungal therapy, in at least some cases.

Clinical Features Age and sex predilection: Erythroplakia has been observed to show male predilection and most common in 6th and 7th decade of life.

Figure 12.9 Erythroplakia on right side showing red lesion

the number of underlying blood vessels through which the blood flows, which in turn may be secondary to localized inflammatory or immunological responses caused by the dysplastic, i.e. ‘foreign,’ epithelial cells. In some cases, the color may result from a lack of surface keratin or extreme thinness of the epithelium. Homogeneous form: Commonly found on buccal mucosa and soft palate and rarely on tongue and floor of mouth. Homogeneous form appears as a bright red, soft, velvety lesion with straight or scalloped, well-demarcated margins. It is often quite extensive in size. Regardless of the cause of the color change, the typical lesion is less than 1.5 cm. in greatest diameter and half are less than 1.0 cm, but examples larger than 4 cm have also been seen. It usually quite sharply demarcated from the surrounding pink mucosa and its surface is typically smooth and regular in coloration.

Location: It occurs on all mucosal surfaces of the head and neck area. Half of all cases, however, are found on the vermilion or intraoral surfaces, with the rest being evenly divided between the larynx and the pharynx. Vermilion lesions are relatively common and are most often seen on the lower lip. Intraorally, the lateral and ventral tongue, oral floor and soft palate are most frequently involved. Erythroplakia, as the name obviously implies, is asymptomatic.

Granular or speckled form: These are soft, red lesions that are slightly elevated with irregular outlines and granular or fine nodular surface speckled with tiny white plaques.

Appearance: It is non-elevated, red macule or patch on an epithelial surface (Fig. 12.9). The exact cause of the red appearance is unknown, but may be related to an increase in

Erythroleukoplakia: It is quite common to see erythroplakia admixed with or adjacent to leukoplakia in mouth. In such lesions, the red areas are the sites most

Smooth erythroplakia: This is soft to palpation and has often been described as having a velvety feel. The pebbled lesions tend to be somewhat firm, but erythroplakia never actually becomes hard or indurated, until an invasive carcinoma develops within it.

Premalignant Lesions and Conditions

likely to contain or to develop dysplastic cells and should therefore be the sites most readily biopsied and most carefully examined clinically. Erythroplakia interspersed with patches of leukoplakia in which erythematous areas are irregular and often not as bright as homogeneous form, are most frequently seen on tongue and floor of mouth. The borders may be well circumscribed or blend impercibly with surrounding oral mucosa. Unlike leukoplakia, erythroplakia is seldom multiple and rarely covers extensive areas of mouth. Also unlike leukoplakia, erythroplakia seems seldom to expand laterally after initial diagnosis, although this may be an artifactual feature because most lesions are completely removed or destroyed immediately after formal diagnosis.

Histopathological Features It exhibits epithelial changes ranging from mild dysplasia to carcinoma in situ and even invasive carcinoma (Fig. 12.10). Epidermoid carcinoma may show any degree of differentiation from poorly to well differentiated. It appears multicentric in origin. The carcinoma in situ shows epithelial dysplasia throughout the entire thickness of the epithelium, without invasion into the underlying connective tissue. Connective tissue rete pegs extend very high into the epithelium and the epithelium over the tips of these rete pegs is often very thin, capillaries in these superficial pegs are frequently dilated and the absence of any significant amount of surface orthokeratin or parakeratin or at the most only thin layer, also contributes to the red color of the lesion.

The spinous layer contains cells displaying atypia, hyperchromatism, pleomorphism and increase in number of mitotic figures.

Diagnosis Differentiation of erythroplakia with malignant changes and early squamous cell carcinoma, from the benign inflammatory lesions of oral mucosa is enhanced by use of 1 percent toludine blue test. The solution is applied locally by swab or oral rinse. Malignant type retains it, owing to increased nuclear DNA content of tumor cells.

Management Incisional biopsy is always the preferred method for establishing a microscopic diagnosis of suspicious intraoral lesions. Since erythroplakia is so closely correlated with severe dysplasia, carcinoma in situ and invasive carcinoma, incisional biopsy is especially indicated. Excisional biopsy of a potential malignancy may result in undertreatment and violation of surgical oncologic principles. The definitive treatment of erythroplastic lesions remains controversial. A conservative surgical procedure such as mucosal stripping is often performed, with minimal damage to the deeper connective tissues. This has the distinct advantage of preserving tissues for microscopic evaluation of potential regions of invasion. Destructive techniques such as laser ablation, electrocoagulation and cryotherapy have also proved to be effective. The key to therapy in this disease is extended clinical follow-up. Patients should be examined every 3 months for the first postoperative year and every 6 months for an additional 4 years. After that, annual re-evaluation with a thorough head and neck examination is advisable. Elimination of a suspected irritant. Points to Remember Erythroplasia of Queyrat, absence of surface keratin layer, nonelevated, red macule or patch on an epithelial surface, homogeneous form, granular or speckled form, smooth erythroplakia, erythroleukoplakia, mild dysplasia to carcinoma in situ, atypia, hyperchromatism, pleomorphism, toludine blue test, laser ablation, electrocoagulation, cryotherapy.

CARCINOMA IN SITU Figure 12.10 Erythroplakia showing carcinoma in situ with

hyperchromatism

It is also called intraepithelial carcinoma. Severe dysplastic changes in a white lesion indicate considerable

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risk of development of cancer. The more severe grade of dysplasia merges with the condition known as carcinoma in situ. It is more common on skin but can also occur on mucous membrane.

Clinical Features Age and sex distribution: Male predilection and occurs more commonly in elderly persons. Location: It common sites are floor of mouth, tongue and lips. Appearance: Lesion appearance may be like leukoplakia, like erythroplakia. It may be a combination of leukoplakia and erythroplakia, ulcerated lesion, ulcerated and white lesion, red and ulcerated lesion or may be nonspecific.

Histopathological Features Keratin may or may not be present in/on the surface of lesion but if present is more likely to be parakeratin, rather than orthokeratin (Fig. 12.11). There is loss of orientation of cells and their polarity. There is sharp line of division between normal and altered epithelium extending from the surface, down to the connective tissue rather than blending of the epithelia. In some cases, there appears to be hyperplasia of the altered epithelium, while in others there may be atrophy. An increase in nuclear/cytoplasmic ratio and nuclear hyperchromatism are sometimes seen. It is also unusual

to find multiple areas of carcinoma in situ interspersed by essentially normal appearing epithelium producing multifocal carcinoma in situ.

Management No uniformly accepted treatment. Lesion may be surgical excise, cauterized and even exposed to solid carbon dioxide. Points to Remember Intraepithelial carcinoma, combination of leukoplakia and erythroplakia, parakeratin, loss of orientation of cells, blending of the epithelia, hyperplasia of the altered epithelium, nuclear/cytoplasmic ratio, nuclear hyperchromatism.

Bowen’s Disease It is localized intraepidermoid carcinoma that may progress to invasive carcinoma over many years, which is characterized by progressive scaly or crusted plaque like lesion. It can be caused by sun exposure and arsenic ingestion.

Clinical Features It occurs on male and female genital mucosa and in oral mucosa as erythroplakia, leukoplakia or erythematous lesion. It appears as a slowly enlarging erythematous patches with little to suggest the malignant process. There is a red and slightly scaly area on the skin, which eventually enlarges and turns into white or yellowish lesion. When these scales are removed it produced a granular surface without bleeding.

Histopathological Features There are intra-epithelial features of malignancy. The epithelial cells of the lesion lie in complete disarray with highly atypical hyperchromatic nuclei and multiple nuclear forms.

Management Use of freezing technique, diathermy, cauterization, radiotherapy or application of cytotoxic drugs. Points to Remember Figure 12.11 Carcinoma in situ showing nuclear hyperchromatism

(Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, CDCRI, Rajnandgao, Chhattisgarh, India)

Intraepidermoid carcinoma, caused by sun exposure, slowing enlarging erythematous patches, red and slightly scaly area, intraepithelial features of malignancy, freezing technique, diathermy, cauterization, radiotherapy.

Premalignant Lesions and Conditions

ORAL LESION ASSOCIATED WITH USE OF TOBACCO 233

Smoker’s Palate or Stomatitis Nicotina It is also called nicotine palatinus. It is seen in persons who are heavy pipe and cigar smokers. As such it does not have premalignant potential as this occur in response to heat of rather than chemical in tobacco smoke. In some region smoking is done reversely with the lit end held in mouth. This will produce palatal keratosis and is called reverse smoker’s palate. Clinical Types ∙ ∙ ∙

Mild: Consisting of red, dot like opening on blanched area. Moderate: Characterized by well define elevation with central umbilication. Severe: Marked by papules of 5 mm or more with umbilication of 2 to 3 mm.

Figure 12.12 Stomatitis nicotina showing red spot

representing palatal salivary gland duct

Clinical Features Age and sex distribution: It is usually seen in men who are pipe smokers. It is common in middle age and elderly adults. Location: Most commonly affected site is palate. The lesion is well developed and prominent on keratinized hard palate. It is restricted to the area which is exposed to heavy cigarette smoke. Sign: There is redness and inflammation of the palate. The palate develops diffuse, grayish-white, thickened, multinodular papular appearance. There is small red spot in the center of each tiny nodule, representing a dilated and sometimes partially occluded orifice of an accessory palatal salivary gland duct around which inflammatory cell infiltration is prominent. The epithelium around the duct shows excessive thickening and keratinization (Figs 12.12 and 12.13). It represent focal thickening surrounding the orifice of the salivary gland which appears as white umblicated nodule with red center that may be stain brown by deposits of tar. There is discrete elevated striae with an appearance somewhat similar to pumice. Tonsillar pillars are usually erythematous. Discoloration is homogeneous with the exceptions of numerous erythematous spot.

Figure 12.13 White plaques seen on palate in patient with

stomatitis nicotina

Dried mud appearance: In some cases palatal keratin may become so thickened and fissured that it gives dried mud appearance. Palatal Changes in Reverse Smoking • K eratosis: Diffuse whitening of the entire palatal mucosa. • Excrescences: 1–3 mm elevated nodules, often with central red dots corresponding to the opening of palatal mucous glands. • Patches: Well defined, elevated white plaques, which could qualify for the clinical term leukoplakia. • Red areas: Well defined reddening of the palatal mucosa. • Ulcerated area: Crater like areas covered by fibrin. • Nonpigmented areas: Area of palatal mucosa which is devoid of pigmentation.

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Histopathological Features

Clinical Features

There is hyperkeratosis and acanthosis of palatal epithelium. There is also chronic inflammation of subepithelial connective tissue and mucous gland. There is also squamous metaplasia of excretory duct and hyperplastic ductal epithelium may be seen. Epithelium lining of minor salivary gland often shows squamous cell metaplasia and hyperplasia. Obstruction of duct may lead to formation of retention cyst. Periductal inflammatory cell infiltrate composed of lymphocytes and plasma cells accompanied capillary proliferation and dilation in zone.

Location: It occurs in mucosal surface, where snuff is habitually held.

Management It is completely reversible once the habit is discontinued. The lesions usually resolve within 2 weeks of cessation of smoking. Biopsy of nicotine stomatitis is rarely indicated. But biopsy should be performed on any white lesion of the palatal mucosa that persists after 1 month of discontinuation of smoking habit. Points to Remember Stomatitis nicotina, redness and inflammation of the palate, diffuse, grayish-white, thickened, multinodular papular appearance, pumice appearance, tonsillar pillars are usually erythematosus, discoloration is homogeneous, dried mud appearance, hyperkeratosis, acanthosis of palatal epithelium, squamous metaplasia of excretory duct, periductal inflammatory cell infiltrate.

Sign: There is painless loss of gingival tissue in the area of tobacco contact. This can be accompanied by destruction of alveolar bone. Tooth wear: There can be localized or generalized wear of tooth surface. Brown black extrinsic stains are found on enamel. Smokeless tobacco keratosis: It is thin, gray, or grapy white plaque which is translucent with margin blends gradually into the surrounding mucosa. Snuff pouch: The mucosa has soft velvety feel and if you stretch the mucosa it will reveal distinct pouch which is caused by flaccidity in chronically stretched tissue of area of placement of tobacco (Fig. 12.14). Mucosa usually appears fissured and rippled when not stretched. It resembled a sand on a beach after an ebbing tide.

Histopathological Features The squamous epithelium is hyperkeratinized and acanthotic with or without intracellular vacuolization. Chevrons: These are pointed projection of parakeratin above the superficial epithelial layer. Increase subepithelial vascularity and vessels engorgement are often seen.

Snuff Dipper Lesion It is also called smokeless tobacco keratosis, snuff pouch;, tobacco pouch keratosis and spit tobacco keratosis. The compound N-nitroso-nor-nicotine (NNN), which is derived partly from bacterial action on nicotine during the curing process, is contributed by the action of salivary nitrites, when tobacco is held in the mouth; occurs in greater concentration in snuff tobacco. Clinical Lesion of Smokeless Tobacco • H yperkeratosis or erythematous lesion of oral mucosa • Gingiva and periodontal inflammation • Combination of above • Cervical erosion of teeth.

Figure 12.14 Snuff dipper lesion showing hyperkeratosis

Premalignant Lesions and Conditions

Management If habit is eliminated, majority of the lesion disappear in about 2 weeks. Long exposure to snuff may results in malignant changes in the lesion. Points to Remember Smokeless tobacco keratosis, snuff pouch, painless loss of gingival tissue, tooth wear, smokeless tobacco keratosis, if you stretch the mucosa it will reveal distinct pouch, sand on a beach after an edding tide, chevrons, increase subepithelial vascularity.

Cigarette Smoker’s Lip Lesion They are generally flat or slightly elevated nodular white lesion on one or both lips, corresponding to the site at which the cigarette is held and apparently smoked down to an extremely short length. There is increased redness and stippling of lip in localized area. It has elliptical, circular or irregular borders. Pale to white and were slightly elevated with nodular or papillary shape (Fig. 12.15).

LICHEN PLANUS Erasmus Wilson described it in 1869. Various mucosal surfaces may be involved, either independently or concurrently, with cutaneous involvement or serially. Oral mucosa is frequently involved. It is a probable precancerous condition. Lichen planus is a common inflammatory disease of the skin presenting with characteristic violaceous, polygonal,

Figure 12.15 Cigarette smoker lip lesion

and pruritic papules. The disease may also affect the mucosa, hair and nails. Relatively common dermatological disorder occurring on skin and oral mucous membrane and refers to lace-like pattern produced by symbolic algae and fungal colonies on the surface of rocks in nature (lichens). The term planus is Latin word meaning flat. Etiology • • • • • • • • • •

Cell-mediated immune response Haptens Immunodeficiency Genetic factors Infections Drugs and chemicals Psychogenic factor Habit Deficiency of vitamin B1, B6 and C Electric.

Etiology Cell-mediated immune response: It is a cell mediated immune response associated with lymphocyte-epidermal interactions, resulting in degeneration of basal cell layer. Possible hypothesis are alternation of keratinocytes as a result of unknown events resulting in antigenic alternation of these cells thereby stimulating immunological reaction or a primary immunologic reaction causing alternation and degeneration of keratinocytes. Cell-mediated immune response may be caused by various mononuclear cells, i.e. Langerhans cell, macrophages predominantly T lymphocytes, lymphoblast cells, B lymphocytes and mast cells. These cells infiltrate the upper part of lamina propria of sub mucosa. In this cell-mediated response Langerhans cells are potent antigen presenting cells, lymphocytes are effective cells and keratinocytes are target cells. The macrophages are mostly mature, which probably have functional role with mononuclear cells is suggesting of cell-to-cell cooperation. Recent hypothesis of pathogenesis of lichen planus: In a genetically predisposed individual, haptens (certain drug or dental material), conventional antigen or super-antigen of oral microbial origin can induce cell-mediated immune response resulting in subepithelial T cell infiltration of the site in oral mucosa with cytokine generation HSP-60 and C 1/10 expression by basal keratinocytes. If individual is not predisposed to react to HSP-60, then non specific mucositis

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occur. If the individual has genetic predisposition, it results in autoimmune reaction → activation of cytotoxic T cell → destruction of basal keratinocytes → oral lichen planus. 236

Autoimmunity: The activated T lymphocytes also secrete gamma interferons which induce keratinocytes to produce HLA-DR and increase their rate of differentiation with formation of thickened surface. Antigenic information is transferred from Langerhans cells to lymphocytes, when there is mutual expression of HLA-DR. Lymphocytes normally are attracted towards HLA-DR expressing keratinocytes and may contact the epithelial cell. During this contact, inappropriate epithelial antigenic information may be passed to lymphocytes due to HLA-DR linkage. With this mechanism, self antigen may be recognized as foreign bodies, leading to destruction of basal cells, resulting in an autoimmune response. Autoimmune disorders classically have female predilection and are associated with serum antibodies with hypergamma-globulinemia. There are numerous studies which show immune deposits in lichen planus affected tissues but it is not specific. Immunodeficiency: There has been report of decreased serum levels of IgG, IgA, or IgM in lichen planus and the possibility of it as a manifestation of immunodeficiency has been raised. But at the same time, reports of normal concentrations of IgA and IgM are found; therefore the role of immunodeficiency is questionable. Genetic factors: Cases of lichen planus are reported in families, twins and husband and wife. Clinically, familial lichen planus is somewhat unusual as it appears to affect young patients, is severe, often extensive, involves skin nails and mucous membrane and is persistent. It has also been suggested that familial cause might be environmental and related to infection, rather than to genetics. Infections: A bacterial etiology may be there but results are not confirmed. Spirochetes and rod-like bodies resembling bacteria have also been detected. Drugs and chemicals: It is also called lichenoid reaction. Although the clinical disease of lichen planus has an immunological basis, some persons with lichen planus have a diathesis for the disorder. The tissues of a person with diathesis react in a special way to certain extrinsic stimuli, making it more susceptible to certain diseases. Drugs act to increase temporarily the specific antigenic stimulus and hence increase the reaction. If the drug is withdrawn at a later time, the antigenic stimulus is reduced,

followed by reduction in clinical severity. It is suggested that drugs that are known to induce lichenoid response, act as agents which amplify the disorder, rather than induce it. To implicate a drug responsible for a lichenoid reaction can be difficult as there is no specific test for it. Association between dental filling material and lichen planus has also been suggested. Psychogenic factor: A relationship of lichen planus with stress is quoted and neurogenic basis is suggested. Observation mostly in nervous and highly stressed persons is associated with emotional upset, over work and some form of mental strain. Habit: Oral lichen planus has shown association with tobacco habit. Chewers of tobacco and betel have increased prevalence of oral lichen planus. Smoking may play a role in initiating oral lichen planus of plaque type. Miscellaneous: Occurrence of lichen planus is also suggested in association with deficiency of vitamin B1, B6 and C, electric potential difference, anemia and patients with secondary syphilis. It can also occur in some cases due to trauma and malnutrition. Exacerbation of lichen planus also correspond to periods of emotional upset, overwork, anxiety, hysteria attack, depression and some form of mental strain. Types of Lichen Planus • • • • • • • • • • • • • •

Reticular Papular Plaque Atrophic Classical Erythematous Ulcerative Hypertrophic erosive Bullous Hypertrophied Annular Actinic Follicular Linear

Clinical Features Age and sex distribution: It occurs in adulthood with age range for males as 35 to 44 years and for females 45 to 54 years. It has more predilections for females.

Premalignant Lesions and Conditions

Incidence: Prevalence of lichen planus in general population is about 0.9 to 1.2 percent and prevalence of oral lichen planus is reported between 0.1 and 2.2 percent. Location: It may involve skin, oral and other mucous membranes. About 50 percent of the patients with skin lesions have oral lesions whereas 25 percent of all lichen planus have only oral lesions. Oral lesions coexisting with genital mucosal lesions are known as vaginogingival syndrome. Other mucosal surfaces including larynx, glans penis, esophagus, stomach, nasal and vulva may get involved. Symptoms: The chief complaint is usually of intense pruritus. The itching associated with LP usually provokes rubbing of the lesions, rather than scratching. Signs: The lesions have a characteristic violet hue. They are flat-topped, shiny, polygonal papules and plaques. The surface is dry with thin, adherent scales. Six P of lichen planus: Six ‘P’s characterize the lesions of lichen planus They are planar, polygonal, purple, pruritic, papules and plaques. Cutaneous: Common sites are flexor surface of wrist and forearm, inner surface of knees and thigh and the trunk, usually the lumbar and sacral areas. The skin lesions appear as small, angular, flat topped papules, only a few millimeter in diameter, which may be discrete or gradually coalesce into larger plaque and is covered by fine glistening scales. Primary symptom is severe pruritis that may be intolerable. Papules are sharply demarcated from surrounding skin, which appears red but soon takes reddish purple or violaceous blue color. Later, dirty brown color develops. Center of papule may be slightly umblicated.

Oral Lichen Planus Location: Common sites are buccal mucosa (84%) and to lesser extent tongue, lips, gingiva, floor of mouth and palate. Patient may report with burning sensation of oral mucosa. Appearance: Oral lesion is characterized by radiating white and gray velvety thread-like papules in a linear, angular or retiform arrangement forming typical lacy, reticular patterns, rings and streaks over the buccal mucosa and to a lesser extent on the lip, tongue and palate. Wickham’s striae: Tiny white elevated dots are present at the intersection of white lines, called as Wickham’s striae (Fig. 12.16). Reticular type: It is most common form and it is mostly bilateral. It consists of slightly elevated fine whitish lines that produce lace-like pattern of fine radiating lines, called as Wickham’s striae. The lesion may present radiating white thread-like papules in a linear, annular or retiform arrangement. A tiny white dot is frequently present at the intersection of white lines (Figs 12.17 and 12.18). Papular: Whitish elevated lesions of 0.5 to 1 mm in size, well seen on keratinized areas of oral mucosa. Papules are spaced apart; still close enough to give pebbled white or gray color. Sometimes they coalesce. Most often, papules are seen at the periphery of reticular pattern (Fig. 12.19). Plaque: It is seen on dorsum of tongue and buccal mucosa. In case of plaque of tongue, disappearance of the tongue papillae is seen. It spreads in concentric peripheral growth.

Wickham’s striae: These are very fine grayish lines which cover the papules. Graham-little syndrome: Alopecia occurs in some patients which may be termed lichen planus planopilaris (Graham-Little syndrome). Nail changes, particularly longitudinal ridging and grooving may be seen. Variant: Various variants of lichen planus like hypertrophied, actinic, ulcerative, linear forms, etc. are present, but in dental point of they are not found intraorally so they are not discuss here. Koebner phenomenon: Fresh lesions may appear on scratch marks or at sites of other nonspecific trauma.

Figure 12.16 Lichen planus showing Wickham’s Striae (Cour­ tesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

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Figure 12.17 Reticular types of lichen planus showing

Figure 12.19 Papular type of lichen planus showing whitish

annular arrangement

elevated lesion

common site is buccal mucosa, especially into posterior and lateral margins of tongue. It is often associated with striated or keratotic component. Hypertrophic form: It appears as well circumscribed, elevated and white lesion resembling leukoplakia. Annular form: Appears as round or ovoid, white outline with either pink or reddish pink center. In about 11 percent of cases, oral lichen planus may be associated with pigmentation (Fig. 12.20). Points to Remember Figure 12.18 Reticular types of lichen planus

It consists of either pearly white or grayish white plaque. Such plaques generally range from slightly elevated and smooth to slightly irregular form. Atrophic form: Appears as smooth, red, poorly defined area, often but not always, with peripheral striae evident. The attached gingiva is frequently involved in this form of lichen planus in a so-called desquamative gingivitis pattern. At the margins of atrophic zones, whitish keratotic striae are usually evident, radiating peripherally and blending into surrounding mucosa. The gingiva tends to show patchy distribution overall the four quadrants in a relatively symmetrical pattern. It is always symptomatic with complain of pain and burning in the areas of involvement. Bullous form: It consists of vesicles and bullae and there which are short lived. These upon rupturing, leave an ulcerated extremely uncomfortable surface. The most

Vaginogingival syndrome, intense pruritus, flat-topped, shiny, polygonal papules and plaque, Six ‘P’ of lichen planus—planar, polygonal, purple, pruritic, papules, plaques. • Cutaneous: Violaceous blue color, Wickham’s striae, Graham-Little syndrome, Koebner phenomenon • Reticular type: Slightly elevated fine whitish lines, Wickham’s striae, linear, annular or retiform arrangement, a tiny white dot • Papular: Whitish elevated lesions pebbled white or gray color • Plaque: It is seen on dorsum of concentric peripheral growth, pearly white or grayish white plaque • Atrophic form: Smooth, red, poorly defined area, desquamative gingivitis • Bullous form: Vesicles and bullae, leave an ulcerated lession • Hypertrophic form: Well circumscribed, elevated white lesion • Annular form: Appears as round or ovoid, white outline.

Premalignant Lesions and Conditions

basal cell degeneration induced by the inflammatory process. Ulcerative lichen planus: Chronic ulcers occur on the feet. It may accompany oral ulcer and loss of nails. Lichen planus pigmentosus: Described mainly from India and Middle East, these lesions present with deeply pigmented macules on the face and extremities. Variations in shape: Linear lichen planus: This may follow marks of injury by koebnerization, or may occur spontaneously in long linear arrays or rarely in a dermatome in a zoster-like fashion.

Figure 12.20 Annular types of lichen planus of labial mucosa

showing round appearance

Clinical Variation of Lichen Planus In many cases, the clinical picture may differ from the classical one, the variations being in morphology and configuration or there may be modifications of clinical features by the site of involvement. Variations in morphology: Hypertrophic lichen planus: This may occur as a sole manifestation or as a part of a more generalized subacute disease. The lesions are elevated, warty, pigmented plaques typically occurring on the shin or around the ankle. These lesions tend to be persistent. Atrophic lichen planus: The lesions are few in number. There are depressed and pigmented lesions. Follicular lichen planus: It also known as lichen planopilaris, this may accompany typical lesions or may be the sole morphologic type. There are small lesions centered around hair follicles. Lesions on scalp may result in alopecia. The combination of follicular lichen planos with scarring alopecia of scalp and non-scarring alopecia of axilla and pubis or other areas is known as GrahamLittle syndrome. Actinic lichen planus: Described mainly from the Middle East and India, these lesions are common on the face and present as hyperpigmented patches with a surrounding zone of hypopigmentation. Bullous lichen planus: Vesicles and bullae may occur on typical lesions of lichen planus in this variant, due to severe

Annular lichen planus: These lesions have central depressed areas with raised margins. Typically occurs on penis. Guttate lichen planus: Large number of drop-shaped lesions. Variation by site: Oral: Oral lesions frequently occur in lichen planus. Genital: Annular plaques often occur on glans penis, vulval or vaginal lesions, often presenting with chronic ulcers, may rarely occur. Nails: Nail dystrophies may occur in lichen planus. The various changes that may occur are—thinning of nail plate, longitudinal ridging, onycholysis, subungual hyperkeratosis and pterygium formation (fusion of proximal nail fold with the nail plate). Palms and soles: Lichen planus of these locations lack the typical color; they are yellowish rather that violaceous papules and plaques. Scalp: Follicular lesions with scarring alopecia are seen at this site. Special variant: Drug-induced lichenoid reactions: A number of drugs may induce development of lesions that clinically and histologically resemble idiopathic lichen planus. The principal offenders are: gold, penicillamine, betablockers, antimalarials, captopril, lithium, carbamazepine, chlorpromazine, thiazides, methyldopa, INH, PAS and NSAIDs. Lichen planus pemphigoides: Bullous lesions occur on lesions as well as normal skin. This appears to be a variant with combined features of lichen planus and bullous pemphigoid.

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Lichenoid contact dermatitis: Contact with color film developer containing para-phenyldiamine may give rise to lichen planus like lesions on hands. Amalgams in dental filling material may also give rise to lichenoid oral lesions. Lichen planus-lupus erythematosus overlap: Lesions with atrophic center violaceous border occur mainly on hands and feet. Immunohistologic evidence of both lichen planus and lupus erythematous, are present.

Histopathological Features (Figs 12.21 to 12.23) Hyperorthokeratosis and hyperparakeratosis, acanthosis with intercellular edema of spinous cells occurs in some instances. Civatte bodies are often seen in the epithelium mostly in the spinous and basal cell layers and lamina propria. They appear as round or ovoid, well defined eosinophilic globule with a maximum size of about 20 µm, probably representing fibrillar transformation degeneration and premature cell death of basal keratinocytes. Saw tooth appearance of the rete pegs is seen. Necrosis or liquefaction degeneration of basal cell layer with appearance of a band of eosinophilic coagulum in place of the basal layer. There is also thickening of granular cell layer with band like dense inflammatory cellular infiltrate, containing lymphocytes and occasional plasma cells, in the upper lamina propria. Sometimes, the necrotic material is exuded into lamina propria (apoptosis). The material may be taken up by

Figure 12.22 Lichen planus showing 1-saw tooth rete pegs and hydropic degeneration of basal cells, 2-orthokeratosis, juxtaepithelial band of epithelial cells

Figure 12.23 Lichen planus showing parakeratinized stratified squamous epithelium connective and tissue shows a juxtaepithelial band of chronic inflammatory cells (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Figure 12.21 Lichen planus showing subepithelial

inflammation and saw tooth appearance

phagocytes or provide a matrix for the deposition of serum protein including immune component, resulting in colloid bodies formation. Cells from the lamina propria may also contribute to the formation of colloid bodies. Cellular infiltrate consists of lymphocytes but plasma cell and histiocytes are also present sometimes. Mast cells are observed sometimes below the subepithelial infiltrate. In deeper layers they contain granules

Premalignant Lesions and Conditions

but undergo degranulation. It is suggested that mast cells participate in recruitment of lymphocytes to subepithelial infiltrate. Ryan suggested that the pattern of striae of Wickham’s is due to absence of capillaries in the center with growing vessels at the periphery. Immunofluorescent study: It is positive for direct immunofluorescence reaction with IgA, IgM, IgG antisera. Most constant feature is presence of sub-epithelial deposits of fibrinogen and antigenically related substance, which can be stain by anti-fibrinogen antisera.

Histopathological Features of Different Types of Oral Lichen Planus Reticular: This shows hyperparakeratosis or hyperorthokeratosis. In some cases, both types of keratinization may be seen. Granular cell layer is also seen. It also features epithelial hyperplasia, although atrophy is present in some cases. Accentuation of rete pegs in the typical sawtooth configuration is uncommon. Basal cell layer shows liquefaction degeneration. Cellular infiltrate is primarily of lymphocytes, plasma cells may be seen. Papular: Keratosis, usually hyperkeratosis or parakeratosis, may be extensive and stratum corneum may show considerable increase in width. Parakeratosis is found more commonly than hyperkeratosis, although alternate areas of both types may be present. Acanthosis is not usually seen. Epithelium shows moderate hyperplasia and saw tooth configuration of rete pegs is rarely observed. Basal cell layer shows liquefaction degeneration and it consists of inter and intra-cellular vacuoles. Juxtaepithelial connective tissue consists of broad band of lymphocytic infiltration. Occasional plasma cell and histiocytes may be seen. Inflammatory cells usually penetrate into lower layers of epithelium and are seen between degenerating epithelial cells. Plaque: Marked hyperorthokeratosis and hyperparakeratosis is seen in connection with stratum granulosum. Epithelial hyperplasia as well as atrophy is seen. A narrow zone, free of inflammatory cells is seen in relation with basement membrane. Lymphocytic juxtaepithelial infiltration is seen in connective tissue stroma. Atrophic: The epithelium is thin. There is little keratinization at the surface and stratum corneum tends to blend into stratum spinosum. The basal cells present hydropic degeneration. Rete pegs are absent. Pattern is similar to desquamative gingivitis.

Bullous: It shows hydropic degeneration of basal cell layer. Due to this, there is collection of edema at the epithelial connective tissue interface, resulting in the formation of subepithelial bulla. The bulla or vesicle contains clear fluid and occasionally hemorrhage. A broad band of lymphocytic cells is seen in the upper corium, prior to rupture of vesicle or bulla. Points to Remember • R eticular: Hyperparakeratosis or hyperorthokeratosis, granular cell layer, epithelial hyperplasia, saw-tooth configuration • Papular: Keratosis, hyperkeratosis or parakeratosis, broad band of lymphocytic infiltration • Plaque: Hyperorthokeratosis, hyperparakeratosis, stratum granulosum, lymphocytic juxtaepithelial infiltration • Atrophic: Epithelium is thin, stratum corneum blend into stratum spinosum • Bullous: Hydropic degeneration of basal cell layer, vesicle contains clear fluid, A broad band of lymphocytic cells.

Malignant Potential The incidence of malignant transformation ranges form 0.4 to 12.3 percent. In India, the incidence of malignant transformation is 0.4 percent. Carcinoma development is more common in women than in men. Atrophic, erosive and ulcerative lesions showing erythroplakic component and tobacco chewers are indicated to be more cancer prone.

Management Removal of cause: The causative factor is removed and this may lead to resolution of lesion subsequently. This can be particularly applicable to lichenoid drug eruption. Corticosteroid: In most patients with erosive and ulcerative lesion steroids are commonly used. The rationale behind their use is their ability to modulate inflammation and immune response. Small and moderately sized painful lesions can be treated with beclomethasone dipropionate spray, triamcinolone acetonide in gel or cream base. Topical and intralesional routes are used when systemic steroids are contraindicated. These routes are useful when the patient refuses needle injection or when treating painful gingival sites, where injection delivery is impossible. The topical, injectable and systemic routes are used when there is no systemic contraindication and a full steroid dose is required. In case of

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some painful gingival lesions topical steroids may be applied using soft custom trays by coating steroids on the undersurface of the tray. This tray anchors to the dental arch while covering the painful gingival lesion. Earlier regime consists of triamcinolone acetonide topically, methylprednisolone 40 mg/ml as injectable and prednisolone 5 mg tablet as systemic steroid therapy. Injection triamcinolone acetonide 10 mg/ml was also used in patients with serious complain, in a dose of 0.1 mL/cm2. This earlier regime called for topical delivery QID, for 3 or more weeks, once a week intralesional injection, for 3 weeks (usually 0.5–1.5 mL) and systemic steroid (prednisolone 5 mg tab) in tapering doses of 30 mg/day for the first of 3 weeks, 15 mg/day for the second week and 5 mg/day for the third and final week. Topical application of fluocinolone acetonide for 4 weeks is also effective in curing the disease. Another regime consisting of prednisolone and levamisole has also been tried successfully recently. This systemic regime calls for prednisolone 5 mg and levamisole 50 mg tablets for first three days of rest and this schedule to be followed for two to three more weeks. Topical application of antifungal agent: Steroid therapy is routinely accompanied by antifungal treatment as steroid therapy tends to generate an oral fungal infection. The prophylactic antifungal therapy usually consists of clotrimazole oral torches. Nystatin and ketoconazole can also be used. Vitamin A (Retinoid) analog: Retinoids are useful usually in conjunction with topical corticosteroids as adjunctive therapy either topically or systemically. This is because of their anti-keratinizing and immuno-modulating effects. They are particularly effective against keratinized reticular and plaque variants. Topical vitamin A acid cream (0.1%) Tretinoin, beta altransretinoic acid, systemic etretinate and systemic and topical isotretinoin are also useful in resolution of the lesions, but withdrawal of the medication leads to rapid recurrence to the lesion very oftenly. The side effects of retinoids are more and it includes foci of erythema during and after the topical treatment. For systemic retinoids, it includes liver dysfunction, cheilitis and dryness of mucous membrane. A new systemic retinoid; temarotene, has been reported effective and free of side effects, other than a slight increase in liver enzymes. Cyclosporine: It is a selective inhibitor of CD4 helper T lymphocytes that is used systemically to achieve immunosuppression. It can be used both, topically and systemically. The lesion shows complete healing with no recurrence following 8 weeks of systemic cyclosporine 8

mg/kg/day. Oral lesions can be treated using cyclosporine as a rinse and expectorant. It is used as 5 mL rinse, TID, for 8 weeks. Surgical therapy: It is indicated when conventional methods fail in ulcerative lesion and small solitary lesions. In some cases, cryosurgery and cauterization have also been tried. Psychotherapy: Emotional status of the patient is important in the development of this disease. In some cases, the lesion may regress when the patient is made aware of psychogenic implication of the condition and the nature of emotional stress is understood. When the lesions are asymptomatic and there is no source of emotional distress it is often advisable to refrain from therapy as failure to eradicate the lesion by medication may trigger the patient into becoming fearful of cancer. Tranquilizers have been also been tried to reduce anxiety. Dapsone therapy: Dapsone diamino-diphenylsulfone is an antibacterial sulfone. It is postulated that this particular agent may help to control the lymphocyte-mediated progress of lichen planus by modulating the release of inflammatory or chemotactic factor for mast cells or neutrophils. It is used in severe form of erosive lesions. PUVA therapy: In this form of therapy, psoralens and high intensity long wave ultraviolet (PUVA) light is used as a therapeutic agent. The lesion shows improvement during and immediately after the treatment. Points to Remember Removal of cause, corticosteroid, beclomethasone dipropionate spray, triamcinolone acetonide in gel or cream, topical application of antifungal agent, Vitamin A (Retinoid) analog, cyclosporine, surgical therapy, psychotherapy, dapsone therapy, PUVA therapy.

Erosive Lichen Planus It presents as chronic multiple oral mucosal ulcers, which occur when there is extensive degeneration of basal cell layer of epithelium.

Etiology Drug therapy like NSAIDs, hydrochlorothiazide, penicillamine, angiotensin converting enzyme inhibitors. Chronic hepatitis: Underlying medical disorders like chronic hepatitis.

Premalignant Lesions and Conditions

Dental restoration: Reaction to dental restorations. Graft versus host disease: Graft versus host disease due to bone marrow transplantation can cause lichen planus. Stress: Emotional stress can lead to erosive lichen planus.

Clinical Features Age and sex distribution: Female to male ratio is 2:1. Average age is 50 years. It is primarily a disease of whites, but it may be seen in blacks. Location: Common site is buccal mucosa and lingual mucosa. Symptoms: There is complain of burning sensation and pain. Appearance: After rupture of vesicles, eroded or frankly ulcerated lesion are seen which appears as a raw painful areas (Fig. 12.24). Lacy white pattern may be present. Eroded and frankly ulcerated lesions are irregular in size and shape and appear as raw and painful areas. The surface is generally granular and brightly erythematous and may bleed upon slight provocation or manipulation. A fibrinous plaque or pseudomembrane may be seen over erosion, while later is significant. Bullous type: In case when erosive component is severe and epithelial separation is from underlying connective tissue occur which result in rare form called bullous lichen planus. Malignant potential: Malignant potential is 1 to 25 percent. Present for a week to month and heal in periods

of 10 days to 2 weeks. They may change the pattern of presentation and involvement from time to time.

Histopathological Features In the erosive form, the epithelium is completely missing or only remnants of epithelial tissues are seen. Erosive lesion appears as ulceration, epithelial thinning and eventual destruction. Hemorrhage may be noted. It shows classical feature of lichen planus, i.e. hydropic degeneration of basal cell layer with juxtraepithelial inflammatory cell infiltrate. The basal cells are gradually destroyed and overlying epithelium becomes thin and atrophic. Eventually, epithelium undergoes necrosis and an area of ulceration appears. Ulcerated area, if infected may show altered population of inflammatory infiltrate with polymorphonuclear leukocytes predominating at the ulcerated surface, which is covered by fibrin. Points to Remember Burning sensation and pain, eroded or frankly ulcerated lesion, lacy white pattern, brightly erythematosus, erosive component is severe, malignant potential is 1 to 25%, epithelium is completely missing, ulceration, epithelial thinning, hemorrhage, juxtraepithelial inflammatory cell infiltrate, polymorphonuclear leukocytes.

ORAL SUBMUCOUS FIBROSIS It is a chronic and high-risk precancerous condition. The condition was prevalent in the days of Sushruta (600 B.C.), a great practitioner of ancient medicine where he labeled this condition as ‘Vidhari’. After lapse of many years, Schwartz (1952) was the first person to bring this condition again into limelight. He described the condition as ‘atrophica idiopathic mucosae oris’. After that the condition has also been described as idiopathic scleroderma of mouth, idiopathic palatal fibrosis and sclerosing stomatitis.

Definition

Figure 12.24 Erosive lichen planus showing raw painful area

It is an insidious, chronic disease affecting any part of the oral cavity and sometimes pharynx, although occasionally preceded by and/or associated with vesicle formation, it is always associated with juxtaepithelial inflammatory reaction followed by fibroelastic changes of lamina propria, with epithelial atrophy leading to stiffness of oral mucosa and causing trismus and inability to eat.

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Etiology 244

• • • • • • • • • • •

Chilies Tobacco Lime Betel nut Nutritional deficiency Defective iron metabolism Bacterial infections Collagen disorders Immunological disorders Genetic susceptibility Altered salivary composition.

Etiology Chilies: The use of chilies (Capsicum annum and Capsicum frutescence) have been thought to play an etiological role in oral submucous fibrosis. Capsaicin is the active ingredient of chilies. It is the vanillylamide of 8-methyl-6-nonenic acid, which is the active irritant of the chilies. Tobacco: It is a known irritant and causative factor in oral malignancy. It may act as a local irritant. Lime: Lime is used with betel nut for chewing. It causes local irritation and damage to the mucosa with vesicle and ulcer formation in susceptible individuals. It acts as a local irritant. Betel nut: The term areca nut is used to denote the unhusked whole fruit of the areca nut tree and term betel nut is used exclusively to refer to the inner karnel or seed which is obtained after removing husk. The betel nut has psychotropic and antihelmintic property due to presence of areca alkaloids, predominantly arecoline. These alkaloids have powerful parasympathetic properties which produce euphoria and counteract fatigue. Areca nut is found to contain different types of alkaloids like arecoline, arecadine, arecalidine, guvacoline, guvacine and isoguvacine. In a habitual betel nut chewer, oral submucous fibrosis may be caused by the amount of tannic acid contained in the betel nut, the influence of mixed calcium powder and the conditional action of arecoline content in betel nut, affecting the vascular supply of oral mucosa and causing neurotropic disorder. Nitrosation of arecoline leads to the formation of areca nut specific nitrosamine namely nitrosoguvacoline, nitrosoguvacine and 3-methyl nitrosomino pripionitrile, which they alkylate DNA. Metabolism of this areca nut specific nitrosamine will lead to formation of cyanoethyl,

which adducts with o’methyl guanine in DNA. Prolonged exposure to this irritant leads to malignant transformation. Recently suggested pathogenesis of oral submucous fibrosis is by dual action of areca nut. It is suggested that arecoline stimulates fibroblastic proliferation and collagen synthesis. The flavanoid catachin and tannins are also components of areca nut and they stabilize the collagen fibrils rendering them resistance to degradation by collagenase. The attendant trismus is the result of juxtaepithelial hyalinization and secondary muscle involvement. Glycogen consumption is physiologically related to cellular activity. Overactivity of muscle results in excessive glycogen consumption, leading to glycogen depletion. The increased muscle activity and diminished blood supply, following connective tissue changes; owing to extensive oral submucous fibrosis leads to muscle degeneration and fibrosis. Nutritional deficiency: The disease is characterized by repeated vesiculations and ulcerations of oral cavity. A subclinical vitamin B complex deficiency has been suspected in such cases. The deficiency could be precipitated by the effect of defective nutrition due to impaired food intake in advanced cases and may be the effect, rather than the cause of the disease. Defective iron metabolism: Microcytic hypo chromic anemia with high serum iron have been reported in submucous fibrosis but as such, there is no definite proof available to support this cause effect relation. Bacterial infections: Streptococcal toxicity is also a factor in etiology of oral submucous fibrosis, as in some other collagen disorder such as rheumatic disease. Klebsiella rhinoscleromatis may be a factor in cause of submucous fibrosis. Collagen disorders: Oral submucous fibrosis is thought to be localized collagen disease of oral cavity. It is linked to scleroderma,rheumatoid arthritis, Duputreyen’s contracture and intestinal fibrosis. A link between scleroderma and oral submucous fibrosis has also been suspected on the basis of similarity of histological characteristics. Immunological disorders: Raised ESR and globulin levels are indicative of immunodeficiency disorder. Serum immunoglobulin levels of IgA, IgG and IgM are raised significantly in oral submucous fibrosis. These raised levels suggest an antigenic stimulus in the absence of any infection. Circulating auto antibodies are also present in some cases of oral submucous fibrosis.

Premalignant Lesions and Conditions

Genetic susceptibility: The familial occurrence of oral submucous fibrosis has also been reported. Altered salivary composition: The study of saliva in cases of oral submucous fibrosis has shown increased pH, increase in salivary amylase, low levels of calcium, increase in alkaline phosphatase and potassium and normal levels of salivary immunoglobulin. The fibrin precipitating factor in saliva has been attributed to the increased plasma fibrinogen. This is likely due to increased dietary content of fibrin. Pathogenesis • Increased collagen production • Stabilization of collagen • Decreased collagen breakdown.

Pathogenesis Oral submucous fibrosis results from increased production of collagen by fibroblasts. In addition to this there is decreased breakdown leading to accumulation of excessive amounts of collagen. There are various mechanisms by which this occurs: ∙ Increased collagen production ∙ Stabilization of collagen ∙ Decreased collagen breakdown.

Increased Collagen Production Under the influence of areca nut fibroblasts differentiated into phenotypes that produce more collagen. The alkaloids present in areca nut arecadine and arecoline are responsible for this. Arecadine is more important. Arecoline gets converted in arecadine which is the active metabolite. There is dose dependent increase in production of collagen by fibroblasts under influence these factors. Various cytokines are increased in oral sub mucous fibrosis. These are TGF-β, PDGF, bFGF. These are fibrogenic growth factors that stimulate collagen production. Another cytokine that has anti-collagen effect is IFN-a. This is decreased in OSMF. Thus overall there is stimulation of collagen synthesis.

Stabilization of Collagen Structure Betel nut contains tannin. Tannin has ability to stabilize collagen by cross-linking it. This cross-linked collagen is more resistant to degradation.

Another component of betel nut that aids this crosslinking is copper. Copper is present in betel nut in high amounts. It is a constituent of enzyme lysyl oxidase. This enzyme causes cross-linking and makes collagen resistant to degradation.

Decreased Collagen Breakdown Due to action of tannin and copper collagen that is produced in OSMF is highly resistant to remodeling and phagocytes. It is fibroblasts that bring about remodeling and phagocytes of collagen. As in OSMF these fibroblasts are affected they cannot degrade collagen. Thus in oral submucous fibrosis there is increased production and decreased degradation of collagen. This leads to accumulation of collagen in oral mucosa. Pathogenesis of oral submucous fibrosis is shown in Flow chart 12.2.

Clinical Features Age and sex distribution: It affects both sexes. The age group varies, although majority of patients are between 20 and 40 years of age. Location: The most frequent location of oral submucous fibrosis is the buccal mucosa and the retro molar areas. It also commonly involves soft palate, palatal fauces, uvula, tongue and labial mucosa. Sometimes, it involves the floor of mouth and gingiva. Onset: The onset of the condition is insidious and is often of 2 to 5 years of duration. Symptoms: The most common initial symptom is burning sensation of oral mucosa (stomatopyrisis), aggravated by spicy food, followed by either hyper salivation or dryness of mouth. Vesiculation, ulceration, pigmentation, recurrent stomatitis and defective gustatory sensation have also been indicated as early symptoms. Referred pain in the ears and deafness, due to occlusion of Eustachian tube and a typical nasal voice has been reported. Signs (Fig. 12.25): Gradual stiffening of the oral mucosa occurs in few years after the initial symptoms appear. This leads to inability to open the mouth. Later on patients experience difficulty in protruding the tongue. When the fibrosis extends to pharynx and esophagus, the patient may experience difficulty in swallowing the food. The most common and earliest sign is blanching of mucosa, caused

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Textbook of Oral Pathology Flow chart 12.2 Pathogenesis of oral submucous fibrosis

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Table 12.5 Changes in oral submucous fibrosis

Early changes • • • •

Burning sensation excerbated by spicy food Vesiculation Blanching of mucosa Leathery mucosa

Late changes • • • •

Fibrous bands within mucosa Limitation of mouth opening Narrowing of oropharyngeal orifice with distortion of uvula Woody changes to mucosa and tongue.

Affected Sites and Their Signs Figure 12.25 Oral submucous fibrosis showing fibrous band

and decreased mouth opening

by impairment of local vascularity. The blanched mucosa becomes slightly opaque and white. The whitening often takes place in spots so that the mucosa acquires a marble like appearance. Blanching may be localized or diffuse, involving greater part of the oral mucosa or reticular, in which blanching consists of blanched area with intervening clinically normal mucosa, giving it a lace-like appearance. As disease progresses the mucosa becomes stiff and vertical fibrous bands appear there (Table 12.5).

Lips (36%): Mucosa is blanched, becomes rubbery and is characterized by the presence of circular bands around the rima oris like a thin band. In severe labial involvement, the opening of mouth is altered to an elliptical shape (elliptical rima oris), lips become leathery and it become difficult to evert them. Buccal mucosa (98%): The affected mucosa becomes coarse, blanched and inelastic. In advanced cases, the mucosa becomes tough and leathery with numerous vertical fibrous bands. Soft palate (49%) and uvula: Involvement of soft palate is marked by fibrotic changes and a clear delineation of the

Premalignant Lesions and Conditions

soft palate from hard palate. The mobility of soft palate is restricted. Uvula, when involved, is shrunken and in extreme cases, it becomes bud-like. 247

Palatal fauces: In the soft palate the bands radiate from pterygomandibular raphe to the anterior faucial pillars. The faucial pillars become thick and short and tonsils may get pressed in between fibrosed pillars. Tongue (37%): The initial change is depapillation, usually in the lateral margins. Tongue becomes smooth; its mobility, especially in protrusion, becomes impaired. Patient cannot protrude the tongue beyond the incisal edges. Floor of mouth (29%): When floor of mouth is affected, it becomes inelastic. Gingiva: When affected, it becomes fibrotic, blanched and inelastic.

Figure 12.26 Submucous fibrosis showing atrophic epithelium

(Courtesy: Dr Sangmesh Halawar, Reader, Department of Oral Pathology, CDCRI, Rajnandgao, Chhattisgarh, India)

Associated Features Pigmentation: Hyperpigmentation or occasional loss of pigmentation is very common in association with oral submucous fibrosis. Many a times pigmentation changes in vermilion border are so striking that this disease can be suspected even before examining the patient. Vesicle (32%): It is usually found in areas of redness in the soft palate, the anterior faucial pillar, buccal mucosa or the mucosal surface of lip, particularly the lower lip. The vesicles are painful and they soon rupture leaving behind superficial ulceration. Often there is history of vesiculation following the intake of spicy food, suggesting an allergic reaction to spicy food. Ulceration (43%): Ulceration often develops in the course of disease, particularly in advanced cases. In advanced cases, epithelium becomes atrophic, which render it fragile and vulnerable to ulceration. Petechiae: These are small raised reddish blue spots which sometimes occur in oral submucous fibrosis. It may be few or many. They occur most commonly on tongue and the labial and buccal mucosa. The petechiae are transient in nature and do not require any specific treatment.

Histopathological Features (Figs 12.26 to 12.28) Epithelium: In most of the cases, the oral epithelium is markedly atrophic. The atrophic epithelium exhibits intercellular edema (18%), signet cells (13%) and epithelial

Figure 12.27 Oral submucous fibrosis Oral submucous fibrosis showing (1) abundant deposit of collagen fibers; (2) flattening of rete pegs; (3) juxtaepithelial inflammatory cells

atypia (7%). Sometimes, the atrophic epithelium is associated with hyperorthokeratosis and pyknotic changes in the nuclei of basal cell layer. There is liquefaction degeneration of the basal layer of cells. Rete pegs are completely lost. Connective tissue: It shows vesicles, which are caused by subepithelial accumulation of fluid. The inflammatory cells are mostly mononuclear; eosinophils and occasional plasma cell may be seen.

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Figure 12.28 Oral submucous fibrosis (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

the juxtaepithelial basement membrane. Occasionally, thickened collagen bundles are still seen separated by slight residual edema. The fibroblastic response is less marked; the cells present being mostly adult fibrocytes with elongated, spindle-shaped nuclei and scanty cytoplasm. Blood vessels are either normal or constricted, as a result of increased surrounding fibrous tissue. The inflammatory exudate consists of lymphocytes and plasma cells, although occasional eosinophils may be present. 4. Advanced stage: Collagen is completely hyalinized and is seen as a smooth sheath with no separate bundles. Edema is absent. The hyalinized area is devoid of fibroblasts, although a thin elongated cell or vestigial nucleus is seen in a rare interval along the fiber bundle. Blood vessels are completely obliterated or narrowed. The inflammatory cells are lymphocytes and plasma cells.

Epithelial Atypia in Oral Submucous Fibrosis

Staging of Oral Submucous Fibrosis

The features most often associated are irregular epithelial stratification, increased number of mitotic figures, nuclear pleomorphism, hyperchromatism and loss of polarity of cell. Another striking feature is spongiosis, especially in basal cell layer. A considerable number of signet cells are also seen, mostly located in basal layer. Marked reduction in melanin pigmentation in basal cell layer.

There are various schemes for staging of oral submucous fibrosis. These schemes help clinicians in determining the severity of the disease and to modify the treatment accordingly (Haider et al).

Grading of Oral Submucous Fibrosis

Functional Staging (Table 12.7)

Pindborg has described the connective tissue changes in four consecutive stages as follows 1. Very early stage: It is characterized by finely fibrillar collagen dispersed with marked edema. The fibroblastic response is strong with plump young cells containing abundant cytoplasm. The blood vessels are sometimes normal, but more often they are dilated and congested. The inflammatory cells mainly polymorphs with occasional eosinophils are present. 2. Early stage: The juxtaepithelial area shows early hyalinization. The collagen is still seen as separated bundles which are thickened. Plump young fibroblasts are present in moderate numbers. The blood vessels are often dilated and congested. The inflammatory cells are mostly mononuclear lymphocytes eosinophils and occasional plasma cell. 3. Moderately advanced stage: The collagen is moderately hyalinized and amorphous changes start from

Functional staging is based on amount of mouth opening. It is measured between the central incisors of maxilla and mandible.

Clinical Staging (Table 12.6) It is based on bands seen in the oral cavity.

Table 12.6 Clinical staging of oral submucous fibrosis

Clinical stage

Clinical features

1

Faucial bands only

2

Faucial and buccal bands

3

Faucial, buccal, and labial bands

Table 12.7 Functional staging of oral submucous fibrosis

Functional staging

Amount of mouth opening

A

20 mm

B

11–19 mm

C

10 mm

Premalignant Lesions and Conditions

Malignant Potential Oral cancer originates in submucous fibrosis from diverse intraoral location, without any noticeable predilection for any specific site. Atrophic epithelium first becomes hyperkeratotic and later, intracellular edema and basal cell hyperplasia develop eventually, following epithelial atypia with moderate epithelial hyperplasia and then, carcinoma can develop at any time. To substantiate the precancerous nature of the condition, following points are noted: ∙ ∙ ∙ ∙ ∙

High occurrence of submucous fibrosis in oral cancer patient. Higher incidence of oral cancer in patient with oral submucous fibrosis. Histological diagnosis of carcinoma, without the clinical suspicion of it. Higher prevalence of leukoplakia among oral submucous fibrosis patients. Higher frequency of epithelial dysplasia.

The WHO Collaborating Center for Oral Precancerous Lesions has concluded that although oral submucous fibrosis predisposes to cancer, it is not absolutely conclusive. It is highly probable that such relationship does exist. Following facts support this hypothesis: The frequency of oral leukoplakia in oral submucous fibrosis patient is 6 to 8 times higher than in control group. Carcinoma patients exhibiting oral submucous fibrosis have a frequency with exceed the 1.2 percent of submucous fibrosis in general population. Immunological alternations observed in oral submucous fibrosis are almost similar to that observed in oral cancer.

Management Restriction of habit/behavioral therapy: The preventive measure should be in the form of stoppage of habit, which can be encouraged through public education. Affected patients should be explained about the disease and its possible malignant potential. Improvement in clinical features like gradual increase in inter-incisal opening has been observed in most of the patients who discontinue the habit. Medicinal therapy: A vitamin rich diet along with iron preparation is helpful to some extent but has little therapeutic value in relieving trismus. Iodine-B-complex preparation (Injection Ranodine) is a combination of iodine preparation with synthetic vitamin B complex.

Steroids: Hydrocortisone injection along with procaine hydrochloride injection locally in the area of fibrosis. Injections are given fortnightly. The early cases show good improvement with this therapy. Systemic steroid can also be given in severe cases. Placental extract: Injection of placentrix can also be given. Hyaluronidase can be given. Oral physiotherapy: Oral exercises are advised in early and moderately advanced cases. This includes mouth opening and ballooning of mouth. This is thought to put pressure on fibrous bands. Forceful mouth opening have been tried with mouth gag and acrylic surgical screw. Points to Remember Burning sensation of oral mucosa, referred pain in the ears, inability to open the mouth, difficulty in protruding the tongue, difficulty in swallowing the food, blanching of mucosa, bud-like uvula, pigmentation, vesicle, ulceration, petechiae, oral epithelium is markedly atrophic, connective tissue shows vesicles, inflammatory cells are mostly mononuclear, eosinophils, epithelial atypia, pleomorphism, hyperchromatism, loss of polarity of cell, restriction of habit/behavioral therapy, vitamin rich diet, hydrocortisone injection, placental extract, oral physiotherapy.

DYSKERATOSIS CONGENITA It is also called Zinssner-Engman-Cole syndrome. It is a well recognized but rare genokeratosis, which is probably inherited as X linked recessive characteristic. Disease manifested has three typical signs: oral leukoplakia, dystrophy of nails and pigmentation of skin.

Clinical Features Age and sex distributions are almost exclusively seen in males during first 10 years of life. Nail changes are the first manifestation, becoming dystrophic and shedding some time after the age of 5 years. Grayish brown pigmentations appear in some time which is seen usually on trunk, neck and thigh. The skin may become atrophic, telangiectatic and face appears red. Other minor manifestations are frail skeleton, mental retardation, small sella turcica, dysphagia, transparent

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tympanic membrane, deafness, epiphora, eyelid infection, urethral anomalies, small testes and hyperhydrosis of the palms and soles. Development of aplastic anemia and thrombocytopenia occur usually in second decade of life.

Oral Manifestations Age: The oral lesions have onset between the age of 5 to 14 years. Location: Most common sites are tongue and buccal mucosa. Appearance: It appears as diffusely distributed vesicles and ulcerations, followed by accumulation of white patches of necrotic epithelium (Fig. 12.29) and sometimes, superimposed monolial infection. After sometime, in the age group of 14 to 20 years, there are repeated recurrent ulceration and development of erythroplasia or red mucosal lesion. Finally between the age of 20 and 30 years, there is development of erosive leukoplakia and carcinoma.

Histopathological Features The skin lesion shows increased number of melanin containing chromatophores and increased vascularity. Depending upon the stage of disease epithelium may show dysplasia.

Management Symptomatic management of oral mucosal lesion should be done. Points to Remember Zinssner-Engman-Cole syndrome, leukoplakia, dystrophy of nails, pigmentation of skin, grayish brown pigmentations on trunk, mental retardation, development of aplastic anemia, tongue diffusely distributed vesicles and ulcerations, repeated recurrent ulceration, development of erythroplasia, increased number of melanin containing chromatophores.

LUPUS ERYTHEMATOSUS It is characterized by presence of abnormal antibodies and immune complex. Types • S ystemic lupus erythematosus: If multiorgan involvement occurs. • Discoid lupus erythematosus: It is also called chronic cutaneous lupus erythematosus. If it is confined to skin and mucosa. • Subacute cutaneous erythematosus: It present features of systemic as well as discoid type.

Etiology Genetic predisposition: Relative of patients have higher incidences autoantibodies, immune deficiency and connective tissue disease. This tendency is greatest among identical twins Immunological abnormality possibly mediated by viral infection: Immune complex consisting chiefly of nucleic acid and antibody account for majority of the tissue change seen. Autoimmune disease: As these patients develop antibodies to many of their own cells.

Figure 12.29 Dyskeratosis congenita lesion on tongue

Deposition of antigen: Antibody complexes. Endocrine (high incidence in females in pregnancy): Finding of increased estrogen level. Biochemical increase in excretion of metabolic products, particularly tyrosine and phenylalanine, in certain SLE patient.

Premalignant Lesions and Conditions

Discoid Lupus Erythematosus Clinical Features Age and sex distribution: It occurs in 3rd and 4th decades, female predilection in the ratio of 5:1. Location: Most common sites are face, oral mucosa, chest, back and extremities. Appearance: It is a circumscribed, slightly elevated, white patch that may be surrounded by red telangiectatic halo. Cutaneous lesions: These are slightly elevated, red or purple macules; that are often covered by gray or yellow adherent scales. Carpet track extension: Forceful removal of scale results in ‘carpet track extension’, which has dipped into enlarged pilosebaceous canals. The lesion increases in size by peripheral growth. Periphery of the lesion appears pink or red, while the center exhibits an atrophic scarred appearance. Butterfly distribution on macular region and across the bridge of the nose is present.

Oral Manifestations Location: Most common sites are buccal mucosa, tongue, palate and vermilion border of lip. Appearance: It begins as erythematous area, sometimes slightly elevated, but more often depressed, usually with induration and typically with white spots.

Symptoms: It is manifested by symptoms of fever and pain in the muscle and joints. It may present as itching or burning sensation as well as area of hyperpigmentation. Severely intensifies after exposure to sunlight. Cutaneous lesion: The cutaneous lesion consists of erythematosus patches on the face, which coalesce to form roughly symmetrical pattern over the cheeks and across the bridge of the nose, in a so called butterfly distribution. Skin lesions are widespread, bilateral with signs of acute inflammation. This finding helps to differentiate between skin lesions of DLE and SLE. Other manifestation: There is involvement of various organs including kidneys and heart. In kidney, fibrinoid thickening of glomerular capillaries produce the characteristic ‘wire loop’ which may be sufficient to result in renal insufficiency. Heart may suffer a Libman-Sacks endocarditis involving valves as well as fibrinoid degeneration of epicardium and myocardium.

Oral Manifestation Location: The most common sites are buccal mucosa, lip and palate. Patient complains of burning sensation, xerostomia or soreness of mouth. Appearance: The intraoral lesion is composed of a central depressed red atrophic area surrounded by 2 to 4 mm elevated keratotic zone that dissolves into small white lines (Fig. 12.30).

Signs: Occasionally, superficial painful ulceration may occur with crusting or bleeding, but no actual scale formation. Symptoms: There may be burning and tenderness which may be intermittent or disappear if the lesion becomes inactive. The margins of the lesion are not sharply demarcated. Fine white striae radiate out from the margins. Central healing may result in depression. Erythematous, atrophic plaque, surrounded by keratotic border may involve the entire lip.

Systemic Lupus Erythematosus Clinical Features Age and sex distribution: It occurs in 3rd (female) and 4th (male) decades and has female predilection (8:1). Location: It is characterized by repeated remissions and exacerbations with common sites being face, neck, upper arm, shoulders and fingers.

Figure 12.30 Lesion seen on palate of patient with systemic

lupus erythematosus

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Lesions similar to DLE, except that hyperemia, edema and extension of lesion is more pronounced. 252

Signs: There is greater tendency to bleed and petechiae, suspected ulcerations surrounded by red halo. Lupus cheilitis: The lip lesions appear with central atrophic area with small white dots surrounded by keratinized border, which is composed of small radiating white striae. There is occasional ulceration of central area.

Laboratory Findings LE cell inclusion phenomenon with surrounding pale nuclear mass apparently devoid of lymphocytes is present. It is characterized by presence of abnormal serum antibodies and immune complexes. There is also anemia, leukopenia and thrombocytopenia, with sedimentation rate increased. Serum gamma globulin increased and Coomb’s test is positive.

Figure 12.31 (1) The hair follicles cut in cross section; (2) Degeneration of basal cell layer; (3) Dense aggregate of chronic inflammatory cells; (4) Keratin plugging. (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H Kavalapur Sangli, Maharashtra, India)

Histopathological Features (Figs 12.31 and 12.32) Hyperorthokeratinization, hyperparakeratinization with keratotic plugging, atrophy of the rete pegs and liquefaction degeneration of basal layer is preset. There is perivascular infiltration of lymphocytes and their collection about dermal appendages, basophilic degeneration of collagen and elastic fibers with hyalinization, edema and fibrinoid change. Skin lesions show hyperkeratosis, with keratin packed into the openings of the hair follicles, called follicular plugging. Degeneration of the basal cell layers is seen common in both skin and oral lesions. The underlying connective tissue stroma shows patchy to dense aggregates of chronic inflammatory infiltrate. Differential diagnosis with lichen planus: LE shows perivascular infiltrate, PAS positive material in the basement membrane zone and subepithelial edema which may form vesicle.

Figure 12.32 SLE with keratin plugging (KP)

Management It is treated by systemic corticosteroids therapy and should be managed by physician. Anti-malarial drugs can be used in some cases.

Premalignant Lesions and Conditions

Points to Remember • D iscoid lupus erythematosus: Circumscribed, slightly elevated, white patch red telangiectatic halo, elevated cutaneous lesions, carpet track extension, Butterfly distribution of macular region, erythematous area on tongue, fine white striae radiate out from the margins. • Systemic lupus erythematosus: Fever and pain in muscle and joints, cutaneous lesion consists of erythematosus patches, wire loop, Libman-Sacks endocarditis, central depressed red atrophic area surrounded by 2 to 4 mm elevated keratotic zone in palate, lupus cheilitis • Histopathological: LE cell inclusion phenomenon, hyperorthokeratinization, hyperparakeratinization with keratotic plugging, perivascular infiltration of lymphocytes, follicular plugging.

BIBLIOGRAPHY 1. Axe, ll T, Holmstrup P, Kramer IRH, Pindborg JJ, Shear M. International seminar on oral leukoplakia and associated lesions related to tobacco habits. Community Dent Oral Epidemiol. 1984;12:145-54. 2. Axe’ ll T, Pindborg JJ, Smith CJ, van der Waal I and an International Collaborative Group on Oral White Lesions. Oral white lesions with special reference to precancerous and tobacco-related lesions: conclusions of an international symposium held in Uppsala, Sweden, May 18–21, 1994. J Oral Pathol Med. 1996;25:49-54. 3. Bremmer JF, Braakhuis BJM, Ruijter-Schippers HJ, et al. A non invasive genetic screening test to detect oral preneoplastic lesions. Lab Invest. 2005;85:1481-8. 4. Epstein JB, Wan LS, Gorsky M, Zhang L. Oral lichen planus: progress in understanding its malignant potential and implications for clinical management. Oral Surg Oral Med Oral Pathol. 2003;96:32-7. 5. Gupta PC, Mehta FS, Daftary DK, et al. Incidence rates of oral cancer and natural history of oral precancerous lesions in a 10-year follow-up study of Indian villagers. Community Dent Oral Epidemiol. 1980;8:287-333. 6. Handley TP, McCaul JA, Ogden GR. Dyskeratosis congenita. Oral Oncol. 2006;42:331-6. 7. Hansen LS, Olson JA, Silverman S. Proliferative verrucous leukoplakia. A longterm study of thirty patients. Oral Surg Oral Med Oral Pathol. 1985;60:285-9. 8. Johnson NW, Ranasinghe AW, Warnakulasuriya KAAS. Potentially malignant lesions and conditions of the mouth

9. 10. 11.

12.

13. 14. 15.

16.

17.

18. 19. 20.

21.

22.

23.

and oropharynx; natural history—cellular and molecular markers of risk. Eur J Cancer Prev. 1993;2:31-51. Meghji S, Warnakulasuriya S. Oral submucous fibrosis: an expert symposium. Oral Dis. 1997;3:276-91. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47:207-14. Pindborg JJ, Reichart PA, Smith CJ, van der Waal I. World Health Organization International Histological Classification of Tumours. Histological typing of cancer and precancer of the oral mucosa. Berlin: Springer; 1997. Reibel J. Prognosis of oral pre-malignant lesions: significance of clinical, histopathological and molecular biological characteristics. Crit Rev Oral Biol Med. 2003;14:47-62. Reichart PA, Philipsen HP. Oral erythroplakia – a review. Oral Oncol. 2005;41:551-61. Silverman S. Oral lichen planus: a potentially premalignant lesion. J Oral Maxillofac Surg. 2000;58:1286-8. Thompson PJ. Field change and oral cancer: new evidence for widespread carcinogenesis? Int J Oral Maxillofac Surg. 2002;31:262-6. Thornhill MH, Sankar V, Xu XJ, et al. The role of histopathological characteristics in distinguishing amalgamassociated oral lichenoid reactions and oral lichen planus. J Oral Pathol Med. 2006;35:233-40. van der Meij EH, Schepman K-P, van der Wall I. The possible malignant character of oral lichen planus and oral lichenoid lesions: a prospective study. Oral Surg Oral Med Oral Pathol. 2003;96:164-71. Waal van der I, Axe, ll T. Oral leukoplakia: a proposal for uniform reporting. Oral Oncol. 2002;38:521-6. Warnakulasuriya S. Histological grading of oral epithelial dysplasia: revisited. J Pathol. 200;194:294-7. World Health Organization. Report of a meeting of investigators on the histological definition of precancerous lesions. Geneva: World Health Organization; 1973, Can 731. World Health Organization. World Health Organization Classification of Tumours. In: Barnes L, Eveson JW, Reichart P, Sidransky D (Eds). Pathology and Genetics. Head and Neck Tumours. Lyon: International Agency for Research on Cancer (IARC) IARC Press, 2005.pp.177-9. World Health Organization Collaborating Centre for Oral Precancerous lesions. Definition of leukoplakia and related lesions: an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol. 1978;46:518-39. Zain RB, Ikeda N, Gupta PC, et al. Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25–27, 1996. J Oral Pathol Med. 1999;28:1-4.

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MULTIPLE CHOICE QUESTIONS 254

1. Following are the examples of precancerous lesion except: a. OSMF b. Leukoplakia c. Erythroplakia d. Cheilitis 2. Following are the examples of precancerous condition except: a. OSMF b. Lupus erythematosus c. Oral lichen planus d. Carcinoma in situ 3. Mother of pearl appearance seen in: a. Leukoplakia b. OSMF c. Leukoedema d. Bowen’s disease 4. Leukoplakia seen amongst clay pipe smokers and betel quid chewers are generally: a. Nodular type b. Verrcous type c. Homogeneous type d. Ulcerated type 5. ‘Oral florid papillomatosis’ is the extensive lesions of: a. Homogeneous leukoplakia b. Nodular leukoplakia c. Verrucous leukoplakia d. None

6. Syndrome associated with lichen planus is: a. Hanhart’s syndrome b. Graham Little syndrome c. Grinspan syndrome d. Both b and c 7. Wickham’s striae is characteristic feature of: a. Leukoplakia b. Lichen planus c. Erythroplakia d. Both a and b 8. Most common type of oral lichen planus is: a. Reticular type b. Bullous type c. Plaque type d. Atrophic form 9. Civatte bodies are seen in: a. Bowen’s disease b. c. Lichen planus d.

Leukoplakia OSMF

10. The most common and earliest sign seen in OSMF: a. Blanching of mucosa b. Wickham’s striae c. Bleeding of mucosa d. None

13

Malignant Tumors

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe), Ashok Mhaske

Chapter Outline ÂÂ Classification ÂÂ Etiology and risk factors for oral cancer ÂÂ Oral squamous cell carcinoma • Carcinoma of floor of mouth • Carcinoma of alveolar ridge • Carcinoma of buccal mucosa • Carcinoma of labial mucosa • Carcinoma of palate • Carcinoma of maxillary sinus • Multiple carcinomas ÂÂ Metastatic carcinoma ÂÂ Basal cell carcinoma ÂÂ Adenosquamous carcinoma ÂÂ Basaloid squamous carcinoma ÂÂ Sinonasal undifferentiated carcinoma ÂÂ Verrucous carcinoma ÂÂ Transitional cell carcinoma ÂÂ Malignant melanoma ÂÂ Spindle cell carcinoma ÂÂ Adenoid squamous cell carcinoma

INTRODUCTION Oral cancer although prevalent worldwide, but is very common in some countries such as India, Pakistan and Taiwan, and in some areas of France. Oral cancer most commonly occurs in middle-aged and older individuals, although number cases of these malignancies are also being reported in younger adults in recent years.

ÂÂ Nasopharyngeal carcinoma ÂÂ Merkel cell carcinoma ÂÂ Fibrosarcoma ÂÂ Malignant fibrous histiocytoma ÂÂ Synovial sarcoma ÂÂ Liposarcoma ÂÂ Chondrosarcoma ÂÂ Mesenchymal chondrosarcoma ÂÂ Osteosarcoma ÂÂ Ewing’s sarcoma ÂÂ Malignant hemangioendothelioma ÂÂ Malignant hemangiopericytoma ÂÂ Neuroblastoma ÂÂ Angiosarcoma ÂÂ Olfactory neuroblastoma ÂÂ Neurofibrosarcoma ÂÂ Leiomyosarcoma ÂÂ Rhabdomyosarcoma ÂÂ Malignant granular cell myoblastoma ÂÂ Alveolar soft part sarcoma

Cancer is Latinized from Greek word Karkinos, meaning crab denoting how carcinoma extends its claws like a crab into the adjacent tissues. Oral cancer can be divided into three categories: carcinomas of the oral cavity proper, carcinomas of the lip vermilion, and carcinomas arising in the oropharynx, from an epidemiological and clinicopathological pers pective.

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Common Sign and Symptoms 256

• Sore in the mouth that bleeds easily and does not heal • Pain in the mouth that does not go away • A lump or thickening in the cheek • A white or red patch on the gums, tongue, tonsil, or lining of the mouth • A sore throat or a feeling that something is caught in the throat • Difficulties in chewing, swallowing, or moving the tongue or jaw. Etiology of Oral Cancer • Actinic radiation • Familial and genetic • Atmospheric pollution • Orodental factors • Immunity • Smokeless tobacco • Smoking • Alcohol • Syphilis • Diet deficiency and deficiency status • Ionizing radiation • Trauma • Virus • Intraoral lesions like chronic ulceration and fissure, lichen planus, candidosis, leukoplakia, median rhomboid glossitis, Plummer-Vinson syndrome, submucus fibrosis, oral melanosis, discoid lupus erythematosus and epidermolysis bullosa.

CLASSIFICATION It is discussed in Table 13.1.

ETIOLOGY AND RISK FACTORS FOR ORAL CANCER The etiology of SCC of the oral cavity has been studied comprehensively last few decades. Various risk factors have been proposed as etiologic agents for the development of OSCC. Actinic radiation: It is a minor etiologic factor in cases of lip cancer. Lip cancer occurs more commonly in fair skinned people who are generally engaged in outdoor occupation, such as farming and fishing.

Table 13.1  WHO classification of malignant tumor of oral cavity

Malignant epithelial tumor Squamous cell carcinoma •  Verrucous carcinoma •  Basaloid squamous cell carcinoma •  Papillary squamous cell carcinoma •  Spindle cell carcinoma •  Acantholytic squamous cell carcinoma •  Adenosquamous carcinoma •  Carcinoma cuniculatum Lymphoepithelial carcinoma Epithelial precursor lesions Soft tissue tumors Kaposi sarcoma Lymphangioma Ectomesenchymal chondromyxoid tumor Focal oral mucinosis Congenital granular cell epulis Hematolymphoid tumors Diffuse large B-cell lymphoma (DLBCL) Mantle cell lymphoma Follicular lymphoma Extranodal marginal zone B-cell lymphoma of MALT type Burkitt lymphoma T-cell lymphoma (including anaplastic large cell lymphoma) Extramedullary plasmacytoma Langerhans cell histiocytosis Extramedullary myeloid sarcoma Follicular dendritic cell sarcoma/tumor Mucosal malignant melanoma Secondary tumors

Familial and genetic: There is little evidence that there is familial and genetic predisposition for the development of oral cancer. Lip cancer is amongst the sites which show strongest cancer clustering within families. But it also reflects the fact that families tend to have same occupation, i.e. fishing and farming, which is related with ultraviolet exposure. Oral cancers are more prevalent in black as compared to white. Atmospheric pollution: Parts of the urban/rural difference in incidence of head and neck cancers have been related to atmospheric pollution. Sulphur dioxide and smoke concentration in the atmosphere are positively correlated with squamous cancer of larynx and pharynx. The impact on cancer of the mouth is likely to be less, but merits careful

Malignant Tumors

study. Blue collar workers exposed to dust or inhalation of organic and inorganic agents are at increased risk of cancers of mouth. Orodental factors: It is more prevalent in patients with poor oral hygiene, faulty restorations, sharp teeth, ill fitting dentures and those with syphilitic glossitis. Immunity: The increasing incidence of oral cancers is clearly age-related, which may reflect declining immune surveillance with age. It may occur in immuno-suppressed patients following organ and bone marrow transplantation. HIV/AIDS patient are at increased risk of oral cancer. Smokeless tobacco: Taken together; the effect of tobacco use, heavy alcohol consumption and poor diet can probably explain over 90 percent of cases of oral cancer. Much of tobacco in the world is consumed without combustion, by being placed into contact with mucous membrane, through which nicotine is absorbed. It contains potent carcinogens like nitrosamine, polycyclic hydrocarbons and polonium and metabolites of these constituents, which have been the suggested etiologic factors in oral cancer (Table 13.2). Smoking: Tobacco smoke contains carbon monoxide. It is an important factor in the development of oral cancer. Study shows that cigar and pipe smoking increase the risk of cancer than cigarette smoking. It has been stated that the pooling of carcinogens in saliva gives rise to cancer in the floor of mouth and ventral and lateral tongue. Smoking is strongly associated with soft palate cancer than anterior sites. Table 13.2  Forms of oral smokeless tobacco

Some common forms of oral smokeless tobacco are as follows: Pan/paan/betal quid—it contains areca nut, betel leaf, slaked lime, catechu, condiments with or without tobacco. Khaini—it contains tobacco and lime. Mishri—it is burned tobacco. Zarda—boiled tobacco. Gudakhu—it contains tobacco and molasses. Mawa—tobacco, lime and areca. Nass—tobacco, ash, cotton or sesame oil. Naswar/niswar—tobacco, lime, indigo, cardamom, oil and menthol. Shammah—tobacco, ash and lime. Toombak—tobacco and sodium bicarbonate

Alcohol: All forms of alcohol; including hard liquor, wine and beer have been implicated in the etiology of oral cancer. The mechanism by which alcohol affects includes the dehydrating effect of alcohol on the mucosa which increases mucosal permeability and the effects of carcinogens on the mucosa. Beverage congeners include nitrosamines and impurities which can act as carcinogens. Most heavy alcohol consumer also uses tobacco so it is difficult to separate the ill effects individually. Syphilis: It is traditionally associated with oral cancer. Diet deficiency and deficiency status: Nutritional deficiency and liver dysfunction can also play a role in it. The relationship between sideropenic dysphagia and oral cancer is well-established. Ionizing radiation: Carcinoma of buccal mucosa may occur as a complication of long-term radiotherapy. Trauma: Trauma in combination with other factors like chronic cheek biting, denture use and irregular teeth may act as a co-carcinogen and may promote transformation of epithelial cells. Phenolic agents: There is increase risk for workers who are working in wood products industry which are exposed to chemical such as phenoxyacetic acids. Virus: The possibility of type I herpes simplex virus being associated with oral cancer has been suggested. Other viruses which can lead to oral cancer are human papilloma virus and HIV virus. Intraoral lesions: Some intraoral lesion can be responsible for the oral malignancy. They are as follows: – Chronic ulceration and fissure: It can cause oral cancer particularly of lip. – Lichen planus: Reports of carcinoma supervening on lichen planus have been made in some cases. – Candidiasis: It is possible precursor of carcinoma. Candidal infection is often associated with acanthosis and parakeratosis. – Leukoplakia: It is common premalignant condition seen in oral cavity. Nodular leukoplakia show higher rates of epithelial dysplasia. – Median rhomboid glossitis: In some cases, it has followed by cancer. – Plummer-Vinson syndrome: The atrophic changes in the mucous membrane of the upper alimentary tract that occur in this syndrome predispose to malignancy.

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– Submucous fibrosis: It is precancerous condition occur in oral cavity. – Oral melanosis: It appears to be associated with oral cancers in India. – Discoid lupus erythematosus: A number of cases of carcinoma of lip developing in the lesion of lupus erythematosus have been reported. – Epidermolysis bullosa: It is occasionally followed by carcinoma.

RISK FACTORS It is discussed in Table 13.3.

EPITHELIAL TUMORS Oral Squamous Cell Carcinoma Squamous cell carcinoma (SCC) is the most frequent of oral carcinomas. Majority of oral carcinomas are squamous cell carcinomas. It represents 90 percent of all malignant tumors occurring in the mouth and jaws. It is defined as “A malignant epithelial neoplasm exhibiting squamous differentiation as characterized by the formation of keratin and/or the presence of intercellular bridges”. The oral lesion often invades the jaw. It frequently involves buccal Table 13.3  Risk factors for oral cancers (adapted from JCDA April 2008, Vol. 74, No. 3, page no 269-272)

Very strong risk factors (> 10-fold increased risk) •  Increased age • Using tobacco and alcohol, especially combined use (risks for heavy smokers and drinkers are increased more than 30fold) •  Using smokeless tobacco, including snuff and chewing tobacco •  Chewing betel quid, areca nut and paan •  Being immunologically compromised (e.g. after bonemarrow transplantation) Strong risk factors (4- to 10-fold increased risk) •  Smoking cigarettes •  Drinking alcohol •  Having a human papilloma virus infection, especial type Moderate risk factors (≤ 4-fold increased risk) •  •  •  •  • 

Being male Smoking pipes and cigars Smoking marijuana Being exposed to environmental tobacco smoke Having low fruit and vegetable intake

sulcus, floor of mouth, tongue throat may occur at any intraoral site.

Location SCC can occur either in: (1) the nasal cavity and paranasal sinuses, (2) the nasopharynx, (3) the hypopharynx, larynx, and trachea, or (4) the oral cavity and oropharynx. Commonly involved areas are the posterior/lateral borders of the tongue and lower lip and less frequently the floor of mouth, alveolar mucosa, palate and buccal mucosa. It may be solitary and multifocal. The 2005 World Health Organization (WHO) classi­ fication of Head and Neck Tumors (Barnes et al., 2005) distinguishes different types of SCC: • Conventional • Verrucous • Basaloid • Papillary • Spindle cell (Sarcomatoid) • Acantholytic • Adenosquamous • Cuniculatum Each variant can arise in any one of the 4 above mentioned head and neck regions, except for the cuniculatum type which only develops from the oral mucosa.

Clinical Features Age and sex distribution: It predominately, it occurs in males with ratio of 2:1, older than 50 years with an average age of approximately 60 years. Appearance: Clinically, majority of oral cancers are characterized by ulceration and indurated margins with certain variations depends upon site of occurrence. Sign and symptoms: Patient may present with awareness of a mass or lump in the head and neck region or complain of long duration, non-healing ulcer in the oral cavity (Figs 13.1 and 13.2). Lesion may be asymptomatic or may become symptomatic due to involvement of vital structure or superadded infection. In certain case paresthesia can be evident in patients. Function of organ is impaired. The clinical appearance of a carcinomatous ulcer is that one of irregular shape, induration and raised everted edges. Usually have broad base and are dome like or nodular. Surface may range from granular to pebbly to deeply creviced. In some cases, surface may be entirely necrotic

Malignant Tumors

tumor to adjacent tissues, i.e. overlying bone suggests involvement of periosteum and possible spread to bone.

Histopathology Features The histopathological features are graded into three types depending upon the degree of differentiation of the neoplastic proliferating cell type: Well differentiated or highly differentiated squamous cell carcinoma Moderately differentiated squamous cell carcinoma Poorly differentiated squamous cell carcinoma. Common Features of all Carcinomas Figure 13.1  Squamous cell carcinoma of mandibular buccal

mucosa showing extraoral growth

• Epithelial dysplasia • Keratinization varies with degree of differentiation. • Local invasion by break in the basement membrane and invasion and proliferation into the underlying connective tissue—this is clinically manifested as fixation and induration of the lesion. •  Metastasis by blood or lymphatic channels histopathologically seen as invasion of tumor cells into the capillaries and lymphatic ducts permeation. • Perinueral invasion—some of the tumor cells may have a typical invasion pattern along the nerve sheath.

Well Differentiated Squamous Cell Carcinoma (Figs 13.3 to 13.5)

Figure 13.2  Carcinoma palate spreading on the alveolar

mucosa and vestibule

and have ragged whitish gray appearance. It may be completely red or red surface may be sprinkled with white necrotic or keratin area. Base and borders are firm to palpate and the lesion may get fixed after infiltration into underlying tissues. Lymph nodes: Superficial and deep cervical nodes are commonly affected. They become enlarged and are firm to hard on palpation. The nodes are non-tender unless associated with secondary infection or an inflammatory response. It may be nodular or polypoid and pink to red and have at least one ulcerated patch on their surface. Fixation of nodes to adjacent tissues occurs later. Fixation of primary

It consists of sheets and nest of cells with characteristic appearing of squamous origin. These cells are generally large and show distinct cell membrane. They resemble the cells of squamous epithelium, both structurally and functionally. The intercellular bridges are prominent. The nuclei are distinctly dark staining and hyperchromatic due to increase in condensed chromatin. Increased number of mitotic figures, less as compared to moderately differentiated carcinoma is evident. Other prominent feature includes multiple nucleoli and increased nucleo-cytosplasmic ratio. Most prominent feature is presence of individual cell keratinization and formation of numerous keratin pearls of varying size. Each keratin pearl consists of a central area of keratin surrounded by whorls of prickle cells. Pleomorphism of cells, keratinization, and keratin pearls (Figs 13.6 and 13.7) deep to epithelial surface and loss of intercellular bridges or cohesiveness may be seen.

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Figure 13.3  Well differentiated squamous cell carcinoma

(low power)

Figure 13.4  Well differentiated squamous cell carcinoma

showing hyperchromatism

Moderately Differentiated/Less Well Differentiated Squamous Cell Carcinoma (Figs 13.8 to 13.13) The tumor cells are less differentiated and have less resemblance to squamous epithelium. The characteristic shape of an epithelial cell may not be evident. The cell to cell contacts and relation and arrangement are altered. The greater number of mitotic figures shows that the growth rate is more rapid. This may be varied size and shape.

Figure 13.5  Well differentiated squamous cell carcinoma

showing keratin pearl

Figure 13.6  Keratin pearls in well differentiated squamous

cell carcinoma

The keratinization is absent as the cells cannot in size and shape. Keratin pearls may not be present function to the differentiation point of keratin formation. Numerous epithelial islands of prickle cells with peripheral basal cells may be seen.

Poorly Differentiated Squamous Cell Carcinoma This is the tumor with proliferating anaplastic cells, highly invasive with poor prognosis. The tumor cells bear

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261

Figure 13.7  Formation of keratin pearl in concentric rings

Figure 13.10  Moderately differentiated squamous cell carcinoma showing less differentiated epithelial islands in the stroma

Figure 13.8  Moderately differentiated squamous cell

Figure 13.11  Moderately differentiated carcinoma with high

carcinoma with greater number of mitotic figures

Figure 13.9  Moderately differentiated squamous cell

carcinoma showing pleomorphism of cells

mitosis and epithelial pearl formations

Figure 13.12  Moderately differentiated carcinoma (high

power)

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262

Figure 13.13  Poorly differentiated squamous cell carcinoma

Figure 13.14  Radiograph showing destruction of bone in

showing lack of cohesiveness

mandible due to malignancy

little resemblance to their cells of origin and often will present diagnostic difficulties because of the primitive and uncharacteristic histological appearance. These cells show lack of cohesiveness and are extremely vagarious. The mitotic figures are extremely high.

Radiological Features On the radiographic there is destruction of bone. The appearance which is seen as moth eaten with ill-defined ragged margin (Figs 13.14 and 13.15). Points to Remember • Mass or lump, non-healing ulcer in the oral cavity, irregular shape, induration and raised everted edges, broad base, surface may range from granular to pebbly to deeply creviced, lymph nodes become enlarged firm to hard on palpation, moth eaten with ill defined ragged margin •  Well differentiated squamous cell carcinoma— resemble the cells of squamous epithelium, increased number of mitotic figures, multiple nucleoli and increased nucleo-cytosplasmic ratio, individual cell keratinization, keratin pearls, pleomorphism of cells, keratinization, and keratin pearls • Moderately differentiated/less well differentiated squamous cell carcinoma—cell to cell contacts, greater number of mitotic figures, keratinization is absent •  Poorly differentiated squamous cell carcinoma— proliferating anaplastic cells, highly invasive, lack of cohesiveness, extremely vagarious.

Figure 13.15  Moth eaten appearance of squamous cell

carcinoma

Different Types of Carcinoma According to Site Below we have described different types of carcinoma according to their location. Carcinoma of tongue and lip are described in chapter of disease of tongue and lip respectively.

Carcinoma of Floor of Mouth Sex distribution: It is seen more commonly in men. Appearance: It is seen most frequently in the anterior portion of floor. The typical carcinoma of the floor of mouth is an indurated ulcer (Fig. 13.16) of varying size, on one side of the midline.

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263

Figure 13.16  Carcinoma of floor of mouth showing

Figure 13.17  Malignancy of lower alveolar ridge

ulcerative growth

showing growth

Sign and symptoms: It may take form of wart like growth, which tend to spread superficially rather than in depth. Carcinoma in close relation to teeth may cause loosening or exfoliation and root resorption. It may or may not be painful. In some cases there may be referred pain in the ears. There may be excessive salivation. The proximity of this tumor to the tongue produces some limitation of motion of these organs, often induces peculiar thickening or slurring of the speech. Metastatic: Carcinoma of floor of mouth may invade the deeper tissues and may even extend into the sub-maxillary and sublingual glands. Metastasis from the floor of the mouth are found most commonly in the sub-maxillary group of lymph nodes and since the primary lesion frequently occurs near the midline where a lymphatic cross drainage exists, contra-lateral metastasis is often present.

Figure 13.18  Carcinoma of buccal mucosa showing

extending extraorally

Carcinoma of Alveolar Ridge (Fig. 13.17) It is cause by ill fitting dentures, smoking, and alcohol. It is presented as ulcer or growth on alveolar ridge. Symptoms: Numbness, mobility teeth, pain, bleeding, dysphagia. Sign: There is invasion to adjacent structures—buccal mucosa, floor of mouth. Metastasis occurs into upper deep jugular nodes.

Carcinoma of Buccal Mucosa (Figs 13.18 to 13.21) Location: The lesions develop most frequently along or inferior to a line opposite the plane of occlusion. It usually occurs opposite to the 3rd molar.

Figure 13.19  Carcinoma of buccal mucosa showing intraoral

ulceration

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Carcinoma of Labial Mucosa (Fig. 13.22) It is frequently encountered in person who habitually keeps a mixture of tobacco lime in the labial groove.

264

Location: The lower labial mucosa is more commonly involved than the upper. Signs and symptoms: The most common initial signs and symptoms are growth or swelling, soreness and ulceration. Advanced lesion may be ulcerative-infiltrative type. Lymph node involvement may occur, which may be unilateral or bilateral. Most common lymph nodes involve is submandibular lymph nodes. Figure 13.20  Carcinoma of buccal mucosa showing

ulcerative growth on cheek

Carcinoma of Palate Sex distribution: It is common in area where reverse smoking is practiced. It is seen more amongst women as compared to men, in case of reverse smoking. Appearance: Palatal cancer usually manifest as a poorly defined ulcerated painful lesion on one side of the midline. Most of the lesions are exophytic and with broad base and nodular surface. It frequently crosses the midline and may extend laterally to include tonsillar pillars or even the uvula. The tumor of hard palate may invade the bone or occasionally the nasal cavity while infiltrating lesions of the soft palate may extend into the nasopharynx.

Figure 13.21  Carcinoma seen as an ulcerative fungating

growth in buccal vestibule

Appearance: The tumor begins as small nodules and enlarges to form a wart like growth which ultimately ulcerates. The lesion is often painful. There is induration and infiltration of deeper tissues. Extension into the muscle of neck, alveolar mucosa and ultimately into bone may occur. Some cases appear to be growing outward from the surface rather than invading the tissues is called as exophytic or verrucous growth. Metastasis: The most common site of metastasis is the submaxillary lymph nodes.

Figure 13.22  Carcinoma of labial mucosa showing

ulceration

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Carcinoma of Maxillary Sinus (Figs 13.23 to 13.25) It is most common primary tumor of paranasal sinuses comprising 80 to 90 percent of cancers in this site.

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Cause: It is caused by sinusitis, snuff and smoke and occupational hazards like in boot and shoe manufacturing and nickel worker. Age and sex distribution: Mean age of occurrence is 60 years. Males are commonly affected more than females in the ratio of 2:1.

Figure 13.25  CT scan showing increase radiopacity in right

maxillary antrum with destruction of borders

Figure 13.23  Maxillary sinus malignancy showing intraoral

ulceration

Symptoms: There is facial pain, swelling, nasal obstruction and lymphadenopathy. Medial wall involvement leads to nasal obstruction, discharge, bleeding and pain. Epiphora will result if the lacrimal sac or naso-lacrimal duct is obstructed. Involvement of the floor of the sinus leads to expansion of the alveolus, unexplained pain, and numbness of teeth, loose teeth and swelling of the palate or alveolar ridge and ill-fitting dentures. It may erode the floor and penetrate the oral cavity. Lateral wall involvement leads to facial and vestibular swelling, pain and hyperesthesia of maxillary teeth. Roof involvement leads to diplopia, proptosis and pain over the cheek and upper teeth. Posterior wall involvement leads to painful trismus, obstruction of Eustachian tube causing stuffy ear, referred pain and hyperesthesia over the distribution of second and third division of trigeminal nerve. It may involved infraorbital nerve and produces paresthesia of the cheek or erodes blood vessels giving rise to epistaxis. Paresthesia of mandibular nerve can also occur if the tumor invades the cranium.

Multiple Carcinomas

Figure 13.24  Extraoral swelling seen in maxillary sinus

malignancy

Patient who is having one carcinoma of mouth or throat are increase risk of additional malignancy of upper aerodigestive tract, esophagus, stomach, lungs or other sites. This is common in patients who take alcohol and smoke after the therapy.

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The tendency to develop multiple mucosal cancers which sometime called as field cancerization reflects diffuse exposure to local carcinogen. The reason for this is that the whole mucosa is often in an abnormal state for long periods, prior to the development of over cancer. The most common finding is that there is area of atrophy, either adjacent to a carcinoma or randomly distributed.

Management Average time delay between onset and examination is 4 to 9 months and detection and Accurate diagnosis is 5 to 6 months. Removal of any local irritants (smoking, spices, spirit, sepsis and syphilis) is very important as part of treatment. Biopsy is mandatory in every case of carcinoma. Surgery: Cryosurgery, laser surgery and radical surgery. Radiation and chemotherapy can also be performed. Commonly used chemotherapeutic agents are cisplatin, carboplatin, 5-fluorouracil and taxanes are used. Points to Remember •  Carcinoma of floor of mouth: Anterior portion of floor, indurated ulcer, wart like growth, loosening of teeth, root resorption, slurring of the speech, Metastatic to sub-maxillary and sublingual glands. •  Carcinoma of alveolar ridge: Ill fitting dentures, numbness, mobility teeth, dysphagia, metastasis to upper deep jugular nodes. • Carcinoma of buccal mucosa: Small nodules and enlarges to form a wart like growth, extension into the muscle of neck, metastasis to submaxillary lymph nodes. •  Carcinoma of labial mucosa: Swelling, soreness, lymph node involvement, submandibular lymph nodes. •  Carcinoma of palate: Reverse smoking, poorly defined ulcerated painful, crosses the midline, infiltrating lesions of the soft palate. • Carcinoma of maxillary sinus: Sinusitis, snuff, facial pain, nasal obstruction, medial wall involvement, involvement of the floor of the sinus, lateral wall involvement, roof involvement, posterior wall involvement, paresthesia of mandibular nerve. • Multiple carcinomas: One carcinoma of mouth with malignancy of upper aerodigestive tract, field cancerization. • Management: Surgery, radiation, chemotherapy.

METASTATIC CARCINOMA It is also called as secondary carcinoma. It is the most common malignant tumor in the skeleton. This tumor is transported to an area distant from its origin and establishes a new foot holds and are said to have metastasized. Although the metastatic carcinoma of jaw is uncommon, its reorganization is important because the jaw tumors may be the first indication that the patient has a malignant disease. Metastasis carcinoma occurs to soft tissue as well as bone. For soft tissue metastasis is usually blood borne metastasis usually by Batson’s plexus (valveless vertebral venous plexus which allow retrograde spread of tumors cells, bypassing filtration through lungs). For bone metastasis it occurs through hematogenous route. Oral diagnostician can make an invaluable contribution of pathologic process of bone. Most common sites of origin are breast, lung, kidney, thyroid, prostate and colon.

Clinical Features Location: For jaw metastatic mandible is involved much more frequently than maxilla, especially in the region near premolars and molars as tumor metastasizes to those bones which are rich in hemopoietic marrow. It is said that blood flow rate is decreased in areas of hemopoietic marrow and this predisposes tumor emboli to settle and grow in these areas. This hypothesis is consistent with jaw metastases as hemopoietic marrow is most routinely found at this site. The other sites involved are maxillary sinus, anterior hard palate and mandibular condyle. For soft tissue metastatic gingiva followed by tongue is involved. Age: It is found in patients between 40 and 60 years of age and there may be history of primary tumor. Appearance: Early lesion is nodule or dome with shaped smooth surface and due to trauma may get ulcerated. Symptoms: There may be pain followed by paresthesia or anesthesia of lip or chin. Sign: Teeth in this region may become loose or exfoliate and root resorption may occur. On occasion, tumor may breach the outer cortical palate of jaws and extend into surrounding soft tissue or presents as an intraoral mass. Metastatic tumors are diagnosed only when the sockets of extracted teeth do not heal because of periodontal disease. If invasion occurs in muscle then their function is impaired.

Malignant Tumors

Numb chin syndrome: When there is involvement inferior alveolar nerve in mandible due to metastatic when there is unexplained loss of sensation of lip and chin. All the soft tissues curetted from an extraction socket, even in absence of clinical suspicion should be submitted for histological examination.

267

Radiological features: Loss of bony support, involving one or several adjacent teeth, in the absence of generalized periodontitis is an important symptom. There may be pathological fracture of the jaw or hemorrhage from the tumor site. Extraction socket fails to heal or enlarged. Patient may have moth eaten appearance (Fig. 13.26).

Histopathological Features It is well differentiated tumor or poorly differentiated which resembles features of primary tumor (Fig. 13.27).

Management Prognosis is poor and death occurs within a short time. It can be treated by chemotherapy, radiation therapy, surgery, and immunotherapy and hormone therapy. Points to Remember Root resorption, mandible is involved, lesion is nodule or dome with shaped smooth surface, paresthesia or anesthesia of lip teeth, loose or exfoliate, numb chin syndrome, pathological fracture of the jaw, moth eaten appearance, well differentiated tumor or poorly differentiated.

Figure 13.27  Metastatic carcinoma showing well differentiated carcinoma (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

BASAL CELL CARCINOMA It is also called as basal cell epithelioma or Rodent ulcer. It arises from basal layer of epidermis or from the hair follicle.

Etiology The specific factor in sunlight responsible for skin carcinogenesis appears to be ultraviolet radiation. Other factors are also responsible like burn scars and ionizing radiation. General atrophy associated with aging process, at least, predispose to development of skin cancer.

Clinical Features Age and sex distribution: It occurs in middle aged or elderly person usually in 4th decade of life. Blond people with fair complexion who have spent much of their lives outdoors are often victim of these lesions. It is much more common in men than women because men are exposed to the environmental elements more than women. Location: It develops most frequently on exposed surface of skin (Figs 13.28 and 13.29), middle thirds of face and the scalp. There is also involvement of lip. The upper lip is involved more commonly than the lower lip.

Figure 13.26  Metastatic tumor showing destruction

Signs: It begins as a small, slightly elevated papule which ulcerates, heals over and then breaks down again to form crusted ulcer. It develops a smooth, rolled border

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Clinical Variant of Basal Cell Carcinoma 268

Figure 13.28  Basal cell carcinoma showing extensive

destruction of face

Noduloulcertive: Firm painless papule that enlarge •  and develop into central depression and umblicated appearance. • Pigmented basal cell carcinoma: Melanin produc­tion gives brown, black, or bluish color. • Sclerosing (morpheaform) basal cell carcinoma: It mimic scar tissue. Slight elevation at the edges of tumor. Superficial basal cell carcinoma: Multiple lesion •  appear as well demarcated scaly patches with threadlike border. • Nevoid basal cell carcinoma: Basal cell carcinoma associated with syndrome.

Histopathological Features (Figs 13.30 to 13.32) It is characterized by appearance of nests, islands or sheets of cells showing indistinct cell membranes with large deeply staining nuclei and variable number of mitotic figures. The periphery of cell nests is composed of a layer of cells, usually well polarized, that are strongly suggestive of cell of the basal cell layer of skin. The basal cell is a pluripotential cell which may develop in several directions. It may form hair, sebaceous glands, sweat glands or squamous epithelium and eventually keratin. Histological Types of Basal Cell Carcinoma

Figure 13.29  Melanoma showing diffuse border

representing tumor cells spreading laterally beneath the skin. Untreated lesion continues to enlarge and infiltrate the adjacent and deeper tissues and it may even erode deeply into the cartilage or bone. Due to its invading and destructive infiltration into adjoining tissues, it gradually increases in size and accounts for its synonym rodent ulcer. It is never seen in oral cavity unless it arrives there by invasion and infiltration from a skin surface. Occasionally, it may metastasize to lymph nodes.

• Adenoid basal cell carcinoma: It represent neoplasm which mimics glandular formation. • Cystic basal cell carcinoma: Presence of many cyst in the lesion. •  Keratotic basal cell carcinoma: Formation of parakeratotic cells and horn cysts and attempted formation of hair structures to the trichoepithe­ lioma. • Solid or primordial basal ell carcinoma: Cells have little tendency to differentiate.

Management Surgical excision or X-ray radiation can be given. Mohs micrognathic surgery: This technique used frozen section evaluation of specially mapped and marked

Malignant Tumors

surgical specimen to determine whether tumor tissue left behind. If it is left behind surgeon can immediately return and remove more tissue. Photodynamic therapy is useful for superficial variety of basal cell carcinoma. Points to Remember Basal cell epithelioma, ultraviolet radiation, exposed surface of skin, smooth, rolled border, invading and destructive infiltration, rodent ulcer, indistinct cell membranes, basal cell is a pluripotential cell, Mohs micrognathic surgery, photodynamic therapy.

Figure 13.30  Basal cell carcinoma showing sheets and nest

of hyperchromatic epithelial cells

ADENOSQUAMOUS CARCINOMA It is combination of adenocarcinoma and squamous cell carcinoma.

Clinical Features Age and sex distribution: It is seen in older individual with more commonly seen in male. Location: It is seen on tongue, oral floor and other mucosal surface. Appearance: It appear as nodular broad based painful mass with or without surface ulceration. Sign: There is metastasis deposit in the lymph nodes of neck.

Histopathological Features Figure 13.31  Basal cell carcinoma (low power)

There is presence of features of squamous cell carcinoma and ductal adenocarcinoma. Glandular portion seen in deeper portion of the tumor.

Management Radical surgical excision with radiation therapy is the treatment of choice. Points to Remember Nodular broad based painful mass, metastasis deposit in lymph nodes of neck, ductal adenocarcinoma, features of squamous cell carcinoma, radical surgical excision.

BASALOID SQUAMOUS CARCINOMA Figure 13.32  Basal cell carcinoma (high power)

It is also called as basaloid squamous cell carcinoma. It occur in alcohol user and person who smoked tobacco.

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Clinical Features 270

Age and sex distribution: It is seen in 4th to 7th decade of life with male predilection.

SINONASAL UNDIFFERENTIATED CARCINOMA

Location: It is seen in larynx, pyriform sinus, tongue base but any region of aerodigestive tract can be affected.

It is highly aggressive neoplasm of nasal cavity and paranasal sinuses. The cells of origin are from schneiderian membrane or olfactory epithelium.

Appearance: It appears as a fungating mass or ulcer and interferes with swallowing.

Clinical and Radiological Features

Sign: There is cervical metastasis.

Age and sex distribution: There is tendency to older patient with more prevalence in males.

Histopathological Features There is superficial well differentiated or moderately differentiated squamous cell carcinoma. The deeper component shows an invasive basaloid epithelium arranged in islands, cords and glandlike lobules (Fig. 13.33). There is also palisading peripheral cells, necrosis of central region. Basaloid cells and islands of cells are surrounded by mucoid stroma.

Management Surgery followed by radiotherapy is recommended treatment for the patients. Points to Remember Basaloid squamous cell carcinoma, fungating mass or ulcer, interferes with swallowing, cervical metastasis, superficial well differentiated or moderately differenti­ated squamous cell carcinoma, cords and glandlike lobules.

Figure 13.33  Basaloid squamous cell carcinoma showing

gland like structure

Location: It involve sinonasal tract including nasal cavity, maxillary sinus, ethmoid sinuses. Lesion may extend nasopharynx, orbit and cranial cavity. Sign and symptoms: There is nasal obstruction or discharge, epistaxis, swelling and pain, orbital involvement lead to proptosis, periorbital swelling, diplopia, and vision loss. Radiographic features: Large expansile sinonasal mass with bony destruction and invasion of adjacent structure.

Histopathological Features It is characterized by trabecular, ribbons, sheets, and nest of polygonal cells with minimal cytoplasm (Fig. 13.34). There are numerous mitotic figures. There is also tumor necrosis, apoptosis, and lymphovascular invasion.

Management Complete surgical therapy with adjunct radiation or chemotherapy.

Figure 13.34  Sinonasal carcinoma showing nest of

polygonal cells

Malignant Tumors

Points to Remember Nasal obstruction or discharge, epistaxis, expansile sinonasal mass, trabecular, ribbons, sheets, nest of polygonal cells with minimal cytoplasm, numerous mitotic figures apoptosis, lymphovascular invasion.

VERRUCOUS CARCINOMA It is also called as Snuff Dipper’s cancer, Ackerman’s tumor. The verrucous carcinoma (VC), a low-grade variant of squamous cell carcinoma, has been reported in the head and neck area, with predilection by oral cavity and larynx. The clinical presentation of verrucous carcinoma often shows a local invasive pattern without any distant metastases and excellent prognosis. The establishment of clinical or histopathological diagnosis of verrucous carcinoma in the oral cavity may be difficult to interpret. This complexity has been attributed to the indolence of the tumor’s grow, its benign histological features, and the lack of awareness by the pathologist of the tumor’s gross appearance.

Symptoms: Pain and difficulty in mastication are common complain. Regional lymph nodes are often tender and enlarged simulating metastatic tumor, but the node involvement is usually inflammatory. Signs: They appear papillary in nature with pebbly surface which is sometimes covered by a white leukoplakic film. They have rugae-like folds with deep cleft between them. In some cases, there may be warty fungating mass. Large broad lesion with minimum to extensive elevation above surface of the mucosa. Margins are well-defined and show rim of slightly elevated normal mucosa (Figs 13.35 to 13.37).

Etiology The etiological factor of verrucous carcinoma in the oral cavity is not completely established, although the lesion had been associated with tobacco use and human papilloma virus (HPV). There is co-relation between tobacco chewing habit and occurrence of high percentage of VC. It occurs usually in a person habitual to hold the quid in the buccal sulcus.

Clinical Features

Figure 13.35  Verrucous carcinoma showing papillary growth (Cour­­tesy: Dr Aparna Thombre, Reader, Department of Oral Path­ ology, VSPM Dental College and Hospital, Nagpur, Mah­a­rashtra, India)

Age and sex distribution: It is generally seen in elder population with mean age of occurrences range from 50 to 80 years with a male predominance and the median age is 67 years. Location: Verrucous carcinoma (VC) may occur in several locations in the head and neck and in the genitalia. The oral cavity is the most common site of this tumor, with more affinity for buccal mucosa, gingiva or alveolar ridge. Other extra oral sites involved are larynx, external auditory meatus, lacrimal duct, skin, scrotum, penis, vulva, vagina, uterine cervix, perineum, and leg and odontogenic cyst linings. Onset: Oral lesion is slow growing, chiefly exophytic and only superficial invasive, at least until late in the course of the disease and has a low metastatic potential.

Figure 13.36  Verrucous carcinoma showing papillary growth

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Figure 13.37  Verrucous carcinoma on lower alveolar ridge

Figure 13.38  Verrucous carcinoma showing downgrowth of

epithelium into connective tissue

Lesion on the mandibular mucosa grows into overlying soft tissue and rapidly becomes fixed to the periosteum, gradually invading and destroying the mandible.

Histopathological Features There is marked epithelial proliferation with downgrowth (Figs 13.38 and 13.39) of epithelium into connective tissue but usually without the pattern of true invasion. The epithelium is well differentiated and shows little mitotic activity, pleomorphism or hyperchromatism. Cleft like spaces lined by a thick layer of parakeratin extend from the surface deep into the lesion is seen. Parakeratin plugging (Fig. 13.40) also occurs the epithelium. Parakeratin lining of clefts with parakeratin plugging is the hallmark of verrucous carcinoma. Even though the lesion may be very extensive, basement membrane will be intact. When the lesion becomes infected, focal intraepithelial abscesses are often seen. Chronic inflammatory cell infiltration in the underlying connective tissue may or may not be present. All bulbous rete pegs of the epithelium tend to project into the underlying connective tissue, at more or less the same level and this is called as pushing margin. Downgrowth of epithelium in connective tissue show pushing borders which are rather small that invasive extension. Abundance of keratin is seen on the surface and with invaginating epithelium as keratin plugging (Figs 13.41A and B).

Figure 13.39  Verrucous carcinoma showing parakeratin

plugging

Management Prognosis in verrucous carcinoma is very good because of absence or late appearance of metastases.

Figure 13.40  Verrucous carcinoma showing parakeratin

plugging and blunt rete pegs

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273

A

B

Figures 13.41A and B  Histopathological picture of verrucous carcinoma (Courtesy: Dr Aparna Thombre, Reader,

Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Excisional Surgery is considered as the treatment of choice. The extent of surgical margin and the adjuvant radiotherapy are still controversial. Points to Remember Snuff Dipper’s cancer, Ackerman’s tumor, tobacco use, human papilloma virus, slow growing, pain and difficulty mastication, papillary pebbly surface, deep cleft between warty fungating mass, invading and destroying the mandible, marked epithelial proliferation with downgrowth, epithelium is well differentiated, cleft like spaces lined by a thick layer of parakeratin, parakeratin plugging, pushing margin, downgrowth of epithelium, excisional surgery.

exophytic or fungating growth. Swelling of regional lymph node is most common occurrence.

Histopathological Features The transitional cell is a moderately large, round or polyhedral and exhibits a lightly basophilic cytoplasm and has indistinct cell outlines. The tumor consists of cells arranged and growing in solid sheets or in cords and nests. The nuclei are large and round and they exhibit varying degree of mitotic activity. Keratinization and pearl formation is not evident.

Management X-ray radiation is most commonly the accepted treatment.

TRANSITIONAL CELL CARCINOMA

Points to Remember

These lesions arise chiefly from the tonsil, base of the tongue and nasopharynx. It is extremely malignant, running a rapid clinical course, metastasizing widely and causing very early death.

Primary lesions, slightly elevated, frankly ulcerated, granular eroded surface, moderately large, round or polyhedral and exhibits a lightly basophilic cytoplasm, solid sheets or in cords.

Clinical Features Age: Mean age of occurrence is 44 years. Symptoms: There may be sore throat, nasal obstruction, defective hearing or ear pain, headache, dysphagia, epistaxis and ocular symptoms. Signs: The primary lesions are very small often completely hidden, usually slightly elevated and either frankly ulcerated or presenting a granular eroded surface. The tumor is indurated and in some instances appears as an

MALIGNANT MELANOMA Melanoma is the third most common skin cancer and accounts for 5 percent of the total. It is a neoplasm of epidermal melanocytes. It is one of the biologically unpredictable and deadly of all human neoplasms. Sunlight is very important etiological factor in cutaneous melanoma. People with a sunburn tendency are at high-risk. The fair skinned people are more prone for development of the tumor.

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Types 274

• • • •

Superficial spreading melanoma Nodular melanoma Lentigo maligna melanoma Acral lentiginous melanoma.

Clinical Features Melanoma tends to have two growth phases, i.e. radial growth phase and vertical growth phase. Radial growth phase is common in superficial spreading melanoma, Lentigo maligna melanoma and acral lentiginous melanoma. In this lesion melanocytes spread horizontally through basal layer of epidermis. Later on it invade underlying tissue casing vertical growth phase. Vertical growth phase is seen in nodular melanoma from the beginning.

Superficial Spreading Melanoma It is the most common cutaneous melanoma. Age and sex distribution: The majority of case diagnosed in the 5th to 7th decade of life. It is more common in males as compared to females in the ratio of 2:1. Location: It also occurs on skin of face, head and neck, chest, abdomen and extremities. In male, it is common in interscapular areas of males and back of legs in females. Appearance: The lesion presents as a tan brown, black or admixed lesion on sun exposed skin, in especially in blacks. It begins as pigmented macule in superficial radial growth pattern, restricted mostly to epithelium and junction. In advanced cases, melanoma present as an ulcerated, fungating growth which is associated with bleeding. The radical growth phase may last for several months to several years. The vertical growth phase is characterized by increase in size, change in color, nodularity and at times, ulceration. Some lesions are devoid of pigmentation which is called as amelanotic melanoma.

Nodular Melanoma Location: They have a predilection for occurrence on head and neck in male. Appearance: Color varies from mucosal pink through brown and blue to black. It is firm on palpation. It has got erythematous borders which surround the tumor.

There is rapid infiltration in nodular type of melanoma. It may be focal or diffuse. Many times it may ulcerate and hemorrhage may be seen. In later stages, it becomes more diffuse, nodular and tumefactive with foci of hypo and hyperpigmentation. It presents as a sharply delineated nodule with some degree of pigmentation.

Lentigo Maligna Melanoma Location and sex: It has got predilection for exposed parts. It occurs more often in women than in men. Hutchinson’s freckles: This is procurer lesion of Lentigo maligna melanoma. Appearance: It is pigment macule with ill-defined margins. It occurs characteristically as a macular lesion of the malar skin. It grows slowly in radial phase, with around the central axis and in a superficial manner. As the disease advances, invasion and metastasis are frequent.

Acral Lentiginous Melanoma Location: It is the most common melanoma in blacks and also most common form in oral cavity. It typically on the soles of hands and mucous membranes. Appearance: It begins as a dark pigmented, irregularly margined macule which further develops into a nodular growth.

Oral Manifestations Age and sex distribution: It is an uncommon neoplasm of the oral mucosa and it is more common in men than in women with the overall age of occurrence being 55 years, with most cases occurring between 40 to 70 years. Location: It has got definite predilection for palate and maxillary gingiva/alveolar ridge followed by buccal mucosa, mandibular mucosa, tongue, lips and floor of mouth. Sign: Focal pigmentation (Fig. 13.42) preceding the development of actual neoplasm frequently occurs, several months to years before clinical symptoms appear. Symptoms: The lesions usually appear as deeply pigmented areas, at times ulcerated and hemorrhagic, which tend to increase progressively in size. Oral melanomas are generally painless. The lesion presents as a soft, darkish

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Figure 13.42  Melanoma in lower mandibular region showing

Figure 13.43  Vertical growth phase of the malignant epitheloid

pigmentation

cells invading the connective tissue malignant melanoma

brown or black mass. It may have a nodular or a papillary surface. There may be ulcerations and bleeding of the oral mucosa. There is minimum induration and no rolled margins are seen. There is also loosening of teeth may be a concomitant clinical finding. Radiological features: The tumor causes extensive destruction of the underlying bone which is seen radiologically as radiolucency with ill-defined border. Clinical Features (ABCDE Criteria) to differentiate between Melanoma and Melanocytic Nevus • A – Asymmetry • B – Border irregularity with notching • C – Color variegation (brown to black, white, red and blue) • D – Diameter greater than 6 mm • E – Evolving lesion with change in size, shape and color.

Figure 13.44  Pagetoid arrangement of tumor cells in

melanoma

Histopathological Features (Figs 13.43 to 13.46) The cutaneous lesions are seen initial at the junctional zone of epithelium and connective tissue. Later the tumor cell proliferation is seen throughout the thickness of the epithelium and spread laterally along the basal cell layer and downward into the connective tissue. Atypical melanocytes are seen which are usually larger than normal melanocytes and have varying degrees of nuclear pleomorphism and hyperchromatism.

Figure 13.45  High power view of melanoma

Textbook of Oral Pathology Table 13.4  Grading of malignant melanoma

Various grades of malignant melanoma (Clarks)

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Grade I: Malignant cells are confined within the epithelium. Grade II: Malignant cells have invaded into the papillary dermis. Grade III: Malignant cells have invaded into the level of reticular dermis. Grade IV: Malignant cells have completely invaded the reticular dermis. Grade V: Malignant cells have extended into the subcutaneous fat.

Figure 13.46  Malignant melanoma showing

spindle shaped cells

Superficial spreading melanoma: The melanocytes are distributed in a so-called pagetoid manner or sheets. When melanocytes penetrate basement membrane, a florid hostcell response of inflammatory cell chiefly lymphocytes develops. Macrophages and melanophages may be present. The melanocytes are limited to the epithelium only. Nodular melanoma: The connective tissue invasion or deeper lesins are nodular melanomas. It is characterized by large, epitheloid melanocytes within the connective tissue. Small ovoid and spindle shaped cells may be present. The tumor cell may invade and ulcerate the overlying epithelium and penetrate the deep soft tissue. This is the vertical growth phase in nodular type of melanoma. Lentigo melanoma: It is characterized by increased number of atypical melanocytes with the basal epithelial layer. The epithelium becomes atrophic and dermal collagen shows the effect of sun damage. If skin appendages are present they are often involved with atypical melanocytes as well. Acral lentiginous melanoma: This is more commonly seen on palate and demonstrated numerous atypical melanocytes along the epithelium with invasion into the superficial lamina propria.

Histological Grading and Staging of Malignant Melanoma (Table 13.4) It depends upon the depth upto which malignant cells have invaded or infiltrated into the connective tissue.

TNM Staging of Cutaneous Melanoma (by Greene Fl, Page DL, Fleming ID at AJCC Cancer Staging Manual 2002) Size T1: ≤ 1 mm T2: 1.01–2 mm T3: 2.01–4 mm T4: > 4 mm (a-without ulceration b-with ulceration) Lymph nodes N0: No lymph nodes involved N1: One lymph nodes N2: Two or three lymph nodes involved without nodal metastasis N3: Four or more matted nodes with metastatic nodes (a-microscopic, b-macroscopic, c-in transit metastasis without metastatic nodes) Metastasis M0: No distant metastasis M1a: Distant skin, subcutaneous or nodal metastasis M1b: Lung metastasis M1c: All other visceral metastasis or any distant metastasis with elevated serum lactate dehydrogenase. Staging of Melanoma • • • • • • •

Stage IA: T1a N0 M0 Stage IB: T1b N0 M0/ T2a N0 M0 Stage IIA: T2a N0 M0/T3b N0 M0 Stage IIB: T3b N0 M0/T4a N0 M0 Stage IIC: T4b, N0 M0 Stage III: any T N1 M0, any T N2, M0, any T N3 M0 Any M1.

Malignant Tumors

Management It is treated by surgical irradiation, immunotherapy and by chemotherapy or, by combination of these methods. Survival rate is very poor and are worse with metastases. Points to Remember Radial growth phase, vertical growth phase Superficial spreading melanoma: Cutaneous •  melanoma, tan brown, black or admixed lesion, pigmented macule, advanced cases ulcerated, fungating growth, amelanotic melanoma, pagetoid manner or sheets, melanocytes penetrate basement membrane, macrophages and melanophages. • Nodular melanoma: Color varies blue to black, rapid infiltration in nodular, diffuse, nodular and tumefactive, sharply delineated nodule, invasion or deeper lesions are nodular melanoma, epitheloid melanocytes, ovoid and spindle shaped cells. • Lentigo maligna melanoma: Hutchinson’s freckles, pigment macule with ill-defined margins, invasion and metastasis, increased number of atypical melanocytes epithelium becomes atrophic. •  Acral lentiginous melanoma: Soles of hands and mucous membranes, dark pigmented, irregularly margined macule, numerous atypical melanocytes along the epithelium. • Oral manifestations: Palate and maxillary gingiva/ alveolar ridge, focal pigmentation, soft, darkish brown or black mass. • Radiological features: Extensive destruction of the underlying bone.

SPINDLE CELL CARCINOMA It is also known as Lane tumor, polypoid squamous cell carcinoma or carcinosarcoma. It occurs chiefly in respiratory and alimentary tracts. It is a variant of squamous cell carcinoma. There is proliferation of spindle cells believed to be arising from the surface epithelium. Spindle cells are anaplastic type of carcinoma cells.

Clinical Features Age and sex distribution: It is more common in male with mean age of occurrence of 57 years. Location: Lower lip, tongue and alveolar ridge or gingiva with remainder scattered at other site.

Sign and symptoms: There is swelling, and presence of a non-healing ulcer. The initial lesions appear either with a polypoid, exophytic or endophytic configuration. The lesion is fleshy. Pain and paresthesia are prominent features.

Histopathological Features It will show foci of surface epidermoid carcinoma or epithelial dysplasia of surface mucosa, usually just at the periphery and often quite limited. Proliferation and dropping off of basal cell to spindle cell. The tumor cells are arranged in different patterns such as fasciculated, myxomatosis or streaming. The Spindle cells are characteristic elongated with elliptical nuclei, although pleomorphic cell are also common. Spindle cells are atypical mesenchymal cells. Giant cells and inflammatory cell infiltrates are often present.

Management Surgical removal of tumor with or without radical neck dissection and radiation therapy is used. Points to Remember Lane tumor, swelling, non-healing ulcer, polypoid, exophytic or endophytic configuration, epithelial dysp­ lasia, mucosa, dropping off, spindle cells are characte­ ristic elongated with elliptical nuclei, surgical removal of tumor.

ADENOID SQUAMOUS CELL CARCINOMA It is also called as adenoacanthoma. It arises from pilosebaceous structures or senile keratosis with acantholysis.

Clinical Features Age and sex distribution: Females are affected more with age ranging from 20 to 50 years and older. Location: It more commonly occurs on lip and also in head and neck region. The lower lip is affected more commonly than upper lip and it is also common on the vermilion border of lip. Sign and symptoms: It appears as simply elevated nodules that may be slow crusting, scaling or ulcerated. Sometimes, there are elevated or rolled borders of the lesion.

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Histopathological Features

Histopathological Features

This is an adenoid variant of conventional squamous cell carcinoma. It shows proliferation of surface dysplastic epithelium into the connective tissue as in typical epidermoid carcinoma. The lateral and deep extension of this epithelium show the characteristic solid and tubular ductal structures which are lined by a layer of cuboidal cells and often contain or enclose acantholytic or dyskeratotic cells. There is heavy chronic inflammatory infiltration in the corneum, which always show basophilic degeneration: typical of solar damage.

It shows three patterns: Keratinizing squamous cell carcinoma: It is same as that of other squamous cell carcinoma. Differentiated nonkeratinizing carcinoma: Broad interconnecting bands of oval or round cells are organized in plexiform and papillary patterns. They are mature without keratin formation.

Management

Undifferentiated nonkeratinizing carcinoma: It consist of sheets of lesion cells with less distinct margin which show no differentiation in most cases. Tumor cell also mixed with lymphoid cells normally found at anatomic site (Fig. 13.47).

Prognosis is good and metastasis is rare. It is treated by surgical excision.

Management

Points to Remember Adenoacanthoma, head and neck region, elevated nodules, crusting, scaling or ulcerated, proliferation of surface dysplastic epithelium, solid and tubular ductal layer of cuboidal cells, heavy chronic inflammatory infiltration.

NASOPHARYNGEAL CARCINOMA

Radiotherapy to nasopharynx and neck is treatment of choice. Points to Remember Waldeyer’s tonsillar tissue, enlarge, firm to hard cervical lymph node, otitis media, otalgia, CNS involvement, Keratinizing squamous cell carcinoma, differentiated nonkeratinizing carcinoma, undifferentiated nonkerati­ nizing carcinoma.

These are tumors arise from lining epithelium of lymphoid rich nasopharynx, palatine tonsil and base of tongue. These three sites are called Waldeyer’s tonsillar tissue or Waldeyer’s ring. It is thought to be caused by Epstein-Barr virus, diets deficient in vitamin C, consumption of salt fish which contain carcinogen N-Nitrosamine.

Clinical Features Age and sex distribution: It is seen in 4th to 6th decade of life. Male to female ratio is 3:1. Sign and symptoms: There is enlarge, firm to hard cervical lymph nodes due to metastasis. Primary lesion is very difficult detect clinically. If it arises at eustachian tube then otitis media, otalgia or hearing loss can occur. There may be nasal obstruction and pharyngeal pain. CNS involvement: Tumor may invade through foramina lacerum into brain produce CNS symptoms.

Figure 13.47  Undifferentiated type of nasopharyngeal

carcinoma

Malignant Tumors

MERKEL CELL CARCINOMA It is also called as Merkel cell tumor, neuroendocrine carcinoma of skin, small cell carcinoma of skin, trabecular carcinoma of skin. It is more common associated with ultraviolet light exposure. It can be associated with immunosuppressed individual like HIV infection, patient with chronic lymphocytic leukemia. This tumor cells contain cytoplasmic granules which resembles neurosecretary granules found within the epidermal Merkel cells of touch receptor region.

Clinical Features Age and sex distribution: It is more commonly seen in older individual with slight male predilection. Location: It is seen on skin of the face, lower lip, pharyngeal, laryngeal and vaginal mucosa. Sign and symptoms: It appear as slowly enlarging dome shaped nodules with smooth surface and prominent surface vessels. It is red and violaceous with size less than 5 cm.

It can occur in any location being the bone extremities the main affected site. It arises in the periosteal tissue or endosteally or can arise from pre-existing lesion such as fibrous dysplasia, chronic osteomyelitis, Paget’s disease, post radiation cases. In case of fibrosarcoma of oral cavity, the tissue of origin seems to be the periosteum rather than mucosal connective tissue. Type of Fibrosarcoma According to Location • Central fibrosarcoma • Periosteum type fibrosarcoma Grade • Low-grade • High-grade Differentiation • Well differentiated • Less differentiated.

Histopathological Features

Clinical and Radiological Features

It consists of infiltrating sheets with strands of moderately sized uniform undifferentiated basophilic cells in the dermis and subcutaneous fat. Pseudoglandular trabecular Cribriform (Swiss Chesse) and sheetlike patterns can be seen. Tumor cells have prominent nuclei with abundant mitotic figure and scant cytoplasm.

Age and sex distribution: It can occur at any age with mean age of occurrence of 50 years with male predominance with duration of lesion from few weeks to 20 years (Figs 13.48 to 13.50).

Management

Location: Fibrosarcomas of the head and neck region with the neck being the most common site (25%), followed by face (20%), scalp (16%), and maxillary sinus (12%). Only 12 percent of the fibrosarcoma were located intraorally,

Wide local excision can be done. Points to Remember Neuroendocrine carcinoma of skin, Merkel cells, enlarging dome shaped nodules, infiltrating sheets with strands of moderately sized uniform undifferentiated basophilic cells, Swiss Cheese, abundant mitotic figure.

FIBROUS CONNECTIVE TISSUE Fibrosarcoma Fibrosarcoma is a malignant neoplasm of the fibroblastic origin. Fibrosarcoma accounts for approximately 15 percent of all soft tissue sarcomas which represent only 1 percent of all malignant tumors of the head and neck region.

Figure 13.48  Extraoral swelling in fibrosarcoma

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Figure 13.49  Intraoral growth seen in fibrosarcoma (Courtesy:

Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Signs: It produces solitary, soft, firm, fleshy, rounded to lobulated mass that is grossly white to tan yellow. Small tumors may be well circumscribed, partly or completely encapsulated. Involvement of TMJ and para-mandibular musculature results in trismus. Sensory neural abnormalities may occur if it involves peripheral nerves. Initially they resemble benign fibrous outgrowth, but they grow rapidly to produce large tumor. Large tumors are prone to ulceration and hemorrhage. Secondary infections are seen in some cases. Pathological fracture may occur if the lesion in intraosseous. Maxillary lesions are quite destructive and invade the antrum. They tend to penetrate the cortex and spread along the periosteum. The clinical behavior of the fibrosarcomas is characterized by a high local recurrence rate and a low incidence of regional lymph node and/or distant hematogenous metostasis. However, hematogenous metastasis may involve the lungs, mediastinum, abdominal cavity and bone. Local recurrence poses a serious and complex problem with occurrence of infiltration, local destruction, airway compression, esophageal compression and extension into the mediastinum.

Radiological Features Radiographically, an osteolytic lesion is usually present, with ill-defined borders; however, fibrosarcoma of the jaws cannot be distinguished from other destructive lesions of the bone.

Histopathological Features (Figs 13.51 to 13.55) Figure 13.50  Irregular radiolucency seen in posterior area of

bone (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

approximately half of them in the lower jaw. Intraorally, it is commonly associated with cheek, maxillary sinus, pharynx, palate, lip and periosteum of maxilla and mandible. Symptoms: Clinically, in the oral cavity the major symptoms are pain, swelling, and sometimes associated with loosening of the teeth, paresthesia and occasionally ulceration of the overlying mucosa.

It is characterized by high degree of rapid proliferation of fibroblasts. It is associated with formation of collagen and reticular fibers. Cells are spindle shaped and show elongated nuclei. Associated fibers are generally arranged in interlacing bands or fascicles. In well differentiated tumors, fibroblasts are regular in size and shape. The prominent collagen bundles tend to be arranged in a typical herring bone pattern. Mitotic figures are prominent in small group of poorly differentiated tumors. Fibrosarcoma can be graded in low and high grade of malignancy. Its histological grading is based on the degree of cellularity, degree of cellular differentiation, mitotic activity, the amount of collagen produced by the tumor cells and the extent of necrosis.

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A

Figure 13.53  Fibrosarcoma (high power)

B Figures 13.51A and B  Fibrosarcoma (Courtesy: Dr Aparna

Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Figure 13.54  High power view of fibrosarcoma showing high

mitosis (arrows) in the fibroblast cells. The cells are arranged in whorled pattern

Figure 13.52  Fibrosarcoma showing whorled arrangement of

malignant fibroblasts, (Whr) collagen fibers arranged in herring bone pattern (Herr), abnormal mitosis (Mito)

Low grade fibrosarcoma show spindle cells arranged in fascicles with low to moderate cellularity with a herring bone appearance. There is a mild degree of nuclear pleomorphism and rare mitosis, with a collagenous stroma. High-grade lesion showed an intense nuclear pleomorphism, greater cellularity, and atypical mitosis. The nuclei can be spindle shaped oval or round nuclei. The histological appearance of high-grade fibrosarcoma may be similar to other tumors, as malignant fibrous histiocytoma, liposarcoma or synovial sarcoma (Table 13.5). Histologically, it is often difficult to distinguish fibrosarcomas from other soft tissue sarcomas and diagnosis is often achieved by exclusion.

Textbook of Oral Pathology

Types • Giant cell • Inflammatory • Myxoid • Storiform • Pleomorphic • Angiomatoid.

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Clinical Features Sex distribution: There is slight male predilection and malignant variety is common in adults.

Figure 13.55  High power view of fibrosarcoma showing high mitosis (arrows) in the fibroblast cells. The cells are arranged in whorled pattern

Variants of Fibrosarcoma • Sclerosing epitheloid type • Myxoid type • Fibromyxoid type.

Management Radical surgical excision is most commonly used treatment modality. Points to Remember Pain, swelling, solitary, soft, firm, fleshy, rounded to lobulated mass, involvement of TMJ, prone to ulceration and hemorrhage, high local recurrence rate, hematogenous metastasis, radiographically, an osteolytic lesion ill-defined borders, formation of collagen, reticular fibers, herring bone, mitotic figures are prominent, show spindle cells arranged in fascicles, an intense nuclear pleomorphism, greater cellularity, and atypical mitosis.

MALIGNANT FIBROUS HISTIOCYTOMA It is also called as malignant fibroxanthoman. Neoplasm that exhibits both histiocytic and fibrocytic features are referred to as histiocytomas. It is one of the more common soft tissue sarcoma of soft tissues of body.

Location: In the head and neck area, more commonly encountered in the paranasal sinuses or centrally, within the jaw. Appearance: Occasionally it arises in the oral cavity and in the lateral neck, it appears as indurated swelling. Metastasis in nearly one-fourth of cases has been reported.

Histopathological Features It presents with variety of patterns. The spindle cells are arranged in fascicles with a pinwheel or storiform pattern (Fig. 13.56). The deep seated tumors contain both epithelioid histiocytes and spindle shaped fibroblast. Both cell component display marked hyperchromatism, pleomor­ phism and atypical mitosis with many multinucleated cells exhibiting angulated cytoplasmic borders.

Management It is treated by surgical excision or radiation with 5 year survival rate in 20 to 60 percent of cases. Points to Remember Malignant fibroxanthoma, indurated swelling, pinwheel or storiform pattern, epithelioid histiocytes, spindle shaped fibroblast, hyperchromatism, pleomorphism, mitosis.

SYNOVIAL SARCOMA It is uncommon malignancy which occur near and large joints and bursae.

Malignant Tumors Table 13.5  Difference between high grade, low grade and fibromatosis

Cellularity Nuclear overlap Hyperchromasia Nucleoli

Fibromatosis Low to mod Absent Absent Inconspicuous

Low grade fibrosarcoma Low to mod Present Present Prominent

Mitotic activity Necrosis Vessel wall infiltration Herring bone pattern Collagen fibers bundles

1+ Absent Absent Absent Abundant

1+ to 3 + Rare Rare Present Abundant

High grade fibrosarcoma Mod to severe Absent Present More prominent and pleomorphic More than 3+ Present (Hemorrhage) Present Present (less distinct) Less collagen fibers

Management Early radical resection is the best method of treatment. Points to Remember Painless deep seated swelling, biphasic cellular pattern of cleft like slit like spaces lined by cuboidal epithelial like cells.

ADIPOSE TISSUE Liposarcoma Figure 13.56  Fibrous histiocytoma showing pinwheel pattern

Clinical Features Age and sex distribution: It is predominately disease of young adults mean age being 19 years. Location: Intraoral sites are cheek, tongue, floor of mouth and soft palate. It is seen at para-articular sites like bursae or tendon sheath. Signs and symptoms: There is painless deep seated swelling which may produce difficulties in breathing or swallowing.

Histopathological Features It is characterized by biphasic cellular pattern of cleft like or slit like spaces lined by cuboidal epithelial like cells. The space may contain PAS positive mucoid material. There may be fibrosarcoma like proliferation of cells, with associated collagen or reticulum.

Liposarcoma is a malignant mesenchymal neoplasm that arises from adipose tissue, most commonly in the retroperitoneum and lower extremities. It is extremely uncommon malignant tumor of head and neck region. There is morphological diversity of liposarcoma reflects the great variation in biological behavior of the tumor. It ranges from tumors with low metastatic potential, that is, WDLPS, to tumors with high propensity to metastasize, that is, the round cell (RC) variant of MLPS or PLPS. In addition to histological distinctiveness, anatomical location impacts upon prognosis, given that local control is a prime concern for curative intent.

Clinical Features Age and sex distribution: It most frequently occurs in adults over the age of 40 years with predilection in males in ratio of 2:1. Appearance: It has a slow, silent growth, submucosal or deep in location, producing firm, resilient lesions, sometimes lobulated and often suggestive of cyst.

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On gross inspection, as less yellow and less lobulated. Histological Types of Liposarcoma

284

• • • • •

Well differentiated liposarcoma Myxoid cell liposarcoma Round cell liposarcoma Pleomorphic liposarcoma Dedifferentiated liposarcomas.

Histopathological Features Histologically, it is classified into well differentiated, myxoid/round cell, and pleomorphic types. In general, it consists of fat cells (Figs 13.57 and 13.58) and lipoblast in varying degrees of differentiation and anaplasia with variable stromal component. In well differentiated type this demonstrates scattered lipoblast and atypical hyperchromatic stromal cells. Myxoid type demonstrated proliferating lipoblast within myxoid stroma which contain rich capillary network. Round cell demonstrates less differentiated rounded cells. Pleomorphic type exhibits extreme cellular pleomor­ phism and bizarre giant ells. Dedifferentiated type shows poorly differentiated, nonlipogenic sarcomatous changes.

Figure 13.57 Liposarcoma showing large fat cells (L)— lipoblast cells, surrounded by collagen fibers (CL) (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, CDCRI, Rajnandgaon, Chhattisgarh, India)

Management It is treated by surgical excision with or without radiation therapy. Points to Remember Slow, silent growth, submucosal, lobulated, well differentiated, myxoid/round cell, pleomorphic types, lipoblast, fat cells, atypical hyperchromatic stromal cells, myxoid type, round cell, pleomorphic type, dedifferentiated type.

CARTILAGE Chondrosarcoma Chondrosarcomas are rare malignant tumors characte­rized by the formation of cartilage, but not bone, by tumors cells. They are also called as chondrogenic sarcoma. It develops from natural cartilage or a benign cartilaginous tumor. Most of them develop from cartilage located in bone either centrally in bone (medullary cavity) or peripherally, from the cartilage cup of an osteo-chondroma.

Figure 13.58  Liposarcoma showing large fat cell-lipoblast

cells, surrounded by collagen fibers

Chondrosarcomas of the maxillofacial region, accoun­ ting for 1 to 3 percent of all chondrosarcomas of the entire body, arise predominately in the maxilla with a predilection for the anterior maxillary region, and occur at lower incidence in the mandible. Types Primary: They directly arise from the cartilage. Secondary: It develops in a pre-existing benign cartilaginous tumor.

Malignant Tumors

Clinical Features Age and sex distribution: It develops during 3rd through 6th decades and male to female ratio is 2:1. Secondary chondrosarcoma occur at early age than the primary type of chondrosarcoma.

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Location: It is rare in jaws and may occur in maxilla or mandible. Often found in anterior alveolar process of maxilla and in mandible it is found at angle and alveolar ridge of premolar-molar region. The preferred site in the mandible is the molar region. Other infrequently site in mandible are the ramus, condyle, coronoid process, or symphysis. It is a slow growing and less malignant. Symptoms: Chondrosarcomas of jaws are most commonly present as a painless swelling or mass of long duration, and pain, paresthesia, trismus, and loosening of the teeth are associated with the evolution of the disease. Teeth adjacent to the lesion are resorbed, loosened and get exfoliated. Sign: In some cases, there may be hemorrhage from the neck of teeth. There may be sensory nerve deficit, proptosis and visual disturbances. If swelling erodes through the cortical plate, it tends to be tender, smoothly contoured firm mass due to presence of cartilage. Mucosal covering appears normal in early stage but later it ulcerates and develops necrotic surface, if chronically traumatized. If it occurs in/ or near the temporomandibular joint region, trismus and abnormal joint function may result (Figs 13.59 and 13.60). Maxillary lesion may cause nasal obstruction, congestion, epistaxis, photophobia or visual loss. Metastatic spread by vascular channel. Malignant cells may erode through wall or venules and extend along inside the venules without adhering to vessels wall but still altered at their site of entry. Lung is common region of metastasis.

Figure 13.59  Chondrosarcoma of condyle showing swelling

in condylar region

Figure 13.60  Chondrosarcoma of palate showing smooth

contoured mass

Radiological features: Radiographically, the appear­ance of the lesion varies from ill-defined radiolucency to obvious radiopacity, but these findings are not pathognomonic. CT and MRI can provide important insight in determining the nature and extent of the lesion, but a definitive diagnosis has to be made by histologically examination (Fig. 13.61).

Histopathological Features (Figs 13.62 and 13.63) Histological appearance of chondrosarcoma is more or less same as that of chondroma. It is composed of hyaline cartilage. Cells are of variable size and binucleated cells are present.

Figure 13.61  CT scan of chondrosarcoma showing

radiopaque lesion

Textbook of Oral Pathology

Grade III chondrosarcoma: They are highly cellular with prominent spindle cell proliferation. Mitosis is prominent. Chondroma and chondroblastic osteosarcoma tumors are difficult to differentiate with chondrosarcoma. Chondroma predominantly occurs in small bone and is extremely rare in the jaw and facial bones. It is important to differentiate chondrosarcoma from chondroblastic osteosarcoma in the jaw, because the reported prognosis for the former is more favorable than for the later. The absence of osteoid and neoplastic bone rules out chondroblastic osteosarcoma.

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Histological Variant of Chondrosarcoma

Figure 13.62 Chondrosarcoma showing variable form of

cartilage cells—normal appearing cartilage cells (NC), clear cells of cartilage (CL), binucleate cells in other area (BC), normal hyaline cartilage (HY)

• C  lear cell chondrosarcoma: Cell with abundant clear cytoplasm. It is low grade lesion • Dedifferentiated chondrosarcoma: It high grade lesion with mixture of well differentiated chondrosarcoma and malignant mesenchymal fibrosarcoma • Myxoid chondrosarcoma: It is mainly soft tissue tumor with proliferation of cells with clear, vacuolated or eosinophilic cytoplasm • Mesenchymal: It is separated variety and discuss separately in this chapter.

Management

Figure 13.63  Chondrosarcoma showing binucleated cells

The signs of malignancy in tumor are increased cellularity with an increased number of cells with plump nuclei. The clear cell chondrosarcoma consist of single or clustered benign cells and tumor cells with clear cytoplasm. Grade I chondrosarcoma: It resembles to chondroma. It contain chondroid matrix, chondroblast, plump chondroblast, binucleated chondrocytes. Grade II chondrosarcoma: It has got low mitotic rate, increase cellularity at periphery of lobules. Cartilaginous tissue tend to be more myxoid with less prominent hyaline matrix.

Radical resection is the most effective primary modality for the treatment of chondrosarcoma, because the tumors are commonly considered to be radio resistant. Radiotherapy or chemotherapy is usually reserved for locally recurrent or residual tumors and surgically unresectable tumors. The five-year survival rate for chondrosarcomas of the jaws and facial bones was reported to be 67.6 percent. Chondrosarcoma of the mandibular symphysis have a more favorable prognosis than those of the other mandibular sites as well as maxilla. The prognosis of chondrosarcomas depends on the size, location, grade and surgical respectability of the tumors. Points to Remember Chondrogenic sarcoma, a painless swelling or mass of long duration, hemorrhage from the neck of teeth, temporomandibular joint region, trismus, nasal obstruction, congestion, epistaxis, photophobia, metastatic spread by vascular channel, ill-defined radiolucency to hyaline cartilage, plump nuclei, grade I chondrosarcoma, grade II chondrosarcoma, grade III chondrosarcoma, radical resection.

Malignant Tumors

MESENCHYMAL CHONDROSARCOMA In jaws occur in somewhat older person then in other Mesenchymal chondrosarcoma (MCS) is one of the most unusual neoplasms. It was first described by Bernstein and Lichtenstein in 1959 as a distinct variant of chondrosarcoma (CS). It is more commonly occur second and third decades of life. It contains mesenchymal cells. It tends to metastasize to unusual locations and that too after long period of time. Most of the tumors arise in bone but an appreciable number occur in soft tissues.

Clinical and Radiological Features Location: It is most commonly seen in maxilla, skull bone, mandible and ribs. It also occurs in tubular bones and pelvis. Age: It is seen in younger age group than usual type of chondrosarcoma. It is usually seen between the ages of 10 to 30 years. Sign and symptoms: There may be pain due to compression of nerve. In some cases, there may be swelling. Pathological fracture may also occur. Radiological features: Radiolucency with infiltrative margin with stippled calcification present in some cases.

Histopathological Features The mesenchymal chondrosarcoma consist of sheets of small, round or ovoid, undifferentiated cells interspersed by small islands of well differentiated cartilage which often show calcifications and metaplastic bone formation.

Management The prognosis is poor and most patients die due to metastasis. Surgical excision with wide margin is most recommended treatment of this malignancy. Points to Remember Mesenchymal cells, pain due to compression of nerve, radiolucency with infiltrative margin, small, round or ovoid, undifferentiated cells, surgical excision with wide margin.

BONE Osteosarcoma It is also called as osteogenic sarcoma. It is the most common primary malignant tumor of bone and relatively rare in oral and facial region.

skeletal site. Mandible is most common primary site (due to primary growth center). In maxilla, the alveolar ridge is frequent site of origin. It is derived from osteoblasts in which tumor cells contain high level of alkaline phosphates. Types of Osteosarcoma • Parosteal (Juxtacortical) osteosarcoma • Periosteal osteosarcoma • Extra-osseous • Intraosseous (well differentiated) • Intracortical • Multifocal synchronous • Asynchronous • Postradiation osteosarcoma Histological • Fibroblastic • Osteoblastic • Chondroblastic • Telangiectatic • Small cell • High grade

Classification Location Parosteal (Juxtacortical) osteosarcoma: It is uncommon, extremely rare in the jaws and is characterized by slow growth. It has good prognosis due to low tendency of tumor for metastasis. The tumor grows from external surface of the bone. It is more common in femur; as well as in the jaw. Periosteal osteosarcoma: It is an aggressive variant of parosteal type of osteosarcoma but with better prognosis than conventional intra-medullary osteosarcoma. Extraosseous: Osteosarcoma of soft tissue in absence of primary skeletal tumor and occur in breast, liver and kidney. It is highly aggressive type of tumor.

Etiology Postradiation osteosarcoma: This can develop after 3 years of radiation. Frequency is related to radiation dose. Traumatic irritation may be causative factor for osteosarcoma. Osteogenic sarcoma may be seen in fibrous dysplasia and Paget’s disease. Other causes which can cause osteosarcoma are genetic mutation and some viral causes.

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Age and sex distribution: It has got bimodal age distribution first in 10 to 20 years and second is in older than 50 years. It is more common in males. Location: It is more common in long bones like femur and tibia and in jaw bone. It is equal in maxilla and mandible. In the mandible, lesion is seen in body and in maxilla it occurs in antrum or alveolar ridge. It grows rapidly with a doubling time of 32 days and shows recurrence and early metastasis via blood stream to lungs. Symptoms: Swelling of a short history and is usually always accompanied by pain. Affected tooth may become displaced or loose. Numbness of lip and chin in majority of case is due to involvement of inferior alveolar nerve. There may be trismus and hemorrhage. Signs: There may be history of tooth extraction with nodular or polypoid reddish granulomatous appearing mass growing from tooth sockets. Expansion is very firm due to dense fibrous tissue which is produced. Initially, swelling is smoothly contoured and covered by normal mucosa. When expansion becomes chronically traumatized, mucositis develops on surface. Later, the surface gets ulcerated and looks like whitish gray in color. From maxillofacial point of view, it may mimic the periapical inflammation (misdiagnosed or underdiagnosed). Gross specimen usually appears white tan, yellow in color and can be firm in consistency. Exophthalmos, blindness, nasal obstruction and epistaxis can be seen later stage of tumor progression. Radiological features: Sun ray appearance (Fig. 13.64) can be seen on periapical radiograph. There is symmetrical widening of periodontal ligament which can be evident panoramic radiograph. There is spiking resorption of roots of teeth involved by tumors. In some cases Codman’s triangle can be seen.

Histopathological Features (Figs 13.65 and 13.66) A tumor is characterized by proliferation of both, atypical osteoblasts and their less differentiated precursors. Pleomorphism occurs in size and shape of cells which show large, deep staining nuclei and are arranged in disorderly fashion about the trabeculae.

Figure 13.64  Sun ray appearance seen in osteosarcoma

Figure 13.65  Osteosarcoma showing bone formation

Osteoid and bone formation occur in irregular pattern and sometimes, in solid sheets, rather than in trabeculae. Vascular channels can be present in the tumor and may be prominent and this is called as telangiectatic type of tumor. Infiltrative stroma is formed by spindle, oval or polyhedral cells with hyperchromatic nuclei. A highly variegated and anaplastic morphology may be presented. Sarcomatous connective tissue stroma is best seen in peripheral zone, central portion is tends to be richer in osteoid and osseous matrix.

Laboratory Investigation Serum alkaline phosphates level is increase in osteosar­ coma.

Malignant Tumors

systemic chemotherapy is critical for the treatment of patients with osteosarcoma. Points to Remember Osteogenic sarcoma, parosteal (Juxtracortical) osteo­ sarcoma, periosteal osteosarcoma, extra-osseous, doubling time of 32 days, pain, affected tooth may become displaced, granulomatous appearing mass, expansion is very firm, sun ray appearance, symmetrical widening of periodontal ligament, Codman’s triangle, atypical osteoblasts, pleomorphism, vascular channels, spindle, oval or polyhedral cells with hyperchromatic nuclei. Figure 13.66 Osteosarcoma showing abnormal bone or osteoid (abB), large osteoblasts cells (lo), blood elements (bl) (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, CDCRI, Rajnandgaon, Chhattisgarh, India)

Peripheral (Ojuxtacortical) Osteosarcoma This osteosarcoma does not involve medullary cavity. Peripheral osteosarcoma originates adjacent to cortex of bone. These occur in long bone but some cases are reported in jaw bone. There are two types of it, i.e. parosteal and periosteal. Parosteal type: It is lobulated nodules attached to cortex by short stalk. It is low grade sarcoma with better prognosis. Histologically it shows spindle cell fibroblast like proliferation which contains well-developed trabecular of bone. Periosteal types: Is it sessile lesion arise within cortex and elevates overlying periosteum. It produces significant peripheral periosteal new bone formation. It may perforate periosteum and invades soft tissue. Histologically it shows primitive sarcomatous cell within tumor with chondroblastic differentiation. There is also presence of osteoid and immature bone formation.

Management Osteosarcoma was treated primarily with surgical resection with clear margins. Still more than 80 percent of patients subsequently developed recurrent disease that typically presented as pulmonary metastases. This high recurrence rate could be attributed to the fact that most patients have micrometastatic disease at the time of diagnosis. Hence, the use of adjuvant

EWING’S SARCOMA It was first described in 1921 by James Ewing. It is also called as round cell sarcoma or endothelial myeloma. It is a distinctive tumor of bone of uncertain histogenesis. Some studies suggest its neuroectodermal origin. As it is having an origin from the mesenchymal connective tissue of bone marrow it is placed here in the category of bone tumors. It represents as third most common bone tumor after osteosarcoma and chondrosarcoma. It may arise from endothelial elements in the marrow. It may be a secondary deposit of neuroblastoma. It may arise from reticulum cell lining of the marrow spaces. So consider it to be a metastatic tumor, the primary of which is located in different sites, including bronchus.

Clinical Features Age and sex distribution: It occurs between the ages of 5 to 25 years with a male to female ratio of 2:1. Location: The bones affected are the long bone of extremities although the skull, clavicle, ribs, shoulder and pelvic girdles are involved. 10 to 15 percent occur in jaw, usually in mandible. It is a very rapidly growing highly invasive tumor with early and widespread metastasis. Symptoms: Initially, patient present himself with complaint of intermittent pain eventually becomes continuous and associated rapid growth of the tumor causing the enlargement of bone. During the attacks of pain the tumor enlarges visibly. It is associated with febrile attacks and leukocytosis. It may metastasize to other bones.

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Signs: The swelling is hard but occasionally it may be soft and fluctuant. In the early lesion, when the tumor is intraosseous, swelling is firm. When the tumor breaks through the cortex, it spreads extensively in the soft tissues and forms a soft mass which may ulcerate. Swelling is warm and tender. There may be hyperemia of the overlying tissues, suggesting inflammatory condition. The patient may have low grade fever, facial neuralgias, lip paresthesia. Teeth may become mobile and paresthesia may develop. There may be and sinusitis.

Radiographic Features There is large destructive lesion in the diaphysis or metaphysis with a moth-eaten appearance. Lesion may be purely lytic or have variable amounts of reactive new bone formation. Periosteal reaction may give onion skin or sunburst appearance.

Figure 13.68  Ewing’s sarcoma (low power)

Histopathological Features (Figs 13.67 to 13.69) It is a cellular neoplasm which is composed of solid sheets or masses of small round cells with very little stroma, although few connective tissue septa can be seen. The tumor comprises of small, characteristically round, neoplastic cells with large oval hyperchromatic nuclei; the tumor cells have vague indistinct (scanty) cytoplasm and cytoplasmic membrane.

Figure 13.69  Ewing sarcoma

The tumor cells are usually spread out or arranged in large sheets. Mitoses are common, and pseudorosette patterns are typical. Occasionally, the cells are arranged around blood vessels, giving rise to rosette formation. It presents high degree of cellularity, and very little intracellular stroma. Large cell (atypical) Ewing’s sarcoma: Some lesion may contain foci of larger cells.

Management Figure 13.67  Ewing’s sarcoma showing round cells (ro),

arranged in sheets separated by connective tissue septae (ct)

Surgery, X-ray radiation can be used but survival period is very less. Prognosis is poor, death occurs within a year of diagnosis.

Malignant Tumors

Points to Remember Round cell sarcoma, endothelial elements in the marrow, intermittent pain, swelling is hard, soft and fluctuant, moth-eaten appearance, onion skin or sunburst appearance, masses of small round cells, round, neoplastic cells, pseudorosette patterns, rosette formation, large cell (atypical).

VASCULAR Malignant Hemangioendothelioma The term malignant hemangioendothelioma was sugges­ted originally by Lichtenstein. It is a neoplasm of mesenchymal origin which is angiomatous in origin and derived from the endothelial cells. It is also called hemangioendothelial sarcoma.

Each vessel in turn is surrounded by a connective tissue sheath, outside of which are found masses of tumor cells. The tumor cells may appear large or small, round or spindle shaped and show tendency for concentric layering about the capillaries. Cellular pleomorphism can also occur.

Management Surgery and X-ray radiation can be given. Points to Remember Localized swelling, dark red or bluish red, purely lytic lesion that erodes and expands the cortex, neoplasm of vascular origin, irregular vascular channels, atypical endothelial cells, pericytes, concentric layering, cellular pleomorphism.

Clinical Features

Malignant Hemangiopericytoma

Age and sex distribution: It has slight predilection for females. It can arise at any age and has been found at birth also.

Hemangiopericytoma was initially described by Stout and Murray in 1942. It is a soft tissue tumor derived from mesenchymal cells with pericytic differentiation.

Location: It may occur anywhere in the body but most commonly found in skin and subcutaneous tissues. In oral cavity, it can occur on lips, palate, gingiva, tongue and centrally within the maxilla and mandible.

Clinical Features

Symptoms: Localized swelling with pain may be the feature of lesion.

Location: It can occur at any site in the oral cavity. Two types have been described, infantile and adult. Infantile lesions manifestation are usually congenital or in early age till 1 year. Pediatric lesions present as skin or oral soft tissue multinodular mass which respond well to chemotherapy and some spontaneous regressions are reported. Adult lesions behave aggressively and have poor prognosis.

Signs: It appears as flat or slightly raised lesion of varying size, dark red or bluish red, sometimes ulcerated and show a tendency to bleed even after slight trauma. Bone may be involved by tumor producing a destructive process.

Radiographic Features There are no distinctive features of this lesion. It produces a purely lytic lesion that erodes and expands the cortex; frequently, it is associated with a mild periosteal reaction.

Histopathological Features Malignant hemangioendothelioma is a neoplasm of vascular origin characterized by irregular vascular channels lined with atypical endothelial cells. The tumor reproduces the normal arrangement of capillary endothelial channels surrounded by pericytes. There is profuse proliferation of occult capillaries.

Age and sex distribution: There is no sex predilection with age ranging from birth to old age.

Appearance: Clinical presentation is non-specific and pain is a late feature. It presents as a soft tissue mass slowly growing. Occasional cases have been reported with association of hypoglycemia due to the secretion of insulin like growth factor. Signs and symptoms: It is usually painless. The lesions are firm, apparently circumscribed and often nodular. It may or may not exhibit redness indicative of vascular nature. Majority of tumors grow rapidly and are therefore of short duration.

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Radiologic findings: They are not specific, they consist of a well circumscribed, faintly radiopaque soft tissue mass that often displaces adjacent structures. Cystic changes are also seen.

Angiosarcoma

Histopathological Features

Location: It is more commonly seen in head and neck region, scalp and forehead. Intraorally it is seen on tongue and mandible.

Microscopically it is characterized by the so-called pericytoma pattern with tightly packed cells around the thin walled capillaries. It shows proliferation of capillaries surrounded by masses of round or spindle shaped cells which are called as pericytes. It resembles to Glomus tumor but lack its organoid pattern, encapsulation and clinical manifestation of pain. Factors such as mitotic activity, cellularity, hemorrhage, and necrosis help in grading the tumor. It mimics fibrous histiocytoma, synovial sarcoma histologically (Fig. 13.70).

Management It is treated by surgical removal of the lesion with utmost care to control hemorrhage.

This is rare and arises from blood and lymphatic vessels.

Clinical Features

Age: It is common in older individual. Appearance: It start as simple bruise to nodular or ulcerated lesion.

Histopathological Features It is characterized by infiltrative proliferation of endothelium line blood vessels which form as anastomosing network. There is hyperchromatic and atypical endothelial cells. Increase mitotic activity is also seen.

Management Radical surgical excision is the treatment of choice.

Points to Remember

Points to Remember

Infantile lesions, multinodular mass, pain, lesions are firm, circumscribed often nodular, well circumscribed, faintly radiopaque soft tissue mass, pericytoma pattern round or spindle shaped cells, mitotic activity, cellularity, hemorrhage, and necrosis.

Simple bruise to nodular or ulcerated lesion, infiltrative proliferation of endothelium, hyperchromatic and atypical endothelial cells, radical surgical excision.

NEURAL TISSUE Neuroblastoma

Figure 13.70  Hemangiopericytoma showing proliferation of

pericytes surrounding the blood vessels

Peripheral neuroblastic tumors (PNTs including neuroblastoma, anglioneuroblastoma, and ganglioneuroma) are common solid tumors in infancy and childhood. Because of their diverse clinical behaviors: such as involution/spontaneous regression, maturation, and aggressive progression, they were often described as enigmatic in the past. The unpredictable nature and variable clinical behaviors of PNTs have been recognized for decades, and there currently are concerted efforts to identify reproducible and robust prognostic factors that allow treatment to be tailored to the individual cases. Neuroblastomas begin in the abdomen in the adrenal gland or next to the spinal cord, or in the chest. Neuroblastoma can spread to the bones (face, skull, pelvis, shoulders, arms, and legs), bone marrow, liver, lymph nodes, skin, and around the orbits.

Malignant Tumors

The cause of the tumor is unknown. Neuroblastoma is most commonly diagnosed in children before age 5. The disorder occurs in approximately 1 out of 100,000 children and is slightly more common in boys. In most patients, the neuroblastoma has already spread when it is first diagnosed. After leukemia it is the most common malignancy of children.

Clinical Features

Clinical Features Age and sex distribution: It is more common in adults with no sex predilection. Location: It is seen in nasal cavity close to the cribriform plate. It can extend into paranasal sinus. Sign and symptoms: Patient may complaint of nasal obstruction, anosmia, epistaxis and pain.

Age: It usually occurs in children under the age of 5 years.

Histopathological Features

Location: It sometimes arises in the nerves or ganglia of the sympathetic system in the neck, thorax or abdomen. Oral cavity and nasal sinuses are involved. Oral involvement is usually due to metastasis and it occurs in mandible and maxilla.

It consists of small, round to ovoid basophilic cells which are arranged in sheets and lobules. Rosette and pseudorosette formation can be seen.

Symptoms and sign: The first symptoms are usually fever, malaise, and pain. There may also be loss of appetite, weight loss, and diarrhea. Other symptoms depend on the site of the tumor, and may include bone pain or tenderness. Difficulty breathing or a chronic cough. Enlarged abdomen, flushed, red skin, pale skin and bluish color around the eyes, profuse sweating and tachycardia.

Surgical excision with adjuvant radiation therapy.

Histopathology The tumor varies very much in its degree of differentiation. The least well differentiated tumor consists of small round cells arranged merely in diffuse masses. In some cases, differentiating cells begin to form groupings; generally referred to as rosettes and the cell themselves develop neurofibrillary processes. These processes become young nerve fibers and form tangled masses in the centers of rosettes.

Management Radiotherapy and chemotherapy can be given. Points to Remember Peripheral neuroblastic tumors, difficulty breathing or a chronic cough, enlarged abdomen, flushed, red skin, pale skin, rosettes, neurofibrillary processes, tangled masses.

Olfactory Neuroblastoma It is also called as esthesioneuroblastoma. It is tumor of upper nasal vault and arises from olfactory epithelium.

Management

Points to Remember Esthesioneuroblastoma, nasal obstruction, anosmia, epistaxis and pain, small, round to ovoid basophilic cells, Rosette and pseudorosette formation.

Neurofibrosarcoma They arise from Schwann cells or perineuronal fibroblasts they are also called as malignant peripheral nerve sheath tumors, malignant Schwannoma and neurosarcomas or neurogenic sarcoma, account for about 10 percent of soft-tissue sarcomas, and approximately half of these lesions occur in the setting of neurofibromatosis type 1 (NF1).

Clinical Features Age and sex distribution: Neurofibrosarcomas occur only rarely in the head and neck region and are most common in young adults (mean age 40 to 46 years). The mean age of occurrence in patients with neurofibromatosis is 29 to 36 years, although such lesions have been described in younger patients. Location: In the oral regions, the mandible, lips and buccal mucosa are most commonly involved. Appearance: The tumors present as rapidly enlarging masses, sometimes with associated pain. Malignant transformation usually occurs in association with a large, diffuse neurofibroma in cases of NF1.

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It may show widening of the inferior alveolar canal, with or without destruction of surrounding bone and involvement of the inferior alveolar nerve.

Histopathological Features Microscopically the tumor shows fascicles of atypical spindle-shaped cells, which may resemble those of fibrosarcomas but which are usually more irregular, with wavy or comma-shaped nuclei. The plumps spindle shaped cells are arranged in streams and cords with random nuclei. Some less cellular myxoid areas may also be seen. Positive immunostaining for S100 protein is often helpful, but a definitive diagnosis of neural origin is often difficult. It exhibits variation in degree of malignancy, i.e. tumors that are relatively acellular and show little cellular pleomorphism to tumors that are highly cellular with pleomorphism and bizarre mitotic activity.

Management Surgery and radiation can be given and it has got marked tendency for local recurrence. The prognosis for patients with neurofibrosarcomas arising de novo is about 50 percent for 5-year survival, whereas it is 15 percent for neurofibrosarcoma arising in cases of neurofibromatosis. Wide excision is done. The affected nerve should be resected over 5 cm from its encasement by the tumor.

if present, it is seen commonly on cheeks and floor of mouth. Signs and symptoms: The lesion appears as painful swelling. Secondary ulceration of mucosal surface can occur. They tend to metastasize through hematogenous route.

Histopathological Features There is presence of mitosis, nuclear pleomorphism, hyperchromatism and bizarre cell forms. There is fascicles of spindle shaped cells with abundant eosinophilic cytoplasm and blunt ended, cigar shaped nuclei (Fig. 13.71). Proliferating smooth muscles cells are arranged as interlacing bands or cords.

Management Patient should undergo radical surgical excision with adjunctive chemotherapy or radiation therapy. Points to Remember Painful swelling, hematogenous route, mitosis, nuclear pleomorphism, hyperchromatism, cigar shaped nuclei, proliferating smooth muscles cells.

Rhabdomyosarcoma It is a malignant neoplasm of skeletal muscle origin and it is uncommon in oral cavity.

Points to Remember Malignant peripheral nerve sheath tumors, rapidly enlarging masses, widening of the inferior alveolar canal, fascicles of atypical spindle-shaped cells, plumps spindle shaped cells, little cellular pleomorphism.

MUSCLE Leiomyosarcoma It is a malignant tumor of smooth muscle origin.

Clinical Features Age and sex distribution: It can occur at any age with no sex predilection. Location: It is usually seen in uterine wall and gastrointestinal tract. It is very rare in oral cavity and

Figure 13.71  Leiomyosarcoma showing highly cellular tumor,

cellular atypia, cigar shaped nuclei with increased mitosis

Malignant Tumors

Clinical Features Age: It is most common soft tissue sarcoma in children and adolescents.

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Location: It is a mass occurring in any region of the head and neck where striated muscle or its mesenchymal progenitor cells exist. Intraorally, the tonsils and soft palate are most frequently involved. Appearance: Typically, it is a rapidly growing soft tissue mass. It forms polypoid fleshy growth beneath the mucous membrane, with club like extensions at periphery. Spread: It may spread by either lymphatic or hematogenous routes. Signs and symptoms: Depending upon of the size of lesion, there may be divergence of eyes, abnormal phonation, dysphagia, cough, aural discharge or deviation of the jaw. The overlying skin is usually erythematous or telangiectatic. The lesions are occasionally ulcerated and may invade the underlying bone and develop distant metastasis.

Figure 13.72  Rhabdomyosarcoma (low power)

Types (Histological) • Pleomorphic: It occurs most common in extremities and in older individuals. • Alveolar: It is found in head and neck region and in extremities, with early age of occurrence. • Embryonal: It is found in the genitourinary tract and in nasopharynx, with cases reported in oral cavity in the upper and lower labial folds. • Botryoid: Is a malignant tumor of vagina, prostate and base of bladder in young children.

Histopathological Features (Figs 13.72 and 13.73) Pleomorphic rhabdomyosarcoma: It is composed chiefly of spindle cells in haphazard arrangement. These cells are generally large and show considerable variation in appearance. The nuclei are ovoid or elongated with packed chromatin. The nuclei are situated often in an expanded end of cells. The racquet cell. Strap-like and ribbon cells typically show process of long streaming cytoplasm. The cytoplasm is eosinophilic and intra-cytoplasmic longitudinal fibrils as well as transverse cross striations may be seen. Cytoplasmic vacuoles are present as a result of large amount of glycogen in the cells. Multinucleated giant cells are often seen.

Figure 13.73  Rhabdomyosarcoma (high power)

Alveolar rhabdomyosarcoma: It is characterized by spaces lined by epithelium like cells which appear to be dropping off from collagen. The cells are often small, monomorphic, round or ovoid with dark staining nuclei. Cells floating in the alveolar spaces are common. Embryonal rhabdomyosarcoma: Here four types of cells are present—eosinophilic spindle cells, usually arranged in interlacing fascicles. Round eosinophilic cells, large and intermediate in size, with small nucleus and interspersed among other cell types. Broad elongated eosinophilic cells occasionally with cross striations. Small, round and spindle cells with dark staining nuclei and little cytoplasm is present. Botryoid type: It is sparsely cellular and has a pronounced myxoid stroma. Cambium layer (increase cellularity).

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It is treated by chemotherapeutic agents and radiation. It has got poor prognosis.

Points to Remember Alveolar soft-part sarcoma, muscles of extremities, slow growing, well circumscribed masses, finely granular cytoplasm, uniform pseudo-alveolar or organoid pattern.

Points to Remember •  Growing soft tissue mass, club like extensions, divergence of eyes, abnormal phonation, dysphagia, cough, aural discharge • Pleomorphic rhabdomyosarcoma: Spindle cells, racquet cell. Strap-like, ribbon cells, nuclei are ovoid, cytoplasmic vacuoles • Alveolar rhabdomyosarcoma: Dropping off cells, monomorphic, round or ovoid with dark staining nuclei • Embryonal rhabdomyosarcoma: Eosinophilic spindle cells, round eosinophilic cells, broad elongated eosinophilic cells, round and spindle cells • Botryoid type: Sparsely cellular, myxoid stroma.

Malignant Granular Cell Myoblastoma It is also called as alveolar soft-part sarcoma. It is thought to be of striated muscle origin.

Clinical Features Age and sex distribution: It is predominantly a tumor of females, occurring usually in teens or early twenties. Occasional cases also occur in older patients. Location: The lesion occurs with greatest predilection in muscles of extremities. Sign and symptoms: They are usually slow growing, well circumscribed masses.

Histopathological Features The tumor is composed of large cells with finely granular cytoplasm that is not as eosinophilic as the cells of rhabdomyosarcoma. These cells have a uniform pseudo-alveolar or organoid pattern arranged in relation to numerous delicates endothelial lined vascular channels and septa. The pattern is reminiscent of that seen in the nonchromaffin paraganglioma.

Management Due to the high recurrence rate, radical surgical excision is the treatment of choice.

Alveolar Soft Part Sarcoma It is rare neoplasm of uncertain histogenesis.

Clinical Features Age and sex distribution: It is most common in young adults and children with female predilection in the ratio of 2:1 in younger patient and male in the adults. Location: It is seen on lower extremities, head and neck region, orbit and tongue. Appearance: It is slow growing painless mass.

Histopathological Features It composed of groups of large, polygonal cells which are arranged in central alveolar spaces. These cells have abundant granular, eosinophilic cytoplasm and vesicular nuclei. PAS stains reveal diastase resistant crystal which under electron microscope rhomboid, polygonal or rod shaped structure with regular lattice work pattern.

Management Radical surgical excision in conjunction with radiation therapy and chemotherapy. Points to Remember Slow growing painless mass, polygonal cells which are arranged in central alveolar spaces, rhomboid, polygonal or rod shaped structure.

BIBLIOGRAPHY 1. Billings SD, Folpe AL. Cutaneous and subcutaneous fibrohistiocytic tumors of intermediate malignancy: an update. Am J Dermatopathol. 2004;26(2):141. 2. Fletcher CDM, Unni KK, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone, World Health Organization Classification of Tumours, 2002. 3. Folpe AL, Morris RJ, Weiss SW. Soft tissue giant cell tumor of low malignant potential: a proposal for the reclassification of malignant giant cell tumor of soft parts. Mod Pathol. 1999;12(9):894-902.

Malignant Tumors 4. Guccion JG, Enzinger FM. Malignant giant cell tumor of soft parts: An analysis of 32 cases. Cancer. 1972;29(6):1518-29. 5. Kempson RL, Fletcher CDM, Evans HL, Henrickson MR, Sibley RS. Tumors of the Soft Tissues, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 30, 2001. 6. Oliveira AM, Dei Tos AP, Fletcher CD, Nascimento AG. Primary giant cell tumor of soft tissues: a study of 22 cases. Am J Surg Pathol. 2000;24(2):248-56.

7. O’Connell JX, Wehrli BM, Nielsen GP, Rosenberg AE. Giant cell tumors of soft tissue: a clinicopathologic study of 18 benign and malignant tumors. Am J Surg Pathol. 2000;24(3):386-95. 8. Salm R, Sissons HA. Giant-cell tumours of soft tissues.J Pathol. 1972;107(1):27-39. 9. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors, 5th edn, 2008.

MULTIPLE CHOICE QUESTIONS 1.

Individual cell keratinization and keratin pearls seen in: a. Verrucous carcinoma b. Squamous cell carcinoma c. Basal cell carcinoma d. Both a. and b.

9. Most common malignant tumor of bone is: a. Osteosarcoma b. Ewing’s sarcoma c. Round cell carcinoma d. None

2.

‘Rodent ulcer’ refers to: a. Squamous cell carcinoma b. Verrucous carcinoma c. Basal cell carcinoma d. Metastatic carcinoma

10. ‘Racquet cell’, ‘strap- like’ and ‘ribbon’ cells typically seen in: a. Neuroblastoma b. Rhabdomyosarcoma c. Leiomyosarcoma d. Ewing’s sarcoma



3. Histopathologic appearance of nests, islands or sheets of cells seen in: a. Basal cell carcinoma b. Rodent ulcer c. Metastatic carcinoma d. Both a. and b. 4. Carcinoma arises chiefly from the tonsil,base of the tongue and nasopharynx is: a. Squamous cell carcinoma b. Malignant melanoma c. Transitional cell carcinoma d. Rodent ulcer 5.

Sunlight is an important etiological factor in: a. Squamous cell carcinoma b. Basal cell carcinoma c. Malignant melanoma d. Both b. and c.

11. Pel-Ebstein fever is the characteristic feature of: a. Malignant lymphoma b. Non-Hodgkin’s lymphoma c. Hodgkin’s lymphoma d. None 12.

Reed–Sternberg cells is the histologic feature seen in: a. Hodgkin’s lymphoma b. Non-Hodgkin’s lymphoma c. Burkitt’s lymphoma d. Both a. and b.

13. A characteristic ‘starry-sky’ appearance seen in: a. Mycosis fungoides b. Leukemia c. Rodent ulcer d. Burkitt’s lymphoma 14. Oral amyloidosis is the complication of: a. Hairy leukemia b. Plasmacytoma c. Multiple myeloma d. Both a. and b.

6. Parakeratin plugging seen in: a. Verrucous carcinoma b. Liposarcoma c. Osteosarcoma d. Rodent ulcer

15. Egg shell crackling on palpation present in: a. Multiple myeloma b. Chronic leukemia c. Burkitt’s lymphoma d. None



16. Most common primary malignant bone tumor: a. Osteosarcoma b. Osteochondroma c. Ewing’s sarcoma d. Kaposi’s sarcoma

7. A characteristic ‘pushing margin’ histological feature seen in: a. Malignant melanoma b. Verrucous carcinoma c. Basal cell carcinoma d. Both a. and b. 8. ‘Lane tumor’ refers to: a. Fibrosarcoma b. Multicentric oral carcinoma c. Osteosarcoma d. Spindle cell carcinoma

17. Most commonly metastatising tumor in children: a. Osteosarcoma b. Neuroblastoma c. Osteochondroma d. Kaposi’s sarcoma 18. Most common malignancy in AIDS: a. Osteosarcoma b. Neuroblastoma c. Ewing sarcoma d. Kaposi’s sarcoma

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19. Most common salivary gland tumor in bone: a. Mucoepidermoid carcinoma b. Fibroma c. Papilloma d. Squamous cell carcinoma 20. Which of the following tumor is most aggressive: a. Myxoma b. Cementoblastoma c. Ameloblastic fibroma d. Ameloblastic fibro-odontoma 21.

Which of the following does not have a viral etiology: a. Burkitt’s lymphoma b. Nasopharyngeal carcinoma c. Hodgkins lymphoma d. Hepatocellular carcinoma

22. The most common site of metastasis from the mandi­ bular sarcoma: a. Lung b. Liver c. Spleen d. Heart 23. A malignant tumor of the striated muscle: a. Rhabdomyoma b. Rhabdomyosarcoma c. Leiomyoma d. Leiomyosarcoma 24. A rhabdomyoma is a tumor originating from: a. Nerve tissue b. Smooth muscle c. Striated muscle d. Vascular endothelium 25. Sarcoma of soft tissue spreads by: a. Blood vessels b. Lymphatics c. Direct extension d. Local invasion

14

Odontogenic Tumors

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline ÂÂ Classification of odontogenic tumors ÂÂ Development of tooth ÂÂ Stages of tooth development ÂÂ Molecular Pathology of odontogenic tumors ÂÂ Ameloblastoma ÂÂ Variant of ameloblastoma • Desmoplastic ameloblastoma • Extraosseous/Peripheral ameloblastoma • Pituitary ameloblastoma • Adamantinoma of long bones • Unicystic ameloblastoma ÂÂ Squamous odontogenic tumor ÂÂ Calcifying epithelial odontogenic tumor ÂÂ Adenomatoid odontogenic tumor or cyst ÂÂ Continuum concept: (Cahn and Blum)

Odontogenic tumors are lesions derived from epithelial, ectomesenchymal and/or mesenchymal elements that still are, or have been, part of the tooth forming apparatus. These tumors, therefore, are found exclusively within the maxillofacial skeleton (intraosseous or centrally located), or in the soft tissue (gingiva) overlying toothbearing areas or alveolar mucosa in edentulous regions (extraosseous or peripherally located). The tumors may be generated at any stage in the life of an individual. Knowledge of basic clinical features such as age, gender, and location can be extremely valuable in developing differential diagnoses of odontogenic tumors.

ÂÂ Philipsen and Reichart theory ÂÂ Ameloblastic fibroma ÂÂ Ameloblastic fibrodentinoma ÂÂ Ameloblastic fibro-odontoma ÂÂ Odontoma ÂÂ Odontoameloblastoma Odontogenic fibroma ÂÂ Granular cell odontogenic tumor ÂÂ Odontogenic myxoma ÂÂ Cementoma ÂÂ Malignant ameloblastoma and malignant carcinoma ÂÂ Primary intraosseous carcinoma ÂÂ Clear cell odontogenic tumor or carcinoma ÂÂ Malignant changes in odontogenic cyst ÂÂ Ameloblastic fibrosarcoma ÂÂ Odontogenic Fibrosarcoma

Though, the term tumor is used for all lesions or growths originating from the odontogenic tissue, they are considered as a heterogeneous group ranging from hamartomatous or non-neoplastic proliferations to malignant tumors with metastatic capacities.

CLASSIFICATION OF ODONTOGENIC TUMORS (TABLE 14.1) Odontogenic tumors are classified mostly according to the tissue of origin they belong or resemble (Fig. 14.1). There are various schemes of classifying odontogenic tumors.

Textbook of Oral Pathology Table 14.1  Histological classification of odontogenic tumors (World Health Organization classification, 1992)

Benign odontogenic tumors

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Odontogenic epithelium without odontogenic ectomesenchyme

Odontogenic epithelium with odontogenic ectomesenchyme, with or without dental hard tissue

Ameloblastic fibroma Ameloblastoma Ameloblastic fibrodentinoma Squamous odontogenic tumor Calcifying epithelial odontogenic tumor Ameloblastic fibro-odontoma Odontoameloblastoma (Pindborg tumor) Adenomatoid odontogenic tumor Clear cell odontogenic tumor Calcifying odontogenic cyst Complex odontoma Compound odontoma

Odontogenic ectomesenchyme with or without included odontogenic epithelium Odontogenic fibroma Myxoma (Odontogenic myxoma, myxofibroma) Benign cementoblastoma

Malignant tumors Odontogenic carcinomas

Odontogenic sarcoma

Ameloblastic fibrosarcoma Odontogenic carcinosarcoma Malignant ameloblastoma Ameloblastic fibrodentinosarcoma and Primary intraosseous carcinoma Malignant variants of other odontogenic Ameloblastic fibro-odontosarcoma epithelial tumors Malignant changes in odontogenic cysts

Figure 14.1  Probable sources of epithelium for development of odontogenic tumors

Odontogenic Tumors

DEVELOPMENT OF TOOTH To understand the histogenesis of the odontogenic tumors, the knowledge of process of tooth development is mandatory.

Odontogenesis It is a highly coordinated and complex process which relies upon cell to cell interactions that result in the initiation and generation of the tooth. Tooth is derived from complex interactions between ectoderm of the oral cavity and ectomesenchyme. Ectomesenchyme of oral cavity comes from neural crest cells. These are cells derived from neural fold which is formed from ectoderm. Certain cells at the tip of this fold are loose and mobile and have an ability to migrate. The ectoderm along pathways and enter the developing facial region. After reaching or facial region neural crest cells initiate proliferation of oral epithelium at certain areas forming a thick epithelial band. This band forms horse-shoe shaped epithelial sheet in both the arches the free end of the arch gives two extensions in mesiolateral direction. The sheet present laterally is known as vestibular lamina and mesial sheet is known as dental lamina. Growth of dental lamina proceeds and results in formation of rounded localized growth of epithelial cells called as tooth buds. Initially 20 tooth buds corresponding to deciduous tooth germs develop. Dental lamina gives a lingual extension lingual to developing deciduous teeth except molar develops from these extensions. Molars develop from a direct posterior extension of dental lamina.

STAGES OF TOOTH DEVELOPMENT Tooth development is continuous process. During development of tooth germ takes various shapes, based on these shapes tooth development is classified into three stages. Bud stage (round-shaped epithelial condensation): At this stage there is no histodifferentiation or morpho­ differentiation and cells are highly proliferative. There is condensation of ectomesenchyme cells which also proliferate without differentiation. Peripheral epithelial cells are low columnar and central cells are polygonal.

Cap stage: Cap shape of enamel organ due to invagination or pushing of ectomesenchyme into the tooth bud. Tooth bud develops concavity which becomes occupied by mesenchymal cells called as dental papilla. In this stage morphogenesis of tooth begins and continuous till hard tissue formation begins. Histodifferentiation also begins at this stage with tooth germ composed of four distinct cell layers. ∙∙ Outer enamel epithelium: Layer of cuboidal cells covering outer surface of tooth bud. ∙∙ Inner enamel epithelium: Single layer of low columnar cells at the concavity of cap. ∙∙ Stratum intermedium: Several layers of polygonal cells present over inner enamel epithelium. ∙∙ Stratum reticulum: Many layers of polygonal cells occupy space between stratum intermedium and outer enamel epithelium. Dental follicle or sac: A layer of mesenchymal cells, which surrounds the tooth bud and dental papilla. This layer gives rise to periodontal ligament. Bell stage: Morphodifferentiation of enamel organ gets completed in this stage. The concavity of cap further deepens and assumes bell shape. The shape of inner enamel epithelium roughly outlines the shape of the crown. Stratum intermedium: 2 to 3 layers of flatter cells between stellate reticulum and inner enamel epithelium. These cells which contain high amount of enzymes phosphatase enzyme are highly active cells concerned with protein synthesis and together with cells of inner enamel epithelium, act as single functional unit responsible for formation of enamel. These cells divide even after cells of inner enamel epithelium cease to divide. At secretory stage the inner enamel epithelium cells are called as ameloblasts. They are tall columnar cells with nucleus placed away from the basement membrane.

Cell Rest of Malassez and Serrae The cells rests of Malassez are the remnants of the Hertwig’s epithelial root sheath. These are the only odontogenic epithelial cells that remain in the periodontium after the eruption of teeth. Cell rests of Serrae are remnants of dental lamina. They are usually present in the gingiva, but few may be present in the periodontal ligament. These cells are believed to behave in a manner similar to cell rests of Malassez. They possess an inherent potential to diversely transform towards

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various tumor lines by exerting inductive influence on the adjacent connective tissue. They are believed to give rise to most of the peripheral odontogenic tumors. Few epithelial rests, which are derivatives of distal extension of dental lamina are present in the molar region. These also give rise to odontogenic tumors, especially adenomatoid odontogenic tumor and odontogenic keratocyst.

Tooth Germ

Pericoronal Dental Follicle

Ameloblastoma like tumors are seen in sites other than jaws. Craniopharyngioma or pituitary ameloblastoma arises from caniopharyngial duct, a derivative of Rathke’s pouch a derivative of oral epithelium. In long bones, a tumor similar to ameloblastoma called adamantinoma develops. But other than resemblance to ameloblastoma, it is not related to it. Pilomatrixoma is another tumor that shares few features with CEOT. It is thought to originate from hair follicles.

Dental follicle is a soft delicate tissue, which covers the crowns of unerupted teeth. This dental follicle helps in the protection and eruption of newly formed tooth. Dental follicles are comprised of nests of odontogenic epithelium probably derived form the dental lamina, and the reduced enamel epithelium supported by ectomesenchyme of developed tooth. It was observed that nests have a greater proliferative capacity than the cells of the reduced enamel epithelium and thus they are believed to be responsible for development of odontogenic tumors. As age advances chances of alteration in pericoronal tissue increases. In advance age of over 40 years, it is common to find odontogenic carcinomas in pericoronal tissue. Dental follicle of impacted tooth remains in the oral cavity for a very long time. So, it is exposed to various pathological processes for a long time. This may be one of the explanations why many odontogenic tumors are common in molar area of mandible. The commonly occurring lesions are ameloblastoma, carcinomas, calcifying odontogenic cysts, calcifying epithelial odontogenic tumors and odontogenic myxoma.

Cyst Lining It is thought that epithelial lining of odontogenic cyst is a source of epithelium for a variety of odontogenic tumors. This contention is supported by the fact that both cyst and tumors develop from same odontogenic epithelium, so transition from cyst to tumor is possible. Dentigerous cysts are believed to give origin to ameloblastoma. Calcifying epithelial odontogenic cyst exists in spectrum where tumor is one extreme end and simple cyst forms the other end. Few AOT’s are reported in CEOC lining. Adenomatoid odontogenic tumor has a dentigerous relation with the tooth, so it was also believed to originate from dentigerous cyst. Unicystic ameloblastoma is believed to be a cystic counterpart of ameloblastoma. OKC is now classified as a tumor rather than as a cyst by WHO.

The similarity between tooth germ and odontogenic tumors has led to the belief that odontogenic tumor develop from tooth germ. This may be true in case of tumors that develop in the first and second decade of life.

Heterotopic Epithelium

Basal Cells of Oral Epithelium Tooth germs are developed from oral ectoderm as a down growth into the connective tissue. A few basal cells of oral epithelium retain their pluripotentiality and in some cases may give rise to tumors in adults. Few peripheral odontogenic tumors appear as down growth of basal cells. In few cases, epithelial proliferation known as odontogenic epithelial hamartomas (OEH: Also known as odontogenic gingival epithelial hamartias OGEH) believed to be an intermediate stage in development of tumors.

Gubernacular Dentis Gubernacular dentis is fibrous tissue that forms connection between developing permanent teeth and lamina propria of gingiva. These occupy Gubernacular canals found in dried skull. Gubernacular dentis contains central strand of epithelial cells derived from the dental lamina, surrounded by the connective tissue. This connective tissue is organized in two layers. In inner layer, collagen fibers show greater organization and run mainly parallel to long axis of the chord. Outer layer is made up of fewer collagen fibers which are less organized. It is more vascular than the inner layer. It is thought to play a role in eruption of the permanent teeth. Epithelial cells are occurring more numerously in the inner layer like pearls on string. It hypothesized that these epithelial cells undergo proliferation to form odontogenic tumors and hamarto­ matous lesions. But what initiates these cells is not

Odontogenic Tumors

known. It is thought that different variants of adenomatoid odontogenic tumor are derived from gubernacular dentis.

MOLECULAR PATHOLOGY OF ODONTOGENIC TUMORS (TABLES 14.2 AND 14.3) Exact etiology and pathogenesis of odontogenic tumors is unknown. With evolution of immunohistochemistry and other advanced diagnostic techniques it has been found that various molecules and genes are altered in odontogenic tumors. A series of genetic and molecular alterations appear to promote the development and progression of tumors via multiple steps. The odontogenic tumors discussed in this text are according to the most commonly followed 1992 WHO classification.

AMELOBLASTOMA Ameloblastoma is a benign, locally invasive, polymorphic neoplasm, presumably derived from intraosseous remnants of odontogenic epithelium. It is primarily located centrally in the jaw bones. Ameloblastoma presents as a solid, unicystic, or mixed solid and multicystic neoplasm. It is the second most common tumor of the odontogenic tissues after odontomas. It is more common than all other odontogenic tumors except odontomas are combined. Broca in 1868 was the first to report to ameloblastoma. First detailed description of ameloblastoma was given by Falkson in 1879. In 1885 Malassez coined the term Adamantinoma. As this term suggests formation enamel

which is not found in this tumor, Churchil in 1934 suggested alternative name of ameloblastoma which became popular and well accepted. There are different names given to this tumor. These are adamantine epithelioma, adamantinoma, adamantinoblastoma, epithelial odontome and multilocular cyst.

Definitions It has been defined in various ways ameloblastoma has been defined and described by various authors in the literature in the past few decades. The few most commonly referred are: WHO definition: Solid multicystic ameloblastoma is polymorphic neoplasm consisting of proliferating odontogenic epithelium, which usually has a follicular or plexiform pattern, lying in a fibrous stroma. Robinson: Ameloblastoma is a tumor usually unicentric, nonfunctional, intermittent in growth, anatomically benign and clinically persistent. Shafer, Hine and Levy: The ameloblastoma is a true neoplasm of enamel organ-type tissue which does not undergo differentiation to the point enamel formation. Reichart and Slootweg: A polymorphous neoplasm consisting of proliferating odontogenic epithelium, usually occurring in two main patterns. In the follicular type of growth, the tumor consists of enamel organ-like islands or follicles of epithelial cells, while in the plexiform type, the epithelium forms continuous anatomizing strands. In both types, the epithelial tumor components are embedded in mature, connective tissue stroma. Generally, a tumor

Table 14.2  Cytokeratin expression and odontogenic tumors

Tissue

CK7

CK8

CK10

CK13

CK14

CK18

CK19

VIM

Dental germ

+c

-

-

+d

+a

-

+b

-

Reduced enamel epithelium

-

-

-

+e

+

-

-

-

Ameloblastoma

-

-

-

+f

+

-

+f

-

Adenomatoid odontogenic tumor

-

-

-

-

+

-

-

+g

Cacifying epithelial odontogenic tumor

+h

-

-

±i

+

-

±i

+

Ameloblastic fibroma

+h

-

-

+j

+

-

-

-

Odontoma

+

-

-

-

+a

-

-

-

. +, positive; –, negative; ±, weak positive; a–(except)–secretory ameloblasts; b–preameloblasts, ameloblasts, external enamel epithelium; c–Hertwig root sheath, stellate reticulum; d–dental lamina; e–some cells; f–metaplastic scamous cells, inner stellate cells, cystic structures; g–fusiform and ovoid cells near calcified bodies and darker eosinophilic materials; h–one tumor; i–two tumors; j–stellate reticulum or cords (Crivelini et al, (2003).

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Textbook of Oral Pathology Table 14.3  Molecules possibly associated with tumorigenesis and/or tumor cell differentiation (Modified from H Kumamoto)

304

Molecules involved in tumor genesis and differentiation

Oncogenes

Normal cellular genes which promote oncogenesis if they become overactivated

Contribute to neoplastic transformation

Ras

Required for functioning of growth factors

Expressed in odontogenic epithelial cells

Myc

Regulates cell proliferation

Expressed in parabasal epithelial cells of ameloblastoma

Fos

Regulates cell proliferation and differentiation

Gene altered in ameloblastoma-tumor genesis via dysregulation of cell proliferation

Tumor suppressor genes

These inhibit cell proliferation. Loss of genes leads to loss of control of cell proliferation leading to tumorigenesis

p53

It is called as guardian of genome. It and its products control DNA damage, help in repair of damaged DNA, control cell proliferation and cell death

Increased expression in ameloblastomas, malignant ameloblastomas, primary intraosseous carcinomas, and ameloblastic fibro sarcomas Regulators of p53 like MDM, p14ARF are also expressed in odontogenic tumors

APC

This normal inhibits cell proliferation. Loss of function leads to tumorigenesis

Decreased APC expression is possibly involved in oncogenesis or cytodifferentiation of odontogenic epithelium

Retinoblastoma

Controls cell cycle progression

Transgenic mice develop ameloblastoma

DNA-repair genes (hMSH2 and hMLH1)

Abnormality in these genes leads to genetic instability.

Development and progression of these tumors do not depend on a defect in the DNA repair system

Growth factors

Key regulators of cell growth differentiation and proliferation TGF-b, HGF regulate epithelial– mesenchymal interactions HGF essential for morphogenesis of tooth germs

TGF-a and EGFR are involved in odontogenic tumorigenesis TGF-b, HGF regulate or dysregulate epithelial– mesenchymal interactions HGF is associated with the malignant potential of epithelial odontogenic tumors

Telomerase

Anti-aging enzyme. It is responsible for cell immortalization

Telomerase activation is associated with tumorigenesis of odontogenic epithelium

Cell cycle regulators Cyclin D1, p16INK4a, p21WAF1/Cip1, and p27Kip1

Consist of genes and proteins and involved in regulation of progression in the cell cycle. Cyclins, cyclin dependent kinases (CDK) and CDK inhibitors (CDKI) are these regulators.

Proliferation of odontogenic epithelial cells is strictly controlled by these cell cycle regulators

TGF-a, -b, FGF-1, -2, HGF

Cell proliferation markers PCNA, H3, DNA topoisomerase IIa

Reflect proliferation activity and malignant potential Indicators of cell proliferation

Contd...

Odontogenic Tumors

Contd... Molecules involved in tumor genesis and differentiation

305

Apoptosis-related factors

These factors control physiologic cell death. These help in killing of damaged cells and check-in proliferation of cells.

Pro-apoptotic signals Fas, TNFR I, TRAILR I and II

Apoptosis is decreased in odontogenic tumors even Expressed in odontogenic tumors but the mediator of these signals known as caspases 8 is though the signals are present not fully expressed There is increased survival of tumor cell Expressed in various types of tumors

Anti-apoptotic signals Bcl-2, Bcl-x, survivin

Regulators of tooth Involved in positioning and morphogenesis of tooth germs development Msx-1, Msx-2, Dlx2, Barx-1, and Pax-9 SHH, PTCH, SMO, GLI 1 BMP, Wnt, HGF, and FGF

Play a role in epithelial–mesenchymal interactions and cell proliferation during the growth of odontogenic tumors as well as during tooth development

Involved in morphogenesis and cytodifferentiation of tooth germs

Expressed in epithelial components of tumors Hard tissue-related proteins Enamel related proteinsMutation are detected in ameloblastoma amelogenin, enamelin, tuftelin, enamel sin ameloblastin (amelin or sheathlin)

Aberrations of enamel-related proteins are involved in oncogenesis of odontogenic epithelium

These proteins play a role in pathologic mineralization and/or tumor formation

Dentin, bone and cementum related proteins BSP, osteonectin, osteocalcin, osteopontin, DSP, DPP

Help in tumor progression

Matrix-degrading proteinases

Help in tumor remodeling

MMPs-1, -2, and -9 MSP TIMP, heparanase

Expressed in ameloblastoma, myxoma and other Responsible for invasiveness of odontogenic tumors odontogenic tumors

Contd...

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Contd... Molecules involved in tumor genesis and differentiation

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Angiogenic factors VEGF, FGF, HGF, TGF-b Osteolytic cytokines IL-1, IL-6, and TNF-a, PTHrP, RANKL

Necessary for development of vascularity during inflammation and repair Necessary for tumor angiogenesis

Help in tumor angiogenesis and may be involved tumorigenesis or malignant transformation

Maintain bone homeostasis

Responsible for invasion by local resorption of bone

shows one or the other pattern throughout. However, not infrequently both patterns are present in the same tumor. Classification • Central or intraosseous variant: – Follicular or dentigerous type: It is AOT associated with the crown of unerupted tooth. It is usually misdiagnosed as dentigerous cyst. Seventy-one percent of AOTs belong to this group. –  Extra-follicular type: There is no association with tooth. Twenty-one percent AOTs are of this type. •  Peripheral or extraosseous type: This type is presented in gingiva. Only 4 percent are peripherally located.

Etiology Irritation: Ameloblastoma is common in mandibular angle region. Here, there is constant pooling of saliva containing various irritating factors and microorganis. This irritation is thought to cause ameloblastoma. Oral sepsis: In blacks ameloblastoma more common. In such cases, oral hygiene was found to be poor, so it was thought to be a factor.

be polyoma viruses. Recently various studies indicate that human papilloma virus also plays a role in development of ameloblastoma. HPV type 16 or 18 and type 6 have been detected. Few studies have shown that even Epstein-Bar virus genes are present in few ameloblastoma. Chemical carcinogens: Injection of nitrosoureas have been shown to produce ameloblastoma like lesion in animals.

Pathogenesis The resemblance of the tumor epithelium to the normal enamel organ indicates that ameloblastoma arises from dental epithelium. The possibilities for its development are as follows: Enamel organ: Due to histological similarities such as in origin, it has been thought the tumor growth starts at an early age, i.e. during the period of existence of enamel organ but most of the patients are middle aged, i.e. in a period which is long after regression of the enamel organ. However, the occasional occurrence of the tumor as a unilocular cystic lesion surrounding the crown of an unerupted tooth also suggests that in some cases, the enamel organ may give rise to it.

Trauma: A few patients gave history of either trauma or extraction prior to the ameloblastoma. So trauma can be a causative factor for ameloblastoma.

Cell rests: Cell rests of enamel organ either remnants of dental lamina or remnants of Hertwig’s sheath, i.e. epithelial cell rests of Malassez have the potential of transforming into ameloblastoma.

Dietary deficiency: Dietary deficiency has been considered to be a possible factor. For example, pronounced defect in development of tooth germ as seen in rickets may lead to irregularity in the ameloblastic layer.

Epithelium of odontogenic cysts, i.e. from dentigerous cyst and odontoma: This be possible as the epithelium in the wall of the cyst and that of ameloblastoma are derived from the same embryonic source.

Virus: A few ultra structure studies fo amelobasltoma showed presence of viral particles which were thought to

Oral mucosa: Basal cells layer of the oral epithelium of jaws can be the origin. The reason behind this is that

Odontogenic Tumors

there is communication between the tumors and overlying mucosal epithelium as seen in peripheral ameloblastoma. Heterotrophic epithelium: Heterotrophic epithelium in other parts of the body especially of pituitary gland can serve as source of origin. Classification • Solid/Multicystic ameloblastoma – Follicular ameloblastoma – Plexiform ameloblastoma – Acanthomatous ameloblastoma – Granular cell ameloblastoma – Basal cell ameloblastoma – Clear cell ameloblastoma – Keratoameloblastoma – Desmoplastic ameloblastoma • Unicystic ameloblastoma • Peripheral ameloblastoma • Extra oral ameloblastoma – Craniopharyngioma – Adamantinoma of long bones

Classification Ameloblastoma shows different clinical features and radiographic appearances. These clinical-radiographic types are further subdivided on the basis of clincopathology of the tumor. Among the histologic types of ameloblastoma, follicular and plexiform patterns are the most common; less frequent variants are acanthomatous and granular cell types. Less common cellular variants are the desmoplastic ameloblastoma, basal cell ameloblastoma, keratoameloblastoma, papilliferous keratoameloblastoma, clear cell ameloblastoma and unicystic ameloblastoma. Except for the unicystic type, which has a low recurrence rate, no significant differences in the behavior of these variants have been observed (Table 14.4). Few “hybrid forms” having combinations of histologic variants are also reported.

Clinical Features Ameloblastoma accounts for approximately 1 percent of all oral tumors and 11 percent of all odontogenic tumors. Age and sex distribution: It has slight predilection for males and often seen in blacks. Most patients are between 20 to 50 years of age with mean age of discovery being 40 years. The tumor can occur in young children. Unicystic

Table 14.4  Incidence of different types of ameloblastoma

Relative frequency of different types Histologic variants

Frequency

Follicular Plexiform Acanthomatous Granular cell Basal cell Desmoplastic Keratoameloblastoma

33.9 30.2 11.3 3.5 1.4 1.4 0.1

type of ameloblastoma is more common in the 2nd and 3rd decade and the extraosseous form is more common in the older age group. Location: It develops in the molar ramus area (approximately 3/4 of cases) in the mandible and also occurs in maxilla in third molar area, followed by the maxillary sinus and floor of the nose. The right side of the mandible is affected slightly more as compared to the left side. It begins as a central lesion of the bone which is slowly destructive but tends to expand bone rather than perforating it. Symptoms: Patient notices a gradually increasing facial asymmetry. Teeth in involved region are displaced and become mobile. Pain and paresthesia may occur, if the lesion is pressing upon a nerve or is secondarily infected. Signs: In later stages, the lesion may show ovoid and fusiform enlargement that is hard but nontender (Fig. 14.2). As tumor enlarges palpation may elicit a hard sensation or crepitus. Surrounding bone may become thin so that fluctuation and egg shell crackling may be elicited. If it is left untreated for many years, the expansion may be extremely disfiguring, fungating and ulcerative type of growth characteristic of that of carcinoma can be seen. Maxillary ameloblastoma: Maxillary lesions are more dangerous than mandibular lesions due to tendency for the former lesion to spread more extensively in the more porous maxillary bone and possibility of the involvement of the cranial base. It may extend into the paranasal air sinuses, orbit or the nasopharynx.

Radiographic Features (Figs 14.3 and 14.4) In early stages, there is an area of bone destruction which is well defined and is indicative of slow growth with

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Figure 14.2  Ameloblastoma showing huge swelling and

Figure 14.4  CT scan of ameloblastoma

disfigurement

Figure 14.3  Ameloblastoma showing multilocular

Figure 14.5  Gross specimen of ameloblastoma

radiolucency

hyperostotic borders. Margin is smooth, scalloped, well defined and well corticated. There is presence of septa in the lesion. In some cases, number and arrangement of septa may give the area a honeycomb appearance (numerous small compartments) or a soap bubble appearance (larger compartments). In advanced stages, perforated cortical plate. Extensive root resorption may occur. Expansion and thinning of cortical plate occurs leaving thin eggshell of bone.

Histopathological Features Macroscopically it shows hard swelling (Fig. 14.5). Histologically ameloblastoma exists in two main forms, i.e. follicular and plexiform patterns. Other variants are

belong to any one of these patterns. Most of the varieties show follicular pattern.

Follicular Ameloblastoma (Figs 14.6 to 14.10) This is the most commonly encountered type of ameloblastoma. It grows mainly in form of islands, but to the smaller extent cords and strands are also present. The peripheral cells are tall columnar. They show palisading arrangement, where cells are arranged perpendicular to the basement membrane. These cells show reverse polarity of the nucleus, i.e. nucleus is placed away from the basement membrane. Nucleus is hyperchromatic. At the basal area of these cells vacuoles are present.

Odontogenic Tumors

309

Figure 14.6 Follicular ameloblastoma showing follicles (F) of varying size and shape. They are lined by tall columnar ameloblast like cells (A). Centrally stellate reticulum like cells (S) are seen. Sometimes cystic degeneration (CS) may be seen (Courtesy: Dr Raju Ragavendra T)

Figure 14.7  Follicular ameloblastoma showing follicular

spaces

Thus, the peripheral cells resemble preameloblasts and they are called as ameloblast like cells. Cells that are present at the center of islands are star shaped, with interconnecting delicate cytoplasmic processes. These are called as stellate reticulum like cells. Sometimes, there is degeneration in central cells resulting microcystic spaces. These cystic spaces may enlarge exerting pressure on the peripheral cells and making the cubical to flat cells.

Figure 14.8 Follicular ameloblastoma showing palisading, reverse polarity and basal vacuolation of ameloblast like cells surrounding stellate reticulum like cells (High power)

Figure 14.9 High power view of follicular ameloblastoma showing palisading, reverse polarity and basal vacuolation of ameloblast like cells surrounding stellate reticulum like cells (Courtesy: Dr Raju Ragavendra T. Department of Oral Pathology, People Dental Academy, Bhopal, Madhya Pradesh, India)

Plexiform Ameloblastoma (Figs 14.11 and 14.12) In this variant epithelium proliferates in the form of interconnected cords of epithelial cells. These chords create a network like structure. These chords are lined by ameloblast like cells. Stellate reticulum like cells are present in the center. Stellate reticulum like cells are not as prominent as follicular

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Figure 14.10  Follicular ameloblastoma

Figure 14.12  Plexiform ameloblastoma (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Acanthomatous Ameloblastoma (Figs 14.13 and 14.14) This variant closely resembles the follicular ameloblastoma. Here, stallate reticulum like cells shows squamous metaplasia. They loose there star shape and become polygonal. They produce parakeratin at the central portions of island. Sometimes, it is present in the form of keratin pearls.

Granular Cell Ameloblastoma (Fig 14.15)

Figure 14.11  Plexiform ameloblastoma showing cords (C) of

ameloblastic cells creating network like structure in a loose stroma (L). Cells at the center resemble stallate reticulum (S)

ameloblastoma. Sometimes ameloblast like cells are lined back to back with less or no stroma in-between. Supporting stroma tends to be loosely arranged and myxoid. It shows tendency towards cystic degeneration, which is unlike follicular type where cystic degeneration is seen mainly in the epithelium. The growth pattern of plexiform ameloblastoma resembles that of dental lamina stage of tooth development before enamel organ mophodifferentiation. Differentiation towards bud stage of tooth development may be evidenced by rounded nodules of epithelium.

This is also shows follicular arrangement of cells. This shows transformation of stellate reticulum like cells into granular cells. Sometimes, a layer of stellate reticulum may be present at the periphery of granular cells. These granular cells may be cuboidal, columnar or rounded. The granular cells contain no cell organelle except the presence of coarse eosinophilic granules and nucleus is displaced to periphery of cells. The granules pack the cytoplasm and distend it. The nature of granules is not fully understood. Ultrastructural studies indicate that these are lysosomal aggregates. Other studies indicate that the granularity is caused by increased apoptotic cell death and associated phagocytes by neighboring neoplastic cells. Previously it was thought that granular cell ameloblastoma are very aggressive tumors but this notion is not accepted now. There are a few reported cases of plexiform granular cell ameloblastoma.

Odontogenic Tumors

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Figure 14.13 Acanthomatous ameloblastoma showing squ­

amous metaplasia (SM) of stellate reticulum (SR) like cells in the connective tissue (CT)

Figure 14.15  Ameloblastoma showing foci of granular cells (G) in place of stellate reticulum like cells (SR). (Courtesy: Dr Sangamesh Halawar)

Figure 14.14  Acanthomatous ameloblastoma showing

Figure 14.16  Basal cells ameloblastoma

squamous metaplasia of central stellate reticulum cells

Basal Cell Ameloblastoma (Figs 14.16 and 14.17) This type of ameloblastoma shows a close similarity to basal cell carcinoma. The cells are arranged in sheet like pattern rather than islands. All cells including stellate reticulum like cells have a basaloid appearance. This type of ameloblastoma has highest proliferative rate than any other type of ameloblastoma, leading to formation of immature cells which have basal cell like appearance. The typical cellular morphology is often altered, with ameloblast like cells appearing low columnar to cuboidal. There is a loss of reverse polarity and subnuclear vacuolation. But cells retain palisading.

Clear Cell Ameloblastoma Some ameloblastoma may contain cells without eosino­philic cytoplasm and appearing clear. Clear cells are usually present in place of stellate reticulum like cells. These cells contain high amount of glycogen, which results in clear appearance. Clear cell ameloblastoma are very aggressive tumors.

Keratoameloblastoma It consists of keratin filled cystic spaces and solid proliferation of epithelial cells. Cysts are lined by parakeratotic epithelium. The basal layer consists of cuboidal cells, and the rest of the layers of the epithelial lining show loosely arranged epithelial cells. Cysts resemble odontogenic keratocyst.

Textbook of Oral Pathology

Marginal resection (Block resection): It is surgical removal of an intact tumor, with a rim of uninvolved bone. This procedure usually implies maintaining the continuity of the inferior or posterior borders of the mandible. Small solid or multicystic ameloblastomas of the body of the mandible are treated in this way.

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Segmental resection: Surgical removal of a segment of the mandible or maxillary without maintaining the continuity of the bone. Peripheral osteotomy: It is a procedure which allows complete excision of the tumor but at the same time, a part of bone is retained which preserves the continuity of the jaw. Figure 14.17  Basal cell ameloblastoma showing presence of

basaloid cells (B)

The stroma of the tumor consists of dense collagenous fibrous connective tissue septa. Solid component of tumor consists of large solid masses of parakeratin and keratin, surrounded by multilayered squamous epithelium with peripheral, palisaded, cuboidal basal cells. Epithelium of solid areas differs from cystic areas. It is not of uniform thickness, and there is separation and edema between the basal cells and the rest of the epithelium. Although the basal cells are palisaded and demonstrate nuclear polarization, they are cuboidal rather than columnar. Keratoameloblastoma is believed to be a link between a cystic neoplasm-odontogenic keratocyst and a solid neoplasm having same origin. In few cases, epithelial cells surrounding the cystic spaces show papillary projections. Such Keratoameloblastoma are called as papilliferous keratoameloblastoma. In few cases, papilliferous ameloblastoma exist independent of Keratoameloblastoma.

Management Surgical enucleation and curettage with a rim of peripheral normal tissue is usually carried out. Marx and others 16 reported unpublished data from an analysis of 34 mandibular ameloblastoma, which showed that the tumor extended 2.3 to 8.0 mm beyond the radiographic margin. As a result, they have recommended resection of 1 cm of normal appearing bone beyond the radiographic margin which could be the reason for the ill-defined radiographic borders and the high recurrence rate after curettage.

Peripheral ameloblastoma: Peripheral ameloblastomas are relatively innocuous lesions that should be excised with a small margin of normal tissue, and the surgical site reexamined periodically. Points to Remember Molar ramus area, teeth in involved region are displaced, gradually increasing facial asymmetry, eggshell crackling, non-tender, fusiform enlargement, maxillary lesion are more dangerous, area of bone destruction which is well defined, honeycomb appearance, soap bubble appearance, eggshell of bone: •  Follicular ameloblastoma: Form of islands, palisading arrangement, reverse polarity, ameloblastlike cells, delicate cytoplasmic processes • Plexiform ameloblastoma: Interconnected chords of epithelial cells, stellate reticulum-like cells, cystic degeneration • Acanthomatous ameloblastoma: Stellate reticulum like cells shows squamous metaplasia, parakeratin at the central portions of island • Granular cell ameloblastoma: Transformation of stellate reticulum-like cells into granular cells, lysosomal aggregates • Basal cell ameloblastoma: Sheet like pattern rather than islands, immature cells •  Clear cell ameloblastoma: Cells without eosinophilic cytoplasm appearing clear •  Keratoameloblastoma: Keratin filled cystic spaces, dense collagenous fibrous connective tissue septa, separation and edema between the basal cells and the rest of the epithelium •  Management: Surgical enucleation, curettage, marginal resection (Block resection).

Odontogenic Tumors

VARIANT OF AMELOBLASTOMA Desmoplastic Ameloblastoma Desmoplastic ameloblastoma is different from other types of solid multicystic ameloblastoma, so it is thought to be a separate clinico-pathological entity of ameloblastoma and not just histologic subtype. Eversole and others (1984) described 3 cases of a variant of ameloblastoma. The characteristic feature was extensive stromal desmoplasia with small nests, cords and strands of odontogenic epithelium. This variant was included later in the World Health Organization’s Histopathological Typing of Odontogenic Tumors (1992). It differs clinically, radiologically and histologically from classic ameloblastoma.

pattern and indistinct borders. Displacement of teeth can be seen.

Histopathological Features Histologically, desmoplastic ameloblastoma are nonencapsulated tumors. They show presence of large amount of collagen fibers (Desmoplasia) (Figs 14.18 and 14.19). This extensive collagenous stroma contains small islands and nests of odontogenic cells. These islands are compressed by the collagenous dense stroma. The follicles tend to be morphologically irregular due to compression. Peripheral cells are mostly cuboidal, columnar cells are rarely seen.

Clinical Features The incidence of desmoplastic ameloblastoma is low; rates of 0.9 to 12.1 percent of all ameloblastoma have been reported. It has been found more in Chinese, Malaysian and Japanese population: Age and sex distribution: It is seen in patients aged 18 to 70 years, with a mean of 41.2 years. It occurs in older patients than conventional tumor. No difference between sexes has been reported. Location: Desmoplastic ameloblastoma is characteris­ tically seen in anterior maxilla. Sign and symptoms: It presents as a gradual tumor mass in the initial stages which soon acquires an aggressive rapidly growing form the maxilla is expanded anteriorly and obvious facial asymmetry is noted. Ameloblastoma of the posterior maxilla is dangerous because of its close proximity to the orbit, pterygomaxillary fossa and cranium and due to the difficulty in achieving an adequate surgical margin. Intracranial extension can be lethal. The entire maxilla possesses a thin cortical plate that offers little resistance to the tumor, thereby enhancing its rapid spread into the adjacent vital structures.

Figure 14.18 Desmoplastic ameloblastoma showing compressed follicles (F) due to deposition of large amount of collagen fibers in the connective tissue (Desmoplasia, D)

Radiologic Features The radiological appearance is also different than conventional ameloblastoma. Radiologically it appears as a fibro-osseous lesion. It occurs mainly in the anterior region of the jaws and appears radiographically as a diffuse, mixed radiolucent– radiopaque lesion with a honeycomb or soap bubble

Figure 14.19  Desmoplastic ameloblastoma

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Desmoplastic ameloblastoma must be histologically differentiated from ameloblastic fibroma, odontogenic fibroma and squamous odontogenic tumor. As the tumor is non-encapsulated, the cells infiltrate between the trabeculae of the cancellus bone leaving them intact for some time. Thus, the tumor actually extends beyond the radiographic margin, It has been suggested that an altered intracellular distribution of collagen XVII and consequent loss of critical cellular attachments may contribute to the infiltrative and progressive growth characteristics of ameloblastoma. Points to Remember Gradual tumor mass, expanded anteriorly, entire maxilla possesses a thin cortical plate, mixed radiolucent– radiopaque lesion with a honeycomb or soap bubble pattern, Desmoplasia, non-encapsulated tumors, cuboidal, columnar cells, cells infiltrate, trabeculae of the cancellous bone.

Figure 14.20 Peripheral ameloblastoma of follicular type showing stellate reticulum (SR) and ameloblasts like cells (AC) (Courtesy: Dr Sangamesh Halawar)

Management

Extraosseous/Peripheral Ameloblastoma

Local surgical excision: Patient respond well to this

It is a tumor which occurs in the soft tissue outside and overlying the alveolar bone. It originates from either the surface epithelium or the remnants of dental lamina.

Recurrence: Peripheral lesion is relatively innocuous, lacks persistent invasiveness and has a limited tendency of recurrence.

Clinical and Radiological Features

Points to Remember

Location: It is seen on the mandibular gingiva in the molarpremolar region, buccal mucosa and maxillary tuberosity area.

Appears nodular on gingiva, evidence of pressure resorption, histologically, it exhibits the same pattern as seen in intraosseous ameloblastoma, local surgical excision.

Symptoms: The patient complains of a mass which is growing in size and interfering with speech, mastication and esthetics. Sign: Mass is mildly tender on palpation at times ulcerated and bleeding may occur on slight touch. Appearance: The lesion appears nodular on gingiva varying in size from 3 to 2 cm in diameter. Radiological features: Sometimes underlying bone may exhibit evidence of pressure resorption in the form of saucer-shaped depression beneath the tumor.This is called as cupping resorption.

Histopathological Features Tumor may exhibit in one or more areas, continuity with the surface epithelium. Histologically, it exhibits the same pattern as seen in intraosseous ameloblastoma (Fig. 14.20).

Pituitary Ameloblastoma It is also called as craniopharyngioma or Rathke’s pouch tumor. Origin: It occur in anterior lobe, which is of ectodermal origin. The lobe is derived from Rathke’s pouch, an outgrowth of oral ectoderm. The pouch give rise to craniopharyngeal duct, which in due course degenerates itself leaving residues of squamous epithelial cells. From these squamous epithelial cells ameloblastoma like tumor develops. Age: It is most common in childhood and adolescents before the age of 25 years. Location: It may be located within the sella tursica or commonly in suprasellar space. It grows as a

Odontogenic Tumors

pseudoencapsulated mass causing pressure effect and often destroys the pituitary gland. Symptoms: It is related due to destruction of pituitary gland (diabetes insipidus) or due to compression of nearby cranial nerve. Histopathological features: Columnar cells in craniopharyngioma have central nuclei, longitudinal cytoplasmic fibrils. The central areas of the trabeculae of cells that compose the tumor consist of squamous cells showing intercellular bridges, but degeneration and edema are common and produces an appearance superficially similar to stellate reticulum. Frequent presence of calcified material and keratinization in pituitary ameloblastoma. Points to Remember Craniopharyngioma, destruction of pituitary gland, central nuclei, longitudinal cytoplasmic fibril, squamous cells showing intercellular bridges.

Adamantinoma of Long Bones Origin: It is derived from epithelial rests misplaced during the course of development. Trauma causing implantation of epithelium with subsequent tumor formation may cause it.

Pathogenesis of Unicystic Ameloblastoma Three hypothesis are put forward. In dentigerous cyst lining basal cells undergoes transformation into ameloblast like cells, which proliferate either into the lumen or connective tissue forming nodules of ameloblastoma. The follicles of ameloblastoma undergo degeneration leading to formation of a cavity or microcystic space, which enlarges forming large cystic space. Unicystic ameloblastoma arises de novo.

Clinical Features Unicystic ameloblastoma accounts for 10 to 15 percent of all extraosseous ameloblastoma. This variant is believed to be less aggressive. Age: Unicystic ameloblastomas are most often seen in young patients, with about 50 percent of such tumors diagnosed during the second decade of life. Location: More than 90 percent of unicystic ameloblastomas are found in the mandible, usually in the posterior region. Symptoms: The lesion is often asymptomatic, although a large lesion may cause painless swelling of the jaws.

Site: It occurs in tibia, ulna, femur and occasionally in others bone.

Histological Subtypes Unicystic Ameloblastoma

Clinical course: Some lesions behave aggressively and sometimes are metastasizing.

• Luminal • Intraluminal • Intramural.

Histopathological features: It bears a superficial microscopic resemblance to ameloblastoma of jaws. Points to Remember Trauma causing implantation of epithelium, aggressive, superficial microscopic resemblance.

Unicystic Ameloblastoma It is cystic variant of ameloblastoma. It is thought to develop from dentigerous cyst. Unicystic ameloblastoma, is a variant of ameloblastoma first described by Robinson and Martinez in 1977, though refers to those cystic lesions that show clinical and radiologic characteristics of an odontogenic cyst but in histologic examination show a typical ameloblastomatous epithelium lining part of the cyst cavity, with or without luminal and/or mural tumor proliferation.

Histopathological Features (Figs 14.21 to 14.24) Based on the character and extent of tumor cell proliferation within the cyst wall, several histologic subtypes of unicystic ameloblastoma are recognized. Three histopathological variants of unicystic amelo­ blastoma have been described, i.e. luminal unicystic ameloblastoma, intraluminal ameloblastoma and mural unicystic ameloblastoma. Luminal type: In the first type, the tumor is confined to luminal surface of cyst; while the lesion consists of fibrous cyst wall, with a lining that consists partially or totally of ameloblastic epithelium. This demonstrates a basal layer of columnar or cuboidal cells with hyperchromatic nuclei that show reverse polarity and basilar cytoplasmic vacuolization. The overlying epithelial cells are loosely cohesive and resemble stellate reticulum.

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Figure 14.21  Mural ameloblastoma showing cystic lining

Figure 14.24  Unicystic ameloblastoma (Intraluminal)

In the second microscopic variant (intraluminal unicystic ameloblastoma), one or more nodules of ameloblastoma project from cystic lining into lumen of cyst. These nodules may be relatively small or they largely fill the cystic lumen. In some cases, nodules of tumor that project into lumen demonstrate an edematous plexiform pattern that resembles plexiform pattern seen in conventional ameloblastoma. These lesions are referred to as plexiform unicystic ameloblastoma. In the third variant (mural unicystic ameloblastoma), the cystic fibrous wall is infiltrated by of typical follicular or plexiform ameloblastoma islands. The extent and depth of ameloblastic proliferation may vary considerably.

Management Figure 14.22  Unicystic ameloblastoma showing proliferative

epithelial lining

While the first two groups of lesions may be treated successfully by enucleation or curettage, it has been suggested that recurrence following conservative surgery is more likely to occur in the third group and that these lesions should therefore be treated in the same manner as solid ameloblastoma. Its response to enucleation or curettage is more favorable than the classic solid or multicystic ameloblastoma. Points to Remember

Figure 14.23  Unicystic ameloblastoma (Luminal)

Ameloblastomatous epithelium, asymptomatic, luminal blastoma unicystic ameloblastoma, intraluminal amelo­ and mural unicystic ameloblastoma, in luminal type basal layer of columnar or cuboidal cells, in intraluminal unicystic ameloblastoma more nodules of ameloblastoma project from cystic lining into lumen of cyst, in mural unicystic ameloblastoma typical follicular or plexiform ameloblastoma islands.

Odontogenic Tumors

SQUAMOUS ODONTOGENIC TUMOR It is well differentiated odontogenic tumor composed of islands or sheets of squamous epithelium that lack recognizable features of enamel organ differentiation. It is locally infiltrative odontogenic neoplasm.

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Peter and Reichart Definition It is a benign but locally infiltrative neoplasm consisting of islands of well differentiated squamous epithelium in a fibrous stroma. The epithelial islands occasionally show foci of central cystic degeneration.

Origin The origin of squamous odontogenic tumor is not clear. It is believed to originate from the cell rests of Malassez located in periodontal ligament. Peripheral variety may originate from gingival surface epithelium or from the remnants of dental lamina.

Figure 14.25  Squamous odontogenic tumor showing islands containing keratinized squamous cells (S) arranged in islands in loose fibrillar stroma background (ST)

Clinical and Radiological Features Age and sex: There is a wide age distribution in the range of 11 to 67 years with mean age 40 years and females are more commonly affected than the males. Site: It occurs with equal frequency in maxilla and mandible. In maxilla, it occurs in incisor-cuspid area and in the mandible, it has got a predilection for the bicuspid-molar area. Symptoms: It is usually asymptomatic but there may be mobility of the involved teeth, pain, tenderness to percussion and occasionally abnormal sensation. Radiological features: It is well circumscribed radiolucent area which is presented as semicircular or roughly triangular area. Border may or may not be sclerotic.

Histopathological Features (Figs 14.25 and 14.26) It is composed entirely of round to oval islands of squamous epithelium. Sometimes islands have irregular or cord like shape without peripheral palisaded or polarized columnar cells. Islands contain peripheral flat to cuboidal epithelial cells. Central cells show squamous differentiation. They are of very uniform size and shape. They exhibit no pleomorphism, nuclear hyperchromatism or mitotic activity. Sometimes individual cell keratinization may be present. But epithelial pearl formation is not seen.

Figure 14.26  Squamous odontogenic tumor

Microcystic degeneration may be seen few islands. Intraepithelial calcification may be seen in few islands. Calcifications tend to be laminar. Globular, hyaline eosinophilic structure with the islands which are not amyloid are sometime found in this tumor. The fibrous stroma of tumor contains mature bundles of collagen fibers, devoid of any inductive effect.

Management Conservative enucleation and curettage is usually curative with a low recurrence rate.

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Points to Remember 318

Cell rests of Malassez, usually asymptomatic, well circumscribed radiolucent area, round to oval islands of squamous epithelium, peripheral flat to cuboidal epithelial cells, microcystic degeneration, and globular, hyaline eosinophilic structure.

CALCIFYING EPITHELIAL ODONTOGENIC TUMOR It is also called as Pindborg tumor. The calcifying epithelial odontogenic tumor (CEOT) has been reported prior to 1955 under different names, such as ameloblastoma of unusual type with calcification, calcifying ameloblastoma, malignant odontoma, adenoid adamantoblastoma, cystic complex odontoma and as a variant of the simple amelo­ blastoma. The term calcifying epithelial odontogenic tumor (CEOT)’ has been generally accepted and adopted by the WHO in the first edition of Histological Typing of Odontogenic Tumors, Jaw Cysts, and Allied Lesions, where it was recognized as a distinct entity. For more than 30 years the CEOT has been known eponymously as the Pindborg tumor, named after JJ Pindborg who described it as calcifying epithelial odontogenic tumor in 1955. Pindborg reported few cases of intraosseous CEOT. The CEOT is a benign neoplasm located either intraosseously or extraosseously. When occurring intra­ osseously, which is by far the most common location; it may occasionally show local invasiveness. The tumor resembles ameloblastoma for the site and the age. It forms 1 percent of all odontogenic tumors.

Origin Two hypotheses have been suggested for the pathogenesis of the tumor. It develops from the reduced enamel epithelium of the embedded tooth or from stratum intermedium.

Pathogenesis of CEOT The peripheral locations strongly suggested of an origin from the cell rest of dental lamina. Another source might be from the basal cells of the oral epithelium. Most widely accepted origin in current literature is from the disintegration of the dental lamina cell rest (Figs 14.27 and 14.28).

Figure 14.27  Pathogenesis of CEOT arising from reduced

enamel epithelium

Figure 14.28  Cell rest of malassez and cell rest of serrae can

proliferate either into jaw bone or towards gingiva

Clinical Features Age and sex: It is more common in men with an age range of 8 to 92 years with a mean age of 42 years. Location: Both the tumors occur commonly in the mandible than maxilla by a ratio of 2:1. They occur three times in molar region than the premolar. Symptoms: It is asymptomatic and only presenting symptom is a painless swelling. In rare cases, there is associated mild paresthesia. When occurs in maxilla, it may show epistaxis, nasal congestion and head ache. Signs: Cortical expansion occurs. Palpation will show hard tumor with well defined or diffuse border.

Odontogenic Tumors

Peripheral CEOT: It occurs as a painless firm gingival mass clinically diagnosed as fibroma, peripheral giant cell granuloma. The diagnosis is confirmed histopathologically. 319

Radiographic Features The characteristic radiographic appearance is of an irregular, uni or multilocular radiolucent area, containing radiopaque masses of varying size and opacity. In many cases, especially in tumors of relative short duration, the calcified concernments are very minute and may be undetectable on radiographs. Driven snow appearance: Later, it reveals a unilocular or a multilocular cystic lesion with numerous scattered radiopaque foci of varying sizes and density which gives it an appearance as that of ‘driven snow (Fig. 14.29).

Histopathological Features (Figs 14.30 to 14.36)

Figure 14.30 Pindborg tumor showing epithelial cells with

prominent intercellular bridges (ICB) forming eosinophilic material (EM). Few cells show dysplastic features (D)

The tumor consists of sheets, or islands of polygonal cells. The cells have eosinophilic cytoplasm, distinct cell borders and very conspicuous intercellular bridges. Nuclei are pleomorphic with prominent nucleoli; cells with giant nuclei and multiple nuclei are also present. The pleomorphism of nuclei mimics a malignant tumor, but as mitotic figures are rare and clinical behavior is slow growing this possibility is ruled. The connective tissue stroma is scanty and fibrous. Occasionally, cells are arranged in cords and rows mimicking adenocarcinoma. Amyloid like material in CEOT: There is presence of homogeneous eosinophilic substance. This protien­aceous material which has been interpreted as amyloid has also been suggested to be comparable glycoprotein, basal lamina, and keratin or enamel matrix. Figure 14.31  Pindborg tumor showing presence of

Liesengang rings (LR)

Liesegang rings: There are few deposits of calcified material which is said to be cementum like material. There is presence of calcification in large amounts and often in the form of Liesegang rings.

Figure 14.29  Driven snow appearance seen in CEOT

Clear cell variant: A well recognized form of this neoplasm is the clear cell variant which exhibits a clear vacuolated cytoplasm rather than an eosinophilic cytoplasm. The nucleus may remain round or oval in

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Figure 14.32  Calcification seen in CEOT

Figure 14.34  CEOT showing nest and islands of tumor cells

Figure 14.33  CEOT showing Liesegang ring

Figure 14.35 CEOT showing sheets of odontogenic cells with distinct cell membranes and darkly staining nuclei and eosinophilic material

the center of the cells or be flattened against the cell membrane. In some tumors, clear cells comprise the bulk of the tumor cells while in others, it consist of only a few scattered foci.

Management It has limited invasive potential therefore local excision with limited margins is indicated. Simple enucleation or radical resection can be done.

Points to Remember Pindborg tumor, painless swelling, mild paresthesia, maxillary lesion show epistaxis, nasal congestion, cortical expansion, peripheral CEOT, uni or multilocular radiolucent area, driven snow appearance, sheets, or islands of polygonal cells, nuclei are pleomorphic with prominent nucleoli, amyloid like material, Liesegang rings, clear cell variant.

Odontogenic Tumors

Its clinico-pathological profile is unique among the odontogenic tumors. It has sometimes been referred to as the two-thirds tumor because about two-thirds occur in the maxilla, two-thirds occur in young women (preteen and teenage years), two-thirds are associated with an unerupted tooth, and two-thirds of those teeth are canine teeth.

Definition WHO definition: A tumor of odontogenic epithelium with duct like structures and with varying degrees of inductive change in the connective tissue. The tumor may be partly cystic and in some cases the solid lesion may be present only as masses in the wall of a large cyst. It is generally believed that the lesion is not a neoplasm. Figure 14.36  Calcification seen in CEOT

ADENOMATOID ODONTOGENIC TUMOR OR CYST Adenomatoid odontogenci tumor (AOT) is composed of odontogenic epithelium in a variety of histoarchitechtural patterns, embedded in mature connective tissue stroma and characterized by slow but progressive growth. The adenomatoid odontogenic tumors (AOT) or cyst (AOC) represents 3.7 percent of all odontogenic tumors and was considered as one of the variant of ameloblas­ toma. It is much more common than ameloblastoma or the calcifying epithelial odontogenic tumor. It shows a glandular pattern of arrangement of the pre-ameloblasts like tumor cells and was called adenoameloblastoma or adenoid ameloblastoma. Many other different names have been used like adenoid adamantinoma, ameloblastic odontogenic tumor, epithe­ lioma adamantinum or teratomatous odontoma. In contrast to ameloblastoma adenomatoid odonto­ genic tumor is a circumscribed lesion with slow growth. Seventy-five percent of the cases have been reported to be associated with unerupted or impacted tooth, the most common being maxillary canine. Adenomatoid odontogenci tumor (AOT) was first described by Steensland in 1905. The term AOT was coined by Philipsen and Birn in 1969. AOT is histomorphologically similar to dental organ. It is believed to be an attempt at enamel formation by the tumor cells. It is termed recently as a hamartoma and not a tumor. Also recent incidences are reported in association with dentigerous cyst linings as mural nodules thus representing it as an adenomatoid odontogenic cyst due to its cystic presentation.

Types/Classification According to Philipson and Riechart the AOT appears in three different clinicotopographic variants. Terminology suggested for the two central tumor variants serves single purpose of making a distinction between tumors having and those lacking an association with crown of an embedded tooth. These terms do not indicate or suggest any pathologic principle.

Pathogenesis Origin of AOT is a debated issue. Initially it was thought that it is a variant of ameloblastoma as tall columnar cells similar to that found in ameloblastoma are also found here. Because of presence of duct-like structures dual salivary and odontogenic origin was suggested. AOT occurs exclusively within tooth bearing areas of the jaws. This indicates that this tumor is mainly odontogenic. Transmission electron microscopy has shown that cells of AOT resemble enamel organ. Immunohistochemical staining ruled out salivary gland origin and supported odontogenic nature. The epithelium that probably gives rise to AOT is cell rests of dental lamina. Disintegration of dental lamina gives rise to numerous epithelial remnants persisting in the jaws. These rests are distributed in gingiva and few are present in Gubernacular dentis which is connective tissue that occupies Gubernacular canal. Based on this origin pathogenesis of various clinical forms of AOT can be explained (Fig. 14.37). Follicular AOT: Cell rests of Gubernacular dentis start proliferating prior to eruption of permanent tooth. As tumor growth continuous and as tooth begins to erupt contact occurs between the two. This leads to the fusion between

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Figure 14.38  Schematic diagram showing different types of Figure 14.37 Schematic diagram showing origin of AOT

from Gubernacular dentis (GD) which connect gingiva and permanent tooth germ (PTG) and contains many and follicular space (FS)

tumor and reduced enamel epithelium of the erupting tooth. Sooner or later tumor completely embraces the tooth leading to follicular radiological appearance. Extrafollicular AOT: If tumor develops from cell rests situated at the periphery of the Gubernacular dentis or if eruption is not impeded by the tumor tooth may bypass it and erupt into the oral cavity. Thus tumor and tooth are not in contact leading to extrafollicular AOT. It assumes that shape of residual, globulomaxillary, lateral periodontal or radicular cyst on radiograph based on its relation to tooth. AOT occurring in molars likely to originate from distal extension of dental lamina as molars do not have Gubernacular dentis. Peripheral AOT: It is likely to originate from cell rests of Serrae. It is also possible that it develops from cell rest located at the peripheral most part of the Gubernacular dentis (Fig. 14.38).

Clinical Features Some studies have reported incidence in 1.2 percent in Caucasian and 9 percent in African black patients. It represents 3 to 7 percent of all odontotogenic tumors and is a developmental outgrowth of odontogenic tissue.

AOT. Follicular (F), extrafollicular (EXF) and peripheral (P)

Age and sex distribution: It is found in individuals ranging from 3 to 82 years with 70 percent occurrence in 2nd decade with an average age of 16 years. Females are affected more than males in a ratio of 2:1. Site: It occurs more commonly in the maxilla than in the mandible, usually in the anterior region and especially in the cuspid area. It is commonly associated with an unerupted tooth. Symptoms: Most are asymptomatic. Few present as an area of swelling over an unerupted tooth. Some-times it may expand cortical bone but is not invasive. Signs: AOT is frequently associated with an unerupted tooth in which the epithelial proliferation is confined within a connective tissue capsule that is attached to the tooth in manner similar to the attachment of a dentigerous cyst. When the tumor occurs independently of unerupted teeth it is often encapsulated. It may cause delayed eruption of tooth. The tumor causes expansion of bone and fluctuation may be elicited (Figs 14.39 to 14.41). Extraosseous tumor: This uncommon type usually occurs as pink colored mass in gingiva.

Radiographic Features It is well-demarcated mixed radiolucent or opaque lesion. It may or may not be well circumscribed. Borders are sclerotic. Unilocular radiolucency but may contain faint to

Odontogenic Tumors

dense radiopaque foci which may be seen peripherally as the lesion matures. Dense cluster of radiopacities appear as small pebbles. Separation of roots or displacement of a adjacent tooth occurs frequently (Figs 14.42 and 14.43).

Histopathological Features (Figs 14.45 to 14.48)

Figure 14.39  AOT showing swelling and expansion

Macroscopic (Fig. 14.44): Most AOTs are small spherical up to 1 to 3 cm in diameter, the tumor may be or may not be encapsulated. Cut surface shows white to yellow firm surface with or without cystic areas containing yellowish to brown central gelatinous material. The cut section sometimes may be gritty which may represent poorly formed tooth structures or an aberrant type of dystrophic calcification.

Figure 14.40  AOT showing extraoral swelling

Figure 14.42  AOT showing radiolucency

Figure 14.41  AOT appears as a swelling associated with an impacted canine. Over retained deciduous canine can be seen. (Courtesy: Dr Avadhoot Avadhani)

Figure 14.43  AOT radiograph showing inverted pear shaped radiolucency associated with impacted canine. (Courtesy: Dr Avadhoot Avadhani)

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Figure 14.44  AOT gross specimen showing soft tissue mass

around impacted canine (Courtesy: Dr Avadhoot Avadhani)

Figure 14.45  AOT shows many duct like spaces (D) lined by

Figure 14.46  AOT showing many rosette pattern and duct-

like structure

Figure 14.47  Different types of cells and their location in a

single cells and rosette patterns (R)

duct-like pattern

Tumor shows fibrous capsule of variable thickness. The histologic appearance show remarkably identical histologic features. The tumor may be partly cystic but mostly presents as a solid lesion. The tumor shows highly cellular nodules arranged in small nest or island like pattern. There is prominence of duct-like spaces or duct-like arrangement of the tumor cells lined by single or double row of low columnar cells which are reversely polarized (the nuclei are placed away from the duct like spaces or lumen). The lumens of the duct may be empty or contain eosinophilic material. Focal areas show whorled appearance forming Rosette pattern. Rosette is a nodular appearance of

the tumor cells arranged in concentric circles each having eosinophilic material sandwiched between the epithelial layers. The space between the duct-like spaces and rosette patterns is filled by spindle shaped cells. The tumor cells are characteristically preameloblasts like cells and the eosinophilic material is believed to be enamel matrix. The stromal component exhibits fibrocellular tissue characteristically composed of focal areas of eosinophilic matrix material similar to dentinoid. These eosinophilic uncalcified amorphous materials are referred to as Tumor droplets. These eosinophilic tumor droplets are suggested by histochemical studies similar to amyloid. The tumor nests

Odontogenic Tumors

prominent nucleoli. These are present in solid nodules, rosette patterns and duct-like structures. Cell type II: These cell surround the epithelial nodules. These are spindle shaped cells with dark eosinophilic cytoplasm. Nucleus is oval and hyperchromatic. Long axis of these cell are perpendicular to type I cells. Cell type III: These are islands or nodules of polygonal cells having squamous appearance. They contain prominent intercellular bridges. These cells surround the type II cells.

Management

Figure 14.48  AOT showing duct-like spaces

are supported by scanty connective tissue stroma and some spindle cells can be identified surrounding these ducts like spaces. Calcified material is common throughout the tumor which usually is seen at junctions between aggregates of epithelial cells. These calcified material have been shown to resemble enamel, pre-enamel or dentin. Immunohistochemical studies: Classical AOT has shown positivity for CK 5, CK17 and CK19. The classical AOT is negative for CK4, CK10, CK13 and CK 18. Crivelini et al (2003) has detected expression of CK14 indicating its origin from reduced enamel epithelium. Few studies have reported positive reaction for Amelogenin in limited areas in AOT. Takahashi et al observed positive staining for ion binding proteins (Transferrin, Ferritin) and Gao et al studied bone morphogenic protein (BMP) in AOT. BMP showed positive reaction in compound odontome dentinoma and cementifying fibroma whereas it was a negative reaction with AOT, ameloblastoma and CEOT.

Unusual Variants of AOT Sometimes AOT and CEOT like may co-exist. In some cases AOT is found in the wall of CEOC and few cases of AOT with melanin pigmentation are reported. AOT can be present along with odontoma (Adenomatoid odontoma).

Cells of AOT

Adenomatoid odontogenic tumor (AOT) is a small circumscribed tumor and can be successfully managed by conservative surgical enucleation and curettage in contrast to the aggressive treatment regime for ameloblastoma. Prognosis is very good and is and the recurrence rate is minimal up to 0.2 percent. Points to Remember Cuspids area in maxilla, area of swelling over an unerupted tooth, delayed eruption of tooth, extraosseous tumor, well-demarcated mixed radiolucent, dense cluster of radiopacities appear as ‘small pebbles’, fibrous capsule of variable thickness, highly cellular nodules arranged in small nest or island like pattern, single or double row of low columnar cells, reversely polarized, whorled appearance forming Rosette pattern, preameloblasts like cells, tumor droplets, conservative surgical enucleation.

MIXED ODONTOGENIC TUMORS Mixed odontogenic tumors consist of tumors where both epithelium and connective tissue proliferate. The epithelial component resembles ameloblast like cells. Connective tissue resembles dental papilla. The clinical features, radiological features and to some extent histopathological features overlap. These tumors are seen more commonly second decade of life. Radiologically produce radiolucency containing radio opacities. The treatment and prognosis is almost same for these. Thus these tumors are thought to be interrelated. Two hypothesis are proposed in this regard.

Cells of AOT are divided into three types based on morphology.

CONTINUUM CONCEPT (CAHN AND BLUM)

Cell type I: These are cuboidal or columnar cells with pale cytoplasm. They contain vesicular nucleus with one or two

According to this concept ameloblastic fibroma is the tumor that develops during active odontogenic and it develops

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similar tooth, i.e. over the time it matures and finally forms odontoma. During maturation there is gradual formation of dental hard strucutures. Initially there is formation of dentin like structure. This is called as ameloblastic fibrodentinoma. Later enamel also forms leading ameloblastic fibro-odontoma. As maturation progresses fibrous compo­ nent reduces and calcified structures increase. This stage is called complex odontoma. This matures to form compound odontoma. But this theory is not accepted completely. There are various reasons for this. When residual tumor of ameloblastic fibroma is left in the jaw for long time it is observed that it does not develop into other type of odontogenic lesion. Few odontoma develop well after tooth formation.

Philipsen and Reichart Theory But it is clear that odontoma and other lesions cannot exist de novo. They must pass through an initial stage where there is absence of any calcification. This led Philipsen and Reichart put forth another theory where they propose existence of two lines (Table 14.5). Line I: This is neoplastic line, consisting of amelo­blastic fibroma occurring after tooth formation. This does not undergo any maturation. Line II: It is also called as hamartomatous line. This includes the ameloblastic fibroma that occurs during tooth formation. This matures over the time to form complex odontoma. But this line excludes compound odontoma. It is believed that this lesion has a different pathogenesis than complex odontoma. Thus it is believed that few mixed odontogenic tumors are interrelated. They start their develop from ameloblastic fibroma follow stages similar to development of tooth. Complex odontoma is terminal stage after which there is no further growth. Growth of these mixed tumors stop after some time and does not progress further.

Table 14.5  Two lines of mixed odontogenic tumors

Hamartomatous or Line I

Neoplasitc line Line II

Ameloblastic fibroma

Ameloblastic fibroma Ameloblastic fibrodentinoma Ameloblastic fibro-odontoma Complex odontoma

Key Points of Continuum Concept ∙∙ Proposed by Cahn and Blum in 1952 ∙∙ Stated that Ameloblastic Fibroma will, overtime mature and finally result in the formation of odontoma ∙∙ Drawbacks: ∙∙ Residual and recurrent ameloblastic fibroma never show further steps of differentiation and maturation into dental hard tissue formation ∙∙ Ameloblastic fibroma known to occur at ages beyond completion of odontogenesis (beyond 20 years).

AMELOBLASTIC FIBROMA Ameloblastic fibroma is mixed odontogenic tumors in which both epithelial components as well as mesenchymal components proliferate. These cells resemble early functional ameloblasts and primitive mesenchymal components of the dental papilla. It is believed to be precursor of other mixed odontogenic tumors. If this tumor is left undisturbed, it will ultimately differentiate into other lesions terminating in development of compound odontoma. There are several synonyms for this such as fibrous adamantinoma, soft odontoma, soft mixed odontoma and fibroadamanblastoma.

Pathogenesis Ameloblastic fibroma has odontogenic origin. It resembles normal tooth germ just before formation of hard structures. There is failure or alteration in epithelial mesenchymal interactions leading to failure of hard tissue formation. Ameloblastic fibroma exists in two forms. One is neoplastic variety that develops in adults after formation of tooth is over. Other is hamartomatous variety that develops during tooth formation. This is more common.

Clinical Features Age and sex distribution: Most frequently observed during first two decades of life with 40 percent of patients under the age of 10 years. Average age of occurrence is 14.8 years. Few cases are seen in adults as old as 60 years. There is slight predilection for occurrence in males. Male to female ratio is 1.4:1. Site: Developed in premolar molar area of the mandible. Three times more common is mandible than in maxilla. Symptoms: It is painless and expands slowly. There is bulging of the cortical plates rather than erosion through them. There is also migration of involved teeth.

Odontogenic Tumors

Signs: It enlarges by gradual expansion so that the periphery of bone often remains smooth. It is associated with unerupted teeth. It reaches up to an approximate size of 1 to 8.5 cm. It has got a slower clinical growth than ameloblastoma and does not tend to infiltrate between trabeculae of bone.

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Radiographic Features It may present with cyst like area of bone destruction or there may wide area of bone destruction. As it is usually associated with an impacted tooth, it appears as pericoronal radiolucency. It may be either unilocular or multilocular and is associated with unerupted or missing tooth. Margins are well defined often with sclerotic borders (Fig. 14.49).

Histopathological Features (Figs 14.50 and 14.51) This tumor is made up of epithelial and mesenchymal components

Figure 14.50 Ameloblastic fibroma showing islands and

Cords (C ) of odontogenic epithelium made up of ameloblasts like cells (A) and stellate reticulum like cells (S). Connective tissue resembles dental papilla (EM). A cell free zone is seen around the islands (CFZ)

Epithelial components: These are arranged in form islands cords and stands. Islands show presence of tall columnar cells with reverse polarity at the periphery thus resembling the ameloblasts (Ameloblast-like cells). The central area of islands contains star shaped cells resembling stellate reticulum. In cords and small islands, stellate reticulum like tissue is absent so ameloblasts like cells are present in two layers. Cords resemble dental lamina. Mesenchymal components: Mesenchymal compo­ nents resemble dental papilla. These contain rounded or angular

Figure 14.51  Ameloblastic fibroma showing ameloblasts like

cells (Courtesy: Dr Sangamesh Halawar)

Figure 14.49  CT scan of ameloblastic fibroma showing

radiolucent lesion

cells. There is presence of few delicate collagen fibers. One important feature is presence of cell free zone around the epithelial islands. This zone is believed to be due to inductive effect of epithelium and contains excess basement membrane like material. Few ameloblastic fibroma show presence of melanin pigmentation in lesions. Sometimes granular cells similar to those found in granular cell ameloblastoma are found in mesenchymal portion. Such lesions are called granular cell ameloblastic fibroma.

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Management 328

Curettage can be done which has successful results in many cases. Surgical excision of lesion is carried out. Points to Remember •  Fibrous adamantinoma, premolar molar area, painless and expands slowly, cyst like area of bone destruction, unilocular or multilocular •  Epithelial components: Islands cords and stands, tall columnar cells with reverse polarity, cords resemble dental lamina Mesenchymal components: Resemble dental papilla, •  rounded or angular cells, few delicate collagen fibers.

AMELOBLASTIC FIBRODENTINOMA It is very rare neoplasm composed of odontogenic epithelium and immature connective tissue and characterized by the formation of dysplastic dentin. It is similar to ameloblastic fibroma showing formation of dentinoid. It is also called as dentinoma.

Pathogenesis It is hamartomatous lesion of odontogenic origin. It is considered to an intermediate stage between ameloblastic fibroma and ameloblastic fibro-odontoma.

Clinical and Radiological Features

zone. The hard tissue is similar to dentin so it is called as dentinoid. Rarely hard structure show dentinal tubules similar to true dentin.

Management Surgical excision of the lesion should be done. Points to Remember Premolar molar area, painless, gradual expansion, well delineated radiolucency, epithelial and mesenchymal portions are similar to ameloblastic fibroma, cell free zone.

AMELOBLASTIC FIBRO-ODONTOMA It is very rare neoplasm similar to ameloblastic fibroma and ameloblastic fibrodentinoma except the formation of enamel like material.

Pathogenesis Continued maturation of ameloblastic fibrodentinoma leading to formation of enamel gives rise to this tumor.

Clinical and Radiographic Features Age and sex distribution: It is observed during first two decades of life with 99 percent of cases are seen before 20 years. Average age of occurrence is 9.0 years. It is more common in males. Male to female ratio is 1.4:1.

Age and sex distribution: It is observed during first two decades of life with 75 percent of cases are seen before 20 years. Average age of occurrence is 13.6 years. Few cases are seen in adults as old as 60 years. It is more common in males. Male to female ratio is 3:1.

Site: Developed in premolar molar area of the mandible.

Site: Developed in premolar molar area of the mandible.

Ameloblastic fibro-odontoma consists of elements of ameloblastic odontoma and is more aggressive than the common odontoma.

Symptoms and signs: It is painless and expands slowly. It enlarges by gradual expansion so that the periphery of bone often remains smooth. Radiological features: It shows well delineated radiolucency. It contains varying degrees of radio opacity, depending on amount of hard tissue formed. It it associated with unerupted tooth both are closely associated.

Symptoms: The most common presenting complaint is swelling and failure of tooth eruption. The maxillary tumor if large interferes with nasal respiration, eating and speech.

Radiographic features: It shows well delineated unilocular of multilocular radiolucency. Central portion of it contains radio-opaque, masses. These masses irregular in shape and size. They are round and homogeneous.

Histopathological Features

Histopathological Features (Figs 14.52 to 14.55)

Epithelial and mesenchymal portions are similar to ameloblastic fibroma. There is presence of hard tissue around the epithelial cells. This is preceded by cell free

It contains hard and soft structures. Hard tissues are present at the center and they are covered by the peripheral soft tissue.

Odontogenic Tumors

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Figure 14.52  Ameloblastic fibro-odontoma (Ground section-

Figure 14.54  Ameloblastic fibro-odontoma (high power)

dentinoid material)

Figure 14.53  Ameloblastic fibro-odontoma (Ground section-

Figure 14.55  Ameloblastic fibro-odontoma showing ameloblastic

enamel like material)

follicles (A) surrounded by dentin like calcifications (D)

Hard tissue: It consists of dentin like material and enamel like material. Dentin like material is usually present at the central portion. It is covered by enamel like material called enamel oid. Sometimes cementum like material may be found. Soft tissue: It is similar to ameloblastic fibroma. Thus it contains epithelial islands in dental papilla like mesenchymal tissue.

Management Surgical excision of the lesion should be carried out.

Points to Remember Swelling and failure of tooth eruption, unilocular of multilocular radiolucency, central portion of it contains radio paque masses, dentin like material and enamel like material, soft tissue is similar to ameloblastic fibroma.

ODONTOMA It is a hamartoma of odontogenic origin in which both epithelial and mesenchymal cells exhibit complete differentiation with enamel and dentin laid down in abnormal position.

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The term odontoma was applied to wide variety of lesions showing defects in hard tissue formation. But now they are applied only for mixed odontogenic tumor. 330

Definition A malformation in which all dental tissues are represented, individual tissues being mainly well formed but occurring in a more or less disorderly pattern.

Origin They result from extraneous buds of odontogenic epithelial cells from the dental lamina. Odontoma may arise from any of three dental tissues, i.e. enamel, dentin and cementum. Classification • Complex composite odontoma: Nondiscrete masses of dental tissue. •  Compound composite odontoma: Multiple well formed teeth.

Pathogenesis Odontoma are hamartomatous proliferation of odon­ togenic origin. It is thought that local trauma, infection and genetic mutations cause this proliferation of odontogenic epithelium. These result in unsuccessful or altered ectomesenchyme interaction during early or later phases of tooth development leading to haphazard formation of enamel, dentin and cementum. Both the epithelial and mesenchymal cells exhibit complete differentiation with the result that functional ameloblasts and odontoblasts form enamel and dentin. It is laid down in an abnormal pattern because of failure of cells to reach the morphodifferentiation stage. Lesion is composed of more than one type of tissue, for this reason it is called as composite odontome. In some composite odontomes, the enamel and dentin are laid down in such a fashion that the structure bears a considerable anatomical resemblance to that of normal teeth except they are often smaller than the typical teeth, which have been termed as compound composite odontome. When calcified dental tissue are simply arranged in a irregular mass bearing no morphological similarity even to rudimentary tooth then that form is called as complex composite odontome.

Clinical Features Age and sex distribution: Mean age of detection is 14.8 years. Most begin to form while normal dentition is developing. There is slight predilection for occurrence in males. Compound type of odontome is twice as frequently seen complex variety of odontome. Site: Compound occurs in incisor, canine area of maxilla and complex occurs in mandibular 1st and 2nd molar area. Unusual situation include the maxillary sinus, inferior border of the mandible, ramus and condylar region. Signs: It is common for a tooth or teeth to be absent from the arch in the presence of an odontome. Symptoms: Occasionally, it may produce expansion of bone with consequent facial asymmetry. There may be evidence of swelling and infection.

Radiographic Features It appears as an irregular mass of calcified material surrounded by narrow radiolucent bands with a small outer periphery. Compound variety: It shows number of teeth like structures in the region of the canine. There is cluster of small shapeless dense masses of solid tissue having equal or more density, depending on the size of the mass. There may be many masses each of which has own dark line surrounding it. If a large number of teeth are present, the radiopaque mass is surrounded by a radiolucent line that represents the pericoronal space of the unerupted teeth. Borders are well defined in both the cases but vary from smooth to irregular and may have hyperostotic borders. Complex: Complex composite odontoma appears as a dense radiopaque object sometimes lying in clear space. Density is greater than that of bone and to greater than or equal to the teeth (Fig. 14.56).

Histopathological Features (Fig. 14.57) Normal appearing enamel or enamel matrix, dentin, pulp tissue and cementum like tissue which may or may not exhibit normal relation to one another. The lesion is surrounded by fibrous capsule which is partially separated by the fluid; the resultant cyst is usually lined by squamous epithelium. There is presence of ghost cells in odontoma.

Odontogenic Tumors

ODONTOAMELOBLASTOMA It is also called as ameloblastic odontomas. It is a very rare mixed odontogenic neoplasm characterized by the simultaneous occurrence of an ameloblastoma and a compound or complex odontoma in the same tumor mass.

Pathogenesis

Figure 14.56  Radiographic appearance of odontoma

The pathogenesis of odonto-ameloblastoma is unknown. One possible explanation is that the mineralized dental tissues are formed as a hamartomatous proliferation in response to inductive stimuli produced by the proliferating epithelium over the mesenchymal tissue. Other is two tumors developing separately and coming closer to collide each other (Collision tumor).

Clinical and Radiological Features Age and location: It is seen in younger individual and either jaw can be affected. Sign and symptoms: There is pain, delayed eruption, expansion of affected jaw. Radiological features: It is radiolucent process consisting of calcified material.

Histopathological Features (Fig. 14.58) The epithelial proliferation form islands or intermingled cords that produce the follicular or plexiform patterns typical of ameloblastoma. Unlike conventional ameloblastoma, these induce the production of mineralized dental tissues on the adjacent Figure 14.57  Odontoma showing well formed dentin (D) and

enamel (Enamel space, ES)

Management Mass has to be removed if it is causing periodontal diseases. Points to Remember Epithelial cells from the dental lamina, hamartomatous proliferation of odontogenic origin, compound occurs in incisor, canine area of maxilla, complex occurs in mandibular 1st and 2nd molar area, tooth is absent, expansion of bone, teeth like structures in compound variety, borders are well defined, dense radiopaque object sometimes lying in clear space in complex variety, normal appearing enamel or enamel matrix, dentin, pulp tissue cementum like tissue, ghost cells.

Figure 14.58  Odontoameloblastoma showing dentinoid (D)

and ameloblastic follicle (AF)

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mesenchymal cells and may respond to this change with the production of enamel.

are well defined and sclerotic. Larger lesions cause root divergence and resorption.

Management

Histopathological Features (Fig. 14.59)

It should be treated in same manner as that of ameloblastoma.

Odontogenic fibroma are composed of fibrous tissue of variable cellularity and density; variable amount of inactive appearing odontogenic epithelium; and variable presence of calcifications resembling dysplastic dentin, cementum-like tissue or bone. Mesenchyme also varies in fibrosis. Few lesions are highly fibrous while few contain less collagen fibers. Few lesions contain myxoid tissue. Cellularity is sparse to moderate. Sometimes eosinophilic amorphous globules representing enamel matrix protein are seen. Many calcifications are seen. These are not specific. Epithelial islands are few to numerous. They are inactive looking and does not play any role in the growth of the tumor.

Points to Remember Collision tumor, pain, delayed eruption, expansion of affected jaw radiolucent process consisting of calcified materiae, follicular or plexiform patterns, mineralized dental tissues on the adjacent mesenchymal cells.

ODONTOGENIC FIBROMA It is fibroblastic neoplasm containing varying amounts of apparently inactive odontogenic epithelium. It is found around the crown of unerupted tooth resembling a small dentigerous cyst. But some say that it is a hyperplastic dental follicle and not an odontogenic tumor. It may occur centrally or in the periphery. Peripheral variant clinically mimics fibroma. Clinical types • Central odontogenic fibroma • Peripheral odontogenic fibroma Histological types • Simple odontogenic fibroma • WHO type.

Simple odontogenic fibroma: This lesion resembles dental follicle. It contains mature fibrous tissue with sparsely scattered inactive odontogenic epithelial rests. It is composed of stellate fibroblasts with fine collagen fibrils in which rests of odontogenic epithelium and dystrophic calcification may or may not be present. WHO type: It is more cellular fibrous tissue with collagen fibers arranged in interlacing bundles. Odontogenic epithelium in form of long strands or isolated nests is present. In some areas, calcified material resembling dysplastic dentin or cementum like material may be present.

Pathogenesis It is said that WHO type of odontogenic fibroma originates from periodontal ligament and simple type is originating from dental follicle.

Clinical and Radiological Features Age and sex distribution: It occurs more frequently in older individual with mean age of 40 years. There is marked female predilection. Site: It is more common in maxilla and in anterior region. Symptoms: It is generally asymptomatic except for the swelling of the jaws. Signs: It may cause localized bony expansion or loosening of teeth. Radiological features: It produces an expansile radiolucency similar to that of ameloblastoma. Margins

Figure 14.59  Odontogenic fibroma showing stellate fibroblasts and immature collagen fibers thus resembling dental papilla (Courtesy: Dr Sangamesh Halawar)

Odontogenic Tumors

Management Treated with enucleation and curettage. Surgical excision and usually it does not recur. Points to Remember Asymptomatic, localized bony expansion, expansile radiolucency, root divergence, fibrous tissue of variable cellularity, dysplastic dentin, simple odontogenic fibroma, WHO type.

GRANULAR CELL ODONTOGENIC TUMOR It is also called as granular cell odontogenic fibroma. It is very rare tumor.

Clinical and Radiological Features Age and sex distribution: It is more commonly seen older than 40 years of age. It is more commonly seen in female as compared to male. Location: It is more commonly located in premolar molar area of mandible. Symptoms: It is usually asymptomatic and painless expansion of jaw is seen Radiological features: It is presented as well defined radiolucency which can be unilocular or multilocular with some calcification.

Histopathological Features It is composed of large eosinophilic granular cells. There are also cords or small island of odontogenic epithelium see among the granular cells. Cementum like calcification is seen in this tumor.

Management This tumor responds well to curettage Points to Remember Granular cell odontogenic fibroma, painless expansion, well defined radiolucency, large eosinophilic granular cells, cementum like calcification.

ODONTOGENIC MYXOMA It is also called as odontogenic fibro-myxoma, myxofibroma. It is a rare locally invasive neoplasm consisting of rounded

and angular cells lying in an abundant mucoid stroma. It accounts for 3 to 6 percent of odontogenic tumors.

Pathogenesis Origin is not clear. Various tissues are thought to be a source this tumor. This includes dental papilla, dental follicle, and periodontal ligament. Other possible sources are fibroblastic or fibroblastic-histolytic cells. The myxomatous tissue arises as a direct outgrowth of dental papilla of tooth or as an indirect effect of odontogenic epithelium on mesenchymal tissue. Thought to occur due to degeneration of odontogenic fibroma.

Clinical Features Age and sex: It is slightly more common in females with an age range of 10 to 30 years. Site: Mandible is more commonly affected than maxilla by a ratio of 3:1. Premolar-molar area in mandible and zygoma in maxilla. Rarely tumor may appear in the condylar region. Symptoms: It is associated with congenitally missing teeth. The growth rate is slow and pain is variable. There is a hard swelling which may be sometime large enough to produce facial asymmetry. Signs: Sometimes it perforates the cortical plate producing a bosselated surface (several small nodules on the surface). It can invade maxillary sinus and cause exophthalmos. Appearance: It may appear as fusiform swelling that may be hard and or may be covered by a layer of bone of only eggshell.

Radiographic Features It may be either unilocular or multilocular. It may be mixed radiopaque-radiolucent lesion. Margin are usually well defined but sometimes it may be poorly defined. It may be scalloped between the roots of adjacent teeth. Tennis racket or honey comb appearance: Locules are small and uniform with typical honeycomb appearance or strings of tennis racket (Fig. 14.60). Soap bubble appearance: Exceptionally, fine septa cross the radiolucent area producing a soap bubble appearance.

Histopathological Features It is made up of loosely arranged, spindle shaped and stellate cells, many of which have long fibrillar processes that tend to intermesh.

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they are surrounded by a zone of hyalinization or cell free zone. The intercellular substance is mucoid. The tumor is usually interspersed with a variable number of tiny capillaries and occasionally strands of collagen.

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Management Tumors may be difficult to enucleate due to their loose consistency, therefore surgical excision is indicated. Resection with generous amount of surrounding bone. Points to Remember

Figure 14.60  Tennis racket pattern seen in odontogenic

myxoma

Myxofibroma, premolar-molar area bosselated surface, congenitally missing teeth, fusiform swelling, mixed radiopaque-radiolucent lesion, tennis racket or honey comb appearance, soap bubble appearance, loosely arranged, spindle shaped and stellate cells, mucoid material, zone of hyalinization.

Cementoma It is also called as cementoblastoma or true cementoma. It is a true neoplasm of functional cementoblasts, which forms large masses of cementum or cementum-like tissue on the tooth root.

Pathogenesis It is derived from the mesenchymal cells of periodontal ligament and cementoblasts. It evoles in three stages: Osteolytic stage: There is periapical bone resoption. This stage radiographically appears as radiolucent lesion. Osteolytic-osteoblastic stage (Cementoblastic stage): It is characterized by both breakdown of bone and formation of cementum. Appears mixed radiolucency.

Figure 14.61  Odontogenic myxoma showing

loose mucoid tissue

Collagen fibers are sparse and delicate. Some have a tendency to form large amount of collagen fibers and have been designated as fibromyxomas. The space between the cells and fibers is filled by large amount of mucoid material (Fig. 14.61). Some may exhibit marked cellularity and atypia and have a more aggressive course. Few odontogenic epithelial cells in form of cords and nests are present. In some tumors

Maturation stage: This is inactive stage where calcification increases.

Clinical and Radiological Features Age and sex: It occurs most frequently under the age of 25 years and with no significant sex predilection. Site: Mandible is affected three times more frequently than the maxilla. Mandibular first molar is the most frequently affected tooth; other involved teeth are the mandibular second and third molars. Symptoms: Associated tooth is vital unless coinci­dentally involved. In some cases, pain may be there.

Odontogenic Tumors

Signs: Lesion is slow growing and may cause expansion of cortical plates of bone. Radiographic features: There is an area of increased density surrounded by the dark line of the fibrous capsule and with a thin white line of the adjacent cortical layer of the bone.

Histopathological Features Gross specimen shows troth attached to the mass of cementum (Fig. 14.62). Cementoma contains trabeculae of cementum which are lined by plump active cemetocytes (Fig. 14.63). These trabeculae contain several basophilic lines called reversal lines.

Trabeculae are separated by marrow spaces which contain dialated blood vessels and few cells. At the periphery of the lesion a soft tissue rimming consisting of numerous cementoblasts and multinucleated cementoblasts is seen. This mass is usually attached to the root of the tooth.

Management It consists of surgical extraction of tooth with attached calcified mass. Points to Remember Cementoblastoma or true cementoma, tooth is vital, slow growing, increased density surrounded by the dark line of the fibrous capsule, plump active cemetocytes, reversal lines, multinucleated cementoblasts.

MALIGNANT TUMORS Malignant Ameloblastoma and Malignant Carcinoma In some cases ameloblastoma can undergo malignant transformation. It is occur in less than 1 percent of all ameloblastoma. It is a rare type of tumor and diagnosis depends upon presence of metastases, which is in some cases is seen in lymph nodes and lungs.

Terminology Figure 14.62  Gross specimen of cementoma

Malignant ameloblastoma are those ameloblastomas that metastasize but in which the metastatic lesion do not show any histological difference from the primary tumor, i.e. it show histopathological features of ameloblastoma in primary as well as metastatic deposit. Ameloblastic carcinoma: It is lesion similar to ameloblastoma but that shows obvious histological malignant transformation in the primary, in recurrence as well in metastatic deposit.

Pathogenesis

Figure 14.63  Cementoblastoma showing excessive

cementum formation (CT) around root (R)

Malignant ameloblastomas originate from solid ameloblastoma which have been treated surgically but recur after sometime. Because of repeated surgeries tumor cells gain entry into blood vessels and lymph channels and get disseminated to distant organs mainly lung where they proliferate forming new tumor. Other sites include bones such as skull, vertebrae and femur, cervical lymph nodes, liver, brain spleen and kidney.

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Some ameloblastic carcinomas originate from preexisting solid or multicystic ameloblastoma. Cells of such pre-existing tumors dedifferentiated over time forming carcinoma. Some tumors originate de novo as ameloblastic carcinoma.

Clinical and Radiological Features Age and sex: Male are affected more commonly than female. It occurs in 1st to 6th decade with mean age of diagnosis 28 to 32 years. Site: It is almost exclusively in the mandible. Symptoms: Swelling followed by pain and/or rapid growth. Sign: Teeth may be displaced and loosened. Tenderness of overlying soft tissue is present. There may be paresthesia of nerves depending upon site, such mental nerve, infraorbital nerve paresthesia. Sites for metastasis: Lungs, spleen, kidney, lymph nodes and ileum are commonly site where metastasis can occur. Radiological features: It has well defined border with cortication, presence of crenations or scalloping in the perimeter. There may be loss of cortical boundary and breaching of the cortical boundary with soft tissue spread. It is either unilocular or multilocular giving the appearance of honey comb or soap bubble pattern. Most of the septa are robust and thick. Teeth may be displaced and may exhibits root resorption. Lamina dura may be lost. Bony borders may be effaced or breached. The mandibular neurovascular canal may be displaced or eroded.

Histopathological Features Malignant ameloblastoma resemble ameloblastomas of jaw from which they have metastasized. Most of the lesions are of mixed variety or of plexiform type. Other type may also produce metastasis. In ameloblastic carcinoma cells at the center become condensed and hypercellular. Tumor shows cellular features of malignancy such as nuclear enlargement, hyperchromatic, mild pleomorphism, increased nucleous to cytoplasmic ratio increased mitotic activity and abnormal mitosis. In some cases keratin pearl formation and individual cell keratinization may be seen (Fig. 14.64).

Management It is treated with en bloc resection. Radiation therapy and chemotherapy for pulmonary metastasis.

Figure 14.64  Ameloblastic carcinoma mild pleomorphism

Points to Remember Mandible, swelling followed by pain, displaced teeth, paresthesia of nerves, well defined border with cortication, honey comb or soap bubble pattern, lamina dura may be lost, malignant ameloblastoma resemble ameloblastomas of jaw, in ameloblastic carcinoma, nuclear enlargement, hyperchromatic, mild pleomorphism, increased nucleous to cytoplasmic ratio.

Primary Intraosseous Carcinoma It is also called as central mandibular carcinoma, primary intraosseous carcinoma, primary epithelial tumor of the jaw, primary intra-alveolar epidermoid carcinoma and central squamous cell carcinoma. It develops within the depth of the jaw. It is rare and may remain silent until they have reached a fairly large size.

Origin Malignant transformation of epithelial lining of odonto­ genic or non-odontogenic cyst can occur. Malig­ nant transformation of ameloblastoma by metastases from different sites and in case of maxilla may arise from primary tumor of the maxillary sinus. The tumor arises from the cell rests of the odontogenic epithelium or from the epithelial remnants at the site of fusion between two embryonic processes. In normal situation for some of the original cells of the dental lamina or enamel organ to remain in the jaw long after the function of these cells are completed. Malignant tumor may develop from these cells.

Odontogenic Tumors

Types • Those arising from odontogenic cysts. •  Those arising from ameloblastoma either well differentiated (malignant ameloblastoma) or poorly differentiated (ameloblastic carcinoma). • Those arising de novo from odontogenic epithelium residues, either keratinizing or non-keratinizing.

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Clinical Features Age and sex distribution: There is a wide range of age distribution with majority of cases occurring in 6th and 7th decade of life. It is more common in males than in females with a ratio of 2:1 and more common in mandible than in maxilla. Symptoms: The early symptom is swelling of the jaw with pain and mobility of the teeth before ulceration has occurred. Pathological fracture and lip paresthesia also occurs. Signs: There is rapid expansion and destruction of jaw bones. Tumor invades the periodontal ligament and the alveolar bone, destroying it. There may be lymphadenopathy. Surface epithelium is normal. Occasionally the pulp of the teeth may be invaded by neoplasm. Perforation of cortical plate may occur. Extraction of teeth result in nonhealing socket and sometimes tumor may protrude from the nonhealed socket.

Radiological Features It presents as a diffuse radiolucency similar to other central malignant neoplasms of the jaws. Its borders become ragged and there is no evidence of bone formation within the tumor. There is expansion and distortion of the cortical plates of the jaw bone. They may cause destruction of the antral or nasal flows, loss of cortical outline of the mandibular neurovascular canal and effacement of the lamina dura.

Histopathological Features (Fig. 14.65) It has an alveolar or plexiform pattern with peripheral cells of the tumor masses showing palisading arrangement, thereby resembling odontogenic epithelium. It is usually of basal cell type although on occasion, spinous cells may be found. The tumor cells themselves generally exhibit nuclear pleomorphism and hyperchromatic, mitotic activity.

Figure 14.65  Primary intraosseous carcinoma

Excessive proliferation of neoplastic epithelium cells either in form of diffuse sheets or epithelial islands. Areas of acanthotic changes with epithelial pearl formation are often seen. There is presence of rim of ameloblast like cells in the position which is usually assumed by the basal cell in conventional squamous cell carcinoma. Points to Remember Central mandibular carcinoma, swelling of the jaw with pain, rapid expansion and destruction of jaw bones, nonhealing socket, diffuse radiolucency, expansion and distortion of the cortical plates, alveolar or plexiform pattern, nuclear pleomorphism and hyperchromatic, mitotic changes activity, areas of acanthotic changes.

Clear Cell Odontogenic Tumor or Carcinoma It is rare odontogenic tumor showing highly aggressive behavior.

Clinical and Radiological Features Age and sex: Most cases reported in women over 60 years of age. Site: Both maxilla and mandible have been involved. Symptoms: It may present as asymptomatic or painful bony swelling. Radiological features: Unilocular radiolucency with ill defined margins.

or

multilocular

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Histopathological Features

Histopathological Features

Biphasic pattern: There are nests of epithelial cells with clear or faintly eosinophilic cytoplasm admixed with eosinophilic polygonal cells.

It usually shows well differentiated squamous cell carcinoma.

Monophasic pattern: There is only clear cell arranged in nest and cords and is separated by thin strands of hyalanized material. Palisading pattern: Peripheral cells may demonstrate palisading. Mitoses are sparse and clear cells contain small amount of glycogen.

Management Tumors demonstrate aggressive local behavior and potential lymphatic and pulmonary metastases and therefore should be treated with extensive resection. Points to Remember Asymptomatic or painful bony swelling, unilocular or multilocular radiolucency ill defined margins, biphasic pattern, monophasic pattern, palisading pattern, treated with extensive resection.

Management It is same as with primary intraosseous carcinoma. Points to Remember Carcinoma ex odontogenic cyst, fistula formation, smooth border of cyst is lost, ill defined, well differen­ tiated squamous cell carcinoma.

Ameloblastic Fibrosarcoma It is the malignant counterpart of the ameloblastic fibroma in which mesenchymal elements have become malignant. Odontogenic epithelium remains benign. It is also called as ameloblastic sarcoma.

Clinical Features Age and sex: It is very rare and most frequently occurs in young adults with an average age of occurrence being 27 years. There is more common in males. Site: It more frequently occurs in mandible than in maxilla.

Malignant Changes in Odontogenic Cyst It is also called as carcinoma ex odontogenic cyst. It is uncommon but in some cases there may be chance that, there are carcinomatous changes found in odontogenic cyst. In some cases adjacent carcinoma may involve otherwise unrelated cyst.

Clinical and Radiological Features Site: It can affect any cyst in the jaw. But keratocyst is more likely to undergo malignant changes than other cysts. Symptoms: The most common complain is pain, which is dull and of several months duration. If upper jaw is involved sinus pain and swelling may be present. Signs: Pathological fracture, fistula formation and regional lymphadenopathy may occur. Radiological features: Smooth border of cyst is lost or becomes ill defined. In advanced lesion has an ill defined, infiltrative periphery that lacks any cortication. There is thinning and destruction of lamina dura of adjacent teeth.

Symptoms: It is uniformly painful, generally grows readily and causes destruction of bone with loosening of teeth. Sign: There may be ulceration and bleeding of the overlying mucosa. Swelling is usually soft in consistency.

Radiological Features Radiographically, radiolucencies with irregular and indistinct margins are characteristic. Large radiolucencies with a multilocular appearance and gross expansion and thinning of the cortical bone may be seen (Fig. 14.66).

Histopathological Features There are no apparent remarkable changes in the odontogenic epithelium. It remains similar to ameloblastic fibroma. In some lesions, it is diminished in quantity, apparently as a result of overgrowth of the malignant mesenchymal portions of the lesion. It is mesenchyme that exhibits malignant features. Mesenchymal tissue exhibits a remarkable increase in cellularity; the malignant fibroblast being polygonal to fusiform, bizarre and pleomorphism, with hyper- chromatic

Odontogenic Tumors

Clinical Features It is a destructive lesion which produces a fleshy, bulky growth. It as such is asymptomatic but pain may be present in many cases.

Histopathological Features

Figure 14.66  Ameloblastic fibrosarcoma showing irregular

radiolucency

It is identical with that of fibrosarcoma of non-odontogenic origin. The cellular element may or may not be prominent than the fibrillar component. The cells often exhibit considerable mitotic activity. They resemble immature fibroblasts and appear as elongated cells containing ovoid nuclei with varying degree of pleomorphism and are situated in a fibrous meshwork which may or may not exhibit foci of odontogenic epithelium.

Management nuclei and numerous atypical mitotic figures. Stroma is myxoid with less collagen fibers. In some cases dysplastic dentin or small amount of enamel can be seen. Some have called this as ameloblastic dentinosarcoma or ameloblastic fibro-odontosarcoma. Ameloblastic carcinosarcoma: In rare cases there is malignant transformation of epithelial and mesenchymal elements in ameloblastic fibroma. This is called as ameloblastic carcinosarcoma.

Management Radical resection such as hemimandibulectomy or hemimaxillectomy can be done. Recurrence is common and prognosis is poor. Points to Remember Ameloblastic sarcoma, painful destruction of bone, ulceration and bleeding of the overlying mucosa, radio­ lucencies with irregular indistinct margins, mesenchymal tissue exhibits increase in cellularity, stroma is myxoid, ameloblastic dentinosarcoma or ameloblastic fibroodontosarcoma, ameloblastic carcinosarcoma, radical resection.

Odontogenic Fibrosarcoma It is the malignant counterpart of odontogenic fibroma. It originates from same mesenchymal tissue, as same in central fibroma.

Radical surgical removal with resection of the jaw. Prognosis is poor. Points to Remember Asymptomatic, cellular element may or may not be prominent, mitotic activity, immature fibroblasts, elong­ ated cells.

BIBLIOGRAPHY 1. Casaroto AR, Toledo GL, Filho JL, et al. Ameloblastic carcinoma, primary type: case report, immunohistochemical analysis and literature review. [Case Reports, Journal Article, Review] Anticancer Res. 2012;32(4):1515-25. 2. Chen Y, Li TJ, Gao Y, Yu SF. Ameloblastic fibroma and related lesions: a clinicopathologic study with reference to their nature and interrelationship. J Oral Pathol Med. 2005. 3. Darlington CG, Lefkowitz LL. A pathologic study of “socalled” dental tumors. Am J Clin Path. 1936,6:330-48. 4. Dayi E, Gurbuz G, Bilge OM, Ciftcioglu MA. Adenomatoid odontogenic tumour (adenoameloblastoma). Case report and review of the literature. Aust Dent J. 1997. 5. Etit D, Uyaroglu MA, Erdogan N . Mixed odontogenic tumor: ameloblastoma and calcifying epithelial odontogenic tumor. Indian J Pathol Microbiol. 2010;53(1):122-4. 6. Fitzgerald GM. Multiple composite odontomas coincidental with other timorous conditions; report of a case. J Am Dent A, I943;30:I408-I7. 7. Friedrich RE, Scheuer HA, Fuhrmann A, et al. Radiographic findings of odontogenic myxomas on conventional radio­ graphs. [Journal Article] Anticancer Res. 2012;32(5): 2173-7.

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8. Gardner DG, Corio RL. The relationship of plexiform unicystic ameloblastoma to conventional ameloblastoma. Oral Surg Oral Med Oral Pathol. 1983,56(1):54-60. 9. Gunhan O, Erseven G, Ruacan S, Celasun B, Aydintug Y, Ergun E, Demiriz M. Odontogenic tumours. A series of 409 cases. Aust Dent J. 1990. 10. Gupta N, Saxena S, Rathod VC, Aggarwal P. Unicystic ameloblastoma of the mandible. J Oral Maxillofac Pathol. 2011;15(2):228-231. 11. Hansen LS, Eversole LR, Green TL, Powell NB. Clear cell odontogenic tumor—a new histologic variant with aggressive potential. Head Neck Surg. 1985. 12. Ide F, Mishima K, Saito I, Kusama K. Rare peripheral odontogenic tumors: report of 5 cases and comprehensive review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008. 13. Kumamoto H, Ohki K, Ooya K. Association between vascular endothelial growth factor (VEGF) expression and tumor angiogenesis in ameloblastomas. J Oral Pathol Med. 2002. 14. Kumamoto H. Molecular pathology of odontogenic tumors. J Oral Pathol Med. 2006. 15. Lawal AO, Adisa AO, Olusanya AA, et al. “Hybrid” ameloblastoma: a report of two cases. [Case Reports, Journal Article] Afr J Med Med Sci. 2011;40(4):413-5. 16. Madras J, Lapointe H. “Keratocystic odontogenic tumour: reclassification of the odontogenic keratocyst from cyst to tumour”. J Can Dent Assoc. 2008;74(2):165-5. 17. Mahadesh J, Rayapati DK, Maligi PM, Ramachandra P. Unicystic ameloblastoma with diverse mural proliferation a hybrid lesion. Imaging Sci Dent. 2011;41(1):29-33.

18. Maria A, Sharma Y, Malik M. Calcifying epithelial odontogenic tumor: a case report: J Oral Maxillofac Oral Surg. 2010;9(3):302-6. 19. Philipsen HP, Reichart PA, Zhang KH, Nikai H, Yu QX. Adenomatoid odontogenic tumor: biologic profile based on 499 cases. J Oral Pathol Med. 1991. 20. Philipsen HP, Reichart PA. Classification of odontogenic tumours. A historical review. J Oral Pathol Med. 2006. 21. Piloni MJ, Keszler A, Itoiz ME. “Agnor as a marker of malignant transformation in odontogenic keratocysts”. Acta Odontol Latinoam. 2005;8(1):37-42. 22. Ramesh RS, Manjunath S, Ustad TH, Pais S, Shivakumar K. Unicystic ameloblastoma of the mandible—an unusual case report and review of literature. Head Neck Oncol 2010;2:1. 23. Reichart PA, Philipsen HP, Sonner S. Ameloblastoma: biological profile of 3677 cases. Eur J Cancer, B, Oral Oncol. [1995] 24. Thoma KH. Cementoblastoma. Internat J Orthodont, I937, 23,I127-37. 25. T Thoma KH. Oral Pathology. The CV Mosby Co, St. Louis, 1941;pp.9I4-69. 26. Zanakis S, Maria F, Dicoglou C, Dendrinos C. Calcifying epithelial odontogenic tumor: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(6):e11720. 27. Zhong Y, Wang L, Lit T, et al. Calcifying epithelial odontogenic tumor showing malignant transformation: a case report and review of the literature: Chin J Dent Res. 2010;13(2):157-62.

MULTIPLE CHOICE QUESTIONS

1. At which stage there is no histo or morphodifferentia­ tion seen: a. Bud stage b. Cap stage c. Bell stage d. Advance bell

4. Liesegang rings is the histopathological feature seen in: a. Ameloblastoma b. CEOT c. Cementoblastoma d. All of the above





2. Ameloblastoma which shows palisading, reverse polarity and basal vacuolation of ameloblast like cells is: a. Plexiform type b. Follicular type c. Basal cell type d. Both a. and b. 3. ‘Rathke’s Pouch tumor’ refers to: a. Squamous odontogenic tumor b. Ameloblastic fibroma c. Pituitary ameloblastoma d. Odontoma

5. Duct like spaces lined by single cells and rosette pattern seen in: a. AOT b. Ameloblastic fibroma c. Odontogenic fibroma d. Myxoma

6. Genes which are considered as ‘guardian of genome’ is: a. APC b. Retinoblastoma c. Ras d. p53

Odontogenic Tumors 7. Antiaging enzyme refers to: a. Telomerase b. Kinase c. Lipase d. None 8. Ameloblastic follicles surrounded by dentin like calcifications is the histopathological feature of: a. Compound odontoma b. Ameloblastic fibro-odontoma c. Complex odontoma d. CEOT 9. Stellate fibroblasts and immature collagen fibers resembling dental papilla is the histopathological feature of: a. Odontoameloblastoma b. Myxoma c. Odontogenic fibroma d. Complex odontoma 10.

Excessive cementum formation seen in: a. Benign cementoblastoma b. Malignant ameloblastoma c. Odontogenic fibroma d. Complex odontoma

11. All of the following lesions may be classified as odontogenic tumors EXCEPT: a. Acanthomatous amelobastoma b. Myxoma c. Branchial cleft cyst d. Simple ameloblastoma 12.

Ameloblastoma most frequently occurs in: a. Mandibular molar region b. Maxillary molar region c. Mandibular premolar region d. Maxillary premolar region

13.

Compound odontoma shows on a radiograph as: a. Supernumerary teeth b. Radiolucent and radiopaque areas c. Masses of calcified areas d. Distinguishable tooth – like structures

14. Which of the following is the most common lesion of the mandible? a. Adamantinoma b. Osteogenic sarcoma c. Squamous cell carcinoma d. Osteoclastoma 15. Robinson’s classification of ameloblastoma does not include: a. Multicentric b. Nonfunctional c. Anatomically benign d. Clinically persistent

16. Adenomatoid odontogenic tumor is most commonly found in: a. Anterior mandible b. Posterior maxilla c. Anterior maxilla d. Ramus of mandible 17. Which of the following is a true neoplasm of functional cementoblasts: a. Periapical cemental dysplasia b. Familial cemental dysplasia c. Benign cementoblastoma d. Hyercementosis 18. Which of the following is odontogenic tumor? a. Astrocytoma b. Arrhenoblastoma c. Ameloblastoma d. Granular cell tumor 19.

Adamantinoma is: a. A tumor from embryonal cells of developing teeth b. Also known as Ameloblastoma c. Is a complication of dentigerous cyst d. All of these

20. The most common odontogenic tumor which occurs in relation to an unerupted tooth in anterior maxilla is: a. Odontogenic adenomatoid tumor b. Odontoma c. Myxoma d. Cementifying fibroma 21. Dentigerous cyst is likely to cause which neoplasm? a. Ameloblastoma b. Adeno carcinoma c. Fibrosarcoma d. All of these 22.

Radiographic finding in Pindborg tumor is: a. Sun burst appearance b. Onion-peel appearance c. Driven-snow appearance d. Cherry-blossom appearance

23. Resorption of teeth is caused by: a. Cysts b. Benign tumors c. Malignant tumors d. All of these 24. Which of the following tumor occurs in minor salivary gland? a. Pleomorphic adenoma b. Adenocarcinoma c. Mucoepidemoid carcinoma d. Warthin’s tumor 25.

Ghost cells are seen in: a. Ameloblastic fibrodontoma b. Calcifying odontogenic tumor c. Compound odontoma d. All of these.

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Cyst of Orofacial Region

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline                     Â

Definitions Theories of cyst enlargement Dentigerous cyst Eruption cyst Odontogenic keratocyst (OKC) Primordial cyst Gingival cyst of newborn Gingival cyst of adult Lateral periodontal cyst Glandular odontogenic cyst Palatal cyst of newborn (Epstein’s pearls, Bohn’s nodules) Calcifying epithelial odontogenic cyst Inflammatory radicular cyst Residual cyst Inflammatory collateral cyst Paradental cyst Mandibular buccal infected cyst Suppurating cyst Healingcyst Nasoplalatine cyst Median palatine cyst

INTRODUCTION Cyst has been known to arise in man (ever since he has teeth) and in certain animals. All it takes is some odontogenic epithelium plus some unknown initiating factor which stimulates it to proliferate to cause this destructive lesion,

                     Â

Nasoalveolar cyst Median mandibular cyst Globulomaxillary cyst Traumatic bone cyst Aneurysmal bone cyst Sinus mucocele Antral pseudocyst Dermoid and epidermoid cyst Retention cyst Branchial cleft cyst Oral lymphoepithelial cyst Anterior median lingual cyst Oral cyst with gastric or intestinal epithelium Cystic hygroma Follicular cysts of the skin Nasopharyngeal cyst Thymic cyst Parasitic cyst Hydatid cyst Cysticercosis cellulose Jaw cyst-basal cell nevus-bifid rib syndrome Treatment of cysts

which can be found from the mildest form to a greatly disfiguring form. Cysts of jaws are of great clinical importance, not only because they often attain a large size and therefore produce facial asymmetry, disturbance of dentition, neurological symptoms and predispose the jaws to fracture

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but particularly because they have a very high frequency of occurrence.

DEFINITIONS By killey and key 1966: This entity constituted an epithelium-lined sac filled with fluid or semifluid material. By some unknown author 1966: A cyst is an abnormal cavity in hard and soft tissue which contains fluid, semifluid, or gas and is often encapsulated and lined by epithelium. By Kramer in 1974: Pathologic cavity having fluid, semifluid, or gaseous content but not always is lined by epithelium.

CLASSIFICATION By Shear (A) Epithelial Odontogenic Developmental ∙ Dentigerous cyst (follicular) cyst ∙ Eruption cyst ∙ Primordial cyst ∙ Gingival cyst of adults ∙ Lateral periodontal cyst ∙ Calcifying odontogenic cyst. Inflammatory Cyst ∙ Radicular cyst ∙ Residual cyst ∙ Inflammatory collateral cyst ∙ Paradental cyst. Nonodontogenic ∙ Nasopalatine duct (incisive canal) cyst ∙ Median palatine median alveolar and median mandibular cysts ∙ Globulomaxillary cyst ∙ Naso-labial cyst. (B) Nonepithelial ∙ Simple bone cyst (traumatic solitary hemorrhagic bone cyst) ∙ Aneurysmal bone cyst. (C) Cysts associated with maxillary antrum ∙ Benign mucosal cyst of the maxillary antrum ∙ Surgical ciliated cyst of maxilla.

(D) Cysts of the soft tissue of the mouth, face and neck ∙ Dermoid and epidermoid ∙ Branchial cleft cyst (lympho-epithelial) ∙ Thyroglossal duct cyst ∙ Anterior medial lingual cyst ∙ Oral cyst with gastric or intestinal epithelium ∙ Cystic hygroma ∙ Cysts of salivary glands ∙ Parasitic cyst, hydatid cyst, cysticercosis cellulosae.

THEORIES OF CYST ENLARGEMENT The exact mechanism is not known, but it could be that the mechanism-governing enlargement of cysts of the jaws is the same irrespective of the type of cysts. The various steps involved in the formation of a cyst seem to be as follows: ∙ The attraction of fluid into the cystic cavity. ∙ The retention of fluid into the cavity. ∙ The production of raised internal hydrostatic pressure. ∙ The resorption of surrounding bone with an increase in the size of bone cavity. Harries Classification of Theories of Cyst Enlargement Mural growth • Peripheral cell division • Accumulation of cellular content Hydrostatic enlargement • Secretion • Transudation and exudation • Dialysis Bone resorbing factor

Mural Growth (Fig. 15.1) Peripheral Cell Division Peripheral enlargement is attributed to active cell division of the lining epithelium in response to an irritant stimulus. Cyst regression occurs following the removal of such stimulus. The theory has been criticized on the basis that such regression would lead to an irregularly thickened inner surface because of the resistance of the surrounding bone. However, this ignores the possibility that the cyst wall is not only well supported by its fluid content but

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Dialysis: The mean osmolality of the cystic fluid is 10 miliosmoles higher than that of serum. This gradient is attributed to the accumulation of the low molecular weight cells shed from the lining epithelium and maintained by inadequate lymphatic access to the cyst lumen, the consequence is net entry of fluid from the capsule capillaries into the cystic lumen.

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Bone Resorbing Factor (Fig. 15.3)

Figure 15.1 Cyst enlargement by active proliferation

Vital cyst tissue in culture has been shown to release a potent bone resorbing factor, which is predominately a mixture of prostaglandin E2 (pgE2) and prostaglandin E3 (pgE3). The source of this resorbing factor appears to be the capsule and leukocyte content. Prostaglandin release is reduced in some cysts when the epithelium is removed

of the cyst wall

can also actively resorb bone sufficiently and rapidly to accommodate the expanding perimeter.

Accumulation of Cellular Content Kramer has suggested that keratocyst enlarges by the increasing accumulation of mural squames as they are cast off from the living epithelium. The characteristic finger like projections of growth represents local areas of increased cell division. An alternative explanation for this elongation is that keratocyst although persistent in their growth are poor bone resorbers and simply extend preferentially along the less dense cancellous bone with little resorption and expansion of dense cortex.

Figure 15.2 Enlargement of cyst by hydrostatic pressure

Hydrostatic Enlargement (Fig. 15.2) Growth is attributed to the distension of the cystic wall by fluid that has accumulated by one or more of the following processes. Secretion: Apart from the occasional goblet cells usually found in follicular cyst, there is little morphological evidence of intracystic secretion. Transudation and exudation: These have been proposed mainly for the enlargement of the follicular and periodontal cyst respectively. This conclusion was derived from an examination of the protein content and specific gravity of the cystic fluid. The presence of fibrin and cholesterol in periodontal and follicular cysts suggests that hemorrhage also contributed to the cystic fluid.

Figure 15.3 Cyst enlargement by bone resorption

Cyst of Orofacial Region

before culture but it is not clear whether the reduction results from the removal of an epithelial inductive effect or whether it merely reflects the loss of prostaglandin produced within the epithelium. The mechanism of prostaglandin production is not known. One possibility is that production takes place in the capsule under the influence of epithelial proliferation, lysosomal phospholipase from fibroblasts and polymorphonuclear leukocytes; breaking down of phospholipid cell membrane to produce arachidonic acid which is converted by the ubiquitous enzyme prostaglandin synthetase to prostaglandin.

the degeneration of stellate reticulum at an early stage of tooth development resulting into cyst formation associated with enamel hypoplasia. The fluid is pressure incites a proliferation of the outer enamel epithelium, which remains attached to the tooth at the cementoenamel junction; the inner enamel epithelium is then pressed onto the crown surface.

Pathogenesis

venous outflow and thereby induces rapid transudation of serum across the capillary walls. The increased hydrostatic pressure exerted by this pooling of fluid causes separation of the crown from the follicle, with or without reduced enamel epithelium. Further the osmolality of the cyst fluid is modified by various factors such as increased permeability to passage of greater quantities of proteins, increased amount of glycosaminoglycans, predominantly hyaluronic acid and heparin and chondroitin sulfate in the cyst wall causes expansile growth rapidly. Thus in each theory, the fluid generates the cystic proliferation by its hyperosmolar content created by cellular breakdown and cell products, causing an osmotic gradient to pump fluid into the cyst lumen.

Extrafollicular theories/causes: This theory suggest that the cyst forms by accumulation of fluid in between the unerupted tooth and the reduced enamel epithelium. Other theory says that the crown of a permanent tooth may erupt into a radicular cyst of a deciduous tooth. As the incidence of radicular cyst is uncommon with the deciduous teeth, the possibilities are rare of these type of cysts. The cyst DENTIGEROUS CYST may occur if a impacted tooth erupts into an existing Dentigerous cyst is the developmental odontogenic cyst odontogenic keratocyst. This incidence is uncommon; the of epithelial origin. It is also called as ‘follicular cyst’ features are more of OKC than the dentigerous cyst (Fig. or ‘pericoronal cyst’. It is the most common type of Schematic diagram). odontogenic cyst which encloses the crown of an unerupted Main’s theory (1970): Impacted tooth exerts pressure on tooth by expansion of its follicle and is attached to the neck. its follicle due to the eruptive force. This obstructs the Though a number of pathogenesis theories have put forth, the cyst has been demonstrated as originating from the dental follicle surrounding the tooth after crown completion. Thus it can be intrafollicular or extrafollicular. Intrafollicular theories/causes (Fig. 15.4): It occurs due to fluid accumulation between the layer of reduced enamel epithelium, i.e. inner and outer enamel epithelium after formation of crown. Within the enamel organ itself by

Clinical Features Some of the asymptomatic cysts are discovered by radiographs, when the X-rays are taken for a missing tooth or for malaligned teeth. Age and sex distribution: As it arises from the follicle of an unerupted tooth, it is usually found in children and adolescents with a higher incidence in 2nd and 3rd decades. It is equal in both sexes.

Figure 15.4 The cyst forms by accumulation of fluid in between the unerupted tooth and the reduced enamel epithelium (extrafollicular origin)

Site: It is most commonly associated with mandibular 3rd molars and maxillary canines which are most commonly impacted. It may also be found enclosing a complex compound odontome or involving a supernumerary tooth.

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Size: They vary in size from a little more than the diameter of the involved crown to an expansion that causes progressive but painless enlargement of jaws and facial asymmetry. Teeth: Teeth adjacent to the developing cyst and involved teeth may get severely displaced and resorbed. There may be displacement of third molars to such an extent that it sometimes comes to lie compressed against the inferior border of the mandible. Symptoms: Generally, it is painless but may be painful if it gets infected. When dentigerous cyst expands rapidly to compress sensory nerve it produces pain which may be referred to other sites and described as headache. Signs: Dentigerous cyst has a tendency to grow or expand laterally so it causes obvious buccal expansion of cortical plates (Figs 15.5 and 15.6). In some cases pathological fracture can occur. Cystic involvement of an unerupted third molar may result in hollowing out of the entire ramus extending up to the coronoid process and condyle as well as the body causing expansion of cortical plates. In the case of a cyst associated with maxillary cuspids, expansion of the anterior maxilla often occurs and may superficially resemble acute sinusitis or cellulitis. Associated disease: Bilateral cysts are found in association with basal cell nevus syndrome, cleidocranial dysplasia and a rare form of amelogenesis imperfecta. Blue domed cyst: When it contains blood, then it is called as ‘blue domed cyst’.

Figure 15.6 Intraoral swelling seen in anterior region

due to dentigerous cyst

Radiographic Features It is well defined radiolucency usually associated with hyperostotic borders unless they are secondarily infected and is seen around an unerupted tooth. Usually, it is unilocular but some times it may appear multilocular, this image is caused by ridges in the bony wall and not by the presence of bony septa. The bony margins are well defined and sharp (Figs 15.7 to 15.9). Associated tooth may be displaced in any direction. It is usual for those unerupted teeth which become surrounded by the growing cyst to retain their follicle for a time at least, which serves to indicate that the tooth is actually outside the cyst. Radiological types: It is mainly three type, i.e. central variety (in it crown is enveloped symmetrically), lateral type (cyst on one aspect of the crown), circumferential type (in it the entire tooth appears to be enveloped by the cyst) (Figs 15.10A to C).

Histopathological Features (Figs 15.11 to 15.14)

Figure 15.5 Dentigerous cyst associated with impacted canine

clinically showing swelling on left maxillary region

It is composed of thin cystic wall. The lining is a thin layer of nonkeratinized stratified squamous epithelium. In very few instances the lining may be keratinized and it may be mistaken as keratocyst or keratin may be produced rarely as due to metaplastic changes. As the lining is derived from reduced enamel epithelium it is 2 to 4 cell layer thick primitive type of epithelium. The cells are cuboidal or low columnar. Retepegs formation is absent except in cases that are secondarily

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A

B

Figure 15.7 Dentigerous cyst showing radiolucency which

is well defined (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

C Figures 15.10A to C (A) Central variety; (B) Lateral variety;

(C) Circumferential variety

Figure 15.8 Bilateral dentigerous cyst

Figure 15.9 Dentigerous cyst showing well defined

radiolucency

Figure 15.11 Dentigerous cyst with thin lining resembling

reduced enamel epithelium with no rete pegs

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A Figure 15.12 Inflammation in dentigerous cyst with lining of

variable thickness. The stroma of connective tissue is organized, fibrous and shows vascular proliferation and juxta epithelial inflammatory infiltrate

B Figures 15.14A and B Dentigerous cyst with secondary infec-

tion. (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Figure 15.13 Dentigerous cyst with thin lining resembling

reduced enamel epithelium. The connective tissue is delicate as of primitive type (high power)

infected. As the connective tissue wall is derived from the dental follicle of developing enamel organ, it is a loose connective tissue stroma. Young fibroblasts are present in the stroma which is rich in acid mucopolysaccharide. Inflammation in dentigerous cyst: The epithelial lining shows variable thickness in response to inflammation. Budding or proliferation of the epithelium into the connective tissue wall may be seen. Inflammatory cells infiltrate the connective tissue mostly juxtaepithelial.

Occasional islands of odontogenic epithelium are observed. The connective tissue wall is frequently quite thickened and composed of organized fibrous connective tissue. Rushton bodies within the lining epithelium which are peculiarly seen as linear or hairpin shaped curved bodies have been reported as a result of inflammation. Cholesterol clefts also may be noted. Metaplasia in dentigerous cyst: The cell lining may show metaplastic changes in the form of mucous producing cells or secretory cells such as goblet cells. Pseudostratified ciliated columnar epithelium also has been reported. Rarely sebaceous glands in the walls are observed. The content of the cystic lumen is usually thin watery yellow fluid and is occasionally blood tinged.

Cyst of Orofacial Region

Management

An eruption cyst is in fact a dentigerous cyst occurring when a tooth is impeded in its eruption within the soft Treatment of dentigerous cyst depends upon the size of the tissues overlying the bone, whereas the dentigerous cyst cyst. develops around the crown of an unerupted tooth which is Surgical: Smaller lesions can be surgically removed with lying in the bone. This cyst has often been termed ‘eruption little difficulty. The larger cyst involves surgical drainage cyst’ or ‘eruption hematoma’. and marsupialization. This procedure results in relief It is essentially a dilation of the normal tooth caused of pressure and gradual shrinking of the cystic lesion by by accumulation of tissue fluid or blood. Cyst usually peripheral opposition of new bone. develop due to collagen deposition in the gingival Decompression: Small acrylic button or short section of connective tissue which results in thicker less penetrable rubber–is placed in preformed surgical opening in cyst pericoronal roof. which keeps opening open and permits drainage. Clinical and Radiological Features Recurrence is relatively uncommon unless there has been fragmentation of the cystic lining with remnants Location: In 11 percent of cases it occurs during the eruption of incisors and in 30 percent of cases it occurs allowed to remain. during eruption of canines and molars.

Potential Complication There are several potential complications besides the possibility of recurrence following incomplete surgical removal. These include: Ameloblastoma: The development of an ameloblastoma either from the lining epithelium of the cyst or rests of odontogenic epithelium in the wall of the cyst which is also called as mural ameloblastoma. Mucoepidermoid carcinoma: The development of mucoepidermoid carcinoma, which is a malignancy of salivary glands, associated with the lining epithelium or dentigerous cyst which contain mucous secreting cell as a result of mucous metaplasia.

Appearance: Clinically the lesion appears as a circumscribed, fluctuant, often translucent swelling of the alveolar ridge over the site of eruption of the tooth. Eruption hematoma: When the circumscribed cystic cavity contains blood the swelling appears purple or, deep blue, hence it is termed ‘eruption hematoma’. The lesion is called ‘eruption cyst’ because of their association with erupting teeth. The cause for development of this form of dentigerous cyst is not known. Radiographic features: Radiographically expansion of the normal follicular space of erupting tooth crown. In some cases there is saucer shaped excavation of bone projecting very slightly into the cavity (Fig. 15.15).

Points to Remember Mandibular 3rd molars, teeth severely displaced and resorbed, painless, expand laterally, pathological fracture, basal cell nevus syndrome, cleidocranial dysplasia, Blue domed cyst, unilocular, margins are well defined, nonkeratinized stratified squamous epithelium, cells are cuboidal or low columnar, retepegs formation is absent, loose connective tissue stroma, young fibroblasts, Inflammation in dentigerous cyst, Rushton bodies, metaplasia in dentigerous cyst, marsupialization, decompression, complication like ameloblastoma mucoepidermoid carcinoma.

ERUPTION CYST A specific type of cyst, which must be classified as a form of dentigerous cyst, is frequently associated with the erupting deciduous or permanent teeth in children.

Figure 15.15 Radiographic appearance of eruption cyst

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Histopathological Features 350

The underlying lamina propria of surface oral epithelial of cyst shows inflammatory cell infiltrate. The deep portion of the cyst shows nonkeratinizing squamous epithelium.

Management Simple excision of roof of cyst will allow eruption of associated teeth. Points to Remember Eruption hematoma, cyst usually develop due to collagen deposition in the gingival connective tissue. Eruption hematoma expansion of the normal follicular inflammatory cell infiltrate. T nonkeratinizing squamous epithelium.

ODONTOGENIC KERATOCYST Odontogenic keratocyst (OKC) is a developmental odontogenic cyst of epithelial origin. The OKC was previously termed primoidial cyst by Robinson (1945). According to Pindborg and Hansen the designation keratocyst was used to described any jaw cyst exhibiting keratinization in their lining which may occur in follicular, residual and very rarely in a radicular cyst. Recently in World Health Organization (WHO) classification of odontogenic tumor this cyst has given a name of keratocystic odontogenic tumor. 11 percent of all jaw cysts are OKC. OKC is not a clinical diagnosis but a designation for a group of cysts of possibly diverse origins which have a number of highly characteristic microscopic and clinical features in common with highest recurrence rate than any of the odontogenic cyst. In general, thin connective tissue wall and thin squamous type epithelial lining (4 to 8 cell thick) that contains keratin which is either para (87%) or ortho (13%) and without rete pegs. The basal layer is either columnar or cuboidal epithelium and its prickle cells are present and they are vacuolated. In some cases, bud-like proliferation from the basal layer into adjacent connective tissue wall or proliferation of islands of odontogenic epithelium that may be present in the wall giving rise to satellite microcysts which support the fact that OKC’s have a high recurrence rate. 5 percent of dentigerous and radicular cysts are keratocysts and a variety of many primordial, gingival, lateral periodontal

and residual cysts are of keratocyst variety. According to browne, odontogenic keratocyst is a histopathological term and should be restricted to its original sense and to describe the nature of the cyst. To avoid confusion between primordial cyst and keratocyst, Browne suggested that the term primordial cyst should be restricted to describe the origin and odontogenic keratocyst should be restricted to describe the nature of the cyst.

Odontogenic Keratocyst as a Benign Neoplasm Odontogenic keratocyst is considered in newer classifications of the odontogenic neoplasms (see chapter of odontogenic tumors) as a neoplasm than a cyst for the following reasons. Aggressive clinical behavior than any other cyst, asymptomatic till it reaches a large size and it tends to extend through the medullary cavities rapidly as in some reported cases complete hollowing of the ramus of mandible, including the condylar and coronoid process has been recorded before any symptoms. In maxilla, if it occurs, it may involve the entire maxillary sinus in a similar fashion. Highest turnover rate of the epithelium occur in OKC than any other cyst. High mitotic count of basal and para basal layers is present. The studies for mean mitotic counts- shows the proliferative index OKC (mean = 8), nonodontogenic cyst (mean = 2.3) and radicular cyst (mean = 4.5). The proliferative index is more similar to those seen in ameloblastoma and dental lamina. (Richard Jordan, oral and maxillofacial surgery clinics of north America - 2003). Active collagenase aids to rapid growth and extension of the cyst. In view of the established association of OKC and Nevoid basal cell carcinoma syndrome it was strongly hypothesized that the keratocyst might express proteins not commonly expressed in normal epithelia. Other ultra structural and histochemical studies have proved that altered gene expression of the epithelial cells as suggested by gp38 positivity (epithelial-specific cell surface glycoprotein) which is seen in cells with neoplastic potential. p53 protein: A mutant product of the tumor suppressor gene p53 was shown to have an increased expression. This is seen in malignant cells and not in normal cell cycle. Ki-67 is an antigen or cell specific marker for proliferating cells; it is also shown to be in higher reactivity for parakeratinized OKC.

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PCNA: Proliferating cell nuclear antigen, is widely regarded as a marker for replication and is associated with DNA repair processes and stimulation growth factors. This immunohistochemical expression is also raised in the lining cells.

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AgNOR: Argyrophillic nucleolar organizing regions are shown to be more. The mean number of AgNORS per nucleus was significantly more in the inflammed odontogenic keratocyst than in any other inflamed cyst.

Origin of Cyst The OKC is originating from the odontogenic epithelium; Dental lamina or it is remnants which possesses marked growth potential or alternatively from proliferation of basal cells as ‘basal cell hamartomas’ which are offshoots of the basal cells.

Figure 15.16 Odontogenic keratocyst showing extraoral

swelling in the ramus area

Clinical Features

Recurrence

Age and sex distribution: Odontogenic keratocyst occurs over a wide age range and cases have been recorded as early as the first decade and as late as the ninth with age group 4 to 84 years. It is initiated early in life, during the period of tooth development with a peak incidence in 2nd and 3rd decades. It is found more frequently in males than in females and this sex predilection is more pronounced in blacks than in whites.

Rate of recurrence of odontogenic keratocyst is very high. There are number of reasons for it. Occurrence of satellite cyst, which is a bud-like projection of basal cell layer into the connective tissue which is retained during the enucleation procedure. Some instances of recurrence are likely because of new cyst formation rather than true recurrence. Secondarily, its lining is very thin and fragile particularly when the cyst is large and therefore more difficult to enucleate than a cyst with thick wall. Portion of the lining may be left behind and constitute the origin of recurrence. Enucleation in one piece may be more difficult with cysts which have a scalloped margins and this may explain the higher recurrence rate than those with smoother contour. Toller suggested that there may be an intrinsic growth potential in the epithelial lining which may be responsible for a higher recurrence rate. It may arise from proliferation of the basal cells of the oral mucosa particularly in the third molar area and ascending ramus of the mandible. It is referred that there is often a firm adhesion of the cyst to overlying mucosa and it is recommended that mucosa should be excised with them in an attempt to prevent possible recurrence from the residual basal cell proliferation.

Site: It is more common in mandible with a greater incidence at the angle and extending for varying distance into the ascending ramus and forward into the body. Symptoms: It is asymptomatic unless they become secondarily infected, in which case patient complains of pain, soft tissue swelling and drainage. The maxillary sinus gets infected in the initial phase of cyst enlargement, so these OKC may manifest earlier than the duration taken by the mandibular cyst to manifest. Occasionally, paresthesia is experienced of the lower lip or teeth with mandibular cases. Signs: The lesion can lead to pathologic fracture. Those that occur in the maxilla causes buccal expansion (Fig. 15.16). On aspiration there is odorless creamy or caseous content. Multiple odontogenic keratocyst are found in Gorlin Goltz syndrome, Marfan syndrome, Ehler’s Danlos syndrome and Noonan’s syndrome.

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Radiological Types of Keratocyst (Fig. 15.19) Majority of lesions are unilocular with smooth borders but • Envelopment type: It is referred to a variety of some unilocular lesions are large with irregular borders. keratocyst which embraces an adjacent unerupted Radiolucency is usually hazy due to keratin filled cavity tooth. and it is surrounded by thin sclerotic rim due to reactive • Replacement: Those which forms in the place of osteocytes. normal teeth. Bone can expand in anterior posterior direction (Figs • Extraneous: Those in the ascending ramus away 15.17 and 15.18) and perforate the buccal and lingual from the teeth. cortical plates of bone and involve the adjacent soft tissue. • Collateral: Those adjacent to the root of teeth which Downward displacement of the inferior alveolar canal are indistinguishable radiologically from the lateral and resorption of the lower cortical plate of the mandible periodontal cyst. may be seen as well as perforation of bone and a pathologic fracture may occasionally occurs. Histopathological Features

(Figs 15.20 to 15.28)

Figure 15.17 OKC showing large radiolucency

in mandibular ramus area

Figure 15.18 OKC showing anteroposterior extension

Macroscopic features: The odontogenic keratocyst gross pathological features are characteristic as the cysts are hardly received intact in the laboratory. The small cysts may have a well defined cystic wall, but the large cyst almost always show thin walled, collapsed folded or detached linings. The lumen of keratocyst may be filled with thin straw colored fluid or with thick creamy material. The odontogenic keratocyst shows two types of linings, i.e. parakeratinized stratified squamous epithelium. The parakeratinized epithelium is more common, (80-90%) cases. The orthokeratinized OKC shows less common occurrence. The characteristic feature of the lining of is pathognomic corrugated, with a regular thickness of the epithelium between 5-8 cell layers. The lining is without rete ridges. The basal cell layer is columnar with palisaded arrangement of the nuclei. The nuclei tend to be placed

Figure 15.19 Types of OKC: 1. Replacemental,

2. Envelopmental, 3. Extraneous, 4. Collateral

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at places

Figure 15.23 Inflamed OKC with epithelial discontinuity and inflammatory infiltrate. Note the basal cells with palisading nuclei

Figure 15.21 Inflamed OKC with epithelial discontinuity

Figure 15.24 Higher magnification view showing severe

and inflammatory infiltrate

epithelial dysplasia and basal cell proliferation

Figure 15.22 OKC lined by corrugated parakeratinized stratified epithelium. The epithelium is collapsed and folded

Figure 15.25 OKC lined by orthokeratin

Figure 15.20 Cystic epithelium shows folding and detachment

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Figure 15.26 Odontogenic keratocyst showing parakeratinized stratified squamous epithelium with dark hyperchromatic basal cell layer (low power) and organized collagenous connective tissue stroma

Figure 15.27 Odontogenic keratocyst—parakeratinized stratified squamous epithelium with dark hyperchromatic basal cell layer (high power)

away from the basement membrane The nuclei of the basal cells are darkly staining, show basal cell hyperplasia, this is not present in other keratocyst. Highly aggressive OKC shows moderate to severe epithelial dysplasia. The fibrous capsule is thin with relatively few cells widely separated by a stroma which is often in mucopolysaccharide and resembles mesenchymal connective tissue. In the inflamed cases the epithelium might lose the keratinization and develop rete ridges. Connective tissue shows islands of odontogenic epithelium forming small duplicate daughter cysts or small satellite cysts. The satellite cysts are more common in patients with multiple cysts and nevoid basal cell carcinoma syndrome. Another most important feature of this cyst is that there is a weak epithelial–connective tissue attachment. This causes the detachment of the epithelium and further recurrences as it becomes difficult during removal of the cyst. Other less common findings are mucous metaplasia, Rushton bodies and cholesterol clefts in inflammed cysts. Sometimes lumen contains a great deal of keratin, while at other times it has little. Cholesterol as well as hyaline bodies at the site inflammation, may also be present. Orthokeratinized stratified squamous epithelium: Nowaday this cyst is called as separated entity. Cyst lining is composed of stratified squamous epithelium lined by orthokeratotic surface of varying thickness. Keratohyaline granules are prominent in superficial epithelial layer. There is thin epithelial lining.

Management Enucleation of entire cyst with vigorous curettage of the cystic wall should be done. Periodic post-treatment examination should also be carried out to check recurrence. Points to Remember

Figure 15.28 Odontogenic keratocyst show high proliferative index (PCNA) the basal cells shows typical arrangement of palisading or parallel orientation of nuclei called ‘tomb stone’ or picket fence arrangement

Common in mandible, asymptomatic, pain, soft tissue swelling, pathologic fracture, on aspiration there is odorless creamy or caseous, Gorlin Goltz syndrome, Marfan syndrome, Ehler’s Danlos syndrome, Noonan’s syndrome, satellite cyst, bud-like projection of basal cell layer, lining is very thin, enucleation in one piece may be more difficult, proliferation of the basal cells of the oral mucosa, unilocular with smooth borders, hazy radiolucency, bone can expand in anterior posterior direction, parakeratinized stratified squamous epithelium, lining is without rete ridges, mucopolysaccharide, satellite cysts, weak epithelial – connective tissue attachment, cholesterol, Orthokeratinized stratified squamous epithelium, keratohyaline granules, enucleation.

Cyst of Orofacial Region

PRIMORDIAL CYST It is one of the less common types of odontogenic cysts. As described earlier, it was named by Robinson in 1945. He defined a primoidial cyst as “a cyst which arises by breakdown of the stellate reticulum of the enamel organ before any hard tissue is formed and hence which may be one of the normal series or a supernumerary”. It originates when cystic changes take place in the stellate reticulum of the tooth germ before any calcified enamel or dentin has been formed. So it is found in place of a tooth rather than directly associated with it. It may originate from the enamel organ of supernumerary tooth or from the remnants of dental lamina. There is lot of controversies and confusion regarding the primordial cyst and odontogenic keratocyst. As the origin is same this cyst is term as odontogenic keratocyst and primordial cyst are used synonymously. In 1992 WHO listed odontogenic keratocyst as term used for this type of cyst. Primordial cyst described below is for the sake of completion and for academic point of view so that student should know about it.

Clinical Features Age and sex distribution: It is found in children and young adult between 10 to 30 years of age, although it may persist in older age group and occurs with equal frequency in both the sexes. Site: It can arise in any portion of the jaw, but most often seen in the ascending ramus of the mandible and in from third molar area. It is occasionally associated with an over retained erupted deciduous tooth. Symptoms: It has a tendency to painlessly enlarge and slowly replace large portions of cancellous bone before expansion of the cortical plate by way of which it reveals its presence. Pain which is associated with a large cyst is caused by infection that may follow the perforation of the expanded cortical plate.

In other cases, the epithelium may exhibit a surface layer of orthokeratin, while the spinous layer may be relatively thin or be of moderate thickness. The basal cell layer is not prominent and is sometimes with an atypical corrugated appearance, while the remainder of the epithelium is exceptionally uniform in thickness, usually 6 to 10 cells thick with extremely prominent basal layer. The cells are arranged in a ‘picket fence’ or ‘tombstone pattern’ and showing no rete peg formation.

Management Surgical enucleation should be done. Regular check up due to a high recurrence rate. Points to Remember Cystic changes take place in the stellate reticulum, ascending ramus of the mandible, painlessly enlarge, intact or interrupted layer of stratified squamous epithelium, ‘picket fence’ or ‘tombstone pattern’ and showing no rete peg formation.

GINGIVAL CYST OF NEWBORN It is also called an alveolar cyst of newborn. It is seen on alveolar mucosa of infant. It is derived from the remnants of the dental lamina. It is found on the crest of the maxillary and mandibular dental ridges. The cyst apparently originated form remnants of dental lamina.

Clinical Features Appearance: They appear as small, multiple whitish papules on the alveolar mucosa (Fig. 15.29). They spontaneously rupture in oral cavity. Size: It is not more than 2 to 3 mm.

Histopathological Features There is thin flattened epithelial lining with para-keratotic luminal surface. Lumen contains keratin aceous debris.

Histopathological Features

Management

This is similar to that of other odontogenic cysts. It is lined on the inner surface facing the lumen by an intact or interrupted layer of stratified squamous epithelium. In some cases, the epithelium is non-keratinized and exhibits a very prominent spinous layer with elongated and some times confluent retepegs. Basal cell layer is present but is not prominent.

No treatment is necessary as they rupture easily in oral cavity. Points to Remember Alveolar cyst of newborn, remnants of the dental lamina, small, multiple whitish papules, thin flattened epithelial lining, keratin aceous debris.

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the radiolucency is dark and sharply demarcated and a communication with the periodontium is indicated then the lesion is more likely to be lateral periodontal cyst that has eroded outward. These assumptions based on radiological features and can be confirmed by surgical exploration when the lesion is being removed.

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Etiology and Pathogenesis

Figure 15.29 Small nodule seen on upper gingiva

There are degenerative changes in proliferating epithelial tissue. Remnants of dental lamina, enamel organ or epithelial islands of periodontal membrane can cause gingival cyst of adults. Traumatic implantation of epithelium can also lead to gingival cyst. It also arises from post functional rests of dental lamina.

Clinical Features

GINGIVAL CYST OF ADULT Gingival cyst appears as a dome shaped swelling in the attached gingiva. It is soft tissue counterpart of lateral periodontal cyst. It is an uncommon cyst occurring either on free or attached gingiva. Although, it has been customary to consider these cysts as a distinctly different entity, their clinical appearance and behavior, morphologic and histochemical features and site of occurrence are so similar in appearance that they are in reality the intraosseous and extraosseous manifestations of the same pathoses. Bhasker grouped the gingival and lateral periodontal cysts together as gingival cyst and considered that they both arise from extraosseous odontogenic epithelium. Some cases have shown a circumscribed radiolucency indicative of lateral periodontal cyst, which he believed were because of cup shaped depressions on the periosteal surface of cortical plates produced by enlargement of the gingival cysts. Buchner and Hansen also suggested them to be distinct entities based on its pathological origin. The gingival cyst may certainly occur without bone involvement and may produce a gingival swelling. Most of the times, the swelling goes unnoticed. It is improbable though not impossible that a cyst originating in the gingival soft tissue could enlarge sufficiently to produce radiolucency by obvious bone erosion without producing any gingival swelling. In the case of a lesion, which has produced both gingival swelling and radiolucency, faint shadow (which is due to surface depression) indicates gingival cyst. Where

Age and sex distribution: The gingival cyst may occur at any age, but it is most common in adults in the 5th and 6th decade of life with predilection for males. Site: The location of the lesion closely follows that of lateral periodontal cyst. It is more common in mandible in premolar and canine region. Maxillary gingival cyst is seen in incisor, canine and premolar area. Appearance: The surface may be smooth and the color may appear as that of normal gingiva or bluish and may appear red when it is blood filled as a result of recent trauma. It is dome like swelling. Symptoms: It is slowly enlarging, painless swelling, usually less than 1 cm in diameter and may occur in attached gingiva or the interdental papilla. Signs: The lesions are soft and fluctuant and adjacent teeth are usually vital during surgical exploration. Slight erosion on the surface of the bone may be observed without extension into the periodontium. Radiological features: There may be superficial cupping out of bone (Fig. 15.30).

Histopathological Features The lining epithelium is generally identical to that found in lateral periodontal cyst. In cases of traumatic implantation type of gingival cyst, calcification or ectopic ossification, on rare occasions, it may be associated with cystic lesion. The epithelium ranges in thickness from simply one layer to several layers of cells. The layer consists of flat or cuboidal cells with thin stratified squamous epithelium.

Cyst of Orofacial Region

Figure 15.30 Gingival cyst showing superficial cupping

in the bone

Small nests of glycogen rich clear cells can be seen in connective tissue.

Management Surgical excision of the lesion in adults is usually recommended and the lesion does not tend to recur. A neoplastic potential has never been reported. Points to Remember Dome shaped swelling, remnants of dental lamina, enamel organ or epithelial islands of periodontal membrane, smooth surface, slowly enlarging, painless swelling, lesions are soft, small nests of glycogen rich clear cells, calcification or ectopic ossification.

LATERAL PERIODONTAL CYST They are named so, due to its location. Lateral periodontal cyst arises in the peridontium and located in the interproximal bone between the apex and the alveolar crest. The lateral periodontal cyst is uncommon but a well recognized type of developmental odontogenic cyst. The designation lateral periodontal cyst is confined to that cyst, which occurs as a result of inflammatory etiology and the diagnosis of collateral keratocyst has been excluded on clinical and histological ground.

Pathogenesis and Etiology Origin initially as a dentigerious cyst developing along the lateral surface of the crown and as the tooth erupt the cyst

assumes a position in approximation to the lateral surface of the root. Origin from proliferation of cell rests of Malassez in the periodontal ligament although the stimulus for this proliferation is unknown. Origin simply as a primordial cyst of a supernumerary tooth germ, since the predilection for occurrence of the lateral periodontal cyst in the mandibular bicuspid area corresponds well with the known high incidence of supernumerary teeth in the same region. Origin from proliferation and cystic transformation of rests of dental lamina (which is in post functional state and therefore has only limited growth potential), that is in accordance with the usual small size of the cyst. Recent theory suggests that the lateral periodontal cyst and gingival cyst of adult share the common histogenesis from post functional dental lamina rests. These two cysts represent basically the central or intraosseous and peripheral or extra-osseous manifestations of the same lesion. Types • Inflammatory: It occurs near alveolar crest. Pocket content may irritate and stimulate rest of Malassez. • Developmental: It is associated with developing tooth germ.

Clinical and Radiological Features Age and sex distribution: The lateral periodontal cyst occurs chiefly in adults with an age range from 22 to 85 years with a mean age of 50 years. It shows a male predilection for occurrence. Site: The most frequent location of lateral periodontal cyst reported on lateral surface of the roots of vital teeth in mandibular canine and premolar region and is followed by the anterior region of the maxilla. Symptoms: Gingival swelling may occur on the facial aspect and in these types of cases, it must be differentiated from the gingival cyst. In gingival cyst the overlying mucosa is blue but in lateral periodontal cyst the overlying mucosa appears normal. Sign: When the cyst is located on the labial surface of the root, it appears as a slight obvious mass, overlying the mucosa. The associated tooth is vital. If the cyst becomes infected, it may resemble a lateral periodontal abscess.

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Radiographic features: The intra-bony lateral periodontal cyst is seen as a round or ovoid well defined radiolucency with hyperostotic borders (Fig. 15.31). Most of them are less than 1 cm in diameter except the botryoid variety which may larger ad multilocular. Botryoid odontogenic cyst: This term was proposed by Waldron, which refers to a multilocular periodontal cyst. It resembles a cluster of lateral periodontal cysts exhibiting some difference. The lesion is multilocular with thin fibrous connective tissue septa. It is clear from numerous reports of recurrence that the botryoid odontogenic cyst requires careful excision.

Histopathological Features (Fig. 15.32) It is lined by a layer of stratified squamous epithelium with connective tissue wall. Cuboidal and columnar cell may be found compassing the lining. The epithelium consists of flattened squamous cells. Many of the lining cells have clear vacuolated glycogen rich cytoplasm. The lumen cyst show focal thickened plaque of proliferating lining cell. These are especially prominent in botryoid cyst.

Management The lateral periodontal cyst must be surgically removed if possible without extracting the associated tooth. If this can not be accomplished, the tooth must be sacrificed. There is a tendency for recurrence for this type of cysts following its surgical excision.

Figure 15.32 Lateral periodontal cyst show thin nonkeratinized

stratified squamous epithelium

Points to Remember Gingival swelling a round or ovoid well defined radiolucency with hyperostotic borders, Botryoid odontogenic cyst, layer of stratified squamous epithelium, cuboidal columnar cell, flattened squamous cells, focal thickened plaque of proliferating lining cell. These are especially prominent in botryoid cyst.

GLANDULAR ODONTOGENIC CYST It is also called as ‘Sialo odontogenic cyst’, or ‘mucoepidermoid cyst’. The term most descriptive of the lesion is probably mucoepidermoid odontogenic cyst because of the presence of both secretory elements and stratified squamous epithelium. The mucous and cylindrical cells form an integral part of the epithelial component with mucinous material within the cystic space. Gardner, who favors the name glandular, suggests that the features and biological behavior are sufficiently distinct for it to be regarded as a distinct entity. It also shows glandular or salivary features. The typical feature of the cyst is that it is intrabony radiologically and which can recur if not adequately excised.

Clinical and Radiological Features Figure 15.31 Lateral periodontal cyst showing radiolucency

on the lateral surface of teeth

Age and sex distribution: It occurs over a wide age range with mean age of occurrence 48 years.

Cyst of Orofacial Region

Location: It has got strong predilection for anterior region of jaw with many lesions crossing the midline. Sign and symptoms: They are small lesion less than 1 cm in diameter to large destructive lesion that may involve most of the jaw. Large lesion can cause expansion which can cause pain or paresthesia. Radiologically, it is a unilocular or multilocular radiolucency with either smooth or scalloped margins.

Histopathological Features

lingual aspect of the dental ridge and on the palate away forms the raphe. The nodules are considered remnants of mucous gland and are histologically different from Epstein’s pearls.

Clinical Features Age: These cysts are rarely seen after 3 months of age. Site: They tend to cluster along the junction of the hard and soft palate in a linear fashion or are scattered over the hard palate.

Histologically, shows cystic space lined by non-keratinized epithelium. The fibrous cyst wall is usually devoid of any inflammatory cell infiltrate. Superficial epithelial are cuboidal to columnar resulting in an uneven hobnail with papillary surface. Cilia and mucicarminopphilic material are also present. Mucous cells may or may not be present.

Symptoms: Occasionally, they become large to be clinically obvious as small discrete white swellings of the alveolar ridge.

Management

Signs: It is raised nodules, usually multiple, measuring a fraction of a millimeter to 2-3 mm in diameter. These probably correspond to those structures described as ‘predeciduous dentition’ in older literature.

It should be treated by enucleation or curettage can be done. Points to Remember Sialo odontogenic cyst, secretory elements and stratified squamous epithelium, less than 1 cm in diameter, pain or paresthesia, unilocular or multilocular radiolucency, nonkeratinized epithelium, uneven hobnail with papillary surface, cilia and mucicarminopphilic.

PALATAL CYST OF NEWBORN (EPSTEIN’S PEARLS, BOHN’S NODULES)

Appearance: Clinically it appears as small whitish projection of the alveolar ridge of the jaws of infants giving rise mistaken appearance of a tooth. Sometimes appearing blanched as though from internal pressure.

Histopathological Features These are true cysts with thin epithelial lining and show lumen filled with desquamated keratin, occasionally containing inflammatory cells. Dystrophic calcification and hyaline bodies of Rushton, commonly seen in dentigerous cyst, are also sometimes seen her.

Management

No treatment is required as these lesions almost invariably disappear by opening onto the surface of the mucosa or Small development cysts are common finding in the palate through disruption by erupting teeth. of newborn. These are inclusion cyst occur due to epithelial entrapment in the fusion of palate. Points to Remember

Pathogenesis Epstein's pearls: These are cystic keratin filled nodules found along the midpalatine raphe probably derived from entrapped epithelial remnants along the line of fusion. Bohn’s nodules: These are keratin filled cyst scattered over the palate most numerous along the junction of hard and soft palate and apparently derived from palatal salivary gland structure. It is formed along the buccal and

Epstein’s pearls, Bohn’s nodules, small discrete white swellings of the alveolar ridge, lumen filled with desquamated keratin, dyystrophic calcification and hyaline bodies of Rushton.

CALCIFYING EPITHELIAL ODONTOGENIC CYST It is also called as ‘keratinizing and calcifying odontogenic cyst’, ‘dentinogenic ghost cell tumor’, calcifying cystic

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odontogenic tumor’, ‘calcifying ghost cell odontogenic cyst’ and ‘Gorlin’s cyst’ as it was first described by Gorlin in 1962. The lesion is unusual in that it has some features suggestive of cyst but also has many characteristic of a solid neoplasm. Most cases of calcifying odontogenic cyst arise centrally within the bone, but it may occur peripherally in the soft tissue overlying the tooth bearing area. Central calcifying odontogenic cyst is also known as intraosseous odontogenic cyst. Types (Praetorius) • Simple unicystic type • Unicystic odontome producing type • Unicystic ameloblastomatous proliferating type.

Figure 15.33 CEOC showing calcification in the anterior

region

Clinical Features Age and sex: Age distribution from 10 to19 years with a mean age of 36 years. However, there may be another peak incidence through the seventh decade. It is slightly more prevalent in women. Site: 3/4th of the lesions occur centrally, with about equal in both jaws and 75 percent occuring anterior to the first molar. Symptoms: It is slow growing, painless, nontender swelling of the jaws. Occasionally some patients may complain of pain. Signs: In some cases, cortical plate over the expanding lesion may be destroyed and cystic mass may be palpable with patients reporting of discharge. Aspiration yields viscous granular yellow fluid. Teeth: Adjacent teeth may be displaced.

Radiographic Features The central lesion may appear as a cyst like radiolucency. Margin may be well defined outline or irregular in shape with poorly defined borders. It may contain small foci of calcified material that are only microscopically apparent (Fig. 15.33). In some cases, it is completely radiolucent while in other cases an increasing amount of calcified material may be seen as white flecks. It may be unilocular or multilocular.

Histopathological Features (Figs 15.34 to 15.37) The epithelium of the cystic lining is chiefly low cuboidal or squamous type and is two or three layers thick. Focal areas of stellate reticulum and ghost cell may be present. Ghost cells according to some authors are abnormal keratin; they are pale eosinophilic swollen epithelial cells, which have lost the nucleus and nuclear membrane. They have affinity for calcification. More accepted is the concept that they are product of coagulative necrosis of the epithelial cells as some amount of calcified material may be seen. Masses of ghost cells may fuse to form large sheets of amorphous, acellular material. Multiple daughter cyst can be seen in fibrous wall and foreign body reaction to ghost cell can be seen. Unicystic odontome producing type: About 20 percent of COC are associated with odontoma. It show features of complex or compound odontoma plus features of COC. Unicystic ameloblastomatous proliferating type: Epithelial proliferation resembling ameloblastoma can intermixed with ghost cell. Odontogenic ghost cell carcinoma: There lesion have cellular pleomorphism and mitotic activity with invasion of surrounding tissue can occur.

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Figure 15.34 Unicystic CEOC showing ameloblastomatous

proliferation of the epithelial lining

Figure 15.35 Ghost cells are pale eosinophilic swollen epithelial cells that have lost its nucleus and nuclear membrane

Management Enucleation and curettage should be done. Malignant transformation has been recorded. Points to Remember Keratinizing and calcifying odontogenic cyst, slow growing, painless, nontender swelling, expanding lesion, margin may be well defined outline or irregular, small foci of calcified material, epithelium low cuboidal or squamous type, ghost cells, coagulative necrosis of the epithelial cells, multiple daughter cyst, Unicystic odontome producing type, unicystic ameloblastomatous proliferating type, odontogenic ghost cell carcinoma.

Figure 15.36 Basophilic dystrophic calcifications in ghost cells

Figure 15.37 Dentinoid material induced by the adjacent

odontogenic epithelial islands

INFLAMMATORY RADICULAR CYST It is also called as ‘apical periodontal cyst’, ‘periapical cyst’, or ‘dental root end cyst’. It is a common sequel in progressive changes associated with bacterial invasion and death of the dental pulp. It most commonly occurs at the apices of teeth. The radicular cyst is classified as an inflammatory cyst because this process is thought to initiate the growth of the epithelial component. It may be classified as odontogenic cyst because of its origin in cell rests of Malassez which are remnants of Hertwig’s root sheath and is a product of the odontogenic epithelial layer.

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The epithelium may be derived in some cases from respiratory epithelium of the maxillary sinus, when the periapical lesion communicates with the sinus wall, oral epithelium proliferates apically from the periodontal pocket and oral epithelium forms a fistulous tract.

Pathogenesis Periradicular inflammatory changes cause the epithelium to proliferate. As the epithelium grows into a mass of cells, the center losses the source of nutrition from the periapical tissue. These changes produce necrosis in the center and a cavity is formed and cyst is created. Another theory is that an abscess cavity is formed in the connective tissue and is lined with proliferating epithelial tissue. Figure 15.38 Swelling seen in palate due to radicular cyst

Types • Periapical pocket cyst: There is incomplete epithelial lining due to extension of apical portion into cyst lumen • Periapical true cyst: There is complete epithelium baglike structure which are separated from tooth apex • Lateral radicular cyst: It appear along lateral aspect of root.

Clinical Features Age and sex distribution: Peak frequency occurs in the 3rd decade and there are large numbers of cases in the 4th and 5th decades after which there is a gradual decline. Although dental caries is more common in deciduous teeth in the first decade but radicular cysts are not often found in deciduous teeth may be because teeth tend to drain more readily than the permanent teeth and the antigenic stimuli which evoke the changes leading to the formation of radicular cyst may be different. There is male predominance, as females are less likely to neglect their maxillary anterior teeth and males are more likely to sustain trauma to their maxillary teeth. It shows a higher frequency of occurrence in whites. Site: Maxillary anterior are more commonly affected. Also in addition to caries, maxillary teeth are more prone to traumatic injuries which lead to pulp death. Symptoms: It represents an asymptomatic phase in periapical inflammatory process following death of the dental pulp. It is associated with non vital tooth. Sigs: It rarely causes nontender expansion of the overlying cortical bone. The associated tooth is not sensitive to

(Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

percussion. Swelling may be bony hard or crepitations may be present as bone is thinned or it may be rubbery or fluctuate, if the bone is completely destroyed (Fig. 15.38). Complication: Ameloblastoma, epidermoid carcinoma and mucoepidermoid carcinoma may arise in the epithelial lining of periapical cyst.

Radiographic Features It appears as a rounded or pear shaped radiolucency at the apex of non sensitive tooth or with non vital tooth. Radiolucency is more than 1.5 cms in diameter but usually less than 3 cms in diameter. It has got well defined outline with thin hyperostotic borders (Figs 15.39A and B). Adjacent tooth are usually displaced and rarely resorbed. There is also buccal expansion and if it involves maxillary area then displacement of antrum can occur. In case of lateral radicular cyst discrete radiolucency along the lateral surface of tooth can be seen.

Histopathological Features (Figs 15.40 to 15.44) Macroscopic features: The contents of radicular cysts are usually a soft brown material, often with glistening, oily, yellowish flecks. Nodules of opaque yellow crystalline material, representing cholesterol, maybe seen protruding into the lumen or within the wall is seen. The apical periodontal cyst is usually lined by stratified squamous epithelium. Occasionally, it is lined

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A Figure 15.41 Radicular cyst showing arcading growth pattern

of epithelium

B Figures 15.39A and B Well-defined radiolucency in radicular

cyst (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India) Figure 15.42 Radicular cyst histopathological picture (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Figure 15.40 Linear, straight or curved, hairpin shaped

Rushton bodies. Some show concentric lamellations

by pseudostratified, columnar or respiratory type of epithelium, when it occurs in the teeth that involve the maxillary sinus. The lining shows variation in thickness with rare keratin formation. Rushton bodies often found in great numbers in the epithelium of apical periodontal cyst is seen. These are linear arch shaped calcification. In some cases hyaline bodies (pulse granuloma, giant cell hyaline angiopathy) can seen scattered at the wall of cysts. These are small circumscribed pools of eosinophilic material which exhibits corrugated periphery of condense collagen.

Textbook of Oral Pathology

Management Root canal treatment: It is the treatment of choice as in many cases, radicular cyst resolve after root canal treatment. The reason behind it is that as drainage is established, the inflammatory process subsides and the fibroblast start producing collagen. The pressure of proliferating-collagen reduces the blood supply to the epithelium lining and causes it to degenerate. Macrophages remove the degenerating epithelial tissue.

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Extraction: If the lesion fails to resolve, extraction of associated tooth is carried out. Enucleation and marsupialization: Enucleation or marsupialization of a larger lesion is done. Figure 15.43 Lining of radicular cyst showing presence

of Rushton bodies

Points to Remember Apical periodontal cyst, maxillary anterior, nonvital tooth, bony hard, crepitation, complication like ameloblastoma, epidermoid carcinoma, mucoepidermoid carcinoma, rounded or pear shaped radiolucency, well defined outline, stratified squamous epithelium, Rushton bodies, hyaline bodies, parallel bundles of collagen fibers, collection of cholesterol cleft.

RESIDUAL CYST It is a cyst that either remained as such in the jaw when it is associated tooth was removed or was formed in residual epithelium of cell rests from a periodontal ligament of the lost tooth. Low grade inflammation of parent cyst might predispose formation of residual cyst. Figure 15.44 Cholesterol clefts in radicular cyst

Connective tissue that makes up the wall of apical periodontal cyst is composed of parallel bundles of collagen fibers with variable number of fibroblasts and small blood vessels. The universal occurrence of an inflammatory infiltrate in the connective tissue immediately adjacent to the epithelium is characteristic feature. Collection of cholesterol cleft with associated multinucleated giant cells is found in the wall of the lesion. The lumen of the cyst usually contains fluid with a low concentration of protein. Lumen may contain cholesterol or keratin.

Clinical and Radiological Features Age and sex: Cyst is common in patients older than 20 years with an average age of about 52 years. It is twice more common in male than female. Site: Higher incidence in the maxilla. Mostly found on alveolar process or body of the tooth bearing area with some cysts described in the lower ramus of the mandible. Symptoms: It is asymptomatic with a previous history of pain in the tooth. Size: It is seldom more than 5 to 10 mms in diameter. Radiological features: Pre-extraction radiographs show tooth with an evidence of deep caries or fracture

Cyst of Orofacial Region

more readily from the lateral periodontium which is closely associated with gingival crevice.

PARADENTAL CYST It was first described by Craig in 1976. It is a cyst of inflammatory origin occurring on the lateral aspect of the root of partially erupted mandibular third molar with an associated history of pericornitis.

Origin

Figure 15.45 Residual cyst showing radiolucency

adequate for pulp involvement and/or an associated cyst. Thin radioopaque margins are common with unilocular appearance although the infected cyst will not have such well defined margins (Fig. 15.45).

Management Enucleation: If the cyst is not large and patient’s age and health will tolerate the insult, the cyst wall should be completely enucleated. The extent of repair of the defect will depend on the size of the cyst and health of the patient. Marsupialization: In the cases where the surgical procedure must be as atraumatic as possible, marsupialization or decompression may be used. Excision: Complete excision and replacement with autogenously bone graft or single segment of bone fixed in it. Points to Remember Asymptomatic with a previous history of pain, evidence of deep caries, pre-extraction radiographs, thin radiopaque margins.

INFLAMMATORY COLLATERAL CYST It is cyst which arises in the periodontium on the lateral aspect of an erupted tooth as a result of inflammatory process in the periodontal pocket. They arise by proliferation of cell rests of Malassez in the lateral periodontium. They are rare as drainage occurs

Cell rests of Malassez can be the origin, but argument is that if rests of Malassez were responsible then the lesion should be equally distributed around the root surface. Second theory is that it originates from the reduced enamel epithelium as the presence of reduced enamel epithelium over the enamel projection might be the source and could explain the common location of the cyst.

Clinical and Radiological Features Age and sex: It occurs between 10 to 39 years of age. It is most commonly in the third decade of life. It shows predilection for males. Site: Usually associated with the third molar on the buccal surface and covers the bifurcation. It may occur bilaterally. Signs: The involved tooth is vital. Radiographic features: There is well demarcated radiolucency occurring distal to the partially erupted tooth but there was often buccal superimposition. The radiolucency sometimes extends apically but an intact periodontal ligament space provided the evidence that the lesion did not originates at the apex.

Histopathological Features It is lined by proliferating, nonkeratinized squamous epithelium of varying thickness. The fibrous capsule is the seat of an intense chronic or mixed inflammatory cell infiltrate.

Management The lesion is treated by surgical enucleation. Points to Remember Cell rests of Malassez, vital tooth, well demarcated radiolucency, distal to the partially erupted tooth proliferating, nonkeratinized squamous epithelium.

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It is also called as ‘buccal bifurcation cyst’. It is an inflammatory cyst occurring on the buccal surface of mandibular molars usually first molar in young children.

Pathogenesis It has been thought to be occur due to buccal enamel extension into the bifurcation area. This extension predispose for pocket formation in teeth which could enlarge to form a cyst in response to pericoronitis.

Clinical and Radiological Features Age: A younger age group than the paradental cyst. Site: It affects the mandibular first and second molars more commonly rather than the wisdom teeth. The cyst always is situated on the buccal surface of the mandibular molar most frequently the first permanent molar after their partial or complete eruption. Symptoms: There may be discomfort, pain, tenderness and rarely suppuration. Swelling particularly, if inflamed, is the clinical feature most likely to induce the patient to seek advice. Facial swelling may follow and this may be inflamed.

Points to Remember Buccal bifurcation cyst, enamel extension into the bifurcation, discomfort, pain, tenderness, inflamed swelling, vital pulp, associated tooth tilted, new bone may be laid down linear band or laminated, nonkeratinizing stratified squamous epithelium, chronic inflammatory cell infiltrate.

SUPPURATING CYST When pyogenic organisms are present in sufficient number to produce changes in the cyst, suppuration will result. The thin white line which represents the cortex of the cyst becomes less dense and thinner and may be entirely lost. In rare cases there is slight irregularity of the walls of the cyst, with some decalcification extending into the bone to a short distance. In the place of thin white cortex, there is sometimes a broad band of sclerosed bone which is less dense but wider than a normal cortex and presents a granular appearance.

HEALING CYST

A cyst that is cause by an infected tooth often heals after removal of that tooth. One of earliest changes is the gradual loss of the cortical layer of bone which lines most of the Teeth: The associated tooth is usually tilted, so that the cysts. apices are adjacent to the lingual cortex, a feature which is At the same time, if the cyst becomes infected, the bone demonstrable in occlusal radiographs. in the immediate vicinity of the walls becomes radiolucent Radiological features: Due to involvement of the as a result of hyperemia. After the period of time, there is periosteum new bone may be laid down either as a single gradual lessening of radiolucency of the cavity and a return linear band or laminated, if there two or more layers. of the surrounding bone to a normal density. Sometimes, the new bone may be homogeneous. The The dark shadow of the cavity is replaced by a grey inferior margins of the cyst are concave and rarely, the cyst one and it is apparent that the cavity is becoming smaller. may extend to the inferior border of the mandible but not A large cyst may fail to heal completely, resulting in a leading to any external deformity. smaller cyst. This is due to the retention of some part of the epithelial wall of the cyst, which has continued its activity. Signs: Usually, a vital pulp and intact lamina dura.

Histopathological Features

It is not specific and show nonkeratinizing stratified squamous epithelium with areas of hyperplasia. There is also chronic inflammatory cell infiltrate present.

Management It is generally agreed that enucleation of the cyst without removal of the associated tooth is the treatment of choice.

NONODONTOGENIC CYSTS Nasopalatine cyst It is also called as ‘nasopalatine duct cyst’, ‘incisive canal cyst’, ‘median anterior maxillary cyst’ or ‘vestigial cyst’. It is the most common nonodontogenic cyst in the oral cavity. It is the most common nonodontogenic cyst.

Cyst of Orofacial Region

Origin It is developmental in origin and arises in the incisive canal when embryonic epithelial remnants of the nasopalatine duct undergo proliferation and cystic transformation. They are found to form in the canal or at the oral terminus of the canal. It is generally agreed that the nasopalatine duct cyst is an entity. It may occur with in the nasopalatine canal or in the soft tissue at the opening of the canal where it is called as cyst of the palatine papilla.

Etiological Factors Trauma: In the form of direct blow to the incisive canal or indirectly from mastication, particularly when ill-fitting dentures are involved, have been suggested. But if this is true, the cyst would likely be found more often and there would not be a male predilection. Bacterial infection: Either from the nasal cavity or from the oral cavity, stimulates to the epithelial remnants to proliferate has been suggested as a cause. However, since an open connection with the oral cavity or the nasal cavity is extremely rare, an evidence for the bacteria is lacking. Retention phenomenon: Blocked duct of mucus glands and an accumulation of secretion would be responsible for the cystic expansion.

covered by normal mucosa, unless it is ulcerated. If cyst expands, it may penetrate the labial plate and produce a swelling below the maxillary labial frenum. Teeth: Roots of central incisors diverge. It may bulge into the nasal cavity and distort nasal septum. Cyst of palatine papillae: Sometimes cyst formed in palatine papilla will be evident as an elevation or a soft round swelling of palatine papilla which extends posteriorly along the midline of the palate. It occurs anterior to the incisive foramen below the periosteum and does not enter invades.

Radiological Features Image of radiopaque anterior nasal spine may superimpose over the dark cystic cavity giving it a heart shape or shape of inverted tear drop (Fig. 15.46). Two separated cysts may develop in two canals and cause paired cysts like radiolucency. Cyst in canal cavity also erodes the bone posterior to the canal and creates impression of midpalatal cyst. Cyst of palatine papillae: The cyst in the palatine papillae is not usually apparent because it does not cause enough pressure on the bone to cause discernible bone resorption but it can produce some bony erosion.

Histopathological Features

Epithelium: Some workers believe that it is derived from (Figs 15.47 to 15.49) the epithelium included in the lines of fusion of embryonic The cystic epithelial lining depends upon the proximity of facial processes. the lesion to the nasal cavity. The most superficially located Clinical Features cysts are lined with respiratory epithelium while those in Age and sex distribution: Most cases discovered in the 4th and 6th decades and it is also frequently found in edentulous patients. It is three times higher in males than in females and found equally in blacks and whites. Symptoms: There is a small well defined swelling just posterior to the palatine papilla. Sometime it may become infected, producing pain. Patients complain of salty taste in mouth produced by small sinus or remnant of nasopalatine duct that permits cystic fluid to drain into oral cavity. Burning sensation and numbness may be experience due to pressure on the nasopalatine nerve. Sometimes cystic fluid may drain and patient reports a salty taste. Signs: Swelling is fluctuant and bluish if it is near the surface. It opens by a tiny fistula on or near the palatine papilla. In such cases a tiny drop of watery fluid or pus may be elicited by pressure in this area. Deeper cysts are

Figure 15.46 Nasopalatine canal cyst showing

radiolucency in canal region

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Figure 15.47 Nasopalatine cyst lined by respiratory epithelium and connective tissue capsule with prominent neurovascular bundle

Figure 15.49 Stratified squamous epithelium lining

nasopalatine duct cyst

before dentures are introduced. You can also go for enucleation and if it is large, then marsupialization. Points to Remember Incisive canal cyst, cyst of the palatine papilla, small well defined swelling just posterior to the palatine papilla, salty taste, fluctuant bluish swelling, tiny fistula, diverge roots, heart shape or shape of inverted tear drop, paired cysts like radiolucency, respiratory epithelium, stratified squamous variety, simple columnar epithelium, simple cuboidal epithelial, collections of mucus glands.

MEDIAN PALATINE CYST Figure 15.48 High power view shows pseudostratified ciliated

columnar epithelium

the inferior position close to the oral cavity are composed of epithelium of stratified squamous variety. In some cases simple columnar epithelium and simple cuboidal epithelial can also be seen. The connective tissue wall of this cyst frequently shows inflammatory infiltration. Collections of mucus glands are also often present as well as several large blood vessels and nerves. In the cystic fluid, erythrocytes, leukocytes, desquamated epithelial cells, tissue debris and bacteria can be found.

It is very difficult to distinguish from the nasopalatine cyst. Normally there is septopalatal contact, fusion and lamination of adult epithelial surfaces followed by breakdown (of opposing epithelial surface) into epithelial remnants and actual fusion by inter-shelf mesenchymal bridge. In cases, due to continued differentiation of these epithelial remnants pathological median palatine cyst is formed. It may be the only true fissural cyst in oral region. It is now felt that it represent posterior extension of incisive canal cyst.

Clinical and Radiological Features

Management

Site: It is very rare and develops in midline of the hard palate posterior to pre-maxilla.

Its removal is not indicated unless there are clinical symptoms. Removal is indicated in edentulous patients

Symptoms: If it becomes larger, then it bulges into the oral cavity and produces a swelling in the roof of mouth.

Cyst of Orofacial Region

Signs: It is fluctuant and nontender. Overlying mucosa is normal. Corticated plate is rapidly perforated as the cyst grows. If floor of nasal fossa is eroded, cyst may be superiorly displaced. Teeth: Maxillary teeth are vital and aspiration produces amber colored fluid. Radiological features: Radiolucent lesion is behind the incisive canal in premolar-molar area. Well defined borders which are hyperostotic. Nasal septum image crosses the septum and appears on occlusal radiographs.

Histopathological Features The lining of such cyst usually consists of stratified squamous epithelium overlying relatively dense fibrous connective tissue band which may show chronic inflammatory cell infiltration. In some cases, it may be lined by pseudo-stratified ciliated columnar epithelium or even a ‘modified’ squamous epithelium.

Clinical Features Age and sex distribution: It ranges from 12 to 75 years with a mean age of 41 with peak in the 3rd decade. Women are more commonly affected. Symptoms: It may cause pain and difficulty in breathing through the nose. There is swelling of the nasolabial fold and nose. Signs: Swelling is fluctuant. There is flaring of ala and distortion of nostril and fullness of upper lip below the nasal vestibule. It may bulge into the nasal cavity and cause some obstruction. Infection may drain into the nasal cavity. Superficial erosion of the outer surface of the maxilla may be produced by pressure of the nasoalveolar cyst.

Radiographic Features

There is increased radiolucency of alveolar bone beneath the cyst and above the apices of incisors. Cyst causes erosion of the underlying bone by virtue of its presence Management and pressure. Usual outline of inferior border of nasal fossa is Surgical excision is done. Care should be taken not be distorted resulting in posterior convergence of the perforate the nasal mucosa. Healing defect is protected by margins. a acrylic stent prefabricated. The actual shape and position of the cyst can be demonstrated by aspirating the typical cyst fluid and Points to Remember replacing it with radio-contrast material. A tangential view Only true fissural cyst in oral region, swelling in the roof then demonstrates the kidney shaped lesion below the nasal of mouth, fluctuant, nontender, nasal fossa is eroded, fossa and above the apices of the incisors. vital teeth, aspiration amber colored fluid, radiolucent lesion in premolar molar area, stratified squamous Histopathological Features epithelium. It may be lined by pseudostratified columnar epithelium which is sometimes ciliated often with goblet cells or by NASOALVEOLAR CYST stratified squamous epithelium. Inflammation may be seen in the lesion if it is secondary It is also called as ‘nasolabial cyst’ or ‘Klestadt’s cyst’. It infected. is a soft tissue cyst, which involves the bone secondarily.

Pathogenesis

Management

Some state that it is a fissural cyst arising from epithelial It should be excised using an intraoral approach. There is rests in the fusion lines of globular process, lateral nasal no tendency to recur. process and maxillary process. Points to Remember Others state that it is actually a merging of mesenchymal Nasolabial cyst, Klestadt’s cyst, pain, difficulty in processes and not a fusion per se, so there is no epithelial breathing, swelling is fluctuant, superficial erosion of the entrapment in the nasooptic fissure. They state that the outer surface maxilla, increased radiolucency of alveolar location of nasoalveolar cyst strongly argues in favor of its bone apices of incisors, pseudo-stratified columnar development from the embryonic nasolacrimal duct that epithelium, inflammation. initially lies on the surface.

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medullary space of bone after trauma heals in most cases by organization of the clot and eventual formation of This cyst has got question existence. Theoretically it connective tissue and formation of new bone. represent fissural cyst in the anterior midline of the According to the traumatic injury theory, however it is mandible due epithelium entrapment during the fusion of suggested that after traumatic injury to an area of spongy halves of the mandible during embryonic life. bone containing hemopoietic marrow enclosed by layer But as mandibles develop as a single bilobed of dense cortical bone, there is failure of organization of proliferation of mesenchymal with central isthmus in the blood clot and for some unexplained reasons subsequent midline, which after growth is eliminated. So there is no degeneration of the clot that eventually produce an empty fusion occur and so no entrapment. So the term median cavity within the bone. mandibular cyst should be discarded. In the development of the lesion, the trabeculae of bone Cyst occurring in this region are of odontogenic origin, in the involved area become necrotic after degeneration of i.e. either radicular cyst, OKC or lateral periodontal cyst. the clot and bone marrow, although some viable marrow tissue must persist to initiate resorption of the involved GLOBULOMAXILLARY CYST trabeculae. The lesion then appears to increase in size by steady It is also called as ‘intra-alveolar cyst’. It occurs in expansion produced by a progressive infiltrating edema on globulomaxillary area. It was considered to be an inclusion or developmental cyst that arises from entrapped non- the basis of restriction of venous drainage. This expansion odontogenic epithelium in globulomaxillary suture which tends to cease when the cyst like lesion reaches the cortical occurs at the junction of globular portion of the medial layer of the bone, so that expansion of the involved bone is not a common finding in the solitary bone cyst. nasal process and maxillary process. It also origin from bone tumors that have undergone Development of anterior maxilla occurs by merging of cystic degeneration, as a result of faulty calcium metabolism growth center and not by fusion of facial processes so no such as that induced by parathyroid disease. entrapment occur so it can not exist. It also has a origin from necrosis of faulty marrow due Cysts which are present in this region are either periapical cyst, odontogenic keratocyst, dentigerous cyst to ischemia. The end result of low grade chronic infection. A result of osteoclastic activity resulting from disturbed or lateral periodontal cyst. So as fissural cyst does not exist in this region the use circulation caused by trauma thereby creating an unequal balance of osteoclastic activity and repair of bone. of term globulomaxillary cyst should be discarded.

NONEPITHELIAL CYSTS Traumatic Bone Cyst It is also known as ‘solitary bone cyst’, ‘hemorrhagic bone cyst’, ‘extravasation cyst’, ‘simple bone cyst’, ‘unicameral cyst’ and ‘idiopathic bone cavity’. It is an unusual lesion which occurs with considerable frequency in the jaws as well as in other bones of the skeleton. The traumatic bone cyst is a misnomer, since these intrabony cavities are not lined by epithelium. It results from trauma induced intramedullary hematoma with subsequently result in bone resorption and cavitations during hematoma resolution.

Pathogenesis It originates from intramedullary hemorrhage following traumatic injury. Hemorrhage occurring within the

Clinical Features Age and sex: The traumatic bone cyst occurs most frequently in young persons at an age of 6 to 20 years with a male predominance as they are exposed to traumatic injury most frequently than females with the ratio being 3:2. Site: It is usually found in mandible anywhere from the symphysis to the ramus, but about one third are found in the maxilla, usually in the anterior region. Symptoms: It is asymptomatic in most cases but occasionally, there may be evidence of pain and tenderness. Signs: Cortical swelling or slight tooth movement are not the usual finding and the teeth are vital. Aspiration: Needle aspiration is actually unproductive and if it is productive it contains either a small amount of straw colored fluid shed off necrotic blood clot and fragment of fibrous connective tissue.

Cyst of Orofacial Region

Radiographic Features

Management

It appears as a radiolucent lesion with a spectrum of well defined to moderately defined borders (Fig. 15.50). Most cases are unilocular with a fairly regular border. There is evidence of hyperostotic borders around the entire lesion but occasionally such border is lacking. Most characteristic radiographic feature of this cyst is scalloped superior or occlusal margins where it extends between the roots of the teeth. Teeth may be superimposed with the root or ‘scallop’ superiorly between the roots. Occasionally lamina dura of the tooth may be absent and even less frequently the root may show resorption. It rarely causes cortical expansion but if it occurs it is mostly buccal. Surface is smooth, the cortical plates are not disrupted and pathological fracture does not result. The cavity occupies the position in the body of the jaw, but it may extend to involve the alveolar process.

This lesion must be surgically exposed to rule out the possibility that the lesions of serious nature are not being confronted. When the correct diagnosis is determined, enucleation and curettage are carried out. Now a day intralesional injection of steroids is also one of the treatment modalities.

Histopathological Features

ANEURYSMAL BONE CYST

The simple bone cyst consists of loose vascular fibrous tissue membrane of variable thickness with no epithelial lining. Fragments of fibrin with enmeshed red cells may be seen. Hemorrhage and hemosiderin fragments are usually present and scattered small cells are often found. Stringy lacelike dystrophic calcification is also seen in some cases.

It is an uncommon hemorrhagic lesion of the bone which is rarely seen in the jaw. It was first described as a clinicopathological entity by Jaffe and Lichtenstein in 1942. It is most often categorized as to be a tumor like reactive lesion of bone. The name of this entity is misleading, in that, it does not contain vascular aneurysms and it is not a true bony cyst. It represents an exaggerated localized proliferative response of the vascular tissue. It may be similar to peripheral and central giant cell granuloma to which it resembles in some ways including the histological presence of giant cells.

Points to Remember Solitary bone cyst, simple bone cyst, intramedullary hemorrhage, symphysis to the ramus, asymptomatic, cortical swelling, unproductive needle aspiration, radiolucent lesion well defined to moderately defined borders, scalloped superior or occlusal margins, vascular fibrous tissue, fragments of fibrin with enmeshed red cells, stringy lacelike dystrophic calcification.

Pathogenesis

Figure 15.50 Traumatic bone cyst showing well defined border

Persistent local alteration in hemodynamics leads to increased venous pressure and development of dilated and engorged vessels in transformed bone area. Resorption of bone occurs, to which giant cells are related and this is replaced by connective tissue, osteoid and new bone. It has exuberant attempt at repair of hematoma of bone, similar to that of central giant cell granuloma. But, in the case of aneurysmal bone cyst, it is postulated that hematoma maintains a circulating connection with the damaged vessel.

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This would lead to a slower flow of blood through the lesion and account for a clinical “welling” of blood. This is the only difference between the aneurysmal cyst and the giant cell granuloma that is in later lesion, the blood vessels fail to retain circulating connection with lesion. Biesecker and his associates have proposed a new hypothesis for etiology and pathogenesis of this lesion that a primary lesion of the bone initiates an arteriovenous fistula and thereby creates, via its hemodynamic forces, a secondary reactive lesion of the bone. Thus occurrence of this cyst is secondary in association with osseous lesions like nonosteogenic fibroma, benign osteoblastoma and hemangioma of bone.

Clinical Features Age and sex distribution: Although, it may be seen in adults, it is more commonly seen as abnormalities of older children and adolescents with more than 90 percent of lesions occuring in individuals younger than the age of 30 years. It is more common in females than in males. Site: It is most commonly seen in long bone or in the vertebral column. Intraorally it usually involves the mandibular molar region as compared to anterior region. Symptoms: Aneurysmal cyst of the jaw produces a firm swelling which may be painful and tender on motion. Swelling becomes progressively worse and the rate of development is often described as rapid. Sometimes patient may complain of difficulty in opening the mouth, i.e. if there is impingement of the lesion on the capsule of temporomandibular joint (TMJ). Signs: Usually there is tilting or bodily displacement of teeth in the affected areas though it does not devitalize the affected tooth. Excessive bleeding may occur. When the lesion perforates the cortex and is covered by periosteum or only a thin shell of bone, it may exhibit springiness or egg shell crackling, but it is not pulsatile. Bruit is not heard.

Radiographic Features The aneurysmal bone cyst is an expansile osteolytic process within the affected bone and is projected as a definite radiolucency. Invariably, fine septa are seen crossing through the lesion in a random pattern. The term ‘soap bubble’ may be applied to describe an occasional multilocular radiographic appearance. Margin are somewhat less regular and distinct than odontogenic cyst but more discrete than a central malignancy.

Simple tilting and bodily displacement of erupted teeth is seen. Some degree of external root resorption may be seen though it will not devitalize the tooth. There is also buccal and lingual expansion of the cortex often marked and described as ballooning or blowing out.

Histopathological Features (Figs 15.51 and 15.52) The lesion consists of mainly capillaries and blood filled spaces of varying sizes, lined by flat spindle shaped cells and separated by delicate loose textured fibrous tissue. It contains many cavernous sinusoidal blood filled spaces which may or may not show thrombosis. Young fibroblasts are numerous in the connective tissue stroma. Most of the cysts contain small multinucleated giant cells with a patchy distribution. Scattered trabeculae of osteoid and woven bone are seen.

Management Surgical curettage or partial resections are the primary forms of treatment for aneurysmal bone cyst. Cryosurgery and immediate packing with bone chips is the treatment of choice. The recurrence rate is fairly high, ranging form 5 to 19 percent after curettage. Thus indicate the need for careful follow-up. Points to Remember Persistent local alteration in hemodynamic, welling” of blood, mandibular molar region, firm swelling, painful, tender on motion tilting or bodily displacement of teeth, springiness or egg shell crackling, expansile osteolytic, soap bubble, flat spindle shaped cells, young fibroblasts, scattered trabeculae of osteoid and woven bone.

CYSTS OF THE MAXILLARY SINUS Sinus Mucocele The Mucocele of the maxillary antrum is a true cyst filled with mucus and lined by the mucoperiosteum of the involved maxillary sinus. A true antral mucocele sometimes completely fills the sinus and is caused by blockage of the ostium, which may be secondary to inflammatory changes associated with chronic rhinosinusitis.

Pathogenesis Blockage of sinus ostium: The ostium block results in mucus retention which results in cyst initiation. This is

Cyst of Orofacial Region

Clinical and Radiological Features Sigs: Mucocele may cause expansile ballooning resulting into destruction and perforation of the surrounding bone and displacement of adjacent structures. Sometimes it presents severe signs to warrant as another aggressive disease. There may be nasal blockage, or proptosis. Site: Mucocele are more common in frontal and ethmoid sinus than the maxillary sinus. The incidence accounts only for 10 percent.

Figure 15.51 Aneurysmal bone cyst with cavernous

sinusoidal blood filled spaces

Age: Age affected is middle age group with average being 48.2 years. It usually occupies the entire sinus. Cystic structure is filled with mucus and lined by antral epithelium. Associated with blockage of the ostium and may be secondary to chronic sinusitis. Radiographic features: There can be cloudy radiopacity which may be noticeable but in the early lesion the bony walls of the antrum appear normal. As the lesion develops there may be a well-defined radiolucency with expansion and perforation of the bone margins (Fig. 15.53). The lesion is often quite spherical in outline. There is always medial expansion .The lesion may also raise the orbital floor or the anterior wall of the antrum. Expansion of the thicker lateral wall is rare.

Figure 15.52 Multinucleated giant cells seen

further added by the increase in the protein content and osmolarity of the cyst resulting in expansion by hydrostatic pressure. This is accompanied by inflammation and activation of bone resorbing factors and osteoclasts which allow bony expansion and destruction of adjacent tissues. Trauma or surgery to sinus: This type of cyst called as ‘surgical ciliated cyst’, traumatic ciliated cyst’, or postoperative maxillary cyst’. Most frequently seen after Caldwell Luc operation. In his sinus lining becomes separated from main body of sinus and forms epithelium line cavity in which mucin is secreted.

Figure 15.53 Mucocele in left maxillary sinus showing

perforation of border of maxillary sinus

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The maxillary mucocele is lined by normal antral mucosa, covered by ciliated respiratory type epithelium or flattened simple cuboidal or squamous epithelium. There may be chronic inflammation in the wall and if there is an associated allergic sinusitis.

Management As these cysts are expansile and destructive surgical removal should be done. Points to Remember Blockage of sinus ostium, trauma or surgery to sinus, expansile ballooning destruction and perforation of the surrounding bone occupies the entire sinus, cloudy radiopacity, expansion and perforation of the bone margins, ciliated respiratory type epithelium flattened simple cuboidal or squamous epithelium.

ANTRAL PSEUDOCYST

Radiological features: The cysts appear as spherical, ovoid or dome-shaped radiopacities which have a smooth and uniform outline. They may have a narrow or broad base. They vary in size from minute to very large and may occasionally occupy the entire maxillary sinus.

Histopathological Features It has a smooth blue surface, is thin-walled and contains mucinous material. Microscopically, a pseudocyst shows pools of mucoid material lined by inflamed fibrous connective tissue which in places may be the raised periosteum. Collection of cholesterol cleft and scattered small dystrophic calcification can be seen. Antral mucosa may be seen on one aspect. Ducts may be seen. A calculus or mucus plug may be evident.

Management Retention cysts and pseudocyst are not destructive and usually remain static, many appear to regress spontaneously, and as they usually cause little discomfort surgical intervention may not be necessary.

These are dome shaped cyst seen on sinus floor.

Pathogenesis These are the result of focal accumulations of inflammatory exudate that lift the antral mucosa away from the underlying bone. This will cause sessile elevation of sinus floor. The exudate is surrounded by connective tissue and epithelial lining is superior to the fluid. There is increase prevalence of this lesion in winter months. So many authors believed that upper respiratory infection can lead to this cyst.

Clinical Features Age and sex distribution: These cysts are seen in the age group 21 to 30 years with equal incidences in both sexes. Site: Usually the cyst occurs singly, but in a few instances they may be multiple and sometimes bilateral. Symptoms: These may be asymptomatic, the lesions being discovered only in the course of routine radiological examination. Patients may complain of a wide range of symptoms such as a localized dull pain in the antral region, or fullness or numbness of the cheek, nasal obstruction, postnasal drip and a copious discharge of yellow fluid from the nostrils. The symptoms may be associated with sinusitis.

Points to Remember Focal accumulations of inflammatory exudate asymptomatic, localized dull pain in the antral region, spherical, ovoid or dome-shaped radiopacities, mucinous material, inflamed fibrous connective tissue, cholesterol cleft, calculus, mucus plug.

RETENTION CYST They arise from partial blockage of duct of seromucous glands. They may arise from invagination of respiratory epithelium. They are located around the ostium or in antral polyps. Histopathologically sinus retention cyst show focal dilatation of duct associated with seromucous glands of sinus lining.

SOFT TISSUE CYST Dermoid and Epidermoid Cyst It may occur as developmental anomalies and about 1 to 2 percent occurs in oral cavity. The lumen of simple cyst filled with cyst fluid or keratin and no other specialized structure, is called as ‘epidermoid cyst’.

Cyst of Orofacial Region

If lumen contains sebaceous material as well as keratin then it is called as ‘dermoid cyst’. If lumen contains elements such as bone, muscle or teeth from various germinal layer is called as ‘teratoma’. Dermoid cyst is lined by epidermis and skin appendages are present in the fibrous wall. Epidermoid cyst is lined by epidermis, but contains no appendages.

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Pathogenesis It is most likely site for their origin is anteriorly, between the contributions from the mandibular arches to the tongue. Implantation keratinizing epidermoid cyst may occur in other parts of the mouth as a result of trauma. Types • Median variety – Supramylohyoid variety – Inframylohyoid variety • Lateral variety – Supramylohyoid variety – Inframylohyoid variety.

Figure 15.54 Dermoid cyst seen on forehead of the patient

Clinical Features Age and sex: It occurs at any time from birth to adolescence and it is small in infancy and large in adolescence. Mainly it is apparent between 12 to 25 years of age and occurrence is equal in both sexes. Site: Midline of the floor of mouth is the commonest location of these cysts which may cause a swelling in the midline of the neck or some times, it may be lateral. Symptoms: Swelling is slow and painless. It may interfere Figure 15.55 Dermoid cyst lined by keratinized epidermis with breathing, speaking, closing the mouth and eating. Sigs: The size may vary up to several centimeters in diameter. Fluctuation test is generally positive. If superficial, it is yellow to white and surface is smooth and non ulcerated until traumatized. Soft to firm, fluctuant, rubbery or cheesy sharply delineated with straw colored fluid (Fig. 15.54). It may be fluctuant and doughy depending on the content. It does not move with protrusion of the tongue or deglutition. Double chin variety: It occur in inframylohyoid variety when it causes swelling in the sub-mental area and it give rise to a ‘double chin’ appearance.

and shows dermal appendages, the lumen is filled with keratin

Histopathological Features (Fig. 15.55) They are lined by orthokeratinized epidermis. Cysts of the floor of the mouth lined predominately by secretory epithelium are probably of salivary duct origin. Dermoid cyst is characterized by presence of one or more dermal appendages such as hair follicles, sweat glands or sebaceous glands in the wall with the lumen usually filled with keratin.

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Surgical excision is the treatment of choice. It should be excised through the floor of mouth by retracting the posterior border of the mylohyoid muscle. Points to Remember Midline of the floor of mouth, painless swelling, fluctuation test positive, soft to firm, rubbery or cheesy, double chin appearance, orthokeratinized epidermis, one or more dermal appendages.

BRANCHIAL CLEFT CYST It is also called as cervical lymphoepithelial cyst.

Pathogenesis It develop from remnant of branchial cleft as these cyst occur in embryonic gill arch apparatus. Another version is that it arises from parotid epithelium that becomes entrapped in upper cervical lymph nodes during embryonic life. They usually develop from 2nd branchial arch.

Clinical Features Age: It occurs in the age group of 20 to 40 years. Site: Location is superficially in the neck, close to the angle of the mandible, anterior to the sternocleidomastoid muscle. Two third appear on left side and one third appear on right side. Appearance: The neck lesions vary in size from small to very large (about 10 cms in diameter) soft fluctuant mass. Symptoms: There is swelling, which may be progressive or intermittent and pain may also be a feature.

Histopathological Features (Fig. 15.56) Cyst is lined by stratified squamous epithelium which may or may not be keratinized. Wall of cyst contain lymphoid tissue, germinal center formation.

Management Surgical removal should be done and this cyst never recurs. Points to Remember Anterior to the sternocleidomastoid muscle, soft fluctuant mass, pain, stratified squamous epithelium, lymphoid tissue, germinal center formation.

Figure 15.56 Branchial cyst lined by stratified squamous

epithelium. The cystic wall typically contains lymphoid tissue

ORAL LYMPHOEPITHELIAL CYST It originates from cystic transformation of glandular epithelium entrapped within the oral lymphoid aggregates during embryogenesis. Epithelium in lymphoepithelial cyst might be derived from the ductal epithelium of salivary glands. Lymphoid tissue consists of Waldeyer’s ring which includes palatine tonsil, lingual tonsil and pharyngeal adenoids. This tissue has a close relationship overlying mucosal epithelium. This epithelium invaginates into tonsillar tissue resulting in pouches or tonsillar crypts. These crypts filled with keratin debris producing keratin filled cyst below the mucosal surface.

Clinical Features Age: The age ranges from 16 to 69 years with a there was male to female ratio of 3:1. Site: It affects mainly the floor of mouth and the tongue. These cyst may develop in the area of palatine tonsil. Appearance: The cyst appears as a nonulcerated freely movable mass which has been present for a period ranging from 1 month to a year. Symptoms: Patients may complain of swelling and discharge. Sigs: Size may vary from few mm to 2 cm fairly mobile, superficial soft fluctuant, sharply delineated swelling. The usual observation was of round or oval swelling of the oral mucosa of normal color but when large swelling they were yellow or white in color.

Cyst of Orofacial Region

Histopathological Features

Pathogenesis

Cyst lined with thin stratified squamous epithelium, usually parakeratinized devoid of rete pegs. The lining epithelial is quite thin; lacking rete pegs and is usually parakeratinized and occasionally orthokeratinized. The lumen of the cyst often contains sloughed epithelial cells, lymphocytes and eosinophilic amorphous coagulum. Occasionally, lining epithelium is of columnar type with or without goblet cells.

Gorlin pointed out that in the 3 to 4 mm embryo, the undifferentiated primitive stomach lies in the mid-neck region, not far from anlage of the tongue. Gastric mucosa has been shown to occur in the esophagus of 7.8% of infant and in 51 percent of these, heterotrophic tissues were located in the upper third. They suggested that in the sublingual region of the oral cavity and in the region of apex and dorsum of tongue, the ectodermal and endodermal epithelia fuse and this will explain presence of heterotrophic gastric or intestinal mucosa.

Management Local surgical excision should be carried out. Points to Remember Nonulcerated freely movable mass, swelling, parakeratinized devoid of rete pegs, sloughed epithelial cells, lymphocytes.

THYROGLOSSAL DUCT CYST It is described in chapter of tongue.

ANTERIOR MEDIAN LINGUAL CYST It is also called as intralingual cyst of foregut origin.

Clinical Features Age: It is a rare lesion and is commonly found in children. It can be present since birth and recurrence is common. Site: It is a fluctuant swelling in anterior half of the tongue. Symptoms: There may be difficulty in feeding.

Clinical Features Age and sex: Most cases occur in infants and young children between the ages of 2 to 11 years. The male to female ratio is 3:1. Site: Common location in the anterior part of the tongue, floor of mouth and submandibular gland. The cyst may be enclosed entirely within the tongue or floor of mouth or may communicate with the surface.

Histopathological Features The cyst may be lined partly by stratified squamous epithelium and partly by gastric or intestinal mucosa.

Management Surgical excision. Recurrence is rare but has been reported. Points to Remember Oral alimentary tract cyst, anterior part of the tongue, stratified squamous epithelium, gastric or intestinal mucosa.

Histopathological Features It is lined by pseudo-stratified ciliated columnar epithelium and by cuboidal epithelium. Points to Remember Intralingual cyst of foregut origin, fluctuant swelling, difficulty in feeding, pseudo-stratified ciliated columnar epithelium.

ORAL CYST WITH GASTRIC OR INTESTINAL EPITHELIUM It is also called as ‘oral alimentary tract cyst’.

CYSTIC HYGROMA It is a developmental abnormality in which there is progressive dilatation of lymphatic channels.

Clinical Features Site: It frequently involves the neck and face, although it can occur anywhere in the body. Age: It is often present at birth and most cases are diagnosed before the age of 2 years. Symptoms: Those that involve facial tissue produce a swelling often painless and usually compressible.

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Signs: The overlying skin may be blue and the swelling transilluminates. There may be a history of gradual or sudden enlargement. 378

Histopathological Features Histologically, the cystic hygroma consists of dilated cystic spaces lined by endothelial cells.

Management Complete surgical removal of the mass should be done. Points to Remember Swelling often painless, blue overlying skin, dilated cystic spaces lined by endothelial cells.

FOLLICULAR CYSTS OF THE SKIN These are keratin filled lesion which arises from hair follicle. These cyst arise after localized inflammation of hair follicles. Types • Infundibular cyst or epidermoid cyst: It is derived from follicular infundibulum • Pilar, tricholemmal or isthmuscatagen cyst: These are located on scalp • Epidermal inclusion (implantation) cyst: These occur after traumatic implantation of epithelium.

Clinical Features Age and sex distribution: Young patient have it on face and older patient have it on back. Males are commonly affected than female. In case of pilar cyst female is commonly affected than male. Location: It is seen in head, face, neck, and back of the patient. Appearance: It appear as nodular fluctuant subcutaneous lesion which can be associated with inflammation.

Management Conservative surgical excision can be carried out. Points to Remember Head, face, nodular fluctuant subcutaneous lesion, stratified squamous epithelium resembling epidermis, multinucleated giant cells.

NASOPHARYNGEAL CYST They are rare clinical entities. They may be classified as congenital or acquired and in midline or lateral. They are lined by ciliated or non ciliated columnar epithelium with areas of squamous metaplasia in response to inflammatory stimuli. Lymphoid follicles are present in the wall. Congenital midline cyst arises either from the pharyngeal bursa or from Rathke’s pouch. Cysts arising from Rathke’s pouch are exceedingly rare. They have a median base attached to the nasopharyngeal vault and lie anterior to the usual site of origin of retention and pharyngeal bursa cyst. They are lined by stratified squamous epithelium, in keeping with their ectodermal origin.

THYMIC CYST They are rare clinical entities, which arise, in persistent thymic tissue, which may occur in any location between the angle of the mandible and midline of the upper neck to the sternal notch. Histologically, the cyst is lined by squamous and cuboidal epithelium and thymic tissue is present in the wall.

CYSTS OF SALIVARY GLANDS It is described in chapter of salivary gland disorders.

PARASITIC CYST Hydatid Cyst

Sign: Lesion is movable and shells out easily.

It is also called hydatid disease or echinococcosis. It is caused by the larvae E. granulosus, the dog tapeworm and E. multilocularis.

Histopathological Features

Pathogenesis

Cavity is lined by stratified squamous epithelium resembling epidermis. Granular cell layer is also seen. In some case prominent granulomatous inflammatory reaction like multinucleated giant cells can be seen in lesion. Pilar cyst granular cell layer is absent.

This tapeworm lives in the intestinal tract of the dog. Its ova are excreted in the faeces of the dog and may be ingested by the intermediate host like cattle sheep and pigs. Man is also susceptible as an intermediate host as dogs are common household pets, so may accidentally ingest the

Cyst of Orofacial Region

ova. The ingested ova hatch in the upper gastrointestinal tract, from where the small embryo permeate the intestinal mucosa and are distributed through the blood vessels and lymphatics to all parts of the body.

Clinical Features Site: It is more common in liver, but others are found in lung, bones and brain. Symptoms: Usually they are asymptomatic but they enlarge progressively to cause pressure symptoms. Signs: Liver involvement causes hepatomegaly and jaundice. Pulmonary hydatid cyst may cause shortness of breath and hemoptysis. Complications: Rare complication of hydatid cyst includes rupture, suppuration and calcification of the cyst.

Management The ideal treatment for hydatid cyst is surgical. Limiting contact between dogs and humans and deworming dogs at regular intervals are useful steps towards prevention. Points to Remember Echinococcosis, larvae E. granulosus, asymptomatic, hepatomegaly, jaundice, intraorally tongue, painless, progressively increasing, soft, elastic, speech and mastication difficulties, outer layer fibrous tissue chronic inflammatory cells, intermediate layer white, nonnucleated and consists of numerous delicate laminations, innermost layer nucleated germinal layer, hydatid sand.

CYSTICERCOSIS CELLULOSE

Oral Manifestations

Pathogenesis

Site: Intraorally, found in tongue and angle of mandible.

Man develops cysticercosis through the larval form, cysticercus cellulose, of the pork tapeworm Taenia solium. He can act as both the intermediate and the definitive host. The adult worm may be ingested from inadequately heated or frozen pork. Alternatively, man may ingest the cysticerci themselves from infested pork and these develop into adult worms. These lives attach to the wall of the small intestine where they fully grow and at times reach a length of 7 mm. Gravid proglottids or eggs begin to drop off and are passed in the feces. In this way, man through contaminated food or from their own dirty hands may ingest them or they may be regurgitated into the stomach. In the stomach, their covering is digested off and the larval forms are hatched. These penetrate the intestinal mucosa and are then distributed through the blood vessels and lymphatics to all the parts of the body where they develop into cysticerci.

Appearance: Oral hydatid cyst presents as painless, progressively increasing, soft, elastic and well circumscribed fluctuant swelling. Symptoms: They may pose speech and mastication difficulties.

Histopathological Features The mature cyst consists of three layers, one of host and two of parasitic origin. The outer layer which is derived from the host is made up of fibrous tissue and is infiltrated by chronic inflammatory cells, eosinophils, lymphocytes and giant cells. The intermediate layer is white, non-nucleated and consists of numerous delicate laminations. It usually shrinks away from the outer fibrous layer when the tension within the cyst is relieved. Innermost layer is a nucleated germinal layer. The cystic fluid is usually clear, albumin free and contains the so called hydatid sand consisting of brood capsule and scolices. The brood capsules or daughter cysts develop originally as minute projections of germinative layer which develops a central vesicle and become a minute cyst. Scolices of the head of the worm develop in the inner aspect of the brood capsule. It is when they separate from the germinative layer that they form the hydatid sand.

Clinical Features It depends upon the site and the number of the cysticerci in the body. During the stage of invasion there are no symptoms or slight muscular pain and mild fever may be present. CNS involvement produces serious effects.

Oral Manifestations There is very little report about cysticercosis of oral region. In oral cavity, most common site involved is the tongue. Other sites involved are cheek and lips. There is

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a firm mass and contains watery fluid and coiled white structure apparently attached to the inner aspect of cyst (Fig. 15.57A). It is a painless, well circumscribed, elastic and fluctuant swelling.

Histopathological Features It shows dense fibrous outer capsule which is derived from host tissue (Fig. 15.57B). This contains a fairly dense inflammatory cell infiltrate consisting predominantly of lymphocytes, plasma cells and histiocytes. Few foci of dystrophic calcification are present in this capsule and some of these are concentrically laminated. Within the capsule is a delicate double layered membrane Figure 15.58 Lesion show delicate double layered membrane consisting of the outer acellular hyaline, eosinophilic layer and inner cellular layer (High power view)

consisting of an outer acellular hyaline, eosinophilic layer and an inner sparsely cellular layer (Fig. 15.58). This layer has a loose attachment to the fibrous capsule and is readily torn away from it. The cyst lies within this membrane and contains larval form of T. solium.

Management Cutaneous cyst should be surgically removed. Mebendazole has some value in the treatment. Pork should be properly cooked as preventive measures. Figure 15.57A Gross specimen hydatid cyst

Points to Remember Taenia solium, no symptoms, tongue common site, fairly dense inflammatory cell infiltrate consisting, foci of dystrophic calcification, larval form of T. solium, mebendazole.

SYNDROMES ASSOCIATED WITH ODONTOGENIC CYSTS Jaw Cyst-Basal Cell Nevus-bifid Rib Syndrome It is also called as ‘nevoid basal cell carcinoma’, ‘Gorlin’s and Goltz’s syndrome’. It is transmitted as autosomal dominant trait with poor degree of penetrance and variable expressivity.

Clinical Features Figure 15.57B Cysticercosis cellulose the outer fibrous

capsule and inner T. solium (Low power view)

Age: It appears early in life after 5 years and before 30 years.

Cyst of Orofacial Region

Cutaneous anomalies: Basal cell carcinoma, dermal cyst and tumors, palmar pitting, palmar and plantar keratosis and dermal calcinosis. Nevoid basal cell carcinoma is brownish colored papules predominant on skin, neck and trunk. Skin lesions are small, flattened, flesh colored or brownish papules occurring anywhere in the body, but are prominent on the face and trunk. Basal cell carcinoma is less aggressive in this syndrome than in solitary basal cell carcinoma. Skeletal abnormalities: Rib anomalies and brachymetacarpalism, bifid rib, agenesis, deformity and synostosis of rib; kyphoscoliosis, vertebral fusion, polydactyly and shortening of metacarpals. Ophthalmologic abnormalities: Hypertelorism with wide nasal bridge, dystopia canthorum, congenital blindness and internal strabismus. Neurological anomalies: Mental retardation, calcification of falx cerebri and other parts of dura, agenesis of corpus callosum, congenital hydrocephalus and occurrence of medulloblastomas. Sexual abnormalities: Hypogonadism in males and ovarian tumors.

Oral Manifestations Jaw lesions appear as multiple odontogenic keratocysts usually appearing in multiple quadrants. Mild mandibular proganthism is seen.

Radiographic Features Jaw cysts appear as a multiple cyst like radiolucency of variable size varying from few millimeters to several centimeters. They occur most frequently in premolarmolar region. Radiopaque lines of calcified falx cerebri are prominent on PA projection.

Histopathological Features They are odontogenic keratocyst. They have more satellite cyst, solid island of epithelial proliferation. Foci of calcification is also seen.

Management Complete enucleation of the lesion of OKC should be done. Periodic examination and genetic counseling should be done.

Points to Remember Cutaneous anomalies, skeletal abnormalities, ophthalmologic abnormalities, neurological anomalies, sexual abnormalities, multiple odontogenic keratocysts, radiolucency of variable size, foci of calcification, calcified falx cerebri.

TREATMENT OF CYSTS Regression of Cysts without Surgical Treatment There is good evidence that some small radicular cyst will regress if the necrotic pulp remnant and bacteria are removed from the root canal of the causative tooth and the canal is effectively filled. Circumscribed rounded zone of periapical bone destruction perhaps up to 1.5 cm in diameter will be seen in some patients to reduce in size and resolve over a period of month.

Marsupialization of Dental Cysts It is known as ‘Partsch’s operation’ as it is discovered by Partsch. It involves making an opening into the cyst as large as practical and packing the cavity. It is a more effective way of emptying a cyst.

Indications Age: In a young child, with developing tooth germs. Proximity to vital structure: When proximity of the cyst to vital structure can create an oronasal or oroantral fistula or injure the neurovascular structure, this treatment modality should be considered. Eruption of teeth: In a young patient with a dentigerious cyst, marsupialization will permit the eruption of the unerupted tooth or any other developing tooth which has been displaced. Vitality of teeth: When the apices of many adjacent erupted teeth are involved within a large cyst, enucleation can prejudice the vitality of these teeth.

Advantages ∙ ∙

The procedure at least for large cysts, is technically simple. Even quite large cysts can be dealt with under local anesthesia. As anesthesia of deeper recesses is not

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∙ 382

∙ ∙ ∙ ∙ ∙

essential and this is particularly an advantage in the maxilla. Because the deeper part of the lining is not disturbed, adjacent important structures are not put at risk, i.e. the blood vessels to the apices of adjacent vital teeth, the inferior dental neurovascular bundle and the integrity of lining of the antrum or nose are well preserved. Marsupialization may be the best way to conserve the tooth of origin of a dentigerous cyst and to permit its eruption. It is the simplest way to treat a fracture complicating a large cyst of the mandible. Prevents oronasal and oroantral fistula. It reduces operating time and blood loss and helps in the shrinkage of cystic lining. Alveolar ridge is preserved.

Disadvantages ∙

∙ ∙ ∙ ∙ ∙ ∙

The need for regular postoperative care, possibly over a substantial period of time. It is necessary to supervise healing so that opening remains large in proportion to the underlying cavity. A rapid reduction in the size of the opening may be difficult to prevent. Indeed an opening into a large cyst in the ramus may present significant problems. Uneven reduction in size of the cavity may result in slit like cavity, difficult to keep clean. The need for greater attention to the details of surgical technique than is at first apparent, to avoid complications. Risk of invagination and new cyst formation. Prolonged follow-up visits and periodic irrigation. Regular adjustments of plug.

Enucleation Enucleation allows for the cystic cavity to be covered by a muco-periosteal flap and the space fills with blood clot which will eventually organized and form normal bone.

Indications ∙ ∙

Treatment of odontogenic keratocyst. Recurrence of cystic lesion of any cyst type.

Advantages ∙ ∙ ∙ ∙

Primary closure of the wound. Healing is rapid. Post operative care is reduced. Thorough examination of the entire cystic cavity can be done.

Disadvantages ∙ ∙ ∙ ∙ ∙

After primary closure, it is not possible directly observe the healing of the cavity as with marsupialization. In young persons, the unerupted teeth in a dentigerious cyst will be removed with the lesion in this mode of treatment. Removal of large cysts will weaken the mandible making it prone to jaw fracture. Damage to adjacent vital structures. Pulpal necrosis.

BIBLIOGRAPHY 1. Al-Talabani NG and Smith CJ. Experimental dentigerous cysts and enamel hypoplasia: their possible significance in explaining the pathogenesis of human dentigerous cysts. Journal of Oral Pathology. 1980;9:82-91. 2. Browne RM. The odontogenic keratocyst: clinical aspects. British Dental Journal. 1970;128:225-31. 3. Browne RM. The odontogenic keratocyst-histological features and their correlation with clinical behaviour. British Dental Journal. 1971a;131:249-59. 4. Dominguez FV and Keszler A. Comparative study of keratocysts, associated and non-associated with nevoid basal cell carcinoma syndrome. Journal of Oral Pathology. 1988;17:39-42. 5. Gardner DG and Gullane PJ. Mucoceles of the maxillary sinus. Oral Surgery, Oral Medicine, Oral Pathology. 1986;62:538-43. 6. Gardner DG, Kessler HP, Morency R and Schaffner DL. The glandular odontogenic cyst: an apparent entity. Journal of Oral Pathology. 1988;17:359-66. 7. Killey HC and Kay LW. Benign mucosal cysts. In: Kay L.W., ed. Oral Surgery IV (Transactions of the Fourth International Conference on Oral Surgery). Copenhagen: Munksgaard; 1973. pp. 169-74. 8. Killey HC, Kay LW and Seward GR. Benign Cystic Lesions of the Jaws, their Diagnosis and Treatment, 3rd edn.Edinburgh and London: Churchill Livingstone; 1977. 9. Main DMG. Epithelial jaw cysts: a clinicopathological reappraisal. British Journal of Oral Surgery. 1970a;8:114-25. 10. Main DMG. The enlargement of epithelial jaw cysts. Odontologisk Revy. 1970b;21:29-49. 11. Motamedi MH. Aneurysmal bone cysts of the jaws: clinicopathological features, radiographic evaluation and treatment analysis of 17 cases. Journal of Craniomaxillofacial Surgery. 1998;26:56-62. 12. Motamedi MH. Destructive aneurysmal bone cyst of the mandibular condyle: report of a case and review of the literature. Journal of Oral and Maxillofacial Surgery. 2002;60:1357-61.

Cyst of Orofacial Region 13. Motamedi MHK and Talesh KT. Management of extensive dentigerous cysts. British Dental Journal. 2005;198:203-6. 14. Mourshed F. A roentgenographic study of dentigerous cysts. I. Incidence in a population sample. Oral Surgery, Oral Medicine, Oral Pathology. 1964a;18:47-53. 15. Mourshed F. A roentgenographic study of dentigerous cysts. II. Role of roentgenograms in detecting dentigerous cyst in the early stages. Oral Surgery, Oral Medicine, Oral Pathology. 1964b;18:54-61. 16. Mourshed F. A roentgenographic study of dentigerous cysts. III. Analysis of 180 cases. Oral Surgery, Oral Medicine, Oral Pathology. 1964c;18:466-73. 17. Myall RWT, Eastep PB and Silver JG. Mucous retention cysts of the maxillary antrum. Journal of the American Dental Association. 1974;89:1338-42. 18. Myoung H, Hong SP, Hong SD, et al. Odontogenic keratocyst: review of 256 cases for recurrence and clinicopathologic parameters. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001;19:328-33. 19. Nagao Y, Nakajima T, Fukushima M and Isbiki T. Calcifying odontogenic cyst: a survey of 2 cases in the Japanese literature. Journal of Maxillofacial Surgery. 1983;11:174-9. 20. Nair PNR. Review. New perspectives on radicular cysts:do they heal? International Endodontic Journal. 1998;31:155-60. 21. Nair PNR. Non-microbial etiology: periapical cysts sustain post-treatment apical periodontitis. Endodontic Topics. 2003;6:96-113. 22. O’Hara AJ, Collins T and Howell JM. Gingival eruption cysts induced by cyclosporine administration to neonatal dogs. Journal of Clinical Periodontology. 2002;29:507-13. 23. Ohishi M, Ishii T, Shinohara M and Horinouchi Y. Dermoid cyst of the floor of the mouth: lateral teratoid cyst with sinus tract in an infant. Oral Surgery, Oral Medicine, Oral Pathology. 1985;60:191-4. 24. Pindborg JJ and Hansen J. Studies on odontogenic cyst epithelium. 2. Clinical and roentgenologic aspects ofodontogenic keratocysts. Acta Pathologica et Microbiologica Scandinavica (A). 1963;58:283-94. 25. Pindborg JJ and Hjørting-Hansen E. Atlas of Diseases of the Jaws, 1st edn. Copenhagen: Munksgaard; 1974. 26. Pindborg JJ, Kramer IRH and Torloni H. Histological Typing of odontogenic Tumours, Jaw Cysts, and Allied Lesions. 1st edn. Geneva: World Health Organization; 1971. 27. Pindborg JJ, Philipsen HP and Henriksen J. Studies onodontogenic cyst epithelium keratinization in odontogenic

28.

29.

30. 31. 32.

33.

34.

35.

36. 37.

38.

39.

40.

cysts. In: Fundamentals of Keratinization. Washington DC: American Association for the Advancement of Science; 1962. p. 151. Reichart PA and Philipsen HP. Aneurysmal bone cavity (Aneurysmal bone cyst). In: Odontogenic Tumors and Allied Lesions, 1st edn. London: Quintessence; 2004. pp. 335-41. Robinson L and Hjørting-Hansen E. Pathologic changes associated with mucous retention cysts of minor salivary glands. Oral Surgery, Oral Medicine, Oral Pathology. 1964;18:191-205. Saunders IDF. Bohn’s nodules: a case report. British Dental Journal. 1972;32:457-8. Scully C and Burkhardt A. Tissue markers of potentially malignant human oral epithelial lesions. Journal of Oral Pathology and Medicine. 1993;22:246-56. Shear M. The aggressive nature of the odontogenickeratocyst: is it a benign neoplasm? A review. Part 3. Immunocytochemistry of cytokeratin and other epithelial cell markers. Oral Oncology. 2002c;38:407-15. Shrestha P, Yamada K, Higashiyama H, Takagi H and Mori M. Epidermal growth factor receptor in odontogenic cysts and tumors. Journal of Oral Pathology and Medicine. 1992;21:314-7. Svensson B and Isacsson G. Benign osteoblastoma associated with an aneurysmal bone cyst of the mandibular ramus and condyle. Oral Surgery, Oral Medicine, Oral Pathology. 1993;76:433-6. Takeda Y and Yamamoto H. Case report of a pigmented dentigerous cyst and a review of the literature on pigmented odontogenic cysts. Journal of Oral Science. 2000. Toller PA. Origin and growth of cysts of the jaws. Annals of the Royal College of Surgeons of England. 1967;40:306-36. Vencio EF, Mota A, Pinho C de M and Filho AAD. Odontogenic keratocyst in maxillary sinus with invasive behaviour. Journal of Oral Pathology and Medicine. 2006;35:249-51. Weidner N, Geisinger KR, Sterling RT, Millerm T and Yen TSB. Benign lymphoepithelial cysts of the parotid gland. A histologic, cytologic and ultrastructural study. American Journal of Clinical Pathology. 1986;85:395-401. Wilson DF and Ross AS. Ultrastructure of odontogenic keratocysts. Oral Surgery, Oral Medicine, Oral Pathology. 1978;45:887-93. Wood RE, Nortje CJ, Padayachee A and Grotepass F. Radicular cysts of primary teeth mimicking premolar dentigerous cysts: report of three cases. Journal of Dentistryfor Children. 1988;55:288-90.

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MULTIPLE CHOICE QUESTIONS 384

1. Which one of the following is an example of nonodontogenic cyst: a. Eruption cyst b. Nasolabial cyst c. Primordial cyst d. Glandular odontogenic cyst





2. Following are the cysts of soft tissues of mouth, face and neck except: a. Dermoid cyst b. Thyroglossal duct cyst c. Paradental cyst d. Cystic hygroma 3. A thin layer of nonkeratinized stratified squamous epithelium with absence of rete pegs is histopathological feature of: a. OKC b. Eruption cyst c. Primordial cyst d. Dentigerous cyst 4. Multiple OKC are found in the following syndromes, except: a. Gorlin-Goltz syndrome b. Marfan syndrome c. Costen syndrome d. Noonan’s syndrome





5. A corrugated parakeratinized stratified epithelium without rete ridges seen in: a. OKC b. Dentigerous cyst c. Gorlin’s syndrome d. Glandular odontogenic cyst 6. ‘Picket fence’ or ‘tombstone pattern’ seen in: a. Dentigerous cyst b. Primordial cyst c. Radicular cyst d. Dental lamina cyst 7. Focal areas of stellate reticulum and ghost cells present in: a. Gingival cyst of adults b. Lateral periodontal cyst c. Gorlin’s cyst d. Radicular cyst

8. Arcading pattern of ret pegs and Rushton bodies present in: a. Radicular cyst b. Gorlin’s cyst c. Paradental cyst d. Nasopalatine cyst 9. Cholesterol clefts is present in: a. Median mandibular cyst b. Radicular cyst c. Nasopharyngeal cyst d. Traumatic bone cyst 10. Connective tissue capsule with prominent neurovascular bundle and respiratory epithelium present in: a. Nasopalatine cyst b. Radicular cyst c. Paradental cyst d. Dentigerous cyst 11. Dentigerous cyst associated with: a. Gardner syndrome b. Ectodermial dysplasia c. Maroteaux-Lamy syndrome d. Gorlin-Goltz syndrome 12. Percoronal cyst is: a. OKC b. Gorlin cyst c. Dentigerous cyst d. Gingival cyst of newborn 13. Gingival cyst of newborn originates from:a: a. Remnants of dental lamina b. Epithelial rest of Malassez c. Oral epithelium d. None of the above 14. Bohn’s modules present on: a. Hard Palate b. Soft Palate c. Junction of hard and soft palate d. None of the above 15. Features of basal cell nevus syndrome are: a. Palmar and plantar keratosis b. Bifid rib c. Multiple odontogenic keratocyst d. All of the above

Cyst of Orofacial Region 16. The radiological variant of the dentigerous cyst may be: a. Lateral type b. Circumferential type c. Central type d. All the above

17. The treatment of choice of eruption cyst is: a. Surgical newborn b. Curettage c. Marsupilization d. No treatment

18. Nodules filled keratin are found along the midpalatine raphe are: a. Dental lamina cyst b. Bohn’s modules c. Epstein’s pearls d. None of the above

19. Histologic features which are considered as manifestations of developing neoplasia in a dentigerous cyst is/area: a. Hyperchromatism of basal cell nuclei b. Palisade arrangement with polarization of basal cells c. Cytoplasmic vacuolization with inter cellular spacing of lining epithelium d. All of the above 20. ‘Envelopment’ radiological type of keratocyst is referred as: a. Those which forms in place of normal teeth b. Those in the ascending ramus away from the teeth c. It is referred to a varity of keratocyst which embraces an adjacent unerupted tooth d. None of the above

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16

Periodontal Pathology

Vivek Thombre, Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline          Â

Fibromatosis gingiva Retrocuspid papilla Gingival inflammation or gingivitis Necrotizing ulcerative gingivitis Desquamative gingivitis Plasma cell gingivitis Granulomatous gingivitis Gingival abscess Pericoronal abscess Chronic inflammatory enlargement

Diseases of the periodontium are commonly encountered in daily practice. It is one of the implicated causes of loss of teeth in adults. In nearly every case, the condition begins as a minor localized disturbance which unless adequately treated, may gradually progress to the resorption of alveolar bone and exfoliation of tooth. Periodontal diseases are classified mainly into two groups, on the basis of pathological process, i.e. inflammation (gingivitis, periodontitis) and dystrophy (gingivosis and periodontosis).

FIBROMATOSIS GINGIVA It is also called elephantiasis gingivae, congenital macrogingivae. It is a slowly progressive diffuse over­ growth of gingival fibrous connective tissue. Inconsistent with the name, the disorder bears no relationship with the hypercellular and neoplastic fibromatosis that can occur

        Â

Gingival enlargement due to drugs Pregnancy tumor Granuloma pyogenicum Periodontal pockets Adult periodontitis Rapidly progressive periodontitis Aggressive periodontitis/Juvenile periodontitis Papillion-Lefevre syndrome Haim-Munk syndrome

in soft tissue and bone. It may be familial, i.e. hereditary having autosomal dominant as well as recessive type or idiopathic.

Clinical Features Age: It may be present at birth or may become apparent with eruption of deciduous or permanent teeth. Mostly, the enlargement begins before age of 20. Syndrome associated: The familial variations may occur as an isolated finding or in association with one of the hereditary syndrome like Zimmermann­Laband, Murray­ Puretic­Drescher, Rutherford, Multiple Hamartoma, and Cross Syndrome. Other findings such as hypertrichosis, epilepsy, mental retardation, sensinural deafness, hypothyroidism, chondrodystrophia, and growth hormone deficiency are associated with gingival fibromatosis.

Periodontal Pathology

Appearance: It is manifested as dense smooth diffuse or nodular overgrowth of gingival tissue of one or both arches that usually occurs at the time of eruption of teeth. It has a characteristic pebbled and finely stippled surface. In some cases, surface has a nodular appearance and may develop numerous papillary projections. Tissue is of normal or pale color. In some cases, it may appear pink. It is often so firm, leathery and dense that it prevents normal eruption of teeth. Sign and symptoms: It is not painful and shows no tendency for hemorrhage. Extent may be such that the crown of fully erupted teeth may be hidden. Typically, extension past the alveolar mucosal junction into the mucobuccal fold is not seen, but palatal extension can cause significant distortion of the contour of the palate and, many of the times almost can meet in the midline (Figs 16.1 and 16.2). The dense firm gingival swelling results in varying spacing between the teeth and change in profile and facial appearance. The frenular attachments may appear to divide the gingival tissues of the alveolar ridge into lobules.

387

A

Histopathological Features (Fig. 16.3) Epithelium is thickened with elongation of rete pegs that extend deeply into the underlying fibrous connective tissue. The bulk of the tissue is composed of dense fibrous connective tissue which is hypocellular and hypovascular. Bundles of collagen fibers are coarse and show few interspersed fibroblasts or blood vessels. B Figures 16.2A and B Fibromatosis gingivae preventing

normal eruption of teeth

Mucoid changes in fibrous tissue are frequent and occasional presence of giant cells has been noted. Inflammation is mostly absent or mild, and dystrophic calcification is sometimes seen. The covering epithelium is usually mildly acanthotic and some hyperkeratosis may be present. Electron microscopic study shows both fibroblasts and myofibroblast like cells.

Management

Figure 16.1 Dense nodular overgrowth seen in patient

of fibromatosis gingivae

Surgical correction (gingivectomy) should be done along with instructions for oral hygiene and follow­up, as there is tendency for recurrence within a few years. In severe cases, selective extraction of teeth is required to achieve normal morphology of gingiva.

Textbook of Oral Pathology

The covering epithelium often is thin and atrophic, although rete ridges may appear narrow and elongated. The underlying connective tissue is sometimes highly vascularized and may exhibit large stellate fibroblasts as well as occasional epithelial rests. The stellate fibroblasts may contain several nuclei.

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Management It disappears with the age so no treatment is necessary for this disease. Points to Remember Figure 16.3 Histopathological picture of fibromatosis

gingivae

Points to Remember Elephantiasis gingivae, Zimmermann­Laband, hypertri­ chosis, epilepsy, mental retardation, diffuse or nodular overgrowth of gingival tissue, pebbled and finely stip­ pled surface, teeth may be hidden, elongation of rete pegs, collagen fibers are coarse, surgical correction (gin­ givectomy).

RETROCUSPID PAPILLA It is a small elevated nodule located on the lingual mucosa of the mandibular cuspids.

Clinical Features Age and sex distribution: It is extremely common in children usually between the age of 8 to 16 years. The prevalence in adults drops to 6 to 19 percent, suggesting it as an anatomic variation that disappears with age. There is no sex predilection. Location: It is located lingual to the mandibular cuspids, between the free gingival margin and the mucogingival junction. Appearance: It is a soft, well­circumscribed, sessile, mucosal nodule, commonly bilateral. Typically appears as a small, pink papule that measures less than 5 mm in diameter.

Histopathological Features The structure appears as an elevated mucosal tag, often showing mild hyperorthokeratosis or hyperparakeratosis, with or without acanthosis.

Lingual to the mandibular cuspids, soft, well­circum­ scribed, sessile, mucosal nodule, mild hyperorthokerato­ sis or hyperparakeratosis, rete ridges may appear narrow and elongated, stellate fibroblasts.

GINGIVAL INFLAMMATION OR GINGIVITIS It may occur in an acute, subacute, or chronic form. Etiology Local factors • • • • • • •

Microorganisms Calculus Food impaction Faulty or irritating restorations or appliances Mouth-breathing Tooth malposition Chemical and drug application

Systemic factors • • • • • •

Nutritional disturbances Pregnancy Diabetes mellitus Psychiatric phenomena Hormonal changes Allergy and hereditary factor.

Etiology Local Factors Microorganisms: The plaque associated with gingivitis is complex and heterogeneous. In early stages of gingivitis, the Actinomyces group of organisms are the dominant genus in the supragingival plaque. In children, flora associated with gingivitis is different as compared to adults. In

Periodontal Pathology

children, it is associated with L. eptotrichia, Selenomonas and some Bacteroides. In patient with persistent gingivitis, there is appearance of gram negative rods and filamentous microorganism which are followed by spirochetes. There is an increase of P. intermedia in pregnancy gingivitis. Calculus: Either supragingival or subgingivae or both cause irritation of the contacting gingival tissue. This irritation is produced by the by­products of the microorganisms or by the mechanical friction resulting from the hard, rough surface of the calculus. Food impaction: The impaction of food and accumulation of debris on the teeth due to oral negligence results in gingivitis. The degradation products of food debris may also prove irritating to the gingival tissues. Faulty or irritating restorations or appliances: Faulty restoration may act as an irritant to gingival tissues and thereby induce gingivitis. Overhanging margins of proximal restorations may directly irritate the gingiva and in addition allow the collection of food debris and organisms which add further insult to these tissues. Prosthetic and orthodontic appliances impinging on the gingival tissues produce gingivitis as a result of pressure due to and of the trapping of food and microorganisms. Mouth-breathing: Drying of the oral mucous membrane, because of mouth­breathing, due to environment of excessive heat or from excessive smoking, will result in gingival irritation with accompanying inflammation. Tooth malposition: Teeth which have erupted or which have been moved out of physiologic occlusion, due to repeated subjected to abnormal forces during mastication. Chemical and drug application: Many drugs like phenol, silver nitrates, volatile oils or aspirin, if applied to gingiva will provoke an inflammatory reaction.

Systemic Factors Nutritional disturbances: Nutritional imbalance is fre­ quently manifested as changes in the gingiva and deeper underlying periodontium. Pregnancy: Gingiva undergoes changes during pregnacy which are termed as ‘pregnancy gingivitis’.

Hormonal changes: Puberty, menstruation may also result in gingival inflammation. Others: Allergy and hereditary factor can also play important role in gingivitis. Types of Gingivitis (According to Course and Duration) • Acute gingivitis: It is a painful condition that comes on suddenly and is of short duration. • Subacute gingivitis: It is a less severe phase of the acute condition. • Recurrent gingivitis: It reappears after having been eliminated by treatment or disappears spontaneously and then reappears. • Chronic gingivitis: It comes slowly, is of long dura­ tion and is painless unless complicated by acute and subacute exacerbations. According to Distribution • Localized gingivitis: It is confined to the gingiva in relation to a single tooth or a group teeth. • Generalized gingivitis: It involves the entire mouth. • Marginal gingivitis: It involves gingival margins but may include a portion of the contiguous attached gingiva. • Papillary gingivitis: It involves the interdental papillae and often extends into the adjacent portion of the gingival margin. • Diffuse gingivitis: It affects the gingival margins, attached gingiva and interdental papillae. Types of Gingivitis • • • • • •

Plaque-related gingivitis Necrotizing ulcerative gingivitis Medication influence gingivitis Allergic gingivitis Specific infection-related gingivitis Dermatosis-related gingivitis.

Clinical Features

Diabetes mellitus: It is reported in association with severe periodontal diseases and gingival inflammation.

Symptoms: The earliest symptoms of gingival infla­ mmation are increased gingival fluid production and bleeding from the gingival sulcus on gentle probing and loss of stippling.

Psychiatric phenomena: It appears to have a definite influence upon the severity of periodontal disease.

Signs: Gingiva become light red. With progression, the area becomes reddened and edematous. Subsequently, the

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gingiva becomes brighter red or magenta. The color may be sometimes reddish blue or deep blue, if venous stasis has occurred (Figs 16.4 and 16.5). The color change starts in the interdental papillae, gingival margins and spreads to the attached gingiva. The consistency of gingiva may be spongy that pits on pressure and there may be marked softness of the gingiva. Sometimes in inflammation, there may be gingival enlargement because of edema or fibrosis and it may lead to changes in the contour of gingiva. The margins often appears blunted, receded, or hyperplastic.

Chronic hyperplastic gingivitis: When the chronic inflammation causes enlargement of due edema and fibrosis, is called chronic hyperplastic gingivitis.

Histopathological Features

It will reveal infiltration of the connective tissue by varying numbers of lymphocytes, monocytes and plasma cells. Polymorphonuclear leukocytes are occasionally noted, particularly beneath the crevicular epithelium which is non­ keratinized and irregular. It is infiltrated by inflammatory cells and is frequently ulcerated. The capillaries of the connective tissue may be engorged Puberty gingivitis: At the time of puberty, there is the increase chances of gingivitis. This is called puberty and sometimes may increase in number. Areas of fibrosis, hyperemia, edema and hemorrhage may be present. gingivitis.

Histopathological Types Early lesion: It follows when an infiltrate of lymphocytes, plasma cells, neutrophils, mast cells and macrophages appear in addition to the polymorphonuclear leukocytes. There is destruction of collagen. Initially, there is developmental of rete pegs with increases number of neutrophils in junctional epithelium.

Figure 16.4 Gingival inflammation presented

as redness of gingiva

Established lesion: In this stage, gingival pocket is formed and the infiltrate contains a predominance of plasma cells and lymphocytes; polymorphs continued to predominate in the junctional epithelium. The junctional epithelium shows elongated rete pegs in connective tissue with destruction of basement membrane. There is also cellular debris seen within the widened intercellular spaces of junctional epithelium. Advanced lesion: In this stage, there is marking of the initiation of periodontitis.

Management The local irritants should be removed at this stage. Thorough plaque control should be done with scaling and polishing. Use of chlorhexidine, on a short­term basis. Points to Remember

Figure 16.5 Localized gingivitis seen in lower anterior region

Loss of stippling, bleeding from the gingival sulcus on gentle probing, light red gingiva, gingiva may be spongy, puberty gingivitis, chronic hyperplastic gingivitis, lym­ phocytes, monocytes, plasma cells, polymorphonuclear leukocytes, infiltrated by inflammatory cell, fibrosis, hy­ peremia, edema and hemorrhage (chlorhexidine).

Periodontal Pathology

NECROTIZING ULCERATIVE GINGIVITIS It is an endogenous oral infection that is characterized by necrosis of gingiva. It is also called trench mouth due to its prevalence in combat trenches. Other synonyms for this are Vincent’s infection, acute ulceromembranous gingivitis, fusospirochetal gingivitis and acute ulcerative gingivitis. Tissue destruction is caused by endogenous organisms that act either on the tissue or, indirectly by triggering an inflammatory reaction. Recently, several investigators have discontinued the use of the word “acute” because, there is no chronic form of the disease.

Etiology

prevalence in the normal population is less than 0.1 percent; however, in stressed populations, the frequency increases up to 7 percent. In developing countries, ANUG typically occurs in very young children suffering from malnutrition. Symptoms: Onset is sudden with pain, tenderness, profuse salivation and peculiar metallic taste. There is spontaneous bleeding from gingival tissue. There is also a loss of sense of taste and diminished pleasure from smoking. The typical fetid odor ultimately develops, which may be extremely unpleasant. Teeth seem slightly to be extruded and are sensitive to pressure or have a woody sensation. They are slightly movable and the patient is unable to eat properly. Gingiva may become superficially stained with brown color. There is blunting of interdental papillae.

Signs: A typical lesion consists of necrotic punched out, crater like ulcerations developing most commonly on the interdental papillae and marginal gingiva. Removal of the lesion leaves raw surface. The surface of gingival crater is covered by a gray, pseudomembranous slough, demarcated from the reminder of the gingival mucosa by pronounced Local predisposing factors: Local factors like poor oral linear erythema (Fig. 16.6). hygiene, pre­existing marginal gingivitis and faulty dental If untreated, then it may result in progressive destruction restorations, deep periodontal pockets offered favorable of the periodontium, loss of attachment and denudation environment for occurrence of the disease. It is also seen of the roots (necrotizing ulcerative periodontitis) in area of gingiva traumatized by opposing in malocclude accompanied by increase in the severity of complications. teeth (Local trauma). As tobacco smoke has a direct toxic Regional lymph nodes are enlarged. There may be a effect on the gingiva, smoking and emotional stress can slight elevation of temperature. In some cases, process predispose for ANUG. may spread to adjacent soft tissue such as cheek, lip, Nutritional deficiency: Nutritional deficiency like vita­ tongue, palate and pharyngeal area (necrotizing ulcerative min C, vitamin B2 accentuate the severity of the pathologic mucositis; necrotizing stomatitis). changes induced by the fusospirochetal bacterial complex. Role of bacteria: It is caused by fusiform bacilli and spirochetes. In addition to this, species of Treponema, Selenomonas, and Fusobacterium, besides Prevotella intermedia are also responsible for acute necrotizing ulcerative gingivitis (ANUG).

Debilitating disease: Chronic diseases like leukemia, aplastic anemia, syphilis, severe gastrointestinal distur­ bances and AIDS can act as predisposing factors. Psychosomatic factors: The disease often occurs in association with a stress situation as well as with increase in adrenocortical secretion. Other systemic factors like inadequate sleep, marked malnutrition, immunosuppression and recent illness.

Clinical Features Age: It is most commonly seen in the age group of 16 to 30 years. Incidence: It can be seen in children from a low socioeconomic group, in underdeveloped countries. Several investigators have reported a higher frequency in whites. The

Figure 16.6 Necrotizing ulcerative gingivitis showing necrotic

tissue in lower anterior region

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Histopathological Features 392

It appears as a nonspecific acute necrotizing inflammation of the gingival margin involving, both, stratified squamous epithelium and the underlying connective tissue. The surface epithelium is destroyed and is replaced by a pseudomembranous meshwork of fibrin, necrotic epithelial cells, polymorphonuclear neutrophils and various types of microorganisms. The underlying connective tissue markedly appears with intense acute or mixed inflammatory infiltrate and extensive hyperemia with numerous engorged capillaries and a dense infiltration of PMN. Numerous plasma cells may appear in the periphery of infiltrate. Necrotic material and extensive bacterial colonization often are seen microscopically.

Treatment should include instructions on oral hygiene and patient motivation; identification and resolution of any predisposing factors. Follow­up appointments are necessary to reinforce the home care instructions and to rule out recurrence.

DESQUAMATIVE GINGIVITIS It is described as gingival epithelium that spontaneously sloughs or can be removed with minor manipulation. It is a clinical manifestation of several different vesiculoerosive diseases.

Etiology Dermatological diseases: Like lichen planus, mucous membrane pemphigoid, bullous pemphigoid or pemphigus.

Management

Infections: Tuberculosis, chronic candidiasis, histoplas­ The involved areas are isolated with cotton rolls and dried. mosis. Other diseases like endocrine imbalance, chronic infec­ A topical anesthetic is applied and after 2 to 3 minutes, the tion and drug reaction, abnormal response to irritation and areas are gently swabbed with a cotton pellet to remove the pseudomembrane and nonattached surface. After the idiopathic causes. It can be caused by chemical burns. area is cleansed with warm water, the superficial calculus Clinical Features is removed. The patient is told to rinse the mouth every 2 hours, with a glassful of an equal mixture of warm water Age and sex distribution: Both sexes are affected but it is and 3 percent hydrogen peroxide. Twice daily rinse with more prevalent in women and occurs after age of 40. 0.12 percent chlorhexidine is also effective. Appearance: Gingiva becomes bright red, edematous and Patients with severe ANUG and lymphadenopathy desquamation of the surface epithelium of the attached are treated with antibiotics Penicillin V­250 or 500 mg, gingiva is also seen. The facial surface is involved more 6 hourly or erythromycin 250 or 500 mg, 6 hourly with frequently than the lingual gingiva (Fig. 16.7). metronidazole 400 mg, 8 hourly, for 7 days are the drugs of choice. Scaling is performed, if sensitivity permits. After the disease process is diminished, complete gingival curettage and root planning is done. Supportive treatment consists of copious fluid consumption and administration of nutritional supplements. Points to Remember Trench mouth, Vincent’s infection, low socioeconomic group, profuse salivation, metallic taste, fetid odor, woody sensation, crater like ulcerations, gray, pseu­ domembranous slough, necrotizing ulcerative peri­ odontitis, necrotizing ulcerative mucositis, necrotizing stomatitis, nonspecific acute necrotizing inflammation, pseudomembranous meshwork of fibrin, necrotic epi­ thelial cells, polymorphonuclear neutrophils, extensive hyperemia, topical anesthetic, Penicillin V, metronida­ zol, erythromycin.

Figure 16.7 Denudation of gingiva seen

in desquamative gingivitis

Periodontal Pathology

It is usually manifested in three forms, i.e. mild, moderate and severe. Mild: It may be diffuse and extends throughout the gingiva. It is painless. Moderate: There is a patchy distribution of bright red and gray areas involving the marginal and attached gingiva. The surface is smooth, shiny and normally resilient. Patient may complain of a burning sensation and sensitivity to thermal changes. There is slight pitting on pressure and epithelium is not firmly adherent to the underlying tissues.

Topical corticosteroid ointment and creams such as triamcinolone 0.1 percent fluocinolone 0.05 percent is applied and gently rubbed into the gingiva several times daily. Patients whose conditions are resistant to corticoster­ oids often respond to dapsone or sulfapyridine. In cases that demonstrate negative immunofluorescent findings, therapy with estrogens have been attempted with equal results. Points to Remember Red, edematous and desquamation of the surface epithe­ lium of the attached gingiva, mild forms, moderate form, severe form, burning sensation, sensitivity to thermal changes, speckled gingiva, spontaneous desquamation, formation of bubbles, blast of air, epithelium may be thin atrophic, tetracycline therapy, doxycycline monohydrate, topical corticosteroid ointment, dapsone or sulfapyridine.

Severe form: It is characterized by scattered irregularly shaped areas, in which gingiva is denuded and strikingly red in appearance. The overall appearance of gingiva is speckled. There is blister formation, spontaneous desquamation, or zones of erosion. If blisters are present, then they are filled with clear fluid or can be contaminated with blood. Epithelium is friable and can be easily removed from the underlying connective tissue leaving PLASMA CELL GINGIVITIS a red surface that bleeds readily to minimum trauma. A blast of air directed at the gingiva causes elevation of This is also called atypical gingivostomatitis. the epithelium and consequent formation of bubbles. Cause Yellowish fibrinopurulent membranes cover areas of frank It usually caused by allergic reaction to chewing gum, erosion, and significant pain is usually present. herbal toothpaste, mint candy and peppers used for cooking.

Histopathological Features

Histopathological features may mimic either bullous lesions of mucous membrane pemphigoid or lichenoid reaction. Sometimes, epithelium may be thin and atrophic with little or no keratin at the surface and dense diffuse inflammatory cells in the underlying connective tissue. Rete pegs are blunted and there may be clefting below the basement membrane with edema and a mild chronic inflammatory infiltrate.

Management

Clinical Features Onset: There is rapid onset of sore mouth, which is aggravated by dentifrice or spicy food. Appearance: Gingiva appears diffusely enlarge with bright erythema and loss of stippling (Fig. 16.8). Spread: In some cases, spread of this disease is reported form lip and tongue.

Histopathological Features

There is psoriasiform hyperplasia and spongiosis of A complete history should be taken to uncover a possible surface epithelium present. There is also intense exocytosis coexistent extraoral cause. Before definitive treatment, all and neutrophilic microabscess. Lamina propria contains numerous dilated vascular possible local irritants should be removed. channels with chronic inflammatory infiltrates which is The patient must be carefully instructed in plaque control and instructed for using a soft toothbrush, oxidizing composed of plasma cells. mouthwash (hydrogen peroxide 3% diluted to one part Management peroxide and two parts of warm water) should be use twice Elimination of possible allergen should be carried out. daily. Topical and systemic immunosuppressive agents like Improvement has been noticed with tetracycline betamethasone rinse, fluocinonide gel, topical triamcitherapy. Doxycycline monohydrate 100 g daily for 4 to 11 nolone and topical fusidic acid should be given. weeks.

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Foreign body gingivitis: It can cause area of erythematous and atrophic mucositis which can resembles gingival lichen planus. 394

Histopathological Features There is the focal collection of histiocytes mixed with intense lymphocytes infiltrates. In some cases, multinucleated giant cell can be seen. Foreign bodies appear as black or brown­black granules.

Management Surgical excision of affected tissue is the therapy of choice. Points to Remember Figure 16.8 Plasma cell gingivitis with bright erythema

Points to Remember Atypical gingivostomatitis, allergic reaction, gingiva ap­ pear diffusely enlarge, bright erythema, psoriasiform hy­ perplasia, spongiosis of surface epithelium, neutrophilic microabscess, plasma cells, betamethasone rinse, fluo­ cinonide gel, topical triamcinolone, topical fusidic acid.

GRANULOMATOUS GINGIVITIS In some cases, patient have localized area of granulomatous inflammation of gingiva without signs and symptoms of granulomatous disease which is termed granulomatous gingivitis.

Red or red­white macules, pain and sensitivity, foreign body gingivitis, histiocytes mixed with intense lymphocytes infiltrates.

GINGIVAL ABSCESS It is localized, painful, rapidly expanding lesion that is usually of sudden onset.

Etiology It results from bacteria carried deep into the tissue, when a foreign substance such as a toothbrush bristle, a piece of applecore or a lobster shell fragment is forcefully embedded into the gingiva.

Clinical Features

Cause

Location: It is limited to the marginal gingiva or the interdental papilla.

It is thought to be cause by introduction of dental material into the connective tissue deep to sulcular epithelium. The most common material which can cause are silver, copper, calcium, phosphorus and iron. This is also called foreign body gingivitis.

Signs: In early stages, it appears as a red swelling with a smooth and shiny surface (Fig. 16.9). Within 24 to 48 hours, the lesion usually becomes fluctuant and pointed with a surface orifice, from which an exudate may be expressed. The adjacent teeth are sensitive to percussion.

Clinical Features

Histopathological Features

Age: It can occur at any age but more commonly seen in adults.

It consists of a purulent focus in the connective tissue, surrounded by a diffuse infiltration of polymorphonuclear leukocytes, edematous tissue and vascular engorgement. The surface epithelium has a varying degree of intra­ and extracellular edema, with invasion of leukocytes and ulceration.

Appearance: It appears as red or red­white macules involving interdental papillae but can occurs on marginal gingiva. Symptoms: Pain and sensitivity are common findings.

Periodontal Pathology

this fluctuance is digitally ascertained, incision and drainage should be carried out, followed by warm saline rinses at frequent intervals. Symptoms: Pain, malaise, leukocytosis and swelling of peritonsillar region. The patient complaints of foul taste and inability to close the jaws. The pain may radiate to the throat, ear, or floor of the mouth. Signs: It may result in cellulitis and muscular trismus. There is also regional lymphadenopathy, submaxillary and pharyngeal abscess. Operculum may get traumatized by opposing teeth during mastication. Edema, visible in both submandibular area and peritonsillar region occurs. There is an extreme tenderness on palpation of the abscess. Figure 16.9 Gingival abscess presented as red swelling

Histopathological Features

Gingivitis is present and the pocket lining is hyperplastic, with extensive exocytosis of acute inflammatory cells. Management Connective tissue stroma is hyperemic which shows After topical anesthesia is applied, the fluctuant area acute inflammatory cells consisting predominantly of of the lesion is incised with a blade and the incision is lymphocytes and plasma cells, but with a variable number gently widened to permit drainage. The area is cleansed of polymorphonuclear leukocytes. Mostly, large microbial with warm water and covered with a gauze pad. After the colonies representing plaque and calculus are found. bleeding stops, patient is instructed to rinse every 2 hours with a glassful of water. Complications Points to Remember Marginal gingiva or the interdental papilla a red swelling with a smooth and shiny surface, fluctuant surface orifice, adjacent teeth are sensitive polymorphonuclear leukocytes, vascular engorgement, intra­ and extra­ cellular edema.

PERICORONAL ABSCESS It is also called pericoronitis. It is the infection of soft tissues surrounding the crown of an impacted or partially erupted tooth when food debris and bacteria are present beneath the gingival flap overlying the crown.

Clinical Features The most common type of pericoronal infection is found around the mandibular 3rd molar. Pericoronal infection of infancy: Pericoronal infection of infancy is often associated with the supradental tissues, involving the superior portion of the follicle and the overlying mucoperiosteum, which may become inflamed. It ultimately develops into small fluctuant abscess. When

The involvement may become localized in the form of a pericoronal abscess. It may spread posteriorly into the oropharyngeal area and medially, to the base of the tongue. Peritonsillar abscess, cellulitis and Ludwig’s angina are common.

Management Antibiotics: Immediately, antibiotics should be started. Most commonly used antibiotics are phenoxylmethyl penicillin 250 mg four times daily. In pericoronitis due to ulceromembranous gingivitis metronidazole 200 g three times daily for 7 days is given. Drainage: Careful probing should be done around the 3rd molar, which permits entry into the expanded follicle and allows evacuation of pus and other septic material. The patient is instructed to use warm salt water rinses and to return in 24 hours. Extraction: When the symptoms become subacute, then the impacted 3rd molar should be extracted. Operculectomy: Sometimes when the retention of 3rd molar is necessary, the inflamed tissue surrounding the occlusal portion of the tooth should be excised.

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Extraction of maxillary 3rd molar: Maxillary 3rd molar can be a contributing factor to the pericoronal infection of the mandibular 3rd molar. In such cases, especially when the mandibular 3rd molar is fully erupted in proper place, the maxillary 3rd molar should be extracted prior to the retention of the mandibular 3rd molar, considering the recurrent nature of the inflammatory episode. Points to Remember Pericoronal infection of infancy, fluctuance is digitally ascertained, pain, malaise, leukocytosis, muscular trismus, cellulitis, hyperplastic gingiva, exocytosis of acute inflammatory cells, acute inflammatory cells, antibiotics, drainage, extraction, operculectomy. Figure 16.10 Inflammatory enlargement of gingiva showing

CHRONIC INFLAMMATORY ENLARGEMENT

ballooning of the interdental papilla (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Etiology It can be caused by prolonged exposure to dental plaque, which may occur due to poor oral hygiene, abnormal relationship of adjacent and opposing teeth, lack of tooth function, overhanging margins of dental restoration and improperly contoured dental restoration or pontics. It can also caused by food impaction, irritation from clasps or saddle areas of removable prosthesis and nasal obstruction. Habits: Such as mouth­breathing can cause gingival en­ largement, which is more common in the anterior region.

Clinical Features The enlargement is generally papillary or marginal and localized or generalized. It originates as a slight ballooning of the interdental papilla or the marginal gingiva. Signs: In early stages, it produces a life preserver-like bulge around the involved teeth. It increases in size, until it covers a part of the crown. Lesions may be deep red or bluish red (Figs 16.10 and 16.11). They are soft and friable, with a smooth and shiny surface and tendency to bleed. It progresses slowly and painlessly, unless complicated by acute infection or trauma. Sometimes, enlargement can occur as a discrete, sessile or pedunculated mass, resembling a tumor. They may undergo spontaneous reduction in size, followed by exacerbation and continued enlargement. Painful

Figure 16.11 Inflammatory hyperplasia on gingiva

ulceration, sometimes, occurs between the mass and the adjacent gingiva.

Histopathological Features It shows exudative and proliferative features of chronic inflammation. Lesions may contain preponderance of inflammatory cells and fluid with vascular engorgement, new capillary formation, associated with degenerative changes. Areas of fibrosis, hyperemia, edema, and hemorrhage may be present (Fig. 16.12).

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Figure 16.12 Inflammatory cells seen in gingival enlargement

Figure 16.13 Drug-induced gingival enlargement showing

lobulated appearance

Points to Remember Prolonged exposure to dental plaque, papillary enlarge­ ment, preserver­like bulge around teeth, smooth and shiny surface, tendency to bleed, sessile or pedunculated mass shows exudative and proliferative features of chronic inflammation, inflammatory cells, vascular engorgement, new capillary formation.

GINGIVAL ENLARGEMENT DUE TO DRUGS It refers to an abnormal growth of the gingival tissues secondary to use of systemic medication. The increased gingival size is due to the production of an increased amount of extracellular matrix, mainly collagen. It can be caused by Dilantin sodium, cyclosporine or nifedipine.

Clinical Features Onset: Gingival hyperplasia may begin as early as two weeks after Dilantin therapy. Location: The hyperplasia is generalized throughout the mouth, but it is most severe in maxillary and mandibular anterior region. Signs: The first change noted is a painless bead-like enlargement in the size of the gingiva, starting with one or two interdental papillae. The surface of gingiva shows an increase in stippling and finally, a cauliflower, warty or pebbled surface (Figs 16.13 and 16.14).

Figure 16.14 Drug-induced enlargement showing

bead-like enlargement

As the enlargement increases, the gingival tissue becomes lobulated and clefts are seen between each enlarged gingiva. Palpation reveals that the tissue is dense, resilient and insensitive. It shows little tendency to bleed (Fig. 16.15). They may develop massively, covering a considerable portion of the crown. They may interfere with occlusion. The presence of an enlargement makes plaque control difficult, resulting in a secondary inflammatory process that complicates the gingival hyperplasia.

Histopathological Features The stratified squamous epithelium covering the tissue is thick and has a thin keratinized layer. The rete pegs are

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398

Figure 16.15 Drug-induced gingival enlargement (Courtesy: Aparna Thombre, Reader, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

extremely long and thin, sometimes called ‘test tube’ pegs, with considerable confluence. Mitotic figures are seldom seen. The bulk of tissue is made up of large bundles of fibers, interspersed with fibroblasts and fibrocytes. There may be a pronounced hyperplasia of the connective tissue and the epithelium. There is acanthosis of epithelium and the elongated rete pegs extend deep into the connective tissue (Fig. 16.16). In patients with secondary inflammation, there is increased vascularity and a chronic inflammatory cellular infiltrate that mostly consists of lymphocytes and plasma cells.

Management Discontinuation of medication often results in cessation of lesion. Substitution of drugs which are causing it should be done. Systemic or topical folic acid has been effective in some cases of hyperplasia. In some cases, metronidiazole or azithromycin is also useful in cyclosporine induce enlargement.

Figure 16.16 H&E stained section shows proliferative stratified squamous epithelium with elongated rete pegs with underlying connective tissue shows densely arranged collagen fiber bundle with few fibroblasts, inflammatory cells and blood vessels

PREGNANCY TUMOR It is also known as granuloma gravidarum. It is an inflammatory reaction to the local irritants. It is pyogenic granuloma occurring in pregnancy.

Clinical Features Age: Such lesions may begin to develop during the first trimester, and their incidence increases up through the 7th month of pregnancy. It usually appears after 3rd month of pregnancy. The gradual rise in development of these lesions throughout pregnancy may be related to the increasing levels of estrogen and progesterone.

Points to Remember

Appearance: The lesions appear as discrete, mushroom like, flattened spherical masses, that protrude from the gingival margins or more frequently from the interproximal space and are attached by sessile or pedunculated base (Figs 16.17 and 16.18). It tends to expand laterally. The pressure from the tongue and the cheek perpetuates its flattened appearance.

Dilantin sodium, cyclosporine or nifedipine, hyperplasia is generalized, painless bead like enlargement, test tube rete pegs, fibroblasts and fibrocytes, hyperplasia of the connective tissue and the epithelium, elongated rete pegs, discontinuation of medication, topical folic acid, metronidiazole or azithromycin.

Sign and symptoms: It is generally dusky red or magenta; it has a smooth glistening surface that frequently exhibits numerous deep red, pinpoint markings. The consistency varies from semifirm, but may have a varying degree of softness and friability. It is usually painless, unless its size and shape foster the accumulation of debris under its

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Figure 16.17 Pregnancy tumor showing mushroom

like enlargement

Figure 16.19 Pregnancy tumor showing edema

and engorged capillaries

The surface is usually ulcerated and replaced by a thick fibrinopurulent membrane. Between the capillaries, there is moderately fibrous stroma, with a varying degree of edema and leukocytic infiltration.

Management Most gingival enlargement during pregnancy can be prevented by the removal of local irritants and institution of a fastidious oral hygiene. Usually, treatment should be avoided unless significant functional or esthetic problems develop. The lesion mostly resolves spontaneously after parturition. Points to Remember Figure 16.18 Pregnancy tumor presented as pinpoint marking

margin or interfere with occlusion, in which cases painful ulceration may occur.

Histopathological Features It consists of a central mass of connective tissue, the periphery of which is outlined by thick stratified squamous epithelium with prominent rete pegs. The connective tissue consists of numerous, diffusely arranged, newly formed and engorged capillaries, lined by cuboids endothelial cells (Fig. 16.19). The epithelium exhibits some degree of intracellular or extracellular edema with prominent intercellular bridges and leukocytic infiltration.

Granuloma gravidarum, first trimester, discrete, mushroom like, flattened spherical masses, expand laterally, flattened appearance, numerous deep red, pinpoint markings, semifirm, thick stratified squamous epithelium, lined by cuboids endothelial cell, prominent intercellular bridges and leukocytic infiltration, edema and leukocytic infiltration, removal of local irritants.

GRANULOMA PYOGENICUM It is also called pyogenic granuloma. It is a non-specific, tumor-like, conditional enlargement of the gingiva that is considered as an exaggerated conditional response to minor trauma. Inspite of its name, it is not a true granuloma.

Textbook of Oral Pathology

Clinical Features 400

Location: The lesions are slightly more common on the maxillary gingiva than the mandibular gingiva; anterior areas are more frequently affected than the posterior areas. The lesions are more common on the facial aspect than the lingual aspect. Some extends between the teeth and involve both the facial and the lingual gingiva. In some cases, this can also occur on lip, tongue and buccal mucosa. Appearance: It varies from a discrete spherical, tumor­ like mass with a pedunculated attachment to a flattened, keloid like enlargement with a broad­base. Some lesions although are sessile. Size: They vary from small growths to larger lesions that may measure several centimeters in diameter. Sign and symptoms: The mass is painless and the surface is characteristically ulcerated and the color appears bright red or purple color and either friable or firm, depending on its duration. In majority of the cases, it presents with surface ulceration and purulent exudation. Young pyogenic granuloma are highly vascular in appearance whereas older lesions tend to become more collagenized and pink (Fig. 16.20).

Histopathological Features It appears as a mass of granulation tissue with chronic inflammatory cell infiltration (Fig. 16.21).

Figure 16.21 Pyogenic granuloma showing capillary

proliferation (c) and inflammatory infiltrates

Microscopic examination shows a highly vascular proliferation that resembles granulation tissue. Endothelial proliferation and formation of numerous vascular spaces are the prominent features. The blood vessels are engorged. The surface epithelium is usually ulcerated and replaced by thick fibrinopurulent membrane. A mixed infiltration of neutrophils, plasma cells, and lymphocytes is evident. Neutrophils are mostly evident near the ulcerated surface; chronic inflammatory cells are found deeper in the specimen. The surface is atrophic in some areas and hyperplastic in others. Older lesions may have areas with a more fibrous appearance.

Management Removal of lesion, along with elimination of irritating factors. Occasionally, recurrence is seen and re­excision is necessary. Points to Remember

Figure 16.20 Granuloma pyogenicum presented

as discrete spherical tumor like mass

Pyogenic granuloma, non­specific, tumor­like, condi­ tional enlargement of the gingiva, keloid like enlarge­ ment, painless surface, ulcerated bright red color, fri­ able or firm, chronic inflammatory cell infiltration, endothelial proliferation, infiltration of neutrophils, plasma cells.

Periodontal Pathology

PERIODONTAL POCKETS Classification • Gingival pocket (relative or false): It is formed by gingival enlargement, without destruction of the un­ derlying periodontal tissues. The sulcus is deepened because of the increased bulk of the gingiva. • Periodontal pocket (absolute or true): There is destruction of the supporting periodontal tissue; progressive pocket deepening leads to destruction of the supporting periodontal tissues and loosening and exfoliation of the teeth. • Suprabony pocket (supracrestal or supra-alveolar): In it, bottom of the pocket is coronal to the underlying alveolar bone. • Infrabony (intrabony, subcrestal or intra-alveolar): In it, bottom of the pocket is apical to the level of the adjacent alveolar bone.

Pathogenesis Periodontal pockets are caused by microorganisms and their products, which produce pathologic tissue changes that lead to the deepening of the gingival sulcus. Pocket formation starts as an inflammatory change in the connective tissue wall of the gingival sulcus. The cellu­ lar and fluid inflammatory exudates cause degeneration of the surrounding connective tissues, including the gingival fibers. Just apical to the junctional epithelium, an area of destroyed collagen fibers develops and becomes occupied by inflammatory cells and edema. Collagen loss may occur due to enzymes, like colla­ genase and other lysosomal enzymes from polymorphonu­ clear leukocytes and macrophages, which become extracel­ lular and destroy the collagen. As a consequence of loss of collagen, the apical portion of the junctional epithelium proliferates along the root, extending in finger like projections. As the apical portion migrates the coronal portion of the junctional epithelium detaches from the root. As a result of inflammation, polymorphonuclear neutrophils invade the coronal end of junctional epithelium. An increase in number of these cells, results in loss of tissue cohesiveness and tissue detachment from the tooth surface. Thus, the bottom of the sulcus shifts apically, result­ ing in deepening of the periodontal pocket.

Clinical Features Symptoms: Gingival bleeding or/and suppuration, tooth mobility and diastema formation may be present.

401

Figure 16.22 Periodontal pocket is examined

with the help of periodontal probe

Signs: In some cases, pus may be expressed by applying digital pressure. When explored with a probe, the inner aspect of the periodontal pocket is generally painful. There may be bluish red, thickened marginal gingiva and a bluish red vertical zone from the gingival margin to the alveolar mucosa (Fig. 16.22).

Histopathological Features There may be circulatory stagnation, destruction of the gingival fibers and surrounding tissues, which results in discoloration. There is an atrophy of the epithelium and edema, which results in a shiny surface of lesion. There is an increased vascularity, thinning and degeneration of the epithelium with close proximity to the engorged vessels.

Management Pocket irrigation: Devices like squeeze bottles and blunt hypodermic needles can be use to irrigate the pocket with chemotherapeutic agents. Flap surgery to eliminate pockets. Points to Remember Deepening of the gingival sulcus, gingival bleeding, suppuration, explored with a probe painful inner aspect periodontal pocket, circulatory stagnation, destruction of the gingival fibers, an atrophy of the epithelium, an increased vascularity, thinning and degeneration, pocket irrigation.

Textbook of Oral Pathology

ADULT PERIODONTITIS 402

It is also called slowly progressive periodontitis, chronic adult periodontitis and chronic inflammatory periodontitis.

Etiology Local factors: It occurs in association with plaque, calculus and poor oral hygiene. Systemic disease: Development of systemic disease like diabetes mellitus, hormonal alteration or an immunologic defect can accelerate periodontal destruction. Types of Adults Periodontitis • Mild periodontitis: It is characterized by an attach­ ment loss of 1 to 2 mm, minimum furcation invasion and little tooth mobility. • Moderate periodontitis: It exhibits 3 to 4 mm of probing attachment loss, early to moderate furcation invasion and slight to moderate tooth mobility. • Severe periodontitis: Probing attachment loss of 5 mm or more, with significant furcation invasion often through and through, with excessive tooth mobility.

Clinical Features It generally affects both the sexes equally and is seen in older age groups more frequently. It is usually generalized, although some areas may be involved more deeply than others.

Figure 16.23 Gingival recession of lower anterior region

in periodontal disease

Histopathological Features The enlarged free marginal gingiva is densely infiltrated with lymphocytes and plasma cells. The apical borders of the inflamed area approach the crest of the alveolar bone and the crestal fibers of the periodontal ligament. The crevicular epithelium shows various areas of proliferation and often, tiny ulcerations. There is appearance of giant cells and osteoclasts on the surface of the bony crest. Principal periodontal ligament fibers become disorganized and are detached from the tooth.

Management

Symptoms: It is usually painless, but sometimes exposed Scaling, curettage and periodontal surgery can be done root may be sensitive to heat and cold, in absence of caries. depending upon the depth, type of pocket and the type of Areas of localized deep pain, sometimes radiating deep the bone loss associated. into the jaws are established. Points to Remember Signs: The characteristic finding in it is gingival inflammation, which results from accumulation of plaque and loss of periodontal attachment. The gingiva is slightly or moderately swollen and exhibits alteration in color from pale to magenta. There is also loss of stippling and gingival bleeding, which may be either spontaneous or easily provoked. There is presence of pocket with variable pocket depth. Both, horizontal and angular bone loss can be found. Tooth mobility is found in advanced cases, where bone loss has been considerable. Teeth give off a rather dull sound when tapped with a metal instrument. The embrasures may be open because the interdental papillae are deficient. Gingival recession is a common phenomenon in later stages of disease, which may expose the cementum (Fig. 16.23).

Slowly progressive periodontitis, painless or localized deep pain, gingival inflammation, gingiva swollen with color from pale to magenta, tooth mobility, gingival recession, infiltrated with lymphocytes, giant cells and osteoclasts on the surface.

RAPIDLY PROGRESSIVE PERIODONTITIS Rapidly progressive periodontitis or generalized aggressive periodontitis may not represent a distinct disease entity but, rather, may be a collection of young adults with advanced periodontal disease. There is poor serum antibody response to infecting agents.

Periodontal Pathology

Etiology Microorganisms responsible are Actinobacillus actinomycetemcomitans, P. intermedia, P. gingivalis, B. forsythus, F. nucleatum, Camphylobacter rectus, Spirochetes, etc. Altered chemotactic response to neutrophils has been re­ ported in some cases.

403

Clinical Features Rate of destruction is rapid over a period of time, as compared to slowly progressive periodontitis. The lesions are more generalized and all or most of the teeth are affected, without any definite pattern of distribution. Age: The age of onset of the disease ranges from the middle to late teens and till 30 years of age. There is marked episodic destruction of periodontal attachment and alveolar bone. Signs: Gingiva is acutely inflamed, often proliferated, ulcerated and fiery red. Bleeding may occur spontaneously, or on slight provocation. In some cases, gingiva appears pink and free of inflammation; but in spite of this, deep pockets can be revealed on probing (Figs 16.24A and B). In contrast to the localized variant, heavy plaque, calculus, and marked gingival inflammation may be present. Some patients may have systemic manifestations like weight loss, mental depression and general malaise.

Histopathological Features It is as not different from chronic periodontitis. Definitive diagnosis should be made on the basis of clinical,

Figure 16.24B Rapidly progressing periodontitis presented as

destruction of periodontal ligament

radiographic, histopathological, and microbiologic findings together with family history and leukocyte function tests.

Management If microflora contains gram­positive microorganisms, then it should be treated with 250 mg amoxicillin and 125 mg potassium clavulanate three times daily, for 14 days, along with scaling and root planning. If flora is gram­ negative, then clindamycin should be given with dose of 150 mg, four times a day, for 7 days, along with scaling and root planning. If surgery is required, it is performed 2 days after the initiation of the antimicrobial therapy. Chlorhexidine rinses are used for 2 weeks postsurgery. Revaluation is done and oral prophylaxis is carried out once a month for 6 months and then every 3 months thereafter. Points to Remember Actinobacillus actinomycetemcomitans, marked epi­ sodic destruction of periodontal attachment, gingiva is acutely inflamed, spontaneous bleeding, systemic manifestations like weight loss, amoxicillin, potassium clavulanate, clindamycin.

AGGRESSIVE PERIODONTITIS/ JUVENILE PERIODONTITIS

Figure 16.24A Periodontitis showing severe bone destruction

It is also called periodontosis. It is an autosomal recessive and X­linked character. It is an aggressive, but uncommon form of periodontitis found in children and young adults.

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It is a disease of the periodontium, occurring in an otherwise healthy adolescent and is characterized by a rapid loss of alveolar bone about one or more teeth of the permanent dentition.

Causes Inherited defect in neutrophilic chemotactic function, which affects the ability of polymorphonuclear leukocytes to phagocytose and degranulate, thus impairing the host resistance is responsible for juvenile periodontitis. Several authors describe it as a hereditary and familial pattern. Microorganisms responsible are usually gram­ negative anaerobic rods, along with minimum amount of attached plaque.

Location: It can be localized or generalized and maxillary teeth are more frequently affected than mandibular, with strong left­right symmetry. Teeth more commonly affected are 1st molars and incisors. There is an increase in the number of affected teeth with advancing age, which leads to widely accepted assumption that the disease starts with a localized lesion and at later stages becomes generalized. Signs: The most striking feature is the lack of clinical inflammation, despite the presence of deep periodontal pocket. Presence of deep pockets with secondary inflammation may occur. Deep, dull radiating pain may occur with mastication, due to irritation of the supporting structures by mobile teeth and impacted food.

Symptoms: Initial complain is mobility and pathological drifting of first molars and incisors. Classically, the clinician Actinobacillus actinomycetemcomitans can produce sees a distolabial migration of the maxillary incisors, with substances that can kill PMNs and monocytes, thereby a diastema formation. Subgingival calculus is uncommon. compromising the patient’s ability to fight the invading As the disease process continues, denuded root surfaces bacteria or their products. These leukotoxins may be become sensitive to thermal and tactile stimuli. Periodontal abscess may form at this stage and regional counteracted by the development of serum antibodies. lymph node enlargement may occur. The rate of bone loss Inhibition of PMNs may be induced by some gram negative bacteria. Endotoxins from Actinobacillus is three to four times faster than in typical periodontitis. actinomycetemcomitans can induce Schwartzman reaction, Rapid and typically angular loss of alveolar bone occurs, macrophage toxicity, platelet aggregation, complement which may progress to tooth loss. In classic cases an arc­ shaped zone of bone loss extends from the distal aspect activation and bone resorption. Actinobacillus actinomycetemcomitans, Capnocyto- of the second bicuspid to the mesial aspect of the second phaga and Bacteroides can produce proteolytic enzymes molar. One of the striking features is a robust serum that can destroy collagen, activate complement system or antibody response to infecting agents. degrade immunoglobulins. Actinobacillus actinomycet- Radiological features: There is vertical bone resorption emcomitans and Capnocytophaga can produce fibroblast which is bilateral and symmetrical. inhibiting factors, which impair the defense mechanism. Polyclonal B-lymphocyte activation by periodontal bacte­ Histopathological Features ria may result in production of antibodies which are unre­ A thin, frequently ulcerated pocket epithelium, infiltrated lated to the activating agent. by numerous leukocytes covers large area of inflammatory

Mechanism of Bone Loss

Types of Aggressive • Localized aggressive periodontitis or juvenile periodontitis • Generalized aggressive periodontitis or juvenile periodontitis.

Clinical Features Age and sex distribution: Juvenile periodontitis affects both, males and females and is seen most frequently in the periods between puberty and 20 years of age.

cell accumulation, composed mainly of plasma cells and blast cells with lymphocytes and macrophages present in small numbers. There is a proliferation of the epithelial attachment along the root surface. There is also slight cellular infiltration in the connective tissue.

Management Standard periodontal therapy: It includes scaling and root planning, curettage, flap surgery with and without bone grafts, root amputation, hemisection, occlusal adjustment and strict plaque control.

Periodontal Pathology

Antibiotic therapy: Tetracycline 250 mg, four times a day 7 days is given or doxycycline 200 mg stat followed by 100 mg once a day for 14 days. 405

Points to Remember Periodontosis, neutrophilic chemotactic function, Actinobacillus actinomycetemcomitans, lack of clinical infla­ mmation, deep periodontal pocket, diastema formation, periodontal abscess, bilateral vertical bone resorption, numerous leukocytes, inflammatory cell accumulation, lymphocytes and macrophages, epithelial attachment along the root surface, antibiotic therapy.

PAPILLON-LEFEVRE SYNDROME

A

It is an autosomal recessive and inherited disorder. It is a triad of hyperkeratosis of palms of the hand and soles of feet; extensive prepubertal destruction of the periodontal bone supporting the dentition, usually extensive genera­ lized horizontal bone loss and calcification of dura is seen.

Clinical Features (Figs 16.25A and B) There is reddened, scaly, rough palms and soles, inflamed gingivae and dramatic bone destruction seen in both deciduous as well as permanent dentitions. Onset: It usually begins after eruption of the primary second molars. There is loss of entire primary dentition by the age of 5 years and loss of secondary dentition by the age of 20 years. Sign and symptoms: Mobility and migration of the teeth are observed consistently, and mastication often is painful because of the lack of support. When the teeth are absent, the alveolar mucosa is normal in appearance. Gingival swelling and severe halitosis can also occur. Although other pathogenic bacteria have been isolated from sites of active disease, A. actinomycetemcomitans has been directly related to the periodontal destruction. There are also indications that leukocyte dysfunction may be induced by infection with A. actinomycetemcomitans (secondary to generated leukotoxins).

Histopathological Features It includes marked chronic inflammation of the lateral walls of the pocket, with predominantly plasma cell infiltrate, considerable osteoclastic activity and apparent lack of osteoblastic activity.

B Figures 16.25A and B Papillion-Lefevre syndrome

The crevicular epithelium is hyperplastic with exocytosis. An extremely thin cementum is present. The underlying connective tissue exhibits increased vascularity and mixed inflammatory cellular infiltrates, mixed infiltrates consist of polymorphonuclear leukocytes, lymphocytes, Histiocytes and plasma cells.

Management Management should be carried out with the help of antibiotics, mechanical plaque control and management of skin lesion. With the use of mechanical plaque control and appro­ priate antibiotics (amoxicillin and potassium clavulanate or ofloxacin) directed towards A. actinomycetemcomitans, the course of the disease may be altered.

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The progression of the attachment loss is drastically slowed down and the teeth that erupt after the initiation of therapy do not develop periodontal destruction. Long term maintenance consists of meticulous oral hygiene, chlorhexidine mouth rinses, frequent oral prophylaxis by professional, and periodic appropriate antibiotic therapy is necessary. Points to Remember Hyperkeratosis of palms of the hand and soles of feet, destruction of the periodontal bone, calcification of dura, plasma cell infiltrate, osteoclastic activity, lack of osteoblastic activity, hyperplastic with exocytosis in crevicular epithelium, increased vascularity and mixed inflammatory cellular infiltrates, leukocytes, lymphocytes, Histiocytes and plasma cells, amoxicillin and potassium clavulanate or ofloxacin.

HAIM-MUNK SYNDROME In this, there is plamoplanter keratosis, progressive periodontal disease, recurrent skin infection and skeletal manifestation is seen. Periodontal disease is of milder as compared to Papillon­Lefevre syndrome.

BIBLIOGRAPHY 1. American Academy of Peridontology. Parameter on plaqueinduced gingivitis. J Peridontol. 2000;71 (Suppl):851­2. 2. American Academy of Peridontology. Position paper. Treatment of gingivitis and periodontitis. J Peridontol. 1997;68:1246­53. 3. American Academy of Peridontology: Position paper, periodontal diseases of children and adolescents. J Periodontol. 1996;67:57­62. 4. American Academy of Periodontology: Concensus report: aggressive periodontitis, Ann Periodontol. 1999;4:53. 5. American Academy of Periodontology: Informational paper. The pathogenesis of periodontal diseases. J Periodontol. 1999;70:457­70. 6. American Academy of Periodontology: Parameter on acute periodontal diseases. J Peridontol. 2000;71(Suppl):863­6. 7. Bakaeen G, Scully C. Hereditary gingival fibromatosis in a family with Zimmerman­Laband syndrome. J Oral Pathol Med. 1991;20:457­9. 8. Barker DS, Lucas RB. Localized fibrous overgrowth of the oral mucosa. Br J Oral Surg. 1967;5:86­92. 9. Becks H. Normal and pathologic pocket formation. J Am Dent Assoc. 1929;16:2167.

10. Bhaskar SN, Jacoway JR. Pyogenic granuloma-clinical features, incidence, histology, and result of treatment: report of 242 cases. J Oral Surg. 1966;24:391­8. 11. Buchner A, Merrell PW, Hansen LS, et al. The retrocuspid papilla of the mandibular lingual gingiva, J Periodontol. 1990;61:586­90. 12. Butler RT, Kalkwarf KL, Kaldahl WB. Drug­induced gingival hyperplasia: phenytoin, cyclosporine, and nifedipine. J Am Dent Assoc. 1987;114:56-60. 13. Ciancio SG. Agents for the management of plaque and gingivitis, J Dent Res. 1992;71:1450­4. 14. Daley TD, Nartey NO, Wysocki GP. Pregnancy tumour. An analysis. Oral Surg Oral Med Oral Pathol. 1991;72:196­9. 15. Damm DD, Cibull ML, Geissler RH, et al. Investigation into the histogenesis of congenital epulis of the newborn. Oral Surg Oral Med Oral Pathol. 1993;76:205­12. 16. Dongari A, McDonnell HT, Langlais RP. Drug induced gingival overgrowth, Oral Surg Oral Med Oral Pathol. 1993;76:543­8. 17. Flemmig TF. Periodontitis. Ann Periodontol. 1999;4:32-7. 18. Hartnett AC, Shiloah J. The treatment of acute necrotizing ulcerative gingivitis, Quintessence Int. 1991;22:95­100. 19. Hattab FN, Rawashdeh MA, Yassin OM, et al. PapillonLefevre syndrome: a review of the literature and report of 4 cases. J Periodontol. 1995;66:413­20. 20. Hirschfeld I. Hypertrophic gingivitis; its clinical aspect. J Am Dent Assoc. 1932;19:799. 21. Ishikawa I, Umeda M, Laosrisin N. Clinical, bacteriological, and immunological examinations and the treatment process of two Papillon­Lefevre syndrome patients. J Periodontol. 1994;65:364­71. 22. Jacobs MH. Pericoronal and Vincent’s infections: bacteriology and treatment. J Am Dent Asso. 1953;30:392. 23. Johnson BD, Engel D. Acute nectrotising ulcerative gingivitis: a review of diagnosis, etiology and treatment, J Peridontol. 1986;57:141­50. 24. Jorgenson RJ, Cocker ME. Variation in the inheritance and expression of gingival fibromatosis, J Periodontol. 1974;45:472­7. 25. Kerr DA. Granuloma pyogenicum. Oral Surg Oral Med Oral Pathol. 1951;4:158­76. 26. Liakoni H, Barber P, Newman HN. Bacterial penetration of pocket soft tissues in chronic adult and juvenile periodontitis cases. An ultrastructural study. J Clin Periodontol. 1987;14:22. 27. Lindhe J, Liljenberg B. Treatment of localized juvenile periodontitis: results after 5 years. J Clin Periodontol. 1984;11:399­410. 28. Listgarten MA, Hellden L. Relative distributions of bacteria at clinically healthy and periodontally diseased sites in humans. J Clin Periodontol. 1978;5:665.

Periodontal Pathology 29. Low SB, Clancio SG. Reviewing nonsurgical periodontal therapy, J Am Dent Assoc. 1990;121:467-70. 30. Loyola AM, Gatti AF, Santos Pinto D Jr, et al. Alveolar and extraalveolar granular cell lesions of the newborn: report of case and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84:668­71. 31. Moskow BS, Polson AM. Histologic studies on the extension of the inflammatory infiltrate in human periodontitis. J Clin Periodontol. 1991;18:534­42. 32. Newman MG, Carranza FA Jr, Takei HH. Clinical periodontology. Philadelphia: WB Saunders; 2001.p.9. 33. Oikarinen K, Salo T, Kaar ML, et al. Hereditary gingival fibromatosis associated with growth hormone deficiency. Br J Oral Maxillofac Surg. 1990;28:335­9. 34. Penarrocha­Diago M, Bagan­Sebastian JV, Vera­Sempere F. Diphenylhydantoin­induced gingival overgrowths in man; a clinic­pathological study. J Periodontol. 1990;61:571­4. 35. Perkins AE. Acute infections around erupting mandibular third molar. Br Dent J. 1944;76:199.

36. Preus HR. Treatment of rapidly destructive periodontitis in Papillon­Lefevre syndrome: laboratory and clinical observations. J Clin Periodontol. 1988;15:613­39. 37. Ronbeck BA, Lind PO, Thrane PS. Desquamative gingivitis: preliminary observations with tetracycline treatment. Oral Surg Oral Med Oral Pathol. 1990;69:694­7. 38. Seymour RA, Jacobs DJ. Cyclosporin and the gingival tissues, J Clin Periodontol. 1992;19:1­11. 39. Sheiham A. Is the chemical prevention of gingivitis necessary to prevent severe periodontitis? Periodontol 2000. 1997;15:15­24. 40. Tinanoff N, Tanzer JM, Kornman KS, et al. Treatment of periodontal component of Papillon­Lefevre syndrome. J Clin Periodontol. 1986;13:6­10. 41. Yih W-Y, Maier T, Kratochvil FJ, et al. Analysis of desquamative gingivitis using direct immunofluorescence in conjunction with histology, J Periodontol. 1998;69:678­ 85.

MULTIPLE CHOICE QUESTIONS







1. Trench mouth refers to: a. ANUG b. Desquamative gingivitis c. Fibromatosis gingival d. Congenital epulis 2. A typical necrotic punched out, crater like ulceration seen on the interdental papaillae in: a. Papillon­Lefevre syndrome b. Epulis c. ANUG d. None



7. The red complex associated with bleeding on probing is comprised of: a. E.corrodens, A.actinomycetem, Capnocytophaga b. A.naeslundii, A.viscous, A.odontolyticus c. P.gingivalis, T.forsythia, T.denticola d. Streptococus, Fusobacterium, Camphylobacter

3. Elephantiasis gingivae refers to: a. ANUG b. Granuloma pyogenicum c. Epulis d. Fibromatosis gingiva 4. Following are the drug responsible for gingival enlargement, except: a. Dilantin sodium b. Ciprofloxacin c. Cyclosporine d. Nifedipine 5. Reddened, scaly, rough palms and soles, inflamed gingivae and horizontal bone destruction seen in: a. Nager’s syndrome b. Papillion­Lefevre syndrome c. Patau’s syndrome d. ANUG

6. Which of the following indices is used to measure periodontal destruction: a. Russell’s peridontal index b. Extent and severity index by carlos and coworkers c. Both a and b d. None of the above



8. Plaque differs from materia alba: a. Presence of bacteria b. Presence of glycoprotein c. Presence of salvia d. Absence of glycoprotein 9. Electronic instrument used to measure gingival crevicular fluid: a. Pericheck b. Periotemp c. Periscan d. Periotron 10. Which of the following is not implicated in the etiology of periodontal disease: a. Bacteriodes b. Veionella c. Neisseria d. Eikenella

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16. The organism least likely to be found in normal gingival crevice: a. Fusobacterium b. Actinomyces c. Diptheroides d. Streptococci species

11. Breakdown of periodontal fibers in periodontitis is due to bacterial enzyme: a. Collagenase b. Hyaluronidase c. Coagulase d. None of the above 12. Corncob appearance seen in: a. Supragingival calculus b. Subgingival calculus c. Supragingival plaque d. Subgingival plaque 13. Red complex includes: a. P.Gingivalis b. A.actinomycetem comitans c. Terenella forsythia d. All of the above 14. Suprabony pocket is: a. Base of the pocket is apical to crest of the alveolar bone b. Base of the pocket is coronal to crest of the alveolar bone c. Pocket is at the level of CEJ d. None of the above 15. Radiographic feature of peridontitis is: a. Widening of peridontal ligament space b. Alvealor bone destruction c. Loss of lamina dura d. All of the above



17. The number of bacteria in the oral cavity is greater: a. In morning b. After meals c. At night d. After brushing 18. Bacterial communication with each other in a biofilm is known as: a. Corncob formation b. Coaggregation c. Quarum sensing d. Translocation

19. Plaque differs from materia alba: a. Presence of bacteria b. Presence of glycoprotien c. Presence of salvia d. Absence of glycoprotien 20. Which of the following is not implicated in the etiology of periodontal disease: a. Bacteriodes b. Veionella c. Neisseria d. Eikenella

17

Salivary Gland Pathology

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline                         Â

Classification of salivary gland Development of salivary gland Parotid salivary gland Submandibular gland Sublingual gland Aberrancy Aplasia and hypoplasia Hyperplasia of salivary gland Atresia Accessory duct Diverticuli Sialorrhea Xerostomia Sialolithiasis Strictures and stenosis Mucocele (mucous extravasation phenomenon) Salivary duct cyst or mucus retention cyst Ranula Sialosis (sialadenosis) Allergic sialadenitis Mumps Cytomegalovirus inclusion disease Bacterial sialadenitis Sjögren’s syndrome Mikulicz’s disease or benign lympho-epithelial lesion

                       Â

Uveoparotid fever Tumors of salivary glands Histogenesis Theories of salivary gland tumor histogenesis General features of salivary gland tumorsClinical staging of salivary gland tumors Pleomorphic adenoma Basal cell adenoma Canalicular adenoma Warthin’s tumor Oncocytoma Myoepithelioma Ductal papillomas Mucoepidermoid carcinoma Central mucoepidermoid carcinoma Acinic cell adenocarcinoma Adenoid cystic carcinoma Polymorphous low grade adenocarcinoma Malignant mixed tumor Carcinoma ex-pleomorphic adenoma Carcinosarcoma Metastasizing mixed tumor Connective tissue tumors Necrotizing sialometaplasia

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CLASSIFICATION OF SALIVARY GLAND DISORDERS

DEVELOPMENT OF SALIVARY GLAND (FIGS 17.1A TO E)

(A) Developmental Disorders • Aberrancy • Aplasia and Hypoplasia • Hyperplasia • Atresia • Accessory Ducts • Diverticuli • Congenital Fistula (B) Functional Disorders • Sialorrhea • Xerostomia • Allergic • Associated with Malnutrition and Alcoholism (C) Obstructive Disorders • Sialolithiasis • Mucus Plug • Stricture and Stenosis • Foreign Bodies • Extra-ductal Causes (D) Cyst • Mucocele • Ranula (E) Asymptomatic Enlargement • Sialosis (cont on next page) • Oncocytoma • Monomorphic Salivary Adenomas Benign but often recurrent • Pleomorphic Adenoma • Mucoepidermoid Tumor (Low Grade) • Acinic Cell Tumor (Some) Malignant • Carcinoma in Pleomorphic Adenoma • Adenoid cystic carcinoma • Mucoepidermoid tumor(high grade) • Acinic cell tumor (some) • Squamous carcinoma • Adenocarcinoma • Undifferentiated carcinoma (F) Infection • Viral Infection • Bacterial Infection • Mycotic Infection (G) Autoimmune Disorders • Sjögren’s Syndrome • Mickulicz’s Disease • Uveoparotid Fever • Recurrent Non-specific Parotitis (H) Neoplasms Benign but seldom recurrent • Warthin’s Tumor

The three major sets of salivary gland- the parotid, submandibular and sublingual originate in a uniform manner by oral ectodermal epithelium buds invading the underlying mesenchyme. The parotid gland buds are the first to appear at the 6th week of intrauterine life, on the inner cheek, near the angles of mouth and grow back towards the ear. In the parotid and ear region, the epithelial cord of cells branches and canalizes to provide the acini and ducts of the gland. The duct and acinar system are embedded in a mesenchymal stroma, get organized into lobules and become encapsulated. The parotid gland duct, although repositioned, traces the path of embryonic epithelial cord in the adult. The submandibular gland buds also appear in the 6th week of intrauterine life as a grouped series, forming epithelial ridges on the either sides of the midline, in the floor of the mouth. An epithelial cord proliferates back into the mesenchyme beneath the developing mandible to branch and canalize, forming the acini and ducts of submandibular gland. The mesenchymal stroma is separated off the parenchyma lobules and provides a capsule for the gland. The sublingual glands arise in the 8th week of intrauterine life, as a series of about ten epithelial buds, just lateral to the submandibular gland anlage. These branch and canalize to provide a number of ducts opening independently beneath the tongue. The minor salivary glands begin their development during the third month of life. These glands arise from the oral ectodermal and endodermal epithelium. Labial glands arise during the 9th week of intrauterine life and are morphologically mature by 25th week. Classification of Salivary Glands • Exocrine glands: These are the glands whose products are carried away by the ducts leading from the gland. • Mesocrine glands: The secretory product pass through the cell walls losing the cytoplasm. • Serous salivary gland: The salivary glands which produce a thin watery secretion are called serous. • Mucous salivary gland: These produce a thick, viscous substance called mucous. • Seromucous salivary gland: Salivary glands which produce serous and mucous in varying quantities. • Major salivary gland: These are large salivary glands which are located outside the oral cavity and convey their secretions through their ducts. • Minor salivary gland: These are smaller salivary glands confined to the mucous and submucous coat of the oral cavity.

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A

B

C

D

E

Figures 17.1A to E Development of salivary gland systematic approach

MAJOR SALIVARY GLANDS

It then runs for a short distance obliquely forward, between the buccinator and mucous membrane of the oral cavity Major salivary glands are parotid, submandibular and and opens on the oral surface of the cheek, opposite the sublingual. upper second molar.

Parotid Gland It comes from the word para- around and otic-ear. It is like an inverted flattened pyramid. It is the largest of the salivary glands weighing about 15 grams each. It lies between the mastoid process and vertical ramus of the mandible. The bulk of the parotid gland is situated in the retromandibular fossa. It is wedge shaped, with the broad edge of the wedge lying subcutaneously and the apex lying deep between the parotid fascia. It is divided into superficial and deep lobes by the facial nerve and its branches. It forms an irregular lobulated yellowish mass, lying below the external acoustic meatus, between the mandible and the sternocleidomastoid. A small part of it, more or less detached lies between the zygomatic arch superiorly and the parotid duct inferiorly is named accessory part of the gland.

Blood supply: Parotid gland is supplied by the external carotid artery and its branches near the gland. Lymphatic drainage: Drains first to the parotid nodes and from there to the upper deep cervical nodes. Nerve supply: It is supplied by auriculotemporal nerve, plexus around the external carotid artery and greater auricular nerve.

Submandibular Gland

It is a round biconvex salivary gland situated in the anterior part of the digastric triangle. It is irregular in form and about the size of a walnut. It is enclosed by two layers of deep cervical fascia. The inner surface of the submandibular gland is in contact with stylohyoid, digastric and styloglossus muscle, posteriorly and with the Stensen’s duct: The parotid duct which is called ‘Stensen’s’ hyoglossus and posterior border of the mylohyoid muscle, duct is about 5 cm long and has thick walls. It emerges anteriorly. from the substance of the gland to course anteriorly until it reaches the anterior border of the masseter muscle Wharton’s duct: The submandibular duct which is called at the point of upper and middle thirds. When it crosses ‘Wharton’s duct’, is about 5 cms long and its wall is much the masseter muscle it receives the duct of the accessory thinner than that of parotid duct. It emerges from the middle lobe. Around the border of the masseter muscle, the duct of the deep surface, of the superficial part, of the gland. It turns sharply medially, often embedded in a furrow of the runs forward, beneath the deep part of the gland, between protruding buccal fat pad. In its medial course, the duct the mylohyoid and hyoglossus muscle. It runs further reaches the outer surface of the buccinator muscle, where it forward between the medial surface of the sublingual gland perforates in an oblique direction anteriorly and medially. and the genioglossus muscle and finally ends by opening

Textbook of Oral Pathology

into the summit of the sublingual papilla, situated in the floor of the mouth, on the side of the frenulum. The last few millimeters of the duct are often slightly widened. 412

Arterial supply: The arteries supplying the submandibular gland are derived from the lingual and facial branches of external carotid artery. Venous drainage: It drains into facial and lingual vein. Nerve supply: Its nerve supply is from the branches of submandibular ganglion through which it receives fibers from chorda tympani. Lymphatic drainage: It passes to the submandibular lymph node.

Sublingual Gland It lies above the mylohyoid and below the mucosa of the floor of mouth. It is medial to the sublingual fossa of the mandible, on either side of the symphysis menti and lateral to genioglossus muscle. It has about 15 ducts which open directly into the floor of mouth.

the mandible is found posterior to the first molar and often has a small communication with a major salivary gland. Developmental lingual salivary gland depression: The aberrancy of the salivary gland tissue represents only an extreme example of the condition known as the developmental lingual mandibular salivary gland depression. It is the developmental inclusion of the glandular tissue within or more commonly, adjacent to the lingual surface of the body of the mandible, in a deep well circumscribed depression. Mandible develops around the lobe during development. It was first described by Stafne in 1942 and hence referred to as Stafne’s cyst. It is rare with incidence of 4 in every adults. Males are affected more commonly than females. It is asymptomatic and only diagnosed on radiographical examination. Microscopically salivary gland tissue may be seen. Gingival salivary gland choristoma: Salivary tissue is regularly found in lymph nodes within the neck and can be mistaken for metastatic disease, if found in a neck dissection specimen. Ectopic salivary gland tissue has been reported to occur in the gingiva, where it may be described as ‘gingival salivary gland choristoma’.

Bartholin’s duct: The duct of sublingual gland is called ‘Bartholin’s duct’. They are eight to twenty in number. Some of the smaller sublingual ducts open into the Clinical significance: They may become site for developsublingual fold, in the floor of the mouth, on either side ment of a retention cyst or neoplasm. of lingual frenum. Some open into the submandibular duct Points to Remember and others unite to form the “principle sublingual duct” Ectopic salivary gland, developmental lingual salivary which opens in the floor. gland depression, inclusion of the glandular tissue, Blood supply: It is supplied by sublingual and submental Stafne’s cyst’, gingival salivary gland choristoma site arteries. for development of a retention cyst. Nerve supply: It is by lingual and chorda tympani nerve. Lymphatic drainage: It passes to the submandibular lymph nodes.

ABERRANCY

APLASIA AND HYPOPLASIA Aplasia or agenesis is the congenital absence of the salivary gland. It was first described by Gruber in 1885. Aplasia may occur in association with other developmental abnormalities such as atresia of lacrimal puncta and congenital malformation of temporomandibular component.

It is defined as that situation in which the salivary gland tissue develops at a site where it is not normally found. It is also called ectopic salivary gland. Causes Ectopic salivary tissue can develop anywhere within the territory of the first and second branchial arches, in the It results due to regional action of some disturbing influence in early fetal development. Macdonald suggested eclateral neck, pharynx or middle ear. todermal origin for this anomaly.

Clinical Features

Location: True aberrant salivary glands are most frequently reported in the cervical region, near the parotid gland or body of the mandible. The salivary gland tissue in

Clinical Features Any one of the glands or group of glands is missing, either unilaterally or bilaterally (Fig. 17.2).

Salivary Gland Pathology

HYPERPLASIA OF SALIVARY GLAND Sometime it is also called Adenomatoid hyperplasia of minor salivary gland.

Causes Hormonal disorders: Endocrine disorders and menopause. Metabolic disorders: Gout, diabetes mellitus. Autoimmune: Sjögren’s syndrome, Waldenstrom macroglobulinemia. Syndrome: Aglossia-adactylia syndrome, Heerfordt’s syndrome and Felty’s syndrome. Figure 17.2 Hypoplasia of the unilateral parotid gland (Plain

CT). Size of the left parotid gland (yellow arrow) is remarkably smaller compared with normal size of the right parotid gland (red arrow) (Courtesy: M Shimizu)

Symptoms: Patient complains of xerostomia, which may be so severe as to necessitate the constant sipping of water throughout the day and particularly, during meal times. The lack of saliva results in rampant dental caries and early loss of deciduous and permanent teeth.

Miscellaneous: Hepatic disease, starvation, alcoholism, inflammation, benign lympho-epithelial lesion, adiposity, hyperthermia, oligomenorrhea and certain drugs.

Clinical Features Location: It is more common in minor salivary glands of the palate. It is seen on the hard palate or at junction of hard and soft palate Signs: It is usually asymptomatic palatal gland hyperplasia appears as small localized swelling of varying size, measuring from several millimeters to 1 cm. The lesion has an intact surface and is firm, sessile and normal in color.

Signs: The oral mucosa appears dry, smooth, or sometimes pebbly and shows a tendency for accumulation of debris. Patients exhibit characteristic cracking of lips and fissuring of the corners of mouth. Hypoplasia of salivary glands is Histopathological Features rare but hypoplasia of parotid gland has been reported to be The mass appears microscopically as a closely packed present with Melkerson Rosenthal syndrome. collection of normal appearing mucous acini, with the usual intermingling of normal ducts. LADD: Lacrimo-auriculo-dento-digital syndrome. In this, hypoplasia of lacrimal and salivary gland can occur Management in association with cup shaped ears, dental and digital As it cannot be differentiated from minor salivary gland anomalies. tumors, it becomes essential to excise it for microscopic examination. Management Institution of scrupulous oral hygiene in an attempt to decrease dental caries and preserve the teeth as long as possible. Points to Remember Artesia of lacrimal puncta, xerostomia, oral mucosa appears dry, cracking of lips, Melkerson Rosenthal syndrome, lacrimo-auriculo-dento-digital syndrome, scrupulous oral hygiene.

Points to Remember Adenomatoid hyperplasia of minor salivary gland, minor salivary glands of the palate, small localized swelling of varying size, normal appearing mucous acini.

ATRESIA It is the congenital occlusion or absence of one or two major salivary gland ducts.

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Usually the submandibular duct in the floor of the mouth fails to canulate during embryological development. The newborn infant presents, within 2 or 3 days of life, with submandibular swelling on the affected side due to the presence of a retention cyst. It may produce a relatively severe xerostomia.

ACCESSORY DUCT An accessory parotid lobe is the most common developmental anomaly. It occurs in as many as 20 percent of subjects. Its position is constant, arising from the horizontal component of the parotid duct as it crosses the masseter muscle. Its importance lies in the fact that any of the diseases that can affect the salivary glands, may involve the accessory lobe and lead to diagnostic confusion, as the possibility is not considered. This is because the symptoms and signs are not within the normal anatomical territory of the parotid. Presence of additional duct in some salivary glands has been reported.

DIVERTICULI They are small pouches or out pocketing of the ductal system of one of the major salivary glands. Their presence leads to recurrent episodes of acute parotitis.

SIALORRHEA Excess saliva production is called ‘Sialorrhea’.

Causes It may results from local irritation, aphthous ulcer, ill fitting denture, rabies, heavy metal poisoning, medication such as antipsychotic agent, cholinergic agonist. Protective buffering system – episodic hypersecretion to neutralized stomach acid in gastroesophageal reflux disease also can cause Sialorrhea. Various disorders like mental retardation, cerebral palsy, Parkinson’s disease and amyotrophic lateral sclerosis can also cause Sialorrhea.

Clinical Features Symptoms: There is social embarrassment due to drooling of saliva. Sign: There is maceration around mouth, chin, and neck which can get secondary infected.

Idiopathic paroxysmal sialorrhea: There is excessive salivation lasting for 2 hr 5 minutes which is associated with nausea and epigastric pain.

Management Speech therapy: This can be used to control neuromuscular control. Anti-cholinergic medication: Transdermal scopolamine is used. Intraglandular injection of botulinum toxins as also been successful. Surgical technique like relocation and ligation of ducts of gland can be done. Points to Remember Aphthous ulcer, ill fitting denture maceration around mouth, idiopathic paroxysmal sialorrhea, speech therapy, anti-cholinergic medication, intraglandular injection of botulinum toxins.

XEROSTOMIA It is dry mouth in which there is reduced secretion of saliva.

Causes It can be caused by systemic disease salivary gland aplasia, water/metabolic loss, radiation therapy, chemotherapy, Sjögren's syndrome, diabetes, HIV infection, sarcoidosis and graft versus host resistance. Local factors like decrease mastication, smoking and mouth breathing can also cause xerostomia. Medication like antihistamine (diphenhydramine), decongestant, antidepressant, and sedative and anticholinergic agent can also cause xerostomia.

Clinical Features Symptoms: There is reduction of salivary secretion and residual saliva appears as foamy or thick and ropey. Patient complaint of difficulty in mastication and swallowing Sign: Mucosa is dry and gloves can stick to it. There is also atrophy of filiform papillae. There is increase prevalence of candidiasis, dental caries in the patient of xerostomia.

Management Artificial saliva can be given. Sugarless candy should be used to stimulate saliva.

Salivary Gland Pathology

Systemic pilocarpine can be used as sialagogue. Another sialagogue which can be used is cevimeline hydrochloride an acetyl choline derivative. Submandibular gland calculi more common due to following reasons: Anatomic factors • The length and irregular course of Wharton’s duct • The submandibular gland and ductal system lies in a dependent position • The greater size and position of the orifice • The orifice is much smaller than duct lumen Physiochemical factors • High mucin content of saliva • Great degree of alkalinity with high percentage of organic matter • Greater concentration of calcium and phosphate salts • Low content of carbon dioxide • Richness in phosphatase enzyme. Points to Remember Reduction of salivary secretion, dry mucosa, candidiasis, dental caries, artificial saliva, systemic pilocarpine.

SIALOLITHIASIS It is the also called salivary gland stone or salivary gland calculus. These are stones within major and minor salivary glands. These are the most common calcifications found in soft tissues of oro-orbital region. It is the formation of calcific concretions within the parenchyma or ductal system of the major or minor salivary glands.

Composition The calculus consists of laminated layers of organic material, covered with concentric shells of calcified material. The crystalline structure is chiefly hydroxyapatite and contains octacalcium phosphate. The chemical composition is principally calcium phosphate and carbon with traces of magnesium, potassium, chloride and ammonium.

Metabolic mechanism: In the presence of coexisting inflammation, a metabolic mechanism favors precipitation of salivary salts into the matrix.

Clinical and Radiological Features Age and sex distribution: They are usually encountered in middle-aged patients with slight predilection for occurrence in men. It usually occurs as a solitary concretion varying in size from a few millimeters up to several centimeters. Symptoms: The symptoms of sialolithiasis vary but intraglandular stones seem to cause less severe symptoms than the extra-glandular or intra-ductal types. On occasions, there may be complete absence of subjective symptoms. Many patients complain of moderately severe pain and intermittent transient swelling during meals, which resolves after meals. As the calculus itself rarely blocks a duct completely, the swelling subsides as salivary demand diminishes and as saliva seeps past the partial obstruction. The occlusion of the duct prevents the free flow of saliva and this stagnation or accumulation of saliva, when under pressure, produces pain. If no treatment is instituted, it appears as a pronounced exacerbation characterized by an acute suppurative process with attendant systemic manifestations such as fever and malaise. Signs: Pus may exude from the duct orifice. The soft tissues surrounding the duct show a severe inflammatory reaction, which may appear as swelling, redness and tenderness. Stones in the more peripheral portion of the duct may often be palpated, if they are of sufficient size. Sometimes, the overlying mucosa may ulcerate over the stone allowing the calculus extends into the oral floor. No saliva is seen to be coming out through the duct orifice. If stone is present in one duct only then saliva will not come out from that duct. It can be tested by placing two dry swabs one on each orifice and some lemon juice is dropped on the dorsum of the tongue. A minute later patient is asked to move the tongue up. The swab on the orifice of the duct where the stone is impacted will remain dry, whereas the other swab will be wet.

Stones in minor salivary glands: Sialolithiasis of minor salivary gland is a rare occurrence. The most common site is Etiology and Pathogenesis buccal mucosa either near the commissure or in proximity Neurohumoral mechanism: A neurohumoral condition, to the mandibular mucobuccal fold. It is more common leading to salivary stagnation, results in a nidus and matrix after the age of 39 years. The lesions appear as firm, freely movable masses, deeply situated into the mucosal surface. formation.

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Radiological features: It appear as radiopaque mass on radiograph (Fig. 17.3). 416

Histopathological Features Macroscopic features: It appears as hard mass which is round, oval or cylindrical. They are yellow or white or yellow-brown in color (Fig. 17.4). It is seen as calcific concretions arranged in concentric laminations around the amorphous debris (Fig. 17.5). There is also metaplasia of lining cells with inflammatory infiltrates surrounding it. Sialoliths are

Figure 17.5 Concentric laminations seen in sialolithiasis

also irregular, hexagonal and needle like plate shaped crystals.

Diagnosis

Figure 17.3 Sialolith in Parotid Stenson’s duct (arrow).

(Courtesy: Dr Swapnil Moghe, Senior Lecturer, Department of Oral and Maxillofacial Surgery, People Dental Academy, Bhopal, Madhya Pradesh, India

Palpation is an indispensable tool in the diagnosis of sialoliths. Palpation of the suspected gland frequently reveals it to be larger or firmer than the normal gland of the opposite side. Digital manipulation will produce a flow of saliva through the duct orifice and will allow visual inspection of the salivary fluid. During examination, the soft tissues overlying the duct should be manually stretched. Often, the physical distortion caused by the presence of calculus will become apparent. In addition yellowish color of the calcific deposits may be seen through the distended and thinned mucous membrane. A metallic duct probe can also be of value. Careful probing of the duct with a metallic probe will indicate the existence as well as the location of calculus. Radiographic examination usually reveals the presence of calcific deposits. Sialography is an invaluable aid in isolating the sialoliths which had not been identified on the standard intraoral and extraoral radiography.

Management

Figure 17.4 Parotid duct stone removed. (Courtesy: Dr Swapnil Moghe, Senior Lecturer, Department of Oral and Maxillofacial Surgery, People Dental Academy, Bhopal, Madhya Pradesh, India

Manual manipulation of stone within the duct should be carried out. Surgical approach should be taken for large stone Shock wave lithotripsy, salivary gland endoscopy and radiologically guided basket retrieval are newer technique that can be carried out.

Salivary Gland Pathology

Points to Remember Salivary gland stone or salivary gland calculus, laminated layers of organic material, hydroxyapatite octacalcium phosphate, moderately severe pain, intermittent transient swelling, severe inflammatory reaction surrounding the duct, stones in minor salivary glands, radiopaque mass on radiograph, stone is of yellow or white or yellow-brown, calcific concretions, metaplasia of lining cells.

STRICTURES AND STENOSIS It is cause by irritation from prosthetic appliances, maloccluded or malpositioned teeth, acute trauma with resultant edema and/ or scarring and intraductal tumor formation. Types • Papillary obstruction • Duct obstruction

Types Papillary obstruction: It may be either acute ulcerative obstruction or chronic fibrotic stenosis. Acute ulcerative obstruction is usually caused by acute trauma to the papilla and is treated conservatively with saline rinses and salivary gland massage. The ulcer generally heals without scarring and the symptoms will subside in such cases. In chronic fibrotic papillary obstruction, irritations to papilla has been recurrent and scarring exists. Duct obstruction: It may be due to a variety of factors. In cases of ductal obstruction secondary to acute trauma treatment is directed towards providing the duct patency until the edema is resolved. When the ductal obstruction occur secondary to irritation or scar contracture, sialograms are helpful in localizing the status of gland. If the gland is healthy, progressive and frequent dilatation of involved duct with lacrimal probes is generally successful in relieving the symptoms and signs. If this does not prove beneficial, ductoplasty is indicated.

MUCOCELE (MUCOUS EXTRAVASATION PHENOMENON) It is a term used to describe the swelling caused by pooling of saliva at the site of injured minor salivary gland. It is also know mucus escape phenomenon.

It is not a true cyst as it lack epithelial lining. Retention mucocele also known as ‘salivary duct cyst’ is separated entity so this is described under separate heading.

Pathogenesis Obstruction of salivary gland duct leads to its dilatation proximal to the obstruction, with the formation of epithelial lining retention cyst. Cut or traumatic defect of a salivary gland is responsible for the production of mucus extravasation mucocele. There is accumulation of mucus in the connective tissue and with the continuous pooling of saliva a clearly demarcated cavity develops which has no epithelial lining.

Clinical Features Age and sex distribution: Age of the patient varies with peak frequency in the 3rd decade but most of the cases occur before the age of 50. Retention cysts occur most often in older patients, where as mucus extravasation cysts occur in younger patients. Equal in sex frequency, with most cases are reported in white. Location: They are very common and occur most frequently on the inner aspect of lower lip; but may also occur on the palate, cheek, tongue and floor of mouth. Symptoms: The lesion may lie fairly deep in the tissues or be exceptionally superficial. Patient may complain of painless swelling which is frequently recurrent. The swelling may suddenly develop at meal time and may drain simultaneously at intervals. Signs: The mucocele may be only 1 to 2 mm in diameter, but is usually larger; majority of them being between 5 to 10 mm in diameter. Superficial cyst appears as bluish mass, as the thin overlying mucosa permits the pool of mucus fluid to absorb most of visible wavelength of light. If inflamed, it is fluctuant, soft, nodular and dome shaped elevation. Deeper lesions have the color of normal mucosa and are firmer. The swelling is round or oval and smooth. It is either soft or hard depending upon the tension in the fluid. It cannot be emptied by digital pressure. On aspiration, it yields sticky viscous clear fluid (Figs 17.6 and 17.7). Superficial mucocele: It can be seen in soft palate, retromolar and along the posterior border of buccal mucosa. They presented as single or multiple tense vesicle with less than 4 mm in diameter. This lesion burst leaving painful

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Figure 17.6 Mucocele presented as dome shaped elevation

Figure 17.8 Mucocele showing cyst irregularly shaped area

on lower lip

of mucous pool surrounded by inflammatory cell reaction

Figure 17.7 Mucocele presented as bluish swelling on lower lip (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Figure 17.9 Mucocele showing circumscribed appearance

(Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra)

In well defined cysts the periphery consists of ulcer which heal in few days. Vesicular appearance occur due to superficial spilling of mucin causing separation of granulation tissue or condensed fibrous tissue or both and is infiltrated by vacuolated macrophages, lymphocytes and epithelium from connective tissue. polymorphonuclear leukocytes, including eosinophils. One Histopathological Features or more dilated ducts are present and sometimes a breach (Figs 17.8 to 17.10) may be seen in the duct. Poorly defined cysts consist of irregularly shaped, poorly defined pools containing faintly eosinophilic mucinous Management material and numerous vacuolated macrophages which are Complete excision of the mucocele under local anesthesia. To prevent recurrence adjacent minor salivary gland should sometimes called muciphage. Some of these cysts are smaller and others extend be removed. Injection of steroid and cryosurgery can be tried. widely into the connective tissue.

Salivary Gland Pathology

Histopathological Features The lumen of cyst like cavity is filled with an eosinophilic coagulum, containing variable numbers of cells chiefly leukocytes and mononuclear phagocytes. The second group of well-defined cysts may be partially or completely lined by epithelium. The epithelium varies, it may consist of one or two layer of cuboidal cells or a thicker pseudo stratified columnar epithelium.

Management Conservative surgical excision of isolated cyst should be carried out. Figure 17.10 Mucocele seen under high power showing

muciphages

Points to Remember Mucus escape phenomenon, obstruction of salivary gland, inner aspect of lower lip, painless swelling, bluish mass, dome shaped elevation, superficial mucocele, sticky viscous clear fluid, muciphage, vacuolated macrophages, lymphocytes, polymorphonuclear leukocytes, complete excision.

SALIVARY DUCT CYST OR MUCUS RETENTION CYST It is caused by obstruction of minor salivary gland duct which causes the backup of saliva. This continuous pressure dilates the duct and forms a cyst like lesion. It is lined by epithelium. It is also called mucus duct cyst, sialocyst.

Clinical Features Age: It is more commonly seen in the adult patient.

Points to Remember Mucus duct cyst, sialocyst, parotid gland, bluish, firm on palpation, mucous retentions cysts, eosinophilic coagulum, one or two layer of cuboidal cells.

RANULA It is derived from Latin word Rana tigerina, i.e. frog belly.

Definition The term ranula is used for the mucocele occurring in the floor of the mouth, in association with ducts of submandibular or sublingual glands. Types of Ranula • Superficial: The superficial variety may develop as a retention or extravasation phenomenon associated with trauma to one or more of the numerous excretory ducts of the sublingual salivary gland. • Plunging or cervical: It ramifies deeply into the neck.

Location: It is seen in parotid gland, intraorally it is floor of mouth, buccal mucosa and lips.

Clinical Features

Sign: They are firm on palpation.

below the tongue and on the side of frenum.

Mucous retentions cysts: Some patient develop prominent ectasia of excretory ducts of salivary gland resulting in mucus retention cyst. Lesion present is painful nodules from which mucus or pus can be expressed.

Appearance: They produce blue swelling like a frog’s belly; hence it was given the term ‘ranula’ (‘ranula’ in Greek mean frog’s belly). The overlying mucosa is normal in appearance.

Age and sex distribution: They are usually unilateral. Appearance: They appear bluish depending on the depths It is usually in children and young adults with no sex of cyst below the surface. Cyst adjacent to submandibular predilection. gland duct may have amber color. Location: The typical position is on the floor of the mouth,

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Symptoms: It develops as slowly enlarging painless mass on one side of the floor of mouth. When the swelling suddenly grows it may be painful. Big ranula may cause difficulty in speech or eating. Signs: It is spherical or dome shaped with only top half is visible. It is smaller in early morning and largest just before meals, due to increased secretory activity in periods of gustatory stimulation and water absorption from the pooled mucus during inactive period. It is soft and tends to fluctuant (Fig. 17.11). It cannot empty by pressure and is non-pulsatile. Fluctuation and transillumination: Both tests are positive. The ranula is typically known as brilliant translucent swelling. Aspiration yields sticky clear fluid. Points to Remember Rana tigerina, blue swelling like a frog’s belly, painless mass, spherical or dome shaped, non-pulsatile, fluctuation and transillumination tests are positive. Plunging ranula: Bidigital palpation, cervical prolongation, partial excision with marsupialization.

Plunging Ranula When intrabuccal ranula has a cervical prolongation, it is called deep or plunging ranula. It is derived from cervical sinus. It lies along the posterior border of the mylohyoid muscle and appears in the submandibular region. Sometimes, plunging ranula herniated through the mylohyoid muscle and cause a swelling in suprahyoid or infrahyoid region.

Bidigital palpation: To inspect plunging ranula, bidigital palpation should be performed. On finger is placed inside the mouth on the ranula and the other finger is place on the swelling in the submandibular region. If pressure on the first finger causes sense of fluctuation on 2nd finger or vice versa, then it is plunging ranula.

Histopathological Feature Histopathological appearance is same as that seen in mucocele.

Management Surgical excision: They are best treated by surgical excision including a portion of the surrounding tissues. Partial excision with marsupialization: The major part of the cyst wall together with its overlying mucous membrane is excised.

SIALOSIS (SIALADENOSIS) It is characterized by non-neoplastic non-inflammatory enlargement of the salivary gland.

Cause The condition is found in association with systemic diseases especially cirrhosis, diabetes, ovarian and thyroid insufficiency, alcoholism and malnutrition. There is dysregulation of autonomic innervations of the salivary acini, causing an aberrant intracellular secretory cycle. This lead to excessive accumulation of secretory granules with marked enlargement of aciner cells.

Clinical Features Sex distribution: More commonly affects the females. Location: The enlargement is usually bilateral and may present a course of recurrent painless enlargement of gland. The parotid gland is more frequently affected. Symptoms: Swelling of the preauricular portion of the parotid gland is the most common symptom, but retromandibular portion of the gland may also be affected. Sialographic features: It will show leafless tree appearance.

Histopathological and Laboratory Features Figure 17.11 Ranula seen as bluish swelling in the floor of

mouth

Laboratory finding: A characteristic alteration in the chemical constituents of saliva is a distinguishing feature

Salivary Gland Pathology

of sialosis. Significant elevation of salivary potassium and concomitant decrease in salivary sodium is observed. Microscopically there is hypertrophy of acinar cells. The nuclei are displaced to cell base, and cytoplasm is engorged with zymogen granules.

Management The underlying cause should be treated, which will help in reducing the swelling. Points to Remember Non-neoplastic non-inflammatory enlargement of the salivary gland, recurrent painless enlargement of gland, leafless tree appearance, significant elevation of salivary potassium, hypertrophy of acinar cells, zymogen granules.

ALLERGIC SIALADENITIS In some cases, it may not appear as a true hypersensitivity reaction but rather as a toxic or idiosyncratic reaction to drugs that cause a decreased salivary flow, resulting in secondary infection. Various drugs which have been reported to cause allergic sialadenitis include sulfisoxazole, phenothiazines, iodine containing compounds, mercury, thiouracil and phenylbutazone.

MUMPS It is an acute contagious viral infection, characterized chiefly by unilateral or bilateral swelling of the salivary glands. It mainly affects major salivary glands, but also affects the testis, meninges, pancreas, heart and mammary glands. It is also called endemic parotitis.

Etiology It is endemic in most urban population. It is caused by paramyxovirus family with genus Rubella virus. It usually spreads from human reservoir, by airborne infection of infected saliva and possibly urine.

Clinical Features Age, sex and incubation period: It has got incubation period of 2 to 3 weeks. It is more common in boys than in girls and most often seen between the ages of 5 to 15 years. Prodromal symptoms: It is preceded by onset of headache, chills’ moderate fever, vomiting and pain below the ear which lasts for about one week.

Symptoms: The parotid gland is most commonly involved and it is usually bilateral. Submandibular gland may also be involved, although this is less noticeable and cause less pain. Both the parotid glands may involve simultaneously, but more commonly one parotid gland swells 24 to 48 hours after the other. It is then followed by sudden onset Mechanism: The exact mechanism of salivary gland of salivary gland swelling which is firm somewhat rubbery enlargement and loss of function following administration or elastic and without purulent discharge from the salivary of these drugs is not known. Most of the drugs cause gland duct. decrease in capillary permeability, where as others cause Signs: The enlargement of parotid gland causes elevation of sodium and chloride retention, which subsequently leads ear lobule and it produces pain upon mastication especially to edema. while eating sour food (Fig. 17.12). Papilla on the opening Symptoms: The clinical appearance of allergic sialadenitis of parotid duct is often puffy and reddened. varies, but in most of the cases there is bilateral parotid Epididymo-orchitis: This is common finding seen in gland enlargement following the administration of the drug. mumps. Affected testicle exhibits rapid swelling with pain The enlargement may be painful and is usually associated and tenderness. After resolution atrophy occur in testicle. with conjunctivitis and skin rashes. Other systemic disease like oophoritis, mastitis, It is a self limiting disease and needs no treatment. But menigoencephalitis, cerebellar ataxia, hearing loss, panin some cases, secondary bacterial infection may develop creatitis, arthritis, carditis and decrease renal function can and need treatment. occur. Points to Remember

Diagnosis

Sulfisoxazole, phenothiazines, iodine containing compounds, mercury, thiouracil and phenylbutazone, bilateral parotid gland enlargement.

The presence of parotitis and accompanying systemic signs of viral infections. Salivary amylase level is increased. A paramyxovirus may be isolated from saliva for as long as

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Site: In newborns, infection is generalized and is usually fatal with involvement of liver, lungs and central nervous system. 422

Signs: Infants who survive the infection may have permanent central nervous system involvement, including metal retardation and seizures. There may be hepatosplenomegaly, hemolytic anemia and hemorrhagic tendency. It may cause clinical disease of salivary gland, causing enlargement of the gland.

Laboratory Investigations Figure 17.12 Mumps showing swelling and elevation of

ear lobules (Courtesy: Dr Swapnil Moghe, Senior Lecturer Department of Oral and Maxillofacial Surgery, People Dental Academy, Bhopal, Madhya Pradesh, India)

6 days before and up to 99 days after the appearance of salivary gland swelling.

Management Most of the cases are self limiting, with salivary gland enlargement subsiding within a week. Prevention with live attenuated vaccine is the best method of controlling the disease. Symptomatic treatment is given to control pain and swelling. Points to Remember Paramyxovirus family with genus Rubella virus, prodormal symptoms, bilateral parotid gland swelling, rubbery or elastic, elevation of ear lobule, epididym-oorchitis, ophoritis, mastitis, menigoencephalitis, cerebellar ataxia, hearing loss, pancreatitis, arthritis, carditis, salivary amylase level increased, live attenuated vaccine.

CYTOMEGALOVIRUS INCLUSION DISEASE

Intranuclear and cytoplasmic inclusions in the cells of salivary glands are constant features of the disease. Points to Remember Salivary gland virus disease, infection is generalized, central nervous system involvement, heapatosplenomegaly, enlargement of the gland.

BACTERIAL SIALADENITIS It is also called suppurative parotitis.

Etiology Microorganisms: It is most commonly caused by penicillin resistant Staphylococcus aureus or streptococci viridians. Predisposing factors: It can occur in conditions such as dehydration, malnutrition, cancer and surgical infections. Oral hygiene: Poor oral hygiene is an important contributory factor. Drugs: Drugs like anti-Parkinson’s, diuretics and antihistaminic have been reported to be a contributory factor for acute bacterial sialadenitis. Types of Bacterial Sialadenitis • • • •

Acute bacterial sialadenitis Chronic bacterial sialadenitis Subacute necrotizing sialadenitis Chronic sclerosing sialadenitis

It is also called salivary gland virus disease. It is caused by cytomegalovirus, a herpes virus. It is common in immunosuppressed adult. Although it is congenital in nature, it is usually secondary to concurrent disease which has caused debilitation.

Clinical Features

Clinical Features

Acute Bacterial Sialadenitis

Age: It affects primarily in newborn infants and children, but adults are also affected.

Age: Most of the cases occur in adults but neonates and childhood form of the disease may occur.

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Location: Unilateral involvement of parotid gland is common. Symptoms: It begins with the elevation of body temperature and sudden onset of pain at the angle of the jaw which is intense when the extensive infection is contained within the confines of the parotid capsule. The localized symptoms are accompanied by fever, leukocytosis and other generalized signs and symptoms of acute bacterial infection. Signs (Fig. 17.13): Parotid gland is tender, enlarged and the overlying skin is warm and red. The swelling usually causes elevation of the ear lobule and the overlying skin is characteristically warm and red. Early in the disease, flecks of purulent material can be expressed from the salivary duct orifice. Intraorally the parotid papilla may be inflamed and pus may exude or be milked from the duct of the affected gland (Fig. 17.14). Cervical lymphadenopathy usually develops.

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Figure 17.14 Parotid infection showing purulent discharge

from the duct (Courtesy: Dr Swapnil Moghe, Senior Lecturer Department of Oral and Maxillofacial Surgery, People Dental Academy, Bhopal, Madhya Pradesh, India)

Chronic Bacterial Sialadenitis It is usually caused by Streptococcus viridans, E. coli or proteus. As compared to acute parotitis, it can be seen in normal children or in as in adults. Age: The childhood form commonly begins between the ages of 3 to 5 years and is usually unilateral. Signs: It appears as a unilateral swelling at the angle of the jaw in a patient with the history of similar occurrence. Salivary flow is accompanied by flecks of purulent Figure 17.15 Chronic bacterial sialadenitis presenting as

swelling at angle of jaw (Courtesy: Dr Chole, Modern Dental College, Indore, Madhya Pradesh, India)

material. After several recurrences, fibrosis of the glandular parenchyma occurs, which leads to decreased salivary flow. The pain is usually minimal and antibiotic therapy resolves the infection within a week. Recurrent form is most often due to duct obstruction, congenital stenosis, Sjögren’s syndrome, or previous viral infection or allergy.

Chronic Sclerosing Sialadenitis It is also called Kuttner’s disease. Figure 17.13 Bacterial sialadenitis showing enlargement of

parotid gland

Location: It is common in submandibular gland. It is cause by salivary ductal calculi causing subsequent pyogenic bacterial infections (Fig. 17.15).

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Appearance: It is a chronic inflammatory disease of the major salivary glands characterized by enlargement of the glands, resulting in fibrous tumor like masses. 424

Subacute Necrotizing Sialadenitis It is most commonly seen in teenagers and young adults. It involves minor salivary gland or hard and soft palate. There is a painful nodule covered by intact erythematous mucosa.

Histopathological Features Acute sialadenitis: There is accumulation of neutrophils in ductal system and acini. Chronic sialadenitis: There is scattered or patchy infiltration of salivary parenchyma by lymphocytes and plasma cells.

Points to Remember Acute type: Sudden onset of pain, overlying skin is warm and red, flecks of purulent material, accumulation of neutrophils in ductal system. Chronic type: Streptococcus viridans, E. coli or proteus, unilateral swelling at the angle of the jaw, recurrent form scattered or patchy infiltration of salivary parenchyma chronic inflammation Kuttner’s disease: Chronic sclerosing sialadenitis, salivary ductal calculi causing subsequent pyogenic bacterial infections, chronic inflammatory disease of the major salivary. Subacute necrotizing sialadenitis: Mixed inflammatory infiltrate, neutrophils, lymphocytes Management: Meticulous oral hygiene, parenteral antibiotics, patient hydrated.

Subacute necrotizing sialadenitis: There is heavy mixed inflammatory infiltrate consisting of neutrophils, SJÖGREN’S SYNDROME lymphocytes, histiocytes and eosinophils. Acinar cell are It is a chronic inflammatory disease that predominately lost and remaining exhibits necrosis. affects salivary, lacrimal and other exocrine glands. It was Chronic sclerosing sialadenitis: It can lead to chronic first described by Henrik Sjögren in 1933. It predominately inflammation, ensuing in the atrophy of mucous and affects middle aged and elderly women. serous cells and hyperplasia of the involved connective Types tissue leading to formation of the tumor like swollen masses. • Primary Sjögren’s or sicca syndrome sicca: It also

Management Meticulous oral hygiene should be practiced. Soft diet should be given as chewing is painful. It is treated aggressively because even with antibiotics death can result in debilitated patients. Specimen of purulent material should be immediately sent to laboratory for sensitivity and culture. Treatment usually starts with high dose of parenteral antibiotics active against penicillin resistant staphylococcus. The patient must be adequately hydrated and the electrolyte balance should be properly maintained with intravenous fluids. Salivation should be stimulated to facilitate drainage by sucking the sour hard candy. Oral hygiene should be maintained by debridement and irrigation. If improvement does not occur surgical drainage of the affected gland should be performed.

called sicca syndrome and it consists of dry eyes (xerophthalamia) and dry mouth (xerostomia). Eye lesion called keratoconjunctivitis sicca (sicca mean dry) • Secondary Sjögren’s syndrome: It consists of dry eyes, dry mouth and collagen disorders usually rheumatoid arthritis or systemic lupus erythematous.

Etiology and Pathogenesis Immunological findings: The lesion in this syndrome is immunologically mediated inflammatory exocrinopathy. It begins with periductal infiltration of the tissue by mononuclear cells. Autoantibodies: The B cell hyperactivity may result from deficiency of suppressor T lymphocytes or B lymphocytes by producing autoantibodies against them. Antinuclear antibodies found in patients with Sjögren’s syndrome are

Salivary Gland Pathology

directed against many nuclear antigens, most commonly to DNA histone. Patients with secondary Sjögren’s syndrome tend to develop antibodies against the EBV-associated nuclear antigen antibodies rheumatoid arthritis nuclear antigen (RANA). Polyclonal hyperglobulinemia: Serum immunoglobulin levels of IgG and IgM are also raised. B2 microglobulin: Serum salivary level of B2 microglobulin is raised in minority of patients and correlates with salivary lymphocyte infiltrate.

Etiology • • • • • • • • • •

Immunological findings Autoantibodies Polyclonal hyperglobulinemia B2 microglobulin Immune complex Cell mediated immune response Natural killer cell activity Virologic aspect Genetic aspect Lympho-proliferative malignancy

Immune complex: Circulating immune complexes are found in patients with primary and secondary Sjögren’s Clinical Features syndrome.

Oral

Cell mediated immune response: Delayed hypersensitivity response to skin testing is more depressed in patients with secondary Sjögren’s syndrome than in patient with primary Sjögren’s syndrome. Lymphokine production in response to antigen present in normal salivary tissue, is increased in patients with Sjögren’s syndrome.

Symptoms: Xerostomia is a major complaint in most of the patients. But many patients do not complain of dry mouth, but rather of an unpleasant taste, difficulty in eating dry food, soreness or difficulty in controlling dentures. Pus may be emitted from the duct. Angular stomatitis and denture stomatitis also occur. Dry mouth may be accompanied Natural killer cell activity: Augmented natural killer by unilateral or bilateral enlargement of parotid gland, cell activity is impaired in some patients with Sjögren’s which occurs in about one third of the patients and may syndrome. Although natural killer cells provide a defense be intermittent. Enlargement of submandibular gland may against viral infection and tumor, their role in Sjögren’s also occur. syndrome is unclear. Signs: Clinically, the mouth may appear moist in early Virologic aspect: Culture of saliva does not show any stages of Sjögren’s syndrome but later, there may a lack specific microorganisms and serologic studies have of the usual pooling of saliva in the floor of the mouth and failed to show increased titers of antibodies, except to frothy saliva may form along the lines of contact with oral soft tissue. In advanced cases the mucosa is glazed, dry cytomegalovirus (CMV). and tends to form fine wrinkles. Soreness and redness of Genetic aspect: Genetic effects of Sjögren’s syndrome mucosa is usually the result of candidial infection. depend on HLA-Linked and non HLA-Linked genes. In some patients, there may be clicking quality of their Relatives of a patient with Sjögren’s syndrome often show speech, caused by sticking of the tongue to the palate. a high incidence of connective tissue diseases. Primary The tongue typically develops a characteristic lobulated, Sjögren’s syndrome is associated with HLA-B8 and DR3 and usually red surface with partial or complete depapillation. secondary Sjögren’s syndrome is associated with HLA-B8 There is also decrease in number of taste buds, which leads DR4 and BW44. to an abnormal and impaired sense of taste. Dental caries is severe and gross accumulation of Lympho-proliferative malignancy: Enlargement of salivary glands in patients with Sjögren’s syndrome is plaque may be obvious. Periodontal disease can also occur. occasionally massive and associated with enlargement Sjögren’s syndrome is the most common underlying of regional lymph nodes, a condition known as ‘pseudo cause of acute bacterial sialadenitis in ambulated patients. lymphoma’. Malignant B cell lympho-proliferation has Such infections are usually either staphylococcal or pneumoccocal and usually cause swelling of the salivary been shown to affect patients with Sjögren’s syndrome.

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island. Lymphocytic infiltration of the glands with ensuing atrophy of glands also occurs.

Laboratory Investigations

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Rose Bengal staining test: Keratoconjunctivitis sicca is characterized by corneal keratotic lesion, which stains pink when rose Bengal dye is used. Schirmer test: The reduced lacrimal flow rate is measured by this test. A strip of filter paper is placed in between the eye and the eyelid to determine the degree of tears which is measured in millimeter. When the flow is reduced to less than 5 mm in a 5 minute sample, patient should be considered positive for Sjögren’s syndrome. Sialometry: Salivary flow rate estimation is a sensitive indicator of salivary gland function. Parotid glands make syndrome the major contribution to total salivary flow and are the most consistently affected glands in patients with Sjögren’s gland. The overlying skin is red, tender and shiny. The syndrome. Stimulated flow rate in symptomatic primary regional lymph nodes may be enlarged and tender. and secondary Sjögren’s syndrome is usually below 0.5 to On sialography it can show snowstorm or cherry 1.0 ml/minute (normal 1 to 1.5 ml/minute). blossom appearance (Fig. 17.16). Sialochemistry: Parotid saliva in Sjögren’s syndrome General contains twice as much total lipid and has elevated content Keratoconjunctivitis sicca: The patient usually complains of phospholipids and glycolipids than the normal saliva. of dry eyes or continuous irritation in the eyes. Severe lac- The sodium chloride and phospholipids levels are higher in rimal gland involvement may lead to corneal ulceration as saliva of Sjögren’s syndrome patient. Figure 17.16 Snowstorm appearance seen in Sjögren‘s

well as conjunctivitis.

Immunologic: A routine autoantibody profile can Connective tissue disorders: In patients with secondary usually be carried out with the particular aim of detecting Sjögren’s syndrome, rheumatoid arthritis is typically rheumatoid and antinuclear factors. long standing and clinically obvious. Patients may have Hematological investigations: It is necessary, particularly small joint and ulnar deviation of fingers and rheumatoid to exclude anemia. ESR or plasma viscosity, leukopenia nodules. occasionally may also be found. Dryness of pharynx, larynx and nose are noted by some patients. This is accompanied by lack of secretion in the Microbiological investigations: A swab from oral mucosa upper respiratory tract, may lead to pneumonia. Vaginal should be taken to confirm candidiasis, if there is soreness and erythema. Examination of pus is also of course essential dryness may be also complained by some females. as a guide to antimicrobial treatment, if acute sialadenitis develops. Histopathological Features There may be intense infiltration of the glands by lymphocyte cells replacing all acinar structure. In some cases, there may be proliferation of ductal epithelium and myoepithelium to form epimyoepithelial

Salivary gland biopsy: The changes in minor glands of lower lip show close correlation with those in the major salivary glands and provide a safe and convenient source of material.

Salivary Gland Pathology

Diagnostic Criteria I. Ocular symptoms: Dry eyes for more than 3 months, recurrent sensation of sand or gravel in the eyes and use of tear substitute more than 3 time per day. II. Oral symptoms: Dry mouth more than 3 months, recurrent or swollen salivary gland and drinking liquid to aid in swallowing. III. Ocular sign: Positive Schesmer test, positive rose Bengal score or other ocular dye score. IV. Histopathology in minor salivary gland focal lymphocytic sialadenitis with focus score (number of lymphocytic foci per 4 mm2) more than 1. V. Salivary gland involvement: unstimulated whole salivary flow ≤ 1.5 ml in 15 minutes. Parotid sialography showing diffuse sialectasias and salivary scintigraphy showing delayed uptake and delayed excretion. VI. Autoantibodies to Ro (SS-A) or La (SS-B) antigen. Primary Sjögren syndrome: Present of any four of six items presented above as long as item IV, VI is positive. Presence of any three of the four objective criteria. Secondary Sjögren syndrome: Connective tissue disease with item I and Item II plus any two from III, IV, V, VI.

MIKULICZ’S DISEASE OR BENIGN LYMPHOEPITHELIAL LESION It was first described by Mikulicz in 1888 as symmetric or bilateral, chronic, painless enlargement of lacrimal and salivary glands. It exhibits both inflammatory and neoplastic characteristics. Initially, Mikulicz’s disease was confused with disease processes such as leukemia and tuberculosis. In 1909 Campbell Howard went further and limited Mikulicz’s disease to merely a clinical syndrome. Classification • Mikulicz’s disease proper: lacrimal and salivary gland swelling only. • Pseudoleukemia: Lacrimal and salivary gland swelling plus lymphatic system involvement. • Leukemia: Lacrimal and salivary gland swelling plus hematopoietic involvement.

Clinical Features Age and sex distribution: It more commonly occurs in women in middle and later life. Location: It is manifested as a unilateral or bilateral enlargement of parotid and/or submandibular gland.

Management

Symptoms: The onset of the lesion is sometimes associated Most of the patients are treated symptomatically. with fever, upper respiratory tract infection, oral infection, Keratoconjunctivitis is treated by instillation of ocular tooth extraction or some local inflammatory disorders. In lubricants, such as artificial tears coating methylcellulose some cases there is mild local discomfort, occasional pain and xerostomia. and xerostomia is treated by saliva substitutes. Scrupulous oral hygiene and frequent fluoride Signs: There is often diffuse, poorly outlined enlargement application is indicated to reduce these problems. of salivary gland rather than formation of a discrete tumor Bromhexine can be used in some cases of Sjögren’s nodule. The enlargement varies in size but generally few syndrome. Surgery for enlargement of salivary gland centimeters in diameter. There is history of alternating is only recommended when the enlargement is causing increases and decreases in the size of mass, from time to discomfort to the patient. time. The duration of the tumor mass may be only a few months or many years. Points to Remember Xerostomia, unpleasant taste, lack of the usual pooling of saliva, clicking’ quality of their speech, dental caries, acute bacterial sialadenitis, snowstorm or cherry blossom appearance, keratoconjunctivitis sicca, connective tissue disorders, dryness of pharynx, larynx and nose, infiltration of the glands by lymphocyte cells, epimyoepithelial island, rose Bengal staining test, schirmer test, sialometry, sialochemistry, immunologic, ocular lubricants, bromhexine, scrupulous oral hygiene.

Histopathological Features

It is characterized by orderly lymphocytic infiltration of the salivary gland tissue, destroying or replacing the acini, with presence of islands of epithelial cells, which probably represent residual of gland. The epithelium consists of ducts showing cellular proliferation and loss of polarity. As the disease persist solid nest or clumps of poorly defined epithelial which termed epimyoepithelial islands is also present. Such islands arise as result of proliferation of

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ductal cells and peripheral myoepithelial cells. In advanced cases there is deposition of eosinophllic hyaline material in the epithelial islands. 428

Nerve involvement: The most common nerve involved is facial nerve. There is unilateral or bilateral seventh nerve paralysis. The neurological signs may precede, follow or appear simultaneously with parotid swelling. Trigeminal Management paresthesia, eyelid ptosis, polyneuritis, intercostal neuralSurgical excision and radiation can be given. Prognosis is gia and spinal nerve impairment accompanied by weakness and muscle atrophy have been reported. good. Points to Remember Unilateral or bilateral enlargement of parotid, submandibular gland, fever, upper respiratory tract infection, oral infection, diffuse, poorly, enlargement of salivary gland, lymphocytic infiltration, cellular proliferation and loss of polarity, ‘epimyoepithelial islands’.

Histopathological Features It will reveal a characteristic sarcoid nodule.

Management It is largely symptomatic as it may undergo spontaneous remission. Corticosteroid can be used in cases of acute exacerbation.

UVEOPAROTID FEVER

Points to Remember

It is a form of sarcoidosis and it is also called Heerfordt’s syndrome.

Heerfordt’s syndrome, prodormal symptoms, submandibular, sublingual and lacrimal gland swelling, sarcodial lesion, an inflammation of the uveal tract, facial nerve involvement causing paralysis, sarcoid nodule.

Triad • Uveitis: Inflammation of uveal tract of the eye. • Parotid swelling: Firm, painless and bilateral enlargement of parotid gland. • Facial palsy

TUMORS OF SALIVARY GLANDS

Salivary gland tumors are considered to have a special interest by pathologist because of its challenging variation in the appearance. No other tissue in the body produces the diversity in histopathological appearance as salivary gland Etiology tumor does. Tuberculosis was earlier thought to be the causative agent. Salivary tumors are said to be relatively uncommon Hereditary factor, autoimmune mechanisms are also lesions. The incidence is 3 to 5% of the tumors. It is considered etiological factors for it. important to note that neoplasms arise not only in major salivary glands, but also in minor salivary glands. Clinical Features In major salivary glands the most common site is parotid It usually occurs in 3rd and 4th decades of life. (64–80%) whereas submandibular gland and sublingual Prodromal symptoms lasting from a few days to glands show incidence of 8 to 11% and 1% respectively. several weeks are the usual initial signs of the disease and It is important to note that neoplasms arise not only in complains include fever, malaise, weakness, nausea and major salivary glands, but also in minor salivary glands. night sweat. It appears as a bilateral, firm, painless parotid Neoplasms in minor salivary glands are 9 to 23% of all swelling. tumors, palate being the most frequent site (42–54%). Signs: Submandibular, sublingual and lacrimal gland swelling may develop independently or during the course of the parotid swelling. The parotid swelling lasts from several months to several years. Sarcodial lesion may also be found in the oral cavity. Uveitis: It is an inflammation of the uveal tract, is a feature of this disease. Although ocular symptoms are usually bilateral, they become more apparent before the appearances of parotid swelling.

HISTOGENESIS The basal cells of the excretory duct and intercalated duct play a major role in the development of salivary gland. Basal cell of excretory duct forms columnar and squamous cell of the duct. The basal cells of intercalated duct gives rise to acinar cell, striated duct cells and myoepithelial cells. These two basal cells are said to be reserve cells or progenitor cells in salivary gland development (Fig. 17.17).

Salivary Gland Pathology

Ductal displacement: The ducts adjacent to the tumor are usually stretched around this is known as ball in hand appearance. Retention of contrast media in the displaced ducts during the emptying phase is seen.

Palpation of Tumor

Figure 17.17 Schematic diagram of salivary tree showing

acinus (A), intercalated ducts (ID-pink), striated ducts (SD-green), terminal secretory ducts (TSD-yellow) and myoepithelial cells (M)

THEORIES OF SALIVARY GLAND TUMOR HISTOGENESIS There are two hypothesis suggested in the development of salivary gland neoplasms. Well differentiated cells of the salivary gland unit form the neoplasm of their differentiated counterparts. According to this;



Acinar cell → Acinar cell carcinorma Striated duct cells → Oncocytic tumors Excretory duct cells → Squamous cell carcinoma and mucoepidermoid carcinoma Intercalated duct → Adenocarcinomas

Bicellular theory: These theories suggest that undifferentiated ‘reserve’ cell, i.e. basal cells of the excretory and intercalated duct are responsible for formation of the majority of neoplasms. According to this theory, dedifferentiation of already specialized cells such as acinar and striated duct cells duct not required for development of salivary gland neoplasms.

GENERAL FEATURES OF SALIVARY GLAND TUMORS Sialographic Appearance of Intrinsic Tumor of Salivary Glands An area of under filling within the gland, due to ductal compression by the tumor is seen.

Firmness of the tumor: Firmness results from dense aggregates of nests and cords of closely packed tumor. Fibrous tissue and hyaline area as well as cartilage like and bone like tissue. Softness results from fluid produce and retention phenomenon. Firm Tumor • Pleomorphic adenoma • Adenoid cystic carcinoma • Mucoepidermoid tumor of high grade • Carcinoma in pleomorphic adenoma • Acinic cell carcinoma • Oncocytoma Soft Tumor • Well differentiated mucoepidermoid tumor • Papillary cyst adenoma • Mucus producing adenocarcinoma • Warthin’s tumor

CLINICAL STAGING OF SALIVARY GLAND TUMORS By Spiro Staging of salivary gland neoplasms appear to have been initiated by Spiro. It is as follows: • T1-0 to 3 cm and solitary and freely mobile and CRVII intact • T2-3.1 to 6 cm and solitary and freely mobile or skin fixation and CRVII intact • T1- 6 cm or multiple nodules or ulceration or deep fixation or CRVII dysfunction • Patient with T1 and T2 lesion are placed into stage I and II respectively • Any patient with clinical evidence of metastasizes to lymph nodes or with T3 lesion is considered to be in stage III

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By American Joint Committee Primary Tumor 430

• Tx: Tumor that cannot be assessed by the rules. • T0: No evidence of primary tumor • T1: Tumor 2 cm or less in diameter, without significant local extension • T2: Tumor 2-4 cm in diameter without significant local extension • T3: Tumor more than 4 cm but not more than 6 cm in diameter without significant local extension. • T4a: Tumor over 6 cm in diameter without significant local extension. • T4b: Tumor of any size with significant local extension. Nodal Involvement (N) • Nx: Regional lymph node cannot be assessed • N0: No regional lymph node metastasis • N1: Clinical or histologically positive regional lymph nodes. Distant Metastasis (M) • Mx: Distant metastasis cannot be assessed • M0: No distant metastasis • M1: Distant metastasis Stage grouping is performed as follows: • • • •

Stage I: T1N0M0 or T2N0M0 Stage II: T3N0M0 Stage III: T1 or T2, N1 M0, or T4a or T4b N0 M0 Stage IV: T3 N1 M0, T4a or T4b N1 M0, any T any N M1

BENIGN TUMORS PLEOMORPHIC ADENOMA Pleomorphic adenoma is most common of the entire salivary gland tumor. The term pleomorphic adenoma was suggested by Willis characterizing the unusual histological pattern of the lesion (pleomorphic or mixed appearance). The morphologically diverse appearance of tumor is its pathognomic feature. This tumor is derived from a mixture of ductal and myoepithelial elements. It is said that the pleomorphic adenoma is the only tumor which shows remarkable diversity from one tumor to the next, as well as in different areas of the same tumor.

The nomenclature of this tumor as mixed tumor and pleomorphic adenoma describe the histologic appearance and not the clinical behavior and manifestation. The ability of the tumor cells to differentiate into epithelial and mesenchymal cells leads to formation of mixed picture showing fibrous, hyalinised, chondroid, myxoid areas along with areas of epithelial cells with metaplasia. Thus the term mixed tumor means the varied histopathological appearance due to differentiation of the tumor cells and it does not signify teratomatous origin. Other names suggested for this tumor are iceberg tumor, endothelioma, branchioma, or enchondroma, enclavoma.

Histogenesis and Pathogenesis The suggested theories of origin are as: Pleomorphic adenomas arise from myoepithelial cell and intercalated duct reserve cells. There are evidences for ulstrastructural similarities between the neoplastic cells and the suggested cells of origin. The proposed There is presence of myoepithelial cells and reserve cells, arranged in intercalated duct. Also the morphologic diversity of the tumor showing mixed tumor appearance with areas of fibrous mucinous chondroid and osteoid areas seen are suggested due to myoepithelial cells. The appearance of ductal pattern and areas of squamous cells are suggested to be from intercalated duct reserve cells. Batsakis theory: The reserve cells can differentiate into ductal and myoepithelial cells and undergo subsequent mesenchymal metaplasia. Thus the intercalated duct reserve cell is the histogenetic precursor of pleomorphic adenoma. Dardick’s theory: This theory suggests that any neoplastically altered epithelial cells can differentiate multidirectionally and the origin cannot be from intercalated and myoepithelial cells.

Clinical Features Sex and age: Women to men ratio is 6:4. It is common in 4th to 6th decades but also seen in young adults and children. Site: Parotid 90 percent and intraoral palatal gland on lip. Lower pole of superficial lobe of parotid gland is most commonly affected site. (Fig. 14.2) upper lip and buccal mucosa are very uncommonly affected. Appearance: Palatal tumors present as smooth surfaced dome shaped lesions or tumor mass. Ulceration may be

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Figure 17.18 Pleomorphic adenoma of parotid gland

Figure 17.19 Pleomorphic adenoma gross specimen showing

showing huge swelling

firm to hard mass exhibiting a cut potato appearance

seen if traumatized. Palatal tumors are immobile due to scribed, encapsulated and sometimes shows infiltration of their location and microanatomy but lip and buccal mucosa capsule by tumor cells. tumors are mobile (Fig. 17.18). Palatal pleomorphic adenoma usually shows infiltration of capsule beneath the epithelial surface. There are Symptoms: Small, painless, quiescent nodule which considerable variations with arrangement of epithelial and slowly begins to increase in size, sometimes intermittently. stromal components between different areas of tumor. The growth is a slow growing firm mass and the patient will The tumor can be described on the basis of the be usually aware of the lesion for months and years before following 3 components: an epithelial cell component, a seeking professional help in diagnosis and treatment. If myoepithelial cell component and a stromal (mesenchymal) neglected the tumor can grow to very huge size. component. Shape: The tumor tends to be round or oval when it is Epithelial component: The epithelial component consists small, as it grows bigger it becomes lobulated. of epithelial duct like cells, polygonal cells, cuboidal cells, Size: It may increase to cricket ball size or even more, spindle cells arranged in different patterns. The epithelial weighing in pounds and in intraoral cases, not more than 1 cells may be arranged in sheets, clumps, islands or interlace to 2 cm in diameter. strands. Cuboidal cells shows duct like arrangement. These Surface: Its surface is smooth. Sometime it is bosselated ducts like spaces may contain eosinophilic coagulum and mucoid material. Epithelial cells resembling squamous and is occasionally crossed by deep furrows. cells have distinct intercellular bridges. Cystic spaces are Consistency: It is firm and rubbery to feel. Sometimes also uncommonly seen. cystic degeneration may be seen. Myoepithelial component: Few stellate cells or spindle cells called myoepithelial cells are also seen with variable Histopathological Features morphology. These cells have rounded eccentric nucleus Macroscopic (Fig. 17.19): Encapsulated lesion with firm and eosinophilic hyalinized cytoplasm resembling rubbery consistency. Minor salivary gland tumor may not plasma cells. These cells are called plasmacytoid cells. show a well defined capsule. The gross cut surface of the Hyaline cells are also seen with dense eosinophilic firm mass shows a cut potato surface sometimes associated cytoplasm. with small cystic areas with mucoid, hemorrhagic areas. Pleomorphic adenoma exhibits wide cytologic and ar- Stromal component: The stromal changes are highly chitectural diversity. The tumor is typically well circum- variable and are believed to be produced by myoepithelial

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cells. Loose myxoid material may be seen with wide intercellular spaces and faint staining characteristics, foci of hyalinized C.T, areas of chondroid or cartilage like material. Osteoid or bone like material may be seen in between tumor cells (Figs 17.20 to 17.24). When the tumor is highly cellular or having predominantly epithelial component then it is often referred to as cellular adenoma. If myoepithelial cell component predominant, it is often referred to as myoepithelioma. The background of the tumor is made by stroma

Figure 17.22 Pleomorphic adenoma showing ductal spaces

(D) filled with eosinophilic material. Chondroid areas (C) are seen

Figure 17.20 Pleomorphic adenoma showing presence of duct like spaces (D), eosinophilic material (E), and mucous acini (M) peripherally capsule (C) is seen

Figure 17.23 Pleomorphic adenoma showing chondroid

areas (C) and island of squamous metaplasia (SM)

containing areas with mucoid deposition giving myxomatous appearance. Sometimes they show plasma cell like appearance called plasmacytoid myoepithelial cells. Types (Histological) of Pleomorphic Adenoma (Foot and Frazel 1954) Figure 17.21 Pleomorphic adenoma showing chondroid area

(Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

• • • •

Principally myxoid Myxoid–cellular components in equal proportions Predominantly cellular Extremely cellular

Salivary Gland Pathology

BASAL CELL ADENOMA It is a types of monomorphic adenoma. It was first described by Kleinsasser and Klein in 1967. It is a neoplasm of uniform distribution of basaloid epithelial cells. Characteristic features of monomorphic adenoma are the composition of the tumor by isomorphic/monomorphic cells distributed in various pattern of arrangement.

Histogenesis The isocellular cells resemble the reserve cells of intercalated duct. So the histogenetic source according to Batsakis is suggested to be from these basal cells. Figure 17.24 Pleomorphic adenoma myxoid area (Courtesy: Dr

Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

Management

Clinical Features Age and sex: It is more common in females with 2:1 predilection. Older age group, usually over 60 years of age are affected.

Surgical excision: Tumor and the involved lobe of gland Site: It occurs primarily in major salivary glands is removed. particularly in the parotid gland and intraorally, upper lip. Recurrence rate is 5 to 30 percent due to hypocellularity, Signs and symptoms: Size is less than 3 cm in diameter. incomplete resection and encapsulation. The tumor shows painless slow growth and presents as freely movable mass like pleomorphic adenoma. Signs of Malignant Transformation include • • • •

Accelerated growth rate Tumor irregularity on palpations Necrosis and painful ulceration Facial nerve involvement.

Points to Remember Adenomas arise from myoepithelial cell and intercalated duct reserve cells, Batsakis Theory, Dardick’s theory, parotid gland, smooth surfaced dome shaped lesions, painless, quiescent nodule, bosselated surface, firm consistency, firm rubbery consistency of excised section, infiltration of capsule beneath the epithelial surface, epithelial component consist of epithelial duct like cells, polygonal cells, cuboidal cells, spindle cells arranged in different patterns, myoepithelial component consist of myoepithelial cells which have rounded eccentric nucleus and eosinophilic, stromal component shows loose myxoid material, cellular adenoma, Myoepithelioma, myxomatous appearance, plasmacytoid myoepithelial cells, surgical excision.

Membranous basal cell adenoma: This occur in association with skin appendage tumors like dermal cylindromas and trichoepitheliomas.

Histopathological Features It is encapsulated well circumscribed tumor. The isomorphic cells are arranged into different patterns further classifying tumor into four types. Solid variant: The tumor cells are arranged into nests sheets islands with minimal connective tissue stroma. The cells have a basaloid appearance and resemble basal cell carcinoma. Confirmative diagnosis is made on the bases of clinical behavior and degree of dysplasia (Figs 17.25 and 17.26). Trabecular types: Epithelial cells form narrow cord like strands in a background of loose fibrillar stroma. Tubular variant: The epithelial cells form small round duct like structures which may be in combination with trabecular pattern.

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Management It is treated by surgical excision and recurrence is seldom seen.

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Points to Remember Reserve cells of intercalated duct, parotid gland, painless slow growth freely movable mass, membranous basal cell adenoma, isomorphic cells, solid variant arranged into nests sheets islands with minimal connective tissue stroma, trabecular types form narrow cord like strands, tubular Variant cells form small round duct like structures, membranous Variant arranged in zig saw puzzle pattern. Figure 17.25 Basal cell adenoma showing uniform appearing basaloid cells (B) in supporting stroma (S)

CANALICULAR ADENOMA It is types of monomorphic adenoma. The name itself implies the histologic appearance of the tumor. The cells are arranged in canalicular pattern or branching cord like pattern, hence the name. It is an uncommon neoplasm of columnar epithelial cells.

Clinical Features Age and sex: It is common in patients in 3rd to 6th decade. There is predilection in females. Site: It originates primarily in the intraoral accessory glands. It occurs in upper lips followed by palate, buccal mucosa and lower lip.

Figure 17.26 Basal cell adenoma showing cells arranged in

nests sheets Island (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

Membranous variant: Multiple large islands of tumor cells are arranged in zig saw puzzle pattern. These islands are surrounded by hyaline material resembling a double basement membrane. Histological Types of Basal Cell Adenoma • • • •

Solid variant Trabecular types Tubular variant Membranous variant

Symptoms: It presents as a slowly growing, well circumscribed, firm nodule, which is particularly on the lip and is not fixed. It may be moved through the tissues for some distance.

Histopathological Features It is composed of long strands or cords of epithelial cells, almost arranged in a double row and usually showing a party wall (Figs 14.10 and 14.11). Cystic spaces of varying sizes are enclosed by these cords. The cystic spaces are usually filled by an eosinophilic coagulum. The supporting stroma is loose and fibrillar with delicate vascularity (Figs 17.27 and 17.28).

Management It can be treated by simple enucleation and surgical excision. Recurrence rate is rare.

Salivary Gland Pathology

Development Heterotopic salivary rest theory: Tumor arises from salivary gland tissue entrapped with para-parotid or intraparotid lymph nodes during embryogenesis. Another theory suggests that there is neoplastic proliferation of parotid ductal epithelium and concomitant secondary proliferation of lymphoid tissue. Hypersensitivity theory: Allegra suggested that it is most likely a delayed hypersensitivity response. The lymphocytes being an immune reaction to the salivary ducts which undergo oncocytic change.

Clinical Features Figure 17.27 Canalicular adenoma showing anastomosing

narrow cords of epithelium (E) in loose stroma (S)

Age and sex: It is common in men (male to female ratio is 5:1). It is common in 6th decade. Site: The tumor occurs almost exclusively in the parotid gland. It always occurs in the lower portion of the parotid gland. The tumor is generally superficial. lying just beneath the parotid capsule or protruding through it. Symptoms: The usual complaint is painless slow growing tumor over the angle of jaw. Involvement may be bilateral or may be multifocal. Sign: The tumor does not attain a large size and the usual size is 1-3 cm in diameter. It is spherical in shape. Surface is smooth and it is well circumscribed, movable. It classically feels doughy and compressible on palpation. It is firm on palpation and is clinically indistinguishable from other benign lesions of parotid gland.

Figure 17.28 Canalicular adenoma showing double row of

Histopathological Features

The tumor is made up of epithelial and lymphoid tissue. It is an adenoma exhibiting cyst formation, with papillary projections into the cystic spaces and lymphoid matrix forming the connective tissue core of the papillae (Figs WARTHIN’S TUMOR 17.29 to 17.33). The epithelial cells, covering the papillary projection, It is also called adenolymphoma and papillary cystadenoma lymphomatosum and brachial cyst of parotid. This tumor are columnar or cuboidal cells usually arranged in two was first described by Hildebrad in 1895, later by Albrecht rows. and Arzt in 1910 reported few cases. The name papillary Outer cell layer is made up pseudociliated columnar cystadenoma lymphomatosum was given by Warthin in cells with eosinophilic granular cytoplasm. Nucleus is polarized away from the basement membrane. The inner 1929 in USA. Now it is recognized as Warthin’s tumor. The tumor shows papillary projection of the epithelium layer is made up of low cuboidal cells. Basement membrane into the cystic cavity formed in the existing adenoma. Thus distinctly separates epithelium from the lymphoid tissue. There is frequently an eosinophilic coagulum present it is a cyst in an adenoma showing papillary folds of the within the cystic spaces which appears as a chocolate epithelial lining.

cells of showing party wall appearance. Stroma shows loose stroma. Epithelial chords (EC), Stroma (S)

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Figure 17.29 Warthin’s tumor showing papillary projections

with lymphoid cores cystic cavity seen in background

Figure 17.30 Warthin’s tumor showing cystic space (CS) containing papillary projection (PP) lined by epithelium (E). Lymphoid stroma (LS) containing germinal center (GC) is present beneath the epithelium

colored fluid in the gross specimen. The lymphoid tissue beneath the epithelium shows germinal center formation. The abundant lymphoid component may represent the normal lymphoid tissue of the lymph node, within which the tumor developed or it may actually represent a reactive cellular infiltrate which involves both, humoral and cell mediated mechanism.

Management Superficial parotidectomy and it seldom recurs after removal.

Figure 17.31 Warthin’s tumor showing cystic space (CS) and double row of cells. Outer cells (PC) are tall columnar with nucleus polarized away from basement membrane. Inner cells (IC) are cuboidal. These cells enclose lymphoid stroma (LS)

Figure 17.32 Papillary projections in Warthin’s tumor are

lined by outer columnar cells and inner cuboidal cells

Points to Remember Adenolymphoma, heterotopic salivary rest theory, neoplastic proliferation of parotid ductal epithelium, hypersensitivity theory, parotid gland, painless slow growing tumor, spherical in shape, surface is smooth, columnar or cuboidal cells, pseudociliated columnar cells with eosinophilic granular cytoplasm, eosinophllic coagulum, reactive cellular infiltrate, superficial parotidectomy.

Salivary Gland Pathology

Size: The tumor usually measures 3 to 5 cm in diameter and appears as a discrete encapsulated painless mass which is sometimes nodular. Pain is generally absent. Oncocytosis or nodular oncocytic hyperplasia: an interesting condition called oncocytosis of parotid gland has been described which is characterized by nodules of oncocytes involving the entire gland or a large portion. In this there is transformation of ductal and acinar cells into oncocytes. In some cases entire gland is replaced by oncocytes (diffuse hyperplastic Oncocytosis).

Histopathological Features Oncocytoma is a well circumscribed tumor. It is composed of oncocytes, which are large cells with eosinophilic Figure 17.33 Warthin’s tumor showing cystic space (CS) and granular cytoplasm and distinct cell membrane (Fig. 17.34). double row of cells. Outer cells (PC) are tall columnar with The cytoplasmic granularity is because of exclusion of nucleus polarized away from basement membrane. Inner cells other cell organelles and their replacement by abundant (IC) are cuboidal. These cells enclose lymphoid stroma (LS) uniform mitochondria which makes the cell to appear (Low magnification) swollen. Oncocytes are arranged in solid sheets and sometimes tend to be arranged in narrow rows, cords and may demonstrate alveolar or lobular pattern. ONCOCYTOMA These cells exhibits few mitotic figures are closely Oncocytoma is a tumor of oncocytes. Oncocytes are large packed and there is little supportive stroma. Lymphoid epithelial cells that contain brightly eosinophilic granular tissue is frequently present. cytoplasm. This is due to abundant mitochondria packing in the cell cytoplasm. It is also called oxyphilic adenoma, Management acidophilic adenoma. It is an uncommon tumor composing Surgical excision should be done. Tumor does not tend to less than 1 percent of salivary neoplasms. These cells are recur. Malignant transformation is very rare. predominately seen in duct lining of glands in elderly persons.

Pathogenesis As the tumor is exclusively seen in older age group it is suggested that the oncocyte are the result of degeneration of the salivary gland parenchyma. Another school of thought is that it is a metaplastic process seen in hyperplasia of salivary parenchyma. This further could proliferate into neoplastic state. Some suggest that it is not neoplasm but merely a nodular hyperplasia.

Clinical Features Age and sex: It is more common in women than in men and occurs almost exclusively in older persons. Site: It usually occurs in the parotid gland.

Figure 17.34 Oncocytoma with oncocytes showing dense

eosinophilic cytoplasm

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Points to Remember 438

Oxyphilic adenoma, acidophilic adenoma, degeneration of the salivary gland parenchyma, hyperplasia of salivary parenchyma, oncocytosis or nodular oncocytic hyperplasia, diffuse hyperplastic oncocytosis, discrete encapsulated painless mass. Oncocytes are large cells with eosinophilic granular cytoplasm and distinct cell membrane abundant uniform mitochondria, arranged in solid sheets, few mitotic figures.

MYOEPITHELIOMA It is an uncommon salivary gland tumor. Sheldon in 1943 seperated this as a different entity from pleomorphic adenoma as these tumors were composed predominantly of basket cells or myoepithelial cells.

Figure 17.35 Myoepithelioma showing capsule (C) and myoe-

pithelial cells (EC) producing hyaline eosinophilic material (E)

Clinical Features Age and sex: It occurs in adults and has equal sex distribution. Site: Parotid gland is most commonly involved and the palate is the most frequent intraoral site of occurrence. The clinical features are same as pleomorphic adenoma.

Histopathological Features The tumor is composed of spindle shaped myoepithelial or plasmacytoid or combination of the two cell types (Figs 14.35 and 14.37). These cells may be set in myxomatous background, which vary from scanty to copious.

Figure 17.36 Myoepithelioma showing plasmacytoid cells (P)

and material (E)

Management Surgical excision should be carried out. Points to Remember Parotid gland, spindle shaped myoepithelial or plasmacytoid, myxomatous background.

DUCTAL PAPILLOMAS It is salivary gland tumor which is characterized by papillomatous pattern. Many times squamous papilloma will arise at the site where minor salivary gland duct merge with the surface epithelium. So this type of squamous papilloma will contain scattered mucous cells within the exophytic growth. This type is called ductal papilloma.

Clinical Features Intraductal papilloma: It is present as an exophytic lesion with a papillary surface and is pedunculated. It is usually reddish in color and present on the buccal mucosa or palate Inverted ductal papilloma: It appears as a submucosal nodule beneath normal appearing overlying surface mucosa. It is commonly seen on lower lip. It is asymptomatic and sometimes may present with a surface opening or pit or indentation in surface. Sialadenoma papilliferum: It is a salivary gland analogue of the syringo-cystadenoma paipilliferum of skin. The lesion occurs in adults as an exophytic papillary lesion of the hard palate.

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Figure 17.37 Myoepithelioma showing spindle cell

Figure 17.39 Inverted ductal papilloma showing papillary

projections into the stroma

proliferation

consist exophytic papillary projection covered by stratified squamous epithelium. These ductal cells have oncocytic appearance. Inflammatory infiltrate of plasma cells, lymphocytes and neutrophil is present. Inverted ductal papilloma: There is proliferation of squamoid epithelium with multiple thick bulbous papillary projections that fill the ductal lumen. This epithelium communicated with surface through small pore like opening (Fig. 17.39).

Management It is treated by excision, including the base and it does to recur after completely removed. Figure 17.38 Ductal papilloma showing papillary

proliferations from ductal lining

Histopathological Features Intraductal papilloma: It consists of non keratinized epithelium of the columnar type, supported by cores of vascular fibrous connective tissue. It is lined by single or double row cuboidal or columnar epithelium. There is multiple arborizing papillary projection into the cystic lumen (Fig. 17.38). Sialadenoma papilliferum: It consists of luminal layer of columnar cells resting on a cuboidal basal layer. It

Points to Remember • I ntraductal papilloma: Exophytic lesion with a papillary surface non keratinized epithelium of the columnar type, single or double row cuboidal or columnar epithelium. • Inverted ductal papilloma: Submucosal nodule, lower lip, proliferation of squamoid epithelium, bulbous papillary projections. • Sialadenoma papilliferum: It is a salivary gland analogue of the syringo-cystadenoma paipilliferum skin, luminal layer of columnar cells, exophytic papillary projection, plasma cells, lymphocytes.

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MALIGNANT SALIVARY GLAND TUMORS 440

MUCOEPIDERMOID CARCINOMA The term mucoepidermoid carcinoma (MEC) was introduced in 1945 by Stewart, Foote and Becker. MEC comprises between 2.8 percent and 15.5 percent of all salivary gland tumors, between 12 percent and 29 percent of malignant salivary gland tumors, and between 6.5 percent and 41 percent of minor salivary gland tumors, representing the most common type of malignant minor salivary gland tumor in most series. About half the cases occur in the major salivary glands, >80 percent of these occur in the parotid, 8 to 13 percent occur in the submandibular gland, and 2 to 4 percent involve the sublingual gland. In the minor salivary glands MEC most commonly arises on the palate, but a significant number may also be found in the retromolar area, floor of the mouth, buccal mucosa, lip, and tongue. Rarely, MEC can arise as primary jaw or heterotopic intranodal tumors, or as laryngeal, lacrimal, nasal, paranasal, tracheal, or pulmonary tumors (Figs 14.18 and 14.19). It consists, of both, mucus secreting as well as epidermoid type of cells as its name suggests. The biologic behavior of the mucoepidermoid carcinoma is graded on the basis of clinical and histological features.

Histogenesis

Onset: It appears as a slowly enlarging painless mass, which simulates pleomorphic adenoma. It is usually not completely encapsulated and often contains cysts which may be filled with viscid mucoid material. The tumor of low grade malignancy usually appears as a slowly enlarging, painless mass, which simulates pleomorphic adenoma. It seldom exceeds 5 cm in diameter. The tumor of high grade malignancy grows rapidly and does produce pain as an early symptom. Ulceration is seen in cases which have an aggressive clinical course (Figs 17.40 and 17.41).

Figure 17.40 Intraoral ulceration seen on left side due high

grade mucoepidermoid tumor

It is an accepted hypothesis that the tumor develops from an excretory duct reserve cell (Dardick’s theory).

Etiology The most commonly implicated etiologic factor is radiation; as according to a study many as 44 percent of patients with a history of a radiation-associated salivary tumor developed MEC (Kaste et al. 1994). Latency period in this group is reported to range from 7 to 32 years.

Clinical and Radiological Features Age and sex: It is most frequently seen in the 35 to 65 year age group but may be found at any age. It has a slight predilection for women. Site: About 60 percent occur in parotid gland and 30 percent in the minor salivary glands, especially those of the palate. Other common intraoral sites are buccal mucosa, tongue and retromolar area.

Figure 17.41 Mucoepidermoid carcinoma of left parotid

gland showing ulceration of skin

Salivary Gland Pathology

It tends to infiltrate the surrounding tissues and in high percentage of cases it metastasizes to the regional lymph nodes. Distant metastases to lungs, bones, brain and subcutaneous tissue are common. Much more various findings such as lacrimation, trismus, nasal discharge, and blood tinged saliva and facial nerve paralysis are seen in high grade malignant lesions. Intraoral lesions with bony erosion may show numbness of teeth.

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Radiological features: CT scan is more useful in delineated margin of the lesion (Fig. 17.42).

Histopathological Features (Figs 17.43 to 17.51) The term mucoepidermoid itself signifies that it is composed of mucus-secreting cells and epidermoid type cells. Third type of cells commonly seen is intermediate cells. Mucous cells are cells with foamy cytoplasm filled with mucin. Epidermoid cells are large polygonal cells with prominent nuclei, distinct cell membranes, intercellular bridges, abundant eosinophilic cytoplasm. Epidermoid cells are occasionally associated with keratin production including pearl formation. These tumors show great variability in the composition of cell types in a given tumor. Cellular pleomorphism and atypia may be found and range from minimal to severe. The intermediate cells are small, round basaloid cells. These cells are seldom the dominant cell, although

Figure 17.43 Mucoepidermoid carcinoma showing presence

of clear cells (CC)

Figure 17.44 Mucoepidermoid carcinoma low power

Figure 17.42 CT scan showing extent of palatal

mucoepidermoid carcinoma palate

it appears that it may undergo transformation into either mucus or epidermoid cells. Sometimes cluster of clear cells, often in abundance, may be present which are generally containing mucinous material and glycogen. If the clear cell population predominate then it is called clear cell variant of MEC. Occasional MECs will be associated with a prominent oncocytic component and are referred to as the oncocytic variant. Ductal proliferation adjacent to the tumor is common. These tumors show sheets or nests of epidermoid cells and similar nests of mucous cells, usually arranged in a glandular pattern and showing microcyst formation. These

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Figure 17.45 Low grade mucoepidermoid carcinoma showing presence of mucous cells (MC) and epidermoid cells (EC) in equal proportions. Large mucous containing cystic space (CS) are seen

Figure 17.46 Mucoepidermoid carcinoma showing large

17.47 High grade mucoepidermoid carcinoma showing predominate epidermoid cell (EC) only few mucous cells (MC) and few cystic spaces (CS)

Figure

Figure 17.48 Cystic areas in MEC

cystic areas containing mucin

cysts may rupture liberating mucus, which may pool in the connective tissue and evoke inflammatory reaction. In such cases lymphocytes are seen. Tumor is graded on the bases of proportion of epidermoid and mucous cells, degree of cystic transformation of the tumor, and degree of cellular atypia. It graded into three types:

cells are seen in the tumor mass. Few epithelial nests are seen. Intermediate grade: The cystic transformation is less as compared to low grade. There is predominance of intermediate cells although areas of mucous and epidermoid cells are seen. Cellular atypia is minimal.

High grade: The predominant cellularity is of epidermoid Low grade: It predominantly shows mucous cells and cells with varying dysplastic features. These cells show abundant extracellular mucin. Several cystic areas lined by considerable cellular atypia.

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Figure 17.49 Mucoepidermoid carcinoma showing

epidermoid cells and mucous cells

Figure 17.51 Clear cells showing vacuolated cytoplasm in

mucoepidermoid carcinoma (high power)

Grading Criteria • The degree of tumor invasion, • Anaplasia pattern of invasion, • Degree of maturation of the-various cellular components, • Mitotic rates, • Presence or absence of necrosis, • Neural or vascular invasion, • Proportion of tumor composed of cystic spaces relative to solid growth.

Management Figure 17.50 Intermediate cells in mucoepidermoid

carcinoma

Surgical excision followed by radiotherapy is recommended for intermediate grade tumors and high grade tumors. Low grade tumors can be managed by surgery alone. Points to Remember

Grading (Brandwein et al) • Grade I-Prominent goblet cell component, cyst formation intermediate cells may be prominent circumscribed growth pattern • Grade II-Intermediate cells predominate over mucinous cells mostly solid tumor squamous cell may be seen • Grade III- Squamous cells predominate intermediate and mucinous cells must also be present, mostly solid variant.

Parotid gland, minor salivary glands, slowly enlarging painless mass, low grade malignancy, high grade malignancy grows rapidly, ulceration, distant metastases to lungs, bones, brain, lacrimation, trismus, nasal discharge, blood tinged saliva, facial nerve paralysis, numbness of teeth, mucous cells, epidermoid cells, cellular pleomorphism, intermediate cells are small, round basaloid cells, cluster of clear cells, clear cell variant of MEC, oncocytic variant, microcyst formation.

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Clinical Features Sex: It is more common in females than males. 444

Site: It occurs in mandible in premolar-molar area. It does not extend anteriorly beyond the premolar region. Symptoms: Patient complain of painless swelling. There may be paresthesia of inferior alveolar nerve. Sign: Swelling may cause facial asymmetry. Tenderness is present. Regional lymph nodes are enlarged. Radiological features: It present as a unilocular or multilocular expansile mass. Margin often well defined, well corticated and often crenated or undulating in nature. It has got soap bubble or honey comb internal structure.

A

Histopathological Features It is similar to that of intraosseous mucoepidermoid carcinoma. Most of the lesions are low grade tumor.

Management It is treated surgically with en block resection. Neck dissection and postoperative radiation therapy may be required for control of nodal disease. Points to Remember

B Figures 17.51A and B Acinic cell carcinoma showing clear

cells arranged acinar pattern

Intraosseous mucoepidermoid carcinoma, entrapment of retromolar mucous glands, premolar-molar area in mandible, painless swelling, facial asymmetry, soap bubble or honey comb, multilocular expansile mass, neck dissection, postoperative radiation therapy.

CENTRAL MUCOEPIDERMOID CARCINOMA

ACINIC CELL ADENOCARCINOMA

It may originate from entrapment of retromolar mucous glands within the mandible, which subsequently undergo neoplastic transformation. It may also form from developmentally included embryonic remnants of the sub-maxillary gland within the mandible and neoplastic transformation of the mucous secreting cells commonly found in the epithelial lining of dentigerous cyst.

Site: It arises exclusively in the superficial lobe and tail of the parotid gland. The most common intraoral sites are the buccal mucosa and lip.

It is also called acinic cell or serous cell adenoma. This It is also called an intraosseous mucoepidermoid is low grade malignancy. It accounts for approximately carcinoma. It is an extremely rare tumor originating in the 1 percent of all salivary gland tumors. bone and is believed to be derive from salivary gland tissue Clinical Features entrapment in developing bone. Age and sex: It occurs in middle age and twice common in women. Origin

Symptoms: It is painless and grows slowly. Sign: Exact delineation of the lesion is difficult and attachment to the overlying skin and muscle may occur. Some of these lesions run a rapid course with hematogenous

Salivary Gland Pathology

and lymphatic metastases, while others are more slowly Symptoms: The most common initial symptom is presence progressive. Locally invasive growth may be encountered of mass followed by local pain, facial nerve paralysis in in some lesions. It resembles to pleomorphic adenoma and case of parotid tumor and tenderness. is encapsulated and lobulated in appearance. Sign: Some of the lesions exhibit surface ulceration. Other findings include nasal obstruction, proptosis, sinusitis, ear Histopathological Features infection, epistaxis, signs of cranial nerve involvement and It is surrounded by a thin capsule, may be composed of visual disturbances. cells of varying degrees of differentiation. Well differentiated cells bear remarkable resemblance Histopathological Features to normal acinar cells, whereas less differentiated cells (Figs 17.52 to 17.58) resemble embryonic ducts and immature acinar cells (Fig. FNA cytology: It presents characteristic appearance of the 17.53). tumor. Smears are cellular with a monomorphic population The tumor cells can be arranged in solid masses or in acini like groups. There are four types of growth pattern seen: solid, papillary-cystic, follicular and microcystic. Lymphoid elements are commonly found in parotid acinic carcinomas.

Management Surgical excision is done. Recurrence rate varies form 8 to 59 percent. Points to Remember Acinic cell or serous cell adenoma, exclusively in the superficial lobe, painless, locally invasive growth, well differentiated cells, immature acinar cells, solid, papillary-cystic, follicular and microcystic.

ADENOID CYSTIC CARCINOMA

Figure 17.52 Adenoid cystic carcinoma showing presence of

cribriform pattern (low power)

It is also called cylindroma, adenocystic carcinoma and basaloid mixed tumor. Adenoid cystic carcinoma arises from major and minor salivary glands and accounts for one fourth of malignant salivary gland tumors. It is a slow-growing malignant tumor that might be aggressive, with a high incidence of distant metastasis. Apart from the salivary glands, adenoid cystic carcinoma also has been reported in other locations, including the breast, lung, larynx, and trachea. The morphologic features of adenoid cystic carcinoma are similar, regardless of site. Adenoid cystic carcinoma spreads by direct extension, perineural invasion, and hematogenous metastasis. Lymphatic spread is uncommon.

Clinical Features Age: It occurs in the 5th and 6th decade of life. Site: Most common glands involved are the parotid, sub maxillary and the accessory glands in palate and tongue.

Figure 17.53 Adenoid cystic carcinoma showing tubular and

cribriform pattern (Courtesy: Dr Sangamesh Halawar)

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Figure 17.54 Solid pattern of ACC showing sheets of uniform

Figure 17.56 Characteristic feature of ACC is perineural

appearing cells

invasion by tumor cells (TC); (N) Nerves

Figure 17.55 ACC showing tubular pattern (T). Hyperchromatic

Figure 17.57 Low power view of adenoid cystic carcinoma

epithelial cells (E) showing no dysplasia form ducts (D)

solid pattern showing large islands or sheets of tumor cells with little tendency for cyst formation

of small basaloid cells with high nuclear/cytoplasmic ratios, coarse chromatin, and small nucleoli. Also present are variable amounts of acellular hyaline stroma in globular or cylindromatous formations typically identified in aspirates of the cribriform and tubular subtypes.

Tubular pattern: The stromal connective tissue becomes hyalinized and surrounds the tumor cells, forming a structural pattern of cylinder or tubular from which the lesion originally derived the name cylindroma.

Cribriform pattern: It is composed of small, deeply staining uniform cells resembling basal cells that are commonly arranged in anastomosing cords or may contain a mucoid material producing the typical cribriform honey comb or Swiss cheese pattern.

Solid variant: It consist of larger island or sheets of tumor cells. There is also cellular pleomorphism and mitotic activity and focal necrosis in the center of the tumor island. In some cases delicate anastomosing cords of neoplastic cells are dispersed throughout an abundant stroma.

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Figure 17.58 High power view of adenoid cystic carcinoma solid type-showing cells arranged in sheets. Cells are hyperchromatic with little atypia. Few cystic spaces are seen

Figure 17.59 Polymorphous low grade adenocarcinoma

showing intraoral ulceration

Management Surgical and in some cases it is accompanied by X-ray radiation. Recurrence rate is about 60 to 92 percent. Long-term follow-up is hence essential. The incidence of metastases is more and the organs involved include cervical lymph nodes, lungs, brain, liver and kidneys. Points to Remember Cylindroma, adenocystic carcinoma, parotid, sub maxillary, presence of mass, local pain, facial nerve paralysis, surface ulceration, FNA cytology shows monomorphic population of small basaloid cells with high nuclear/cytoplasmic ratios, coarse chromatin, and small nucleoli, cribriform pattern composed of small, deeply staining uniform cells resembling basal cells cribriform ‘honey comb’ or ‘Swiss cheese’, tubular pattern becomes hyalinized tumor cells, solid variant consist of larger island or sheets of tumor cells.

POLYMORPHOUS LOW-GRADE ADENOCARCINOMA It is also called lobular carcinoma, terminal duct carcinoma. It is a malignant epithelial tumor showing which is highly malignant and metastasize to regional lymph nodes and general viscera.

Figure 17.60 CT scan of polymorphous low grade carcinoma

Clinical Features Location: It is seen exclusively in minor salivary gland. Mostly occur on hard and soft palate, upper lip and buccal mucosa. Age and sex distribution: It is more common in adults with female predilection. Sign and symptoms: There is painless mass which can be associated with bleeding and discomfort. Tumor can erode underlying bone (Figs 17.59 and 17.60).

Textbook of Oral Pathology

Histopathological Features (Figs 17.61 and 17.62) 448

Tumor cells are round, polygonal shape with indistinct margin and pale eosinophilic cytoplasm. Polymorphous growth of cell occurs like solid pattern, cords, duct, cystic or cribriform pattern. Peripheral cells infiltrative invading adjacent tissue in single line fashion. Perineural invasion can also be seen.

Management Wide Surgical excision of the tumor should be carried out. Points to Remember Lobular carcinoma, terminal duct carcinoma, painless mass, bleeding, discomfort, round, polygonal shape tumor cells, solid pattern, cords, duct, cystic or cribriform pattern, perineural invasion.

MALIGNANT MIXED TUMOR It is uncertain that these tumors represent the previously benign lesions which have undergone transformation into malignant form or malignant lesion right from the onset. It accounts for 1% of all parotid tumors and 7% of all malignant tumors. Types • Carcinoma ex-pleomorphic adenoma (carcinoma ex-mixed tumor) • Carcinosarcoma • Metastasizing mixed tumor.

Clinical Features Carcinoma Ex-Pleomorphic Adenoma (Fig. 17.63) Age: The tumor occurs from 2nd to 9th decades, but most frequently in 5th and 6th decade. The average age of patients with malignant pleomorphic adenoma is about ten years older than the patients with benign form of the disease. Location: It is most commonly seen in parotid gland. Other less common location is minor salivary gland on the palate.

Figure 17.61 Histopathological picture of polymorphic low

grade carcinoma (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

Figure 17.62 Polymorphous low grade adenocarcinoma

Sign and symptoms: The tumors are usually larger than benign ones. There is often fixation of the tumor to underlying structures as well as to overlying skin or mucosa. Pain is more frequently a feature of malignant, than the benign pleomorphic adenoma. Parotid tumor may produce facial palsy (Fig. 17.64).

Figure 17.63 Carcinoma ex-pleomorphic adenoma involving

facial nerve causing Bell’s palsy masked eyes of patient

Salivary Gland Pathology

449

Figure 17.64 Malignant pleomorphic adenoma showing

Figure 17.65 Malignant pleomorphic adenoma (Courtesy: Dr

cellular atypia

Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

Carcinosarcoma

Management

It is rare and most of the cases seen in parotid gland with some lesion seen in submandibular as well as minor salivary gland. Other signs and symptoms are similar to that of carcinoma ex-pleomorphic adenoma.

Surgical excision should be done. These neoplasms exhibit a high recurrence rate after surgical removal as well as a high incidence of regional lymph node involvement. Carcinosarcoma can be treated with radical surgical resection with radiation therapy.

Metastasizing Mixed Tumor Primary tumor seen in parotid gland. Metastasis occurs in bones and lungs, regional lymph nodes, skin and liver.

Histopathological Features (Fig. 17.65) Carcinoma Ex Pleomorphic Adenoma In some cases malignant component may overgrow the benign component so that the benign component is difficult to demonstrate and in some cases benign component is more with few malignant foci may be found. There is presence of nuclear hyperchromatism and pleomorphism, increased or abnormal mitosis and destruction of normal tissues. There is destructive infiltrative growth at the periphery, with excessive hyalinization.

Carcinosarcoma

Points to Remember Carcinoma ex-pleomorphic adenoma: Parotid gland, usually larger than benign, pain, facial palsy, malignant component may over grow, nuclear hyperchromatism, pleomorphism, abnormal mitosis, infiltrative growth at the periphery. Carcinosarcoma: Parotid gland, signs and symptoms same as above, sarcomatous as well carcinomatous changes. Metastasizing mixed tumor: Parotid gland, metastasis occurs in bones and lung, features of benign pleomorphic adenoma seen at primary and metasize site.

It is biphasic tumor which can show sarcomatous as well CONNECTIVE TISSUE TUMORS carcinomatous changes. Epithelial changes resemble that Hemangioma is the only common tumor of this group and of adenocarcinoma and connective tissue resembles that of the most frequently seen in young infants. The involve chondrosarcoma. gland appears hypertrophied. There is blue discoloration of the overlying skin. Metastasizing Mixed Tumor Lipoma may occur in the parotid gland. The facial nerve, This has got features of benign pleomorphic adenoma both occasionally gives rise to a neural tumor. True sarcoma is in primary as well as in metastatic sites. extremely rare.

Textbook of Oral Pathology

NECROTIZING SIALOMETAPLASIA 450

It is a non-neoplastic inflammatory self healing reaction of salivary gland tissues, which both clinically and histologically mimics a salivary gland malignancy. It usually affects the minor salivary glands. It was predicted that trauma causes ischemia of the minor salivary glands. This benign self limiting lesion has been often confused with malignancy thereby causing unnecessary surgery.

Etiology and Pathogenesis (Flow chart 17.1) Local ischemia, which may be due to physical, chemical, infective or local vasculitis. Trauma form various factors such as denture wearing and recent surgery may be a causative factor. In some cases, smoking and alcohol intake can lead to this condition.

Clinical Features Age and sex: It is more common in males than females. It occurs in 4th and 5th decade. Location: Most of the cases occur in palate, although cases of lip or retromolar pad also have been reported. Symptoms: It is usually painless or may cause only slight pain. The patient may have numbness in the palate, or area of looseness in palate. Pieces of tissue may fall out from the palate. There may be referred pain to ear or pharynx. Signs: There may be early mild swelling to more advanced and cancerous appearing ulcer. The lesion begins as a larger ulcer or ulcerated nodule, which may be unilateral Flow chart 17.1 Events in necrotizing sialometaplasia

or bilateral. The ulcer is well demarcated from surrounding normal tissue and often has an inflammatory reaction around the edge of the lesion. Margins of ulcer in some cases may be indurated and inflamed. Size: The lesion itself is most often a deep, craterlike, non draining ulcer 1 to 3 cm in diameter. The lesion is covered by an inflammatory exudate and necrotic debris however the margins of ulcer are usually clean, sharp and the granulation tissue often can be seen at the superficial aspect.

Histopathological Features It is characterized histologically by an ulcerated mucosa, pseudoepitheliomatous hyperplasia of the mucosal epithelium, acinar necrosis and squamous metaplasia of salivary ducts. There is preservation of the lobular architecture, despite necrosis and inflammation. Inflammatory cells may be found in and around the lobular areas of necrosis. Granulation tissue and fibrosis present in variable amounts.

Management It is a self limiting condition. It does not require any treatment. The healing occurs in six to twelve week via secondary intention. Debridement and saline rinses may aid the healing process. Points to Remember Trauma causes ischemia of the minor salivary glands, painless, numbness in the palate, pieces of tissue may fall out from the palate, ulcer is well demarcated from surrounding normal tissue, deep, craterlike, pseudoepitheliomatous hyperplasia of the mucosal epithelium, lobular areas of necrosis, debridement and saline rinses.

BIBLIOGRAPHY 1. Batsakis JG, Luna MA. Undifferentiated carcinomas of salivary glands. J Laryngol Otol. 1987;101(9):962-6. 2. Batsakis JG. Salivary Gland neoplasm: an outcome of modified morphogenesis and cytodifferenciation. Oral Surg Oral Med Oral Pathol. 1980;49:229-32. 3. Chidzonga MM, Perez VML, Alvarez ALP. A clinicopathologic study of parotid tumors. J Oral Maxillofac Surg. 1994;52:1253-6. 4. Cohen MA. Pleomorphic adenoma of the cheek. Int J Oral Maxillofac Surg. 1986;15:777-9.

Salivary Gland Pathology 5. Eveson JW, Cawson RA. Salivary gland tumours: a review of 2410 cases with particular reference to histological types, site, age and sex distribution. J Pathol. 1985;146: 51-8. 6. Gerhard Seifert, Leslie H Sobin. The world health organization’s histological classification of salivary gland tumors. A commentary on the second edition. Cancer. 1992;70(2): 379-85. 7. Gnepp DR. My journey into the world of salivary gland sebaceous neoplasms. Head Neck Pathol. 2012;6(1):101-10. 8. Goode RK, Auclair PL, Ellis GL. Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer. 1998;82:1217-24. 9. Gustafsson H, Dahlqvist A, Carlsoo B. Mucoepidermoid carcinoma in a minor salivary gland in childhood. Laryngol Otol. 1987;101:1320-3. 10. Guzzo M, Andreola S, Sirizzotti G, Cantu G. Mucoepidermoid carcinoma of the salivary glands: clinicopathologic review of 108 patients treated at the National Cancer Institue of Milan. Ann Surg Oncol. 2002;9:688-95. 11. Healey WV, Przin KH, Smith L. Mucoepidermoid carcinoma of salivary gland origin. Classification, clinical-pathologic correlation, and results of treatment. Cancer. 1970;26:368-88. 12. Hicks MJ, el-Naggar AK, Flaitz CM, Luna MA, Batsakis JG. Histocytologic grading of mucoepidermoid carcinoma of major salivary glands in prognosis and survival: a clinicopathologic and flow cytometric investigation. Head Neck. 1995;17:89-95. 13. Hübner G, Klein HJ, Kleinsasser O, Schiefer HG. Role of myoepithelial cells in the development of salivary gland tumors. Cancer. 1971;27(5):1255-61. 14. Ishibashi N, Yanagawa T, Yamagata K, Karube R, Shinozuka K, Nagata C. 15. Luukkaa H, Klemi P, Leivo I, Koivunen P, Laranne J, Makitie A, et al. Salivary gland cancer in Finland 1991-96:

an evaluation of 237 cases. Acta Otolaryngol. 2005;125:20714. 16. Margaret SB, Katya I, Derrick IW. Muco epidermoid carcinoma. A clinicopathologic study. Am J Surg Pathol. 2001;25:835-45. 17. Naunheim MR, Lin HW, Faquin WC. Intercalated duct lesion of the parotid. Head Neck Pathol. 2012;6(3):373-6. 18. Noguchi M, Onizawa K, Bukawa H. Basal cell adenoma arising in a minor salivary gland of the palate. Oral Maxillofac Surg. 2012;16(1):111-4. 19. Plambeck K, Friedrich RE, Bahlo M, Bartel-Friedrich S, Klapdor R. TNM staging, histopathological grading, and tumor-associated antigens in patients with a history of mucoepidermoid carcinoma of the salivary glands. Anticancer Res. 1999;19:2397-2404. 20. Przewony T, Stodulski D, Stankiewicz C. Major salivary gland disorders in children and adolescents]. Otolaryngol Pol. 2011;65(5):350-6. 21. Rodriguez-Cuevas S, Labastida L, Baena L, Gallegos F. Risk of nodal metastases from malignant salivary gland tumors related to tumor size and grade of malignancy. Eur Arch Otorhinolaryngol. 1995;252:139-42. 22. Seethala RR. Histologic grading and prognostic biomarkers in salivary gland carcinomas. Adv Anat Pathol. 2011;18(1): 29-45. 23. Spiro RH. Salivary Neoplasms: overview of a 35 year experience with 2807 patients. Head Neck Surgery. 1986; 8:177-84. 24. Vaidya AD, Pantvaidya GH, Metgudmath R, Kane SV, D’Cruz AK. Minor salivary gland tumors of the oral cavity: a case series with review of literature. J Cancer Res Ther. 2012;8 Suppl 1:s111-5. 25. Vander Poorten VL, Balm AJ, Hilgers FJ, Tan IB, LoftusColl BM, Keus RB, et al. The development of a prognostic score for patients with parotid carcinoma. Cancer. 1999;85: 2057-67.

MULTIPLE CHOICE QUESTIONS

1. The first gland appear during intrauterine life is: a. Sublingual gland b. Parotid gland c. Submandibular gland d. Minor glands



4. Wharton’s duct is associated with: a. Parotid gland b. Sublingual gland c. Submandibular gland d. Both b and c



2. The largest salivary gland is: a. Parotid gland b. c. Sublingual gland d.



5. The most common gland involved in sialolithiasis is: a. Parotid gland b. Submandibular gland c. Sublingual gland d. Both a and b



3. The duct associated with parotid gland is: a. Bartholin’s duct b. Wharton’s duct c. Stensen’s duct d. None



6. ‘Mucinophages’ a histopathological feature seen in: a. Sialosis b. Stenosis c. Strictures d. Mucocele

Submandibular gland Accessory ducts

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7. ‘Epimyoepithelial island’ a histopathological feature seen in: a. Sjögren’s syndrome b. Pleomorphic adenoma c. Uveoparotid fever d. Mumps



8. A chocolate colored eosinophilic coagulum seen in: a. Brachial cyst of parotid b. Warthin’s tumor c. Monomorphic adenoma d. Both a and b



9. Histopathological feature showing nests of epidermoid cells and mucous cells present in: a. Mucoepidermoid carcinoma b. Warthin’s tumor c. Ductal papillomas d. Myoepithelioma

10. Numbness in the palate, or area of ‘looseness’ in palate is the clinical feature of: a. Small cell carcinoma b. Necrotizing sialometaplasia c. Salivary duct carcinoma d. None 11. Mikulicz’s disease is: a. An inflammatory disease b. Neoplastic disease c. An autoimmune disease d. Viral infection 12. The histogenesis of pleomorphic adenoma is from which cell: a. Myoepithelial cell b. Intercalated duct cell c. Epithelial cell d. Neural crest cell

13. Tender submandibular swelling is mostly due to: a. Ludwig’s angina b. Stone or sialolithiasis c. Enlarged lymph nodes d. All of the above



14. The most common complication of mumps is: a. Myocarditis b. Uveitis c. Orchitis d. Conjunctivitis

15. A parotid fatty change is sign of: a. Aging b. Alcoholism c. Malnutrition d. None of the above 16. Which of the following is of salivary gland origin? a. Acinic cell carcinoma b. Chondrosarcoma c. Granular cell tumor d. None of the above

17. The most common site for ectopic salivary gland tumor: a. Tongue b. Cheek c. Palate d. Neck 18. Sialography is used to detect anomaly of: a. Salivary duct only b. Salivary gland c. Salivary gland and duct d. Salivary gland tumors



19. Ranula is associated with: a. Mucus retention phenomenon only b. Mucus retention cyst only c. Mucus extravasation cyst only d. Both (b) and (c)



20. Mucoceles are most commonly found in: a. Frontal sinus b. Maxillary sinus c. Ethmoid sinus d. None.

18

Bacterial Infection

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline  Impetigo  Erysipelas  Syphilis • Primary syphilis • Secondary syphilis (disseminated syphilis) • Tertiary syphilis • Congenital syphilis  Gonorrhea  Leprosy (Hansen disease)  Tuberculosis  Actinomycosis  Noma

The literal meaning of the word ‘disease’ is ‘loss of ease’. The oral cavity reflects the state of systemic health more frequently than other parts of the body. Even in ancient time, examination of mouth and tongue was given great importance. The oral tissues are in direct physical continuity with rest of the body and they are also related via blood, lymphatics and nerve pathways. Furthermore, systemic influence such as endocrinological, immunological and psychological factors has an important role in the balance between oral health and disease. During both, development and maintenance, local and systemic factor are concerned in disease process of mouth. Oral health must be considered in relation to general health. The dentist’s role in general health is based on the fact that, he is the first person to see the oral lesion. In preventive dentistry, the utmost principle is of early diagnosis. Dentist

           Â

Scarlet fever Diphtheria Tularemia Rhinoscleroma Granuloma inguinale Streptococcal tonsillitis and pharyngitis Tonsillar concretion and tonsillolithiasis Lymphogranuloma venereum Myiasis Cat scratch disease Pyostomatitis vegetans Sinusitis

have an important note in preventive medicine as many systemic diseases have primary oral manifestations.

IMPETIGO It is also called ‘impetigo vulgaris’. It is acute superficial, purulent infection of the skin. It is caused by Streptococcus pyogenes and Staphylococcus aureus. In many patients with impetigo bacteria remain in nose and spread on skin at the site of scratches and abrasion. It is contagious and spread in crowded condition.

Predisposing Factors Poor hygiene, crowded living conditions, pre-existing eczema and scabies and reduced resistance due to preceding influenza or herpes simplex infection can lead to this disorder.

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• Non-bullous impetigo (impetigo contagiosa) • Bullous impetigo (staphylococcal impetigo) • Impetiginized dermatitis.

Clinical Features Age: The disease is mainly seen in pre-school children and young adults. Site: The face (angle of mouth, lips and nose) is most common location. Non-bullous impetigo: It is also called impetigo contagiosa. Facial lesion have linear pattern that corresponds to fingernail scratches. The lesions frequently begin as red, itchy spots. The close set, round or oval, flat, pustular vesicles with a characteristic stuck on appearance subsequently develop. Vesicles which are formed quickly rupture and covered with adherent thick ambar crust. This is described as ‘cornflakes glued to surface’. Some of the lesions may become confluent. The surrounding skin is erythematous with lymphadenopathy, which becomes tender. Bullous impetigo: It is caused by S. aureus. There is superficial vesicle which rapidly enlarged to form larger flaccid bullae. Bullae may rupture and develop thin brown crust which is described as ‘lacquer’. Cellulitis and pneumonia can occur in some cases. Impetiginized dermatitis: There is secondary involvement of areas of dermatitis.

Histopathological Features (Fig. 18.1) Pustules filled mainly with neutrophils leukocytes are seen directly beneath the horny layer of the epithelium. The spinous layer below show spongiosis and migration of leukocytes from the connective tissue, where a slight to moderately, severe inflammatory infiltrate of neutrophils and lymphocytes is seen. At the later stage when the bulla ruptures, the horny layer is absent and a crust composed of fibrin and neutrophils, leukocytes may be found resting on the remaining epithelial layers.

Figure 18.1 Histopathological features of impetigo

Antibiotics: Antibiotic like cephalexin, trimethoprim, sulfamethoxazole, dicloxacillin, flucloxacillin and amoxicillin clavulanic acid are shown good results. This should be given for one week. Points to Remember • Impetigo vulgaris, Streptococcus pyogenes • Non-bullous impetigo: Impetigo contagiosa, stuck on appearance, cornflakes glued to surface. • Bullous impetigo: Superficial vesicle, lacquer, cellulitis • Impetiginized dermatitis: Secondary involvement of areas of dermatitis • Histopathological: Neutrophils leukocytes spongiosa, migration of leukocytes, severe inflammatory infiltrate, fibrin and neutrophils, topical mupirocin, fusidic acid, antibiotics.

ERYSIPELAS It is an acute, superficially spreading infection of the dermis, usually of the face, with a well demarcated, slightly indurated erythema and progressive lymphangitis.

Causes

It is caused by group A streptococci. The microorganisms are thought to enter the tissues through a small break in the Management mucosa or the skin, such as fissure, abrasion, erosion or Topical therapy: Topical mupirocin, fusidic acid are excoriation. Postsurgical erysipelas is caused by transmission of effective in dealing non bullous impetigo. Before topical application removal of crusts with clean cloth sock in streptococci from the nose, throat, or hands of the patient or from, the attendant or visitors. warm soapy water is recommended.

Bacterial Infection

Nephrotic edema, lymphedema, dysgammaglobulinemia, malnutrition and alcoholism are known predisposing factors.

Clinical Features Age and sex distribution: The newborn and infants are highly susceptible, but elderly are also affected. It is more common in women in 5th decade and in men, in 7th decade. Location: The most common location is on abdomen, face, scalp and legs. The incubation time it thought to be from few hours to several days. Prodormal symptoms: It is characterized by malaise, vomiting, headache, pyrexia and chills. Symptoms: Erysipelas begins abruptly with a local sensation of burning and itching. The general condition of the patient worsens with toxemia, high fever, insomnia and restlessness. Appearance: A small area of the skin then becomes intensely red and swollen. Subsequently, bright red plaques develop and spread rapidly. Blisters, which breakdown to form large ulceration, may develop on the red lesion. The lesion has an elevated, edematous, sharp border and an irregular outline. Saint Anthony’s fire: Many times this term is used to describe erysipelas. The reason for this is that French house of St. Anthony; an 11th century hospital had a fiery red wall similar to color of erysipelas. Facial lesion: It has got butterfly distribution resembling lupus erythematous. Many times affected skin have surface texture that resemble orange peel. Regional lymph nodes become enlarged and tender. The untreated acute stage of erysipelas resolves after 3-10 days, leaving dry, desquamating and sometimes partially ulcerated skin. Complication: If therapy is not initiated then complications like gangrene, necrotizing fasciitis, toxic shock syndrome with multiple organ failure, thrombophlebitis can occur.

Oral Manifestations It is uncommon in oral, pharyngeal and nasal mucosa. Erysipelas which develops in the oral, pharyngeal or upper respiratory tract mucosa result in the same constitutional reaction, as described for skin lesion. There is severe local pain, redness and swelling. Edema may involve the tongue, uvula, and epiglottis and may lead to serious consequences.

The submandibular lymph nodes become markedly tender and swollen.

Histopathological Features Edema and dilatation of the lymphatics and capillaries occurs. A marked and diffuse inflammatory infiltrate, predominately of neutrophils, is seen throughout dermis, occasionally extending into the subcutaneous fat.

Management Penicillin is the drug of choice. Other antibiotics which can be given are erythromycin, cephalexin, fluoroquinolones can be given. After giving antibiotics therapy initially skin involvement enlarges due to release of toxins from dying streptococci. Points to Remember Group A streptococci, postsurgical erysipelas abdomen, face, scalp and legs, prodormal symptoms, local sensation of burning, skin intensely red and swollen, Saint Anthony’s fire, facial lesion butterfly distribution, regional lymph nodes enlarged, complication like necrotizing fasciitis, toxic shock syndrome, edema involve the tongue, submandibular lymph nodes, edema and dilatation of the lymphatics and capillaries, diffuse inflammatory infiltrate, penicillin.

SYPHILIS It is also called ‘Lues’. It occurs most exclusively by venereal contact, in overcrowded living and primitive housing conditions. It is cause by Treponema pallidum. This organism is vulnerable to drying so primary mode of transmission is from sexual contact. Oral sex has important role in transmission of this disease nowadays. Syphilis has got three stages out of which two stages are contagious. Types Acquired syphilis • Primary • Secondary • Tertiary • Quaternary • Latent phase Congenital Early syphilis Late syphilis

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Acquired syphilis: Contacted primarily as venereal disease due to sexual intercourse with infected partner ∙ Primary: This occur usually after 3 to 9 days after exposure. ∙ Secondary: It occur after 4 to 10 weeks of primary infection. ∙ Tertiary: It appear after secondary after third year to patient life. ∙ Quaternary syphilis: The atypical malignant progression of tertiary neurosyphilis in immunocompromised HIV individuals is referred to as quaternary syphilis. ∙ Latent phase: This phase occur after secondary syphilis. It last from 1 to 30 years without any sign and symptoms. Congenital: It is manifested within 2 years of life. Early syphilis: Primary syphilis, secondary syphilis and the early latent phase of the disease are grouped as early syphilis. Early syphilis may last up to two years and is infectious.

round, indurated and with rolled raised edges. It begins as a papule, before proceeding to ulceration and varies in size from 5 mm to several centimeters. It is painless, unless superinfected. It disappears without therapy after 10 days. Regional lymph nodes become firm enlarged, rubbery in consistency and non tender. Classic signs: The combination of indurated ulcer on appropriate mucosal surface and enlarged, nontender, regional lymph nodes which are painless, discrete and rubbery in consistency-constitute the classic signs of primary syphilis.

Oral Manifestations Location: Oral lesions of primary syphilis are rare and occur at the site of entry of Treponema. Chancre has been described on lips, in males (upper lip) and in females (lower lip), oral mucosa, lateral surface of tongue, soft palate, tonsillar area, pharyngeal lesion and gingiva. Transmission can occur during kissing as a consequence of sexual practice among homosexual and heterosexuals, or by contact with objects such as mouth piece of musical instruments and medical or dental instruments.

Late syphilis: While late latent and tertiary are grouped as late syphilis. Late syphilis is locally destructive and Appearance: It has narrow copper colored, slightly raised noninfectious. borders with reddish brown base in center. It measures from 0.5 to 2 cm in diameter. Intraoral chancres are slightly Epidemiology painful due to secondary infection and are covered with There is decreased incidence after introduction of penicillin grayish white film. Occasionally, it retains white sloughy in late 1940s. Patient infected with Treponema pallidum material. They are contagious. and HIV may exhibit a malignant form of syphilis with Primary involvement of tonsils is manifested by slow development of standard serologic response to considerable edema, redness, ulcerated and eroded lesion. syphilis. The tertiary manifestations lead to considerable Regional lymphadenopathy occurs. morbidity and mortality. Extraoral lip chancre may have more typical brown crusted appearance which may be multiple (Fig. 18.2). Primary Syphilis Lower lip involved more frequently. Oral chancre heals Clinical Features spontaneously in 3 to 6 weeks leaving small scars. Lesion develops at the site of inoculation approximately Histopathological Features (Fig. 18.3) 3 to 90 days after contact with infection. Surface epithelium is ulcerated in this stage. The chancre Location: It occurs most frequently on penis in males is microscopically characterized by presence of dense and vulva or cervix in females. Recently, occurrence on infiltrate of plasma cells, lymphocyte, macrophages and a extragenital sites have increased as a result of increase in proliferative granulation tissue. orogenital sex and increased contact among the infected Obliterative endarteritis, characterized by perivascular homosexuals. Extragenital sites of involvement include infiltration of inflammatory cells is seen. fingers, perianal region, nipples and lips, tonsils and Deeper tissues show endothelial proliferation, swelling intraoral structures such as tongue and palate. and perivascular cuffing by inflammatory cell infiltrate. Appearance of chancre: It is slightly raised, ulcerated, Proliferative granulation tissue is present at the margin nontender, nonbleeding, firm plaque which is usually of ulcer. Plasma cells are numerous.

Bacterial Infection

Symptoms: Fever, headache, anorexia, pain in joints and muscles occurs. Generalized lymphadenopathy, which is painless, discrete and nonadherent to the surrounding tissues, may be seen. Generalized symmetrical enlargement of the lymph nodes in posterior cervical, suboccipital, supratrochlear and inguinal regions is seen.

Figure 18.2 Syphilitic ulcer on the lip which has got ill

defined border

Lues maligna: This is explosive and widespread form characterized by necrotic ulceration on face and scalp. Mucous patches are small, smooth, erythematous areas or superficial grayish erosions found on mucus membrane of vulva, penis, or in oral cavity, on palate and tonsils. Condyloma latum are grayish, moist, flat topped, extra large plaque which sometimes coalesce into larger plaques, found on moist mucocutaneous surfaces such as vulva, anus, scrotum, thigh and axilla. Split papule is a double papule which occurs at skin folds and angle of mouth. There is positive serological test. Patient may enter the phase of latency without treatment.

Oral Manifestations Mucous patches: Mucous membrane analog of papular or macular skin eruptions. If it found on tongue, buccal mucosa, tonsillar and pharyngeal region and lips. It appears as slightly raised grayish white lesions surrounded by erythematous base. They are covered by grayish white membrane. Trauma results in raw bleeding surface.

Figure 18.3 Nonspecific infection of the syphilis (IC) and an

ulcerated surface epithelium (U)

Secondary Syphilis (Disseminated Syphilis) Clinical Features Organisms proliferate and spread by the way of blood stream to produce lesions elsewhere. It usually appears within 4 to10 weeks after primary lesion. Appearance: When appear on skin, they manifest as fine macular or papular rash, sometimes accompanied by alopecia. Circinate lesions on face are characteristic of secondary syphilis. The lesions either resolve completely or leave residual areas of hypo- or hyperpigmentation.

Snail track ulcers: Confluence and coalescence of these glistening mucous patches gives rise to the so called ‘snail track ulcers’. It is often painless but mild to moderately painful. Split papule: Split papule is a raised papular lesion developed at the commissure of lip and with a fissure separating the upper lip portion from lower lip portion. They are called split papules as they are cracked in the middle giving a ‘split pea appearance’. They are highly infectious. Condyloma latum: They are flat silver gray wart like papule, sometimes having ulcerated surface. They are painless. Regional lymphadenopathy is usually present.

Histopathological Features The macular lesion shows inflammatory cell infiltration and obliterative endarteritis.

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The papular lesion exhibits endothelial proliferation, swelling and perivascular chronic inflammatory cell infiltration. Condyloma latum reveals hyperplastic epithelium with hyperkeratosis and acanthosis.

Tertiary Syphilis Clinical Features Age: It may occur at any age from the third year up to the patient’s life. In tertiary syphilis, 1/3rd develop benign or gummatous form, 1/3rd cardiovascular form and 1/3rd neurosyphilis, i.e. general paresis and tabes dorsalis. Gumma: It is due to a chronic destructive granulomatous process which occurs anywhere in the body. Gumma is the result of hypersensitivity reaction between hyperergic host and Treponema. There are two types of gumma, i.e. central and cortical. The characteristic gumma is a chronic granulomatous and usually localized lesion, which later ulcerates which may be nodular. Punched out ulcer with vertical walls and dull red granulomatous base is the typical clinical feature of ulcerative gummatous lesion. Cutaneous lesions heal slowly and leave behind tissue paper like scars. Single cerebral gumma may produce symptoms suggestive of brain tumor.

irritability, fatigue, mental sluggishness and carelessness in personal habits. Loss of fine muscular coordination as indicated by inability to enunciate clearly or to perform delicate tasks with the hands. Involvement of spinal cord is late manifestation characterized by paresthesia, burning and prickling sensation in the extremities. Patient may get unrealistic ideas of wealth or ability. Cardiovascular syphilis: It occurs in 10 percent cases of late syphilis. Involvement of CVS in tertiary syphilis affects aorta and aortic valve and 80 percent of deaths occur due to it. Medial necrosis and destruction of elastic tissue occurs in the wall of large blood vessels. Dilatation and aneurysm occurs.

Oral Manifestations They manifest any time during 3 to 10 years after the primary infection. Gumma can occur anywhere in the jaw but are more frequently on palate, mandible and tongue.

Gumma: It may manifest as solitary, deep, punched out mucosal ulcer. It usually starts as small, pale, raised, nodular mass in the midline of the palate which ulcerates and rapidly progresses to the zone of necrosis. It may cause perforation of palatal vault. Lesion is sharply demarcated and the necrotic tissue at the base of the ulcer may slough away leaving punched-out defects. Breathing Neurosyphilis: It occurs due to obliteration of small vessel and swallowing difficulty may be encountered by the artery involving vasa vasorum of aorta and other large patient. Numerous small healed gummata in tongue results vessels of the central nervous system (neurosyphilis). There are saddle deformities of nose. Neurosyphilis is in series of nodules or scars in deeper areas of the organ, manifested as tabes dorsalis and general paresis. Tabes giving the tongue an upholstered or tufted appearance. dorsalis is the syphilitic involvement of dorsal column of Chronic superficial interstitial glossitis: The tongue spinal cord and dorsal root ganglion. General paresis is may be involved diffusely with gumma presenting as syphilitic involvement of cerebral tissue. lobulated large and irregular shaped pattern. This is called Tabes dorsalis: Patient looses the positional sense of his lower extremities and walks with a slapping step. Burning and pricking sensation of the extremities, paresthesia, or at times, actual anesthesia of the part may accompany the characteristic gait. Positive Romberg’s sign—person is unable to stand erect unaided with his eyes closed. Short, shooting, knife-like pains may be experienced in the abdominal region called ‘tabetic crises’, which results from involvement of the dorsal root ganglion. Charcoat joint – trophic changes consist of deep perforating ulcers and painless destruction of larger joints. General paresis: Argyll Robertson pupil—pupils that react to accommodation but not to light. Increased

as interstitial glossitis. It is exclusive found in males and is considered as pre-cancerous because of predictions to undergo carcinomatous transformation. Leutic glossitis: Diffuse atrophy and loss of dorsal tongue papillae is called leutic glossitis. Loss of papillae is probably due to endarteritis leading to circulatory deficiency of lingual vasculature.

Histopathological Features Gumma is characterized by central zone of coagulation necrosis and peripheral rim rich in fibroblasts, which appear plump and often resemble epithelioid cells. There is also pseudoepitheliomatous hyperplasia.

Bacterial Infection

Fibroblasts are plump and they often resemble epithelioid cells. Occasional presence of giant cells and regular presence of chronic inflammatory cells like plasma cells, lymphocytes and histiocytes. Points to Remember Lues, Treponema pallidum. • Primary syphilis: Penis, vulva or cervix in females, chancre are raised, ulcerated, nontender, nonbleeding, firm plaque, regional lymph nodes are nontender with rubbery in consistency, chancre can be seen on lips, transmission kissing, colored, slightly raised borders with reddish brown base, involvement of tonsils, extraoral lip chancre, dense infiltrate of plasma cells, lymphocyte, macrophages, perivascular infiltration of inflammatory cells, endothelial proliferation • Secondary syphilis: Fine macular or papular rash, circinate lesions on face, generalized lymphadenopathy, lues maligna, mucus patches, condyloma latum, split papule, positive serological test, snail track ulcers, inflammatory cell infiltration, obliterative endarteritis, endothelial proliferation, chronic inflammatory cell infiltration, hyperplastic epithelium with hyperkeratosis • Tertiary syphilis: Gummatous form, cardiovascular form, neurosyphilis, tabes dorsalis, general paresis, argyll Robertson pupil, aorta and aortic valve, gumma on palate, upholstered or tufted appearance tongue, chronic superficial interstitial glossitis, leutic glossitis, central zone of coagulation necrosis and peripheral rim rich in fibroblasts, fibroblasts are plump, giant cells, plasma cells, lymphocytes and histiocytes.

Congenital Syphilis It is infection of fetus established by the passage of spirochetes from mother, through the placenta. Maternal transmission during first two stages results in stillbirth, miscarriage and infant with congenital anomalies.

with maculopapular eruptions, other than mucocutaneous lesion and loss of weight. Location: The lesions can be seen in spleen, kidney, bones and CNS. Bullae, vesicle and superficial desquamation with cracking and scaling of reddened soles and palms, petechiae, mucous patches and condyloma latum. After 2 years, interstitial keratitis, vascularization of cornea, 8th nerve deafness, arthropathy, signs of congenital neurosyphilis, gummatous destruction of palate and nasal septum develop. Saber shins or anterior tibial bowing. Higoumenakis’s sign: Irregular thickening of sternoclavicular portion of clavicle. Unexplained nerve deafness, retinal and corneal damage can also occurs.

Oral Manifestations Postrhagadic scarring and syphilitic rhagades: Postrhagadic scars are linear lesions found around oral and anal orifices. They result from diffuse leutic involvement of the skin in these areas from 3rd to 7th week after birth. They appear as red or copper colored linear areas covered with a soft crust. Rhagades are said to be more frequent on the lower lip. Healed syphilitic rhagades appear as ordinary cicatrices. The linear scars are radially arranged and perpendicular to the mucocutaneous junction, which are more prominent on lower lip near angle of mouth. Diminished coloring of lip is evident and mucocutaneous border is indistinct. Hutchinson’s triad: It consist of hypoplasia of permanent incisors and 1st permanent molars, eight nerve deafness and interstitial keratitis. Changes in dentition: Retarded root resorption of deciduous dentition. There may be ‘marring’ of permanent incisors present in congenital syphilis. 6 to 28 percent of the incisors and 3 to 37 percent of the molars have hypoplasia. The crown of the first molar in congenital syphilis is irregular and enamel of the occlusal surface and occlusal third of the tooth appears to be arranged in agglomerate mass of globules, rather than in well formed cusp.

Screw drive shaped incisors: Constriction of crown toward incisal edge screw results in driver or peg shaped Transplacental infection after 18-week gestation is related incisor. In addition, incisal edge is usually notch which may to development of immune complement rather than any be due to the absence of central tubercle or calcification toxic effect on organism. center. It is manifested within the first 2 years of life (neonatal Rounding of mesial and distal incisal line angles occurs. congenital syphilis) as rhinitis and chronic nasal discharge There is spacing between cuspid and incisors.

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Moon molars: In molars positioning of the cusps toward the central portion of the crown, gives the tooth a bud shaped or a shrunken occlusal form called as mulberry molars or Moon’s molars. Affected molars are dirty yellow in color due to hypocalcification.

Management Benzathine penicillin: Single dose of parenteral long acting benzathine is given for primary and secondary syphilis. In case of tertiary syphilis IM penicillin is given weekly for three weeks. Patient who are allegoric to penicillin doxycycline is given.

Carabelli cusp: Prominent accessory mesiolingual cusp of upper molar (Carabelli cusp). Malocclusion and open Jarisch Herxheimer reaction: This is occur after bite is present. In congenital syphilis characteristic shape administration of penicillin to patient. This occurs of tooth crown can be identified on radiograph. secondary to release of endotoxin when antibiotics kill large number of organism. There is mild fever, malaise, Points to Remember headache and increase in skin and mucosal lesion. Transplacental infection, neonatal congenital syphilis, rhinitis, chronic nasal discharge, interstitial keratitis, GONORRHEA vascularization of cornea, 8th nerve deafness, saber It is primarily an infection of the genitourinary tract shins or anterior tibial bowing, Higoumenakis’s mucosa. Occasionally it can involve extra-genital sites. sign, Postrhagadic scarring and syphilitic rhagades, Local infection may occur at extra-genital site (Rectal and Hutchinson’s triad, i.e. hypoplasia of permanent incisors pharyngeal gonorrhea). permanent molars, eight nerve deafness, retarded root Rectal mucosa is affected in 30 to 50 percent of women resorption of deciduous dentition, screw drive shaped with urogenital gonorrhea. Uncomplicated local infection at incisors, Moon molars, Carabelli cusp. other extra-genital sites is rare in adults. Initially, urogenital infection is symptomless and associated with purulent Diagnosis of Syphilis urethral discharge, which responds to antibiotic therapy. The presence of clinical manifestations together with history of a sexually active person should give clue to the Etiology diagnosis of acquired syphilis. It is caused by gram-negative intrabacillary located Dark field examination microscopy: It is the most useful method of identifying spirochete in primary acquired and occasionally, secondary syphilis. Not reliable for oral lesions, since the normal flora contains nonpathogenic treponema which are difficult to distinguish from T. pallidum. Lesion biopsy: Histopathological examination of suspected lesion, stained by silver impregnation technique, is useful particularly when the lesion contains few organisms, as may be in case of tertiary lesion. For oral lesions this technique is of considerable value. VDRL and RPR: Venereal disease research laboratory and rapid plasma regain test are can also be done. These tests are positive after 3 weeks of infection. Fluorescent treponeal antibody absorption (FTAABS), T. pallidum paticle agglutination assay (TPPA) and microhemagglutination assay for antibody T. pallidum (MHA-TP) are some highly sensitive serological test.

diplococcus Neisseria gonorrheae. It is an oval, paired, gram-negative microorganism. Early sexual awakening, prostitution and varied sexuality are believed to be responsible for the increase incidence of gonorrhea.

Pathogenesis Once the gonococci are directly deposited on the genitourinary tract mucosa during sexual intercourse, they penetrate through the intercellular spaces of the epithelium and reach the subepithelial connective tissue. Within 2 to 3 days of infection, an intense inflammatory reaction occurs resulting in characteristic mucopurulent discharge through urethral lumen. A chronic stage may be reached, if untreated and spread is either by direct extension through lymphatics or hematogenous route.

Clinical Features Age and sex distribution: It is primarily a disease of young adults between the age of 15 to 24 years and is more common in males, as compared to females.

Bacterial Infection

Symptoms occur in 1 day to 2 weeks, following contact with infected persons. There is profuse purulent urethral discharge with frequent micturition, followed by dysuria. In some of the patients, there may be fever and headache. In females, acute gonorrhea includes urethral, cervical and vaginal discharge.

hematogenous spread. Difficulty in jaw movements due to pain and swelling of single or both joints is the presenting symptom. Cervical lymphadenopathy and fever may be present. Rarely, perforation to the tympanic plate occurs. It may lead to fibrous ankylosis because articular cartilage is destroyed.

Pelvic inflammatory disease: This is complication occur in females and it results due to organism involving uterus and ovarian tubes. Patient complaints of abdominal cramps and abnormal bleeding.

Diagnosis

Disseminated gonorrhea: Some patient will have disseminated gonorrhea which results in myalgias, arthralgias, polyarthritis and dermatitis. The skin lesion consists of discrete papule with hemorrhagic component and seen on extremities. Gonococcal ophthalmia neonatorum: This occur due infection of eye due to infected mother. There is perforation of globe of eye and blindness. There is conjunctivitis and mucopurulent discharge.

Oral Manifestations Pharyngeal gonorrhea: It is higher in pregnant women (2–15%), sexually active homosexuals (2–25%) and heterosexuals practicing oral sex. History of fellatio is more associated with pharyngeal gonorrhea. Sore throat and evidence of pharyngitis. Pharyngeal gonorrhea is a term used for patients in whom Neisseria gonorrheae is isolated from nasopharynx. Gonococcal stomatitis: Incidence is very rare and often shows multiple, painful and round elevated gray white eroded spots, with or without pseudomembrane formation. Regional lymphadenopathy may be seen. Acute gingivitis develops around extraction site in patient who practices fellatio repeatedly for days after extensive dental extraction. The wide range of lesion may develop in gonococcal stomatitis, i.e. isolated ulcers, gingivitis and membranous gingivostomatitis. Lips may develop acute painful ulcerations, limiting the motion. Gingiva may become erythematous, with or without necrosis. The tongue may present red, dry ulcerations or become glazed and swollen with painful erosion with similar lesions on buccal mucosa and palate. Temporomandibular joint involvement: Gonococcus infection involving articulating joint is most common form of extragenital gonorrhea. Any joint may be affected, the commonest being knee, ankle and wrist. TMJ is affected in 14 percent of patients. It occurs as a result of

In all forms of it, including those of oral cavity and pharynx, the diagnosis rests on the identification of organism. Method used include gram stained smear, culture studies and direct fluorescent antibody test (Fig. 18.4).

Management Oral ciprofloxacin: This if first line therapy for gonorrhea. Other fluoroquinolones like levofloxacin and ofloxacin can also be used. Other drugs which used are broad-spectrum cephalosporin antibiotic like ceftriaxone 125 to 250 IM plus doxycycline 100 mg orally; twice a day for 7 days should be given. Points to Remember Intrabacillary located diplococcus Neisseria gonorrhea, profuse purulent urethral discharge, pelvic inflammatory disease, disseminated gonorrhea which results in myalgias, arthralgias, gonococcal ophthalmia neonatorum, pharyngeal gonorrhea, gonococcal stomatitis with or without pseudomembrane formation, lips develop acute painful ulcerations, temporomandibular joint involvement, ceftriaxone, oral ciprofloxacin.

Figure 18.4 Neisseria gonorrhea

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LEPROSY (HANSEN DISEASE) 462

It is a chronic infectious disease which has predilection for the skin, nerves and mucous membrane. It probably originated in tropic and spread to the east. Leprosy has always been considered in superstitious dread and the person suffering from leprosy was considered unclean and socially outcasted.

Etiology The leprae bacillus, Mycobacterium leprae, first observed by Hansen in 1868. It is not been possible to grow the bacillus in culture media. It is an acid fast, gram positive, non motile bacterial with affinity for Schwann cells and cells of reticuloendothelial system. Types • • • • • • • •

Tuberculoid (TT) Lepromatous (LL) Borderline tuberculoid (BT) Borderline lepromatous (BL) Polyneuritic Maculoanesthetic Indeterminate Erythema nodosum leprosum.

Pathogenesis Entry of bacilli that reaches the lymphatic and bloodstream are taken up by Schwann cells peripheral nervous system, where they start multiplying. If the host cell-mediated immunity is adequate bacilli are destroyed and there is no disease. Host immunity is unstable and suboptimal. Restricted multiplication of bacilli. Lesion will develop, when there is relatively good immunity but not enough to eliminate the infection, a localized type of disease called as tuberculoid type. When the host cell immunity is deficient a generalized form of the disease lepromatous leprosy develops. In between these two polar varieties of the disease there is a wide spectrum of manifestations, categorized as borderline leprosy.

Clinical Manifestations General Features Age and sex distribution: Males are affected more commonly than females with ratio of 3:1. It has got incubation period of 2 to 5 year during which patient passes through silent or latent period.

Sign and symptoms: Toward the end of this stage the symptoms are those of irritation of nerve ending in the skin, persistent or recurrent paresthesia and numbness- localized to certain area with no accompanying visible alteration in the corresponding skin.

Tuberculoid Type It is a benign form of leprosy involving the skin nerves and regional lymph node. Appearance: Lesions are hypopigmented, erythematous and flat or raised cutaneous lesions. Nerve involvement with loss of different types of sensation is also manifest. Early tuberculoid leprosy: It is manifested by hypopigmented macules which are sharply demarcated and hypesthetic. Intermediate tuberculoid lesion: Later the lesions are larger with elevated and circinate margin. There is peripheral spread and central healing. Fully develop lesion: In this lesions are densely anesthetic and loose normal skin organs (sweat glands and hair follicles). There may be severe neuritic pain. Loss of eyebrows and eyelashes is prominent feature of later involvement. The sequelae of peripheral nerve involvement may develop in some cases and this may give rise to muscle atrophy, like contracture of hands and feet, loss of phalanges, lagophthalamus, exposure keratitis and corneal ulceration leading to blindness.

Borderline Type It represent wide clinical picture and it is subdivided into borderline tuberculoid and borderline lepromatous types. Skin and nerve involvement is characterized by flat and raised asymmetrical areas of hyper-pigmentation with well defined or ill defined margins. The raised lesions are rubbery or soft in consistency and erythematous. The edges of skin lesion are sharply demarcated, in tuberculoid type and sloping in cases of lepromatous type. The surface of lesion is dry and rough in tuberculoid type, while it is smooth and shiny in lepromatous form.

Lepromatous Leprosy This form is more commonly seen in children and female are affected more as compared to males. Location: This malignant form of the disease produced widespread involvement of body skin, peripheral nerves,

Bacterial Infection

mucous membrane, lymph nodes, eyes, skeleton tastes and other internal organs. It develops early as erythematous macules or papules without subsequently lead to progressive thickening of skin and the characteristic nodules (Fig. 18.5). The borders of the lesion are ill defined and centers of the lesion are indurated and convex. Leonine facies: Loss of lateral portion of eye brow is common. Much later, the skin of face and forehead become thickened and corrugated (leonine facies) and earlobe becomes pedunculous; nasal stiffness, epistaxis, hoarseness and saddle nose also occur. Painless inguinal and axillary lymphadenopathy is common along with sterility and gynecomastia. Nerve involvement is a late phenomenon. It runs chronic course and seldom causes sudden death.

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Figure 18.6 Claw hand seen in leprosy patient

Claw hand: This is one of the typical features of leprosy (Fig. 18.6).

Erythema Nodosum Leprosum They occur in lepromatous and borderline lepromatous patients, most frequently in the later half of the initial year of treatment. Tender, inflamed subcutaneous nodules develop, usually in crops. Each nodule lasts a week or two, but new crop may appear. Low grade fever, lymphadenopathy and arthralgia can accompany severe erythema notosum leprosum (ENL). Leporma: This is common feature of erythema nodosum leprosum (Fig. 18.7).

Figure 18.7 Leproma manifested as nodular swelling in

leprosy

Orofacial Manifestations (Fig. 18.8) Depending on the type and duration of the disease, all patients with lepromatous leprosy show facial and oral manifestations and it is rare in tuberculoid and borderline leprosy. Appearance: The lesions are macular or raised, welldefined, hypopigmented, unhydrotic and hyperesthetic or anesthetic. Lepromatous infiltration of the helical and lobes of ear are characteristic of the rare stage of the disease. Advanced cases are characterized by nodular involvement of facial, cutaneous and subcutaneous structure.

Figure 18.5 Macular lesion seen on leg in leprosy

Neural changes involving face: Peripheral nerves such as facial and trigeminal nerve are frequently involved. Facial paralysis is observed in 3 percent of cases, complete

Textbook of Oral Pathology

the tooth diameter is suddenly and concentrically reduced, while the less marked cases exhibit a well demarcated, tapering and shortening of root. Transient interruption of odontogenesis results in slight, circumferential hypoplasia of enamel and cementum. In long standing lepromatous leprosy invasion of the pulp by granulomatous tissue causes pulpal necrosis leading to a pinkish discoloration of crown. Anterior teeth are most commonly affected.

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Facies leprosa: It is triad of consist of atrophy of anterior nasal spine, atrophy of anterior maxillary alveolar ridge and endonasal inflammatory changes.

Histopathological Features (Fig. 18.9) Figure 18.8 Facial appearance in leprosy

(note the saddle nose)

or partial facial paralysis may occur either unilaterally or bilaterally. Paralysis of the orbicularis muscle results in facial disfigurement, difficulties in phonation and mastication as well as drooling. Involvement of trigeminal nerve results in hypoesthesia and anesthesia. Skeletal changes involving the face: Rhino maxillary changes termed facies leprosa consist of atrophy of anterior nasal spine, atrophy and recession of the maxillary alveolar process confined to the incisor region and endonasal inflammation. Destruction of facial cartilage and bone is caused by direct infiltration and secondary infection. From nasal mucosa, granulomatous tissue invades cartilage and bone resulting in nasal collapse and a specific chronic osteomyelitis. Collapse of the nose (saddle nose) is also observed. Loss of anterior nasal spine and resorptive changes of premaxilla occur only in later stage of the disease.

The typical granulomatous nodules show collection of epithelioid cells and lymphocytes, multinucleated giant cells in a fibrous stroma. Langerhans type giant cells are present. Vacuolated macrophages called lepra cells are scattered throughout the lesion and often contain the bacilli.

Diagnosis Skin smears should be examined as a routine with ziehlnelson stain. The percentage of solid bacilli in a smear is known as morphological index. Skin, mucosal and nerve biopsy for histopathological examination are helpful in doubtful cases. Lepromin test is non-specific test to determine the hypersensitivity reaction and is useful in determining the immunological status of patient for classification of leprosy.

Oral and dental lesions: It is more commonly seen in lepromatous leprosy although clinical changes of oral mucosa have been described in borderline leprosy. Involvement of oral mucosa, premaxilla, soft palate, uvula, tongue, gingiva and periodontium has been reported. Lepromas: Small tumor like masses called lepromas develop on the tongue, lips or hard palate. These nodules have a tendency to break down and ulcerate. Gingival hyperplasia with loosening of teeth has been also reported. Tooth changes: In association with severe and granulomatous infiltration of pre-maxilla in childhood,

Figure 18.9 Leprosy showing epithelioid cells (EC) and giant

cells (GC)

Bacterial Infection

Management

acquiring this disease. It can rarely be transmitted through the placenta from the diseased mother to fetus. Tuberculoid type of leprosy is treated with 6 months Microorganisms may become disseminated by either regimen of rifampin and dapsone. blood stream or lymphatic spread. Infection can occur Lepromatous leprosy is treated with 24 months of through ingestion of unpasteurized infected cow milk. rifampin, dapsone, and clofazimine. Physiotherapy: This is given after lesion is resolve for Etiology the reconstruction of damage. Causative organism: The first member identified as tuberculous bacillus and designate as mycobacterium tubercuPoints to Remember losis. Other microorganisms associated are Mycobacterium Mycobacterium leprae bovis, Mycobacterium kansasii and Mycobacterium xenopi • Tuberculoid type: Hypopigmented macules sharply and Mycobacterium malmoense. The organism is anaerodemarcated, lesion circinate margin, lesions are bic, non-motile, Ziehl-Neelsen, rod shaped and is stained densely anesthetic and, loss of eyebrows, eyelashes, with special Ziehl Neelsen stain. peripheral nerve involvement • B orderline type: Skin and nerve involvement, asymmetrical areas of hyperpigmentation, lesions are rubbery or soft • Lepromatous leprosy: Erythematous macules, loss of lateral portion of eyebrow, nasal stiffness, epistaxis, hoarseness, saddle nose, claw hand • Erythema nodosum leprosum: Tender, inflamed subcutaneous nodules, Leproma • Orofacial manifestations: Lesions are macular or raised, well-defined, hypopigmented, unhydrotic and hyperesthetic, facial paralysis, rhino maxillary changes termed facies leprosa, oral and dental lesions, leproma on the tongue, gingival hyperplasia, tooth diameter is suddenly and concentrically reduced, facies leprosa • Histopathological features: Collection of epithelioid cells, lymphocytes, multinucleated giant, Langerhans type giant cells, lepra cells • Management: Tifampin and dapsone.

TUBERCULOSIS It is a systemic infectious disease of worldwide prevalence and of varying clinical manifestations. It is an infectious granulomatous disease caused by acid fast bacilli Mycobacterium tuberculosis or rarely, Mycobacterium bovis.

Transmission and Prevalence Prevalence is more in the low income group with low socioeconomic and unhygienic condition. Most infection results from direct person to person spread through airborne droplet from patient with active disease. The common cause of entry of the bacillus in body is by inhalation. Infants and young children are at risk in

Constitutional factor: Low income group, low and unhygienic living conditions, malnutrition and overcrowding are constitute for tuberculosis infection.

Pathogenesis Initial tuberculosis usually occurs in lungs but occasionally occurs in tonsil or alimentary tract. Patients primary infection and the associated lymph node lesions heal and calcify. In some cases, caseous tuberculosis focus ruptures into vein and produces acute dissemination throughout the body, a condition called as acute miliary tuberculosis. Meningitis often complicates this condition. Progressive pulmonary tuberculosis may develop directly from a primary lesion or may occur following reaction of an incompletely healed primary focus. Postprimary pulmonary tuberculosis is a condition in which liquefied center of tuberculosis pulmonary infection is discharged into sinus. Extension of infection into pleura causes tuberculosis pleurisy. Types • • • • •

Miliary tuberculosis Pott’s disease Scrofula Primary tuberculosis Secondary tuberculosis.

Types Miliary tuberculosis: It spreads through blood stream and there is wide involvement of many organs like kidney, liver and is called as miliary tuberculosis. Pott’s disease: If tubercular involvement of spine occurs in children, then it is called Pott’s disease.

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Scrofula: If it spreads by lymphatics to lymph nodes, it is called scrofula. 466

Primary tuberculosis: It occur in unexposed people and involved lung. Primary infection results in localized fibrocalcified nodule at the site of involvement. Secondary tuberculosis: Reactivation of infection occur in compromised host.

Clinical Features Symptoms: Patient may suffer episodes of fever and chills, easy fatigability and malaise. There may be gradual loss of weight accompanied by persistent cough with or without hemoptysis. Local symptoms depend upon the tissue or organs involved. Consumption: This is wasting syndrome occur in tuberculosis with patient’s body was being consumed or destroyed. Tubercular lymphadenitis may progress to acute abscess or remain as granulomatous lesion. In any case, swelling of neck is present which is tender, painful and often show inflammation of the overlying skin. When abscess forms, it perforates and discharges pus (Fig. 18.10). Pulmonary tuberculosis: A persistence cough, hemoptysis abundant sputum is usual features of pulmonary tuberculosis. There is also evening rise in temperature of 0.5° to 2°F, night sweats. Lupus vulgaris: It is term used for the involvement of skin of the patient.

Scrofula: In glandular form of the disease, there is marked enlargement of the cervical lymph nodes with caseation and frequent breakdown of the gland. Such tuberculosis infection is called ‘scrofula’. These types of infection occur due contaminated milk from the cows. Cold abscess: The chronicity of the infection and the lack of marked pain or acute inflammatory symptoms have resulted in the term ‘cold abscess’.

Oral Manifestations They are relatively uncommon and seen in middle and older age groups, as cleansing action of saliva and its antibacterial properties, in general also provide protection against tubercle bacilli. Location: Tongue is most commonly affected followed by palate, lips, buccal mucosa and gingiva. Majority of oral lesions are secondary to infection in some other parts of body. Tubercular ulcer: The lesion may be preceded by an opalescent vesicle or nodule, a result of caseation necrosis. It breaks down into an ulcer which is usually superficial or deep and painful. It tends to increased slowly in size. In area of trauma may be mistaken as traumatic ulcer or carcinoma. Ulcers are nonspecific in their clinical presentation and for this reason they are overlooked by the clinician. The typical tuberculosis lesion is an irregular lesion with ragged undermined edges, minimum induration and often with yellowish granular base. The mucosa surrounding the ulcer is inflamed and edematous. Primary lesion: It develop when bacteria are directly inoculated in the oral tissue of a person who has not acquired immunity to the disease. It involves gingiva, tooth extraction socket and buccal fold. Secondary lesion: Infection is carried in by hematogenous route or through break in the tissue surface, is deposited in the submucosa, subsequently proliferates and ulcerates the overlying mucosa. It occurs more frequently in cases of extra-pulmonary tuberculosis.

Figure 18.10 Tubercular lymphadenitis showing swelling in

the submandibular region (Courtesy: Dr Chole)

Sentinel tubercle: Tiny, single and multiple nodules called ‘sentinel tubercle’ may also be seen surrounding the ulcer. At the mucocutaneous junction, tubercular ulcers are usually extremely shallow with granulating base. Crusting and oozing is seen when the lesion involves adjacent cutaneous surface. They are usually painful. The nodular form of tuberculosis presents as single or multiple

Bacterial Infection

nodules of variable sizes, which initially may appear a semitransparent lesion of pinhead size. They are gray in color and size of variable consistency. Miliary tubercle: Miliary tubercle of oral mucosa are occasionally seen in miliary tuberculosis which is a result of acute dissemination of the infection through hematogenous and lymphatic channel. The oral lesion appears as small, gray tubercle with the tendency to break down and ulcerate. Tubercle involvement of the periapical tissue and tooth socket has been reported. The socket may be filled with so called tuberculosis granulation tissue, consisting of many small, pink and red elevations. Tuberculosis gingivitis is an unusual form which may appear as diffuse, hyperemic or nodular papillary proliferation. Jaw involvement: It may involve maxilla or mandible. Jaw bone involvement occur as a result of either deep extension of a gingival lesion, from infected extraction socket, an extension of tubercular granuloma at the apex of tooth or by means of hematological spread. It may result in more diffuse form of osteomyelitis and is normally more serous than infections from periapical lesion. Tubercular involvement of jaw bone causes swelling and the symptoms include difficulty in eating, trismus, paresthesia of the lower lip and enlargement of the regional lymph nodes. Fistulae drain either intraorally or extraorally often with blue margins. In some case destructive involvement may reach to the TMJ area.

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Figure 18.11 Tuberculosis showing giant cells and

lymphocyte with tubercle follicle

Histopathological Features (Figs 18.11 to 18.14) Areas of infection demonstrate the formation of granuloma, which are circumscribed collection of epithelioid histiocytes, lymphocytes and multinucleated giant cells. There is also central caseous necrosis. This granuloma is called tubercular granuloma.

Figure 18.12 Tubercular granuloma presented (Courtesy: Dr

Sangmesh Halawar, Reader, Department of Oral Pathology, CDCRI, Rajnandgao, Chhattisgarh, India)

Tuberculin skin test: The Mantoux test is the preferred skin test for detecting tuberculosis. It involves the injection Diagnosis of 5 tuberculin units of purified protein derivatives, Microscopy: A pulmonary TB suspect should submit 3 usually 0.1 mL intradermal. The skin test is read on the sputum samples for microscopy. Morning sample is ideal. basis of millimeters of induration produced by PPD. Ten to fifteen millimeters induration is required for the test to Staining method: Ziehl-Neelsen, carbol fuschin be positive. or kinjouncarbol fuschin have been use for staining mycobacterium. Management Polymerase chain reaction: This technique amplifies even very small proteins of predetermined target region of Mycobacterium tuberculosis complex DNA.

Eight weeks course of isoniazid, rifampin, and pyrazinamide which is followed by 16 week course of rifampin and isoniazid.

Textbook of Oral Pathology

ACTINOMYCOSIS It is a chronic granulomatous suppurative and fibrous type of disease caused by anaerobic, gram +ve, non-acid fast bacteria. Most common are Actinomycosis israeli, A. naeslundii, A. viscosus and A. odontolyticus. The organism is considered to be transitional form between bacteria and fungi. The term Actinomyces was given by Harz to refer the ‘ray like appearance’ of the organism in the granule. The breach in the continuity of mucosa caused either by trauma or surgery, if the prerequisite for majority of actinomycosis infections.

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Types Figure 18.13 Tuberculosis

• • • • •

Cervicofacial Abdominal Pulmonary Cutaneous Central: Here, the infection is from the tooth or its membrane and is accompanied by radiographic changes. • Peripheral: The peripheral types originate in the soft tissues and do not involve bone.

Predisposing Factors There are various predisposing factor which may lead to actinomycosis. They are trauma, presence of carious teeth, secondary bacterial invasion and hypersensitivity reaction.

Clinical Features Figure 18.14 Langhans giant cell showing horse shoe shaped

arrangement of nuclei at periphery in tuberculosis

Points to Remember Acid fast bacilli Mycobacterium tuberculosis, low income group fever and chills, gradual loss of weight persistent cough, consumption, tubercular lymphadenitis, pulmonary tuberculosis, lupus vulgaris, scrofula, cold abscess, tubercular ulcer with ragged undermined edges oral tissue, sentinel tubercle, miliary tubercle, tubercle involvement of the periapical tissue, diffuse form of osteomyelitis, TMJ involvement, formation of granuloma, central caseous necrosis, tubercular granuloma, tuberculin skin test, 8 weeks course of isoniazid, rifampin and pyrazinamide.

Cervicofacial Form Age and sex distribution: It is most common type of actinomycosis and is commonly seen in adult males. Cervicofacial actinomycosis infections are endogenous in origin and occur when dental plaque, calculus or gingival debris contaminate the relatively deep wounds around the mouth. Location: Submandibular region is the most frequent site of infection. It usually spreads by direct tissue extension. Cheek and masseter region and parotid gland may also be involved. Symptoms and signs: The classical signs are chronic, low, grade persistence infection. Trismus is a common feature, before the formation of pus. The first sign of infection is characterized by the presence of a palpable mass. Mass is wooden indurated

Bacterial Infection

Subcutaneous Form

area of fibrosis which later on form central softer area of fibrosis. There may associate changes detectable at the portal of entry such as nonhealing tooth socket, exuberant granulation tissue or periosteal thickening of the alveolus. Development of fistula is common (Fig. 18.15). Skin surrounding the fistula is purplish. Adjacent tissues have doughy consistency.

Infection result from traumatic transplantation of organism, usually due to human bites. Lesion seen as subcutaneous swelling which enlarges slowly softens and ruptures through the sinuses. Occasionally, these lesions burrow through deeper tissue and invade bones.

Sulfur granules: Several hard circumscribed tumor like swelling may develop and undergo breakdown, discharging a yellow fluid containing the characteristic submicroscopic sulfur granules.

Location: Organism may enter the tissue through oral mucous membrane and may either remain localized in the adjacent soft tissue or spread to involve salivary glands, bone or skin of face and neck.

Abdominal Form

Signs: It produces swelling and induration of tissue. It may develop into one or more abscesses, which tend to discharge upon the skin surface liberating pus, which contains typical sulfur granules. There may be nonhealing tooth socket, exuberant granulation tissue and periosteal thickening of alveolus. Skin overlying abscess is purple red and indurate or fluctuant. It is common for sinus, through which the abscess has drained, to heal but due to chronicity, new abscesses are formed and perforate through skin surface. There is disfigurement of face. Infection may involve maxilla and mandible. There is formation of periapical granuloma. On the tongue, the lesion is a painful nodule which eventually ulcerates. Untreated cases may reach to the point where the tongue may become fixed.

Abdominal actinomyces is extremely serious form of the disease. Cause: Trauma, due to surgery or other causes such as fish bone or chicken bone injury, usually precedes the onset of the disease. Symptoms: Generalized symptom of fever, chills, vomiting, develop followed by symptoms of involvement of organs, such as liver and spleen. Sign: There is palpable abdominal mass. Intestinal manifestations develop later.

Pulmonary Form It produces findings such as fever and chills, accompanied by a productive cough and pleural pain. Pleural invasion resulting in empyema and there may be formation of sinus.

Oral Manifestations

Tonsillar hyperplasia: Involvement of tonsillar crypts produce hyperplasia of tonsil secondary actinomycosis infestation of the crypts. Actinomycotic osteomyelitis of mandible and maxilla can occur. It is described as ill-defined radiolucency surrounded by radiopacity.

Histopathological Features (Figs18.16 to 18.19)

Figure 18.15 Fistulae seen in actinomycosis patient

Ray fungus appearance: Round or lobulated colony meshwork of filaments stain with hematoxylin and peripheral club shaped ends of filaments stain with eosin. The typical lesion, whether in the soft tissue or in bone, is granulomatous one showing central abscess formation within which there are characteristic colonies of microorganisms are present. Colonies consist club shaped filament that form radiating rosette pattern.

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Figure 18.16 Actinomycosis showing central abscess

Figure 18.18 Actinomycosis

formation (sulfur granules)

Figure 18.17 Actinomycosis colony (AC) in a sea of

lymphocytic infiltration (IC)

Colonies appear to be floating in a sea of polymorphonuclear leukocytes, often associated with multinucleated giant cells and macrophages.

Management Actinomyces infection produces a reactive inflammatory response which causes an area of necrosis and scar tissue around the abscess. This results in decrease in the vascular

Figure 18.19 Actinomycosis (low power)

supply to the affected region and hence makes penetration of antibiotics difficult. Therefore, two fold therapy including antibiotics and surgery is necessary. Antibiotics which are used are penicillin, amoxicillin, and tetracycline. Cervicofacial actinomycosis require course of 5 to 6 weeks while deep seated infection require course of 12 months. Surgical excision of sinus tract with drainage of abscess should be done.

Bacterial Infection

Points to Remember Anaerobic, gram +ve, nonacid fast bacteria Actinomycosis israeli • Cervicofacial form: Endogenous in origin, submandibular region, chronic, low, grade persistence infection, trismus, palpable mass, sulfur granules • Abdominal form: Serious form, generalized symptom of fever, chills, vomiting, palpable abdominal mass • Pulmonary form: Fever, chills, productive cough, pleural pain. • Subcutaneous form: Traumatic transplantation of organism, subcutaneous swelling • Oral manifestations: Swelling and induration of tissue, exuberant granulation tissue, red skin, periapical granuloma, painful nodule on tongue, tonsillar hyperplasia, actinomycotic osteomyelitis of mandible • Histopathological features: Ray fungus appearance, central abscess formation, club shaped filament, radiating rosette pattern, polymorphonuclear leukocytes, multinucleated giant cells, antibiotics, surgery.

NOMA It is also called ‘Cancrum oris’, ‘gangrenous stomatitis, ‘orofacial gangrene’ and necrotizing stomatitis’. It is rapidly spreading gangrene of oral and facial tissues occurring usually in debilitated or nutritionally deficient person. The word noma is derived from Greek word nomein meaning to devour. It is cause by Fusobacterium necrophorum and Prevotella intermedia. Other organism which are associated with noma are Borrelia vincentii, Porphyromonas gingivalis and Staphylococcus.

Common sites are areas of stagnation around fixed bridge or crown. First sign: The commencement of gangrene is denoted by blackening of skin. Small ulcers of gingival mucosa spread rapidly and involve the surrounding tissues of jaws, lips and cheeks by gangrenous necrosis. This is called necrotizing ulcerative mucositis. Symptoms: Odor is foul. Patients have high temperature during the course of the disease, suffer secondary infection and may die from toxemia or pneumonia. Overlying skin is inflamed, edematous and finely necrotic which results in formation of line of demarcation between healthy and dead tissue. In advanced stage, there is blue-black discoloration of the skin. As gangrenous process advances, slough appears and soon separated, leaving a perforating wound in the involved area. Large masses may be sloughed out leaving the jaws exposed. Infection spread through anatomic barrier such as muscle (Fig. 18.20). Noma neonatorum is arises in first month of life in low birth weight infants who also demonstrate malnutrition and debilitating illness.

Management Parenteral fluid should be given urgently to correct dehydration and electrolyte balance. Penicillin and metronidiazole are first line of antibiotics which are used in case of noma. Conservative debridement of necrotic area should also be carried out.

Predisposing Factors It occurs in persons who are undernourished, debilitated from infections such as diphtheria, dysentery, measles, and pneumonia, scarlet fever, syphilis, tuberculosis and blood dyscrasias. It can also occur due to excessive mechanical injury, infection by Vincent’s organisms, leukemia, sickle cell trait, stress and chemotherapeutic agents can cause noma.

Clinical Features Age: It is seen chiefly in children, but can be found in adults in certain conditions like in malnourished states.

Figure 18.20 Blackish discoloration with ulceration seen in

case of gangrenous stomatitis (Courtesy: Dr Tapasya)

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Cancrum oris, Fusobacterium necrophorum, Prevotell intermedia, blackening of skin, necrotizing ulcerative mucositis, skin is inflamed, edematous, necrotic, blueblack discoloration of the skin, noma neonatorum, penicillin, metronidiazole.

SCARLET FEVER It is also called ‘scarlatina’. It is predominately occurs in children during winter months, caused by infection with group-A streptococci of beta hemolytic type that elaborate erythrogenic toxins.

Clinical Features Incubation period is 3 to 5 days. Sign and symptoms: The desquamation of skin begins around the middle of the second week after the onset. Patient exhibits severe pharyngitis and tonsillitis, chills, fever and vomiting. Throat becomes highly erythematous and exudation is common. There may be enlargement and tenderness of regional lymph nodes. Characteristic diffuse, bright scarlet to dusky red skin rash which appears on the second or third day of the illness (Fig. 18.21). It is described as ‘sunburn with goose pimple’. Pinhead punctuates areas of normal color project through

erythema giving skin of trunk and extremities sandpaper texture. After 3 to 4 days, the rash fades. This rash is due to toxic injury to the vascular endothelium which produces dilation of the small blood vessels and consequent hyperemia. Pastia’s line: These are transverse red streaks occur in the skin fold secondary to capillary fragility in the zone of stress. After rash is fade desquamation of face produce small flakes and that of skin produce thicker and larger flakes. Complication like retropharyngeal abscess, sinusitis, pneumonia, otitis media, acute rheumatic fever, glomerulonephritis, arthralgias, meningitis and hepatitis can occur.

Oral Manifestations ‘Stomatitis scarlatina’ accounts for the chief oral manifestation of scarlet fever. Mucosa of palate may appear congested and throat is often fiery red. The face, especially the temples and cheeks are flushed and red, but pale area of circumoral pallor is often seen around the mouth. The tonsils and faucial pillars are usually swollen and sometimes covered with grayish exudate. White strawberry tongue: Tongue exhibits white coating and fungiform papillae are edematous and hyperemic, projecting above the surface as small red knobs and it is called as ‘strawberry tongue’. Red raspberry tongue: Coating of tongue is soon lost, beginning at the tip and lateral margins and the organ becomes deep red, glistening and smooth, except for swollen hyperemic papilla. The tongue in this phase is called ‘raspberry tongue’. At the height of skin eruption oral mucosa is uniformly congested and the breath is fetid. In severe cases of scarlet fever, ulceration of buccal mucosa and palate have been reported. In some cases hypoplasia of teeth is seen in permanent teeth, if conditions occur at the time of tooth developments.

Histopathological Features

Figure 18.21 Rash of scarlet fever seen on the skin of the

hand (Courtesy: Dr Pincha)

The pharyngeal mucosa may display superficial necrosis, pseudomembranous exudate and microbial colonies. The submucosa will evidence an acute or subacute inflammatory cell infiltration. Tongue will show vasodilation with inflammatory cell infiltration, being nonspecific mucositis.

Bacterial Infection

Management Antibiotics: Penicillin is the drug of choice, since group A streptococci are generally, highly sensitive to this antibiotics. The species are also sensitive to other antibiotics like erythromycin, tetracycline and Chloramphenicol. Points to Remember Scarlatina, group-A streptococci of beta hemolytic type, throat erythematous, bright scarlet to dusky red skin rash, sunburn with goose pimple, sandpaper texture, Pastia’s line, retropharyngeal abscess, sinusitis, pneumonia, stomatitis scarlatina, white strawberry tongue, red raspberry tongue, ulceration of buccal mucosa, superficial necrosis, pseudomembranous exudate, microbial colonies, inflammatory cell infiltration, vasodilation, erythromycin, tetracycline.

DIPHTHERIA It is an acute contagious disease caused by gram +ve bacillus Corynebacterium diphtheriae, also called klebs loeffler bacillus. It is transmitted by droplet infection or direct contact.

Pathogenesis The portal of entry is the upper respiratory tract and rarely skin, genitalia, eye and middle ear. The bacilli settle on the mucous membrane or upper respiratory tract and lead to inflammation and necrosis of mucosal cells. The infection may spread to adjacent areas. In the primary invasive region, it forms a thick, firm, leathery, blue white pseudomembrane composed of bacteria, necrotic epithelium, macrophages and fibrin. A narrow zone of inflammation surrounding the area is seen. When the diphtheria bacteria multiply in the local tissues, they produce powerful exotoxins. This exotoxin diffuses through the body through a hematogenous route. Heart, muscle, kidney, peripheral nerves and adrenal glands are thus involved. Death may be caused by heart failure, airway obstruction which is cause by edema or by the effect of toxin.

Clinical Features Age and incubation period: It occurs most frequently in children, during the fall and winter months. Incubation period is two days.

Symptoms and sign: There is restlessness, malaise, headache, fever and occasional vomiting. Within a short time, patient complaint of sore throat. Mild redness and edema of pharynx with cervical lymphadenopathy occur. Nasal regurgitation of liquids during drinking. Bull neck: There may be swelling of the neck, called ‘bull neck’. Larynx is edematous and is covered by pseudomembrane. It produces a mechanical respiratory obstruction and typical croup. There is generalized polyneuritis with weakness; paresthesia may follow in the next 10 to 14 days. Cutaneous diphtheria is characterized by chronic skin ulcer.

Oral Manifestations There is formation of patchy ‘diphtheritic membrane’ which begins on tonsils and enlarges, becoming confluent over the surface. It is thick and grayish in color. It tends to adhere and leave a raw bleeding surface on removal. After sometime this membrane develop patches of green and black necrosis. A soft palate temporary paralysis usually during 3rd and 5th week of the disease occurs. The paralysis usually disappears in a few weeks or few months, at the most. Diptheric membrane covering may involve entire soft palate, uvula, larynx or trachea resulting in stridor and respiratory difficulty.

Prevention The disease may be prevented by prophylactic active immunization with diphtheria toxoid. Antitoxin should be administration in combination with antibiotics to prevent further toxin production. Antibiotics used are erythromycin, procaine penicillin, IV penicillin.

Management The patient should be isolated and bed rest is very essential. Points to Remember • C orynebacterium diphtheriae, klebs loeffler bacillus, listlessness, malaise, headache, fever, sore throat • Bull neck, larynx is edematous, polyneuritis, diphtheritic membrane, green and black necrosis, soft palate temporary paralysis, stridor, active immunization, antitoxin.

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TULAREMIA 474

It is caused by gram negative bacillus Francisella tularensis. also known as rabbit fever, deer fly fever. It is contacted through infected rabbits, muskrats, ground squirrels and other wild germ, particularly of rodent family. Types • • • • •

Cutaneous Ophthalmic Pleuropulmonary Oral Abdominal

Clinical Features Incubation period: Incubation period is up to seven days. Symptoms: Patient usually suffers a sudden headache, nausea, bony pain, profuse sweat, vomiting, chills and fever. Signs: A single cut or sore on the skin develops into a suppurative ulcer. Lymphatic vessels become swollen and painful and the lymph nodes are remarkably enlarged. The eyes also become involved with conjunctivitis developing through localization of disease in the conjunctival sac.

Oral Manifestations Primary infection of the mouth usually occurs from eating infected meat. Location: It is common on soft palate, tongue gingiva and angle of mouth. It is usually accompanied by sever pain. Appearance: The ulcer is shallow with whitish fibrinous pseudomembrane, but may extend more deeply with superinfection of Vincent’s organism. There may be generalized stomatitis develops. Single nodular masses eventually develop into abscess. The tonsil, posterior pharyngeal wall, soft palate, base of the tongue and buccal mucosa may be covered by a grayish white membrane simulating the appearance of diphtheria. Regional lymphadenitis may arise in sub-maxillary and the cervical groups of nodes. Cervical lymph nodes are tender, enlarged and may suppurate.

Laboratory Diagnosis Serology: An agglutination test is used to demonstrate a rising titer of antibody in the serum of patients of F. tularensis. Skin testing: Intradermal injection of an extract of F. tularensis gives a positive delayed hypersensitivity reaction in 1st or 2nd week of illness.

Management Antibiotics of choice are streptomycin and tetracycline, either alone or in combination. Points to Remember Francisella tularensis, sudden headache, nausea, suppurative ulcer, conjunctivitis, on soft palate, fibrinous pseudomembrane, generalized stomatitis, grayish white membrane, regional lymphadenitis, skin testing, streptomycin, tetracycline.

RHINOSCLEROMA It is unusual chronic infection caused by bacillus Klebsiella rhinoscleromatis and it is common in Europe and central and South America. Rhinoscleroma is a chronic, slowly progressive, inflammatory disease of the upper respiratory tract. Rhinoscleroma is found predominantly in rural areas with poor socioeconomic conditions.

Clinical Features Age: It is common between the ages of 20 to 40 years. Location: Usually found in upper respiratory tract, often originating from nose, but involvement of lacrimal glands, orbit, skin, paranasal sinus and intracranial invasion have been describe. Rhinitis stage: In this stage, there is nasal obstruction, nasal deformity and epistaxis. There is also swelling of upper lip and sore throat. Infiltrative stage: It is characterized by nasal obstruction, due to the presence of exuberant granulation tissue. Hoarseness results due to laryngeal involvement. Anesthesia of soft palate is common in this stage. Nodular stage: The proliferation of nasal masses may produce configuration known as ‘Hebra nose’. Posterior extension of the lesion may produce laryngeal and tracheal obstruction of varying degrees.

Bacterial Infection

Complications include scleromatous infiltration of eustachian tube and unilateral scleroma of maxillary sinus.

Oral Manifestations Oral lesion appears as proliferative granulomatous lesion of lip, soft palate and tonsil. There is also anesthesia soft palate and enlargement of uvula. Taste sensation is also impaired.

Histopathological Features Epithelial squamous metaplasia with subepithelial infiltrate of polymorphonuclear cells and granulation tissue are seen. There is presence Mikulicz cells and Russell bodies.

Management Antibiotics like ciprofloxacin, doxycycline, and fluoroquinolones can be given. Usually combination therapy is advice. Surgical debridement could also be considered if there is significant airway obstruction or cosmetic deformity. Points to Remember Bacillus Klebsiella rhinoscleromatis, upper respiratory tract, rhinitis stage, infiltrative stage nasal obstruction, nodular stage Hebra nose, scleromatous infiltration of eustachian tube, proliferative granulomatous lesion of lip, anesthesia soft palate, impaired taste sensation, epithelial squamous metaplasia, polymorphonuclear cell, mikulicz cells, fluoroquinolones, ciprofloxacin, doxycycline.

GRANULOMA INGUINALE It is also called ‘granuloma venereum’, ‘donovanosis’. It is found in inguinal and anogenital region and is caused by Donavan granulomatosis and is a chronic slowly progressing, mildly contagious disease.

Clinical Features Age and incubation period: It chiefly affects adult black of either sex, but may occur in any race. Although the exact incubation period for granuloma inguinale is unknown, it ranges from a day to a year, with the median time being 50 days. Appearance: Lesion begins as a small papule that ulcerates, increases in size and eventually gives rise to velvety, beefy, granulating and spreading ulcerative lesion of inguinal and anogenital region.

Inguinal ulceration is commonly secondary to the genital lesion and arises initially as fluctuant swelling known as pseudo-bubo. Metastatic spread to bone and soft subcutaneous tissue has been reported.

ORAL MANIFESTATIONS Oral lesion appears to be the most common extragenital form of granuloma inguinale. Oral lesions occur either as a result of autoinoculation through infected fingers or through oral coitus. Location: It is most commonly found on lips, buccal mucosa or palate or they may diffusely involve the mucosal surface. Lesions of lip are characterized by extensive superficial ulceration with well-defined elevated, granulomatous margins. It may be of three types, i.e. ulcerative, exuberant and cicatricial. Ulcerative: It is painful sometimes bleeding is associated with it. Exuberant: It appears as proliferative granular mass with an intact epithelial covering. The mucous membrane is inflamed and edematous. Cicatrical: Fibrous scar formation may be come extensive.

Histopathological Features Donavon bodies present in smears which are recognized as large, gram negative oval bacteria with intense bipolar staining (safety pin appearance). There is granulation tissue with infiltration of polymorphonuclear leukocytes and plasma cells. There is marked overlying pseudoepitheliomatous hyperplasia.

Management The recommended antibiotic for granuloma inguinale is either trimethoprim/sulfamethoxazole or doxycycline. Alternatives include ciprofloxacin, erythromycin, or azithromycin. The antibiotic should be given for at least a 3-week. Points to Remember Granuloma venereum, donavonosis, small papule that ulcerates, inguinal ulceration, autoinoculation through infected fingers, oral coitus, lesions of lip, ulcerative, exuberant, and cicatrical types, donavon bodies, safety pin appearance, infiltration of polymorphonuclear leukocytes, trimethoprim or sulfamethoxazole.

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STREPTOCOCCAL TONSILLITIS AND PHARYNGITIS

TONSILLAR CONCRETION AND TONSILLOLITHIASIS

It is caused by a, b hemolytic streptococci. Viruses can also cause this disease. They are Epstein Barr virus, adenovirus, and enteroviruses. Spread of this infection occur by person to person contact, from children to parent by means respiratory droplet and oral secreation.

Usually tonsil demonstrated crypts which are deep to increase surface area for interaction between immune cells of lymphoid tissue and oral environment. These crypts filled with keratin and foreign material which sometime become mass of foul smelling material. This is called tonsillar concretion. If there is calcification occur it is called tonsillolith.

Clinical Features Age: It is commonly seen children of 5 to 15 years of age: Sign and symptoms: There is sudden onset of sore throat, fever, dysphagia, tonsillar hyperplasia, cervical lymphadenopathy and yellowish tonsillar exudate. There is also beefy red and swollen uvula, excoriated nares and scarlatiniform rash (Fig. 18.22).

Management It is self-limiting and resolve in 3 to 4 days. Penicillin is drug of choice as group A streptococci are sensitive to it. Other antibiotics like cephalosporin drug (cephalexin, cefadroxl and cefouroxime) can also be given. Points to Remember a, b hemolytic streptococci, sore throat, fever, dysphagia, beefy red and swollen uvula, penicillin.

Clinical Features Age and sex distribution: It can be seen in childhood to old age. Male affected more commonly than female. Sign and symptoms: Patient complaint of foul smell. In some cases there may be recurrent infection leading pain, ulceration, chronic sore throat, irritable cough, and otalgia. There is sensation of foreign object seen in the throat which get relieved after removal of tonsillar plug. Radiographic feature: On panoramic radiograph radiopaque object is superimposed on the midportion of mandibular ramus.

Management They are not treated unless significant hyperplasia of tonsil is present. Local excision can be done of deeper tonsillolith. If there is evidence of recurrent tonsillitis tonsillectomy can be performed. Points to Remember Foul smell, sore throat, irritable cough, radiopaque object, local excision, tonsillectomy.

LYMPHOGRANULOMA VENEREUM It is a venereal disease caused by one of the three strains of Chlamydia trachomatis.

Clinical Features

Figure 18.22 Swollen uvula seen in streptococcal pharyngitis

Symptoms: There may be fever, chills, headache and malaise. It persists as firm, tender enlargement of inguinal lymph nodes. Nodes are tender and adherent to the underlying tissues.

Bacterial Infection

Enlargement of lymph nodes both above and below the inguinal ligament, is characteristic feature called ‘groove sign’. Overlying skin becomes reddened and dusky and multiple purulent fistulae develop over enlarged glands. In females, placenta is frequently involved. Marked scarring and local edema frequently develops secondary to suppurative lymphadenitis.

Oral Manifestations It results due to orogenital contact or anti-inoculation. Tongue is the most common site. Appearance: Lesion consists of small, slightly painful superficial ulceration with non-indurated borders which appear on lip. In long standing infection, there is zone of cicatrical refraction, dark red area with loss of superficial epithelium, or opaque lichenoid grayish papules. Dysphagia, red soft palate and small red granulomatous lesions accompanied by regional lymphadenopathy, are commonly associated symptoms. Cervical lymphadenopathy is present. Skin covering the swollen nodes is violaceous and indurated usually with one or more draining sinuses.

Management

Types • Cutaneous or dermal myiasis: It affects skin. • Myiasis of external orifices: It includes nasal, oral, vaginal and anal myiasis. • Myiasis of internal organs: It includes intestinal and urinary myiasis. • Accidental myiasis: Larvae ingested along with food. • Semi specific: When larvae are laid on necrotic tissue. • Obligatory: When larvae affect undamaged skin.

Clinical Features It is characterized by papular or migratory lesions. Papular lesions are itchy and occasionally painful. Open lesion may produce serious discharge and larvae may be detected through the opening (Figs 18.23 and 18.24). Migratory lesions are superficial, red tunnel like lesions, which form creeping eruptions.

Oral Manifestation Appearance: It presents as an erythematous, edematous or granulomatous lesion. Symptoms: Itching or pain may be present. These lesions pulsate with movement of larvae.

Antibiotics which are given are doxycycline, erythromycin, and azithromycin. Points to Remember Chlamydia trachomatis, enlargement of inguinal lymph nodes, groove sign, cicatrical refraction, dark red area with loss of superficial epithelium, cervical lymphadenopathy, doxycycline, erythromycin.

MYIASIS It is referred to the invasion of living tissues by the larvae of certain species of flies. Oral myiasis is a rare condition that refers to the invasion of tissue of the oral cavity by fly larvae. The term myiasis (Greek: myia= fly, iasis = disease) was coined by Hope in 1840.

Figure 18.23 Larvae seen in lesion of oral cavity

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centimeter in diameter. The overlying skin may be inflamed. The lymph nodes gradually become soft and fluctuant, owing to necrosis and suppuration. The lymphadenopathy may persist for one to six months.

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Symptoms: In early stage, low grade fever, headache, chills, nausea, malaise or even abdominal pain may occur. Other manifestations include nonpruritic macular or maculopapular rash, parotid swelling, conjunctivitis and grad mal seizures.

Figure 18.24 Oral myiasis showing detachment of palate

and larva in the palate

Signs: An opening is present from which larvae can come to surface of the lesion.

Management Surgical removal of larvae and irrigation of the tissue with hydrogen peroxide is effective method of choice. Points to Remember Larvae, open lesion serious discharge larvae may be detected, migratory lesions, itching or pain, hydrogen peroxide.

CAT SCRATCH DISEASE It is also called ‘cat scratch fever’. Disease is recognized in 1931 but the exact cause is unknown. Viral as well as bacterial agents have been proposed as the cause of this disease. But in 1988 the causative was named which initially called Rochalimaea henselae but was reclassified as Bartonella henselae.

Clinical Features Age and incubation period: The incubation time of the disease ranges from 3 to 30 days. It occur at any age, but predominant in children and young adults. It is thought to arise after traumatic break in skin due to scratch or bite of household cat. Within few days of indolent primary lesion, often papules or vesicle develop at the site of injury. Lymphadenitis: Within one to three weeks, lymphadenitis develops. The nodes are painful and may be several

Oculoglandular syndrome of parinuad: Primary lesion of eye can result in conjuctival granuloma with preauricular lymphadenopathy. This occur when person touches fur moistened with cat saliva during grooming. After this if individual rub eye this syndrome results. In dental point of view there may be involvement of preauricular, submaxillary or cervical chain of nodes.

Histopathological Features Involved lymph nodes manifest reticuloendothelial hyperplasia, focal granuloma, suppuration and necrosis with capsular thickening. Necrosis is surrounded by band of histiocytes and neutrophils. Epithelioid cells and multinucleated giant cells are occasionally seen. In some cases necrosis is absent but areas of karyorrhexis are present with proliferation of plump vascular channels which also exhibits thickened eosinophils walls. Organism can be demonstrated by immunoperoxidase technique.

Management The disease has a benign course and treatment is symptomatic including aspiration of the nodes, if it becomes necessary. The application of local heat and analgesic should be carried out. In case of severe and infection of immunocompromised patient antibiotics like azithromycin, erythromycin, doxycycline, rifampin, ciprofloxacin and gentamicin can be used. Points to Remember Rochalimaea henselae, after traumatic break in skin due to scratch or bite of household cat, lymphadenitis, low grade fever, headache, chills, oculoglandular syndrome of parinuad, preauricular, submaxillary or cervical chain of nodes, reticuloendothelial hyperplasia, focal granuloma, suppuration, histiocytes, neutrophils, epitheloid cells, karyorrhexi, azithromycin, erythromycin, doxycycline.

Bacterial Infection

PYOSTOMATITIS VEGETANS

Management

It is an uncommon inflammatory disease of the oral cavity. The name is given as there is a similarity between it and the skin lesions in a dermatologic disease known as pyodermatitis vegetans. Pyostomatitis vegetans is an inflammatory stomatitis and most often seen in association with inflammatory bowel disease, namely ulcerative colitis and Crohn’s disease. It may occur due to intestinal disturbances.

It is not specific. It is found that the oral lesions are regressed when the intestinal disturbance is brought under control with the help of sulfasalazine or systemic corticosteroids.

Clinical Features Location: This lesion may occur in any area of oral cavity, except in tongue. It is multiple in numbers. It is painless. Appearance: Oral lesions consist of large number of broad base papillary projections, tiny abscess or vegetations developing in areas of intense erythema. These small projections are red or pink in color, but on careful examination may show tiny pustules beneath the epithelium, which liberate a purulent material when ruptured. This is called ‘snail tract’ ulceration. When, condition is present, buccal and labial mucosal lesions have many folds and papillary projections may develop on these folds. Yellow vesicles discharged small amount of purulent material. These leave ulceration, which may coalesce into larger areas of necrosis. Buccal mucosa show ‘cobblestone’ appearance, while vestibular lesions appeared as folds and ulcers, the lips are diffusely swollen and indurated, gingival and alveolar mucosal lesions are granular with erythematous swelling and palatal lesions appear as multiple aphthous ulcers.

Histopathological Features The papillary projections generally show an intact stratified squamous epithelium with an underlying loose connective tissue, which is generally densely infiltrated by large number of plasma cells, lymphocytes and occasional polymorphonuclear leukocytes. It is arranged in pattern of small abscess or spreads diffusely throughout the tissue. Tiny areas of focal necrosis and micro abscess formation, either intraepithelial or subepithelial, are common features of this lesion. Focal areas of degeneration and necrosis of the overlying epithelium are present.

Points to Remember Broad base papillary projections, snail tract ulceration, buccal mucosa show ‘cobblestone’ appearance, intact stratified squamous epithelium, loose connective tissue, plasma cells, lymphocytes, polymorphonuclear leukocytes, focal areas of degeneration, microabscess formation, sulfasalazine systemic corticosteroids.

SINUSITIS Inflammation of the mucosa of the paranasal sinuses is referred to as sinusitis. When maxillary sinus is involved it is called maxillary sinusitis. When all the sinuses are involved it is called a pansinusitis. The most common organism responsible for acute sinusitis is Streptococcus pneumonia, Haemophilus influenzae and Moraxella catarrhalis. Oraganism responsible for chronic sinusitis are Streptococcus, Bacteroides or Veillonella spp. If sinusitis occur secondary to odontogenic infection causative organism is Peptostreptococcus spp., Fusobacterium spp., and Prevotella spp. Etiology • • • • • • • • • • • • • • •

Periapical infection from the teeth Oroantral fistula Periodontitis Traumatic Dental material in the antrum Implant Infected dental cyst Common cold Allergic rhinitis Deviated nasal septum Direct bacterial contamination Immune deficiency Influenza Blood borne infection Disease of maxillary sinus

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during diving, when pressure changes in the nose force nasal secretion into the sinus.

Periapical infection from the teeth: It may follow dental infection particularly from upper molar and premolar teeth. The anatomic proximity of the roots of the maxillary bicuspids and molar teeth to the floor of the sinus leads to potential infection of the sinus by direct extension of an apical abscess.

Immune deficiency: Sinusitis can occur in immune deficiency state, like leukemia, lymphoma and AIDS.

Oroantral fistula: The accidental opening in the floor of the maxillary sinus during dental extraction is called oroantral opening.

Disease of maxillary sinus: Benign mucosal cyst or tumors of the maxillary sinus can also lead to maxillary sinusitis.

Periodontitis: It may spread from a deep pocket of marginal periodontitis. Traumatic: Injury of facial bones especially nasal bones and malar bones. Dental material in the antrum: Perforation of endodontic filler substance. If root canal is overfilled then there are more chances of gutta purcha point to be inserted into the maxillary sinus. Implant: Implants are used in the upper edentulous jaw to aid the retention of dentures or bridges or replace missing teeth. Implants are also used when there is insufficiency of bone to support the denture. In these cases as bone is thin implant can penetrate the nose or sinus. Infected dental cyst: Cyst which have become infected and involve the maxillary sinus can also cause sinusitis.

Nondental Causes Mechanical Obstruction of Ostium Common cold: It is most common cause of mechanical obstruction of ostium. It will produce inflammatory edema of the nasal mucosa which obstruct the antronasal duct and cause mucus to accumulate in the sinus. Trapped mucous becomes secondarily infected by local commensal bacteria. Allergic rhinitis: It may cause maxillary discomfort due to edema round the ostium and retention of secretion. Other conditions: Deviated nasal septum, presence of nasal polyp and prolonged nasotracheal intubation can cause stagnation and relative anaerobiasis. Direct bacterial contamination: Infected material may also be introduced directly by jumping or hydrosliding feet first into contaminated water without holding the nose or

Influenza: It can also occur in influenza when bacteria invade as secondary microorganisms. Blood borne infection: It can also occur in some cases of blood borne infection.

Clinical Features Acute Maxillary Sinusitis Symptoms: The main symptom is severe pain which is constant and localized. Pain may be felt in the area of eyeball, cheek and frontal region. Pain may be exacerbated by stooping or lowering the head. Postnasal drip causing irritation, stuffiness and nasal discharge. Pain may be referred to various areas including the teeth, orbit, head and ear. Pain in the teeth may be referred to the premolars and molars on the affected side. Pain is increased by biting on the affected side but unaffected by drinking hot, cold or sweet fluids. Teeth in the involved side become sore and painful. Difficulty in breathing is common. Generalized toxemia develops, i.e. fever with chills, dizziness, malaise and nausea. Nasal discharge is watery in the beginning but later becomes mucopurulent. The nasal mucosa of the anterior nares may show reddening and inflammation and there may be presence of pus. In cases of sinusitis from infected teeth, the discharge has a foul odor. There is tenderness to pressure or swelling over the involved sinus. Since, the anterolateral and posterolateral sinus walls are thinnest in the area above the tooth root, thumb pressure on the cheek here is the best way to elicit tenderness externally. Premolar and molars on the affected side may be sensitive to percussion. Intraorally, there may be a mucobuccal swelling, reddening and pain near the sinus region.

Chronic Chronic sinusitis is recurring episode of acute sinusitis or symptomatic sinus disease lasting longer than 3 months. It develops as a result of neglected and overlooked dental focus of infection. The lining becomes thicker and irregular.

Bacterial Infection

General symptoms of chronic sinusitis include sense of tiredness, low grade fever and feeling of being unwell. Stuffy sensation over the affected side of the face is present. Nasal obstruction, nasal discharge and headache are the related symptoms.

Radiological Features

lymphocytic infiltration of the lining tissue with squamous metaplasia of the epithelium.

Management Removal of the cause: Removal of dental infection and other causes which are causing sinusitis.

Antibiotic: Antibiotics of choice are amoxicillin, There is increase radiodensity in the maxillary sinus (Fig. amoxicillin-clavulanate, trimethoprim, sulfamethoxazole. 18.25). Other therapy like analgesic, nasal decongestant, steam inhalation can be used. Lab Findings In case of chronic sinusitis surgical management like Elevated leukocyte count is seen. antral lavage, antrostomy and transnasal endoscopic surgery is performed. Histopathological Features

Acute Sinusitis

Points to Remember

The lining of the maxillary sinus may show a typical acute inflammatory infiltrate with edema of the connective tissue and often hemorrhage. Sometimes squamous metaplasia of the specialized ciliated columnar epithelium occurs.

Pansinusitis. Streptococcus pneumoniae, Haemophilus influenzae • Acute: Postnasal drip, severe pain, teeth in the involved side become sore and painful, nasal discharge, reddening of nasal mucosa, tenderness to pressure, premolar, molars sensitive to percussion, acute inflammatory infiltrate with edema of the connective tissue and squamous metaplasia. • Chronic: Sense of tiredness, low grade fever, feeling of being unwell, increase radiodensity in the maxillary sinus, cellular proliferation, thickening and the development of numerous sinus polyps, hyperplastic granulation, ciliated columnar epithelium. • Management: Analgesic, decongestant, steam inhalation, antral lavage, antrostomy.

Chronic Sinusitis The fundamental pathologic changes are that of cellular proliferation. The mucosal lining of the maxillary sinus shows remarkable thickening and the development of numerous sinus polyps. Polyps are simply hyperplastic granulation tissue with lymphocytes and sometimes plasma cell infiltration. Tissues covered by ciliated columnar epithelium tend to fill the sinus and obliterate it and in some cases there is mild

BIBLIOGRAPHY

Figure 18.25 Opacification seen in right maxillary sinus due

to sinusitis (Courtesy: Dr Ashok L)



1. Alfieri N, Fleury RN, Opromolla DV, et al. Oral lesions in borderline and reactional tuberculoid leprosy. Oral Surg Oral Med Oral Pathol. 1983;55(1):52-7. 2. Ayangco L, Rogers RS, Sheridan PJ. Pyostomatitis vegetans as an early sign of reactivation of Crohn’s disease: a case report. J Periodontal. 2002;73:1512-6. 3. Barrett AW, Dorrego MV, Hodgson TA, et al. The histopathology of syphilis of the oral mucosa. J Oral Pathol Med. 2004;33:286-91. 4. Berthold P. Noma a forgotten disease. Dent Clin North AM. 2003;47:559-74. 5. Bezerra SM, Jardim MM, Silva VB. Granuloma inguinale (Donovanosis). An Bras Dermatol. 2011;86(3):585-6. 6. Chong FY, Thirumoorthy T. Blistering erysipelas: not a rare entity. Singapore Med J. 2008;49(10):809-13.

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7. Cooper MM, Steinberg JJ, Lastra M, et al. Tonsillar calculi: report of case and review of literature. Oral Surg Oral Med Oral Pathol. 1983;55:239-43. 8. Eng HL, Lu SY, Yang CH, et al. Oral tuberculosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;81:415-20. 9. Enwonwu CO, Falkler WA jr, Phillips RS. Noma (Cancrum oris); lancet. 2006;368:147-56. 10. Ganesan K, Mizen K. Cat scratch disease. An unusual cause of facial palsy and partial ptosis: case report. Oral Maxillofac Surg. 2005;63(6):869-72. 11. Ghafoor M, Halsnad M, Fowell C, et al. Impetigo presenting as an acute necrotizing swelling of the lower lip in an adult patient. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113(6):e22-4. 12. Ghosh S, Gadda RB, Vengal M, et al. Oro-facial aspects of leprosy: report of two cases with literature review.Med Oral Patol Oral Cir Bucal. 2010;15(3):e459-62. 13. Giunta JL, Fiumara NJ. Facts about gonorrhea and dentistry. Oral Surg Oral Med Oral Pathol. 1986;62:529-31. 14. Goens JL, Schwartz RA, DeWolf K. Mucocutaneous manifestations of chancroid, lymphogranuloma venereum and granuloma inguinale. Am Fam Physician. 1994;49:4158, 423-5. 15. Henry J. Oral myiasis: A case study. Dent Update. 1996;23:3723. 16. Jacobsen PL, Casagranande AM. Sinusitis as a source of dental pain. Dent Today. 2003;22:110-3. 17. Kaya A, Deveci K, Uysal IO, et al. Tularemia in children: evaluation of clinical, laboratory and therapeutic features of 27 tularemia cases. Turk J Pediatr. 2012;54(2):105-12. 18. Klotz SA, Ianas V, Elliott SP. Cat-scratch Disease. Am Fam Physician. 2011;83(2):152-5. 19. Kumar R, Chakraborti A, Aggarwal AK, et al. Streptococcus pyogenes pharyngitis and impetigo in a rural area of Panchkula district in Haryana, India. Indian J Med Res. 2012;135:133-6. 20. Lele MV. Oral manifestations of rhinoscleroma. J Indian Dent Assoc. 1969;41(10):277-81. 21. Little JW. Gonorrhea: an update. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:137-43. 22. Little JW. Syphilis an update. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100:3-9. 23. Lopatin AS, Sysolyatin SP, Sysolyatin PG, et al. Chronic maxillary sinusitis of dental origin: is external surgical approach mandatory? Laryngoscope. 2002;112:1056-9. 24. Mahajan VK, Sharma NL: Scarlet fever.Indian Pediatr. 2005;42(8):829-30. 25. Margileth AM, Wear DJ, English CK. Systemic cat scratch disease: a report of 23 patients with prolonged and recurrent severe bacterial infection. J Infect Dis. 1987;155:390-402. 26. Markiewicz M, Suresh L, Margarone J, et al. Pyostomatitis vegetans: a clinical marker of silent ulcerative colitis. J Oral Maxillofac Surg. 2007;65:346-8.

27. Mattos-Guaraldi AL, Moreira LO, Damasco PV, et al. Diphtheria remains a threat to health in the developing world-an overview. Mem Inst Oswaldo Cruz. 2003;98(8):987-93. 28. Meyer I, Shklar G. The oral manifestation of acquired syphilis. Oral Surg Oral Med Oral Pathol. 1967;23:45-61. 29. Miller M, Haddad AJ. Cervicofacial actinomycosis: a diagnostic challenge. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85:496-508. 30. Morais S, Teles A, Ramalheira E, et al. Streptococcal pharyngitis: clinical suspicion versus diagnosis. Acta Med Port. 2009;22(6):773-8. 31. Nagler R, Peled M, Laufer D. Cervicofacial actinomycosis: a diagnostic challenge. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;83:652-6. 32. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edn. Saunder Elsevier, 2009 33. Nikolaeva IN, Astafeva NV, Barer GM, et al. Diphtheria of the oral mucosa: Stomatologiia (mosk). 1995;74:26-8. 34. Novilli MR, Haddock A, Eveson JW. Orofacial Myiasis. Br J Oral Maxillofac Surg. 1993;31:367. 35. Ochs MW, Dolwick MF. Facial erysipelas: a report of case and review of literature. J Oral Maxillofac Surg. 1991;49:1116-20 36. Ozcn E, Ural A, Oktemer TK, et al. Bilateral tonsillolithiasis a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:e17-8. 37. Reichart P. Facial and oral manifestation in leprosy : an evaluation of seventy cases. Oral Surg Oral Med Oral Pathol. 1976;41:385-99. 38. Rendell JR. McDougall AC. Reddening of upper central incisor associated with periapical granuloma in lepromatous leprosy. Br J Oral Surg. 1976;13:271-7. 39. Rinaggio J. Tuberculosis. Dent Clin North Am. 2003;47:44965. 40. Scully C, Williams G. Oral manifestations of communicable diseases.Dent Update. 1978;5(5):295, 298-311. 41. Tan SL, Neoh CY, Tan HH. Rhinoscleroma: a case series. Singapore Med J. 2012;53(2):e24-7. 42. Thornhill MH, Zakrzewska JM, Gikes JJH: pyostomatitis vegetans: Report of three cases: and review of literature. J Oral Pathol Med. 1992;21:128-33. 43. Torres-Urquidy MH, Wallstrom G, Schleyer TK. Detection of disease outbreaks by the use of oral manifestations.J Dent Res. 2009;88(1):89-94. 44. Velho PE, Souza EM, Belda Junior W. Donovanosis. Braz J Infect Dis. 2008;12(6):521-5. 45. Yang SG, Dong HJ, Li FR, et al. Report and analysis of a scarlet fever outbreak among adults through food-borne transmission in China. J Infect. 2007;55(5):419-24. 46. Yepes JF, Sullivan J, Pinto A. Tuberculosis: medical management update. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98:267-73.

Bacterial Infection

MULTIPLE CHOICE QUESTIONS







1. Red itchy spots affecting face with round or oval pustular vesicles caused by S. pyogenes is a. Syphilis b. Impetigo contagiosa c. Impetigo vulgaris d. Both b and c 2. Painless regional lymph nodes, discrete and rubbery in consistency is the classical signs of a. Late syphilis b. Primary syphilis c. Congenital syphilis d. Impetigo vulgaris 3. Circinate lesions on face accompanied by alopecia is the characteristic feature of a. Primary syphilis b. Congenital syphilis c. Late syphilis d. Secondary syphilis 4. Snail track ulcers, split papule, and condyloma latum is the oral manifestation of a. Secondary syphilis b. Primary syphilis c. Tertiary syphilis d. Gonorrhea



5. Gumma formation, neurosyphilis and tabes dorsalis is the feature of a. Gonorrhea b. Leprosy c. Noma d. Tertiary syphilis



6. Leonine facies, pedunculus earlobe is the feature of a. Lepromatous leprosy b. Tuberculosis c. Actinomycosis d. Scarlet fever



7. Langerhan’s type giant cells and lepra cells are the histopathological feature of a. Tuberculosis b. Leprosy c. Noma d. None



8. Langerhan’s giant cells having horse-shoe shaped nuclear arrangement is seen in a. Gonorrhea b. Leprosy c. Tuberculosis d. Tertiary syphilis



9. The characteristic submicroscopic sulfur granules is the feature of a. Lepromatous leprosy b. Tuberculosis c. Actinomycosis d. Scarlet fever

10. Strawberry and raspberry tongue is the oral manifestations of a. Tuberculosis b. Leprosy c. Noma d. Scarlet fever

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Fungal or Myocotic Infection

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline  Candidiasis  Oral candidiasis • Thrush or pseudomembranous candidiasis • Acute atrophic candidiasis or erythematous candidiasis • Chronic hyperplastic candidiasis • Id reaction • Candida associated lesion  Chronic mucocutaneous candidiasis  Forms of candidiasis  Histoplasmosis  Blastomycosis

CANDIDIASIS It is also called as ‘candidosis’. Candidiasis is the disease caused by infection with yeast like fungus Candida albicans.

Classification 1st Oral candidiasis Acute ∙ Acute pseudo membranous Candidiasis (thrush) ∙ Acute atrophic Candidiasis (antibiotics sore mouth) Chronic ∙ Chronic atrophic Candidiasis. – Denture stomatitis – Median rhomboid glossitis. – Angular cheilitis ∙ Id reaction. ∙ Chronic hyperplastic Candidiasis.

          Â

Mucormycosis Cryptococcosis Coccidioidomycosis Geotrichosis Sporotrichosis Rhinosporidiosis Aspergillosis Paracoccidioidomycosis Toxoplasmosis Leishmaniasis Trichinosis

Chronic mucocutaneous candidiasis ∙ Familial CMC ∙ Localized CMC ∙ Diffuse CMC ∙ Candidiasis endocrinopathy syndrome Extraoral candidiasis ∙ Oral Candidiasis associated with extraoral lesions orofacial and intertriginous sites (candidal vulvovaginitis, intertriginous candidiasis) ∙ Gastrointestinal candidiasis ∙ Candida hypersensitivity syndrome Systemic candidiasis ∙ Mainly affect the eye, kidney and skin.

Classification 2nd Candidiasis of nails and skin ∙ Candidal onychia ∙ Candidal paronychia.

Fungal or Myocotic Infection

Candidiasis confined to skin ∙ Interdigital candidiasis ∙ Intertriginous candidiasis ∙ Candidids (moniliids). Candidiasis confined to mucosa Oral mucosa ∙ Acute oral candidiasis – Acute pseudomembranous candidiasis (thrush) – Acute atrophic candidiasis (antibiotics sore mouth) ∙ Chronic oral candidiasis – Chronic atrophic candidiasis (denture sore mouth) – Chronic hyperplastic candidiasis. Gastrointestinal mucosa ∙ Pharyngeal candidiasis ∙ Esophageal candidiasis ∙ Intestinal candidiasis.

∙

In condition with minor immunological or other systemic defect ∙ Chronic mucocutaneous candidiasis (CMC) syndromes – Familial mucocutaneous candidiasis – Candidiasis endocrinopathy syndrome – Localized chronic mucocutaneous candidiasis – Diffuse chronic mucocutaneous candidiasis – Chronic mucocutaneous candidiasis in association with thymoma. Confined to mucocutaneous junctions ∙ Candidal angular cheilitis ∙ Perianal candidiasis. Systemic candidiasis ∙ Candidal endocarditis ∙ Candidal septicemia ∙ Candidal meningitis.

Causative Organisms

Respiratory mucosa ∙ Bronchial candidiasis. Genitourinary mucose ∙ Candidal vulvovaginitis. Mucocutaneous candidiasis Confined to mucocutaneous surface ∙ In condition with major immunologic defect – Swiss-type agammaglobulinemia – Hereditary thymic dysplasia – Di George syndrome – Acquired immunodeficiency syndrome (AIDS)

It is most commonly cause by Candida albicans (the yeast like fungus occur in yeast and mycelial forms). Other organisms which are responsible for candidiasis are Candida stellatoidea, Candida tropicalis, Candida parapsillosis, Candida pseudotropicalis, Candida famata, Candida rugosa, Candida krusei and Candida guilliermondi. Morphologically Candida can exist in three forms, i.e. yeast cells, pseudohypha and chlamydospore forms. Candida albicans is the commonest pathogen of all Candida species and it appears as moist creamy colonies

Conditions associated with increased vulnerability of oral candidiasis and their mechanism

Category

Condition

Mechanism

Altered local resistance to infection

Poor oral hygiene

Promotes organism adherence and colonization

Xerostomia

Absence of antimicrobial and flushing effect of saliva

Recent antibiotics treatment

Inhibits competitive oral bacteria

Dental appliance

Isolated mucosa from saliva and functional cleansing serve as organism reservoir

Early infancy

Immune competence has not completely developed

Genetic immune deficiency

Specific humoral or cellular immune defects

AIDS

Deficient cellular immune response

Corticosteroids therapy

Inhibition of immune function

Pancytopenia

Depletion of circulating leukocytes cause by chemotherapy, aplastic anemia and similar hemopoietic disorders

Anemia, malnutrition, malabsorption

Epithelial thinning and altered maturation, poor tissue oxygenation

Diabetes mellitus

Recurring hyperglycemia and mild ketoacidosis

Advanced systemic disease

Metabolic toxicity or limited blood perfusion of tissue

Compromised immune system function

Generalized patient debilitation

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and on blood agar as dull grey colonies. Candida albicans is component of normal oral microflora with 50 percent of people carried it without clinical evidence of infection. 486

Predisposing Factors Marked changes in oral microbial flora owing to administration of antibiotics (broad spectrum), corticosteroids, immunosuppressive agents can lead to candidiasis. Changes in microbial flora also can occur due to excessive use of antibacterial mouth rinses, xerostomia secondary to anticholinergic agent or salivary gland disease and and radiation to head and neck. Chronic local irritant like denture, orthodontic appliance and heavy smoke may predispose to candidiasis. Acute and chronic disease such as leukemia, lymphoma, diabetes and tuberculosis can also lead to candidiasis. Malnutrition states such as low serum vitamin A, pyridoxine and iron levels, age (infancy, pregnancy, old age), hospitalization and oral epithelial dysplasia, endocrinopathies such as hypoparathyroidism, hypothyroidism and Addison’s disease also leads to candidiasis. Primary and acquired immunodeficiency states such as hypogammaglobulinemia also act as predisposing factors. Tight and close fitting garments encourage the growth of Candida. Areas around the indwelling catheter are also involved.

Figure 19.1 Candidiasis presented as white plaque in the

palate

ORAL CANDIDIASIS Oral involvement is probably the most common manifestation of human candidal infection. It can occur either solely confined to the oral mucosa or as a part of any of the several mucocutaneous candidiasis syndromes. Different types of oral candidiasis can occur. This are described below.

Figure 19.2 Thrush showing white patches on tongue

They are painless and noticed on careful examinations. They may be removed with little difficulty.

Clinical Features

Location: Common sites are roof of the mouth, retromolar area, and mucobuccal fold. But it is common on any other mucosal surface and it is common in women as compared to male. Prodormal symptom like rapid onset of bad taste may be there. Spicy food will cause discomfort. Patient may complain of burning sensation and there may be history of dryness of the mouth.

In neonates, oral lesions start between the 6th and 10th day after birth. Infection is contracted from the maternal vaginal canal where Candida albicans flourishes during the pregnancy. The lesions in infants are described as soft white or bluish white, adherent patches on oral mucosa which may extent to circumoral tissue (Figs 19.1 and 19.2).

Signs: Inflammation, erythema, and painful eroded areas may be associated with this disease. Sometimes typical, pearly white or bluish white plaque curdy, loosely adherent patches are present on part of oral mucosa. Mucosa adjacent to it appears red and moderately swollen. Lesions are relatively inconspicuous.

Thrush or Pseudomembranous Candidiasis It is the superficial infection of upper layer of oral mucus membrane and results in formation of patchy white plaque or flecks on mucosal surface.

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487

Figure 19.3 Red area in palate after removal of patches

Figure 19.4 Candidiasis showing organism in the corneum

layer taking up magenta red color (Arrow)

White patches of it are easily wiped out with wet gauze which leaves either a normal or erythematous area or atrophic area (Fig. 19.3). Deeper invasion by the organism leaves an ulcerative lesion upon the removal of patch. Erythematous or white area may develop beneath the complete denture or partial denture. It is occasionally associated with (coexist with) dysplastic or carcinomatous change.

Histopathological Features (Figs 19.4 to 19.6) Fragments of the plaque material may smear on a microscopic slide, with 20 percent potassium hydroxide and examined for hyphae. There is presence of yeast cells and hyphae or mycelia in the superficial and deeper layer of involved epithelium. The submucosa may be free from any infection or may contain a chronic inflammatory cell infiltrate. On staining with PAS organism was identified by bright magenta color. Hyphae are varying in length showing branching. Hyphae are accompanied by yeasts, squamous epithelial cells. Potassium hydroxide (KOH) can also be use for rapid evaluation of Candida species. In this background of epithelial cells lyses allowing resistant yeasts and Hyphae to visualize. Identification of organism can be made by culture. Culture is made by rubbing sterile cotton swab over the lesion and then streaking the swab on the surface of Sabouraud’s agar slant. Candida albicans is seen as creamy smooth surface colonies after 2 to 3 days of incubation at room temperature.

Figure 19.5 Candidiasis

Figure 19.6 Filamentous organism of Candida in magenta

color PAS stain

Textbook of Oral Pathology

Points to Remember 488

Soft white or bluish white, adherent patches on oral mucosa, rapid onset of bad taste, mucosa, moderately swollen, white patches of it are easily wiped out, presence of yeast, hyphae or mycelia, yeasts, squamous epithelial cells, potassium hydroxide (KOH), rapid evaluation of Candida species, Candida albicans is seen as creamy smooth surface colonies.

Acute Atrophic Candidiasis or Erythematous Candidiasis It is also called as antibiotics sore mouth. When the white plaque of pseudomembranous candidiasis is removed, often red atrophic and painful mucosa remains.

Figure 19.7 Atrophic candidiasis showing red lesion in the

center of tongue

Clinical Features Chronic Hyperplastic Candidiasis

Appearance: In this type, lesion appears as red or erythematous rather than white, thus resembling the pseudomembranous type in which white membrane has been wiped off.

It is also called as candidal leukoplakia because of its firm presentation and adherent white patches occurring in the oral mucosa. This is rare type of candidiasis.

Location: It can occur at any site but it usually involves the tongue and tissue underlying an appliance.

Clinical Features

Symptoms: Patient usually described vague pain or a burning sensation. If the discomfort is not spontaneous, pain can be elicited by mild abrasive pressure with cotton gauze. Sign: Careful examination reveals a few white thickened foci that rub off leaving a painful surface. Lesion closely resembles erosive lichen planus and erythroplakia.

Age: It is predominantly occurs in men of middle age or over. Cause: The majority of these patients are heavy smokers. It occurs on cheek, lip and tongue. Appearance: There is firm, and white leathery plaques are found.

Histopathological Features

Symptoms: Lesions may persist without any symptoms for years. Many women with oral candidiasis also report symptoms of vaginal itching and discharge indicative of vaginal candidiasis.

Atrophic epithelium containing few hyphae in the superficial layer is present. Lamina propria shows mild acute inflammatory infiltrate and increased vascularity. Occasionally, microabscesses may be seen superficial epithelial areas.

Sign: It does not rub off with lateral pressure. Lesion range from slightly white to dense white with cracks and fissures occasionally present. The borders are often vague, which mimic the appearance of epithelial dysplasia (Fig. 19.8). It may occur as a part of chronic mucocutaneous candidiasis.

Bald tongue: There is diffuse loss of filiform papillae resulting in bald appearance of tongue (Fig. 19.7).

Points to Remember

Histopathological Features

Antibiotics sore mouth, red or erythematous rather than white, vague pain or a burning sensation, white thickened foci, bald tongue, atrophic epithelium, mild acute inflammatory infiltrate, microabscesses increased vascularity.

Epithelial dysplasia is seen but it is reversible. There is mycelial invasion of the deeper layers of mucosa and skin occurs. Epithelium is usually parakeratinized. There is acanthosis of spinous layer and bulbous elongated retepegs.

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489

Figure 19.8 Chronic hyperplastic candidiasis showing

leathery plaque

There is also pseudoepitheliomatous hyperplasia and microabscesses formation. It contains inflammatory exudates and chronic inflammatory cell infiltration of polymorphonuclear neutrophils in the cornium. Points to Remember Candidal leukoplakia, heavy smokers, firm, and white leathery plaques, white to dense white with cracks and fissures, epithelial dysplasia, mycelial invasion, acanthosis of spinous layer, bulbous elongated retepegs, pseudoepitheliomatous hyperplasia.

Id Reaction

Figure 19.9 Denture stomatitis presented as erythematous

area in maxillary area

Appearance: It exhibits patchy distribution often associated with speckled curd like white lesion (Fig. 19.9). Symptoms: There is soreness and dryness of mouth. Sign: Palatal tissue is bright red somewhat edematous and granular. Red patches may be erythematous or speckled. The redness of mucosa is rather sharply outlined and restricted to the tissue actually in contact with the denture. The multiple pinpoint foci of hyperemia usually involving the maxilla frequently occur. Histopathological features: Epithelium is atrophic and there are superficially oriented mycelia. Intense chronic inflammatory infiltrate in lamina propria is seen.

A person with chronic Candida infection may develop secondary response characterized by localized or generalized sterile vesicopapular rash that is believed to be allergic response to Candida antigen (also called monolids).

Management: Troches containing clotrimazole and Nystatin 4 to 5 times after meal and bed time.

Candida Associated Lesion

There is debate that it is form of chronic atrophic candidiasis but area of anterior 2/3 of tongue affect by median rhomboidal glossitis is frequently followed by Candida infection. It is described in detail in chapter of tongue disorders.

Denture Stomatitis It is also called chronic atrophic candidiasis. It is common clinical manifestation of erythematous candidiasis. Candida albicans is always found in this lesion but the typical white patch of thrush does not usually develop in it. It occurs due to tissue invasion but organism effect of fungal toxin hypersensitivity to fungus. Location: It is usually found under complete denture and partial denture and found mostly in women and always include palate.

Median Rhomboidal Glossitis

Points to Remember • D enture stomatitis: Chronic atrophic candidiasis, speckled curd like white lesion, soreness, palatal tissue is bright red, epithelium is atrophic • Median rhomboidal glossitis: Anterior 2/3 of tongue, Candida infection.

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Management 490

Removal of the causes: Replacement of denture or relining or adding mycostatin suspension below it while insertion in mouth in case of angular cheilitis and denture sore mouth. The denture must be cleaned thoroughly and regularly and should be kept in hypochlorite solution in right. Withdrawal or change of antibiotics use if feasible. Oral candidiasis may be treated either topically or systemically. Treatment should be maintained for 7 days. Response to treatment is often good; oral lesions and symptoms may disappear in a fairly short period (ranging from 2–5 days), but relapses are common because of the underlying immunodeficiency. As with other causes of oral candidiasis, recurrences are common if the underlying problem persists. Topical treatments are preferred because they limit systemic absorption, but the effectiveness depends entirely on patient compliance. Following are most commonly used topical treatment. Clotrimazole: It is an effective topical treatment (one oral troche [10 mg tablet]) when dissolved in the mouth five times daily. Used less frequently, one vaginal troche can be dissolved in the mouth daily. 1 percent gentian violet can be use but it is not ideal because of the superficial necrosis of mucosa it may produce and also because of the unsightly staining. Nystatin preparations: It includes a suspension, a vaginal tablet, and an oral pastille. Nystatin vaginal tablets (one tablet, 100,000 units, dissolved in the mouth three times a day). Nystatin oral pastille (available as a 200,000 unit oral pastille, one or two pastilles dissolved slowly in the mouth five times a day). Nystatin oral suspension 100,000 units/cc, 1 teaspoon of which is mixed with 1/4 cup of water and used as oral rinse. Topical creams and ointments: Containing nystatin, ketoconazole, or clotrimazole may be useful in treating angular cheilitis. Another therapeutic choice is amphotericin B (0.1 mg/mL). Five to 10 mL of oral solution is used as a rinse and then expectorated three to four times daily. Mycostatin cream 1 lacks unit or lactose containing vaginal tablet keeps under the tongue. The addition of absorbable corticosteroids and antibiotic agents to

mycostatin cream and ointment accelerate the symptomatic effect. Amphotericin B 0.08 mg/kg 2 to 3 hourly in ointment or cream base, suspension. Elixir containing both tetracycline and amphotericin B may also prove to be beneficial in acute atrophic candidiasis. Rinses: Mycostatin rinses for 7 to 10 days 3 to 4 times a day. 0.2 percent chlorhexidine solution, use of 1 percent chlorhexidine gel in denture stomatitis. Systemic Treatment: Several agents are effective for systemic treatment. Nystatin 250 mg TDS for 2 week followed by 1 troche per day for third week. Ketoconazole is a 200 mg tablet taken with food once daily. Patient compliance is usually good. Careful monitoring of liver function is necessary for long-term use because of reported side effects, including hepatotoxicity. Lack of efficacy of ketoconazole may occur because of poor absorption in those with an abnormally high gastric pH. Fluconazole is a triazole antifungal agent effective in treating candidiasis (100 mg tablet taken once daily for 2 weeks). Several studies suggest fluconazole is effective as a prophylactic agent, although the most effective prophylaxis dosing regimen is still unclear. Numerous reports, however, describe oral and esophageal candidiasis failing to respond to treatment with fluconazole, and in some of these cases investigators isolated resistant strains. Itraconazole (100 mg capsules) may be used for the treatment of oral candidiasis (200 mg daily orally for 14 days). Itraconazole oral suspension is now available (200 mg daily for 2 weeks. Salivary levels of itraconazole are maintained for several hours after administration. Ketoconazole, fluconazole, and itraconazole may interact with other medications including rifampin, phenytoin, cyclosporine A, terfenadine, digoxin, coumarinlike medications, and oral hypoglycemic medications. Points to Remember Removal of the causes, clotrimazole, nystatin preparations, topical creams and ointments, mycostatin cream, amphotericin B, mycostatin rinses, nystatin, ketoconazole, itraconazole, fluconazole.

Fungal or Myocotic Infection

CHRONIC MUCOCUTANEOUS CANDIDIASIS Classification Types • • • • •

Chronic familial mucocutaneous candidiasis Chronic localized mucocutaneous candidiasis Endocrinopathy candidiasis syndrome Chronic diffuse mucocutaneous candidiasis Chronic mucocutaneous candidiasis in association with thymoma.

Etiology It occur due to defect in cellular immunity, defect in structure of epidermis, diabetes, pregnancy and steroids.

and often laryngeal involvement. Cutaneous involvement is characterized by raised, crusty proliferative lesions predominately on the skin of face and scalp. These lesions are also called candidal granuloma. Oral lesions are widespread, proliferative and raised white lesions. Chronic mucocutaneous candidiasis in association with thymoma: Rarely patient with thymoma manifest chronic mucocutaneous candidiasis. Oral and skin surface are usually involved.

Management For resistance form of CMC and for systemic candidiasis miconazole (250 mg 6 hourly), 5-flucytosine (200 mg daily) in addition to amphotericin B is available. Transfusion of transfer factor and transplantation of culture of thymic fragments have been used to correct T cell deficiency associated with CMC.

Clinical Features Chronic familial mucocutaneous candidiasis: It is an inherited disorder, probably an autosomal recessive disorder and affects both sexes. It is characterized by candidiasis of mouth, nails, and skin. Children under the age of 10 years show superficial candidal infection. Oral candidiasis is chronic hyperplastic exhibiting firm white patches involving either buccal or lingual mucosa. Chronic localized mucocutaneous candidiasis: This form occurs early in life with oral mucosal, skin and nail involvement. There is also presence of chronic oral candidiasis and hypoplastic infection of nails fold in infancy. Oral lesion includes white patches characterized by horny masses mainly found on face and scalp. Patient show increase tendency to fungal and bacterial infection in the absence of immunological or genetic defect. Candidiasis endocrinopathy syndrome: It is also genetically transmitted characterized by early onset and Candida lesion of skin, scalp, nails and mucous membrane. There is subsequent appearance of hypoparathyroidism, hypoadrenocorticism and other endocrine abnormalities. There is also occurrence of dental hypoplasia and severe caries. There may be balanitis and vulvovaginitis, keratoconjunctivitis, alopecia and juvenile cirrhosis can also occurs. Chronic diffuse mucocutaneous candidiasis: It is of late onset and exhibits extensive raised crusty sheets involving the limbs, groin, face, scalp and shoulders. Mucocutaneous candidiasis is characterized by extensive oral, pharyngeal

Points to Remember • C hronic familial mucocutaneous candidiasis: Candidiasis of mouth, nails, and skin • Chronic localized mucocutaneous candidiasis: Chronic oral candidiasis, hypoplastic infection of nails • Candidiasis endocrinopathy syndrome: Candida lesion of skin, scalp, nails and mucous membrane, hypoparathyroidism, hypoadreno-cortism • Chronic diffuse mucocutaneous candidiasis: Mucocutaneous candidiasis, extensive raised crusty sheets, candidal granuloma • Chronic mucocutaneous candidiasis in association with thymoma: Thymoma manifest chronic mucocutaneous candidiasis, • Management: Miconazole, 5-flucytosine, amphotericin B.

FORMS OF CANDIDIASIS Candidal onychia and paronychia: Candidal infection of nail and of the soft tissue on the sides and at the base of the nail is common in housewife, nurses, and dishwasher, bartenders, and fruit pickers. Involved nail show green black discoloration and transverse ridges. Soft tissues are inflamed and tender. Treatment is by daily topical application of amphotericin B lotion or nystatin ointment. Interdigital candidiasis: It is also called erosion inter­ digitalis. It is commonly involved 3rd and 4th fingers. It

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is characterized by pruritic, inflamed, and scaling lesions between fingers. 492

Intertriginous candidiasis: Candida infection of skin surface such as waist, groin, armpit, elbows, submammary area, gluteal fold, axilla, scrotum. Opposing skin surface in these sites, particularly in obese person prevent adequate ventilation and remain moist favoring candidal growth. Candida has characteristic way of causing dry pustulation with desiccation in lower level of stratum cornium of skin. Lesions are very tender. Lesion spread from affected skin as an area of glaze red skin or an easily detached overlying epidermis, i.e. often invaded leaving paper like fungal lesion along the margin. Satellite lesion may develop around deeper denuded tissue. Gastrointestinal candidiasis: An extension of oral infection may occasionally lead to either pharyngeal or esophageal involvement. It presents as acute enterocolitis, diarrhea, as proctitis with anal puritis of perineal eczemation. Dysphagia, chest pain, and gastrointestinal tract (GIT) bleeding may be presenting symptoms. Esophageal candidiasis: Esophageal candidiasis with or without gastric ulceration are common forms of GIT candidiasis. It is diagnosed by characteristic appearance of edematous ulcerated mucosa on barium swallow. Bronchial candidiasis: It is a chronic infection of bronchial mucosa which may last for years without producing severe discomfort. It mimics chronic bacterial infection of the bronchus and chronic cough with mucoid sputum is common symptoms experience by the patients. Diagnosis is established by the demonstration of Candida in sputum and through culture studies. It includes systemic use of antifungal agents. Candidal vulvovaginitis and balanitis: Candida vulvovaginitis is a common form of candidiasis, which increases during pregnancy, diabetes, and uses of antibiotics. Candidal inflammation of glans penis may occur due to sexual contact. Diabetic women and those on long term drug therapy are prone to develop vaginal infection. It is characterized by erythematous plaques on the glans, penis and around the prepuce. Symptoms usually clear up on topical application of antifungal agents. Candidal endocarditis: It is characterized by fever, dyspnoea and edema of congestive cardiac failure. Vascular vegetations of candidal growth often result in embolization to major vessels. The disease is fetal in majority of cases.

Candidal meningitis: It is predominately disease of male children characterized by variable features ranging form stiffness of the neck, hemiplegia and other neurological signs. The finding of Candida in spinal fluid is of diagnostic importance. The condition is fatal in half of the cases. Candidal septicemia: It occurs in those with severe oral and esophageal thrush. Features include fever, chills, shock and coma. Condition can be fatal if not treated in time.

HISTOPLASMOSIS It is also called Darling’s disease. It is caused by Histoplasma capsulatum, a dimorphic fungus that grows in the yeast form in infected tissue. Humid areas with soil enriched by bird or bat excrement are suited for growth of this organism. This is reason this disease is more commonly found in fertile valley region. Infection results from inhalation of dust contaminated with dropping, particularly from infected birds. Types • Acute primary histoplasmosis • Progressive disseminated histoplasmosis • Chronic cavitary histoplasmosis.

Clinical Features Acute primary histoplasmosis: There is chronic low grade fever, malaise, headache and productive cough. There may be pleuritic pain. Primary infection is mild, manifesting as self limited pulmonary disease that heals to leave fibrosis and calcification. Chest radiograph may show patchy infiltrate which may exhibit signs of calcification. Progressive disseminated histoplasmosis: It is common in children and elderly. It is manifested by hepatosplenomegaly and lymphadenopathy. Patients with disseminated form show evidence of bone marrow involvement by anemia and leukopenia. There is also kidney involvement with gastrointestinal and oropharyngeal ulcerative lesions. Chronic cavitary histoplasmosis: It closely mimics chronic cavitary tuberculosis. The cavitary lesions are bilateral and are found in the upper lung fields. Symptoms include cough, dyspnea and weight loss.

Oral Manifestations Oral lesions are common in the progressive disseminated form.

Fungal or Myocotic Infection

Location: It is seen on buccal mucosa, gingiva, tongue, palate or lip. Symptoms: Patient may complain of sore throat, painful chewing, hoarseness, difficulty in swallowing.

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Signs: Oral lesions are nodular, ulcerative or vegetative. If left untreated it will progress to form firm papule or nodules which ulcerate and slowly enlarge. Ulcerated area covered by nonspecific gray membrane and is indurated (Fig. 19.10).

Histopathological Features The organisms are found in large numbers in phagocytic cells and appear as tiny intracellular structures measuring little more than 1 micron in diameter (Fig. 19.11). Biopsy shows small oval yeasts with in macrophages and reticuloendothelial cells as well as chronic granuloma, epithelial cells, giant cell with caseation necrosis. The mucosal epithelium shows ulceration, in majority of the cases. In nonulcerated areas, pseudoepitheliomatous hyper­ plasia is often seen. The submucosa shows a dense infiltrate of granulocytes, lymphocytes, plasma cells and histiocytes. Multinucleated giant cells and caseation necrosis are often seen. Causative organism is identified with PAS stain.

Management Ketoconazole: Ketoconazole is given for 6 to 12 months.

Figure 19.11 Histoplasma capsulatum organism

Supportive cares: In case of acute histoplasmosis supportive care with analgesic and antipyretic should be given. Amphotericin B: This is indicated in case of disseminated histoplasmosis. Points to Remember • A cute primary histoplasmosis: Pleuritic pain, fibrosis, calcification, patchy infiltrate • Progressive disseminated histoplasmosis: Hepatosplenomegaly, lymphadenopathy, bone marrow involvement by anemia • Chronic cavitary histoplasmosis: Cavitary lesions are bilateral cough, dyspnoea and weight loss • Oral manifestations: Buccal mucosa, sore throat, painful chewing, hoarseness, nodular, ulcerative or vegetative, nonspecific gray membrane • Histopathological: Tiny intracellular structures, small oval yeasts, macrophages, reticuloendothelial cells, ulceration, pseudoepitheliomatous hyperplasia, dense infiltrate of granulocytes, lymphocytes, plasma cells • Ketoconazole, amphotericin B.

BLASTOMYCOSIS

Figure 19.10 Ulcerative lesion seen in female patient in

histoplasmosis. It is mistaken as malignancy of mandibular vestibule

It is cause by blastomyces dermatidis. Organism is a normal inhabitant of soil and that is the reason for it to be common in agricultural worker. It is transmitted through the respiratory tract. Infection with blastomycosis begins in a vast majority of cases by inhalation, as primary pulmonary infection.

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Types 494

• • • •

Acute blastomycosis Primary pulmonary blastomycosis Cutaneous blastomycosis Disseminated or systemic blastomycosis.

Clinical Features Age and sex distribution: It is more commonly seen in male as compared to female in the ratio of 9:1. It is seen in middle age group. Acute blastomycosis: It resemble pneumonia and patient complaint of high fever, chest pain, malaise and productive cough. Primary pulmonary blastomycosis: It follows a chronic course with malaise, low grade fever and mild cough. If untreated, shortness of breath, weight loss and blood tinged sputum are encountered. It mimic tuberculosis. Cutaneous blastomycosis: Infection of skin, mucosa and bone may also occur, resulting from metastatic spread of organism through lymphatic system. Skin and mucosal lesion starts as subcutaneous nodule and progresses to well circumscribed indurated ulcer. Elevated, verrucous, crusted and single or multiple lesions developing on exposed part of the body, particularly on hands and face. Lesion leaves a slanted serpiginous border with a tendency towards healing in the center. When the crust is lifted, pus exudes. Disseminated or systemic blastomycosis: It results from the spread of infection from pulmonary form. Bones are involved in larger number of cases. Liver, kidney, spleen and gastrointestinal tract may be involved. Cerebral abscess are rare, but may occur as a result of brain involvement.

Oral Manifestations It may be primary or secondary to some infection elsewhere in the body. Symptoms and sign: Oropharyngeal pain, accompanied by the enlargement of cervical lymph nodes, may be a presenting sign of oral disease. Appearance: There is nonspecific, painless verrucous ulcer with indurated borders often mistaken for squamous cell carcinoma. Other lesions are hard nodules and appear as sessile projection, granulomatous appearing plaque.

Histopathological Features The inflamed connective tissue shows occasional giant cells, macrophages and the typical round organisms, often budding, which appear to have a doubly refractile capsule (Fig. 19.12). Organism is characterized by doubly refractive cell wall with a broad attachment between budding daughter cells and parent cell. Microabscesses are frequently found and if the lesion is not ulcerated overlying pseudoepitheliomatous hyperplasia may be prominent.

Diagnosis The index of suspicion should increase when chronic, painless, oral ulcer appears in an agricultural worker or when review of system reveals pulmonary symptom. Diagnosis is made on the basis of biopsy and on culturing the organism from tissue.

Management Intravenous amphotericin B is indicated only if the patient is seriously ill and not improving clinically. This is given for 8 to 10 weeks causes’ resolution of the disease. Itraconazole – It is indicated in chronic cases. Points to Remember Blastomyces dermatidis • Acute blastomycosis: Pneumonia, high fever, chest pain, malaise and productive cough • Primary pulmonary blastomycosis: Malaise, low grade fever, mild cough, shortness of breath • Cutaneous blastomycosis: Subcutaneous nodule, well circumscribed indurated ulcer, slanted serpiginous border • Disseminated or systemic blastomycosis: Bones are involved, cerebral abscess • Oral manifestations: Enlargement of cervical lymph nodes, non-specific, painless verrucous ulcer with indurated borders • Histopathological features: Occasional giant cells, macrophages, typical round organisms, often budding, doubly refractive cell wall, microabscess, pseudoepitheliomatous hyperplasia • Management: Traconazole, Intravenous amphotericin B.

Fungal or Myocotic Infection

There is increased lethargy, progressive neurologic deficit and ultimately death. Fungus invades artery to cause fibrosis and ischemia. There is appearance of a reddish black nasal turbinate and septum. Nasal discharge caused by necrosis of nasal turbinate.

Oral Manifestations

Figure 19.12 Blastomyces dermatidis

If there is involvement of maxillary sinus patient will exhibit intraoral swelling in the region of alveolar process or palate. It this is untreated then ulceration of palate, due to necrosis and invasion of palatal vessels can occur (Fig. 19.13). Ulcer may be seen on gingivae, lip and alveolar bone. It is large and deep, causing denudation of underlying bone. Radiological features—There is opacficiation of sinus wall with patchy effacement of bony walls of the sinus.

MUCORMYCOSIS

Histopathological Findings

It is also called as phycomycosis, Zycomycosis. It is caused by saprobic fungus of class Zygomycetes like Absidia, Mucor, and Rhizopus. It is more common in patients with decreased resistance, due to diseases like diabetes, tuberculosis, renal failure, leukemia, cirrhosis and in severe burn cases. Growth of these fungi is enhanced by iron and patient who are taking iron chelating agent like deferoxamine are also at increase risk of mucormycosis.

The tissue involved by mucormycosis shows necrosis and chronic inflammatory infiltrate. The vessels in the area may be thrombosed with organisms in the lumen. Culture studies are essential to identify the order family and genus of fungus. The organism appears as large, nonseptate hyphae with branching at obtuse angle. Round and ovoid sporangia are also seen. There is extensive tissue destruction which disturbs normal blood flow resulting in infarction and necrosis.

Types • S uperficial: It involves external ear, fingernails and skin. • Visceral: – Pulmonary – Gastrointestinal – Rhinocerebral or rhinomaxillary form.

Management Surgical debridment is the treatment of choice.

Clinical Features Rhinomaxillary form begins with inhalation of fungus by susceptible individual. Infection usually arise in lateral wall of nose and maxillary sinus; may rapidly spread by arterial invasion to involve the orbit, palate, maxillary alveolus and ultimately the cavernous sinus and brain through hematogenous spread and may cause death. Ptosis, proptosis, fever, swelling of cheek and paresthesia of face can occur. Intracranial involvement may be manifested by cranial neuropathy, especially of the trigeminal and facial nerve.

Figure 19.13 Mucormycosis showing deep ulceration of the

palate (Courtesy: Dr Ashok L)

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Systemic Amphotericin—It should be given in high doses. 496

Points to Remember Rhinomaxillary form, arterial invasion to involve the orbit, ptosis, proptosis, fever, swelling of cheek, paresthesia of face, intracranial involvement, cranial neuropathy, reddish black nasal turbinate, nasal discharge, involvement of maxillary sinus, denudation of underlying bone, opacification of sinus wall, necrosis, chronic inflammatory infiltrate, large, nonseptate hyphae, systemic amphotericin.

Cryptococcal meningitis: Meningoencephalic lesions produce a variety of neurologic signs and symptoms, generally associated with increased intracranial pressure. Radiographic features: The radiograph of chest shows infiltrates and occasionally ‘coin’ lesion.

Oral Manifestations Location: Lesion of hard palate, soft palate, gingiva, extraction socket, tongue and tonsillar pillar are common. Appearance: They appear as simple nonspecific, single or multiple ulcers. They are nodular and granulomatous, which may ulcerate during the course of disease.

CRYPTOCOCCOSIS

Histopathological Features

It is also called torulosis. It is a chronic fungal infection caused by Cryptococcus neoformans and Cryptococcus bacillispora. The causative organism is gram positive, budding, yeast-like cell with an extremely thick, gelatinous capsule, measuring 5 to 20 microns in diameter. Organism lives in deposit of excreta left by pigeon bird. It can grow in soil and in infected tissue. Infection occurs due to inhalation of airborne microorganism. It has increased incidence in immunosuppressive patients.

In tissue section it appears as a small organism with round or ovoid structure with a large clear halo, sometimes described as tissue microcyst (Fig. 19.14). The tissue reaction is generally granulomatous type; epitheloid cell proliferation is minimal. Multinucleated giant cells as well as inflammatory cell infiltrate are common.

Diagnosis The organisms can be cultured on Sabouraud’s glucose agar.

Types

Management

• • • •

Mild to moderate cases can be treated with ketoconazole for 6 to 12 weeks.

Primary cryptococcal infection Disseminated cryptococcal infection Cryptococcal meningitis Cutaneous cryptococcal infection.

Clinical Features There is slight predilection for middle aged males. Primary cryptococcal infection: The infection usually occurs in lungs. It may be asymptomatic and in some cases, patient may complain of cough with mucoid expectoration. Occasionally, pleuritic pain and hemoptysis can also occur. Disseminated type: Disseminated infection common in patients who are immunocompromised. There is involvement of meninges, skin, bone and prostate gland. Cutaneous type: The skin lesion appears as multiple brown papules which ultimately ulcerate, the clinical picture is nonspecific. The lesion discharge pus like material which is rich in organisms.

Figure 19.14 Cryptococcus organisms

Fungal or Myocotic Infection

The severe form requires amphotericin­B, intravenously for up to 10 weeks. This can be combined with flucytosine in case of cryptococcal meningitis. Points to Remember Torulosis, Cryptococcus neoformans, primary cryptococcal infection in lungs cough with mucoid expectoration and pleuritic pain, disseminated type in immunocompromised with involvement of meninges, skin, bone, cutaneous type with multiple brown papules and puslike material, cryptococcal meningitis, coin’ lesion, lesion of hard palate are simple non-specific, single or multiple ulcers, tissue microcyst, tissue reaction granulomatous type, multinucleated giant cells, flucytosine and ketoconazole.

COCCIDIOIDOMYCOSIS It is also called valley fever, desert fever or coccidiodal granuloma. The disease appears to be transmitted to man and animals by inhalation of dust contaminated by the spores of the causative organism, Coccidioides immitis. Coccidioides immitis is dimorphic organism which appears as mold in soil and as yeast in tissue of infected host. Infection is spread by means of inhalation of arthrospores. Types • Primary nondisseminated coccidioidomycosis – Primary pulmonary coccidioidomycosis – Primary cutaneous coccidioidomycosis • Progressive disseminated coccidioidomycosis.

Clinical Features Age and sex distribution: It is common in all age groups and predominately seen in males. Symptoms occur usually 14 days after the inhalation of fungus. Infection is common in summer months, especially after periods of dust storm. It is self limiting and runs its course within 10 to 14 days. Primary pulmonary coccidioidomycosis: The patient generally develops manifestations suggestive of respiratory disease such as cough, pleural pain, headache and anorexia. Patient may also complaint of low grade fever and joint pain.

Primary cutaneous coccidioidomycosis: Skin lesions are also present, like erythema nodosum of erythema mul­ tiforme. Primary lesions, when they occur, are associated with regional lymphadenopathy. Granulomatous, verrucous or necrotic ulcers exuding thick pus are seen on involved skin surface. Valley fever: This is hypersensitivity reaction which occur in conjunction with coccidioidomycosis is term as valley fever. Progressive disseminated coccidioidomycosis: The disease usually runs rapid course and the dissemination extends from the lungs to various viscera, bones, joints, skin and central nervous system, where meningitis is the most frequent cause of death.

Oral Manifestations Lesions of head and neck, including the oral cavity, occur with some frequency. Appearance: The lesions of oral mucosa and skin are proliferative, granulomatous and ulcerated lesions that are nonspecific in their clinical appearance. These lesions tend to heal by hyalinization and scar formation. Radiological features: Lytic lesions of bones of jaw may develop.

Histopathological Features The tissue reaction is similar to any specific granuloma. There is accumulation of large mononuclear cells, lymphocytes and plasma cells. Foci of coagulation necrosis are often found in the center of small granulomas and multinucleated giant cells are scattered throughout the lesion. The organism is found within the cytoplasm of giant cells, as well as is lying free in the tissue. Organism is round spherules which may contain numerous endospores.

Management Amphotericin B has been found to be an effective chemotherapeutic agent for the disease. It is given in case of immunosuppressed patient, severe pulmonary infection, pregnant patient and patient who appear to be life threatening situation. Long-term therapy is required for complete cure. Other drugs like fluconazole, itraconazole can also be used.

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Points to Remember 498

Valley fever, desert fever, coccidioides immitis, cough, pleural pain, headache, anorexia, erythema nodosum of erythema multiforme, regional lymphadenopathy, valley fever, disseminated extends from the lungs to various viscera, bones, joints, lesions of oral mucosa and skin are proliferative, granulomatous, lytic lesions of bones of jaw, large mononuclear cells, plasma cells, foci of coagulation necrosis, round spherules, amphotericin B, fluconazole, itraconazole.

GEOTRICHOSIS Geotrichosis is an infrequent opportunistic mycosis caused by yeasts. The main etiologic agent is Geotrichum candidum, which belongs to the class Hemiascomycetaceae. Geotrichum candidum is a cosmopolitan microorganism and habitual contaminant. It has been isolated from various sources such as fruits and vegetables, soil, and plants. Several studies have proven that it is a commensal in humans and part of the normal flora of the skin, mouth and gastrointestinal tract. It is found in patients with debilitating diseases. Most of the reported clinical cases have occurred in immunosuppressed patients or immunosuppressive disorders.

Clinical Features Location: It has been reported to pathologically affect the bronchi, lungs, and bowel, and only seldom the mouth, skin and nails. Lung involvement produces symptoms of pneumonitis or bronchitis. The expectoration is often tinted with blood. Oral features: They are similar to candidiasis or thrush, being white, velvety, patch like covering of the oral mucosa, isolated or diffuse in distribution. Tonsillar lesions are common in association with oral lesions.

Histopathological Features The organism is small, rectangular shaped; spores measuring approximately 4 to 8 microns, often with rounded ends (Fig. 19.15). The tissue reaction is nonspecific and of acute inflammatory type.

Management It includes topical and systemic application of nystatin and amphotericin B.

Figure 19.15 Rectangular shaped organism of geotrichosis

Points to Remember Geotrichum candidum, lung involvement pneumonitis or bronchitis, candidiasis or thrush, being white, velvety, patch like covering of the oral mucosa, small, rectangular shaped; spores.

SPOROTRICHOSIS It is also called Rose gardener’s disease. It is a fungal infection caused by Sporotrichum schenckii. The disease predominately affects skin. Because roses can spread the disease, it is one of a few diseases referred to as rosethorn or rose-gardeners’ disease, because Sporotrichum schenckii is naturally found in soil, hay, sphagnum moss, and plants, it usually affects farmers, gardeners, and agricultural workers. It is caused by exposure to a wide variety of animals, both domestic and wild. It may be cause by accidental injury from the thorns of some plants or bushes, accidental laboratory or clinical inoculation in hospital workers.

Clinical Features Location: The incubation period is from week to 3 weeks. It involves the skin, subcutaneous tissues and oral nasal and pharyngeal mucosa. Cutaneous or skin sporotrichosis: It most common form. There is nodular lesions or bumps in the skin, at the point of entry and also along lymph nodes and vessels. The lesion initially small and painless, and ranges in color from pink to purple. It the lesion left untreated, the lesion becomes

Fungal or Myocotic Infection

larger and look similar to a boil and more lesions will appear, until a chronic ulcer develops. Usually, cutaneous sporotrichosis lesions occur in the finger, hand, and arm. The skin lesion often described as sporotrichotic chancre. Regional lymphadenopathy is generally developed and it may ulcerate and drain. The fungus follows lymphatic channels in the body. Small ulcers appear in lines on the skin as the infection goes up an arm or leg. These sores do not heal unless they are treated and may remain for years. The nodules may drain small amounts of pus from time to time. Pulmonary sporotrichosis: This rare form of the disease occur when Sporotrichum schenckii spores are inhaled. Symptoms of pulmonary sporotrichosis include productive coughing, nodules and cavitations of the lungs, fibrosis, and swollen hilar lymph nodes. Patients with this form of sporotrichosis are susceptible to developing tuberculosis and pneumonia. Disseminated sporotrichosis: The infection can spread to joints and bones (called osteoarticular sporotrichosis) as well as the central nervous system and the brain (called sporotrichosis meningitis). The symptoms of disseminated sporotrichosis include weight loss, anorexia, and appearance of bony lesions.

Oral Manifestations Nonspecific ulceration of the oral, nasal and pharyngeal mucosa also occurs. Long standing lesions become granulomatous, vegetative or papillomatous. Pain is present and the cervical lymph nodes are always enlarged.

Histopathological Features The fungus is small, ovoid branching organism with septate hyphae showing budding form. It is only 3 to 5 microns in diameter and can be cultured on Sabouraud’s medium (Fig. 19.16). The tissue reaction is a granulomatous one with epithelioid cells, multinucleated giant cells of Langhans type and lymphocytes, often surrounding a central area of purulent or caseous necrosis. Polymorphonuclear leukocytes are prominent with pseudoepitheliomatous hyperplasia of the overlying epithelium of skin or mucosal lesion.

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Figure 19.16 Hyphae of sporotrichosis

Management It includes oral administration of potassium iodide in suitable doses. The skin infection is usually treated with an antifungal medicine called itraconazole. Points to Remember Rose Gardner disease Sporotrichum schenckii, cutaneous or skin sporotrichosis, sporotrichotic ‘chancre’. Regional lymphadenopathy, fungus follows lymphatic channels, pulmonary sporotrichosis, disseminated sporotrichosis, osteoarticular sporotrichosis, non-specific ulceration of the oral, nasal pharyngeal mucosa, septate hyphae budding form, granulomatous one with epihtheloid cells, polymorphonuclear leukocytes, pseudoepitheliomatous hyperplasia, oral administration of potassium iodide.

RHINOSPORIDIOSIS Rhinosporidiosis is a mucosal and cutaneous mycosis caused by Rhinosporidium seeberi. Laryngeal rhinosporidiosis too has been described and may be due to inoculation from the nose during endotracheal intubation. After inoculation the organism replicate locally resulting in the hyperplasia of host tissue and localized immune response. The infection results from a local traumatic inoculation with the organism while swimming or bathing in freshwater ponds, lakes or rivers.

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Clinical Features 500

Location: It is more common on oropharynx, nasopharynx, larynx, skin, eyes and genital mucosa. Though, the floor of the nose and inferior turbinate are the most common sites, the lesions may appear in elsewhere too. Traumatic inoculation from one site to others is common Symptoms: Initial symptoms include nasal irritation, accompanied by mucoid discharge. Other symptoms includes epistaxis, local pruritus, rhinorrhea, coryza with sneezing, post nasal discharge with cough, foreign body sensation, and increased tearing and photo phobia in cases of infection of palpebral conjunctiva. Sign: The skin lesion appears as small verrucae or warts, which ultimately become pedunculated. Posteriorly, these polypoid masses may extend into the pharynx. The lesions are soft, friable and highly vascular. Genital lesion resembles condyolomas. Lesion bleeds easily upon manipulation. It has got strawberry like appearance.

Oral Manifestations Location: The soft palate appears to be the most frequent site of oral involvement. Signs: It is accompanied by a mucoid discharge and appears as soft, reddish pink, polypoid growth of tumor like nature which spreads to the pharynx and larynx. The lesions are vascular and bleed readily.

Histopathological Features

Points to Remember Rhinosporidium seeberi, local traumatic inoculation with the organism while swimming or bathing nasal irritation, epistaxis, local pruritus, rhinorrhea, coryza, small verrucae or warts, strawberry like appearance, soft, reddish pink, polypoid growth of tumor like nature which spreads to the pharynx and larynx, focal abscess formation acute and chronic inflammatory cells.

ASPERGILLOSIS It is a fungal infection caused either by sensitization to, parasitic colonization of, or tissue invasion by species of genus Aspergillus. It is second to candidiasis, as an opportunistic infection, in immunocompromised patients like AIDS, uncontrolled diabetes mellitus, leukemia etc. Aspergillus species stays in soil, water, and decaying organic debris. Most commonly species are Aspergillus flavus and Aspergillus fumigates.

Clinical Features Location: The respiratory tract, external auditory canal, nasopharynx, cornea, gastrointestinal tract and occasionally the skin may be the primary sites of infection. Symptoms: In some cases, there may be asthmatic episode in sensitive persons. Sign: It may present swelling, ulceration, crusting and necrosis of anterior turbinates, nasal septum and nasal wall. Allergic fungal sinusitis: In some patient, allergy affecting sinus is present.

The organisms appear as sporangia containing large number of round or ovoid endospores with size of 5 to 7 microns in diameter. The surrounding tissue reaction itself is a nonspecific, consisting of a vascular granulation tissue with focal abscess formation and occasional multinucleated giant cells. Both, acute and chronic inflammatory cells are present in variable number.

Disseminated aspergillosis: It occur in immunocompromised patient. Patient complaint of chest pain, cough, fever.

Management

Appearance: A lesion on the palate is manifested as a painful ulcer, surrounded by a ring of black necrotic tissue.

Surgical excision—Wide excision with electro-coagulation of the lesion base. Medical treatment is not so effective but treatment with a year long course of dapsone has been reported.

Oral Manifestations Location: It is rare but in some cases, involvement of palate and tongue can occur. Soft palate involvement seems to be more common in upper respiratory tract involvement.

Oropharyngeal aspergillosis: In patients with hemato­ logical malignancies, presents as yellowish-black ulceration of soft palate and posterior part of tongue. These

Fungal or Myocotic Infection

patients complain of intense local pain, oral bleeding and dysphagia. Aspergilloma: Sometime low grade infection of maxillary sinus may results in mass of fungal hyphae which is called as aspergilloma. After some time mass will undergo calcification resulting in antroliths.

Histopathological Features Granulomatous reactions are seen in majority of the lesions and consist of central necrosis surrounded by epitheloid cells and fibrosis. Giant cells and chronic inflammatory infiltrates are seen in connective tissue. Organism shows varying number of branching septate hyphae 3 to 4 mm in diameter. These hyphae have tendency to branch at acute angle and to invade adjacent small blood vessels (Fig. 19.17).

Management Amphotericin B is the treatment of choice in case of aspergillosis. Recent studies show that voriconazole is more effective in treating this patients. Disseminated aspergillosis in immunocompromised patients should be treated on an individual basis with intravenous antifungal agents and surgical debridement.

Points to Remember Genus Aspergillus, asthmatic episode, ulceration, crusting and necrosis of anterior turbinates, allergic fungal sinusitis, disseminated aspergillosis, oropharyngeal aspergillosis, aspergilloma, granulomatous reactions, giant cells, chronic inflammatory infiltrate, branching septate hyphae, voriconazole, amphotericin B.

PARACOCCIDIOIDOMYCOSIS It is also called ‘South American blastomycosis’. It is caused by Paracoccidioides brasiliensis. It is usually found in South American population of farmers.

Clinical Features Age and sex distribution: It is seen in male in the ratio of 15:1. This can be due to protective effect of female hormone. It is more commonly seen in middle age grouped. Pulmonary infection: pulmonary in nature

Initial

infection

is

usually

Addison disease: Adrenal involvement can occur due to hematgenous or lymphatic spread resulting in hypoadrenocorticism.

Oral Manifestations Location: It is occur on alveolar mucosa, gingiva, palate, buccal mucosa and pharynx. Appearance: There is mulberry like ulceration affecting.

Histopathological Features There is pseudoepitheliomatous hyperplasia with ulceration in surface epithelium. There is also presence of epihtheloid macrophages and multinucleated giant cells. Organism are scatter and large showing multiple daughter buds on the parent cells which resemble appearance as ‘Mickey mouse ears’ or the spokes of ship’s steering wheel’ (mariner wheel).

Management Figure 19.17 Branching organisms of aspergillosis

Sulfonamide derivative—These are used since long back to treat this infection

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Other drugs which can be use are intravenous amphotericin B, oral itraconazole and ketoconazole. 502

Points to Remember Paracoccidioides brasiliensis, pulmonar infection, Addison disease, mulberry like ulceration, pseudoepitheliomatous hyperplasia, epihtheloid macrophages, Mickey mouse ears’ or the spokes of ship’s steering wheel’ (mariner wheel), sulfonamide derivative.

TOXOPLASMOSIS It is cause by obligate intracellular protozoal organism Toxoplasma gondii. Cats are considered to be host for this organism. It is more commonly seen in immunocompromised individual like AIDS, transplant recipient and cancer patients.

Points to Remember Toxoplasm gondii, cervical lymphadenopathy, disseminated type, congenita toxoplasmosis, accumulation of eosinophilic macrophages, macrophage accumulate, sulfadiazine, pyrimethamine.

LEISHMANIASIS It is caused by the genus Leishmania which consist of three flagellate protozoa, which cause variety of distinct infections in man and are transmitted by sandfly bites. Types • V isceral leishmaniasis: It is also called Kalaazar. It is caused by Leishmania donovani. • Cutaneous leishmaniasis: It is caused by Leishmania braziliensis.

Clinical Features

Clinical Features

Symptoms: They are mild and consist of low grade fever, cervical lymphadenopathy, fatigue, and muscle and joint pain. In some cases submental and buccal lymph nodes can be enlarged.

Visceral leishmaniasis: Incubation period is 2 weeks to 2 years. Onset may be insidious with a low grade fever or it may be abrupt with sweating and high intermittent fever. Cough and diarrhea can also develop. The spleen becomes enlarged, often massively. If not treated, patient will become anemic and wasted. There is also abdominal discomfort, fever that lasts for weeks; may come and go in cycles, night sweats, thinning hair and weight loss.

Disseminated type: This occurs in immunocompromised individual and manifested as encephalitis, pneumonia, myositis and myocarditis. There may be disorientation, lethargy and headache. Congenita toxoplasmosis: This occur when mother contract disease during pregnancy with organism crossing the placental barrier. In this case there may be blindness, mental retardation and delayed psychomotor development.

Histopathological Features Lymph nodes show reactive germinal center exhibiting accumulation of eosinophilic macrophages. Macrophage accumulate at subcapsular and sinusoidal region of node.

Management If exposure is suspected during pregnancy combination of sulfadiazine and pyrimethamine should be given. This will prevent transmission of organism to fetus. Severe cases can also be treated by same combination.

Mucocutaneous leishmaniasis: Incubation period is 1 week to 1 month. It is usually seen in young men. There is past history of superficial ulcer of skin, caused by bite of an infected sandfly, which heals with depressed scar. Nasal mucosa becomes congested and ulcerates. Later, all the soft tissues of nose may be destroyed.

Oral Manifestations Visceral leishmaniasis: There may be increase pigmentation of face. There may be spontaneous bleeding, edematous gingiva and loose teeth. Mucocutaneous leishmaniasis: Mucosal lesion usually occurs 1 to 2 years after skin lesion. Lips, soft palate and larynx may be involved. The mucosal lesions are long standing, destructive, granulating ulcers which in many instance cause severe mutilation of structure involved. Regional lymphadenopathy is common.

Fungal or Myocotic Infection

Histopathological Features Dense dermal infiltrate of lymphocytes, plasma cells, histiocytes, epithelioid cells and occasionally eosinophils and giant cells. Sometimes neutrophils are present throughout the reticular dermis. The organisms are round to oval basophilic structures with eccentrically located kinetoplast. In case of chronic lesion there is mild to moderate mononuclear infiltrate (lymphocytes and plasma cells) near the granuloma together with fibrosis and telangiectasia.

Management Amphotericin is the drug of choice for visceral leishmaniasis. In mucocutaneous lesion, small lesion may be treated by freezing with liquid carbon dioxide, curettage or infiltration with 1 to 2 mL sodium stib gluconate. If the lesions are multiple parenteral injection of amphotericin B should be given. Points to Remember Leishmania three flagellate protozoa, visceral leishmaniasis, cough, diarrhea, low grade fever, abdominal discomfort, mucocutaneous leishmaniasis, history of superficial ulcer of skin, bite of an infected sandfly, pigmentation of face, lips, soft palate and larynx shows destructive, granulating ulcers, dense dermal infiltrate of lymphocytes, round to oval basophilic structures with eccentrically located kinetoplast, mononuclear infiltrate, freezing with liquid carbon dioxide, sodium stib gluconate.

TRICHINOSIS It is caused by Trichinella spiralis, which is small, spiral, thread like organism. Human infection occurs as a result of eating parasitized food, usually pork, which has not been completed cooked.

Clinical Features Most common site involved are striated muscle, masseter, neck muscle and diaphragm. Symptoms: There is fever, facial and periorbital edema, muscle pain and eosinophilia.

Oral Manifestations Location: Tongue is the most common site involved. It also occurs in muscles attached to mandible, in mandibular alveolar process and in gingival tissues.

Symptoms: Trismus, muscular cramps of the facial muscle, jaw and tongue can occur. There is also monotony of speech. Signs: There may be petechiae of buccal mucosa, palate and floor of mouth. There is also bleeding from gingiva, lips and nose.

Histopathological Features Larva cause inflammation and destruction of muscle fibers. A fibrous hyaline develops around a single coiled larva. The histiocytes and giant cells may surround it.

Management There is no specific treatment for trichinosis and in severe cases, prognosis is poor. Points to Remember Trichinella spiralis, striated muscle, masseter, fever, facial and periorbital edema, tongue, trismus, muscular cramps, petechiae of buccal mucosa, inflammation, destruction of muscle fibers.

BIBLIOGRAPHY 1. Aarestrup FM, Guerra RO, Vieira BJ. Oral manifestation of sporotrichosis in AIDS patients, et al. Oral Dis. 2001;7(2):134-6. 2. Abbas K, el Toum IA, el Hassan AM. Oral leishmaniasis associated with kala-azar. A case report: Oral Surg Oral Med Oral Pathol. 1992;73(5):583-4. 3. Ajit Daharwal, Hansa Banjara, Digvijay Singh, et al. A rare case of laryngeal rhinosporidiosis. J Laryngol Voice. 2011;1:30-2. 4. Alexandro Bonifaz, Denisse Vázquez-González, Berenice Macías, et al. Oral geotrichosis: report of 12 cases: Journal of Oral Science. 2010;52(3):477-83. 5. Allen CM. Diagnosing and managing oral candidiasis. J AM Dent Assoc. 1992;123:77-82. 6. Arnold MG, Arnold JC, Bloom DC, et al. Head and neck manifestation of disseminated coccidioidomycosis. Laryngoscope. 114:747-2 7. Azaz B, Milhem I, Hasson O. Acquired toxoplasmosis of submandibular lymph node in 13 year old boy case report: Pediatric Dent. 1994;16:378-80. 8. Barbeau J, Seguin J, Goulet J, et al. Reassessing the presence of Candida albicans in denture related stomatitis. Oral Surg OraL Med Oral Pathol Oral Radiol Endod. 2003;95:51-9. 9. Castling B, Layton SA, Pratt RJ. Cutaneous leishmaniasis. An unusual cause of facial swelling. Oral Surg Oral Med Oral Pathol. 1994;78(1):91-2.

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10. Correa MEP, Soarees AB, de Souza CCA, et al. Primary aspergillosis affecting the tongue of a leukemic patients. Oral Dis. 2003;9:49-53. 11. Falworth MS, Herold J. Aspergillosis of the paranasal sinus: a case report and radiographic review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;81:255-60. 12. Fotos PG, Vincent SD, Hellstein JW. Oral candidosis: a clinical historical and therapeutic features of 100 cases: Oral Surg Oral Med Oral Pathol. 1992;74:41-9. 13. Heinic GS, Greenspan D, MacPhail LA, et al. Oral Geotrichum candidum infection associated with HIV infection. A case report: Oral Surg Oral Med Oral Pathol. 1992;73(6):726-8. 14. Huang JS, Kok SH, Lee JJ, et al. Extensive maxillary sequestration resulting from mucormycosis: Br J Oral Maxillofac Surg. 2005;43:532-4. 15. Lador N, Polacheck I, Gural A, et al. Trifungal infection of the mandible: a case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:451-6. 16. Leal-Alcure M, Di Hipolito-Junior O, Paes de Almeida O, et al. Oral histoplasmosis in HIV negative patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:E33-36. 17. Leitner C, Hoffmann J, Zerfowski M, et al. Mucormycosis: a necrotizing soft tissue lesion of the face. J Oral Maxillofac Surg. 2003;61:1354-8. 18. Mehrabi M, Bagheri S, Leonar MK, et al. Mucocutaneous manifestation of cryptococcal infection: a report of case and review of literature. J Oral Maxillofac Surg. 2005;63:1543-9. 19. Miloro M, Kinney LA. Trichinosis of the lateral pterygoid mtuscle: Oral Surg Oral Med Oral Pathol. 1994;78(3):276-7.

20. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edn. Saunder Elsevier; 2009. 21. Ogata Y, Okinaka Y, Takahashi M. Antroliths associate with aspergillosis of the maxillary sinus: a report of case. J Oral Maxillofac Surg. 1997;55:1339-41. 22. Reder PA, Neel B. Blastomycosis in otolaryngology: a review of large series. Laryngoscope. 1993;103:53-8. 23. Rose HD, GIngrass DJ. localized oral blastomycosis mimicking actinomycosis. Oral Surg Oral Med Oral Pathol. 1982;54:12-4. 24. Samarnayake LP. Oral mycoses in HIV infection. Oral Surg Oral Med Oral Pathol. 1992;73:171-80. 25. Schmidt-Westhausen A, Grunewald T, Reichart PA, et al. Oral cryptococcosis in patient with AIDS: a case repot: Oral Dis. 1995;1:77-9. 26. Scully C, Paes De Almeida O. Orofacial manifestation of the systemic mycoses. J Oral Pathol Med. 1992;21:289-4. 27. Sposto MR, Mendes-Giannini MJ, Moares ER, et al. Paracoccidiodomycosis manifesting as oral lesion: clinical cytological and serological investigation. J Oral Pathol Med. 1994;23:85-7. 28. Sposto MR, Scully C, Paes de Almeida O, et al. Oral Paracoccidiodomycosis: as study of 36 south American patient: Oral Surg Oral Med Oral Pathol. 1993;75:461-5. 29. Terai H, Shimahara M. Atrophic tongue associated with Candida: J Oral Pathol Med. 2005;34:397-400. 30. Zegarelli EV, Kutscher AH, Osipow J. Trichinosis found during xamination of oral inflammatory tumor: report of case. J Oral Surg. 1965;23(7):655-6.

MULTIPLE CHOICE QUESTIONS 1. Antibiotics sore mouth refers to: a. Median rhomboidal glossitis b. Acute atrophic candidiasis c. Thrush d. Bronchial candidiasis

3. ‘Darling’s disease refers to: a. Blastomycosis b. Cryptococcosis c. Histoplasmosis d. Systemic candidiasis

2. Presence of yeast cells and hyphae or mycelia in the epithelium of: a. Oral thrush b. Median rhomboidal glossitis c. Acute atrophic candidiasis d. Bronchial candidiasis

4. Fungal infection Sporotrichum schenckii causes: a. Coccidioidomycosis b. Sporotrichosis c. Rhinosporidiosis d. Aspergillosis 5. Tissue microcyst or a large clear halo is the feature of: a. Blastomycosis b. Cryptococcosis c. Histoplasmosis d. Systemic candidiasis

20

Viral Infection

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline  Human herpes virus  Herpes simplex infection • Primary herpes simplex infection • Recurrent or secondary or recrudescent herpetic infection  Measles  Varicella zoster infection • Chicken pox • Herpes zoster • James Ramsey Hunt syndrome  Rubella

 Enteroviruses • Herpangina • Acute lymphonodular pharyngitis • Hand foot mouth disease  Foot and mouth disease  Condyloma acuminatum  Verruca vulgaris  Focal epithelial hyperplasia  Molluscum contagiosum infection  Cytomegalovirus infection  Infectious mononucleosis

Oral cavity is prone for viral infection. Many viruses can cause distinct clinical and pathological features in the oral cavity. Virus which can affect the oral cavity are described in Table 20.1.

All of above virus cause infection and remain latent for the life of individuals. These viruses shed in saliva or genital secretion providing avenue for infection of new hosts.

HUMAN HERPES VIRUS

HERPES SIMPLEX INFECTION

The word herpes means to creep or crawl. Herpes virus family is called as Herpetoviridae. Human acts as natural source. All herpes contain DNA nucleus which can remain latent in host neural cells, thereby evading host immune response. Member of herpes family are herpes simplex virus type I (HSV I or HHV 1), type II (HSV2 or HHV 2), Varicella zoster virus (VZV or HHV 3), Epstein Barr virus (EBV or HHV 4), cytomegalovirus (CMV or HHV5), HHV6, HHV7 and HHV 8.

It is the most common viral disease which can affect the human being and which can cause vesicular eruption on the skin. This is usually cause by HSV 1. Infection caused by HSV 2 usually occurs below the waist, i.e. in genital region. But due to change in sexual habit (oro-genital sex) now a day HSV 2 can be seen causing the infection above the waist. It is primarily occur in early childhood due to frequent exchange of salivary and nasal secretions. HSV II viruses remain latent in lumbosacral ganglion.

Textbook of Oral Pathology Table 20.1 Viruses causing disease in oral cavity

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Name of virus

Disease cause

HSV1 or HHVI

Herpetic gingivostomatitis (primary and secondary)

HSV II or HHV II

Genital infection

Varicella-zoster HHV II

Chickenpox, shingles

EBV HHV IV

Mononucleosis, Burkitt’s lymphoma, hairy leukoplakia, nasopharyngeal carcinoma

Cytomegalovirus HHV V

Salivary gland enlargement

HHV6

Roseola infantum

HHV8

Kaposi Sarcoma

Papilloma viruses

Oral papilloma, wart, heck disease, condyloma acuminatum

Coxsackie viruses

Herpangina, hand foot and mouth disease

Measles virus

Measles

Mumps virus

Mumps, parotitis.

Herpes simplex virus does not survive in external environment and infection results from contact with infected person. Crowding and poor oral hygiene can lead to infection. Herpes simplex virus nowaday has been implicated in number of other disease like erythema multiforme, aphthous ulceration, cluster headache, number of cranial neuropathies. Herpes simplex virus may aid in carcinogenesis through promotion of mutations. Oncogenic role of HSV remain doubtful.

Pathogenesis Contact with individual: There is direct physical contact between infected individual and seronegative host (not previously infected with the virus). Binding of virus to cell surface: After the contact virus binds with surface of cell with the help of heparin sulfate. Activation of genes: After binding there is activation of specific genes (immediate early (IE), early (E), and late (L) genes). Incubation period: This range from several days to 2 weeks. After this individual can experience primary gingivostomatitis with focus at the site of contact. Latent phase: One primary infection is over virus moves along the periaxon sheath of trigeminal nerve to trigeminal ganglion. Other ganglion where this virus can remain latent are no dose

ganglion of vagus nerve, dorsal root ganglion and brain. Here it remain latent or in sequestered state. During this phase no major histocompatibility (MHC) antigen is expressed, so there is no T cell response during this phase. Reactivation of virus: It may occur due to sunlight (fever blister), cold (cold sore), trauma, stress, or immunosuppression. It usually occurs due to breakdown of focal immunosurveillance or there is alternation in local inflammatory mediators which allows virus to replicate. This will results in recurrence of lesion at the site of primary infection. This virus travel by the same path which is used while going in latency phase. At this site replication of virus occur resulting in focal infection. There is no systemic symptoms occur as humoral and cell mediated immunity are sensitized for HSV antigen.

Types • • • • • • •

Primary herpes simplex infection Recurrent herpes labialis (RHL) Recurrent intraoral herpes (RIH) simplex infection Herpetic whitlow Herpes gladiatorum or scrumpox Herpes barbae Eczema herpeticum or Kaposi’s varicelliform eruption.

Clinical Features Primary Herpes Simplex Infection It is exposure of individual without antibodies to the virus. It occurs at young age. Development of lesion before ages of 6 months is rare as it is protected by maternal anti-HSV antibodies. Virus is taken by sensory nerves and transported to autonomic ganglion where it remains latent. Ganglions where it can remain latent are trigeminal ganglion, nodose ganglion of vagus nerve, dorsal root ganglion. Transmission: It occurs during close personal contact. Primary infection of newborn is believed to be caused by vaginal secretions during birth, which results in viremia and disseminated infection of brain, liver, adrenals and lungs. Prodormal signs and symptoms: Prodromal symptoms precede local lesion by 1 to 2 days and it includes fever, headache, malaise, nausea, vomiting and within a few days, mouth becomes painful. There is also irritability, pain upon swallowing and regional lymphadenopathy. Appearance: Small vesicles, which are thin walled, surrounded by inflammatory base are formed. They quickly

Viral Infection

rupture leaving small, shallow, oval shaped discrete ulcers. The base of the ulcer is covered with grayish white or yellow plaque. The margins of the sloughed lesions are uneven and are accentuated by bright red rimmed, well demarcated, inflammatory halos. The individual ulcer differs in size from 2 to 6 mm. As the disease progresses several lesions may coalesce, forming larger, irregular lesions. In severe cases, excoriation involving the lips may become hemorrhagic and matted with serosanguinous fibrin like exudate and parting of the lips during mastication and speech, may become extremely painful and difficult. Marginal acute gingivitis: There is appearance of generalized marginal acute gingivitis. Entire gingiva is edematous and swollen and small gingival ulcers are seen. Examination of posterior pharynx reveals inflammation. Cervical and submandibular lymphadenopathy can also occur. Lesions begin healing in a week to 10 days and leave no scar. HSV may confine to saliva for up to 1 month after onset of disease (Fig. 20.1). Pharyngotonsillitis can also occur as primary infection. Numerous vesicle develops on the tonsils and posterior pharynx. Vesicle rupture to form shallow ulceration. There is formation of diffuse gray yellow exudate over the ulcer. In some cases satellite vesicle of perioral skin is seen.

RECURRENT OR SECONDARY OR RECRUDESCENT HERPETIC INFECTION Recurrent infections are limited to localized portions of skin and mucous membrane. Spontaneous recurrence can occur and affect the area supplied by sensory ganglion. Antibodies can shed infectious viral particle without active infection. In some cases virus may spread to other site in same host to become latent at the sensory ganglion of the new location. If it occurs on lip, it is called as recurrent herpes labialis (cold sore, fever blister). If occurs intra-orally it is called as recurrent intra-oral herpes infection (Fig. 20.2). Predisposing factors: Condition such as old age, Ultraviolet light, stress, fatigue, heat cold, pregnancy, allergy, trauma and dental therapy and menstruation can predispose this condition. Recurrent herpes simplex infection may occur at widely varying intervals, from nearly every month in some patients to only about once a year or even less in others. Lesions may develop lips or intraorally. Prodormal symptoms: Lesion is preceded by tingling and burning sensation and feeling of tautness, swelling or slight soreness subsequent development of vesicle. Appearance: It is accompanied by edema at the site of the lesion, followed by formation of clusters of small vesicles.

Figure 20.1 Marginal gingivitis with lip lesion in primary

Figure 20.2 Secondary infection due to herpes virus causing

herpes simplex infection

vesicle present on lower lip

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It ranges from 1 to 3 mm in diameter, to 1 to 2 cm. But sometimes, it is large enough to cause disfigurement. These gray or white vesicles rupture quickly leaving small red ulcerations, sometimes with slightly erythematous halo on lip covered by brownish crust on lips. In RIH vesicles break rapidly to form small red ulceration, sometimes with slight erythematous halo. Cluster of small vesicles or ulcers 1 to 2 mm in diameter are commonly found on gingivae, palate and alveolar region. The lesions gradually heal within 7 to 10 days and leave no scars. Secondary infection in immunodeficiency patient results in more severe symptoms as compared to normal person. These infections also can spread to many site and not restricted to one sight.

Different Forms of Herpes Simplex Infection Herpetic whitlow: It is also called herpetic paronychia. Dentist may experience primary or secondary lesion of fingers from contact with lesions of the mouth or saliva of the patients who are asymptomatic carriers of HSV; called as herpetic whitlow. Incidence varies according to socioeconomic group. In case of herpetic whitlow axillary or epitrochlear lymphadenopathy may be present. Herpes gladiatorum or scrumpox: This usually occurs in wrestlers and rugby players by the contaminated areas of abrasion. Herpes barbae: Herpes simplex infection spreading over the bearded region of the face due to minor injury cause by daily shaving. Eczema herpeticum or Kaposi’s varicelliform eruption: This is development of life threatening HSV infection occur with skin disease like eczema, pemphigus, darier’s disease.

Histopathological Features

Figure 20.3 Simplex infection showing ballooning degeneration (BD), vesicle formation (V) inflammatory cells (IC)

Multinucleated giant cells: This can be seen after rupture of vesicle at the edge of ulceration. Intraepithelial vesicle: Intercellular edema may lead to development of intraepithelial vesicle which is made up of fibrin polymorphonuclear leukocytes and degenerated cells.

Diagnosis HSV isolation or culture: Isolation and neutralization of virus in tissue culture is most positive method of identification. This can be done by direct fluorescence assay or polymerase chain reaction. Rabbit kidney and human amnion are sensitive to HSV. Antibody titer: Antibodies to HSV appear in a week and react peak in 3 weeks.

Management

Intra-nuclear inclusions: Lipschutz bodies which are eosinophilic, ovoid, homogenous structure within the nucleus, tend to displace the nucleolus and nuclear chromatin peripherally. The displacement of chromatin often produces a peri-inclusion halo.

Acyclovir suspension rinses and swallow method: This is more useful in primary infection with HSV. In this 200 mg of adults dose is given (children 15 mg/kg) five times daily. Significant resolution of infection can be seen.

Ballooning degeneration: Infected cells in HSV infection exhibits acantholysis, nuclear enlargement. This is called as ballooning degeneration. The acantholytic epithelial cells are termed as Tzanck cells (Fig. 20.3).

Topical antiviral drug: Topical agents interrupts viral replication through inhibition of DNA polymerization. Acyclovir when used topically is convert into form that inhibit viral DNA polymerase. It is done by thymidine

Viral Infection

kinase (virus induced enzyme). Topical acyclovir can be initiated in given in 5 percent dose. Systemic antiviral drugs: Acyclovir is given in the dose of 200 to 400 mg tablet 5 times daily. Other antiviral drugs which can be used are valacyclovir, famciclovir. Valacyclovir should be given initially 2g stat after the symptoms appear, after this another 2 g can be given after 12 hours. Symptomatic treatment: Topical anesthetics spray 1 percent dyclonine hydrochloride decreases the mucosal discomfort. Tetracaine lollipops can also be used for numbing of affected mucosa. Topical anti-infective agents can also be given for relief of the patient. Recurrent herpes labialis: Acyclovir ointment, penciclovir ointment can give minimum reduction in the healing time. We can also give 10 percent n-docosanol cream. Prophylactic use antiviral: This can be done when condition causing recurrence are identified, e.g. dental procedure. In this case acyclovir 400 mg BD, valacyclovir 1 g daily or famciclovir 250 mg BD can be given. This can be given one day prior to the procedure or any known trigger. Immunocompromised host with HSV infection often required intravenous antiviral medication. Points to Remember HSV 1 • Primary herpes simplex infection: Young age, prodromal symptoms precede local lesion by 1 to 2 days, fever, headache, thin walled, small vesicles surrounded by inflammatory base, base of the ulcer grayish white or yellow plaque, several lesions may coalesce, forming larger, irregular lesions, marginal acute gingivitis, pharyngotonsillitis • Recurrent or secondary or recrudescent herpetic infection: As recurrent herpes labialis (cold sore, fever blister), recurrent intra-oral herpes infection, predisposing factors old age, ultraviolet light, stress, edema at the site of the lesion, formation of clusters of small vesicles, vesicles break rapidly, small red ulceration • Histopathological: Lipschutz bodies which are eosinophilic, ovoid, ballooning degeneration, Tzanck cells, multinucleated giant cells, intercellular edema may lead to development of intraepithelial vesicle • Management: Acyclovir suspension rinses and swallows method, topical antiviral drug, valacyclovir, famciclovir.

MEASLES It is also called rubeola or morbilli. It is an acute contagious dermatotropic viral infection, primarily affecting children and occurs many times in epidemic form. It is cause by family paramyxovirus genus morbillivirus. Spread of disease occurs by direct contact with a person or by droplet infection, the portal of entry being the respiratory tract.

Clinical Features Incubation period is 8 to 10 days and affected patient are infectious 2 days before symptoms appear and 4 days after appearance of rash. Symptoms: There is onset of fever, malaise, cough, conjunctivitis, photophobia, lacrimation and eruptive lesions of skin and oral mucosa occurs. Otitis media and sore throat can occur. Skin eruption begins on face, in the hair line and behind the ear and spread to neck, chest, back and extremities. Appearance: It appears as tiny red macules or papules which enlarge and coalesce to form blotchy discolored irregular lesions, which blanch on pressure. Fade away in 4 to 5 days with fine desquamation. There are three stages of this infection with each stage lasting for 3 days and justifying the designation of nine days measles. First 3-day stage: There are three Cs in this stage. These are Coryza (runny nose), cough and conjunctivitis. There is also presence of koplik spot in this stage. Second 3-day stage: In this, fading of koplik spot with appearance of morbilliform (maculopapular and erythematous) rash present on face followed by trunk. Third 3-day stage: Fever ends with rash fading and it demonstrated brown pigmentatory staining. Desquamation of skin is present in the area of rash. Complication like otitis media, pneumonia, persistence bronchitis, acute appendicitis and sub-acute sclerosing pan-encephalitis can occur.

Oral Manifestations Oral lesions precede 2 to 3 days before cutaneous rash and are pathognomonic of this disease.

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Points to Remember 510

Figure 20.4 Koplik spot seen in measles

Location: The most common site is buccal mucosa. Koplik spots (Fig. 20.4): Intraoral lesions are called as Koplik’s spots and occur in 97 percent of cases. They are small, irregularly shaped flecks which appear as bluish white specks surrounded by bright red margins. It has been describe as ‘grain of salt’ of red background. Generalized inflammation, congestion, swelling and focal ulceration of gingiva, palate, throat may occur.

Histopathological Features Koplik spot represent areas of focal hyperparakeratosis which exhibits spongiosis, intercellular edema, dyskeratosis, and epithelial syncytial giant cells in epithelium. There is pink staining inclusion in the nuclei or less commonly in the cytoplasm. This inclusion represents microtubular aggregates characteristic of the paramyxovirus. There is also micro-abscess formation, epithelial necrosis and ulceration.

Management The patient should be isolated, if possible as it is contagious disease. Vaccine: This should be given to children between the age of 12 and 15 months. Ribavirin, immunoglobulin, interferon and vitamin A should be given.

Rubeola, paramyxovirus genus morbillivirus, otitis media, malaise, cough, conjunctivitis, photophobia, tiny red macules or papules which enlarge, nine days measles, first 3-day stage coryza, cough, conjunctivitis, second 3 day fading of Koplik spot with appearance of morbilliform (maculopapular and erythematous) rash, third 3 days stage fever ends with rash fading, complication like otitis media, pneumonia, orally buccal mucosa shows Koplik spots which are small, irregularly shaped flecks, bluish white specks, grain of salt, of focal hyperparakeratosis, spongiosis, intercellular edema, dyskeratosis, epithelial syncytial giant cells, pink staining inclusion, micro abscess formation, epithelial necrosis, vaccine, ribavirin, immunoglobulin, interferon and vitamin A.

VARICELLA ZOSTER INFECTION It is an acute disease caused by varicella zoster virus, which is a DNA virus similar to HSV and causes both, primary and recurrent infection. After primary disease is healed, VZV becomes latent in the dorsal root ganglion of spinal nerve or extra-medullary ganglion of cranial nerve. VZV becomes reactivated causing lesions of localized herpes zoster. Patients with HIV infection, leukemia and those on immunosuppressive therapy have an increased susceptibility to severe or potentially fatal herpes zoster. Herpes zoster infection can be deep seated and disseminated causing pneumonia, meningocephalitis and hepatitis. Types • Chickenpox (Varicella) • Shingles (herpes zoster) or zona • James Ramsey Hunt syndrome.

Chickenpox It is also called as ‘varicella’. It is an acute viral disease occurring in children and most commonly in winter and spring months.

Clinical Features Transmission: Incubation period is two weeks and mode of transmission is by air borne droplet or direct contact

Viral Infection

with infected persons, with the probable port of entry being respiratory tract. Prodromal symptoms: It is characterized by prodromal occurrence of headache, nasopharyngitis and anorexia, followed by maculo-papular or vesicular eruptions on skin and low grade fever. This exanthema is very pruritic.

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Appearance: These eruptions usually begin on the trunk and spread to involve the face and extremities. They occur in successive crops so many vesicles in different stages of formation or resorption may be found. Dewdrop on rose petal: The centrally located vesicle is surrounded by zone of erythema. This is called as dewdrop on rose petal appearance. Skin lesion: The skin eventually ruptures, forming a superficial crust and heals by desquamation. The disease runs its clinical course in a week to ten days, seldom leaving any after effects. Occasionally, secondary infection of vesicle results in the formation of pustules which may leave small pitting scar upon healing. Complication like Reye’s syndrome, secondary skin infection, encephalitis, cerebellar ataxia, pneumonia, gastrointestinal disturbance and hematologic event can occur.

Oral Manifestations Location: Small blister like lesions occasionally involve the oral mucosa chiefly buccal mucosa, tongue, gingiva, lip, palate as well as the mucosa of pharynx. Appearance: The mucosal lesion, initially a slightly raised vesicle with a surrounding erythema, ruptures soon after formation and forms a small eroded ulcer with red margins, closely resembling aphthous lesion.

Histopathological Features The cytological studies are identical to that of herpes simplex infection. These viruses cause acanthylosis with formation of numerous free floating Tzanck cells. There is also nuclear margination of chromatin and occasional multinucleation. Virus isolation (Fig. 20.5) in cell culture is done by fluorescein conjucted VZV monoclonal antibodies can be performed.

Figure 20.5 Chickenpox virus

Management Symptomatic: Warm baths with soap or baking soda, application of calamine lotion and systemic diphenhydramine are used for management of pruritus. Antipyretic other than aspirin is given. Antiviral medication like acyclovir, valacyclovir and famciclovir if administer within 24 hours of rash has reduce duration and severity of infection. Intravenous administration is done in case of immunocompromised patients. Purified varicella zoster immune globulin can be given to modify clinical manifestation of disease. Vaccine: Vaccine for chickenpox is recommended for children between 12 to 18 months of age. Vaccine use is live attenuated varicella vaccine. Points to Remember Varicella, prodromal symptoms headache, nasopharyngitis, anorexia, eruptions begin on the trunk, dewdrop on rose petal appearance, skin lesion forming a superficial crust, complication like Reye’s syndrome, secondary skin infection, encephalitis, mucosal lesion slightly raised vesicle, acanthylosis, Tzanck cells, nuclear margination of chromatin, multinucleation, virus isolation, systemic diphenhydramine, acyclovir, valacyclovir and famciclovir, purified Varicella zoster immune globulin vaccine.

Textbook of Oral Pathology

HERPES ZOSTER 512

It is also called shingles or zona. It is an acute infectious viral disease of extremely painful and incapacitating nature, characterized by inflammation of dorsal root ganglion, associated with vesicular eruptions of skin and mucous membrane of the area supplied by the affected sensory nerve.

Clinical Features (Figs 20.6 to 20.10) Predisposing factors: Herpes zoster may be predisposed by trauma, malignancy or tumor involvement of dorsal root ganglion, local X-ray radiation or immunosuppressive therapy. Prodormal period of 2 to 4 days in which shooting pain, paresthesia, burning and tenderness appears along the course of affected nerve. During initial viral replication active ganglionitis develop which result in neuronal

Figure 20.8 Healed vesicle of herpes zoster causing

discoloration

A Figure 20.6 Intact vesicle seen in the case of herpes zoster

infection

B Figures 20.9A and B Lesion of herpes zoster on face

Figure 20.7 There is corneal scarring and ulceration occur

on the face in case of herpes zoster

Figure 20.10 Healed lesion of herpes zoster

Viral Infection

necrosis and severe neuralgia. This is responsible for intense pain that precede the rash. Appearance: Unilateral vesicles on an erythematous base appear in clusters, chiefly along the course of nerve and giving picture of a single dermatome involvement. Vesicle turns into scab in 1 week and healing takes place in 2 to 3 weeks. Nerves commonly affected are C3, T5, L1, L2 and 1st division of trigeminal nerve. It may affect motor nerve. Herpes zoster ophthalmicus: Involvement of 1st division leads to corneal scarring and blindness which are presumably related to viral spread, neural damage, vasculitis and inflammatory immune response. If Hutchison’s sign (cutaneous zoster of the side of tip of nose) is present, then the probability of ocular involvement is more. Zoster sine herpete (zoster without rash) in some cases there is recurrence of zoster infection without vesicle of skin or mucosa. Patient had severe pain and hyperesthesia of specific dermatome. Exanthema resolves within 2 to 3 weeks. On healing, scarring with hypo or hyperpigmentation can also occur.

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Figure 20.11 Vesicle seen onto the lip and buccal mucosa

Post-herpetic neuralgia: Pain may continue for weeks to months. This unfortunate sequel called as post-herpetic neuralgia occurs in elderly persons due to inflammation, fibrosis and scarring of nerve and may cause severe stabbing pain after the skin lesions has healed. Light touch over the involved area may give elicit painful response which is called a tactile allodynia.

Oral Manifestations (Figs 20.11 and 20.12) Location: It results from involvement of 2nd and 3rd divisions of trigeminal nerve. It may be found on buccal mucosa, tongue, uvula, pharynx and larynx. Symptoms: Lesions of oral mucosa are extremely painful. The lesions rupture to leave areas of erosion. Trigeminal herpes zoster occurring during tooth formation causes pulpal necrosis and internal root resorption. Findings are similar to herpes infection, but it is associated with neurogenic pain of unilateral nature and segmental distribution of the lesion. Involvement of bone can occur which result in necrosis. This can occur due to damage of the blood vessel supplying alveolar ridge and teeth leading to focal ischemic necrosis.

Histopathological Features These are similar to primary infection. Viral isolation can be done with fluorescent antibody stained smear or

Figure 20.12 Ulcer occurring on dorsal surface of tongue

fluorescent conjugated monoclonal antibody. Antibody titer increased. Points to Remember Shingles, zona, predisposing factors trauma, malignancy, prodormal period of 2 to 4 days shooting pain, paresthesia, burning, unilateral vesicles on an erythematous base appear in clusters, single dermatome involvement, nerves affected are C3, T5, L1, L2 and 1st division of trigeminal nerve, herpes zoster ophthalmicus, Hutchison’s sign, zoster sine herpete, scarring with hypo or hyperpigmentation, postherpetic neuralgia, tactile allodynia, lesions of oral mucosa are extremely painful, trigeminal herpes zoster, pulpal necrosis, internal root resorption, bone can occur which result in necrosis, viral isolation, acyclovir, diphenhydramine, live attenuated VZV vaccine.

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It is zoster infection of geniculate ganglion with involvement of the external ear and oral mucosa and facial paralysis. The clinical manifestation of it is facial paralysis as well as pain of the external auditory meatus and pinna of the ear. In addition, vesicular eruption occurs in the oral cavity and oro-pharynx with hoarseness of voice, tinnitus, vertigo and occasional other disturbances.

Management Acyclovir: 800 mg five times daily which is associated with significantly accelerated healing within 48 hours of the onset of rash. Symptomatic: Diphenhydramine can be given for itching, antibiotics for secondary infection. Postherpetic neuralgia: To control postherpetic neuralgia, prednisone 40 to 60 mg daily for 1 to 2 weeks. Steroid injection can be given in a patient with age more than 60 years, for the treatment of post-herpetic neuralgia. Live attenuated VZV vaccine: It can be given in adults after the age of 60 years. It prevent prevalence of postherpetic neuralgia.

RUBELLA It is also called German measles. It is cause by Rubivirus of family Togavirus. This infection occurs in spring and winter by respiratory droplet.

Clinical Features Age and incubation period: It is more adolescents and adults. Incubation period is form 14 to 21 days and infected patient is contagious for 1 week before exanthema to 5 days after rash. Prodromal symptoms: It includes fever, headache, malaise, anorexia, malagia, mild conjunctivitis, coryza, pharyngitis and lymphadenopathy. Appearance: Rash present on face and neck and spread to entire body. It is presented as discrete pink macules, then papules and ultimately results in flaky desquamation. Rash is resolve by three day giving designated 3 days measles.

Congenital rubella syndrome (CRS): This is present in children after birth and occur due to transmission from infected mother. Classic triad consists of deafness, heart disease and cataracts. Complication: It includes arthritis, encephalitis, and thrombocytopenia.

Oral Manifestations Forchheimer sign: It consist of small, discrete, dark red papule which develop on soft palate and extend to hard palate. This occur simultaneously with rash and last only to 12 to 14 hours. In some cases palatal petechiae can also occur.

Management Non-aspirin antipyretics and antiprutitics may be given. Passive immunity is acquired by giving human rubella immunoglobulin. It should be given within two days of exposure. Points to Remember German measles, rubivirus of family Togavirus, prodromal symptoms includes fever, headache, malaise, anorexia, malagia, rash present on face, discrete pink macules, congenital rubella syndrome, complication includes arthritis, encephalitis, Forchheimer sign consist of small, discrete, dark red papule, antiprutitics, nonaspirin antipyretics.

ENTEROVIRUSES Human enteroviruses are classified into echoviruses, coxsackieviruses A and B, polioviruses and enteroviruses 71. Coxsackieviruses are named after town in upper New York where they were first discovered. They are divided into 2 groups. Type A - 24 types Type B - 6 types. These viruses can cause hepatitis, meningitis, myocarditis, pericarditis and respiratory disease. Frequently occurs in epidemic, with highest frequency from June to October. It appears to be transmitted from one person to another through contact. Most cases transmitted from fecal oral route. It is occur in poor hygiene and crowding condition. Frequent hand washing is required to diminish spread of infection in epidemic.

Viral Infection

Types • Herpangina • Hand foot and mouth disease • Acute lymphonodular pharyngitis.

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Herpangina It is also called as ‘aphthous pharyngitis’, ‘vesicular pharyngitis’. Herpangina is cause by A1 to A10, A16, and A22. It can also be cause by coxsackieviruses B2 to B6, echovirus 9, 16 or 17 and enteroviruses 71.

Clinical Features Age and incubation period: Majority affected are young children aged 3 to 10 years. Incubation period is of 2 to 10 days. Prodormal symptoms: Initially, generalized symptoms of fever, chills, headache, anorexia, prostration, abdominal pain and sometimes vomiting. Sore throat, dysphagia and occasionally, sore mouth can occur. Location: It occur on posterior pharynx, tonsil, faucial pillars and soft palate. Appearance: Lesion starts as punctuate macule which evolves into papules and vesicles. Within 24 to 48 hours, vesicles get ruptured forming small 1 to 2 mm ulcers. Ulcers show a gray base and inflamed periphery. They generally heal without treatment in 1 week (Figs 20.13 and 20.14).

Figure 20.14 Same patient after treatment

Histopathological Features In these areas of affected epithelium exhibits intracellular and intercellular edema, that leads to spongiosis and formation of intraepithelial vesicle. There is rupture of vesicle with formation of subepithelial vesicle. There is also epithelial necrosis and ulceration.

Laboratory Diagnosis No ballooning degeneration seen in this condition which is helpful to distinguish herpangina from herpes simplex and herpes zoster.

Management Self limiting and supportive treatment by proper hydration and topical anesthetic, when eating or swallowing is difficult. Points to Remember Aphthous pharyngitis, generalized symptoms of fever, chills, headache, anorexia, prostration, posterior pharynx, punctuate macule which evolves into papules and vesicles, intracellular and intercellular edema, spongiosis, formation of intraepithelial vesicle, no ballooning degeneration seen, supportive treatment.

Acute Lymphonodular Pharyngitis Figure 20.13 Herpangina showing lesion in palate

It is caused by A10 and is same as herpangina. It is self limiting and only supportive care is indicated.

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Clinical Features

Oral Manifestations

Age: The disease affects predominantely children and young adults, occasionally older adults can also be affected.

Location: The most common sites for oral lesions are hard palate, tongue and buccal mucosa.

Location: The lesion appears on uvula, soft palate, anterior pillars and posterior oropharynx. It has got 5 days incubation period and course may run for 4 to 14 days, with local oral lesions resolving within 6 to 10 days.

Symptoms: A sore mouth with refusal to eat is one of the most common findings in this disease.

Symptoms: The chief complain is of sore throat, 41°C temperature, mild head ache, anorexia and loss of appetite. Appearance of lesion: It consists of raised, discrete, and whitish to yellowish solid papules of 3 to 6 mm in diameter, surrounded by narrow well defined zone of erythema. Lesion is non-vascular, non-ulcerated, tender, superficial and bilateral.

Histopathological Features The papular lesion consists of densely packed nodules of lymphocytes. In some cases, overlying epithelium has shown inclusion bodies which in some instance were intra-nuclear, but in other cytoplasmic.

Signs: The tongue may become red and edematous. Oral lesions are more extensive than herpangina. Clinical manifestations last for 3 to 7 days.

Laboratory Findings Intracytoplasmic viral inclusion can be seen in vesicular scrapping of the lesions. There is rise in acute or convalescent serum antibody titer to Coxsackie A16.

Management No specific treatment is necessary since the disease is self limiting and generally regresses within one to two weeks. Points to Remember Appearance of maculo-papular, exanthematous and vesicular lesions of skin, anorexia, low grade fever, sore mouth, tongue may become red, intracytoplasmic viral inclusion can be.

Points to Remember Uvula, soft palate, anterior pillars, 5 days incubation period, sore throat, anorexia, loss of appetite, raised, discrete, and whitish to yellowish solid lesion, narrow well defined zone of erythema, densely packed nodules of lymphocytes, inclusion bodies.

Hand Foot Mouth Disease It is cause by A16, A5, A9, A10, echovirus 9, and enteroviruses 71.

Clinical Features Age: It primarily affects children between the age of 6 months and 5 years. Appearance: It is characterized by appearance of maculopapular, exanthematous and vesicular lesions of skin, particularly involving the hands, feet, legs, arms and occasionally buttocks. Symptoms: There is anorexia, low grade fever and sometimes lymphadenopathy, diarrhea, nausea and vomiting.

FOOT AND MOUTH DISEASE Foot and mouth disease (FMD) is an animal disease caused by an RNA aphthovirus, belonging to the picornaviridae family. Foot and mouth disease is the most contagious of all infectious diseases in animals, affecting cattle and swine most severely. It also affects sheep, goats, deer and other cloven-hoofed ruminants. Infected animals present fever and blister-like sores in the mouth, on the teats and between the hooves. Disease in humans has been reported mainly in connection with consumption of unpasteurized milk, dairy or unprocessed meat products from infected animals or as a result of direct contact with infected animals (e.g. farmers and veterinarians).

Clinical Features The incubation period in humans is two to six days. Symptoms: Symptoms are mostly mild and self-limiting. It is manifested by fever, nausea, vomiting, malaise and

Viral Infection

appearance of ulcerative lesions of oral mucosa and pharynx. Sign: Development of vesicle on skin also occurs in some cases, usually on the palms of hands and soles of feet.

Appearance: Small keratotic warts occurring alone or in clusters on oral mucosa can be seen. The enlargement may be larger than 1 cm in diameter.

Oral Manifestations

Signs: The lesion is sharply delineated and may appear sessile and pedunculated. It presents as discrete papillomatous growth.

Location: It can occur at any site, but lips, tongue, palate and oro-pharynx appear to be affected.

Laboratory Investigation

Appearance: These lesions begin as small vesicles which rapidly rupture but heal within two weeks.

Virus isolation can be done by staining of viral antigen DNA by hybridization restriction, endo-nuclease analysis and polymerase chain reaction.

Management No treatment is necessary and recovery commonly occurs within a week of the last blisters forming. Points to Remember RNA aphtovirus, most contagious, fever, nausea, vomiting, malaise, development of vesicle on skin, oropharynx, small vesicles which rapidly rupture.

CONDYLOMA ACUMINATUM It is also called as genital wart, venereal wart or verruca acuminate. It is caused by human papillomavirus (HPV) 2,6,11, 16, 18, 31, 53, and 54. It can be transmitted from mother to infant, at birth and resulting syndrome is called as juvenile onset respiratory papillomatosis.

Clinical Features

Histopathological Features The papillomatous projection making up the verrucoid lesion generally shows a parakeratotic surface with marked underlying acanthosis. Thin connective tissue support papillary projection which are blunted and broader, impairing appearance of keratin filled crypts between prominences. Vacuolated cells in the spinous layer are common. The supporting connective tissue is usually edematous, with dilated capillaries and a chronic inflammatory cell infiltrate (Fig. 20.15). Prickle cells shows pyknotic, crinkled or raisin-like nuclear surrounded by clear zones (koilocytes).

Management Genital warts are treated by excision, electro or cryosurgery, CO2 laser therapy.

Age and incubation period: Incubation period is around 1 to 3 months after sexual contact. It is commonly seen in teenager and young adults. Location: It develop on external genitals, perianal mucosae, and adjacent skin as well as in vaginal and anal canal. Wart growth is favored by moist warm environment of perianal skin and mucosal surface. Appearance: They are pink, fleshy, sessile, blunted surface papillomatous lesions. It proliferates and coalesces rapidly to form diffuse papillomatous clusters of varying size. Recurrence is common.

Oral Manifestations Location: It may involve gingiva, cheek, lip, hard palate, tongue and floor of mouth.

Figure 20.15 Vacuolated cells seen in condyloma

acuminatum

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Application of chemical agents such as podophyllin, cantharidin and 5-fluorouracil is also helpful. Immuno-modulating agent such as interferons can also be used. Points to Remember Genital wart, venereal wart, juvenile onset respiratory papillomatosis, perianal mucosae, pink, fleshy, sessile, blunted surface papillomatous lesions, involve gingiva, small keratotic warts occurring alone or in clusters on oral mucosa, lesion is sharply delineated, verrucoid lesion, parakeratotic surface, acanthosis, keratin filled crypts between prominences, vacuolated cells, dilated capillaries and a chronic inflammatory cell infiltrate, prickle cells, pyknotic, crinkled or raisin-like nuclear excision, electro or cryosurgery, CO2 laser therapy podophyllin, cantharidin, 5-fluorouracil.

VERRUCA VULGARIS It is also called as ‘common wart’. It is benign viruses induce cause by human papillomavirus (HPV) types 2,4,6, and 40. It can spread to other area by auto inoculation.

Clinical Features Age: It is seen in children as well as some lesion seen in adults. Location: The skin of hands, and in case of oral cavity it is seen on vermilion border, labial mucosa and anterior tongue. Appearance: It appear as painless papule or nodule with papillary projection or rough pebbly surface. It can be pedunculated or sessile. Sign and symptoms: Skin lesion are pink, yellow or white and oral lesion are always white. Common wart can enlarge rapidly to its maximum size of less than 5 mm. Keratin horn or cutaneous horn: Extreme accumulation of compact keratin may results in hard surface projection several millimeters in height. This is called as cutaneous or keratin horn.

Cupping effect: Elongated rete ridges tend to converge toward the center of lesion. Other features include pyknosis (small dark nuclei), hypergranulosis (prominient granular cell layer), clumped keratohyaline granules and abundant koilocytes seen in superficial spinous layer.

Management Topical salicylic acid, topical lactic acid or liquid nitrogen cryotherapy. Surgical excision indicated in large and atypical lesion. Points to Remember Human papillomavirus, skin of hands, painless papule or nodule with papillary projection, skin lesion are pink, yellow or white, keratin horn or cutaneous horn, proliferation of hyperkeratotic stratified squamous epithelium, cupping effect, pyknosis, hypergranulosis, clumped keratohyaline, topical salicylic acid, topical lactic acid or liquid nitrogen cryotherapy.

FOCAL EPITHELIAL HYPERPLASIA It also called as Heck disease, multifocal epithelial hyperplasia, multifocal papilloma virus epithelial hyperplasia’. It is viral induced oral mucosal hyperplastic response characterized by multiple, more or less papillomatous like lesion. It is possibly cause by virus (may be papovavirus group). Some lesion may be seen in HIV seropositive patient.

Clinical Features Age and sex distribution: It occurs predominately in children between ages of 3 to 18 years. Location: Common sites are lip, buccal mucosa, commissure, tongue and less commonly on the gingiva, and anterior faucial pillar.

Histopathological Features

Appearance: It present as multiple nodular lesions with sessile base. It can occur in cluster or in a isolated crops. Sometime it is present as flat, slightly raised whitish plaque on roughened surface.

There is proliferation of hyperkeratotic stratified squamous epithelium arranged in finger like or pointed projection with connective tissue cores.

Sign: They become less conspicuous when the mucosa is stretched. It is non-tender. After drying, the lesion it reveals finely granular surface texture. These lesions are

Viral Infection

soft having size of 1 to 5 mm in diameter with same color as adjacent mucosa.

at the time of onset of sexual activity, poverty, overcrowding and poor hygiene. These cases are also reported in HIV infection, atopic dermatitis and Darier’s disease.

Cobblestone or fissured appearance: Sometimes cluster so closely together that they appear as cobblestone or fissured appearance. They are pale to normal in color. They often appear to undergo spontaneous regression after 4 to 6 months.

Age and incubation period: Incubation period is 14 to 50 days. It is more common in children and young adults.

Histopathological Features

Site: It is more common on skin or inner thigh lower abdomen or external genitals.

There is thickening of spinous layer with presence of mitosoid cells (altered nucleus which resembles mitotic figure) in the upper layer. It compromised hyperplastic epithelium without keratosis and thickening or elongation of rete pegs. The lamina propria of the underlying connective tissue may occasionally show some signs of inflammation. There is acanthosis with mild hyperparakeratosis usually present over the surface. Lymphocyte infiltration with occasional collection of polymorphonuclear leukocytes with some focal areas of liquefaction degeneration of the basal layer may be found. There is lack of pronounced elongation of thin rete ridges. The ridges are themselves are widened, which are confluent and club shaped.

Management These are harmless lesion and it will regress spontaneously. Surgical approach: Lesion can be removed with the help of cryotherpay, laser ablation or simple excision. Topical interferon-b and systemic interferon-α can also produce results in some cases.

Clinical Features

Appearance: It manifests as multiple or isolated discrete elevated nodules, or sometimes papules, with depressed centers, which may be keratinized and are normal or slightly red in color. Signs: These lesions are hemisphere in shape, usually about 5 mm in diameter. Some of lesion are surrounded by mild inflammatory erythema and slightly tender or pruritic.

Oral Manifestations Site: It usually occurs in children, on the face, due to shared sleeping accommodation. Most commonly involved sites are lips, tongue and buccal mucosa. Appearance: Lesions are similar to skin lesions.

Histopathological Features It shows thickening and down growth of epithelium with the formation of large eosinophilic intra-cytoplasmic inclusion bodies known as Henderson-Paterson inclusion or simply molluscum bodies, measuring approximately 25 microns in diameter (Fig. 20.16). These bodies characteristically

Points to Remember Heck disease, papovavirus group, multiple nodular lesions with sessile base, less conspicuous when the mucosa is stretched, cobblestone or fissured appearance, thickening of spinous layer, mitosoid cells (altered nucleus which resembles mitotic figure), hyperplastic epithelium, signs of inflammation, lymphocyte infiltration, lack of pronounced elongation of thin rete ridges, topical interferon-b.

MOLLUSCUM CONTAGIOSUM INFECTION It is caused by virus molluscum contagiosum of pox group. It occurs due to intimate skin contact. There is marked increase

Figure 20.16 Molluscum bodies in contagiosum

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are accumulated in the crater formed by the distinctive central umblicated or the dome shaped lesion. 520

Management It is self limiting and regresses spontaneously within 1 to 2 months. It includes curettage, followed by local cautery, cryotherapy. Topical application of caustic acid and irritants such as phenol, TCA, podophyllin and cantharidin can be done. In immunocompromised patient antiviral agents like cidofivir can be effective. Points to Remember Molluscum contagiosum of pox group, multiple or isolated discrete elevated nodules, hemisphere in shape, down growth of epithelium, intra-cytoplasmic inclusion, Henderson-Paterson inclusion, molluscum bodies, central umblicated or the dome shaped lesion, caustic acid, cidofivir, phenol, TCA, podophyllin.

CYTOMEGALOVIRUS INFECTION It is cause by cytomegalovirus (CMV or HHV-5). It may be clinically expressed or latent. This virus remains latent in salivary gland cells, endothelium, macrophages and lymphocytes. When expressed, it results in characteristic enlargement of cells with prominent and pathognomonic, intranuclear and intracytoplasmic inclusions. It is widespread with prevalence rates based on the presence of CMV antibodies, ranging from 80 to 100 percent, in most adult population. Blood and transplanted tissues are also potential means of transmission of virus to susceptible individuals, rather than saliva, urine, serum, vaginal secretion. Infants can acquire it in utero from maternal virus reactivation during pregnancy.

Sign: There is also hepatosplenomegaly, jaundice, petecheal hemorrhages, pneumonia, cerebral calcification and hearing defect can also occur.

Oral Manifestations Signs: There is presence of gingivitis, gingival hyperplasia and oral ulcer (Fig. 20.17). Acute sialadenitis: This can be present in patients who are immunocompromised. In this case xerostomia is present and gland is painful. Developmental tooth defect: This is present due to neonatal CMV infection. There is diffuse enamel hypoplasia, attrition, hypomaturation and yellow coloration due to underlying dentin.

Histopathological Features There are changes within the vascular endothelial cells. Scattered infected cells are swollen showing intracytoplasmic and intranuclear inclusion and prominent nucleoli. This enlarge cells are called owl eye cells. Salivary gland epithelium can also show owl eye cells.

Management Prevention by passive immunization with hyper immune gamma globulin can be successful. Ganciclovir is recommended for management of CMV infection. It gives relief in 75 percent of cases of

Clinical Features Age: It is seen in infant and young age group. Symptoms: It may be accompanied by mononucleosis like illness or severe illness with neurologic abnormalities. Patient complaint of fever, joint and muscle pain, shivering, abdominal pain, nonproductive cough, macular rash and diarrhea.

Figure 20.17 Gingivitis in patient with cytomegalovirus

infection

Viral Infection

immunocompromised patient. Other antiviral drug which can be used are foscarnet, cidofivir and valganciclovir. Symptomatic treatment is given in patient who are not immunocompromised. Antipyretic medication with NSAIDs can be recommended. Points to Remember Cytomegalovirus, latent in salivary gland cells, mononucleosis like illness, hepatosplenomegaly, jaundice, petecheal hemorrhages, acute sialadenitis, developmental tooth defect, vascular endothelial cells, intracytoplasmic, intranuclear inclusion, prominent nucleoli, owl eye cells, hyper immune gamma globulin, ganciclovir, foscarnet, cidofovir.

INFECTIOUS MONONUCLEOSIS It is also called as glandular fever, kissing disease, mono. It is a benign acute infectious disease caused due to the Epstein Barr virus, a herpes virus which infects the B-lymphocytes. The mechanism of human transmission is not entirely known but one important mean is thought to be through deep kissing so this condition is also called as kissing disease. EBV is present in oropharyngeal secretions and mixed saliva during active phase.

headache, arthralgias, paresthesia, depression and cognitive deficit.

Oral Manifestations Location: Tiny petechiae appear on the soft palate, labial and buccal mucosa during the course of the disease (Fig. 20.18). Acute gingivitis and stomatitis may be present and the lesion normality persisting for 3 to 11 days. The organism responsible for gingivitis is fusospirochetal. Intraorally, the most prominent sign is enlargement and inflammation of the tonsils along with sore throat and difficulty in swallowing. Quite commonly the tonsils are covered by a white or grayish pseudomembrane. 1/3rd of the patients with hemorrhagic tendency exhibit oronasopharyngeal bleeding, including bleeding from gingiva. Transient oral ulcerations and lymphadenopathy can also occur.

Hematological Findings There is an absolute and relative increase in mononuclear cells which exhibit pleomorphism and an oval and kidney shaped nucleus with a non granular or foamy cytoplasm. The hemoglobin and platelet counts are normal. An increase in white blood cell count and positive Paul Bunnel test are pathognomonic of this disease.

Clinical Features

Diagnosis

Age and incubation period: It varies from 10 to 40 days and the disease occurs chiefly in children and young adult in 15 to 30 age groups.

Paul Bunnel test for infectious mononucleosis. Leukocyte count is between 4000 to 15000/dL.

Location: Anterior and posterior cervical nodes are enlarged and only slightly tender on palpation. Symptoms: The patient usually complaint of sore throat accompanied by fever usually 101°F to 103°F and extreme fatigability. Occasionally, there is a complaint of headache, photophobia, nausea, vomiting, diarrhea and presence of erythematous macular rash (morbilliform skin rash). Signs: Physical examination reveals enlarged palatine tonsils with copious amount of cheesy yellow exudate filling tonsillar crypt. Enlargement of the superficial lymph nodes, particularly the posterior cervical and splenomegaly are common manifestations. Chronic fatigue syndrome: In these syndrome patient complaints of chronic fatigue, fever, pharyngitis, myalgias,

Figure 20.18 Petechiae seen in palate in patient with

infectious mononucleosis

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Heterophill antibody test positive, atypical lymphocytes and clinical signs and symptoms make a diagnostic triad. 522

Management Symptomatic: Nonaspirin containing antipyretics and NSAIDs can be used to reduce common symptoms. Corticosteroid: This should be used properly and in life threatening situation. It reduces the duration of fever and shrinkage of tonsil. Antiviral agents like acyclovir, valacyclovir and famciclovir can be used. Acute tonsillectomy can be performed if it causing airway obstruction. Points to Remember Glandular fever, kissing disease, mono, anterior and posterior cervical nodes are enlarged, sore throat, fever, morbilliform skin rash, enlarged palatine tonsils, chronic fatigue syndrome, tiny petechiae on soft palate, acute gingivitis, stomatitis, enlargement and inflammation of the tonsils, oronasopharyngeal bleeding, mononuclear cells, increase in white blood cell count, positive Paul Bunnel test, corticosteroid, acute tonsillectomy, acyclovir.

BIBLIOGRAPHY 1. Anderson KM, Perez-Montiel D, Miles L, et al. The histologic differntriation of oral condyloma acuminatum from its mimics. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;96:420-8. 2. Arduino PG, Porter SR. Oral and perioral herpes simplex virus type I (HSV-1) infection review of its management: Oral Dis. 2006;12:254-70. 3. Barrett AP, Katelaris CH, Morris JGL, et al. Zoster sine herpete of the trigeminal nerve. Oral Surg Oral Med Oral Pathol. 1993;75:173-5. 4. Buchner A. Hand foot and mouth disease: Oral Surg Oral Med Oral Pathol. 41:333-7. 5. Carlos R, Sedano HO. Multifocal papilloma virus epithelial hyperplasia. Oral Surg Oral Med Oral Pathol. 1994;77:631-5. 6. Cohen SG, Greenberg MS. Chronic oral herpes simplex virus infection in immunocompromised patient. Oral Surg Oral Med Oral Pathol. 1985;59:465-71. 7. Courant P, Sobkov T. Oral manifestation of infectious mononucleosis. J periodontal. 1979;40:279-83. 8. Dewan P, Gupta P burden of Congenital Rubella Syndrome (CRS) in India: a systematic review; Indian Pediatr. 2012;49(5):377-99.

9. Epstein JB, Scully C. Cytomegalovirus a virus of increasing relevance to oral medicine and pathology. J Oral Pathol Med. 1993;22:348-53. 10. Epstein JB, Sherlock CH, Wolber RA. Oral manifestation of cytomegalovirus infection. Oral Surg Oral Med Oral Pathol. 1993;75:443-51. 11. Fornatora ML, Reich RF, Gray RG, et al. Intraoral molluscum contagiosum: report of cases and review of literature: Oral Surg Oral Med Pathol Oral Radiol Endod. 2001;92:318-20. 12. Guggenheimer J, Nowak AJ, Michaels RH Dental manifestations of the rubella syndrome. Oral Surg Oral Med Oral Pathol. 1971;32(1):30. 13. Katz J, Guelmann M, Stavropolous F, et al. Gingival and other oral manifestations in measles virus infection. J Clin Periodontol. 2003;30(7):665-8. 14. Laskaris G. Oral manifestations of infectious diseases. Dent Clin North Am. 1996;40(2):395-423. 15. Ledesma-Montes C, Vega Memije E, Garces-Ortiz M. et al. Multifocal epithelial hyperplasia: report of nine cases. Med ral Patol Oral Cir Buccal. 2005;10:394-401. 16. López-Sánchez A, Guijarro B, Hernández Vallejo G. Human repercussions of foot and mouth disease and other similar viral diseases. Med Oral. 2003;8(1):26-32. 17. Meer S, Coleman H, Altini M, et al. Mandibular osteomyelitis and tooth exfoliation zoster CMV co infection: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:70-5. 18. Mendieta C, Miranda J, Bruet LI, et al. Alveolar bone necrosis and tooth exfoliation following herpes zoster infection: a review of literature and case report. J Periodontal. 2005;76:148-53. 19. Nesbit SP, Gobetti JP. Multiple recurrence of oral erythema multiforme after secondary herpes simplex: a report of two case: J AM Dent Assoc. 1986;112:348-52. 20. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edn. Saunder Elsevier, 2009. 21. Reborn GW, Grace MGA. Recurrent herpes simplex labialis: selected therapeutic options. J Can Dent Assoc. 2002;133:303-9. 22. Sabella C. Measles: not just a childhood rash. Cleve Clin J. 2010;77(3):207-13. 23. Simon PA. Oral condyloma acuminatum as an indicator sexual abuse: dentistry role. Quintessence Int. 1998;29:455-8. 24. Slote J, Saygun I, Sabeti M, et al. Epstein barr virus in oral disease. J Periodontal Res. 2006;41:235-44. 25. Torres R, Cottrell D, Reebye UN. Ulcerative tongue lesion secondary to cytomegalovirus. J Mass Dent Soc. 2004;53:36-7. 26. Whitaker SB, Wiegand SE, Budnick SD. Intraoral molluscum contagiosum. Oral Surg Oral Med Oral Pathol. 72:334-6. 27. Woo SK, Challacombe SJ. Management of recurrent oral herpes simplex infection. Oral Surg Oral Med Oral Pathol. Oral Radiol Endod. 2007;S12.e1-S12.e18. 28. Zenner D, Nacul L. Predictive power of Koplik’s spots for the diagnosis of measles’. Infect Dev Ctries. 2012;6(3):271-5.

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MULTIPLE CHOICE QUESTIONS 1. Ballooning degeneration, vesicle inflammatory cells seen in: a. Herpes simplex b. Measles c. Herpes zoster d. Herpangina

formation

and

2. Presence of Koplik spot and microtubular aggregates is the histopathological feature of: a. Herpes simplex b. Measles c. Herpes zoster d. Herpangina 3. Floating Tzanck cells is the characteristic feature of: a. Herpes simplex b. Measles c. Herpes zoster d. Chicken pox 4. Herpes zoster is also called as: a. Morbilli b. Shingles c. Zona d. Both b and c



5. A zoster infection of geniculate ganglion with involvement of the external ear and oral mucosa is: a. Fanconi’s syndrome b. First arch syndrome c. James Ramsay Hunt syndrome d. Eagle’s syndrome

6. Following are the Coxsackievirus infection, except: a. Herpangina b. Acute lymphonodular pharyngitis c. Zona d. Hand foot mouth disease 7. A characteristic corrugated and white appearance of tongue which cannot be rub off is: a. Kaposi’s sarcoma b. Candidiasis c. Hand foot mouth disease d. Hairy leukoplakia 8. Most common tumor associated with AIDS is: a. Kaposi’s sarcoma b. AOT c. CEOT d. Melanoma 9. Interweaving band of spindle shaped and plump endothelial cell is the feature of: a. Kaposi’s sarcoma b. Candidiasis c. Hand foot mouth disease d. Hairy leukoplakia 10. Tzanck cells, ballooning degeneration and Lipschutz bodies are present in: a. Herpangina b. Acute lymphonodular pharyngitis c. Zona d. Secondary herpetic infection

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Acquired Immunodeficiency Syndrome Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline                Â

Definition AIDS related complex Prevalence Etiology Characteristic of HIV virus Mechanism of action Transmission Clinical features Oral manifestations Candidiasis Kaposi’s sarcoma Hairy leukoplakia Periodontal disease associated with HIV Non-Hodgkin lymphoma Recurrent herpes labialis Oral human papilloma virus lesions

Acquired immunodeficiency syndrome (AIDS) is a devastating fatal disease, which is in epidemic form throughout the world. It is an incurable viral STD caused by human immunodeficiency virus (HIV). It stands for: ∙ A: Acquired, i.e. contagious not inherited ∙ I: Immune, i.e. power to receive disease ∙ D: Deficiency ∙ S: Syndrome, i.e. number of signs and complains indicative of particular disease. Four identified etiological agents are of substantially lenti virus (HIV-I an HIV-II) that cause slow infection in which sign and symptoms only appear after many months or years of infection and two member of oncovirus (HTLV-I

               Â

Herpes zoster HIV associated salivary gland diseases Idiopathic thrombocytopenic purpura Mycobacterium infection Hyperpigmentation Histoplasmosis Recurrent aphthous stomatitis Molluscum contagiosum Oral squamous cell carcinoma Diagnostic tests Screening test for AIDS Enzyme-linked immunosorbant assay The Western Blot method Viral culture and polymerase chain reaction Surrogate marker for progression of HIV-I infection Management

and HTLV-II) that are capable of oncogenic transformation and are usually associated with leukemia or lymphoma. The case of AIDS was detected in June 1981 when 5 young homosexuals men came with the suffering from rare lung infection due to microorganism called Pneumocystis carinii. In India, the first description of AIDS came in Madras where 6 women out of 125 who were screened were HIV positive in high-risk group of prostitutes. The AIDS appear to be endemic in central and equatorial Africa and it may be old disease of Africa that has gone unrecognized. The HIV-1 infection has also become the primary emphasis of effort at controlling

Acquired Immunodeficiency Syndrome

sexually transmitted diseases (STDs). Moreover, the knowledge gain about sexual and other behavior associated with transmission of HIV, as well as strategies that have been effective in modifying those behaviors, is transferable to other sexually transmittable and bloodborne infections and has revolutionized standard approaches to the control of these infections. Oral and perioral lesions are common presenting features in patient with human immunodeficiency virus and may have deterioration of general health and a poor prognosis.

DEFINITION World Health Organization (WHO) has given following definition of AIDS: One or more opportunistic infections listed in clinical features that are at least moderately indicative of underlying cellular immune deficiency. Absence of all known underlying causes of cellular immune deficiency (other than HIV infection) and absence of all other causes of reduced resistance reported to be associated with at least one of those opportunistic diseases.

CLASSIFICATION 1st Classification (given in 1993) by Center for Disease Control (CDC) CD4 + T-cell categories

A Asymptomatic, acute HIV and PGL

B Symptomatic, not A or C conditions

C AIDS indicator condition

More 500/µL

A1

B1

C1

200 to 499/µL

A2

B2

C2

Less than 200/µL AIDS indicator T-cell count

A3

B3

C3

Category A: In adolescent less than 13 years with documented HIV infection: ∙ Persistence generalized lymphadenopathy ∙ Active condition.

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Category B: Condition is attributed to HIV infection or indicative of defect in the cell-mediated immunity. ∙ Bacillary angiomatosis ∙ Oropharyngeal and vulvovaginal candidiasis ∙ Cervical carcinoma in situ ∙ Constitutional symptoms like fever (38.5˚C) and diarrhea ∙ Oral hairy leukoplakia and herpes zoster ∙ Idiopathic thrombocytopenic purpura.

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Category C: AIDS indicative condition ∙ Candidiasis of bronchi, trachea or lung and esophageal candidiasis

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Invasive cervical cancer Disseminated or extrapulmonary coccidioidomycosis, extrapulmonary cryptococcosis Chronic intestinal cryptosporidiosis more than 1 month duration Cytomegalovirus retinitis with loss of vision HIV related encephalopathy Herpes simplex bronchitis, pneumonitis and esophagitis Kaposi sarcoma, Burkitt’s lymphoma and immunoblastic lymphoma Mycobacterium tuberculosis infection at any pulmonary or extrapulmonary sites Pneumocystic carinii pneumonia and recurrent pneumonia Progressive multifocal leukoencephalopathy Toxoplasmosis of brain and wasting syndrome Recurrent Salmonella septicemia.

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Group I: Acute infection Group II: Asymptomatic infection Group III: Persistence generalized lymphadenopathy. Group IV: Other disease – Subgroup A: Constitutional diseases – Subgroup B: Neurological diseases – Subgroup C: Secondary infectious diseases -

-

C1: Specified secondary infectious diseases listed in CDC surveillance definition for AIDS. C2: Other specified secondary infectious stages.

– Subgroup D: Secondary cancer – Subgroup E: Other conditions.

AIDS RELATED COMPLEX For clinical and research studies, persons exhibiting complex clinical problems and immunological or hematological abnormalities on the laboratory tests, have been classified as having AIDS related complex (ARC). The ARC requires any two or more symptoms and two or more abnormal laboratory findings. It must be present for at least 3 months.

Symptoms

Laboratory findings

• Lymphadenopathy • Weight loss of 15 lbs or 10% of body weight • Fever of 38.5˚C which is intermittent or continuous • Diarrhea, fatigue and malaise • Night sweats

• • • • • • •

Decreased number of T helper cell Decreased ratio of T helper cells to T suppressor cells Anemia or leukopenia or thrombocytopenia or lymphopenia Increased serum globulin level Decreased blastogenic response of lymphocytes to mitogen Increased level of circulating immune complex Cutaneous anergy to multiple the skin test antigens

PREVALENCE It is more common in Western countries particularly in the United State. Largest population of AIDS is in homosexuals, intravenous drug users and, heterosexuals with sexual contact with AIDS patient. Patients who received transfusion of blood or blood pigments donated by the person with risk factors. Ninety-two percent of victims are males, 6.5 percent female with 1 percent children. It is common at the age of 25 to 49 years.

Etiology T lymphocytes: There is quantitative and qualitative deficiency of T4 helper cells in AIDS patients, which lead to certain investigators to focus their efforts on determining if etiologic agent was a virus that manifested a particular tropism for T4 helper lymphocytes. HTLV-III virus: Dr Robent C Galleo determined that type C retrovirus was tropic for T4 lymphocytes in adult T-cell leukemia/lymphoma. He named the virus, Humans T-cell leukemia/lymphoma virus (HTLV–I). So it is considered to be etiological agent for AIDS. But as it causes lymphoproliferation in T-cell leukemia, where as AIDS is a disease of lymphodepletion. The answer came in the discovery of type D retrovirus of HTLV family that has been termed as HTLV-III. LAV virus: On the other hand, virus called lymphadenopathy associated virus (LAV), was being isolated from the AIDS patient in Europe. HTLV-III and LAV is closely related members of same class of virus. Finally, it is proved that HTLV and LAV are cytopathic human T–lymphocytotropic viruses that manifested selective infectivity for the helper/inducer subset of T-cells that as phenotypically designated reactivity with monoclonal antibody T4 or Leu3. HIV: In order to avoid different nomenclatures retrovirus responsible for the AIDS are named ‘Human immunodeficiency virus’ which belong to family of retroviruses. Risk person: Six groups are at risk of developing AIDS. These are homosexuals or bisexuals—71.4 percent, intravenous drug users—18.4 percent, hemophilia, recipient of multiple blood transfusion, infant born of parents belonging to first three high-risk groups and heterosexual contacts of high-risk group.

Acquired Immunodeficiency Syndrome

CHARACTERISTIC OF HIV VIRUS The HIV is a spherical enveloped virus, about 90 to 120 nm in size (Fig. 21.1). The nucleocapsid has an outer icosahedral shell and inner cone shaped core, enclosing the ribonucleoproteins. The genome is diploid, composed of two identical single stranded, positive sense RNA copies. Inside the envelope is a protein core, which contain enzymes reverse transcriptase, intregrase, protease, etc. all essential for viral replication and maturation. When the virus infects a cell, the viral RNA is transcribed by the enzymes, first into single stranded DNA and then to double stranded DNA (provirus), which is integrated into the host cell chromosomes. The virus is extremely sensitive to heat, thus boiling and autoclaving are very effective measure of inactivating the virus.

Mechanism of Action The HIV attacks the immune system of the body. Due to that an individual is not able to protect himself from potentially harmful organism. Normal mechanism: Pathogenic viruses → identified by macrophage → it activates T lymphocytes → it get differentiated into effecter cell like T helper cell or T4 and T suppresser cell or T8 → T4 cells secrete various lymphokines which induce lymphocyte to differentiated into plasma cell → it secrete specific antibodies against viral antigen → it destroy the virus. Mechanism in AIDS: HIV virus is lymphotropic virus → its primary target is T4 cell → when the virus enters the bloodstream, it integrates into gene into DNA of some primary

T4 lymphocyte → this viral DNA then becomes integrated into the host chromosomes → the chromosomal integration is prerequisite for replication of retroviruses, but also for the latency → once the viral genes are integrated into cells of own DNA, they can apparently remain dormant for an indefinite period of time, without causing its affects. This is called ‘incubation period’ → once the viral gene is activated, virus particles convert T4 lymphocytes into AIDS virus factory → when the number of T4 lymphocyte is severely depleted, the immune system collapses and variety of infections occur → at this stage patient is said to have AIDS.

Transmission Repeated intimate contact: It is in 90 percent of cases. It depends upon number of sexual partners, receptive anal intercourse and presence of other STDs. All these are in high-risk group. Prostitution is a major heterosexual factor associated with AIDS. Use of contaminated blood products: Intravenous drug users, HIV contaminated blood transfusion, blood clotting concentrate and organ transplantation. Perinatal transmission: It occurs in 13 percent among children born to HIV seropositive mother. Other nosocomial routes: Transmission from patient to patient due to reuse of contaminated and shared needles. Professional hazards: The risk of transmission from HIV infected patient to health care workers is more than health care workers to patient.

CLINICAL FEATURES (FIG. 21.2) Protozoan and helminthes infection: Cryptosporidiosis (intestinal) causing diarrhea for over one month. The most common opportunistic infection is by Pneumocystis carinii which causes pneumonia. CNS infection or other disseminated infections and toxoplasmosis. Fungal infection: Candidiasis causing esophagitis, cryptococcosis causing CNS infection, disseminated histoplasmosis and bronchial or pulmonary candidiasis. Bacterial infections: Mycobacterium avium intracellulare causing infection disseminated beyond lung and lymph node. Mycobacterium tuberculosis will cause tuberculosis.

Figure 21.1 HIV virus

Viral infections: Cytomegalovirus causing infection in the internal organs other than liver, spleen and lymph nodes. Herpes simplex virus, causing chronic mucocutaneous infection with ulcers persisting more than one month.

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Figure 21.2 Features of HIV infection

Malignancy: Kaposi’s sarcoma and squamous cell carcinoma. Lymphoma limited to bronchi and nonHodgkin’s lymphoma. AIDS dementia complex: This occur in patient with HIV infection and causes progressive encephalopathy.

ORAL MANIFESTATIONS Oral manifestations of HIV disease are common and include oral lesions and novel presentations of previously known opportunistic diseases. Careful history taking and detailed examination of the patient’s oral cavity are important parts of the physical examination and diagnosis requires appropriate investigative techniques. Early recognition, diagnosis and treatment of HIVassociated oral lesions may reduce morbidity. The presence of these lesions may be an early diagnostic indicator of immunodeficiency and HIV infection may change the classification of the stage of HIV infection and is a predictor of the progression of HIV disease. Around 95 percent of AIDS patients have head and neck lesions and about 55 percent have important oral manifestation. They are described below.

Oral Disorders in HIV Disease ∙ Fungal More common – Candidiasis Less common – Aspergillosis – Histoplasmosis – Cryptococcus neoformans – Geotrichosis ∙ Bacterial More common – HIV gingivitis – HIV periodontitis – Necrotizing gingivitis Less common – Mycobacterium avium intracellulare – Klebsiella pneumoniae – Enterobacter cloacae – E. coli – Salmonella enteritidis – Sinusitis – Exacerbation of apical periodontitis – Submandibular cellulitis

Acquired Immunodeficiency Syndrome

∙

∙

∙ ∙

∙

Viral More common – Herpes simplex – Varicella zoster – Epstein-Barr virus including hairy leukoplakia Less common – HPV virus – CMV virus Neoplasm More common – Kaposi’s sarcoma Less common – Non-Hodgkin lymphoma – Squamous cell carcinoma Lymphadenopathy Neurologic disorders Less common – Paresthesia – Facial palsy – Hyperesthesia – Dysphagia Miscellaneous Less common – Recurrent apthous ulceration – Progressive necrotizing ulceration – Toxic epidermolysis – Delayed wound healing – Thrombocytopenia – Xerostomia and sicca type syndrome – HIV embryopathy – Hyperpigmentation – Granuloma annulare – Exfoliative cheilitis – Lichenoid and other drug reaction.

EC-Clearinghouse Classification of Oral Manifestation of HIV Group I—strongly associated with HIV infection ∙ Candidiasis ∙ Hairy leukoplakia ∙ Kaposi’s sarcoma ∙ Non-Hodgkin’s lymphoma ∙ Periodontal disease (linear gingival erythema, necrotizing gingivitis and necrotizing periodontitis).

Group II—less commonly associated with HIV infection ∙ Bacterial infection (Mycobacterium) ∙ Melanotic hyperpigmentation ∙ Necrotizing ulcerative stomatitis ∙ Salivary gland disease ∙ Thrombocytopenia purpura ∙ Oral ulceration NOS (not otherwise specified) ∙ Viral infections like herpes simplex, zoster, papillomavirus. Group III—seen in HIV infection ∙ Bacterial infection (Actinomyces israelii, E. coli, Klebsiella pneumonia) ∙ Cat scratch disease ∙ Epithelioid angiomatosis ∙ Drug reaction ∙ Fungal infection other than candidiasis ∙ Neurologic disturbance ∙ Recurrent aphthous stomatitis ∙ Viral infection like cytomegalovirus, molluscum contagiosum.

Candidiasis Oral candidiasis is most commonly associated with Candida albicans, although other species, such as C. glabrata and C. tropicalis, are frequently part of the normal oral flora. A number of factors predispose patients to develop candidiasis: infancy, old age, antibiotic therapy, steroid and other immunosuppressive drugs, xerostomia, anemia, endocrine disorders and primary and acquired immunodeficiency. Candidiasis is a common finding in people with HIV infection. Reports describe oral candidiasis during the acute stage of HIV infection, but it occurs most commonly with falling CD4+ T-cell count in middle and late stages of HIV disease. Several reports indicate that most persons with HIV infection carry a single strain of Candida during clinically apparent candidiasis and when candidiasis is quiescent.

Clinical Features Location: Patient with a HIV usually has lesion of hard palate and soft palate. Appearance: The clinical appearances of oral candidiasis vary. The most common presentations include

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clinical lesions are examined using potassium hydroxide (KOH), PAS, or Gram’s stain. Smear shows candidal organism embedded in superficial keratin.

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Management Topical clotrimazole is treatment option in case of candidiasis associated with HIV infection. Systemic fluconazole is given if the CD4+ count is below 50 cell/mm3. In some patient itraconazole and intravenous amphotorecin B are given to combat severe infection. Points to Remember Figure 21.3 Candidiasis in AIDS patient

pseudomembranous, hyperplastic, angular, and erythematous candidiasis, which are equally predictive of the development of AIDS and angular cheilitis (Fig. 21.3). Symptoms: These lesions may be associated with a variety of symptoms, including a burning mouth, problems in eating spicy food and changes in taste. All three of these common forms may appear in one individual. Pseudomembranous candidiasis (Thrush): Characteristic creamy white, removable plaques on the oral mucosa are caused by overgrowth of fungal hyphae mixed with desquamated epithelium and inflammatory cells. The mucosa may appear red when the plaque is removed. This type of candidiasis may involve any part of the mouth or pharynx. Erythematous candidiasis: Erythematous candidiasis appears as flat, red patches of varying size. It commonly occurs on the palate and the dorsal surface of the tongue. Erythematous candidiasis is frequently subtle in appearance and clinicians may easily overlook lesions, which may persist for several weeks if untreated. Angular cheilitis: Angular cheilitis appears clinically as redness, ulceration and fissuring, either unilaterally or bilaterally at the corners of the mouth. It can appear alone or in conjunction with another form of candidiasis.

Histopathological Features Candida is a commensal organism in the oral cavity. Candidiasis is diagnosed by its clinical appearance and by detection of organisms on smears. Smears taken from

C. glabrata and C. tropicalis, falling CD4+ T-cell count, pseudomembranous, hyperplastic, angular, and erythematous candidiasis, burning mouth, smears, embedded in superficial keratin, topical clotrimazole, systemic fluconazole, itraconazole and intravenous amphotorecin B.

Kaposi’s Sarcoma It is also called angioreticulo-endothelioma. It is the most common tumor associated with AIDS and occurs in 1/3rd of AIDS patients.

Etiology There is higher incidence of Kaposi’s sarcoma is in homosexual men with AIDS as compared to heterosexuals with AIDS. It has been suggested that there is transmissible agent prevalence in homosexual population, which stimulate certain factor such as angiogenesis protein that may be critical in the pathogenesis of neoplasm. The patient with AIDS often shows clustered lesion in the oral cavity, which suggests direct inoculation of mucosa with sexually transmitted agent. Some theories suggests role of cytomegalovirus in the pathogenesis of Kaposi’s sarcoma, but studies on prevalence of antibodies to cytomegalovirus in patient with classic and epidemic Kaposi’s sarcoma have failed to demonstrate role of cytomegalovirus. Nowadays, it has been stated that Kaposi’s sarcoma is associated with human herpes virus (HHV 8). The HHV 8 is detected in oral epithelial cells and in oropharynx. Types • • • •

Classic African (cutaneous variant) African (lymphadenopathy variant) Kaposi’s sarcoma associated with AIDS.

Acquired Immunodeficiency Syndrome

Epidemiology and Form Kaposi’s sarcoma appears in various forms like classic, African (cutaneous variant), African (lymphadenopathy variant) and Kaposi’s sarcoma associated with AIDS. Classic type is a rare neoplasm and occurs in the older man. Usually, it appears as blue-black macule on the lower extremities. It is slow growing and rarely involves the lymph nodes and visceral organs. African Kaposi’s sarcoma is considered an endemic disease and affects children, 10-year-old or younger patients, more common in men than women. It appears as exophytic growth located in legs and arms. This form is locally aggressive and lymph nodes involvement is rare. The lymphadenopathic form occurs in children of 10 years age and younger with same frequency in men and women. The visceral and massive nodal involvement is common. Kaposi’s sarcoma is observed in patients with kidney transplantation and in patients who receive the immunosuppressive drugs for variety of diseases. Drugs such as prednisolone, cyclosporine and cyclophosphamide have been associated with development of Kaposi’s sarcoma. It usually affects legs, arms, lymph nodes and visceral organs.

Clinical Features Age and sex distribution: It is more common in male as compared to female in ratio of 20:1. It can occur at any age but most common in 5th, 6th, 7th decade except in Africa where it more common in children.

on any part of the oral mucosa including the gingiva, soft palate, buccal mucosa and in the oropharynx. It can involve either alone or in association with skin and disseminated lesions. It may be the first symptom of AIDS. Appearance: It can appear as a red, blue, or purplish lesion. It may be flat or raised solitary or multiple. Occasionally, yellowish mucosa surrounds the lesion. The lesions may enlarge, ulcerate and become infected. Good oral hygiene is essential to minimize these complications. Sign: It may vary in size from few millimeter to a centimeter or more in diameter and are tender and painful.

Histopathological Features It consists of interweaving band of spindle shaped and or plump endothelial cell and atypical vascular channels, enmeshed in reticular or collagen fibers. It consists of numerous, small capillary type blood vessels, which may or may not contain blood. Inflammatory cell infiltration is common (Fig. 21.4). In late stage, lesion consists of well defined nodules or lesions with diffuse involvement of the lamina propria. Histopathological Stages • P atch stage (macular): In this proliferation of miniature vessels • Plaque stage: It shows further proliferation of vascular channels with development of spindle cells • Nodular stage: Spindle cell increase to form nodular tumor like mass.

Site: Commonly affects skin, oral and visceral organs. It occurs commonly in head and neck region. Tip of nose is peculiar and frequent location of it. It can involve lymph nodes, soft tissue, extremities, GIT, lung, liver, pancreas, spleen and adrenal gland. Appearance: It begins as multinucleated neoplastic process that manifests as multiple red or purple macules and in more advanced stage, a nodule occurring on the skin or mucosal surface. Sign: Size of it ranges from a few millimeters to a centimeter or more in diameter and are usually tender on palpation. It is slow growing but can behave as a very aggressive lesion with rapid visceral involvement.

Oral Manifestations Location: It has tendency to involve the oral cavity, with hard palate as the most common site. But lesions may occur

Figure 21.4 Capillary blood cell seen in Kaposi’s sarcoma

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Management

Clinical Features

Treatment is determined on the basis of the number, size and location of the oral lesions. The choice of therapy depends on the effect of treatment on the adjacent mucosa, pain associated with treatment, interference with eating and speaking and the patient’s preference. It is important to perform thorough dental prophylaxis before initiating therapy for lesions involving the gingiva. Response to therapy is improved if all local plaque and calculus are removed. Local application of sclerosing agents may reduce the size of oral lesions. Local treatment is appropriate for large oral lesions that interfere with eating and talking. Oral lesion can be treated surgically or with localized intralesional chemotherapy. Intralesional vinblastine, radiation therapy, intravenously interferon alpha and sclerotherapy with 3 percent sodium tetradecyl sulfate.

Location: It is unique and significant lesion which primarily occurs unilaterally or bilaterally on the lateral border of tongue. It can also occur on dorsum of the tongue, buccal mucosa, floor of mouth, retromolar area and soft palate. Many time lesion start on lateral border and spread to entire dorsum of tongue.

Points to Remember Angioreticulo-endothelioma, affects skin, multinucleated neoplastic process that manifests as multiple red or purple macules, hard palate, most common site, red, blue, or purplish lesion, yellowish mucosa surrounds the lesion, spindle shaped and or plump endothelial cell, numerous, small capillary type blood vessels, Inflammatory cell infiltration, thorough dental prophylaxis, intralesional vinblastine, radiation therapy, intravenously.

Hairy Leukoplakia Oral hairy leukoplakia, which presents as a non-movable, corrugated or “hairy” white lesion on the lateral margins of the tongue occurs in all risk groups for HIV infections, although less commonly in children than in adults. It occurs in about 20 percent of persons with asymptomatic HIV infection and becomes more common as the CD4+ T-cell count falls.

Appearance: There is characteristic corrugated and white appearance. It does not rub off and may resemble the keratotic lesion. The surface is irregular and may have prominent folds or projections, sometimes markedly resembling hairs. Occasionally, however, some areas may be smooth and flat (Fig. 21.5). Pseudo hairy leukoplakia: Sometimes, the white lesion satisfies many criteria for diagnosis of hairy leukoplakia, but if EBV not present this is called ‘pseudo hairy leukoplakia’. Presence of hairy leukoplakia is fairly indicator of HIV pro-sensitivity and is predictor of deficiency immunocompetence.

Histopathological Features Histologically lesion shows hyperkeratosis, acanthosis, contain Epstein-Barr virus and no or minimum inflammation. Balloon cells: The epithelial exhibits band-like zone of lightly stained cells with abundant cytoplasm in the upper spinous layer. Nuclear beading: There is presence of scattered cells with nuclear clearing with pattern of peripheral margination of

Etiology Exact etiology is not known but Epstein-Barr virus has identified in these lesions. One hypothesis is that basal epithelial cells of lateral margin of tongue normally harbors EBV in majority of adult population, who are EBV sero-positive and carrier of that disease. It is found primarily in homosexual male. Direct infection of Langerhans cell due to HIV induced loss of factor essential for their integrity and function, permit reactivation of EBV with frequent epithelial hyperplasia.

Figure 21.5 Hairy leukoplakia showing characteristic

corrugated appearance

Acquired Immunodeficiency Syndrome

chromatin on superficial epithelium. This is called nuclear beading. Immunochemistry tissue in situ hybridization, noninvasive tissue in situ hybridization, or electron microscopy does demonstrate of Epstein-Barr virus. The lesion of leukoplakia consists of Langerhans cells.

Management Hairy leukoplakia usually is asymptomatic and does not require treatment. Hairy leukoplakia is almost always a manifestation of HIV infection and clinicians should arrange evaluation of HIV disease and appropriate treatment for patients with hairy leukoplakia. Hairy leukoplakia has disappeared in patients receiving high-dose acyclovir for herpes zoster, presumably because of the anti-EBV activity of acyclovir. Doses of acyclovir (2.5–3 mg per day for 2–3 weeks) usually eliminate HL, but the lesion usually recurs with cessation of treatment. Elimination or almost complete clinical resolution of the lesion has occurred in patients treated with agents such as desciclovir (an analog of acyclovir), phosphonoformate, Retin A and podophyllin resin, although lesions tend to recur within few months. Occasionally, Candida albicans may be found in HL lesions. Antifungal medications like topical clotrimazole, topical nystatin 10000 unit/g 5 times a day can be given. Systemic agent like ketoconazole 200 mg BD a day, acyclovir, azidothymidine and retinoid acid podophyllin resin can also be given. Points to Remember

Clinical Features Site: It often occur in clean mouths, where there is very little plaque or calculus to account for the gingivitis. Sign: The onset is often sudden, with rapid loss of bone and soft tissue. Patients sometimes complain of spontaneous bleeding. Linear gingival erythema: In this condition gingiva may be reddened involving the free gingival margin. There is linear band of erythema which can extend 3 mm apically. The diagnosis of this should be done if gingivitis does not respond to improved plaque control (Fig. 21.6). Necrotizing ulcerative gingivitis: In these ulcers occurs at the tips of the interdental papilla and along the gingival margins and often elicits complaints of severe pain. The ulcers heal, leaving the gingival papillae with a characteristic cratered appearance. Necrotizing ulcerative periodontitis may present as rapid loss of supporting bone and soft tissue. Typically, these losses occur simultaneously with no formation of gingival pockets, sometimes involving only isolated areas of the mouth. Teeth may loosen and eventually fall out, but uninvolved sites can appear healthy. There is loss of more than 6 mm attachment. Necrotizing stomatitis may develop and areas of necrotic bone may appear along the gingival margin. The bone may eventually sequestrate. Patients with necrotizing ulcerative periodontitis and necrotizing stomatitis frequently complain of extreme pain and spontaneous bleeding.

Nonmovable, corrugated or hairy white lesion on the lateral margins of the tongue, Epstein-Barr virus, does not rub off, pseudo hairy leukoplakia, hyperkeratosis, acanthosis, balloon cells, nuclear beading, demonstrate of Epstein-Barr virus, Langerhans cells, high-dose acyclovir, desciclovir, phosphonoformate, Retin A, podophyllin resin, antifungal medications like topical clotrimazole, topical nystatin 10000.

Periodontal Disease Associated with HIV Periodontal disease is a fairly common problem in both asymptomatic and symptomatic HIV-infected patients. Form • • •

Linear gingival erythema Necrotizing ulcerative gingivitis Necrotizing ulcerative periodontitis.

Figure 21.6 Linear gingival erythema

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Appearance: Herpes labialis occurs as characteristic lip lesion consisting of vesicles on an erythematous base that Clinicians should refer patients to a periodontist or dentist heals within 7 to 10 days. The recurrent herpes labialis for management. (RHL) are small, shallow, irregular and erosive-like lesion The following protocol has achieved reasonable that may coalesce and seen to occur only on keratinized success: plaque removal, local debridement, irrigation epithelium like that of gingiva, hard palate or dorsal surface with povidine-iodine, scaling and root planning and of tongue. maintenance with a chlorhexidine mouth rinse once or Diagnosis is made by isolation of virus from ulcer. twice daily. Antiviral drugs like acyclovir 30 mg/kg/day should be The use of systemic antibiotics like metronidazole has given. In case of resistant infection foscarnet is preferred. been given in patient which has got extensive involvement. Points to Remember Linear gingival erythema, necrotizing ulcerative gingivitis, necrotizing ulcerative periodontitis, necrotizing stomatitis, plaque removal, local debridement, irrigation with povidine-iodine, scaling and root planning, metronidazole.

Non-Hodgkin Lymphoma This is the second most common malignancy in HIV infection. It may cause by EBV virus infection and HHV 8.

Clinical Features Site: It is seen in extranodal location. CNS is the most common site of involvement. Intraorally, it can be seen on gingiva, palate, tongue, tonsil, and maxillary sinus. Sign: There is loss of periodontal attachment and loosening of teeth. Appearance: There is erythematous and soft tissue enlargement seen in oral cavity.

Management Combination of chemotherapy and radiotherapy is effective. Points to Remember EBV virus infection and HHV 8, CNS involvement, gingiva, loss of periodontal attachment, erythematous and soft tissue enlargement, chemotherapy, radiotherapy.

UNCOMMON ORAL MANIFESTATION OF HIV Recurrent Herpes Labialis Recurrent herpes labialis mainly appears as herpes labialis and recurrent intraoral herpes. It is cause by HSV.

Points to Remember HSV, vesicles on an erythematous base, antiviral drugs.

Oral Human Papilloma Virus Lesions It is cause by human papilloma virus. Oral warts, papillomas, skin warts and genital warts are associated with the human papilloma virus (HPV) lesions. Because the HPV types found in oral lesions in HIV-infected persons are different from the HPV types associated with anogenital warts, clinicians should probably not use the term condyloma acuminate to describe oral HPV lesions. Location: Lesions caused by HPV are common on the skin and mucous membranes of persons with HIV disease. Anal warts have frequently been reported among homosexual men. It can be found on any mucosal surface and are contagious to both host and sex partner. Appearance: HPV lesions in the oral cavity may appear as solitary or multiple nodules. They may be sessile or pedunculated and appear as multiple, smooth-surfaced raised masses resembling focal epithelial hyperplasia or as multiple, small papilliferous or cauliflower-like projections. Histopathologically lesion is sessile or papillary which is covered by acanthotic or hyperplastic stratified squamous epithelium. Affected epithelium demonstrated vacuolization of numerous epithelial cells which is called ‘koilocytosis’.

Management Simultaneous irradiation of all lesions and care of infected partner. Local excision and cauterization of base. Points to Remember Oral warts, papillomas, skin warts, homosexual men, solitary or multiple nodules, small papilliferous, cauliflower-like projection, koilocytosis, acanthotic or hyperplastic stratified squamous epithelium.

Acquired Immunodeficiency Syndrome

Herpes Zoster It occurs more frequently in HIV infected patients and carries poor prognosis. The occurrence of unilateral vesicles that break and scab is characteristic of this infection. They are selflimiting. When herpes zoster infection involvements occur intraorally, it will lead to sequestration of bone with loss of teeth. Main complication is neuropathy after inflammation. Diagnosis is made by cytological smear and finding of multinucleated giant cells.

Management Systemic acyclovir 800 mg orally or 15 to 30 mg/kg/day IV 8 hourly for 10 to 15 days. Points to Remember Occurrence of unilateral vesicles, sequestration of bone, loss of teeth, neuropathy, systemic acyclovir.

HIV Associated Salivary Gland Diseases Salivary gland disease associated with HIV infection (HIVSGD) can present as xerostomia with or without salivary gland enlargement. Reports describe salivary gland enlargement in children and adults with HIV infection usually involving the parotid gland. The etiology of HIV-SGD is as yet unknown. It has been postulated that cytomegalovirus infection has got predilection for salivary glands. Cytomegalovirus infection produces inflammation which causes reduced salivary production. Sign: The enlarged salivary glands are soft but not fluctuant, but the enlarged parotid glands can be a source of annoyance and discomfort. Xerostomia is sometimes seen in individuals with HIV-SGD. HIV-infected patients may also experience dry mouth. Diffuse infiltrative lymphocytosis syndrome: It is seen in HIV infected salivary gland disease. There is salivary gland enlargement. The glandular involvements result from infiltration of CD8 lymphocytes.

Management Antiretroviral therapy is useful in this case. Removal of the enlarged parotid glands is rarely recommended. For

individuals with xerostomia, the use of salivary stimulants such as sugarless gum or sugarless candies may provide relief. Candies that are acidic should be avoided as frequent use may lead to loss of tooth enamel. The use of salivary substitutes may also be helpful. An increase in caries can occur, so fluoride rinses (that can be bought over the counter) should be used daily and visits to the dentist should occur two to three times per year. Points to Remember Xerostomia, parotid gland, cytomegalovirus infection, enlarged salivary glands, diffuse infiltrative lymphocytosis syndrome, antiretroviral therapy.

Idiopathic Thrombocytopenic Purpura Reports have described idiopathic thrombocytopenic purpura (ITP) in HIV-infected patients. It can be cause by direct infection by HIV, immune dysfunction, alteration of platelet production and drug reaction. Oral lesions may be the first manifestation of this condition. Petechiae, ecchymosis and hematoma can occur anywhere on the oral mucosa. Spontaneous bleeding from the gingiva can occur and patients may report finding blood in their mouth on waking.

Management HAART has reduced the prevalence of thrombocytopenia. Other approach like splenectomy, intravenous immunoglobulin, platelet transfusion is given. Points to Remember Infection by HIV, immune dysfunction, alteration of platelet production, petechiae, ecchymosis and hematoma, spontaneous bleeding.

Mycobacterium Infection It can results in tuberculosis which is cause by Mycobacterium tuberculosis. It involves tongue, gingiva, and buccal mucosa, floor of mouth, lip and palate. Appearance: There is chronic ulceration, exophytic proliferation Diagnosis: It is difficult as maximum cases do respond to tuberculin skin test. Confirmative diagnosis is done by AFB stained section of biopsy material.

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Triple drug regimen is used. It includes rifampicin, isoniazid, and pyrazinamide with ethambutol. Points to Remember Chronic ulceration, exophytic proliferation, triple drug regimen.

Hyperpigmentation Hyperpigmentation of skin, nail and mucosa is seen in HIV patient. There is increase melanin pigmentation occur in basal layer of affected epithelium. In some cases, adrenocortical destruction occur due to HIV resulting in addisonian pattern of pigmentation.

Histoplasmosis It is cause by Histoplasma capsulatum. It is most common type of fungal infection seen in patient with HIV other than candidiasis. Sign: There is fever, splenomegaly and pulmonary infiltrate. Appearance: Orally, it is presented as indurated mucosal ulceration with raised border. Histopathologically, fungal organism are visible within the cytoplasm of histiocytes and multinucleated giant cells.

Management Intravenous amphotericin B is useful in this case.

Recurrent Aphthous Stomatitis In HIV infection all three forms of aphthous ulceration like minor, major and herptiform is seen. There is well defined ulceration seen in the oral cavity.

Management It is done with the help of topical and intralesional corticosteroids.

Molluscum Contagiosum It is infection of skin cause by pox virus. Location: It is seen on genital, trunk and facial region. Appearance: Lesion are small, waxy, dome-shaped papules with center depressed crater. In HIV infection, this are hundred in number.

Histopathologically surface epithelium forms several hyperplastic down growth. There is presence of molluscum bodies which are large intracytoplasmic inclusion.

Management There is resolution of lesion after giving HAART therapy.

Oral Squamous Cell Carcinoma Squamous cell carcinoma of oral cavity, pharynx, and larynx has been seen in the HIV infected patients. The HIV infection accelerated the development of squamous cell carcinoma due to impaired immune surveillance.

Management It is same as that of squamous cell carcinoma.

DIAGNOSTIC TESTS Diagnosis of AIDS can be made by history and medical examination for symptoms and signs. Individual is generally young and in high risk group. There are several circumstances in which, it is important for dentist to know HIV antibody status. To ensure accurate differential diagnosis and appropriate treatment of the oral lesions those are associated with development of AIDS. To assess the risk to dental health care worker (HCW) after needle stick or other injury from contaminated once by contact with patients blood and saliva. To convey with communicable disease control (CDC) guideline that all HCW engaging in invasive dental practice should be aware of HIV antibody status.

SCREENING TEST FOR AIDS Enzyme-linked Immunosorbent Assay (Fig. 21.7) Enzyme-linked immunosorbent assay (ELISA) is a color reaction test in which prepared whole HTLV III virus particle which acts as antigen, will bind with antibodies to HTLV III in an infected human serum. Then this complex is added to goat antihuman antibody labeled with chemical enzymes, which gives color reaction with particular chemicals e.g. orange color with peroxides labeled goat antihuman antibody. ELISA test is simple and convenient to perform; it is very sensitive for small amount of HTLV III antibodies and in initial screening tests.

Acquired Immunodeficiency Syndrome

antigen or reverse transcriptase assay provide method that specifically demonstrates the presence of virus in given patient or specimen. The variable amount of virus present in peripheral blood monocytes at different stage of infection and degree of immunosuppression both influence the extent HIV-I viremia. Polymerase chain reaction technique has provided an opportunity for detection of very small amount of an infectious agent like HIV-I based on reported cycle of enzymatic duplication of number of copies of either DNA or RNA specific for microorganism. Figure 21.7 ELISA kit for detection of AIDS

It is not 100 percent reliable because it is not completely specific only for HTLV II antibodies and reacts with other related viral antibodies and other nonspecific chemicals giving false positive result of about 5 to 25 per 1000 patients. In case of positive test, there is strong indication of past exposure and infection with virus but this does not show whether the patient is infectious because it does not show whether virus is still active or has been destroyed.

The Western Blot Method The prepared HTLV III virus particles consists of specific HTLV III specific proteins separated by a process called electrophoresis and subsequent transfer of nine protein bands to nitrocellulose membrane strip, which are reacted with patient’s serum followed by an enzyme linked antihuman antibody and enzyme substance. Positive test is indicated when the treated, i.e. HTLVIII specific nitrocellulose strip are exposed to infected human serum and a goat antihuman antibody strip display the characteristic band detected for each of three (env, pol and gag) group of viral protein on exposure to X-ray film. Those that react with only one of these three groups of antigens are termed indeterminate and those react with only non viral proteins are negative. It is more specific for HTLV III antibodies and is used to eliminate false positive result.

Viral Culture and Polymerase Chain Reaction Cultivation of HIV from blood and other body fluids and tissues with detection of the increased filter by either HIV

Surrogate Marker for Progression of HIV-I Infection The absolute CD4+ T-cell lymphocyte count correlate best with progression of HIV-I related immune dysfunction. Other serum neoprotein beta-2-microreceptor HIV P24 antigen interleukin-2 receptor IgA and impaired delayed type of sensitivity are also used.

MANAGEMENT Various drugs are used for immunotherapy are as follows: Interferon: It is a useful therapeutic agent in this syndrome of infection and neoplasms in view of their antiviral antiproliferative and immunomodulater activity. The interferon is a glycoprotein produced by a number of different types cells. Type I interferon (alpha and beta) are produced by leukocytes and fibroblasts. Type II interferon (gamma) is produced by lymphocytes and monocytes. Low doses of interferon enhance the antibody formation and lymphocyte blastogenesis. They also prolong cell cycle and cause inhibition of intracellular enzyme system (antineoplastic effect). The gamma interferon stimulate macrophage oxidative metabolism and have antimicrobial effect. Thymic replacement therapy: The thymic epithelium plays an important role in transformation of blood borne precursor cell into mature T-cells. Thymic hormones or factor mediates this effect, since the immune system in AIDS is characterized by numerical and functional defects of T-cell lymphocytes, it will correct the immune defect. Transplant of fetal thymus of cultural thymic epithelium and injection of thymic hormone have been successfully utilized in treatment of AIDS.

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Lymphokines and cytokines: Lymphokines are materials produced by lymphocyte. Interleukin-I is macrophage product. In in vitro system interleukin-I enhance plague forming cells responses and the generation of cytotoxic T-cell alloantigen. In the presence of macrophage, interleukin-1 stimulates the production of interleukin-2, which stimulates and maintains the growth of T-cell activated by antigens. Various studies have conformed that purified interleukin-2 (which stimulate and maintain growth of T-cell activated by antigen), preparation in in vitro system can normalize lymphocyte reaction in high percentage of individuals with unexplained lymphadenopathy and immunologic abnormalities, but the result are not significant in patients with AIDS. Bone marrow transplantation: Syngeneic (identical twin) allogenic (HLA/NHC matched) bone marrow transplantation has been successful in reconstituting immune function in the patients with severe congenital immune defects. If this could be therapeutic in patient with AIDS that have appropriate marrow donor. Monoclonal antibodies therapy: In this, antibodies are directed against T-cell differentiation antigens as a result of that number of circulating leukemic cells are decreased in patients with adult T-cell active lymphoblastic leukemia. Pharmacological immunomodulation: Amitidine, isoprinosine and retinoid are also used but results are insignificant. Intravenous immunoglobulin therapy: It reduces incidence of bacterial and viral infection. Infusion of hyperimmune gamma globulin enriched for neutralizing antibodies for LAV/HTLV-III could prove beneficial for individuals with AIDS or ARC who have inadequate specific antibodies. Antiviral drug HPA–23: It is an oraganometallic compound of tungsten and antimony, azidothymidine. It is analogs of thymidine. It appears to inhibit multiplication of HTLV-III virus and cyclosporine. It shows marked increase in T lymphocyte population. HAART therapy—nowadays introduction of highly active antiretroviral therapy (HAART) results in long survival of the patient. The HAART includes two nucleoside analog reverse transcriptase inhibitor, at least one protease inhibitor and/or one non-nucleoside analog reverse transcriptase inhibitor. Nucleoside analogue

reverse transcriptase inhibitors, which are used are abacavir, didanosine, emtricitabine, lamivudine, stavudine. Nonnucleosides used are capravirine, delavirdine, efavirenz and nevirapine. Protease inhibitor used is amprenavir, darunavi, indianvir, tipranvir.

PREVENTION ∙ ∙ ∙ ∙ ∙ ∙

Educational counseling of general public Avoid sexual contact with suspect and in high-risk group Use of disposable syringes and needles Blood donor should be properly screened Avoid multiple sex partners, intimate kissing and oral contact Educate healthcare workers on safety measures.

BIBLIOGRAPHY 1. Baccaglini L, Atkinson JC, Patton LL, et al. Management of oral lesion in HIV positive patients: Oral Surg Oral Med Oral Pathol Oral Radiol. 2007;103(Supp 1);S50.e1-23. 2. EC:Clearinghouse on oral problems related to HIV infection and WHO collaborating center on oral manifestation of immunodeficiency virus: classification and diagnostic criteria for oral lesion in HIV infection. J Oral Pahtol Med; 1993;22:289-91. 3. Epstein JB, Cabay RJ, Glick M. Oral malignancies in HIV disease: change in disease presentation, increasing understanding of molecular pathogenesis and current management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100:571-8. 4. Frezzini C, Leao JC, Porter S. Current trends in HIV disease of mouth. J Oral Pathol Med. 2005;34:513-31. 5. Greenspan D, Greenspan JS. Significance of oral hairy leukoplakia: Oral Surg Oral Med Oral Pathol. 1992;73:1514. 6. Holmstrup P, Westergaard J. HIV infection and periodontal disease: periodontal. 1998;18:37-46. 7. Lager I, Altini M, Coleman H. Oral Kaposi’s sarcoma: a clinicopatholgoic study from south Africa. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;96:701-10. 8. Miziara ID, Weber R. Oral candiadisis and oral hairy leukoplakia as predictor of HAAAT failure in Brazilian HIV infected patients. Oral Dis. 2006;12:402-7. 9. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edn, Saunder Elsevier; 2009. 10. Piluso S, Ficarra G, Lucatorto FM, et al. Cause of oral ulcer in HIV infected patients: a study on 19 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82:166-72.

Acquired Immunodeficiency Syndrome

MULTIPLE CHOICE QUESTIONS 1. HIV is: a. 90–120 nm c. 70–120 nm

b. d.

80–120 nm 50–100 nm

2. AIDS dementia complex causes: a. Progressive encephalopathy b. Regressive encephalopathy c. Both a and b d. None of the above 3. Most common fungal oral manifestation of HIV is: a. Kaposi’s sarcoma b. Candidiasis c. RAS d. Dysphagia 4. Most common tumor associated with AIDS is: a. Squamous cell carcinoma b. Hodgkin’s lymphoma c. Non-Hodgkin’s lymphoma d. Kaposi’s sarcoma

5. Causative organism for hairy leukoplakia is: a. EBV b. HPV c. Rota virus d. None of the above 6. ELISA is a: a. Color reaction test c. PCR

b. d.

Electrophoresis test None of the above

7. Balloon cells and nuclear beading are seen in: a. Hairy leukoplakia b. Pseudo hairy leukoplakia c. Non-Hodgkin’s lymphoma d. All of the above 8. The following are the histopathological stages of Kaposi’s sarcoma except: a. Patch stage b. Plaque stage c. Nodular stage d. Bullous stage

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Odontogenic Infection and Pulp Pathology Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe), Seema Vaidya

Chapter Outline     Â

           Â

Effect of infection on host Pathophysiology of infection Pulp Classification of pulpitis Pulpitis • Reversible pulpitis • Chronic hyperplastic pulpitis • Irreversible pulpitis Pulp degeneration Pulp calcifications Necrosis of pulp Cracked tooth syndrome Periapical abscess Periodontal abscess Acute exacerbation of a chronic lesion Periapical granuloma Periapical scar Osteomyelitis Acute suppurative osteomyelitis Chronic suppurative osteomyelitis

Infection is a clinicopathological entity involving invasion of the body by pathogenic microorganisms and reaction of the tissues to microorganisms and their toxins. Soft tissue infections of head and neck are commonly encountered in routine practice in dentistry. These infections may be odontogenic or nonodontogenic in origin. Once the infection extends past the apex of the tooth the pathophysiology of the infectious process can vary, depending upon the number and virulence of

Infantile osteomyelitis Diffuse sclerosing osteomyelitis Primary chronic osteomyelitis Chronic tendoperiostitis SAPHO syndrome CRMO Focal sclerosing osteomyelitis (condensing osteitis) Osteomyelitis with proliferative periostitis Radiation osteomyelitis Cellulitis Ludwig’s angina Fatal complications of oral infection • Bacterial meningitis • Brain abscess • Cavernous sinus thrombosis • Odontogenic infection of orbit • Mediastinitis • Necrotizing fascitis  Oral foci of infections  Dry socket            Â

the microorganisms, the host resistance and anatomic geography. These odontogenic infections can become severe, lifethreatening facial space infections. These infections have the potential to spread through facial planes of head and neck there by compromise the vital structures in these regions, e.g. intracranial odontogenic infection leading to necrotizing fascitis of head and neck. Most odontogenic infections can be managed successfully with minimal

Odontogenic Infection and Pulp Pathology

complications. The key to successful management is sound surgical principles. The relationship between the host and microbes is a dynamic one. Usually, host resistance is the dominant factor. On the other hand, when the host resistance is lowered, microbes predominate and clinical infection occurs. In establishing the presence of infection there is interaction between three viz factors host, environment and microbes. A compromised patient is more likely to have infection and this infection can rapidly acquire a serious form. Hence, patient history is more important so as to recognize the patient ability to defend himself against the infection. The adverse relationship between the host and the infectious microorganism can be best understood by imagining a balance on which the pathologic attribute of microbes are weighed against the protective mechanisms of the host. Body defends against the microbial invasion by three major defenses local defense, cellular defense and humoral defense. The microorganisms on the other hand use two weapons in this battle, i.e. virulence and number of microbes.

occur due to neutralization of host defence. There is fever, endotoxic shock and intravascular coagulation. The pathogen or its products, in certain situations, may combine with antibodies or sensitized mononuclear leukocytes to produce harmful immunologic effects called hypersensitivity reaction. Compromised host: It is a person whose defense mechanisms have been lowered as a result of diabetes, tuberculosis, rheumatic fever, malignancy, radiation therapy, use of therapeutic immunosuppressive drug or antibiotics, extensive skin burns, genetic deficiency of immune system and malnutrition. Spread of Infection • Direct invasion or extension • Spread by lymphatic system • Spread by blood vessels.

PATHOPHYSIOLOGY OF INFECTION

The body’s response to infectious agent is inflammatory, which is essentially a protective phenomenon. Hence, the cardinal signs of inflammation are present, to some degree, Factors for Host Defense in nearly all patients with infection. Local defense Redness (rubor) is seen when the infection is close to the tissue surface, which is secondary to the intense • Epithelial lining hyperemia caused by increased vasodilation of arterioles. • Secretory and drainage system Calor or heat is due to inflow of relatively warm blood • Microbial floral interference from deeper tissues, increased velocity of blood flow and • Mucosal immune system increased rate of metabolism. Humoral factor Dolor or pain results from pressure on sensory nerve • Immunoglobulin endings, from distension of tissues caused by edema or • Complement system spread of infection. Release of substance like kinins, Cellular component histamines or bradykinin is also responsible for pain. It is the most universal sign of infection. • Polymorphonuclear leukocytes Swelling accompanies infection, unless the infection • Lymphocyte. is confined to bone which cannot swell. It is due to the accumulation of fluid, exudate or pus. EFFECT OF INFECTION ON HOST Loss of function is another sign of infection. A patient Infectious agents initiate, in the host, a series of reactions immobilizes the painful part in the most comfortable that are collectively called inflammatory reaction. This position he can find. Hence, when the masticatory muscles response results in generation and release of mediators, are involved, there is limitation of jaw movement. Fever occurs in some cases, which reflect a nonmicrovascular changes and mobilization and activation of leukocytes, all designed to eliminate the infectious specific physiologic response of host to tissue injury. pathogens and repair tissue injury. Therefore, these This injury results in increase of substance called pyrogen from endogenous (injured tissue) and exogenous source reactions are protective in nature. Direct injury to the host cells, enhancement of the (infecting agent). In clinical fever, it appears that the parasite’s invasiveness and amplification of these effects hypothalamic regulating center is stimulated by endogenous

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pyrogen, which is activated by bacterial endotoxin release from granulocytes, monocytes and macrophages. 542

Cardinal Sign of Inflammation • • • • • •

Redness (rubor) Calor or heat Dolor or pain Swelling Loss of function Fever.

PULP

2nd Classification According to involvement • Focal or subtotal or partial pulpitis: In it inflammatory process is confined to a portion of the pulp, usually a portion of the coronal pulp. • Total or generalized pulpitis: In it most of the pulp is involved. According to severity • Acute • Chronic According to presence or absence of direct communication between the dental pulp and oral environment • Pulpitis aperta (open pulpitis): In it pulp is communicated with the oral cavity. • Pulpitis clausa (closed pulpitis): No communication exists.

The pulp is the formative organ of the tooth. It builds primary dentin during the development of the tooth, secondary dentin after tooth eruption and reparative dentin in response to stimulation as long as the odontoblasts remain intact. The pulp has been described as both a highly resistant organ and as an organ with little resistance or recuperating ability. It is a delicate connective tissue liberally interspersed with tiny blood vessels, lymphatics, myelinated and unmyelinated nerves, and undifferentiated connective tissue cells.

The initial response to injury to pulp is same as that of other tissue, but the end results is different due to rigid dentinal wall of pulp chamber.

CLASSIFICATION OF PULPITIS

Pathogenesis

1st Classification Pulpitis (Inflammation) Reversible • Symptomatic (acute) • Asymptomatic (chronic) Irreversible • Acute – Abnormally responsive to cold – Abnormally responsive to heat • Chronic – Asymptomatic with pulp exposure – Hyperplastic – Internal resorption Pulp degeneration • Calcific • Others Necrosis

PULPITIS

Some stimuli of short duration, such as cutting dentin may cause short-term vasodilation and a reversible increase in vessel wall permeability. More severe stimuli and a greater degree of cell damage cause more marked vasodilatation and the movement of polymorphonuclear leukocytes into the injured tissues. These acute inflammatory reactions are usually limited to the odontoblast and subodontoblastic regions adjacent to the dentinal tubules involved. Odontoblastic nuclei may be displaced into the tubules, due to either increased local tissue pressure or dentinal fluid during the injury. It is reversible, if the etiological factors are removed. Repair involves the return to normal tissue fluid dynamics, exit of polymorphonuclear leukocytes from the area and the re-differentiation of odontoblasts if they have damaged. The pulpal tissue after repair is usually less vascular, more fibrous and less cellular than before and may be less able to withstand a subsequent insult.

Odontogenic Infection and Pulp Pathology

If stimuli are not removed, pulpal damage can overwhelm the system and spread progressively to apical portion of pulp. This will result in pulpal necrosis.

Causes Mechanical cause: It includes traumatic accident, iatrogenic damage for dental procedure, attrition, abrasion. Thermal cause: It may cause through uninsulated metallic restoration, during cavity preparation, polishing. Chemical cause: It arises from erosion or inappropriate use of acidic dental material. Bacterial cause: It can damage the pulp through the toxins secreted by bacteria from caries.

Clinical Features Reversible Pulpitis It is a mild-to-moderate inflammatory condition of the pulp caused by noxious stimuli in which the pulp is capable of returning to un-inflamed state following removal of the stimuli. Pulp hyperemia: It is the earliest form which is sometimes known as pulp hyperemia. There is excessive accumulation of the blood within the pulp tissue leading to vascular congestion. Symptoms: It is characterized by sharp pain lasting for a moment. It is more often brought on by cold than hot food or beverages and by cold air. It does not occur spontaneously and does not continue when the cause has been removed. Tooth responds to electric pulp testing at lower current.

i.e. change of position, exacerbates the pain which is due to change in intrapulpal pressure. Referred pain: Patient may complain of pain referred to adjacent teeth to the temporal region or sinuses when an upper posterior tooth is involved, or to the angle, when lower posterior tooth is affected. In later stages, pain is more severe and is generally described as boring, gnawing or throbbing or as if tooth is under constant pressure. Patient is often awake at night due to pain. Pain is increased by heat and is sometimes relieved by cold, although continued cold may intensify the pain.

Chronic Hyperplastic Pulpitis It is also called pulp polyp or pulpitis aperta. It is essentially an excessive, exuberant proliferation of chronically inflamed dental pulp tissue. It occurs due to long standing low grade infection. Mechanical irritation from chewing and bacterial infection often provides the stimuli. Teeth involved: Teeth most commonly involved are deciduous molars and first permanent molars as they have an excellent blood supply because of a large root opening, and this coupled with high tissue resistance and reactivity in young person’s accounts for unusual proliferative properties of the pulp tissue. It is asymptomatic and it is seen only in teeth of children and young adults. Appearance: Polypoid tissue appears as a fleshy, reddish pulpal mass filling most of the pulp chamber or cavity or even extending beyond the confines of the tooth (Fig. 22.1). Sometimes, mass if large enough interferes with

Irreversible Pulpitis It is a persistent inflammatory condition of the pulp, which may be symptomatic or asymptomatic and is caused by a noxious stimulus. Symptoms: In early stages of irreversible pulpitis, a paroxysm of pain may be caused by the following: sudden temperature changes like cold, sweet and acid foodstuffs. The pain often continues when the cause has been removed and it may come and go spontaneously. Nature of pain: Pain is sharp, piercing or shooting and is generally severe. It may be intermittent or continuous, depending on the degree of pulpal involvement and depending on whether it is related to an external stimulus. Figure 22.1 Chronic hyperplastic candidiasis showing reddish The patient may also state that bending over or lying down pulpal mass

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comfortable closure of teeth. Polypoid tissue is less sensitive than normal pulp tissue and more sensitive than the gingival tissue. 544

Signs and symptoms: It may cause discomfort during mastication, due to pressure of food bolus. This tissue bleeds easily because of rich network of blood vessels. The tooth may respond feebly or not at all to the thermal test. There is presence of squamous covering as a result of grafting of exfoliated epithelial cells from adjacent oral mucosa.

Histopathological Features (Figs 22.2 to 22.4) It may range from hyperemia to mild-to-moderate inflammatory changes to the area of the involved dentinal tubules such as dentinal caries. Microscopically one sees involved reparative dentin, disruption of the odontoblastic layer, dilated blood vessels, extravasation of fluid (edema) and the presence of immunological response. Chronic inflammatory cells predominate. In some cases acute inflammatory cells can also be seen. In irreversible pulpitis the postcapillary venules become congested and affect the circulation within the pulp, causing pathologic changes such as necrosis. These necrotic areas attract polymorphonuclear leukocytes by chemotaxis and start an acute inflammatory reaction. After phagocytosis, the polymorpho-nuclear leukocytes, which have a short life span, die and release lysosomal enzymes. The lysosomal enzymes lyse some of the pulpal stroma and together with the cellular debris of the dead polymorphonuclear leukocytes form purulent exudates (pus). The inflammatory reaction produces micro-abscess (acute pulpitis). The pulp trying to protect itself walls off the areas of the micro-abscess with fibrous connective tissue. The surrounding pulp tissue exhibits fibrosis and mixture of plasma cells, lymphocytes and histiocytes. In some cases within a few days, the acute inflammation spreads to involve most of the pulp so that neutrophilic leukocytes fill the pulp. The entire odontoblastic layer degenerates. As pulp is closed, there is rise in pressure and the entire pulp tissue undergoes rapid disintegration, forming numerous small abscesses. Eventually the entire pulp undergoes liquefaction and necrosis which is called acute suppurative pulpitis.

Figure 22.2 Necrosis of pulp in pulpitis

Figure 22.3 Pulp hyperemia showing cellular infiltrate and

inflammatory cells

Figure 22.4 Pulp hyperemia showing many dilated blood

vessels and necrotic area in the center

Odontogenic Infection and Pulp Pathology

In chronic hyperplastic pulpitis the surface of the pulp polyp is covered by stratified squamous epithelium. Such epithelium may be derived from gingiva or freshly desquamate epithelial cells of the oral mucosa or tongue. The tissue in the pulp chamber is often transformed into granulation tissue which projects from the pulp into the carious lesion. The granulation tissue is a young vascular tissue containing polymorphonuclear neutrophils, lymphocytes and plasma cells. The granulation tissue may become epithelized as a result of implantation of epithelial cells on its surface. Granulation tissue is made up of delicate connective tissue fibers interspersed with a variable number of small capillaries. Inflammatory cell infiltration chiefly lymphocytes and plasma cells are also seen.

Points to Remember Stimuli of short duration, mechanical cause, thermal cause, chemical cause, bacterial cause: • •

•

• Clinical Differences between Reversible and Irreversible Pulpitis The pain of irreversible pulpitis is more severe and lasts longer. In reversible pulpitis, the cause of pain is generally traceable to a stimulus such as cold water or air whereas in irreversible pulpitis, the pain may come without any apparent stimulus.

Management Prevention is the best management for it. It is done by periodic care, early insertion of a filling if a cavity has developed. Removal of noxious stimuli should be done. In early stages pulpotomy (removal of the coronal pulp) and placing material that favors calcification such as calcium hydroxide over the entrance of root canals. Root canal filling with inert material like gutta percha should be done. Complete removal of the pulp or pulpectomy and placement of an intracanal medicament to act as a disinfectant or obtundent such a cresatin, eugenol or formacresol is carried out in irreversible pulpitis. In case of hyperplastic pulpitis elimination of polypoid tissue, followed by extirpation of the pulp is done. After removing the hyperplastic tissue bleeding can be controlled by pressure. Extraction of tooth can also be done.

•

Reversible pulpitis: Mild noxious stimuli, pulp hyperemia, sharp pain lasting for a moment, brought on by cold Irreversible pulpitis: Paroxysm of pain, sudden temperature changes like cold, pain often continues cause has been removed and it may come and pain is sharp, piercing or shooting, referred pain, later stages, pain is more severe, patient is often awake at night due to pain Chronic hyperplastic pulpitis: Pulp polyp, pulpitis aperta, polypoid tissue appears as a fleshy, reddish pulpal mass filling most of the pulp chamber, discomfort during mastication Histopathological features: Hyperemia, mildto-moderate inflammatory changes, disruption of the odontoblastic layer, dilated blood vessels, extravasation of fluid (edema), chronic inflammatory cells predominate, polymorphonuclear leukocytes by chemotaxis, lysosomal enzyme, microabscess, chronic hyperplastic pulpitis, stratified squamous epithelium, delicate connective tissue fibers interspersed with a variable number of small capillaries Management: Removal of noxious stimuli, pulpotomy, pulpectomy, elimination of polypoid tissue.

PULP DEGENERATION Degeneration is usually present in older aged people. It is a result of persistent, mild irritation in teeth of younger people.

Clinical Features In early stages, there are no symptoms and no clinical findings. As degeneration progresses, the tooth may become discolored and the pulp within does not respond to stimuli.

Types Calcific degeneration: A part of pulp tissue is replaced by calcific material that is pulp stones and denticles are formed. The calcific material has a laminated structure like

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546

the skin of an onion and lies unattached within the body of pulp. In another type of calcification the calcified material is attached to the wall of the pulp cavity and is an integral part of it which is called diffuse calcification. Atrophic degeneration: It is observed in older people. The pulp tissue is less sensitive than normal. Fibrous degeneration: It is characterized by replacement of the cellular element by fibrous connective tissue. On removal from the root canal, the pulp has the characteristic appearance of a leathery fiber (Fig. 22.5). Pulp artifacts: Vacuolization of the odontoblasts was once thought to be a type of pulp degeneration characterized by empty spaces formally occupied by odontoblasts. It is an artefact caused by poor fixation of the tissue specimen. Tumor metastasis: It is rare except possibly in the terminal stages. It may occur due to direct local extension from the jaw. Points to Remember No symptoms, no clinical findings, calcific degeneration, atrophic degeneration, fibrous degeneration, pulp artifacts, tumor metastasis.

PULP CALCIFICATIONS Various forms of pulp calcifications are found within the pulp which may be located in the pulp chamber or in the root canals. It can occur in any sex and in any teeth in the dental arch.

Figure 22.5 Fibrosis of pulp seen as replacement of cellular

element by fibrous connective tissue

Etiology There is no clear-cut etiology. There is strong association between chronic pulpitis and presence of pulpal calcification. But pulp calcification can be found in unerupted teeth. Extremely high percentage of pulp stones yield pure growth of streptococci on culture but often the affected teeth are normal. Sundell Schematic Presentation Local metabolic dysfunction = trauma = hyalinization of injured cells = vascular damage = thrombosis = vessels wall damage = fibrosis = minerlization (nidus formation) = growth = pulp stone Classification of Pulp Stone • Denticle • Pulp stones – True - Free - Attached – False - Free - Attached • Interstitial

Classification There are of following types: Denticle: It occur due to epitheliomesenchymal interaction within developing pulp. They develop during the formation and root and form before completion of primary dentin. So denticle will become attached to or embedded in the dentin. Pulp stone: Also called pulp nodules. It is of following types: ∙ True: They are made of localized masses of calcified tissue that resembles dentin due to their tubular structure. Tubules are irregular and few in number. It is more common in pulp chamber than root canals. They are subdivided into: – Free: It lies entirely within pulp tissue and is not attached to the dentinal wall. – Attached: These are continuous with the dentinal wall. ∙ False: It is composed of localized mass of calcified material and they do not exhibit dentinal tubules. Nodule appears to be made up of concentric layers

Odontogenic Infection and Pulp Pathology

∙

or lamellae deposited around a central nidus. It is composed of cells around which laid down is a layer of reticular fibers that subsequently calcifies. They are again classified as free or attached. They are larger than true denticles and they may fill nearly the entire pulp chamber. Interstitial: As the concentric deposition of calcified material continues it approximates and finally is in apposition with the dentinal wall where it may be surrounded by secondary dentin then it is called an interstitial pulp stone.

Diffuse linear calcification: It is also called calcific degeneration. It is amorphous unorganized linear strands or columns parallel with blood vessels and nerves of pulp. It contains fine fibrillar irregular calcification.

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Figure 22.6 Radiopaque pulp stone seen in the pulp chamber

Clinical and Radiographic Significance As such they have very little clinical significance. Usually it is discovered on the radiograph only as radiopacity. Sometimes, it may cause pain from mild pulpal neuralgia to severe excruciating pain resembling that of tic douloureux as the denticle can impinge on the nerve of the pulp. Difficulty may be encountered in extirpating the pulp during root canal therapy. In some cases pulp calcification may become large enough to interfere with root formation which may lead to periodontal destruction and tooth loss. In some condition like dentin dysplasia (type II), tumoral calcinosis, calcinosis universalis and Ehlers Danlos syndrome you may observe calcification. Radiographic features: It is radiopaque on the resultant radiograph. It can be seen hanging in pulp chamber or it is attached to wall of pulp chamber (Fig. 22.6).

Histopathological Features (Figs 22.7 to 22.9) Denticle consists of tubular dentin which surround central nest of epithelium. After some time it degenerated and tubules undergo necrosis. Pulp stone shows central amorphous mass of calcification which is surrounded by concentric lamellar rings. In some cases fibrillar irregular calcified material can be seen at the periphery of pulp stone. Diffuse calcification consists of fine fibrillar and irregular calcification which developed in pulp chamber and canals. This is deposited in linear fashion.

Figure 22.7 Pulp calcification

Management No treatment is necessary as tooth is asymptomatic. Care should be taken while undergoing root canal therapy for tooth having pulp stone. Points to Remember Discovered on the radiograph, difficulty during root canal therapy, periodontal destruction, radiopaque on the resultant radiograph, denticle consists of tubular dentin, pulp stone, central amorphous mass of calcification, diffuse calcification consists of fine fibrillar and irregular calcification.

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Liquefaction necrosis: It results when proteolytic enzymes convert the tissue into softened mass, liquid or amorphous debris. 548

Clinical Features It causes no painful symptoms. Sign: Discoloration of the tooth is the first indication that the pulp is dead (Fig. 22.10). The tooth with partial necrosis can respond to thermal changes owing to presence of vital nerve fibers passing through the adjacent inflamed tissue. History of severe pain lasting from a few minutes to a few hours, followed by complete and sudden cessation of pain. Figure 22.8 Pulp calcification (Courtesy: Dr Sangamesh

Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

Histopathological Features Necrotic pulp tissue, cellular debris and microorganisms may be seen in the pulp cavity. The periapical tissue may be normal or slight evidence of inflammation of the apical periodontal ligament may be seen.

Management Preparation and obturation of root canals should be carried out. Points to Remember Discoloration of the tooth, history of severe pain, necrotic pulp tissue, cellular debris, microorganisms, obturation of root canals. Figure 22.9 Diffuse calcification presented as linear strands

NECROSIS OF PULP It is the death of pulp. It may be partial or total depending on whether a part or the entire pulp is involved. It is sequelae of inflammation and can also occur following trauma, in which the pulp is destroyed before an inflammatory reaction.

Types Coagulation necrosis: The soluble portion of tissue is precipitated or is converted into a solid material. Caseation is a form of coagulation necrosis in which the tissue is converted into a cheesy mass consisting chiefly of coagulated proteins, fats, and water.

Figure 22.10 Necrotic pulp showing discoloration of tooth

Odontogenic Infection and Pulp Pathology

CRACKED TOOTH SYNDROME The term cracked tooth syndrome (CTS) refers to an incomplete fracture of a vital posterior tooth that involves the dentine and occasionally extends into the pulp. Parafunctional habits such as bruxism are also associated with the development of this condition.

Clinical Features Age: The condition presents mainly in patients aged between 30 and 50 years.

Bite test: Crack can be confirmed by selective biting pressure using a cotton roll or a small wooden stick to allow selective localization of such pressure. Pain increases as the occlusal force increases, and relief occurs once the pressure is withdrawn.

Management It is treated by splinting of the offending cusp with a cusp protecting restoration or by removing the split cusp and then restoring the tooth. Points to Remember

Location: Mandibular second molars, followed by mandibular first molars and maxillary premolars. Symptoms: Patient complains of pain ranging from mild to excruciating, at the initiation or release of the biting pressure. It can mimic the condition as severe as trigeminal neuralgia. A crack may involve enamel and dentine only or it may also involve the pulp and symptoms will vary accordingly (Fig. 22.11). Pain occurs due to fluid movement within the dentinal tubules causing stimulation of sub-odontoblastic nerve fibers. The fluid movements are induced by pressure changes when biting with the offending cusp. Sign: If the crack involves dental pulp, direct bacterial invasion will occur with predictable pulpal inflammation and resultant pulpitic pain. Fiberoptic examination: Close examination of the crown of the tooth may disclose a crack in enamel, which may be better visualized by using a dye or by trans-illuminating the tooth with fiberoptic light.

Mandibular second molars, pain ranging from mild to excruciating, fluid movements are induced by pressure change, fiberoptic examination, bite test, splinting of the offending cusp.

PERIAPICAL ABSCESS An abscess is a localized collection of pus, surrounded by an area of inflamed tissue in which hyperemia and infiltration of leukocytes is marked.

Bacteriology Staphylococci are frequently associated with abscess formation. They produce the enzyme called coagulase which causes fibrin deposition and thus helps in walling off the lesion. Coagulase promotes virulence by inhibiting phagocytosis. Small pockets of necrotic tissue are formed within cellulites, which coalesce and enlarge, compressing the surrounding fibrous connective tissue. Thus an abscess is generated, which is a collection of pus surrounded by a wall of fibrous connective tissue.

Types ∙ ∙

Acute periapical abscess: It is also called acute alveolar abscess. Chronic alveolar abscess: It is a long standing, low grade infection of the periradicular tissues.

But as this acute and chronic process both have acute inflammatory reaction so this term may be wrong to used. Instead it should be used as symptomatic and asymptomatic.

Etiopathogenesis Figure 22.11 Cracked tooth syndrome

It may be result of trauma or chemical or mechanical irritation. The immediate cause is the bacterial invasion of

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dead pulp. When inflammatory response may extend into adjacent periapical alveolar bone, it will initiate necrosis of periapical tissue and diffuse rarefaction of bone, leading to formation of periapical abscess with symptoms of acute inflammation. Primary or necrotic abscess are pulpo-periapical inflammatory conditions associated with teeth, which have not developed apparent periapical radiolucent lesion; usually described as acute apical periodontitis or acute periapical abscess. The surrounding tissue attempt to localize the pyogenic infection by forming enclosure of granulation tissue; this in turn is surrounded by fibrous connective tissue; this results in well circumscribed lesion containing necrotic tissue. Well circumscribed lesion may form sinus due to inability of the body to completely contain or localized the causative organisms, increase in number of causative organisms, lowering of patient’s general resistance and trauma or surgical intervention. Enlarging dentoalveolar abscess contains purulent material that is under pressure due to the production of pus— the purulent material travels along path of least resistance, until it reaches the surface, where due to limitation of periosteal layer, it temporally forms subperiosteal abscess. Eventually, it erodes through the periosteum and penetrates the soft tissue, again, following the path of least resistance. Path of least resistance is determined by the location of breakthrough in the bone and the anatomy of muscles and fascia plane in the area.

Clinical and Radiological Features

The tissues at the surface of swelling appear taut and inflamed. The surface of tissue become distended from the pressure of underlying pus and finally ruptures due to pressure and lack of resistance caused by continued liquefaction. When the maxillary anterior teeth are involved, swelling of upper lip may extend to one or both eyelids. When the maxillary teeth are involved, the cheek may swell to an immense size, distorting the patient’s face. It may results in buccal space infection (Fig. 22.12). When the maxillary posterior teeth are involved, there is possibility of maxillary sinus to involvement. When the mandibular posterior teeth are involved, swelling of the cheek may extend to ear. Sudden decrease in pain signals the formation of sinus. Tooth is tender, vitality test is negative. Draining fistulas are also commonly associated with chronic alveolar abscess. Majority opens on labial and buccal aspect of alveolus, as apices of both maxillary and mandibular teeth are located nearer to the buccal than the lingual cortical plate. In maxilla, roots of lateral incisors and molars are close to palatal cortical plate, so sinus appear there (Fig. 22.13). Most root tips lie below the mylohyoid muscle, so pus drains into the submandibular space. Sinus opening appears as a small ulcer. At the opening of sinus mass of inflamed granulation tissue is found, it is called parulis or gum boil. Occasionally, after temporary emphysema, sinus heals and form slightly raised pale papule. As the pus accumulates, another signs formation may take place eventually.

Symptoms: Pain is severe and of throbbing type. Periapical abscess may confine to osseous structures and during the early period of abscess formation, may cause excruciating pain without observable swelling. The patient may appear pale, irritable and weak from pain, loss of sleep as well as from absorption of septic products. He may have slight fever (99 to 100°F). Sign: Patients experience sensitivity or pressure in the affected area. Ice relives the pain and heat intensifies it aspiration yield yellowish pus. The tooth becomes more painful, appears elongated and mobile. In acute periapical infection, tooth is sensitive to percussion and movement. There is also painful lymphadenopathy. After some period the affected pulp is necrotic and does not respond to electric current or to application of cold. Swelling is usually seen in adjacent tissues adjacent to the affected tooth.

Figure 22.12 Periapical infection from tooth which involve

buccal space

Odontogenic Infection and Pulp Pathology

Fibroblast may start to form capsule at the periphery. Sinus tract are generally lined by granulation tissue. In addition, chronic inflammatory cells are also present.

Management

Figure 22.13 Intraoral swelling seen on palatal side in patient

Establish drainage immediately, if possible: It may be done by opening the pulp chamber and passing file through the canal into the periapical region. Trephination opening through mucosa and bore to the abscess at apex. Through and through drain is placed in the abscess and irrigated with 1:1 mix of 3 percent H2O2 and normal saline solution. Antibiotics like Penicillin 500 mg, QID, for 5 days and analgesics should be given. In 24 to 48 hours, it can be determined if the tooth can be treated endodontically or extraction is necessary. Warm saline mouth rinse often aid in localizing the infection and maintaining adequate drainage, before endodontic treatment or extraction. If there is need of retention of offending tooth, necrotic pulp should be opened and tooth should be treated endodontically. Points to Remember

Figure 22.14 Periapical loss of bone due to periapical

abscess

Radiological features: There is loss of lamina dura with destruction of bone in periapical area (Fig. 22.14)

Staphylococci, acute periapical abscess, chronic alveolar abscess, bacterial invasion of dead pulp, pain is severe throbbing type, pale, irritable and weak from pain, painful lymphadenopathy, tooth becomes more painful, appears elongated, tissues at the surface of swelling appear taut, sudden decrease in pain signals the formation of sinus, draining fistulas, parulis or gum boil, there is loss of lamina dura with destruction of bone, polymorphonuclear leukocytes, inflamed connective canal appears to be devoid of tissue macrophages and granulation tissue, fibroblast, establish drainage immediately, antibiotics, warm saline mouth rinse.

Histopathological Features

PERIODONTAL ABSCESS

Central region of necrosis contain dense accumulation of polymorphonuclear leukocytes, surrounded by inflamed connective tissue wall of varying thickness. Acute abscess contain necrotic and unidentical soft tissues. There is an empty space, where suppuration has occurred. The root canal appears to be devoid of tissue and instead, microorganism and debris may be observed. In case of chronic condition macrophages and granulation tissue are present. Lymphocytes and plasma cells are found at the periphery of the abscessed area.

It is usually culmination of a long period of chronic periodontitis.

Causes Many cases of periodontitis arise in the patients who are going periodontal therapy due to incomplete removal deep of calculus. There is also microbial penetration of surrounding tissue. Other factors which can cause periodontal abscess are diabetes, trauma, enamel pearls.

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tissue, as the epithelial lining of the crevice has been destroyed by the inflammatory process. It usually occurs in pre-existing periodontal pocket. When There is also large colonies of microorganism can also such pocket reaches sufficient depth of about 5 to 8 mm, the be present. soft tissues, around the neck of the tooth may approximate the tooth so tightly that orifice of the pocket is occluded. Management Bacteria multiply in the depth of pocket and cause sufficient irritation to form an acute abscess, with exudation of pus Incision and drainage: Primary treatment for relief of into this area. It results in sufficient swelling to destroy the acute symptoms is incision of the fluctuant abscess, from the depth of the abscess cavity to the gingiva. The incision cortical plates of bone. should extend into the soft tissues of the root surface. If the surrounding tissue is normal, the tooth may be retained and Clinical and Radiological Features debridement of the root surface by removal of granulation It starts at the gingival crevice and extends down on one or tissue should be done. more surface of the root, frequently as far as apical region. Treatment for new attachment and new tissue Symptoms: Acute episode usually has sudden onset with regeneration should be performed. However, if the roots extreme pain. There is also distension and discomfort. are denuded beyond the apical thirds of the root, the tooth Signs: They are associated with swelling of the soft tissues should be extracted and curettage should be carried out to overlying the surface of the involved root (Fig. 22.15). remove the granulation tissue from the socket. Tooth is tender and mobile. Pus usually exudes from the Antibiotics: Antibiotics of choice is penicillin. gingival crevice. Other features includes lymphadenopathy, fever, Points to Remember leukocytosis, foul taste. Incomplete removal deep of calculus, sudden onset with Radiographic features: There is bone loss associated extreme pain, soft tissues overlying the surface of the with affected teeth. In some cases infection can spread to involved root, lymphadenopathy, fever, leukocytosis, periapical region causing periodontal-endodontic lesion. foul taste, bone loss associated with affected teeth, central cavity filled with pus walled off on one side by Histopathological Features the root, large colonies of microorganism, incision and It consist of a central cavity filled with pus walled off on drainage, new attachment and new tissue regeneration, one side by the root and on the other side by connective antibiotics.

ACUTE EXACERBATION OF A CHRONIC LESION It is an acute inflammatory reaction superimposed on an existing chronic lesion, such as on cyst or granuloma. It is also called phoenix abscess due to mythical bird that would die only arise again from its own ashes.

Causes

Figure 22.15 Swelling in soft tissue due to periodontal

abscess

The peri-radicular area may react to noxious stimuli form a diseased pulp with chronic peri-radicular disease. At times, because of an influx of necrotic product from a diseased pulp or because of bacteria and there toxins, this apparently dormant lesion may react and cause an acute inflammatory response.

Odontogenic Infection and Pulp Pathology

Clinical Features Symptoms: At the onset, tooth may be tender to touch. Patients complain of intense pain, local swelling and possibly associated cellulitis. Signs: Mucosa over the radicular area may be sensitive to palpation and may appear red and swollen. The patient has history of traumatic accident that turned the tooth dark after a period of time or of postoperative pain in a tooth that had subsided until the present episode of pain. Lack of response to vitality test points to diagnosis necrotic pulp. Radiological features: There is radiolucency seen at the apex of tooth (Fig. 22.16).

Histopathological Features Area of liquefaction necrosis with disintegrating polymorphonuclear neutrophils and cellular debris is seen. These are surrounded by infiltration of macrophages and some lymphocytes. These abscesses can maintain soft tissue component.

Management Drainage, either via the root canal or by incision, if there is localized swelling. Antibiotics and analgesic: Appropriated antibiotics and analgesic should be given.

Points to Remember Phoenix abscess, tooth may be tender to touch, mucosa over the radicular area may be sensitive to palpation, lack of response to vitality test, radiolucency seen at the apex of tooth, area of liquefaction necrosis, disintegrating polymorphonuclear neutrophils, drainage, antibiotics and analgesic.

PERIAPICAL GRANULOMA It is the most common type of pathologic radiolucency encountered in dentistry. It is a growth of granulation tissue continuous with the periodontal ligament resulting from the death of the pulp and diffusion of bacteria and bacterial toxins from the root canals into the surrounding periradicular tissues through the apical and lateral foramina.

Etiopathogenesis It occurs as a response to intense and prolonged irritation from infected root canals producing extension of chronic apical periodontitis beyond the periodontal ligament. The expanding inflammation and increased vascular pressure result in abscess formation and resorption of the bone in the affected area, which in cause of time is replaced by granulation tissue. It is the result of a successful attempt by the periapical tissues to neutralize and confine the irritating toxic product that is escaping from the root canal. But continuous discharge into the periapical tissues induces a vascular inflammatory response. Insult from diseased pulp represents broad spectrum of inflammatory mediations like prostaglandins, kinin and endotoxins. Elevated level of IgG in pulpoperiapical lesion.

Clinical and Radiological Features The tooth is nonvital, i.e. it does not respond to thermal and electric pulp test. Symptoms: Mild pain can be occasionally experienced while biting or chewing on solid foods. Sensitivity occurs due to hyperemia, edema and inflammation of the apical periodontal ligament.

Figure 22.16 Phoenix abscess seen as radiolucency in

relation to first molar

Sign: Tooth may be darker in color, because of the blood pigments that diffuse into the dentinal tubules. There is, seldom, swelling or expansion of the overlying cortical bone. Tooth may feel to be slightly elongated in the socket.

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Radiological features: The lesion is radiolucent well circumscribed less than 1.5 cm in diameter. Margin are well defined usually but in some cases it can be ill defined (Fig. 22.17). Types of Granuloma According to Histopathology • • • •

Exudative Granulomatous Granulofibrosis Fibrous.

Histopathological Features (Fig. 22.18) It consists of proliferating endothelial cells capillaries, young fibroblasts minimum amount of collagen and

occasionally, nests of odontogenic epithelium, Russell’s bodies (scattered eosinophilic globules of gamma globulin), pyronine bodies (cluster of lightly basophilic particles), foam cells and cholesterol clefts. New capillaries are lined by swollen endothelial cells. There is more inflammation in the center with fibrosis at the periphery. Connective tissue is more prominent on the periphery and the bundles of collagen become condensed there, apparently as a result of the slow expansion of the soft tissue mass, resulting in formation of a continuous capsule separating the granulation tissue from the bone. Epithelial rest of Malassez may be seen with granulation tissue. Lymphocytes, plasma cells, macrophages and foreign body multinucleated giant cells may also be present. Occasionally, cholesterol clefts may form the major portion; then it is called as cholesterol granuloma of the jaw.

Management Extraction of the involved tooth should be done. Under certain conditions, root canal therapy, with or without subsequent apicectomy are the treatment options. NSAID should be given in periapical granuloma for combating inflammation. Reason for Failure of Treatment

Figure 22.17 Periapical granuloma showing well defined

radiolucency less than 1.5 cm in diameter

• • • • • • • •

Transforming into cyst Persistent pulpal infection Extraradicular infection Accumulation of endogenous debris Periapical foreign material Fibrous scar formation Maxillary sinus involvement Periodontal disease.

Points to Remember Growth of granulation tissue, nonvital tooth, mild pain, tooth may be darker in color, radiolucent well circumscribed less than 1.5 cm in diameter, proliferating endothelial cells capillaries, Russell’s bodies, pyronine bodies, foam cells, cholesterol clefts, more inflammation in the center, epithelial rest of Malassez, multinucleated giant cells, cholesterol granuloma.

Periapical Scar Figure 22.18 Periapical granuloma

It is a possible end point of healing. It is composed of dense fibrous tissue and is situated at the periapex of pulp

Odontogenic Infection and Pulp Pathology

less tooth, in which usually, the roots canal have been successfully filled.

Formation of Scar Irritant substance confined in the periapical area. It leads to accumulation of chronic inflammatory cells. Young fibroblasts, endothelial cells and capillaries proliferate, which lead to granuloma formation. After endodontic treatment, the granuloma resolves, but in some cases, granulation tissue gets slowly organized with the production of more and more collagen fibers, which in turn leads to scar formation.

Clinical Features

Points to Remember After endodontic treatment, tooth is nonvital, periapical radiolucency, spindle shaped fibroblast, hyalinization.

OSTEOMYELITIS It is the inflammation of the bone marrow that produces clinically apparent pus and secondarily affects the calcified components. It is infection of the bone that involves all the three components viz. periosteum, cortex and marrow. It may be defined as an inflammatory condition of the bone that begins as an infection of medullary cavity and the haversian system and extends to involve the periosteum of the affected area.

It occurs usually after endodontic treatment and in patients treated by periapical curettage or root resection. It is more common in anterior region of maxilla. Tooth Predisposing Factors is nonvital and the patient is asymptomatic. Certain predisposing factors play an important role in the Radiologically periapical radiolucency is seen (Fig. onset and severity of the osteomyelitis, in addition to the 22.19). virulence of microorganism.

Histopathological Features It will show spindle shaped fibroblast scattered throughout the dense collagen bundles, which show advanced degree of hyalinization.

Management No treatment is necessary for this periapical scar.

Conditions affecting host resistance: Diabetes mellitus, tuberculosis, severe anemia, leukemia, agranulocytosis, acute illness such as influenza, scarlet fever, typhoid and exanthematous fever, sickle cell anemia, malnutrition and chronic alcoholism. Conditions affecting jaw vascularity: Metastasis from remote area of infection such as another bony site, skin and kidneys, radiation, osteoporosis, osteopetrosis, fibrous dysplasia, bone malignancy and peripheral vascular disease. Etiology of Osteomyelitis • • • • • •

Odontogenic infections Compound fractures of the jaws Traumatic injury Middle ear infection and respiratory infection Furunculosis of chin Peritonsillar abscess.

Etiology Odontogenic infections which can be periapical or periodontal infection, pericoronal infection and infection from infected dental cyst. Figure 22.19 Periapical scar seen as radiolucency at the apex of central incisor (Courtesy: Dr RN Modi, Professor and Head, Department of Oral Medicine and Radiology, Hitkarini Dental College, Jabalpur, Madhya Pradesh, India)

Compound fractures of the jaws: Generally, these fractures are compound through the tooth socket into the mouth and rarely, to the skin.

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Traumatic injury: Local traumatic injury of the gingiva rise to increased intra-medullary pressure, which results leads to periostitis, in patients with low resistance to in compression of vasculature, vascular collapse, venous infection and later to osteomyelitis. stasis and ischemia. 556

Middle ear infection and respiratory infection: Via hematogenous route, either from middle ear infection or from infection of the upper respiratory tract.

Elevation of periosteum: Pus travels through the Haversian and Volkmann’s canals and accumulates beneath the periosteum, elevating it from the cortex, thereby further reducing the blood supply.

Furunculosis of chin: Furunculosis of chin, i.e. spread Necrosis of bone: The reduced blood supply leads to slow through lymphatic channel via infected lymph nodes. necrosis of the bone. Peritonsillar abscess: Peritonsillar abscess has also been reported to cause osteomyelitis of the ramus of Penetration of periosteum: If the pus continues to accumulate the periosteum is penetrated and mucosal and mandible. cutaneous fistulae develop and thereby discharging the Pathogenesis of Osteomyelitis purulent pus. Compromised blood supply = inflammatory reaction = After therapy: As the therapy begins to be effective and disorganization of clot = mechanical trauma = the host resistance increases, the process become chronic. accumulation of pus = elevation of periosteum = necrosis Inflammation regresses, granulation tissue forms and of bone = penetration of periosteum = involucrum = new blood vessels are formed which cause lysis of bone; sequestra = cloacae = systemic spread of infection = thus causing fragments of necrotic bone from the viable necrosis of bone. bone.

Pathogenesis Compromised blood supply is a critical factor in the establishment of osteomyelitis. The virulent microorganisms get entry in the medullary cavity via many routes like odontogenic infections, compound fractures, periostitis, hematogenous route and lymphatic channel. Inflammatory reaction: These microorganisms cause intense inflammatory reaction within the marrow of the bone. Pain is a feature of this stage. Localization of infection: Most of the odontogenic infections, like periapical and periodontal infections, are localized by pyogenic membrane or soft tissue abscess walls. Disorganization of clot: However, disorganization of this pyogenic membrane occurs by virulent microorganism or by chronic movement of the unreduced fractures of jaws. Mechanical trauma: Mechanical trauma, due to chronic movement of unreduced fractures, burnishes the bone and causes ischemia, thereby introducing the microorganisms deep into the underlying tissues. Accumulation of pus: When this protective barrier breaks, the pus accumulated in the medullary cavity gives

Involucrum: Small sections of necrotic bone may be completely lysed, while large one get localized and get separated from the shell of the new bone by a bed of granulation tissue. This dead bone surrounded by viable bone is called involucrum. Sequestra: Small pieces of necrotic bone are called as sequestra, which are avascular and which harbor microorganisms. These sequestra need to be removed, otherwise they continue to be chronically infected and infect the surrounding granulation tissue and cause further sequestration, which weakens the bone and may cause pathologic fracture. Cloacae: An involucrum contains one or more holes on the surface which lead into channels, which can be traced to end in the depth of the bone at the site of an area of bone destruction around the sequestrum. These orifices are termed ‘cloacae’. Pus finds its way from the depth of the bone to the surface, through the cloacae. The presence of cloacae indicates that there is a dead bone or a foreign body at the deep end. Systemic spread of infection: Besides the pathogenic activity of the virulent microorganisms, these microorganisms precipitate thrombi formation by virtue of their destructive lysosomal packages. The coagulum

Odontogenic Infection and Pulp Pathology

provides the host medium for further pathogenic proliferation as well as an isolating barrier from the host immune response. It also allows systemic spread of infection. Necrosis of bone: The necrosis of bone is brought about by thrombosis of the vessels or compression of the vasculature. The necrosis of bone, with superadded infection forms a base line pathogenesis of the osteomyelitis. Compression of neurovascular bundles can result in osteomyelitis mediated anesthesia.

Occurrence It is more common in men, than women. It occurs in mandible in premolar area because cortical plate of the bone in mandible is dense it takes longer for sinus formation and release and hence, the infection gets directs into spongiosa and spreads. Other reason for occurrence in mandible are removal of posterior mandibular teeth attended by more damage to the bone, mandible is less vascular than maxilla and thin cortical plates and relative paucity of medullary tissue in the maxilla precludes confinement of infection within the bone and permits dissipation of edema and pus into the soft tissues and paranasal sinuses. Infantile osteomyelitis is more common in maxilla than mandible, as it spreads by hematogenous route and maxilla has more blood supply than mandible. Microbiology of Osteomyelitis Staphylococcus aureus and Staphylococcus albus, hemolytic streptococci, gram negative organisms like Klebsiella, Pseudomonas, Proteus, E. coli. Anaerobic microorganisms like pepto-streptococci, Bacteroides and fusobacteria. Some specific forms like Mycobacterium tuberculosis, Treponema pallidum and A. israelii. Following parameters should be used for recognition of pure anaerobic or mixed anaerobic infection: ∙ ∙ ∙ ∙

Presence of foul smelling exudate. Sloughing of necrotic tissues or gas in the necrotic tissue. Gram stain revealing multiple organisms of different morphological character. Presence of sequestra.

Classification According to anatomic location of infectious process: • Intra-medullary • Sub-periosteal • Periosteal According to duration and severity: • Acute • Chronic Depending upon the presence or absence of suppuration: Suppurative • Acute suppurative osteomyelitis • Chronic suppurative osteomyelitis – Primary – Secondary Infantile osteomyelitis Nonsuppurative • Chronic nonsuppurative – Focal sclerosing – Diffuse sclerosing • Radiation osteomyelitis • Garre’s sclerosing osteomyelitis • Osteomyelitis due to specific infection: – Actinomycosis – Tuberculosis – Syphilis. Clinical Staging of Osteomyelitis • Initial stage: Spontaneous pain (localized). • Acute stage (Suppurative stage): In this stage, there is severe pain, soreness and looseness of the involved teeth. – Early acute stage: In reference to the involved tooth, progressive sensitivity of the adjacent teeth to percussion and pain of the involved side – Late acute stage: Paresthesia or anesthesia of the lip region supplied by the mental nerve. Other systemic symptoms can occur. • Osteonecrotic stage: Diminished spontaneous pain, abscess formation and pus discharge. • Sequestrum stage: Lack of symptoms sequestrum formation visible on the radiograph.

ACUTE SUPPURATIVE OSTEOMYELITIS It is serious sequelae of periapical infection there is often a diffuse spread of infection throughout the medullary

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spaces, with subsequent necrosis of variable amount of bone. There is insufficient time for body to react to the presence of inflammatory infiltrate. This process is of less than one month of duration.

Clinical Features In early acute suppurative osteomyelitis: It has rapid onset and course, severe pain, paresthesia or anesthesia of the mental nerve. At this stage the process is truly intramedullary, therefore swelling is absent, teeth are not mobile and fistulae are not present. In established suppurative osteomyelitis: In this type there is deep intense pain, anorexia, fetid oral odor malaise and fever, regional lymphadenopathy. There is also soreness of involved teeth which become loose within 10 to 14 days. Pus exudes around the gingival sulcus or through mucosal and cutaneous fistula. There is firm cellulitis of cheek and abscess formation with localized warmth and tenderness on palpation. The patient feels toxic and dehydrated.

Figure 22.20 Necrotic bone seen in case of osteomyelitis

Radiological features: The radiograph shows ill defined radiolucency. In some cases periosteal new bone formation can be seen. Sequestration can be seen as radiopaque structure in the radiolucency.

Histopathological Features It usually consists of necrotic bone. The medullary spaces are filled with inflammatory exudate that may or may not progress to the actual formation of pus (Figs 22.20 and 22.21). The inflammatory cells are chiefly neutrophilic polymorphonuclear leukocytes, but may show occasional lymphocytes and plasma cells. The osteoblastic rimming of the bony trabeculae is generally destroyed. Depending upon the duration or the process, the trabeculae may loose their viability and begin to undergo slow resorption. The periphery of the bone and haversian canals contains necrotic debris with acute inflammatory infiltrate.

Management Antibiotics therapy: If abscess formation is seen antibiotics medication like aqueous penicillin, clindamycin, cephalexin, cefotaxime, tobramycin and gentamicin. Incision and drainage: When early diagnosis is made, drainage of the fluctuant areas should be carried out under

Figure 22.21 Acute suppurative osteomyelitis showing inflammatory infiltrate (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

antibiotic cover. After pus is evacuated, drains are placed. The consistency, color and odor of the pus may provide important clues to the diagnosis and initial treatment. Points to Remember Rapid onset and course, paresthesia or anesthesia of the mental nerve, deep intense pain, anorexia, fetid oral odor, pus exudes around the gingival sulcus, cellulitis of cheek, ill defined radiolucency, necrotic bone, inflammatory exudate, neutrophilic polymorphonuclear leukocytes, lymphocytes, plasma cells, trabeculae may loose their viability, haversian canals contains necrotic debris, antibiotics therapy, incision and drainage.

Odontogenic Infection and Pulp Pathology

CHRONIC SUPPURATIVE OSTEOMYELITIS Chronic osteomyelitis develops without initial acute stage, if the virulence is of low grade. Chronic osteomyelitis is persistent abscess of the bone that is characterized by usual complex inflammatory process including necrosis of mineralized and marrow tissues, suppuration, resorption sclerosis and hyperplasia. It occurs as defensive response lead to production of granulation tissue which forms dense scar tissue to wall of infection.

Clinical Features Virulence of the microorganism is low and the host resistance is high. This type is not preceded by an episode of acute symptoms.

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Figure 22.23 Extraoral discharging sinus in osteomyelitis

Symptoms: It has insidious onset with slight pain, slow increase in jaw size and a gradual development of sequestra without fistula. Signs: Local tenderness and swelling develop over the bone in the area of abscess. Intraorally and extraorally sinus develops intermittently and drains small amount of pus and then gradually heals. Sinus extends from medullary bone, through cortical plate, to mucus membrane or skin. Sinus may be at a considerable distance from the offending infection. It is painless unless there is an acute or sub-acute exacerbation (Figs 22.22 and 22.23). Involvement is single feeder vessels may lead to necrosis of entire quadrant of jaw in long standing chronic osteomyelitis.

Figure 22.24 Sequestra seen as radiopaque structure in

osteomyelitis

Radiographic features: It shows patchy, ragged and illdefined radiolucency which contain central radiopaque sequestra. Surrounding bone show increase radiodensity (Fig. 22.24).

Histopathological Features There is significant soft tissue component which consist of inflamed fibrous connective tissue in areas of intertrabecular bone. Scattered sequestra and pockets of abscess formation are common (Figs 22.25 and 22.26).

Management Figure 22.22 Exposed bone seen clinically as sequestra

It is difficult to manage by drugs as dead bone and organism are surrounded by wall of fibrous connective tissue.

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Supportive therapy: Patients is suffering from osteomyelitis required adequate rehydration in the form of fluids. Rich nutritional diet should be given. Multivitamin supplements should be given.

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Sequestrectomy: It is the removal of sequestra which are small pieces of necrotic bone that are avascular and harbor microorganisms. Saucerization: It means excision of the margins of necrotic bone, overlying the focus of osteomyelitis which allows better visualization of sequestra and excision of margins of the affected bone.

Figure 22.25 Suppurative osteomyelitis showing

inflammatory cells

Decortication: Decortication of mandible refers to removal of the chronically infected and inferior cortical plates, 1 to 2 cm beyond the area of involvement. Thus, access is provided to the medullary cavity. Hyperbaric oxygen therapy: In this patient is placed in multiplace/monoplace chamber and a concentration of 100 percent O2 is given. Duration of treatment is of 1.5 to 2 hours for 5 to 6 days in a week, for a total of 60 treatments. Points to Remember Slight pain, slow increase in jaw size, local tenderness, intraorally and extraorally sinus, shows patchy, ragged and ill defined radiolucency, soft tissue component which consist of inflamed fibrous connective, scattered sequestra, pockets of abscess formation, antibiotics, irrigation and debridement of the necrotic areas, extraction of offending tooth, supportive therapy, sequestrectomy, saucerization, decortications, hyperbaric oxygen therapy.

Figure 22.26 Chronic suppurative osteomyelitis seen as

scattered sequestra and pockets of abscess formation

Antibiotics: These are similar to used in case acute osteomyelitis. Irrigation and debridement of the necrotic areas— thorough debridement of the affected areas should be carried out. Debride any foreign bodies, necrotic tissue or sequestra. These areas may be irrigated with hydrogen peroxide and saline.

INFANTILE OSTEOMYELITIS It is a rare type of osteomyelitis seen in infants few weeks after the birth. It usually involves the maxilla.

Route of Infection Hematogenous route: Infantile osteomyelitis is usually transferred through the hematogenous route. Trauma: Prenatal trauma of oral mucosa from obstetrician’s finger.

Extraction of offending tooth: Extraction of carious teeth Infection: Infection from mucous bulb used to clear the with periapical infection, should be done. It should be airway immediately after birth. carried out to remove the source of infection from the oral cavity. Infected nipple: Infected human or artificial nipple.

Odontogenic Infection and Pulp Pathology

Clinical Features Location: It is more common in maxilla due to hematogenous route. The infection is thought to arise in maxillary antrum or lacrimal sac. It appears to center in the region of first deciduous molars and the adjacent portion of maxilla, although it may involve the inferior aspect of the orbit. Symptoms: There is fever, anorexia and dehydration. In some cases, convulsions and vomiting may occur. Signs: There is redness and edema of eyelids, alveolar bone and palate of the affected side. Intracanthal swelling, palpebral edema, conjunctivitis and proptosis may result. Maxilla on affected side is swollen both buccally and palatally, especially in the molar region. Sinus develops and discharges pus intraorally and extraorally. Complications may occur like TMJ infection and devitalization of adjacent tooth germs may occur. Points to Remember Hematogenous route, common in maxilla, fever, anorexia and dehydration, redness and edema of eyelids, alveolar bone, intracanthal swelling, complications may occur like TMJ infection.

Radiographic features: Increase radiodensity seen around sites of chronic infection. This area can be multifocal involving the entire quadrant.

Histopathological Features It shows dense irregular trabeculae of bone, some of which are bordered by an active layer of osteoblasts. The bone, in some lesions, shows a pronounced ‘mosaic’ pattern, indicative of repeated periods of resorption followed by repair. The haversian canals are scattered with little marrow spaces. The soft tissue between the individual trabeculae is fibrous and show proliferative fibroblasts and occasional small capillaries focal collections of lymphocytes and plasma cells. Polymorphonuclear leukocytes may be present, if the lesion is undergoing an acute phase. Necrotic bone surrounded by inflamed granulation tissue.

Management Resolution of infection—this will help in remodeling in some patients. If secondary osteomyelitic occur in patients with long term alveolar resorption, the patient should be treated in same way as that of acute and chronic osteomyelitis.

Diffuse Sclerosing Osteomyelitis

Points to Remember

Reactive proliferation of bone is the primary response in diffuse sclerosing osteomyelitis due to a balance between the virulence of infection and resistance of host. It is analogous to focal form of the disease. It occurs due to low grade infection. This term should be used when an obvious infectious process directly responsible for sclerosis of bone. In this chronic bacterial infection of intraosseous nature creates mass of chronically granulation tissue which incites sclerosis of bone.

Reactive proliferation of bone, mandibular jaw, complains of pain and tenderness, jaws may be slightly enlarged, increase radiodensity, mosaic pattern, haversian canals are scattered, proliferative fibroblasts, capillaries focal collections of lymphocytes, polymorphonuclear leukocytes, resolution of infection.

Clinical and Radiological Features Age and sex distribution: It can occur at any age but most common in older persons. It has got no sex predilection.

Primary Chronic Osteomyelitis It gets often confused with chronic suppurative osteomyelitis. In this case association with bacterial infection is not so obvious and suppuration and sequestration is absent. This condition does not respond long term antibiotics therapy.

Clinical and Radiological Features

Location: It is common especially in mandibular jaw in an Location: It is isolated process seen in the mandible. edentulous area. Symptoms are very mild to absent. During the period of Age: It is seen in two peaks one seen in adolescence and growth the patient complains of pain and tenderness. Pain other in adults after 5th decade. persists for few weeks to months to even years. Symptoms: Recurrent pain, swelling, local induration and Signs: Jaws may be slightly enlarged on the affected side. limited mouth opening is present.

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Sign: Regional lymphadenopathy and reduce sensation in the distribution of inferior alveolar nerve can be seen. 562

Fascial asymmetry: It is seen and takes year to resolve secondary to slow remodeling. Radiographic features: It demonstrated areas of radiolucent osteolysis mixed with zone of sclerosis. Osteolytic area are not continuous and alternate with zones of sclerosis. Bone is thickened with periosteal reaction which is more solid as compared to laminated proliferate periostitis of inflammatory origin.

Histopathological Features In the areas of sclerosis irregular trabecular of pagetoid bone are present with prominent reversal line, osteoblastic rimming and focal areas of osteoclastic activity. Intra-trabecular fibrosis with scattered lymphocytes and plasma cells is present. Other features include microabscess formation, hyalinization around small blood vessels and subperiosteal bone formation also occurs.

muscle mainly masseter and digastric. Many people believe that this is variation of primary chronic osteomyelitis in which parafunctional habits exacerbate. Microbiological culture is negative in chronic tendoperiostitis.

Clinical and Radiological Features Age: It is more commonly seen in 3rd and 4th decade of life. Symptoms: Recurrent pain, swelling of cheek and trismus are present. Radiological features: Sclerosis is usually found on the anterior region of mandibular angle and posterior portion of mandibular body. These are the area where attachment of masseter and digastric muscle occur. In the area of sclerosis radiolucent zone appear. There is erosion of inferior border of mandible occur.

Histopathological Features

Management

There is sclerosis and remodeling of the cortical and subcortical bone with increase in bone volume.

Elimination of infection should be carried out.

Management

Surgical decortication: It should be done and it will help decrease the intensity and frequency of symptoms.

Treatment should be done to resolution of muscle overuse. It should be done by muscle relaxation, rotation exercise, occlusal splint therapy, myofeedback and muscle relaxant drug like diazepam and mefenoxalon should be used.

IV bisphosphonates: IV bisphosphonates like alendronate, disodium clodronate and pamidronate can results in complete disappearance of pain and dramatic suppression bone turnover. Other drugs like corticosteroids, NSAIDs and calcitonin can also help in relieving the symptoms. Points to Remember Recurrent pain, swelling local induration, regional lymphadenopathy, Fascial asymmetry, radiolucent osteolysis mixed with zone of sclerosis, trabecular of pagetoid bone, intra-trabecular fibrosis, microabscess formation, hyalinization around small blood vessels, subperiosteal bone formation, surgical decortications, IV bisphosphonates.

Points to Remember Reactive alternation in bone, overuse of masticatory muscle, recurrent pain, swelling of cheek and trismus, sclerosis, sclerosis and remodeling of the cortical and subcortical bone with increase in bone volume, muscle relaxation, rotation exercise, occlusal splint therapy, myofeedback.

SYNOVITIS, ACNE, PUSTULOSIS, HYPEROSTOSIS AND OSTEOMYELITIS SYNDROME

It consists of synovitis, acne, pustulosis, hyperostosis and osteomyelitis. Clinical presentation of chronic tendoperiostitis is similar Cause of SAPHO syndrome is not exactly known, but it that of primary chronic osteomyelitis. is thought to be genetic in origin. There is abnormal immune It occur due to reactive alternation in bone occur due response to microorganism cross reacts with normal bone to parafunctional habits. There is overuse of masticatory or joint leading to variety of clinical manifestation.

Chronic Tendoperiostitis

Odontogenic Infection and Pulp Pathology

This syndrome occurs usually younger than 60 years of age. Osteolytic area are scattered randomly within areas of sclerotic bone. Bones involved are anterior chest wall, clavicles, ribs, spine, pelvis, and long bone. Periosteal new bone formation is also present which leads to enlargement of affected bone. After some days bone become more sclerotic with less periosteal apposition resulting in decrease in size of the bone. External bone resorption and deformity of the mandible are characteristic of these syndrome.

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Points to Remember Synovitis, acne, pustulosis, hyperostosis, osteomyelitis, osteolytic area are scattered randomly, periosteal new bone formation, external bone resorption and deformity of the mandible.

CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS It is chronic recurrent multifocal osteomyelitis. In this there is involvement of multiple bones and it is widespread variant primary chronic osteomyelitis. There is metachronous involvement of multiple bone like clavicle, humerus, radius, femur, or tibia. Mandibular involvement in CRMO occur in less than 10 percent of cases.

Focal Sclerosing Osteomyelitis (Condensing Osteitis) It is nonsuppurative inflammatory condition often seen in dentulous jaw. When the resistance of the alveolar bone to odontogenic infection is high or the virulence of the organisms is low, a chronic condition characterized by the formation of focal areas of sclerosis around the roots of the teeth can possibly result. There is deposition of new bone along the existing trabeculae, a process known as appositional bone deposition.

Clinical and Radiological Features Age: It occurs almost in young person before the age of 20 years. Location: The tooth commonly affected is mandibular first molar with a large carious lesion. It is associated with nonvital teeth or in teeth undergoing the process of degeneration.

Figure 22.27 Condensing osteitis seen as increase

radiodensity

Symptoms: Tooth is usually asymptomatic. But in some cases, patient may report pain or tenderness on percussion or palpation. Radiological features: There is uniform zone of increase radiodensity in the periapical area of tooth (Fig. 22.27). There is also widening of periodontal ligament space.

Histopathological Features It appears as an area of dense bone with trabeculae borders lined by osteoblasts. Chronic inflammatory cells, plasma cells and lymphocytes are seen in the scanty bone marrow.

Management Endodontic therapy: Endodontic therapy should be carried out. Points to Remember Formation of focal areas of sclerosis around the roots of the teeth, mandibular first molar with a large carious lesion, asymptomatic, uniform zone of increase radiodensity, osteoblasts, chronic inflammatory cells, plasma cells, lymphocyte, endodontic therapy.

Osteomyelitis with Proliferative Periostitis It is also called periostitis ossificans. There is bone formation within periosteal reaction. It is characterized by formation of hard bony swelling at the periphery of the jaw. It is essentially a periosteal osteosclerosis analogous to the endosteal sclerosis of chronic, focal and diffuse sclerosing osteomyelitis.

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Initially it was called Garre’s osteomyelitis by the reported case in literature by Carl Garre in 1893. It has been stated that he stated case report with inflammatory periosteal hyperplasia demonstrating the onion skin like reduplication of cortical plate. But has Garre does not have specimen and at that time X-rays are not discovered. So use of this term should be discarded and it should be called osteomyelitis with proliferative periostitis. These types of lesion occur when periosteum possesses high potential for osteoblastic activity, infection is mild, and there is fine balance between resistance of host and number and virulence of organisms.

Causes It is cause by dental caries, fracture, buccal bifurcation cyst, and nonodontogenic infection.

Clinical and Radiological Features

Figure 22.28 Osteomyelits with proliferative periostitis

Management

Age and sex distribution: It occurs mainly below 30 Removal of cause: Extraction of offending tooth or endodontic therapy should be done. years; males are affected more commonly than females. Location: Most frequently involve the anterior surface of tibia and femur. Mandible is affected more commonly than maxilla. It commonly occurs at the inferior border of mandible, in first molar region.

Points to Remember Periostitis ossificans, hard nontender swelling with medial and lateral expansion of jaw, secondarily infected discomfort, lymphadenopathy, hyperpyrexia, radiopaque lamination of bone parallel to each other, supracortical and sub-periosteal mass, osteoblasts bordering many of the trabeculae, trabeculae arranged parallel to each other, retiform fibrous, diffuse or patchy sprinkling of lymphocytes, removal of cause.

Sign: It is presented as hard nontender swelling with medial and lateral expansion of jaw. Mass varies in size from 1 or 2 cm to the involvement of the entire length on the affected side. Cortex may become 2 to 3 cm thick. It may become secondarily infected and cause considerable discomfort. Lymphadenopathy, hyper pyrexia and leukocytosis are common findings. Radiation Osteomyelitis Radiological features (Fig. 22.28): There is radiopaque lamination of bone which runs parallel to each other. The radiolucent separation is seen between new bone and original cortex. Within new bone area of small sequestra osteolytic radiolucencies is present.

Histopathological Features The supracortical and sub-periosteal mass is composed of much reactive new bone and osteoid tissue, with osteoblasts bordering many of the trabeculae. These trabeculae often are oriented perpendicular to the cortex, with the trabeculae arranged parallel to each other or show a retiform pattern. The connective tissue between the bony trabeculae is rather fibrous and shows a diffuse or patchy sprinkling of lymphocytes and plasma cells.

It is an infection of the irradiated bone.

Etiopathogenesis After exposure to radiation (40 to 80 Gy), bone undergoes marked decreased in vascularity. Such bone has poor defensive process and susceptible to traumatic injury. It draws infection from extraction wound and infected pulp, severe periodontitis and denture stomatitis. It will cause death of bone cells and result in progressive obliterative arteritis. This results in aseptic necrosis of the portion of bone directly in beam of radiation, with compromised vascularity in the adjacent bone. Pathogenic organisms are introduced into this irradiated bone through odontogenic infections, compound fractures of the jaws and mucosal lacerations. The organisms most commonly found are Staphylococcus

Odontogenic Infection and Pulp Pathology

These enzymes break down fibrin, connective tissue ground substance and cellular debris, thus facilitating rapid spread of bacterial invaders. In some cases cellulitis of face can occur secondary to Clinical Features infection from dens evaginutus teeth. It occurs with a triad of radiation, trauma and infection. At least 50 percent of facial cellulitis cases in the Effective response to infection becomes markedly pediatric population have been reported to be caused by odontogenic infections. diminished. aureus, Staphylococcus epidermidis. Higher incidences in jaw are recorded due to higher degree of infections and frequent trauma to these bones.

Location: It is common in mandible than maxilla as irradiation is often directed to mandible. Sex distribution: It is common in males due to their probable involvement in traumatic events and increased risk of oral cancer. Symptoms: Intense pain and facial fistula develop from the subperiosteal tissues. Spread is diffuse and throughout with signs of inflammation and swelling.

Management It is directed at control of infection and penicillin is the antibiotic of choice. Points to Remember Common in mandible, intense pain, and facial fistula, penicillin.

CELLULITIS

Clinical Features Sign and symptoms: There is widespread swelling, redness and pain without definite localization. There is presence of tenderness on palpation. Tissues are grossly edematous (Fig. 22.29). There is marked induration, hence tissues are firm to hard on palpation. Tissues are often discolored; temperature is elevated with malaise and lethargy. Usually massive cellulitis will ultimately suppurate, particularly if bacteria are staphylococcal. Depending upon the location and proximity to anatomic structures that guide the progress, the pus may evacuate into nose, maxillary sinus, oral vestibule, floor of mouth, infra-temporal fossa and into fascial spaces (Fig. 22.30). Infections arising in maxilla perforate the outer cortical layer of bone, above the buccinators attachment and, cause swelling of upper half of face. If infection in mandible perforates the outer cortical palate, below the buccinators attachment, there is diffuse

It is also called Phlegmon. Occasionally, the infectious process progresses out of the bone, despite the use of supportive therapy and the patient develops cellulitis, either in vestibular region or extraorally. It is a potential complication of acute dental infection. Cellulitis may be defined as a nonsuppurative inflammation of the subcutaneous tissues extending along the connective tissue planes and across the intercellular spaces. If improperly managed, cellulitis of the head and neck region can lead to more severe systemic complications including sepsis, airway obstruction, central nervous system involvement and mortality.

Bacteriology and Causes The alpha hemolytic streptococci are the classic etiologic agent. They produce enzymes like streptokinase and hyaluronidase.

Figure 22.29 Patient having cellulitis showing swelling on left side

face which involving submandibular space, pterygomandibular space

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tooth and specific antibiotic cover bring about resolution of the process. Antibiotics like clindamycin was administered intravenously.

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Points to Remember Phlegmon, widespread swelling, redness and pain, tissues are grossly edematous, marked induration, temperature is elevated, pus may evacuate into nose, maxillary sinus, oral vestibule, floor of fascial spaces, swelling of upper half of face, diffuse swelling of the lower half of face, diffuse exudation of polymorphonuclear leukocytes, occasional lymphocytes, surgical incision and drainage. Figure 22.30 Submandibular space infection causing cellulitis

swelling of the lower half of face, which then spreads superiorly as well as cervically. If maxillary tooth is involved, there may be redness of eye.

Laboratory Findings ESR and white blood cell count are raised.

Histopathological Features Diffuse exudation of polymorphonuclear leukocytes and occasional lymphocytes, with considerable serous fluid and fibrin, causing separation of connective tissue or muscle fibers. It presents only a nonspecific picture of diffuse acute inflammation.

Management Surgical incision and drainage: It is performed when the presence of pus is diagnosed. In case of large cellulitis, a superficial erythematous spot develops, which is pathognomonic of pus near the superficial surface. These superficial fluctuant areas can be incised and drained under local anesthesia. Usually ring block of peripheral skin, as a wheel is made for skin anesthesia. Knife is introduced in the most inferior portion of the fluctuant area. A small sinus forcep is introduced in the wound, opened in several directions and pus is drained. A rubber drain is placed in the deepest portion of the wound, so that just 12 cm lie above the source of the skin, where it is sutured. A large dressing is applied. When no superficial spot is present, fluctuance is more difficult to determine, particularly if deep pus is suspected. Usually, extraction of the offending

LUDWIG’S ANGINA It is a condition which was first described by Ludwig in 1936. The word angina means sensation of choking or suffocation. It is the most commonly encountered neck space infection.

Definition This condition may be defined as an overwhelming, rapidly spreading, septic cellulitis involving submandibular, submental and sublingual spaces bilaterally. Once infection enter submandibular space it can extent into lateral pharyngeal space and retropharyngeal space which later may spread into mediastinum. Etiology • • • • •

Odontogenic infection Trauma Sialadenitis Calculi Osteomyelitis.

Etiology Odontogenic infection: It is usually an extension of odontogenic infection from mandibular molar teeth into the floor of mouth. The 2nd and 3rd molars are the teeth most commonly involved. Trauma: It may also be caused by oral soft tissue laceration and punctured wounds of the oral floor. Sialadenitis: Submandibular gland sialadenitis and infected malignancy may be sometimes contributory to Ludwig’s angina.

Odontogenic Infection and Pulp Pathology

Calculi: Salivary calculi or from intravenous injection of the internal jugular vein, especially in drug abusers. Osteomyelitis: Osteomyelitis in compound mandibular fracture.

the roof of the mouth and the posterior pharyngeal wall; when this occurs, acute respiratory obstruction is likely to occur. Two large potential spaces at the base of the tongue are involved, i.e. submental and sublingual.

Woody tongue: Involvement of sublingual space results in elevation and posterior enlargement and protrusion of Streptococci are the most commonly reported organism tongue. This is called woody tongue. Floor of mouth appears erythematous and edematous. from the culture. Other microorganisms are a hemolytic streptococci, Bacteroides, Klebsiella, Fusiform bacilli and Stiffness in tongue movement generally develops. The patient develops a toxic condition and speech becomes E. coli. impaired. Clinical Features Larynx and glottis become edematous. As the disease continues the swelling starts involving the neck above the There are three typical appearances of Ludwig’s angina: level of hyoid which is called as bull neck. First: It is characterized by brawny indurations. Tissues The patient always has fever and there is considerable are board like and do not pit on pressure. No fluctuance salivation, as the patient is unable to swallow. There are is present. The tissues may become gangrenous and when chills accompanied with fever. There is an inability to cut, they have a peculiar lifeless appearance. A sharp swallow and to eat. limitation is present between the infected tissues and Respiratory distress is common. There is also neck surrounding normal tissues. pain, redness of neck, fever, weakness, fatigue, excessive Second: Three facial spaces are involved bilaterally, tiredness, confusion or other mental changes, difficult i.e. submandibular, submental and sublingual. If the breathing and earache. There is an intense pain on tongue involvement is not bilateral, the infection is not considered movement and the patient may be severely dehydrated, owing to inability to take anything by mouth. If the swelling a typical Ludwig’s angina. has spread into the pterygoid region, then there is difficulty Third: The mouth is open (Fig. 22.31) and the tongue is in opening the mouth. lifted upwards and backwards, so that it is pushed against

Bacteriology

Fatal Complications Respiratory obstruction: The infection of Ludwig’s angina tends to spread through the connective tissues which cover the small muscles of the larynx and between the muscles of the floor of mouth. The epiglottis and larynx become edematous along with the posterior aspect of the tongue. The tongue gets elevated and gets pressed upward and backward, causing pressure on the larynx. Therefore, dyspnea occurs in paroxysm. Ultimately, death occurs due to respiratory embarrassment.

Generalized Septicemia Erosion of the carotid artery: Late spread of infection to lateral pharyngeal space can also cause erosion of the carotid artery. Cavernous sinus thrombosis with subsequent meningitis may be sequelae of it. Figure 22.31 Patient of Ludwig angina showing typical open

mouth appearance

Others: Mediastinum extension, pharyngomaxillary space extension, osteomyelitis and airway obstruction.

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Prevention 568

Regular visits to the dentist and prompt treatment of oral/ dental infections can prevent the conditions that increase the risk of developing Ludwig’s angina.

Laboratory Findings A moderate leukocytosis is found. Fusiform bacilli and spiral forms, various staphylococci, diphtheria and may other microorganisms have been cultured on different occasions.

Management Intense and prolonged antibiotic therapy: Penicillin is to be administered IM or IV, in high doses, because it is the empirical antibiotic of choice and the oral flora, including most of anaerobes, are sensitive to it. Recently, combination of gentamicin and cloxacillin has been proved successful. Establishment and maintenance of an adequate airway are the essentials of therapy: Tracheostomy is a routine procedure, but it is often difficult to perform in the late stages. Attempt at blind intubations is often time consuming. Recently, successful intubations with fiberoptic laryngoscope have been introduced as a worthwhile technique in the therapy of Ludwig’s angina. In the late stage, cricothyroidotomy may be performed as an emergency procedure. Incision and drainage (Fig. 22.32): It is done for the release of tissue tension. A horizontal incision, midway

between the chin and hyoid bone, is a classic approach to surgical drainage of Ludwig’s angina. It may be carried out under local anesthesia. Supportive therapy: Parenteral hydration, high protein diet and vitamin supplements. Extraction of offending tooth. Points to Remember Streptococci, brawny indurations, tissues are board like, peculiar lifeless appearance, facial space, submandibular, submental and sublingual, mouth is open, woody tongue, floor of mouth appears erythematous, larynx and glottis become edematous, bull neck, respiratory obstruction, erosion of the carotid artery, cavernous sinus thrombosis, intense and prolonged antibiotic therapy, establishment and maintenance of an adequate airway are the essentials of therapy incision and drainage, supportive therapy.

FATAL COMPLICATIONS OF ORAL INFECTION Bacterial Meningitis It is the most common neurologic complication resulting from oral and maxillofacial infections. In this condition bacteria infect arachnoid pia mater and CSF. The infection quickly spreads from its point of origin, via CSF, to the entire subarachnoid space.

Bacteriology Microorganisms responsible are Staphylococcus; Streptococcus, pneumococci, Proteus, Klebsiella and H. influenzae are common pathogens causing meningitis secondary to head and neck infection.

Clinical Features Symptoms: Patient complaint of headache, chills, fever and nausea, pain in back and stiffness of neck. Kernig’s sign: It is assessed with the patient lying supine, with the hip and knee flexed to 90 degrees. In a patient with a positive Kernig’s sign, pain limits passive extension of the knee.

Figure 22.32 Ludwig’s angina is drained surgically

Brudzinski’s sign: It occurs when flexion of the neck causes involuntary flexion of the knee and hip. Diagnosis is made by lumbar puncture and CSF examination.

Odontogenic Infection and Pulp Pathology

Management It is a medical emergency and prompt intravenous antibiotics should be started, after antibiotic sensitivity testing. Points to Remember Staphylococcus, Streptococcus, pneumococci, Proteus, Klebsiella, headache, chills, fever and nausea, pain in back, Kernig’s sign, Brudzinski’s sign intravenous antibiotics.

Brain Abscess It can develop from bacteremia associated with odontogenic infections.

Pathogenesis Once the bacteria’s reach the brain tissues. It results in local cerebritis. Inflammatory exudates collects along with degenerative leukocytes. Septic thrombosis of blood vessels occurs. Cerebral edema develops around the infected area. As the abscess grows, its center becomes pus filled with a capsule of granulation tissue at its periphery. As the abscess increases in size, it may rupture into the ventricular system and the result is usually fatal. If it extends to subarachnoid space, meningitis may develop.

Clinical Features Symptoms: Headache due to rise in intracranial pressure can occur. There is also nausea, convulsions and vomiting may occur. Signs: Dysphagia and visual defects, if it involves the temporal lobe. Papilledema and convulsions are common features. If abscess is present on motor cortex then patient will suffer from hemiparesis, and if abscess is in frontal lobe, confusion and stupor will occur. Diagnosis is made by radionuclide scanning and CT scanning.

Management Drainage of the abscess via catheter through a bur hole is the treatment of choice. Once the size of the abscess is decreased the complete capsule should be excised. Some surgeons prefer to do craniotomy initially and then excise the entire abscess.

Points to Remember Headache, dysphagia, visual defects, papilledema, hemiparesis, confusion and stupor, drainage of the abscess.

Cavernous Sinus Thrombosis It is one of the most dreaded and life-threatening complication due to intracranial spread of infection from odontogenic source.

Etiology The bacteria can reach cavernous sinus through anterior pathway, posterior pathway or direct extension. Anterior pathway: It results from maxillary anterior teeth, perforation of maxillary bone, canine space involvement formation of septic thrombus, it transfer from retrograde fashion from angular vein, inferior ophthalmic vein through inferior orbital fissure into cavernous sinus. Posterior pathway: Infection from maxillary premolar and molar, buccal and intratemporal space involvement, infection spread through emissary vein from pterygoid venous plexus to inferior petrosal sinus and cavernous sinus. Direct extension through skull, by an abscess located in deep spaces such as in intratemporal space. The direct antral infection may also give rise to this disease.

Bacteriology Many organisms have been found in culture of CSF including Pseudomonas, Corynebacterium, Staphylococcus albus, Streptococcus, Diplococcus pneumoniae and Proteus. Most common organism is Staphylococcus aureus.

Clinical Features Eye lesion: Proptosis or protrusion of eye is seen as a result of decreased venous drainage, chemosis and edema of eyelid, which is secondary to venous stasis. Limitation of extra-ocular movements occurs because of involvement of 3rd, 4th and 6th cranial nerves. Cranial nerve palsy of 3rd, 4th and 6th nerve is usually evident due to irritation caused by pressure of venous congestion. There is rapid progression of signs and symptoms from one eye to other eye, due to spread of infection through inter-cavernous sinus. Symptoms: There is high spiking fever, severe headache, stiffness of neck, ocular palsy and facial weakness.

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Investigations 570

Lumbar puncture should be made. CSF shows neutrophils, decreased glucose concentration and elevated protein concentration. Blood culture and sensitivity should be done.

Management Massive doses of antibiotics, with proper surgical intervention at the primary site of infection are essential. The initial drug of choice is IV chloramphenicol 1 gm, after every 6 hours. An attempt should be made to identify the causative organism by culture from the source of infection or from blood culture, so that precise antibiotic sensitivity can be established. Anticoagulant therapy to prevent further thrombosis and dissemination of septic emboli is given. Points to Remember Proptosis or protrusion of eye, cranial nerve palsy, high spiking fever, severe headache, neutrophils, decreased glucose concentration, IV chloramphenicol, anticoagulant therapy.

Odontogenic Infection of Orbit (Fig. 22.33) Odontogenic infection can spread to orbit through several routes. Infection of premolars and molars can perforate the maxillary buccal plate and can spread to pterygopalatine and infra-temporal fossa and reach the orbit, via inferior orbital fissure.

The maxillary anterior teeth can produce orbital cellulitis by retrograde spread through vessels like anterior facial, angular and ophthalmic vein. Progress of orbital infection posteriorly may involve the superior orbital fissure and spread to cavernous sinus via superior ophthalmic vein.

Clinical Features Sign and symptoms: It may result in temporary loss of visual acuity. Long term ophthalmologic sequelae include permanent loss in visual acuity, residual proptosis, diplopia and blindness. When later CNS is involved, hemiparesis, seizures and death have also been reported.

Management When orbital infection is suspected, early aggressive antibiotic therapy and surgical intervention, following appropriate consultation, should be initiated to prevent serious ocular complications and CNS involvement. Points to Remember Infection of premolars and molars temporary loss of visual, CNS, hemiparesis, early aggressive antibiotic therapy.

Mediastinitis It is usually a late complication of facial infection. The process occurs because it gives a pathway for spread of pus and infection from submandibular region, floor of mouth and from all the related spaces in neck, beneath the investing layer to deep cervical fascia. Following this pathway, infection can come into close relationship with trachea, larynx and great vessels and eventually reach the mediastinum. The most common anatomic pathway is lateral pharyngeal space, through visceral space inferiorly, which may occur causing weakening and rupture of pleura.

Clinical Features

Figure 22.33 Infection of orbit as a complication of

odontogenic infection

Symptoms: Usually there is chest pain and severe dyspnea with unremitting fever and evidence of swelling on the lateral aspect of neck of the affected side. Involvement of one or two facial spaces is usually preceded by these signs and symptoms. Progressive septicemia, mediastinal abscess, pleural effusion, empyema, compression of mediastinum veins

Odontogenic Infection and Pulp Pathology

with decreased venous return to heart and pericarditis may occur, with death as the final step. Hemorrhage secondary to erosion of internal carotid artery or one of its branches is the most common cause of death in deep space infection.

Management Utmost priority is to be given for airway control. In such cases, either emergency tracheostomy or cricothyroidectomy may be performed. Specific antibiotic therapy—in high doses intensive antibiotic therapy instituted. Surgical drainage of mediastinum should be done. Points to Remember Submandibular region, floor of mouth, lateral pharyngeal space, chest pain and severe dyspnea, progressive septicemia, hemorrhage secondary to erosion of internal carotid artery, tracheostomy or cricothyroidectomy, specific antibiotic therapy.

The progression of disease can be alarmingly rapid with skin color changing from red blue to gray in as early as 36 hours leading to frank cutaneous gangrene due to thrombosis of nutrient vessels, usually by 4th or 5th day. Skin bullae may develop, but lymph adenitis is usually not seen. Skin death subsequent to subcutaneous necrosis is common. Systemic complications such as neck organ involvement, pneumonia, pulmonary abscess, vascular erosion, venous thrombosis and cranial neuropathies occurs.

Histopathological Features The pathological changes of necrotizing fasciitis (NF) include thrombosis of blood vessels, suppuration and necrosis of the superficial fascia with subcutaneous fat.

Management

Spectrum of antibiotics should include drugs active against anaerobic organisms such as metronidiazole. Continuous wound care is of utmost important. Irrigation with hydrogen peroxide, followed by dressing of charcoal lime and boric acid solution soaked gauze should Necrotizing Fasciitis be applied. This condition was first recognized in 1924 by Meleney. It Hyperbaric oxygen therapy has been used, but its value is defined as rapidly progressing necrosis of subcutaneous is not proven. tissue and fascia, usually sparing the muscles and Blood transfusion and general supportive measures accompanied by toxicity, high fever and apathy. must be given. As soon as disease is controlled split skin It is multimicrobial infection which spread very quickly. graft should be applied, if necessary for reconstruction. Importance of Streptococcus pyogenes, a major cause of It is important that airway be maintained open, since severe necrotizing and fulminating infection, must not be they may be compromised as a result of inflammation. forgotten. Intubation may be difficult and tracheostomy may be It is characterized by the formation of large necrotic required. lesions and gas, located in the subcutaneous tissue and Points to Remember superficial fascia. As the disease progresses, muscles and skin involvement develop, giving rise to myonecrosis, that Multimicrobial infection, large necrotic lesions, tender passes through the infected fascia. erythematous cellulitis with ill defined margins, red Immunosuppressed states of peripheral vascular disease blue to gray, skin bullae, systemic complications such like diabetes mellitus have been reported the most common as neck organ involvement, pneumonia, thrombosis of predisposing factors. Other diseases which can cause are blood vessels, necrosis of the superficial fascia with malignancy, alcoholism. subcutaneous fat, metronidiazole, continuous wound care, hyperbaric oxygen therapy, blood transfusion.

Clinical Features

Symptoms: A tender erythematous cellulitis with ill ORAL FOCI OF INFECTIONS defined margins presents the patient with high fever and apathy. Pain can be severe, but the affected area of Infected periapical lesion: Particularly those of chronic skin becomes anesthetic, secondary to cutaneous nerve nature an area usually surrounded by the fibrous capsule, destruction, which can occur before clinical gangrene. which effectively walls off or separates the area of

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infection from the adjacent tissues but do not prevent the absorption of bacteria or toxins. Periapical granuloma has been described as a manifestation of vigorous body defense and repair reaction, while cysts merely a progressive form of granuloma. Abscess occurs when the reparative and defensive phase is minimum. Majority of investigators indicate that an unusually high percentage of periapical granuloma are the biologically sterile and for this reason the possibility such lesions giving rise to focal infection is minimum. Teeth with infected root canals: These are potential sources of dissemination of microorganisms and toxins. Most commonly it shows occurrence of a hemolytic Streptococcus; which is the most important in etiology of rheumatoid arthritis and rheumatic fever. Periodontal disease: It is equally significant as potential source of infection. The usual organism recovered is Streptococcus viridans. Simple massage of gingiva may result in transitory bacteremia. The rocking of teeth in their socket by forceps, before extraction, has been shown to favor bacteremia in patients who have periodontal disease. Due to pumping action during extraction microorganism may be forced from the gingival cervix into the capillary of gingiva as well as into the pulp of tooth and thus, will results in bacteremia. Oral prophylaxis may be followed by bacteremia. So it is mandatory to administer the antibiotics to the children who area diagnosed rheumatic or congenital heart disease; to prevent the positive consequences of bacterial endocarditis.

Significance of Oral Foci of Infection There are reports that the oral foci of infection either cause, or aggravate many systemic disorders. Most common are as follows: Arthritis: It is of mainly rheumatoid and rheumatic fever type. Arthritis of rheumatoid type is of unknown etiology. These patients have high antibody titer to group of hemolytic streptococci. It is tissue hypersensitive reaction. There are some points in favor of septic foci theory: streptococcal infection of throat, tonsils or nasal sinus may precede the initial or recurrent attack, dramatic improvement occurs sometimes after the removal of septic foci and temporary bacteremia may occur immediately after tonsillectomy, tooth extraction or after vigorous massage of gums. Against the theory, there are some points: often no infective focus can be found, usually when focus is extirpated, no dramatic

result is found and sulfonamide, antibiotics and vaccine have failed to produce desirable results. Valvular heart diseases: Sub-acute bacterial endocarditis is without doubt related to oral infections. There is close similarity, in most instances, between the etiologic agent of the disease and microorganisms in the oral cavity, dental pulp and in periapical lesions. Symptoms of subacute bacterial endocarditis have been observed in some instances shortly after extraction of teeth. Transient bacteremia frequently follows tooth extraction. Streptococci of viridans type cause majority of sub-acute bacterial endocarditis. After tooth extraction, there is streptococcal bacteremia, so there is occurrence of subacute bacterial endocarditis after dental operations, dental extractions. Premedication of the patient should be done before extraction. Gastrointestinal disease: Some workers state that constant swallowing of microorganisms might lead to variety of gastrointestinal diseases. Gastric and duodenal ulcers are produced by injection of streptococci. Ocular diseases: Factor supporting the hypothesis of Woods the role of foci of infection in ocular diseases. Many ocular diseases occur in which no systemic cause, other than presence of remote foci of infection can be demonstrated. Numerous instances of prompt and dramatic healing of ocular diseases are reported following the removal of these foci. Occasionally, sudden transient exacerbation is observed, after the removal of teeth and tonsils. Presence of blood stream infection in early stages of ocular disease, are evident. Iritis may be produced by intravenous injection of microorganisms, e.g. streptococci. There is some objection to these points, i.e. many healthy people have focal infections, but do no have ocular diseases, spontaneous care may occur if nothing is done and positive blood cultures are rare in acute iritis. Skin diseases: Some forms of eczema and possibly urticaria, can be related to oral foci of infection. If the relationship does not exist, the mechanism is probably sensitization, rather than metastatic spread of the microorganisms. Renal disease: Microorganism most commonly involved in urinary infection are E.coli, staphylococci and streptococci. Streptococci hemolyticus seems to be the most common. Streptococci are uncommon inhabitants of dental root canals or periapical and gingival areas. Since the microorganisms commonly involved in renal infection so it appear that there is little relationship between oral foci of infection and renal disease.

Odontogenic Infection and Pulp Pathology

DRY SOCKET It is also called alveolar osteitis and fibrinolytic alveolitis. It occurs due to disruption of clot which occur secondary to transformation of plasminogen to plasmin with lysis of fibrin and formation of kinin.

Cause (Fig. 22.34) Local factors like trauma, poor oral hygiene, traumatic extraction, use of oral contraceptive, and presurgical infection can lead to dry socket. Use of tobacco produce like smoking, also lead to dry socket. Heavy sucking, splitting and inadequate irrigation can also be causative organism.

Clinical Features Location: It is more commonly seen in mandibular posterior region. Age: It is usually seen in more in 3rd and 4th decade of life. Symptoms: There is severe pain, swelling can also occur. Some time pain radiated to ipsilateral ear, temporal region and eye. Sign: There is bare bony socket, after clot is lost. The bone is very sensitive to percussion. Lymphadenopathy is also present.

Management Irrigation: Irrigation of socket with the help of warm saline should be done. Home irrigation with chlorhexidine should be done by the patients.

Figure 22.34 Cause of dry socket

Analgesic: Potent analgesic should be given. Obtundent dressing: Dressing of idoform gauze with eugenol reduce the symptoms. This dressing should be change every 24 hours. Antibiotics: This should be place intra-alvolar. Antibiotics used are tetracycline, lincomycin, clindamycin and metronidiazole. Points to Remember Fibrinolytic alveolitis, severe pain, swelling, bare bony socket, sensitive to percussion, irrigation of socket, analgesic, obtundent dressing, antibiotics.

BIBLIOGRAPHY 1. Adekeye EO, Cornah J. Osteomyelitis of the jaw: a review of 141 cases. Br J Oral Maxillofac Surg. 1985;23:24-35. 2. Hadi Al, Hamasha A, Darwazeh O. Prevalence of pulp stones in Jordanian adults. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;86:730-32. 3. Allan BP, Egbert MA, Myall RW. Orbital abscess of odontogenic origin. Case report and review of the literature. Int J Oral Maxillofac Surg. 1991;20(5):268-70. 4. Antunes AA, de Santana Santos T, de Carvalho RW, et al. Brain abscess of odontogenic origin. J Craniofac Surg. 2011;22(6):2363-5. 5. Arsenault M, Anderson RD, Dyment H, et al. Facial cellulitis secondary to dens invaginatus: a case report. J Can Dent Assoc. 2010;76:a114. 6. Awing MN. The etiology of dry socket. Int Dent J. 1989;39:236-40. 7. Balternsperger M, Gratz K, Bruder E, et al. Is primary chronic osteomyelitis a uniform disease: proposal of a classification based on retrospective analysis patients treated in past 30 years. J Craniomaxillofac Surg. 2004;32:43-50. 8. Blum IR. Contemporary views on dry socket (alveolar osteitis) a clinical appraisal of standardization, Etiopathogenesis and management: a critical review. Int J Oral Maxillofac Surg. 2003;31:309-17. 9. Caso A, Hung LK, Beirne OR. Prevention of alveolar osteitis with chlorohexidine: a meta analytic review: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;99:155-59. 10. Christensen GJ. Tooth preparation and pulp degeneration. J Am Dent Assoc. 1997;128(3):353-4. 11. Colina M, Bettoli V, Pretolani S, et al. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome: Comment on the article by Zhao et al. J Dermatol. 2012;39(7):659-60. 12. Dahlen G. Microbiology and treatment of dental abscess and periodontal-endodontic lesions: periodontal 2000;28:206-39.

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13. Deng R, Yang X, Hao J. Effective medical treatment in patients with SAPHO syndrome involving the mandible: Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114(3):401-3. 14. de-Vicente-Rodríguez JC. Maxillofacial cellulitis. Med Oral Patol Oral Cir Bucal. 2004;9(Suppl:133-8), 126-33. 15. Dolan RW, Chowdhury K. Diagnosis and treatment of intracranial complication of paranasal sinus infection: J Oral Maxillofac Surg. 1995;53:1080-7. 16. Eliasson S, Halvarsson C, Ljungheimer C. Periapical condensing osteitis and endodontic treatment. Oral Surg Oral Med Oral Pathol. 1984;57:195-9. 17. Eufinger H, Machtens E. Purulent pansinusitis, orbital cellulitis and rhinogenic intracranial complications. J Craniomaxillofac Surg. 2001;29(2):111-7. 18. Eversole LR, Stone CE, Strub D. Focal sclerosing osteomyelitis/focal periapical osteopetrosis: a radiographic pattern. Oral Surg Oral Med Oral Pathol. 1984;58:456-60. 19. Eyrich GKH, Baltensperger MM, Bruder E, et al. Primary chronic osteomyelitis in childhood and adolescence: a retrospective analysis of 11 cases and review of literature. J Oral and Maxillofac Surg. 2003;61:561-73. 20. Farrier JN, Kittur MA, Sugar AW. Necrotising fasciitis of the submandibular region; a complication of odontogenic origin. Br Dent J. 2007;202(10):607-9. 21. Garatea-Crelgo J, Gay-Escoda C. Mediastinitis from odontogenic infection. Report of three cases and review of the literature. Int J Oral Maxillofac Surg. 1991;20(2):65-8. 22. Groot RH, van Merkesteyn JP, van Soest JJ, et al. Diffuse sclerosing osteomyelitis (chronic tendoperiostitis) of the mandible a 11 years follows up. Oral Surg Oral Med Oral Pathol. 1992;74:557-60. 23. Groot RH, van Merkesteyn JP. Bras Diffuse sclerosing osteomyelitis and florid osseous dysplasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;81:333-42. 24. Heyeraas KJ, Sveen OB, Mjor IA. Pulp dentin biology in restorative dentistry part 3-pulpal inflammation and its sequale: Quintessence Int. 2001;32:611-25. 25. Iwu CO. Ludwig angina: report of seven cases and review of current concept of management. Br J Oral Maxillofac Surg. 1990;28:189-93. 26. Kawai T, Hiranuma H, Kishino M, et al. Gross periostitis ossificans in mandibular osteomyelitis: review of the English language literature and radiographic variation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;82:376-81. 27. Kawai T, Murakami S, Sakuda M, et al. Radiographic investigation of mandibular periostitis ossificans in 55 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82:704-14. 28. Kenwood M, Seow WK. Sequelae of trauma to the primary dentition. J Pedod Spring. 1989;13(3):230-8.

29. Kim IK, Kim JR, Jang KS, et al. Orbital abscess from an odontogenic infection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(1):e1-6. 30. Koorbusch GF, Fotos P, Terhark K. Retrospective assessment of osteomyelitis: etiology, demographics, risk factors and management in 35 cases. Oral Surg Oral Med Oral Pathol. 1992;74:149-54. 31. Kuriyama T, Absi EG, Williams DW, et al. An outcome audit of the treatment of acute dentoalveolar infection: impact of penicillin: Br Dent J. 2005;198:759-63. 32. Lynch CD, McConnell RJ. The cracked tooth syndrome. J Can Dent Assoc. 2002;68(8):470-5. 33. Mathews DC, Sutherland S, Basrani B. Emergency management of acute apical abscess in the permanent dentition: a steminatic review of literature: J Can Dent Assoc. 2003;69:660-60i-661. 34. Meng HX. Periodontal abscess: Ann Periodontal 1999:4:7982. 35. Michaelson PL, Holland GR. Is pulpitis painful. Int J Endod. 2002;35:829-32. 36. Nair PN, Sjögren U, Figdor D, et al. Persistent periapical radiolucencies of root-filled human teeth, failed endodontic treatments, and periapical scars. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87(5):617-27. 37. Nair PNR, Pajarola G, Schroeder HE. Types and incidence of human periapical lesion obtained with extracted tooth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1993;81:93-102. 38. Neville BW, Damm DD, Allen CM, Bouquot JE, oral and maxillofacial pathology, 3rd edn, Saunder Elsevier, 2009. 39. Ogundiya DA, Keith DA, Mirowski J. Cavernous sinus thrombosis and blindness as a complication of odontogenic infection. J Oral Maxillofac Surg. 1989;47:1317-21. 40. Parekh S, Kyriazidon A, Bloch Zupan A, et al. Multiple pulp stone and shortned root of unknown etiology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;101:e139-42. 41. Roccia F, Pecorari GC, Oliaro A, et al. Ten years of descending necrotizing mediastinitis: management of 23 cases. J Oral Maxillofac Surg. 2007;65(9):1716-24. 42. Schofield ID, Abbott W, Popowich L. Osteoradionecrosis of maxillae. Oral Surg Oral Med Oral Pathol. 1978;45(5):692-5. 43. Schulz M, von Arx T, Altermatt HJ, et al. Histology of periapical lesions obtained during apical surgery Endod. 2009;35(5):634-42. 44. Selden HS. Radiographic calcification normal or abnormal- a paradox. J Endod. 1991;17:34-7. 45. Skouteris CA, Velegrakis G, Christodoulou P. Infantile osteomyelitis of the maxilla with concomitant subperiosteal orbital abscess: a case report. J Oral Maxillofac Surg. 1995;53(1):67-70.

Odontogenic Infection and Pulp Pathology 46. Suei Y, Taguchi A, Tanimoto K. Diagnosis and classification of mandibular osteomyelitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100:207-14. 47. Tlougan BE, Podjasek JO, O’Haver et al. Chronic recurrent multifocal osteomyelitis (CRMO) and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome with associated neutrophilic dermatoses: a report of seven cases and review of the literature. Pediatr Dermatol. 2009;26(5):497-505. 48. Toran KC, Nath S, Shrestha S. Odontogenic origin of necrotizing fasciitis of head and neck—a case report: Kathmandu University Medical Journal 2004;2(4):361-3.

49. Van Merkesteyn JPR, Bakker DJ, van Der Waal I, et al. Hyperbaric oxygen treatment of chronic osteomyelitis of the jaw. Int J Oral Surg. 1984;13:386-95. 50. Wood RE, Nortje CJ, Grotepass F, et al. Periostitis ossificans versus Garre’s osteomyelitis: part I: what did Garre really say? Oral Surg Oral Med Oral Pathol. 1988;65;773-7. 51. Yadav S, Verma A, Sachdeva A. Facial necrotizing fasciitis from an odontogenic infection. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113(2):e1-4. 52. Yamada T, Mishima K, Imura H, et al. Osteomyelitis of the mandible secondary to infantile osteopetrosis: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(6):e25-9.

MULTIPLE CHOICE QUESTIONS





1. ‘Phlegmom’ refers to: a. Ludwig’s angina c. Brain abscess

b. d.

Cellulitis Both a and b

2. Brawny indurations, board like tissues which do not pit on pressure is the classical feature of: a. Septicemia b. Cellulitis c. Ludwig’s angina d. Sinusitis 3. Pain in the area of eyeball, postnasal drip and stuffiness is the feature of: a. Cellulitis b. Septicemia c. Maxillary sinusitis d. Mediastinitis 4. Kernig’s and Brudzinski’s signs are positive in: a. Bacterial meningitis b. Necrotizing fasciitis c. Bacteremia d. Mediastinitis



5. Cranial nerve palsy of 3rd, 4th, 6th nerve is the clinical feature of: a. Cavernous sinus thrombosis b. Bacterial meningitis c. Bacteremia d. Maxillary sinusitis













6. Dilation of pulp vessels, edema fluid collection and hemoconcentration is the histopathological feature of: a. Chronic pulpitis b. Focal reversible pulpitis c. Pulp hyperemia d. Both b and c



7. Acute suppurative pulpitis where the entire pulp undergoes liquefaction and necrosis is the feature of: a. Acute pulpitis b. Reversible pulpitis c. Chronic pulpitis d. All of the above





8. Formation of granulation tissue and deposition of collagen on the surface of the pulp tissue in awide open exposure is called as: a. Pulp abscess b. Suppurative pulpitis c. Ulcerative pulpitis d. Pulp calcification



9. A productive pulpal inflammation due to an extensive carious exposure of a young pulp is: a. Pulpitis aperta b. Pulp polyp c. Chronic hyperplastic pulpitis d. All of the above 10. In pulp polyp the teeth most commonly involved are: a. Central incisors b. 2nd molars c. 1st molars d. Premolars 11. Localized mass of calcified material which do not exhibit dentinal tubules is: a. False denticle b. True denticle c. Attached denticle d. Free denticle 12. Cracked tooth syndrome can be confirmed by: a. Using a dye b. Fiber optic light c. Selective biting pressure d. All of the above 13. An acute inflammatory reaction superimposed on an existing chronic lesion is called: a. Acute periapical abscess b. Phoenix abscess c. Condensing osteitis d. None 14. The infection of bone that involves all the three components viz periosteum, cortex and marrow is called: a. Osteomyelitis b. Periapical granuloma c. Osteosclerosis d. Condensing osteitis 15. Scattered sequestra and pockets of abscess formation is the feature of: a. Radiation osteomyelitis b. Chronic suppurative osteomyelitis c. Garre’s osteomyelitis d. Periapical granuloma

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Bone Disease Manifested in Jaw Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe), Pranoti Pradhan

Chapter Outline Fibro-osseous lesions Classification Fibrous dysplasia Cherubism Central giant cell granuloma Paget’s disease Cemento-osseous dysplasia • Periapical cemento-osseous dysplasia • Florid osseous dysplasia • Focal cemento-osseous dysplasia  Familial gigantiform cementoma  Ossifying fibroma, cementifying fibroma and cementoossifying fibroma       Â

           Â

Juvenile ossifying fibroma Osteoporosis Infantile cortical hyperostosis Osteopetrosis Osteogenesis imperfecta Pierre Robin syndrome Marfan’s syndrome Down’s syndrome Achondroplasia Osteosclerosis Massive osteolysis Gardner’s syndrome

Bone is a dense calcified tissue which is specifically affected by a variety of disease that often causes it to react in a dynamic fashion. These diseases of bone may arise at any age; some are congenital and present at birth, while other develop in early childhood or in young adulthood.

tissue containing a newly formed mineralized tissue. Broadly they can be of the following categories: Developmental or hamartomatous lesions. Reactive or dysplastic lesions. Neoplasms.

FIBRO-OSSEOUS LESIONS

CLASSIFICATION

In it normal bone is replaced by benign fibrous tissue showing varying amounts of mineralization. The subject of benign fibro-osseous enlargement of the jaws has many facets, the most sinister of which is the possibility that a healthy goodlooking person may take on a monstrous appearance. Fibro-osseous lesion is not a specific diagnosis but a process. They are a diverse group of processes that are characterized by replacement of normal bone by fibrous

1st Fibro-osseous Lesions of Medullary Bone Origin ∙ ∙ ∙ ∙ ∙

Fibrous dysplasia Fibro-osteoma Cherubism Juvenile ossifying fibroma Giant cell tumor

Bone Disease Manifested in Jaw

∙ ∙ ∙

Aneurysmal bone cyst Jaw lesions in hyperparathyroidism Paget’s disease.

Fibro-osseous Lesions of Periodontal Origin ∙ ∙ ∙ ∙ ∙

Periapical cemental dysplasia Florid osseous dysplasia Cemento-ossifying fibroma Cementifying fibroma Ossifying fibroma.

FIBROUS DYSPLASIA Definition: Fibrous dysplasia of bone, a disturbance of medullary bone maintenance in which the bone undergoing physiologic lysis is replaced by abnormal proliferation of fibrous tissue, resulting in asymmetric distortion and expansion of bone, maybe confined to one bone (monostotic fibrous dysplasia) or involve multiple bones (polyostotic fibrous dysplasia). Dysplasia means abnormal tissue development. It arises from the bone forming mesenchyme in the spongiosa and develops by proliferation of fibrous tissue. Lichtenstein in 1938 coined the term ‘fibrous dysplasia’. It is also called fibrocystic disease, osteitis fibrosa localisata, focal osteitis fibrosa and fibroosteodystrophy.

Etiology FD is a genetic non-inherited condition caused by genetic mutation in the gene GNAS1 on chromosome 20, that encodes the alpha subunit of the stimulatory G proteincoupled receptor, Gsa. The activating mutations occur post-zygotically, replacing the arginine residue amino acid with either a cystein or a histidine amino acid. The mutation selectively inhibits GTPase activity, resulting in constitutive stimulation of AMP-protein kinase A intracellular signal transduction pathways. The systemic manifestations of the mutated Gsa protein-coupled receptor complex include autonomous function in bone through parathyroid hormone receptor; in skin through melanocyte-stimulating hormone receptor; in ovaries through the follicle-stimulating hormone receptor; and in the thyroid and the pituitary gland, through the thyroid and growth hormone receptors respectively.

Types 1st Types • M onostotic fibrous dysplasia: In it, only one bone is involved. • Polyostotic fibrous dysplasia: In it, more than one bone is involved – Jaffe-Lichtenstein syndrome: Pigmented lesions of the skin or ‘café au lait’ spots. – McCune-Albright’s syndrome: Pigmented lesions of the skin plus endocrine disturbances of various types.

2nd according to Stewart Types • M onostotic: Indicates involvement of a single bone. • Monomelic: It refers to the involvement of one extremity and is rarely found. • Polyostotic: Many bones involved. • Albright’s syndrome. Subclinical fibrous dysplasia: Many a times an unsuspected lesion of fibrous dysplasia comes to light accidentally on routine radiographic examination, without any clinical evidence of the suspected disease. Such examples are termed as sub-clinical fibrous dysplasia.

Clinical Features Monostotic Fibrous Dysplasia Age and sex distribution: Fibrous dysplasia discovered in young patients, usually in children younger than 10 years affecting both the sexes equally. Sites: Monostotic fibrous dysplasia involves only one bone and presents no extra-skeletal effects, other than occasional pigmented skin lesions. This type accounts for about 80 to 85 percent of all cases. Most frequent sites are ribs, femur, maxilla and mandible. Symptoms: Painless swelling of the bone is most common complaint patient gives (Fig. 23.1). Polyostotic fibrous dysplasia (Jaffe’s type): Sex predilection: Polyostotic fibrous dysplasia involves multiple bones, with female to male ratio of 3:1.

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Oral Manifestations Monostotic 578

Site: Maxilla is more commonly affected than mandible, with most changes occurring in the posterior region. Most common area involved is premolar-molar area.

Figure 23.1 Fibrous dysplasia showing swelling in the palate

Café au lait spot: The skin lesions consist of irregularly pigmented, light brown melanotic spots, described as ‘cafe au lait spot’. These pigmented lesion maybe congenital and pigmented oral mucosal macules also may be present. The margins of the café au lait spots are typically very irregular, resembling a map of coast line of Maine. Recurrent bone pain is the most common presenting skeletal symptom. Skeletal lesions may be unilateral in distribution or may involve nearly all bones of the body. Spontaneous fracture is a common complication. In rare cases, continuous and inexorable extension results in great deformity and blindness. Albright’s syndrome Albright’s syndrome, in addition show, endocrinal disturbances like precocious puberty, goiter, hyperthyroidism, hyperparathyroidism, Cushing’s syndrome and acromegaly. Albright’s syndrome is exclusively found in females. Vaginal bleeding has been noted. Secondary sexual characteristics such as pubic and axillary hair and development of breasts are evident by the age of 5 years. It may result in crippling deformities or fracture. Precocious puberty is rare in boys and is manifested as gynecomastia. Long bones are frequently affected. Bone and skin lesions found in polyostotic form are unilateral. Skeletal lesions become static with the cessation of growth but proliferation may continue, particularly in the polyostotic form. Another disorder characterized by fibrous dysplasia with intramuscular myxomas is termed Mazabraud syndrome.

Symptoms: There may be unilateral facial swelling, which is slow growing with intact overlying mucosa. Swelling is usually painless but patients may feel discomfort in some cases and while others complain of frank pain. Enlarging deformities of alveolar process mainly buccal and labial cortical plates is seen (Fig. 23.1). In mandible, it causes protuberant excrescence of the inferior border of mandible. The teeth present in the affected area are either malaligned and tipped or displaced. Dental anomalies such as supernumerary teeth have been reported in connection with the monostotic fibrous dysplasia. These supernumerary teeth often remain impacted and may affect the eruption of normal teeth. Craniofacial fibrous dysplasia: If fibrous dysplasia extends to involve the maxillary sinus, the zygomatic process, floor of orbit and sometimes toward the base of the skull, it is known as craniofacial fibrous dysplasia. It results in severe malocclusion and marked facial deformity. Craniofacial lesions may lead to anosmia (loss of sense of smell), deafness and blindness. There may be proptosis of the affected eye. Polyostotic (Jaffe’s type): Expansion and deformities of jaws occurs. The eruption pattern of teeth is disturbed because of loss of support of the developing teeth. There is asymmetry of facial bones. There is ballooning of jaws, so there is gross enlargement and deformity. In some cases, intraoral pigmentation can be seen.

Radiological Features Ground glass appearance: Patient usually get ground glass appearance which results from superimposition of myriad of poorly calcified bone trabecular arranged in disorganized pattern (Fig. 23.2). Margin of the lesion is not well demarcated and it blends imperceptibly into the adjacent bone. There is expansion of lingual and buccal cortical plates. In some cases superior displacement of inferior alveolar canal is seen. In earlier stages lesion may be radiolucent or mottled.

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579

Figure 23.2 Fibrous dysplasia showing ground glass

appearance of the lesion

Figure 23.3 Chinese letter pattern bony trabaculae seen in

fibrous dysplasia

In case of involvement of maxilla lesion may cause displacement of sinus floor superiorly and obliteration of maxillary sinus can occur.

Laboratory Examination Serum calcium and serum phosphorus concentration, as well as serum alkaline phosphatase activity usually are within normal limits. But in rare instances particularly when the polyostotic lesions are numerous and active, the serum alkaline phosphatase levels may be elevated in 50 percent of the cases.

Histopathological Features Monostotic fibrous dysplasia: The lesion is essentially a fibrous bone made up of proliferating fibroblast in a compact stroma of interlacing collagen fibers. Irregular trabeculae of bone are scattered throughout the lesion, with no definite pattern of arrangement. Some of these trabeculae are C-shaped and described as Chinese character shaped (Fig. 23.3). These trabeculae are usually woven bone, but may be lamellar. In some cases it has been shown that classic fibrous dysplasia of jaws undergoes progressive maturation to a lesion consisting of lamellar bone in a moderately cellular connective tissue stroma. The bony trabeculae in these mature lesions tend to run parallel to one another (Figs 23.4 and 23.5). Polyostotic fibrous dysplasia: The lesions are composed of fibrillar connective tissue within which are numerous

Figure 23.4 Fibrous dysplasia showing irregularly shaped

trabecular of woven bone in fibrous stroma

trabeculae of coarse, woven bone, irregular in shape but evenly spaced, showing no relation to functional pattern. The osteocytes are quite large and collagen fibers of these trabeculae can often be seen into the fibrous tissue. These trabeculae have typically wide osteoid seams. Osteoclastic activity may be seen where the calcification of osteoid extends to the surface of the trabeculae.

Management Surgical removal of lesion should be carried out if necessary.

Textbook of Oral Pathology

appearance of affected children. It is autosomal dominant inherited fibro-osseous disease that affects only the jaws causing bony expansion. Cherubism is a rare hereditary developmental condition, manifested in childhood by bilateral enlargement of jaws giving a cherub like appearance to the face. “Cherubs” are referred to the plumped cheek little angels in the paintings of Renaissance.

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Classification

Figure 23.5 Fibrous dysplasia showing broad trabeculae of

bone within fibrous connective tissue (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

Osseous contouring: It is necessary for correcting the deformity for esthetics or preesthetic purposes. Smaller lesion of mandible is surgically resected entirely. In large and diffuse lesions particularly of maxilla may require surgical reduction of lesion to an acceptable contour without complete removal. But the regrowth of lesion usually occurs with time. Points to Remember Monostotic, polyostotic, GNAS1 on chromosome 20, Café au lait spot, map of coast line of Maine, recurrent bone pain, spontaneous fracture, endocrinal disturbances, secondary sexual characteristics, crippling deformities, precocious puberty, Mazabraud syndrome, protuberant excrescence, supernumerary teeth, severe malocclusion, anosmia, ballooning of jaws, ground glass appearance, displacement of inferior alveolar canal, displacement of sinus floor, proliferating fibroblast, C-shaped, Chinese character shaped, trabeculae parallel to one another woven bone, osseous contouring.

CHERUBISM It is also known as familial fibrous dysplasia of the jaws, disseminated juvenile fibrous dysplasia, familial multilocular cystic disease of the jaws and Hereditary fibrous dysplasia of the jaws. The clinical entity was first described by Jones in 1933 who coined the term ‘Cherubism’ reflecting the characteristic chubby facial

It depends on the severity and location of the lesion and the extent to which jaws are affected: ∙ Grade I: The fibro-osseous expansion tends to be bilateral and symmetrical. It is primarily in the ramus of the mandible. ∙ Grade II: In more severe cases the ramus and the body of the mandible are involved resulting in congenital absence of the third and occasionally the second mandibular molar teeth. In this group the tuberosity region of the maxillae are also affected. ∙ Grade III: In these cases, the lesions affect the mandible and maxilla entirely and may result in considerable facial deformities.

Etiology It is autosomal-dominant, fibroblast/giant cell-containing condition. It may be secondary to somatic mutation, mapping to chromosome 4p16.3. There is possible linkage/ association with Noonan’s syndrome. It is caused by anomalous development of dental structures, latent hyperparathyroidism, a hormone dependent benign neoplasm, trauma, an aberration in ossification, and disturbance in the development of bone forming mesenchyme.

Clinical Features Age and sex distribution: Early childhood between the ages of 2 to 4 years males are affected about twice as frequently as females. Site: It shows predilection for angle of mandible bilaterally (Fig. 23.6) and occasionally posterior maxilla. Chubby appearance: In the rapidly increasing stage, the child assumes a chubby, cherubic facial appearance, especially if combined with involvement of the orbital floor with upward displacement of the globe and exposure of the scleral rims (Fig. 23.7).

Bone Disease Manifested in Jaw

Figure 23.6 Cherubism showing swelling intraorally

Swelling is firm and hard on palpation. Overlying mucosa is intact and non-painful. The alveolar process are so wide, as to occupy almost the whole of the roof of the mouth; the actual palate being reduced to a narrow fissure between the two approximating alveolar process. There may be enlargement of sub-mandibular lymph nodes. There is rapid increase in size up to 7 to 8 years of age, after which the lesions become static or progress very slowly until puberty. After puberty the maxillary lesions tend to regress. The mandibular lesions progress slowly up to the age of 20 years and then regress; the facial appearance almost returns to normal in the 4th and 5th decade of life. The fibrous replacement of bone displaces the deciduous dentition. The primary teeth may be irregularly spaced and some may be absent. There is premature loss of primary teeth. The developing permanent teeth are affected, giving rise to displaced unerupted or absent teeth along with malocclusion.

Radiological Features There is multilocular expansile radiolucency which is located bilaterally in the mandibular posterior location.

Laboratory Findings Serum calcium, phosphorus and alkaline phosphatase levels are within normal limits. But in active cases, serum alkaline levels may be raised.

Histopathological Features (Fig. 23.8) Figure 23.7 Chubby face appearance seen in cherubism

Symptoms: The patient may have difficulty in speech, deglutition, mastication, respiration and limited jaw movement. Bilateral enlargement of mandible in this condition produces full, round lower face. Bilateral enlargement of maxilla gradually follows. Eye raised to heaven: Pulling or stretching of skin of the cheek, depresses the lower eyelid, exposing a thin line of sclera and resulting in the so called “eyes raised to heaven” look. Tumor encroachment on the orbital floor often causes partial obliteration of the palatal vault with resulting V shaped cleft.

Histopathology is characterized by similar picture as that of central giant cell granuloma. Vascular fibrous tissue consists of giant cells. The giant cells are small and aggregated focally. In some cases perivascular cuffing by the eosinophils may be seen. It also contain large number of fibroblast and small blood vessels. Sprinkling inflammatory cells can be found in this condition. Epithelial remnants of developing teeth are sometimes scattered throughout the lesion.

Management Surgical procedures should be delayed, as long as possible, as the cystic lesion defect usually becomes static and regresses during adulthood. Occasionally, surgical contouring of the lesions is necessary to improve esthetics and in case of active growth.

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74 percent cases in younger than 30 years. It is more commonly seen in females. Site: Mandible is twice as frequently involved than maxilla, with anterior half showing greatest incidence with fairly high percentage crossing the symphysis. The most common sites are anterior and bicuspid region in mandible, the canine fossa, and ethmoid region in maxilla.

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Expansion of bone: The earliest sign of the lesion may be expansion of bone with premature loosening and shedding of deciduous teeth. There is jaw swelling associated with facial asymmetry. Figure 23.8 Cherubism (Courtesy: Dr Sangamesh Halawar,

Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

Points to Remember Familial fibrous dysplasia of the jaws, autosomal-dominant, angle of mandible bilaterally, chubby appearance, round lower face, eye raised to heaven, ‘V’ shaped cleft, premature loss of primary teeth, multilocular expansile radiolucency, giant cells, perivascular cuffing, fibroblast, sprinkling inflammatory cells, surgical contouring.

CENTRAL GIANT CELL GRANULOMA The WHO has defined it as an intraosseous lesion consisting of cellular fibrous tissue that contains multiple foci of hemorrhage, aggregations of multinucleated giant cells and occasionally trabeculae of woven bone. Some authors separate central giant cell granuloma (CGCG) into two types, referring to its clinical and radiographic features as. Nonaggressive lesion which is usually slows growing and asymptomatic. Aggressive lesion which is usually found in younger patients and is painful, grows rapidly, is larger overall, and often causes cortical perforation and root resorption and has a tendency to recur. It is a non-neoplastic bone disease reactive to some unknown stimulus. It was first described in the jaws by Waren 1837. It has been called osteoclastoma, myeloid sarcoma, chronic hemorrhagic osteomyelitis and giant cell reparative granuloma.

Symptoms: Usually painless, but local discomfort may be noted. Palpation may elicit tenderness. Growth is slow. Teeth in the area may become mobile but maintain their vitality, until they are exfoliated. Sign: The swelling is smooth, and palpation can reveal a rubbery, elastic sensation where the bone has thinned.

Radiological Features Radiologically it appears as radiolucent area which can be unilocular or multilocular. Margin of the lesion are noncorticated. This lesion crosses the midline (Fig. 23.9).

Histopathological Features (Figs 23.10 to 23.13) It is made up of a loose fibrillar connective tissue stroma with many interspersed proliferating fibroblast and small capillaries. Multinucleated giant cell are prominent thorough the connective tissue which may vary in size from case to case and may contain several dozen nuclei. The multinucleated giant cells show a patchy distribution and are usually associated with areas of hemorrhage.

Clinical Features Age and sex distribution: Lesion of adolescent and young adult with 60 percent cases in younger than 20 years and

Figure 23.9 Radiolucent defect seen in mandible which

crosses the midline of central giant cell granuloma

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Figure 23.10 Central giant cell granuloma giant cells

Figure 23.13 Giant cell granuloma showing few giant cells and bony trabeculae

There are also numerous foci of old extravasated blood and associated hemosiderin pigment. The majority of giant cells contain round nuclei but, some cells may have pyknotic appearance. Older lesions show considerable fibrosis of stroma. Foci of osteoid and newly formed bone are occasionally present within the lesion. Ultra structurally, the proliferating cells include spindleshaped fibroblasts, myofibroblasts, and inflammatory mononuclear cells.

Management Figure 23.11 Central giant cell granuloma

It is treated by enucleation, curettage and partial resection. The lesions considered on clinical and radiological grounds to be potentially aggressive show a higher frequency for recurrence. Different modalities have been investigated for aggressive lesions alternative to surgery as corticosteroids, calcitonin and interferon alfa-2a. Corticosteroids: Weekly injection in the tumor for 6 weeks has been use successfully. Points to Remember

Figure 23.12 Giant cell granuloma

GNAS1 on chromosome 20, Gsaα protein-coupled receptor complex, painless swelling, expansion of bone, facial asymmetry, local discomfort, unilocular, multilocular, margin non-corticated, loose fibrillar connective tissue stroma, proliferating fibroblast, multinucleated giant cell, hemosiderin pigment, fibrosis of stroma.

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PAGET’S DISEASE 584

It is also called osteitis deformans. It was discovered in 1877 by Sir James Paget. It is a condition characterized by abnormal and anarchic resorption and deposition of bone resulting in distortion and weakening of affected bone. The disease is initiated by an intense wave of osteolytic activity with resorption of normal bone resulting in irregularly shaped resorption followed by vigorous osteoblastic activity forming woven bone after variable period. The etiology of Paget’s disease is unknown but inflammatory, genetic and endocrine may be contributing factors. Recurrent mutation in sequestosome 1 gene (SQSTM1) has been identified in both familial and sporadic cases.

Clinical Features It is seen most frequently in Britain and less frequently in North America and Western Europe. Age and sex distribution: It occur predominantly in patients over 40 years of age with a slight predilection for men. Male to female ratio is 2:1. Sites: It is prone to occur in the axial skeleton especially the skull, femur, sacrum and pelvis. The disease maybe monostotic (i.e. limited to one bone), most cases of Pagets disease are polyostotic (i.e. more than one bone is affected) Symptoms: First complains may be that patient needs to buy a hat of larger size because of skull enlargement. Bone pain is a consistent symptom and most often directed towards weight bearing areas. Deafness occurs due to involvement of the petrous portion of temporal bone with compression of cochlear nerve in the foramen. Mental disturbance, dizziness also occurs. Neuralgic pain: The patients may have ill defined neuralgic pain as a result of restriction of foramina and canals, which occurs due to pressure created by mass on structures passing through the foramina. Bowing of legs, curvature of spine and enlargement of skull occur in some cases. The involved bones are warm to touch because of increased vascularity and are prone to fracture. Involvement of weight bearing bones which lead to bowing deformity which results in simian (monkeylike) stance. Grotesque facial appearance caused by bony deformities. Broadening and flattening of the chest and spinal curvature. The patient assumes waddling gait.

Complication of Paget’s disease is development of osteosarcoma which is malignant tumor of the jaw bone.

Oral Manifestations Maxilla is involved three times more commonly than mandible. It is bilaterally symmetrical in the involved jaw. There is movement and migration of affected teeth, malocclusion and in edentulous patient poor fit of denture. Increase in alveolar width associated with flattening of palate when maxilla is involved. As the disease progresses the mouth may remain open exposing the teeth as the lips are too small to cover the enlarged jaws (Fig. 23.14). Leontiasis ossea: Maxillary involvement results in enlargement of middle third of face which results in lionlike facial deformity (leontiasis ossea). Extraction sites heal slowly and incidences of osteomyelitis are higher. Extraction may be further complicated by excessive bleeding from highly vascular abnormal bones in the lytic phase of disease.

Radiological Features In early stage there is decrease radiodensity of the bone with alteration in the trabecular pattern. In the skull large area of radiodensity can be see which is called osteoporosis circumscripta. After this area of sclerotic bone is formed which tend to become confluent and it appear as cotton wool appearance.

Laboratory Investigations Serum alkaline phosphatase level is increased, occasionally, attending the level of 200 or more KA units.

Figure 23.14 Increase in alveolar width seen patient with

Paget’s disease

Bone Disease Manifested in Jaw

Serum calcium and serum phosphorus levels are within normal limits. Urinary hydroxyproline levels increase from normal levels of 440 mg/24 hours to 1 g/24 hours. Newer and more sensitive markers of bone resorption are N-telopeptides, C-telopeptides and pyridonoline cross linked assays.

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Histopathological Features (Figs 22.15 to 23.17) Collagen fibers within the lamellar bone loose their normal orientation and run in many directions.

Figure 23.17 Paget disease showing sclerotic bone

Figure 23.15 Paget disease showing reversal line

Normal hematopoietic marrow is replaced by cellular large vascular channels resulting in marked increase in vascularity. A highly fibrous connective tissue replaces the marrow. Basophilic reversal lines are seen in the bone. These lines indicate the junction between the alternating resorptive and formative phases of bone and result in jigsaw puzzle or mosaic pattern of bone. One of the most characteristic feature of this bone if the formation of ‘mosaic’ bone, a descriptive term used to indicate the appearance of bone which has been partially resorbed and then repaired leaving deeply staining hematoxyphlic reversal lines. Osteoclasts increase in size and number and are morphologically abnormal. Later in the disease process osteoblastic activity increases while osteoclastic activity decreases and the bone becomes sclerotic. Inflammatory edema of marrow is common and focal collection of lymphocytes may be observed. The proliferation of bone and concomitant hypercementosis result in obliteration of periodontal ligament.

Management

Figure 23.16 Paget disease (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

Paget’s disease is a chronic and slow progressing disease. In asymptomatic patients, treatment is often not initiated until the serum alkaline phosphatase is more than 25 to 50 percent. Antiresorptive therapy is recommended in patients with bone pain, headache related to skull involvement, deafness or visual disturbances, bone fractures. Calcitonin and bisphosphonates etidronate, a parathyroid hormone antagonist produced by the thyroid gland,

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suppresses bone resorption and also relieves pain and decrease serum alkaline. Now this agents are supplanted by newer bisphosphonates alendronate and risedronates. Single infusion therapy with zoledronic acid can give good results. Points to Remember Osteitis deformans, polyostotic, hat of larger size, neuralgic pain, bones warm to touch, simian (monkey like) stance, Grotesque facial appearance, osteosarcoma, migration of affected teeth, increase in alveolar width, lion like facial deformity (leontiasis ossea), osteomyelitis, osteoporosis circumscripta, cotton wool appearance, serum alkaline phosphatase increased, collagen fibers, marked increase in vascularity, basophilic reversal lines, jigsaw” puzzle, mosaic pattern, osteoclasts, inflammatory edema of marrow, hypercementosis antiresorptive therapy, calcitonin and bisphosphonates etidronate, a alendronate, risedronates, zoledronic acid.

Cemento-osseous Dysplasia These occur in tooth bearing region of the jaws and they are most common fibro-osseous lesion seen in clinical practice. These occur in close approximation with periodontal ligament and exhibits histopathological similarities with it. Some author believes that it is defect in extra ligamentary bone remodeling that may be triggered by local factors. Hormonal imbalance may be causative factors for this disease. Histopathological features of all three variant are same. Types • • •

Focal cemento-osseous dysplasia Periapical cemento-osseous dysplasia Florid cemento-osseous dysplasia.

Clinical Features Focal Cemento-osseous Dysplasia Age and sex distribution: Over 90 percent of cases occur in female as compared to male with mean age of occurrence 38 years. Site: It exhibits single site of involvement. Posterior region of the mandible is the most common site of involvement. Symptoms: It is asymptomatic and discovered routinely on radiographic examination.

Periapical Cemento-osseous Dysplasia It is also called osseous dysplasia, cemental dysplasia or cementomas. Age and sex distribution: It is seen in age group of 30 to 50 years. Females are affected more commonly in the ratio of 10:1. Site: It has predilection for periapical region of anterior region of the mandible. Symptoms: It is asymptomatic and discovered routinely on radiographic examination. Teeth are vital.

Florid Osseous Dysplasia Age and sex distribution: Females are exclusively affected. Most common age is middle age, with a mean age 42 years with predilection for blacks. Site: The lesion is restricted to the jaw bone with mandible being most commonly affected. Lesion is multifocal with bilateral involvement. In some extensive cases all the four quadrants are get involve. Symptoms: Patients may complain of intermittent poorly localized pain in the affected bone area, with or without an associated bony swelling. Signs: There is a painless expansion of the alveolar process of mandible. Mucosal ulceration with fistulous tract may be present. Teeth are vital.

Radiological Features Focal cemento-osseous dysplasia: It can appear as completely radiolucent lesion to dense radiopaque lesion. Radiopaque lesion has got thin radiolucent rim. Size of lesion is not more than 1.5 cm. Lesion is well defined with irregular border. Periapical cemento-osseous dysplasia: Early lesions are circumscribed area of radiolucency in the apex of tooth. This can affect many teeth in the same region. In later stage lesion gets mature and pattern of mixed radiolucent-radiopaque appear. In the end stage there is circumscribed radiopaque lesion surrounded by radiolucent rim. Size is usually less than 1 cm in diameter. Florid osseous dysplasia: It has got initially radiolucent lesion which later on become mixed and completely radiopaque. Radiopaque lesion is surrounded by thin radiolucent rim.

Bone Disease Manifested in Jaw

In some cases of florid dysplasia cemento-osseous material may get deposited directly on the surface of the root of teeth resulting in thickened root apices. It is surrounded by radiolucency causing hypercementosis like appearance (Fig. 23.18).

Histopathological Features All the three variant of cemento-osseous dysplasia have common histopathological features. The tissue specimen consists of cellular mesenchymal tissue which consists of spindle shaped fibroblast and collagen fibers. Numerous blood vessels may be present. In the fibrous connective tissue there is present of woven bone, lamellar bone and cementum like particle (Fig. 23.19). With maturation bone trabecular pattern become thick curvilinear structure which resembles to shape of ginger roots. In the final stage there is trabecular fuse and lobular masses which composed of sheets of fused globules of acellular and disorganized cemento-osseous material.

Management If teeth present effective oral hygiene should be maintained since with this disease, patients exhibit poor healing and osteomyelitis may develop after tooth loss. As there formation of sequestration which occurs due to osteomyelitis saucerization of bone can result speeding of healing. Many times onset of symptoms occurs after extraction of teeth as sclerotic masses appear in the oral cavity, elective extraction of teeth should be avoided. Points to Remember Focal cemento-osseous dysplasia Over 90 percent female, posterior region of the mandible, asymptomatic, completely radiolucent to dense radiopaque lesion, size not more 1.5 cm. Periapical cemento-osseous dysplasia Osseous dysplasia, females 10:1, periapical region of anterior region of the mandible, asymptomatic, circumscribed area of radiolucency, mixed radiolucentradiopaque, radiopaque lesion with radiolucent rim. Florid osseous dysplasia Females, multifocal with bilateral involvement, intermittent poorly localized pain, a painless expansion, mixed and completely radiopaque, hypercementosis like appearance. Histopathology and management

Figure 23.18 Radiopaque lesion of florid dysplasia

Spindle shaped, collagen fibers, woven bone, lamellar bone, cementum like particle, shape of ginger roots, lobular masses, effective oral hygiene, saucerization of bone.

FAMILIAL GIGANTIFORM CEMENTOMA Gigantiform cementoma earlier use as the synonym for florid osseous dysplasia. But nowaday this is called separate entity. It is disorders of gnathic bone which lead to formation of massive sclerotic mass of disorganized mineralized material. It is autosomal dominant disorders which demonstrated high penetrance with variable expressivity.

Clinical Features Figure 23.19 Cemento-osseous dysplasia showing cemental

masses

Age and sex distribution: It is most commonly seen in first and second decade of life without any sex predilection.

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Facial asymmetry: Gnathic enlargement in patient results in significant facial deformity. If not treated this osseous involvement ceases during fifth decade. 588

Symptoms: There is impaction, malposition, and malocclusion of involved dentition. Patient also complaint of anemia, multifocal polypoid adenomas of uterus, bone fragility and tendency to long bone fracture.

Radiological Features There are multiple radiolucencies in the periapical region which with progression appears as mixed radiolucent radiopaque region within the involved quadrant. With maturation lesion become more radiopaque with thin radiolucent line surrounding the radiopacities.

cementifying fibroma and tumors characterized by both types of cells, but probably the same progenitor cells, thus giving rise to the well recognized hybrid form of the tumor, i.e. the cemento-ossifying fibroma. It is understood that these are three sub-classifications of an otherwise identical lesion.

Clinical Features Ossifying fibroma (Figs 23.20 and 23.21) Age and sex distribution: It is a rare neoplasm and occurs at any age, but usually is found in the young adult with females more commonly affected than males.

Histopathological Features These are same as that of cemento-osseous dysplasia.

Management Improvement of esthetic by shave down surgical procedure has been attempted. In some cases extensive resections of altered bone with reconstruction of the facial skeleton with produce good results. Points to Remember Gnathic bone, massive sclerotic mass, facial asymmetry, impaction, malposition, anemia, multifocal polypoid adenomas, radiolucencies, mature lesion radiopaque with radiolucent line, shave down surgical procedure.

Figure 23.20 Ossifying fibroma seen in upper maxillary

region of the jaw

OSSIFYING FIBROMA, CEMENTIFYING FIBROMA AND CEMENTO-OSSIFYING FIBROMA These are characteristically encapsulated neoplasms consisting of highly cellular fibrous tissue in which bone formation occurs. They may show a locally aggressive behavior. There is remarkable similarity in clinical and radiological features of these lesions. There is also considerable similarity and even overlap in histological features of these lesions. For this reason it is suggested that: They are three separate/distinct benign tumors identical in nature, except for the cells undergoing proliferation. The osteoblasts with bone formation in ossifying fibroma, cementoblasts with cementum formation in

Figure 23.21 Ossifying fibroma (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Bone Disease Manifested in Jaw

Symptoms: There are mild deformities and displacement of teeth. It is slow growing. Cortical plates of bone and overlying mucosa or skin are almost invariably intact.

Cemento-ossifying Fibroma Signs and symptoms: Pain and paresthesia may result from pressure on adjacent nerves. The lesion grows spherical in shape buccally and lingually causing bulging of lower border of the mandible. Cortical erosion is rare.

Radiological Features

Figure 23.22 Well-defined and unilocular lesion of ossifying

fibroma (Courtesy: Dr Aparna Thombre, Reader, Department of Oral Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Site: It shows a predilection for premolar-molar area of the mandible. Mostly in facial bones in mandible and in maxilla, it is often located in the canine fossa and zygomatic arch. In some cases, there may be involvement of the anterior base of skull and of temporal bone. Facial asymmetry: Occasional facial asymmetry is seen in some of the cases. Symptoms: When in maxilla, symptoms may include nasal stuffiness and epiphora on the affected side. There may be associated exophthalmos, with visual disturbances, depending on the extent of compression of its orbital content by the tumor. The lesion is slow growing and in some cases, there is displacement of teeth. Bony cortex and covering mucosa remain intact. The lesion may be slow growing initially, with a rapid increase in size in a relatively short time. If sinus is affected it may fill the sinus completely and expands the sinus wall.

Cementifying Fibroma Age and sex distribution: It may occur at any age, but it is more common in the young and middle aged adults with a mean age of 35 years. Female are affected more commonly than males by ratio of 2:1.

The lesion is well-defined and unilocular with some cases showing sclerotic border. Resorption of root is common features of this disease (Fig. 23.22). Large lesion shows downward bowing of the inferior cortex of the mandible.

Histopathological Features Ossifying fibroma (Figs 23.23 to 23.25): Large number of fibroblasts, with flat elongated nuclei is present within the network of interlacing collagen fibers. Chinese letter shaped islands of bone or calcification distributed throughout the connective tissue. As the lesions mature, the islands of ossification increase in number enlarge and ultimately coalesce. Cementifying fibroma (Fig. 23.26): Cementifying fibroma is composed of cellular fibrous connective tissue that contains cementum like spherules. It is composed of many delicate interlacing collagen fibers arranged in discrete bundles, interspersed by large number of active, proliferating fibroblasts or cementoblasts. The connective tissue characteristically presents many small foci of basophilic masses of cementum like tissue. These are irregularly round, ovoid or slightly elongated, often lobulated. As the lesion matures, the islands of cementum increase in number enlarge and ultimately coalesce.

Management Enucleation: Small, clinical encapsulated lesion are treated by conservatively enucleation. Resection: It is recommended if the there is involvement of inferior border, extension into maxillary sinus occurs.

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Figure 23.23 Ossifying fibroma showing Chinese shaped

island of bone

Figure 23.24 Ossifying fibroma (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

Figure 23.25 Ossifying fibroma (Courtesy: Dr Aparna Thombre, Reader, Department of Oral

Pathology, VSPM Dental College and Hospital, Nagpur, Maharashtra, India)

Points to Remember Young adult, premolar-molar area of the mandible, facial asymmetry, nasal stuffiness, epiphora, slow growing, displacement of teeth, pain, paresthesia, well defined, unilocular, downward bowing of the inferior cortex of the mandible, fibroblast, elongated nuclei, Chinese letter shaped islands of bone, cellular fibrous connective tissue, cementoblasts, proliferating fibroblasts, cementum like spherules.

JUVENILE OSSIFYING FIBROMA Figure 23.26 Cementifying fibroma (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

It is also called juvenile active ossifying fibroma, ‘juvenile aggressive ossifying fibroma. It is differentiated from ossifying fibroma on the basis of age, site and clinical behavior.

Bone Disease Manifested in Jaw

Types • •

Trabecular Psammomatoid.

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Clinical Features Age and sex distribution: It occur in patient younger than 6 months to older than 70 years. There is slight male predilection. Trabecular form: It is seen in younger patient with mean age 11 years. Psammomatoid form: Mean age of occurrence is 22 years. Sign: Cortical expansion may results in facial enlargement. Lesion in paranasal sinus: Lesion in sinus may results in penetration of orbital, nasal and cranial cavities. It can results nasal obstruction, exophthalmos or proptosis. Rarely temporary and permanent blindness occur. Intracranial extension: Lesion derived from cribriform plate may extent intracranialy. Rarely patient may suffer from meningitis.

Radiological Features The lesions are well circumscribed radiolucency which may contain central radiopacities. In some cases ground glass appearance can be seen. If it involve sinus there is clouding of sinus can occur.

Figure 23.27 Juvenile ossifying fibroma with cellular fibrous

tissue with ossicle

Points to Remember Juvenile active ossifying fibroma, lesion in paranasal sinus, intracranial extension, well circumscribed radiolucency, ground glass appearance, clouding of sinus, cellular fibrous connective tissue, myxomatous foci, trabecular pattern, psammomatoid pattern, complete local excision.

OSTEOPOROSIS

There is reduction in the inorganic constituent. There is abnormal persistence of calcified cartilage. Spongy Histopathological Features portion of affected bone ultimately becomes a solid Tumors consist of cellular fibrous connective tissue. block of calcified cartilage leaving inadequate space for Cytoplasm of individual cells is hard to discern. Myxomatous hemopoiesis. It is characterized by low bone mass and micro-architectural bone fragility. It is usually rarefaction foci are associated with pseudocystic degeneration. Areas of hemorrhage and small cluster of multinucleated of bone resulting from deficiency of bone matrix rather than deficit mineral (Fig. 23.28). giant cells are seen. Trabecular pattern: It shows irregular strands of highly cellular osteoid encasing plump and irregular osteocytes. These are lined by plump osteoblasts and multinucleated osteoclasts. Psammomatoid pattern: Concentric lamellated and spherical ossicle that have basophilic centers with peripheral eosinophils osteoid rims (Fig. 23.27).

Management For smaller lesion complete local excision with curettage is sufficient. In large lesion wider resection can be done.

Types Primary (associated with aging). Secondary (reduction of histologically normal bone that has been accelerate by abnormal or iatrogenic circumstance such as corticosteroid or heparin therapy or condition such as malnutrition and scurvy.

Mechanism of Bone Loss It is caused by imbalance between bone resorption and bone formation with an exaggeration of resorption, reduction in bone formation or combination of both.

Textbook of Oral Pathology

Contraceptive drug can also cause osteoporosis; as after administration of contraceptive drug, there is increase in level of cortisol. Combination of these two compounds leads to production of abnormal megakaryocytes, which in turn leads to formation of abnormal sticky platelets. These sticky platelets fuse to form thrombi which occlude small vessels in the tissue due to which the bone dies and get resorbed.

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Figure 23.28 Left side showing normal bone matrix and right

side showing osteoporotic bone

Postmenopausal and senile: It occurs due to overall decrease in anabolic hormones (estrogen) in postmenopausal women. There may be lag in formation of bone and since bone resorption is continued, it results in osteoporosis. After the age of 60 years, generalized atrophy of bone occur (senile osteoporosis). Senile osteoporosis is caused by decrease in calcium absorption, vitamin D absorption and metabolism with age, which in turn decreases the anabolic hormones, muscular proteins and flow of blood to bone. By virtue of this condition, bone resorption occurs. Another cause of bone resorption in adults is that, in elderly person altered hormonal function lead to formation of small thrombi which plug small vessels in bone and cause loss of bone vitality and hence resorption. Cushing’s syndrome: The symptoms are caused by an increased output of glucocorticosteroids, especially cortisol. The excess cortisol acts to produce osteoporosis by two ways: 1. It contributes to the degradation of proteins and severely limits the formation of bone matrix by reducing the amount that each osteoblast synthesizes. 2. It promotes the formation of osteoclasts from the osteogenic undifferentiated cells and thus enhances bone resorption. Drug induced osteoporosis: Prolonged administration of cortisol and cortisone show Cushing like syndrome and cause osteoporosis in the same way as that in Cushing syndrome.

Malnutrition state: Sufficient protein must be absorbed from intestine to supply constant need for matrix formation. Deficiency causes osteoporosis and may result from protein poor diet or from GIT disturbances such colitis, regional arteritis. Vitamin C deficiency may weaken sinusoidal vessel walls in medullary bone which tend to dilate and rupture, resulting in pooling of blood and hypoxia, which leads to loss of vitality and removal of bone by physiologic osteoclast. Progesterone: There is interaction between the progesterone compounds and increased level of cortisol by stress, leading to formation of multiple small thrombi. The thrombi occlude small vessels of osseous tissue, which results in death and resorption of bone, leading to osteoporosis. Thyrotoxic osteoporosis: It is usually seen in children with hyperthyroidism. Thyroxin mediates the action of cortisol on bone and an excess of thyroxin results in a more efficient utilization of steroids. Thus, there is increased resorption.

Clinical Features It is either present at birth (congenital) or developed in early life (infantile). Bones are fragile and susceptible to fracture. These fractures typically affect the forearm (Colle’s fracture), spine (vertebral fracture) and hip (femur fracture). Congenita form inherited as an autosomal recessive disorder is invariably fatal in early life due to massive hemorrhage, anemia and rampant bone infections occurring due to progressive loss of bone marrow and their cellular products. Percussion over the affected vertebrae is painful. Symptoms: Osteoporotic patient may notice gradual loss of height due to shortening of trunk. In advanced cases clinical onset is often characterized by attack of severe pain which is aggravated by movements and occurs after trauma. Osteomyelitis may occur due to relatively avascular and there may be bone pain.

Bone Disease Manifested in Jaw

Oral Manifestations There is marked predilection for development of osteomyelitis. Patient can also suffer from fracture of jaws during tooth extraction. Other features include enamel hypoplasia, arrested root development, retardation of tooth eruption, early loss of teeth, missing teeth and malformed teeth. Teeth are poorly calcified and are prone to caries.

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Radiographic Features Radiographs may show osteopenia. This finding indicates that at least 30 percent of the bone mass has been loss (Fig. 23.29).

Laboratory Findings Patients manifest anemia due to replacement of hemolytic marrow by bone. Hepatomegaly may be present. Red blood cell (RBC) count below 1,000,000 per cubic meter. Increased serum phosphatase levels.

Histopathological Features There is endosteal production of bone with an apparent concomitant lack of physiologic bone resorption. Osteoblasts are prominent but osteoclasts are seldom found. Trabeculae are in disorder arrangement and atrophic (Fig. 23.30). Marrow tissue is fibrous. Bone is markedly deficient in collagen matrix.

Management The goals of osteoporosis treatment are to control pain from the disease, slow down or stop bone loss and prevent bone fractures with medicines that strengthen bone.

Figure 23.30 Osteoporotic bone showing atrophic trabeculae

Bisphosphonates are the primary drugs used to both prevent and treat osteoporosis in postmenopausal women. Calcitonin is a medicine that slows the rate of bone loss and relieves bone pain. It comes as a nasal spray or injection. Hormone replacement therapy estrogens are rarely used anymore to prevent osteoporosis and are not approved to treat a woman who has already been diagnosed with the condition. Points to Remember Postmenopausal and senile, Cushing’s syndrome, drug induced osteoporosis, malnutrition state, progesterone, thyrotoxic osteoporosis, Colle’s fracture, vertebral fracture, gradual loss of height, osteomyelitis, enamel hypoplasia, arrested root development, retardation of tooth eruption, osteopenia, anemia, increased serum phosphatase levels, osteoblasts, fibrous marrow tissue, bisphosphonates, calcitonin, hormone replacement therapy.

INFANTILE CORTICAL HYPEROSTOSIS It is also called Caffey’s disease, Caffey-Silverman syndrome. It was first described in detail in 1945. It is characterized by unusual cortical thickening of certain bones and it occurs in two forms, i.e. autosomal dominant form and sporadic form. It can represent as autosomal dominant trait.

Etiology Figure 23.29 Osteopenia in patient with osteoporosis

It may be an embryonic osteodysgenesis consequent to local defect in blood supply to the area.

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Inherited defects of arterioles supplying the affected part results in hypoxia producing focal necrosis of overlying soft tissue and periosteal proliferation. Allergy can be basis of disease, edema and inflammation producing periosteal elevation and subsequent deposition of calcium.

Clinical Features Age and sex distribution: It is equal in males and females, with average onset at 9 weeks of age, with most of the cases arising before 6 months. Sites: Bones commonly affected are mandible, clavicle, scapula, frontal bone and ulna. There is bilateral involvement in every case. Of all these bone clavicle and mandible are the most common sites. Symptoms: Infants will develop fever and become hyperirritable. Soft tissue swellings have a sudden onset, especially in the facial area and early in disease, they may be warm and tender. Swelling is devoid of clinical signs of inflammation on the overlying skin. Swelling disappears slowly, but may suddenly recur at the same place or new site may be involved. Other features are pseudo-paralysis, pleurisy and dysphasia.

Oral Manifestations

Histopathological Features In the early stages of infantile cortical hyperostosis shows inflammation of the periosteum and adjacent soft tissues. After infection resolves, the periosteum remains thickened, and subperiosteal immature lamellar bone can be seen on biopsy, while the bone marrow spaces contain vascular fibrous tissue. Eventually, the inflammation and subperiosteal changes resolve, and hyperplasia of lamellar cortical bone can be seen.

Management No specific treatment exists for infantile cortical hyperostosis. The disease is self-limited and usually resolves without sequelae. Points to Remember Caffey’s disease, inherited defects, allergy, infants fever, hyperirritable, soft tissue swellings, pseudo-paralysis, pleurisy, dysphasia, mandible, malocclusion, enamel hypoplasia, periosteal new bone, anemia, leukocytosis, elevated erythrocyte sedimentation rate, inflammation of the periosteum, subperiosteal immature lamellar bone, hyperplasia of lamellar cortical bone.

OSTEOPETROSIS

Mandible is one of the most common bones affected in It is also called Marble bone disease, Albers-Schonberg disease, osteosclerosis fragilis generalisata. infantile cortical hyperostosis. It is a rare disorder characterized by an increase in Patient may have malocclusion and enamel hypoplasia density of bones, resulting from a defect in remodeling may be present. caused by failure of normal osteoclast function in which Radiological Manifestation becomes hard and brittle. Radiographs initially show layers of periosteal new bone Types formation with cortical thickening. Periosteal new bone may cover the diaphysis of the • Infantile: Severe disease that is termed as malignant bone, causing an increase in diameter of the bone. Over osteopetrosis. time, the periosteal new bone density increases, becoming • Intermediate osteopetrosis: This is less severe variant homogenous with the underlying cortex. Eventually the of malignant osteopetrosis. bone remodels and resumes a normal appearance. • Transient osteopetrosis: There is radiographic evidence of diffuse sclerosis and associated marrow Laboratory Findings failure but resolve without specific therapy. Anemia, leukocytosis, elevated erythrocyte sedimentation • Adult osteopetrosis: It is discovered later in life and rate, monocytosis and increased serum alkaline phosis termed as benign osteopetrosis. phatase levels.

Bone Disease Manifested in Jaw

Clinical Features

Laboratory Findings

Malignant Osteopetrosis

Red blood cell count below 1,000,000 cells per cu mm. The serum calcium and phosphate levels are usually within normal limits. Elevated serum acid phosphate levels have been reported in patients with benign dominant osteopetrosis.

It is developed as autosomal dominant trait. Almost everyone has a varying degree of poor skeletal development, if the disease appears early in life. Subsequent skeletal deformities occur later due to bending of the long bones and improper healing after pathological fractures. As a result of continuous bone deposition and lack of bone resorption, the foramina of cranial nerves are constricted; hence there is loss of hearing, disturbed vision, which diminishes progressively. Facial nerve palsy is also seen. Due to displacement of hematopoietic bone marrow normocytic anemia ensues and the hematopoietic function is assumed by the liver, spleen and the lymphnodes resulting in hyperplasia of lymphoid tissues and hepatosplenomegaly. There is also frontal bossing, obliteration of maxillary sinus and possible hydrocephalus and mental retardation.

Benign Osteopetrosis It discovered later and have less severe manifestation. It is inhibited as autosomal dominant trait. There is significant sclerosis in the axial skeleton as compare to long bone. Forty percent of patients are asymptomatic and marrow failure is rare. Cranial nerve compression and fracture of bone can occur.

Oral Manifestations Osteomyelitis of jaws associated with osteopetrosis probably follows the obliteration and fibrosis of marrow is caused by reduced osseous circulation. It is most common in mandible and occasionally, in maxilla. Paranasal sinus may become readily obliterated. There may be enamel hypoplasia, defective dentine, disturbed tooth development, small pulp and tendency towards caries.

Radiological Features There is widespread increase in skull density distinction between cortical and cancellous bone is lost. Roots of teeth are difficult to visualize due to density of surrounding bone.

Histopathological Features It is characterized by the endosteal production of bone, with an apparent concomitant lack of physiologic bone resorption. Osteoblasts are prominent, but osteoclasts are seldom found. The predominance of bone formation over resorption typically leads to the persistence of cartilage cores of bony trabeculae, long after their replacement should occurred in endochondral bones. The trabeculae are disorderly in arrangement and the marrow tissue present is usually fibrous. There is globular amorphous bone deposition in marrow space.

Management There is as such no effective treatment for osteopetrosis. Prognosis of adults form is good and survival is long as compared to infantile form where patient dye during first decade of life. Bone marrow transplantation can give good results. Therapy like interferon gamma-Ib in combination with calcitriol shown to reduce bone mass. Other treatment modalities like administration of corticosteroid, parathormone, macrophage colony stimulating factors and erythropoietin has also been suggested. Performing dental extraction has a risk of osteomyelitis and jaw fracture. Points to Remember Marble bone disease, bending of the long bones, pathological fractures, constricted foramina of cranial nerves, loss of hearing, facial nerve palsy, normocytic anemia, hyperplasia of lymphoid tissues, hepatosplenomegaly, frontal bossing, osteomyelitis of jaws, paranasal sinus obliterated, enamel hypoplasia, small pulp, increase skull density, red blood cell below 1,000,000, osteoblasts, fibrous marrow tissue, bone marrow transplantation, calcitriol, interferon gamma-Ib.

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OSTEOGENESIS IMPERFECTA 596

It is also called brittle bone, Lobstein disease. It is a serious disease of unknown etiology. It represents a hereditary autosomal dominant trait. Types Type 1 Osteogenesis imperfecta Type 2 Osteogenesis imperfecta Type 3 Osteogenesis imperfecta Type 4 Osteogenesis imperfecta.

Clinical Features Many infants with this disease are stillborn or die shortly after birth. There is extreme fragility and porosity of bones with an attendant proneness of fracture. Fracture heals readily but new bone is of similar imperfection. It is common for fracture to occur while the infant is walking or crawling. There is formation of hyperplastic callus, which may mimic osteosarcoma, take place. Blue sclera: There is occurrence of pale blue sclera which is thin; pigmented choroids show through and produce the blue color. There is deafness due to osteosclerosis; laxity of ligament and peculiar shape of the skull. There is also abnormal electrical reaction of muscle, increased tendency for capillary bleeding. Type 1 Osteogenesis imperfecta: It is most common and mildest form. It is inherited as autosomal dominant trait patients have mild-to-moderate bone fragility. The sclera is blue in all ages and these aids in diagnosis. Type 2 Osteogenesis imperfecta: This type is severe form. It has extreme bone fragility and frequent fractures. It is inherited both as autosomal dominant and recessive traits. Many patients are stillborn and 90 percent die before 4 weeks of age. Type 3 Osteogenesis imperfecta: This type has moderateto-severe bone fragility. It can be inherited both autosomal dominant and recessive patterns. The sclera is normal or blue, if discoloration is present then it fades as the child grows. Type 4 Osteogenesis imperfecta: This type is associated with mild to moderately severe bone fragility. This variant appears as an autosomal dominant trait. The sclerae may be

Figure 23.31 Patient with osteogenesis imperfecta showing of

bowing of leg

pale blue in early childhood, but the blue color fades later I life (Fig. 23.31).

Oral Manifestations Most of the times, osteogenesis imperfecta is associated with dentinogenesis imperfecta. Sometimes, there is also hypoplasia of teeth, class I malocclusion and greater incidence of impacted 1st and 2nd molars. Deciduous teeth are poorly calcified and semitranslucent or waxy. Appearance of teeth is faint dirty pink, half normal size, with globular crowns and relatively short roots in proportion to other dimension.

Radiographic Features The radiographic features of osteogenesis imperfect include osteopenia, bowing, angulation or deformity of long bones, multiple fractures and wormian bones in skull.

Histopathological Features It exhibits thin cortices, sometimes being composed of immature spongy bone, while the trabeculae of cancellous bone are delicate and often show micro-fractures. Osteoblastic activity appears retarded and imperfect and for this reason thickness of long bones is deficient. There is failure of fetal collagen to be transformed into mature collagen.

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Progressive intermolecular cross-linkage of adjacent collagen molecule is only sometimes evident, which a characteristic of normal collagen maturation. 597

Management Management consist physiotherapy, rehabilitation, and orthopedic surgery. Use of bisphosphonates can provides relief from pain, reduces risk of fracture and improved mobility. Points to Remember Brittle bone, extreme fragility, porosity of bones, fracture infant while walking, blue sclera, deafness, hypoplasia, impacted, faint dirty pink teeth, osteopenia bowing, angulation, multiple fractures, wormian bones, immature spongy bone, trabeculae show micro-fractures, crosslinkage, collagen molecule, physiotherapy, rehabilitation, bisphosphonates.

PIERRE ROBIN SYNDROME It is also called Robin anomalad Pierre Robin sequence. It result arrested development. It is discovered in 1923 by physician name Pierre Robin.

Pathogenesis Mechanical theory: This theory is the most accepted. The initial event, mandibular hypoplasia, occurs between the 7th and 11th week of gestation, which keeps the tongue high in the oral cavity, causing a cleft in the palate by preventing the closure of the palatal shelves. This theory explains the classic inverted U-shaped cleft and the absence of an associated cleft lip. Neurological maturation theory: A delay in neurological maturation has been noted on electromyography of the tongue musculature, the pharyngeal pillars, and the palate, as has a delay in hypoglossal nerve conduction. The spontaneous correction of the majority of cases with age supports this theory.

Figure 23.32 Bird facies seen in Pierre Robin syndrome

the characteristic bird facies (Fig. 23.32). Mandibular hypoplasia yields a retrognathic appearance. Cleft palate: There is abnormal descent of tongue between the palatal shelves resulting in cleft palate. Breathing difficulty: There is respiratory difficulty due to failure of support of tongue musculature because of micrognathia, allowing the tongue to fall down and backwards, partially obstructing the epiglottis. There may be congenital heart defects, other skeletal abnormalities and ocular lesions. Mental retardation is also a common finding.

Management Breathing support and feeding assistance are necessary during infancy. Surgical closure of cleft palate and orthodontic treatment are indicated. Points to Remember Pierre Robin sequence, mechanical theory, neurological maturation theory, triad mandibular hypoplasia, cleft palate, glossoptosis.

Clinical Features Triad: It consists of cleft palate, micrognathia and glossoptosis. Mandibular hypoplasia: Arrested development and ensuing hypoplasia of mandible ultimately produce

MARFAN’S SYNDROME It is also called Marfan-Achard syndrome, arachno dactyly. It is hereditary disease transmitted as autosomal dominant trait. It is basically a disease of connective tissue related

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to defective organization of collagen which is abnormally soluble. 598

Clinical Features There is excessive length of the tubular bones resulting in disproportionately long thin extremities. The finger and toes are long, thin and tapering so that the name spider finger has been applied (Fig. 23.33). The shape of face and skull is characteristically long and narrow. There is hyperextensibility of joint with habitual dislocations, kyphosis or scoliosis and flatfoot. Bilateral ectopia lentis: It caused by weakening or rupture of the suspensory ligaments. Cardiovascular complications like aortic aneurysm and aortic regurgitation, valvular defects and enlargement of the heart are common.

Oral Manifestations

Points to Remember Arachnodactyly, long thin extremities, spider finger, long and narrow face, bilateral ectopia lentis, cardiovascular complications, high arched palatal vault, multiple odontogenic cysts of maxilla, bifid uvula.

DOWN’S SYNDROME It is also called Trisomy 21 syndrome and mongolism. It is associated with subnormal mentality in which an extremely wide variety of anomalies and functional disorders may occur. It results from excessive chromosomal material involving all or a portion of chromosome 21. Types • • •

Typical type – trisomy–21 with 47 chromosomes (95 percent of cases). Translocation type – 46 chromosomes. Chromosomal mosaicism.

High arched palatal vault is very prevalent. Bifid uvula, malocclusion and multiple odontogenic cysts of maxilla Clinical Features (Fig. 23.34) and mandible can also occur. There may be temporomandibular dysarthrosis. In some Facial characteristic: There is midface dysplasia, nose cases of Marfan calcification in the pulp can also occur. malformations including a flat broad bridge of the nose is present. Ear malformations, including “lop” ears, low-set Management ears and ears with a flat or absent helix have been reported. People with Marfan syndrome should take antibiotics before Eye malformations like epicanthal folds with slanting dental procedures to prevent endocarditis. Pregnant women almond-shaped eyes (narrow palpebral tissue slanting with Marfan syndrome must be monitored very closely toward the midline), which was responsible for the term because of the increased stress on the heart and aorta. mongoloid, are also reported. It exhibit brachycephaly

Figure 23.33 Radiograph of hand of patient with

Marfan syndrome

Figure 23.34 Clinical features of Down syndrome

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(broad, short head) and lack of supraorbital ridges and hypotelerism (secondary to hypoplasia of the central face) are common findings. Congenital cardiopathies: Incidence of mitral valve prolapse, aortic regurgitation is reported. Upper respiratory tract infections: The higher incidence of upper respiratory tract. Infections seen in persons with Down Syndrome is thought to be due to their impaired immunologic response to infectious or inflammatory diseases. Alzheimer dementia: Neurological signs of Alzheimer disorder, as evidenced by post-mortem findings. Atlantoaxial instability: The incidence of atlanto-axial instability in persons with Down syndrome has been reported as ten to twenty percent. This condition refers to an abnormal increase in mobility of the upper two cervical vertebra (Cl/C2) due to congenital ligamentous laxity. Other problems: Patient complaint of delayed speech and a husky quality of voice, hearing impairments, risk for cataracts.

Oral Manifestation Periodontal disease: Inadequate oral hygiene may lead to early onset fulminating periodontal disease in these individuals. It is common to see alveolar bone loss in persons with DS at age 6 to 16 years. This increased incidence of periodontal disease is directly related to the reduced immunologic response to infections and inflammatory disease reported in these individuals. NUG: Several reports have indicated a high incidence of necrotizing ulcerative gingivitis (NUG) in these individuals. Malocclusion: There is an increased incidence of malocclusion in individuals with DS, particularly Class III malocclusions. The higher incidence of Class III malocclusions is due to the underdevelopment of the midface (nasal, premaxillary and maxillary bones) not to prognathism. Delayed eruption: The teeth of people with Down syndrome, both baby teeth and permanent teeth, may come in late compared to children without Down syndrome. Small and missing teeth: Frequently, people with Down syndrome have smaller than average teeth, and missing teeth.

Other problems: The incidence of macroglossia, fissured tongue and protruding tongue due to forward position of the mandible and open mouth is a common finding. Also, increases in bifid uvula and submucous clefts and cleft palates have been reported in this population.

Management Down syndrome is a permanent genetic disability. Management consist of pursuing mega-vitamin therapy in addressing the lowered immune response to infection seen in persons with Down Syndrome. Cosmetic facial surgery: These procedures would include augmentation of the nasal, cheek and chin areas, glossectomies and lateral canthoplasty. Points to Remember Trisomy 21 syndrome, midface dysplasia, lop ears, almond-shaped eyes, brachycephaly, hypotelerism, congenital cardiopathies, upper respiratory tract infections, Alzheimer dementia, atlanto-axial instability, periodontal disease, NUG, malocclusion, delayed eruption.

ACHONDROPLASIA It is also called chondrodystrophia fetalis. It is a disturbance of endochondral bone formation, which results in a characteristic form of dwarfism. It is a hereditary condition, which is transmitted as an autosomal dominant trait.

Clinical Features Signs: Patient is quite short, usually less than 14 meters in height and thickened muscular extremities, brachycephalic skull and bowed legs. Hands are usually small and fingers are stubby. The base of the skull is small and constricted as a result of retarded growth of the cartilaginous portions. The calvarium is large and bulges frontally and laterally. There is also depression of the bridge of nose. Lumbar lordosis with prominent buttocks and protruding abdomen is often present. Joints exhibit limitation of motion. Arms do not hang freely at the sides and the elbows cannot be straightened.

Oral Manifestations Maxilla is often retruded because of restriction of growth at the base of skull which may produce relative mandibular proganthism.

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Congenital missing teeth with disturbances in shape of teeth may also occur. 600

Histopathological Features Retardation or even aplasia of zone of provisional calcification of endochondral growth occurs. Cartilage columns lack orderly arrangement, fail to calcify properly and are not resorbed and replaced by bone in the usual fashion. Chondrocyte development is defective; the orderly longitudinal growth of bone is disrupted, resulting in stunting of bones.

Radiographic features: Seen most commonly in mandibular first molar area. There is presence of radiopaque sclerotic bone. It is well-defined, rounded elliptic mass.

Histopathological Features It consists of thickened trabeculae and concomitant decrease in the size and number of marrow spaces, vascularity and number of lacunae.

Management No treatment is required for the disease.

Management

MASSIVE OSTEOLYSIS

There is no specific treatment but it is desirable to monitor the progress of affected children to offer support and to detect early the occurrence of any complications. Occupational therapists can be helpful in advising on such issues.

It is also called vanishing bone, disappearing bone, phantom bone, progressive osteolysis or Gorham syndrome. It is characterized by spontaneous, progressive resorption of bone with ultimate total disappearance of bone. Destroyed bone is replaced by vascular proliferation.

Points to Remember Chondrodystrophia fetalis, stubby fingers, large calvarium, lumbar lordosis, retruded maxilla, missing teeth, provisional calcification of endochondral growth, defective chondrocyte.

OSTEOSCLEROSIS There is a focal area of increase radiodensity due to unknown cause. So it is called idiopathic osteosclerosis, dense bone island, bone ebnuration, bone whorl, bone scar, focal periapical osteosclerosis, enostosis. They are localized growth of compact bone that extends from the inner surface of cortical bone into the cancellous bone.

Clinical Features Age: Patient is usually over the age of 12 years. Location: It is asymptomatic and more common in mandible than maxilla and commonly found in premolar molar area. Sign: It is a mass of compact bone within the spongiosis, which does not cause expansion. A rare condition in which there are thousands of dense islands of bone scattered through the skeleton is known as osteopoikile or osteopoikilosis.

Cause Cause is unknown. Initially, it is thought that hyperactivity of osteoclast may lead to destruction of the bone. Some author believed that massive osteolysis may relate to proliferation of blood and lymphatic vessels which can become multicentric. It has been termed as angiomatosis of bone.

Clinical Features Age and sex distribution: It is most common in older children and young and middle age adults, affecting both sexes equally. Sites: The most commonly affected bones are the clavicle, scapula, humerus, ribs, ilium, ischium and sacrum. Symptoms: The disease may or may not be painful, begins suddenly and advance rapidly, until the involved bone is replaced by a thin layer of fibrous tissue surrounding a cavity.

Oral Manifestations The patients may present with pain or facial asymmetry, or both and there is pathologic fracture of bone following even minor trauma. There may be complete destruction of mandible; maxilla is less commonly affected.

Bone Disease Manifested in Jaw

Radiological Features It consist intramedullary radiolucent foci varying size with irregular and diffuse margin. After some period large area bone disappears. There is loss of lamina dura and thinning of cortical plates occurs.

Histopathological Features There is replacement of bone by connective tissue containing many thin walled blood vessels or anastomosing vascular spaces lined by endothelial cells (Fig. 23.35). There chronic inflammatory infiltrate of lymphocytes and plasma cells.

GARDNER’S SYNDROME Gardner’s syndrome is an autosomal dominantly inherited disorder with variable penetrance, characterized by multiple supernumerary teeth, multiple osteomas of bony skeleton, intestinal polyposis, and various skin and soft tissue tumors. Multiple sebaceous cysts are also associated. Manifestation of Gardner’s syndrome is thought to be due to abnormal growth of all three primordial germ layers.

Clinical Features

Multiple polyps of the colon appear in the second decade of life. Although asymptomatic, malignant changes or risk of colonic cancer is almost 100 percent by the age of fifty. Management Skeletal abnormalities are localized cortical skeletal There is no specific treatment; although surgical resection thickening of long tubular bones and osteomas of the ceases the progress of the disease. mandibular ramie are characteristic of this syndrome. In some cases estrogen, magnesium, calcium, Osteomas are noted during puberty. vitamin D, fluoride, calcitonin, alpha-2b interferon and In some cases increase incidence of thyroid carcinoma chemotherapeutic agents can also be given. is also seen. Radiation therapy is most successful and widely Oral Manifestation accepted mode of therapy. In some cases zoledronic acid can also be given. Large osteoma in condylar region may limit the mandibular opening. Points to Remember Dental anomalies noted are supernumerary teeth, Vanishing bone, angiomatosis of bone, involved bone odontomas, multiple unerupted teeth and multiple caries. is replaced by a thin layer of fibrous tissue, facial Sebaceous or epidermoid cyst appear later in life over asymmetry, complete destruction of mandible; maxilla, the face, scalp and extremities. loss of lamina dura, intramedullary radiolucent foci, Lipomas are frequently noted in the subcutaneous many thin walled blood vessels or anastomosing vascular tissue. Fibromas are also reported. spaces, zoledronic acid, estrogen, magnesium, calcium, Radiographic Features vitamin D, fluoride, calcitonin, alpha-2b interferon. Osteoma appears as areas of increase density which varies in size.

Histopathological Features Osteomas are generally of compact type.

Management Prophylactic colectomy is indicated in Gardner syndrome as it has got high incidence of malignant transformation Removal of osteomas of jaw and epidermoid cyst can be carried out for esthetic reason. Points to Remember

Figure 23.35 Vascular channels seen in massive osteolysis

Multiple polyps, osteoma, supernumerary teeth, odontomas, sebaceous or epidermoid cyst, lipomas, prophylactic colectomy.

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BIBLIOGRAPHY 602

1. Abdelsayed RA, Eversole LR, Singh BS, et al. Gigantiform cementoma: A clinicopathological presentation of 3 cases Oral Surg Oral Pathol Oral Radiol Endod. 2001;91;438-44. 2. Adornato MC, Paticof KA. Intralesionla injection for treatment of central giant cell granuloma. J Am Dent Assoc. 2001;132:186-90. 3. Akintoye SO, Lee JS, Feimster T, et al. Dental characteristics of fibrous dysplasia and McCune Albright syndrome. Oral Surg Oral Pathol Oral Radiol Endod. 2003;96:275-82. 4. Akintoye SO, Otis LL, Atkinson JC, et al. Analysis of variable parnoramic radiographic characteristics of maxilla mandibular fibrous dysplasia in McCune Albright syndrome. Oral disease. 2004;10:36-43. 5. Al-Saleem A, Al-Jobair A. Achondroplasia: Craniofacial manifestations and considerations in dental management. The Saudi Dental Journal (2010), doi:10.1016/j. sdentj.2010.07.001. 6. Albuquerque MA, Melo ES, Jorge WA, et al. Osteomyelitis of the mandible associated with autosomal dominant Osteopetrosis, a case report. Oral Surg Oral Pathol Oral Radiol Endod. 2006;102:94-8. 7. Bauss O, Neter D, Rahman A. Prevalence of pulp calcifications in patients with Marfan syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106(6):e5661. 8. Binger T, Rticker M, Spitzer WJ. Dentofacial rehabilitation by osteo-distraction, augmentation and implantation despite osteogenesis imperfecta. Int J Oral Maxillofac Surg. 2006;35:559-562. 9. Butler J, Healy C, Toner, et al. Gardner syndrome – a review and report of cases. Oral Oncol Extra. 2005;41:89-92. 10. Bütow KW, Hoogendijk CF, Zwahlen RA. Pierre Robin sequence: appearances and 25 years of experience with an innovative treatment protocol. J Pediatric Surg. 2009;44(11):2112-8. 11. Carrillo R, Morales A, Rodriguez-Peralto JL, et al. Benign fibroosseous lesion in paget disease of the jaws. Oral Surg Oral Pathol. 1991;72:588-592. 12. Cheng YSL, Wright JM, Walstad WR, et al. Osteosarcoma arising in Paget disease of bone. Oral Oncol. 2002;38:78592. 13. Cohen MM, et al. Dental and Facial Characteristics in Down’s syndrome. J Dent Res. 1965;44(suppl):197-208. 14. DeLange J, van den Akker HP. Clinical and radiological features of central giant cell lesion of the jaw. Oral Surg Oral Pathol Oral Radiol Endod. 2005;99:464-70. 15. El MOfty S. Psammomatoid and trabeculae juvenile ossifying fibroma of the craniofacial skeleton two distinct entities. Oral Surg Oral Pathol Oral Radiol Endod: 2002;93:296-304.

16. Eversole LR, Leider AS, Nelson K. Ossifying fibroma: a clinico-pathologic study of 64 cases. Oral Surg Oral Pathol. 1985;60:505-11. 17. Filho AM, de castro Domingos, de Freitas DQ, et al. Osteopetrosis – a review and report of two cases. Oral Disease. 2005;11:46-9. 18. Geist JR, Katz JO. The frequency and distribution of idiopathic osteosclerosis. Oral Surg Oral Med Oral Pathol. 1990;69;388-93. 19. Groot RH, van Merkesteyn JPR, Bras J. Diffuse sclerosing osteomyelitis and florid osseous dysplasia: Oral Surg Oral Pathol Oral Radiol Endod. 1996;81:333-42. 20. Holroyd I, Doku HC, Carter BL, et al. Gorham’s disease: A case (including dental presentation) of vanishing bone disease. Oral Surg Oral Pathol Oral Radiol Endod. 2000;89:125-9. 21. Kamoun-Goldrat A, Martinovic J, Saada J, et al. “Prenatal cortical hyperostosis with COL1A1 gene mutation”. Am J Med Genet. 2008;146A(14):1820-4. 22. Lidsky ME, Lander TA, Sidman JD. Resolving feeding difficulties with early airway intervention in Pierre Robin Sequence. Laryngoscope. 2008;118(1):120-3. 23. MacDonald-Jankowski DS. idiopathic osteosclerosis in jaws of Briton and of the Hong Kong Chinese: radiology and systemic review. Dentomaxillofac Radiol. 1999;28:357-63. 24. MacDonald Jankowski DS. Cemento-ossifying fibromas in the jaws of hong Kong Chinese. Dentomaxillofac Radiol. 1998;27:298-304. 25. Melrose RJ, Abrams AM, Mills BG. Florid osseous dysplasia, a clinico-pathologic study of thirty four cases: Oral Surg Oral Pathol. 1976;41:62-82. 26. Mignogna MD, Fedele S, Lo Russo L, et al. Treatment of Gorham’s disease with zoledronic acid. Oral Oncol. 2005;41:747-50. 27. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edn. Saunder Elsevier; 2009. 28. Oreland A, et al. Malocclusions in physically and/or mentally handicapped children Swed Dent Jour. 1987;11(3):103-19. 29. Otomo-Corgel J. Osteoporosis and osteopenia: implications for periodontal and implant therapy, Periodontol 2000. 2012;59(1):111-39. 30. O’Connel AC, Marini JC. Evaluation of oral problems in an osteogenesis imperfecta population. Oral Surg Oral Pathol Oral Radiol Endod. 1995;887:189-96. 31. Penarrocha M, Bonet J, Minguez M. Cherubism: A clinical, radiographic, and histopathological comparison of 7 cases: J Oral Maxillofac Surg. 2006;64:924-30. 32. Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004;363:1377-85. 33. Ricalde P, Ord RA, Sun CCJ. Vanishing bone disease in five year old: report of case and review of literature. Int J Oral Maxillofac Surg. 2003;32:222-6. 34. Rossbch HC, Letson D, Lacson, et al. Familial gigantiform cementoma with brittle bone disease, pathologic fracture

Bone Disease Manifested in Jaw and osteosarcoma: a possible explanation of ancient mystery: pediatric blood cancer. 2005;44:390-6. 35. Smith J, Eveson J. Paget disases of bone with particular reference to dentistry. J Oral Pathol. 1981;10:233-47. 36. Starropoulos F, Katz J. Central giant cell granulomas: A system review of the radiographic characreristic with addition of 20 new cases. Dentomaxilllofac Radiol. 2002;31:213-7. 37. Von Wowern N. Cherubism: A 36 years long term follow up 2 generation in different families and review of literature. Oral Surg Oral Pathol Oral Radiol Endod. 1981;10:233-47; 2000;90;765-72.

38. Waldoron CA. Fibro-osseous lesion of the jaw: J Oral Maxillofac Surg. 1993;51:828-35. 39. Williams HK, Mangham C: SpeIght PM. Juvenile ossifying fibroma: an analysis of eight cases and comparison with other fibro-osseous lesion: J Oral Pathol Med. 2000;29: 13-8. 40. Yonetsu K, Yuasa K, Kanda S. Idiopathic osteosclerosis of the jaw; panoramic radiographic and computed tomographic finding. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;83:517-21.

MULTIPLE CHOICE QUESTIONS 1. In monostotic fibrous dysplasia there is an involvement of: a. Multiple bone b. Multiple bone with pigmentation c. Single bone d. Single bone and endocrinal disturbance 2. Multiple bone involvement accompanied by pigmented lesion plus endocrine disturbance seen in: a. Albright’s syndrome b. Down’s syndrome c. Cherubism d. Marble bone disease 3. C–shaped or Chinese character shaped trabeculae of bone seen in: a. Polystotic fibrous dysplasia b. Monostotic fibrous dysplasia c. Both d. None 4. ‘Eye raised to heaven’ look is the clinical feature seen in: a. Marfan’s syndrome b. Fibrous dysplasia c. Albright’s syndrome d. Cherubism 5. ‘Osteitis deformans’ refers to: a. Paget’s disease b. Cherubism c. Osteoporosis d. Osteopetrosis

6. ‘Jigsaw puzzle’ or ‘mosaic pattern’ of bone seen in: a. Cherubism b. Paget’s disease c. Fibrous osseous dysplasia d. Achondroplasia 7. ‘Marble bone disease’ refers to: a. Osteopetrosis b. Osteoporosis c. Albers-Schonberg disease d. Both a and c 8. Extreme fragile bones, pale blue sclera is the clinical feature seen in: a. Osteogenesis imperfecta b. Lobstein disease c. Robin anomalad d. Both a and b 9. ‘Spider finger’ is a clinical feature of: a. Marfan’s syndrome b. Down’s syndrome c. Brittle bone disease d. Lobstein disease 10. Down’s syndrome is associated with: a. Trisomy of 21 chromosome b. Deletion in 5 chromosome c. Trisomy of 13 chromosome d. None

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Diseases of Lip

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline         Â

Anatomy Congenital lip pits Commissural pits Double lip Cleft lip and palate Glandular cheilitis Granulomatous cheilitis Angular cheilitis Eczematous cheilitis

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Contact cheilitis Actinic cheilitis Exfoliative cheilitis Plasma cell cheilitis Carcinoma of lip Chapping of the lips Actinic elastosis Lip ulcers due to caliber persistent artery

CLASSIFICATION OF LIP DISORDERS

ANATOMY

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Lips are fleshy folds lined by skin externally and mucous membrane internally. The upper and lower lips close along the red margin which represents the mucocutaneous junction. The lips are covered with skin on the external surface and mucous membrane on the inner surface, which has profuse salivary glands. The lip extends from the lower end of the nose to the upper end of the chin. The upper lip borders onto the nose and is separated form the cheek by a variably deep groove called as nasolabial groove. The lower lip is separated from the chin proper by a more or less sharp and deep groove that is convex superiorly called as labiomental groove. Oral commissural is the angle where the upper and lower lip meets. The upper lip includes the philtrum, a midline depression, which can be followed to the nose. Each lip mainly consists of bundles of striated muscle, orbicularis oris, superficial fascia and submucosa. The skin of the lip contains sweat glands, hair and sebaceous gland. The dermal papillae are numerous, with rich capillary supply, which produce reddish pink color of the lips.

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Developmental: – Congenital lip pits – Commissural lip pits – Double lip – Cleft lip and cleft palate Cheilitis: – Glandular cheilitis – Granulomatous cheilitis – Angular cheilitis – Contact cheilitis – Eczematous cheilitis – Actinic cheilitis – Exfoliative cheilitis – Plasma cell cheilitis – Cheilitis due to drugs Carcinoma of lip Miscellaneous: – Chapping of lips – Actinic elastosis – Lip ulcers due to caliber persistent artery.

Diseases of Lip

Vermilion zone: It is the transitional zone between the skin and the mucous membrane. The vermilion zone contains no hair or sweat glands and contains a few sebaceous glands. In some people, sebaceous glands may be seen as creamy yellow dots. Fordyce’s spots along the border between vermilion border and the oral mucosa can also occur. Submental artery to the lower lip and inferior and superior labial arteries to the upper lip supply the lip. Anterior facial vein and its branches corresponding to the facial artery provide the venous drainage of lips. Lymphatic drainage is from central part of lower lip lymphatics drain to the submental node and rest of the lip to submandibular nodes. Mental nerve and superior labial nerve are the nerve supply of the lip.

DEVELOPMENTAL DISTURBANCE OF LIP Congenital Lip Pits It is also called as paramedian lip pits, congenital fistulas of the lower lip. They arise from persistent lateral sulci on the embryonic mandibular arch.

Etiology It is inherited as autosomal dominant trait. There is notching of lips at an early stage of development with fixation of tissues at the base of the notch. It may occur due to failure of complete union of embryonic sulci of the lip.

Clinical Features Sex distribution: It is more commonly seen in females. Location: It is common on vermilion border of either lips and most commonly on lower lip. Lip pits or fistula is unilateral or bilateral depression. Size: It may be up to 3 to 4 mm in diameter and may extend as deep as 2 cm and communicated with underlying minor salivary glands. Sign: In some cases, sparse mucus secretion may be visible from the base of the pit. Lips, sometimes appear swollen, accentuating the appearance of the pit. Syndrome associated: Congenital lip pits may occur in association with Van der Woude’s syndrome (cleft lip, cleft palate and congenital lip pits) popliteal pterygium

syndrome (popliteal webbing, cleft lip/palate, genital abnormalities, and congenital bands connecting the upper and lower jaw).

Histopathological Feature It shows the tract lined by stratified squamous epithelial. Chronic inflammatory cell infiltrate is noted in the surrounding connective tissue.

Management Surgical excision for cosmetic purpose should be carried out. Points to Remember Paramedian lip pits, congenital fistulas, autosomal dominant trait, vermilion border, sparse mucus secretion, Van der Woude’s syndrome, popliteal pterygium syndrome, stratified squamous epithelial, chronic inflammatory cell infiltrate, surgical excision.

Commissural Pits Commissural lip pit occur due to failure in fusion of embryonic process. These are invagination occur on lip.

Clinical Features Age and sex distribution: It is more common amongst males and black people are affected more than white people. It is more common in male as compare to female. Location: Commissural pit appears as a unilateral or bilateral pit at the corner of the mouth on the vermilion surface. If it is unilateral, it occurs on the right side of the lip. It is localized at angle of mouth with the tract diverging dorso-laterally into the cheek (Fig. 24.1). Sign: In some cases small amount of fluid can be seen from the pit when the pit is squeezed which may occur from minor salivary gland. Size: Ranges from a shallow dimple to a tract measuring 4 mm in length and tissue slightly raised above the opening.

Histopathological Features There is narrow invagination line by stratified squamous epithelium. Ducts from minor salivary gland may drains into the invagination.

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hangs loosely over the margin of the lid) and nontoxic thyroid enlargement.

Histopathological Features

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There is abundance of minor salivary gland. Ascher’s syndrome shows hyperplasia of the lacrimal gland or prolapse of orbital fat.

Management Surgical excision of excess tissue can be perform for esthetics purpose. Points to Remember Figure 24.1 Commissural pit seen at angle of mouth

Management No treatment is necessary as it is asymptomatic. In cases of secondary infection surgical excision should be carried out. Points to Remember Failure in fusion of embryonic process, unilateral or bilateral pit, the corner of the mouth on the vermilion surface, shallow dimple to a tract measuring 4 mm, narrow invagination, stratified squamous epithelium.

Double Lip It is an anomaly characterized by a fold of excess tissue on the inner mucosal surface of the lip. It may be congenital or acquired because of trauma to the lip. The congenital variety occurs as a result of persistence of horizontal sulcus which is situated between pars glabrosa and pars villosa of the lip. The acquired variety occur due sucking of lip inside the oral cavity.

Clinical Features Location: Upper lip is more commonly affected than a lower lip. It usually occurs on inner aspect of upper lip. Cupid bow: When upper lip is tensed double lip resembles cupid bow. It is associated with Ascher’s syndrome which consists of double lip, blepharochalasis (it is drooping of the tissue between eyebrow and edge of the upper eyelid so that it

Cupid bow, Ascher’s syndrome, abundance of minor salivary gland.

Cleft Lip and Palate It occurs along many planes as a result of fault or defect in the development.

Etiology Hereditary: It is one of most important factors to be considered in the etiology. Genetic: The main possible mode of transmission is by a single mutant gene; producing a large effect or by number of genes (polygenic inheritance), each producing small effects which together create this condition. Nutritional disturbances: Riboflavin deficient diet can produce cleft palate and cleft lip. Developmental: Physiological, emotional and traumatic stress during developmental stages. Defective vascular supply: Defective vascular supply to the area may lead to ischemia which in turn may lead to cleft formation. Mechanical disturbances: Here, the size of tongue may prevent union of the parts. Infection: Infection and lack of inherent developmental force. Miscellaneous: Steroid therapy during pregnancy, alcohol, toxins in the circulation.

Development of Cleft Mandibular cleft lip occurs due to failure of copula to give rise to mandibular arch or persistence of the central groove

Diseases of Lip

of mandibular process. Maxillary cleft lip occurs due to failure of mesodermal penetration and obliteration of the ectodermal groove separating that mesodermal mass which actually constitutes the facial process. Either absence or deficiency of these mesodermal masses or their failure to penetrate the ectodermal grooves leads to breakdown of the ectoderm, causing cleft formation. The cleft of lip occurs earlier and inhibits tongue migration, which may then prevent horizontal alignment and fusion of the palatal shelves. In unilateral cleft lip, the floor of the nose communicates freely with the oral cavity, maxilla on the cleft side is hypoplastic, columella is displaced to the normal side and the nasal ala on the cleft side is laterally, posteriorly and inferiorly displaced. The lower lateral cartilage of the nose is lower on the cleft side, its lateral cruz is longer and the angle between the medial and lateral cruz is more obtuse. The muscles of the orbicularis oris do not form a complete sphincter but instead are directed superiorly to the ala nasi, laterally and the base of the columella. medially. In bilateral cleft lip, the central portion of the alveolar arch is rotated anteriorly and superiorly. The medial or prolabial segment of skin contains no muscle or vermilion. In palatal clefts, the muscles of soft palate are hypoplastic and insert in the posterior margin of the remaining hard palate rather than the midline raphe. Cleft palate occurs due to disturbances in normal fusion of palatal shelves; failure to unite due to lack of force, interference by the tongue or a disparity in the size of parts involved. Cleft of soft palate and uvula do not appear to be formed as a result of nonfusion of parts but rather as posterior extension of palatal process; thus cleft of these parts is basically extension of a cleft of hard palate. Clefts of the primary palate occur anterior to the incisive foramen. Clefts of the secondary palate are due to lack of fusion of the palatal shelves and always occurs posterior to the incisive foramen. The secondary palate closes 1 week later in females, which may explain why isolated clefts of the secondary palate are more common in females. A cleft lip increases the probability of development of cleft palate (Fig. 24.2).

Types of Cleft in Orofacial Region Cleft lip: It is a birth defect that results in a unilateral or bilateral opening in the upper lip between the mouth and the nose. It is also called as harelip. It is wedge shaped defect resulting from failure of two parts of the lip to fuse into a single structure.

Cleft palate: Cleft palate is a birth defect characterized by an opening in the roof of the mouth caused by a lack of tissue development. Lateral facial cleft: It is cause by lack of fusion of maxillary and mandibular process. It extends from commissure toward the ear. This will results in macrostomia. This can occur in syndrome like mandibulofacial dysostosis, hemifacial macrostomia. Oblique facial cleft: It extend from upper lip to eye. It may involve nostril or may bypass nose laterally to reach to eye. This may results due to failure of fusion of lateral nasal process with maxillary process. Median cleft of lip: It occur due to failure of fusion of medial nasal process. It may be associated with oro-facialdigital syndrome and Ellis-van Creveld syndrome. Classification 1st • Unilateral incomplete • Unilateral complete • Bilateral incomplete • Bilateral complete. 2nd by Veau’s • Cleft lip – Class I: A unilateral notching of vermilion not extending into the lip. – Class II: A unilateral notching of vermilion with cleft extending into lip but not including the floor of the nose. – Class III: A unilateral cleft of vermilion extending into the floor of the nose. – Class IV: Any bilateral cleft of the lip, whether this is complete or incomplete. • Cleft palate – Class I: Involving only soft palate. – Class II: Involving soft and hard palate but not alveolus. – Class III: Involving soft and hard palate and alveolus of one side. – Class IV: Involving both the soft and hard palate and alveolus on both sides of the pre-maxilla.

Clinical Features General: It is more common in boys than in girls. It is more frequently seen on the left side than on the right

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Speech problem is serious and tends to increase due to mental trauma. There is defect in smelling due to contamination of the nasal mucous membrane with the oral organism through the cleft palate. The alveolar cleft interferes with the dental lamina and the upper lateral incisors may be small, absent or even duplicate. Cleft of palate may also vary in severity, involving uvula or soft palate or extending all the way through the palate and indirectly to the alveolar ridge on one or both sides (Figs 24.4 and 24.5). Isolated cleft palate is associated with other developmental abnormalities like congenital heart disease, polydactyly and syndactyly, hydrocephalus, micro-cephalus, clubfoot, supernumerary ear, spina bifida, hypertelorism

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Figure 24.2 Cleft involving lip as well as palate in a child

side. Left side is involved in 70 percent of the cases. A typical patient with cleft palate, cleft lip and ridge exhibits a large defect with a direct opening in the nasal cavity. Disturbances in the dental structures are seen in this region so that teeth may be missing, deformed, displaced or divided, thus producing supernumerary teeth. Cleft lip: A unilateral cleft involves only one side of the lip; a bilateral one involves both sides and later gives rise to hair lip. Incomplete cleft lip extends for varying distances forward to the nostril, but not up to the nostril. The upper part of lip has fused normally. Complete cleft lip extends into nostril and palate is commonly involved. It is often associated with flattening and widening of the nostril of the affected side. Sucking become difficult to some extent but not greatly. There is defective speech particularly with the labial letters B, F, M, P and V. Cleft of mandibular lip or jaws are rare. There is soft tissue mass between the ends of the bone, uniting the tongue to the lip, so that tongue is bound down (Fig. 24.3). Cleft palate: There may be cleft of the hard and soft palate or in some cases, cleft of soft palate alone. Entire pre-maxillary portion of bone may be missing and in such instances, the cleft appears to be entirely a midline defect. Cross bite due to medial collapse of premaxilla. Eating and drinking is difficult due to regurgitation of food and liquid through the nose.

Figure 24.3 Cleft of lip without involvement of palate

Figure 24.4 Cleft involving palate see as defect

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A

B Figures 24.5A and B Cleft lip and palate

and mental deficiency. Isolated cleft palate is more common in females as compared to male. Airway problems may arise in children with cleft palates, especially those with concomitant structural or functional anomalies. For example, Pierre-Robin syndrome is the combination of micrognathia, cleft palate and glossoptosis. Affected patients may develop airway distress from their tongue becoming lodged in the palatal defect. Ear infection and respiratory tract infection.

Cheiloplasty: It is surgical closure of the lip. A general ‘rule of tens’ is used in determining optimal timing of lip closure, i.e. 10 weeks of age, 10 pounds of body weight and 10 gm of Hb. At the time of lip closure, when an infant is under general anesthesia, an impression is made for the new obturator.

Submucous palatal cleft: In this defect exists in underlying musculature of soft palate. The overlying mucosa is intact in this case. It has been seen as bluish midline discoloration.

Palatoplasty: It is performed to close an opening in the palate. Surgeons may close the palate in one surgery, when the child is about one year of age or the palate may be closed in two stages, the soft palate first followed by the hard palate.

Syndrome Associated with Cleft Palate • • • • • • • • •

Pierre-Robin syndrome Goldenhar syndrome Median cleft face syndrome Oral facial digital syndrome Apert’s syndrome Nagar syndrome Otopalatodigital syndrome Down’s syndrome Marfan syndrome

Management The complete rehabilitation of the condition requires a multi-disciplinary approach.

Obturator: Between 3rd and 9th months of age, an obturator is used to provide cross-arch stability, support and to prevent collapse of maxillary arch.

Bone grafting: Sometimes closure of palatal cleft may be done by bone grafting. Orthodontic therapy: Orthodontic therapy is done to correct malocclusion. Cleft rhinoplasty: To improve nasal function and correct the distortion. Speech therapy: Speech therapy is given to improve pronunciation of the words. Psychotherapy: Psychological management is necessary. Feeding plate: To overcome initial feeding problems, feeding plate is used which acts as an obturator to prevent nasal reflux.

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Points to Remember 610

Unilateral cleft, bilateral hair lip, incomplete cleft lip, complete cleft lip extends into nostril and palate, defective speech B, F, M, P and V, cleft palate premaxillary portion, cross bite, eating and drinking, speech problem, isolated cleft palate, airway problems, Pierre-Robin syndrome, ear infection and respiratory tract infection, submucous palatal cleft, cheiloplasty, obturator, palatoplasty, bone grafting, orthodontic therapy, cleft rhinoplasty, speech therapy, psychotherapy, feeding plate.

CHEILITIS Glandular Cheilitis It is also called as cheilitis glandularis. It is an uncommon condition in which lower lip becomes enlarged, firm and finally everted.

ETIOLOGY It occurs due to chronic exposure to sun, wind and dust as well as use of tobacco. In several cases, emotional disturbances, as well as familial occurrence, suggesting a hereditary pattern is observed. Inflammation of enlarged heterotopic salivary glands may also leads to glandular cheilitis. Types

Clinical Features Age distribution: It is more common in adults but sometimes it can also occur in children. Site: Lower lip is involved more often than the upper lip. Signs: Labial salivary glands become enlarged and sometimes nodular. Orifices of secretory ducts are inflamed and dilated appearing as small red macules over the mucosa. Viscid mucous secretion may seep from these openings of everted hypertrophic lips. Volkmann’s cheilitis: It is more severe suppurative form of glandular cheilitis. The lip is considerably and permanently enlarged and is subjected to episodes of pain, tenderness and increased enlargement. The surface is covered by crust and scales beneath which the salivary duct orifice may be discovered (Fig. 24.6). Malignant transformation: It is apparently pre-malignant and epidermoid carcinoma can be associated with it in 18 to 35 percent of cases.

Histopathological Features There is presence of stratified squamous epithelium which covers inflammatory connective tissue. In a milder form, there is some fibrosis surrounding the salivary glands and in the more severe forms, there may be a dense, inflammatory infiltrate. The underlying salivary gland tissue shows hypertrophy and inflammation. In some cases there is dysplastic changes can be seen in the epithelium.

• Simple • Superficial suppurative type (Baelz’s disease) • Deep suppurative type (cheilitis glandularis apostematosa, myxadenitis labialis).

Types Simple: Multiple, painless, pinhead sized lesions with central depression and dilated canals present. Superficial suppurative type (Baelz’s disease): It is characterized by painless swelling, induration, crusting and superficial ulceration of lip. Deep suppurative type (Cheilitis glandularis aposte­ matosa, myxadenitis labialis): Deep seated infection with abscess and fistula tract that eventually forms a scar.

Figure 24.6 Volkmann’s cheilitis seen as crusted area

Diseases of Lip

Management Vermilionectomy: Due to high incidence of associated malignancy, a vermilionectomy or surgical stripping of lips has been recommended. If the lips are grossly enlarged, excision of an elongated ellipse of tissue may be required. Points to Remember Cheilitis glandularis, inflammation of enlarged heterotopic salivary glands, secretory ducts are inflamed, Volkmann’s cheilitis, stratified squamous epithelium, fibrosis surrounding the salivary glands, dense, inflammatory infiltrate, vermilionectomy, dysplastic changes.

Granulomatous Cheilitis It is also called as Miescher’s syndrome or cheilitis granulomatosa. It is a condition of unknown etiology that is not related to cheilitis glandularis except by the similarity in the clinical appearance of the two diseases.

Clinical Features Age and sex distribution: It is seen in adults as well as in children and there is female predilection. Sign and symptoms: There is diffuse swelling of the lips, especially the lower lip (Fig. 24.7). In some cases, an attack

is accompanied by fever and mild constitutional symptoms including headache and even visual disturbances. Enlarged lip can create cosmetic problems, difficulty during eating, drinking or speaking. In some cases, scaling, fissuring and vesicles or pustules have been reported. The swelling is usually soft and exhibits no pitting on pressure. Swelling eventually becomes firmer and acquires the consistency of that of hard rubber. The regional lymph nodes are enlarged in some cases, but not always. The skin and adjacent mucosa may be of normal color or erythematous. It is associated with Melkersson-Rosenthal syndrome which consists of fissured tongue and facial paralysis.

Histopathological Features (Fig. 24.8) It consists of chronic inflammatory cell infiltrate particularly peri and paravascular aggregation of lymphocytes, plasma cells and histiocytes. There is focal noncaseating granuloma formation with epitheloid cells and Langhans type of giant cells. There is generalized edema and dilated blood vessels present in the connective tissue.

Management Corticosteroid injection: Repeated injection of triamcinolone into the lips every few weeks may be effective. Cheiloplasty: Surgical stripping of lip can be done.

Figure 24.7 Cheilitis granulomatosa showing

Figure 24.8 Histopathological picture of granulomatous

diffuse swelling of lip

cheilitis

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Points to Remember 612

Miescher’s syndrome, fever, headache, cosmetic problems, scaling, fissuring and vesicles or pustules, regional lymph nodes, Melkersson-Rosenthal syndrome, chronic inflammatory cell infiltrate, lymphocytes, plasma cells and histiocytes, focal noncaseating granuloma, corticosteroid injection.

Angular Cheilitis It is also called perleche, angular cheilosis.

Diseases of skin: Atopic dermatitis involving the face is often associated with angular cheilitis. The incidence also appears to be increased in seborrhoeic dermatitis. Other factors: Hypersalivation, Down’s syndrome, large tongue and constant dribbling being the contributory factors. A rare cause is the presence of a sinus of developmental origin at the angles of the mouth.

Clinical Features Age: It occurs in young children as well as in adults.

Signs: It is characterized by feeling of dryness and a burning sensation at the corners of the mouth. It is usually Microorganisms: It is caused by Candida albicans, but a roughly triangular area of erythema and edema at one or more, commonly both the angles of mouth (Fig. 24.9). also staphylococci and streptococci. Epithelium at the commissures appears wrinkled and Mechanical factors: Over closure of jaws such as in somewhat macerated. In time, wrinkling becomes more edentulous patients or in patients with artificial dentures pronounced to form one or more deep fissures or cracks which lack proper vertical dimensions. In it, folds are which appear ulcerated but which do not tend to bleed, produced at the corners of the mouth in which saliva although a superficial exudative crust may form. tends to collect and the skin becomes macerated, Linear furrow or fissures radiating from the angle of fissured and secondarily infected. Prognathism may give mouth (rhagades) are seen in more severe forms, especially rise to a similar state of affair in young. The recurrent in denture wearers. If the lesion is not treated, they often trauma from dental flossing may occasionally be also show a tendency for spontaneous remission. implicated.

Causes

Nutritional deficiency: It can also occur due to riboflavin, folate and iron deficiency with a superimposed fungal or bacterial infection. General protein deficiency can also cause cheilitis.

Management Removal of cause: Underlying primary cause should be identified and treated. A course of vitamin B and iron supplements is useful in these cases. Fusidic acid ointment: It is used in staphylococcal infection. The lesions should be swabbed first and then fusidic acid ointment or cream should be applied at least four times a day. Miconazole may be preferred, if angular cheilitis is due to candidiasis (cream applied locally together with an oral gel). Gentian violet application: In some cases it is useful. Points to Remember Perleche, epithelium macerated, rhagades, dryness and a burning sensation, fusidic acid ointment, Miconazole, gentian violet application.

Eczematous Cheilitis Figure 24.9 Angular cheilitis presented as fissuring and crack

at the corner of mouth

The lips are involved secondary to atopic eczema but possibility of contact dermatitis must also be considered.

Diseases of Lip

The Management of atopic eczema of the lips is with an emollient and topical steroids.

Contact Cheilitis

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Contact cheilitis is an inflammatory reaction of the lips provoked by the irritants or sensitizing action of chemical agents in direct contact with them.

Causes Lipsticks: They are composed of mineral oils and waxes which form the stick; castor oil as a solvent for the dyes, lanolin as an emollient preservative, perfumes and color. The color includes azo dyes and eosin, which is a bromofluorescein derivative. Sunscreen applied in the form of lipstick can also cause contact cheilitis. Some also contain ditrimethylolpropane triethylhexanoate which can cause allergic reaction. Lipsalves and other medicaments: Lipsalves containing lanolin are frequently applied for dryness or chapping. Phenyl salicylates and antibiotics have also been incriminated as a cause of cheilitis. Mouthwashes and dentifrices: Essential oils such as peppermint, cinnamon, clove, spearmint and bactericidal agents can cause cheilitis. Propolis, derived from resin and collected by bees, is a well known sensitizer which has been used in toothpastes. Dental preparations: Mercury and eugenol may cause cheilitis in the absence of stomatitis. Allergy to epimine containing materials used for crowns and bridges can cause cheilitis.

Figure 24.10 Cheilitis occurs due to lipstick allergy

Pigmented contact cheilitis: It is cause due to paraphenulen diamine use in hair dye.

Management Topical steroids will give symptomatic relief. Avoidance of specific allergens: The offending substance must be traced and avoided. Points to Remember Lipstick cheilitis, persistent irritation, pigmented contact cheilitis, topical steroids, avoidance of specific allergens.

Actinic Cheilitis

It is also called as actinic keratosis or solar cheilosis, farmer’s lip, sailor’s lip. Foods: Oranges, mangoes and artichokes are among the It is a pre-malignant sq. cell lesion resulting from long food plants which occasionally cause allergic cheilitis and term exposure to solar radiation and may be found at the dermatitis of the skin around the lips. vermilion border of lip as well as other sun exposed surfaces. Miscellaneous objects: Metal hair clips, metal pencils, Etiology cobalt paint on blue pencil can also cause cheilitis. Paraphenylene diamine (PPD) is a coal-tar derivative Chronic sun exposure is the main cause so it usually occurs in hot, dry regions, in outdoor workers and in fair skinned that is widely used as a permanent hair dye. people.

Clinical Features

Location: Lipstick cheilitis is usually confined to the vermilion borders but more often extends beyond that (Fig. 24.10). Sign and symptom: There may be persistent irritation and scaling or a more acute reaction with edema and vesiculation. There is also dryness, crusting, fissuring, erythema.

Clinical Features Site: The lower lip is more commonly affected than the upper lip as it receives more solar radiation than the upper lip. Age and sex distribution: It has got strong male predilection in the ratio of 10:1 than female. The reason

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Figure 24.11 Actinic cheilitis showing scaling and dry

Figure 24.12 Actinic cheilitis atrophic epithelium

for this is due to fact that females had sunscreen effect of lipstick. It is also less common in blacks due to protective effect of melanin. It is more seen in older individual than 45 years of age.

Nuclear atypia and abnormal mitoses can be seen in more severe cases and some develop into invasive squamous cell carcinoma. The collagen generally shows basophilic degeneration.

Sign: In the early stages, there may be redness and edema but later on, the lips become dry and scaly (Fig. 24.11). If scales are removed at this stage, tiny bleeding points are revealed. With the passage of time, these scales become thick and horny with distinct edges. Epithelium becomes palpably thickened with small grayish white plaques. Vertical fissuring and crusting occurs, particularly in the cold weather. At times, vesicle may appear which rupture to form superficial erosions. Secondary infection may occur. Eventually warty nodules may form which tend to vary in size with fluctuation in the degree of edema and inflammation. Signs of Malignant Transformation • • • •

Ulceration in actinic cheilitis Red and white blotchy appearance Indistinct vermilion border Generalized atrophy or focal areas of whitish thickening • Persistent flaking and crusting and indurations at the base of keratotic lesion.

Histopathological Features It shows flattened or atrophic stratified epithelium beneath which is a band of inflammatory infiltrate in which plasma cells may predominate (Fig. 24.12).

Management Topical fluorouracil: For mild cases, application of 5 percent fluorouracil three times daily for 10 days is suitable. It produces brisk erosion but lips heal within 3 weeks. Application of 5-fluorouracil to the lip will produce erythema, vesiculation, erosion ulceration, necrosis and epithelization. In some cases, podophyllin is also used. Rapid freezing with CO2 snow or liquid nitrogen on swab stick is used to remove superficial lesions. Vermilionectomy (Lip shaves): Under local anesthesia, the vermilion border is excised by a scalpel and closure is then achieved by advancing the labial mucosa to the skin. Postoperative complications include paresthesia, lip pruritis and labial scar tension. Laser ablation: Carbon dioxide laser therapy has been used to vaporize the vermilion. Good results with no postoperative paresthesia or significant scarring have been reported. Following Management, prevention of recurrence by regular use of sunscreen lip salves is advisable. Liquid or gel waterproof preparation containing para-aminobenzoic acid probably gives the best protection.

Diseases of Lip

Points to Remember Actinic keratosis, solar cheilosis, redness and edema, tiny bleeding points, grayish white plaques, secondary infection, vertical fissuring and crusting, atrophic stratified epithelium, nuclear atypia and abnormal mitoses, basophilic degeneration, topical fluorouracil, rapid freezing with CO2, vermilionectomy (lip shaves), laser ablation.

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Exfoliative Cheilitis It is a chronic superficial inflammatory disorder of the vermilion border of lips characterized by persistent scaling.

Causes This can occur due to excessive production and subsequent desquamation of superficial keratin. Some cases may occur due to repeated lip sucking, chewing or other manipulation of the lips. Cases which occur due to chronic injury is called factitious cheilitis. In some cases diffuse infection secondary to Candida infection occur at the areas of low grade trauma of vermilion border of lip. This type is called cheilocandidiasis.

Clinical Features Age and sex distribution: Most cases occur in girls and young women and majority have personality disorders. Location: The process starts in the middle of the lower lip and spreads to involve the whole of the lower lip or both the lips. Sign: It consists of scaling and crusting, more or less confined to the vermilion borders and persisting in varying severity for months or years. Later vermilion border is covered with thickened yellowish hyperkeratotic crust that can be hemorrhagic (Fig. 24.13). Symptoms: The patient complains of irritation or burning and can be observed frequently biting or sucking the lips. Circumoral dermatitis: There is involvement of perioral skin which is presenred as areas of crusted erythema.

Management Elimination of cause: This will result in resolution of the lesion. Psychotherapy: This can be given for stress reduction. It is given in combination with tranquilizers.

Figure 24.13 Exfoliative cheilitis

Other therapy like corticosteroids, topical tacrolimus, sunscreen and moisturizing preparation is useful. Points to Remember Desquamation of superficial keratin, scaling and crusting, more or less confined to the vermilion borders, irritation or burning, circumoral dermatitis, psychotherapy, corticosteroids, topical tacrolimus, sunscreen.

Plasma Cell Cheilitis It is an idiopathic benign inflammatory condition characterized by dense plasma cell infiltrate in the mucosa close to the body orifice. It is thought to be cause by traumatic, genetic, hormonal, and autoimmune factors have been regarded as possible etiologic factors.

Clinical Features Site: It can affect penis, vulva, lips, buccal mucosa, palate, gingiva, tongue, epiglottis and larynx. Signs: It presents as circumscribed patches of erythema, usually on the lower lip in elderly persons.

Histopathological Features It is histologically characterized by plasma cell infiltrates into the mucosa. There is also presence of dilated blood vessels.

Management Steroid: It responds to topical application of powerful steroids or to intradermal injection of triamcinolone.

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Other therapy: It includes oral griseofulvin, and topical cyclosporine Topical calcineurin inhibitors are effective for plasma cell cheilitis. Agents used are pimecrolimus and tacrolimus. Points to Remember Circumscribed patches of erythema, plasma cell infiltrates topical calcineurin inhibitors, steroid.

Carcinoma of Lip Squamous cell carcinoma is the most common malignancy to affect the vermilion zone.

Clinical Features Age and sex distribution: There is peak appearance in 6th and 7th decade of life. It is more common in males as compared to females.

Figure 24.14 Malignancy of lip presented as ulcerative

growth on lower lip

Location: It is most common on the lower lips of fair skinned people and persons who work in outer climate. It usually begins on vermilion border of the lip to one side of the midline and it may be covered with a crust due to absence of saliva. Preceding factors: It is preceded by actinic cheilitis which is characterized by innocuous looking white plaque on the lip. Symptoms: Patient may complain of difficulty in speech, difficulty in taking food and inability to close the mouth. There is also pain, bleeding and paresthesia. Sign: It often commences as a small area of thickening, induration and ulceration or irregularity of the surface. In some cases it commence as a small warty growth or fissure on the vermilion border of the lip. Crater like lesion having a velvety red base and rolled indurated borders are present. As the lesion enlarge it takes papillary or an ulcerative form. In untreated cases there is total destruction of lip and invasion of cheek, the gums and the mandible (Figs 24.14 and 24.15). Papillary lesion grows slowly and infiltrated the deeper tissue relatively late whereas ulcerative growths invade early. It may metastasize and it usually ipsilateral. Carcinoma of the upper lip metastasizes earlier and more frequently than carcinoma of the lower lip. It involves submaxillary and submental lymph nodes first and then deep cervical nodes. It is spread by direct extension into

Figure 24.15 Granulomatous ulcerative growth seen in

malignancy

surrounding structures and by metastasis which is through lymphatic channels.

Histopathological Features They are mostly well differentiated malignancies.

Management Surgical: Prognosis is good if the treatment is done before metastasis. The best results are seen when the entire lip mucosal field is removed with early lesion.

Diseases of Lip

Points to Remember

Clinical Types

Lower lips, preceded by actinic cheilitis, difficulty in speech, thickening, induration and ulceration or irregularity of the surface, papillary lesion grows slowly, metastasizes, submaxillary and submental nodes, well differentiated malignancies, surgical.

• C utis rhomdoidalis: Thickened skin with furrow giving an appearance of rhomboidal network. • Dubreuilh’s elastoma: Diffuse plaque like lesions. • Nodular elastoidosis: Nodular lesion.

Histopathological Features

MISCELLANEOUS Chapping of Lips It is a reaction to adverse environmental conditions in which keratin of the vermilion zone loose its plasticity, so that lip becomes sore, cracked and scaly. The affected subjects tend to lick the lips or to pick at the scales which may make conditions worse. It is caused by exposure to freezing cold or to hot, dry wind, but acute sunburns can cause very similar changes. Management is by application of petroleum jelly and avoidance of the causative environmental conditions. Points to Remember Lip becomes sore, cracked and scaly exposure to freezing cold or to hot petroleum jelly.

Actinic Elastosis It is also called solar elastosis or senile elastosis.

Causes It is caused by prolonged exposure to UV light. UV radiation can produce collagen degeneration in the dermis and extent of this effect is dependent upon factors such as the thickness of stratum corneum, melanin pigment, clothing or chemical sunscreens.

Clinical Features On the labial mucosa exposed to sun, white area of atrophic epithelium develops with underlying scarring of the lamina propria. In outdoor elderly population, lips may show actinic elastosis in which vermilion border blends with the skin surface. Signs: Clinical features include leathery appearance, laxity with wrinkling and various pigmentary changes.

The underlying connective tissue shows band of amorphous, acellular, basophilic changes.

Management Topical application of retinoic acid is helpful. Points to Remember Solar elastosis, UV light, white area of atrophic epithelium, which vermilion border blends with the skin surface, pigmentary changes, leathery appearance, band of amorphous, acellular, basophilic changes, topical application of retinoic acid.

Lip Ulcers due to Caliber Persistent Artery A caliber persistent artery is defined as an artery with a diameter larger than normal near a mucosal or external surface. Such artery in the lip causes chronic ulceration which can be mistaken for squamous cell carcinoma. The ulcer is attributed to continual pulsation from the large artery running parallel to the surface.

BIBLIOGRAPHY 1. Baker SR, Krause CJ. Carcinoma of lip: Laryngoscope. 1990;90:19-27. 2. Carinci F, Pezzetti F, Scapoli L, et al. Recent development in orofacial cleft genetics. J Craniofacial Surg. 2003;14:130-43. 3. Cohen DM. Green JG, Dickmann SL. Concurrent anomalies cheilitis glandularis and double lip: report of case. Oral Surg Oral Med Oral Pathol. 1988;66:397-9. 4. Connolly M, Kennedy C. Exfolitivateive cheilitis successfully treated topical tacrolimus. Br J Dermatol 2004;151:241-242. 5. Daley TD, Gupta AK. Exfoliative cheilitis. J Oral Pathol Med 1995;24:177-9. 6. Derijcke A, Eerens A, Carels C. The incidence of oral clefs: a review. Br J Oral Maxillofac Surg. 34:488-94.

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7. Eski M, Nisanci M, Atkas A, et al. congenital double lip: a review of 5 cases. Br J Oral Maxillofac Surg. 2007;45:68-70. 8. Everett FG, Wescott WB. Commissural lip pit. Oral Surg Oral Med Oral Pathol.1961;14:202-209. 9. Gomez Dusao AJ, Seoane J, Vazquez-Garcia, et al. Ascher syndrome: report of two cases. J oral Maxillofac Surg. 1997;55:88-90. 10. Gurvinder PT, Amrinder JK, Harshmohan. Plasma cell cheilitis: Indian journal of dermatology: 1999;44(3)135-7. 11. Hanami Y, Motoki Y, Yamamoto T. Successful treatment of plasma cell cheilitis with topical tacrolimus: report of two cases. Dermatol Online J. 2011;17(2):6. 12. Harada K, Sato M, Omura K. Long term maxillomandibular skeletal and dental changes ij children with cleft lip and palate after maxillay distraction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:292-9. 13. Kaugars GE, Pillon T, Sirsky JA, et al. Actinic cheilitis: a review of 152 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88:181-6. 14. Markopoulos A, Albanidou-Farmaki E, Kayavis I. Actinic cheilitis: clinical and pathological characteristic in 65 cases: Oral Dis. 2004;10:212-216. 15. Mehta V, Nayak S, Balachandran C. Pigmented contact cheilitis to paraphenylenediamine. Indian J Dermatol. 2010;55(1):119-20. 16. Miura M, Isami M, Yagami, et al. A allergic contact cheilitis caused by ditrimethylolpropane triethylhexanoate in a lipstick. Contact Dermatitis. 2011;64(5):301-2. 17. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edn, Saunder Elsevier, 2009.

18. Ohman SC, Dahlen G, Molelr A, et al. Angular cheilitis: a clinical and microbial study: J Oral Pathol. 1986;15:213217. 19. Onfre MA, Brosco HB, Taga R. Relationship between lower lip fistulae and clef lip and/or palate in van der Woude syndrome. Cleft palate craniofac J. 1997;34:261-5. 20. Park KK, Brodell RT, Helms SE. Angular cheilitis, part 1: local etiologies: Cutis. 2011;87(6):289-95. 21. Park KK, Brodell RT, Helms SE. Angular cheilitis, part 2: nutritional, systemic, and drug-related causes and treatment: Cutis. 2011;88(1):27-32. 22. Precious DS, Delaire J. Clinical observations of cleft lip and palate. Oral Surg Oral Med Oral Pathol. 1993;75(2):141-51. 23. Sharon E Jacob, Elise M Herro. Allergic Contact Cheilitis: the dermatologist. 2011;19(8):18-22. 24. Souissi A, El Euch D, Mokni M, Badri T, et al. Congenital lower lip pits: a case report. Dermatol Online J. 2004; 10(2):10. 25. Stoopler ET, Carrasco I, Stanton DC, et al. Cheilitis glandularis: an unusual histopathological presentation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003; 95:312-7. 26. Visscher JG, Schapveld M, Otter R, et al. Epidermology of caner of lip in the netherland. Oral Oncology. 1998; 34:4216. 27. Worsaae N. Christensen KC, Schiodt M, et al. MelkerssonRosenthal and cheilitis granulomatous: a clinicopathologic study of thirty-three patient with special reference to their oral lesion. Oral Surg Oral Med Oral Pathol. 1982;54:40413.

MULTIPLE CHOICE QUESTIONS 1. Arteries supplying blood to lower lip is: a. Submental artery b. Superior labial artery c. Inferior labial artery d. Sublingual artery



2. Congenital lip pits are associated with: a. Rabbit syndrome b. Van der Woude’s syndrome c. Kawasaki syndrome d. Both a. and b. 3. Double lip is associated with: a. Ascher’s syndrome b. c. Miescher’s syndrome d.

Down’s syndrome None

4. Following are the syndromes associated with cleft palate ,except: a. Pierre Robin syndrome b. Apert’s syndrome c. Rabbit syndrome d. Nagar syndrome 5. More severe suppurative form of glandular cheilitis is called as: a. Miescher’s syndrome b. Perleche c. Exfoliative cheilitis d. Volkmann’s cheilitis

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Tongue Disorders

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline                 Â

Embryology of tongue Anatomy of tongue Surface Papillae Muscle Arterial supply Venous drainage Nerve supply Lymphatic drainage Functions of tongue Classification of tongue disorders Aglossia and microglossia Macroglossia Ankyloglossia Cleft tongue Ankyloglossum superius syndrome Lingual varicosities

INTRODUCTION The tongue makes up a large part of the oral cavity and can be affected in numerous lesions. The tongue may be affected as a part of oral disease or as a signs of a systemic disease. The word tongue is derived from Latin word lingua and Greek word glossa. It is partly oral (anterior 2/3rds of tongue) and partly pharyngeal (posterior 1/3rd of tongue).

EMBRYOLOGY OF TONGUE The tongue develops from the ventral wall of the primitive oropharynx and may be conceived as a mucosal pocket

                Â

Lingual thyroid nodule Patent thyroglossal duct cyst Lingual polyp Lingual cyst Fissured tongue Median rhomboid glossitis Benign migratory glossitis Hairy tongue Crenated tongue Foliate papillitis Leukokeratosis nicotina glossi Depapillation of the tongue Dysgeusia and hypogeusia Dyskinesia Paralysis of tongue Squamous cell carcinoma Pigmentation of tongue

filled with striated muscle. It is derived principally from the primordia of the branchial arches in such a way that the body of the tongue comes from the 2nd arch, whereas the root comes from the 3rd, 4th and possibly the 5th arch. During the 4th week of development, paired lateral thickening of mesenchymal appears on the internal aspect of 1st branchial arch, to form the lingual swelling. Between and behind the swelling there appears median eminence called tuberculum impar. But soon, elevations of the ventromedial portion of the 1st arch arise on each side of tubercle and merges with each other. The tuberculum impar is a transient elevation with its caudal border marked by a blind pit, the foramen caecum,

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from which the thyroid glands develop as an endodermal outgrowth. Anterior 2/3rds is formed by fusion of tuberculum impar and two lateral lingual swelling. The posterior 1/3rd of the tongue has a more complicated developmental origin. It first exists as a central mound called the copula, which is the result of fusion of the 3rd branchial arches. The endodermally derived mucosa of the 2nd to 4th branchial arches and the copula, provide covering for the posterior thirds of the tongue. A V-shaped terminal sulcus, whose apex is the foramen caecum, signifies the mobile body of the tongue from its fixed root.

ANATOMY OF TONGUE

by a sickle shaped fold of mucous membrane called lingual frenulum. On the ventral surface, lingual veins are often visible as bluish streaks. At the lateral side of the vein is a fringed fold of mucous membrane called the plica fimbriata or fimbriated fold. Anteriorly, on either side of the frenulum, the caruncles opening for the submandibular ducts are visible. Taste buds: These are peripheral gustatory organs which are composed of modified epithelial cells. They are most numerous on the sides of circumvallate papillae and less on the walls surrounding the foliate papillae. They are more numerous in infants than in adults. With age, they undergo atrophy.

Surface

PAPILLAE

The tongue is a muscular organ situated in the floor of mouth, associated with the function of deglutition, taste and speech. It lies partly in the mouth (oral part), which compromises the anterior 2/3rds and in the pharynx (pharyngeal part), which comprises the posterior 1/3rd. Both the parts are separated by the inverted V shaped sulcus called the sulcus terminalis. Tongue has a base, body and circum tip. It has two surfaces, a dorsal and a ventral surface. The dorsal surface is divided into an oral and pharyngeal part and the ventral surface is confined to the oral cavity only. At the apex of sulcus terminalis, there is a depression, called the foramen cecum. In the anterior part of the tongue, the mucous membrane is thin with reduced lamina propria and is closely attached to the underlying muscular tissue. The color of the anterior part of the mucous membrane is pink and is marked by a variety of papillae that gives the tongue a characteristic roughness. The anterior part of the tongue is divided in half by the median lingual sulcus. The posterior part also called pharyngeal part or base of the tongue is located posterior to the palatoglossal arch. The surface without papillae shows a slightly corrugated appearance, due to the underlying lymphoid tissue called the lingual tonsil. The root of the tongue is attached to the epiglottis by a medial fold (the glossoepiglottic fold). Laterally, pharyngoepiglottic (glossopharyngeal) folds pass from the sides of the tongue and pharyngeal wall to the epiglottis. The root of tongue is attached to the hyoid bone, below and the mandible above. The ventral surface is smooth and purplish with no papillae. The tongue is connected to the floor of the mouth

There are four types of papillae: circumvallate, fungiform, filiform and foliate papillae. Circumvallate papillae: They are usually 8 to 12 in number and are the largest of the papillae. They are situated in a row parallel to and close to the sulcus terminalis. Papillae are 1 to 3 mm in diameter and are flattened with a circular depression. They are surrounded by a moat-like trough. The fungiform papillae: They are smaller than the vallate papillae and are distributed over the dorsal surface of the tongue, being most numerous on the anterior part. They are round and mushroom-shaped and is distinguished from the filiform papillae by their larger size and bright red color. Their number is about 100/cm2 on the tip and 50/cm2 in the middle. They carry taste buds. The filiform papillae: These are smallest, but most numerous and are evenly distributed over the dorsum and are often arranged in rows parallel to the sulcus terminalis, except for the tip where they run transversely. The papillae are conical, broadest at the base and whitish due to marked degree of keratinization. The concentration of papillae in man is calculated about 500/cm2. They are more heavily concentrated in center of dorsum of tongue. The foliate papillae: They are vertical folds of the mucosa located at the margins of the tongue, just anteriorly to the palatoglossal arch. Papillae simplices: They are connective tissue papillae, which are similar to the papillae of dermis of skin. They are present beneath the entire tongue surface, including the mucosal papillae described above.

Tongue Disorders

MUSCLE The muscles of tongue are grouped into two sets: (1) extrinsic set (2) intrinsic set. The extrinsic muscles include genioglossus, hyoglossus, styloglossus and palatoglossus. Genioglossus: It is the largest and arises from the upper mental spine and spread in a fan-like fashion and is inserted into the tongue from its tip to the root. It draws the tongue forward and acting together this muscle is able to flatten the tongue, making a concavity from side to side. Hyoglossus: It is a flat, quadrilateral muscle arising from the hyoid bone. It runs as thin plate upward, connect with fibers from the styloglossus and enter the tongue lateral to the genioglossus. It depresses the tongue. Styloglossus: It originates from the styloid process, passes downwards and forwards and inserts into the side of the tongue, connecting with fibers from the hyoglossus. The styloglossus draws the tongue upwards and backwards. Palatoglossus: It originates from the palate and runs in the palatoglossus arch, continuing into the side and dorsum of the tongue. Intrinsic muscles: These are situated inside the tongue and constitute a greater part of the organ. They are divided into the superior longitudinal, inferior longitudinal, transverse and the vertical muscles. Superior longitudinal: It arise from submucous fibrous layer close to the epiglottis and from the median fibrous septum. If runs forward to the edges of tongue, some its fibers being inserted into mucous membrane. It shortens the tongue and makes the dorsum concave, by the turning the tip and side of the tongue upward. Inferior longitudinal: It is a narrow band lying close to the inferior surface of tongue, between genioglossus and hyoglossus. It extends from the root apex of the tongue, some of its posterior fibers being connected with the body of hyoid bone. In front, it blends with the fibers of styloglossus. It shortens the tongue and makes its dorsum convex by pulling the tip of tongue downwards. Transverse muscle: It originates from the median fibrous septum and runs in horizontal course, laterally to be inserted into submucous fibrous tissue. By their action, intrinsic muscles alter the shape of the tongue making it narrow and elongated.

Vertical muscle: It is found at the borders of anterior part of tongue. Its fibers extend from dorsal to ventral surface, mainly near its lateral borders, but fibers are interspersed through the tongue. It makes the tongue broad and flattened.

ARTERIAL SUPPLY The lingual artery, a branch of the external carotid, is the main vessel supplying the tongue. Before the artery reaches the posterior edge of the hyoglossus muscle, it gives off a branch to the hyoid bone area. In its course below the hyoglossal muscle, it gives off a lingual dorsal artery, which runs steeply upward dividing into many branches supplying the base of tongue and posterior part of the dorsum. The root of the tongue is also supplied by the ascending pharyngeal and tonsillar arteries. At the lower border of the anterior part of the hyoglossal muscle, the lingual artery gives off the sublingual artery, which supplies the sublingual region medial to the sublingual gland.

VENOUS DRAINAGE Deep lingual vein is the largest and the principal vein of the tongue. Deep lingual vein originates near the tip of the tongue and runs backward, close to the mucous membrane on the ventral surface of the tongue. It joins the sublingual vein, at the posterior border of the hypoglossal muscle to form the vena comitans of the hypoglossal nerve, which drains to the facial or internal jugular vein. The dorsal lingual vein drains the dorsum and sides of the tongue. It joins the sublingual veins, which follow the artery deep to the hypoglossal muscle and enter the internal jugular vein, near the hyoid bone.

NERVE SUPPLY All the muscles of the tongue, except the palatoglossus are supplied by the hypoglossal nerve. The palatoglossus is supplied by the pharyngeal plexus. Lingual branch of mandibular nerve is nerve for general sensation for anterior 2/3rds of tongue. Glossopharyngeal nerve is the nerve for general sensation for posterior 1/3rd of the tongue. Posterior most part of tongue is supplied by vagus nerve, through internal laryngeal nerve. Taste sensation is carried out by chorda tympani branch of facial nerve for anterior 2/3rds and glossopharyngeal nerve for posterior 1/3rd.

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The tip of the tongue drains bilaterally into the submental nodes. Right and left halves of rest of the anterior 2/3rds of the tongue, drain unilaterally to submandibular lymph nodes. A few central lymphatic, drains laterally into the same nodes. Some of the lymph vessels, from the lateral margins of the tongue, drain to the jugulodigastric nodes. The posterior 1/3rd of the tongue drain bilaterally to the juguloomohyoid nodes, in which most of the lymph drains from the tongue.

FUNCTIONS OF TONGUE Speech: It is the result of interaction between different organs. Even small changes in the position or shape of the tongue may cause disturbance in speech. Tongue is one of the organs in the oral cavity, which interrupts the air passage through mouth or pharynx thereby producing consonants. Certain consonants like c, d, j, i, n, t, z, l, g, etc. requires movement of tongue. Mastication: The tongue has a direct crushing effect on food by pressing it against the hard palate. The tongue pushes the food onto the occluding surfaces and helps to mix in the saliva. The sensory ending on the tongue enable to select those parts of the food mass that are sufficiently well masticated to be ready for swallowing. Deglutition: When the food bolus is placed on dorsum of tongue, it is pressed lightly against the hard palate just behind the incisors. It is a coordinated muscular activity involving the tongue and constrictor muscle of the pharynx, to close the palatal velum and the epiglottis. It allows the passage of the bolus into the esophagus, without regurgitation into the nose or lower respiratory tract. The process is initiated by the voluntary action of collecting food onto the tongue and propelling it backwards into the pharynx. The muscles involved in this process are the mylohyoid and the pharyngeal constrictors. Bolus is pushed backwards by raising the back of tongue. Food bolus is sucked from mouth into pharynx, by creating a negative pressure, while airways are still closed by rapid relaxation of muscles of tongue and pharynx. Digestion: Tongue has a slight digestive function by virtue of salivary lipase, present in serous lingual salivary glands.

Taste: It acts as a special sense organ of taste, by virtue of presence of numerous taste buds. The tip of the tongue is most sensitive to substances eliciting a sweet sensation. The lateral margins are most sensitive to substances causing sour sensation. The base of the tongue is most sensitive to substances eliciting a bitter sensation. The salty quality is more widespread, but is greatest at the tip. Barrier function: Mucosa covering the tongue acts as a barrier protecting the deeper tissues from mechanical damage. It also prevents entry of microorganisms and toxic substances. Jaw development: Muscular pressure from the tongue is an important factor in determining the shape of the mandibular arch. Thermal regulation: It is more pronounced in dogs, where there is a considerable loss of heat from the tongue. Secretion: Major secretion of tongue is provided by salivary glands activity which maintains the moist surface of oral mucosa. Defense mechanism: Secretory immunoglobulin system of tongue plays an important role in body defense. Maintenance of oral hygiene: By virtue of its movement it can reach all parts of the oral cavity removing food debris from the gums, vestibule and floor of mouth. Thus it helps in maintenance of oral hygiene. Sucking: Tongue also plays an important role in sucking in both bottle feeding and breast feeding. General sensitivity: Due to extreme sensory innervations terminating in both simple and organized nerve endings, there is perception of heat, cold, pressure and chemical discrimination. Symbolic function: Functions that are traditionally associated with the tongue, but that have no anatomic and physiologic basis should be mentioned because images of this type are well established cultural and literary tradition. It must frequently influences a patient perception of a lingual abnormality. Expressions such as ‘speaking with a forked tongue’ or ‘speaking in different tongue’ all describe the mental attitude and behaviors, by which they are expressed.

Tongue Disorders

CLASSIFICATION OF TONGUE DISORDERS ∙

∙

∙

Local tongue ditsorders: – – – – – – –

∙

Aglossia and microglossia Macroglossia Ankyloglossia Cleft tongue Ankyloglossum superius syndrome Lingual varices Lingual thyroid nodule Variations in tongue movement Patent thyroglossal duct cyst Tongue thrusting Lingual polyp Reactive lymphoid aggregate Lingual cyst Fissured tongue Median rhomboidal glossitis Benign migratory glossitis Hairy tongue Crenated tongue Foliate papillitis Leukokeratosis nicotine glossi

∙

∙

Depapillation of tongue: Local disease – – – – – – –

Eosinophilic granuloma Traumatic injuries Lesions due to automutilation Allergic stomatitis Facial hemiatrophy Cranial arteritis Chronic candidiasis

Systemic disease – – – – – – – – – – –

Iron deficiency anemia Plummer Vinson syndrome Pernicious anemia Niacin deficiency Folic acid deficiency Peripheral vascular disease Dermatomyositis Diabetes Syphilis Zoster infection Tuberculosis

Neurological disease: – – – –

Congenital and developmental disorders: – – – – – – – – – – – – –

∙

∙

∙

Glossodynia Dyskinesia Paralysis Oropharyngeal dysphagia

Cyst: – Anterior median lingual cyst – Bronchogenic cyst – Epidermoid and dermoid cyst – Gastric mucosal cyst – Parasitic cyst – Thyroglossal duct cyst Benign tumor: – Fibroma – Glomus tumor – Granular cell tumor – Leiomyoma – Rhabdomyoma – Plasmacytoma Premalignant lesion and conditions – Leukoplakia – Lichen planus – Oral submucous fibrosis Malignant tumor: – Squamous cell carcinoma – Malignant lymphoma – Malignant melanoma – Metastatic tumor – Sarcoma Miscellaneous: – Pigmentation of tongue – Phlebectasia.

AGLOSSIA AND MICROGLOSSIA Definition Aglossia: It is the complete absent of tongue at birth. Microglossia: It is the presence of small rudimentary tongue.

Causes It usually occurs in syndromes such as hypoglossiahypodactylia syndrome, Pierre Robin syndrome. It is also associated with cleft lip and palate.

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Clinical Features

Classification

Symptoms: Patient encounters difficulty in eating and speaking.

Congenital Macroglossia

Signs: Patient may have high arched palate and a narrow constricted mandible. It is usually associated with other oral or generalized malformations. There may be an airway obstruction, due to negative pressure generated by deglutition and inspiration. Microglossia is frequently associated with hypoplasia the mandible and lower incisor may be missing.

Management Nonsurgical technique such as positioning, nasogastric intubution and temporary endotracheal intubation can be carried out to prevent airway obstruction. Points to Remember Hypoglossia-hypodactylia syndrome, Pierre Robin syndrome, difficulty in eating and speaking, high arched palate, narrow constricted mandible, hypoplasia the mandible, lower incisor may be missing positioning, nasogastric intubution.

MACROGLOSSIA Macroglossia is tongue enlargement, which leads to functional and cosmetic problems. Although this is a relatively uncommon disorder, it may cause significant morbidity. Normal speech and swallowing reflexes require normal tongue anatomy and function. Swallowing begins as the tongue mixes food with saliva to form a food bolus, which is then propelled into the pharynx by the tongue. Articulation also depends on the tongue’s ability to alter the impedance of air and change the resonant characteristics of the upper airway. In macroglossia, increased tongue bulk may impair these functions. Types Congenital macroglossia Acquired • Hypertrophic • Inflammatory • Neoplastic Relative macroglossia Apparent macroglossia

It is present since birth.

Acquired Macroglossia Hypertrophic: In it, muscles of the tongue are hypertrophic. It usually occurs in mentally retarded patients. Inflammatory: It may involve the tongue partially or completely. It is due to various causes like syphilitic, Ludwig’s angina, etc. Neoplastic: It can be based on benign and malignant tumors.

Relative Macroglossia It is a condition, in which a normal sized tongue appears abnormally large, if it is particularly enclosed within a small oral cavity.

Apparent Macroglossia It is a condition where the tongue appears large due to poor muscular control of the tongue, although there is no increase in the bulk of tongue tissue.

Etiology Congenital: It includes hemangioma, lymphangioma and lingual thyroid. Inflammatory: Inflammatory causes include tuberculosis, actinomycosis, dental infection, syphilitic gumma, Riga disease, ranula and sublingual calculus. Traumatic: Traumatic causes include dental irritation, hematoma and postoperative edema. Neoplastic: The neoplastic causes can be divided into malignant and benign lesions; with the malignant lesions including carcinoma and sarcoma. The benign lesions include granular cell tumor, neurofibroma, leiomyoma and lipoma. Metabolic: Metabolic causes are myxodema, amylodosis, lipoid proteinosis, chronic steroid therapy and acromegaly. Muscular hypertrophy: Overdevelopment of musculature, this may or may not be associated with generalized muscular hypertrophy or hemi hypertrophy.

Tongue Disorders

Clinical Features

Management

Age: Macroglossia is most prominent in infants, but tongue size may remain above normal in childhood and adolescence (Fig. 25.1). As hyoid descends with age, macroglossia may improve.

Orofacial therapy uses a palatal device to stimulate muscular tone and proper tongue position. Surgical approach: Majority of the cases of macroglossia are treated surgically. Indications for surgery include airway obstruction, speech difficulties, dysphagia and cosmetics. The procedure of choice is partial glossectomy. Surgical goal is to reduce the tongue size and thus improve the condition. Removal of primary cause and correction of the dental arch deformity and malocclusion by orthodontic treatment is done. Correction of defective articulation by speech therapy is carried out.

Symptoms: This includes tongue protrusion, which exposes the tongue to trauma. This exposure also leads to mucosal drying and recurrent upper respiratory tract infections. Other symptoms include swallowing difficulties, airway obstruction, drooling and failure to thrive. The enlargement is generalized and may cause variety of difficulties with speech, feeding and airway problems. Patient is having lisping speech. Signs: It may produce displacement of teeth and malocclusion, due to the strength of muscles involved and pressure exerted by the tongue on teeth. Crenation or scalloping of the lateral borders of the tongue; the tips of scalloping fit into the interproximal spaces between the teeth occurs. In edentulous patient tongue appear as elevated and spread out laterally causing difficulty in wearing a denture. It is associated with syndromes like Beckwith’s Wiedemann syndrome which includes neonatal hypoglycemia, mild microcephaly, umbilical hernia, fetal visceromegaly and postnatal somatic gigantism.

Histopathological Features It shows hypertrophy and hyperplasia of muscle cells.

Points to Remember Tongue enlargement, tongue protrusion, swallowing difficulties, airway obstruction, drooling, lisping speech, crenation or scalloping of the lateral borders of the tongue, Beckwith’s Wiedemann syndrome, hypertrophy and hyperplasia muscle cells, palatal device.

ANKYLOGLOSSIA It is also called tongue-tie. It is a condition in which the lingual frenulum is either too short or anteriorly placed limiting the mobility of the tongue. Reports of partial ankyloglossia affecting several generations, suggest a possible genetic basis for the minor variation in the attachment of the genioglossus muscle. It may be traumatic or congenital.

Types Complete: Fusion of tongue and the floor of mouth. Partial: Short lingual frenum.

Clinical Features Symptoms: It may limit the movement of the tongue. In extreme cases of ankyloglossia, nursing and feeding problems can occur. There is also recurrent tongue biting, poor sucking and inability to chew some food. Speech abnormalities: It was felt that tongue-tie was associated with speech abnormalities, especially lisping and inability to pronounce certain sounds and words, viz. t, d, n, l, as, ta, te, time, etc. Figure 25.1 Macroglossia showing large tongue

Signs: When there is an attempt to stick the tongue out, there may be a V shaped notch at the tip. Physical

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CLEFT TONGUE It is also called bifid tongue. It is the condition in which there is cleavage of the tongue due to lack of fusion of the lateral halves. Completely bifid or cleft tongue is rare.

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Pathogenesis

Figure 25.2 Short frenum due resulting in ankyloglossia

examination will easily demonstrate the short or anteriorly placed lingual frenulum (Fig. 25.2). Patients have midline mandibular diastema and inability to clean the teeth and lick the lips with tongue. Dyspnea: Recently, it is suggested that ankyloglosssia can cause upward and forward displacement of epiglottis and larynx which results in dyspnea. Syndromes associated with ankyloglosssia are ankyloglossum superius syndrome, rainbow’ syndrome, Fraser’s syndrome and orofacial digital syndrome.

Management Physician education, parental education and reassurance should be given to the patient. Surgery: Indication for surgery, i.e. frenectomy are as follows: If complete fusion of tongue is present then it requires surgery. When nursing and feeding become a problem, surgery is indicated. Children between 2 to 4 years, with poor development of speech and anxious parents desire for the necessary treatment. In cases, where tongue tie has recurred after snipping.

Development of tongue occur in 4th week of intrauterine life. It originate from a median swelling, the tuberculum impar and two lateral lingual swellings joining this central structure. These lateral lingual structures grow rapidly to cover the tuberculum impar to form the anterior twothirds of the tongue. When this process is disturbed, tip of the tongue is divided longitudinally for a certain distance giving rise to cleft tongue/bifid tongue.

Clinical Features Sign: Partially cleft tongue is manifested as deep grooves in the midline of dorsal surface. Food debris and microorganisms may collect in the base of cleft and cause irritation. Syndromes associated: Seen with oral-facial-digital syndrome, with thick fibrous bands in lower anterior mucobuccal fold, which eliminate the sulcus and is associated with clefting of hypoplastic mandibular alveolar process. Bifid tongue has also been associated with diabetic mother syndrome, tongue piercing.

Management Surgical correction of defect can be carried out. Points to Remember Bifid tongue, deep grooves in the midline, oral-facialdigital syndrome, diabetic mother syndrome.

ANKYLOGLOSSUM SUPERIUS SYNDROME It is characterized by the attachment of the tongue to the hard palate and by limb malformation.

Points to Remember Tongue-tie, nursing and feeding problems, speech abnormalities, V shaped notch at the tip, midline mandibular diastema, dyspnea, ankyloglossum superious syndrome, rainbow’ syndrome.

Etiology A genetic disorder is the most important cause of this syndrome. Intrauterine environmental factors can also cause this syndrome.

Tongue Disorders

Clinical Features It is a very rare disorder and is associated with jejunal and ileal Atresia. Patient has difficulty in speech and mastication. Patient may have difficulty in swallowing.

Management Surgical separation of the tongue from the palate. Points to Remember Jejunal, ileal atresia, difficulty in swallowing.

There appears to be no significant relationship between the presence of leg varicosities and sublingual varices.

Histopathological Features Vessels are dilated with presence of smooth muscle and elastic fibers. Secondary thrombosis may lead to occluded lumen with platelets and erythrocytes. Older thrombi may result in dystrophic calcification resulting in formation of phlebolith.

Management

LINGUAL VARICOSITIES A varix is a dilated, tortuous vessel, most commonly a vein, which is subjected to increased hydrostatic pressure and is poorly supported by the surrounding tissues. Varicosities involving the lingual veins are relatively common, and are seen on ventral or lateral surface of tongue. These may occur due to loss tonicity of supporting tissue.

Clinical Features Age and sex distribution: It is seen after the age of 50 years without sex predilection. Signs: Patient is symptom free with lesion appearing as blue or purple shot-like clusters of vessels on the ventral surface and lateral borders of the tongue as well as in the floor of the mouth (Fig. 25.3).

As these are asymptomatic no treatment is necessary for this. Points to Remember Varix, varicosities blue or purple shot-like clusters, presence of smooth muscle and elastic fibers, platelets erythrocyte.

LINGUAL THYROID NODULE The thyroid gland develops in the embryo from the ventral floor of the pharynx, by means of an ectodermal invagination of diverticulum. The tongue forms at the same time from this pharyngeal floor and is anatomically associated with thyroid gland by connection through the thyroglossal tract, the lingual remnant of which is known as the foramen caecum. The lingual thyroid is an anomalous condition in which follicles of thyroid tissue are found in the substance of the tongue, possibly arising from a thyroid anlage that failed to migrate to its predestined position or from anlage remnants that became detached and were left behind.

Etiology Functional insufficiency of the chief thyroid gland in neck and failure of the primitive thyroid anlage to descend are the cause of the condition.

Clinical Features Age and sex distribution: Females are more affected as compared to males in a ratio of 7:1 due to hormonal influence. The age of onset ranges from birth to the 6th decade, with a peak in the 2nd decade. Figure 25.3 Lingual varicosity seen on ventral

surface of tongue

Signs: It is manifested as a nodular mass in or near the base of the tongue, in general vicinity of the foramen caecum. It is often but not always, in the midline (Fig. 25.4).

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as an autosomal dominant trait. It is the ability to fold back the tip of the extended tongue, without the aid of the teeth. Trefoil tongue: Clover leaf pattern.

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Gorlin sign: Extensibility of the tongue, both, forward to touch the tip of nose and backwards into the pharynx.

PATENT THYROGLOSSAL DUCT CYST It is also called thyroglossal tract cyst.

Development

Figure 25.4 Lingual thyroid nodules present on posterior

aspect of tongue

Symptoms: There may be complains of dysphagia, dysphonia, dyspnea, hemorrhage with pain or feeling of tightness or fullness in the throat. Thyroid scan: Diagnosis is well established by using iodine isotopes as it has affinity for the thyroid tissue. Rarely there are incidence that carcinoma can arise in the lingual thyroid nodules.

Histopathological Features They resemble either normal thyroid tissue or thyroid tissue of an embryonal or fetal type. It characteristically has an incomplete or poorly defined capsule. Follicular cells sometime atrophic in nature.

Management Thyroxin should be given to reduce the size of swelling. When swelling is causing difficulty to the patient in spite of thyroxin therapy, excision or ablation with radioiodine is indicated. Points to Remember Ectodermal invagination of diverticulum, nodular mass near the base of the tongue, dysphagia, dysphonia, dyspnea, iodine isotopes normal thyroid tissue, follicular cells, thyroxin.

VARIATIONS IN TONGUE MOVEMENT Ability to curl up the lateral borders of the tongue into a tube is noted in 65 percent of Caucasians and is inherited

Thyroid gland develops from an anlage of endothelial cells in the midline of the floor of pharynx, between the first and second branchial arches, just posterior to tubercular impair. These cells sink into the base of developing tongue descend into the neck and proliferate below the larynx to form thyroid gland. Along this path epithelial tract or duct is formed which maintain an attachment to base of the tongue. Thyroglossal duct become associated with hyoid bone. After hyoid bone is mature duct passes in front and beneath hyoid bone. These tracts undergo atrophy and obliterates. However, some remnants of this epithelium may persist and give rise to cyst which is called thyroglossal duct cyst. Inflammatory conditions lead to reactive hyperplasia of the lymphoid tissue adjacent to the remnants of thyroglossal tract may stimulate the epithelial remnants themselves have been mentioned, as has a blocked thyroglossal duct with an accumulation of secretion.

Clinical Features Age and sex predilection: It usually occurs in young persons with no sex predilection. Site: It is seen above the thyroid, in vicinity of the hyoid bone, in midline of the neck. It can occur anywhere from foramina caecum area of tongue to superasternal notch. Cyst developing in an area of thyroid cartilage are deflected lateral to midline due to sharp anterior margin of thyroid cartilage. Symptoms: Pain may occur if the cyst is infected. If they are located high in the tract they may cause dyspnea. Sign: It is a firm cystic mass in which formation of fistula may take place. It is compressible. It yields yellow fluid on aspiration. Swelling is fluctuant and movable. The cysts are usually in the midline and produce a softer, movable sometimes fluctuant or tender swelling. Consistency is often firm or hard depending upon the tension of fluid

Tongue Disorders

within the cyst. Cyst moves with deglutition as swelling is attached to hyoid bone by fibrous tissue. It also moves with protrusion of tongue.

It is a circumscribed, sessile or pedunculated lesion. It may sometimes cause asphyxia in neonates. Management: It consists of surgical removal. 629

Fistulous tract: In some cases fistulous tract to the skin or mucosa develop which may be due infection.

LINGUAL CYST

Histopathological Features

It is a rare lesion. It is also called gastric cyst or enterocystoma. It arises as a result of epithelial entrapment during fissural closure of the lateral lingual processes.

They are lined by pseudo-stratified columnar epithelium which may be ciliated or by stratified squamous epithelium. The connective tissue wall of the cyst frequently contain small patches of lymphoid tissue, thyroid tissue and mucous glands (Fig. 25.5).

Management Sistrunk operation involves the removal of a 1 cm block of tissue surrounding the duct and the duct should be traced down to the pyramidal lobe of thyroid gland and to the foramen caecum at the base of tongue. Points to Remember Thyroglossal tract cyst, in vicinity of the hyoid bone, in midline of the neck, pain, located high dyspnea, firm cystic mass, yellow fluid on aspiration, fistulous tract, pseudostratified columnar epithelium, small patches of lymphoid tissue, Sistrunk operation.

LINGUAL POLYP It can occur at any age, with no sex predilection.

Clinical Features Site: It is located in the anterior midline of the tongue. Signs: It is movable and compressible (Fig. 25.6).

Histopathological Features It is lined by aberrant gastric epithelium hence it is referred to as gastric cysts. Some of the lesion are lined by columnar, respiratory and stratified squamous epithelium.

Management Surgical: Surgical removal of the cyst is carried out. Points to Remember Enterocystoma, anterior midline of the tongue, movable, compressible, aberrant gastric epithelium, columnar, respiratory and stratified squamous epithelium.

FISSURED TONGUE It is also called scrotal tongue, plicated tongue and lingua dissecta.

Figure 25.5 Thyroid follicles, mucous glands and duct in the

wall of thyroglossal duct cyst

Figure 25.6 Lingual cyst of newborn seen as growth

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A tongue with or without a central fissure shows parallel fissures lateral to the midline or fissures at right angle to the long axis of the tongue. Fissure tongue is characterized by furrows, one extending anteroposteriorly and others laterally over the entire anterior surface. Types • Foliaceus • Cerebriform • Plicated.

Etiology It is genetically determined and seen in mentally retarded and psychotic individuals. It is autosomal dominant trait with incomplete penetrance. Extrinsic factors like chronic trauma or vitamin deficiency.

Clinical Features Well marked fissuring increases with age, as does the number, width and depth of the fissures in affected individuals. It is manifested as small furrows or grooves on the dorsal surface, often radiating out from the central groove along the midline of the tongue (Fig. 25.7). It is usually painless, except in some occasional cases in which food debris tends to collect in the groove and produce irritation. Pattern: Six different patterns of tongue fissuring were observed, i.e. plication, central longitudinal fissuring,

double fissures, and transverse fissuring arising from a central fissure, transverse fissuring with a central fissure and lateral longitudinal fissuring. Syndrome: It is associated with Melkerson Rosenthal syndrome which includes cheilitis granulomatosa, facial paralysis, fissured tongue and non-pitting, noninflammatory painless edema of face.

Histopathological Features It shows hyperplasia of the rete pegs and loss of keratin on the surface of filiform papillae. Papillae are separated by grooves. There is formation of microabscess in the upper epithelial layer as polymorphonuclear leukocytes are migrating into the epithelial.

Management As food and debris can act as source of infection, patient should be advice to clean the teeth very frequently. Points to Remember Plicated tongue, small furrows or grooves on the dorsal surface, painless, plication, central longitudinal fissuring, double fissures, transverse fissuring patterns, Melkerson Rosenthal syndrome, hyperplasia of the rete pegs, microabscess.

MEDIAN RHOMBOID GLOSSITIS It is also called central papillary atrophy of tongue. It is a developmental defect resulting from an incomplete decsent of tuberculum impar and entrapment of a portion between fusing lateral halves of the tongue. It is a benign lesion of the tongue, characterized by rhomboid or oval shaped changes of the tongue mucosa in the midline, just anterior to the foramen cecum.

Pathogenesis It is a congenital abnormality of the tongue due to failure of tuberculum impar to retract or withdraw before fusion of lateral halves of the tongue, so that a structure devoid of papilla is interposed between it.

Etiology Developmental: The persistent tuberculum impar suggests its developmental origin. Figure 25.7 Fissure tongue showing furrow

Fungal infection: Fungal infection with Candida albicans can be causative factors.

Tongue Disorders

Diabetes: Median rhomboid glossitis is more common in a diabetic, than in nondiabetic subjects. Other factors: Other factors such as smoking, denture wearing can also cause.

Clinical Features Age and sex predilection: Males predominate over females (3:1). It is common in adults with age ranging from 15 to 84 years. Location: It is located just anterior to the foramen cecum on dorsal surface of the tongue, in midline and anterior to the circumvallate papillae. Signs: It appears as an ovoid, diamond or rhomboidal shaped reddish patch or plaque on the dorsal surface of the tongue, immediately anterior to the circumvallate papillae. In some cases flat or slightly raised area stands out from rest of the tongue because it has no filiform papillae (Fig. 25.8). The surface is dusky red and completely devoid of filiform papillae and usually smooth. The texture may be varied from a reddish, smooth, granular surface to a lobulated and indurated surface. Symptoms: While most of the cases are asymptomatic, some patients complain of persistent pain, irritation, or pruritus. Kissing lesion: When lesion of median rhomboidal glossitis touched the palatal surface and it causes palatal inflammation, which is called the kissing lesion.

Histopathological Features There is loss of papillae with varying degrees of hyperparakeratosis. There is proliferation of spinous layer with elongation of rete pegs, which may branch and anastomose. Lymphocytic infiltration within connective tissue and numerous blood vessels are seen. Connective tissue also shows increased vascularity and chronic inflammatory infiltrate. Degeneration and hyaline formation, within underlying muscles is seen. When present fungal hyphae are usually found in the parakeratin or in the very superficial spinous layer of epithelium or in both. Epithelium is devoid of filiform papillae and is slightly thickened. There is also elongation and branching of rete pegs.

Management If candidal organism is found, it is treated with an antifungal agent. Only in longstanding cases, cryosurgery or an excisional biopsy is indicated. Points to Remember Central papillary atrophy of tongue, failure of tuberculum impar anterior to the circumvallate papillae, ovoid, diamond or rhomboidal shaped reddish patch or plaque, lobulated and indurated surface, persistent pain, irritation, or pruritis, kissing lesion, loss of papillae, hyperparakeratosis, lymphocytic infiltration, degeneration and hyaline formation devoid of filiform papillae, elongation and branching of rete pegs. antifungal agent.

BENIGN MIGRATORY GLOSSITIS It is also called geographic tongue, wandering rash, glossitis areata exfoliativa and erythema migrans, erythema areata migrans, stomatitis areata migrans. It refers to irregularly shaped reddish areas of depapillation and thinning of dorsal tongue epithelium that is surrounded by a narrow zone of regenerating papillae which are whiter than the surrounding tongue surface.

Etiology

Figure 25.8 Median rhomboidal glossitis showing ovoid-

shaped lesion

Immunological reaction, allergic, emotional stress, hereditary factors, infections and nutritional deficiencies can be etiological factors. In patients with geographic tongue, there is a high frequency of history of asthma, eczema and hay fever.

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Types of Benign Migratory Glossitis 632

Type I Type II Type III • Fixed form • Abortive forms Type IV

Classification Type I: Lesion confined to the tongue, with both active and remission phases. No other lesion elsewhere in the oral cavity. Type II: As type one with similar lesions elsewhere in the mouth.

Figure 25.9 Geographic tongue presented as

Type III: Lesions on the tongue that are not typical and that may be accompanied by lesions elsewhere in the mouth. It consists of two forms: 1. Fixed form: A few areas of the tongue are affected, but no movement is observed. They may disappear only to recur at the same area. 2. Abortive forms: This form starts as yellow-white patches, but disappear before acquiring the typical appearance of geographic tongue.

or lesion sometimes appears inflamed, while the border is outlined by thin yellowish white line or band. Fungiform papillae persist in the desquamated areas as small elevated red rods. Area of desquamation remains for a short time in one location and then heals and appears in another location thus giving rise to the term migration. Condition may persist for weeks or months and then regress spontaneously only to recur at a later date.

Type IV: No tongue lesions are present, but geographic areas present elsewhere in the mouth.

Clinical Features Age and sex distribution: It is common in young and middle-aged adults, with an age range of 5 to 84 years with a predilection for females. Site: Lesion confines to dorsal surface and lateral border of the tongue, but may occur on the ventral surface. It is extremely variable in size and diameter and it may be single or multiple. Symptoms: It is asymptomatic, but the patient may complain of burning sensation that is made worse by spicy or citrous food. Signs: Initially appears as a small erythematous, nonindurated, atrophic lesion, bordered by a slightly elevated distinct rim that varies from gray white to light yellow (Fig. 25.9). Loss of filiform papillae produces pink to red smooth shiny surface except the residual fungiform papillae. Multiple areas of desquamation of filiform papillae, in an irregular circinate fashion are seen. Central portion

erythematous area

Ectopic geographic tongue: Lesion is not always restricted to tongue and similar irregular or circinate lesions occur elsewhere in oral cavity and are called ectopic geographic tongue or erythema circinate migrans or annulus migrans.

Histopathological Features Filiform papillae are lost (Fig. 25.10) and at the margins of the lesion, there is usually hyperparakeratosis and some acanthosis. Parakeratin is desquamated with marked migration of polymorphonuclear leukocytes and lymphocytes into epithelium. This produce degeneration of epithelial cells and microabscess formation, called Munro’s abscess, near the surface. There is also an inflammatory cell infiltration in the underlying connective tissue, chiefly neutrophils, lymphocytes and plasma cells. Due to neutrophil infiltrate there is destruction epithelium which produces atrophic mucosa.

Management Topical local anesthetic agents like lidocaine, dyclonine hydrochloride or diphenhydramine can be given.

Tongue Disorders

Figure 25.10 Benign migratory glossitis showing loss of

filiform papillae

Oral use of certain drugs (sodium perborate, sodium peroxide and antibiotics like penicillin and aureomycin) can also cause hairy tongue. Extensive X-ray radiation around head and neck for the treatment of tumors may be cause for hairy tongue. It also occurs in patient with intermaxillary fixation and with disturbed orophysiology, due to recent surgery in the oral cavity. A lowered pH of oral secretion, which blocks the normal desquamation of epithelial cells covering the filiform papillae results in overgrowth of filiform papillae. Debilitating diseases in which the tongue movement is limited by some illness. Various foods, particularly coffee and tea, probably contribute o the diffuse coloration. Hairy tongue is also found in patient who are heavy smokers.

Clinical Features Bland diet, elimination of irritants and psychological reassurance is useful. Topical corticosteroids and topical application of salicylic acid and tretinoin (retinoic acid or Vitamin A) for external use can also be helpful. Points to Remember Geographic tongue, wandering rash, dorsal surface and lateral border of the tongue, burning sensation, small erythematous, nonindurated, atrophic lesion, multiple areas of desquamation, irregular circinate fashion, migration, ectopic geographic tongue, filiform papillae are lost, hyperparakeratosis acanthosis, polymorphonuclear leukocytes, Munro’s abscess, inflammatory cell infiltration, local anesthetic agents, topical corticosteroids.

Location: The lesion involves the dorsum, particularly the middle and posterior one-third. In heavily keratinized surface layers of filiform papillae, continuous desquamation through friction of tongue with food, palate and upper anterior teeth occurs and is replaced by new epithelial cells. Symptoms: Papillae which are of considerable length will occasionally brush the palate and may produce gagging. There is hypertrophy of filiform papillae. The papillae may reach a length of 2 cm. Signs: The papillae are elongated, sometimes markedly so and have the appearance of hair (Fig. 25.11). The hyperplastic papillae then become pigmented by the

HAIRY TONGUE It is also called lingua villosa, coated tongue and black hairy tongue. It designates an overgrowth of the filiform papillae on the dorsum of the tongue with accumulation of keratin giving the tongue a superficial resemblance as that of hairiness.

Etiology There may be delayed shedding of the horny layer of the filiform papillae or there may be an increase in the rate of formation of keratin. Fungal organisms like Candida albicans and systemic disturbances (anemia, gastric upset).

Figure 25.11 Hairy tongue showing elongated papillae

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colonization of chromogenic bacteria, which can impart a variety of colors ranging from green to brown to black. This gives it a coated or hairy appearance and retains debris and pigments from substances such as food, tobacco, smoke and candy. Earthy or encrusted tongue: Extreme degree of coating occurring in dehydrated, debilitated and terminally ill patient can lead to a very thick, leathery coating on the tongue which is referred to as ‘earthy’ or ‘encrusted’ tongue. It is heavily coated with bacteria and fungi and forms a thickened malted layer. Color may be varied from yellowish white to brown or even black depending upon their staining by extrinsic factors such as tobacco, certain foods, medicines or chromogenic organisms of the oral cavity.

Histopathological Features The filiform papillae are extremely elongated and hyperplastic with keratosis. External colonization of the papillae by basophilic microbial colonies is a prominent feature.

Management Brushing of the tongue twice daily for 2 minutes, making gentle movements over the involved area towards the tip of the tongue. The topical application of podophyllum in acetone and alcohol suspension seems to be quite effective. Application of topical keratolytic agents and prescription of yogurt or other Lactobacillus acidophilus cultures have been used in the treatment of this disease. Points to Remember Lingua villosa, papillae of considerable length, brush the palate gagging, papillae appearance of hair, pigmented green to brown to black colors, earthy or encrusted tongue, hyperplastic, keratosis, basophilic microbial colonies, podophyllum, topical keratolytic agents.

CRENATED TONGUE The term is applied to a condition in which indentations of teeth are observed at the lateral margins of the tongue. It may occur due to abnormal tongue pressure habits and tongue thrusting habits. Any enlargement of the tongue may cause indentations on the teeth. Often, impression of teeth is seen on the tongue. It is usually an asymptomatic and harmless condition.

FOLIATE PAPILLITIS One foliate papilla is present in newborn at each side of the tongue, consisting of 4 to 8 leaves and located at the junction of the anterior two-thirds of the tongue and the base. The folds are separated by grooves of different depths, perpendicular to the longitudinal axis of the tongue. In adults, they are barely noticeable, but sometimes they swell. Foliate papillae frequently become inflamed and enlarged, so that it is clinically evident. Such enlargement is usually bilateral. This reactive lingual tonsil has often been called foliate papillitis. Hypertrophy of lymphoid tissue may be followed by secondary traumatization resulting in a so-called foliate papillitis.

Clinical Features Symptoms may be partly due to upper respiratory tract infections and partly due to irritation. Age and sex distribution: It is more common in women, usually in the second half of life. It is seen in children. Site: The condition may be bilateral with a duration varying from few weeks to many years. Symptoms: Soreness, tenderness, pain and occasionally, a sour or metallic taste. Sign: Clinically, the patient presented a pronounced enlargement of one foliate papilla.

Histopathological Features The lesion had polypoid morphology and the mass appeared microscopically as aggregates of lymphoid tissue showing a reactive hyperplasia.

Management It consists of elimination of irritating factors such as sharp edges of teeth and dentures. If necessary, surgical removal may be performed. Points to Remember Reactive lingual tonsil, bilateral, soreness, tenderness, pain, enlargement of one foliate papilla, aggregates of lymphoid tissue, elimination of irritating factors.

LEUKOKERATOSIS NICOTINA GLOSSI It is also called smoker’s tongue. It is homogeneous, like leukoplakia with evenly distributed, pinpoint, hemispheri-

Tongue Disorders

cal depressions, showing a so-called golf ball appearance. As a result of heavy smoking, there is loss of papillae. No other clinical features are found in these patients.

a large permanent cleft of the tongue. Cotton roll ulcers are rare, but may occur on the borders of the tongue. Such ulcers are not indurated and can be extremely painful.

DEPAPILLATION OF THE TONGUE

Lesions due to Automutilation

Local Disease

Injuries to the tongue can occur due to self inflicted bites. It usually occurs in mentally handicapped persons.

Eosinophilic Granuloma It is not related with eosinophilic granuloma of bone. It is also called ulcerated granuloma eosinophilicum diutinum, traumatic granuloma or reparative lesion. The cause of the lesion is unknown. It is characterized by a well demarcated proliferative ulceration covered by thick masses of fibrin and detritus. Age and sex distribution: It may occur at any age and does not show a sex predilection. Site: It is located on the dorsum, margin or inferior surface of the tongue. Some of the cases are also found on labial mucosa, floor of the mouth, alveolar ridge and gingiva. Sign: The lesions are ulcerative, not indurated and rather well circumscribed. There is putrid odor. The ulceration is probably due to moist environment and frequent traumatization. It can be confused with squamous cell carcinoma. Histopathologically it will show masses of eosinophilic granulocytes as well as neutrophils, plasma cells and histiocytes. The presence of mast cells also has been reported. Proliferation of capillaries and myoblasts are other common findings. Management: When one is dealing with an eosinophilic granuloma, spontaneous healing can be expected in a matter of weeks.

Traumatic Injuries Cause: The tongue may be repeatedly traumatized, either mechanically or chemically. It is associated with jagged teeth, rough margins of restorations and inadvertent contact of tongue with dental medicaments such as phenol and eugenol. Sign: Localized area of depapillation is often noted with papillary regeneration around such areas. A sharp edge of the tooth may cause a yellowish, not indurated and well circumscribed ulcer at the borders of the tongue. Severe damage of the tongue may occur during epileptic seizures. Prolonged oral intubation may cause

Allergic Stomatitis It refers to edematous changes in part or all of the oral and lingual mucosa, due to hypersensitivity reaction. Cause: It can occur due to certain drugs like antibiotics, cancer chemotherapeutic agent and anticholinergic agents. It can also occur due to variety of allergens such as monomer of the denture, mouthwashes, chewing gum and lipstick. Signs: There is edematous swelling of the tongue. There is depapillation of the tongue.

Facial Hemiatrophy It is characterized by unilateral atrophy of the skin, subcutaneous tissues and muscle of the face. There is atrophy of half of the tongue.

Cranial Arteritis Rheumatic polymyalgia and temporal arteritis is an inflammatory condition of large and median sized arteries in elderly persons. There is no sex predilection Symptoms include headache, fever, sweating, malaise, fatigue, anorexia and weight loss. Blindness is the most severe complication. Sign: Several cases of painful ulceration and gangrene of the tongue, as a result of arteritis, have been reported. There is also lingual pain and intermittent blanching of the tongue also has been described. Early use of adequate corticosteroid therapy at the level of 40 to 60 mg daily is required for the treatment of suspected cranial arteritis.

Chronic Candidiasis Chronic atrophic candidiasis can be present on the dorsum of the tongue. It is difficult to distinguish it from median rhomboidal glossitis. It is diagnosed by scraping and cytological examination.

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Systemic Disease Iron Deficiency Anemia 636

There is inhibition of epithelial reproduction, secondary candidiasis and chronic xerostomia. There are atrophic changes on the dorsum of the tongue. It first appears at the tip and lateral borders with loss of filiform papilla. In extreme cases, the entire dorsum becomes smooth and glazed. The tongue may be very painful and is either pale or fiery red.

Plummer Vinson Syndrome Sideropenic anemia shares atrophic glossitis, angular cheilitis, generalized atrophic oral mucosa, oral ulceration and secondary candidiasis. The tongue may be red or pale, painful and fissured. There is also dysphagia and dystrophy of nails.

Pernicious Anemia The patient suffers from general weakness, burning or itching sensation from the oral mucous membrane with disturbance of taste and occasional dryness of mouth. There may be paresthesia, atrophy of filiform and fungiform papillae (Fig. 25.12). In advanced cases, dorsum of the tongue becomes completely atrophic, smooth and fiery red surface. Tongue appears flabby because the normal muscle tonus is reduced.

Niacin Deficiency Deficiency of niacin results in a disease called pellagra. The tongue become fiery red and devoid of papillae.

The filiform papillae are most sensitive and disappear first. The fungiform papilla may become enlarged. In advanced cases, all the papillae are lost and reddening become intense. In this, tongue may become so swollen that indentation from teeth are found along borders of the tongue.

Folic Acid Deficiency There is marked glossitis. The tongue is fiery red and atrophy filiform and fungiform papillae. The tongue is often swollen and small cracks may appear on the dorsum of the tongue.

Peripheral Vascular Disease It includes scleroderma and lupus erythematous. Fibrosis of submucosal tissue secondary to the obliteration of small vessels by an autoimmune process is responsible for a scarred, shrunken and atrophic appearance of the tongue in scleroderma. Isolated irregular areas of lingual mucosa, atrophy and ulceration caused by arteritis, are seen in lupus erythematous. In scleroderma, the tongue shrinks, losing its mobility and papillary pattern. The color of tongue changes to a vivid appearance due to circulatory disturbances. In the end stages, the tongue lies as a stiff, reduced body in the floor of mouth.

Dermatomyositis It is a clinical syndrome consisting of polymyositis associated with skin lesions. The oral mucosa may show dark red or bluish erythema. In the early stages, tongue is markedly swollen and later becomes harder. In the late phase, tongue is atrophic.

Diabetes Decreased nutritional status of the lingual papillae, as a result of vascular changes affecting subpapillary dorsal capillary plexus supplying it, causes atrophic glossitis. Central papillary atrophy of the dorsum in which low flat papillae are noticed just anterior to the row of circumvallate papillae, is associated with diabetes.

Syphilis

Figure 25.12 Depapillation of tongue seen in nutritional

deficiency

Depapillation of the tongue usually occurs in secondary and tertiary syphilis. In secondary syphilis mucous patch occur, which may be single or multiple on the tongue. Tongue in tertiary syphilis may show gumma formation.

Tongue Disorders

A more diffuse, chronic, nonulcerating, irregular induration, with an asymmetrical pattern of grooves and smooth atrophic field covering the entire dorsum is seen. Gumma is often developed in chronic interstitial glossitis. There is atrophy of filiform and fungiform papillae.

Zoster Infection It is a viral infection caused by herpes zoster virus. Numerous vesicles occur on the ventral surface of the tongue.

Tuberculosis The most frequent involved area is dorsum of the tongue. There is ulceration with irregular outline and undermined borders, covered by yellowish gray fibrinous layer. There is usually pain associated with ulceration. Points to Remember • E osinophilic granuloma: Ulcerated granuloma, traumatic granuloma, dorsum, margin or inferior surface of the tongue, ulcerative, well circumscribed, eosinophilic granulocytes, neutrophils, plasma cells, histiocytes. • Traumatic injuries: Jagged teeth, rough margins of restorations, localized area of depapillation, papillary regeneration, epileptic seizures cleft of the tongue, cotton roll ulcers • Lesions due to automutilation: Self inflicted bites, mentally handicapped persons • Allergic stomatitis: Antibiotics, cancer chemotherapeutic, edematous swelling of the tongue • Facial hemiatrophy: Atrophy of half of the tongue • Cranial arteritis: Rheumatic polymyalgia, headache, fever, sweating, malaise, fatigue, painful ulceration and gangrene of the tongue • Chronic candidiasis: Chronic atrophic candidiasis, scraping • Iron deficiency anemia: Inhibition of epithelial reproduction, atrophic changes on the dorsum of the tongue, entire dorsum becomes smooth and glazed. • Plummer Vinson syndrome: Atrophic glossitis, angular cheilitis, generalized atrophic oral mucosa, tongue may be red • Pernicious anemia: Weakness, burning or itching sensation, paresthesia, atrophy of filiform and fungiform papillae, tongue appears flabby • Niacin deficiency: Pellagra, filiform papillae, reddening

• F olic acid deficiency: Marked glossitis, tongue is often swollen • Peripheral vascular disease: Scleroderma, lupus erythematous, Isolated irregular areas of lingual mucosa, atrophy and ulceration caused by arteritis, vivid appearance • Dermatomyositis: Tongue is markedly swollen and becomes harder • Diabetes: Low flat papillae • Syphilis: Secondary and tertiary syphilis, asymmetrical pattern of grooves and smooth atrophic field • Zoster infection: Numerous vesicles • Tuberculosis: Ulceration with irregular outline.

DYSGEUSIA AND HYPOGEUSIA It is also called phantom taste or distorted taste. Dysgeusia is defined as persistent abnormal taste and hypogeusia is defined as diminished taste sensation.

Causes Local factors: Loss of taste sensation may occur due to candidiasis, oral trichomoniasis, xerostomia, periodontitis or gingivitis. Systemic factor: Systemic disease like vitamin deficiency, zinc deficiency, liver dysfunction, pesticide ingestion, radiotherapy, chronic gastritis, lead poisoning, cystic fibrosis, and Sjögren’s syndrome. Drugs factors: There are many drugs which can cause dysgeusia. Some example are phenindione, chlorpheniramine maleate, metronidiazole, vincristine, thiouracil, captopril, amphotericin B, etc.

Clinical Features Symptoms: Patient complaint of altered taste which sometime he described as metallic, foul and rancid. Phantom taste: In this case no stimulus is required to define altered taste.

Management Correction of underlying cause: This should be done to provide relief to patient. Points to Remember Distorted taste, altered taste, correction of underlying cause.

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DYSKINESIA

Tardive Dyskinesia

It is defined as an impairment of voluntary motion, causing movements that are incomplete or only partial.

Vermicular movements: Fine tremors and fasciculations of the tongue are described as ‘vermicular movements’.

Generalized Neurological Disease

Fly-catcher’s tongue or Bon-Bon sign: Rapid darting movements of the tongue is ‘Fly-catcher’s tongue or ‘bonbon’ sign.

Huntington’s chorea: It is a hereditary disease manifesting progressive degeneration of the nerve elements and characterized by choreiform hyperkinesia including grimacing of face. The speech may be affected early, due to the involuntary movements of the tongue. Gilles de la Tourette’s syndrome: It is characterized by motor incordination and tics, with echolalia and coprolalia. The patient exhibits bizarre facial tics, protrusion of the tongue and the tendency for lip licking. Chorea minor: It is a disease of the childhood, characterized by the occurrence of rapid irregular, aimless involuntary movements of the muscles of the extremities, face and trunk. The tongue is protruded quickly and rapidly withdrawn to prevent biting of the tongue by involuntary movements of the jaw muscle.

Amyotrophic Lateral Sclerosis It is a chronic progressive disease of an unknown cause characterized by atrophy and fasciculations of the wasted muscle. It involves demyelination of the corticobulbar tracts and degeneration of cranial nerve motor nuclei. The muscles of palate, pharynx and tongue are commonly affected. Speech may be slurred eating solid food and drinking can cause choking. Early stage: Hypoglossal nerve involvement results in flaccidity, symmetric weakness, and slowness of movement and atrophy of tongue. Middle stage: In the middle stage a gradual and generalized weakening of the tongue occurs. This is accompanied by spasticity, which results in reduced rate, range and force of articulatory tongue movements. Late stage: In the late stage, there is virtually unintelligible articulation.

Buccolingual Masticatory Syndrome This syndrome consists of repetitive, nonrhythmic abnormal movements that occur at the speed of normal voluntary movements. Spontaneous dyskinesia: It consists of movement of mandible and protrusion of the tongue or the lips.

Rabbit syndrome: When Bon-Bon sign is associate with smacking movement of the lips with constant lip tremor, it is referred as rabbit syndrome. Points to Remember • G eneralized neurological disease: Huntington’s chorea, Gilles de la Tourette’s syndrome, chorea minor • Amyotrophic lateral sclerosis: Atrophy and fasciculations of the wasted muscle, flaccidity, slowness of movement and atrophy of tongue, unintelligible articulation • Buccolingual masticatory syndrome: Repetitive, nonrhythmic abnormal movements, spontaneous dyskinesia • Tardive dyskinesia: Vermicular movements, Flycatcher’s tongue or Bon-Bon sign, Rabbit syndrome.

PARALYSIS OF TONGUE It is also called glossoplegia. It usually occurs due to unilateral injury of the nucleus in the medulla or the peripheral hypoglossal nerve.

Causes It may be caused by acute anterior poliomyelitis, infectious polyneuritis, neurofibromatosis, syringobulbia, irradiation of head and neck and compression by a tortuous internal carotid artery in the neck.

Clinical Features Sign: There is paralysis and atrophy of the muscles of one half of the tongue (Fig. 25.13). The affected tongue deviates towards the paralyzed side when protruded. The movements towards the normal side are weak or absent. When the tongue lies on the floor of the mouth, it may deviate or curl slightly toward the healthy side and movements of the tongue towards the back of the mouth on the healthy side are impaired. If the paralysis is not accompanied by atrophy, the tongue may appear to bulge slightly and to be higher and somewhat more voluminous on the paralyzed side.

Tongue Disorders

Clinical Types • • • •

Ulcerative variety Warty growth An indurated plaque or mass A fissure.

Clinical Features Age and sex distribution: Carcinoma of the tongue is disease of middle and later decades of life, with mean age at presentation being about 60 years. Males are more commonly affected than females.

Figure 25.13 Paralysis of tongue showing deviation

When atrophy supervenes, paralyzed side becomes smaller and the tongue may become curved towards the paralyzed side with sickle shaped deformities. In some cases, hypoglossal nerve may be affected bilaterally, causing impairment of the tongue, mobility in lateral direction and atrophy of sides of the tongue. It can be seen in syndromes like Dejerine (anterior bulbar syndrome), Jackson-Mackenzie (vagoaccessoryhypoglossal syndrome), Collet-Sicard, Duchenne, Mobius and Tapia. Points to Remember Glossoplegia, peripheral hypoglossal nerve, tongue deviates towards the paralyzed side, tongue may appear to bulge, Dejerine (anterior bulbar syndrome).

SQUAMOUS CELL CARCINOMA It is the most common oral carcinoma with 60 percent cases arising from the anterior 2/3rds of the tongue and remainder from the base.

Etiology There are many etiological factors responsible for tongue cancer. Most commonly associated factor is alcohol and tobacco smoke. These two has got maximum risk for all head and neck cancer. Other factors which can be responsible are candidiasis, syphilis, chronic dental trauma and chronic superficial glossitis.

Location: The majority of tongue carcinoma occurs on lateral border of anterior 2/3rds of the tongue and undersurface of the tongue. The lesions on the posterior border of the tongue are usually of higher grade malignancy, metastasize earlier and often have a poor prognosis. Cancers located in the anterior 2/3rds of the tongue are detected in early stages, as compared to those in the posterior 1/3rd of the tongue. Signs: The most common presenting signs of carcinoma of tongue is a painless mass or ulcer, although in most patients the lesion ultimately becomes painful, especially when it becomes secondarily infected. Symptoms: Excessive salivation gradually appears along with the growth. In late stages, saliva becomes blood stained. As the patient is unable to swallow saliva, offensive smell in the mouth occurs due to bacterial stomatitis. There is complained of sore throat and pain in case of lesions on posterior border of the tongue. Immobility of tongue: Patient may complaint of immobility of the tongue which occurs due to extensive carcinomatous infiltration of the lingual musculature. It becomes worse when floor of mouth is involved and ultimately, it causes difficulty in speech. Hoarseness of voice and dysphagia is present when the carcinoma involves posterior 3rd with involvement of pharynx and larynx. Carcinoma of the tongue may be seen in four varieties. 1. Ulcerative variety: Is usually seen near the edge of the tongue. The ulcer looks irregular and the edges are raised and everted. The floor is covered by yellowish grey slough. Base is indurated. 2. Warty growth: It usually possesses a broad and indurated base (Fig. 25.14). It is developed on excess proliferating growth of filiform papillae. Rarely, does it take cauliflower type look.

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Posterior 3rd: It drains into jugulodigastric group of the upper deep cervical nodes on both sides of the neck. Blood: It is rare and extremely late in occurrence. It is only seen when the growth is in extreme posterior part of the tongue.

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Management

Figure 25.14 Carcinoma of tongue showing ulcerative and

indurated growth

3. An indurated plaque or mass: In this case a typical indurated submucous plaque, can be felt. 4. A fissure: It is usually presented as a chronic fissure which does not to heal. The tumor may begin as a superficially indurated ulcer with a slightly raised border and may proceed either to develop a fumigating, exophytic mass or to infiltrate the deep layers of the tongue, producing fixation and induration without much surface changes. At an early stage tongue cancer may appear as thickened, leucoplakic patches, or as a nodule.

Surgery: If the growth is less than 1 cm in diameter, it should be removed along with a wide margin of mucosa, not less than 1 cm. If it is localized to anterior 2/3rds of the tongue, partial glossectomy or subtotal glossectomy should be carried out. When the growth reaches within 2 cm of jaw, hemimandibulectomy may be required with excision of the growth. Radiotherapy: When the growth is more than 1 cm in diameter in anterior 2/3rds, the preliminary treatment is radiotherapy in the form of interstitial radiotherapy. Prognosis: The 5 years survival rate of cancer tongue is not more than 25 percent. Points to Remember Alcohol, candidiasis, syphilis, lateral border of anterior 2/3rds of the tongue, painless mass or ulcer, excessive salivation, immobility of tongue, ulcerative variety, warty growth, indurated plaque or fissure, local spread, lymphatic spread, blood spread, surgery, radiotherapy.

Spread of Carcinoma

Complications

Local spread: It spreads by infiltration and invasion.

Patient usually dies due to cancerous cachexia, starvation, inhalation bronchopneumonia, asphyxias and hemorrhage from involved cervical lymph nodes.

Carcinoma of anterior 2/3rds of the tongue: It usually starts on the lateral margins of the tongue and invades the floor of the mouth early, but it does not extend to the other side across the midline. Carcinoma of posterior 1/3rd of the tongue: It tends to spread to the corresponding tonsils, epiglottis and soft palate.

Lymphatic Spread Tip of the tongue: Carcinoma of tip of the tongue may drain to the submental nodes, but may also drain to the jugulo-omohyoid nodes. Anterior 2/3rds: It drains into the submandibular lymph nodes.

PIGMENTATION OF TONGUE The tongue may exhibit various patterns of racial melanin pigmentation. Endogenous pigmentation is rarely identifiable on the dorsum because of the thickness of the epithelium, but jaundice may be apparent under the thinner ventral mucosa. In some cases extensive melanin pigmentation can occur on tongue (Fig. 25.15). Exogenous pigmentation of filiform papillae of the normal and coated or hairy tongue is very common and result from microbial growth, metabolic products, food debris and dyes from candy, beverages and mouth rinses.

Tongue Disorders

Figure 25.15 Melanin pigmentation seen in tongue

Pigmentation of the tongue has been described by a commonly used anti-chemotherapeutic agent doxorubicin hydrochloride, which also discolor patient’s urine, nail beds and skin folds. Extravasation of red cells around lingual varicosities may give patchy, bluish red discoloration. The thin tissue overlying a ranula is said to have a greenish blue appearance. Points to Remember Racial melanin pigmentation, endogenous pigmentation, exogenous pigmentation, extravasation of red cells, patchy, bluish red discoloration, greenish blue appearance.

BIBLIOGRAPHY 1. Allard RHB. The thyroglossal cyst: head, Neck Surg. 1982;5:134-46. 2. Baughman RA. Median rhomboidal glossitis: developmental anomaly: Oral Surg Oral Med Oral Pathol. 1971;31:56-65. 3. Bolling RP, Sabeeh V, Stewart JM Jr, et al. Ankyloglossum superius syndrome: diagnosis and surgical management. J Craniofac Surg. 2007;18(5):1094-7. 4. Chidzonga MM, Shija JK. Congenital cleft of the lower lip, bifid tongue with ankyloglossia, cleft palate and submental epidermoid cyst: report of a case. J Oral Maxillofac Surg 1998;46:809-12 5. Danser MM, Mantilla Gomez S, Van Der Weijden GA. Tongue coating and tongue thristing and tongue brushing: A literature review: In J Dent Hygiene. 2003;1:151-8.

6. Diaz-Arias AA, Bickel JT, Loy TS, et al. Follicular carcinoma with clear cell changes arising in lingual thyroid. Oral Surg Oral Med Oral Pathol. 1992;74;206-11. 7. Di Felice R, Lombardi T. Foliate papillitis occurring in a child: a case report. Ann Dent. 1993;52(2):17-8. 8. Eidelman E, Chosack A, Cohen T. Scrotal tongue an Dgeographic tongue: polygenic and associated traits. Oral Surg Oral Med Oral Pathol. 1976;42:591-6. 9. Espelid M, Bang G, Johannessen AC, et al. Geographic stomatitis report of 6 cases: J Oral Pathol Med. 1991;20:425428. 10. Ettinger RL, Manderson RD. A clinical study of sublingual varices: Oral Surg Oral Med Oral Pathol. 1974;38:540-5. 11. Ewart NP. A lingual mucogingival problems associated with ankyloglosssia: a case report: N Z dent J. 1990;86:16-7. 12. Farman AG. Hairy tongue (lingua villosa): J Oral Med. 1977;32:85-91. 13. Fleming PS, Flood TR. Bifid tongue - a complication of tongue piercing. Br Dent J. 2005;198:265-6. 14. Garavello W, Spreafico R, Gaini RM. Oral tongue cancer in young patients: A matched analysis. Oral Oncol 2007;43:894-7. 15. Hall DMB, Renfre MJ. Tongue tie: Arch Dis Child. 2005;90:1211-5. 16. Jainkittivong A, Aneksuk V, Langlais RP. Oral mucosal condition in elderly dental patients. Oral Dis. 2002;8:218:23. 17. Kalan A, Tariq M. lingual thyroids: A clinical evaluation and comprehensive management. Ear Nose Throat J. 1999;78:345-9. 18. Mouradian MS, Chan KM, Jeerakathil T, Shuaib A Transient total tongue paralysis from simultaneous central and peripheral lesions. J Neurol Neurosurg Psychiatry. 2001;70:806-80. 19. Mustafa Goregen, Ozkan Miloglu, Mustafa Cemil Buyukkurt, et al. Median Rhomboid Glossitis: A Clinical and Microbiological Study. Eur J Dent. 2011;5(4):367-72. 20. Myer CM III, hotaling AJ, Reilly JS. The diagnosis and treatment of macroglossia in children. Ear Nose Throat J. 1986;65:444-8. 21. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edition, Saunder Elsevier; 2009. 22. Osaki T, Ohshima M, Tomita Y, et al. Clinical and phusiological investigation in patient with taste abnormality; J Oral Pathol Med. 1996;25:38-43. 23. Patil RA, Hiray YA, Kasture SB. Reversal of reserpineinduced orofacial dyskinesia and catalepsy by Nardostachys jatamansi. Indian J Pharmacol. 2012;44(3):340-4. 24. Prasad KC, Bhat V. Surgical management of lingual thyroid: A report of four cases: J Oral Maxillofac Surg. 2000;58:2237.

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25. Schmidt BL, Dierks EJ, Homer L, Potter B. Tobacco smoking history and presentation of oral squamous cell carcinoma. J Oral Maxillofac Surg. 2004;62:1055-8. 26. Shulman JD, Carpenter WM. Prevalence and risk factors associated with geographic tongue among US adults: Oral Dis. 2006;12:381-6. 27. Southam JC, Ettinger RL. A histological study of sublingual varices. Oral Surg Oral Med Oral Pathol. 1974;38;879-86. 28. Sunira Chandra, Vaishali Keluskar, Anjana Bagewadi, et al. Extensive physiologic melanin pigmentation on the tongue: An unusual clinical presentation, Contemp Clin Dent. 2010;1(3):204-6. 29. van der Waal I, Pindborg JJ. Diseases of the tongue. Chicago: Quintessence; 1986.

30. van der Wal N, van der Kwast WA, van der Waal I. Median rhomboid glossitis: A follow-up study of 16 patients. J Oral Med. 1986;41:117-20. 31. Wang J, Goodger NM, Pogrel MA. The role of tongue reduction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95:269-73. 32. Yasuda Y, Kitai N, fujii Y, et al. Report of patient with hypoglossia-hypodactylia syndrome and review of literature: clef palate Craniofac J. 2003;40:196-202. 33. Yifat Manor, Amos Buchner, Michael Peleg, et al. Lingual cyst with respiratory epithelium: An entity of debatable histogenesis: Journal of Oral and Maxillofacial Surgery. 1999;57(2):124-7.

MULTIPLE CHOICE QUESTIONS 1. The largest papillae are: a. Filiform papillae b. c. Circumvalate papillae d.

Fungiform papillae Foliate papillae

2. Most numerous and smallest papillae are: a. Papillae simplices b. Filiform papillae c. Fungiform papillae d. Foliate papillae 3. Muscle depresses the tongue is: a. Hyoglossus b. Genioglossus c. Palatoglossus d. Vertical muscle 4. All the muscle of tongue are supplied by hypoglossal nerve, except: a. Hyoglossus b. Palatoglossus c. Genioglossus d. Styloglossus 5. Fissured tongue is associated with: a. Melkerson-Rosenthal syndrome b. Apert’s syndrome c. Parkes Weber syndrome d. Sturge-Weber syndrome

6. Geographic tongue is refer to: a. Hairy tongue b. Glossitits c. Crenated tongue d. Benign migratory glossitis 7. Loss of filiform papillae and munro’s abscess is the histopathological feature of: a. Erythema migrans b. Geographic tongue c. Both a and b d. Lingua dissecta 8. In hairy tongue, there is a hypertrophy of: a. Fungiform papillae b. Filiform papillae c. Circumvalate papillae d. Foliate papillae 9. Extensibility of tongue, both, forward to touch the tip of nose and backward in to the pharynx refer to: a. Gorlin sign b. Bon-Bon sign c. Rabbit syndrome d. Vermicular movements 10. Rapid darting movement of tongue is: a. Bon-Bon sign b. Rabbit syndrome c. Fly-catcher’s tongue d. Both a and c

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Temporomandibular Joint Pathology Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline     Â

Coronoid hyperplasia Condylar hyperplasia Condylar hypoplasia Bifid condyle Osteoarthritis

Temporomandibular joint (TMJ) is a unique joint in which translatory as well as rotational movements are possible and where both the ends of bone articulate, in the same plane, with that of other bone. It is also called as ginglymodarthrodial type of joint, meaning that it has a relatively sliding type of movement between bony surfaces, in addition to hinge movement, common to diarthrodial joint.

    Â

Rheumatoid arthritis Ankylosis Subluxation (hypermobility) Synovial chondromatosis Temporomandibular joint dysfunction

Site: It is unilateral or bilateral. Bilateral seen more commonly than unilateral. Restricted mandibular movement: Coronoid process impinged on posterior surface of zygoma, deviation of mandible towards affected site.

Radiographic Feature

CORONOID HYPERPLASIA

There is irregular nodular growth of tip of coronoid process. In bilateral type there is regular elongation of both process.

This is rare anomalies which may results in limitation of mandibular movements.

Management

Cause It has got hereditary nature as cases are seen in family. Other factors which can be causative factor for coronoid hyperplasia are endocrinal, tumor affecting coronoid process.

Clinical Features Age and sex distribution: It is more common in male in the ratio of 5:1. It is more commonly seen at the puberty.

Surgery: Surgical removal of elongated coronoid process. Points to Remember Unilateral or bilateral, restricted mandibular movement, deviation of mandible, irregular nodular growth regular elongation.

CONDYLAR HYPERPLASIA There is excessive growth of one condyle.

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Cause

Types

It is as such idiopathic in nature, but in some cases local circulatory problems, endocrine disturbances and trauma are thought to be causes.

Congenital: It is associated with head and neck syndrome like mandibulofacial dysostosis, Goldenhar syndrome.

Clinical Features Age: It is more commonly seen in adolescents and young adults. Signs: There is facial asymmetry, prognathism cross bite and open bite. Radiographic features: There is enlargement of condylar head and elongation of neck of condyle (Fig. 26.1).

Histopathological Features During active phase there is proliferation of condylar cartilage is seen.

Acquired: Is results from defect in growth center of condyle in developing stage. It is usually cause by trauma during infancy or childhood.

Clinical Features Site: It can be unilateral or bilateral. Signs: There is class II malocclusion with smaller size of mandible. Unilateral hyperplasia shows depression on the affected side. There is also deviation of midline towards the affected side while opening of the mouth.

Management

Radiographic features: There is short condylar process, small sigmoid notch, poorly formed condylar head (Fig. 26.2).

Unilateral condylectomy: It can be done in some patient.

Management

Points to Remember Proganthism cross bite, enlargement of condylar head, proliferation of condylar cartilage, unilateral condylectomy.

CONDYLAR HYPOPLASIA

Costochondral rib graft can be place to establish active growth center. Points to Remember Mandibulofacial dysostosis class II malocclusion, depression on the affected side, small sigmoid notch, costochondral rib graft.

It is the underdevelopment of mandibular condyle.

Figure 26.1 CT scan of hyperplasia of condyle

Figure 26.2 Hypoplasia of condyle on left side

Temporomandibular Joint Pathology

Etiopathogenesis

Figure 26.3 Bifid condyle showing bilobed pattern

BIFID CONDYLE In this double headed mandibular condyle. They have medial and lateral head divided by anteroposterior groove. Cause of this thought to be traumatic in origin. Trauma can occur in childhood. Other factor which though to causing it are abnormal muscle attachment, teratogenic agent and persistence of fibrous septum. Bifid condyle is asymptomatic and discover on routine radiograph. Radiograph will show bilobed pattern of the condyle (Fig. 26.3). No treatment is necessary for this case as it is asymptomatic. Points to Remember Double headed mandibular condyle, traumatic, abnormal muscle attachment, persistence of fibrous septum, bilobed pattern of the condyle.

OSTEOARTHRITIS It is also called as osteoarthrosis or degenerative arthritis. It is primarily a disorder of movable joints characterized by deterioration and abrasion of the articular cartilage with formation of new bone at the joint surface. There is destruction of the soft tissue component of the joint and subsequent erosion with hypertrophic changes in bone. There is breakdown of the connective tissue covering of the condyle, articular eminence and the disk. Articular eminence shows resorption and the underlying bone becomes sclerotic.

The lesion is brought about either by an increase in the functional demands of the healthy tissue or by deterioration in the functional capacity of the tissue. Breakdown of the joint may occur when the tissues are subjected to repetitive overload in excess of their functional capacity or with normal load when the capacity is reduced as a part of aging process. By another theory, bone growth does not cease completely after puberty and remodeling of the joint progresses under functional demands. Degenerative joint disease may develop when the remodeling rate of bone exceeds that of the cartilaginous repair. The gross evidence of these changes is the formation of marginal osteophytes with development of new bone in the area adjacent to the cartilage. There is slower replacement of chondroblast and chondrocytes in joint cartilage. Fibrocartilage of TMJ force fibers to work longer and becomes susceptible to fatigue. The matrix is having less water become desiccated and brittle. There is diminished blood flow to TMJ producing poor nutrition to the joint. After continuous joint use surface fiber break down exposing underlying bone. This bone then undergoes degenerative destruction and proliferation.

Clinical Features Age and sex distribution: It occurs in patients older than 40 years of age and 85 percent of them are older than 70, with a mean age of 53 years. Females are affected 6 times as frequently as males. Location: It is common in many joints, but it is not frequently found in TMJ. Symptoms: Unilateral pain over the joint, which may be sensitive to palpation, occurs. Pain on movements or biting occurs, which may limit mandibular function. Pain is usually located to the immediate preauricular region. Signs: There is deviation of the jaw towards the affected side. Stiffness of the joint is present. There is presence of crepitation of the joint; the sound indicates degeneration within the articulating surfaces of the joint or disc. There is limitation of jaw movements, which becomes increasingly apparent with function. Muscle guarding: Patient exhibits tenderness of the muscle due to constant strain on muscle. This strain is due to attempt to keep painful joint immobile. This is called as muscle guarding.

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Figure 26.4 Ely cyst in osteoarthritis of TMJ

Early signs may progress to spasm of the masticatory muscles resulting in stiffness and locking of the jaw. If not treated at this point it may lead to irreversible changes in the TMJ. Normal course is between 1 to 3 years. Severe symptoms last for about nine months, but gradually burn out leaving little or no disability.

Radiographic Features Osteophytes: There is formation of protuberance of bone in the joint. This is called osteophytes. There is narrowing and obliteration of joint space. There is also presence of radiolucent subchondral cyst or ely cyst (Fig. 26.4), ossicles (ossification within the synovial membrane), osteosclerosis and flattening of articular surface.

Histopathological Features The earliest changes occur in the articular covering of the condyle. It shows that the cells tend to clump together and become unevenly distributed throughout the fibrous matrix. At this stage, the subarticular bony end plate may still be intact, but later osteoclastic resorption of the bone takes place. Vertical splitting of the articular layer takes place and this is followed by fragmentation and loss of articular surface, with exposure of the underlying bone. Attempted repair by proliferation of overlying articular tissue downward into the resorbing areas of subarticular bone is sometimes seen and this leads to uneven thickening of the articular surface. Osteophytic lipping was found only on the anterior surface of the condyle. Destruction of the articular

cartilage, in turn, causes erosion and perforation with ultimate destruction of the inner articular disc. Secondary arthritic changes in the articular disc may result in flattening of the disc. Initial destruction of the soft tissue component of the joint occurs with subsequent erosion and hypertrophic changes in the bone. The connective tissue covering the condyle eminence and disc breaks down. The bony surface of the condyle and articular eminence shows resorption with the underlying bone becomes sclerotic. The bone beneath the cartilage contains osteocytes, fatty degeneration or necrosis of marrow, marrow fibrosis, infiltration by chronic inflammatory cells, large degenerative space (subchondral cyst). There is also formation of metaplastic bone (ossicles), or hyaline cartilage granules (chondral bodies).

Management Elimination of the cause: It includes occlusal adjustment or replacement of the missing teeth and ill fitting prosthesis, grinding, treatment of caries and periodontal disease. Low dose doxycycline and NSAIDs can reduce the symptoms of osteoarthritis. We can also give physiotherapy, myotherapy, corticosteroids and occlusal splints. Points to Remember Degenerative arthritis, increase in the functional demands, unilateral pain over the joint, crepitation of the joint, muscle guarding, spasm of the masticatory muscles, osteophytes, subchondral cyst, ossicles, osteosclerosis, flattening of articular surface, proliferation of overlying articular tissue, osteophytic lipping, flattening of the disc, fatty degeneration or necrosis of marrow, marrow fibrosis, chronic inflammatory cells, large degenerative space, hyaline cartilage granules,low dose doxycycline, NSAIDs, physiotherapy, myotherapy, corticosteroids and occlusal splints.

RHEUMATOID ARTHRITIS It is a debilitating systemic disease of unknown origin, characterized by progressive involvement of the joint, particularly bilateral involvement of large joints. Bony components of the TMJ are affected secondary to the granulomatous involvement of the synovial membrane that subsequently spreads to the articular surface of the condyle.

Temporomandibular Joint Pathology

Etiopathogenesis Its manifestations are probably due to a two phase process. Phase one result from some systemic infection, which evokes an inflammatory response within the joint. Phase two as an autoimmune reaction to the antigen generated by the initial inflammation itself or it may be associated with derangement of the immune response to the exogenous antigen. It may results from cross reaction of antibodies generated against hemolytic streptococci or other micro-organism. In the active phase, TMJ may get involved bilaterally. The joint space enlarges with synovial effusion which attacks the fibrocartilage and ultimately produces erosion of the underlying bone. This causes pain, stiffness and limitation of movement. The process then enters the healing phase, where the symptoms subside and remodeling of the articular surface occurs. Bony components of the TMJ are affected secondary to the granulomatous involvement of its synovial membrane that subsequently spreads to the articular surface of the condyle. However, chronic phase may follow before healing occurs. Here, there is proliferation of the synovial membrane due to inflammation this is called as pannus formation. This pannus then encroaches the joint space and causes destruction of the articular cartilage. In this lipping of the condyle and marginal proliferation is seen, this result in narrowing of joint space. Here, predominant clinical findings are crepitus, pain on biting and tenderness. The granulomatous tissue replaces the articular surface and small adhesions develop between the articular surface and disk. Psychosomatic: Emotional trauma, anxiety and environmental strain can lead to the onset of rheumatoid arthritis. Immunological: The presence of rheumatoid factor in the serum and synovial fluid of affected patients suggests immunological etiology. Also present are plasma cells and lymphocytes on histological examination.

Clinical Features General Age and sex distribution: It more commonly occurs in temperate climate and has its highest incidence in women from 20 to 50 years of age. Symptoms: It include bilateral stiffness, crepitus, tenderness and swelling over the joint. Fever, malaise,

fatigue, weight loss, pain and stiffness in the limb are also evident. Polyarthritis develops subsequently, large and weight bearing joints are frequently affected. Spindle appearance of finger: Swelling of the proximal but not the distal, interphalangeal joints gives the finger a spindle appearance and swelling of the metatarsophalangeal joints results in broadening of feet. Subcutaneous nodules: There is formation of subcutaneous nodules on the pressure points, sites of friction and various vascular lesions, both necrotizing and obliterative types. Severe deformities of extremity can occur as a result of joint collapse, tendon rupture and muscle involvement. Signs: The joint may become red, swollen and warm to touch. Muscle atrophy around the joint is common. In hands, it may produce an ulnar drift. Bursitis can also occur. Anvil shape joint: Joint involved in arthritis have got characteristic anvil shape with irregular flattening of central articular surface and splaying of the lateral bone.

TMJ Involvement It can be acute or chronic and usually, it is bilaterally involved. Acute case: In acute cases, there is bilateral stiffness, deep seated pain, tenderness on palpation and swelling over the joint. There is limitation in opening of mouth. Chronic cases: In chronic cases, crepitus is the most frequent finding. Functional disturbances like deviation on opening and inability to perform lateral excursions are common. Anterior open bite is present due to bilateral destruction and antero-posterior positioning of the condyle. Fibrous ankylosis of the joint which may be partial or complex occurs in long term. Pain on biting is referred to the temporal region, ear and angle of mandible.

Radiographic Features There is flattened condylar head with irregular surface (Fig. 26.5). There is also anterior displacement of the condyle.

Histopathological Features Proliferation of synovial lining cells with intense infiltration of lymphocytes, plasma cells and polymorphs. As the inflammation becomes chronic, granulation tissue spreads across the cartilagenous articular surface

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Points to Remember Autoimmune reaction, pannus formation, psychosomatic, immunological, spindle appearance of finger, polyarthritis, subcutaneous nodules, anvil shape joint, red joint, muscle atrophy around the joint, anterior open bite, fibrous ankylosis of the joint, flattened condylar head, anterior displacement of the condyle, proliferation of synovial lining cells, rice bodies, rose Waller test is positive, intra-articular corticosteroid injections, rest to the joint, systemic glucocorticoids therapy.

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ANKYLOSIS Figure 26.5 Flattened condylar head in rheumatoid arthritis

undermining the margins and eventually eroding the adjacent bone. Later on, the fibrous tissue becomes dense and it may unite the head of the condyle to the articular fossa. Rice bodies: Synovial membrane protrude in the joint space as villi which undergo necrosis resulting in rice bodes which are small whitish villi fragments composed of cellular debris admixed with fibrin and collagen.

Investigations Rose Waller test is positive in 70 percent of the patients with rheumatoid arthritis. Antinuclear antibodies are detected by indirect immunofluorescence. Analysis of synovial fluid is essential for the immediate diagnosis of joint infection, inflammation and degenerative disease.

Management Adequate rest to the joint, soft diet is advocated. Treatment should be given for suppression of the active process, preservation of function and prevention of deformities. Intra-articular corticosteroid injections, non-steroidal anti-inflammatory drugs, immunomodulator, slow acting anti-rheumatic drug can be given. Systemic glucocorticoids therapy: This can give relief to many patient. Local treatment is done with heat, diathermy, jaw exercise or a mouth stretcher. Muscle strengthening exercise and hydrotherapy.

Ankylosis, a Greek word which means stiff joint. It is an abnormal immobility and consolidation of the joint. Types •  •  •  •  •  • 

True (intra-articular)  False (extra-articular)  Bony  Fibrous Partial Complete.

Classification True (intra-articular): It is any condition that produces fibrous or bony adhesion between the articular surfaces of the TMJ. False (extra-articular): It is the one which results from pathologic conditions outside the joint, that result in limited mandibular mobility. Bony: If bone is present between the articulating surfaces and prevents movements, it is called as bony ankylosis. Fibrous: If the medium which prevent, the movements is fibrous, it is called as fibrous ankylosis. Partial: If there is incomplete union between the articulating surfaces, it is called as partial ankylosis. Complete: If there is complete union between the articulating surfaces, it is called as complete ankylosis.

Etiology False Myogenic: The most common problem associated with muscle origin is fibrosis, which may result from chronic

Temporomandibular Joint Pathology

infection of the elevator muscles of mastication. Myositis ossificans can also produce limitation of opening. Neurogenic: They include epilepsy, brain tumor, bulbar paralysis and cerebrovascular accidents.

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Psychogenic: Here the affected persons exhibit no pain, but cannot get the jaws separated also called as hysterical trismus and is apparently produced due to fright. Bone impingement: The most common is coronoid impingement. Malformation of coronoid such as exostosis or elongation can cause the mandible to impinge on the posterior aspect of the zygoma, when opening is attempted. The formation of fibrous adhesions or cicatrical bands of scar tissues usually occurs after a traumatic accident or burns. Neoplastic disease like osteochondroma.

Figure 26.6 Intraoral view of patient who is having ankylosis

showing trismus

True Congenital: Abnormal intrauterine development, birth injuries and congenital syphilis. Trauma: Trauma to the chin forcing the condyle against the glenoid fossa, particularly with bleeding in the joint. Malunion of condylar fractures. Injuries associated with fracture of the malar-zygomatic compound. In the case of injury to the joint, there is hemorrhage within and outside the joint capsule. Injury occurs during the period of active bone formation. There is immobility of the jaw due to pain or treatment and ankylosis is take place. Inflammatory: Primary inflammation of the joint. Inflammation of the joint secondary to a local inflammatory process (otitis media, osteomyelitis, etc). Inflammation of the joint secondary to a blood stream infection (septicemia, scarlet fever, gonorrhea). Rheumatoid arthritis is the most common cause of bilateral ankylosis. Gonococcal arthritis can also cause ankylosis of TMJ. Inflammation secondary to radiation therapy. Others: Loss of tissue with scarring and metastatic malignancy.

Clinical Features (Figs 26.6 to 26.9) General Age: It is seen primarily in a young age or between 1 to 10 years. Symptoms: Pain and trismus is present which is directly related to the duration of ankylosis. Depending upon the

Figure 26.7 Extraoral view of unilateral ankylosis showing

fullness on affected side

duration, there may poor oral hygiene, carious teeth and periodontal problems malocclusion.

Unilateral Unilateral ankylosis is more common than bilateral ankylosis. Mouth opening is impossible, but the patient may be able to produce several mms of interincisal opening. Asymmetry of the face with fullness on the affected side and relative flattening on the unaffected side. In unilateral ankylosis, patient’s face is deviated towards the affected side. The chin is retracted on the affected side and slightly bypasses the midline. There is slight gliding movement towards the affected side. Cross bite is present.

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Figure 26.8 Unilateral ankylosis showing deviation of

mandible on affected side

Bilateral Face is symmetrical with micrognathia. There is bird face appearance. No gliding movement. With bilateral ankylosis, neither protrusive nor lateral movements are possible. An attempt at forced opening in bony ankylosis, there is no pain but in case of fibrous ankylosis there is pain. Due to long standing ankylosis, atrophy or fibrosis of muscles of mastication may result. In case of congenital ankylosis, there is difficulty of introducing the nipple into the mouth of newborn infants. Class II malocclusion, protrusive incisors and anterior open bite are also the features. It is due to the patient’s attempt at forcing food through the anterior teeth for a period of years.

Histopathological Features Atrophic or destructive changes in the cartilagenous component of the joint with loss of meniscus are a constant finding. There is progressive destruction of the joint tissue with narrowing of the joint space. Normal soft tissues are replaced by thick fibrous bands, which blend in with the periarticular tissue. An overall flattening of articulation, with glenoid fossa and articular eminence becoming less pronounced and condylar process become enlarged. The enlarged condyle is composed of dense sclerotic bone. Apparent union of injured parts is by granulation tissue → it is replaced by dense fibrous connective tissue → formation of fibrous cartilage → metaplasia of

Figure 26.9 Bilateral ankylosis showing bird face appearance

fibrous cartilage → direct transformation into bone → ankylosis.

Management Brisement force, condylectomy, gap arthroplasty is performed. Points to Remember Stiff joint, myogenic, neurogenic, psychogenic, bone impingement, neoplastic disease, congenital, trauma, inflammatory, pain, trismus, asymmetry of the face, fullness on the affected side, relative flattening on the unaffected side, patient’s face is deviated towards the affected side, bird face appearance, class II malocclusion, protrusive incisors and anterior open bite, thick fibrous bands, loss of meniscus, brisement force, condylectomy, gap arthroplasty.

SUBLUXATION (HYPERMOBILITY) It is the unilateral or bilateral positioning of the condyle anterior to the articular eminence, with repositioning to normal accomplished physiologic activity. It is self reducing incomplete dislocation, which generally follows stretching of the capsule and ligaments.

Etiology It is caused by long continuous opening of mouth, oral surgical procedures, osteoarthritis, psychiatric problem, use of phenothiazine derivatives.

Temporomandibular Joint Pathology

Clinical Features

Predisposing Factors

It may be unilateral or bilateral. Symptoms: Cracking noise, temporary locking of the condyle and immobilization of the jaw. Patient describes weakness of the joint while yawning. Pain is associated with last few millimeters of mouth opening. Signs: The condyle may get locked when the mouth is opened widely and upon closing, it will return with a jumping motion, accompanied by a sound caused by movement of the condyle over the articular eminence. On palpation click on opening and sliding of condyle over the articular eminence, are common.

Drugs such as thiazide diuretics, operations, trauma, alcohol and rapid weight loss can lead to gout.

Radiological Features Radiograph shows excessive excursion of the condyle from rest position to the position when jaw is opened wide.

Histopathological Features

Clinical Features Acute Gouty Arthritis Site: Initially, metacarpophalangeal joints are commonly involved. Later foot, ankles, hand, wrist and elbow may be affected. Symptoms: There is excruciating pain, which is worse at night. Sometimes it is associated with anorexia, fever and general malaise. Signs: Joint returns to normal after few days, with desquamation of the overlying skin.

Chronic Tophaceous Gout

Due to long standing opening the ligament and capsule are stretched. As the ligament does not contain elastic fibers, once it is stretched beyond its capacity, it does not come back to its normal length. The lax capsule and over stretched ligament are responsible for subluxation.

Symptoms: As the disease becomes chronic, pain and stiffness persist, with irregular swelling.

Management

TMJ Involvement

Shrinking of the capsule by a sclerosing agent will cause fibrosis of the capsule. It will limit the condylar excursion without deleterious effects on motion and cartilaginous surface of the articulating surface of the condyle. The solution used is 5 percent sodium psylliate or 5 percent intracaine in oil base.

It is seen in middle age with equal sex distribution. It has a hereditary tendency.

Points to Remember Positioning of condyle anterior to the articular eminence, cracking noise, temporary locking of the condyle, weakness of the joint while yawning, click on opening, excessive excursion of the condyle, lax capsule, over stretched ligament, sclerosing agent, 5 percent sodium psylliate.

GOUT It is a chronic metabolic disorder characterized by acute exacerbations of joint pain and swelling associated with an elevated blood uric acid and deposition of crystals of monosodium urate.

Tophi: Tophi are found in cartilage of the ear, nose or eyelids. In half the cases, palms of hands may show white streaks along the creases.

Symptoms: Sudden excruciating pain in the TMJ, followed by rapidly developing swelling. Signs: Tenderness of the affected area with limitation of movements occurs. Deviation to the affected side while opening the jaws.

Radiographic Features Punched out radiolucency can be seen on the condylar cartilage. Severe destruction of the cartilage can also be seen in some areas.

Histopathological Features Gross examination of the articular cartilage reveals white chalky deposits. This deposit is also often found in the synovial and adjacent tissues. The cartilage may be fragmented. Early findings in gout are crystalline deposits of uric acid which are diffuse in nature.

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Microtophi: This is followed by small accumulations (microtophi) with surrounding granulomatous foreign body reaction, which contains pleomorphic, non-nucleated and foreign body giant cells.

Management Diet should be low in uric acid and fat, i.e. sweetbread, meat, extract peas, beans. Increased elimination of uric acid by uricosuric agents like colchicine 0.5 mg every 2 hourly, to a maximum of 6 mg in 24 hours. Points to Remember Elevated blood uric acid, acute gouty arthritis, chronic tophaceous gout, excruciating pain, stiffness, tophi, punched out radiolucency on the condylar cartilage, white chalky deposits, fragmented cartilage, crystalline deposits of uric acid, microtophi, uricosuric agents, colchicine.

SYNOVIAL CHONDROMATOSIS It is also called chondometaplasia. It is a benign chronic progressive metaplasia that will not resolve spontaneously. Although it is non-neoplastic, it may resemble a malignant condition histologically.

Pathogenesis It denotes the condition whereby a cartilaginous focus develops within the synovial membrane of the joint. This is generally believed to occur through metaplasia of mesenchymal cell rests in the underlying connective tissue of the membrane. There is formation of metastatic foci. Eventually, they are detached from the affected membrane and become cartilaginous mobile bodies within the joint cavity. Many of these cartilaginous foci then undergo calcification. These joint bodies acquire a perichondrium, which enables them to grow by proliferation of chondrocytes. Trauma may be a predisposing factor, others factors are malocclusion, occlusal habits, and subluxation or tension sites.

Symptoms: Facial pain, limitation of motion and deviation towards the affected side. Signs: Crepitus, preauricular swelling, enlarged joint with effusion and local tenderness.

Radiological Features Loose bodies: These are rounded, irregularly shaped and variable sized radiopaque structure in the joint. There is also widened joint space, and condylar head irregularities.

Histopathological Features There is nodule of loose cartilage in the joint space. There is also presence of inflamed synovial membrane. Cartilage is consist of hyperchromatic and binucleated chondrocytes.

Management Surgery: These bodies, if symptomatic should be removed. Removal of metaplastic foci and synovectomy are the preferred treatment. Points to Remember Chondometaplasia, metaplasia of mesenchymal cell, metastatic foci, trauma, facial pain, crepitus, preauricular swelling, loose bodies, nodule of loose cartilage, inflamed synovial membrane, hyperchromatic and binucleated chondrocytes surgery.

TEMPOROMANDIBULAR JOINT DYSFUNCTION The syndrome of signs and symptoms of TMJ is termed as temporomandibular joint dysfunction (TMD). In TMD affected parts are teeth, jaws, joints and muscles.

Clinical Features Age and sex distribution: It is seen in women as compare to men. It is more common in middle age group.

Age and sex distribution: Female to male ratio is 3:1 with greatest incidence at 40 to 60 years of age.

Symptoms: Patient complaint of pain at the preauricular area. This pain may get radiated to temporal, frontal or occipital areas. Pain may be presented as headache, tinnitus (ringing in ear), otalgia (pain in ear) or toothache.

Site: This disease commonly affects large joint like knee, elbow, hip and shoulder. TMJ can also be involved.

Signs: Palpation of TMJ may evoke pain. Pain is also present on the mandibular movements.

Clinical Features

Temporomandibular Joint Pathology

Myospasm: Muscle splinting can lead to involuntary muscle contraction called as myospasm. Myofascial trigger point: These are the circumscribed area within the muscle which causes referred pain on palpation and it may be constant source of deep pain.

Radiological Features There is widened joint space, anteriorly displaced meniscus. Osteophytes: These are irregular joint surface with protuberance.

Management Conservative treatment: There should rest to the join, application of cold or heat, occlusal splint and physical therapy. Surgical management: It is done in severe cases of TMD. Points to Remember Headache, tinnitus, otalgia, toothache, myospasm, myofascial trigger point, osteophytes, conservative treatment, surgical management.

BIBLIOGRAPHY 1. Al Mobireek AF, Darwazeh AM, Hassanin MB. Experimental induction of rheumatoid arthritis in temporomandibular joints of guinea pig: a clinical and radiological study. Dentomaxillfac Radiol. 2000;29:286-90. 2. Antoniades K, Hadijipetrou L, Antoniades V, et al. Bilateral bifid mandibular condyle: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:535-8. 3. Ardekian L, Faquin W, TRoulis MJ, et al. Synovial chondromatosis of the temporomandibular joint: report of case and analysis of eleven cases. J Oral Maxillofac Surg. 2005;63:941-7. 4. Berger SS, Stewart RE. Mandibular hypoplasia secondary to perinatal trauma: J Oral Surg. 1977;35:578-82. 5. Cacoppi JT, et al. Condyle destruction concomitant with advanced gout and rheumatoid arthritis-Report of a case. Oral Surg Oral Med Oral Pathol. 1968;25:919-21. 6. Chidzonga MM. Temporomandibular joint ankylosis a review of thrity two case. Br J Oral Maxillofac Surg. 1999;14:136-8. 7. Dijkgraaf LC, Spijkervet FK, de Bont LG. Arthroscopic finding in osteoarthritis temporomandibular joint. J Oral Maxillofac Surg. 1999;57:255-68. 8. Eskanu V, Behnia H, Javadi H, et al. Histopathological comparison of normal and hyperplastic condyles. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;96:711-7.

9. Greene CS, Laskin DM. Long-term evulation of treatment for myofascial pain dysfunction syndrome: A comparative study. J Am Dent Assoc. 1983;107:235-8. 10. Gynther GFW, Tronje G, Holmlund AB. Radiographic changes in the temporomandibular joint in patient with generalized osteoarthritis and rheumatoid arthritis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;81:613-8. 11. Hall RE, Orbach S, Landesberg R. Bilateral hyperplasia of coronoid process: a report of two cases. Oral Surg Oral Med Oral Pathol. 1989;67;141-5. 12. Izumi M, Isobe M, Toyama M, et al. Computed tomographic features of bilateral coronoid process hyperplasia with special emphasis of patents without interference between the process and the zygomatic bone. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;99:93-100. 13. Karlis V, Glickman RS, Zaslow M. Synovial chondromatosis of temporomandibular joint with intracranial extension Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;86:664-6. 14. Kleinman HZ. Gout of the TMJ: Oral Surg Med Oral Pathol. 1969;27:281-2. 15. Manganello Souza LC, Mariani PB. Temporomandibular joint ankylosis: a report of 14 cases. Int J Oral Maxillofac Surg. 2002;32:24-9. 16. Matheus RA, Ramos-Perez FM, Menezes AV. The relationship between temporomandibular dysfunction and head and cervical posture, J Appl Oral Sci. 2009;17(3):2048. 17. Merril RG. Habitual Subluxation and recurrent dislocation in a patient with Parkinson’s disease: J Oral Surg. 1968;26:473-7. 18. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edn, Saunder Elsevier, 2009. 19. Palton DW. Recurrent subluxation of TMJ in psychiatric illness. Brit Dent J. 88:153(4):141-4. 20. Petito AR, Bennett, J, Assael LA, et al. Synovial chondromatosis of the temporomandibular joint. Varying presentation of 4 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90:758-64. 21. Sano T, Westesson PL, Larheim TA, et al. Osteoarthritis and abnormal bone marrow of the mandibular condyle. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87:243-52. 22. Sarma UC, Dave PK. Temporomandibular joint ankylosis: An Indian experience. Oral Surg Oral Med Oral Pathol. 1991;72:660-4. 23. Slootweg PJ, Muller H. Condylar hyperplasia: A clinicopathological analysis of 22 cases. J Maxillofac Surg. 1986;14:209-14. 24. Stefanou EP, Fanourakis IG, Vlastos K, et al. Bilateral bifid mandibular condyle: report of four cases: Dentomaxillofac Radiol. 1998;27:186-8.

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25. Wiberg B, Wanman A. Signs of osteoarthrosis of temporomandibular joints in young a clinical and radiological study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;86:158-64.

26. Yatani H, Minakuchi H, Matsuka Y, et al. The long term effect of occlusal therapy on self administered treatment outcome of TMD: J Orofacial Pain. 1998;12:75-88.

MULTIPLE CHOICE QUESTIONS 1. Following are the inflammatory disturbances of TMJ, except: a. Traumatic arthritis b. Osteoarthritis c. Ankylosis d. Rheumatoid arthritis 2. Which one of the following is associated with extraarticular disturbances of TMJ: a. Costen syndrome b. Trotter’s syndrome c. MPDS d. Both a and c

3. Resorption of articular eminence and sclerotic underlying bone seen in: a. Osteoarthritis b. Rheumatoid arthritis c. Costen syndrome d. Ankylosis 4. Rose Waller test is done to investigate: a. Ankylosis b. Rheumatoid arthritis c. Hypermobility d. Both b and c 5. Bird face appearance is the clinical feature of : a. Unilateral ankylosis b. Hypermobility c. Bilateral ankylosis d. Both a and c

27

Chemical and Physical Injuries Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline                     Â

Linea alba Habitual cheek or lip biting Traumatic ulcer Electrical and thermal burns Anesthetic necrosis Chemical burns Smoker melanosis Drug induced discoloration of oral mucosa Cutright lesion Traumatic sequestration Methamphetamine abuse lesion Submucosal hemorrhage Oral lesion as complication to anti-neoplastic therapy (non-infectious) Cervicofacial emphysema Myospherulosis Attrition Abrasion Erosion Abfraction Dentinal sclerosis Secondary and tertiary dentin

 Resorption of teeth • External resorption • Internal resorption  Hypercementosis  Cementicles  Bruxism  Traumatic lesion due sexual habit  Oral piercing and other body modification  Fracture of teeth  Amalgam tattoo  Bismuthism  Plumbism  Mercurialism  Argyria  Arsenism  Auric stomatitis  Inflammatory fibrous hyperplasia  Inflammatory papillary hyperplasia  Epulis granulomatosum  Nodular fasciitis  Uremic stomatitis  Traumatic keratosis  Bisphosphonates associated osteonecrosis

LINEA ALBA

Etiology

Linea alba refers to the line of keratinization, found on the buccal mucosa parallel to the line of occlusion expanding to a triangular area inside each labial commis­ sure.

It occurs due to variation in dietary and oral hygiene practice, frequent frictional contact with food and teeth. Effect of smoking, food texture and other environmental irritants can cause linea alba.

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HABITUAL CHEEK OR LIP BITING It is also called Morsicatio buccarum. The Morsicatio comes for Latin word morsus meaning bite. Superficial lesions produced by frequent and repeated rubbing, sucking or chewing movements that abrade the surface of a wide area of lip or cheek mucosa without producing discrete ulceration.

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Etiology Unconscious nervous habits, uncontrolled tongue thrusting and neuromuscular disorders such as tardive dyskinesia. Occlusal discrepancies, rough tooth surface, stress and anxiety can also lead to habitual cheek biting. Figure 27.1 Increase line of keratinization seen in linea alba

Clinical Features Location: Common sites are buccal mucosa at line of occlusion and where the mucosa overlies the bone as in hard palate and gingiva. Appearance: It is white line extending horizontally from commissures to most posterior teeth (Fig. 27.1). Palate and gingiva appear whiter than the adjacent mucosa of the soft palate and alveolar gingiva, buccal and lingual sulcus. It is more prominent in people with little overjet of molars and premolars.

Histopathological Features Epithelium is keratinized under normal conditions and exhibits stratum granulosum, well developed rete-pegs and densely collagenous lamina propria that merges with periosteum. Increased thickness or hyperorthokeratosis is seen. Sometime intracellular edema of the epithelium and mild chronic inflammation of underlying connective tissue can occur.

Clinical Features Age and sex distribution: It can occur at any age with no sex predilection. It is usually occur on the buccal mucosa at the level of occlusion. Appearance: Usually there is opaque white appearance and is homogenous. In some cases, there is macerated and reddened area usually with patch of partly detached surface epithelium (Fig. 27.2). Sign and symptoms: It may have sharply delineated borders or in some cases it may be poorly outlined. In some cases, contused margins present with transient whitish tags of necrotic tissue around the ulcer. It feels rough to examiner’s fingers. Area becomes thickened, scarred and paler than surrounding mucosa. Morsicatio labiorum: When lesion of nibbling presents on labial mucosa it is called morsicatio labiorum.

Management No treatment is required for this condition. Points to Remember Buccal mucosa at line of occlusion, white line extending horizontally from commissures, keratinized, stratum granulosum, well developed rete­pegs, hyper­ orthokeratosis, sometime intracellular edema of the epithelium.

Figure 27.2 Habitual cheek biting showing lesion in

retromolar area

Chemical and Physical Injuries

Morsicatio linguarum: When lesion presents on tongue it is called morsicatio linguarum.

Histopathological Features Long established lesion may be associated with areas of keratosis and increased thickness of epithelium. There may be hyperorthokeratosis, hyperparakeratosis, and acanthosis. Depending upon degree of irritation, the underlying submucosa may show an inflammatory cell infiltrate. In some cases clusters of vacuolated cells are present in the superficial portions of the prickle cell layer.

Management Small doses of diazepam 5 to 10 mg at bed time for the management of neurological disorders. Plastic occlusal night guard to control the habit of cheek biting should be used. Points to Remember Morsicatio buccarum, opaque white appearance, sharply delineated borders, transient whitish tags, Morsicatio labiorum, Morsicatio linguarum, keratosis and increased thickness of epithelium, hyperorthokeratosis, hyper­ parakeratosis, acanthosis, diazepam, plastic occlusal night guard.

TRAUMATIC ULCER It is a frequently encountered ulcerative lesion of mouth. The common term used to denote a traumatic ulcer is decubitus ulcer, tropic ulcer, neutrons-tropic and Bednar’s ulcer.

Clinical Features Age and sex distribution: It occurs in persons of any age, with equal frequency in both the sexes. Location: It may involve any region of the mouth but is common on tongue, in mucobuccal fold, gingiva and palate. Appearance: The appearance of the traumatic ulcer varies markedly depending on the site of the injury, the nature and severity of trauma and the degree of secondary infection present. Single uncomplicated ulcer: The most common variety of traumatic ulcer is single uncomplicated ulcer which generally is of moderate size (from several millimeters to a centimeter or more in diameter), round, oval or elliptical in shape and flat or slightly depressed. Its surface consists of a serosanguinous or grayish serofibrinous exudate. It may be composed of a grayish necrotic slough which when removed, reveals a red raw tissue base. The lesion is surrounded by a narrow border of redness. There is tenderness and pain in the area of lesion and it will be helpful to identify the cause of lesion. It may persist for few days and may last for weeks. Ulcer on vermilion border may have crusted surface due to absence of saliva. Painful regional lymphadenopathy also occurs. Complicated ulcer: In still other instances, the traumatic lesions are large and irregular. These are the result of unusually severe traumatic episodes, such as a blow or a fall and are often accompanied by considerable edema, inflammation and swelling of the neighboring tissues (Fig. 27.3).

Causes Mechanical or physical: It includes biting, sharp or mal­ posed teeth or roots, sharp food, stiff tooth brush bristles, sharp margins of crown, fillings, denture, orthodontic appliances and faulty instrumentation. Chemical: It results from caustic substances such as silver nitrate, phenol, TCA, formocresol, eugenol, eucalyptus oil, phosphorus and acetylsalicylic acid. Thermal: Excessive heat in the form of hot fluid or food, on rare occasion the application of the dry ice, reverse smoking and hot instrumentation. Electrical current application to the oral tissues may result in destruction and consequent ulceration, e.g. galvanism. Others: Radiation burns, self­inflicted and iatrogenic.

Figure 27.3 Soft tissue traumatic ulcer on upper lip

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Infected ulcer: The infected ulcer is larger more irregular and more protruding than the non­infected one and often it is covered with a thick layer of necrotic slough through which purulent exudate may be observed. Eosinophilic ulceration: This type of ulceration appear similar to traumatic but underlying proliferative granulation tissue can results raised lesion. Radiation burns: Acute reaction occurs during the course of radiotherapy due to direct tissue toxicity. Ulcer resolves over several weeks following the completion of therapy. Chronic complication or late radiation reaction occurs due to change in the vascular supply, fibrosis in connective tissue and muscle and change in cellularity of tissues. Mucositis occurs when the rate of epithelial growth and repair are affected by radiation, resulting in epithelial thinning, erosion and ulceration. The first sign of mucositis may be whitish appearance of the mucosa due to hyperkeratinization and intra­epithelial edema or a red appearance due to hyperemia. Pseudomembrane formation, most likely represents ulceration with fibrinous exudate, oral debris and microbial component. Radiation has more marked effect on rapidly proliferating epithelium and therefore, mucositis involves the non­keratinized mucosa first.

Histopathological Features (Fig. 27.4) Simple ulcers are covered by fibro-purulent membrane that consists of fibrin intermixed with neutrophils. Adjacent surface epithelium may show hyperplasia with or without hyperkeratosis. Inflammatory infiltrate consist lymphocytes, neutrophils.

Vascular connective tissue deep into the ulcer can become hyperplastic which may results in surface elevation. Atypical eosinophilic ulceration shows deeper tissue replaced by highly cellular proliferation of large lymphoreticular cells.

Management Usually the simple and uncomplicated traumatic ulcer heals uneventfully in 5 to 10 days after onset and even without treatment. However in the presence of secondary infection or repetitive trauma longer healing period is required. Causative agent should eliminate. Persistent ulcer: Triamcinolone acetonide in emollient base before bed time and after meals. Chlorhexidine mouth wash or even topical local anesthetic should be given to relive acute symptoms of pain. A persistent ulcer, not responding to the foregoing regimen, should be surgically excised and the entire tissue must be sent for histopathological examination. Points to Remember Decubitus ulcer, tropic ulcer, single uncomplicated ulcer serosanginous or grayish serofibronous exudate with narrow border of redness, complicated ulcer consi­ derable edema, inflammation and swelling, infected ulcer thick layer of necrotic slough, eosinophilic ulceration, radiation burns, fibro­purulent membrane, hyperplasia with or without hyperkeratosis, highly cellular proliferation of large lymphoreticular cells.

ELECTRICAL AND THERMAL BURNS Burns cause transient non-keratotic, white appearance of the mucosa which is attributed to superficial pseudomembrane composed of coagulated tissue with an inflammatory exudate (saliva protects oral mucosa). Chronic mild burns results in keratotic white lesions while intermediate burns cause localized mucositis and severe burns coagulate the surface of the tissue and produces diffuse white lesions. If coagulation is severe, tissue can not be scraped off easily leaving raw and bleeding painful surface.

Clinical Features

Figure 27.4 Traumatic ulcer showing proliferation with

vascular connective tissue

Electrical burns can be contact type (electrical current passing through the body from the point of contact to the ground site) or arc type (saliva act as conducting medium and an electrical arc flow between the electrical source and

Chemical and Physical Injuries

mouth). Electrical burns usually occur in children younger that 4 years of age with oral commissures is commonly involved. Edema is developed which is followed by necrosis of affected area after 4 days. Bleeding may occur due to exposure of vasculature which should be closely monitored in this case. After some time adjacent teeth become non­ vital with or without necrosis of alveolar bone. There may be contracture of mouth opening after healing. Thermal burns can be cause by hot food, beverages. There is pain which last for short duration. It is seen anterior 1/3rd of tongue and palate. It may produce coagulation necrosis of superficial tissue that appears whitish. In some cases, there may be frank ulceration and stripping of mucosa. Red area is tender to painful; it may blanch on pressure and there is bleeding on manipulation. Surface layer of epithelium is desquamated. It can be manage by systemic analgesics and topical hydrocarbon in emollient base. Pizza burns: Central palatal burns, whitish gray or ulcerated lesions of the middle third of the hard palate. These also present superficial necrosis and ulceration due to combination of heat of the cheese and its adhesion to blister epithelium (Fig. 27.5). CO2 burns (snow) (dry ice): Children affected commonly. Tongue and lip are most common sites. Frost bite of lip— it is also called Popsicle panniculitis. There is persistent swelling and redness. It occurs due to prolonged contact of ice cream and other frozen confectionaries or very cold metal, glass object, with child’s lip. Epithelium becomes dry and rougher than surrounding tissues.

Management Tetanus immunization: It should be done in patient with electrical burn. Macrostomia prevention technique: Splinting is maintain for 6 to 8 months to ensure proper scar maturation. Antibiotics and corticosteroid are given for control of infection and inflammation. Points to Remember • E lectrical burn: Transient non­keratotic, white appearance of the mucosa, contact type, arc type, bleeding may occur due to exposure of vasculature, teeth become non­vital with or without necrosis of bone. • Thermal burns: Coagulation necrosis of superficial tissue, red area is tender, pizza burns, CO2 burns (snow) (dry ice), frost bite of lip, popsicle panniculitis, tetanus immunization, macrostomia prevention technique, antibiotics and corticosteroid.

ANESTHETIC NECROSIS In some cases after administration of local anesthesia there is ulceration and necrosis at the site of injection. This is cause by localized ischemia, which may occur due to faulty technique.

Clinical Features Location: Hard palate is common site for anesthetic necrosis. It appear after several days after injection. Appearance: Well circumscribed are of ulceration develop at the site of injection.

Management As such no treatment is needed as ulceration heal automatically. Points to Remember Necrosis hard palate, well circumscribed are of ulceration.

CHEMICAL BURNS Figure 27.5 Pizza burn seen in palate

Burns due to caustic chemical agents will produce coagulation necrosis of the epithelium with subsequent

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inflammation. Large number of chemical and drugs comes in contact with the oral tissue. Many time patient place the chemical like aspirins, sodium perborate to get relief from oral problems. Causes • • • • • • • • •

Aspirin and aspirin–containing compounds Tooth-ache drop burns Phenol Ethyl alcohol burns Vitamin C tablet Acid burns Ingestion Hydrogen peroxide Silver nitrate.

Figure 27.6 Sloughing of tissue in chemical burn

Causes Aspirin and aspirin: Containing compounds: it occur when it is kept in mucobuccal fold to relive tooth­ache. It is available as tablet as well as powder form. Tooth-ache drop burns: Such drops contain creosote, guiacol and phenol derivatives. Extensive mucosal necrosis with underlying bone loss has been seen in patient using phenol derivative. Phenol: It has been use as cavity sterilizing agents and cauterizing material. Ethyl alcohol burns: Topical application of ethyl alcohol solution which results in sloughing of the oral mucosa. Some of the mouth wash contain 25 percent ethyl alcohol. Vitamin C tablet: In some cases, it can causes burns of oral mucosa. Acid burns: If the rubber dam placement is ineffective then acid used to etch tooth surface may come in contact with the oral mucosa. Ingestion: Chemical burns of the oral cavity can result when the children mistakenly drink household chemical and with suicide attempts by ingestion of caustic material. Hydrogen peroxide: It is use for the treatment of periodontitis. Concentration higher than 3 percent will result in mucosal damage. Silver nitrate: It is the treatment modality of aphthous ulceration. It will also results more mucosal damage so its use should be discouraged. In some cases their use can lead to necrotic defect in the oral cavity.

Clinical Features Appearance: Irregularly shaped, white pseudomembrane covered lesion develops. The lesion is usually painful. Gentle lateral pressure causes the white material to slide away exposing an exquisitely painful central ulceration and more adherent patches of white material in the periphery (Fig. 27.6). Aspirin burns are focal with sharply delineated borders. Diffuse border may present if the burn is more extensive. In the tooth­ache drop burn there may be sloughing of oral mucosa. Cotton roll burns: It is also called cotton roll stomatitis. Sometime when cotton is used, caustic material can leak in it and it held against the mucosa for longer period of time. This will lead to injury to mucosa. In some cases mucosa can adhere to dry cotton role which will results in striping of the epithelium in the area. Caustic material injected into bone during endodontic procedures can result in bone necrosis, pain and perforation into the soft tissue.

Histopathological Features It causes coagulation necrosis of the epithelium. The upper layer shows a homogenous appearance with loss of structure and failure of nuclei to take stain. Inflammatory cell infiltrates with the underlying connective tissue can be seen. Hyperkeratosis and acanthosis of oral mucosa is present.

Chemical and Physical Injuries

Management Palliative care with a topical anesthetic or a bland coating suspension is used. These are accomplished by the use of Orabase gel or palliation may result form anesthetics effects of an antihistaminic mouth rinse in combination with kaopectate. Painful lesion heals quickly.

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Points to Remember White pseudomembrane covered lesion, painful, sharply delineated borders, cotton roll burns, cotton roll stomatitis, by bone necrosis, pain and perforation, coagulation necrosis, inflammatory cell infiltrates, hyperkeratosis, acanthosis, topical anesthetic. Figure 27.7 Smoker melanosis showing pigmentation

SMOKER MELANOSIS Oral pigmentation increase in heavy smokers. Melanins have ability to bind to noxious substance. Exposure to polycyclic amines like nicotine and benzpyrene has stimulated melanin production by melanocytes which are also bind strongly with nicotine. This may be protective mechanism of body to avoid harmful effect of tobacco smoke.

Clinical Features Age and sex distribution: It is seen in adults with female predilection. The reason for female predilection occur due to synergistic effect of female sex hormone when combined with smoking. Location: It is seen on anterior facial gingiva in cigarette smoker and commissural and buccal mucosa in case of pipe smokers. Reverse smoker show it in hard palate. Appearance: There is areas of melanin pigmentation which appear black or blue in color (Fig. 27.7).

Histopathological Features There is increase melanin pigmentation of basal cell layer of the surface epithelium (Fig. 27.8). There is also collection of incontinent melanin pigmentation in the superficial connective tissue

Management Biopsy should be done if change occur like surface elevation otherwise pigmentation cease after discontinuation of smoking.

Figure 27.8 Smoker melanosis showing melanin pigmentation

Points to Remember Nicotine and benzapyrene, anterior facial gingiva, melanin pigmentation which appear black or blue, increase melanin pigmentation of basal cell layer of the surface epithelium.

DRUG INDUCED DISCOLORATION OF ORAL MUCOSA Oral mucosal discoloration occurs due to much medication. This can occur due to phenolphthalein, minocycline, tranquilizers, antimalarial medication, estrogen, chemo­ therapeutic agents.

Textbook of Oral Pathology

CUTRIGHT LESION It is also called reactive osseous and chondromatous metaplasia. There is cartilaginous metaplasia secondary to chronic denture trauma.

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Clinical Features Sign and symptoms: There is extremely tender localized area on the alveolar ridge which can be having local enlargement. Knife edge like crest will present as susceptible for this lesion Location: It is common on posterior mandible and rarely seen in maxillary ride and anterior mandibular ridge. Figure 27.9 Pigmentation of lower lip occur due to drug

Clinical Features Appearance: There is diffuse melanosis of the skin, mucosal surface (Fig. 27.9). Sex: Females are more commonly affected due to interaction with sex hormones. Phenolphthalein pigmentation: There are numerous small, well circumscribed areas with hyperpigmentation on the skin. Minocycline pigmentation: This cause discoloration of the bone and teeth. Affected bone is dark green which is presented as blue­gray discoloration of the translucent oral mucosa. There is linear band above attached gingiva. Pigmentation due to antimalarial drug: There is blue black discoloration which is limited to hard palate. Estrogen pigmentation: It results in diffuse brown melanosis of the skin.

Management Discontinuation of drug will give reversal of the lesion. Points to Remember Phenolphthalein, minocycline, tranquilizers, phenol­ phthalein pigmentation shows small, well circum­ scribed hyperpigmentation, minocycline pigmentation shows dark green bone with blue­gray discoloration of the translucent oral mucosa. pigmentation due to antimalarial drug is blue black, estrogen pigmentation is diffuse brown melanosis.

Histopathological Feature There is mass of hypercellular periosteum which blends into areas of osseous and chondromatous tissue. Bone and cartilage show hypercellularity, pleomorphism, nuclear hyperchromatism and binuclear and multi­ nucleated cells.

Management Recontouring of thin mandibular ridge with graft material will alleviated the symptoms. Points to Remember Reactive osseous and chondromatous metaplasia, extremely tender localized area, knife edge like crest, hypercellular periosteum which blends into areas of osseous and chondromatous tissue, hypercellularity, pleomorphism, nuclear hyperchromatism, recontouring of thin mandibular ridge.

TRAUMATIC SEQUESTRATION It is also called oral ulceration with bone sequestration, spontaneous sequestration. It usually occurs in site where bone prominence is covered by thin mucosal surface. It may cause by loss of blood supply by periosteal microvasculature to the bone which lead to focal bone necrosis and sequestration.

Clinical Features and Radiological Features Location: It is seen on lingual surface of posterior mandible along the mylohyoid ridge. Exostosis is often involved with mandibular tori most commonly affected.

Chemical and Physical Injuries

Appearance: Mucosa show ulceration for long period of time. Most cases are unilateral but some cases may be bilateral. Symptoms: There is pain which is of variable intensity. Radiological features: Occlusal radiograph may show faint radiopaque mass.

Histopathological Features The sequestra consist of well organized lamellar bone. There is also loss of osteocytes for their lacunae. Bacterial colonization with peripheral resorption can also be seen.

Management Surgical removal of dead bone results in healing. Points to Remember Sequestration, spontaneous sequestration, lingual surface of posterior mandible, ulceration for long period of time, show faint radiopaque mass, well organized lamellar bone, bacterial colonization, peripheral resorption, surgical removal.

METHAMPHETAMINE ABUSE LESION Methamphetamine, i.e. meth is a CNS stimulant drug. This drug is used in case of narcolepsy and attention deficit hyperactivity. As this drug give greater energy, euphoria and more physical ability, abuse of the drug is increasing. This drug can be smoked, snorted, injected or taken orally. Effect of this drug is around 12 hours and many people used this drug more than 2 to 3 times per day. This drug has many name like chalk, crank, crystal, glass, ice, meth and speed.

Clinical Features Age: Most of the user of this drug is between the ages of 19 to 40 years.

Parasitosis (formication): This is neurosis that produces sensation of snakes and insects crawling on or under the skin. Patient will try to remove the insect by picking at the skin with fingernail resulting in traumatic injury. Speed bumps, meth sores or crank bugs: This term used for facial appearance of the patient after factitial damage due to fingernail injury. Rampant dental caries: This occur due to drug related xerostomia and poor oral hygiene of the patients.

Management Use of local anesthesia with epinephrine will lead hypertensive crisis in this patient. So oral physician should be very careful while dealing the patients. Management of rampant dental caries and xerostomia should be done accordingly. Points to Remember CNS stimulant drug, chalk, crank, crystal, glass, ice, meth and speed insomnia, aggressiveness, hyperactivity, psychological addiction, violent behavior, parasitosis (formication), sensation of snakes, speed bumps, meth sores or crank bugs, rampant dental caries.

SUBMUCOSAL HEMORRHAGE This type of hemorrhage occurs after minor trauma. Types • P etechiae: These are minute hemorrhage in the skin, mucosa or serosa • Purpura: If large area is involved it is termed as purpura • Ecchymosis: Accumulation greater than 2 cm is called ecchymosis • Hematoma: If accumulation produce mass it is termed as hematoma. It is caused by blunt trauma.

Short-term effect: It includes insomnia, aggressiveness, hyperactivity, tachycardia, xerostomia, tremor and vomit­ ing.

Clinical Features

Long-term effect: Strong psychological addiction, vio­ lent behavior, anxiety, confusion, depression, paranoia, delusion, mood change.

Appearance: These are non­blanching flat or elevated area. Color of this lesion varies from red or purple to blue to black.

There is also cardiovascular, CNS, hepatic gastrointestinal, renal and pulmonary disorders.

Location: It is most commonly seen on labial or buccal mucosa.

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Sign and symptoms: Pain may be present. Hematoma formation associated with surgical implant may present with damage to soft tissue. 664

Antral hematoma: Patient with antral hematoma may have nasal bleeding, headache, malar swelling, facial paresthesia and hyposmia.

Management No treatment is for smaller lesion, if the lesion is large surgical exploration with isolation and repair of damaged vessels. Points to Remember

discomfort and difficulty in intake of food. The surface epithelium may show ulceration or atrophy. Later changes show an inflammatory cell infiltrates in the submucosa with an attenuated spinous cell layer (Fig. 27.11). Pseudomembrane formation: After this the mucous membrane begins to break down and leads to the formation of white to yellow pseudomembrane (Fig. 27.12). Taste buds: Dose in therapeutic range can cause extensive degeneration of the histological architecture of taste buds. Patient usually notices loss of taste during 2nd or 3rd week after radiotherapy. Bitter and acid flavors are severely affected when the posterior third of the tongue is irradiated

Non­blanching flat or elevated area, pain, antral hematoma.

ORAL LESION AS COMPLICATION TO ANTI-NEOPLASTIC THERAPY (NONINFECTIOUS) There is always death of normal cells occur when patient undergoing radiation or chemotherapy. Both radiation and systemic chemotherapy can cause significant oral problems. Painful mucositis and dermatitis are the most frequent manifestation of radiation injury. Oral lesion seen in almost all patient of radiation therapy of head and neck, around 75 percent of patient getting bone marrow transplantation and chemotherapy.

Figure 27.10 Dermatitis in patient after receiving radiotherapy

Clinical Features Dermatitis: Excessive exposure will cause dermatitis. Repeated exposures have a cumulative effect (the tissue does not return to original state due to irreparable damage). There is dryness, erythema, thickening, desquamation and cracking of hands may also occur. Epilation can be cause by radiation. It is often seen in association with dermatitis. Hair loss can be permanent. Radiation dermatitis can also become chronic and is characterized by dry, smooth, shiny, atrophic, necrotic and ulcerated area (Fig. 27.10). Mucositis: It is redness and inflammation of the mucous membrane and it is commonly seen during radiation therapy as well as patient receiving chemotherapy. It occurs due to death of the cells of oral mucous membrane. By the end of therapy, the mucositis is very severe, with maximum

Figure 27.11 Mucositis in patient receiving radiotherapy

Chemical and Physical Injuries

will show fibro atrophy after radiation. Radiation can also affect developing facial bone resulting in micrognathia. Osteoradionecrosis: It is the most serious clinical complication that occurs in bone after irradiation. When the changes in a bone are so severe that bone death results, the condition is known as osteoradionecrosis. Bone infection occurs either due to radiation induced breakdown of the oral mucous membrane, mechanical damage to the weakened oral mucous membrane, through periodontal lesion or from radiation caries. Osteoradionecrosis is more common in mandible than in maxilla due to rich vascular supply of the maxilla.

Management Figure 27.12 Pseudomembrane formation in patient who are

receiving radiotherapy

and taste of salt and sweet are affected when anterior third of tongue is irradiated.

Mucositis: A low cost salt and soda has been effective in management of mucositis. Cryotherapy (placement of ice chips in the mouth 5 minutes before chemotherapy and continuous 30 minutes after chemotherapy) has been shown to reduce prevalence and severity of mucositis.

Xerostomia: The parenchymal component of salivary gland is more radiosensitive (parotid gland is more radiosensitive than submandibular or sublingual gland). Exposure to radiation leads to injury of these parenchymal cells leading to xerostomia. The extent of reduced salivary flow is dose dependent and it is zero when dose reaches 60 Gy. The mouth becomes dry, tender, and swallowing is difficult and painful since the residual saliva also loses its normal lubricating properties. Because of small amount of thick, viscous, acidic saliva such patient are prone to carries which is known as radiation carries. After months, the inflammatory response becomes more chronic and the glands demonstrate progressive fibrosis, adiposis, loss of fine vasculature and concomitant parenchymal degeneration, resulting in xerostomia.

Xerostomia: Avoid use of tobacco product as it reduces the salivary secretion. Use of salivary substitute and systemic therapy like bethanechol and anetholtrithione can be used.

Hemorrhage: It occur secondary to thrombocytopenia which develop due to bone marrow suppression. Oral petechiae and ecchymosis are present which can be seen on labial mucosa, tongue, and gingiva.

These occur due to introduction of air into subcutaneous tissue or fascial spaces. This air may spread through retropharyngeal and mediastinal areas.

Trismus: Tonic muscle spasm with or without fibrosis of muscle of mastication may lead to trismus in the patient. Developmental abnormalities: Irradiation of teeth during developmental stage retards their growth severely. Children receiving radiation therapy to the jaws may show defect in the permanent dentition such as retarded root development, dwarfed teeth or failure to form one or more teeth. Pulp

Loss of taste: Zinc sulfate supplements appear to be beneficial. Osteoradionecrosis: Therapy include antibiotics, debride­ ment, irrigation and removal of disease of bone. Points to Remember Dermatitis, mucositis, pseudomembrane formation, loss of taste, xerostomia, hemorrhage, trismus, osteoradio­ necrosis, developmental abnormalities.

CERVICOFACIAL EMPHYSEMA

Causes • C ompressed air: Compressed air from air driven handpiece can cause it • Difficult extraction: It can occur after difficult extraction • Increase intraoral pressure: This can occur due to sneezing or blowing after oral surgical procedure.

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Clinical Features 666

Sign and symptoms: There is soft tissue enlargement due to presence of air in deeper tissue. Enlargement can increase and spread due to edema and inflammation. There is also pain, facial erythema, dysphagia, and dysphonia and vision abnormalities. Pneumoparotid: This occur when air enter parotid gland duct, leading to enlargement of parotid gland. Stensen duct has fold which seals as soon as pressure increase intraorally. If there is more pressure increase this sealing does not takes place and pneumoparotid can occur. Hamman’s crunch: Cardiac auscultation will reveal crepitus synchronous with heart beat in case of mediastinal involvement

Figure 27.13 Myospherulosis showing bag of marbles

appearance

Management Broad spectrum antibiotics should be given. Points to Remember Soft tissue enlargement due to presence of air, pneumo­ parotid, Hamman’s crunch.

MYOSPHERULOSIS It occurs due to placement of topical antibiotics in petrolatum base jelly at surgical site.

Clinical Features Location: It can occur at any site in the bone or soft tissue. In bone it occurs at previous extraction site usually in the mandibular region. It can also be seen in paranasal sinus area. Appearance: There is swelling which can be associated with pain and purulent discharge. On exploration lesion is black, greasy, tarlike material.

Histopathological Features There is dense collagenous tissue which is mixed with granulomatous inflammatory response showing macro­ phage and multinucleated giant cells. Bag of marbles appearance: In the connective tissue there are cyst like space which contain brown to black staining spherules. Spherules are surrounded by outer membrane called parent body. This appearance is called bag of marbles. Spherules represent red blood cells which are altered by medication. The dark color is due to degradation of hemoglobin (Fig. 27.13).

Management Surgical removal of foreign material and associated tissue should be done. Points to Remember Swelling, pain, purulent discharge, black, greasy, tarlike, granulomatous inflammatory response, bag of marbles appearance.

ATTRITION It is the physiologic wearing away of teeth because of tooth to tooth contact, as in mastication. It develops from word attritum (action of rubbing against another surface). It plays an important physiological role as it helps to maintain an advantageous crown­root ratio and gains intercoronal space of 1 cm, which facilitates third molar eruption. Types • P hysiological attrition: Attrition which occur due to normal aging process, due to mastication. • Pathological attrition: It occurs due to certain abnormalities in occlusion, chewing pattern or due to some structural defects in teeth.

Etiology Factors for Pathological Attrition Development: Malocclusion and crowing of teeth, may lead to traumatic contact during chewing, which may lead to more tooth wear.

Chemical and Physical Injuries

Acquired: Due to extraction of teeth. Extraction causes increased occlusal load on the remaining teeth, as the chewing force for the individual remains constant. 667

Abnormal chewing habits: Parafunctional chewing habit like bruxism and chronic persistent chewing of coarse and abrasive food or other substances like tobacco. Occupation: In certain occupations, workers are exposed to an atmosphere of abrasive dust and cannot avoid it getting into mouth. Salivary factor can also play role in attrition. Structural defect: In defects like amelogenesis imperfecta and dentinogenesis imperfecta, hardness of enamel and dentin is reduced and such teeth become more prone to attrition.

Figure 27.14 Attrition of the posterior teeth in mandibular

region

Clinical Features Sex distribution: Men usually exhibit more severe attrition than women due to greater masticatory force.

compensatory growth (dentoalveolar compensation) to some degree.

Site: It may be seen in deciduous as well as permanent dentition. It occurs only on occlusal, incisal and proximal surfaces of teeth. Severe attrition is seldom seen in primary teeth, as they are not retained for any great period. Lingual cusps of maxillary teeth and buccal cusps of lower posterior teeth show most wear.

Dentoalveolar compensation: If attrition affecting the occlusal surfaces of teeth has occurred, then reduction in occlusal face height (vertical dimension of occlusion) and increase in the freeway space could be anticipated. This may be further complicated by forward posturing of mandible. It is often observed, however, that despite overall tooth surface loss, the freeway space and the resting facial height appear to remain unaltered primarily because of dentoalveolar compensation. This is important with respect to patient assessment. If restoration of worn teeth is being planned then the extent of dento­alveolar compensation would appear to determine the dentist’s strategy; defining the need to carry out measures such as crown lengthening, to ensure the same vertical dimension of occlusion and freeway space.

Appearance: The first clinical manifestation of attrition is the appearance of small polished facet on a cusp tip or ridge and slight flattening of an incisal edge. Physiological attrition begins with wearing of the incisal edge of an incisor, which is followed by the palatal cusp of maxillary molars and buccal cusp of mandibular molars. It commences at the time of contact or occlusion. Physiological tooth surface loss results in a reduction, in both vertical tooth height and horizontal tooth width. Sign and symptoms: Due to slight mobility of teeth in their socket (which is a manifestation of resiliency of periodontal ligament) similar facets occur at contact points. When the dentin gets exposed it generally becomes discolored, i.e. brown in color. There is gradual reduction in cusp height and consequent flattening of occlusal inclined plane. There is shortening of the length of dental arch, due to reduction in the mesiodistal diameter of teeth. Secondary dentin deposition occurs (Fig. 27.14). Pathological attrition: If pathologically vertical dimen­ sion of tooth has reduced then, there is the possibility of

Radiological features: Smooth wearing of incisal and occlusal surfaces of involved teeth is evident by shortened crown image (Fig. 27.15). Sclerosis of pulp chamber and canals is seen due to deposition of secondary dentin which narrows the pulp canals. Widening of periodontal ligament space and hypercementosis. In some cases there is loss of alveolar bone.

Management Treatment of patient depends upon degree of wear relative to the age of patient, etiology, symptoms and patient’s desire. Patient should be advised of any possible bruxist

Textbook of Oral Pathology

Etiology It is caused by use of abrasive dentifrices, horizontal tooth brushing, and habitual opening of bobby pins. It may also occur due to holding nails or pins between teeth, e.g. in carpenters, shoemakers or tailors. Improper use of dental floss and tooth picks.

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Clinical Types of Abrasion • • • • • Figure 27.15 Wearing of tooth surface due to attrition

habits. The provision of one of three different sorts of splints could be considered. A soft bite guard can help in breaking a bruxist habit or simply will protect the teeth during the bruxist habit. A localized occlusal interference splint is designed to break the bruxist habit and can be worn easily during the day. A stabilization splint reduces bruxism by providing an ideal occlusion: it also enables the clinician to locate and record centric relation. In case of bruxism, use of night guards may be effective in reducing attrition. Correction of malocclusion, stoppage of tobacco chewing habit and restriction of diet to non­coarse food are useful in avoiding attrition. Non­carious loss of tooth tissue may require treatment for sensitivity, esthetics, function and space loss in the vertical dimension.

Habitual abrasion Occupational abrasion Ritual abrasion Tooth brush injury Dental floss or tooth pick injury.

Clinical Types Habitual abrasion: Habitual pipe smoker may develop abrasion on the incisal edges of lower and upper anterior teeth. Improper and habitual use of tooth prick or dental floss can cause abrasion on the proximal surface of teeth. Occupational abrasion: It occurs when objects and instrument are habitually held between the teeth by people during working. Ritual abrasion: It is mainly seen in Africa. Tooth brush injury (Fig. 27.16): It usually occurs on exposed surfaces of roots of teeth. It occurs due to back and forth movement of brush with heavy pressure causing bristles to assume wedge shaped arrangement between crown and gingiva. In horizontal brushing there is

Points to Remember Occlusal, incisal and proximal surfaces of teeth, small polished facet on a cusp tip, physiological attrition, dentin gets exposed, brown in color, pathological attrition, dentoalveolar compensation, smooth wearing of incisal and occlusal surface, widening of periodontal ligament space, localized occlusal interference splint, correction of malocclusion.

ABRASION It is the pathological wearing away of tooth substance through abnormal mechanical process. It is develop from Latin word abrasum (means scrape off).

Figure 27.16 Abrasion seen in cervical area of teeth

Chemical and Physical Injuries

usually a ‘V’ shaped or wedge shaped ditch on the root at cementoenamel junction. It is limited coronally by enamel. It is more commonly seen on left side of right handed persons and vice versa. Patient develops sensitivity as dentin becomes exposed. The angle formed in the depth of the lesion as well as that of enamel edge is a sharp one. Cervical lesions caused purely by abrasion have sharply defined margins and a smooth, hard surface. The lesion may become more rounded and shallow, if there is an element of erosion present. Exposed dentin appears highly polished. Exposure of dentinal tubules and consequent irritation of the odontoblastic processes stimulates secondary dentin formation which is sufficient to protect the pulp from clinical exposure. Dental floss or tooth prick injury: Cervical portion of proximal surfaces, just above the gingival margin, is affected. Grooves on distal surface are deeper than on mesial surface. Demastication: When tooth wear accelerated by chewing an abrasive substance between opposing teeth and exhibits features of attrition as well as abrasion is term as demastication. Radiological features: It will show radiolucency in cervical area of teeth (Fig. 27.17).

Management Examination and modification of teeth cleaning habits will be indicated. Elimination of causative agent should be carried out. Restoration, for esthetics and to prevent further tooth wear.

Points to Remember Abrasive dentifrices, horizontal tooth brushing, habitual abrasion, occupational abrasion, ritual abrasion, tooth brush injury, ‘V’ shaped or ‘wedge’, dental floss or tooth pick injury, demastication, radiolucency in cervical area of teeth.

EROSION It is the loss of tooth substance by chemical process that does not involve known bacterial action. This word is develop from erosum (corrode). Dissolution of mineralized tooth structure occurs upon contact with acids. Erosion is a chemical process in which the tooth surface is removed in the absence of plaque. Types • I ntrinsic: Erosion that occur due to intrinsic cause, e.g. gastroesophageal reflux, vomiting. • Extrinsic: Erosion occurring from extrinsic sources, e.g., acidic beverages, citrus fruits.

Etiology Local acidosis in periodontal tissue from damage due to traumatogenic occlusion. Chronic vomiting: Complete loss of enamel on lingual surfaces of teeth through dissolution by gastric hydrochloric acid. Vomiting can also occur in alcoholics, peptic ulcer, gastritis, pregnancy and drug side effect. Acidic foods and beverages: Large quantities of highly acidic carbonated beverages or lemon juice can produce erosion. Most of the fruits and fruits juices have a low pH and can cause erosion. Frequent consumption of carbonated drinks, which are acidic in nature, may result in erosion of teeth. Anorexia nervosa: It induces chronic vomiting often after bouts of uncontrolled eating that is interspersed between periods of starvation, because of inner rejection of food. Occupational: Workers involving in manufacturing of lead batteries, sanitary cleaners or soft drinks can develop erosion.

Figure 27.17 Radiolucency in cervical area due to abrasion

Risk factors: Following factors are assume as risk factor for erosion. They are citrus fruits intake, soft drink more than 6 per weeks, bruxism habits, vomiting and symptoms of gastroesophageal reflux disease.

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Clinical Features

ABFRACTION

Location: It occurs most frequently on labial and buccal surfaces of teeth; sometimes may occur on proximal surfaces of teeth. Usually it is confined to gingival thirds of labial surface of anterior teeth. Erosion may involve several teeth of dentition.

It is also called stress lesion. It is derived from Latin ab (away), fractio (breaking).

From extrinsic source, it causes erosion on labial and buccal surface and from intrinsic source; it causes erosion on lingual or palatal source. Appearance: It is usually a smooth lesion which exhibits no chalkiness. Loss of enamel often causes hypersensitivity in teeth and may also trigger secondary dentin formation. Loss of tooth substance is manifested by shallow, broad, smooth, highly polished and scooped out depression on enamel surface adjacent to cementoenamel junction. There may be pink spot on tooth which is attributable to the reduced thickness of enamel and dentin making the pink hue of pulp visible. Perimolysis: Erosion from dental exposure to gastric secretion is called perimolysis. Erosive lesions cause cupping in dentine. When erosion affects the palatal surfaces of upper maxillary teeth, there is often a central area of exposed dentine surrounded by a border of unaffected enamel. In most cases, it results in little more than a loss of normal enamel contour, but in severe cases, dentine or pulp may be damaged.

Management

Causes and Mechanism It has been suggested that the stress lesion or abfraction is a consequence of eccentric forces on the natural dentition. The theory propounds tooth fatigue, flexure and deformation via biomechanical loading of the tooth structure, primarily at the cervical region. Cusp flexure causes stress at the cervical fulcrum and results in loss of the overlying tooth structure.

Clinical Features Location: It usually affects buccal/labial cervical areas of teeth. Commonly affects single teeth with excursive interferences or eccentric occlusal loads. Appearance: It appears as deep, narrow V­shaped notch. The lesion is typically wedge shaped with sharp line angles, but occlusal abfraction may present as circular invaginations (Fig. 27.18). The magnitude of tooth tissue loss depends on the size, duration, direction, frequency and location of the forces. Other factors, such as erosion and abrasion may play a significant role in tooth tissue loss, but the initial force is of biomechanical loading. Points to Remember Stress lesion, excursive interferences or eccentric occlusal loads, deep, narrow V­shaped notch.

In a patient where loss of tooth surface is essentially caused by erosive fluids, advise regarding diet and use of sugar free chewing gum. Prescription of a fluoride mouthwash is certainly indicated here. Modifying brushing habits and restoration of the defect, usually by glass inomer cement should be done. For systemic management of vomiting, patient should be referred to the physician. Points to Remember Smooth lesion which exhibits no chalkiness, shallow, broad, smooth, highly polished and scooped out depression, pink spot, perimolysis, cupping, fluoride mouthwash, glass inomer cement.

Figure 27.18 Abfraction seen at cervical area

Chemical and Physical Injuries

DENTINAL SCLEROSIS It is also called transparent dentin. It is a regressive alternation in tooth substance that is characterized by calcification of the dentinal tubules.

Etiology It is caused by injury to dentin by caries or abrasion, normal aging process, abrasion or erosion of tooth.

Mechanism The mechanism of dentinal sclerosis or deposition of calcium salts is not understood, although most likely source of calcium salt is the fluid or dental lymph within tubules. Increased mineralization of the tooth decreases the conduction of odontoblastic process.

Clinical Features Appearance: If it is examined under transmitted light, a translucent zone is observed; which is due to the differences between the refractive indices of the sclerotic or calcified dentinal tubules and the adjacent normal tubules. It shows advancing carious process. Sclerotic dentin is harder than adjacent normal dentin. It is more highly calcified than normal dentin.

SECONDARY AND TERTIARY DENTIN It is also called irregular dentin. It is the dentin which is formed after the deposition of primary dentin. It serves to prevent involvement or exposure of the pulp cavity. It can be physiological (occur due to age) and reparative (occur due to injury).

Etiology Physiological: Normal aging process, with advancing age deposition of secondary dentin leads to smaller pulp chamber and canal. Reparative: Dental caries, abrasion, attrition, erosion, tooth fracture, cavity preparation, chemical, thermal or mechanical insult.

Terminology Primary dentin: Dentin formed before completion of the crown is called primary dentin. Secondary dentin: Odontoblast that formed primary dentin remains functional and produce secondary dentin.

Early widespread formation of secondary dentin seen in progeria. Calcific metamorphosis: Significant traumatic injury can lead to early obliteration of the pulp chamber and canal is called calcific metamorphosis. Physiological secondary dentin: In functioning teeth deposition begins in the coronal portions of tooth proceeds toward apical area. Tertiary dentin: Localized new dentin laid in areas of focal injury. This is called tertiary dentin. Reactionary dentin: If the stimulus is mild to moderate tertiary dentin produce by surviving odontoblasts and is termed as reactionary dentin. Reparative dentin: If the stimulus is severe and lead to death of primary odontoblast new generation of odontoblast may arise from undifferentiated cell within pulp. This is called reparative dentin. Interface dentin: The initial layer reparative dentin is a tubular and this is called interface dentin or fibro dentin. Dead tract: When primary odontoblast die their dentinal tubules are filled with degenerated odontoblastic process and this is called dead tract.

Clinical Features Location: Anterior teeth exhibit higher incidence of secondary dentin formation than molar teeth. Sign and symptoms: Decrease in tooth sensitivity occurs when secondary dentin formation is extensive. It forms an additional insulating layer of calcified tissue between the pulp and the particular pathological process that initiate the dentinal response. Teeth affected by calcific metamorphosis shows yellow discoloration of teeth (Fig. 27.19). Radiological features: There is accelerated closure of the pulp chamber and canal when compared to adjacent or contralateral teeth.

Histopathological Features (Fig. 27.20) It is well demarcated than primary dentin by deeply staining resting lines. It exhibits fewer tubules. Adventitious secondary dentin is composed of few tubules that may be more tortuous in course. Sometimes, secondary dentin is formed at a rapid rate and odontoblasts may get entrapped producing

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Figure 27.19 Ground section showing tertiary dentin

structure resembling bone. Such calcified tissue is called osteodentin. Tertiary dentin is localized to pulpal end of odontoblastic process. It is localized exclusively adjacent to irritated zone. The tubules are very irregular, tortuous and reduced in number.

Management Root canal treatment should be done.

Figure 27.20 Reparative dentin showing well demarcated resting line with few tubular structure (Courtesy: Dr Sangamesh Halawar, Reader, Oral Pathology, CDCRI, Rajnandgao, Chhattisgarh

Etiology • • • • • • •

Resorption associated with periapical infection Reimplanted teeth Tumors and cysts Excessive mechanical and occlusal forces Impacted teeth Overhanged root canal filling material Idiopathic.

Points to Remember

Etiology

Irregular dentin, decrease in tooth sensitivity occurs, yellow discoloration of teeth, accelerated closure of the pulp chamber, fewer tubules, osteodentin. irregular, tortuous and reduced in number.

Resorption associated with periapical infection: periapical granuloma (arising due to pulpal infection or trauma), causes subsequent resorption of root apex. On the radiograph, it appears as slight raggedness or blunting of the root apex in the early stages.

RESORPTION OF TEETH It is chronic progressive damage or loss of tooth structure due to the action of cells called odontoclasts. It can be physiological as in case of root resorption of deciduous teeth or pathological, which occurs in permanent teeth. Pathological resorption may be external or internal.

External Resorption It is lytic process occurring in the cementum or cementum and dentin of the roots of teeth. It can be resorption occurring at the apex or along the lateral surface of the root or it can be external internal resorption.

Reimplanted teeth: It may result in severe resorption of root. Tooth root is resorbed and replaced by bone which produces ankylosis. Many implanted teeth exhibit complex resorption of root and are gradually exfoliated. Tumors and cysts: Resorption due to tumors and cysts appears to be essentially by pressure phenomenon. In most cases, tissue is present between the tumor and the tooth and it is from this tissue that cells, chiefly osteoclasts arise and initiated root resorption. Cysts like apical periodontal cyst may exert such pressure on the apex of tooth the intervening connective tissue may in turn get stimulated for osteoclasts formation and thus, resorption begins. The

Chemical and Physical Injuries

apex may be lost leaving a flat or scalloped surface at the distal end of the root. Excessive mechanical and occlusal forces: Usually, due to the force that is applied during orthodontic treatment, the patient exhibits multiple areas of root resorption, irrespective of the manner of treatment. Pressure from occlusal forces results in destruction, primarily of bone, then small lacunae often appear on the surface of cementum and ultimately, it extends into the dentin. Impacted teeth: Teeth which are completely impacted or embedded in the bone, occasionally, will undergo resorption of the crown and root. Impacted tooth also may cause resorption of roots of adjacent teeth without itself getting resorbed. This is commonly seen in case of horizontally or mesioangularly impacted mandibular 3rd molars impinging on roots of 2nd molar. Overhanged root canal filling material: In such cases not only the apex get resorbed but more or less, sides of the root are affected. In some cases, all or most of the root disappears and the regenerating bone eventually embraces the root canal filling intimately, so that it appears as if the crown of the tooth is held in position by the root filling. Idiopathic: In this case, burrowing type of external resorption can occur which is usually seen in relation with single or multiple erupted teeth.

Clinical Features Symptoms: The affected tooth is usually asymptomatic. Location: The most frequent site for external resorption is upper incisors, upper and lower bicuspids. Sign: When the root is completely resorbed, the tooth may become mobile. If root resorption is followed by ankylosis then the tooth is immobile, in infraocclusion and with high percussion sound. Invasive cervical resorption: This type of resorption occur in cervical area extend to involve large area of dentin through small opening. Radiographic features: It will show resorption of teeth (Fig. 27.21).

Histopathological Features It is the result of osteoclastic activity on the root surface of the involved tooth.

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Figure 27.21 External resorption of the root of molar

Microscopically it varies from small area of cementum resorption replaced by connective tissue or repaired by new cementum; too large areas of resorption are replaced by osseous tissues and scooped out areas of resorption are replaced by inflammatory or neoplastic tissue.

Management Apicectomy is treatment of choice. If the area is broad and on lateral surface, curettage and filling of resorbed area should be carried out. Points to Remember Lytic process occurring in the cementum, asymptomatic, upper incisors, root resorbed, tooth mobile, invasive cervical resorption, radiographic resorption of teeth, osteoclastic activity, root surface of the involved scooped areas of are resorption, apicectomy.

Internal Resorption It begins certainly in the tooth. It is a condition starting in the pulp, in which the pulp chamber or the root canals or both, of the tooth expand by resorption of the surrounding dentin. It is an idiopathic, slow or fast progressive resorptive process occurring in the dentin or pulp chamber or root canals.

Etiology It can be caused by inflammatory hyperplasia of the pulp, direct and indirect pulp capping, pulpotomy, enamel invagination, acute trauma to teeth and pulp polyp.

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Mechanism 674

Precipitating factor → vascular changes in pulp → inflammation and production of granulation tissue → metaplasia of embryonic connective tissue and macrophages → odontoclast like giant multinucleated cells → resorption of internal wall of pulp. Types • I nternal inflammatory resorption: It occurs due to intense inflammatory reaction within the pulp tissue. • Internal replacement or metaplastic resorption: It occurs due to absence of any inflammatory reaction within the pulp.

Clinical Features Appearance: Pink hued area on the crown of tooth, which represents hyperplastic pulp tissue fitting the resorbed area and showing through the remaining overlying tooth substance. Location: It may affect any tooth in primary and secondary dentitions, with prevalence in permanent dentition. It is more common in central incisor, lateral incisors, premolar and canine and 3rd molar according decreasing frequency. Multiple tooth involvement may be there. Age and sex distribution: It occurs during 4th and 5th decades of life and is more common in males. Symptoms: It is asymptomatic. Pink tooth mummery: The roots of teeth with internal resorption may manifest a reddish area, called the ‘pink spot’ (Fig. 27.22). This reddish area represents granulation tissue showing through the resorbed area of crown.

Figure 27.22 Pink tooth due to internal resorption

Sign: When the lesion is located in the crown of teeth, it may expand to such an extent that the crown shows dark shadow due to necrosis of the pulp tissue. If the resorption is in the root, it may weaken the tooth and result in fracture of the tooth. It may perforate the crown with hemorrhagic tissue projecting from the perforation and result in infectious pulpitis. Radiological features: There is enlargement of canal which is balloon like dilation of canal (Fig. 27.23).

Histopathological Features There is resorption of the inner or pulpal surface of dentin and proliferation of the pulp tissue, filling the defect. It may show occasional osteoclasts or odontoclasts hence it is called odontoclastoma. Pulp tissue usually exhibits chronic inflammatory reaction. Alternating periods of resorption and repair are manifested as irregular lacunae like areas in dentin that are partially or completely filled with irregular dentin or osteodentin. When the root surface is perforated, it is very difficult to determine whether the lesion began externally or internally. Multinucleated giant cells and odontoclasts are also present.

Management Extirpation of pulp with routine endodontic treatment or retrograde filling stops the internal resorption process. Extraction of the tooth, if perforation occurs should be carried out.

Figure 27.23 Internal resorption of incisor

Chemical and Physical Injuries

Points to Remember Pink hued area, central incisor, reddish area, called the pink spot, enlargement of canal osteoclasts or odontoclasts, odontoclastoma, pulp tissue, chronic inflammatory reaction, osteodentin, multinucleated giant cells and odontoclasts, extirpation of pulp.

as cementoblasts and their direct precursors in this area are lost. Instead, it occurs at some distance above the apex as the inflammatory reaction acts as stimulation for the cementoblasts.

HYPERCEMENTOSIS

Tooth repair: Occlusal trauma results in mild root resorption and it is then repaired by cementum formation. Root fracture is also repaired on occasion by deposition of cementum between the root fragments as well as in their periphery.

It is also called cementum hyperplasia or exostosis of root. It is characterized by deposition of excessive amount of cementum on the root surface. New tissue formation is in direct contact with the cementum of roots of teeth.

Osteitis deformans or Paget disease of bone: It is a generalized skeletal disease characterized by excessive amount of cementum formation on roots of teeth and by apparent disappearance of lamina dura of teeth.

Types

Others: Hyperpituitarism, cleidocranial dysostosis can also cause hypercementosis.

• Localized • Generalized.

Clinical Features Age: It is predominately seen in adults.

Types Localized: Hypercementosis of single tooth. It is usually a reactive, inflammation dependent phenomenon seen on singular teeth and usually in relation to periapical osteitis or due to loss of occluding antagonistic teeth. Generalized: Generalized hypercementosis affecting many (all) teeth, but which is seldom recognized as such, occurs with increasing age, i.e. as an age dependent factor. It is also be seen as a sign accompanying specific diseases, as for instance, Paget’s disease of bone. Etiology • • • • • •

Location: Premolar teeth are often affected and often teeth are bilaterally affected and symmetrical in distribution. The permanent teeth are affected more commonly than deciduous teeth. In multirooted teeth, one or more roots are involved. Sign and symptoms: There is no increase or decrease in tooth sensitivity, unless periapical infection is present. Teeth are vital and not sensitive to percussion. There may be difficulty in extraction of teeth. In some cases hypercementosis is so extensive that it causes fusion of two or more adjacent teeth (Fig. 27.24). Roots appear larger in diameter than normal and present rounded apices.

Accelerated elongation of a tooth Inflammation of the root Tooth repair Osteitis deformans or Paget disease of bone Hyperpituitarism Cleidocranial dysostosis.

Etiology Accelerated elongation of a tooth: It occurs due to loss of antagonist. It occurs due to inherent tendency of the periodontium to maintain normal width of the periodontal ligament. Inflammation of the root: It does not occur at the apex of the root directly adjacent to the area of inflammation,

Figure 27.24 Fusion of root due to hypercementosis

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the cementum surface. Cementicles may be composed of fibrillar or afibrillar cementum, or a mixture of the two. They are usually acellular. 676

Types • F ree cementicles: They are not attached to cementum. • Attached or sessile cementicles: They are attached to the cementum surface. • Embedded cementicles: They are incorporated into the cementum layer.

Etiology and Formation Figure 27.25 Hypercementosis

Spike formation of cementum: It is characterized by occurrence of small spikes or outgrowth of cementum on root surface. It occurs in cases of excessive occlusal trauma probably due to deposition of irregular cementum in focal group of periodontal ligament fibers.

Histopathological Features (Fig. 27.25) Excessive amount of secondary or cellular cementum is found to be deposited directly, over typically thin layer of primary acellular cementum. Secondary cementum is called osteocementum due to its cellular nature and its resemblance to bone. Cementum typically arranges in concentric layers around the root and frequently shows numerous resting lines indicated by deeply staining hematoxyphlic lines parallel to the root surface.

Management Treatment of the primary cause should be done.

They represent the areas of dystrophic calcification. Calcification of cell rest of Malassez occurs as a result of degenerative changes. These bodies enlarge by further deposition of calcium salts in the adjacent surrounding connective tissue. The continued proliferation of connective tissue may lead to eventual union of cementicles. It may result from focal calcification of connective tissue between Sharpey’s bundles with no apparent central nidus. This occurs as small round or ovoid globules of calcium salt. Small cementicles tears or fragments of bone detached from alveolar plate, if lying free in the periodontal ligament may resemble cementicles. Cementicles appear to arise through calcification of thromboses capillaries in periodontal ligament.

Clinical Features It may impart rough globular outline to the root surface; size is small, ranging from 0.2 to 0.3 in diameter.

Histopathological Features Cementicles appears in the periodontal ligament space (Fig. 27.26). Size of the cementicle is usually varies.

Points to Remember

Points to Remember

Cementum hyperplasia, exostosis of root, premolar teeth, teeth are vital, fusion of two or more adjacent teeth, spike formation of cementum, secondary or cellular cementum, osteocementum, cementum typically arranges in concentric layers.

Small, spherical particles of cementum, rough globular outline, cementicles appears in the periodontal ligament space, continued proliferation of connective tissue, cementicles.

CEMENTICLES Cementicles are small, spherical particles of cementum that may lie free in the periodontal ligament adjacent to

BRUXISM The word bruxism is taken from the Greek word brychein: gnashing of teeth. Although the term bruxism is not generally known to lay people, it is shorter and more

Chemical and Physical Injuries

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Figure 27.26 Cementicles

convenient than teeth clenching or grinding. Bruxism can perhaps be best defined as the involuntary, unconscious and excessive grinding, tapping, or clenching of teeth. When it occurs during sleep, it may be best called sleep or nocturnal bruxism. A few people, on the other hand, brux while they are awake, in which case the condition may be called wakeful or diurnal bruxism. All forms of bruxism entail forceful contact between the biting surfaces of the upper and lower teeth. It is also called night grinding or bruxomania. It is a habitual grinding of the teeth, either during sleep or as an unconscious habit during waking hours. It is term used both for clenching habit during which pressure is exerted on the teeth and periodontium by the actual grinding or clamping of the teeth and, also to repeated tapping of the teeth.

Etiology Local: Mild occlusal disturbances, unconscious attempt by the patient to established a greater number of teeth in contact or to counteract a local irritating situation. Systemic factors: Gastrointestinal disturbances, subclini­ cal nutritional deficiency and allergy or endocrine distur­ bances have been reported to be the causative factors. Psychological factors: Emotional tension in which patient is unable to express his emotion due to fear, rage, rejection and it becomes hidden in subconscious and later expressed by variety of way like by grinding the teeth. Occupational: Like in cases of watchmaker, persons who chew gum, tobacco or objects such as toothpicks or pencils.

Figure 27.27 Bruxism causing severe attrition of teeth

Clinical Features In grinding and tapping, this is contact which involves movements of the lower jaw and unpleasant sounds which can often awaken housemates. Clenching (or clamping) on the other hand, involves inaudible, sustained, forceful teeth contact unaccompanied by mandibular movements. Teeth: Chronic bruxism may lead to sensitive, worn­out, decayed, fractured, loose or missing teeth. Grinding or clenching breaks down the enamel; sometimes in long­ term bruxers, reducing the teeth to stumps (Fig. 27.27). Instead of a white enamel cover, one often sees the more yellowish and softer dentin. The absence of enamel makes it easier for the bacteria to penetrate the softer part of the teeth and produce cavities. As the teeth wear out, they become shorter. As a result, when the mouth is closed, the upper and lower jaws are nearer than they used to be and so are the nose and chin. The skin now may bag below the eyes and curl around the lips, causing the lips to seemingly disappear. The chin recedes and the person looks comparatively old. Facial muscles: Bruxism involves excessive muscle use leading to a build­up or enlargement (hypertrophy) of facial muscles, especially those of the jaws (where the masseter muscle—the muscle that raises the lower jaw and enables closing the jaws—is located). In long­term bruxers, this build­up may lead to a characteristic square­ jaw appearance. Some patients resort to removing part of the masseter muscle by surgery or injections of toxic

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materials to reduce muscle size and thus partially regain their former, more aesthetically pleasing look.

tension, patients may develop techniques for reducing that tension and hence, bruxism.

Salivary glands: Another example of this spiral involves the occasional inflammation and blockage of some salivary glands. In this case, the masseter muscle becomes disproportionately overdeveloped and blocks the opening of the nearby parotid glands. They, thus interfere with the flow of saliva into the mouth, causing the saliva to accumulate in the glands. This in turn may lead to periodical swelling, pain, inflammation and abnormal dryness of mouth.

Exercise: Quinn suggested isokinetic and stretching exercises of the mandible. Such exercises may or may not help alleviate bruxism, but perhaps may be used to complement other approaches. However, it seems unlikely that they could ever be used as the sole therapeutic approach. Evidence that this approach is effective are non­ existent.

TMJ: Bruxism may also damage the temporomandibular joints. First few signs of temporomandibular joint disorders are TMJ discomfort or pain, soreness of jaws and muscles, clicking or popping sounds when opening the jaws or while chewing and difficulties in opening the mouth fully. Malocclusion: Malocclusion or bad bite is more common among bruxers than in the general population. Bruxism may often involve more pressure on one side of the mouth than on the other, thereby causing malocclusion. As the teeth wear out, the distance between the upper and lower jaw decreases and overclosure may develop. Effect on periodontium: There may be loss of integrity of the periodontal structures resulting in loosening or drifting of the teeth and even gingival recession occurs.

Management Psychotherapy: The belief that bruxism is traceable to stress and other emotional and psychological factors give rise to a variety of psychotherapeutic approaches. For instance, listening to progressive relaxation or autosuggestion tapes just before going to sleep may foster calmness and self­confidence. Wakeful EMG feedback: Another psychological approach to stress reduction resorts to instrumentation. During bruxing, the relevant muscles are active and this increased activity or tension can in turn be measured with an electromyograph (EMG: electro ­ electric; myo ­ muscle; graph ­ record). During treatment sessions at home or the laboratory, the patient sits or reclines comfortably. One or more pairs of recording electrodes are then attached to the surface of the skin in close contact to appropriate muscles (e.g. masseter muscles). These electrodes transmit information about the level of muscle activity to a computer monitor. The patient is instructed to consciously lower that level below a threshold line (also visible on the screen). Gradually, by becoming alert to the presence of muscle

Drugs: Both, the stress and brain malfunction etiological theories give at times, rise to the use of anti­anxiety agents, muscle relaxant and other drugs. Most authorities however feels that at best, drugs in use now are of limited value in the treatment of great majority of chronic bruxers and that they often involve moreover untoward side effects. Evidence that this approach is effective: are non­existent. Equilibration therapy: Some people believe that bruxism is traceable to malocclusion (bad bite). They therefore suggest eliminating this cause through orthodontic adjustment. Splints: By far, the most common treatment regime for bruxism relies on the time­honored procedure of splints like nightguards, biteguards, occlusal splints, biteplates, removable appliances or interocclusal orthopedic appli­ ances and use of manufactured customized appliances. Removable splints are worn at night to guide the movement so that periodontal damage is minimal Points to Remember Grinding and tapping, clenching (or clamping), sensitive, worn­out, decayed, fractured, loose or missing teeth, produce cavities, enlargement (hypertrophy) of facial muscles, inflammation and blockage of some salivary glands, temporomandibular joint disorders, malocclusion, loosening or drifting of the teeth, psycho­ therapy, wakeful EMG feedback, exercise, equilibration therapy, splints.

TRAUMATIC LESION DUE SEXUAL HABIT Orogenital practice is common nowaday inspite it is illegal in many jurisdictions.

Clinical Features Appearance: There is submucosal palatal hemorrhage secondary to felatio. It appears as erythema, petechiae,

Chemical and Physical Injuries

purpura, and ecchymosis of soft palate. The erythrocytic extravasation is results from musculature of the soft palate elevating and tensing against an environment of negative pressure. Oral lesion also occurs due to cunnilingus, resulting in horizontal ulceration of the lingual frenum. As the tongue is thrust forward the taut frenum rubs or rakes across the incisal edges of the mandibular central incisor. Linear fibrous dysplasia also seen in people who repeatedly perform the act of cunnilingus.

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Histopathological Features There is subepithelial accumulation of red blood cells which may separate the surface epithelial from underlying connective tissue. Patchy degeneration of epithelial basal cell layer can occur.

Management No treatment is required. Points to Remember Orogenital practice, felatio, erythema, petechiae, purpura, and ecchymosis of soft palate, horizontal ulceration of the lingual frenum, cunnilingum, linear fibrous dysplasia, subepithelial accumulation of red blood cells.

ORAL PIERCING AND OTHER BODY MODIFICATION Body piercing is ancient practice with association with religious, cultural, superstitious belief. The selected site is pierced with needle and then jewellery of choice is threaded through it, jewellery most often used is gold, silver and stainless steel.

Clinical and Radiological Features

Figure 27.28 Oral piercing in tongue

Acute complication: It includes pain, profuse bleeding, and infection like Ludwig angina, lingual nerve damage, speech impediment and allergy to the jewellery. Chronic complication: Mucosal and gingival trauma, fractured teeth, aspiration of jewellery, gingival recession, hyper salivation and tissue hyperplasia around the posts. Forked tongue: It is also called split tongue, bifid tongue. In this anterior one third of tongue is split down to middle. It is done by pulling fishing line through pierced hole and tightening a loop over the period of 3 weeks. It can also be done with the help of laser or surgical approach for quick results. Complication of this may occur and it includes prolonged hemorrhage, permanent neurovascular damage. Talisman (magical charm): Also called susuk (charm needles or charm pin). Susuk is placed by magician to enhance or preserve beauty, relived pain, bring success to business and provide protection against harm. Susuk is made up of silver or gold of 0.5 mm in diameter and around 1 cm in length.

Age and sex distribution: It is more common in adolescents and young adults with female predilection.

Management

Location: It is more common seen on tongue, lips buccal mucosa, and uvula.

Patient should be encouraged to remove the jewellery. If there is inflammation local debridement, antibiotics therapy and chlorhexidine mouth wash.

Barbell: This is done in case of tongue consisting of metal rod with ball that screw onto each end (Fig. 27.28). Labret: This is seen on lip and consists of ring or rod with flat end attached to the mucosal side and round ball of cutaneous surface.

Points to Remember Barbell, labret, pain, profuse bleeding, and infection, mucosal and gingival trauma, fractured teeth, forked tongue, susuk, talisman (magical charm) pain.

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Figure 27.29 Fracture of crown of tooth central incisor

FRACTURE OF TEETH

Figure 27.30 Root fracture

Dental Crown Fracture (Fig. 27.29)

gingival attachment on the lingual surface. It frequently involves pulp. There is pain during mastication. Tooth is sensitive to occlusal force.

Anterior teeth are commonly involved. It may be caused by fall, accident and blows from foreign bodies.

Vertical Root Fracture

Cracks: It can be seen in indirect light (directing the beam along the long axis of tooth). Uncomplicated fracture: It does not involve dentin and is usually found on mesial or distal corner of maxillary central incisors. Dentin involvement is identified by contrast of color between it and peripheral layer of enamel. Exposed dentin is very sensitive to chemical, thermal and mechanical stimulation. Complicated fractures: There is bleeding from exposed pulp or atleast drop of blood oozes from the pinpoint exposure. Exposed pulp will be sensitive to most forms of stimulation.

Dental Root Fracture (Fig. 27.30) It is common with maxillary central incisors. Coronal fragment is displaced lingually and is slightly extruded. If fracture line is close to the apex then tooth will be more stable. If only movement of crown is detected, root fracture is likely. There is temporary loss of sensitivity. It returns to normal within 6 months.

Crown/Root Fracture Such fracture is likely to be intra and extra alveolar. They are a result of direct trauma. They have labial margin in the gingival third and course obliquely to exist below the

It is also called cracked tooth syndrome. It runs length wise from crown towards apex of tooth. It occurs in endodontically treated tooth as there is weakening of tooth in such cases. It may be caused by traumatic occlusion. It is usually seen in posterior teeth in adults, especially in mandibular molars. Dull pain of long duration which may vary from non existent to mild. It may have periodontal lesions resembling chronic lesion. History of repeated failure of endodontic treatment.

Perforation of the Root The root canal is sometimes penetrated during operative procedures and injury may extend to cause a perforation of the root. The usual site of it is at the apex and the side of the root, but the floor of the pulp chamber and even the side of the crown; near the neck of the tooth may be perforated. In some cases, the shadow of root canal can be seen approaching the side of the root and this can be the evidence of a perforation.

Histopathological Features of Tooth Fracture The clot between root fragments is organized and this connective tissue is subsequently the site of new cementum or bone formation. There is always some resorption of the ends of the fragment but these resorption lacunae ultimately are repaired.

Chemical and Physical Injuries

Points to Remember • D ental crown fracture: Cracks, uncomplicated fracture, complicated fractures • Dental root fracture: Coronal fragment is displaced lingually, temporary loss of sensitivity • Crown/root fracture: Direct trauma, frequently involves pulp • Vertical root fracture: Cracked tooth syndrome, posterior teeth, dull pain • Perforation of the root: During operative procedures • Histopathological: New cementum or bone formation, resorption of the ends of the fragment.

AMALGAM TATTOO

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Figure 27.31 Blue black pigmentation seen due to amalgam

tattoo

Causes It may be condensed in the abraded gingiva during routine amalgam restorative work. It may enter the mucosa lacerated by rotary instruments during removal of old amalgam fillings or crown and bridge preparations of teeth with large amalgam restorations. Broken pieces may be introduced into the socket or beneath the periosteum during extraction of the teeth. Particles may enter the surgical cut during root canal treatment with retrograde amalgam filling. Other cause of exogenous pigmentation are pencil implantation, fragment of broken carborundum disks, dental burs and charcoal denitrifies have also have similar appearing lesion.

Clinical Features Location: The most common sites are gingiva and alveolar mucosa with mandibular region being affected more commonly than maxillary region. Age and sex distribution: It can occur at any age but it is rarely seen below the 12 years as amalgam restorations are not used before the age of 12 years. Females are affected more commonly than males in ratio of 1.8:1. Appearance: It is described as a flat macule or sometimes slightly raised lesion with margins being well defined or diffuse in other. Pigmentation is blue black in color. It may gradually increase in size (Fig. 27.31). Radiological features: Fragment are seen radiopaque.

Histopathological Features Amalgam presents as discrete fine dark growth and irregular solid fragments. Dark granules arranged mainly along collagen bundles and around blood vessels, nerve sheath, elastic fibers and acini or minor salivary glands. Dark granules are present intracellularly within macrophage multi-nucleated giant cell, fibroblasts. Large fragment are surrounded by dense fibrous connective tissue with mild inflammation.

Management Treatment is not necessary. However, if required, excision is done. Points to Remember Gingiva and alveolar mucosa with mandibular region, flat macule or sometimes slightly raised lesion, blue black, discrete fine dark growth and irregular solid fragments, multi­nucleated giant cell, fibrous connective tissue with mild inflammation.

BISMUTHISM Causes Medicinal use of bismuth containing preparation can cause bismuthism. Many proprietary drugs contain bismuth

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salt and bismuth containing pastes may result in bismuth pigmentation. 682

when small piece of white paper is inserted in the gingival sulcus, the presence of pigmented area is verified.

Mechanisms

Points to Remember

This pigment is produced by the action of hydrogen sulfide on the bismuth compound. The hydrogen sulfide is formed through bacterial degradation of organic material of food retention.

Hydrogen sulfide, Bismuth grippe, Bismuth line, metallic taste, annoying gingivostomatitis, blue black’ bismuth line gingival papillae, irregular black collection of pigment, paper test.

Clinical Features Bismuth grippe: Vague gastrointestinal tract disturbances, nausea, bloody diarrhea, bismuth grippe and jaundice can occur. Bismuth line: Sometimes in the long bone, white bands of increase density appear in the ends of the diaphyses immediately adjacent to the epiphyseal lines. This is called bismuth line.

Oral Manifestations Sign and symptoms: Patients often complain of a metallic taste with burning sensation in the oral cavity and annoying gingivostomatitis with symptoms similar to Acute necrotizing ulcerative gingivitis (ANUG). Large, extremely painful, shallow ulcerations are seen at times on the cheek mucosa in molar region. Regional lymphadenopathy may be present. Tongue is frequently enlarged and sore. Blue black bismuth line appears to be well demarcated to eye on gingival papillae. Blue black bismuth sulfide granules formed by action of H2S produced by action of bacteria on organic material remaining in areas of poor oral hygiene.

Histopathological Features The granules of sulfide are seen in the tissue section as small irregular black collection of pigment, sometimes perivascular in location. The material may be present in endothelial cells or in mononuclear phagocytes in the tissue, but usually in intercellular tissue.

Diagnosis An ulcerative gingivostomatitis accompanied by discrete blue black pigmentation of interdental papilla and marginal gingiva in a patient receiving oral or anal administration of bismuth compounds. Paper test: It will indicate whether the pigmentation is actually in gingival tissue. If the pigmentation persists,

PLUMBISM It occurs due to lead poisoning.

Causes It is caused by lead in the paints, glazes, cooking vessels, batteries, ointment and containers. Moonshine an illicit alcoholic beverage distilled in car radiators has been shown to cause acute lead poisoning. Use of tetraethyl lead, an antiknock compound in gasoline, has introduced a new source of lead. Excessive absorption of the lead from automobile exhaust and dust and dirt derived from house paint is known to affect a large number of poor children living in urban areas. Acute exposure can occur in foundries, smelters, battery plants, munitions and garages.

Mechanism of Action Absorption of lead from alimentary tract, lungs and gut → modulated by vitamin D and calcium status of the individual → lead is taken up by circulating erythrocytes and bound to reactive sulfhydryl group of proteins → from the circulation, lead is transferred to all the soft tissues and in high concentration it will inhibit metabolic pathways → in the red cells, lead inhibits enzymes associated with hemoglobin synthesis → hence abnormal activity of the enzymes occur.

Clinical Features Nervous system: Lead has high affinity for cells in central as well as peripheral systems. In acute poisoning, demyelination and axon degeneration occurs. Lead encephalopathy, cerebral palsy, mental retardation, seizures, wrist or foot drop and fatigue can occur. Gastrointestinal tract: There may be serious gastro­ intestinal disturbances like nausea, constipation, vomiting, and colic.

Chemical and Physical Injuries

Neurological value: Abnormal neurological value for the both peripheral and central nervous system.

Management Lead can be removed from body by using a chelating agent such as calcium edetate (EDTA) or penicillamine. Points to Remember

Figure 27.32 Gray black color pigmentation due to lead

Bone: When incorporated in the bone it can interfere with cellular metabolism and changes the rate of bone resorption and apposition.

Oral Manifestations Oral tissues are exposed to lead through direct contact with ingested lead and through secretion of lead in the saliva. Symptoms: There is a metallic taste which is accompanied by excessive salivation and dysphagia. Burtonian line: When exposure to lead is very high and oral hygiene is very poor, a line known as ‘burtonian line’ is seen which is gray black in color and is present along the gingival margin. Lead line is more diffuse than bismuth line (Fig. 27.32). Sign: There is pallor of lip; poor muscle tone and the face appears ashen in color because of associated anemia. There is bilateral parotid gland hypertrophy.

Laboratory Finding Blood changes: These are those of hemolytic anemia with basophilic stippling of the RBCs. Lead level: In children, the level of exposure can be gained by measurement of tooth lead level and in adults the hair lead concentration is commonly used as an indicator. Enzymes level: Measurement of aminolevulinic acid and aminolevulinic acid dehydratase and synthetase level in blood are decreased in lead poisoning as these enzymes are associated with hemoglobin synthesis and lead inhibits hemoglobin synthesis.

Moonshine, demyelination and axon degeneration, lead encephalopathy, cerebral palsy, gastrointestinal disturbances, interfere with cellular metabolism, metallic taste, Burtonian line gray black in color, pallor of lip, aminolevulinic acid and aminolevulinic acid dehydratase and synthetase level in blood are decreased, EDTA) or penicillamine.

MERCURIALISM It may be chronic or acute. It is also called pink disease, swift’s disease, dermato-polyneuritis, and acrodynia. It is an uncommon disease caused due to a mercurial toxicity reaction, either actual mercury poisoning or, more likely, an idiosyncrasy to the metal. Exposure of young children to minute amounts of mercury is responsible for a condition. The exact etiology of it is unknown but it is thought that it may occur due to mercury toxicity.

Causes As a result of occupational contact, drug overdose, suicide attempt or self medication with mercurial compounds. Mercury hazards exist in paints containing mercurial salts such as phenylmercuric propionate. Prolonged administration of mercurial diuretics can also result in mercurialism. Frequent use of night cream containing inorganic salts may produce distinctive discoloration. Mercurial fumes which are produced industrially also result in bone changes in the jaws, if inhaled in quantity. Improper use of dental amalgam alloy can also cause mercurialism.

Clinical Features It occurs most frequently in young infants before the age of 2 years although children can occasionally affected up to age of five years or six years. Gastrointestinal symptoms: Intestinal colic and diarrhea. There is also pharyngitis, dysphagia, nausea, abdominal pain.

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Nervous symptoms: Long continued exposure to mercury vapor can result in permanent neurological changes. Headache, insomnia, tremors of fingers and tongue and mental depression. Renal symptoms: Severe intoxication and it can be the cause of death. Hands, feet, nose and cheeks assume pink color. The nails are shed at the same time with teeth lost prematurely and alopecia is also present. The children will frequently tear their hair out in patches. The skin over the affected area peels frequently during the course of the disease. The patient also have maculopapular rash which is extremely pruritic. Raw beef appearance: The skin of hands, feet, nose, ears and cheek becomes clammy red or pink and has a cold clammy feeling. The appearance is described as resembling raw beef. Severe sweating, extreme irritability, photophobia with lacrimation, insomnia, muscular weakness, tachycardia and hypertension

Oral Manifestations Symptoms: There is marked increase in inflow of ropy viscid saliva, hot mouth, itching sensation and metallic taste are experience. Patient will exhibit profuse salivation and often much dribbling. Mastication is difficult due to pain. The gingiva becomes extremely sensitive or painful and it may exhibit ulceration. Oral mucosal ulceration occurs and spreads to the palate, throat and pharynx. Salivary glands and lymph nodes may be swollen and tongue is enlarged, painful and ulcerated. Tongue tremors may be present. Faint diffuse grayish pigmentation of alveolar mucosa occurs. The gums are of a deeper hue than normal. Lips are dry, cracked and swollen. Sound teeth may exfoliate and one or more teeth may be found on bed in the morning as patients awake. The reason for it is that there is marked periostitis with loosening of the teeth which may lead to exfoliation of teeth. Many time children extract his own teeth with the help of his finger. There may be loosening and premature shedding of teeth often occurs. The loss of teeth sometimes followed by necrosis of bone and there may be sequestrum formation. Bruxism is a common finding.

Management Bed rest and suitable dietary regimen should be adjusted for renal damage. Atropine or belladonna can be prescribed to lessen the salivary flow. Due discontinuation of possible exposure to mercury and administration of BAL (British anti­lewisite) and dimercaprol has been proven successful in most cases unless the disease is of long duration. Points to Remember Pink disease, swift’s disease, intestinal colic and diarrhea, neurological changes. Headache, insomnia, tremors of fingers, renal symptoms, pink color hands, feet, nose, raw beef appearance, dribbling, oral mucosal ulceration, diffuse grayish pigmentation, alveolar mucosa, sound teeth may exfoliate, administration of BAL (British anti­ lewisite).

ARGYRIA It is also called argyrosis which occurs due to chronic exposure to silver compound.

Causes It is cause from local and systemic absorption of silver compounds. It may result from the use of silver containing nasal drops or sprays or silver­arsphenamine injection used to treat syphilis. Chewing pieces of photographic films over an extended period can also result in argyria. Localized argyria can develop following long continued use of silver preparation.

Clinical Features Acute silver intoxication: It can produce coma, pleural edema, hemolysis and bone marrow failure. Appearance: Skin is slate gray, violet or cyanotic and in marked cases, there is even suggestion of metallic luster. The exposed body surfaces including the nail beds are deeply discolored. Pigmentation is distributed diffusely throughout the gingival and mucosal tissue. Oral finding: In oral cavity slate blue silver line present along the gingival margin. In some cases diffuse blue black discoloration.

Chemical and Physical Injuries

Management

Causes

Source of contact should be eliminated.

Gold is useful for the treatment of Rh arthritis, lupus erythematous and leprosy.

Points to Remember

Clinical Features

Argyrosis, silver­ arsphenamine, coma, pleural edema, hemolysis, slate gray, violet or cyanotic, pigmentation, slate blue silver line present along the gingival margin diffuse blue black discoloration.

Dermatitis is the most common complaint which is preceded by pruritus. It will results in alopecia and loss of nails. Purpura and malignant neutropenia can also occur.

ARSENISM

Chrysiasis: Slate blue or purple discoloration of skin can occur. This is called chrysiasis.

It occurs due to arsenic poisoning. Arsenic treatment is useful in case of asthma and skin disorder such as psoriasis.

Causes Industrial exposure or intentional use or due to therapeutic consumption can lead to arsenic poisoning.

Clinical Features Symptoms: Patient may be having chronic gastritis, and colitis. Arsenic keratosis: Keratosis of palms of the hand and soles of feet. Hyperpigmentation: Prolonged exposure to arsenic results in diffuse macular pigmentation or ulceration of the skin.

Oral mucositis: It is the most common complaint of the patient who is receiving gold therapy. There is vesiculation and ulcerations of the oral mucosa. This is common on lateral border of tongue, palate and pharynx. Symptoms: Metallic test often precede the oral mucositis.

Management Discontinuation of gold therapy and alkaline mouth washes should be prescribed. Points to Remember Rh arthritis, lupus erythematous and leprosy, dermatitis, purpura, malignant neutropenia, chrysiasis, slate blue or purple discoloration, oral mucositis, metallic test, alkaline mouth washes.

Oral lesion: Oral tissues are extremely painful, become intensely inflamed and severe gingivitis may develop. Excessive salivation can be done. Tissues are deep red in color. Local contact with arsenic trioxide often produces ulceration.

It is also called denture injury tumor, denture epulis, and epulis fissuratum.

Management

Causes

Surface anesthetic ointment or rinses such as lidocaine or dyclonine solution.

Ill fitting denture is the most common cause for this condition. It occurs due to overextended denture flanges. Other factors which are responsible are ragged margins of teeth, overhanging restorations, sharp spicules of bone, badly fitting clasps and chronic biting of cheek and lips.

Points to Remember Industrial exposure, chronic gastritis, and colitis, arsenic keratosis, hyperpigmentation, painful, become intensely inflamed severe gingivitis, lidocaine or dyclonine solution.

AURIC STOMATITIS It is poisoning occur due to gold which has been used in medicinal treatment.

INFLAMMATORY FIBROUS HYPERPLASIA

Clinical Features Age and predilection: It occur in adult with female predilection. Location: The anterior portion the jaw is more commonly affected that posterior portion. It may occur either in maxilla or mandible.

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Figure 27.33 Inflammatory fibrous hyperplasia due to denture

Figure 27.34 Inflammatory fibrous hyperplasia

Appearance: There is development of elongated rolls of tissue in the mucolabial or mucobuccal fold area, into which the denture flanges conveniently fit. The proliferation of tissue is usually slow.

infiltration in the subepithelial connective tissue. There is also mucopolysaccharide keratin dystrophy, also referred as plasma pooling. Osseous or chondromatous metaplasia: In some case there is formation of osteoid or chondroid which is reactive phenomenon due to chronic irritation of ill fitting denture.

There may be small nodular or polypoid overgrowth of fibrous tissue due to gingival irritation. When the lesions occur in buccal sulcus due to denture flanges, it is called epulis fissuratum. In it, there is concomitant overgrowth of surrounding fibrous tissues with a groove in it (Fig. 27.33) . Leaf like denture fibroma: It is seen on hard palate beneath maxillary denture. This flattened pink mass that is attached to palate by narrow stalk. The edge of lesion is serrated and resembles a leaf. It is also called fibroepithelial polyps. The excess folds of tissue are usually inflamed clinically, although there may be irritation or even ulceration in the base of the fold, into which the denture flange fits. The lesion is firm on palpation.

Histopathological Features (Fig. 27.34) The hyperplastic mass of tissue is composed of an excessive bulk of fibrous connective tissue covered by a layer of stratified squamous epithelium, which may be of normal thickness or show acanthosis. Pseudoepithelioumatous hyperplasia, hyperortho­ keratosis or parakeratosis are often found. The connective tissue is composed chiefly of coarse bundles of collagen fibers with few fibroblasts or blood vessels, unless there is an active inflammatory reaction. There is moderate degree of chronic inflammatory

Management It should be treated with excisional biopsy. Elimination of irritation should be done. Points to Remember Denture injury tumor, overextended denture flanges, elongated rolls of tissue in the mucolabial, mucobuccal fold area, epulis fissuratum, leaf like denture fibroma, excessive bulk of fibrous connective tissue, pseudoepi­ theliomatous hyperplasia, chronic inflammatory infil­ tration, osseous or chondromatous metaplasia.

INFLAMMATORY PAPILLARY HYPERPLASIA It is also called palatal papillomatosis and palatal epithelial hyperplasia. It occurs in 3 to 4 percent of dentures wearers.

Causes Frictional irritation produced by loose fitting dentures on palatal tissues. It occurs in patients who sleep with their dentures on. Full dentures in which relief areas or suction chambers are cut in palatal seating surface appear to be the strongest stimuli for the lesion.

Chemical and Physical Injuries

It is much common in acrylic dentures than in those with metallic dentures. It is more common in patients with poor oral hygiene. In some cases, irritation due to amalgam filling may produce these lesions.

Clinical Features Age and sex distribution: It can arise at any age in adults and has no definite sex predilection. Location: It occurs exclusively on palate beneath the complete or partial denture. It occurs predominately in edentulous patients and the site of lesion corresponds to the denture base. In rare cases, cheek may be involved. Whole palatal mucosa under the denture may be covered with numerous small polypoid masses. Appearance: The lesion presents as numerous closely arranged, red, edematous papillary projections often involving nearly all of the hard palate and imparting to it a ‘warty appearance’. In some cases, it is swollen and papillary projection resembles the surface of ‘overripe berry’. In some cases it produces a ‘cobblestone’ appearance. Sign and symptoms: Lesions are friable, often bleed with minimum trauma and may be covered with thin whitish exudate. The tissue exhibits varying degrees of inflammation, but seldom there is ulceration. These are seldom over 0.3 cm in diameter. The lesion may extend onto the alveolar mucosa. The individual papillae are seldom over a millimeter or two in diameter. When complicated by Candida albicans lesion appears as red to scarlet, soft and bleeds easily in the inflammatory or granulomatous stage (Fig. 27.35).

Histopathological Features It has got exophytic nature. There is varying degree of branching and polypoid proliferation on the epithelial surface. It shows numerous small vertical projections, each composed of parakeratotic or sometimes orthokeratotic stratified squamous epithelium and a central core of connective tissue. Pseudoepitheliomatous hyperplasia is seen.

Management Remove the denture at night to provide rest to the tissue. Conditioning liner should be applied. In cases of fibrosis, surgical removal and curettage, electrosurgery and cryosurgery should be done. In case with superimposed candidal infection, topical application of antifungal agents should be used. Most commonly used is nystatin ointment. Points to Remember Palatal papillomatosis, frictional irritation, palate beneath the complete or partial denture, warty appear­ ance, overripe berry, cobblestone, friable, often bleed with minimum trauma, branching and polypoid proliferation on the epithelial surface, parakeratotic or sometimes orthokeratotic stratified squamous, pseudoe­ pitheliomatous hyperplasia.

EPULIS GRANULOMATOSUM It is reactive hyperplasia that develops within a tooth socket after the extraction or exfoliation of tooth. It is caused by sharp spicules of bone in socket.

Clinical Features Age: It can occur at any age and becomes apparent within 2 weeks after the loss of a tooth. Appearance: It is exuberant dark red granulation tissue extruding from a tooth socket. It is painless growth. The enlargement is soft, hemorrhagic with an erythematous to white, smooth surface.

Management Figure 27.35 Palatal papillary hyperplasia

It is done to remove the granulation tissue and smoothing the socket borders is indicated. It should be done.

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Exuberant dark red granulation, tissue extruding from a tooth socket.

There is frequently patchy chronic inflammatory infiltration, consisting of lymphocytes and occasional plasma cells and macrophages. Fibroblasts tend to be larger than their normal size. The nuclei are plump with prominent nucleoli.

NODULAR FASCIITIS

Management

Points to Remember 688

It is also called pseudosarcomatous fasciitis. It is a proliferative fibroblastic lesion and presents as a tumor like mass with infiltrative properties. It appears to be an inflammatory reactive phenomenon.

Clinical Features Location: Half of the cases are reported on upper limb. Intraorally, the affected sites are subcutaneous tissues overlying the mandible, zygoma, parotid sheath and oral mucosa. Age: It can occur at any age, but 3rd to 5th decades are common. Appearance: It appears as a small lump, which may be painful. The lesion often enlarges rapidly, but only to maximum size of 4 cm, where it remains stationary or regresses.

Histopathological Features There is proliferation of fibroblast (Fig. 27.36) in a rather haphazard manner in a vascular myxoid matrix which is rich in acid mucopolysaccharide. It results in a loose textured feathery appearance.

Figure 27.36 Nodular fasciitis showing proliferation of

fibroblast

Local excision will yield excellent result. Points to Remember Pseudosarcomatous fasciitis, inflammatory reactive phenomenon small lump, painful, proliferation of fibro­ blast, textured feathery appearance, chronic inflamma­ tory infiltration.

UREMIC STOMATITIS Non­keratotic white lesions caused due to elevated creatinine or blood urea nitrogen. It has been suggested to be consequence of strongly alkaline saliva due to ammonia formation from retained urea secreted in the saliva. This will damage oral mucosa.

Clinical Features Age and sex distribution: It is common in young and middle aged adults with no sex predilection. Location: It is seen on tongue, buccal mucosa (Fig. 27.37), and floor of mouth.

Figure 27.37 Lesion of uremic stomatitis

Chemical and Physical Injuries

Appearance: There is extensive pseudomembranous white lesion. There is ammonical odor to breath. In some cases, there is appearance of ulcer occurs. Oral ulceration varies in size and is irregular in shape and usually shallow.

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Histopathological Features The epithelium is lacking, have been replaced by an eosinophilic coagulum with an adjacent inflammatory cell infiltrates.

Management Oral ulcer, if painful may be treated by prescribing a palliative oral rinse such as an antihistamine oral suspension with kaopectate. Points to Remember Elevated creatinine or blood urea nitrogen, pseudo­ membranous white lesion, ammonical odor to breath, epithelium is lacking, adjacent inflammatory cell infiltrates, oral suspension with kaopectate.

TRAUMATIC KERATOSIS

Figure 27.38 Traumatic keratosis

Points to Remember Thickened whitish oral mucosa, local irritants, glassblower’s white patch, hyperkeratosis, parakeratosis and acanthosis.

It refer to isolated area of thickened whitish oral mucosa that is clearly related to identifiable local irritant and resolves following elimination of irritant.

BISPHOSPHONATES ASSOCIATED OSTEONECROSIS

Etiology

These drugs are used in the treatment of malignancy like multiple myeloma, metastatic breast carcinoma and bone disease like Paget disease. These drugs inhibits osteoclast and interfere with angiogenesis. They also the vascular endothelial factor. This are used to slow down osseous involvement There are two generation of bisphosphonates, i.e. first generation with low potency and are readily metabolized by osteoclast and second generation which are more potent and are designated as aminobisphosphonates.

Local irritants like ill fitting denture, sharp clasp and rough edges of restoration. Heavy cigarettes smoking.

Clinical Features (Fig. 27.38) Most common sites are lip and buccal mucosa. There is isolated thickened whitish area. Glassblower’s white patch: It is variant of traumatic keratosis affecting the cheek and lips, which occur in glass factory.

Histopathological Features There is varying degree of hyperkeratosis, parakeratosis and acanthosis.

Management Upon removal of the offending agent, the lesion should resolve within 2 weeks. Biopsies should be performed on lesions that do not heal to rule out a dysplastic lesion.

Pathogenesis Normal bone undergoing resorption and reapposition = osteoclast maintain normal bone by repairing microfracture and resorbs areas of normal bone containing foci of osteocytes = release of cytokines and growth factors which induce formation of active bone forming osteoblasts = bisphosphonates treated bone induce osteoclastic apoptosis = reduction in recruiting additional osteoclast = stimulation of osteoblasts to release osteoclast inhibiting factors.

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Clinical and Radiological Features 690

Location: It is more common in mandible as compared to maxilla. Sign: Affected bone show area of necrosis after minor trauma to bony protuberance like tori and exostosis. Radiographic features: There is increase radiopacity before clinical evidence of frank necrosis. Panoramic radiograph show increase radiodensity of crestal portion of alveolar ridge. In severe cases there is moth eaten appearance with ill defined radiolucency. In some cases sequestra formation can be seen.

Histopathological Features There are irregular trabeculae of pagetoid bone with enlarged and irregular osteoclast which demonstrate numerous intracytoplasmic vacuoles. There is also peripheral resorption with bacterial colonization.

Management Elimination of all dental infection and improve dental health to avoid invasive procedure which may lead to osteonecrosis. Manipulation of bone should be avoided. Endodontic treatment should be done in place of extraction of teeth. In symptomatic patient systemic antibiotics like penicillin with or without metronidiazole, ciprofloxacin, erythromycin and chlorhexidine mouth wash should be given. Points to Remember Drugs inhibits osteoclast and interfere with angiogenesis, bone show area of necrosis, increase radiopacity, frank necrosis, crestal portion of alveolar ridge, pagetoid bone with enlarged and irregular osteoclast, numerous intracytoplasmic vacuoles, penicillin metronidiazole, ciprofloxacin, erythromycin.

BIBLIOGRAPHY 1. Adukauskiene D, Vizgirdaite V, Mazeikiene S. Electrical injuries. Medicina (Kaunas). 2007;43(3):259­66. Review. 2. Ahlberg J, Lobbezoo F, Ahlberg K, Manfredini D, Hublin C, Sinisalo J, Könönen M, Savolainen A. Self­reported bruxism mirrors anxiety and stress in adults. Med Oral Patol Oral Cir Bucal. 2012. 3. Al­Zarea BK. Tooth surface loss and associated risk factors in northern saudi arabia. ISRN Dent. 2012;2012:161565. Epub 2012.

4. Bamise CT, Esan TA, Ajayi JO, Olagundoye O, Oziegbe EO.Dental erosion in a road­side battery technician: case report and a review of the literature. Oral Health Prev Dent. 2008;6(3):249­53. 5. Banoczy J. Oral leukoplakia and other white lesions of the oral mucosa related to dermatological disorders. J Cutan Pathol. 1983;10:238­56. 6. Beck­Mannagetta J, Hutarew G. Pigmented lesions of the oral mucosa. Hautarzt. 2012;63(9):704­9. 7. Beumer J 3rd, Curtis T, Harrison RE. Radiation therapy of the oral cavity: sequelae and management, part 1. Head Neck Surg. 1979;1(4):301­12. 8. Bolewska J, Holmstrup P, Møller­Madsen B, Kenrad B, Danscher G. Amalgam­associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam. J Oral Pathol Med. 1990;19:39­42. 9. Bring support to bruxism sufferers. Br Dent J. 2012;213(5):248. doi: 10.1038/sj.bdj.2012.814. 10. Burton H. On a remarkable effect on the human gums, produced by the absorption of lead. Med Chir Trans. 1840;23:63­79. 11. Carmona IT, Tejeiro JC, Dios PD, Leston JS, Ferreiro MC, Posse JL. Morsicatio linguarum versus oral hairy leukoplakia. Dermatology. 2000;201:281­2. 12. Damm DD, Fantasia JE. Bilateral white lesions of buccal mucosa: morsicatio buccarum. Gen Dent. 2006;54:442­4. 13. DeSesso JM. Teratogen update: inorganic arsenic. Teratology. 2001;64(3):170­3. 14. Donly KJ, Nowak AJ. Oral electrical burns: etiology, manifestations, and treatment. Gen Dent. 1988;36(2):103­7. 15. Dubach P, Caversaccio M. Images in clinical medicine. Amalgam tattoo. N Engl J Med. 2011;364(15):e29. 16. D’Acunto C, Piccolo V, Neri I, Misciali C, Raone B, Russo T, Patrizi A. Pigmented lesion of the floor of oral cavity: what is your diagnosis? Amalgam tattoo (AT). Clin Exp Dermatol. 2012;37(2):205­6. 17. El­Said KF, El­Ghamry AM, Mahdy NH, El­Bestawy NA. Chronic occupational exposure to lead and its impact on oral health. J Egypt Public Health Assoc. 2008;83(5­6):451­66. 18. Ethunandan M, Shanahan D, Patel M. Iatrogenic mandibular fractures following removal of impacted third molars: an analysis of 130 cases. Br Dent J. 2012;212(4):179­84. 19. Farren ST, Sadoff RS, Penna KJ. Sodium hypochlorite chemical burn. Case report. N Y State Dent J. 2008;74(1): 61­2. 20. Flaitz CM, Khan F, Hicks MJ. Oral and maxillofacial pathology. Case of the month. Chemical mucosal burn with purpura. Tex Dent J. 2012;129(1):106­7, 118­21. 21. Fogh­Andersen P, Sørensen B. Electric oral burns in Danish children with special reference to prevention. Scand J Plast Reconstr Surg. 1984;18(1):107­10.

Chemical and Physical Injuries 22. Gilvetti C, Porter SR, Fedele S. Traumatic chemical oral ulceration: a case report and review of the literature. Br Dent J. 2010;208(7):297­300. 23. Glass LF, Maize JC. Morsicatio buccarum et labiorum (excessive cheek and lip biting). Am J Dermatopathol. 1991;13:271­4. 24. Hjorting­Hansen E, Holst E. Morsicatio mucosae oris and suctio mucosae oris: an analysis of oral mucosal changes due to biting and sucking habits. Scand J Dent Res. 1970;78:492­9. 25. Jańczuk Z, Banach Local argyrosis of oral mucosa or amalgam tattoo. A problem in diagnosis and treatment. J. Adv Med Sci. 2006;51 Suppl 1:62­5 26. John Meyer. Radiation Injury: Advances in Management and Prevention. Karger Publishers. 1999 ­ 170 pages. 27. Jones TA, Parmar SC. Oral mucosal ulceration due to ferrous sulphate tablets: report of a case. Dent Update. 2006;33(10):632­3. 28. Kenny DJ, Barrett EJ, Casas MJ. Avulsions and intrusions: the controversial displacement injuries. J Can Dent Assoc. 2003;69(5):308­13. 29. Keown AJ, Lee JJ, Bush MB. Fracture behavior of human molars. J Mater Sci Mater Med. 2012. 30. Kluger N, Francès P. Bluish pigmentation of the gingiva in a homeless patient: a quiz. Burton’s line revealing chronic lead poisoning (plumbism). Acta Derm Venereol. 2012; 92(1):109­10. 31. Kocsard E, Schwarz L, Stephen BS, D’Abrera VS. Morsicatio buccarum. Br J Dermatol. 1962;74:454­7. 32. Landrigan PJ, Todd AC. Lead poisoning. West J Med 1994;161:153­9. 33. Linebaugh ML, Koka S. Oral electrical burns: etiology, histopathology, and prosthodontic treatment. J Prosthodont. 1993;2(2):136­41. 34. Lobbezoo F, Van Der Zaag J, Naeije M. Bruxism: its multiple causes and its effects on dental implants ­ an updated review. J Oral Rehabil. 2006;33(4):293­300. Review. 35. Lockhart PB. Gingival pigmentation as the sole presenting sign of chronic lead poisoning in a mentally retarded adult. Oral Surg Oral Med Oral Pathol. 1981;52:143­9. 36. Malhotra N, Kundabala M, Acharaya S. A review of root fractures: diagnosis, treatment and prognosis. Dent Update. 2011;38(9):615­6, 619­20, 623­4. 37. Manfredini D, Visscher CM, Guarda­Nardini L, Lobbezoo F. Occlusal factors are not related to self­reported bruxism. J Orofac Pain. 2012;26(3):163­7. 38. Marinho DR, Burmann TG, Kwitko S. Labial salivary gland transplantation for severe dry eye due to chemical burns and Stevens­Johnson syndrome. Ophthal Plast Reconstr Surg. 2010;26(3):182­4. 39. McAuliffe P. Types of bruxism. J Ir Dent Assoc. 2012;58(3):138­41.

40. McCullough MJ, Tyas MJ. Local adverse effects of amalgam restorations. Int Dent J. 2008;58(1):3­9. 41. Melis M, Abou­Atme YS. Prevalence of bruxism awareness in a Sardinian population. Cranio. 2003;21(2):144­51. 42. Merchant F, Carpenter T. Blue­gray discoloration of the skin. Am Fam Physician. 2011;84(7):821­2. 43. Miyayama T, Arai Y, Hirano S. [Environmental exposure to silver and its health effects]. Nihon Eiseigaku Zasshi. 2012;67(3):383­9. 44. Noffke CE, Chabikuli NJ, Nzima N.Impaired tooth eruption: a review. SADJ. 2005;60(10):422, 424­5. 45. Obermayer ME. Cheekbiting (Morsicatio buccarum). Arch Dermatol. 1964;90:185­90. 46. Ozcelik O, Haytac MC, Akkaya M. Iatrogenic trauma to oral tissues. J Periodontol. 2005;76(10):1793­7. 47. Ozmeriç N. Localized alveolar bone necrosis following the use of an arsenical paste: a case report. Int Endod J. 2002;35(3):295­99. 48. Panagiotis Kafas, Christos Stavrianos. Thermal burn of palate caused by microwave heated cheese­pie: A case report. Cases Journal. 2008,1:191. 49. Pearce JM. Burton’s line in lead poisoning. Eur Neurol. 2007;57(2):118­9. Epub 2006. 50. Prendergast WD. The classification of the symptoms of lead poisoning. BMJ. 1910;1:1164­6. 51. Review article. Are bruxism and the bite causally related? [No authors listed] Br Dent J. 2012;213(5):227. 52. Ribeiro AC, Simonato LE, Santos­Silva AR, de Moraes NP, Soubhia AM. Formalin burn. Br Dent J. 2010;209(1):4. 53. Ricart J, Martin JM. Acquired amalgam tattoo. A possible diagnostic pitfall. J Cosmet Dermatol. 2011;10(1):70­1. 54. Riva MA, Lafranconi A, D’Orso MI, Cesana G. Lead poisoning: historical aspects of a paradigmatic “occupational and environmental disease”. Saf Health Work. 2012;3(1):11­ 6. Epub 2012. 55. Rogers SN, Vale JA. Oral manifestations of poisoning. Br Dent J. 1993;174(4):141­3. 56. Rostami AM, Brooks JK. Intraoral chemical burn from use of 3 percent hydrogen peroxide. Gen Dent. 2011;59(6): 504­6. 57. Rumayor Piña A, Martínez Martínez M, Toral Rizo VH, Ajudarte Lopes M, Paes de Almeida O. Cutaneous amalgam tattoo in a dental professional: an unreported occupational argyria. Br J Dermatol. 2012. 58. Sarwar AF, Ahmad SA, Khan MH, Sayed MH, Kabir MH. Swelling of vallate papillae of the tongue following arsenic exposure. Bangladesh Med Res Counc Bull. 2010;36(1): 1­3. 59. Sewerin I. A clinical and epidemiologic study morsicatio buccarumlabiorum. Scand J Dent Res. 1971;79:73­80.

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60. Shetty K. Hydrogen peroxide burn of the oral mucosa. Ann Pharmacother. 2006;40(2):351. Epub 2006 Jan 31. 61. Shimoyama T, Kaneko T, Nasu D, Suzuki T, Horie N. A case of an electrical burn in the oral cavity of an adult. J Oral Sci. 1999;41(3):127­8. 62. Shinozaki F, Hayatsu Y, Komatsu Y, Furuta I, Kohama G. Electrical burns of lip and mouth in children. Report of 2 cases. Int J Oral Surg. 1984;13(1):25­30. 63. Spieker RD. Submerged permanent teeth: literature review and case report. Gen Dent. 2001;49(1):64­8; quiz 69­70. 64. Staines KS, Wray D. Amalgam­tattoo­associated oral lichenoid lesion. Contact Dermatitis. 2007;56(4):240­1. 65. Tamir S, Davidovich Z, Attal P, Eliashar R. Peppermint oil chemical burn. Otolaryngol Head Neck Surg. 2005;133(5):801­2. 66. Thomas SS. Electrical burns of the mouth: still searching for an answer. Burns. 1996;22(2):137­40. 67. Tran HT, Anandasabapathy N, Soldano AC. Amalgam tattoo. Dermatol Online J. 2008;14(5):19. 68. Tóth V, Marschalkó M, Hársing J, Kárpáti S. Grayish discoloration of the face—argyria]. Orv Hetil. 2009;150(32): 1503­7. Review.

69. Valencia R, Garcia J, Espinosa R, Saadia M, Valencia E. 14 year follow­up for a severe electrical burn to mouth and lip: case report. J Clin Pediatr Dent. 2010;35(2):137­44. 70. van Wyk CW, Staz J, Farman AG. The chewing lesion of the cheeks and lips: its features and prevalence among a selected group of adolescents. J Dent. 1977;5:193­9. 71. Varkey P, Tan NC, Chen HC. Corrosive injury of oral cavity—a rare presentation. J Plast Reconstr Aesthet Surg. 2006;59(10):1110­3. 72. Venclíková Z, Benada O, Joska L. Monitoring of selenium in oral cavity argyria ­ a clinical and microscopic study. Neuro Endocrinol Lett. 2011;32(3):286­91. 73. Vera­Sirera B, Risueño­Mata P, Ricart­Vayá JM, Baquero Ruíz de la Hermosa C, Vera­Sempere F. Clinicopathological and immunohistochemical study of oral amalgam pigmentation. Acta Otorrinolaringol Esp. 2012. 74. Yanturali S, Yaka E, Ersoy G. Chemical injury to the tongue following contact with sodium hydroxide drain cleaner. Vet Hum Toxicol. 2004;46(6):319­21. 75. Yeroshalmi F, Sidoti EJ Jr, Adamo AK, Lieberman BL, Badner VM. Oral electrical burns in children­a model of multidisciplinary care. J Burn Care Res. 2011;32(2):e25­30.

MULTIPLE CHOICE QUESTIONS 1. Well developed rete pegs and densely collagenous lamina propria is the feature of: a. Linea alba b. Lip biting c. Chemical burns d. Both b and c

4. A characteristic square- jaw appearance is the feature of: a. Osteoradionecrosis b. Bruxism c. Ankylosis d. None

2. Whitish gray or ulcerated lesions of the middle third of the hard palate is due to: a. CO2 burn b. Pizza burn c. Acid burn d. Vitamin C tablet

5. ‘Burtonian line is seen in: a. Copper poisoning b. c. Lead poisoning d.

3. The salivary flow becomes zero when dose reaches: a. 20 Gy b. 30 Gy c. 40 Gy d. 60 Gy

6. Raw beef appearance is the clinical feature of: a. Mercurialism b. Swift’s disease c. Both a and b d. Argyria

Mercury poisoning Thermal burns

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Blood Pathology

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline                       Â

Disease of lymph tissue Lymphoid hyperplasia Disease of red blood cells Anemia Thalassemia Aplastic anemia Hereditary elliptocytosis Hereditary spherocytosis Acute post hemorrhagic anemia Erythroblastosis fetalis Erythropoietic porphyria Iron deficiency anemia Plummer Vinson syndrome Pernicious anemia Polycythemia Vera White blood cell disorders Agranulocytopenia Cyclic neutropenia Lazy leukocyte syndrome Chronic idiopathic neutropenia Chediak Higashi syndrome Disease of platelet Idiopathic thrombocytopenic purpura

DISEASE OF LYMPH TISSUE Lymphoid Hyperplasia Lymph tissue is very important in the defense mechanism of the body. It process foreign antigen like viruses, fungi, and bacteria. The proliferation of lymphoid tissue results

                      Â

Thrombotic thrombocytopenic purpura Aldrich syndrome Familial thrombasthenia Thrombocytosis or thrombocythemia Disease due to clotting defect Hemophilia Von Willebrand’s disease Plasminogen deficiency Factor V deficiency or Parahemophilia Afibrinogenemia and hypofibrinogenemia Dysfibrinogenemia Fibrin stabilizing factor deficiency Macroglobulinemia Malignancy involving blood tissue Hodgkin’s lymphoma Non Hodgkin’s lymphoma Primary reticular cell sarcoma Mycosis fungoides Burkitt’s lymphoma Leukemia Multiple myeloma Plasmacytoma Extranodal NK/T-cell lymphoma

in enlargement called lymphoid hyperplasia. Lymphoid hyperplasia is unusual in the head and neck region, but the diagnosis of it is of clinical importance as it may be confused with malignant lymphoma, both on clinical examination and pathologically. It is also called reactive lymphoid hyperplasia. This entity was first described in 1973 by Adkins.

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Clinical Features 694

Site: Lymphoid hyperplasia is usually affect the lymph nodes in the region anterior cervical chain. It can also affect lymphoid tissue of Waldeyer’s ring, aggregates of lymphoid tissue in the region of oropharynx, the soft palate, the lateral tongue and the floor of the mouth. Lymph nodes: In case of acute infection lymph nodes are soft, tender, and are increase in size. In case of chronic infection lymph nodes are enlarge with rubbery consistency. In chronic cases lymph nodes are non-tender and movable in consistency. This chronic cases may get confused with lymphoma. History will give clue to the diagnosis. History of infection and no progressive enlargement will goes in favor of lymphoid hyperplasia. In some cases buccal lymph nodes are enlarge and present with non-tender, freely movable nodule, less than 1 cm in diameter. It is present in the cheek region. Lingual tonsil (Fig. 28.1): It is located in posterior part of tongue on the dorsolateral aspect. It is normally prominent in the younger individual and it get decrease in size with the age. In some cases tonsil are so enlarge that they can occlude the airway. This type of tonsil is called kissing tonsil. This patient are usually asymptomatic and enlargement is symmetrical. Intraoral lymphoid aggregates: This are usually present in lateral border of the tongue in the posterior region. The color of this can be normal or dark pink (if the aggregates is deeper) and yellowish orange (if it near to the surface). This usually bilaterally symmetrical.

Histopathological Features Germinal center: There is collection of sharply demarcated reactive lymphoblast called germinal center. These

Figure 28.2 Histopathological photographs showing tingible

bodies in lymphoid hyperplasia

centers are interspersed in sheets of well differentiated lymphocyte. The cells of germinal center are transformed B lymphocytes. Tingible bodies: There is presence of phagocytized material called tangible bodies in the cytoplasm of macrophage. They engulf nuclear debris from proliferating lymphocytes (Fig. 28.2).

Management As lymphoid hyperplasia is the benign process, no management is require. In some cases when palatal lymphoid hyperplasia interferes with the prosthesis surgical excision of the lesion can be carried out. Points to Remember Enlargement of lymph nodes, kissing tonsil, lingual tonsil, intraoral lymphoid aggregates, germinal center, tingible bodies.

DISEASE OF RED BLOOD CELLS Anemia

Figure 28.1 Lingual tonsil due to lymphoid hyperplasia

Anemia is the general term which is used for decreases in volume of red blood cells or concentration of hemoglobin. There are various factor which can cause anemia like disturbed iron metabolism (iron deficiency and sideroblastic anemia), deficiency of factor like vitamin B12, folic acid. Anemia also can occur due to chronic infection, connective

Blood Pathology

tissue disorders, secondary to malignancy, in liver disease, endocrine disease. Some disorders of hemoglobin (sickle cell and thalassemia) and anemia due to hemolytic factor can also occur. Generally patient complaint of tiredness, headache and lightheadedness. Pallor of the mucosa and conjunctiva is present in all types of anemia. There are many types of anemia. Some important types are discussed below.

Most of persons expire before the age of 40 years. There is also presence of leg ulcer and gall stones. When associated with folate deficiency, there may be growth retardation and also delayed puberty. Hyperplasia of marrow in first year of life expands the marrow cavity producing bossing of the skull, prominent malar bones and protuberant teeth.

Sickle Cell Anemia

Acute chest syndrome: Pulmonary involvement which is precipitated by fat embolism or community acquired pneumonia is known as acute chest syndrome.

It is autosomal dominant. It was first described by Herrick in 1910. This is the most common type of hemoglobinopathy in which there is a substitution of amino acid glutamine on position 6 present in the chain of the HbA, by valine; giving rise to an abnormal Hb, i.e. hemoglobin S. In homozygous individuals, whole of HbA is replaced by HbS and this is known as sickle cell disease and in heterozygous individuals, only 50 percent of HbA is replaced by HbS and this is known as sickle cell trait. It is chronic hemolytic blood disorder characterized by abnormal hemoglobin (deoxygenated hemoglobin) which under low oxygen tension, results in sickling of cell. When HbS is deoxygenated, it forms structures know as tactoids which distort the RBC membrane and produce characteristic sickle shaped cell which are destroyed by RE cells. Sickle cells increase blood viscosity and tend to reduce blood flow leading to thrombosis and tissue infarction. In addition these cells are phagocyte in large number by mononuclear-phagocyte system which reduce their life span and give rise with hemolysis. Patients may develop severe folic acid deficiency due to increased erythropesis.

Sickle cell crisis: There is a long quit spell of hemolytic latency occasionally punctuated by exacerbations called sickle cell crisis.

Other symptoms: Infarction can only occur in bone and spleen but, other tissues may also be involved. In infants, fingers and toes are commonly affected. Thrombosis of vessels in brain cause severe neurologic disorders like stroke, convulsion, coma, drowsiness as well as speech visual and hearing disturbances. Occlusion of smaller vessels results in headache and cranial nerve neuropathy including palsy and paresthesia. Oral manifestation: The oral mucosa will show pallor and jaundice. There may be delayed eruption and hypoplasia of the dentition, secondary to their general development. Patient is more prone to develop osteomyelitis. This may be due to hypovascularity of the bone marrow secondary to thrombosis. Patient may present with paresthesia of mental nerve which may be secondary to occlusion involving the nerves and blood supply. Mongoloid facies with high cheek bones and bimaxillary proganthism is present. It is due to marrow hyperplasia resulting in an increase in hard palate length and palate alveolar ridge angle.

Clinical and Radiological Features

Radiological features: There is reduced trabecular pattern due to increases hematopoiesis of bone marrow. In some cases hair on end appearance is seen in the skull.

It is common in females and mostly the clinical symptoms become evident before the age of 30 years.

Hematological and Histopathological Findings

Symptoms: Clinical manifestations begin only after several months as fetal Hb protects against sickling phenomenon. It includes dehydration, chills and infection but some time the attack occurs spontaneously. There is fatigue, weakness and shortness of breath. Severe abdominal pain, muscle and joint pain, at high temperature which may result in circulatory collapse. There is painless hematuria. There is enlargement of heart and murmur is found in most of the patients. There is increased susceptibility to infection.

The RBC count may reach level of 10 lac cells or less per cu mm with Hb levels from 5 to 12 g/dL. The sickle hemoglobin molecule undergoes gelation or crystallization, when deoxygenated and this typically distorts the erythrocyte, producing the sickle or boomerang shape (Fig. 28.3). This sickle shaped cells then ‘logjam’ and produce stasis within the microvasculature. Damage to erythrocyte membrane also occurs in sickle cells and leads to their fragmentation and intravascular hemolysis. Reticulocyte count is raised.

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some instance this is most common inherited disorders that affect human beings.

Types

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Alpha thalassemia: There is reduction or absence of chain synthesis. Alpha chains of hemoglobin are required not only for HbA but also for HbF, which is the main hemoglobin type in fetal life. Therefore, major type of alpha thalassemia is incompatible with life and results in hydrops fetalis and intrauterine death of fetus.

Figure 28.3 Sickle cell shaped of red blood cells

Management Prevention of episode by avoiding the precipitating factors is an important aspect of treatment. Patients should avoid becoming chilled, dehydrated or exposed to hypoxia (high attitude). Regular folic acid supplement (5 mg/daily) and blood transfusion should be given. Genetic counseling should be done. Termination of pregnancy if fetus is affected by sickle cell disease. Nowa-day molecular evaluation of DNA of single cell obtained from an embryo that was fertilized from in vitro allow selection of non-affected embryo for uterine implantation. Points to Remember Sickle cell trait tactoids sickle cell crisis, acute chest syndrome, paresthesia of mental nerve, mongoloid facies, hair on end appearance sickle or boomerang, shape, genetic counseling, folic acid supplement.

Thalassemia It is also called Cooley’s anemia, Mediterranean anemia and erythroblastic anemia. Either alpha or beta globulin genes may be affected. The resultant red blood cells have reduced hemoglobin are thin and have shortened life span. It is autosomal dominant. It is an inherited impairment of hemoglobin synthesis in which there is partial or complete failure to synthesize a specific type of globin chain. By

Beta thalassemia: There is reduction or absence of beta chains. Hemolysis is not primarily due to lack of β-globin chains but it is because of the free alpha chains which form insoluble aggregates that precipitate within the RBCs and cause damage to the cell membranes. The red cells which are present are very fragile and survive for only few days in peripheral circulation. In order to maintain the adequate oxygenation the rate of hematopoiesis is increase 30 times than normal to produce massive bone marrow hyperplasia, hepatosplenomegaly. Thalassemia major or homozygous β-thalassemia: Occurs when the patient is homozygous. It is also called Cooley’s anemia. Hemoglobin H disease: It is very mild form of the disease in which the patient may live relatively normal life. There is three altered gene. Hemoglobin Bart disease: In which infants are stillborn or die shortly after birth. Thalassemia intermedia: It is group of disorders characterized by clinical manifestations between major and minor. Thalassemia minor or thalassemia trait: Occurs when the patient heterozygous. Types Alpha thalassemia, beta thalassemia, thalassemia major or homozygous β-thalassemia, hemoglobin H disease, hemoglobin Bart disease, thalassemia intermedia, Thalassemia minor or thalassemia trait.

Clinical, Oral and Radiological Features Beta thalassemia It occurs between the ages of 6 to 24 months and after the age of 6 to 8 months, development and growth of

Blood Pathology

the child is retarded. Survival time is short. The patient first presents with pallor of skin, fever, chills, malaise, generalized weakness, prominent cheek bone and mild hepatosplenomegaly.

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Mongoloid appearance: Bone marrow hyperplasia in early life may produce frontal head bossing and there may be marked overdevelopment of malar bone which is associated with a short nose having a depressed bridge giving the appearance of mongoloid. Deposition of iron in various organs (due to multiple transfusions) leads to signs and symptoms of organ failure. Most patients die in childhood due to anemia and cardiac failure. There is excessive overgrowth of maxilla causing excessive lacrimation and nasal stuffness. The oral mucosa is pale and has a lemon yellow tint because of chronic jaundice. The color is best seen at the termination of hard palate and in the floor of mouth. Rodent facies: There is marked over development of maxilla associated with hyperplasia of alveolar process, which results in anterior open bite and prominent cheek bone producing characteristic ‘rodent facies’. The maxillary teeth are protrudes with spacing between them with a short upper lip due to a lag between the growth of the maxilla and the growth of upper lip. Due to high concentration of iron discoloration of dentin and enamel may be evident. Chip munk facies: There is also saddle nose, prominent malar bone and pneumatization of maxillary sinus. As a result of these skeletal changes, the upper lip is retracted giving the child a ‘chip munk’ facies. There is poor healing after dental treatment. Radiological features: There is prominent hair on end appearance (Fig. 28.4). Alpha thalassemia The clinical findings are severe alveolar bone loss, pronounced spacing of maxillary anterior teeth and mongoloid appearance.

Laboratory Findings The anemia is hypochromic and microcytic. The peripheral smear shows abnormal RBCs. Reticulocyte count is increased. Bone marrow shows increased erythropoietic activity. Serum bilirubin and fecal and urinary urobilinogen are elevated because of severe hemolysis. An elevated fetal hemoglobin is present.

Figure 28.4 Hair on end appearance in patient with thalassemia

Histopathological Findings The presence of typical safety pin cells and nucleated red blood cells in circulation are characteristic.

Management Blood transfusion should be administered every two to three weeks. But major disadvantage of repeated blood transfusion is iron overload (hemochromatosis). It may cause death due to toxic accumulation on heart and liver. To overcome this problems iron chelating agent like deferoxamine should be given. Other therapy like splenectomy, folic acid supplement, surgical correction of abnormal facial appearance should be done. Points to Remember Cooley’s anemia, Alpha thalassemia, Beta thalassemia, Mongoloid appearance, Rodent facies, Chip munk facies, hair on end appearance, safety pin cells and nucleated red blood cells, blood transfusion, splenectomy, folic acid supplement.

Aplastic Anemia It is a rare disorder characterized by peripheral blood pancytopenia (anemia, leukopenia and thrombocytopenia) associated with bone marrow suppression. In most cases bone marrow suppression is not known and hence is known

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as idiopathic aplastic anemia. Fanconi’s anemia is an inherited anemia that manifests in early childhood. In this there is failure of hematopoietic precursor cells to produce adequate number of all types of blood cells.

Etiology

ecchymosis. Large ragged ulcers covered by gray or black necrotic membrane may be present, which are the result of generalized lack of resistance to infection and trauma.

Histopathological and Hematological Findings

Common drugs which can cause aplastic anemia are benzene derivatives, chloramphenicol, amidopyrine, organic arsenicals, colloidal silver, bismuth, mercury, sulfonamides, penicillin and anticancer drugs. Patient with bacterial disease such as tuberculosis and viral infections like hepatitis and infectious mononucleosis can cause pancytopenia. Long-term continuous exposure to small amounts of external radiation or to internally deposited radium or thorium has been followed by the development of aplastic anemia.

RBC count is remarkably diminished, as low as 1 million cells/mm3. WBC count is as low as 2000/mm3 and platelet count may fall below 20000/mm3. The classical finding is that of pancytopenia along with reduction of absolute reticulocyte count. Bleeding time is prolonged and clotting time is normal. Anemia is normocytic with some degree of macrocytosis. Bone marrow is fatty, acellular, and few developing cells (Fig. 28.6). Histopathological features shows acellular bone marrow with extensive fatty infiltrated. There is also presence of many microorganism and inflammatory cells.

Clinical Features

Management

It can occur at any age, but is common in young adults. Patient may feel weakness after slight physical exertion and exhibits pallor of skin.

Withdrawal of offending agent: Withdrawal of offending agents may sometime lead to recovery.

Symptoms: Breathlessness, headache, ankle edema are common clinical features. Numbness and tingling of extremities with edema are often encountered. Anemia may be severe enough to cause anginal pain or congestive cardiac failure. Bleeding: There may be bleeding from various sites like skin, nose, vagina and gastrointestinal tract associated with fever due to infection.

Antibiotics: Appropriated antibiotics should be given to combat infection. Bone marrow transplantation: Now-a-day this therapy has got acceptance to replace defective bone marrow. Immunosuppressive therapy: Anti-hemocyte globulin combine with cyclosporine produced response in majority of cases.

Oral features: The mucosa shows pallor. In some cases, spontaneous hemorrhage may occur form the gingiva can occur (Fig. 28.5). Petechiae, often are present on the soft palate and in severe cases, there may submucosal

Figure 28.5 Diffuse gingival hyperplasia with bleeding

Figure 28.6 Bone marrow of patient having aplastic anemia

Blood Pathology

Other therapy: Stimulation of hemopoiesis by androgens, bone marrow transplantation and anti-fibrinolytic agents. Points to Remember Fanconis anemia, benzene derivatives, breathlessness, ankle edema, bleeding, hemorrhage in gingiva, RBC count 1 million cells/mm3, acellular bone marrow, bone marrow transplantation, immunosuppressive therapy.

Acute Posthemorrhagic Anemia The anemia caused by blood loss may occur in variety of conditions causing bleeding. When blood loss occurs in large amounts in a short period of time, anemia may develop even though iron stores remain adequate. It is called acute posthemorrhagic anemia.

Clinical Features

Symptoms are usually present in childhood. There is mildto-moderate hepatosplenomegaly, jaundice and anemia. A hemolytic and aplastic crisis may be precipitated by infection or may occur with any cause. Such patients will have shivering, fever, marked weakness, vomiting, abdominal pain, dyspnea and palpitation.

The manifestations of hemorrhagic anemia depend on the rate and magnitude of bleeding; the time elapsed since it took place and the site-whether it is external or internal. When the blood loss is about 500 to 1000 mL, most of the patients do not present any symptoms, but few may present with weakness and sweating. With rapid loss of 1000 to 1500 mL, a previously healthy individual may experience lightheadedness and hypotension. When 1500 to 2000 mL of blood is lost, symptoms like sweating, thirst, shortness of breath, clouding or loss of consciousness are seen. The pulse becomes rapid and low in volume, skin become cold and clammy and there is a fall in blood pressure. When rapid loss of blood exceeds 2000 to 2500 mL, severe state of shock is reached.

Hematological Findings

Hematological Features

The peripheral smear shows presence of spherocytes. Reticulocyte count is increased. Hb ranges from 5 to 12 g/dL.

Plasma volume and red cell mass are reduced in proportional amount. Anemia is normocytic and normochromic. Erythropoietin secretion is stimulated which in turn gives rise to hyperplasia of marrow erythroid elements within 3 to 5 days. Increased in reticulocyte number. Neutrophilic leukocytosis often follows hemorrhage and is maximum after 2 to 5 hours.

Hereditary spherocytosis In this disorder, red blood cells are excessively permeable to sodium ion. The osmostic fragility of red cells is abnormal in these conditions. It will lead to loss of cell membrane and gradually the cell becomes spherical in shape and is destroyed by spleen, giving rise to hemolytic anemia.

Clinical Features

Management Splenectomy is the treatment of choice but should be done after the child is 6 years old. Folic acid 5 mg daily. Points to Remember Permeable to sodium ion, hepato-splenomegaly, jaundice, spherocytes, splenectomy. Hereditary elliptocytosis It is a genetically determined abnormality of the red cell shape associated with variable degree of hemolysis.

Clinical Features Most of the patients have no clinical manifestations but few may show signs of chronic hemolytic anemia.

Hematological Findings The peripheral smear shows larger number of elliptocytes. Mild anemia of normocytic, normochromic type.

Management Restoration of blood volume. Intravenous infusion of saline, dextrin, albumin or plasma. Whole blood replacement is the therapy of choice. Points to Remember Blood loss, lightheadedness, shortness of breath, cold and clammy skin, normocytic and normochromic anemia, whole blood replacement. Erythroblastosis fetalis It occurs due to isoimmune antibodies. It is also called hereditary disease of new born (HDN). Congenital hemolytic anemia due to Rh incompatibility results from destruction of fetal blood brought about by a reaction

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between maternal and fetal blood factors. The Rh factor, named after Rhesus monkey, was discovered by Landsteiner and Wiener in 1940 as a factor in human RBC which reacts with rabbit antiserum produced by administration of red bloods cells from Rhesus monkey.

Pathogenesis It occurs due to inheritance, by the fetus, of a blood factor from the father that acts as a foreign antigen to mother. The transplacental transfer of antigen and leak of red cells, from fetus to mother results in immunization of mother and formation of antibodies. When the fetal red cells cross placenta they may stimulate the production of maternal antibodies against the fetal antigens. Some of these antibodies then cross into fetal circulation and cause the destruction of fetal red cells. If the father is Rh-positive and the mother is Rh-negative, fetus inherits Rh-positive antigens, which may act as antigen to the mother and immunize her with resultant antibody formation. The problem is complicated by Rh antigens which are termed as C, D and E. Out of this, D antigen is the strongest and is responsible for the clinical manifestations of erythroblastosis fetalis.

Clinical Features Some infants are stillborn. Those that are born alive have anemia with pallor, jaundice, compensatory erythropoiesis (both medullary and extra-medullary) and edema resulting in fetal hydrops. Kernicterus: It may manifest itself by apathy and poor feeding and later by mental retardation, irritability and cranial nerve palsies. Oral features: It may manifest in teeth by the deposition of blood pigment in enamel and dentin of developing teeth giving them a green, brown or blue hue. It occurs in those portions of the teeth which are being laid down during the time when icterus was at its height. Enamel hypoplasia is also reported occurring in some cases of erythroblastosis fetalis and usually involves the incisal edges of the anterior teeth and middle portion of the deciduous cuspid and first molar crown. There is ring like defect called Rh-hump.

level of 100 units. The peripheral smear shows large number of immature RBCs. There is also evidence of hemolysis. Points to Remember Stillborn, Kernicterus, green, brown or blue hue teeth, enamel hypoplasia, Rh hump, red blood count less the 1,000,000 cells per cubic millimeter. Erythropoietic porphyria Is a group of inherited or acquired disorders characterized by excessive production, accumulation and excretion of some porphyrins and their precursors or by-products. It is a metabolic defect within the maturing erythrocytes resulting in excessive production of uroporphyrinogen-I.

Clinical Features It occurs soon after birth. The urine is burgundy red in color or turns red on exposure to light. Photosensitivity of exposed parts of body leads to formation of blister and scars. There is also hemolytic anemia and splenomegaly. Oral features: There is deposition of porphyrins in dentin, to a lesser extent in the enamel which imparts red or brown color to deciduous and permanent teeth (erythrodontia). The staining by uroporphyrin can be confirmed by ultraviolet light which will produce red fluorescence. Bullous erosions of oral mucosa can be seen. In advanced cases, pigmented atrophic scars on lip are seen resemble the keloid structures. The patient is hence, unable to close his mouth.

Hematological Findings About 50 percent normoblasts, reticulocyte and 50 percent RBCs exhibit intense red fluorescence under fluorescence microscope.

Management Splenectomy, in cases of severe hemolysis may be carried out. Points to Remember Burgundy red urine, erythrodontia, bullous erosions, red fluorescence, splenectomy.

Laboratory Findings

Iron Deficiency Anemia

The red blood count at birth may vary from less the 1,000,000 cells per cubic millimeter to near a normal level. The icterus index is very high and may reach a

Iron is essential for synthesis of ‘hem’ portion of hemoglobin. Iron deficiency anemia is caused by imbalance between iron intake and loss or inadequate utilization. In

Blood Pathology

this iron which is present in the body cannot keep pace with need for iron in the production of red blood cells.

Causes

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It is caused by inadequate intake of iron. It may occur due to malabsorption of iron due to hypochlorhydria and diarrhea. There is increased requirement of iron in a growing child and in pregnancy. Other factors which can cause iron deficiency anemia are increased loss of iron due to injury, recurrent epistaxis, peptic ulcer, blood loss in menstrual flow (menorrhagia), parturition and subtotal or complete gastrotomy.

Clinical Features It occurs chiefly in women in the 4th and 5th decade of life. The patient experiences tiredness, headache, paresthesia and lack of concentration.

Figure 28.7 Atrophy of tongue papillae seen in iron

deficiency anemia

Koilonychias: Nails become brittle, flattened and often show spoon shape (koilonychia). There may be tingling, pins and needle sensation in the extremities. Dysphagia: Some patients develop pharyngeal mucosal thickening and mucosal web formation, giving rise to dysphagia. Gastrointestinal symptoms: Liver and spleen may be palpable. There may be gastrointestinal bleeding and menorrhagia there by setting a vicious circle.

Oral Manifestations Pallor: In iron deficiency there is pallor of oral mucosa and gingiva. The normal pink color is lost due to lack of oxygenated blood in the capillary bed in lamina propria and is associated with lowered levels of hemoglobin. The generalized atrophy of oral mucosa can occur. Tongue: There is redness, soreness or burning of tongue. The filliform papillae over the anterior two-thirds of tongue are the first to undergo atrophy (Fig. 28.7). In severe cases fungiform papillae are also affected leaving the tongue completely smooth and waxy or glistening in appearance. There is cracking and fissuring at the corner of mouth (angular cheilitis). There is softening of epithelium which leads to linear ulceration of the skin, extending up to and beyond the mucocutaneous junction. There may be pain on opening or stretching and rarely, bleeding from ulcerated tissues.

Figure 28.8 Gingival enlargement in iron deficiency anemia

Recurrent aphthous ulceration and candidal lesions can also occur in iron deficiency anemia. Patient may show slow healing after oral surgical procedures. In some cases there may be gingival enlargement (Fig. 28.8).

Hematological Findings The anemia is microcytic and hypochromic (Fig. 28.9) and the peripheral smear shows abnormal forms of RBCs. There is reduced hemoglobin level, as low as 4 g/100 mL. There is normal or slightly reduced RBC count. MCV, MCH and MCHC are all reduced.

Textbook of Oral Pathology

sore mouth and inability to retain dentures. A smooth, red, occasionally enlarged and often sore tongue with fissuring is occurs. The width of mouth is narrowed and the oral mucosa is pale and painful. There is also dry mouth and spoon shaped nails.

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Dysphagia: There are atrophic changes in mucosa of mouth, pharynx, upper esophagus and vulva. This will leads to dysphagia. Esophageal webs: With evaluation with endoscopy it shows abnormal bands of tissue in the esophagus. This is called esophageal web.

Figure 28.9 Hypochromic types of iron deficiency anemia

Koilonychia: There is alternation of the growth pattern with spoon shaped configuration.

Histopathological and Hematological Features

There is marked thinning of epithelium, absence of papillae in the lamina propria and absence of keratohyaline granules.

Hematologic study show hypochromic microcytic anemia. There is atrophic epithelium and atrophy of lamina propria and muscles. There is also presence of submucosal chronic inflammation. In advance cases there may be evidence of epithelial atypia or dysplasia.

Management

Management

Almost all patients can be treated by oral supplements of iron by giving ferrous fumerate or ferrous sulfate. It is given in dose of 300 mg three to four times a day for a period of 6 months.

Dietary iron supplement should be given for the correction of iron deficiency anemia. Esophageal dilation should be done to improve symptoms of dysphagia.

Histopathological Findings

Points to Remember Menorrhagia, Koilonychias, dysphagia, gastrointestinal bleeding, angular cheilitis, redness of tongue, recurrent aphthous ulceration, candidal lesions, microcytic hypochromic anemia, epithelium thinning, iron supplement. Plummer Vinson syndrome It is also called Paterson-Brown-Kelly syndrome or sideropenic dysphagia. It is characterized by dysphagia, iron deficiency anemia, dystrophy of nails (koilonychia) and glossitis.

Clinical Features It is exclusively found in middle aged women. Patient of this syndrome have got characteristic asthenic appearance. Vermilion borders of the lip are very thin and there is often angular cheilitis. Patients complaint of ‘spasm in throat’ or food sticking in throat. There is also complain of

Points to Remember Paterson-Brown-Kelly syndrome dysphagia, iron deficiency anemia, dystrophy of nails (koilonychia) and glossitis.

Pernicious Anemia It is also called primary anemia, Addison’s anemia or ‘Biermer’s anemia’. The term pernicious anemia should be reserved for patients who have B12 deficiency secondary to intrinsic factor deficiency. If there is extrinsic factor deficiency it is called megaloblastic anemia.

Causes It occurs due to atrophy of gastric mucosa resulting in failure to secrete the still unidentified ‘intrinsic factor’. Intrinsic factor is produced by parietal cells of the stomach lining. This intrinsic factor is responsible for absorption of vitamin B12. It is suggested that it is autoimmune disorder, because autoantibodies to gastric parietal cells are often found in serum of patients.

Blood Pathology

Clinical Features It is rare before the age of 30 years and increase in frequency with advancing age. Males are more commonly affected than females. There is usually triad of symptom: Generalized weakness, sore painful tongue and numbness and tingling of the extremities. Other features are fatigability, headache, dizziness, nausea, vomiting, diarrhea, with loss of appetite, shortness of breath, loss of weight, pallor and abdominal pain. Nervous system: Nervous system disorders are also present and manifested by sensory disturbances including the paresthetic sensation of the extremities, weakness, stiffness and difficulty in walking, general irritability, depression, drowsiness as well as incoordination on loss of vibratory sensation. There is also tingling sensation in the fingers and toes that eventually progress to numbness.

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Figure 28.10 Atrophy of tongue papillae in megaloblastic

anemia

Gastrointestinal complaint: Epigastric discomfort, constipation or diarrhea can be seen in these patients.

Oral Manifestations There is glossitis and patient complains of painful and burning lingual sensation which may be so annoying that the dentist is often consulted first. The tongue is generally inflamed often described as ‘beefy red’ in color, either entirely or in patches scattered over the dorsum and lateral border of tongue. There is gradual atrophy of the papillae of tongue that eventuates in a smooth and bald tongue which is often referred as Hunter’s glossitis or Moeller’s glossitis and is similar to the bald tongue of sandwith seen in pellagra (Fig. 28.10). The fiery red appearance of tongue may undergo remission but recurrent attacks are common. Sometimes inflammation and burning involve the entire oral mucosa. Tongue may show lobulations, which may be secondary to decrease in saliva production. There is disturbance in taste sensation with intolerance to dentures and occasional dryness of mouth. Oral mucosa shows greenish yellow color (frequently observed on the skin) at the junction of hard and soft palate, when daylight is used for illumination.

There is atrophy of epithelium with intra or subepithelial chronic inflammatory cell infiltration. Cellular atypia can be seen. Loss of rete ridges is also a features of pernicious anemia.

Histopathological Features

Laboratory Findings

Histologically, oral epithelial cells in pernicious anemia reveal enlarged, hyperchromatic nuclei with prominent nucleoli and serrated nuclear membranes (Fig. 28.11).

The red blood count is decreased often to three or less per cubic millimeter. Many of the cells exhibits macrocytosis, while some exhibit poikilocytosis. Decreased WBC count

Figure 28.11 Megaloblastic anemia showing hyperchromatic

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and mean corpuscular hemoglobin. In advanced cases of anemia, there are polychromatophilic cells, stippled cells, nucleated cells, Howell-Jolly bodies and Cabot rings. Leukocytes are also often reduced in number but are increased in average size. Bone marrow shows great number of immature red cells or megaloblasts with few normoblasts, indicating maturation arrest at the more primitive megaloblasts state. Achlorhydria or lack of gastric hydrochloric acid secretion is a constant feature and pH of the gastric content is usually high. Achlorhydria is associated with atrophy of the gastric mucosa, which commonly occurs in presence of chronic inflammation. Schilling test detects the absence of intrinsic factor.

Management Most of the patients should be given vitamin B12 parenterally but, some of the cases are treated with massive oral dose of vitamin B12. The standard dosage is 100 mg IM every 30 days. Points to Remember Addison’s anemia’ generalized weakness, sore painful tongue, numbness and tingling of the extremities, bald tongue of sandwith, fiery red appearance of tongue, cellular atypia, loss of rete ridges, immature red cells or megaloblasts, vitamin B12 parenterally.

Polycythemia Vera It is defined as abnormal increases in the number of red blood cells in the peripheral blood, usually with an increase hemoglobin level. It is also called polycythemia rubra Vera, Osler’s disease, primary acquired erythrocytosis ‘Vaquez’s disease and erythremia. There is an uncontrolled proliferation of the erythroid stem cells leading to excess of erythroid cell mass in the body (RBCs). There is accompanying increase in the granulocyte and megakaryocytic elements though to a lesser degree. It is believed that single progenitor marrow stem cells become multiplying without regard to normal regulatory hormone like erythropoietin. This will lead to overproduction red blood cells.

Clinical Features The disease is more common in males and usually occurs in middle age or later.

Figure 28.12 Purplish red discoloration of eyes of the patient

Symptoms: Common symptoms are lassitude, loss of concentration, headache, dizziness and blackout, slurring of speech, pruritis, mental confusion and indigestion. Paresthesia is common, usually involving the cranial nerves. Itching: This is very characteristic complaint given by the patient is that there is itching particularly after bathing without evidence of rash. The skin appears flushed or diffusely reddened. Superficial veins are dark enlarged and distended. The tip of the finger usually has a cyanotic appearance. There is also splenomegaly. There is marked purplish red discoloration especially of the head and neck region (Fig. 28.12). Feet and hands, which give the patient an extremely angry appearance. Erythromelalgia is peripheral vascular event which affects hands and feet. There is painful burning sensation associated with erythema and warmth. This again will lead to occlusion of vessels which in turn results in digital gangrene and necrosis. Thrombotic complications may occur with increase viscosity of blood with increase platelet number. It may leads to ischemic attacks, cerebrovascular accidents, myocardial infarction. Oral features: There is purplish red discoloration of the ears, oral mucosa, gingiva and tongue. The tongue may appear as if it had been painted with crystal violet. The gingiva is markedly swollen and bleeds spontaneously, but with no tendency to ulcerations. Petechiae of the oral mucosa are common. In such patients severe hemorrhage may follow surgical procedures.

Blood Pathology

Hematological Findings The hemoglobin level is greater than 18 g/dL with an associated elevation of WBC and platelet count. The bone marrow is hypercellular with erythroid hyperplasia, increased number of megakaryocytes and granulocytes.

Management Phlebotomy: It is removal of excess blood (500 mL) daily. This will reduce the red blood cell. For the management of thrombotic event low dose aspirin, for control of platelet level anagrelide hydrochloride (selective inhibitor of megakaryocytic maturation) should be given. Points to Remember Osler’s disease, itching, angry appearance, thrombotic complications, erythromelalgia, purplish red discoloration of oral mucosa, hemoglobin level < 18 g/dL, low dose aspirin, phlebotomy.

WHITE BLOOD CELL DISORDERS Agranulocytopenia It is also called granulocytopenia, agranulocytic angina, agranulocytosis. It is a serious disease characterized by marked leukopenia with reduction and absence of neutrophilic leukocytes. Types • Primary agranulocytosis: In this, etiology is unknown. • Secondary agranulocytosis: In it, cause is recognized. • Congenital agranulocytosis: Also called Kostmann syndrome. This occurs due to decreased level of the cytokine granulocyte colony stimulating factor • Mild neutropenia: When 1000/mm3 to 2000/mm3 neutrophils are present. • Moderate neutropenia: When 500/mm3 to 1000/ mm3 neutrophils are present. • Severe neutropenia: When fewer than 500/mm3 neutrophils are present. • Agranulocytosis: When no neutrophils are seen in peripheral smear.

or antimetabolics. This results due to inhibition of normal mitotic division and maturation of hematopoietic cells. Deficiency of vitamin B12 and folic acid. Disease causing sequestration of neutrophils includes systemic lupus erythematosus and Felty’s syndrome. It can be associated with leukemia, pancytopenia and hypersplenism.

Clinical Features It can occur at any age but it somewhat more common in adults, particularly in woman. It is also common in professional and in hospital as they have easy access of the offending drugs and often use drug sample injudiciously. Sign and symptoms: The onset may be sudden or gradual. The condition begins with sore throat, high fever and often rigors, which may be followed by prostration. The skin appears pale and anemic and in some cases, jaundiced. There is rapidly advancing necrotic ulceration of throat and mouth with little evidence of pus formation. In most of the cases patient dies within 3 to 5 days due to toxemia and septicemia.

Oral Manifestations The most common sites are gingiva and palate, tonsil and pharynx. There may be associated pain, excessive salivation and spontaneous oral hemorrhage. The oral lesions appear as necrotizing ulcerations of oral mucosa, tonsils or/and pharynx. The lesions appear as ragged and necrotic and are covered with a gray black membrane. The necrotic tissue is often foul smelling. There is lack of inflammation at the margin of lesions. The disease spreads quickly in gingival tissues causing destruction of supporting structures and inevitable loss of deciduous and permanent teeth. This features also resembles pattern of necrotizing ulcerative gingivitis.

Histopathological and Hematological Findings Majority of patients show a leukocyte count below 2000 cells per cumm and granulocyte count below 100 cells per cumm. Hemoglobin and platelet counts are normal. The histopathological features of ulcer shows that reduce or absence of neutrophils. It may show bacterial invasion.

Management Causes It is caused by certain drugs like aminophylline, chlorpromazine and phenylbutazone, benzene, bismuth, chloramphenicol, sulfonamides and use of cytotoxic drugs

If hemoglobin is less than 10 g/dL, transfusion of red cell concentrate is given. In some cases white cell transfusion can be given. Septicemia can be controlled by parenteral antibiotic therapy along with corticosteroid therapy.

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A combination of carbenicillin, methicillin and gentamicin is commonly used because of broad coverage against most organisms. Chlorhexidine containing mouth wash reduce the severity of oral lesion. Points to Remember Aminophylline, sore throat, necrotic ulceration of throat and mouth, excessive salivation, necrotizing ulcerative gingivitis, spontaneous oral hemorrhage, leukocyte count below 2000 cells per cumm, absence of neutrophils, transfusion of red cell concentrate.

Cyclic Neutropenia Figure 28.13 Severe gingivitis in patient with cyclic neutropenia

It is also called periodic neutropenia, and cyclic hematopoiesis. It is a rare disorder characterized by periodic or cyclic diminution in circulating neutrophils due to failure of stem cells of bone marrow. One-third cases are inherited as autosomal dominant trait and two-thirds appear spontaneously during the first few year of life. The patient is healthy between neutropenic periods; but at regular intervals, the absolute neutrophils count falls below 500/ mm3. In some patient it comes to zero. The cause for this disorders mutation of neutrophils elastase (ELA2) gene.

Normal blood count, over a period of 4 to 5 days, begins to show a decline in the neutrophil count compensated by an increased in monocytes and lymphocytes. At the peak of the disease, the neutrophils may completely disappear for one or two days.

Clinical Features

Management

The disease is frequently present during infancy and childhood and both sexes appear to be equally affected. The frequency of neutropenic episodes vary from once in 2 to 4 weeks which last for 3 to 5 days with 21 days gap being the most common.

There is no specific treatment and monitoring the patient for infection during neutropenic period and vigorous early management of infection. Antibiotics should be given to combat infection. In some cases use of corticosteroids, adrenocorticotropin (ACTH) or testosterone modulates sharp reduction in marrow function. Administration of cytokine granulocyte colony stimulating factor (G-CSF) several times in week will correct the lack of production of neutrophils. Oral hygiene should be maintained and patient should be recalled for oral hygiene every 2 to 3 months.

Symptoms: The patients manifest fever, sore throat, stomatitis and regional lymphadenopathy as well as headache, arthritis, cutaneous infection and conjunctivitis. Less frequently patient experience lung, urinary tract infection as well as rectal and vaginal ulcer. In some patients, amyloidosis can occur which is due to repeated, increased antigenic stimulation during neutropenic episodes. The symptoms are milder as compared to agranulocytosis. Oral features: Severe gingivitis and painful ragged ulcers that have a core like center are found on the lip, tongue, palate, gums and buccal mucosa which heal after about two weeks with scarring (Fig. 28.13). Isolated painful ulcer may occur which correspond to the period of neutropenia.

Hematological Findings

Points to Remember Periodic neutropenia, stomatitis, regional lymphadenopathy, amyloidosis, severe gingivitis, no specific treatment.

Lazy Leukocyte Syndrome It is a result of loss of chemotactic function of the neutrophils. The neutrophils present in the blood can not

Blood Pathology

migrate to the site of tissue injury although phagocytic and bactericidal activities are normal. Clinical features: It becomes apparent at the age of 1 to 2 years when complication occurs due to infections. The most common clinical manifestations are stomatitis, otitis media and bronchitis. Oral manifestations: Gingivitis and stomatitis are common oral finding of this disorder. In some cases periodontal disease may be present. Hematological findings: The total leukocyte count is slightly low but the absolute neutrophil count is as low as 100 to 200 cells/mm3. The bone marrow contains normal number of mature neutrophils. Points to Remember Loss of chemotactic function, otitis media, gingivitis, stomatitis, absolute neutrophil count is as low as 100 to 200 cells/mm3.

Chediak Higashi Syndrome It is a congenital autosomal recessive defect of granulocytes and melanocytes. Abnormal granules are seen in all blood granulocytes resulting in decreased chemotactic and bactericidal activity, although phagocytosis remains intact. Clinical features: The characteristic clinical feature of this disease consists of oculo-cutaneous albinism, photophobia, nystagmus and recurrent infections of the respiratory tract and sinuses. There may be neurological and gastrointestinal disturbances. The disease may be associated with malignant lymphoma. Oral manifestations: Ulcerations of the oral mucosa, severe gingivitis and glossitis are the common oral lesions. There may be rarely loss of teeth due to periodontal disease. Hematological findings: Hematological studies show presence of giant abnormal granules in the granulocytes in the peripheral blood as well as in their precursors in the bone marrow. Treatment: Immediate and proper treatment with antibiotics of the infection as soon as they occur is most important. Vincristine, prednisolone and ascorbic acid have been tried as the treatment of this disorder.

Points to Remember Decreased chemotactic and bactericidal activity, oculocutaneous albinism, photophobia, severe gingivitis, glossitis, giant abnormal granules, antibiotics.

Chronic Idiopathic Neutropenia It consists of group of diseases which includes familial neutropenia, chronic benign neutropenia, chronic neutropenia and hyperplastic neutropenia. Etiology is unknown, but they are characterized by a decrease in production of neutrophils below 1500/mm3 in the bone marrow. Some of ethnic group like African and Middle Eastern background will have neutrophils count constantly below 1200/mm3. But this people live healthy life. This type of neutropenia is called benign ethnic neutropenia.

Clinical Features Predominantly in females with some cases being familial. It is usually asymptomatic and free of infection which is due to compensatory monocytosis, which accounts of normal number of phagocytes at the site of tissue injury. Some patients may exhibit recurrent bacterial infections like recurring upper respiratory tract infections, otitis media, bronchitis and furunculosis. When neutrophil count falls below 500/mm3 pulmonary infection can occur.

Oral Manifestations Severe, rapidly advancing periodontal diseases. Gingivae appear intensely red with granulomatous margins. Severe gingival recession, advanced bone loss, mobility, denuded roots and loss of teeth. The second most common finding is recurring oral ulcers and in some cases, maxillary sinusitis can also occur.

Laboratory Findings The bone marrow of patients shows a normal number of immature cells but decrease in number of mature neutrophils. This is called maturation arrest. Absolute neutrophils count may below 500/mm3. Bacterial invasion of the host tissue can be seen.

Management Patient who is having infection can be given antibiotics therapy. Proper oral hygiene should be maintained.

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Patient can be given recombinant human granulocyte colony stimulating factor (G-CSF) which promotes growth and differentiation of neutrophils. 708

Sequestration in the spleen: Usually platelet is sequestered in spleen. So when splenomegaly occurs large number of platelet are sequestered.

Points to Remember

Clinical Features

Familial neutropenia, benign ethnic neutropenia, asymptomatic, recurrent bacterial infections, advance periodontal diseases, recurring oral ulcers, decrease mature neutrophils, recombinant human granulocyte colony stimulating factor.

Clinical evidence is seen when platelet count is below 100,000/mm3. Thrombocytopenic purpura is characterized by spontaneous appearance of purpuric hemorrhagic lesions of skin, which vary in size from tiny red pin point petechiae to large purplish ecchymoses and sometimes, even massive hematoma. Symptoms: The patient also exhibits a bruising tendency. Epistaxis, hematuria and melena are common findings. Intracranial hemorrhage is rare, but can be seen in children and the symptoms are headache, dizziness and confusion.

DISEASE OF PLATELET Idiopathic Thrombocytopenic Purpura It is also called Werlhof’s disease, purpura hemorrhagic and primary thrombocytopenic purpura. It is a disease in which there is an abnormal reduction in the number of circulating blood platelets with normal or raised number of megakaryocytes in the bone marrow. It is thought to be an autoimmune disorder in which a person becomes immunized and develops antibodies against his own platelets.

Causes Decrease production of platelets: It may be results of infiltration of bone marrow by malignant cells or toxic effect of cancer chemotherapeutic drugs. Increased destruction of platelets: It may be cause of immunological reaction which can be precipitated by many drugs. Most common drug is heparin.

Figure 28.14 Idiopathic thrombocytopenic purpura showing

hemorrhage

Oral Manifestations The first manifestation of the disease can be seen in oral cavity in the form of excessive bleeding after tooth extraction. Submucus petechiae and ecchymosis commonly occur especially at the junction of the hard and soft palate. It appears as numerous tiny, grouped clusters of reddish spots, only a millimeter or less in diameter (Figs 28.14 and 28.15). Petechiae do not blanch on pressure which is the distinguishing feature between purpura and telangiectasia. In severe cases, extensive spontaneous gingival bleeding may be seen and this may form foci of secondary infection.

Hematological and Histopathological Findings The platelet count is usually below 60,000 cells per cumm. The bleeding time is prolonged but, the clotting

Figure 28.15 Idiopathic thrombocytopenic purpura showing

purpuric lesion on the soft palate

Blood Pathology

Histopathological Features There are widespread microthrombi in the arterioles, venules and capillaries in all tissues and organs throughout the body. The intravascular thrombi are composed of loose aggregates or platelet that becomes organized into amorphous plugs, which are often replaced by fibrin. This fibrin deposit more readily seen on PAS stain.

Management Corticosteroids, platelet aggregation inhibitors, splenectomy and exchange transfusion. Points to Remember Figure 28.16 Purpura showing megakaryocytic hyperplasia

time is normal. The bone marrow reveals megakaryocytic hyperplasia (Fig. 28.16). When severe bleeding occurs, there may be associated iron deficiency anemia. Gingival biopsy shows presence of fibrin deposit in the small vessels. This can be seen more with PAS stain.

Management Corticosteroids, splenectomy, transfusion, local hemostatic agents should be given to control the bleeding. Points to Remember Werlhof’s disease, sequestration in the spleen, purpuric hemorrhagic lesions of skin, bruising tendency, epistaxis, bleeding after tooth extraction, petechiae, platelet count below 60,000 cells per cumm, presence of fibrin deposit in the small vessels, corticosteroids, local hemostatic agents.

Thrombotic Thrombocytopenic Purpura It is immunologically mediated. It is characterized by occlusion of small arterioles and capillaries of many organs by thrombi formed of fibrin and platelets.

Clinical Features It generally occurs in young adults and more commonly in females than in males. There is thrombocytopenia, hemolytic anemia, fever, transitory neurologic dysfunction and renal failure.

Immunologically mediated, thrombocytopenia, hemolytic anemia, microthrombi, amorphous plugs, corticosteroids, platelet aggregation.

Aldrich Syndrome It is also called Wiskott-Aldrich syndrome. It is X-linked recessive condition. Clinical features: It is characterized by thrombocytopenia, eczema, increased susceptibility to infection and a prolonged bleeding time. Patients commonly manifest boils, otitis media, bloody diarrhea and respiratory infection. There is common occurrence of malignant lymphoma, which is an important feature of this disease. Bleeding occurs from nose, skin and gastrointestinal tract. Oral manifestations: Palatal petechiae are frequently present. Spontaneous bleeding from the gingiva. Laboratory findings: Prolonged bleeding time and there is considerable anisocytosis, alternation in the size and shape of platelets with most platelets smaller than normal. There is decreased production and defective maturation of platelets since normal megakaryocytes may be seen in the marrow. Points to Remember Wiskott-Aldrich syndrome thrombocytopenia, prolonged bleeding time, palatal petechiae, spontaneous bleeding from the gingiva, anisocytosis, platelets size and shape alternation.

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Familial Thrombasthenia

Laboratory Findings

It is also called Glanzmann’s disease. It is hereditary, chronic hemorrhagic disease transmitted as an autosomal recessive trait.

The platelet count is increased and there is abnormal aggregation in response to several aggregating agents. The clotting time, prothrombin time are normal but bleeding time is frequently prolonged.

Clinical features: There is excessive bleeding, either spontaneous or following minor trauma. Both sexes may be affected and onset of menarche may be a critical event. Purpuric hemorrhages of skin are common, as are epistaxis and gastrointestinal bleeding. Hemarthrosis is also noted in some cases. Oral manifestations: Spontaneous bleeding from the oral cavity particularly gingival bleeding. Laboratory finding: Bleeding time is prolonged while clot retraction is impaired. Platelet count is normal as the clotting time. The aggregation of platelet by epinephrine, ADP and thrombin is defective. Management: No specific treatment but patient in oral surgery can be given microfibriallar collagen preparation with fibrinolytic inhibitors. Points to Remember Glanzmann’s disease, purpuric hemorrhages of skin, bleeding time is prolonged.

Thrombocytosis or Thrombocythemia It is characterized by an increase in the number of platelets in the blood in excess of 1000 × 106 /dL. It is of two types, i.e. primary and secondary.

Causes It is caused by polycythemia, myeloid leukemia, anemia, tuberculosis and sarcoidosis. Other diseases which can cause this disorders are hyperadrenalism, rheumatoid arthritis and bronchial carcinoma.

Clinical Features It is a rare disorder of the elderly associated with a tendency to bleed and to have thrombic episodes. Epistaxis, bleeding into the gastrointestinal tract as well as bleeding into the genitourinary tract and central nervous system is common. Hemorrhages in skin are also common.

Oral Manifestations Excessive and prolonged bleeding after extraction of tooth is also common.

Management Certain cytotoxic drugs, heparin, corticosteroid and aspirin in small dose may help to counter act the thrombactive tendency. It responds to radioactive phosphorus. Points to Remember Tendency to bleed, thrombic episodes epistaxis, spontaneous gingival bleeding, platelet count is increased, cytotoxic drugs, heparin.

DISEASE DUE TO CLOTTING DEFECT Hemophilia Hemophilia (hemo-blood, philia-loving) represent bleeding disorders with deficiency of clotting factor. It is a hereditary disorder of blood coagulation characterized by excessive hemorrhage due to a prolonged coagulation time. It is also called Bleeder’s disease, disease of Hapsburgs, disease of Kings. When you bleed, the body launches a series of reactions that help the blood clot. This is called the coagulation cascade. The process involves special proteins called coagulation factors. When one or more of these clotting factors are missing, there is usually a higher chance of bleeding.

Types Hemophilia A: Deficiency of factor VIII or anti-hemophilic factor is the cause of hemophilia. It is transmitted as X-linked recessive character carried on X-chromosome. The males are clinically affected and the females are carriers of the trait. Hemophilia A occurs 10 times more commonly than hemophilia B. Hemophilia B or Christmas disease: It occurs due to hereditary deficiency of factor IX or functionally defective factor IX. It is transmitted as X-linked recessive character through chromosome. It is very rare, compared to hemophilia A. In the laboratory, hemophilia A may be differentiated from hemophilia B by modification of the prothrombin consumption time or the partial thromboplastin time.

Blood Pathology

Hemophilia C: This is very rare form of hemophilia and it occurs due to deficieny of factor XI or plasma thromboplastin antecedent. 711

Types Hemophilia A, Hemophilia B or Christmas disease, Hemophilia C.

Clinical Features Sex predilection: This disorder usually affect the male and female usually carry the trait. This can be transmitted through unaffected daughter to grandson. The sons are hemophilic patient are normal and are not carrier. The heterozygous daughter carry their defect to half of their son and recessive trait to their daughters. Bleeding manifestations usually begin after 6 months of age, when the child begins to move about and tends to fall and sustain injuries, i.e. when spontaneous hemorrhage is noted by the parents. Hemarthrosis: The most common manifestation is hemorrhage into joints which is spontaneous and associated with warmth and muscle spasm. Repeated episodes cause damage to the joint with wasting of the related muscle, leading to deformity and crippling. Hemorrhage into subcutaneous tissues, internal organs and musculature also are frequent and potentially disabling complications. Superficial trauma gives rise to uncontrolled bleeding. Intracranial bleeding is relatively rare unless associated with trauma. Pseudotumor of hemophilia: Sometimes when the hemorrhage in the tissue tumor like mass may be form. This is called pseudotumor of hemophilia. In this condition there is formation of reactive new bone which cause expansion of bone. Oral manifestation: Traumatic injury of the oral cavity may lead to the diagnosis of hemophilia. The anatomic sites involved in persistent oral bleeding are the frenum of lip and the tongue (Fig. 28.17). There is prolonged bleeding after tooth extraction. Hematoma of the floor of mouth may occur and blood may spread via the fascial spaces and produce a hematoma of the larynx, with consequent respiratory embarrassment. Physiological processes of tooth eruption and exfoliation may be associated with severe and prolonged hemorrhage. Gingival hemorrhage is extremely rare and when it does occur, it is the result of gingival injury.

Figure 28.17 Bleeding seen in patient with hemophilia

Hematological Findings Clotting time is prolonged, but however the bleeding time, platelet count and prothrombin time are all normal. The prothrombin consumption time and the partial thromboplastin time may be prolonged in severe cases.

Management Replacement therapy: Various forms of replacement therapy are available like plasma, cryoprecipitate and factor VIII concentrates. The use of aspirin is strictly contraindicated in patient with hemophilia. Aspirin gives adverse effect on the blood platelet factor. Genetic counseling should be provided so that families understand the mechanism of inheritance. Optimal dental care should be done while dealing with surgery in dentistry like periodontal surgery, oral surgery. Consultation with the patient physician is mandatory while dealing with this patient. Clotting factor replacement may cause many time complications. Most common while doing cryoprecipitation (method of concentrating clotting factor from the serum) several viruses like hepatitis viruses, HIV can also become concentrated. So many hemophilic patients are affected with HIV infection. Now-a-day due recombinant DNA technology, this products can be produce without contamination of viral organism. Points to Remember Bleeder’s disease, hemarthrosis, hemorrhage into subcutaneous tissues, pseudotumor of hemophilia, persistent oral bleeding, prolonged clotting time, replacement therapy.

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It is also called pseudo-hemophilia, vascular hemophilia and vascular purpura. It is a rare disorder which is inherited as an autosomal dominant trait in which there is defect in all three components of the hemostatic mechanism; the capillaries, platelets and coagulation mechanism. It is most common hereditary clotting disorder. This is discovered by Erik Adolf von Willebrand in 1926. This is caused by genetic deficiency of plasma glycoprotein called von Willebrand’s factor. This glycoprotein helps in adhesion of platelet at the site of bleeding. This factor also binds to factor VIII acting as transport molecule. It is transmitted as an autosomal-dominant trait and thus there may be evidence of a family history of excessive bleeding. Most forms of the disease show incomplete penetrance of the phenotype and variable expressivity of bleeding symptoms within families.

Clinical Features Excessive bleeding either spontaneously or following even minor trauma, is the chief feature of the disease. The most common sites of bleeding are nose, skin. Bleeding into the gastrointestinal tract, epistaxis and severe menorrhagia are also common. Bleeding tendencies usually appear early in childhood and decrease in middle and old age. Oral features: Gingival bleeding and post-extraction bleeding are the most common oral manifestations. The disease may be discovered after dental extraction. Continuous oral bleeding over long periods of time fosters deposits of hemosiderin and other blood degradation products on the tooth surfaces, turning them brown.

Hematological Findings Prolonged bleeding time ( in some cases over 300 minutes), normal platelet count, failure of aggregation of platelets impaired adherence of platelets and depressed levels of factor VIII are suggestive of this disorder. Low AHG levels and abnormal platelet retention to glass beads. The platelet count and prothrombin consumption are normal. The clotting time usually is normal but capillary fragility is increased.

Management Bleeding episode is best controlled by transfusion of plasma and or cryoprecipitate and by local control of homeostasis.

Points to Remember Pseudo-hemophilia, excessive bleeding, gingival bleeding, epistaxis, severe menorrhagia, prolonged bleeding time, transfusion of plasma.

Plasminogen Deficiency It is also called ligneous conjunctivitis or hypoplasminogenemia. It is rare autosomal recessive disorders cause by mutation of genes responsible for production of plasminogen the precursors to plasmin.

Pathogenesis In clotting mechanism, activation of factor lead to the formation of clot. At the same time, plasminogen is converted into plasmin which is responsible for degradation of clot. In the deficiency state of plasminogen, plasmin cannot be formed so degradation of clot does not takes place. So clot tend to grow and persist.

Clinical Features Age and sex distribution: It is more common in women as compared to men. First decade of life is age of occurrence. Site: Most commonly seen on conjunctiva, laryngeal mucosa, oral mucosa and vaginal mucosa. Conjunctiva: Most common affected site is conjuctival mucosa. There is formation thick, firm plaque which is yellow in color. This resembles woodlike that is reason it is called ligneous (ligneous means woodlike). Oral lesion: They are usually patchy ulcerated papule and nodules with irregular surface seen on gingiva. They tend to wax and wane in severity.

Histopathological Feature There is accumulation of fibrin appear as diffuse sheets of acellular eosinophils material which resembles amyloid. Inflammatory cells and granulation tissue is seen adjacent to fibrin deposit.

Management Damage to tissue should be minimized. Topical heparin with prednisone may be given. Topical or systemic plasminogen yields good results. But these agents are not available commercially.

Blood Pathology

Points to Remember Ligneous conjunctivitis, thick, firm plaque on conjunctiva, patchy ulcerated papule on gingiva, accumulation of fibrin, topical heparin, topical or systemic plasminogen.

Oral features: Orally there is spontaneous gingival bleeding and excessive bleeding after dental extraction. Laboratory finding: Clotting and prothrombin time is infinite. Peripheral blood fails to clot even after addition of thrombin. ESR is zero and cells remain suspended even after 24 hours.

Factor V Deficiency or Parahemophilia

Management

It is a rare htemorrhagic disorder, clinically similar to hemophilia, caused by a deficiency of factor V or proaccelerin. It is inherited as an autosomal dominant trait affecting both sexes.

Transfusion of concentrated fibrinogen during bleeding episode. Prognosis is very poor and patient die in infancy or early childhood.

Clinical features: Spontaneous epistaxis, bleeding into the gastrointestinal tract and menorrhagia are common. Cutaneous ecchymosis and hamartomas are frequently seen, although petechiae are rare. Intraocular hemorrhage and hemorrhage into the central nervous system have been also reported.

Points to Remember

Oral manifestation: Spontaneous gingival bleeding occurs in some cases and prolonged bleeding after extraction of tooth is observed.

DYSFIBRINOGENEMIA

Laboratory finding: Both clotting and prothrombin time are prolonged but, bleeding time is normal. The basic defect is reduction in plasma proaccelerin. Management: Transfusion and freshly frozen plasma are given when there is excessive hemorrhage. Points to Remember Deficiency of factor V, spontaneous epistaxis, menorrhagia, cutaneous ecchymosis, spontaneous gingival bleeding, clotting and prothrombin time are prolonged, transfusion.

Afibrinogenemia and Hypofibrinogenemia It is also called hypofibrinogenopenia. It is very rare disease where blood does not clot as there is absence of fibrinogen. This disease can be congenital or acquired. Congenital is transmitted as autosomal recessive trait occurring in both the sexes. Acquire occur secondary to defective fibrinogen formation. Clinical features: Patient usually suffer from excessive bleeding in the lifetime. It is very difficult to distinguish it from hemophilia. There is also bleeding from nose, in gastrointestinal tract and central nervous system.

Blood does not clot, excessive bleeding, spontaneous gingival bleeding, clotting and prothrombin time is infinite, ESR is zero, transfusion, concentrated fibrinogen.

This disease is transmitted as an autosomal dominant trait which represent the group of familial disorders. In this disease fibrinogen is present in normal amount but structure is defective. Due to this aggregation of fibrin monomers is impeded. Clinically there is mild-to-severe bleeding tendency. In some cases paradoxical thrombosis is also been reported. Prothrombin time and activated partial thromboplastin time is prolonged. Fresh frozen plasma or cryoprecipitate may be transfused in case of bleeding.

Fibrin Stabilizing Factor Deficiency It occurs due to factor XIII deficiency which is discovered by Duckert in 1960. It is autosomal recessive trait. Inherited factor XIII deficiency occur due to mutation in the gene encoding located on chromosome 6. Clinical features: There is severe postsurgical bleeding episodes which can be continuous for more than a day. There is also hemarthrosis, and defective wound healing. There is also bleeding in mouth during teething. Soft tissue bleeding and bruising is also very common. Laboratory finding: Bleeding and clotting time is normal. Measurement of clot stability is diagnostic for deficiency of factor XIII.

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Management 714

Plasma, cryoprecipitate and factor XIII concentrate have been used. Points to Remember Inherited factor XIII deficiency, severe postsurgical bleeding episodes, hemarthrosis, measurement of clot stability, plasma, cryoprecipitate and factor XIII concentrate.

MACROGLOBULINEMIA It is also called Waldenstrom hypergamma-globulinemia or macroglobulinemia of Waldenstrom. This condition is describe in 1948 by Waldenstrom. It occur due to excessive proliferation of B lymphocytes which results in production of large amount of electrophoretically homogeneous IgM globulins which is characteristic of the disease. Clinical features: It is seen in older individual with no sex predilection. Patient complaint of pallor, weakness, weight loss, lymphadenopathy, and hepatomegaly. There is also hemorrhage from nasal cavity, ocular hemorrhage. Oral manifestation: There is spontaneous gingival bleeding, with continuous oozing of blood. Focal area of hypermia with bleeding oral ulcer on the tongue can also occur. Laboratory finding: There is macroglobulinemia and hyperglobulinemia. Patient manifest severe anemia. Bone marrow smears shows increase mononuclear cells.

Management Chlorambucil in high dose can produce remission in some patient. Supportive therapy with whole blood replacement is also a treatment of choice. Points to Remember Waldenstrom hypergamma-globulinemia, lymphadenopathy, pallor, spontaneous gingival bleeding, macroglobulinemia, hyperglobulinemia, chlorambucil.

MALIGNANCY INVOLVING BLOOD TISSUE Hodgkin’s Lymphoma It is lymphoproliferative disorders arising from lymph nodes and from lymphoid components of various organs (Fig. 28.18).

Figure 28.18 Enlargement of lymph nodes in Hodgkin’s

lymphoma

It was first described by British pathologist Thomas Hodgkin in 1832. It is characterized by painless enlargement of lymphoid tissue throughout the body.

Etiology Particularly Epstein-Barr and oncorna virus are being investigated as possible etiological agents. Sometimes, it can occur without any etiological factor.

Clinical Features Age and sex distribution: It is characterized by a bimodal age incidence, peak one in young adults and the second in the 5th decade of life with equal distribution between sexes. Location: The onset is insidious, usually with enlargement of one group of superficial nodes. The cervical lymph nodes are usually the first to be involved but the disease may start in the mediastinal, axillary, abdominal, pelvic or inguinal lymph nodes. Symptoms: The involved nodes are painless. Generalized weakness, loss of weight, cough, dyspnea and anorexia are seen. There is pain in back and abdomen owing to splenic enlargement, due to pressure of enlarged nodes or involvement of vertebrae. Signs: The lymph nodes are discrete and rubbery in consistency with overlying skin being freely mobile. Splenomegaly is usually seen in later stage. Some patients may manifest pruritis. Characteristic features of this disease are: ∙ Pel-Ebstein fever, a cyclic spiking of high fever and generalized severe pruritis of unknown etiology.

Blood Pathology

Pressure of enlarged lymph nodes on adjacent structures may cause dyspnea, dysphagia, venous obstruction, jaundice and paraplegia.



Clinical Stages (ANN Arbor Staging) • S tage I: Involvement of single lymph node region or extra-lymphatic sites. • Stage II: Involvement of two or more lymph node regions or an extra-lymphatic site and lymph node region on the same side of diaphragm. • Stage III: Involvement of lymph node region on the both sides or without extra-lymphatic involvement or involvement of spleen or both. • Stage IV: Diffuse involvement of one of more extralymphatic tissues, e.g. liver or bone marrow. A-No systemic symptoms B-Systemic symptoms such as weight loss, fever, night sweats are present.



– M ixed cellularity: Lymphocytes, plasma cells, eosinophils, easily identified Reed Sternberg cell. – Nodular sclerosis: Sparse lymphocytes, stromal cell, fibrosis and numerous but bizarre Reed Sternberg cell, poor prognosis. – Lymphocyte depletion: Lymphocytes, plasma cells, eosinophils with localized involvement. – Unclassified: Hodgkin’s lymphoma does not resembles any of the above criteria.

Laboratory Investigations Full blood count: Anemia which is normocytic and normochromic is a common finding. The total WBC count is normal but there may be mild eosinophilia. In the terminal stage there, may be leukopenia and thrombocytopenia. ESR and LDH is raised, liver function may be abnormal due to infiltration in liver.

Oral Manifestations

Chest radiography: It is done to permit staging.

Primary jaw lesions are uncommon. Secondary effect can be seen in oral cavity in the form of infection due to reduced host immune response.

Management

Appearance: It may appear in the oral cavity as an ulcer or a swelling or as an intra-bony lesion which presents as a hard swelling.

Histopathological Features It is characterized by replacement of normal lymph node architecture by an admixture of malignant lymphoid cells and non-neoplastic inflammatory cells. Reed Sternberg cells: There are sheets of lymphoid cells with interposed vacuolated spaces containing characteristic bi-nucleated mononuclear cells (owl-eye nuclei). Multinucleated giant cells are also present. Popcorn cells: Malignant cells in lymphocytes predominant resembles the nucleus to kernel of popped corn. Histological Types • N odular lymphocytes predominant Hodgkin’s lymphoma • Classical Hodgkin–lymphoma

– L ymphocyte rich: Abundant lymphocytes, few plasma cells, occasional Reed Sternberg cell, localized involvement on one side of diaphragm and most favorable prognosis.

Radiotherapy: Irradiation treatment 3500 to 4000 rads/ week over the involved region plus all adjacent sites been given in stage I and II. It is also given after chemotherapy, to sites where there was originally bulk disease. Chemotherapy: It is given in stage III and IV. Usually combination is given. First combination is MOPP, i.e. mustine HCl (6 mg/m 2 IV on day 1 and day 8), oncovin which is also called vincristine (1.4 mg/m 2 IV on day 1 and 8), procarbazine (100 mg/m 2) orally from day 1 to 14) and prednisone (40 mg/m 2 orally from day 1 to 14). MOPP combination given in six courses with no drugs is given from day 15 to 28. Second combination is ABVD regimen i.e. adriamycin (25 mg/m 2 IV bolus on day 1,8 and 14), bleomycin (10 mg/m 12 bolus on day 1,14) vinblastine (6 mg/m 2 IV bolus on day 1,14) and decarbazine (375 mg/m 2 IV bolus on day 1,14). The cycle should be repeated on 20th day. Combination: A combination of radiotherapy and chemotherapy may increase the overall response and longterm survival but, it is associated with delayed complications like leukemia, gonadal atrophy and avascular necrosis of bone. Splenectomy: Splenectomy is advocated in many patients, except with stage IV disease.

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Lymphoproliferative disorders, enlargement of one group of superficial nodes, painless, loss of weight, cough, dyspnea, lymph nodes are discrete and rubbery in consistency, Pel-Ebstein fever, cyclic spiking of high fever, oral cavity as an ulcer or a swelling, admixture of malignant lymphoid cells, Reed Sternberg cells, owl-eye nuclei, Popcorn cells, ESR and LDH is raised, radiotherapy, chemotherapy, splenectomy.

Non-Hodgkin’s Lymphoma It is also called lymphosarcoma. In this group, there is neoplastic proliferation of lymphoid cells, usually affecting the B-lymphocytes. Unlike Hodgkin’s lymphoma, the disease is frequently widespread at the time of diagnosis, often involving not only the lymph nodes but also bone marrow, spleen and other tissue. Early involvement of bone marrow is typical of this lymphoma. Types • Nodular • Diffuse

Etiology The etiology is unclear but Epstein-Barr and herpes virus etiology has been suggested. There may be induced immunologic effect permitting a malignant clone to proliferate.

Clinical and Radiological Features Age and sex distribution: It affects persons of all ages from infants to the elderly, but is most common in middle age group. Males are affected more commonly than the females. Location: In the oral cavity it frequently occurs in tonsils. The other sites affected are salivary glands or jaws. Symptoms: The onset of symptoms may be insidious. The patient complaint of tiredness, loss of weight, fever and sweating. Pain is the main symptom of bone involvement which may present as a pathological fracture. Patient may complain abdominal pain, nausea, vomiting, diarrhea or intestinal obstruction which may occur due to involvement of gastrointestinal tract.

Lymph nodes: Painless lymph node enlargement of abdominal and mediastinal region is the most common finding. Very often the first group of lymph nodes affected may be cervical, axillary or inguinal. Signs: Pressure effect of lymphoma may cause dysphagia, breathlessness, vomiting, intestinal obstruction or ascites and paraplegia. If liver and spleen are involved hepatosplenomegaly is present. The growth is fleshy and is prone to ulceration.

Oral Manifestations Occurrence of malignant lymphoma in oral cavity is rare, when present it is more often found to arise from the tonsils, although other oral tissue may also be involved. Palatal lesions have been described as slow growing, painless, bluish soft tissues mass which may be confused with minor salivary gland tumors. Paresthesia of mental nerve has been reported. Sometimes there is pain and neuralgia in the region of 2nd and 3rd division of 5th cranial nerve. In rare cases necrotic proliferation of palate may also be seen. The swelling may ulcerate.

Radiographic Features It shows ill defined or ragged radiolucency. In later stage it may caused expansion of the bone which can perforate the cortex.

Histopathological Features Nodular or follicular: In the nodular pattern, the neoplastic cells tend to aggregate in such a way that large clusters of cells are seen. Diffuse: Diffuse pattern is characterized by a monotonous distribution of cells (Fig. 28.19) with no evidence of nodularity or germinal center pattern. If it arises in lymph node, then tumor destroyed normal architecture of nodes.

Laboratory Investigations Blood count usually shows normal levels but if there is associated hypersplenism or hemolytic anemia the reduced WBC and RBC counts are seen along with reduced hemoglobin levels and reticulocytosis. In some cases there may be slight increase in lymphocytes and thrombocytopenia.

Blood Pathology

PRIMARY RETICULAR CELL SARCOMA It is also called primary lymphoma of bone. 717

Clinical Features Age and sex distribution: It can occur in any age group but it is common amongst young adults under the age of 40 years. It is common in males as compared to females. Location: It is most commonly seen in femur, tibia and humerus. Signs and symptoms: It is usually asymptomatic except for the presence of localized swelling of the involved bone. Regional lymphadenopathy is usually present. Figure 28.19 Diffuse distribution of monotonous abnormal

lymphocytes invading the connective tissues

Moderate degree of anemia will also present when there is considerable bone marrow involvement. Some very aggressive high grade non-Hodgkin lymphomas are associated with very high orate levels which can precipitate renal failure.

Management Chemotherapy: When diagnosed in late stages, chemotherapy is the treatment of choice. In most cases single agent chemotherapy (chlorambucil) is usually given. Combination with prednisolone is also useful. A combination of cyclophosphamide, doxorubicin, vincristine, bleomycin with prednisolone is commonly used. Radiotherapy: Radiotherapy is used to treat local disease and the patient is given a total dose of 150 rads spread over a period of five weeks. Transplantation: Studies of autologous stem cell transplantation are in progress. Points to Remember Lymphosarcoma, Epstein-Barr, herpes virus, tonsils, tiredness, loss of weight, fever and sweating, painless lymph node enlargement of abdominal and mediastinal region, dysphagia, breathlessness, vomiting, intestinal obstruction or ascites and paraplegia, paresthesia of mental nerve, slow growing, painless, bluish soft tissues mass, ill-defined or ragged radiolucency, expansion of the bone, nodular or follicular, diffuse, moderate degree of anemia, slight increase in lymphocytes, chemotherapy, radiotherapy, transplantation.

Oral Manifestations It is not common, but it usually occurs more in mandible than maxilla. Symptoms: Pain is common complaint and usually present for years and more. Signs: There is also presence of expansile mass. The oral mucosa over the involved bone seldom gets ulcerated but at times, appears diffusely inflamed. The teeth usually become exceedingly loose, owing to destruction of bone. When the lesion involves maxilla, there may be evidence of expansion of the bone as well as symptoms of nasal obstruction due to superior growth of tumor into the floor of nasal cavity.

Histopathological Features The primary cells of tumor are identical with that of the soft tissue tumors. There may be inflammatory cell infiltration which can lead to confusion in the diagnosis of the lesion. The individual cells are mixed with both mature appearing lymphocytes and large histiocytoid lymphoblast.

Management Surgical excision or X-ray radiation, as it appears to be radiosensitive. The 5-year survival rate is between 50 and 60 percent. Points to Remember Primary lymphoma of bone, asymptomatic, localized swelling, oral mucosa over the involved bone seldom gets ulcerated, destruction of bone, inflammatory cell infiltration, large histiocytosis lymphoblast.

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MYCOSIS FUNGOIDES 718

It is also called cutaneous T-cell lymphoma. It usually affects the skin. Mycosis fungoides exhibits epidermotrophism (i.e. propensity to invade the epidermis of skin).

Clinical Features Age and sex distribution: It is usually seen in adults with male predilection in male in the ratio of 2:1. Appearance: The disease commences with eczematous lesion, which gradually develop into thickened plaques. Size: It varies in size from few millimeters to centimeters in diameter and finally spread to lymph nodes, spleen and liver. Eczematous stage (erythematous stage): There are well demarcated, scaly erythematous patches with pruritus.

Figure 28.20 Erythematous lesion seen in myocosis fungoides

Plaque stage: Erythematous patches developed into elevated red lesion

microabscess. In some cases, nuclei are so convoluted that they are described cerebriform due to infolding of nuclear membrane.

Tumors stage: Plaque become papules and nodules. In this stage visceral involvement occur.

Tumors stage: There is a dense and diffuse infiltration of lymphoid cells with irregularly shaped nuclei.

Sezary syndrome: There is generalized exfoliative erythroderma, lymphadenopathy, hepatomegaly, splenomegaly with involvement of lung, kidney and CNS. It results in patient death in short period of time.

Management

Oral Manifestation Oral lesions can be the first manifestations and sometimes appear after the skin lesions have been treated and remitted. Location: It is occur on tongue, palate, buccal mucosa, lip, gingiva and tonsil. Appearance: The lesions appear as indurated areas, nodules or erythematous ulceration (Fig. 28.20).

Histopathological Features Eczematous stage: In this psoriasiform pattern of epithelial alteration is seen. Scattered, slightly atypical lymphocytes with parakeratin production seen in the connective tissue papilla of mycosis fungoides. There is also elongation of epithelial rete pegs. Plaque stage: There is infiltration by atypical lymphocytes cells which are called mycosis cells or Sezary cells. Mycosis cells form small intraepithelial aggregates called Pautrier’s

Topical nitrogen mustard, topical carmustine, electron beam therapy, topical corticosteroids and PUVA therapy are effective in mycosis fungoides. Points to Remember Cutaneous T-cell lymphoma, eczematous stage (erythematous stage), plaque stage, tumors stage, Sezary syndrome, oral lesions can be the first manifestation, indurated areas, nodules or erythematous ulceration on tongue, psoriasiform pattern of epithelial alteration, parakeratin production, mycosis cells or Sezary cells, Pautrier’s microabscess, cerebriform, dense and diffuse infiltration of lymphoid cells, topical nitrogen mustard, topical carmustine, electron beam therapy, PUVA therapy.

BURKITT’S LYMPHOMA It was described by Dennis Burkitt in 1950. It is also called African jaw lymphoma. It is a lymphoreticular cell malignancy. In the African form jaw involvement is 75 percent and in cases of the American form, abdomen involvement is more common. It is a B cell neoplasm.

Blood Pathology

Etiology Epstein-Barr virus (EBV) which also causes nasopharyngeal carcinoma and infectious mononucleosis is considered to be the etiological factor. There are higher EBV antibody levels patients of Burkitt’s lymphoma patients. Types • A frican Burkitt’s lymphoma: It is seen in African children with predilection of jaw • American Burkitt’s lymphoma: It is seen other countries with predilection for abdominal • Immunodeficiency associated Burkitt’s lymphoma: It is seen in HIV patients • Endemic Burkitt’s lymphoma: It is seen in Brazil in increase prevalence.

Clinical Features Age and sex distribution: Peak incidences in children between 6 and 9 years. Males are affected more commonly than the females, with a ratio of 2:1. Location: It is more are found in maxilla than in mandible, where it may spread rapidly to the floor of the orbit. Almost always occurs in molar area. In the African form more than one quadrant is involved while in the American form, only one quadrant is involved. The most important hallmark of this tumor is readily of growth with a tumor doubling time of less than 24 hours.

of arch and occlusion. There may be large quantity of mass protruding into the mouth, on the surface of which may be seen rootless, developing permanent teeth. Progress of lesion: Once the tumor perforate the bone it is initially confined by the periosteum, but subsequently it spreads to the soft tissues of the oral cavity and face where rapid tumor growth soon obliterates the entire face and skin becomes tense and shiny.

Radiological Features There is radiolucent destruction of bone with ragged and illdefined margin. There is also patchy loss of lamina dura.

Histopathological Features Monotonous sea of undifferentiated monomorphic lymphoreticular cells, usually showing abundant mitotic activity is seen. There is hyperchromatosis and loss of cohesiveness. Macrophages with abundant clear cytoplasm often containing cellular debris scattered throughout the tumor producing a very characteristic starry sky appearance (Fig. 28.21). This appearance occurs due to less intensely stain macrophages in comparisons with surrounding tissue. Macrophages appear as star against night sky of deeply hyperchromatic neoplastic lymphoid cells. Nuclei are uniform in size, mostly round but occasionally may be ovoid with a slight indentation. The nuclear membrane is prominent.

Signs and symptoms: The most common presenting features are swelling of the jaws, abdomen and paraplegia. It is painless. Peripheral lymphadenopathy is common.

Oral Manifestations It begins generally as a rapidly growing tumor mass of the jaws, destroying the bone with extension to involve maxillary, ethmoid and sphenoid sinus as well as orbit. There may be loosening or mobility of permanent teeth. There is gross distortion of the face due to swelling. Paresthesia and anesthesia of inferior alveolar canal or other sensory facial nerves is common. Gingiva and mucosa adjacent to the affected teeth become swollen, ulcerated and necrotic. As the tumor mass increases, the teeth are pushed out of their sockets. Swelling of the jaw occurs and it may cause facial asymmetry. They are capable of blocking nasal passages, displacing orbital contents and eroding through skin. There is derangement

Figure 28.21 “Starry sky” appearance- Burkitt’s lymphoma

showing uniform distribution of lymphocytes and macrophages with clear cytoplasm interspersed between giving the characteristic appearance

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2nd • Acute lymphoblastic leukemia – L1 : Acute lymphoblastic (principally pediatric) – L2 : Acute lymphoblastic (principally adults) – L3 : Burkitt’s lymphoma • Acute non-lymphoblastic or myeloid leukemia – M0: Myeloblastic (without maturation) – M1: Myeloblastic (with little maturation) – M2: Myeloblastic (with maturation) – M3: Promyelocytic – M4: Myelomonocytic – M5: Monocytic – M6: Erythroleukemia – bizarre, multinucleated, – M7–Megakaryocytic • Chronic lymphatic leukemia • Chronic myeloid leukemia

It is rapidly fatal in the absence of treatment, with death occurring within 6 months. Cytotoxic drugs like cyclophosphamide 40 mg/kg in single IV administration and repeated about 2 weeks later. Vincristine and methotrexate have been successful in some cases. Combination of drugs such as cyclophosphamide, vincristine and methotrexate give better results than any single drug. Majority of patients show dramatic response to the therapy. The swelling regresses and the displaced teeth return to their normal position within 1 to 2 weeks. Points to Remember African jaw lymphoma, EBv virus, maxilla than in mandible, peripheral lymphadenopathy, swelling of the jaws, abdomen and paraplegia, doubling time of less than 24 hours loosening or mobility of permanent teeth. There paresthesia and anesthesia of inferior alveolar canal is teeth are pushed out, derangement of arch and occlusion, patchy loss of lamina dura, radiolucent destruction of bone with ragged and ill-defined margin, undifferentiated monomorphic lymphoreticular cells, usually showing, hyperchromatosis, loss of cohesiveness, macrophages, starry sky appearance, vincristine and methotrexate, cyclophosphamide, vincristine and methotrexate.

Leukemia It is also called leukosis. It is defined as a neoplastic proliferation of WBC in bone marrow, usually in circulating blood and sometimes in other organs such as liver, spleen and lymph nodes. Presence of leukemic cells in bone marrow results in impairment of normal hemopoiesis with resultant anemia, granulocytopenia and thrombocytopenia. Leukemia is a progressive and fatal condition causing death from hemorrhage and infection. There is presence of excessive number of abnormal cells in the peripheral blood but leukemia is considered a primary disorder of bone marrow. Classification 1st • Stem or blast cell leukemia • Subleukemia • Aleukemia • Leukemoid reaction

Types ∙ ∙ ∙ ∙

Stem or blast cell leukemia: When the leukemic cells are too immature to be classified as to cell type, the leukemia is termed as ‘stem’ or ‘blast’ cell leukemia. Subleukemia: When the total WBC is normal and leukemic cells are seen in the peripheral blood is termed as subleukemia. Aleukemia: When no abnormal leukocytes can be found in the peripheral blood (i.e. they can be found only in the bone marrow) the term aleukemia is used. Leukemoid reaction: When the peripheral blood picture in non-leukemic patient resembles that of leukemia it is called a leukemoid reaction. In this, absolute neutrophil count remains above 30,000/mm3.

Classification Acute Acute lymphoblastic leukemia ∙ L1: Acute lymphoblastic (principally pediatric)–in it, small cells predominate and nuclei are generally round. ∙ L2: Acute lymphoblastic (principally adults)–cells are heterogeneous in size and sharp in features, nuclei often show cleft. ∙ L3: Burkitt’s lymphoma–there is homogeneous population of large cells. Nuclei are round to oval with prominent nucleoli. Acute non-lymphoblastic or myeloid leukemia ∙

M0-Myeloblastic (without maturation): Myoblasts predominate with distant nucleoli, few granules are present.

Blood Pathology

∙ ∙ ∙ ∙ ∙ ∙ ∙

M1: Myeloblastic (with little maturation) M2–Myeloblastic (with maturation): Myeloblast and promyelocytes predominate and Auer rods are seen. M3–Promyelocytic: Hypergranular promyelocytes often with Auer rods are seen. M4–Myelomonocytic: Myelocytic and monocytic differentiation evident, myeloid elements resemble peripheral monocytosis. M5–Monocytic: Promonocytes or undifferentiated blast. M6–Erythroleukemia: Bizarre, multinucleated, megaloblastoid erythroblast predominate. M7–Megakaryocytic: Pleomorphic undifferentiated blast cells with anti-platelet antibodies, myelofibrosis is present.

Chronic ∙ ∙

Chronic lymphatic leukemia (lymphogenous, lymphocytic) involving lymphocytes series. Chronic myeloid leukemia (myelogenous, myelocytic) leukemia involving granulocyte series.

Etiology Virus: Epstein-Barr virus, herpes like virus and HTLV (human T-cell leukemic virus) have been considered to be the etiological agents responsible for leukemia. Radiation and atomic energy: If given over the dose of 100 rads, it is known to significantly increase the risk of leukemia. Leukemia among radiologists and Japanese exposed to the atomic blast are more, as compared to other population. It is also common in patients receiving X-radiation for rheumatoid spondylitis.

Immunological deficiency syndrome: The persons suffering with Wiskott-Aldrich syndrome can develop leukemia.

Acute Leukemia Acute leukemia is a disorder in which there is a failure of maturation of leukocytes. As a results, there is an accumulation of immature cells within the bone marrow and later in the blood. It is the most common type of leukemia.

Pathophysiology There is a block in differentiation of leukemic and stem cells and leukemic blasts have prolonged, rather than shortened generation time. Thus, accumulation of leukemic blast in acute leukemia results primarily from failure of maturation into functional stage. As leukemic blast accumulates in the marrow, they suppress the normal hematopoietic stem cells. The mechanism is not fully understood. Suppression part is related to physical replacement of normal precursor cells by expanded clones of leukemic cells. Clinical manifestations result from paucity of normal red cells white cells and platelets, this occur due to myelophthisic anemia, i.e. crowding out of the normal hematopoietic stem cells by malignant proliferation.

Clinical Features Age and sex distribution: It is more common in children and young adults between the age of 15 and 39 years. Males are affected more commonly than females with a ratio of 3:2. There is abrupt stormy onset with pyrexia and enlargement of spleen.

Anticancer drugs: Patient treated with anticancer drug like melphalan and chlorambucil have an increased risk of developing leukemia, usually of acute myelocytic variety.

Symptoms: usually results, from bone marrow suppression and infiltration of other organs and tissues by leukemic cells. Weakness, fever, headache, generalized swelling of lymph nodes, petechiae or hemorrhage in skin and mucous membrane are seen. There is bone pain and tenderness, resulting from marrow expansion, with infiltration of subperiosteum. Central nervous manifestations such as headache, vomiting, nerve palsies resulting form meningeal spread which more common in children than in adults; and more common in ALL than AML.

Genetic and chromosomal factors: Philadelphia chromosome is found in about 15 percent of cases of acute lymphocytic leukemia. It suggests that if one set of identical twins develop leukemia before the age of 6 years, the risk of disease in other twins is 20 percent.

Signs: The clinical features are due to anemia and thrombocytopenia viz pallor, dyspnea, fatigue, petechiae, ecchymosis, epistaxis and melena. Hepatosplenomegaly is present in later stages. There is an increased susceptibility to infection.

Chemical agents: Chronic exposure to aniline dyes; benzene and phenylbutazone have been recognized to be associated with leukemia. Usually in these patients pancytopenia due to marrow hyperplasia occurs prior to leukemia.

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Cervical lymphadenopathy, secondary to pharyngeal sepsis is seen. Intracranial and subarachnoid hemorrhage may result from thrombocytopenia and leukastasis (intravascular clumping of leukemic blasts in the small blood vessels of brain). There is recurrent infection of lungs, urinary tract skin, mouth, rectum and upper respiratory tract, which may result in fever. Chloroma: Localized tumors consisting of leukemic cells are called chloromas, surface of which turn green (chlor) when exposed to light because of the presence of myeloperodioxase.

Oral Manifestations The submental, cervical and pre- and post-auricular lymph nodes may be enlarged and tender. Paresthesia of lower lip and chin may be present. There may be toothache due to leukemic cell infiltration of dental pulp. The oral mucous membrane shows pallor, ulceration with necrosis, petechiae, ecchymosis and bleeding tendency (Figs 28.22 and 28.23). There may be massive necrosis of lingual mucosa with sloughing. There may be crusting of lip occur due to repeated bleeding from lip.

Hematological Findings The total WBC count may vary from a very low count less than 1X106 per cumm to as high as 5000 X 106 per cumm or more. The peripheral smear shows significant number of immature granulocytes or lymphatic precursors or even stem cells. Bone marrow is hypercellular with replacement of normal marrow elements by leukemic blast cells in varying degree. There is an associated normochromic anemia, thrombocytopenia and decrease in normally functioning neutrophils.

Management Phase of induction: It is treated using combination of vincristine (1.4 mg/m 2 every week of 1 month), L-asparaginase (600 units/m 2 biweekly for 1 month) and prednisone (40 mg/m 2 orally daily for 1 month). As the leukemic cells regress, regrowth of normal cells occurs and the patient goes rapidly into remission. Phase of consolidation: In it, drugs uses include daunorubicin, mercaptopurine, cytarabine and methotrexate with intra-thecal therapy using the last two drugs, together with irradiation of the cranium to eradicate, the disease from central nervous system. Radiation reduces the risk of relapse in central nervous system when given with methotrexate.

Gingival hypertrophy: Gingiva shows hypertrophy and cyanotic discoloration. The hypertrophy may be due to leukemic cell infiltration within gingiva or due to local irritants. The gingiva appears boggy, edematous and deep red bleed easily due to ulceration of sulcus epithelium and necrosis of underlying tissue. Mobility of permanent teeth may be present. Oral infections (candidal, viral and bacterial) are serious and potentially fatal complication in leukemic patients.

Transplantation: Allogenic bone marrow transplantation from HLA identical twin is done. Ablative therapy has

Figure 28.22 Bleeding occur from lip in patient of leukemia

Figure 28.23 Crusting of lip occur in patient of leukemia

Phase of maintenance: In this phase, patient receives a repeating cycle of above drugs until two or three years have been completed.

Blood Pathology

been utilized to eradicate the patient’s residual leukemic cells and normal cells with intensive irradiation and chemotherapy. After this reconstruction of the hemopoietic tissue is done with precursor cells from the donor. Acutenon-lymphoblastic leukemia is treated with daunorubicin, cytarabine and 6-thioguanine. All these drugs are very toxic to the normal as well as leukemic cells and therefore, treatment is given in pulses to reduce toxicity. Catabolic products of leukemic cells produce uric acid and cause hyperuricemia, which is prevented by allopurinol. Supportive therapy: Transfusion of red cells and platelets may be required in cases of severe anemia and thrombocytopenia. Combination of higher antibiotics like aminoglycosides with cephalosporin, allopurinol, before starting anti-leukemic agents are given to prevent hyperuricemia. Topical treatment to stop gingival bleeding includes removing obvious local irritants and direct pressure. Use of absorbable gelatin or collagen sponge topical thrombin is helpful. The management of oral ulcers includes topical antibacterials with povidone iodine solution, chlorhexidine rinses or tetracycline rinses. Psychological support is very important as delusion, hallucinations and paranoia are not uncommon during periods of severe bone marrow failure. Points to Remember

Pathophysiology It is associated with the presence of a distinctive chromosomal abnormality, i.e. philadelphia chromosome.

Clinical features Age and sex distribution: The disease occurs chiefly between the age of 35 to 60 years. The disease may be discovered during routine examination, when splenomegaly or an elevated count is noted. Symptoms: There may be slowly advancing anemia with loss of weight, prominence of abdomen and discomfort in the left upper quadrant due to splenomegaly. Attacks of acute left upper abdominal pain may develop due to infarction of spleen. Anemia causes weakness, fatigue and dyspnea on exertion. Signs: As the disease progress thrombocytopenia can cause petechiae, ecchymosis as well as hemorrhage from the skin and mucous membrane. Liver may be enlarged but lymph nodes are normal.

Hematological Findings Examination of blood shows a normocytic and normochromic anemia. WBC count is considerably increased and may be between 50 × 106 and 500 × 106 cells per cu mm. Peripheral smear shows mature leukocytes but, few immature forms may also be present (Fig. 28.24). The platelet count is often high initially but with treatment, it comes down.

Failure of maturation of leukocytes, marrow suppression and infiltration of other organs, headache, vomiting, nerve palsies, pallor, dyspnea, fatigue, petechiae, ecchymosis, cervical lymphadenopathy, chloroma, paresthesia of lower lip, bleeding tendency, pallor, ulceration with necrosis, petechiae, ecchymosis, gingival hypertrophy, WBC count less than 1 × 106 per cumm, immature granulocytes, bone marrow is hypercellular, phase of induction, phase of consolidation, phase of maintenance, transplantation, allopurinol, topical treatment to stop gingival bleeding, psychological support.

CHRONIC MYELOID LEUKEMIA Chronic leukemias are characterized by the presence of large leukemic cells and differentiated WBCs in the bone marrow, peripheral blood and other tissues. It has a prolonged clinical course even without therapy.

Figure 28.24 Chronic myeloid leukemia showing abundant

mature monocytes (mo) in the blood smear

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The treatment of choice is chemotherapy using the drug busulfan given orally in a dose of 4 mg daily or in large doses of 50 to 100 mg spaced 2 to 3 weeks apart. The treatment is continued for 12 to 18 weeks and should be discontinued when WBC count is between 10 x×106 and 20 × 106/cumm, other wise busulphan may cause aplasia of the bone marrow. A combination chemotherapy using a small dose of busulphan 2 mg daily along with mercaptopurine 50 mg daily or thioguanine 80 mg daily is given. Radiotherapy and splenectomy are other treatment of choice. Points to Remember Slowly advancing anemia with loss of weight, prominence of abdomen, weakness, fatigue, petechiae, ecchymosis as well as hemorrhage, WBC count is considerably increased, mature leukocytes, busulfan, combination chemotherapy, mercaptopurine 50 mg daily or thioguanine 80 mg daily.

compression of the central or peripheral nervous system. The most common groups of lymph nodes involved are cervical, axillary and inguinal group. Clinical Staging • S tage A: Lymphocytosis is less than three areas of lymphoid enlargement, no anemia or thrombocytopenia. • Stage B: More than three areas of lymphoid enlargement, no anemia or thrombocytopenia. • Stage C: Anemia or thrombocytopenia, regardless of number of area of lymphoid enlargement.

Oral Manifestations The most common oral finding is hypertrophy of gingiva. Sign and symptoms: There may be ulceration with necrosis and gangrenous degeneration; a dark brown exudate and foul fetor oris are present. The tongue is frequently swollen and dark. There is regional lymphadenopathy. Rapid loosening of teeth due to necrosis of periodontal ligament has been reported. Destruction of alveolar bone also occurs in some cases.

CHRONIC LYMPHATIC LEUKEMIA

Hematological Findings

It is a slowly progressing malignancy involving lymphocytes.

Peripheral blood smear shows mild anemia and a large number of small lymphocytes. Lymphoblasts are rare but increase in the terminal stages of disease. WBC count may increase up to 1000 × 106 per cumm.

Pathophysiology It is characterized by the accumulation of long lived, nonfunctional B lymphocytes.

Clinical Features Age and sex distribution: It occurs more frequently in males and majority of the patients are over 45 years. The onset is very insidious. Symptoms: Tiredness and ill health are common, although some patients are symptom free and the disorder is found incidentally. Bone marrow infiltration causes anemia and thrombocytopenia and results in pallor, weakness, dyspnea and purpura. Signs: There is a moderate enlargement of lymph nodes which are firm, rubbery and discrete. Liver and spleen are usually enlarged and palpable. There is an increased susceptibility to infection as the leukemic B cells are nonfunctional. Leukemic infiltration results in skin nodules, intestinal malabsorption, pulmonary obstruction or

Management General measure to maintain good health, adequate rest, good food and exercise should be advised. Chemotherapy: Chlorambucil 6 to 10 mg/day for 14 days with break of 14 days and cyclophosphamide 2 to 3 mg/kg IV for 6 days. Combination therapy: Cyclophosphamide doxorubicin, vincristine and prednisone have been recommended. Radiotherapy: It is useful for large granular masses, if they cause symptoms. Radiotherapy with very small doses, of only 150 rads over a period of five weeks, is very effective and may induce satisfactory remission. Steroids: If the bone marrow is severely involved initial treatment with prednisone 40 mg daily and 25 to 50 mg daily later should be given.

Blood Pathology

Variation of Leukemia Hairy leukemia: It a variant of chronic lymphatic leukemia in which there is splenomegaly, severe neutropenia, monocytopenia and the characteristic appearance of hairy cells in blood and bone marrow. These hairy cells appear to be a cross between the lymphocytes and monocytes. It occurs mainly in adults and show male predilection. Manifestations result from infiltration of bone marrow, liver, and spleen. Splenomegaly is massive and hepatomegaly is less common. Hairy cell can be identified on the peripheral smear. Prolymphocytic leukemia: It is another variant of chronic lymphatic leukemia in which there is massive splenomegaly with little lymphadenopathy and a very high WBC count. The characteristic cell is a large lymphocyte with prominent nucleus. Aleukemic leukemia: It is the sub-leukemic form of leukemia in which the WBC count of the peripheral blood is normal or even subnormal and abnormal or immature leukocytes may be present. Points to Remember Tiredness and ill health, anemia and thrombocytopenia, moderate enlargement of lymph nodes, increased susceptibility to infection, hypertrophy of gingiva, rapid loosening of teeth, mild anemia, lymphoblasts, WBC count may increase up to 1000 × 106 per cumm, chemotherapy, combination therapy, radiotherapy, steroids.

MULTIPLE MYELOMA It is also called myelomatosis. It is a malignant neoplasm of plasma cells of the bone marrow with widespread involvement of the skeletal system, including the skull and jaws.

Origin It is thought to be multicentric in origin. There is proliferation of a single clone of abnormal plasma cells in the bone marrow. Normal plasma cells are derived from B cells and produce immunoglobulin, which contain heavy and light chain. In myeloma, plasma cells produce immunoglobulin of single heavy and light chain, a monoclonal protein commonly referred as para protein.

In some cases, only light chains are produced and these appear in urine as Bence Jones proteinuria.

Clinical Features Age and sex distribution: The most common age group affected is between 40 and 70 years with male to female ratio 4:1. The skull, clavicle, vertebrae, ribs, pelvis, femur and jaws are involved. Symptoms: Skeletal pain associated with motion or pressure over the tumor masses, is an early symptom. Spontaneous pathological fracture with acute pain may be present. Weakness and pain of back and thorax also may be presenting symptoms. Pain in the involved bone may be aggregated by exercise and relieved by rest. The patient may also complain of tiredness, bleeding tendency and bruising of skin due to anemia and thrombocytopenia. The cause of bleeding is that the abnormal globulins bind with coagulation factors which also increase the viscosity of blood. Patient may complain of vomiting due to increase serum calcium level. Signs: Swelling over the areas of bone involvement may be detectable. There is an increased susceptibility to infection due to abnormal immunoglobulin production by the plasma cells. Hypercalcemia: Mobilization of calcium from the skeleton may cause hypercalcemia resulting in nephrocalcinosis, lethargy, drowsiness and eventually coma, if untreated. Complication: The common cause of death is renal failure, caused by accumulation of abnormal proteins in the renal tissue.

Oral Manifestations Location: Mandible is more commonly involved than the maxilla and particularly angle of the mandible, because of its greater content of marrow. Lesions have also been reported in temporomandibular joints. Symptoms: The patient may experience pain, swelling and numbness of the jaw. Epulis formation or unexplained mobility of teeth are also detectable. Signs: Intraoral swelling tends to be ulcerated, rounded and bluish red similar to a peripheral giant cell lesion. Sometimes, swelling may erode buccal plate and produce rubbery expansion of jaw. Chronic trauma produces an inflamed and ulcerative necrotic surface.

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Secondary signs of bone marrow involvement such as pallor of oral tissue, intraoral hemorrhage and susceptibility to infection may also be seen. 726

Excessive hemorrhage may be caused by thrombocytopenia, secondary to increased proliferation of the plasma cells in marrow. On palpation, swelling is tender and eggshell cracking may be elicited. Oral amyloidosis: It is a complication of this disease. The tongue may be enlarged and studded with small garnetcolored enlargements, including nodes on lip and cheeks. Tongue enlargement may cause impairment of speech, mastication and deglutition. Amyloid can also deposit in the gingivae, where it can cause soreness and inability to wear dentures.

Radiological Features There is multiple well-defined punch out radiolucency. The margins of radiolucency are usually well-defined (Fig. 28.25).

Histopathological Features

in cartwheel (Fig. 28.26) or checkerboard pattern. Russell bodies are common finding in multiple myeloma.

Hematological Findings Bone marrow examination shows an increased number of abnormal plasma cells. There is usually an associated anemia but, WBC and platelet counts are normal. There is increased ESR, serum monoclonal immunoglobulin with reversal of the albumin globulin ratio and increase in total serum protein to a level of 8 to 16 gm%. Bence Jones proteins, which coagulate when the urine is heated to 40°C can be demonstrated in the urine of patients suffering from multiple myeloma. There may be hyperproteinemia due to increase in globulins.

Management Chemotherapeutic agents: General disease is treated with chemotherapeutic agents like melphalan and cyclophosphamide.

Microscopically, it can be classified as plasmocytic or plasmoblastic. The plasmocytic is characterized by small normal appearing plasma cells with a low mitotic index as is associated with a comparatively better prognosis than the plasmoblastic type. The plasmoblastic type shows infiltration by immature, nucleated plasma cell precursors and has a less favorable prognosis. Plasma cells are round or ovoid cells with eccentrically placed nuclei exhibiting chromatin clumping

Management of anemia and hypercalcemia: Patients who present with anemia, hypercalcemia, evidence of renal damage require urgent management with alkalization of urine with oral bicarbonates, high fluid intake, corticosteroids and possibly mithramycin to reduce calcium level.

Figure 28.25 Punched out lesion seen in multiple myeloma

Figure 28.26 Multiple myeloma showing cartwheel pattern

Blood transfusion: It may be required if Hb is less than 10 g/dL. Cell transplantation: Stem cell auto transplant may improve quality of life and prolong survival.

Blood Pathology

Radiotherapy: This is effective for localized pain not responding to simple analgesics and for pathological fractures. Bi-phosphonate therapy: It may reduce bone pain and skeletal events. Others drugs: Alpha interferons may prolong the plateau phase. Inorganic fluoride phosphate to reduce bone pain.

in mucous membranes, which become lobulated as they enlarge but exhibits the tendency to ulcerate. Pain is not prominent symptom unless bone is invaded. There may be bleeding and ulceration of oral mucosa.

Radiological Features There is unilocular radiolucency with no evidence of sclerotic border as seen in multiple myeloma.

Points to Remember

Histopathological Features

Myelomatosis, bence Jones proteinuria, para protein, skeletal pain, swelling over the areas of bone involvement, hypercalcemia, renal failure, mandible is more commonly involved, pain, swelling and numbness of the jaw, intraoral swelling tends to be ulcerated, rounded and bluish red, secondary signs of bone marrow involvement, excessive hemorrhage, oral amyloidosis, multiple well-defined punch out radiolucency, plasmocytic or plasmoblastic, normal appearing plasma cells with a low mitotic index, infiltration by immature, nucleated plasma cell precursors, cartwheel, checkerboard pattern, russell bodies, abnormal plasma cells, chemotherapeutic agents, management of anemia and hypercalcemia, blood transfusion, cell transplantation, radiotherapy, Bi-phosphonate therapy.

It contains densely packed plasma cells and is indistinguishable from the bony lesion in multiple myeloma. There may be considerable nuclear and cellular pleomorphism. Russell bodies (Fig. 28.27) can also be found. It is similar to multiple myeloma.

Laboratory Findings Bence Jones proteins are found in urine, there is also hyperglobulinemia and anemia.

Management It should be treated by conservative process to eradicate the single lesion and this can be accomplished by surgery. Points to Remember

PLASMACYTOMA Extramedullary location without bony involvement may occur in the nasopharynx, nasal cavity, paranasal sinuses and rarely in the oral cavity. It is also called plasma cell myeloma.

Plasma cell myeloma, nares, tonsil, palate, pain and swellings, pathologic fractures, sessile or polypoid reddish masses in mucous membranes, unilocular radiolucency, plasma cells, nuclear and cellular pleomorphism. Russell bodies, Bence Jones proteins.

Clinical Features Age and sex distribution: Mean age of occurrence is 51 years and males are affected more commonly than females. Location: The most common site of occurrence are nares, tonsil, palate tongue, gingivae and the floor of mouth. They are also found in pleura, mediastinum, thyroid, ovary, intestine, kidney and skin. Signs and symptoms: There is pain and swellings are the most common complaints. Pathologic fractures are common. Regional metastasis may develop in small number of cases.

Oral Manifestations It is rare in jaws and can occur in mandible or maxilla. The lesions are described as sessile or polypoid reddish masses

Figure 28.27 Plasmacytoma showing Russell bodies

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EXTRANODAL NK/T-CELL LYMPHOMA Management 728

It is also called angiocentric T-cell lymphoma, midline lethal granuloma, idiopathic midline destructive disease, polymorphic reticulosis, midline malignant reticulosis and angiocentric immunoproliferative lesion. It is characterized by aggressive nonrelenting destruction of the midline structure of the palate and nasal fossa. The word midline lethal granuloma should be used only when as descriptive designation of destructive midline condition. When the other cause of midline destruction has been eliminated the disorders should be classified as natural killer (NK) T-cell lymphoma.

Clinical Features ∙ ∙

Age: It is commonly seen in the adults. Signs and symptoms: Initially, it is localized to nasal region, like nasal stuffiness, epistaxis, and pain. After that swelling of hard and soft palate occur. Necrotic ulceration of palate which enlarge and destroyed the palate (Fig. 28.28). Secondary infection and life-threatening hemorrhage.

Histopathological Features It shows mixed infiltrate inflammatory cells which arranged around the blood vessels. Necrosis is present in lesion which is secondary to infiltration of the blood vessels by tumor cells. Large angular lymphocytes cells with atypical appearance is also seen.

Figure 28.28 Midline lethal granuloma seen in the palate

(Courtesy: Dr Chole)

It is treated by radiotherapy and combination chemotherapy. Points to Remember T-cell lymphoma, midline lethal granuloma, angiocentric immunoproliferative lesion, natural killer (NK) T-cell lymphoma, necrotic ulceration of palate, mixed infiltrate inflammatory cells, necrosis, large angular lymphocytes cells, radiotherapy, combination chemotherapy.

BIBLIOGRAPHY 1. Adeyemo TA, Adeyemo WL, Adediran A, Akinbami AA, Akanmu AS. Orofacial manifestations of hematological disorders: Anemia and hemostatic disorders. Indian J Dent Res. 2011;22:454-61. 2. Barrett AP. Gingival lesion in leukemia and lymphoma: J Periodontal. 1999;70:1247-53. 3. Jham BC, Binmadi NO, Scheper MA, et al. “Follicular lymphoid hyperplasia of the palate: case report and literature review. Journal of Cranio-Maxillofacial Surgery. 2009;37(2):79-82. 4. Bolton-Maggs PH, Young Wan-Yin B, McCraw AH, Slack J, Kernoff PB. Inheritance and bleeding in factor XI deficiency. Br J Haematol. 1988;69:521-8. 5. Brown DL, Sebes JI. Sickle cell gnathopathy: Radiologic assessment. Oral Surg Oral Med Oral Pathol. 1986;61: 653-6. 6. Cannell H. The development of oral and facial signs in b thalassaemia major. Br Dent J. 1988;164:50-1. 7. Chandra J, Ravi R, Singh V, Narayan S, Sharma S, Dutta AK. Bleeding manifestations in severely thrombocytopenic children with immune thrombocytopenic purpura. Hematology. 2006;11:131-3. 8. Estey E, Dohner H. Acute myeloid leukemia: Lancet. 2006; 368:1894-907. 9. Field EA, Speechley JA, Rugman FR, Varga E, Tyldesley WR. Oral signs and symptoms in patients with undiagnosed vitamin B12 deficiency. J Oral Pathol Med. 1995;24:468-70. 10. George ED, Sadovsky R. Multiple myeloma. Reconinition and management: A Fam Physician. 1999;59:1885-94. 11. Girolami A, Luzzatto G, Varvarikis C, Pellati D, Sartori R, Girolami B. Main clinical manifestations of a bleeding diathesis: An often disregarded aspect of medical and surgical history taking. Haemophilia. 2005;11:193-202. 12. Gokbuget AY, Mutlu S, Scully C. et al. Amyloidaceous ulcerated gingival hyperplasia: a newly describe entity related to ligneous conjunctivitis: J Oral Pathol Med. 1997; 26:100-4.

Blood Pathology 13. Gonzalez J, Elizondo J, Trull JM, et al. plasma cell tumors of the condyle. Br J Oral Maxillofac Surg. 1991;29:274-6 14. Harris NL. Hodgkin disease. classification and differentiated diagnosis: Mod Pathol. 1999;12:159-75. 15. Hata T, Aikoh T, Hirokawa M, et al. Mycosis fungoides with involvement of the oral mucosa: Int J Oral Maxillofac Surg: 1998;27:127-8. 16. Kaneda T, Nagayama M, Ohmori M, Minato F, Nakajima J, Shikimori M. Hemarthrosis of the temporomandibular joint in a patient with hemophilia B: Report of case. J Oral Surg 1979;37:513-4. 17. Kolokotronis A, Konstantinou N, Christakis, et al. Localized B cell non-Hodgkin lymphoma of the oral cavity d Maxillofac region: a clinical study. Oral Surg Oral Pathol Oral Med Oral Radiol Endod. 2005;99:303-310. 18. Menasce LP, Shanks JH, Banerjee SS, Harris M, “Follicular lymphoid hyperplasia of the hard palate and oral mucosa: report of three cases and a review of the literature, Histopathology 2001;39(4):353-8 19. Martini MZ, Lopez JS Jr, Gendler JL, da Fonseca EV, Soares HA, Franzi SA. Idiopathic thrombocytopenic purpura presenting as post-extraction haemorrhage. J Contemp Dent Pract. 2007;8:43-9. 20. Morris AL, Stahl SS. Intraoral roentgenographic changes in sickle cell anaemia, a case report. Oral Surg Oral Med Oral Pathol. 1954;7:787-91. 21. Napier SS, Newlands C, benign lymphoid hyperplasia of palate report of two cases and immunohitochemical profile: J Oral Pathol Med. 1990;19:221-5 22. Neville BW, Damm DD, Allen CM, Bouquot JE, oral and maxillofacial pathology, 3rd edn, Saunder Elsevier, 2009. 23. Nishioka GJ, Van Sickels JE, Tilson HB. Hemophilic arthropathy of the temporomandibular joint: Review of the literature, a case report, and discussion. Oral Surg Oral Med Oral Pathol. 1988;65:145-50. 24. Noah B. Sands and Marc Tewfik, “Benign Lymphoid Hyperplasia of the Tongue Base Causing Upper Airway Obstruction,” Case Reports in Otolaryngology, vol. 2011,

Article ID 625185, 2 pages, 2011. doi:10.1155/2011/62518 25. Patton LL, Brahim JS, Travis WD. Mandibular osteomyelitis in a patient with sickle cell anaemia: Report of a case. J Am Dent Assoc. 1990;121:602-4. 26. Ragni MV, Kessler CM, Lozie r JN. Clinical aspects and therapy for hemophilia. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al. (eds). Hoffman Hematology: Basic Principles and Practice. 5th edn. Philadelphia, Churchill Livingstone Elsevier;2008:chap 2005. 27. Rakocz M, Mazar A, Varon D, Spierer S, Blinder D, Martinowitz U. Dental extractions in patients with bleeding disorders. Oral Surg Oral Med Oral Pathol. 1993;75:280-2. 28. Schully C, Gokbuget AY, Allen C et al : oral lesion indicative of plasminogen deficiency (hypoplasminogenemia) Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001; 91:334-7. 29. Sepúlveda E, Brethauer U, Rojas J, Le Fort P. Oral manifestation of Aplastic anaemia in children. J Am Dent Assoc. 2006;137:474-8. 30. Shroyer JV 3rd, Lew D, Abreo F, Unhold GP. Osteomyelitis of the mandible as a result of sickle cell disease: Report and literature review. Oral Surg Oral Med Oral Pathol. 1991;72:25-8. 31. Sirois DA, Miller AS, Harwick RD, et al. Oral manifestation cutaneous T cell lymphoma: a report of eight cases: Oral Surg Oral Med Oral Pathol. 1993;75:700-5. 32. Sonis AL, Musselman RJ. Oral bleeding in classic haemophilia. Oral Surg Oral Med Oral Pathol. 1982;53:3636. 33. Toygar HU, Guzeldemir E. Excessive gingival bleeding in two patients with Glanzman ThrombasteNia. J Periodontol 2007;78:1154-8. 34. Tsui SHC, Wong MH, Lam Wy. Burkitt’s lymphoma presenting as mandibular swelling: report of case and review of publication: Br J Oral Maxillofac Surg. 2000; 38:8-11 35. Weel F, Jackson IT, Crookendale WA, McMichan J. A case of thalassaemia major with gross dental and jaw deformities. Br J Oral Maxillofac Surg. 1987;25:348-52.

MULTIPLE CHOICE QUESTIONS 1. All are the normochromic normocytic types of anemia except: a. Iron deficiency anemia b. Anemia of acute blood loss c. Anemia associated d. Aplastic anemia

2. Which one of the following is the type of hypochromic, microcytic anemia: a. Iron deficiency anemia b. Thalassemia c. Both d. None of the above

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3. Which one of the following is the type of normochromic, macrocytic anemia: a. Iron deficiency anemia b. Pernicious anemia c. Folate and B12 deficiency anemia d. Both b and c

10. Most common type of anemia seen in female: a. Iron deficiency anemia b. Sickle cell anemia c. Both d. Cooley’s anemia

4. In iron deficiency anemia, initially there is a atrophy of: a. Cirumvalate papilla b. Fungiform papilla c. Filliform papilla d. None

11. Enlargement of heart and murmur found in: a. Sickle cell anemia b. Megaloblastic anemia c. Aplastic anemia d. Thalassemia

5. Webs in esophagus or ‘spasm in throat’ is characteristic feature seen in: a. Sjögren’s syndrome b. Burning mouth syndrome c. Patau’s syndrome d. Plummer Vinson syndrome

12. ‘Rh hump’–a ring like defect of teeth seen in: a. Pyruvate kinase deficiency anemia b. Erythroblastosis fetalis c. Post hemorrhagic anemia d. Polycythemia vera

6. ‘Primary anemia’ refers to: a. Pernicious anemia b. c. Aplastic anemia d.

Iron deficiency anemia Megaloblastic anemia

7. Hunter’s glossitis or Moeller’s glossitis seen in: a. Iron deficiency anemia b. Aplastic anemia c. Pernicious anemia d. Both b and c 8. ‘Cooley’s anemia’ refers to: a. Polycythemia vera b. c. Neutropenia d.

G 6 P deficiency Thalassemia

9. Mongolid appearance and rodent facies seen in: a. Iron deficiency anemia b. Megaloblastic anemia c. Thalassemia d. Pyruvate kinase deficiency anemia

13. A crystal violet appearance of tongue is the oral manifestation of: a. Cyclic neutropenia b. Lazy leukocyte syndrome c. Erythroblastosis fetalis d. Polycythemia vera 14. Hemophilia A is cause due to deficiency of: a. Factor v b. Factor viii c. Factor ix d. Factor vi 15. ‘Crush spider’ appearance seen in: a. Osler- Rendu- Weber syndrome b. Christmas disease c. Bernard- Soulier syndrome d. Costen’s syndrome

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Skin Disorders

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline                  Â

Erythema multiforme • Steven Johnson syndrome • Toxic epidermal necrolysis Pemphigus Paraneoplastic pemphigus Bullous pemphigoid Benign mucous membrane pemphigoid Familial benign chronic pemphigus Epidermolysis bullosa Dermatitis herpetiformis Pityriasis rosea Incontinentia pigmenti Acanthosis nigricans Ehlers Danlos syndrome Psoriasis Pachyonychia congenita Porokeratosis Keratosis follicularis Warty dyskeratoma Seborrheic keratosis

                  Â

Mucocutaneous lesions are a group of disease and conditions that affect the skin as well as the mucous membrane. These lesions affecting the oral mucosa may be arising due to infections, allergies, autoimmune diseases. Some of the lesions may be hereditary in origins which are called genodermatosis.

Hereditary mucoepithelial dysplasia Pseudoxanthoma elasticum Hyalinosis cutis et mucosa oris White sponge nevus Hereditary benign intraepithelial dyskeratosis Hereditary hemorrhagic telangiectasia Peutz-Jeghers syndrome Ephelis Actinic Lentigo Sebaceous hyperplasia Lentigo simplex Xeroderma pigmentosum Tuberous Sclerosis Ectodermal dysplasia Cowden Syndrome Graft versus host resistance CREST syndrome Scleroderma Kawasaki disease

Types • Erythema multiforme minor • Erythema multiforme major – Steven Johnson syndrome – Toxic epidermal necrolysis • Herpes associated erythema multiforme.

ERYTHEMA MULTIFORME It is acute inflammatory disease of the skin and mucous membrane that causes a variety of skin lesions, hence the term multiforme.

Types ∙

Erythema multiforme minor: This is self-limiting form.

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• Erythema multiforme major: This is severe form. It is traditionally thought to be synonymous with Steven Johnson syndrome or toxic epidermal necrolysis. But now a day some literature suggested that Steven Johnson syndrome and toxic epidermal necrolysis are different entity. But this classification scheme remains very controversial. • Herpes associated erythema multiforme: Now a day sophisticated technique demonstrated that in some patient of recurrent erythema multiforme there is presence of herpes simplex DNA.

Etiology Immune mediated disease that is indicated by the deposition of immune complexes in the superficial microvasculature of the skin and mucous membrane or cell mediated immunity. Drugs like sulfonamides, trimethoprin, nitrofurantion, phenylbutazone, digitalis, birth control pills and penicillin. Microorganisms like Mycoplasma pneumoniae and herpes simplex virus. Vaccination, radiation therapy and occasionally other disease like Crohn’s disease, ulcerative colitis and infectious mononucleosis.

Clinical Features It is most frequently seen in children and young adults and is rare after the age of 50. It affects males more than females. Sites involved: Most common area, involved are hands, feet, extensor surfaces of elbow and knees. Onset of lesion: It has got acute or explosive onset with generalized symptoms such as fever and malaise. It may be asymptomatic and in less than 24 hours, extensive lesions of oral mucosa may appear.

Figure 29.1 Erythema multiforme showing sloughing of lip

Lip is prominently involved followed by buccal mucosa, palate, tongue and face. Oral lesions start as bullae, on an erythematous base and break rapidly into irregular ulcers (Fig. 29.1). Patient cannot eat or swallow and drools blood tinged saliva. The lesions are larger, irregular, and deeper and often bleed very freely. In full blown cases, lips are extensively involved and large portions of the oral mucosa are denuded of epithelium. Sloughing of mucosa and diffuse redness with bright red raw surface is seen. Healing occurs in 2 weeks.

Histopathological Features (Figs 29.2 and 29.3)

The cutaneous or mucosal lesions generally exhibit intracellular edema of the spinous layer of epithelium and Symptoms: It is characterized by macule or papule, 0.5 edema of superficial connective tissue, which may produce to 2 cm in diameter, appearing in segmental distribution. subepidermal vesicle. There is zone of liquefaction degeneration in the Typical skin lesions, of erythema multiforme may be upper layer of the epithelium with intraepithelial vesicle nonspecific macule, papule and vesicle. formation and thinning, with frequent absence of the Bull’s eye: Target or iris or bull’s eye lesion consists of basement membrane. central bulla or pale clearing area, surrounded by edema Dilatation of the superficial capillaries and lymphatics and band of erythema. This gives concentric ring like in the upper most layer of the connective tissue is prominent appearance. Morbidity is high due to secondary infection, and mixed inflammatory infiltrate with numerous eosinfluid and electrolyte imbalance or involvement of lungs ophils also seen. liver and kidneys. Vesicle formation is seen as intraepithelial or the subepithelial region. Oral Manifestations Necrotic eosinophilic keratinocytes are seen in the Erythema multiforme occurs along with skin lesions in 45 blister area. Inflammatory cells are in abundance in the percent of the cases. vesicle region.

Skin Disorders

Points to Remember Immune mediated disease, drugs, microorganism, Bull’s eye - target or iris or bulls eye lesion, mucosal vesicles, bullae, erythematous base, lips involvement, intracellular edema, liquefaction degeneration, intraepithelial vesicle, dilatation of the superficial capillaries, mixed inflammatory infiltrate, necrotic eosinophilic keratinocytes, prednisolone, prophylactic acyclovir.

Steven Johnson Syndrome

Figure 29.2 Erythema multiforme showing vesicle formation

It is the severe form of erythema multiforme with widespread involvement, typically involving skin, oral cavity, eyes and genitalia. It commences with abrupt occurrence of fever, malaise, photophobia and eruptions on oral mucosa, genital mucosa and skin. Cutaneous lesions: Cutaneous lesions are similar to erythema multiforme and are hemorrhagic, often vesicular or bullous. Eye lesions: It consists of photophobia, conjunctivitis, and corneal ulcerations. Keratoconjunctivitis sicca has also been described and blindness may result, chiefly from intermittent bacterial infection. Genital lesions: Genital lesions are reported to consist of nonspecific urethritis, balanitis and vaginal ulcers.

Figure 29.3 Vesicle formation seen in patient with erythema

multiforme

Management Mild cases: Soft liquid diet and topical anesthetic mouth wash. If the causative organism is identified or suspected it should be discontinued. Moderate to severe erythema multiforme: 30 mg/day prednisolone or methyl prednisolone for several days and tapered after the symptoms subside. Prophylactic Acyclovir to prevent HSV related erythema multiforme.

Complications: Other reported complications are related to respiratory tract involvement such as tracheo-bronchial ulcerations and pneumonia. Oral mucous membrane lesions in Steven Johnson syndrome may be extremely painful and so, mastication becomes impossible. Mucosal vesicles or bullae occur, rupture and leave a surface covered with a thick, white or yellow exudate. Erosions of the pharynx are also common. Lips may exhibit ulcerations with bloody crusting and are often painful.

Toxic Epidermal Necrolysis It is also called Lyell’s disease. It usually results due to increases apoptosis of the epithelial cells. It occur secondary to drug reaction. It usually occurs in the older individual and more seen in female.

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Scalded appearance: It results in sloughing of skin and mucosa in large sheets. The appearance of the patient is like that is badly scalded. 734

Management: It is managed in burn centers where necrotic skin is removed under general anesthesia and healing takes place under sheets of porcine xenografts. Corticosteroid should be avoided in this case. Intravenous administration pooled human immunoglobulin has been results in remarkable resolution of the toxic epidermal necrolysis.

PEMPHIGUS It is autoimmune disease involving the skin and mucosa and characterized by intraepithelial vesicle or bulla formation. Types • • • •

Pemphigus vulgaris Pemphigus vegetans Pemphigus foliaceous Pemphigus erythematosus.

Mechanism Binding of autoantibodies against the epidermal cells glycoprotein, desmoglein 3 and desmoglein 1 which are component of desmosomes (structure that bone epithelial cells to each other). This will in turn inhibit the molecular interaction that is responsible for adherence. This will result in split within the epithelium and blister will for. Separation of cell takes place in lower layer of stratum spinosum.

Pemphigus Vulgaris It is the most common types occur out of above four. Vulgaris in Latin is known as common.

Clinical Features It is seen in 5th to 6th decades of life and male to female ratio is 1:1, with whites more commonly affected. Symptoms: Thin walled bullae or vesicles varying in diameter from few millimeter to several centimeters arise on normal skin or mucosa. Signs: These lesions contain a thin, watery fluid shortly after the development, but this may soon become purulent or sanguineous (Fig. 29.4). They rapidly break and continue to extend peripherally, eventually leaving large areas of denuded skin.

Figure 29.4 Pemphigus present on the back showing vesicle

and bulla formation

Nikolsky’s sign: Characteristic sign of the disease is that pressure to an apparently normal area will result in formation of new lesion. This phenomenon is called Nikolsky’s sign. It results from upper layer of skin pulling away from the basal layer. It is caused by perivascular edema which disrupts the dermal-epidermal junctions. Asboe-Hansen sign: After giving application of pressure to an intact bulla, the bulla will enlarge by extension to apparently normal surfaces. The course of pemphigus vulgaris is a variable one; the disease terminating in death or recovery within a few days or weeks or it may get prolonged over a period of months or even years.

Oral Manifestations In 90 percent, of the cases oral lesions develop and in 60 percent cases they occur first. Initial lesion most frequently occurs on buccal mucosa because the epithelium demonstrates less intercellular substance and fewer intercellular junctions making the area more susceptible to acantholysis. Palate and gingiva are other common sites of involvement. Symptoms and signs: Oral lesions begin as classic bullae on noninflamed base with formation of shallow ulcers as bullae break rapidly. Thin layer of epithelium peels away in an irregular pattern leaving denuded base. Nikolsky’s phenomenon: The oral lesions may exhibit Nikolsky’s phenomenon and may be denuded by peripheral enlargement of the lesion.

Skin Disorders

Lesions bleed easily and are tender on palpation. The pain may be so severe that the patient is unable to eat. The lesion may have ragged borders and be covered with white or blood tinged exudate. Edges of the lesion may extend peripherally. Diffuse erythematous involvement of gingiva.

Pemphigus Vegetans Types • N eumann type: It is more common and early lesions are similar to those seen in pemphigus vulgaris. • Hallopeau type: In hallopeau type; pustules, not bullae, are the initial lesions which are followed by verrucous hyperkeratotic vegetations.

Histopathological Features (Figs 29.5 to 29.9) Basic defect is intraepithelial and is demonstrated as acantholysis (loss of cell to cell attachment) in stratum spinosum. The cellular outlines are round, rather than polyhedral; intercellular bridges are lost (spongiosis) and the nuclei are large and hyperchromatic. Characteristic suprabasilar split intraepithelial separation, which occurs just above the basal layer of the epithelium, is seen. Row of tombstones: Sometimes the entire suprabasal or superficial layers are striped off leaving only the basal layers which is called the row of tombstones.

Clinical Features It occurs in 1 to 9 percent of the cases. The flaccid bullae become eroded and forms vegetations on some of the erosions. These fungoid masses become covered by purulent exudate and exhibit inflamed borders, frequently occur first on nose and in the mouth or axilla. The disease usually terminates in pemphigus vulgaris.

Oral Manifestations Gingival lesions may be lace like ulcers with purulent surface on red base or have granular or cobblestone appearance.

Pemphigus Foliaceus It is a relatively mild form of pemphigus, which is most common in older adults. It is manifested by characteristic early bullous lesions which rapidly rupture and dry to leave masses of flakes on scales suggestive of an exfoliative dermatitis or eczema.

Figure 29.5 Pemphigus vulgaris showing acantholysis (Courtesy: Dr Sangamesh Halawar, Reader, Oral Pathology, CDCRI, Rajnandgaon, Chhattisgarh)

Brazilian pemphigus: It is a mild endemic form of pemphigus foliaceous found in tropical regions, particularly in Brazil. It is seen in children and frequently in family groups.

Pemphigus Erythematosus It is also called Senear-Usher syndrome. It is form of disease which is characterized by the occurrence of bullae and vesicles concomitant with the appearance of crusted patches resembling seborrheic dermatitis or even lupus erythematosus. Most cases ultimately terminate in pemphigus vulgaris or foliaceous. The skin manifestations in any form of pemphigus may be accompanied by fever and malaise.

Figure 29.6 Pemphigus vulgaris showing suprabasilar vesicle

formation

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Figure 29.7 Tzanck smear showing presence of Tzanck cell

A

Figure 29.8 Vesicle seen in pemphigus

B Figures 29.9A and B Tzanck cells in pemphigus

Acantholysis: The spinous cell layer lose their cell contacts and the loose cells assume a rounded shape, forming characteristic cells—“the Tzanck cells.” The diagnostic test of the cytological study of the contents of the vesicle or the lesion shows these cells are termed as Tzanck test.

phonuclear leukocytes and the surface may show suppuration.

Tzanck smear: It is done to demonstrate Tzanck cells which often are found lying freely within the vesicular space. The underlying connective tissue shows mild to moderate chronic inflammatory infiltrate. The underlying connective tissue is densely filled with chronic inflammatory cells, which may also enter the vesicular fluid. As the vesicle and bulla rupture, the ulcerative lesion becomes infiltrated with polymor-

Direct test: Antibody will bind the immunoglobulin deposit in the intercellular substance and show positive fluorescence under fluorescence microscope.

Indirect immunofluorescent antibody test: Antibodies against intercellular substance can be seen in the serum of patient. The titers of antibody are directly related to the level of the clinical disease.

Management Corticosteroids: Corticosteroids usually prednisolone given in combination with immunosuppressive drugs like azathioprine.

Skin Disorders

Plasmapheresis and administration of 8- methoxypsoralen, followed by exposure of peripheral blood to ultraviolet radiation. 737

Points to Remember Thin walled bullae or vesicles, Nikolsky’s sign, AsboeHansen sign, classic bullae on noninflamed base, vegetations, brazilian pemphigus, intraepithelial defect, acantholysis, suprabasilar split, row of tombstones, chronic inflammatory cells, Tzanck test, Tzanck smear, plasmapheresis corticosteroid.

PARANEOPLASTIC PEMPHIGUS It is autoimmune disease which is associated with malignancy like lymphoma, leukemia, etc. The mechanism behind this is that there are abnormal levels of cytokine, interleukin 6 in response to patient tumor. This in turn stimulates abnormal production autoantibodies against antigen associated with desmosomes complex. Recently also it is stated that cutaneous and mucosal damage appear to be mediated by cytotoxic T lymphocytes also can lead to paraneoplastic pemphigus.

Clinical Features There is history of tumors and in some cases it is developed before malignancy identified. So this can be indicative to presence of tumor in the body.

Figure 29.10 Paraneoplastic pemphigus

the intercellular zone of epithelium or linear deposition at the basement membrane.

Management It is serous disorders with high morbidity and mortality rate. Treatment consists of systemic prednisolone combined with immunosuppressive agents. Points to Remember Associated with malignancy like lymphoma, multiple vesiculobullous lesion of skin and oral mucosa, scarring, conjunctivitis, positive deposition of immunoreactants (IgG and complement), subepithelial clefting, intraepithelial clefting, systemic prednisolone.

Signs and symptoms: They appear sudden and polymorphous. There is appearance of multiple vesiculobullous lesion of skin and oral mucosa. Palmar or planter bullae also present. There is also involvement of conjuctival mucosa BULLOUS PEMPHIGOID causing scarring and conjunctivitis. In some cases vaginal It is also called para-pemphigus, or aging pemphigus. In mucosa and mucosa of respiratory tract can be affected. this, the initial defect is subepithelial in the lamina lucida Oral features: The lip shows hemorrhagic crusting region of the basement membrane. It is associated with antisimilar to that of in erythema multiforme. The oral mucosa basement membrane antibodies which are detected in the shows multiple area of diffuse and irregular ulceration. basement membrane. It usually resembles mucous membrane Some patient develop only oro-pharyngeal lesion without pemphigoid but one major difference is that clinical course of cutaneous lesion. bullous pemphigoid is limited and that of mucous membrane pemphigoid is protracted and progressive.

Histopathological Features (Fig. 29.10)

In most of the cases lichenoid mucositis with subepithelial clefting (like pemphigoid) or intraepithelial clefting (like pemphigus) is seen. Direct immunofluorescence studies show positive deposition of immunoreactants (IgG and complement) in

Clinical Features It occurs chiefly in adults over the age of 60 is self-limiting and rarely lasts over 5 years. Skin lesions begin as generalized nonspecific rash, commonly on the limbs, which appear as blisters on

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inflamed skin; itching precedes. It may persist for several weeks to several months before ultimate appearance of vesiculobullous lesions. 738

Vesiculobullous lesion: These vesicle and bullae are relatively thick walled and may remain intact for some days. Rupture does not occur although it does leave raw eroded areas which heal rapidly.

Oral Manifestations Oral lesions are smaller, form more slowly and are less painful. Gingival lesions consist of generalized edema, inflammation, and desquamation and localized areas of discrete vesicle formation. Vesicles and ultimately erosion may develop not only on the gingival tissue but any other area such as the buccal mucosa, palate, floor of the mouth and tongue (Fig. 29.11).

Histopathological Features (Fig. 29.12) The vesicle and bullae are subepidermal and nonspecific. Epithelium appears normal. The vesicle contain fibrinous exudate admixed with occasional inflammatory cells. These cells are usually eosinophils. In severe inflammation the basal keratocytes of mesenchymal demonstrates spongiosis. It is called eosinophilic spongiosis. It also shows stratified squamous epithelium, thin epithelium and subepithelial bulla formation is the characteristic feature of bullous pemphigoid. The vesicle shows moderate numbers of the acute inflammatory cells as eosinophils and chronic inflammatory cell infiltrate within it.

Figure 29.12 Bullous pemphigoid showing separation of the

epithelium at the basement membrane zone

Direct immunofluorescence shows continuous linear band of immunoreactants usually IgG and C3 localized to basement membrane. Indirect immunofluorescence antibody test—lesions will demonstrate circulating IgG antibodies against basement membrane antigen.

Management Systemic steroids in lower doses, for shorter period combined with immunosuppressive drugs and Dapsone. Points to Remember Para-pemphigus, aging pemphigus, skin lesions, generalized nonspecific rash, vesiculobullous lesion, gingival lesions, generalized edema, subepidermal fibrinous exudate, occasional inflammatory cells, eosinophilic spongiosis, systemic steroids.

BENIGN MUCOUS MEMBRANE PEMPHIGOID It is also called cicatricial pemphigoid mucous membrane pemphigoid. It is a disease of unknown etiology but probably is autoimmune in nature. The term pemphigoid is used as it appears clinically similar to pemphigus.

Clinical Features Age and sex distribution: It occurs more commonly in patients over 50 years of age and female to male ratio is 2:1. Figure 29.11 Bullous pemphigoid showing lesion

Sites: Typically, the vesiculobullous lesions occur on the oral mucous membrane, conjunctivae and skin. The other

Skin Disorders

mucous membranes involved are those of nose, larynx, pharynx, esophagus, vulva, vagina and penis. Eye lesion: Most striking features of this disease is involvement of eye. Initially there is subconjuctival fibrosis. After that conjunctiva may become inflamed and eroded. When healing process start there is scarring occurs between bulbar (lining of globe of eye) and palpebral (lining of inner surface of the eyelid) conjunctivae. This will results in adhesion called symblepharons. Scarring can ultimately results in eyelid to turn inward called entropion. These cause eyelashes to rub against cornea and globe called trichiasis. Scarring will close opening of lacrimal gland resulting in dry eyes. Eyes then produce keratin as a protective mechanism but this is opaque material and ultimately blindness occurs. There is formation of scar, i.e. the reason it is called cicatricial pemphigoid (cicatrix meaning scar).

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Figure 29.13 Cicatricial pemphigoid

Dyspareunia: Vaginal mucosal lesion may cause severe pain during attempts of intercourse. This is called dyspareunia. Involvement of esophagus and trachea may cause strictures leading to difficulty in swallowing or breathing.

Oral Manifestations It occurs on gingiva, buccal mucosa and palate. The mouth may be the only site involved. The mucosal lesions are also vesiculobullous in nature, but appear to be relatively thick walled and for this reason may persist for 24 to 48 hours before rupturing and desquamation. After rupture of vesicle surface epithelium is lost leaving raw red bleeding surface (Fig. 29.13). Gingiva is edematous and bright red, involvement is patchy and diffuse. This types of pattern is called desquamative gingivitis. There may be formation of ulcer, which surrounded by zone of erythema. There may be erosion on cheek and vesicles on palate and narrower peripheral extensions. The oral lesions rarely produce scars.

Histopathological Features The vesicle and bullae are subepidermal rather suprabasilar and there is no evidence of acantholysis. The basement membrane structure appears to detach with the epithelium from the underlying connective tissue. So mucosa will show split between surface epithelium and underlying connective tissue. There is nonspecific chronic inflammatory infiltrate of connective tissue chiefly lymphocytes, plasma cells and

Figure 29.14 Cicatricial pemphigoid showing chronic

inflammatory infiltrated

eosinophils (Fig. 29.14). Lesion which is chronic in nature shows granulation tissue and fibrosis. Direct immunofluorescent study will show positive fluorescence for immunoglobulin and complement in basement membrane zone, i.e. in intercellular substance of prickle cell layer of epithelium. Immune deposit mainly consists of IgG and C3. In some cases IgA is also found and if IgG and IgA is found in same patient disease is usually of severe variety. Indirect immunofluorescence studies revealed the presence of tissue bound basement membrane zone antibodies as well as circulating anti-basement membrane zone antibodies in the serum of some patients.

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Management

Histopathological Features

Topical therapy: Application of topical steroid should be done several times per day. In case of gingival lesion flexible mouth guard should be applied for carrier of corticosteroid medication.

It is similar to pemphigus vulgaris but acantholysis is more extensive. Characteristic feature of this disease in occasional intercellular bridges persist so that adjacent epithelial cells still adhere to each other. This gives classic description of the dilapidated brick wall effect.

Systemic therapy: Systemic steroid in combination with immunosuppressive therapy are given. Immunosuppressive agent used should be cyclophosphamide. Recently intravenous human immunoglobulin is effective in managing ocular lesion. Use of dapsone (sulfa derivative) can also aid to relief of sign of the disease. Tetracycline or minocycline and niacinamide given in doses of 0.5 to 2 g have been found to be effective in the management of mucous membrane pemphigoid. Points to Remember Cicatricial pemphigoid, eye lesion called symblepharons, entropion, raw red bleeding surface, desquamative gingivitis, zone of erythema, subepidermal vesicle bullae, chronic inflammatory infiltrate, immune deposit, systemic steroid, cyclophosphamide.

FAMILIAL BENIGN CHRONIC PEMPHIGUS It is also called Hailey-Hailey disease. It is uncommon disease transmitted by irregular dominant gene.

Points to Remember Hailey-Hailey disease, small groups of vesicles, Nikolsky’s sign, raw eroded areas, acantholysis, intercellular bridges.

Epidermolysis Bullosa It is a dermatological disorder in which bullae or vesicles occur on skin or mucous membrane surface spontaneously, shortly after minor trauma. Types • • • • • •

Epidermolysis bullosa simplex Epidermolysis bullosa dystrophic, dominant Epidermolysis bullosa dystrophic, recessive Junctional epidermolysis bullosa Hemidesmosomal Epidermolysis bullosa acquista (acquired).

Types

Epidermolysis bullosa simplex ∙ Generalized form Clinical Features ∙ Localized form (Weber-Cockayne syndrome, recurrent bullous eruption of hands and feet) It is usually manifested during adolescent or young life Epidermolysis bullosa dystrophic, dominant. with no predilection for sex. The most common sites are Epidermolysis bullosa dystrophic, recessive. flexure surfaces of the axillae and groin, the neck and the Junctional epidermolysis bullosa (Epidermolysis bullgenital area. Heat and sweating amplify the outbreak of osa latalis, junctional bullous epidermatosis, Herlitz’s the lesion while spontaneous remission may occur in cold disease). weather. Epidermolysis bullosa acquista (acquired): It is Signs and symptoms: The lesions develop as small groups similar to dystrophic form of the disease but usually with of vesicles appearing on normal or erythematous skin, an adult onset. which soon rupture to leave eroded, crusted areas. Hemidesmosomal: It is most recently discover types of Nikolsky’s sign: They enlarge peripherally but heal in Epidermolysis bullosa. In this mutation of genes associated center with Nikolsky’s sign positive. Tender and enlarged with hemodesmosomal attachment protein such as plectin is associated. regional lymph nodes may also be present.

Oral Manifestations Oral lesions are similar to those occurring on the skin and it develops as crops of vesicle, which rapidly ruptures leaving raw eroded areas.

Clinical Features Epidermolysis Bullosa Simplex It is inherited as autosomal dominant trait and manifests at birth or shortly thereafter. It is characterized by formation

Skin Disorders

of bullae or vesicle on the hands and feet at site of friction or trauma. The knees, elbows and trunk are rarely involved and nails are occasionally affected. When the blister heals within 2 to 10 days there is no resultant scarring or permanent pigmentation. The disease appears to improve at puberty and prognosis is good for normal life span. The localized form is limited to hands and feet only and tends to exacerbate in hot weather.

Epidermolysis Bullosa Dystrophic Dominant Bullae can occur in this type sometimes oral milia can be seen but teeth are unaffected. Gingival recession and reduction in the depth of buccal vestibule may be seen.

Epidermolysis Bullosa Dystrophic Recessive

They may be preceded by the appearance of white spots or patches on the oral mucous membrane or by development of localized areas of inflammation. Lesion can occur on lip as vesicle or bullae (Fig. 29.15). These bullae are painful especially when they rupture or Epidermolysis Bullosa Dystrophic Dominant when the epithelium desquamates. Scar formation results in The onset is at infancy and it may delay until puberty. The obliteration of sulci and restriction of the tongue movement. blister commonly develops on the ankles, knees, elbows, Hoarseness and dysphagia may occur as a result of feet and head. Healing results in scarring which is some bullae of larynx and pharynx. Esophageal involvement times keloid in type. produces serious strictures. Hair may be sparse, while nails are usually dystrophic Dental defects like rudimentary teeth, congenitally or absent with milia present. absent teeth, hypoplastic teeth and crowns denuded of Palmar-planter keratoderma with hyperhidrosis also enamel may be seen. may occur with ichtyyosis and sometimes hypertrichosis.

Epidermolysis Bullosa Dystrophic Recessive It has onset at birth or very shortly thereafter. The typical sites of involvement are the feet, buttock, scapula, elbows, finger and occiput. It is characterized by formation of bullae spontaneously or at sites of trauma, friction or pressure. Nikolsky’s sign is positive in this type of epidermolysis bullosa. The bullae contain a clear, bacteriologically sterile or sometime blood tinged fluid. When these bullae rupture or are peeled off under trauma or pressure, they leave raw, painful surface. The bullae heal by scar and milia formation which may result in afunctional club-like fists. The hair may be sparse, while the nails are usually dystrophic.

Junctional Epidermolysis Bullosa Oral bullae are frequently very extensive and because of their extreme fragility produce serious feeding problems. Severe disturbance in enamel and dentin formation of deciduous teeth also occur.

Histopathological Features Epidermolysis Bullosa Simplex Vesicle and bullae are developed as a result of destruction of basal and suprabasal cells so that some nuclei may persist on the floor of the blister.

Junctional Epidermolysis Bullosa It is extremely sever form of the dystrophic recessive form, which is incompatible with prolonged survival. It has onset at birth, absence of scarring, milia, pigmentation and death within three months of age. The bullae are similar to recessive form but they develop simultaneously and sheets of skin may actually be shed.

Oral Manifestations Epidermolysis Bullosa Simplex Bullae of the oral cavity are reported in occasional cases of generalized epidermolysis bullosa, but teeth are not affected.

Figure 29.15 Child patient having lesion on upper lip

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The individual cells become edematous and show dissolution of organelles and tonofibrils with displacement of the nucleus to the upper end of cells. In localized form, bullae are intraepidermal and suprabasal in location. There is intraepithelial clefting can be seen. Electron microscopy shows perinuclear edema and subnuclear cytolysis.

Epidermolysis Bullosa Dystrophic Dominant The bullae in this form develop as a result of separation through the very thin, irregular PAS positive basement membrane which becomes divided. The basal layer appears normal, although flattened on the roof of the blister and the underlying connective tissue shows absence of elastic and oxytalan fibers.

Epidermolysis Bullosa Dystrophic Recessive The separation and bulla formation occur immediately beneath the poorly defined PAS positive basement membrane which remains attached to the roof of the blister. Fragment of basement membrane may adhere to the dermis but basal layer of cells is normal. The pre-elastic and oxytalan fibers in the connective tissue are increase in number (Fig. 29.16).

Junctional Epidermolysis Bullosa It is similar and identical to those occurring in the dystrophic recessive disease.

Management Drainage of blister: Large blisters should be pricked and the blister fluid released. Dressing, to minimize reaction may be helpful. Antibiotics: Super infections should be treated with appropriate local or systemic antibiotics. Surgical approach: Deformities of hand should be corrected with plastic surgery. In case of dysphagia due to esophageal involvement gastrostomy tube can be place. Management of oral lesion: Atraumatic dental procedure, minimum dental manipulation should be done. If the dental restoration is required. Points to Remember Bullae or vesicle, no scarring, blister, palmar-planter keratoderma, Nikolsky’s sign, milia, pigmentation, bullae of the oral cavity, hoarseness, dysphagia, intraepidermal, supra-basal vesicle, perinuclear edema, subnuclear cytolysis, PAS positive basement membrane, pre-elastic and oxytalan fibers.

DERMATITIS HERPETIFORMIS It is also called Duhring-Brocq disease. It is a rare, benign, chronic, recurrent dermatologic disease of unknown etiology.

Clinical Manifestations It occurs between 20 and 55 years of age, with males affected at least twice as frequently as females. These occur most frequently on buttocks, extremities as well as on the face, scalp and sometimes, the oral cavity. Symptoms: The first manifestation of the disease is usually pruritus and severe burning followed by the development of erythematous papules, vesicles, bullae or pustules. The patient usually shows increased severity in summer months.

Oral Manifestations Vesicles and bullae rupture rapidly to leave areas of superficial ulceration at any intraoral site the characteristic finding.

Histopathological Features

Figure 29.16 Epidermolysis bullosa

The lesion begins with accumulation of neutrophils and eosinophils in the dermal; papillae producing a microabscess. The connective tissue becomes necrotic and the overlying epithelium separates, usually forming a

Skin Disorders

subepithelial vesicle with destruction of the basement membrane. There is also perivascular infiltrate of lymphocytes. There is deposition of IgA along the basement membrane. Electron microscopic study show blister formation below the lamina lucida.

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Laboratory Findings Direct immunofluorescence staining is positive at the epidermal-dermal junction. Patient may develop eosinophilia and sensitivity to halogens (chlorine, bromine, iodine and fluorine), both by patch test and after ingestion.

Management Use of dapsone can give relief to the patient. Points to Remember Duhring-Brocq disease, pruritus, severe burning, erythematous papules, superficial ulceration at intraoral site, neutrophils, eosinophils, subepithelial vesicle, microabscess, eosinophilia, dapsone.

PITYRIASIS ROSEA It is an acute skin eruption of unknown etiology.

Clinical Features It is more common in spring and autumn and it involves young adults chiefly, with no sex predilection. Prodromal features: The generalized outbreak is frequently preceded by the appearance of a primary lesion or herald spot seven to ten days previously. It is characterized by the appearance of superficial, light red macules or papules, generalized over most of the skin surface. Signs and symptoms: The spot is brighter red and larger (3 to 4 cm in diameter) than the multiple eruptions which follow its appearance. The individual exanthematous lesion is commonly ovoid, with long axis parallel to the natural lines of cleavage of skin and are covered by a thin silvery scales (Fig. 29.17). The lesion often manifests mild aching headache and low grade fever and cervical lymphadenopathy.

Oral Manifestations The oral lesion occurs either concomitantly with, or subsequent to the skin manifestations. It can occur on

Figure 29.17 Pityriasis rosea showing exanthematous lesion

buccal mucosa, although tongue and palatal lesions have been reported. Oral lesion appears as erythematous macule, with or without central area of grayish desquamation. The lesion may be single or multiple, irregular in shape, occasionally showing raised borders and vary in size from few millimeter to 1 to 2 cm in diameter.

Histopathological Features It consists of slight acanthosis and focal parakeratosis with microvesiculation or simply sprinkling of leukocytes within the epithelium. There is also edema, hyperemia and perivascular infiltration of lymphocytes, plasma cells and histiocytes.

Management It requires no treatment since the disease is self-limiting and generally undergoes rapid spontaneous regression. Points to Remember Primary lesion, herald spot, exanthematous lesion, erythematous macule, grayish desquamation, acanthosis, focal parakeratosis, microvesiculation.

INCONTINENTIA PIGMENTI It is also called Bloch-Sulzberger syndrome. It is transmitted as X-linked dominant trait. It involves skin, eyes and central nervous system.

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Clinical Features

ACANTHOSIS NIGRICANS

It appears shortly after birth and exclusively seen in females.

It is an acquired disease characterized by development of velvety brownish alteration of the skin.

Vesicular stage: It is characterized by the appearance of erythematous and vesiculobullous lesions on the trunk and extremities which frequently disappear and reappear. Verrucous stage: Then, they is gradually replaced by white keratotic, lichenoid, papillary or verrucous lesions, which then persist for some months. Hyperpigmentation stage: Some of the lesions in infants are brownish gray macules in a streaked, patchy distribution over the trunk and extremities, occurring subsequent to the verrucous keratotic lesions. There is heavy melanin pigmentation of epithelium, dropping down into cluster of chromatophores in the upper dermis (incontinence), which gives the disease its name. Atrophy and depigmentation stage: This stage ultimately occur in the patient. Other defects can be seen like cataract, optic atrophy, strabismus, retrolental fibroplasia, central nervous system involvement and lesions of skeletal system.

Oral Manifestations Both the deciduous and permanent dentitions may be affected. There is delayed tooth eruption, peg and cone shaped crowns, congenitally missing teeth, malformed teeth and additional cusps.

Histopathological Features In early stage there is cleft in the epithelium which consists of eosinophils. During the verrucous stage hyperkeratosis, acanthosis, and papillomatosis is seen. There are also macrophages in the connective tissue with hyperpigmentation.

Management No treatment is necessary for skin disease. Dental defects can be corrected with the assistance of orthodontics and prosthetic dentistry. Points to Remember Bloch-Sulzberger syndrome, vesicular stage, verrucous stage, hyperpigmentation stage, brownish gray macules, atrophy and depigmentation stage, delayed tooth eruption, peg and cone shaped crowns, cleft, hyperkeratosis, acanthosis, papillomatosis.

Types Benign: It may be present at birth or occur later in childhood; appears to be genetic in origin inherited as a dominant characteristic. It can occur with some syndrome like Crouzon syndrome or due to drug ingestion. Malignant: It is associated with internal malignancy like adenocarcinoma of stomach and occurs in older age group. Pseudoacanthosis nigricans: It is most common and is associated with endocrinopathy.

Clinical Features The most common areas involved are axilla, palms and soles and face and neck. Signs: Skin lesions are symmetric with mild hyperpigmentation and mild papillary hypertrophy of only small patchy areas. It usually involve flexural areas of skin. Patches are browns in color and hyperkeratotic. In some cases, it is heavily pigmented, aggressively verrucous lesion involving much of the skin. The verrucous lesions are often pigmented and generalized pruritus is also a common finding.

Oral Manifestations The tongue and lips are most commonly involved, followed by buccal mucosa. There is hypertrophy of the filiform papillae producing a shaggy, papillomatous surface on the dorsal tongue. The lips may be enlarged and covered by papillomatous growths, particularly at the angle of mouth. The buccal mucosa may show a velvety white appearance with occasional papillary lesions.

Histopathological Features There is marked acanthosis, coupled with peculiar parakeratosis (Fig. 29.18). Upward finger like projection of dermal papillae occur. There is also thinning of adjacent epidermis and presence of pseudo horn cyst. Keratinized stratified squamous epithelium shows papillary projections. Hyperkeratosis is a prominent feature. Skin lesions have more deposition of melanin and less acanthosis. Oral lesions show more spinous cell acanthosis and less melanin deposition.

Skin Disorders

Rubber man: In some patients, skin extensibility is pronounced, the patient is known as ‘rubber man’. Papyraceous scarring: This is an unusual healing response that occur to minor injury to skin. It resembles crumpled cigarette paper. Hypertelorism, a wide nasal bridge, epicanthic folds, protruding ears and frontal bossing are often present. Freely movable subcutaneous nodules are frequently found, which represent fibrosed lobules of fat. The scarring of skin following wound healing in these patients is unusual, as the scars tend to spread rather than contract in time. In hypermobility types there is hyperextensibility of the joint. In vascular types there is fragility of skin and blood Figure 29.18 Acanthosis nigricans showing like projection, vessels, resulting in excessive bruising as well as defective parakeratosis and hyperpigmentation. (Courtesy: Dr Sangamesh healing of skin wounds. Rupture of large arteries as well Halawar, Reader, Oral Pathology, CDCRI, Rajnandgaon, as of intestine often occurs, producing a life-threatening Chhattisgarh) situation.

Oral Manifestations Management As such there is no treatment for this disease. Patient should be properly evaluated and if malignancy is present, it should be treated. Points to Remember Brown patches, verrucous pigmented lesions, hypertrophy of the filiform papillae, enlarged lips, acanthosis, pseudo horn cyst, finger like projection of dermal papillae, parakeratosis.

Oral mucosa is of normal color but is excessively fragile and bruises easily. The gingival tissue appears fragile and bleeds after tooth brushing. Hypermobility of temporomandibular joint resulting in repeated dislocations of the jaw have been reported. Gorlin sign: There is ability of the patient to touch their nose with tongue. There may be lack of normal scalloping of the dentinoenamel junction, formation of irregular dentin and increased tendency to form pulp stones with hypoplastic changes in enamel.

EHLERS DANLOS SYNDROME

Lab Findings

It is also called cutis hyperelastica and it is a group of hereditary disorders of connective tissue. There is production of abnormal collagen protein which is structural compound of connective tissue.

Clotting time is normal, but capillary fragility test is usually positive.

Management

There is no specific treatment for this disease, but surgical procedures should be carried out carefully as healing There are mainly seven types of Ehler Danlos syndrome. problems can exist. They are classical (mild and severe), hypermobility, Points to Remember vascular, kyphoscoliosis, arthrochalasis, and dermatoHyperelasticity of skin, rubber man, papyraceous sparaxis. scarring, hypertelorism, frontal bossing, hypermobility Clinical Features of joint, fragility of skin, fragile gingival tissue, hypermobility of temporomandibular joint, Gorlin sign There is hyperelasticity of skin is a feature of this positive capillary fragility test. disease.

Types

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PSORIASIS 746

It is common a dermatological disease characterized by white, scaly papules and plaque on an erythematous base that preferentially affects the extremities and scalp. Word psoriasis comes from Greek word for itching.

Etiology and Precipitating Factors It has been suggested a possible inheritance pattern, possibly transmitted as simple dominant trait. b-hemolytic streptococcal infection often precedes psoriasis. Metabolic disturbances and endocrine dysfunction can also precede psoriasis. There is increase proliferative activity of cutaneous keratinocytes. Activated T-lymphocytes is found to causative mechanism for abnormal production. Antimalarials, b-blocker and lithium may worsen psoriasis and the rash may rebound after stopping systemic corticosteroids or potent local corticosteroid. Anxiety precipitates some exacerbation. Mental anxiety and stress can increase severity of the disease. In areas of skin damage such as scratches or surgical wound.

Clinical Features Age and site distribution: It commonly affects adults and arises in 2nd and 3rd decades of life. It is commonly occur on extremities, and scalp. It is usually chronic with acute generalized exacerbations. It is more severe in winter and less severe in the summer as a result of increase exposure to ultraviolet light. Symptoms: It is characterized by occurrence of small sharply defined, dry papules each covered by delicate silvery scale which appear as resembling a thin layer of mica (Fig. 29.19). Auspitz’s sign: If the deep scale is removed one or more bleeding points are seen. Papules are enlarged at periphery and may form large plaques which are roughly symmetrical. After removal of scale the surface of skin is red and dusky in appearance. In some cases involvement of joint can occur which is term as psoriatic arthritis. This can also involve TMJ. Clinical Types • • • •

Stable plaque psoriasis Guttate psoriasis Pustular psoriasis Erythrodermic psoriasis.

Figure 29.19 Patient is having dusky appearance on leg in

patient of psoriasis

Clinical Types Stable plaque psoriasis: It is most common type. The lesions are red with dry, silvery-white scaling, which may be obvious only after scraping the surface. Guttate psoriasis: It is seen in children adolescents and may follow streptococcal sore throat. Individual lesions are droplet-shaped, small and scaly. Erythrodermic psoriasis: The skin becomes universally red and scaly or more rarely just red with very little scale present. Pustular psoriasis: It is a severe form of psoriasis with eruption of minute pustule with shedding of nails is common.

Oral Manifestations Site: Oral lesions are reported on lip, buccal mucosa, palate, gingiva and floor of mouth. Appearance: They appear as plaques, silvery, scaly lesions with an erythematous base. Sometime they are multiple papular eruptions which may be ulcerated or as small, papillary elevated lesions with scaly surface. Usually four types of oral manifestation occur in patient with psoriasis: The first type consists of minute well defined gray to yellowish white lesion that is round or oval. The second type is characteristic by white, elevated, lacy, circinate lesion on the oral mucosa including the tongue. These eruption parallel those of the skin.

Skin Disorders

The third type consists of a fiery red erythema of the oral mucosa, including the tongue is seen in acute form. The fourth type of oral lesion described in psoriasis is a geographic tongue that occurs most frequently among the patients with psoriasis than without.

Histopathological Features Intraepithelial micro-abscess formation (Munro’s abscess) occurs. It is characterized by uniform parakeratosis, absence of stratum granulosum. Test tube appearance: There is elongation and clubbing of rete pegs. This appearance of rete pegs is termed as test tube appearance (Figs 29.20 and 29.21). The epithelium over the connective tissue is thin and it is from this point bleeding occurs when the scales are removed. Tortuous, dilated capillaries extending high in the papillae are prominent.

Management Topical Agents Emollients: It have modest effect in terms of reducing scale. Dithranol: It is gold standard therapy with dithranol. It normalized differentiation and inhibits proliferation when applied to psoriatic plaques. Tar: Crude tar is used which is pro-inflammatory and action same as dithranol. Calcipotriol: It is vitamin D agonist and it reduces the thickness of plaque. Retinoid: It diminished the induration, scaling and redness of plaque. Corticosteroids: Use of potent topical corticosteroid on the face or hair margins should be under close and expert medical supervision. Ultraviolet light: It is mainstay of management of patient with moderate to severe psoriasis. It is used 3 to 7 times in a week. PUVA therapy: Psoralens are natural photosensitizes found in number of plants. It includes clearance to greater degree than any other therapy. Systemic treatment: Three main systemic agents are using, i.e. methotrexate, oral retinoid and ciclosporin. Points to Remember

Figure 29.20 Psoriasis showing test tube shaped rete pegs

b-hemolytic streptococcal infection rebound rash, dry papules covered by delicate silvery scale, Auspitz’s sign, psoriatic arthritis, scaly lesions, erythematous base, Munro’s abscess, uniform parakeratosis, absence of stratum granulosum, Test tube appearance, Tortuous dilated capillaries, Dithranol, Calcipotriol PUVA therapy.

PACHYONYCHIA CONGENITA It is also called Jadassohn-Lewandowsky syndrome. It is extremely uncommon disease, inherited as an autosomal dominant characteristic with incomplete penetrance.

Clinical Features It usually occurs shortly after birth with no sex predilection. Figure 29.21 Psoriasis showing elongation of rete pegs, It consists of dystrophic changes in the fingernails and hyperkeratosis and inflammation of the papillary connective toenails (Fig. 29.22), hyperkeratotic calluses of the palms tissue (Courtesy: Dr Sangamesh Halawar, Reader, Oral and soles, follicular keratosis about the knees and elbows, Pathology, CDCRI, Rajnandgaon, Chhattisgarh) hyperhidrosis or excessive sweating of the hands and feet.

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Points to Remember Dystrophic changes, follicular keratosis, hyperhidrosis, excessive sweating of the hands and feet, sparse hair, corneal dyskeratosis, painful blister after walking, focal or generalized white, opaque thickening of the mucosa, oral aphthous ulceration, Natal teeth, intra-cellular edema or vacuolization of the spinous cell, perinuclear clearing.

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POROKERATOSIS It is also called Mibelli’s disease and it is autosomal dominant. It is characteristic by faulty keratinization of the skin followed by atrophy. Figure 29.22 Pachyonychia congenita showing dystrophic

nails

Clinical Features

Age sex and site predilection: The majority of begins in early childhood but progression of disease is extremely There is marked thickening, increasing toward the free slow. It appears to occur in males with greater frequency border with nail bed becoming filled with yellowish keratotic debris, often causing the nail to project upward at the free than in female. It occurs most commonly in extremities edge. It is associated sparse hair and corneal dyskeratosis particularly in hands and feet, as well as shoulder, face and neck and the genitalia. producing corneal opacities have been reported. Bullae formation occurs on the feet, and secondary infection of these may lead to crippling deformity. The striking features of this disease is that there is formation of painful blister after few minutes of walking in the warm weather. Thickening of the laryngeal commissures, tympanic membrane and nasal mucosa and mental retardation are also reported.

Oral Manifestations The most common site of occurrence are buccal mucosa, tongue and lips. They consist of focal or generalized white, opaque thickening of the mucosa. There is frequent oral aphthous ulceration is seen. In some cases inflammation of angle of mouth is seen. Natal teeth are also present.

Histopathological Features The mucous membrane exhibits and intracellular edema or vacuolization of the spinous cell reminiscent of white sponge nevus. A nonspecific thickening of the parakeratin and spinous cell layer is seen. There is also acanthosis with perinuclear clearing of the epithelial cells.

Management There is no treatment for this disease as lesion in oral cavity has no tendency for malignant transformation.

Keratotic papules: It consists initially of crateriform keratotic papules which gradually enlarged to form elevated plaques. In some cases there is ring like keratotic lesion of the skin with atrophic center. Signs: Keratotic papules size is ranging in size from a few millimeters to several centimeters. The plaques are surrounded by a distinct raised border of epidermal proliferation. Nails: The nails commonly become thickened and ridged. The central portion of the lesions ultimately becomes atrophic, leaving permanent scarring.

Oral Manifestations It is most commonly seen on upper lip and palate. There is numerous small slightly opalescent ring and serpenginous and hyperemic border studded over the palate.

Histopathological Features The elevated horny margin of the lesion exhibits hyperkeratosis and acanthosis with a deep groove filled with parakeratin and a characteristic absence of the usual underlying granular layer (Fig. 29.23). It constitutes the coronoid lamella which is characteristic of the lesion. The connective tissue beneath the coronoid lamella may exhibits lymphocytes infiltrate. The central portion

Skin Disorders

Skin lesion: In the skin fold the lesion tend to be coalesce and produce verrucous or vegetating macerated, foul smelling masses. Foul odor is results of bacterial degradation of the keratin. Nail changes: Characteristic nail changes are consisting of splintering, fissuring, longitudinal streaking and sub- lingual keratosis.

Oral Manifestations

Figure 29.23 Porokeratosis showing hyperkeratosis and

acanthosis

of the lesion shows epithelial atrophy and occasionally dyskeratosis.

Management There is no treatment for the disease except for removal of individual lesions. Points to Remember Keratotic papules, nails thickened ridged, opalescent ring, serpenginous hyperemic border studded over the palate, hyperkeratosis, lymphocytes infiltrate, parakeratin, coronoid lamella, acanthosis.

Keratotic papule occur on oral mucosa particularly on hard and soft palate, gingiva, tongue have whitish appearance. They are multiple whitish papules which feel rough upon palpation. In some cases it has been described as rough, pebbly areas with verrucous white plaque or as having cobblestone appearance. Papule become confluent as disorder progress.

Histopathological Features The characteristic finding in skin lesion is hyperkeratosis, papillomatosis, acanthosis and peculiar benign dyskeratosis. Corps ronds and grain appearance: Dyskeratosis is characterized by typical cells called corps ronds and grains (cell within cells) (Fig. 29.24). The corps ronds (round bodies) are larger than normal squamous cells and have a round, homogeneous, basophilic nucleus with a dark eosinophilic cytoplasm and distinct cell membrane. Grains (resembles cereal grain) are small, elongated parakeratotic cells situated in the keratin layer.

KERATOSIS FOLLICULARIS It is called Darier’s disease, Darier-White disease and dyskeratosis follicularis. It is autosomal dominant trait with high degree of penetrance and variable expressivity. There is lack of cohesiveness among the surface epithelial cells characterized the disease.

Clinical Features Age, sex and site distribution: It is usually manifested during childhood or adolescence and has equal sex distribution. They are generally distributed above the forehead, scalp, neck, and over the shoulders. Appearance of lesion: The cutaneous lesion appears small, firm papules. They are red when they first appear but characteristically become grayish brown or even purple. It can ulcerate and crust over.

Figure 29.24 Keratosis follicularis showing corps and grain

appearance

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Acantholytic cells are commonly found floating in the lacunae produced by this intraepithelial separation. 750

Management Patient should minimized unnecessary exposure for hot environment. Administration of large dose of retinoid is given. Points to Remember Darier’s disease, cutaneous lesion appears small, firm papules, skin lesion verrucous vegetating macerated, nail splintering and fissuring, sub-lingual keratosis, rough, pebbly areas with verrucous white plaque, cobblestone appearance, Corps ronds and grain appearance, Acantholytic cells, retinoid.

WARTY DYSKERATOMA It is also called isolated Darier’s disease which bears histological similarity to Darier’s disease but it present as single isolated focus

Clinical Features Age and site distribution: It is usually occur in older age group with male predominance. The skin lesion occurs on face, scalp, neck and upper chest. They appear as elevated nodules, umblicated, with raised borders and varying in color from yellow or brown to gray or black (Fig. 29.25). They appear as invariably single lesion varying in size from 1 to 10 mm in diameter. Purulent drainage as well as bleeding occurs in some cases.

Oral Manifestations It is very rare and it is if present found most commonly on the alveolar ridge and palate. Appearance: It appears as small whitish or pink area of the mucosa with a central depression. Focal acantholytic dyskeratosis: It is variant of warty dyskeratoma in which two or three discrete lesion arising adjacent to one another.

Histopathological Features The microscopic finding of skin and mucosal lesion are identical except for the absence of a pilosebaceous structure in the oral lesion. The intraoral lesion exhibits a central orthokeratin or parakeratin core beneath which the epithelium shows a suprabasilar separation resulting in a cleft like space containing acantholytic and benign dyskeratotic cells. The connective tissue papillae are covered usually by a single layer of basal cells while the underlying connective tissue shows a non-specific chronic inflammatory infiltrate. Spinous layer is thickened and contains individually keratinized cells.

Management It should be treated by surgical excision. Points to Remember Elevated nodules, umblicated with raised borders, color yellow or brown to gray or black, whitish or pink area of the mucosa, Focal acantholytic dyskeratosis, pilosebaceous, orthokeratin or parakeratin core, spinous layer thickened, chronic inflammatory infiltrate.

SEBORRHEIC KERATOSIS In this there is benign proliferation of epidermal basal cells. It can cause by chronic sun exposure or it can be hereditary.

Clinical Features Location: It is commonly seen on skin of the face, trunk, and extremities. Age: It is usually presented in during 4th decade of life.

Figure 29.25 Warty dyskeratosis showing elevated lesion

Appearance: Multiple lesion which initially small tan to brown macules which enlarge gradually and elevated. Individual lesions are well demarcated plaque with fissured and pitted surface. They have got stuck onto skin appearance.

Skin Disorders

Dermatosis papulosa nigra: This appear in black and appear as multiple dark brown to black papules scatter about zygomatic and periorbital region. Laser-Trelat sign: Sudden appearance of numerous seborrhoeic keratosis with pruritus has been associated with internal malignancy.

Histopathological Features There are exophytic proliferation of basilar epithelial cells with surface keratinization, acanthosis and papillomatosis. Horn cyst or pseudo horn cyst: The lesion exhibits deep keratin filled invagination which appear cystic on cross section. Squamous eddies: Squamous metaplasia of the lesion cells results in whorled epithelial pattern. Histopathological Types of Seborrhoeic Keratosis • A canthotic form: It exhibits little papillomatosis and marked acanthosis with keratinization • Hyperkeratotic form: There is prominent papillomatosis and hyperkeratosis with minimal acanthosis • Adenoid form: It consists of anastomosing trabecular or lesion cell with little hyperkeratosis or papillomatosis • Inverted follicular keratosis Helwig: It is irritated seborrhoeic which occur chronic trauma. It show mild proliferation into connective tissue and chronic inflammatory cell infiltrate adjacent to lesion.

Management Cryotherapy with liquid nitrogen is treatment of choice.

HEREDITARY MUCOEPITHELIAL DYSPLASIA

Oral Manifestations Oral lesion is fiery red, flat or micropapillary frequently involving gingiva and hard palate. Red enlarged and fissured tongue is common occurrences.

Histopathological Features The oral lesions show a lack of cornified and keratinized cells, thinning of the epithelium and dyskeratosis. There is disorganized maturation pattern. The squamous epithelial cells have high nuclear/cytoplasmic ratio. Cytoplasmic vacuoles appear as grayish inclusion.

Management No specific treatment for the disease. Points to Remember • F ollicular keratosis of the skin, non-scarring alopecia, severe photophobia • Red enlarged and fissured tongue, cornified epithelium, high nuclear/cytoplasmic ratio, dyskeratosis, keratinized cells.

PSEUDOXANTHOMA ELASTICUM It is autosomal recessive and the basic defect involves the structure of elastin, making it susceptible of calcification. It is rare hereditary connective tissue disorder, characterized by generalized degeneration of the elastic fibers with a broad phenotypic expression. The clinical picture consists mainly of cutaneous, ocular, and vascular manifestations.

Clinical Features Age: Although widely variable, the age of onset averages 13 years with no predilection for sex.

It is described by Witkop and associates in 1978. It is autosomal dominant. Mucosal epithelial cells do not develop in normal fashion so the name dysplasia is given.

Appearance: Raised yellowish papules develop on areas of thickened, coarsely grained skin especially around the mouth, neck, axilla, elbows.

Clinical Features

Angiod steaks: Brownish gray streaks of the optic fundus (angiod streaks), recurrent gastrointestinal hemorrhage, and weak pulse, and failing vision is common occurrence. The typical cutaneous lesions are small yellowish papules or larger coalescent plaques with an appearance similar to plucked chicken skin. More severely affected skin results in hanging, redundant folds.

It affects all orofacial mucosa and is characterized by follicular keratosis of the in skin, non-scarring alopecia. Eyelashes and eyebrows are frequently affected. Severe photophobia develops at early age resulting in cataracts, corneal vascularization. Repeated episodes of pneumonia, spontaneous pneumothorax.

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Oral Manifestations 752

Mucous membranes, mainly of the inner aspect of the lower lip are affected. Hound dog appearance: Skin around mouth becomes redundant, producing a hound dog appearance. Lower lip exhibit yellowish intramucosal nodule.

There may be calcification of dorsum sellae. Cutaneous lesions commences as vesicles, upon healing acneform scars develop. Most of the patient exhibits thickened furrowed appearance. In some cases intracranial calcification may lead to seizure disorders.

Histopathological Features

Oral Manifestations

Intramucosal nodules show large number of thickened and twisted elastic and collagen fibers. Skin histopathology involves swollen, irregularly clumped and multiply fragmented elastic fibers in the middle and deep reticular dermis, with secondary calcium deposition.

Most commonly affected area is lower lip. It can be seen on tongue, buccal mucosa. Affected tissue become infiltrated with yellowish white elevated pea sized plaque which gradually increased in size in puberty. Symptoms: Recurrent painful parotitis with stenosis of parotid duct opening occurs. Congenital absence of teeth and severe enamel hypoplasia may occur. Radiating tissue may appear at angle of mouth. Tongue become firm and large and bound to floor of mouth. The dorsum of tongue may losses its papilla and ulcer may develop. Diffuse hyperplastic appearing gingival infiltration is present. There is restriction of oral function such as saliva flow, tooth eruption, and swallowing. There is hypodontia of maxillary lateral incisors and premolars. Lips become thickened and nodular white while tongue becomes thickened, enlarged, very firm to palpation and sometimes bound to floor of mouth.

Management At present, no specific treatment exists. The knowledge, however, of the potential complications may lead physicians to take some necessary precautions. Points to Remember Angiod steaks, raised yellowish papules, Hound dog appearance, multiply fragmented elastic fibers swollen irregularly clumped, twisted elastic and collagen fibers.

HYALINOSIS CUTIS ET MUCOSA ORIS It is also called lipoid proteinosis or Urbach-Wiethe syndrome. It is autosomal recessive trait, characterized by subdermal and submucosal infiltration of a hyaline glycoprotein material. It occurs due to disturbance of mucopolysaccharide metabolism or alteration in formation of lipoprotein.

Clinical Features Age and site distribution: It is mostly seen in young adults with no sex predilection. It is common in mucosal tissue, skin, vessel walls, larynx, and brain. It is also seen in face, eyelids and neck. Symptoms: Laryngeal mucosa and vocal cords are first sites to involve. So patient wills complaint of hoarse voice during childhood. In infancy hoarse cry and inability of the infant to make crying sound. Signs: Patient develops solitary or clustered yellowish white waxy nodules. It is solid in consistency and fixed to underlying tissue. It varies in size from 1 mm to 0.5 cm in diameter. It has nonulcerated surface.

Histopathological Features It shows diffuse hyalinization with prominent hyaline perivascular cuffing. There is deposition of lamellar material around blood vessels nerves, hair follicles and sweat gland. These deposits are PAS positive and show equivocal reaction for amyloid.

Management No known treatment for the disease. Gingivectomy is recommended when diffuse hyperplastic appearing gingival infiltration is present. Points to Remember Hoarse voice, clustered yellowish white waxy nodules, yellowish white elevated pea sized plaque, recurrent painful parotitis, firm tongue, diffuse hyperplastic gingival infiltration, hypodontia, diffuse hyalinization, hyaline perivascular cuffing.

Skin Disorders

WHITE SPONGE NEVUS It is oral genodermatose, which was described by cannon in 1935, hence it is also known as Cannon’s disease. It is also called white folded gingivostomatitis, congenital leukokeratosis, pachyderma oralis or oral epithelial nevi. It is autosomal dominant with irregular penetrance. It appears to represent a defect in epithelial maturation involving tonofilament formation with impaired normal desquamation of the superficial strata of cells.

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Clinical Features Age and site distribution: It has no definite sex predilection with children most commonly affected and may present at birth and may become intense at puberty. The most common sites are cheek, palate, gingiva, floor of mouth, portion of tongue. It may be widespread and may involve entire mucosa. It can also occurs on the mucous membranes of the nose, esophagus, genitalia, and rectum.

Figure 29.26 White sponge nevus showing marked increase

in the spinous cell layer and vacuolated cells

Signs and symptoms: Mucosa appears thickened and folded or corrugated with soft or spongy texture and a peculiar white opalescent line. It has got sodden, furrowed or wrinkled appearance. The lesion varies in extent from a small patch to involvement of a large area of mucosa. Friction may strip superficial keratotic area leaving zone of normal looking epithelium or raw area. Ragged white area may be present which can be removed by gentle rubbing without bleeding. Figure 29.27 White sponge nevus showing inflammatory cell

Histopathological Features (Figs 29.26 to 29.28) Epithelium thickened showing hyperkeratosis, acanthosis with basal layer being intact. In some cases there is extensive keratosis showing basket-weave appearance. The cells of the entire spinous layer exhibit intracellular edema and show pyknotic nuclei. There is also oraganophilic perinuclear cytoplasmic condensation. In addition, parakeratin plugs running deep into the spinous layer are typically found. The submucosa may show a mild inflammatory cell infiltration. The characteristic feature of white sponge nevus is the perinuclear eosinophilic condensation which is more appreciable in exfoliative cytology. This is proved ultra structurally to be tangled masses of keratin tonofilament.

infiltration

Figure 29.28 White sponge nevus showing acanthosis with

clear cytoplasm

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Management

Histopathological Features

There is no specific treatment for this disease but prognosis is very good. Palliative procedure to relive burning and tenderness.

Buccal mucosa exhibits thickening of the epithelium with pronounced hydropic degeneration. Numerous round; waxy-appearing eosinophilic cells resembling minute epithelial pearls are present. There is peculiar intraepithelial dyskeratosis in addition to acanthosis and vacuolization.

Points to Remember Cannon’s disease, thickened corrugated mucosa, raw ragged white area, basket-weave’ appearance, intracellular edema, parakeratin plugs, perinuclear eosinophilic condensation.

HEREDITARY BENIGN INTRAEPITHELIAL DYSKERATOSIS It is also called Witkop-Von Sallman syndrome. It is superficially similar to the white sponge nevus in its hereditary pattern but its clinical and microscopic features are different. It is inherited as autosomal dominant trait and there is defect in keratinization characterized by cytoplasmic accumulation of tonofilament with loss of cellular interdigitation and desmosomes.

Clinical Features It is most commonly seen in children with no sex predilection. It is commonly seen in eyes. Superficial gelatinous looking plaques occur on a hyperemic bulbar conjunctiva. Eye is characterized by superficial, foamy, gelatinous white plaque overlying the cornea, sometimes producing temporary blindness. Eye lesion show seasonal variation tending to appear or increase in severity in the springs and disappear. There may be photophobia and cause by involvement of cornea by plaque formation and scarring.

Oral Manifestations Site predilection: They are most commonly seen in buccal mucosa, floor of mouth, ventral and lateral surfaces of the tongue, the gingiva, and palate. Appearance: It appears generally as white, spongy, macerated lesions of the buccal mucosa with or without folds. These lesions vary from delicate, opalescent white membranous areas to a rough, shaggy mucosa. Lesion frequently involves the corners of the mouth and appears as soft plaques with pinpoint elevation when the mucosa is stretched.

Management No treatment is necessary but its potential for blindness, genetic counseling may be in order. Points to Remember Witkop-Von Sallman syndrome, temporary blindness, photophobia, white, spongy, macerated lesions of the buccal mucosa, pinpoint elevated plaque, hydropic degeneration, round; waxy-appearing eosinophilic cells.

HEREDITARY HEMORRHAGIC TELANGIECTASIA It was first described by Osler in 1901 and it frequently bears his name (Osler-Rendu-Weber syndrome). It is transmitted as an autosomal dominant trait and characterized by bleeding from mucous membrane and telangiectatic lesions on skin and mucosa.

Clinical Features Age and site distribution: They are found most commonly on the skin of the face, finger, toes and on the oral mucous membrane. The lesion may be present in childhood but more often appear in puberty and become progressively worse with increasing age. Telangiectases: The disease is characterized by multiple localized angiomatas or telangiectases on the skin. The lesion bleeds easily, even after slightest trauma. Bleeding is not caused by clotting factor deficiency but as a result of rupture of the weak capillaries. The typical lesion is cherryred to purplish macule or small papule that resembles a crushed spider. The lesion blanches on pressure and regains it’s color when the pressure removed. The telangiectatic areas are not-pulsating. As the affected individual grows, the bleeding episode tend to increase in frequency and intensity. They often give rise to profuse hemorrhage, such

Skin Disorders

as episodes of epistaxis. Severe bleeding may also occur from the gastrointestinal tract.

Oral Manifestations Oral cavity, lips and tongue are most commonly affected. Cherry red, often slightly raised, pin point or slightly larger lesions resembling a crushed spider is seen at any intraoral site, especially at the lip. Severe oral hemorrhage may be experience several times a day for weeks. At times there is gush of blood when involved areas are simply touched with cotton. Hemorrhage can be encountered during dental treatment which encroaches the affected area.

Histopathological Features Intrinsic defect in the endothelial cells permitting their detachment or defect in the perivascular supportive tissue bed, which weakens the vessels.

Diagnostic Criteria Diagnosis of hereditary hemorrhagic telangiectasia is made if patient has three of the following criteria. Recurrent Spontaneous Epistaxis • Telangiectasia of the mucosa and skin • Arteriovenous malformation involving the lungs liver or CNS • Family history of HHT.

Management Sclerosing agent such as sodium morrhuate or sodium tetradecyl sulfate injected into the lesion is useful. Spontaneous hemorrhages may be controlled by pressure packs, particularly nasal bleeding. Points to Remember

Clinical Features Age and sex distribution: There is no sex or racial preponderance. It is seen in childhood. Site: It is seen in periorificial area like mouth, nose, anus and genital region. Skin is affected in half of the patient. Pigmented macules show an increased amount of melanin in the basal layer of the epidermis without any associated increase in the number of melanocytes. The oral mucosa is always involved with affection of buccal mucosa, gums hard palate and lower lips. Lesions are irregularly distributed round, oral or irregularly patch brown or black in color and 1 to 5 mm in diameters. Gastrointestinal polyps are benign hamartomas with relatively less potential for malignant transformation. They may occur throughout the gastrointestinal tract but are commonly observed in the small intestine. The symptoms of Gl Polyps are repeated abdominal colic, rectal, bleeding, hematoma, anemia usually start between 10 and 30 years of age. Apart from an increased risk of malignancy life expectancy is normal.

Histopathological Features Polyp represents overgrowth of intestinal glandular epithelium which are supported by core of smooth muscle. There is also slight acanthosis of the epithelium with elongation of rete pegs. Dentritic process of melanocytes is elongated.

Management Genetic counseling should be done. Points to Remember Periorificial lentiginosis, pigmented macules, gastrointestinal polyps, slight acanthosis, elongated, dentritic process of melanocytes.

Osler-Rendu-Weber syndrome, cherry-red to purplish macule, crushed spider, sclerosing agent sodium morrhuate or sodium tetradecyl sulfate.

EPHELIS

PEUTZ-JEGHERS SYNDROME

It is also called freckle. It is hyperpigmented macule seen on skin which occurs due to increase melanin pigmentation. It has got genetic predisposition. Lesions become more pronounced after sun exposure.

It is also called periorificial lentiginosis. This is an autosomal dominant disorder showing pigmented macules on the oral mucosa and skin associated with gastrointestinal polyposis. A family history is fond in 60 percent of cases.

Clinical Features Age: It is more commonly seen in teenage years.

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Location: It is more commonly seen face, arms, and back of the patients. Macule may be multiple in numbers. 756

Appearance: It is round to oval and remains less than 3 mm diameter with light brown color. It is well demarcated from the surrounding skin.

Points to Remember Lentigo solaris, uniformly pigmented brown to tan macules, lesion may coalesce, elongated rete ridges, club shaped actinic lentigines, cryotherapy.

Histopathological Features

LENTIGO SIMPLEX

It is composed of stratified squamous epithelium with melanin in basal cell layer.

It is benign melanocytic cutaneous hyperplasia of unknown cause.

Management

Clinical Features

The use of sunscreen lotion with help in preventing appearance of new lesion

Age: It is more commonly seen in children

Points to Remember Freckle, face, arms, and back of the patients, round to oval, stratified squamous epithelium with melanin in sunscreen lotion.

ACTINIC LENTIGO It is also called lentigo solaris, solar lentigo, age spot, liver spot, and senile lentigo. It is macule which occurs due to chronic ultraviolent damage to the skin.

Clinical Features Age: It is more commonly seen in people more than 70 years of age. Location: It is seen on dorsa of hand, face, and arms of older white people. Appearance: Individual lesion appear as uniformly pigmented brown to tan macules with well demarcated irregular border.

Location: It occur in areas which is not exposed to sunlight. It is seen skin of trunk and extremities Appearance: It is tan to dark brown color macule with well demarcated border which is less than 5 mm in diameter.

Histopathological Features Basal layer of melanocytes show increase number of benign melanocytes. This are seen clustered at the tip of rete ridges. Melanin incontinence: Abundant melanin and basal keratinocytes seen in melanocytes and papillary dermis in association with melanophages.

Management Conservative surgical excision should be done for esthetic purpose. Points to Remember Benign melanocytic cutaneous hyperplasia, skin of trunk and extremities, tan to dark brown color macule, increase number of benign melanocytes, melanin incontinence, conservative surgical excision.

Sign: Lesion is less than 5 mm in diameter. Lesion may coalesce.

SEBACEOUS HYPERPLASIA

Histopathological Features

In this there is localized proliferation of sebaceous gland of the skin. It can be associated with cyclosporine, systemic corticosteroid, and Muir-Torre syndrome.

There are elongated rete ridges with club shaped actinic lentigines. There is also thinning of epithelium above the connective tissue papillae.

Clinical Features Age: It is seen in older individual in 5th decade of life.

Management Lesion is treated by cryotherapy, laser therapy, and intense pulsed light therapy.

Location: It is seen on skin of face in area of nose, cheeks, and forehead. It can also occur on genital area, chest, and areola.

Skin Disorders

Appearance: It is yellow white nontender papules which are soft in consistency. Sign: Lesion is umblicated with central depression which occur due to ducts of sebaceous gland. Lesion is smaller than 5 mm in diameter. Thick yellow white sebum expressed in the central depressed area after compression of lesion.

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Oral sebaceous hyperplasia: It show cauliflower appearance seen on buccal mucosa.

Histopathological Features There is collection of enlarged sebaceous gland lobule around centrally located sebaceous duct.

Figure 29.29 Pigmentation seen on neck and face due

xeroderma pigmentosum

Management Excisional biopsy, cryosurgery, electrodessication, laser therapy, and photodynamic therapy can be done. It is only done for esthetic reason. Points to Remember Localized proliferation of sebaceous gland of the skin, yellow white nontender papules, lesion is umblicated, central depression, oral sebaceous hyperplasia, collection of enlarged sebaceous gland lobule, excisional biopsy.

Oral feature: Orally squamous cell carcinoma can occur on lower lip and tip of the tongue.

Histopathological Features Malignancy which occurs in this disease has got same manifestation as that seen in other malignancy.

Management

XERODERMA PIGMENTOSUM

Protection: Patient should avoid sunlight and non- filtered light. If they cannot avoid sunlight protective clothing and sunscreen should be used.

It is very rare genodermatosis where cutaneous malignancy develops. It is inherited as autosomal recessive trait.

Topical chemotherapeutic agents: 5-fluorouracil can be used to treat actinic keratosis.

Cause

Points to Remember

There is inability of the epithelial cells to repair ultraviolet induce damage. Due to this mutation in epithelial cells occur resulting in development of skin cancer.

Actinic keratosis, oral squamous cell carcinoma, freckled pigmentation on skin, topical chemotherapeutic agents – 5-fluorouracil.

Clinical Features Age: It usually occurs in first decade of life.

TUBEROUS SCLEROSIS

Site: As this is related to sun exposure head and neck is the most common site of involvement.

It is also called Pringle-Bourneville syndrome. Tuberous sclerosis (TS) is an autosomal dominant disorder with marked variability of expression in a given family.

Skin changes: Skin changes like atrophy, freckled pigmentation and patchy depigmentation occur (Fig. 29.29)

Clinical Features

Actinic keratosis: This can occur in childhood. This can ultimately lead to squamous cell carcinoma or basal cell carcinoma.

Ash-leaf macules: These are hypopigmented macules of ovoid shape seen on the skin. Shagreen patch: These are connective tissue hamartomas.

Textbook of Oral Pathology

Multiple angiofibroma: These are multiple red brown macules and papules are seen about the mouth in the nasolabial folds. 758

Ungual or periungual fibromas: These are seen under the margin of nails. Central nervous system (CNS) findings include epilepsy mental retardation. Hamartomatous proliferation in the CNS develops potato like growth (tubers). That is reason it is called tuberous sclerosis. Other features: Others rare features include are cardiac rhabdomyoma and angiomyolipoma.

Oral Features The oral cavity frequently shows distinctive changes. Angiofibroma, fibromas or papillomas are found on the gingiva, hard and soft palate, buccal mucosa and tongue. They may be white or yellow although they lack any distinctive tint. Both dentitions have tiny pits arising from enamel defects. The pits are often an early diagnostic clue. A high palate, macroglossia, cleft lip and palate and hemangioma have been described. Diagnostic Criteria (One major and two minor criteria should be present) Major criteria • Facial angiofibroma • Hypomelanotic macules • Shagreen patch • CNS hamartomas • Cardiac rhabdomyoma • Renal angiomyolipoma

Management Anticonvulsant agent: It is given for the management of seizure. Maintenance of oral hygiene should be done periodically. Points to Remember Pringle-Bourneville syndrome, Ash-leaf macules, Shagreen patch, multiple angiofibroma, ungual or periungual fibroma, fibromas or papillomas are found on the gingiva tiny pits on dentitions, a high palate, macroglossia, cleft lip, nonspecific fibrous hyperplasia, plump uniform spaced fibroblast, anticonvulsant agent, thin walled vascular channels.

ECTODERMAL DYSPLASIA It is also called hereditary hypohidrotic (anhidrotic) ectodermal dysplasia. It is an X-linked, recessive Mendelian character. It results from aberrant development of ectodermal derivation in embryonic life.

Clinical Features Sex distribution: Males are affected more frequently than females. Appearance: It is characterized by hypotrichosis, hypohidrosis and anhidrosis with saddle nose appearance (Fig. 29.30).

Minor criteria • Enamel pit • Gingival fibromas • Multiple renal cyst • Hamartomatous rectal polyps.

Histopathological Features It is nonspecific fibrous hyperplasia seen in biopsy taken from gingival fibrous papules. Angiofibroma shows delicate fibrous connective tissue which consist of plump uniform spaced fibroblast with interspersed thin walled vascular channels.

Figure 29.30 Patient having saddle nose appearance seen in

case of ectodermal dysplasia

Skin Disorders

The hair of scalp and eyebrows tend to be fine, scanty and blond. Supraorbital and frontal bosses are pronounced (Fig. 29.31). Skin is often dry, soft, smooth and scaly with partial or complete absence of sweat glands. Such patient cannot perspire and they usually suffer from hyperpyrexia and inability to endure warm temperature. Facial appearance of these individual resemble to each other, enough to be mistaken for siblings. In infancy patient cannot regulate skin temperature due to decrease number of sweat gland.

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Figure 29.33 Hypodontia in ectodermal dysplasia affected

child

Oral Manifestations (Figs 29.32 and 29.33)

Figure 29.31 Hereditary ectodermal dysplasia in a child

showing deficiency of hairs, eyelashes, eyebrows

Patient with this abnormality invariably manifest oligodontia or partial absence of teeth, with frequent malformation of any present tooth in deciduous and permanent dentition. Teeth which are present are usually cone shaped. There is reduction of normal vertical dimension of alveolar process as there is absence of teeth. There is also protuberance of lip due above reason. The palatal arch is frequently high and cleft palate may be present. Along with all this, since the salivary gland, including the intraoral accessory gland, are sometimes hypoplastic, they result in xerostomia and dry cracked lips with fissuring at the corners of mouth. In some cases there may be hypoplasia of accessory gland which will results in xerostomia. There is also Hypoplasia of nasal and pharyngeal, mucous gland lead to chronic rhinitis and pharyngitis.

Histopathological Finding There is reduction in the number of sweat gland, hair follicles. Epidermis is thin and flattened. Mucous gland in upper respiratory tract is reduced in number.

Management Figure 29.32 Missing teeth seen in patient with ectodermal

dysplasia

In dental point of view partial and complete dentures should be constructed for both functional and cosmetic purpose.

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Points to Remember

Points to Remember

Hereditary hypohidrotic (anhidrotic) ectodermal dysplasia hypotrichosis, hypohidrosis, anhidrosis, saddle nose appearance hair of scalp fine, scanty, skin dry, soft, smooth and scaly, hyperpyrexia, sibling appearance, decrease number of sweat gland, oligodontia, cone shaped teeth, reduction of normal vertical dimension of alveolar process, xerostomia, hypoplasia of accessory gland, chronic rhinitis pharyngitis, reduction in the number of sweat gland, hair follicles epidermis is thin.

Multiple hamartoma syndrome, multiple hamartomatous papules, acral keratosis, palmoplanter keratosis, Thyroid and breast anomalies, polyposis of the gastrointestinal tract, fibroepithelial hyperplasia.

COWDEN SYNDROME It is also called multiple hamartoma syndrome, PTN hamartoma-tumor syndrome. It is a rare inherited genodermatose. This syndrome was named after the first patient reported. It is inherited as autosomal dominant trait with high degree of penetrance. The gene responsible for this syndrome is mutation PTEN.

Clinical Features Multiple hamartomatous papules: These are present on the skin and oral mucosa. Lesion is smaller than 1 mm. Acral keratosis: This is present on the dorsal surface of hand and appears as warty growth. Palmoplanter keratosis: These are prominent callus like lesion seen on palms and soles. Thyroid and breast anomalies: Patient may suffer from goiter, thyroid adenoma, adenocarinoma and fibrocystic disease of breast. Later on breast cancer can also occur. Polyposis of the gastrointestinal tract: In the gastrointestinal tract presence of polyposis is seen. Oral features: Multiple papular lesions can affect gingivae, dorsal tongue and buccal mucosa. There may be high arch palate, periodontitis and extensive dental caries.

Histopathological Features

GRAFT VERSUS HOST RESISTANCE It usually occurs in person who is receiving allogeneic bone marrow transplantation.

Cause After giving bone marrow transplantation of HLA match individual, the engrafted cells find them in different environment. After this these cells start attacking other cells thinking that they are foreign body. This will results in GVHD (graft versus host resistance).

Clinical Features Acute condition: This occur within first few week after giving bone marrow transplantation. Patient complaint of rash on the body which can become severe sloughing resembling toxic epidermal necrolysis. Patient may having diarrhea, nausea, vomiting and abdominal pain. Chronic condition: This occur after 100 days. This lesion often resembles lesion of systemic lupus erythematous, Sjogren’s syndrome and lichen planus. Oral lesion: There is fine reticular white striae that can resembles oral lichen planus. There may be burning sensation, atrophy of oral mucosa, xerostomia, ulcerative lesion and oral epithelial dysplasia.

Histopathological Features There is hyperorthokeratosis, pointed rete pegs, and degeneration of basal cell layer. In advance cases abnormal deposition of collagen, periductal inflammation of minor salivary gland. There is also gradual aciner destruction and periductal fibrosis.

Oral lesions represent fibroepithelial hyperplasia.

Management

Management

Prevention: Proper HLA matching should be done. Patient can be given immune-modulator like cyclosporine or tacrolimus in combination with prednisolone.

It is not so specific and patient should be treated for tumors.

Skin Disorders

Topical corticosteroid: This may facilitate healing of oral ulceration. Topical tacrolimus and PUVA therapy: This can be given for the management of oral ulceration. Points to Remember HLA match individual, rash on the body, fine reticular white striae, hyperorthokeratosis, pointed rete pegs, degeneration of basal cell layer, deposition of collagen, topical corticosteroid, topical tacrolimus and PUVA therapy.

CREST SYNDROME It is also called acrosclerosis, limited scleroderma. This may be mild variant of systemic sclerosis. CREST Syndrome C- Calcinosis cutis R- Raynauds phenomenon E- Esophageal dysmotility S- Sclerodactyly T- Telangiectasia.

Management Prognosis is better and patient should be monitored regularly. Types of Scleroderma • Diffuse systemic or progressive systemic sclerosis • Localized form – Circumscribed or morphea – Linear scleroderma.

SCLERODERMA It is also called systemic sclerosis, or Hidebound disease. It is a disease which involves connective tissue, blood vessels and lead to fibrosis. It is also called progressive systemic sclerosis. It is called sclera (hard) derma (skin). In this disease there is deposition of dense collagen in the body.

Etiology

Clinical Features

It is caused by an endocrine dysfunction, vascular disease, basically an endarteritis obliterans, nervous disorder, toxic or infectious agents such as shock or pneumonia, influenza, diphtheria and exanthematous disease.

Age and sex distribution: It is more common seen in sixth and seven decade of life with female predilection.

Clinical Features

Calcinosis cutis: It is movable, multiple, nontender subcutaneous nodule. Raynauds phenomenon: It occur when patient hands or feet are exposed to cold temperature. There is dead white color blanching due to vasospasm. After some time it take bluish color due to venous stasis which later on become dusky red hue after warming. Esophageal dysmotility: There is abnormal collagen deposit in epithelial submucosa. Sclerodactyly: Finger undergo permanent flexure resulting in claw deformity. Skin takes shiny appearance. Telangiectasia: In this facial skin and vermilion border of lip is involved. These are same as that of hereditary hemorrhagic telangiectasia.

Histopathological Features They are same as that of systemic sclerosis.

Progressive Systemic Sclerosis Age and sex distribution: It generally begins in childhood or young adult and greatest incidence is between 30 and 50 years of age. Females are more commonly affected with a ratio of 3:1. It usually begins on face, hand or trunk. Symptoms: There is development of indurated edema of skin, neuralgia and paresthesia. Signs: Initial sign of progressive systemic sclerosis (PSS) is frequently Raynaud’s phenomenon, a paroxysm vasospasm of finger. In several months the edema is replaced by tightening and hardening of the skin, which results in difficulty in movements of the affected parts. Hyper pigmentation, telangiectasia and subcutaneous calcification may occur, leading to deformity and severe cosmetic problems along with involvement of internal organs. Skin area has thickened hide bound cavity with lack of mobility of skin, limited mouth opening and renal involvement.

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Localized Form (Circumscribed or Morphea) 762

It usually occurs on the sides of the chest and thighs. It begins with violaceous patches on the skin. These lesions enlarge; become indurated and eventually loose hair and ability to sweat. They may be present for several months to many years. Progressively, these lesions turn into hypo or hyperpigmented areas depressed below the level of skin. They may become stiff and hard and are usually asymptomatic.

Localized Form (Linear) A linear form of disease develops as a thin band of sclerosis that may run the entire length of extremities involving underlying muscle, bones and joints. A band made up of furrow with an elevated ridge on one side is often termed as a coup de sabre since it resembles the mark produced by the blow of saber.

Oral Manifestations The tongue, soft palate, lips and larynx are commonly involved. These are characterized by mild edema, which is followed by atrophy and induration of mucosal and muscular tissue. Microstomia: The lips become thin, rigid and partially fixed, producing microstomia and the oral aperture narrows considerably. Skin folds are lost around the mouth. Tobacco pouch mouth: It can be seen periorally where furrow rows radiate from the atrophic vermilion borders (purse string appearance), creating the so called tobacco pouch mouth. Mouse species: Nasal alae become atrophied resulting in pinched appearance of the nose called mouse species. Tongue: Tongue can become hard and rigid, losing its mobility and papillary pattern, making speaking and swallowing difficult. The color of tongue changes to a livid appearance. In the end stages, the tongue lays as a stiff, reduced body in the floor of mouth. The lingual frenum, which usually reflects the first oral change, shortens, becomes tendinous and finally disappears. Involvement of esophagus causes dysphagia. Involvement of soft tissues around the TMJ leads to restricted movement of mandible, causing a pseudoankylosis. When the facial tissues and muscles of mastication are involved the pressure exerted will cause resorption of mandible at the attachment of masseter

muscle. Gingival hyperplasia may result from calcium channel blocker.

Radiological Features Diffuse widening of periodontal ligament space is present throughout the dentition. There is also resorption of ramus of the mandible, coronoid process, chin, and condyle.

Histopathological Features There is thickening and hyalinization of the collagen fibers in the skin, with loss of dermal appendages, particularly the sweat glands. There is atrophy of the epithelium with loss of rete pegs and increased melanin pigmentation. Subcutaneous fat disappears and the walls of the blood vessels become sclerotic. In the periodontal ligament, there is an increase in collagen and oxytalan fibers, as well as appearance of hyalinization or sclerosis of collagen with diminution in the number of connective tissue cells is usually found.

Management D-penicillamine, a drug has shown promise in the management by decreasing both, the skin thickening and organ involvement by interference with cross linking of collagen and immunosuppression. Points to Remember Systemic sclerosis, Hidebound disease • Progressive systemic sclerosis: Indurated edema of skin, neuralgia and paresthesia, Raynaud’s phenomenon, Hyperpigmentation, telangiectasia, subcutaneous calcification may • Localized form (circumscribed or morphea): Violaceous patches on the skin, hypo or hyper pigmented areas • Localized form (linear): Thin band of sclerosis, coup de sabre since it resembles the mark • O ral manifestations: Mild edema, Microstomia, Tobacco pouch mouth purse string appearance, Mouse species, tongue can become hard, pseudoankylosis, diffuse widening of periodontal ligament space • Histopathological features: Thickening and hyalinization, loss of dermal appendage, atrophy of the epithelium, loss of rete pegs and increased melanin pigmentation, increase in collagen and oxytalan fibers • Management: D-penicillamine.

Skin Disorders

KAWASAKI DISEASE It is also called mucocutaneous lymph node syndrome. Etiology is unknown but has been suggested to be or collagen or vascular disease.

Clinical Features It most commonly occurs in children between 3 months and 12 years of age. Symptoms: There is fever for five days or more, with no response to antibiotics, diarrhea and arthralgia may be present. Signs: There is bilateral congestion of ocular conjunctiva, indurative edema, erythema of palms, soles and membranous desquamation of fingers and toes. In some cases there is presence of polymorphous exanthema of torso without vesicles or crusts. Acute nonpurulent swelling of cervical lymph nodes occurs.

Oral Manifestations Changes in lip and mouth including dryness, redness and fissuring of lips occurs. Strawberry like reddening and swelling of tongue papillae and diffuse reddening of oral and pharyngeal mucosa, sometimes with gingival ulceration.

Laboratory Findings There is proteinuria, leukocytosis, increased sedimentation rate and positive C-reactive protein.

Management As such no treatment is required. Points to Remember Mucocutaneous lymph node syndrome, fever, erythema of palms, soles, membranous desquamation of fingers and toes, strawberry like reddening and swelling of tongue papillae, proteinuria, leukocytosis, increased sedimentation rate.

BIBLIOGRAPHY 1. Abdelsayed RA, Sumner T, Allen CM, et al. Oral recancerous and malignant lesion associated with graft versus host resistance: a report of 2 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;93:75-80.

2. Abel MD, Carrasco LR. Ehler-Danlos syndrome: classification, oral manifestation and dental consideration. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:582-90. 3. Adams AM, MAcleod RI, Munro CS. Symptomatic and symptomatic salivary duct abnormalities in Darier’s disease: a sialographic study. Dentomaxillofac Radiol. 1994;23:2528. 4. Allen CM, Camisa C. Paraneoplastic pemphigus: a review of the literature: Oral Dis. 2000;6:208-14. 5. Auqier–Dunant A, Mockenhaupt M, Naldi L, et al. Correlation between clinical pattern and causes of erythema multiforme, Ste45:ven Johnson syndrome and toxic epidermal necrolysis: Arch Dermatol. 2002;138:1019-24. 6. Bagan J, Muzio LL, Scully C. Mucous membrane pemphigoid: Oral Dis. 2005;11:197-218. 7. Barron RP, Kainulainen VT, Forrest CR, et al. Tuberous sclerosis clinicopathological feature and review of literature: J Craniomaxillofac Surg. 2002;30:361-6 8. Begbiw ME, Wallace GMF, Shovlin CL. Hereditary hemorrhagic telangiectasia (Osler Weber Rendu Syndrome) a view from the 21st century: post grad Med J. 2003;79:1824. 9. Bentolila R, Rivera H. Sanchez-Quevedo MC: incontinentia Pigmenti: a case report: Pediatric Dent. 2006;28:54-7. 10. Black M, Mignogna MD, Scully C. Pemphigus vulgaris. Oral Dis. 2005;11:119-30. 11. Cario F, Rubino J, Routundo R, et al. Oral acanthosis nigricans as a marker of internal malignancy: a case report: J periodontal. 2001;72:1271-5. 12. Celenk P, Alkan A, Canger EM, et al. Fibrolipomatous hamartomas in a patient with tuberous sclerosis report of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;99:202-6. 13. Chau MNY, Raddeb BG. Oral warty dyskeratoma: J Oral Pathol. 1984;13:546-56. 14. Couriel D, aldera H, Champlin R, et al. Acute graft versus host resistance, Pathophysiology, clinical manifestation and management: cancer. 2004;101:1936-46. 15. da Silva Santos PS, Fernandes KS, Magalhães MH. OslerWeber-Rendu syndrome—dental implications. J Can Dent Assoc 2009;75:527-30. 16. Dajani ZA, Mutasim DF. Ectopic facial Hailey-Hailey disease. J Am Acad Dermatol. 2011;65(1):223-4. 17. Demir Y, Karaaslan T, Aktepe F, et al. linear scleroderma: en coup de sabre’, of the cheek: J Oral Maxillofac Surg. 2003;61:1091-4. 18. Economopoulou P, Laskaris G. Dermatitis herpetiformis: oral lesions as an early manifestation. Oral Surg Oral Med Oral Pathol. 1986;62(1):77-80.

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19. Emery MM, Siegfried EC, Stone MS, et al. incontinentia pigmenti: transmission from father to daughter: J AM Acad Dermatol. 1993;29:368-72. 20. Fatahzadeh M, Radfar L, Sirosis DA. Dental care of patient with autoimmune vesiculobullous disease: a case reports and literature review: Quintessence Int. 2006;37:777-87. 21. Fathing P, Bagan JV, Scully C. Erythema multiforme: Oral Dis. 2005;11:261-7. 22. Fine J-D Eady RAJ, Bauer EA, et al. Revise classification system for inherited epidermolysis bullosa: a report of the second international consensus meeting on diagnosis and classification of epidermolysis bullosa: J AM Acad Dematol. 2000;42:1051-66. 23. Frezzini C, Cedro M, Leao JC, et al. Darier disease affecting gingival and oral mucosal surface. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:e29-e33. 24. Goette DK, Carpenter WM. The mucocutaneous marker of pseudoxanthoma elasticum. Oral Surg Oral Med Oral Pathol. 1981;51(1):68-72. 25. Helm TN, Camisa C, Valenzuela R, et al. Paraneoplastic pemphigus: a distinct autoimmune vesiculobullous disorder associated with neoplasia. Oral Surg Oral Med Oral Pathol. 1993;75:209-13. 26. Hunt R, O’Reilly K, Ralston J, Kamino H, Shupack JL Familial benign chronic pemphigus (Hailey-Hailey disease). Dermatol Online J. 2010;16(11):14. 27. Kanak K, Jaiswal AK, Reddy P. Disseminated superficial and warty type of porokeratosis: a rare coexistence: Indian J Dermatol. 2011;56(5):576-7. 28. Kearns G, Sharma A, Perrott D, et al. Placement of endosseous implants in children and adolescent with hereditary ectodermal dysplasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88:5-10. 29. Lallas A, Kyrgidis A, Tzellos TG, et al. Accuracy of dermoscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea. Br J Dermatol. 2012;166(6):1198-205. 30. Leao JC, Batista V, Guimaraes PB, et al. Cowden syndrome affecting the mouth, gastrointestinal and central nervous system, a case report and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;99:569-72. 31. Martelli H, Mourao-Pereira S, Martinis-Rocha T, et al. White sponge nevus: a report of three generation family. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103:43-47. 32. Mignogna MD, Lo Muzio L, Mignogna, et al. Oral pemphigus long term behavior and clinical response to treatment with deflazacort in sixteen cases. J Oral Pathol Med. 2000;29:145-52. 33. Mognogna MD, LoMuzio L, Ruocco V, et al. Early diagnosis of multiple hamartomas and neoplasia syndrome (Cowden disease). The role of dentist: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995;79:295-9.

34. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edition, Saunder Elsevier, 2009. 35. Nordgarden H, Johannessen S, Storhaug K, et al. Salivary gland involvement in hypohidrotic ectodermal dysplasia: Oral Dis. 1998;4:152-4. 36. Paley M, McLoughlin P. Oral problems associated with CREST syndrome: Br Dent J. 1993;175:295-6. 37. Patton LL, Valdez IH: Xeroderma pigmentosum: a review and report of case: Oral Surg Oral Med Oral Pathol: 1991;71:297-300. 38. Pradeep AR, Nagaraja C. Panchyonychia congenita with unsual dental finding: a case report: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:89-93. 39. Ramirez-Amador V, Esquivel Pedraza L, CaballeroMendoza E, et al. Oral manifestation as a hallmark malignant acanthosis nigricans: JJG, Suak JJ, et al. Clinical, histology, cytological and ulstrastructural characteristic of the oral lesion from hereditary mucoepithelial dysplasia. Oral Surg Oral Med Oral Pathol. 1978;46:645-57. 40. Rodu B, Martinez MG Jr. Peutz-Jeghers syndrome and cancer. Oral Surg Oral Med Oral Pathol. 1984;58(5):584-8. 41. Rout PGJ, Hamburger J, Potts AJC. Orofacial radiological manifestation of systemic sclerosis: Dentomaxillofac Radiol. 1996;25:193-6. 42. Rugg EL, Magee GJ, Wilson NJ, et al. Keratin 13 point mutation underlies the herediatary mucosal disorders white sponge nevus. Oral Dis. 1999;5:321-4. 43. Sacks H, Zelig D, Schabes G. Recurrent temporomandibular joint subluxation and facial ecchymosis leading to diagnosis of Ehler Danlos Syndrome. J Oral Maxillofac Surg. 1990;48:641:647. 44. Sadeghi EM. Witkop; the presence of Candida albican in hereditary benign intraepithelial dyskeratosis. Oral Surg Oral Med Oral Pathol. 1979;48:342-6. 45. Said S, Golitz L Vesiculobullous eruptions of the oral cavity: Otolaryngol Clin North Am. 2011;44(1):133-60. 46. Serrano_Martinez MC, Bagan JV, Silvestre FJ, et al. Oral lesion in recessive dystrophic epidermolysis bullosa. Oral Dis. 2003;9:264-8. 47. Siegal MA, Anhalt GJ. Direct immunofluroscence of detached gingival epithelium for diagnosis of cicatricial pemphigoid report of five cases. Oral Surg Oral Med Oral Pathol. 1993;75:296-302. 48. Smith CH. Barker JNWN: Psoriasis and its management: Br Med J. 2006;333:380-4. 49. Stabfird TW, Peterson J, Machen RL. CREST syndrome and periodontal surgery: a case report: J Periodontol. 1999;70:536-541. 50. Westerman AM, Entius MM, de Baar E, et al. Peutz Jeghers syndrome: 78 years follow up of the original family: Lancet: 1999;353:1211-5.

Skin Disorders 51. Williams DM. Vesiculobullous mucocutaneous disease: benign mucous membrane and bullous pemphigoid. J oral Pathol Med. 1990;19:16-23. 52. Williams PM, Conklin RJ. Erythema multiforme: a review and contrast from Stevens-Johnson syndrome/toxic epidermal. Dent Clin North Am. 2005;49:67-76.

53. Younai FS, PheLan JA. Oral mucositis with features of psoriasis a report of case and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84:61-7. 54. Zawar V Giant pityriasis rosea. Indian J Dermatol. 2010;55(2):192-4.

MULTIPLE CHOICE QUESTIONS 1. ‘Bull’s eye’–concentric ring like appearance seen in: a. Psoriasis b. Erythema multiforme c. Porokeratosis d. Ehlers-Danlos syndrome





2. Nikolsky’s sign is the characteristic feature of: a. Pemphigus b. Psoriasis c. Porokeratosis d. None of the above





3. Tzanck cells found in: a. Porokeratosis c. Pemphigus

7. Which one of the following drugs worsen the con dition of psoriasis: a. Antimalarials b. Beta blocker c. Lithium d. All of the above





4. Hailey-Hailey disease refers to: a. Familial benign chronic pemphigus b. Bullous pemphigoid c. Epidermolysis bullosa d. Pityriasis rosea

8. Test tube appearance of rete pegs seen in: a. Pemphigus b. Psoriasis c. Porokeratosis d. Both b and c



9. ‘Basket-weave’ appearance histologic feature seen in: a. White sponge nevus b. Warty dyskeratoma c. Darier’s disease d. Both a and b





b. d.

Erythema multiforme Psoriasis

5. ‘Herald spot’ is the prodormal features of: a. Incontinentia pigmenti b. Acanthosis nigricans c. Dermatitis herpetiformis d. Pityriasis rosea



6. Hyperelasticity of skin , ‘rubber man’ refers to: a. Ehlers-Danlos syndrome b. Bloch-Sulzberger syndrome c. Duhring-Brocq disease d. Hailey-Hailey syndrome

10. Auspitz’s sign seen in: a. Psoriasis c. Darier’s disease

b. d.

Pemphigus Both a and b

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Allergic and Immunologic Diseases of Oral Cavity Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe) Chapter Outline

       Â

Chapter Outline

Introduction/Overview Hypersensitivity reaction Wegner’s granulomatosis Sarcoidosis Drug allergy Allergic contact stomatitis Secondary vaccinia Angioedema

INTRODUCTION/OVERVIEW The word ‘allergy’ was first used by von Pirquet, to denote both host-protective and potentially host-injurious immune responses. Word ‘hypersensitivity’ was first described as denoting the status of a mammalian organism after exposure to an infectious agent. Allergic reactions are a very common and important set of symptoms for clinician to learn to recognize and treat. Allergy is a complex disease and allergic patients present symptoms of varying severity as well as symptoms from different organs, such as eyes, nose, lungs, skin and the gastrointestinal tract.

HYPERSENSITIVITY REACTION A hypersensitivity reaction refers to a state of altered reactivity in which the body mounts an amplified immune response to a substance. In 1963, Gell and Coombs’ classified hypersensitivity reactions into four different groups (Types I, II, III, and IV) which depended upon the severity and latency of a reaction (Table 30.1).

 Apthous stomatitis (Recurrent aphthous ulcers (RAUs) or canker sores)  Behçet’s syndrome  Transient lingual papillitis  Perioral dermatitis  Reiter’s syndrome  Lichenoid contact stomatitis/Lichnoid tissue reaction  Chronic ulcerative stomatitis  Crohn’s disease

Clinically, it is difficult to distinguish between the four types of hypersensitivities as they do not necessarily occur in isolation from each other. Types I, II, and III hypersensitivities are mediated by Antigen-antibodies reaction, whereas, Type IV is mediated cell mediated response (especially T cells and macrophages). Types of Immune Reactions • • • •

Type I reactions (Immediate hypersensitivity) Type II reactions (Complement-mediated cytotoxicity) Type III reactions Type IV reactions (Delayed hypersensitivity).

Types of Immune Reactions (Gell and Coombs’ Classification) Type I reactions (Immediate hypersensitivity)—these are mostly IgE-mediated and their rapid onset, typically within minutes of exposure to antigen, is characteristic. Type II reactions (Complement-mediated cytotoxicity) result from antibody binding to membrane-bound Ag

Allergic and Immunologic Diseases of Oral Cavity Table 30.1 Gell and Coombs’ hypersensitivity reactions

Gell and coombs classification of hypersensitivity reaction Reaction

Description

Antibody involved

Time of onset

Type I

Immediate hypersensitivity (e.g. Allergy)

IgE

1–20 min

Type II

Antibody to soluble antigen (e.g. Hemolytic anemia)

IgG/IgM

--

Type III

Antibody to soluble antigen immune complexes IgG (e.g. serum sickness)

7–10 hrs

Type IV

Delayed-type hypersensitivity

1–3 days

---

Table 30.2 Various methods for detection of type of hypersensitivity reaction

Type

Description

Method of detection

I

An immediate reaction that can result in an anaphylactic Provocation test. Skin test, IgE RAST reaction

II

Cytotoxic reaction mediated by IgM and IgG antibody IgG serum test response to host tissue

III

IgG and IgM antibodies form immune complexes with IgG serum test antigens in the blood

IV

Delayed reaction that is mediated by memory T cells

Skin test

resulting in complement-mediated cytotoxicity or opsonization/inflammation. This class of reactions may be typified by hemolytic anemia and certain drug reactions. Type III reactions occur when antibody binds to soluble allergen to form immune complexes, which can cause any of several kinds of immune complex disease. Type III reactions are the result of deposition of circulating antigenantibody complexes in tissues, as opposed to the binding of antibodies to antigens which are an integral part of a target cell membrane. Type IV reactions (Delayed hypersensitivity)— delayed-type hypersensitivity (DTH) is a synonym for CMI, and signifies to the slower development of such reactions compared with antibody-mediated reactions. A reaction can typically take 12 or more hours to develop. Type IV responses are dependent on T-cell interactions, which recruit other cells to the site of exposure.

Type I hypersensitivity reactions are traditionally recognized through provocation testing or immediate-type skin testing (Table 30.2). Provocation testing involves a masked topical challenge of certain antigens followed by observation of the patient’s dermal response. Clinically, the provocation testing can pose a danger since some antigens may result in a severe anaphylactic reaction. Skin testing is an alternative method which may include skin pricks or patches to determine hypersensitivity. Both the prick test and scratch test involves pricking the skin with a needle or pin containing a small amount of the antigen. A patch test is conducted by applying a patch that contains known antigens to the skin. If there is a visual reddening or swelling at the prick or patch site, the patient is considered allergic to that antigen.

Methods to Identify Hypersensitivity

WEGNER’S GRANULOMATOSIS

Identifying the allergy or hypersensitivity is very important to prevent untoward incident. There are various methods to detect the existence and types of hypersensitivity.

It is a disease of unknown etiology which basically involves the vascular, renal and respiratory systems. It is a granulomatous involvement of blood vessels resulting in

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necrosis of tissue. It is generally thought that the disease is aberrant hypersensitivity reaction to an unknown antigen. 768

Types of Wegner’s Granulomatosis • G eneralized: It involve supper respiratory tract, pulmonary and renal lesions. • Localized: It affects oral and nasal cavity and the lungs.

Clinical Features Age and sex distribution: It usually occurs in 4th or 5th decade of life, with slight predilection for males. Symptoms: The most common symptom of Wegner’s granulomatosis is nasal stuffiness with chronic discharge, which is sometimes bloody. Patient soon develops cough, hemoptysis, fever and joint pains. There is also presence of rhinitis, sinusitis and otitis or ocular symptoms. There are also nonspecific symptoms of malaise, arthralgias and weight loss. Hemorrhagic or vesicular skin lesions are also commonly present. Glomerulonephritis, which develops ultimately to uremia and terminal renal failure.

Oral Manifestations The disease usually starts with tumor like vegetations in mouth and nose. Inflammatory process starts in the interdental papilla, spreading rapidly in to the periodontium. The lesion undergoes necrosis with formation of large perforating ulceration. Strawberry gingivitis—involvement of gingiva is the most common manifestation; which is characterized by ulceration, friable granular lesions or simple enlargement of gingiva. Inflamed, hyperplastic appearing and hemorrhagic gingiva may be found. Strawberry gingivitis is the characteristic feature of it. Oral lesions typically include ulceration of the palate by extension of nose lesions and destruction of nasal septum, poorly healing extraction sites or oroantral fistule. There may be perforation of palate (Fig. 30.1). There may be loosening of teeth, spontaneous exfoliation of teeth diffuse ulcerative stomatitis, post extraction poor healing, cranial nerve palsies and parotid swelling. There are often signs of alveolar bone loss.

Laboratory Findings It includes anemia, leukocytosis, elevated sedimentation rate and hyperglobulinemia. Hematuria with finding of albumin, casts and leukocytes in urine.

Figure 30.1 Wegener’s granulomatosis showing ulceration in

the palate

Histopathological Findings It reveals acute and chronic inflammatory cells, with areas of multinucleated giant cells. Demonstration of neutrophils, cytoplasmic auto antibodies in serum has very recently showed great promise for the immuno-diagnosis of this disease. Involved vessels demonstrate transmural inflammation with heavy neutrophilic infiltration, necrosis and nuclear dust. The oral epithelium may demonstrate pseudoepithelioumatous hyperplasia and subepithelial abscess.

Diagnosis It should be suspected on the basis of clinical symptom and signs. Definitive diagnosis is made by histological examination.

Management First line of treatment is oral prednisolone and cyclophosphamide. Trimethoprim-sulfamethoxazole has also been used successfully in Wegner granulomatosis. Points to Remember Involvement of blood vessels, is nasal stuffiness with chronic discharge, hemoptysis, fever, nonspecific symptoms, malaise, arthralgias, glomerulonephritis, which develops, necrosis with formation of large perforating ulceration, strawberry gingivitis, oroantral fistule, anemia, leukocytosis, elevated sedimentation rate, acute and chronic inflammatory cells, multinucleated giant cells, pseudoepitheliomatous hyperplasia, oral prednisolone and cyclophosphamide. Trimethoprimsulfamethoxazole.

Allergic and Immunologic Diseases of Oral Cavity

SARCOIDOSIS It is also called Boeck’s sarcoid, Besnier-BoeckSchaumann’s disease. This term is given by Boeck given the name of sarcoidosis (meaning flesh like condition). It is a disease of unknown etiology. It is a multisystem granulomatous disease. It is characterized by depression of delayed type of hypersensitivity, suggesting an impaired cell-mediated immunity and raised or abnormal serum immunoglobulin, suggesting lympho-proliferation. There are two types of antigen which are involved, i.e. infectious antigen (mycobacterium, propionibacteria, Epstein-Barr virus, HHV virus) environmental factors like wood dust, pollen, clay and mold.

Clinical Features Age and sex distribution: It has got slight predilection of females with bimodal age incidence years of age and second between 45 to 65 years of age. It shows more prevalence in blacks. Location: Lesions are most common in lungs, skin, lymph nodes, salivary glands, spleen and bones. Symptoms: Mild malaise, fever, weight loss, fatigue and cough can be the chief features of the disease. Signs: It presents most frequently with hilar lymphadenopathy, pulmonary infiltration and skin and eye lesions. Lupus pernio: These are chronic violaceous indurated lesion seen on nose ears lips and face. Erythema nodosum: Scattered, nonspecific tender erythematous nodules seen on lower leg called erythema nodosum. Ocular lesion: There is may be keratoconjunctivitis sicca of lesion. Syndrome associated: It is associated with Lofgren’s syndrome (erythema nodosum, bilateral hilar lymphadenopathy and arthralgias) and Heerfordt’s syndrome (parotid enlargement, anterior uveitis of eye, facial paralysis and fever).

Oral Manifestations Location: It is rare in oral cavity, but cases are reported on lip, palate and buccal mucosa. Appearance: It appears as small papular nodules or plaques or resembles herpetic lesions or fever blister.

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Figure 30.2 Sarcoidosis showing circumscribed collection of

histiocytes, lymphocytes

On the palate and buccal mucosa, it is described as bleb like, containing a clear yellowish fluid or as solid nodules. Sign and symptoms: There is increased incidence of dental caries. There is ulceration of buccal mucosa due to salivary insufficiency. It also appears to produce diffuse destruction of the bone.

Histopathological Features It resembles proliferative noncaseating nodules of tuberculosis. Nests of epithelioid cells with multinucleated giant cells are also present (Fig. 30.2). Fibrinoid necrosis and hyalinization are occasionally found in the center of granuloma. The giant cells may contain ‘Schaumann bodies (degenerated lysomes)’, which are concentrically or eccentrically laminated, calcified bodies. ‘Asteroid bodies (entrapped fragment of collagen)’ are delicate spider like radiating structures that are sometimes seen in the macrophages of sarcoid granuloma. Hamazaki-Wesenberg bodies (large lysosomes) are small yellow brown structures in seen in subcapsular sinus.

Diagnosis Kveim-Siltzbach test: It is an intracutaneous test for the diagnosis of sarcoidosis ‘Kveim-Sitzbach test’ is positive in some cases. In this test, intradermal injection of a saline suspension of known human sarcoid tissue used as an antigen is given to a patient suspected to have sarcoidosis. One month after the injection, any palpable nodule is

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excised and examined histologically for evidence of a sarcoid reaction, or epithelial tubercle. 770

Management Asymptomatic patient requires no treatment but in cases where symptoms are present, corticosteroids can be given. Points to Remember Boeck’s sarcoid’, ‘Besnier-Boeck-Schaumann’s disease, lungs, skin, lymph nodes, mild malaise, fever, weight loss, fatigue hilar lymphadenopathy, Lupus pernio, erythema nodosum, Lofgren’s syndrome, keratoconjunctivitis sicca, palate and buccal mucosa, it is described as bleb like, incidence of dental caries. Proliferative noncaseating nodules of tuberculosis, multinucleated giant cells, fibrinoid necrosis, Schaumann bodies (degenerated lysomes), asteroid bodies (entrapped fragment of collagen)’ Hamazaki-Wesenberg bodies (large lysosomes), KveimSiltzbach test, corticosteroids.

Drugs Involved in IgE Mediated Allergies • • • • •

Foreign proteins Immunoglobulin in preparation Beta-Lactam antibiotics Pyrazolones Quinolones

Drugs Involved in Pseudoallergic Reactions • Radioisotopes (contrast media) • Plasma expanders • NSAID: Acetylsation, diclofenac, mefenamic acid, ibuprofen • Vancomycin • Quinolones.

Risk Factors There are factors which can be responsible for an increased risk of developing a drug allergy. These include age, gender, genetic polymorphisms, certain viral infections and drug-related factors (e.g. frequency of exposure, route of administration, molecular weight) (Table 30.3).

DRUG ALLERGY

Clinical Features

It is also called drug idiosyncrasy, ‘drug sensitivity’ and stomatitis or dermatitis medicamentosa. The term “drug hypersensitivity” refers to objectively reproducible symptoms or signs initiated by exposure to a drug at a dose normally tolerated by nonhypersensitive persons. Drug allergy refers to immunologically mediated drug hypersensitivity reactions. These may be either immunoglobulin E (IgE)–mediated (immediate) or non– IgE-mediated (delayed) hypersensitivity reactions. They may cause acute multiple ulcers and vesicles of oral mucosa or lichenoid reaction. It includes a variety of sensitive reactions. Some patients have greater susceptibility to drugs and manifest reactions more readily than others. Drugs which can most commonly cause drug reactions are aminopyrine, barbiturates, gold, bromide, penicillin, streptomycin, etc. The term Pseudoallergic reactions is referred to the nonimmune-mediated hypersensitivities reactions to drugs. These are as frequent as true Ig E-mediated reactions, are a pathogenetically poorly defined problem. Most of these reactions resemble the clinical features of milder forms of immediate, Ig E-mediated reactions; Pseudoallergic reactions can be elicited by many drugs.

Sign: It is characterized by inflammation, ulceration and vesicle formation with arthralgia, fever and lymphadenopathy. The skin lesion is often of erythematous type, as in erythema multiforme or they may be urticarial in nature (Fig. 30.3). Fixed drug reactions may occur in those who are administrated on repeated occasions, a drug to which they are sensitive. It consists of appearance of same reaction at the same site each time. Table 30.3 Risk factors for the development of drug allergy

Patient-related factors: • • • • •

Age: Young/middle-aged adults > infants/elderly Gender: Women > men Genetic polymorphisms Viral infections: HIV, herpes viruses Previous reaction to the drug

Drug-related factors: • H igh molecular weight compounds and hapten-forming drugs are more immunogenic • Route: Topical > intravenous/intramuscular > oral • Dose: Frequent/prolonged > single dose

Allergic and Immunologic Diseases of Oral Cavity

appear and angioneurotic edema is seen. Ulceration and necrosis of gingiva often resemble ANUG.

Histopathological Features There is nonspecific sub acute mucositis which contain lymphocytes with mixed inflammatory cellular infiltrate of eosinophils and neutrophils. Vacuolar changes of basal cell layer and necrotic epithelial cells are seen.

Management

Figure 30.3 Erythematous fixed drug reaction seen on the

The signs and symptoms of drug allergy regress with discontinuing of the causative drug. The acute signs may be relived by administration of antihistaminic drugs or cortisone.

hand of patient (Courtesy: Dr Sanjay Pincha)

Points to Remember Drug idiosyncrasy, drug sensitivity, stomatitis or dermatitis medicamentosa, erythematous type, skin lesion, fixed drug reactions, same reaction at the same site each time, anaphylactic stomatitis, purpuric spots appear and angioneurotic edema, lymphocytes with mixed inflammatory cellular infiltrate of eosinophils and neutrophils, necrotic epithelial, administration of antihistaminic drugs.

ALLERGIC CONTACT STOMATITIS

Figure 30.4 Extensive erosion of lip seen in the drug allergy

(Courtesy: Dr Amit Parate, Government Dental, College Nagpur, Maharashtra, India)

Oral Manifestations ∙

Anaphylactic stomatitis: The oral lesions are diffuse in distribution and vary in appearance from multiple areas of erythema to extensive areas of erosion or ulceration (Fig. 30.4). ∙ Location: It is most commonly seen in labial mucosa. In the early stages of reaction, vesicle or even bullae may be found on the mucosa. Occasionally purpuric spots

It is caused by delayed type of hypersensitivity reaction to topical antigen. On the skin, it is referred as ‘dermatitis venenata’ and oral lesions are referred as ‘stomatitis venenata’.

Causes It is cause by poison ivy, leather, rubber, nickel, medication or other chemicals. Contact allergy to dental amalgam is caused by mercury, which is released during condensation. Dental and cosmetic preparation like dentifrices, mouthwashes, denture powder, lip stick, cough drop and chewing gums. Dental materials like vulcanite, acrylic, metal alloy base. Dental therapeutic agents like alcohol, antibiotics, chloroform, iodide, phenol, procaine and volatile oils.

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Reason Why Oral Mucosa Less Sensitive to Contact Allergy 772

• Brief period of contact • Dilution of antigen by saliva • Due to limited keratinization haptens binding is difficult and high vascular tendency remove antigen quickly • Allergen may not be recognized.

Clinical Features Sign and symptoms: There are typically itching erythematous areas with superficial vesicle formation, directly at the site where allergen contacts skin. The skin may become thickened and dry. After the rupture of vesicle, erosion may become extensive and if secondary infection occurs, the lesion may be serious. Burning is a more common complaint rather than itching of skin. Localized area of erythema, edema and vesiculation in specific areas of skin or mucosa whenever specific allergen is administered.

Oral Manifestations Allergy to cinnamon oil or formalin present in tooth paste, ice-cream, candy, and soft drinks appears clinically as swelling, cracking and fissuring of lips, perioral desquamation and edema, angular cheilitis, swelling of gingiva and oral ulcerations.

Figure 30.5 Stomatitis venenata showing hyperkeratotic

white lesion

The superficial lamina propria demonstrate heavy inflammatory cell infiltrate which consist of lymphocytes which may be intermixed with plasma cells, histiocytes or eosinophils.

Management It involves the removal of allergen and application of topical corticosteroids. Points to Remember

Acute contact stomatitis: Burning with mild or barely visible redness to brilliantly erythematous lesion with or without edema

Dermatitis venenata, stomatitis venenata, dental amalgam, itching erythematous areas, vesicle, erosion may become extensive, localized area of erythema, edema, allergy to cinnamon oil or formalin, plasma cell gingivitis, acute contact stomatitis, chronic contact stomatitis, patch test, acanthotic with elongated rete peg, thinning of suprapapillary plates, superficial lamina propria demonstrate heavy inflammatory cell infiltrate of lymphocytes, removal of allergen.

Chronic contact stomatitis: It may be erythematous white and hyperkeratotic (Fig. 30.5).

SECONDARY VACCINIA

Plasma cell gingivitis: Another oral manifestation is plasma cell gingivitis, which is characterized by erythematous edematous attached gingiva accompanied by cheilitis and glossitis.

Diagnosis Patch test—suspected allergen is placed on normal non-hairy skin, i.e. on upper portion of back. It remains in contact with skin for 48 hours. Then the patch is removed and after 2 to 4 hours, the area is examined for persistent erythema.

Histopathological Features Epithelium in contact stomatitis form cinnamon flavoring is acanthotic with elongated rete pegs and thinning of suprapapillary plates.

It is also called vaccinia autonoculata. Undesired skin or mucosal lesion, after small pox vaccination, is caused by transfer of the contents of vaccination pustule to other parts of the body. It is followed by formation of secondary lesions usually with weaker reaction than the one seen in case of primary inoculation. Secondary vaccinia may develop at the site of scratching possibly in already existing epithelial defect. Location: Eyes, ears and areas of lips and tongue are possible sites. In this area, a patch develops that becomes

Allergic and Immunologic Diseases of Oral Cavity

vesicular than pustular. After the development of crust, there is repair with scar formation. Other ulcerative lesions such as primary lesion of syphilis, tuberculosis, aphthae of the major type should be differentiated. The history is important as secondary vaccinia appear about 5 to 7 days after inoculation.

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Points to Remember Vaccinia autonoculata, site of scratching possibly, undesired skin or mucosal lesion, after small pox vaccination.

ANGIOEDEMA It is also called Angioneurotic edema, Quincke’s edema, and giant urticaria. It is also called quincke’s edema after the name of clinician who related to changes in alteration in vascular permeability. The term angioneruotic edema is given as patient complaint of chocking sensation and was labeled neurotic. It is common form of edema occurring in both hereditary and nonhereditary forms. It is one form of acute anaphylactic reaction representing response allied to urticaria, allergic rhinitis and asthma.

Mechanism The mechanism of development of swelling is due to vasodilation brought about by the release of histamine like substances with subsequent transudation of plasma.

Causes It appears closely related to general urticaria. It occurs most commonly due to food allergy. In some cases, it is thought that some drugs, endocrine disturbances or focal infection play an important etiologic role.

Clinical Features Age and sex distribution: It affects both sexes equally, but it is infrequent in children while some cases originate at puberty. Location: Most often, the face and lips are involved, but sometimes the tongue also becomes swollen. Appearance: Edema may develop gradually in a matter of hours, but can also progress in minutes. It typically manifests as a smooth, diffuse edematous swelling, parti-

Figure 30.6 Angioedema involving lip

cularly involving the face, around the lips, chin and eyes, the tongue and sometimes, the hands and feet (Fig. 30.6). Sign and symptoms: Parotid gland may be affected in some cases. The eyes may be swollen, shut and lips may be extremely puffy. Symptoms may appear suddenly sometimes may present in morning. A feeling of tenderness or an itching or prickly sensation sometimes precedes the urticarial swelling. Other feature: The skin is of normal color and/or slightly pink. The condition usually last for 24 to 36 hours, although some cases persist for several days. The hereditary forms are more dangerous because there is visceral involvement. Vomiting and abdominal pain may occur and especially, dangerous edema of glottis can result in death through suffocation.

Management When etiological agent such as food can be discovered, its elimination from diet will prevent recurrent attacks. Antihistaminic drugs (50 mg to 75 mg diphenylhydramine hydrochloride) can give prompt relief. Points to Remember Angioneurotic edema’, Quincke’s edema, general urticaria, the face and lips edema, smooth, diffuse edematous swelling, parotid gland may be affected, lips may be extremely puffy, antihistaminic drugs.

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APHTHOUS STOMATITIS (RECURRENT pathogenesis of apthous ulcer, i.e. oral streptococci and Helicobacter pylori. APHTHOUS ULCERS (RAUs) OR CANKER SORES) Etiology

It is a common disease characterized by development of painful, recurrent, solitary or multiple ulcerations of the oral mucosa, with no other signs of any other disease. Classification • M inor aphthae: It is also called ‘canker sores’ or ‘mickulicz’s apthae’ in which the ulcers are less than 1 cm in diameter and heal without scar. • Major aphthae: It is called ‘Sutton’s disease’ or ‘periadenitis mucosa necrotica recurrent’ and the ulcers are over 1 cm in diameter and heal with scarring. • Herpetiform ulcers: Recurrent crops of dozens of small ulcers throughout the oral mucosa. • Recurrent ulcers associated with Behçet’s syndrome. • Simple aphthous: These are lesion which occur in patient with few lesion and heal in 1 to 2 weeks and recur infrequently • Complex aphthous: These are multiple and constant ulceration occur that often develop as older lesion resolve.

Etiology Bacterial infection: A pleomorphic transitional L-form of a-hemolytic Streptococcus and Streptococcus sanguis has been implicated as the causative agent of the disease. Immunological abnormalities: IgG and IgM binding of the epithelial cells of the spinous layer of oral mucosa is seen in patients suffering from recurrent apthous ulcer. Iron deficiency or folic acid deficiency: Small percentage of patients with recurrent aphthae have certain nutritional deficiency. Presence of a deficiency allows the expression of an unrelated, underlying tendency to ulceration. Hereditary: Increased susceptibility to RAS is seen among the children of RAS positive parents. Specific HLA antigen has been identified in RAS patients. There is familial tendency for the occurrence of the disease. Hematological deficiency, serum iron or Vitamin B12 deficiency, secondary malabsorption syndrome such as celiac disease. Micro organisms associated with aphthous ulcers: Several micro organisms have been implicated in the

• • • • •

Bacterial infection Immunological abnormalities Iron deficiency or folic acid deficiency Hereditary Hematological deficiency.

Precipitating Factors • • • • •

Trauma Endocrine conditions Psychic factors Cessation of smoking Allergic factor.

Precipitating Factors Trauma: Local trauma including self-inflicted bites, oral surgical procedures, tooth brushing, needle injections and dental trauma. Endocrine conditions: There is some relation between occurrence of aphthous ulcer and pregnancy, menstruation and menopause. There is remission of ulcers during pregnancy. Incidences of aphthae are greatest during menstruation. Ulcerations are maximum during postovulation period. Psychic factors: Acute psychological problems appear many times, to precipitate the attacks of the disease. Anxiety can also precipitate the attack. Cessation of smoking increases the frequency and severity of RAS. Allergic factor: Patients may have a history of asthma, hay fever and food or drug allergy.

Clinical Features Age and sex distribution: It usually occurs between second and third decades of life. It is common in women than men. Precipitating factor: It may be precipitated by minor trauma, menstruation, URTI or contact with certain foods. Location: It occurs most commonly on buccal and labial mucosa, buccal and lingual sulci, tongue, soft palate, pharynx and gingiva.

Allergic and Immunologic Diseases of Oral Cavity

Appearance: It begins with prodormal burning for 24 to 48 hours, before the ulcer appears. It begins as a single or multiple superficial erosion covered by grey membrane. Localized areas of erythema develop and within hours small white papules form, ulcerate and gradually enlarge over next 48 to 72 hours. Sign and symptom: Lesions are round, symmetric and shallow but no tissue tags are present from the ruptured vesicles. The lesion is typically very painful so, it commonly interferes with eating for several days. Multiple lesions are present but the number and size are frequently varied. Most patients have between 2 to 6 lesions at each episode and experience several episodes a year. The ulcers themselves generally persist for 7 to 14 days. Minor aphthae: Size is 0.3 to 1 cm, heal without scarring, within 10 to 14 days (Fig. 30.7).

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Figure 30.8 Major aphthous ulcer seen in soft palate region

(Courtesy: Dr Amit Parate, Lecturer, Department of Oral Medicine, GDC, Nagpur, Maharashtra, India)

Major aphthae (Fig. 30.8): Develop deep lesions, larger than 1 cm and may reach up to 5 cms in diameter. They interfere with speech and eating. Large portions may be covered with deep painful ulcers. The lesions heal slowly and leave scars, which result in decreased mobility of uvula and tongue and destruction of portions of oral mucosa. Herpetiform ulcers: Multiple small shallow ulcers often up to 100 in number. Found on any intraoral mucosal surface. Begin as small pinhead size erosions that gradually enlarge and coalesce. Lesions are more painful than would be suspected by their size. Present continuously for one to three years, with relatively short remission. Patient gets relief immediately with 2 percent tetracycline mouthwash.

Figure 30.9 Aphthous ulcer showing antischkow cell (Courtesy: Dr Sangamesh Halawar, Reader, Department of Oral Pathology, VPDC and H, Kavalapur, Sangli, Maharashtra, India)

Histopathological Features

Figure 30.7 Aphthous ulcer presented as well defined lesion

Fibrinopurulent membrane covers the ulcerated area. Occasional superficial colonies of microorganisms may be present in this membrane. Intense inflammatory cell infiltrate is present in connective tissue, beneath the ulcer, with considerable necrosis of tissue near the surface of the lesion. Neutrophils are predominant immediately below the ulcer but lymphocyte prevailing adjacent to this. Epithelial proliferation is along the margins’ of the lesion. Anitschkow cells—consists of cells with elongated nuclei, containing a linear bar of chromatin with radiating processes of chromatin extending towards the nuclear membrane (Fig. 30.9).

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The epithelium at margin of the lesion demonstrates spongiosis and numerous mononuclear cells in the basilar one third. A band of lymphocytes intermixed with Histiocytes is also seen in superficial connective tissue.

Management Mild cases: Topical protective emollient base (Orabase). Topical tetracycline mouth wash (250 mg per ml) use four times daily for 5 to 7 days produces good response in nearly 70 percent of the patients. Topical corticosteroid preparation—topical corticosteroid triamcinolone acetonide 3 to 4 times daily should be prescribed. Severe cases: Fluocinolone gel, clobetasol cream or beclomethasone spray. Injection of corticosteroid directly in lesion in, combination of systemic administration of cortisone. Chlortetracycline as mouth rinse to be flushed over the affected region, for at least 2 minutes provides relief from pain. In some cases, dapsone or thalidomide can be used. Interferon alpha, nicotine tablets and colchicine can be used, but it is under investigation. Points to Remember Prodormal burning for 24 to 48 hours, lesions are round, symmetric and shallow, very painful, minor aphthae, major aphthae, herpetiform ulcers, multiple small shallow ulcers often up to 100 in number, fibrinopurulent membrane, Intense inflammatory cell infiltrate, neutrophils are predominant, anitschkow cells, topical protective emollient base, topical corticosteroid triamcinolone acetonide.

Etiology It is caused by immune complexes that lead to vasculitis of small and medium sized blood vessels. There may be inflammation of the epithelium caused by immunocompetent T-lymphocytes and plasma cells.

Clinical Features (Fig. 30.10) The clinical spectrum includes oral and genital ulcerations, uveitis, and vascular, neurological, articular, renal and gastrointestinal manifestations. Age and sex distribution: It begins between 10 to 45 years of age, with a mean age of occurrence of 30 years. It is five to ten times more common in males. Recurring oral ulcers: It may be mild or may be deep, large scarring lesions and may appear anywhere on the oral and pharyngeal mucosa. They are painful lesions. They may range from several millimeters to a centimeter in diameter. These ulcers have erythematous borders and are covered by gray or yellow exudate. Genital lesions: It include ulcers of scrotum and penis in males and ulcers of labia in females. The genital ulcers are small and painful in females. Eye lesions: Consist of uvetitis, retinal internal edema and vascular occultation, optic atrophy, conjunctivitis and keratitis.

BEHÇET’S SYNDROME It is a disease of uncertain etiology that may resemble an infectious origin. It is triad of recurring oral ulcers, recurring genital ulcers and eye lesions. Mucocutanoues lesions are hallmark of the syndrome. It is discovered by Hulusi Behçet in 1937. Behçet disease (BD) is a chronic, relapsing, multisystemic disorder characterized by mucocutaneous, ocular, vascular and central nervous system manifestations. Classification • Mucocutaneous: Oral, genital and skin lesions. • Arthritic: Arthritis, in addition to mucocutaneous lesions. • Neuro-ocular: Neurologic, ocular and mucocutaneous lesions.

Figure 30.10 Signs of Behçet’s syndrome

Allergic and Immunologic Diseases of Oral Cavity

Skin lesions are generally small pustules or papules on the trunk or limbs and around the genital. Pathergy test: Cutaneous hypertrophy to intracutaneous injection or needle sticks (pathergy) with the finding of pustule forming 24 hours after needle puncture. Arthritis: Arthritis is common. Affected joint is red and swollen. CNS involvement: It may occur and it may include brain stem involvement of cranial nerve and neurologic degeneration. Others: Thrombophlebitis, intestinal ulceration, venous thrombosis, renal and pulmonary disease. Diagnostic Criteria Recurrent oral ulcerations at least 3 times in one 12 month period, plus at least two of the following four manifestations Any two of the following: • Recurrent genital lesions. • Eye lesions including uveitis or retinal vasculitis. • Skin lesions including erythema nodosum, pseudofolliculitis and papulo-pustular lesions. • Positive pathergy test.

Points to Remember Recurring oral ulcers, ulcers of scrotum and penis in males and ulcers of labia in female, uvetitis, retinal internal edema, skin lesions are generally small pustules or papules on the trunk, Pathergy test, Arthritis, CNS involvement, thrombophlebitis, endothelial proliferation with vasculitis, leukocytoclastic vasculitis, immunosuppressive drugs and systemic corticosteroids.

TRANSIENT LINGUAL PAPILLITIS It is also called lie bump, tongue torches. It may cause by local irritation, stress, gastrointestinal disease, hormonal fluctuation, upper respiratory infection, and topical hypersensitivity. There is involvement of fungiform papillae of the tongue.

Clinical Features Age and sex distribution: It is more commonly seen in female in middle age group. Localized pattern: This is seen on anterior portion of dorsum surface of tongue. There is mild to moderate pain. There is enlargement of one or more fungiform papillae which are red with yellow and ulcerated cap. Generalized pattern (Fig. 30.11): In this involvement of papillae is more on the tip and lateral portion of dorsal

Laboratory Findings Hypergammaglobulinemia, leukocytosis with eosinophilic and elevated ESR.

Histopathological Features It has got similar appearance as that of aphthous stomatitis. Endothelial proliferation with vasculitis is seen which is called leukocytoclastic vasculitis. Small blood vessels demonstrate intramural invasion by neutrophils, extravasation of red blood cells and fibronoid necrosis of the vessels wall.

Management Patients with life threatening or slight threatening vasculitis are managed with combination of immunosuppressive drugs and systemic corticosteroids.

Figure 30.11 Transient lingual papillitis showing

erythematous papillae

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surface. Papillae are sensitive erythematous, enlarged, with surface erosion. 778

Papulokeratotic variant: It has got diffuse involvement. Papillae are asymptomatic which appear as white elevated papule. There is thickened parakeratotic cap present which bear the name papulokeratotic type.

Histopathological Features There are focal areas of exocytosis or ulceration. There is proliferation of numerous small vascular channels with inflammatory cell infiltrate. In papulo-keratotic variant there is hyperparakeratosis with ragged surface and bacterial colonization. Chronic lymphocytes infiltrate present in superficial lamina propria.

Management Topical corticosteroid, anesthetics and coating agent used to reduce the pain or duration of pain. Points to Remember Lie bump, tongue torches, anterior portion of dorsum surface of tongue, generalized pattern, papulokeratotic variant, white elevated papule, focal areas of exocytosis or ulceration, hyperparakeratosis with ragged surface, bacterial colonization, topical corticosteroid, anesthetics.

PERIORAL DERMATITIS It is inflammatory skin disease which involves circumoral area. It is cause by idiosyncratic response to exogenous substance. The agents used are topical corticosteroid, tartar control toothpaste, bubble gum, moisturizers, night creams and cosmetic products.

Clinical Features

Figure 30.12 Perioral dermatitis showing inflammation

Histopathological Features There is chronic lymphohistiocytic dermatitis which shows spongiosis of hair follicles. In some patient rosacea like pattern in which there is perifollicular granulomatosis inflammation (Fig. 30.12).

Management Discontinuation of topical corticosteroids will results in regression of the lesion. Oral tetracycline, topical metronidiazole or erythromycin has also been successful in many patients. Points to Remember Vermilion border of upper and lower lip, pruritis, zone erythema, chronic lymphohistiocytic dermatitis, rosacea like pattern, perifollicular granulomatosis inflammation, oral tetracycline, topical metronidiazole or erythromycin.

Sex distribution: There is female dominance as they use cosmetic more as compare to male.

REITER’S SYNDROME

Location: It is located skin surrounding the vermilion border of upper and lower lip. There is spared skin between immediately to the vermilion border.

Reiter’s syndrome (RS) is a disease of unknown etiology and is considered as an important complication of nongonococcal urethritis and is often acquired sexually. It is also called reactive arthritis. Classic Reiter’s syndrome is characterized by aseptic inflammatory arthritis, urethritis or cervicitis and conjunctivitis.

Symptoms: Patient may complaint of pruritus. Appearance: There is zone erythema without papules or pustules.

Allergic and Immunologic Diseases of Oral Cavity

Cutaneous manifestations consist of a palmoplantar keratoderma, circinate balanitis or vulvitis, psoriasis-like skin lesions, and buccal ulcerations. RS was first described by Hans Reiter during the First World War though it had been recognized since 1818. Classically, RS is characterized by the triad of urethritis or cervicitis, conjunctivitis, and arthritis.

Triad of Reiter’s Syndrome ∙ ∙ ∙

Urethritis or Arthritis. Conjunctivitis. Mucocutaneous lesions.

Etiology Reiter’s Syndrome (RS) is a genetically determined disease and its association with HLAB27 has been suggested. The RS is triggered by bacterial infection that enters via mucosal surfaces usually, (but not always) associated with human leukocyte antigen (HLA)- B27. It is may be due to pleuropnemonia like organism, variety of infectious agents like bedsonia, mycoplasma, chlymadia, virus, etc. It can be associated with staphylococci and in that case, it is called staphylococcal scalded skin syndrome.

Clinical Features Age and sex distribution: The RS has male preponderance and age range of between 15 to 35 years. Appearance: The disease begins abruptly with diffuse erythema and fever. Large flaccid bullae are formed which contain a clear yellowish fluid. The bullae rupture very easily leaving large areas of skin devoid of superficial epidermis. The urethral discharge is usually associated with an itching and burning sensation. Arthritis: Arthritis is often bilateral, symmetrical and usually poly-articular. Conjunctivitis: Conjunctivitis is often so mild as to be overlooked. Skin lesion: The skin lesions consist of red or yellow keratotic macules which eventually desquamate. Additionally mucocutaneous findings include circinate balanitis in the uncircumcised penis and crusted erosions on the circumcised penis and on the scrotum may be observed.

Oral Manifestations Oral lesions occur in less than 5 percent to about 50 percent of the patients with the disease.

Location: It is seen on the buccal mucosa, lips and gingiva. The lesions appear as painless, red, slightly elevated areas, sometimes granular or vesicular with a white circinate border. Appearance: The palatal lesions appear as small, bright red, purpuric spots which darken and coalesce. Lesions on the tongue closely resemble geographic tongue. They may be mistaken as recurrent aphthous ulcers.

Laboratory Findings Usually, the diagnosis of RS is based on clinical features. There are no definite diagnostic laboratory tests or radiographic findings. The elevated erythrocyte sedimentation rate (ESR) and neutrophilic leucocytosis that suggested a bacterial infection. All the laboratory investigations was negative.

Histopathological Features It consists of parakeratosis, acanthosis and polymorphonuclear leukocyte infiltration of epithelium, sometimes with microabscess formation. Connective tissue shows lymphocytes and plasma cell infiltration.

Management Spontaneous remission. It is treated by antibiotics and corticosteroids. Points to Remember Arthritis, urethritis or cervicitis and conjunctivitis, diffuse erythema and fever, large flaccid bullae, circinate balanitis, crusted erosions, circumcised penis, buccal mucosa, lips and gingiva, painless, red, slightly elevated small, bright red, purpuric spots which darken and coalesce, parakeratosis, acanthosis, polymorphonuclear leukocyte.

LICHENOID CONTACT STOMATITIS/ LICHENOID TISSUE REACTION These types of allergic reaction occur due to dental amalgam, gold restoration, copper, palladium, silver, zinc, etc. On patch testing many patients react to this agents and lesion resolve after offending agents is removed. There is lack of migration in this lesion Lichenoid tissue reaction (LTR) is characterized by epidermal basal cell damage which takes the form of

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liquefaction degeneration or cell death either apoptosis or necrosis with an associated cascade of histological events in epidermis and dermis. The term ‘lichenoid’ refers to papular lesion of certain skin disorders of which lichen planus is the prototype.

Etiology Various factors may produce induce lichenoid tissue reaction lesions such as, mechanical trauma, systemic drugs, contact sensitivity, infective agents including some viruses through cell mediated reaction (Table 30.4). Table 30.4 Most common allergen present in dental materials for specific oral disease. (Adapted from J Am Acad Dermatol 10.1016/j.jaad.2007.04.017. Article in press)

Disease

Allergies

Burning mouth syndrome

Potassium dicyanoaurate Nickel sulfate hexahydrate Gold sodium thiosulfate Palladium chloride Fragrance mix

Lichenoid tissue reaction

Potassium dicyanoaurate Fragrance mix Gold sodium thiosulfate Nickel sulfate hexahydrate Balsam of Peru

Cheilitis

Fragrance mix Gold sodium thiosulfate Dodecyl gallate Caine mix III Benzoic acid

Stomatitis

Mercury Balsam of Peru Gold sodium thiosulfate Nickel sulfate hexahydrate Dodecyl gallate

Gingivitis

Potassium dicyanoaurate Nickel sulfate hexahydrate Palladium chloride Beryllium sulfate tetrahydrate Gold sodium thiosulfate

Orofacial granulomatosis

Nickel sulfate hexahydrate Benzoyl peroxide Dodecyl gallate Gold sodium thiosulfate

Perioral dermatitis

Cobalt chloride Gold sodium thiosulfate Balsam of Peru Nickel sulfate hexahydrate

Recurrent aphthous stomatitis

Vanillin

Role of Plasmacytoid dendritic cell-mediated type I interferon signaling is also postulated. Recent studies have suggested that T-lymphocytes with helper phenotype may play an important role in the pathogenesis of lichenoid tissue reactions (LTR). LTR form are described in Table 30.5.

Clinical Features Location: This is most commonly seen in posterior buccal mucosa, ventral surface of lateral border of tongue. Gingival cuffs adjacent to filling can also be affected. Appearance: The affected area may be white or erythematous with or without peripheral striae. Sign and symptoms: Most of the patient does not have symptoms but in some cases erosion can be seen.

Histopathological Features They exhibits many features of lichen planus with surface epithelium showing hyperkeratotic, atrophic and ulcerated. Table 30.5 Classification of LTR/IFD (Adapted from Journal of Investigative Dermatology (2009); 129: 1088–1099)

Lymphocyte rich LTR/IFD • Autoimmune connective tissue disease – Discoid lupus erythermatosus (LE) • Fixed drug eruption • Keratosis lichenoides chronica • Lichen planus • Lichen striatus • Lichenoid drug reaction • Lichenoid and granulomatous dermatitis • Graft versus host disease • Mycosis fungoides Lymphocyte-poor LTR/IFD • Acute graft versus host skin disease • Autoimmune connective tissue skin disease – LE-acute cutaneous LE/Subacute cutaneous LE – Dermatomyositis – Mixed connective tissue disease • Erythema multiforme- – Erythema multiforme major (Stevens-Johnsons syndrome) and minor – Interface dermatities of HIV infection – Morbilliform exanthems – Virus induced – Drug induced – Paraneoplastic pemphigus – Pityriasis lichenoides

Allergic and Immunologic Diseases of Oral Cavity

There are also areas of hydropic degeneration of basal cell layer with dense bandlike chronic inflammatory cellular infiltrated in lamina propria. Deeper perivascular oriented lymphocytes aggregates can be seen. In the LTR, this characteristic pattern of epidermal basal cell injury/degeneration is intimately associated with a band-like array of mononuclear inflammatory cells in the papillary and mid dermis consisting of activated T cells, macrophages, and dendritic cells. Histological appearances of idiopathic lichen planus and lichenoid drug eruption are very similar. An inflammatory infiltrate located deep to superficial infiltrate in some or all areas; a focal perivascular infiltrate; plasma cells in the connective tissue and neutrophils in the connective tissue are suggested as distinguishing features between OLP and oral LTR. However, these features can be present in other nonlichenoid lesion. Sehgal and co-workers has described the histopathological features of other lichenoid tissue reactions like lesion in their research article which can help in diagnosis. Lichenoid tissue reaction should be differentiated from lichen planus chronic DLE, lichenoid melanodermatitis (LM) or Melanodermatitis toxica, Lichen nitidus (LN) which are discussed in Table 30.6.

Management Improved oral hygiene and removal of amalgam restoration should be replaced with yellow gold/white gold.

Table 30.6 Differential diagnosis of LTR

Lichen planus • B asal cell liquefaction degeneration with large number of Civatte bodies and colloid bodies. • There were significant vasodilatations in upper dermis inside the massive band like infiltrate. • PAS positive basement membrane was disrupted in reaction area. Hypergranulosis was conspicuous. Chronic DLE • S potty lichenoid reaction in the form of basal cell liquefaction degeneration. • Civatte bodies and colloid bodies are infrequent. • Infiltrate is more focal but could be band like. • Epidermal atrophy and thickening of PAS positive basement membrane may be important differentiating features. Lichenoid melanodermatitis (LM) or melanodermatitis toxica • F ocal mild to moderate liquefaction degeneration of basal cells with atrophy of the epidermis. • The infiltrate although band like is less dense with marked pigmentary incontinence in clumps and giant melanophages. • Civatte bodies, colloid bodies were not found and vascular changes were less prominent. Lichen nitidus (LN) • L ocalized basal cell damage with claw like rete ridges clutching a dense infiltrate. • The dermal infiltrate often showed multinucleated giant cell. • Civatte bodies and colloid bodies were not present.

Points to Remember Dental amalgam, gold restoration, copper, palladium with or without peripheral striae, affected area may be white or erythematous, posterior buccal mucosa, surface epithelium showing hyperkeratotic, atrophic, ulcerated, hydropic degeneration of basal cell layer, band-like array of mononuclear inflammatory cells, Improved oral hygiene.

CHRONIC ULCERATIVE STOMATITIS

Appearance: It appear as desquamative gingivitis with ulceration and erosion of the tongue or buccal mucosa. Sign and symptoms: Ulcer is surrounded by zones of erythema and streaky keratosis resembling lichen planus. The ulcer heals without scarring. Migration of ulcer can also be seen.

Histopathological Features

It is immune mediated disorders affecting oral mucosa. Epithelium is more atrophic as compared to epithelium in This patient develop autoantibodies agent 70-kD nuclear lichen planus. Inflammatory infiltrated contain significant protein and cause epithelial growth and differentiation. numbers of plasma cells.

Clinical Features

Management

Age and sex distribution: It is seen in women in sixth decade of life.

Hydroxychoroquine therapy gives good results as compared to corticosteroid.

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Points to Remember Streaky keratosis resembling lichen, ulcer is surrounded by zones of erythema, epithelium is more atrophic, inflammatory infiltrated, hydroxychoroquine.

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CROHN’S DISEASE It is also called regional ileitis, regional enteritis. It is an inflammatory and immunologically mediated condition of unknown cause.

Clinical Features ∙

Age: It is more commonly seen in patient more than 60 years of age. ∙ Gastrointestinal sign: There is abdominal cramping, pain, nausea, and diarrhea and fever, weight loss, malnutrition, anemia, decrease growth and short stature. ∙ Orofacial granulomatosis: There is diffuse or nodular swelling of the oral and perioral tissue. There is also cobblestone appearance of the mucosa. ∙ Mucogingivitis: There is patchy erythematous macules and plaque which involve attached and unattached gingiva. Other features like aphthous like ulceration, and diffuse stomatitis can also occur.

Histopathological Features There is non-necrotizing granulomatous inflammation within submucosal connective tissue.

Management Sulfa drugs—some patient respond well to this medication. Corticosteroid—in severe cases systemic prednisolone can be used. They are more effective when used in combined with azathioprine. Points to Remember Regional ileitis, regional enteritis, gastrointestinal sign, orofacial granulomatosis, mucogingivitis, non-necrotizing granulomatous inflammation, sulfa drugs.

BIBLIOGRAPHY 1. Bakula A, Lugovié-Mihić L, Situm M, Turcin J, Sinkoviéć A. Contact allergy in the mouth: diversity of clinical

presentations and diagnosis of common allergens relevant to dental practice. Acta Clin Croat. 2011;50(4):553-61. Review. 2. Black, CA. Delayed type hypersensitivity: current theories with an historic perspective dermatol. Online J. (May 1999) 5(1):7 at http://dermatology.cdlib.org DOJvol5num1/ reviews/black.htm 3. Buchanan JA, Zakrzewska JM. Burning mouth syndrome. Clin Evid (Online). 2010 19;2010. 1301. 4. Cohen DE, Brancaccio RR, Soter NA. Diagnostic tests for type IV or delayed hypersensitivity reactions. Clin Allergy Immunol. 2000;15:287-305. 5. Cohen DE, Brancaccio RR, Soter NA. Diagnostic tests for type IV or delayed hypersensitivity reactions. Clin Allergy Immunol. 2000;15:287-305. [Medline]. 6. David Saadoun, Bertrand Wechsle. Behçet’s disease. Orphanet Journal of Rare Diseases. 2012;7:20. 7. DeRossi SS, Ciarrocca KN. Lichen planus, lichenoid drug reactions, and lichenoid mucositis. Dent Clin North Am 2005;49:77–89, viii. 8. Fauci AJ, Braunwald E, Isselbacher KJ, et al, (Eds). Harrison’s Principles of Internal Medicine. 14th edn. New York, NY: McGraw-Hill; 1998. 9. Gell PGH, Coombs RRA (Eds). Clinical Aspects of Immunology. 1st edn. Oxford, England: Blackwell; 1963. 10. Hyman MH. Delayed drug hypersensitivity reactions. Ann Intern Med. 2004;140(9):W35; author reply W36. 11. Jacysyn JF, Abrahamsohn IA, Macedo MS. Modulation of delayed-type hypersensitivity during the time course of immune response to a protein antigen. Immunology. 2001;102(3):373-9. 12. Jelinek C. Appendix E: Diagnostic Procedures. Delayed Hypersensitivity Skin Testing. In: Allergy/Immunology Specialist Course Manual. 5th edn. US Army; 1990:E-1-11. 13. Jääskeläinen SK. Pathophysiology of primary burning mouth syndrome. Clin Neurophysiol. 2012;123(1):71-7. Epub 2011 Oct 24. 14. Klasser GD, Epstein JB, Villines D. Diagnostic dilemma: the enigma of an oral burning sensation. J Can Dent Assoc. 2011;77:b146. 15. Kusy RP. Clinical response to allergies in patients. Am J Orthod Dentofacial Orthop. 2004;125(5):544-7. 16. Litsas G. Crohn’s disease of the mouth: report of a case. Eur J Paediatr Dent. 2011;12(3):198-200. 17. López-Jornet P, Camacho-Alonso F, Andujar-Mateos P, Sánchez-Siles M, Gómez-Garcia F. Burning mouth syndrome: an update. Med Oral Patol Oral Cir Bucal. 2010;15(4):e562-8. 18. Middleton E Jr, Reed CE, Ellis EF, et al. (Eds). Allergy: Principles and Practice. 5th edn. St. Louis, Mo: Mosby-Year Book; 1998.

Allergic and Immunologic Diseases of Oral Cavity 19. Minguez-Sanz MP, Salort-Llorca C, Silvestre-Donat FJ. Etiology of burning mouth syndrome: a review and update. Med Oral Patol Oral Cir Bucal. 2011;16(2):e144-8. 20. Minor JS, Epstein JB. Burning mouth syndrome and secondary oral burning. Otolaryngol Clin North Am. 2011;44(1):205-19, vii. 21. Mitchell, Richard Sheppard, Kumar Vinay Abbas Abul K, Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edn. 22. Mock D, Chugh D. Burning mouth syndrome. Int J Oral Sci. 2010;2(1):1-4. Review. PubMed PMID: 20690412. 23. Mohammad R, Halboub E, Mashlah A, Abou-Hamed H. Levels of salivary IgA in patients with minor recurrent aphthous stomatitis: a matched case-control study. Clin Oral Investig. 2012; 20. [Epub ahead of print] 24. Picek P, Buljan D, Rogulj AA, Stipetié-Ovcariéćek J, Catiéć A, Plestina S, Boras VV, Vidovié-Juras D. Psychological status and recurrent aphthous ulceration. Coll Antropol. 2012;36(1):157-9. 25. Rajan TV. The Gell-Coombs classification of hypersensitivity reactions: a re-interpretation. Trends Immunol. 24(7): 376–9. 26. Randomized trials for the treatment of burning mouth syndrome: an evide nce-based review of the literature. Br Dent J. 2012;213(1):21. 27. Roitt IM. Essential Immunology. 9th edn. Oxford, UK: Blackwell Scientific; 1998:Chapters 22-23.

28. Shiohara T, Kano Y. Lichen planus and lichenoid dermatoses. In: Dermatology, Bolognia JL, Jorrizo JL, Rapini RP, (Eds). London: Mosby. 2003. pp.175–98. 29. Slavin RG, Tennenbaum JI, Becker RJ, et al. Cell transfer of delayed hypersensitivity to ragweed from atopic subjects treated with emulsified ragweed extracts. J Allergy. 1963;34:368-73. 30. Sontheimer, Richard D. Lichenoid Tissue Reaction/Interface Dermatitis: Clinical and Histological Perspectives. Invest. Derm. 2009;129;1088–99. doi:10.1038/jid.2009.42; pub lished online 26 February 2009. 31. Spanemberg JC, Cherubini K, de Figueiredo MA, Yurgel LS, Salum FG. Aetiology and therapeutics of burning mouth syndrome: an update. Gerodontology. 2012;29(2):84-9. 32. Uimarães AL, Correia-Silva Jde F, Sá AR, Victória JM, Diniz MG, Costa Fde O, Gomez RS. Investigation of functional gene polymorphisms IL-1beta, IL-6, IL-10 and TNF-alpha in individuals with recurrent aphthous stomatitis. Arch Oral Biol. 2007;52(3):268-72. Epub 2006 Oct 18. 33. Vucicevic Boras V, Savage NW. Recurrent aphthous ulcerative disease: presentation and management. Aust Dent J. 2007;52(1):10-5; quiz 73. 34. Wilson JD. Skin testing in the assessment of cell-mediated immunity. N Z Med J. 1977;85(580):41-4. 35. Shiohara T, Mizukawa Y. The immunological basis of lichenoid tissue reaction. Autoimmun Rev: 2005;4:236-41.

MULTIPLE CHOICE QUESTIONS





1. Undermined edge seen in: a. Tropic ulcer b. c. Malignant ulcer d.

Tuberculosis ulcer Healing ulcer

2. Rolled out (everted) edge is a characteristic feature of: a. Tropic ulcer b. Healing ulcer c. Malignant ulcer d. Venous ulcer 3. Contact allergy of oral lesions is referred as: a. Stomatitis medicamentosa b. Canker sores c. Dermatitis venenata d. Stomatitis venenata







4. Food allergy is the most common cause in: a. Angioedema b. Quincke’s edema c. Giant urticaria d. All of the above. 5. Sutton’s disease refers to: a. Major aphthae b. c. Recurrent ulcers d.

Minor aphthae Herpetiform ulcers

6. Triad of recurring oral ulcers, recurring genital ulcers and eye lesions is the feature of: a. Behçet’s syndrome b. Sutton’s disease c. Book syndrome d. Chemical burns

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Endocrine Disorders

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline       Â

Anatomy and physiology Hyperpituitarism Hypopituitarism or pituitary dwarfism Progeria Hyperthyroidism Hypothyroidism Hyperparathyroidism

      Â

Hypoparathyroidism Pseudohypoparathyroidism Diabetes mellitus Addison’s disease Adrenogenital syndrome Melasma Cushing’s syndrome

Hormones vary tremendously in chemical composition and biologic activity. Various disorders of components of the endocrine system have generalized adverse effects on skeletal system due to altered metabolism.

extent, the pancreas. These glands are connected with the autonomic nervous system, secreting their hormones in response to electrical stimuli originating in higher centers in the brain and reaching them by way of the nerve fibers that link them to that system.

ANATOMY AND PHYSIOLOGY

Pituitary gland: It lies within the sella turcica at the base of brain and it is divided into three distinct lobes. The anterior lobe also called as adenohypophysis originates from epithelium of Rathke’s pouch, the intermediated lobe from dorsal portion of Rathke’s pouch and posterior lobe or nuerohypophysis develops from base of third ventricles. Hormone secreted by anterior lobe are growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), leutinizing hormone (LH) and prolactin. Hormone secreted by intermediated lobe is melanocytes stimulating hormone and by posterior lobe vasopressin and oxytocin. The secretory activities of the pituitary gland are modulated by hypothalamus through a series of complex feedback interaction.

The endocrine system is specifically designed to integrate and control the human body’s innumerable metabolic activities. Its functioning components are the endocrine glands. These units can function individually, in series, or in parallel, their activities being integrated closely. Communication with each other and with the tissues under their control is established by means of hormones, which they produce, store, and release as required and which are distributed throughout the body by means of the circulating blood. In most instances, the agent stimulating or inhibiting their activity is the hormone produced by the corresponding target gland. The exceptions are the adrenal medulla, the posterior pituitary gland, and to a lesser

Endocrine Disorders

Thyroid gland: It is situated in midline of body in the neck, at the level of cricoids cartilage having two lateral lobes which are join by isthmus. Third pyramidal lobe also extends from the isthmus. Embryologically, the thyroid gland develops as a downgrowth from the portion of four pharyngeal pouches. It regulates the basal metabolic rate, stimulates somatic and psychic growth and plays an important role in calcium metabolism. Follicular cells lining the follicles of the gland secrete tri-idothyronin and tetra-idothyronin (thyroxin) which stimulates basal metabolic rate and somatic and psychic growth of the individuals. Para follicular cells lie in between the follicles and they secrete thyrocalcitonin which promotes deposition of calcium salts in skeletal and other tissue and tends to produce hypocalcemia. Around 83 percent of T3 is produced by monodeiodination of T4 in others tissue such as liver, muscle and kidney. T4 is probably not metabolically active until converted to T3 and may be regarded as prohormone. T3 and T4 circulate in plasma protein almost entirely bound to transport plasma proteins mainly thyroxine binding globulin. It is a minute fraction of unbound or free hormone, which diffuse into tissues and exerts its metabolic action. Production of T3 and T4 in the thyroid is stimulated by thyrotropin, a glycoprotein released form thyrotropic cells of the anterior pituitary in response to the hyperthalamic tripeptide, thyrotropic releasing hormone. There is negative feedback of thyroid hormones on the thyrotrophs such that in hyperthyroidism, when plasma concentration of T3 and T4 are raised, TSH secretion is suppressed and in hypothyroidism due to disease of the thyroid gland low T3 and T4 are associated with high TSH level. Parathyroid glands: The four parathyroid glands lie behind the lobes of the thyroid. They are not regulated by pituitary gland, but respond directly to changes in serum ionized calcium concentration. Parathyroid hormone (PTH) is a single chain polypeptide of 84 amino acid which are synthesized by the chief cells and released in response to a fall in serum ionized calcium concentration. The PTH directly promotes reabsorption of calcium from renal tubules and bones. The PTH also has indirect effect, mediated by increasing conversion of 1, 25 hydroxycholecalciferol, which results in increase calcium absorption from the food and enhanced mobilization of calcium from bone. The initial effect of PTH on bone is to stimulate osteolysis, returning from bone to extracellular fluid.

Adrenal gland: The adrenals are triangular-shaped structure that sits on the superior poles of the kidneys. It produce and secretes a number of compounds that are essential for maintenance of life adaptation to stress. Each gland is divided into adrenal medulla and a cortex. Adrenal medulla: It arises form ectodermal tissues and function as a part of the sympathetic nervous system. It manufacture and secretes two catecholamine, i.e. epinephrine and norepinephrine. Epinephrine supports blood pressure by increasing the heart rate. Epinephrine also increases oxygen consumption by the tissue and glucose release by the liver. Norepinephrine increases peripheral resistance by its vasoconstrictor effect. Epinephrine and norepinephrine also exert important metabolic effects by promoting lipodiysis; increase blood sugar levels by stimulating glycogeneolysis, elevating body temperature and increases basal metabolic rate. These compounds aid the body in adapting to stress which is important in the dental sitting because release of endogenous epinephrine during stressful dental procedure can produce significant changes in blood pressure and pulse rate. Adrenal cortex: It secretes three major classes of hormone: glucocorticoids or cortisols, which affects the inflammatory process and carbohydrates and protein metabolism, the mineralocorticoid aldosterone, which affects water and electrolyte balance and sex hormone testosterone, estrogen and progesterone.

DISEASES OF PITUITARY GLAND Hyperpituitarism It results from hyperfunction of anterior lobe of pituitary gland, most significantly with increased production of growth hormone. The usual cause of this condition is a benign, functioning tumor of the eosinophilic cells in the anterior lobe of the pituitary gland. The GH acts directly on some tissue but most its biological effects are accounted by stimulation of secretion of insulin-like growth factor I (IGF-I) and its binding proteins from the lower lobe. Types • G igantism: If the increase occurs before the epiphysis of the long bone are closed. • Acromegaly: If the increase occurs later in life after epiphysis closure.

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Gigantism Generalized overgrowth of most tissue in childhood also occurs. Most of the soft tissue and bones respond to the excess hormone by enlarging. Excessive generalized skeletal growth.

There is temporal headache, photophobia and reduction in vision. The terminal phalanges of the hands and feets become large and the ribs also increase in size. Hypertrophy of soft palatal tissue may cause or accentuate sleep apnea.

Oral Manifestations

Teeth in gigantism are proportional to the size of jaw and the rest of the body and root may be longer than normal. The teeth become spaced, partly because of enlargement of the tongue and party because upper teeth are situated on the inner aspect of the lower dental arch, due to disproportionate enlargement of the two jaws. Mandibular condylar growth is very prominent. Overgrowth of mandible leading to prognathism. Signs: Pituitary tumors may also induce deficiency of Mandible may be of extraordinary proportions creating a other pituitary hormones causing signs of hypogonadism major discrepancy between the upper and lower jaws and a including decreased libido and menstrual problems in pronounced class III malocclusion. women. In some cases, the growth at the condyle exceeds that of the alveolar processes, so that increased in vertical depth Acromegaly (Fig. 31.1) of the ramus is greater than that of the body of the jaw, It is more common in males and occurs most frequently consequently the upper and lower teeth fail to come into in 3rd decade. Bone overgrowth and thickening of the soft proper occlusion. tissue cause a characteristic coarsening of facial features The palatal vault is usually flattened and the tongue termed acromegaly. increase in size and may cause crenation on its lateral Symptoms: Hand and feet become large, with clubbing of border. The lips become thick and Negroid. In edentulous the toes and fingers due to enlargement of the tufts of the patients’, enlargement of the alveolus may prevent the comfortable fit of complete dentures. terminal phalanges. Symptoms: Patient may often have of height to 7 to 8 feet. Patients achieve monstrous size because of tumors of the pituitary gland. Later in life it may show genital underdevelopment and excessive perspiration and they complained of headache, lassitude, fatigue, muscle and joints pain and hot flashes. There is increase in size of calvarium which may lead to change in the hat size.

Radiological Features It shows enlarge sella as a results presence of pituitary adenoma. MRI will diagnose pituitary adenoma.

Laboratory Findings Measurement of serum growth hormone level should be done. This should be done after giving patient a measured quantity of glucose. Normally, this glucose challenge will reduce the production of growth hormone.

Diagnosis It can be made from the characteristic clinical and radiographic findings. Growth hormone concentration can be measured by radioimmunoassay technique.

Management Figure 31.1 Acromegaly of patient showing large head

Trans-sphenoidal surgery may result in cure of GH excess especially in patients with macroadenoma.

Endocrine Disorders

Octreotide, a long-acting analog of somatostatin, lowers GH. It is administered as subcutaneous insulin 2 to 3 times/day. Dopamine antagonists are also used. Growth hormone receptor blocking agent pegvisomant can be use in combination with somatostatin analog. It is injected daily and act on peripheral tissue to inhibit the action of growth hormone. Radiotherapy should be used in some cases, but it is not so effective.

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Points to Remember Excessive skeletal growth, monstrous size, hypogonadism, headache, lassitude, fatigue, coarsening of facial features, clubbing of the toes, temporal headache, photophobia, accentuate sleep apnea, teeth spaced, enlargement of tongue, prognathism, class III malocclusion, crenation on its lateral border of tongue, enlarge sella, trans-sphenoidal surgery, octreotide, pegvisomant.

Hypopituitarism or Pituitary Dwarfism Pituitary is the master gland of the body. It results due to reduced secretion of pituitary hormone, which may occur due to pituitary adenoma that compresses the pituitary gland. It can also occur due to reduce capacity of growth hormone to respond to growth hormone. It is often the consequence of growth of pituitary gland or interference with stalk function. It results in pituitary dwarfism. Pathologic changes can results from a variety of pituitary gland malfunction. Total absence of all pituitary secretions is known as panhypopituitarism. Hypopituitarism that commences after puberty is called as ‘Simmond’s disease’.

Causes It is caused by congenital or due to destructive disease of pituitary gland such as infarct occurring before puberty, space occupying lesions involving the sella turcica like craniopharyngioma, adenomas and sarcoidosis. Sheehan’s syndrome is a form of hypopituitarism caused by infarction of the pituitary associated with postpartum hemorrhage.

Clinical Features The underdevelopment is symmetrical, individual is very small and in some cases, there may be a disproportional shortening of the long bones (Fig. 31.2).

Figure 31.2 Short height of patient of dwarfism

The hallmark of this condition is that the growth is retarded to a greater degree than is bone and dental development. It may occur because of growth hormone and cortisol deficiency. Lack of gonadotropin delays the onset of puberty. The presence of diabetes insipidus associated with a deficient secretion of vasopressin is suggestive of pituitary dysfunction. Growth hormone secretion is lost resulting in lethargy, muscle weakness and increase fat mass in adults. After LH secretion becomes impaired, in the male loss of libido and impotence and in female oligomenorrhea or amenorrhea. The male produce gynecomastia and skin becomes fair and wrinkled. The skull and facial bone are small and there is delay in maturation of the skeleton, and epiphysis may remain nonunited throughout the life.

Oral Manifestations Marked failure of development of maxilla and mandible along lack of condylar growth with short ramus and this can lead to severe malocclusion and crowding of the teeth. The two important hormones excreted by this gland— somatotrophic and thyrotropic are responsible for the normal eruption of teeth and the alveolar growth. Thus in case of hypofunction of this gland, the tooth eruption is

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hampered. The dental arch is smaller than normal and thus cannot accommodate all the teeth resulting in crowding and subsequent malocclusion. The clinical crown appears smaller than normal because even through eruption does occur it is not complete. Eruption is delayed and so the shedding of the deciduous teeth.

Laboratory Findings Radioimmunoassay for human growth hormone shows below normal level of human growth hormone.

Management It is usually directed towards removal of the cause or replacement of the pituitary hormone or those of its target glands. Growth hormone can be produce with recombinant DNA technology. Points to Remember Panhypopituitarism, Simmond’s disease, very small individual, diabetes insipidus, loss of libido, impotence oligomenorrhea or amenorrhea, lack of condylar growth, severe malocclusion, crowding of the teeth, malocclusion, eruption is delayed, replacement of the pituitary hormone.

PROGERIA It is transmitted as autosomal dominant trait. This condition is rare and underlying cause is entirely dependent on pituitary dysfunction. It is regarded as premature senility in an individual of infantile proportions.

Clinical Features Affected infants appear normal at birth, but the typical clinical features become manifested within the first few years. Patient exhibits alopecia, pigmented areas of the trunk, atrophic skin, prominent veins and loss of subcutaneous fat. The individual have high pitched squeaky voice, beaklike nose and hypoplastic mandible. The face is pointed, with the nose resembling the beak of a bird. The head is large, while mandible is small. Exophthalmos and joint deformities may be present. The lip is thin. The intelligence of this patient is either normal or above normal and even at early age patient behave like old person.

Oral Manifestations Accelerated formation of irregular dentin. Delayed eruption of teeth.

Management No treatment and patient usually die before the age of 27 years. Points to Remember Alopecia, pigmented areas of the trunk, high pitched squeaky voice, exophthalmos, delayed eruption of teeth.

HYPERTHYROIDISM It is also called as thyrotoxicosis and it is a syndrome in which there is excessive production of thyroxin in thyroid gland. It is associated with diffuse toxic goiter and less frequently with toxic nodular goiter or toxic adenoma. Excessive thyroxin causes generalized increase in metabolic rate of all body tissues. In patient with thyrotoxicosis, dental treatment can precipitate an acute emergency like thyroid crisis or thyroid storm.

Definition Hyperthyroidism is excessive functional activity of the thyroid gland that can be caused by Graves’ disease, excessive replacement of/or overdose of thyroid hormone.

Causes It is caused by exophthalmic goiter, toxic adenoma, ectopic thyroid tissue, Graves’ disease, multinodular goiter, thyroid adenoma, a pituitary disease involving anterior portion of the gland, choriocarcinoma, excess pituitary TSH, autonomous struma ovarii, polyostotic fibrous dysplasia. This disease is triggered by autoantibodies that are act against receptors for thyroid stimulating hormone (TSH) on the surface of thyroid cells. This in turn will stimulate the thyroid cells to release inappropriate thyroid hormone.

Clinical Features Age and sex predilection: It has predilection for females five to ten times more as compared to male between 20 to 40 years of age. Signs: Thyroid is diffusely enlarged, smooth, possible asymmetrical and nodular, a thrill may be present, may be

Endocrine Disorders

Oral Manifestations There is advanced rate of dental development and early eruption with premature loss of primary teeth. Generalized decrease in bone density or loss of some areas of edentulous alveolar bone. Early jaw development and alveolar bone atrophy.

Laboratory Investigation Plasma levels of T3 and T4 are increased; free thyroxin index is raised in this disorder. Thyroid stimulating hormone is decreased. Anemia may be of moderate-to-severe degree and is seen in patient with prolonged duration of the disease. The anemia is hypochromic and abnormal forms of RBC may be seen. Figure 31.3 Tumor of thyroid gland

tender. Abdomen, liver and spleen may be enlarged (Fig. 31.3). Symptoms: It includes nervousness, fine tremors, and muscle weakness, mood swings from depression to extreme euphoria, emotional liability, hyper-reflexia, ill sustained clonus, proximal myopathy, bulber myopathy and periodic paralysis. There is weight loss despite normal or increases appetite, diarrhea, bowel alterations, anorexia, vomiting and hyerdefaecation. Cardiac features: There is also palpitation, excessive perspiration and irregular heart beat. Increased metabolic activity leads to increased circulatory demands, tachycardia and increased pulse pressure and sometimes congestive cardiac failure. Exertional dyspnea and ankle edema, blood pressure normal, systolic hypertension may be present. Angina and cardiomyopathy and exacerbation of asthma. In thyrotoxicosis, the patient may have bulging eye and partial paralysis of the ocular muscles, retraction and jerky movement, corneal ulceration, optic neuritis, ocular muscle weakness, papilledema, loss of visual activity, exophthalmos. There is amenorrhea, oligomenorrhea, infertility, spontaneous abortion and loss of libido, impotence. Other symptoms: There is increases sweating, pruritis, oncholysis, pigmentation, vitiligo, digital clubbing and pretibail myxedema (bilateral nonpitting edema). Heat intolerance, sweaty and warm extremities, thin shiny skin, pretibial myxedema, increased PR and early fatigue, lymphadenopathy, thirst and osteoporosis occurs.

Histopathological Features Diffuse enlargement and hypercellularity of the thyroid gland is seen. Lymphocytic infiltration of the glandular parenchyma is also observed. There is also hyperplastic thyroid epithelium and little colloid production.

Management Antithyroid drugs: It would be appropriated to give antithyroid drugs for 12 to 18 months to those in whom a single episode was anticipated. Carbimazole for 0 to 3 weeks in 40 to 60 mg daily divided doses; for 4 to 8 weeks in 20 to 40 mg daily divided doses and for maintenance phase to 5 to 20 mg daily. Radioactive iodine: This is common therapy used for patient having Grave’s disease. Thyroid gland takes up iodine as this is critical component of thyroid hormone. So after administration of radioactive iodine, thyroid gland quickly takes up it from bloodstream and sequestrated radioactive material in the glandular tissue. This radioactive material then destroys hyperactive thyroid tissue. Other treatment modalities include subtotal thyroi dectomy, administration of propylthiouracil and meth im azole. Points to Remember Thyrotoxicosis, thyroid crisis, Graves’ disease, hyperreflexia, euphoria, periodic paralysis, tachycardia, increased pulse pressure, bulging eye, partial paralysis of the ocular muscles, optic neuritis, vitiligo, bilateral nonpitting edema, premature loss of primary teeth, decrease in bone density, anemia, hypercellularity of the thyroid gland, hyperplastic thyroid epithelium, carbimazole, radioactive iodine.

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HYPOTHYROIDISM 790

It is caused by insufficient secretion of thyroxin by the thyroid gland. As a failure of thyrotropic function on the part of the pituitary gland or an atrophy or destruction of the thyroid gland leads to an inability of the thyroid to produce sufficient hormone to meet the requirement of the body.

Definition Decreased or deficient secretion of thyroid hormones is caused by thyroiditis, insufficient thyroid replacement, post-thyroidectomy, postradioactive iodine therapy. Types • • • • •

Cretinism Juvenile myxedema Myxedema Primary Secondary.

menorrhagia, and anorexia. In late stages, there is slowing of intellectual and motor activity, absence of sweating, modest weight gain, constipation, peripheral edema, pallor, hoarseness, decreased sense of taste and smell, muscle cramps, aches and pains, dyspnea, anginal pain and deafness. Signs: Dull expressionless face, periorbital edema, sparse hair and skin that feels doughy to touch. There is hypothermia (decrease body temperature) and the patient may be disorientated which may indicate impending myxedematous coma, pulse decreased, blood pressure normal, diastolic hypertension may be present. Facial pallor, puffiness of face and eyelids (myxedema), occasional purpura, thickened nose and lips in more advanced cases, note scars in neck from thyroidectomy. Thyroid gland may be enlarged, thin brittle nails, coarse thin hair, dry rough skin; displaced apical beat may be present. Delayed return of deep tendon reflexes, pleural effusion may be present. There are also watery eyes, brittle hair and patchy alopecia.

Types

Oral Manifestations

Cretinism: If failure of hormone occurs in infancy

Cretinism and Juvenile Myxedema

Juvenile myxedema: If it occurs in childhood

Dental development delayed and primary teeth slow to exfoliate. Enamel hypoplasia can also be seen. Abnormalities of dentin formation lead to enlarge pulp chamber. Maxilla is overdeveloped and mandible is underdeveloped. Retarded condylar growth leads to characteristic micrognathia and open bite relationship. Tongue is enlarged by edema fluid and due to it tongue may protruded continuously and such protrusion may lead to malocclusion of teeth. The base of skull is shortened leading to a retraction of the bridge of the nose with flaring. Face is wide and fails to develop in longitudinal direction. Lips are puffy, thickened and protruding.

Myxedema: If it occur after the puberty. In it there is subcutaneous deposition of hydrophilic mucopolysaccrides Primary: In this thyroid gland is itself abnormal Secondary: In this pituitary gland does not produce an adequate amount of thyroid stimulating hormone.

Clinical Features Cretinism and Juvenile Myxedema It may be present at birth or become evidence within the first few months after birth. Symptoms: Hoarse cry, constipation, feeding problems in neonates, retarded mental and physical growth. Signs: There is delayed fusion of all body epiphysis and delayed ossification of paranasal sinus, partially pneumatization. There is protuberant abdomen with umbilical hernia. The hairs are sparse and brittle, the finger nails are brittle and the sweat glands are atrophic.

Myxedema Symptoms: It may include weakness, fatigue, cold intolerance, and lethargy, dryness of skin, headache,

Myxedema Macroglossia and enlarged lip as a result of the deposition of water and protein. Facial swelling of nonpitting type and mandible is underdevelop. There is a greater tendency to periodontal disease, with alveolar destruction and loosening of the teeth.

Laboratory Findings Thyroid stimulating hormone increased and T3 and T4 decreased. In ECG, a classical sinus bradycardia with low voltage complexes and ST/T wave abnormalities. There is

Endocrine Disorders

raised cholesterol and triglycerides level and low serum sodium.

Complications It is caused by coronary artery disease, congestive heart failure, increased susceptibility to infection and mental disturbances including depression.

Diagnosis Clinical signs and symptoms and radiographic features along with laboratory test revealing reduction in serum T3 and T4 levels are confirmatory.

Management Thyroid preparation: Patients are managed by thyroid preparation. Mainly use is levothyroxine, which is available as 25, 50 and 100 micrograms tablets. It is customary to start slowly and a dose of 50 mg/day should be given for 3 weeks and finally to 150 mg/day. In the elderly and in patient with ischemic heart disease the initial dose should be 25 mg/day. Points to Remember Hoarse cry, pneumatization of sinus, sparse hairs, weakness, anginal pain, dull expressionless face, hypothermia, puffiness of face, enlarged thyroid gland, pleural effusion, primary teeth slow to exfoliate, enamel hypoplasia, maxilla is overdeveloped, retarded condylar growth, enlarged tongue, malocclusion of teeth, wide face, increased thyroid stimulating hormone, thyroid preparation.

HYPERPARATHYROIDISM It is an endocrine disorder in which there is an excess of circulating parathyroid hormone. Excess PTH stimulates osteoclast to mobilize calcium from skeleton leading to hypercalcemia in addition to PTH increased renal tubular reabsorption of calcium. Following is the sequence of event which gives an idea of the reaction promoted by this hormone. The bone and kidney are the target organs of parathyroid hormone which mediates the osteoclast to resorb bone actively. When the bone is resorbed, calcium is released in the extracellular fluid and the serum calcium level is elevated. The parathyroid hormone acts on the epithelium of kidney tubules causing diuresis of phosphorus resulting

in decrease in serum phosphorus level. At the same time, it induces an increase in calcium reabsorption from glomerular filtrate. Parathyroid hormone may also increase the absorption of calcium from the intestine but this is not definitely established. Hence, in a healthy person injection of parathyroid hormone produces an elevated plasma calcium level, a decreased plasma phosphorus level and an increased alkaline phosphatase level.

Types Primary: There is autonomous secretion of parathyroid hormone (PTH) by hyperplasia, benign and malignant tumor of one or more of the four parathyroid glands. Secondary: Compensatory increase in output of PTH in response to hypocalcemia. The underlying hypocalcemia may result from an inadequate dietary intake or poor absorption of vitamin D or from deficient metabolism of vitamin D in the liver or kidney. It effects to restore serum calcium level at the expense of the lots of calcium in bone. Tertiary: Occasionally parathyroid tumor after longstanding secondary hyperparathyroidism develops this condition known as tertiary hyperparathyroidism. The increased parathyroid level produces increased bone resorption and a resultant hypercalcemia. Ectopic: Due to excessive parathyroid hormone synthesized in patient with malignant disease.

Clinical Features Age and sex distribution: Female to male ratio is 3:1. Mainly in 30 to 60 years of age. Classic triad: It has classic triad of stones, bones and abdominal organs. Stones: Renal calculi are common due to elevated level of serum calcium. Metastatic calcification is seen. Bones: There are variety of osseous changes seen in bones. There is also bone and joint pain. Abdominal organs: There is tendency for the development of duodenal ulcers. Other symptoms: There is also hematuria, back pain, urinary tract infection, hypertension are common. Peptic ulcer, psychiatric effect like emotional instability, and sometime pathologic fractures occurs. Gastrointestinal difficulties such as anorexia, nausea, vomiting and crampy pain may be present.

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Pigeon chest: Bone deformities occur such as bending of long bone occasional fracture and collapse of vertebrae and formation of pigeon chest. It is associated with muscle weakness, fatigue, weight loss, insomnia, headache, polydipsia and polyuria.

Oral Manifestations There is gradual loosening drifting and loss of teeth, malocclusion. There is pathological fracture of bone. Cystic lesion involving jaws are seen over 10 percent of cases. Brown tumor is present intraorally (Fig. 31.4).

Radiological Features First signs of disease are subperiosteal resorption of the phalanges of the index and middle fingers. There is also generalized loss of lamina dura surrounding the root.

Figure 31.4 Brown tumor seen in oral cavity

Ground glass appearance: There is blurring of the normal trabecular pattern and decrease in trabecular density. Brown tumor: This are called brown tumor as it resembles brown color in specimen. It appear well demarcated unilocular or multilocular radiolucency (Fig. 31.5). Osteitis fibrosa cystica: There is central degeneration and fibrosis of longstanding brown tumor.

Histopathological Features There is osteoclastic resorption of the trabeculae of the spongiosa and along the blood vessels in the haversian system of the cortex. Fibrosis especially in the marrow spaces is marked. Fibroblasts replace resorbed trabeculae in the fibrotic islands there is recent and old hemorrhage with much hemosiderin is evidence. Large tortuous blood filled sinusoidal channels are lined by a flat endothelial layer. The surrounding tissue is fibroblastic and hypercellular. Multinucleated giant cells lie adjacent to the sinusoids and osteoid trabeculae tend to orient themselves in close proximity to the vascular spaces.

Laboratory Findings The serum calcium level is raised and serum phosphorus level is decreased and serum alkaline phosphatase level is elevated in primary hyperparathyroidism and in secondary hyperparathyroidism the serum calcium level is decreased whereas the serum phosphorus and alkaline phosphatase level are elevated.

Figure 31.5 Radiograph of brown tumor of oral cavity

Diagnosis Serum alkaline phosphatase and serum calcium level is increased. Decreased blood phosphorus level. Increase in circulating hormone demonstrated by radioisotope studies.

Management It often regresses without surgery and the rarefaction disappears. Surgical excision of adenoma. The oral administration of vitamin D in secondary type can prevent skeletal demineralization in most of the cases. Cinacalcet is now a day use in management of overproduction of parathormone associated with secondary hyperparathyroidism. This is calciminetic agents that

Endocrine Disorders

sensitize the calcium receptor of the parathyroid cells to extracellular calcium causing the cell to reduce output of parathormone. Points to Remember Classic triad of stones, bones and abdominal organs, renal calculi, joint pain, abdominal organs, hematuria, peptic ulcer, pigeon chest, loss of teeth, malocclusion, generalized loss of lamina dura, ground glass appearance, brown tumor, osteitis fibrosa cystica, osteoclastic resorption, fibrosis in the marrow, tortuous blood filled sinusoidal channels, hypercellular surrounding tissue, raised serum calcium level, surgical excision of adenoma, cinacalcet.

Oral Manifestations Hypoplasia of enamel, delayed eruption, external root resorption and root dilacerations. There is also blunting of molar roots. Chvostek sign: A sharp tap over the facial in front of ear causes twitching of facial muscle around the mouth which is called as Chvostek sign. Chronic candidiasis is also some time present.

Laboratory Findings The serum calcium level is decreased usually below 7 mg/dL. Serum phosphate level correspondingly elevated. Urinary calcium is low or absent. The PTH can be measured by radioimmunoassay.

HYPOPARATHYROIDISM

Management

It is an uncommon condition in which there is insufficient secretion of parathyroid hormone.

Supplemental calcium and vitamin D depending on severity of the hypocalcemia should be administered. In severe cases intravenous administration of calcium gluconate is the treatment of choice. Teriparatide a recombinant form of the active component of human parathormone.

Etiology It can cause due to inadvertent surgical damage to parathyroid gland and their vascular supply during thyroid gland procedure. Other causes which can cause parathyroid damage from radioactive iodine 131, autoimmune destruction of parathyroid gland, DiGeorge syndrome, and endocrinecandidiasis syndrome.

Clinical Features Tetany: It can lead to tetany in the form of carpopedal spasm of the wrist and ankle joint. There is also stiffness in hands, feet and lips. Symptoms: There is also paresthesia of hands, feet and around the mouth. Tingling in the circumoral area, fingers and toes. Patients may complaint of anxiety, depression, epilepsy and chorea. There is reduction in intellectual capacity due to calcification within the brain. Signs: Patient with hypoparathyroidism manifest short stature due to early closure of certain bony epiphysis. The face is round and the hand shows shortening of the metacarpal bones, so that finger are short. Trousseau’s sign: It is elicited by occluding blood flow to the forearm for 3 minutes with sphygmomanometer cuff applied to the arm and raising the pressure above systolic level. This will induce carpopedal spasm.

Points to Remember Tetany, paresthesia-of-hand feet, tingling in the circumoral area, short stature, Trousseau’s sign, Chvostek sign, decreased serum calcium level, supplemental calcium, teriparatide.

PSEUDOHYPOPARATHYROIDISM Pseudohypoparathyroidism is a condition in which there defect in the response of tissue target cell to normal level of parathyroid hormone. It is also called as Albright hereditary osteodystrophy or acrodysostosis.

Types Pseudohypoparathyroidism type I: There is three subcategories Ia (molecular defect of specific intracellular binding protein Gsα), which prevent the formation of cyclic adenosine monophosphate a critical component in the activation of cell metabolism, Ib (defective receptor of the PTH on the surface of target cells) Ic (defect in adenylate cyclase or subtle Gsα alteration. Pseudohypoparathyroidism type II: Induction of cAMP by PTH in the target cells.

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Symptoms: Mild mental retardation, obesity, round face, short neck and short stature. Midfacial hypoplasia: It is commonly seen in patient with pseudohypoparathyroidism. Signs: Metacarpals and metatarsal are shortened. Osteoma cutis: Subcutaneous calcification.

Oral Manifestations There is generalized enamel hypoplasia, widened pulp chamber. Presence of intrapulpal calcification is also noted which is also term as dagger shaped. Patient also complaint as oligodontia, delayed eruption and blunting of apices of the teeth.

Laboratory Findings There is elevated level of PTH, hypocalcemia, hyperphosphatemia with normal renal function.

Management Administration of vitamin D and calcium should be done. Prognosis is good. Points to Remember Mental retardation, obesity, midfacial hypoplasia, osteoma cutis, dagger shaped intrapulpal calcification, oligodontia, elevated level of PTH, vitamin D.

DIABETES MELLITUS It may cause by autoimmune response. Principal laboratory sign are hypercalcemia. It is common endocrine disorders characterized by chronic hyperglycemia and abnormalities in carbohydrate and lipid mechanism.

Definition Inappropriate hyperglycemia due to tissue resistance to Insulin action, reduced insulin secretion or both.

Etiology It is caused by disorders of carbohydrate mechanism resulting from insulin deficiency or ineffectiveness, producing hyperglycemia and glycosuria. Genetic, autoimmune and pancreatic dysfunction.

Types Primary • Type I or insulin dependent diabetes mellitus (IDDM) • Type II or noninsulin dependent diabetes mellitus (NIDDM) • Nonobese • Obese • Maturity onset diabetes of the young (MODY) Secondary • • • •

Pancreatic disease Endocrine disease Drug induced Genetic syndrome

Impaired glucose tolerance Gestational diabetes.

Types Primary Type I or insulin dependent diabetes mellitus–it occurs due to deficiency. Type II or Noninsulin dependent diabetes mellitus–it occurs due to insulin resistance. – Nonobese – Obese – Maturity onset diabetes of the young (MODY)

Secondary Pancreatic disease (pancreatitis, hemochromatosis, neoplastic disease, pancreatectomy, cystic fibrosis). Endocrine disease—excess endogenous production of hormonal antagonists to insulin, e.g. growth hormone in acromegaly. Drug induced like corticosteroid, thiazide diuretics and phenytoin. Genetic syndrome like Down syndrome, Klinefelter’s syndrome and Turner’s syndrome.

Impaired Glucose Tolerance It is a prediabetic state of hyperglycemia that is associated with insulin resistance. Two-hour glucose levels of 140 to 199 mg per dL on the 75 g oral glucose tolerance test. A patient is said to be under the condition of impaired glucose tolerance (IGI). When

Endocrine Disorders

he/she has an intermediately raised glucose level after 2 hours, but less than would quality for type 2 diabetes millitus. 795

Gestational Diabetes It is a condition in which woman without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy (especially during third trimester).

Etiology Type I Diabetes Mellitus Viruses: Several viruses are been implicated including infection with mumps coxsackie B4, retrovirus, rubella and cytomegalovirus and Epstein-Barr virus. Virus particle known to cause cytopathic or autoimmune damage to beta cells have been isolated from the pancrease. Diet: Bovine serum albumin (BSA) a major constituent of cow’s milk has been implicated in triggering type I diabetes. It has been shown that a child who has taken cow’s milk early in infancy has been more prone to develop type I diabetes mellitus as compared to other who has taken breast milk. Stress: It may precipitate the development of type I diabetes by stimulating the secretion of counter regulatory hormones and possibly by modulating immune activity. Immunological factors: There is evidence that type I diabetes is a T cell-mediated autoimmune disease. There is also HLA linked genetic predisposition. Monocular cell infiltration of pancreatic islets restoration in selective destruction of insulin secreting cells and induction of remission by immunosuppressive drugs such as cyclosporine suggest it immunological etiology.

Figure 31.6 Periodontitis in diabetes patients

Malnutrition: It is proposed that malnutrition in utero and the infancy may damage beta cell development at a critical period predisposing to type II diabetes later in life. Age: Age is an important risk factors for type II diabetes as it is principally disease of middle aged and elderly affecting 10 percent of the population over the age of 65. Pregnancy: During normal pregnancy, insulin sensitivity is reduced through the action of placental hormone and this affect glucose tolerance. The term gestational diabetes refers to hyperglycemia occuring for the first time during pregnancy. Insulin resistance occurs in type II diabetes is due to an abnormal insulin molecule, an excessive amount of circulating antagonists and target tissue defect.

Clinical Features Polydipsia: There is excessive intake of fluid.

Type II Diabetes Mellitus

Polyuria: There is excessive urine passage.

Genetic: The majority of cause of type II diabetes are multifactorial. Various types are associated with it like hepatocyte nuclear factor, glucokinase, and mitochondrial DNA and insulin receptors.

Polyphagia: There is excessive hunger. There is presence of acetone breath. Visual difficulty ranging form progressive color blindness to total blindness that have disease more than 20 years. Coronary artery disease and stroke are frequent complication. Diabetic neuropathy can cause marked irritability. Recurrent vaginal (yeast) infections, recurrent urinary tract infections, recurrent skin infections (especially of feet) and reversible paresthesia of fingers or toe.

Environmental Factors Lifestyle: Overeating, especially when combined with obesity and underactivity is associated with developmental of type II diabetes.

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Nocturia, weight loss, fatigue, obesity usually present in older age group, nausea, vomiting. Temperature, blood pressure may be elevated and peripheral pulses may be reduced. Complication of diabetic mellitus is peripheral vascular disease which can results in kidney failure and gangrenous involvement of the limb.

There is delay in healing of oral wound due to decreased polymorphonuclear chemotaxis. There is also angular cheilosis, altered taste sensation, oral lichen planus, and diffuse enlargement of parotid gland.

Oral Manifestations

Treatment modalities includes diet control, oral hypoglycemic drugs like sulfonylurea, biguanides, alfaglucosidase inhibitors, insulin therapy.

It will influence the onset and course of periodontal disease. Patient with diabetes are more prone to develop periodontal disease than are those with normal glucose metabolism (Fig. 31.6). There is a greater tendency for bleeding on probing. The patient may exhibit a fulminating periodontitis with periodontal abscess formation and inflamed painful abscess and even hemorrhagic gingival papillae, this factor culminated and give rise to tooth mobility, i.e. loose teeth. It will show more severe and rapid alveolar bone resorption and are more prone to develop periodontal abscess. Insulin dependent diabetic children tend to have more destruction around the first molars and incisors than elsewhere. As such diabetes mellitus does not cause periodontal disease directly but it alters the response of the periodontal lesion to local irritants, hastening bone loss and retarding postsurgical healing of the periodontal lesions. Gingival fluid in the diabetes has more glucose level which favors the growth of microflora. Diabetes is considered to be factor for median rhomboidal glossitis as frequency of abnormal blood sugar level in diabetes and predisposition of these subjects to candidiasis. There is also impairment of blood supply to dorsum of tongue due to arteriosclerosis changes in the blood vessels supplying the area. Impairment of local immune mechanism which decrease the concentration of Langerhans cells in the lesion. It is infection with Candida albicans which occur due to encouragement of local multiplication of Candida albicans due to impaired glucose level and immune mechanism. Dry socket develops in diabetes hence they show delayed healing and impaired immunological balance. It is often associated with variety of otherwise unexplained oral symptoms such as burning sensation, atypical paresis, dysethesia and dysgeusia. Diabetes neuropathy is recognized as polymorphic condition as when manifested as polyneuropathy on the assumption the trigeminal nerve might be involved. Increased caries activity occurs due to excessive fluid loss. Patient complained of xerostomia. There is also atrophy of lingual papillae with fissuring and dry tongue.

Management

Points to Remember Polydipsia, Polyuria, Polyphagia, diabetic neuropathy, peripheral vascular disease, periodontal disease, alveolar bone resorption, median rhomboidal glossitis, Candida albicans infection, paresis, dysethesia, increased caries activity, oral hypoglycemic drugs.

ADDISON’S DISEASE It is also called as chronic adrenal insufficiency or hypoadrenocorticism. It was first described by Addison in 1855.

Causes It is caused by tuberculosis, metastatic carcinoma, intradermal hemorrhage, amyloidosis, hemochromatosis, adrenal infarction and congenital adrenal hypoplasia. Drugs causing Addison’s disease are aminoglutethimide, ketoconazole and etomidate.

Types Primary hypoadrenocorticism: Insufficient production of adrenal corticosteroid hormone cause by destruction of adrenal cortex Secondary hypoadrenocorticism: It occur if adrenal gland is not functioning properly.

Clinical Features Age and sex distribution: It is more common in males and, found in all age groups, it is most frequently seen in the 3rd and 4th decade. Symptoms: Feeble heart action, general debility, vomiting, and diarrhea and severe anemia. Patient complained of postural hypotension. Bronzing of skin: The disease is characterized by bronzing of skin, a pigmentation of the mucous membrane. This Hyperpigmentation is more common on sun exposed surface of the skin and overpressure point.

Endocrine Disorders

Decrease cortisol level interferes with the manufacture of carbohydrates from protein, causing hypoglycemia and diminished glycogen storage in the liver. Neuromuscular function is inhibited, producing muscle weakness. There is also reduced resistance to infection, trauma, and stress.

Oral Manifestations The pale brown or deep chocolate pigmentation of the oral mucosa, spreading over the buccal mucosa form the angle of the mouth and/or developing on the gingiva, tongue, lips may be first evidence of disease.

Histopathological Features Biopsy of oral lesion shows acanthosis with silver positive granules in the cells of the stratum germinativum.

Laboratory Investigations The associated anemia is normocytic and normochromic associated with reticulocytosis. There is reduction in the red cell mass. There is high blood levels of potassium and low concentration of sodium and chloride. Elevated blood urea nitrogen. The diagnosis is confirmed by rapid ACTH stimulation test, measurement of serum cortisol level and plasma ACTH level. If serum cortisol level are below 20 µg/dL then the patient has adrenal insufficiency.

Management Glucocorticoids replacement: Cortisol is the drug of choice. In patient who are not critically ill hydrocortisone 15 mg on waking and 5 mg at 6 PM in evening. Supplement mineralocorticoid: Can be given. Points to Remember Feeble heart action postural hypotension, bronzing of skin, muscle weakness, pale brown or deep chocolate pigmentation of oral mucosa, acanthosis, silver positive granules, normocytic anemia, glucocorticoids replacement, supplement mineralocorticoid.

ADRENOGENITAL SYNDROME It refers to any situation in which there is overproduction of androgens. It results when hyperplasia or tumors of the adrenal cortex occur. It may appear at three different times of life, i.e. at birth, in childhood and in adult. Clinical features vary according

to appearance of lesion. In female child, it produces pseudohermaphroditism, while in male child, it produces macrogenitosomia praecox. In the females it produces masculinization and in males in produce sexual precocity. In females it produce virilism and in males it produces feminization. If the disease begins early premature eruption of the teeth may occur. Administration of corticosteroid or estrogen. Points to Remember Pseudohermaphroditism, Macrogenitosomia praecox, masculinization, sexual precocity.

MELASMA It is also called as mask of pregnancy. It is symmetrical hyperpigmentation of sun exposed skin of face and neck. It is thought to be caused by exogenous estrogen and progesterone.

Clinical Features Location: It is seen on midface, forehead, upper lip, chin and arms. Appearance: There is dark brown cutaneous macules which appear bilaterally in the adults women. The pigmentation may remain faint or darken over time

Histopathological Features There is increase melanin deposition in epidermis.

Management Triple combination topical therapy—a combination of hydroquinone, tretinoin and fluocinolone acetonide give good results. Other therapy includes glycolic acid chemical peel, laser therapy, and dermabrasion.

CUSHING’S SYNDROME Cushing’s syndrome arises from excess secretion of glucocorticoids by the adrenal glands. It is described by Harvey Cushing in 1932. It is also called as hypercortisolism.

Etiology It is caused by adrenal adenoma, adrenal carcinoma, adrenal hyperplasia and basophilic adenoma of the anterior lobe

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of pituitary gland. Other factors which are responsible for Cushing’s syndrome are exogenous corticosteroid, ACTH secreting tumor of the anterior pituitary associated with adrenal cortical hyperplasia, ectopically located adrenal like tumor like in ovary, alcohol excess, major depressive illness, and primary obesity.

Clinical Features Female to male ratio is 3:5, seen in 3rd and 4th decades. Signs: Rapidly acquired obesity about upper portion of the body and rounded moon face (Fig. 31.7). There is truncal obesity with prominent supraclavicular and dorsal cervical fat pads giving rise to the buffalo hump appearance at the base of neck. The distal extremities are usually thin. Weakness, hypertension, or concurrent diabetes is usually present. Symptoms: There is alternation in hair distribution. Dusky plethoric appearances with formation of purple striae appear on abdomen. There is also weight loss, menstrual irregularity, hirusitism, backache, obesity, hypertension can also occur.

Oral Manifestations In children growth and development including skeletal and dental age may be retarded. In some instances, there may be osteoporosis of the jaws.

Laboratory Diagnosis Measurement of free cortisol in the urine and assay of effect of dexamethasone on the serum ACTH and cortisol

Figure 31.7 Moon face in Cushing’s syndrome

patient. In normal patient administration of dexamethasone will suppress the normal level of ACTH.

Management If the lesion in the pituitary gland is the cause, therapy usually consist of combination of surgery and radiotherapy. Drugs used—metyrapone in dose of 2 to 6 g per day in divided doses by mouth. Other drug which is given is aminoglutethimide which is anticonvulsant, and it act by blocking steroid synthesis. Points to Remember Hypercortisolism, obesity, moon face, truncal obesity, buffalo hump, dusky plethoric appearances, retarded dental age, metyrapone, aminoglutethimide.

BIBLIOGRAPHY 1. Agashe MV, Rathod CM, Dhamele JA. Congenital pseudoarthrosis of the tibia with localised gigantism in a case of congenital constriction band syndrome: Indian J Plast Surg. 2011;44(1):139-41. 2. Bain S. Physical signs for the general dental practitioner. Case 44. Buffalo hump. Dent Update. 2007;34(4):252. 3. Bergman SA. Perioperative management of the diabetic patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(6):731-7. 4. Borghelli RF, Pettinari IL, Chuchurru JA, et al. Oral lichen planus in patients with diabetes. An epidemiologic study. Oral Surg Oral Med Oral Pathol. 1993;75(4):498-500. 5. Brown MD, Aaron G. Pseudohypoparathyroidism: a case report: Pediatr Dent. 1991;13:106-9. 6. Cohen RB, Wilcox CW. A case of acromegaly identified after patient complaint of apertognathia. Oral Surg Oral Med Oral Pathol. 1993;75:583-6. 7. Cooper DS. hyperthyroidism. Lancet. 2003;362:459-68. 8. Croft LK, Witkop CJ Jr, Glas JE. Pseudohypoparathyroidism: ORal Surg Oral Med Oral Pathol. 1965;20(6):758-70. 9. DanIels JSM. Primary hyperparathyroidism presenting as palatal brown tumor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98:409-13. 10. De Pablos PL, Ramos I, De La Calle H, Brown tumor in the palate associated with primary hyperparathyroidism. J Oral Maxillofac Surg. 1987;45(8):719-20. 11. Elfenbaum A. The adrenogenital syndrome in pedodontology. Dent Dig. 1971;77(9):531-4. 12. Farinazzo-Vitral RW, Motohiro-Tanaka. O, Reis Fraga M, et al. Acromegaly in an orthodontic patient: AM J Orthod Dentofacial Orthop. 2006;130:388-90.

Endocrine Disorders 13. Funatsu M, Sato K, Mitani H. Effect of growth hormone on craniofacial growth. Angle Orthod. 2006;76:970-7. 14. Gardner DG, Majka M. The early formation of irregular secondary dentine in progeria. Oral Surg Oral Med Oral Pathol. 1969;28(6):877-84. 15. Grrenberg MS, Brightman VJ, Lynch MA, et al. Idiopathic hypoparathyroidism, chronic candidiasis and dental hypoplasia. Oral Surg Oral Med Oral Pathol. 1969;28:42-53. 16. Kosowicz J, Rzymski K. Abnormalities of tooth development in pituitary dwarfism. Oral Surg Oral Med Oral Pathol. 1977;44:853-63. 17. Lamberts SWJ, de Herder WW, van der Lely AJ. Pituitary insufficiency. Lancet. 1998;352:127-34. 18. Manfredi M, McCullough MJ, Vescovi P, et al. Update on diabetes mellitus and related oral diseases. Oral Dis. 2004;10(4):187-200. 19. McKenna SJ. Dental management of patients with diabetes: Dent Clin North Am. 2006;50(4):591-606. 20. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edn. Saunder Elsevier; 2009.

21. Newell-Price J, Bertagna X, Grossman AB, et al. Cushing’s syndrome. Lancet. 2006;367:1605-17. 22. Peruse R, Goulet J-P, Turcotte J-Y. Contraindication to vasoconstrictor in density Part II: hyperthyroidism, diabetes, sulfite sensitivity: corticodependent asthma, and pheochromocytoma. Oral Surg Oral Med Oral Pathol. 1992;74: 687-91. 23. Robert CGP, Ladenson PW. Hypothyroidism. Lancet. 2004;363:793-803. 24. Shah SS, Oh CH, Coffin SE, et al. Addisonian pigmentation of the oral mucosa. Cutis. 2005;76:97-9. 25. Sutbeyaz Y, Yoruk O, Bilen H, Gursan N. Primary hyperparathyroidism presenting as a palatal and mandibular brown tumor. J Craniofac Surg. 2009;20(6):2101-4. 26. Walls KK, Ko CW, Reynolds JC, et al. Dental manifestation of autoimmune hypoparathyroidism. Oral Surg Oral Med Oral Pathol. 1993;75:452-4. 27. Yu QX, Zeng LH. Progeria report of a case and review of the literature. J Oral Pathol Med. 1991;20(2):86-8.

MULTIPLE CHOICE QUESTIONS 1. Gland which lies within the sella turcica is: a. Pituitary gland b. Thyroid gland c. Parathyroid gland d. Adrenal gland

6. Increase production of growth hormone results in: a. Gigantism b. Acromegaly c. None d. Both a and b

2. Hormones secreted by anterior lobe of pituitary gland are: a. Growth hormone b. TSH c. Oxytocin d. Both a and b

7. Marked failure of development of maxilla and mandible with lack of condylar growth seen in: a. Hypothyroidism b. Hypopituitarism c. Cushing’s syndrome d. Addison’s disease

3. Hormones secreted by intermediate lobe of pituitary gland is: a. Oxytocin b. Vasopressin c. MSH d. FSH

8. Plasma levels of T3 and T4 increased in: a. Hyperthyroidism b. Hypothyroidism c. Addison’s disease d. All of the above

4. Parafollicular cells of thyroid gland secrete: a. Thyrocalcitonin b. Thyroxin c. Oxytocin d. Vasopressin

9. Polydypsia, polyuria, polyphagia markedly seen in: a. Diabetes mellitus b. Adrenal insufficiency c. Addison’s disease d. Goiter

5. Catecholamine, i.e. epinephrine and nor-epinephrine secreted by: a. Parathyroid gland b. Adrenal gland c. Parotid gland d. Adrenal medulla

10. The pale brown or deep chocolate pigmentation of the oral mucosa seen in: a. Cushing’s syndrome b. Addison’s disease c. Diabetes mellitus d. None of the above

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Nutrition and Oral Cavity

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline  Disturbances in protein metabolism • Protein deficiency • Amyloidosis • Porphyria  Disturbances in lipid metabolism • Classification • Hand – Schuller – Christian disease • Eosinophilic granuloma • Letterer Siwe disease • Gaucher disease • Niemann-Pick disease • Tay Sachs disease  Disturbances in carbohydrate metabolism • Hurler’s syndrome • Hereditary fructose intolerance • Hypoglycemia • Mucopolysaccharidosis  Disturbances in mineral metabolism • Acrodermatitis enteropathica • Hypophosphatasia  Miscellaneous disorders • Malabsorption syndrome

Man is a complex biologic unit in a complex environment. Duncan defined metabolisms as sum total of tissue activity as considered in terms of physicochemical changes associated with and regulated by availability, utilization and disposal of protein, fat, carbohydrate, vitamins, minerals, water and influence which the endocrine exerts on these processes. Alternation from this normal metabolic process constitutes the disturbances of metabolism.

 Disorders of vitamins  Water soluble vitamins • Beriberi • Riboflavin (vitamin B2) • Niacin (vitamin B3) Pellagra • Pantothenic acid (vitamin B5) • Pyridoxine (vitamin B6) • Biotin (vitamin B8) • Folic acid (vitamin B9) • Cyanocobalamin (vitamin B12) • Vitamin C scurvy • Choline  Fat soluble vitamins • Vitamin A (Retinol) hypervitaminosis A • Vitamin D deficient rickets • Osteomalacia • Vitamin D resistant rickets (familial hypophosphatemia, refractory rickets) • Vitamin E (Tocopherol) • Vitamin K (Phylloquinone)  Disorders of bilirubin • Jaundice

DISTURBANCES IN PROTEIN METABOLISM Protein Deficiency It is also called marasmus or kwashiorkor disease. Marasmus is an overall deficit of food intake, notably energy while the kwashiorkor is associated with primary dietary protein deficiency.

Nutrition and Oral Cavity

Protein is the most important group of food stuff. In addition to contributing to cells and intercellular material, proteins also help in the formation of hormones, enzymes, plasma protein antibodies and numerous physiologically important substances.

Etiology Protein deficiency is occur when there is prolonged febrile illness. It can also be seen in massive burns, large chronic ulcer, persistent vomiting and diarrhea. Stress, chronic infections like urinary tract infection, tuberculosis and parasitic infection also leads to protein deficiency. Disease like hyperthyroidism and hypermetabolic state which interfere with utilization can also leads to protein deficiency.

Clinical Features It occurs between the ages of 1 and 3 years in children. Symptoms: There is loss of weight and subcutaneous fats, wasting of muscles, pigmented changes in skin with hair loss, hypotension, weakness, anemia and edema (Fig. 32.1). In severe cases, there is edema, episodes of diarrhea, skin pigmentation, liver enlargement and poor resistance to infection. Kwashiorkor is distinguished from marasmus by the presence of edema and the relatively less severe degree of body wasting.

Oral Manifestations Bright reddening of tongue with loss of papillae occurs. In kwashiorkor patient may have edema of tongue and may develop scalloping around the lateral margins due to indentation of the teeth. Papillary atrophy may be present and dorsum of the tongue assumes an erythematous and smooth appearance. There is bilateral angular cheilosis, fissuring of lip. Loss of circumoral pigmentation also occurs. Mouth becomes dry. However there is reduced carried activity due to lack of substrate carbohydrate. Epithelium easily becomes detached from underlying tissue, leaving raw bleeding surface. Decreased overall growth of jaws, delayed eruption, retarded growth of incisors and molars. The gingiva and periodontal ligament membrane exhibit varying degrees of degeneration. Deciduous teeth of children may exhibits linear hypoplasia of the teeth.

Laboratory Findings It may cause mild anemia which is normocytic and normochromic. The reticulocyte count is normal and the bone marrow tends to become hypocellular.

Management A nutritious, well-balanced diet with lots of fresh fruits and vegetables, grains, and protein will reduce the risk of malnutrition. Points to Remember Marasmus, kwashiorkor disease, prolonged febrile illness, loss of weight, diarrhea, bright reddening of tongue, papillary atrophy, bilateral angular cheilosis, fissuring of lip, delayed eruption, mild anemia, nutritious and well-balanced diet.

Amyloidosis It is also called amyloid disease. It is deposition of extracellular proteinaceous substance called amyloid. The term amyloid comes as it resembles starch (amyl-starch, oid-resembling).

Forms of Amyloid Figure 32.1 Sparse hair in patient with marasmus

Type A (secondary) amyloid is a fibrillar protein of unknown origin that is seen in prolonged inflammatory

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disease, genetic disease and syndromes such as familial Mediterranean fever. Type B (primary) amyloid is thought to be immunologic in origin because of sequence homology with the NH2 terminal end of immunoglobulin light chain. It is commonly seen in patient with multiple myeloma and macroglobulinemia. Type C: It includes amyloid of aging, localized nonspecific amyloid and pheochromocytomas. Types Localized or organ limited amyloidosis Systemic amyloidosis • Primary amyloidosis • Amyloidosis associated with multiple myeloma • Secondary amyloidosis • Familial or heredofamilial amyloidosis • Hormone related amyloid • Hemodialysis associated amyloidosis.

Types Localized or organ limited amyloidosis: It is characterized by small localized deposits of amyloid in the skin, bladder and respiratory tract. Systemic amyloidosis it can occur in various form. They are as follows: ∙ Primary amyloidosis: There is no evidence of preceding or existing disease. ∙ Amyloidosis associated with multiple myeloma. ∙ Secondary amyloidosis: Associated with variety of chronic inflammatory disease. ∙ Familial or heredofamilial amyloidosis: It is rare condition such as familial Mediterranean form or familial amyloidosis with polyneuropathy. ∙ Hormone related amyloid: It is associated with tumors of endocrine cells which secretes peptide hormones. ∙ Hemodialysis associated amyloidosis: Patient who has undergo long term renal dialysis are susceptible to amyloidosis.

Etiology It is caused by collagen diseases like rheumatoid arthritis, chronic infections like tuberculosis, osteomyelitis, regional enteritis and ulcerative colitis and malignant diseases like multiple myeloma, Hodgkin’s lymphoma and renal cell carcinoma.

Clinical Features It commonly affected organs are kidneys, heart, GI tract, liver, respiratory tract, skin, eyes, adrenals, nerves and spleen. There may be primary localized collection of amyloid. Symptoms: The general symptoms are fatigue, weakness, ankle edema, dyspnea, paresthesia, orthostatic hypotension and weight loss. Purpuric spots caused by hemorrhage resulting form amyloid deposits in the blood vessels. Sign: Superficial waxy lesion occurs on the eyelids, nasolabial folds, neck, axilla or perineum and they may bleed on pressure. Congestive cardiac failure is a common problem due to amyloid deposits on myocardium. There is hepatomegaly, malabsorption or colitis may develop.

Oral Manifestations Fibrous glycoproteins are deposited in submucosa as well as in deeper muscular layer of tongue. Skin lesion may diffusely involve the face or may present as small elevated yellow nodules. Symptoms: There are difficulties in chewing, swallowing or talking. The speech difficulties is due paresis of the vocal cord resulting from deposit of amyloid in the upper third of larynx. Sign: Amyloid deposition of tongue will result in macroglossia of tongue. It is seen in both primary and secondary form. Tongue is enlarged and studded with small garnet colored enlargements along with nodes of cheeks and lips. Mobility of the tongue is decreased. Yellowish nodules are present along the lateral border of the tongue and impression from the teeth is also visible. The gingiva may be infiltrated and may be bluish, spongy and hypertrophied. Xerostomia may result from salivary gland involvement.

Histopathological Features There is extracellular deposition in the submucosal connective tissue of amorphous eosinophilic material in the gingiva. This material present is arranged in perivascular orientation or diffusely. Congo red stain should be used for staining which has got affinity for the abnormal protein. In this staining amyloid occur red (Fig. 32.2).

Nutrition and Oral Cavity

Classification ∙ ∙ ∙ ∙ ∙ ∙ ∙ ∙

Erythropoietic porphyria—there is excessive abnormal porphyrins formation in developing erythrocytes. It is localized to bone marrow. Uroporphyria Protoporphyria Hepatic porphyria—in it liver is the site of excessive porphyrin formation. Acute intermittent porphyria Porphyria variegate Porphyria cutaneous tarda Hereditary coproporphyria.

Clinical Features It is transmitted as non-sex linked recessive character and both sexes are equally affected. Figure 32.2 Amyloid deposit seen in histopathological

section of tongue

Diagnosis Scintiscanning with Tc99m to localized soft tissue deposits. Congo red is used to diagnose amyloid which shows birefringence and dichroism.

Management You can treat amyloidosis by alkylating agents like melphalan. Combination therapy using melphalan, prednisone and fluoxymesterone reported significant improvement. Renal transplantation may be indicated. Points to Remember Amyloid disease, caused by collagen diseases, fatigue, ankle edema, purpuric spots, congestive cardiac failure, superficial waxy lesion, macroglossia of tongue, yellowish nodules, infiltrated bluish gingiva, xerostomia, amorphous eosinophilic material, perivascular orientation, Congo red stain, melphalan, prednisone, renal transplantation.

Symptoms: The first sign is excretion of red urine containing uroporphyrin which may be noted at birth or apparent at first two years after birth. Excessive deposition of the excess porphyrin in the skin lead to photosensitivity. It is absent in the neonatal period but may become apparent during first few years after it becomes exposed to sunlight. Signs: Vesicular and bullous eruption appears on face, back and hand, i.e. exposed parts. Vesicle contains a serous fluid which exhibits red fluorescence. Ruptured vesicle heals slowly and leaves depressed pigmented scars. There is often coexisting anemia. In this disease there is abdominal crisis and psychological or metal symptoms. There is demyelination of nerve fibers.

Oral Manifestations The porphyrin has an affinity for calcium phosphate and due to this, deposition of porphyrin occur in dentine. Deciduous and permanent teeth show red or brownish discoloration which under ultraviolet light exhibits red fluorescence due to incorporation of porphyrins during development. Bullous, erosive lesions of oral mucosa may be present. There is also atrophic cheilitis, advanced periodontal diseases.

Porphyria

Histopathological Features

It is a group of disorders in which there is defective metabolism of pyrrole compound. There is excessive concentrations of porhyrins exposed to day-light generate free radicals, leading to cell membrane damage and cell death.

There is subepidermal blister with minimal cell-poor dermal inflammatory infiltrate.

Management About 1 percent of acute attacks of porphyria may be fatal.

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For severe pain, opiates are safe—that is, nonporphyrogenic. Pethidine, morphine, or diamorphine can be given. Chlorpromazine may be helpful to promote relaxation and sleep. Points to Remember Pyrrole compound, excretion of red urine, photosensitivity, vesicular bullous eruption on face, back, red fluorescence, demyelination of nerve fibers, red or brownish discoloration of teeth, bullous, erosive lesions of oral mucosa, atrophic cheilitis, cell-poor dermal inflammatory infiltrate, opiates and chlorpromazine.

DISTURBANCES IN LIPID METABOLISM Lipids are a heterogeneous group of organic compounds which are relatively insoluble in water but, soluble in solvent such as ether, chloroform and benzene. Types of Lipid • Simple lipids • Compound lipids • Derived lipids.

so now this condition is designated as Langerhans cell histiocytes. Langerhans cells are dentritic mononuclear cells normally found epidermis, mucosa, lymph nodes and bone marrow. It is of three types: – Hand-Schuller-Christian disease (disseminated histiocytosis X): Disease involving bone, skin and viscera. – Eosinophilic granuloma of bone (chronic localized histiocytosis X): Solitary or multiple bone lesion without visceral involvement. – Letterer Siwe disease (acute disseminated histocytosis X): Disease with prominent cutaneous, visceral, bone marrow involvement seen in infants. ∙ Lipid reticuloendothelioses: It is disturbance in sphingomyelin and glucosyl ceramide metabolism. Affected person lack certain enzyme which is required for processing of specific lipids, this in turn results in accumulation of the lipids within the cells. ∙ Gaucher’s disease ∙ Niemann-Pick disease ∙ Tay Sachs disease.

Hand-Schuller-Christian Disease

Types of Lipid

It is also called multifocal eosinophilic granuloma ‘chronic disseminated histiocytosis X or xanthomatosis. It is characterized by widespread skeletal and extraskeletal lesions and chronic clinical course. It is result of error in the metabolism of cholesterol and its esters.

∙

Clinical Features

∙ ∙ ∙

Simple lipids: They are esters of fatty acids with various alcohols, i.e. natural fats and waxes. Compound lipids: They are esters of fatty acids containing groups other than and in addition to an alcohol and fatty acids. Derived lipids: They are derivatives obtained by hydrolysis of the simple and compound lipids, which still posses the general characteristics of lipids. Miscellaneous: It includes carotenoids, vitamin E and K.

Classification Histiocytosis X: It is also called non-lipid reticuloendothelioses, idiopathic histocytosis and Langerhans cell disease. It is a inflammatory reticuloendothelioma condition with evidence suggesting that it may be reaction to some type of infection. There is pathological accumulation of histiocytes and eosinophilic leukocytes. Nowaday cells present in the lesion is identified as Langerhans cells,

It is more common in boys than girls 2:1. Occur in early life usually before age of fifteen.

Classic Triad ∙

Single or multiple areas of punched out bone destruction in skull. ∙ Unilateral or bilateral exophthalmos. ∙ Diabetes insipidus. Otitis media and skin may sometime exhibit papular or nodular lesion. Course is chronic with numerous remissions and exacerbation.

Oral Manifestations There is involvement of facial bone which is commonly associated with soft tissue swelling and tenderness causing facial asymmetry. Sore mouth with or without ulcerative lesion, halitosis, gingivitis and suppuration is present.

Nutrition and Oral Cavity

An unpleasant taste, loose and sore teeth with precocious exfoliation and failure of healing of tooth socket following extraction. Loss of supporting alveolar bone mimics advanced periodontal disease.

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Histopathological Features Proliferative histiocytic phase: Accumulation of collection of leukocytes (eosinophilic) scattered throughout the sheets of histiocytes. Vascular granulomatous phase: Persistence of histiocytes and eosinophils sometimes with aggregation of lipid laden macrophages. Diffuse xanthomatous phase: Abundance of foam cells.

Figure 32.3 Histiocytosis X-ray showing radiolucent lesion in

Fibrous or healing phase: Langerhans cells contain rod shaped cytoplasmic structure called Birbeck granules.

the skull

Laboratory Findings Anemia and less frequently leukopenia and thrombocytopenia occur. Serum cholesterol level is normal but tissue cholesterol level is raised.

Management Prognosis of this disease is good and half of the patients undergo spontaneous remission over a period of a year. It is usually treated by curettage or excision of lesion. The lesions which are inaccessible are treated by irradiation. Some patients may be given drug treatment like prednisolone, vinblastine and cyclophosphamide.

Clinical Features It occurs primarily in older children and young adults and proportion of male to female is 2:1. Skull and mandible are common site but femur, humerus, ribs may be affected. Symptom: There may be local pain which may be dull and steady, swelling and tenderness. General malaise and fever may accompany the eosinophilic granuloma of bone. Signs: Lesion is destructive and well demarcated, roughly round or oval in shape (Fig. 32.3). The area destroyed is replaced by soft tissue. Tissue of early lesion is soft and brown and since there is no necrosis, it is not friable. Later it become fibrous and grayish.

Points to Remember

Oral Manifestations

Multifocal eosinophilic granuloma, triad of single or multiple areas of punched out bone destruction in skull, unilateral or bilateral exophthalmos, and diabetes insipidus, facial asymmetry, ulcerative lesion, halitosis, precocious exfoliation, advanced periodontal disease, proliferative histiocytic phase, vascular granulomatous phase, diffuse xanthomatous phase, fibrous or healing phase, Birbeck granules, anemia, curettage, irradiation.

It may occur in jaws and overlying soft tissues. There is loss of superficial alveolar bone often mimicking juvenile periodontitis. Gingivitis and bleeding gingiva, pain or ulceration is present. Loosening and sloughing of teeth often occurs after destruction of alveolar bone. Sockets fail to heal normally.

Eosinophilic Granuloma This term was introduced by Lichenstein and Jaffe in 1940. It is also called unifocal eosinophilic granuloma. It is the lesion of bone which is primarily histiocytes proliferation with an abundance of eosinophilic leukocytes by no intra or extracellular lipid accumulation.

Histopathological Features Primary cell is histocyte which grows in sheets and sheet like structures. It may coalesce to form multinucleated giant cells. When fibrosis occurs eosinophils may disappear.

Management It is usually treated with curettage and X-ray therapy. Symptoms usually subside within 2 weeks after treatment.

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Local pain, general malaise, fever, destructive lesion, friable tissue, juvenile periodontitis, bleeding gingiva, loosening of teeth, histocyte, multinucleated giant cells, curettage, X-ray therapy.

Letterer Siwe Disease It is an acute fulminating disease, which invariably occurs in infants usually before the age of 3 years.

Clinical Features

Gaucher Disease It is most common of lipid reticuloendothelioses. It has got familial tendency and is thought to be due to faulty metabolism of the lipoid, kerasin. The reticular cells and histiocytes are increased in number and many of them become infiltrated with kerasin. It is autosomal recessive. In this disease there is lack of glucocerebrosidase which results in accumulation of glycosylceramide within the lysosomes of cells of macrophage and monocytes lineage.

It is fulminating condition that most often occurs in infants younger than 1 year of age. Symptoms: Initial manifestation is skin rash involving trunk, scalp and extremities. Rash may be erythematous, purpuric and ecchymotic, some time with ulceration. Patient may have persistent low grade spiking fever with malaise and irritability. Signs: Splenomegaly, hepatomegaly and lymphadenopathy is common. Nodular and diffuse involvement of visceral organs particularly in lung and GI tract. Soft tissue and bony granulomatous reaction, hemorrhage, anemia, failure to thrive.

Oral Manifestations Enlargement of the gingival tissue occurs. There may be presence of ulcer on the oral mucosa. Diffuse destruction of bone of maxilla and mandible which may result in loosening and premature loss of teeth.

Histopathological Features Same as others but without foam cells and no fibrosis occurs.

Laboratory Findings Progressive anemia is often present as well as leukopenia or thrombocytopenia.

Types • Type I (chronic non-neuropathic) • Type II (acute neuropathic) • Type III (subacute neuropathic).

Types ∙ ∙ ∙

Type I (chronic non-neuropathic): There is no cerebral involvement. Type II (acute neuropathic): It is characterized by hepatosplenomegaly and central nervous system disorders. Type III (subacute neuropathic): It resembles type II but later onset and more protracted clinical course.

Clinical Features It is mostly seen in adults and progress is slow. Signs: There is enlargement of the lymph nodes, spleen and to a lesser extent the liver. There is hepatosplenomegaly, CNS involvement. Symptoms: There may be bone pain due to changes in bone marrow. There is often bleeding from the nose or form the gums. Teeth extraction from the affected area may result in bleeding complication.

Points to Remember

Pingueculae: The skin is sometimes pigmented and the conjunctival fibrous tissue may be thickened and of brownish discoloration, a condition known as ‘pingueculae’. Erlenmeyer flask deformities are seen in long bone which is characteristic features of disease.

Erythematous purpuric rash, spiking fever, splenomegaly, hepatomegaly, gingival enlargement, diffuse destruction of bone of maxilla and mandible, progressive anemia, poor prognosis.

Oral features: There is ill defined radiolucency which can be seen in mandible without causing devitalization of the teeth. Lamina dura is intact in this case. There is also decrease salivary flow.

Management It has got very poor prognosis and it usually terminates fatally in short period of time.

Nutrition and Oral Cavity

Histopathological Features

Clinical Features

Examination of biopsy of spleen and liver show typical Gaucher cells (Fig. 32.4) which is round pale cell, containing a small eccentric nucleus and wrinkled or crumpled silk cytoplasm. When the bone is involved the bone marrow shows numerous large foamy, slightly granular cells with small round pyknotic nuclei, which are Gaucher cells.

It involves lungs, liver and the nervous system. There is hepatosplenomegaly, retarded physical and mental growth and severe neurological disturbance.

Management The prognosis of malignant infantile form is very poor; the disease results in death usually within the first year. Administration of purified macrophage targeted glucocerebrosidase, an enzyme replacement therapy can exhibits improvement in anemia, in plasma glucocerebrosidase level and decrease in hepatosplenomegaly. Points to Remember Lymph nodes enlargement, bone pain, Pingueculae, Erlenmeyer flask deformities, ill defined radiolucency in mandible, Gaucher cells, wrinkled or crumpled silk cytoplasm, purified macrophage targeted glucocerebrosidase.

Niemann-Pick Disease It is also called sphingomyelin lipidosis. It is characterized by an abnormal storage of phospholipids due to lack of sphingomyelinase. It is present in four forms, i.e. type A, B, C and D. Type A and B caused by deficiency of acid sphingomyelinase and type C and D occur due to mutation of NPC-1 gene involved with cholesterol processing.

Histopathological Features There is presence of foam cells, usually an enlarged reticuloendothelial cell whose cytoplasm contains numerous droplets like inclusion of lipid. Characteristic sea blue histiocytes in bone marrow aspiration.

Management It is only symptomatic to control infection. Death usually occurs within 3 years of age. Enzyme replacement therapy and organ transplantation is carried also carried out. Points to Remember Sphingomyelin lipidosis, hepatosplenomegaly, severe neurological disturbance, foam cells, sea blue histiocytes, enzyme replacement therapy, organ transplantation.

Tay Sachs Disease It is caused by lack of hexosaminidase A. It results in accumulation of ganglioside within lysosomes of neurons.

Clinical Features It may be mild or severe in nature. In severe form neuronal degeneration will occur. There is also blindness, intractable seizures.

Histopathological Features They are same as seen in other lipid reticuloendothelioses.

Management Genetic counseling results in marked decrease in affected patient in last 3 decades. Points to Remember Lack of hexosaminidase, neuronal blindness, genetic counseling.

degeneration,

DISTURBANCES IN CARBOHYDRATE METABOLISM Hurler’s Syndrome Figure 32.4 Gaucher cells

It is disturbance of mucopolysaccharide metabolism, which is characterized by elevated mucopolysaccharide

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excretion ratio and an excessive intracellular accumulation of chondroitin sulfate B and heparin sulfate in those tissue and organ where they are normally found. It is inherited as an autosomal recessive trait.

Clinical Features Age: It usually becomes apparent within first two years of life, progresses during early child hood and adolescence and terminates in death before puberty. Facial features: Head is large, prominent forehead, broad saddle nose and wide nostrils, hypertelorism and puffy eyelids with coarse bushy eyebrows (Fig. 32.5). There is also nasal congestion and noisy breathing. There is progressive corneal clouding, hepatosplenomegaly resulting in protuberance of abdomen. A short neck and spinal abnormalities are typical, while flexion contractures result in the claw hand (Fig. 32.6).

Oral Manifestations

Figure 32.6 Claw hand in Hurler syndrome

body including liver, spleen, reticuloendothelial system, nervous system, cartilage, bone and heart. Abnormal deposits are found in many sites with involved fibroblasts assuming the appearance of clear (gargoyle) cells.

Shortening and broadening of mandible with prominent gonions and wide intergonial distance. There is typical spacing of teeth. Teeth are small and misshapen. There may be gingival hyperplasia, thick lip, large tongue, and open mouth.

There is elevated level of mucopolysaccharides in the urine.

Histopathological Features

Management

There is excessive accumulation of intracellular mucopolysaccharides in many tissues and organs throughout the

Death usually occurs before the age of ten due to pneumonia and cardiac failure.

Laboratory Finding

Points to Remember Prominent forehead, broad saddle nose, corneal clouding, hepatosplenomegaly, claw hand, spacing of teeth, prominent gonions, intracellular mucopolysaccharides, gargoyle cells, death due to pneumonia.

Lipoid Proteinosis It is discussed in skin disorders.

Hereditary Fructose Intolerance It is transmitted as autosomal recessive trait. It results from a deficiency in fructose 1-phosphate aldolase.

Clinical Features

Figure 32.5 Hurler syndrome

It is manifested by hypoglycemia and vomiting after ingestion of fructose containing foods. Affected individuals rapidly acquire an intense aversion to all sweets and fruits.

Nutrition and Oral Cavity

Oral Manifestations There are fewer incidences of caries in these individuals. Points to Remember Deficiency in fructose 1-phosphate aldolase, hypoglycemia, vomiting, fewer caries.

Hypoglycemia It is a subnormal blood glucose level.

Causes It may be caused by delayed meal, inadequate total caloric intake, unusual physical exertion, insulin overdose, and oral hypoglycemic agents.

Clinical Features Symptoms: Sudden onset of hunger, sweating, shakiness, tremor, anxiety, restlessness, faintness, weakness, nausea, palpitations. Progression to mental confusion, bizarre behavior, personality change, reduced level of consciousness, loss of consciousness, seizures. Signs: Pulse rapid, blood pressure may be elevated and moderate hypothermia may be present due to sweating, hyperventilation and vasodilatation. Bizarre or aggressive behavior may be present, staggering gait, may appear drunk, cold, clammy skin.

Laboratory Findings Blood glucose reduced.

Management Glucagons consult physician, ensure that the airway is patent and protected and that ventilation is adequate in the patient with a reduced level of consciousness. Points to Remember Hunger, shakiness, faintness, rapid pulse, elevated blood pressure, staggering gait, reduced blood glucose.

Mucopolysaccharidosis It is heterogeneous group of metabolism which are inherited as autosomal recessive fashion. It is cause by lack normal enzymes needed to process important intercellular substance called glycosaminoglycans which used to known as mucopolysaccharidosis.

Different Types of Glycosaminoglycans • • • •

Heparan sulfate Dermatan sulfate Keratin sulfate Chondroitin sulfate.

Clinical Features Sign and symptoms: Most types of mucopolysaccharidosis syndrome show mental retardation, heavy brow ridges and stiff joint. Cloudy degeneration of corneas which can lead to blindness is also seen in many syndromes. Oral features: There is macroglossia, gingival hyperplasia. There is also thin enamel with pointed cusps on posterior teeth. Syndrome associated: There are various syndrome associated with mucopolysaccharidosis. These are Hurler, Scheie, Hunter, Sanfilippo-A, Sanfilippo-B, Morquio-B, Morquio-A, Maroteaux-Lamy.

Management Life of patient may be increase by allogenic bone marrow transplantation. Enzyme replacement therapy is also available nowaday.

DISTURBANCES IN MINERAL METABOLISM Acrodermatitis Enteropathica It is also called zinc deficiency. Rare disease of infancy and childhood, transmitted as autosomal recessive character. Since supplements appear to be curative even pathogenesis of the characteristic lesions involves a number of etiologic factors.

Clinical Manifestations Age: It is usually occur in childhood after weaning. The primary signs of the disorder are skin lesion, hair loss, nail changes and diarrhea. Erythematous, pustular, moist erosions of the orofacial areas occur as an early manifestation. In fully developed conditions the buttocks, elbows, fingers and toes are affected by vesiculo-bullous rash similar to that affecting the orofacial region. Retarded body growth and mental changes also occur with some frequency.

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Oral Manifestations

Clinical Features

Site: The buccal mucosa, palate, gingiva and tonsils. Large number of children suffer from candidiasis. The perioral area usually being affected resulting in weeping erosions, angular fissuring and spreading dermatitis. There may be numerous small whitish papillomas on the buccal mucosa and borders of the tongue. The oral changes some time described as stomatitis, glossitis and stomatitis producing thrush like picture. Buccal mucosa is present with red and white spots, erosions, ulcers and desquamation. Lesion on the tongue is some time papillated and halitosis is often severe.

Perinatal type: Death in this patient occur due to respiratory failure. There is also marked hypocalcification of the skeletal structure.

Management 220 mg of zinc sulfate three times daily produces remarkable improvement. Points to Remember Zinc deficiency, hair loss, erythematous erosions of orofacial areas, vesiculobullous rash, candidosis, weeping erosions in perioral area, stomatitis, glossitis, stomatitis producing thrush like picture, zinc sulfate.

Hypophosphatasia It is a hereditary disease transmitted as a recessive autosomal characteristic. There is deficiency of serum alkaline phosphate. It resembles rickets. There is low level of serum alkaline phosphatase activity and elevated urinary excretion of phosphorylethanolamine which result in formation of defective bone matrix.

Infantile form: Severe hypocalcemia, bone abnormalities and failure to thrive manifest the infantile form. Patient may complaint of vomiting and hypotonia. Most of the cases are lethal. Deformities of rib lead to pneumonia. Skull defect can leads to increase intracranial pressure. Juvenile form: Hypophosphatasia of childhood is characterized by increased infection, growth retardation and rochite like deformities including deformed extremities, costochondral junction enlargement (rochite rosary) and pulmonary gastrointestinal and renal disorders. Adults form: The adult form includes fracture with a prior history of rickets and osseous radiolucency. Skull: Skull suture close early resulting in bulging suture and grayal marking on internal surface of skull and brachycephalic shape.

Oral Manifestations There is almost total lack of cementum and normally attached periodontal fiber leading to poor support and premature loss of teeth in deciduous teeth (Fig. 32.7). There is also delayed eruption of permanent teeth. Teeth may be hypoplastic. The pulp chamber and root canal are sometimes larger than normal. The roots either fails to develop fully or undergo early resorption of the apices.

Types • • • •

Perinatal Infantile type Juvenile or childhood type Adult type.

Types ∙ ∙ ∙ ∙

Perinatal: It is present at birth and infant rarely survives for more than few hours. Infantile type: They appear normal until 6 months of age then there is sign of failure to grow. Juvenile or childhood type: It appear late and there is wide range of clinical manifestation. Adult type: It very mild type.

Figure 32.7 Hypophosphatasia with intraoral manifestation

Nutrition and Oral Cavity

The alveolar bone which support the teeth fail to develop normally which result in premature loss of primary teeth. There is inflammation of the gingiva.

level and occasional tetany. This disturbance in calcium metabolism may result in osteoporosis and other skeletal anomalies.

Radiographic Features

Symptom: It usually begins with intestinal disturbances including diarrhea, constipation and flatulence. Nervous irritability, numbness and tingling of the extremities occur; malaise and generalized weakness are also common.

Radiographic features are seen in infantile forms are reduce degree of ossification with preponderance of hypomineralized osteoid. In case of juvenile form skull has got beaten copper appearance which shows uniform, poorly defined small radiolucency. This pattern occurs as there is thinning of inner cortical plate due to cerebral gyri.

Histopathological Features There is abundant production of poorly mineralized osteoid. There may be increase amount of woven bone, which is of less mature in nature than a osseous tissue. Exfoliated teeth show absence of cementum on the root.

Management Treatment is usually symptomatic as root cause of this condition cannot be treated. Prosthetic appliance are indicated to replace the missing teeth. Points to Remember Hypocalcification of the skeletal structure, severe hypocalcemia, hypotonia, rochite like deformities (rochite rosary), skull suture close early, grayal marking, premature loss of teeth in deciduous teeth, hypoplastic teeth, inflammation of the gingiva, reduce degree of ossification, beaten copper appearance, poorly mineralized osteoid, woven bone.

MISCELLANEOUS DISORDERS Malabsorption Syndrome It is also called sprue, idiopathic steatorrhea, celiac disease. It includes conditions causing poor digestion or absorption to a variable degree of a number of nutrients, fats, proteins, carbohydrates, vitamins, minerals and water. The defective absorption may be due to defective digestive or defective intestinal absorption.

Clinical Manifestations Excessive amounts of fat are passed in stools, inducing a concomitant excessive loss of calcium which in turn causes calcium deficiency with ensuing low blood calcium

Sign: The skin changes include irregular brownish pigmentation particularly on the face, neck, arms and legs and drying of skin with scaly eruptions.

Oral Manifestations There may be severe glossitis with atrophy of filiform papilla, although the fungiform papillae persist for some time on the atrophic surface. Painful burning sensation of the tongue and oral mucosa are common. There are small projections which are pink or red in color and the erythematous swelling and palatal lesions appear as multiple aphthous ulcers.

Management Administration of vitamin B12 and folic acid is done. Diet must be carefully supervised and supplemented with vitamins and minerals. Points to Remember Sprue, occasional tetany, osteoporosis, diarrhea, constipation, brownish pigmentation of skin, severe glossitis, atrophy of filiform papilla, burning sensation of the tongue, aphthous ulcers, vitamin B12.

Disorders of Vitamins Vitamins are organic substances in food which are required in small amounts but which cannot be synthesized in adequate quantities in the body and which are soluble in either fat or water. Vitamins are needed in small quantities to act as a cofactor in a variety of metabolic reactions. Your body needs only small amounts of vitamins. But because what the body manufacture is often not enough, these must be obtained from your diet and from supplements. Vitamins occur in a natural and in a physiologically inactive form and are called provitamins. They become activated only after conversion within the animals. For example, vitamin A exists in plants in the form carotene, which is activated in the liver.

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Small amounts of vitamins can be synthesized endogenously. For example vitamin D is synthesized from a precursor steroid, niacin from tryptophan which is an essential amino acid, vitamin K and biotin by intestinal microflora. Deficiency of vitamins may be primarily due to vitamin deficient diet or secondarily because of disturbances in intestinal absorption, transport in blood, tissue storage or metabolic conversion.

is limited to about 5 mg per day. It is phosphorylated by the liver and kidneys. In tissues, it is found as thiamin pyrophosphate. Thiamin pyrophosphate is a coenzyme for decarboxylation of pyruvate to acetyl coenzyme A. Any excess supply of thiamine is excreted in the urine.

Causes of Vitamin Deficiency

Nervous system: It plays an important role in the normal functioning of the entire nervous system.

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Decreased amount of intake of essential nutrients. Impaired absorption from the alimentary tract. Increased metabolism due to rapid growth. Inadequate storage, fever and pregnancy.

Water Soluble Vitamins Water-soluble vitamins are found in yeast, grain, rice, vegetables, fish and meat. They are essential coenzymes required in energy releasing mechanisms and in hemopoiesis. They also act as co-enzymes for metabolism of proteins, carbohydrates and fats.

B-complex Vitamins Most of B-complex occurs in nature in the bound form within the cells of vegetables or animal tissues. The digestion for the liberation of vitamins and its absorption is a result of breakdown of cellular structures in the gut. Vitamin B-complex is not stored in appreciable amounts in the body tissues except vitamin B12. Excretion of vitamins occurs in the kidney. The oral signs of deficiency of vitamin-B occur in the oral tissues like tongue, mucous membrane and gingiva. It may result in dermatitis, stomatitis and gastritis and blood and bone marrow disorders. Degenerative changes of brain and nerves are also a characteristic feature of deficiency since nerve tissue depends on glucose. In hemopoiesis, vitamin B12 and folate are essential for maturation of red cell precursors.

Thiamine (Vitamin B1) It is a vitamin for calm nerves. It is also known as aneurin. It was discovered by Eijkman in 1897. It is a colorless basic organic compound composed of a sulfated pyrimidine ring.

Absorption and Excretion It is readily absorbed from both small and large intestine. The capacity of the human intestine to absorb this vitamin

Functions in the Body Growth: It promotes growth, protects heart muscle and stimulates brain action.

Digestion: It aids in digestion especially that of carbohydrates. Diuretic: It is a mild diuretic and it increases urine formation. GIT: It improves peristalsis and helps prevent constipation. Blood cells: It maintain the normal blood count and improves circulation. Others: It also reduces fatigue, increases stamina, prevent premature aging and senility by increasing mental alertness and promotes a healthy skin.

Deficiency Symptoms Nervous disorders: When cells cannot metabolize glucose aerobically, it affects the nervous system first since it depends entirely on glucose for its energy requirements. There is mental depression, nervous exhaustion and insomnia. Digestive symptoms: It occurs due to defective hydrochloric acid production in the stomach. Patient complains of loss of appetite, poor digestion, chronic constipation and loss of weight. Heart: There is accumulation of pyruvic acid and lactic acid derived from it, which produces vasodilatation and increases cardiac output. The heart muscle becomes lazy and fatigued and the auricles or the upper chambers of the heart lose their strength and it gradually enlarges. It may lead to a condition known as hypertrophy of the heart. Beriberi: Prolonged gross deficiency can cause beriberi. There are three types of beriberi: ∙ Wet beriberi ∙ Dry beriberi ∙ Infantile beriberi – Other diseases, which can be associated are

Nutrition and Oral Cavity

∙ ∙ ∙

Wernicke’s encephalopathy Peripheral neuritis Korsakoff’s psychosis Types of Deficiency of Thiamine • • • • • •

Wet beriberi Dry beriberi Infantile beriberi Wernicke’s encephalopathy Peripheral neuritis Korsakoff’s psychosis.

Beriberi

Management Thiamine 50 mg IM for 3 days then 10 mg 3 times daily by oral route.

Dry Beriberi Clinical Features It is a peripheral neuropathy. In long standing cases, there is degeneration and demyelination of both sensory and motor nerve fibers resulting in severe wasting of muscles. Blood pyruvate levels are normal.

Oral Manifestations

Wet Beriberi

There is hypersensitivity of oral mucosa. Pain in the tongue, teeth, jaws and face.

It is marked by cardiac dilation with four chamber enlargement, pallor and flabbiness of myocardium.

Wernicke’s Encephalopathy

Others: It is often precipitated by infection, pregnancy and lactation.

It is commonly seen in alcoholics with persistent vomiting. There is a classical triad of ocular abnormalities, ataxia and confusion. There are facial symmetrical areas of grayish discoloration. There is also bilateral symmetrical ophthalmoplegia and ataxia. Histologically, there is hypertrophy and hyperplasia of small blood vessels. Injection of thiamine should be given. 50 mg by slow intravenous injection followed by 50 mg daily by oral route for a week.

Pathogenesis

Korsakoff’s Psychosis

Deficiency of thiamine, incomplete metabolism of glucose, accumulation of pyruvic acid and lactic acid in tissue and body fluid, dilation of peripheral blood vessels, fluid may leak out through capillaries, producing edema, high cardiac output, heart dilation.

In it, there is a predominant abnormality in mental function which is memory defect. There is profound impairment of memory recall and new learning ability.

Etiology Diet: It is caused due to eating diets in which calories are derived from polished rice. Alcoholics: It is commonly seen in chronic alcoholics due to their poor nutrition in general and also because alcohol interferes with intestinal absorption of thiamine.

Clinical Features Symptoms: Pain in legs after walking due to accumulation of lactic acid. Cardiac signs: There is tachycardia and increased blood pressure, cardiomegaly, increased JVP and palpitations. There is also presence of sinus tachycardia and inverted T waves. Skin is warm due to vasodilation. Edema may develop rapidly to involve leg, face and trunk.

Histopathological Features There is interstitial myocardial edema, swelling of the myofibrils.

Points to Remember Pain in legs, tachycardia, increased blood pressure, swelling of the myofibrils, peripheral neuropathy, hypersensitivity of oral mucosa, ocular abnormalities, ataxia and confusion, impairment of memory recall, hyperplasia of small blood vessels.

Riboflavin (Vitamin B2) It is also called the beauty vitamin. It is a yellowish green fluorescent compound soluble in water. The word riboflavin is derived from two sources ribose, referring to ribose sugar found in several vitamins and enzymes and flavin meaning yellow. It is an essential component of coenzyme flavin mononucleotide and flavin adenine dinucleotide, involved mainly in a wide variety of oxidation-reduction reactions.

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It is stable to boiling in an acidic solution. It is decomposed by heat. It is also destroyed by ultraviolet light. 814

Absorption and Excretion It is readily absorbed from the intestinal tract and is phosphorylated in the wall of the intestine. It is carried to the tissue of the body and incorporated into the cells enzymes. It is stored in liver, kidneys and heart. Riboflavin is excreted primarily in the urine and bile and sweat are other minor routes of excretion.

Function in the Body It is essential for growth and general health. Metabolism: It is involved in the metabolism of carbohydrates, fats and proteins. It is essential for normal tissue maintenance. Nervous system: It helps in functioning of the nervous system. Digestion: It helps in digestion and prevents constipation. Eyes: It alleviates eye strain and it is helpful in counteracting the tendency toward glaucoma. Others: It promotes a healthy skin, nails hair and strengthens the mucous lining of the mouth, lips and tongue.

Causes of Deficiency It occurs due to inadequate diet and also inadequacy of other essential nutrients including vitamins and proteins. Secondary deficiency: It may occur due to diseases of the intestinal tract. Prolong use of psychological drug that interfere with production of flavin monophosphate. Chronic alcoholism, burns and trauma.

Oral Manifestations Tongue: Glossitis which begins with soreness of lip and lateral margins of the tongue. Filiform papillae become atrophic while fungiform papillae remain normal or become engorged and mushroom shaped giving the tongue a reddened coarsely granular appearance. In severe cases, the tongue becomes glazed and smooth due to complete atrophy of the papillae and exhibits a magenta color. Lip: Lips become red and shiny because of desquamation of epithelium. Paleness of lips and cheilitis which is seen as maceration and fissuring at the angle of the mouth. There is maceration at angle of mouth with pain on the opening mouth, it again results in fissuring and cracking with ulceration. As the disease progresses, angular cheilitis spread to the cheek, the tissues bleed easily and are painful if secondarily infected (Fig. 32.8).

Management Riboflavin 25,000 to 50,000 mcg is given daily in divided doses. Points to Remember Beauty vitamin, scaly gray dermatitis, corneal vasodilatation, photophobia, dull or oily hair, glossitis, lips become red, maceration at angle of mouth.

Niacin (Vitamin B3) It is also known as nicotinic acid. Niacin is required for the formation of coenzyme NAD and NADP, which are important pyridine nucleotides which play an important

Deficiency Symptoms It affects the nasolabial fold and ala of the nose which exhibits a scaly gray dermatitis and consists of enlarged follicles around the side of the nose which is plugged with dry sebaceous material. Ocular changes: It consists of corneal vasodilatation, photophobia and superficial interstitial keratitis. There may be itching and burning of the eyes. Skin and nails: It may also result in dull or oily hair, an oily skin, premature wrinkles on the face and arms and split nails. There is also malfunctioning of adrenal glands, anemia, vaginal itching and cataract.

Figure 32.8 Angular cheilitis in riboflavin deficiency

Nutrition and Oral Cavity

role in redox reactions involving carbohydrate, protein and lipid metabolism. Deficiency of niacin leads to a disease called pellagra which means rough skin. 815

Function in the Body Nervous system: It is important for proper blood circulation and healthy functioning of the nervous system. Gastrointestinal tract: It is essential for the proper metabolism of proteins and carbohydrates. Blood vessels: It dilates the blood vessels and increases the flow of blood to the peripheral capillary system. Hormone: It is essential for the synthesis of sex hormone, estrogen, progesterone and testosterone as well as cortisone, thyroxin and insulin.

Figure 32.9 Dermatitis seen in patient with pellagra

Others: It helps to maintain a normal healthy skin.

Pellagra Causes of Deficiency Tryptophan deficiency: If insufficient tryptophan is available for synthesis of niacin. Diet: Dietary deficiency of niacin. High dietary levels of amino acid lucine antagonize the synthesis of NAD and NADP.

extend through the gastrointestinal tract. Diarrhea is caused by atrophy of gastric epithelium followed by submucosal inflammation which is then followed by ulceration. Nervous system: Delirium is the most common mental disturbance in the acute form and dementia in chronic cases. There is also loss of appetite, irritability and burning sensation in different areas of the body.

Oral Manifestations

Miscellaneous: Chronic alcoholism, diarrhea and carcinoid syndrome.

Entire oral mucosa becomes fiery red and painful and salivation is profuse.

Clinical Features

Tongue: The epithelium of the entire tongue is desquamated. The filiform papillae are most sensitive and disappear first; the fungiform papillae may become enlarged. The tongue becomes red swollen and beefy and in animals the deficiency leads to black tongue. In early stages, only the tip and margins of the tongue are swollen and red. In advanced cases, the tongue losses all the papillae and the reddening becomes intense. In this stage, the tongue becomes so swollen that indentation from the teeth are found along the borders of the tongue. The mouth is sore and shows angular stomatitis, cheilitis.

It can be developed in 3 weeks with prodromal symptoms of loss of appetite, vague gastrointestinal disturbances and numbness or burning in various locations. It is called disease of 3-Ds Dermatitis Diarrhea Dementia Skin: There is an erythema resembling severe sunburns appears symmetrically overall parts of the body exposed to sunlight and especially on the neck (Fig. 32.9). Affected area is well demarcated from the normal. In acute cases, skin lesions may produce vesiculation, cracking, exudation, crusting with ulceration and secondary infection. In chronic cases, dermatitis occurs as roughening and thickening of skin with brown pigmentation. Alimentary tract: Anorexia, nausea, dysphagia. Glossitis precedes the skin lesions. Noninfective inflammation may

Symptoms: Tenderness, pain and ulceration begin at the interdental papillae and spreads rapidly. Superimposed ANUG or Vincent’s infection involving the gingiva, tongue and mucosa is common.

Management Niacin 10 mg or 10,000 mcg per day. Vitamin B complex. Alcohol should be stopped.

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Points to Remember 816

Nicotinic acid, disease of 3-Ds, dermatitis, diarrhea, dementia, red swollen tongue, superimposed ANUG, niacin.

Pantothenic Acid (Vitamin B5) It is water soluble vitamin of the B complex group. It was discovered by Roger Williams in 1933. Tissue extracts from a variety of biological materials provided a growth factor for yeast. This growth factor is identified as pantothenic acid, derived from Greek word pantos meaning everywhere. It is a pale yellow oily liquid which is not crystallized, but its calcium crystallizes readily and this is the form in which it is generally available.

Function in the Body Metabolism: It is a part of enzyme system which play a vital role in the metabolism of carbohydrates, fats and protein and in the synthesis of amino acids and fatty acids. It is also essential for the formation of porphyrins, the pigment portion of the hemoglobin molecule. Stimulation of adrenal gland: It stimulates the adrenal glands and increases production of cortisone and other adrenal hormones. Anti-stress factor: It is primarily used as an anti-stress factor and protects against most physical and mental stress. Combat infection: It increases vitality, wards off infections and speeds recovery from ill health. Central nervous system: It helps in maintaining the normal growth and development of the central nervous system. It prevents premature aging and provides protection against any damage caused by excessive radiation.

Deficiency Symptoms Muscle tissue: Chronic fatigue, muscle cramps, painful and burning feet and muscular weakness. Nervous system: Mental depression, irritability, dizziness and insomnia. Gastrointestinal: It may lead to gastric distress and constipation. Others: Increases tendency toward infection, graying and loss of hair, skin disorders, low blood sugar, low blood pressure and duodenal ulcer.

Management It is given in the dose of 1000 mg daily for 6 weeks. Points to Remember Muscle cramps, mental depression, gastric distress, loss of hair.

Pyridoxine (Vitamin B6) It is an important coenzyme in the intermedullary metabolism of amino acids and complex glycolipids. It is a white crystalline substance soluble in water and alcohol.

Deficiency Symptoms Nervous: Peripheral neuropathy, mental retardation, irritability, mental confusion and nervousness. Blood: Anemia, albuminuria and leukopenia. Skin: Dermatitis and eczema. Others: Kidney stones, inflammation of the colon, damage to the pancreas, loss of muscular control, migraine headache and premature senility.

Oral Manifestation Cheilosis: Cracking at the corner of the lip. Glossitis: Inflammation of the tongue. Others: Angular stomatitis, tooth decay and halitosis.

Management 10 to 50 mg daily in divided doses. Points to Remember Peripheral neuropathy, dermatitis, anemia, kidney stones, cheilosis, glossitis.

Biotin (Vitamin B8) It functions as a coenzyme for four carbohydrates involved in fatty acid and amino acid metabolism. Previously was known as vitamin H.

Function in the Body Metabolism: It is involved in the metabolism of carbohydrates, proteins and fats. Hair: It is essential for the growth and health of the hair. It prevents premature graying of the hair as well as hair loss.

Nutrition and Oral Cavity

Others: It helps maintain the skin and nervous system in a sound condition. It controls proper distribution of color pigments.

Pregnancy: It is an important nutrient for the pregnant women and her developing fetus. Folic acid also improves lactation.

Deficiency Symptoms

Others: It helps in building of antibodies which prevent and heal infection. It also produces nucleic acids, RNA and DNA.

Skin: Scaly dermatitis, eczema, seborrhea and prickling of the skin. Hair: It can cause alopecia and dandruff. Nervous: There is confusion, mental depression and drowsiness. Muscle: There is muscular weakness, extreme fatigue and lassitude. Others: Anemia, lack of appetite, hearing abnormalities and lung infections. Oral: The fleshy part of the tongue may waste away.

Management 20 mcg of biotin taken daily for 10 days IM can heal skin lesions. Oral biotin to be taken in amount of 400 mcg daily for 8 to 12 weeks. Shampoo coating 1 percent biotin can be useful in controlling excessive hair loss. Points to Remember Muscular weakness, alopecia, mental depression, scaly dermatitis.

Deficiency Causes Decreased intake: Inadequate diet, impaired absorption, malabsorption states and intrinsic intestinal diseases. Increased loss: Hemodialysis. Increased requirement: The body demands exceed the intake like in pregnancy, infancy, leukemia, hemolytic anemia. Others: Impaired utilization, diseases of the upper small bowel where folate is mainly absorbed and idiopathic.

Clinical Features Anemia: Deficiency of folic acid cause anemia which often occurs in pregnant women and also children. Skin: Loss of hair, grayish brown skin pigmentation can also occurs. Reproductive disorders: Spontaneous abortions, difficulty during labor and high infant death can also occur. Loss of libido occurs in males. Nervous: Dementia, mental depression and fatigue.

Folic Acid (Vitamin B9)

Oral Manifestations

It is also known as folacin or folate. It is a water-soluble vitamin. It is a yellow crystalline substance sparingly soluble in water and soluble in acid solution. It undergoes fairly rapid destruction when heated in neutral or alkaline substances.

Filiform papillae disappear first and fungiform papillae remain prominent. In severe cases, fungiform papillae are lost and tongue becomes thick, smooth and fiery red. Severe ulcerative stomatitis may be seen. Swelling and redness of lips and lateral margin of the tongue.

Functions in the Body Red blood cell (RBC): Folic acid in combination with vitamin B12 is essential for the formation, maturation and multiplication of red blood cells. Nerve: It is necessary for the growth and division of all body cells, including nerve cells and for manufacturing a number of nerve transmitters. Hair and skin: It is essential for the health of skin and hair and helps to prevent premature graying of hair.

Hematological Findings The blood and bone marrow in megaloblastic anemia due to folate deficiency are similar to those in vitamin B12 deficiency except that the serum and red cell folate levels are low.

Management A daily dose of 5,000 to 10,000 mcg of folic acid is sufficient and a maintenance dose of 5000 mcg once in week is given in cases of megaloblastic anemia.

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Points to Remember 818

Anemia, grayish brown skin pigmentation, spontaneous abortions, dementia, mental depression, filiform papillae disappear, ulcerative stomatitis.

Cyanocobalamin (Vitamin B12) Vitamin B12 is a complex organomatrix compound called cobalamine which is cobalt containing porphyrins. It is freely soluble in water. It is resistant to boiling in neutral solution, but it is liable to destruction in the presence of alkalis and acids.

Functions in the Body Red blood cells: Like vitamin B6 it is essential in the production and regeneration of red blood cells. Nervous: It improves concentration, memory and balance and relieves irritability. Metabolism: It is necessary for proper utilization of fats, carbohydrates and proteins for body building. It is also used in metabolism of folic acid. Others: It promotes growth and increases apatite in children.

Causes of Deficiency Congenital: Congenital deficiency without gastric atrophy. Systemic diseases: Diseases of terminal ileum, i.e. Crohn’s disease. Defective absorption: There is defective absorption of vitamin B12. There is chronic atrophic gastritis with failure of production of intrinsic factor. Smoking: Studies show that smokers have lower levels of vitamin B12 and folic acid than non-smoker. Others: Inadequate diet and intrinsic factor deficiency.

Deficiency Symptoms Deficiency of vitamin B12 leads to megaloblastic anemia or pernicious anemia. However, pernicious anemia is a result of deficiency of intrinsic factor, which is essential for absorption of vitamin B12 and hence a deficiency of vitamin B12. It occurs in 5th to 8th decades of life. It is more common in men than in women. There is generalized weakness, numbness and tingling of the extremities.

Fatigue, headache, dizziness, nausea, vomiting, diarrhea, loss of appetite, pallor and abdominal pain.

Oral Manifestations Tongue: There is sore painful tongue, glossitis and glossodynia. Tongue is inflamed and is beefy red in color. Painful and burning lingual sensation occur. Small shallow ulcers resembling aphthous ulcers on the tongue with atrophy of papillae with a loss of normal muscle tone is called Hunter’s glossitis. Fiery red appearance of tongue due to inflammation and burning sensation. Discomfort in wearing dentures is due to weakened muscular tone.

Histopathological Features There is epithelial atrophy, enlarged basal cell nuclei and increased mitosis in basal epithelium. Epithelial dysplasia and nonspecific infiltration of lymphocytes, plasma cells or polymorphonuclear neutrophils (PMNs) in the lamina propria.

Lab Findings There is decrease in the count of red blood cells. Cells show macrocytosis and poikilocytosis. There is increase in hemoglobin content which is proportional to their increased size. Mean corpuscular hemoglobin concentration (MCHC) is normal. In advanced cases, the red blood cell abnormalities are detected like polychromatophilic cells, stippled cells, nucleated cells, Howell-jolly bodies and Cabot’s ring. Achlorhydria due to absence of gastric hydrochloride secretion and pH of gastric content is usually high.

Bone Marrow Findings Increased no of immature red cells or megaloblasts with a few normoblast. Polymacrocytes or large PMNs with large poly labeled nuclei are found. Megakaryocytes appear normal.

Management Oral: In a dose from 6 to 150 mcg. Taken in these doses it helps in the treatment of lack of concentration, fatigue depression, insomnia, anorexia, poor memory and loss of weight. Parenteral: 1000 mcg of vitamin given twice weekly in cases of anemia.

Nutrition and Oral Cavity

Points to Remember Megaloblastic anemia, pernicious anemia, glossitis, glossodynia, Hunter’s glossitis, epithelial atrophy, increased mitosis, plasma cells, poikilocytosis, macrocytosis, lymphocytes.

Vitamin C It is also called ascorbic acid and antibiotic vitamin. It is a modified simple sugar. It is the most active reducing agent. Its highest concentration is in the pituitary, adenoid, eye and WBCs. Stress and corticotrophin leads to loss of ascorbic acid from the adrenal cortex. It is a powerful antioxidant. It is necessary for normal maintenance of intercellular substances of connective tissue in bone and other tissue of mesenchymal origin.

Functions of Vitamin C Synthesis: It is important in the formation of collagen, chondroitin sulfate and neurotransmitter. Maintenance: It is useful for maintenance of folate pool and mobility and phagocytic activity of neutrophils. It is also necessary for maintenance of bones and proper functioning of the adrenal and thyroid glands.

Pathogenesis There is defective formation of collagen in connective tissues because of failure of hydroxylation of proline to hydroxyproline which is a characteristic amino acid of collagen. There is also increase permeability of capillary (hemorrhage), anemia due to erythropoiesis and defective collagen formation.

Clinical Features Infantile scurvy: Lassitude, anorexia, painful limbs and enlargement of costochondral junction. Folliculosis: Hair follicle rises above skin and there are perifollicular hemorrhages, i.e. tiny points of bleeding occurring around the orifice of hair follicles with heaping of keratin like material. Hemorrhage may occur in the joint, into nerve sheath under the nails or conjunctiva. Petechial hemorrhage occurs in buttocks, abdomen, legs, arms, ankle and nail beds. Scorbutic child usually assumes a frog like position and this may reflect as subperiosteal hemorrhage. There is also epistaxis, anemia and delayed wound healing. Edema of the limbs and face is a frequent finding in severe ascorbic acid deficiency. It may lead to premature aging, thyroid insufficiency and lower resistance to all infections.

Absorption: It enhance the absorption of iron in the body.

Oral Manifestations

Metabolism: Tryptophan, nor-epinephrine and tyrosine metabolism require vitamin C.

It occurs chiefly in gingival and periodontal region. Interdental and marginal gingiva is bright red, swollen, smooth, shiny surface producing an appearance known as scurvy bud (Fig. 32.10). In fully developed scurvy, the gingiva becomes boggy, ulcerated and bleeds easily. These types of gingival lesion are termed as scorbutic gingivitis. Color changes to violaceous red. Typical fetid breath of the patient with fusospirochetal stomatitis. In severe cases, hemorrhage and swelling of periodontal ligament membrane occurs followed by loss of bone and loosening of teeth which are exfoliated.

Others: It promotes healing and protects against all forms of stress.

Deficiency Symptoms Mild deficiency may appear in the form of lassitude fatigue, anorexia, muscular pain and greater susceptibility to infection. A prolonged deficiency may cause scurvy.

Scurvy Prolonged deficiency of vitamin C may result in scurvy. It is characterized by: Weakened blood vessels particularly microvessels having least muscular supports. Defective synthesis of osteoid which is derivative of collagen. Impaired wound healing.

Histopathological Features Osteoblasts fail to form osteoid. Cartilage cells of epiphyseal plate continue to proliferate in normal fashion and salts are deposited in the matrix between the columns of cartilage cells. The calcified matrix material is not destroyed so that wide zone of calcified but non-

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make choline from methionine, an amino acid, with the aid of vitamin B12 and folic acid. Functions: It helps in the transportation of fats in the body and prevents accumulation of fat in the liver. In combination with fatty acid and phosphorus, it stimulates the formation of lecithin, an important constituent of nerve cells in the body. It goes directly into the brain cells to produce a chemical that aids memory.

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Deficiency symptoms: It may cause cirrhosis and fatty degeneration of the liver, high blood pressure and atherosclerosis. Doses: It can be given in doses of 1000 to 2000 mg daily in divided doses. Figure 32.10 Showing oral manifestation in scurvy

Points to Remember ossified matrix, called the scorbutic lattice develops in the metaphysis. As the lattice increases in width a more and more fragile zone develops, so that eventually complete fracture of the spicule occurs with separation and deformity of the cartilage shaft joint.

Laboratory Features Anemia in scurvy is mild to moderate but may be severe. It is usually normocytic and normochromic and associated with leukopenia and thrombocytopenia, reticulocytosis and normoblastic hyperplasia of the bone marrow are other changes.

Management Vitamin C 250 mg 3 times daily can be given. Points to Remember Infantile scurvy, folliculosis, hemorrhage in the joint, frog like position, epistaxis, delayed wound healing, scurvy bud, boggy, ulcerated gingiva, scorbutic gingivitis, scorbutic lattice, anemia, leukopenia, thrombocytopenia.

Choline It is a colorless crystalline compound which absorbs water quickly. It is highly soluble in water and alcohol. It is member of vitamin B group. It is present in foods as well as in the body in relatively large amount. The body can

Cirrhosis, high blood pressure, fatty degeneration of the liver.

Inositol It is a crystalline compound which has sweet taste. It is highly soluble in water and is not destroyed by heat in neutral, acid and alkaline media.

Functions in the Body Transportation: It is essential for transportation of fat in the body. Nourishment: It is important in providing nourishment to the brain cells. Lowering cholesterol level: It helps to lower cholesterol levels. Growth of hair: It also promotes the growth of healthy hair and helps to prevent its falling. Prevent eczema: It helps in preventing eczema. Deficiency symptoms: It can cause alopecia or patchy baldness, gastritis hypertension, fatty infiltration in the liver, hardening of the liver and eczema. Doses: It is given in the dose of 2 g a day for 6 to 10 weeks. Points to Remember Alopecia, patchy baldness, fatty infiltration in the liver.

Nutrition and Oral Cavity

FAT SOLUBLE VITAMINS Common Properties ∙ ∙ ∙ ∙

They are soluble in fat. Bile salts are essential for their absorption. They are generally stored in the liver. They are not excreted in urine.

Vitamin A (Retinol) Carotene is a yellow pigment found in vegetable foods. It is converted into vitamin A in the body. Vitamin A or retinol is found in foods of animal origin, while carotene is provided by foods of both plant and animal origin. Vitamin A is stored in liver. As a concentrated solution retinol is light yellow in color. It solidifies when cooled and has a mild pleasant odor.

Functions in the Body Epithelial tissue: Vitamin A helps in maintaining the integrity of epithelial tissue such as epithelial layer of skin, respiratory mucosa and esophagus and gastrourinary tract. Due to this it builds up resistance to respiratory infection. Structural integrity: Its function in the preservation of the structural integrity and normal permeability of the cell membrane as well as that of membrane of intracellular particles such as lysosomes and mitochondria. Bone and teeth: It accelerates the normal formation of bones and teeth. Vision: Vitamin A also has a specific role on the physiological mechanism of vision. Oxygenation: It also increases permeability of blood capillaries thereby contributing to better tissue oxygenation. Aging and senility: It also prevents premature aging and senility. Synthesis: It is required for synthesis of glucocorticoids and cholesterol. Somatic growth: Vitamin A is required for somatic growth.

Deficiency Symptoms Effect on growth: Failure of growth in young and collagenous tissue is affected. Effect on eyes: Night blindness, dry conjunctiva, Bitot’s spot, corneal xerosis, corneal ulceration or keratomalacia

can occur. Xerophthalmia due to decrease in lacrimal secretion. Keratinizing metaplasia: The epithelial cells fail to differentiate. This means that the cells in the basal layer lose their specificity and tend to form a stratified squamous epithelium with keratin production. Keratinizing metaplasia of epithelial cells is usually evident in several organs such as bladder, vagina and skin and predisposes them to infection. Drying of skin and atrophy of sebaceous glands. Effect on reproductive organs: Degeneration of germinal epithelium thus affecting reproduction causes sterility in males and cornification of vaginal epithelium in females. Effects on bone: Imbalance between osteoblasts (bone forming cells) and osteoclasts (bone resorbing cells) causing aberrations in the shape of bone. Skin disorders: It may result in pimples, acne, boils and premature wrinkles.

Oral Manifestations Teeth: Defective formation of enamel in teeth. Odontogenic epithelium fails to undergo normal histodifferentiation and morphodifferentiation, which results in increased rate of cell proliferation. Therefore epithelial invasion of pulpal tissue is characteristic of vitamin A deficiency. There is also distortion of shapes of the incisors and the molars. Hypoplasia of teeth: Since the enamel forming cells are disturbed, enamel matrix is poorly defined so that calcification is disturbed and enamel hypoplasia results. Dentin: Dentine too is atypical in structure, lacking the normal tubular arrangement and containing vascular and cellular inclusions. Caries: There is increased caries susceptibility. Eruption is delayed. In prolonged deficiency, eruption ceases completely. Alveolar bone is retarded in its rate of formation. Gingival epithelium becomes hyperplastic; in prolonged deficiency it shows keratinization. Tissue is easily invaded by bacteria that may cause periodontal disease and microabscess formation. Major and minor salivary glands undergo typical keratinizing metaplasia.

Management of Deficiency Symptoms Depending upon deficiency symptoms it is given in the dose of 7,500 to 15,000 mcg per day for one month.

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Points to Remember 822

Night blindness, Bitot’s spot, xerophthalmia, keratinizing metaplasia, sterility in males, cornification of vaginal epithelium, aberrations in the shape of bone, pimples, acne, defective formation of enamel, hypoplasia of teeth, increased caries susceptibility, delayed eruption of teeth, hyperplastic gingival epithelium.

Hypervitaminosis A If more than 30,000 mcg of vitamin A is taken daily, it can produce toxic effect in adults if continued for many months. In infants, toxic effect can be produced by the intake of more than 5,550 mcg per day. Toxicity symptoms: Painful joints, thickening of long bones, anorexia, low grade fever, loss of hair, hepatomegaly, blurred vision, rashes, irregular menstruation, fatigue and headache. Acute toxicity: It results from a single massive dose and it manifests as abdominal pain, nausea, vomiting, headache, dizziness and sluggishness. Chronic toxicity: It may occur following ingestion of 12,000 mcg or more daily for prolonged periods. It is characterized by joints pain, hair loss, and dryness and fissuring of lips, loss of appetite, low grade fever and weight loss.

It is very important for the proper formation of teeth and bones. It play important role in prevention of dental caries. It is necessary for the healthy functioning of parathyroid gland, which regulates the calcium levels in the blood.

Pathogenesis Overgrowth: There is overgrowth of epiphyseal cartilage due to inadequate provisional calcification and failure of cartilage cells to form a matrix and disintegrates. Formation of irregular masses: There is persistence of distorted, irregular masses of cartilage many of which projects into the marrow cavity. Deposition: Deposition of osteoid matrix on inadequately mineralized cartilaginous remnants. Disruption: Disruption of the orderly replacement of cartilage by osteoid matrix with enlargement and lateral expansion of osteochondral junctions. Microfracture: There is abnormal growth of capillaries and fibroblasts in the disorganized zone because of microfracture and stresses on inadequately mineralized, weak, poorly formed bone. Deformity: Deforming of skeleton due to loss of structural rigidity of the developing bone.

Vitamin D Deficient Rickets

It is also called sunshine vitamin. Vitamin D (1,25-dihydroxycholecalciferol) is one of the compound that are grouped together as the hydroxylated cholecalciferol. If vitamin D deficiency occurs in children and infants it is called rickets and if it occur in adults it is called osteomalacia. Deficiency of vitamin D tends to cause hypocalcemia.

The word ‘Rickets’ refers to any disorder in vitamin D calcium phosphorous axis which results in hypomineralized bone matrix that is failure of endochondral calcification. It develops in an area where sunlight is deficient. It results from inadequate extracellular level of calcium and inorganic phosphate, mineral necessary for new bone to calcify. Osteoid builds in excessive amounts because it fails to mineralize properly. Rickets occur in infants and children and osteomalacia common in adults.

Forms

Clinical Features

D3: It is present in fish liver oils and animal fats. It is called cholecalciferol.

It occurs in infants and children. In the first six months of life, tetany, convulsions are common manifestations due to hypocalcemia. The wrist and ankles are typically swollen. The changes in bone are found in the epiphyseal plates, metaphysis and the shaft.

Vitamin D

D2: It is obtained artificially by irradiation of ergosterol and called ergocalciferol.

Function in the Body The major function of vitamin D is the maintenance of normal plasma levels of calcium and phosphorous.

Craniotabes: Localized area of thinning are sometimes present in the skull, so that a finger can produce indentation. This condition is called craniotabes. There is softening of

Nutrition and Oral Cavity

posterior part of the parietal bone, which may be first sign of the disease. Patients have a short stature and deformed extremities. Children with rickets show bowing of legs. Excess of osteoid produces frontal bossing and squared appearance to the head. Rickety rosary: Deformation of chest results from over growth cartilage or osteoid tissue at the costochondrial junction producing rickety rosary. Pigeon breast: The weakened metaphyseal areas of the ribs are subject to pull of the respiratory muscles and thus bend inwards creating anterior protrusion of the sternum resulting in a pigeon breast deformity. Harrison grooves: The inward pull at the margins of diaphragm creates Harrison’s grooves, girdling the thoracic cavity at the lower margin of the rib cage. Lumber lordosis: The pelvis may be deformed. When an ambulatory child develops rickets, deformities are likely to affect the spine, pelvis and long bones causing lumbar lordosis.

Oral Manifestations Developmental abnormalities of dentine and enamel, delayed eruption and malalignment of teeth. There is higher caries index in rickets as compared to normal. There may be hypoplasia of enamel; enamel may be mottled, yellow gray in color. There are large pulp chamber, high pulp horns and delayed closure of root apices. The osteoid is so soft that teeth are displaced leading to malocclusion of the teeth.

of adequate calcium resulting in softening and distortion of the skeleton. Symptoms: The majority of patients has bone pain and muscle weakness of varying severity. Signs: There is increased tendency towards fracture, peculiar waddling or penguin gait, tetany and green stick bone fractures.

Oral Manifestations There is incidence of severe periodontitis in some cases of osteomalacia.

Biochemical Changes Elevation of serum alkaline phosphatase to three or more times its normal levels. Serum phosphorus is low due to increased phosphorus excretion in response to reduction of serum calcium. Serum calcium levels are usually on the lower side.

Management of Rickets and Osteomalacia Dietary enrichment of vitamin D in the form of milk. If tetany is present, give calcium gluconate IV. Daily dose between 1000 and 2000 IU of vitamin D combined with 500 to 1000 mg of calcium. Hormonal therapy like flucytosine. Curative treatment includes 2000 to 4000 IU of calcium daily for 6 to 12 weeks followed by a daily maintenance dose of 2000 to 4000 IU for a prolonged period. Patients with osteomalacia due to intestinal malabsorption require a larger dose of vitamin D and calcium, i.e. 40,000 to 1,00,000 IU of vitamin D and 15 to 20 gm of calcium lactate per day.

Points to Remember

Points to Remember

Craniotabes, rickety rosary, pigeon breast, Harrison grooves, lumbar lordosis, delayed eruption, malalignment of teeth, higher caries index, delayed closure of root apices, large pulp chamber, high pulp horns.

Adult rickets, bone pain, muscle weakness, increased tendency towards fracture, penguin gait, tetany, severe periodontitis, elevation of serum alkaline phosphatase.

Osteomalacia

Vitamin D Resistant Rickets (Familial Hypophosphatemia, Refractory Rickets)

It is also known as adult rickets and only flat bones and diaphyses of long bones are affected. It is most commonly seen in postmenopause females with a history of low dietary calcium intake and little exposure to UV light.

It is X-linked trait with some defect in reabsorption of metabolism. It has got clinical features which are characteristic of rickets but it does not respond to therapeutic dose of the vitamin.

Clinical Features

Causes

It is seen in adults and pelvic deformities are commonly seen in females. Remodeling of bone occur in the absence

The disease is now recognized as a specific disorder characterized by hypophosphatemia associated with

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decreased renal tubular reabsorption of inorganic phosphates. Familial occurrence being inherited as X-linked dominant trait. Rickets and osteomalacia which does not respond to usual doses of vitamin D. Diminished intestinal calcium and phosphate absorption. Normal vitamin D metabolism and absence of other related abnormalities.

tones of cartilage which extend down toward the shaft and are separated form one another by collection of capillaries. This zone contains trabeculae made of uncalcified cartilage matrix upon which osteoid is deposited on pre-existing bony trabeculae. There is deposition of globular dentin which often exhibits clefting.

Clinical Features

Management

Age and sex distribution: It is first recognized in children when they are about to walk. Males are usually affected more severely than female.

25-hydroxy cholecalciferol in lower doses is useful than conventional vitamin D. Patient should also be given calcitriol and multiple daily dose of phosphate.

Sign: Slight decrease in height of the patient and reduced growth and rickets like bone changes. The lower limb are shortened and bowed. Symptoms: There is enlarged epiphysis, bone pain, muscle weakness and vertebral fracture. Bony outgrowth at the site of muscular attachment and around joints may limit the movement.

Oral Manifestations Dentin changes: Widespread formation of globular hypocalcified dentin with clefts and tubular defects occurring in the region of pulp horns. Gross reduction in amount and quantity of dentin which results in abnormality wide root canal and large pulp chambers with faulty calcification and marked interglobular space in dentin. Pulp horns are elongated and extend high often reaching the DE junction. Because of this defect there commonly is invasion of the pulp by microorganisms without demonstrable destruction of the tubular matrix. Thus there is often periapical involvement of a grossly normal appearing deciduous or permanent tooth. There the development of multiple gingival fistulae. Tract is frequently present to dentinoenamel junction or even outer enamel surface. This tract remains patent and may result in early pulpal infection developing in abscess or carious lesion. There is formation of abnormal cementum.

Histopathological Features Failure of bone salts to be deposited in the cartilage matrix between the rows of hypertrophic cells so that these cells are not invaded and destroyed by capillaries. The histological feature is characterized by a broad zone between the multiplying cartilage cells and the shaft the so called rachitic metaphysis which is composed of

Points to Remember Refractory rickets, decrease in height of the patient, vertebral fracture, bone pain, globular hypocalcified dentin, wide root canal, large pulp chambers, periapical involvement, multiple gingival fistulae, rachitic metaphysis.

Vitamin E (Tocopherol) It is also called anti-aging factor. The word tocopherol is derived from the word tocos meaning child birth and pheros meaning to bear. It is yellow, oily liquid freely soluble in fat solvents. Tocopherol alpha, beta, gamma, lambda have been obtained from natural sources and their relationship with fertility and prevention of muscular dystrophy have been found. They are not destroyed by heat even at room temperature or above 100°C. They are destroyed by UV light.

Functions in the Body Reproductive function: Protective effect of vitamin E on reproduction and prevention of sterility. All the three layers of embryo ectoderm, mesoderm and endoderm are preserved by vitamin E. Blood flow and clotting mechanism: Vitamin E dilates the capillary and enables the blood to flow freely into the blood deficient muscle tissue thus strengthening both the tissue and the nerves supplying them. It also dissolves the blood clot and also prevents their formation. Electron transport system: It functions as a cofactor in the electron transport system. Healing: It prevents the formation of excessive scar tissue and in some instance even melts away unwanted scar tissue.

Nutrition and Oral Cavity

Prevention: It is required for prevention and storage of creatinine in muscles. It has ability to prevent hepatic necrosis in animals. Prevents vitamin A from destruction and helps in its storage in tissue.

Clotting: It prevents hemorrhage only in cases when there is defective production of prothrombin.

Deficiency Symptoms

Effects of Deficiency

Reproductive: Abortion of fetus in females and atrophy of spermatogenic structures in males leading to permanent sterility.

Prolongation of clotting time and a tendency to bleed profusely. There may be nasal bleeding.

Oxidative phosphorylation: It acts as a cofactor in oxidative phosphorylation associated with lipid.

Oral Manifestations

Muscles: It causes degenerative changes in muscles. There is muscle fiber atrophy which is replaced by connective tissue.

Gingival bleeding can also occur in cases of vitamin K deficiency.

Heart: There is necrosis and fibrosis of heart muscles.

Management

Blood capillaries: Deficiency may lead to degenerative changes in the blood capillaries which in turn lead to heart and lung diseases, pulmonary embolism and brain stroke.

It is given in dose of 10 to 20 mg daily.

Oral Manifestations Loss of pigmentation, atrophic degenerative changes in enamel of vitamin E deficient rats.

Management Vitamin E is given in the doses of 100 to 400 mg daily.

Anti-hemorrhagic vitamin, prolongation of clotting time, tendency to bleed, gingival bleeding. Clinical and oral effects of some vitamins are depicted in Table 32.1.

DISORDERS OF BILIRUBIN

Points to Remember

Jaundice

Abortion of fetus, degenerative changes in muscles, necrosis and fibrosis of heart muscles, pulmonary embolism, brain stroke, loss of pigmentation.

It is condition which is characterized by excess bilirubin in the bloodstream. Bilirubin results in yellowish discoloration of the skin and mucosa.

Vitamin K (Phylloquinone) It is essential for the production of a type of protein called prothrombin and other factors involve in the blood clotting mechanism. Hence it is known as anti-hemorrhagic vitamin. It is not easily destroyed by light, heat or exposure to air. It is destroyed by strong, acids, alkalis and oxidizing agents.

Forms ∙ ∙

Points to Remember

K1: It is the form which occurs in plants. K2: it is produced by most bacteria present in human intestine if not supplied in the diet.

Functions in the Body Synthesis: It is essential for the hepatic synthesis of coagulation factors II, V, VII, IX and X.

Causes Hemolytic anemia or sickle cell anemia: There is increase level bilirubin as red blood cells are being broken down at rapid rate so that liver cannot keep space with processing. Liver dysfunction: There is decrease uptake of bilirubin from the circulation or decrease conjugation of bilirubin in liver cells. Gilbert syndrome: Defects in enzyme system will also lead to impaired processing of bilirubin.

Clinical Features Appearance: Patient exhibits diffuse, uniform, yellowish discoloration for skin and mucosa. As bilirubin has got affinity for elastin fiber, the tissue like sclera, lingual frenum, and soft palate which contain elastin fiber are prominently affected.

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Vitamin

General manifestations of deficiency

Oral manifestations of deficiency

Vitamin A

Night blindness Xerophthalmia characterized by dryness in conjunctiva and cornea Bitot spots in forms of triangular plaques in conjunctiva If xerophthalmia persist, destruction of cornea occurs, causing total blindness. This condition is known as keratomalacia

Keratinizing metaplasia of epithelium resulting in increased keratin formation Occlusion of salivary gland ducts with keratin Enamel hypoplasia, atypical dentin formation and epithelial invasion of pulpal tissue are characteristic features Enamel is more severely effected than dentine

Vitamin D (antirachitic vitamin)

Rickets in children Osteomalacia in adults Pigeon chest is one of important feature of rickets The vitamin, which acts more like a hormone, is vitamin D Renal rickets or renal osteodystrophy is seen in patients with chronic renal failure. Renal rickets is mainly due to decreased synthesis of calcitriol in kidney In rickets the plasma calcitriol is decreased and alkaline phosphatase activity is elevated

Delayed eruption of primary and permanent teeth Malalignment of the teeth in the jaws Developmental anomalies of dentine and enamel The teeth shows wide predentin zone with much interglobular dentine The pulp horns are elongated and extend high, reaching the dentinoenamel junction

Vitamin E (antisterility vitamin)

Decreased male fertility Impaired fetal – maternal vascular relationships Encephalomalacia Nutritional muscular dystrophy

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Vitamin K (coagulation vitamin)

Deficiency is uncommon. Brings about post-translational modification of 2,7,9,10 blood clotting factors, particularly prothrombin. So deficiency results in prolong clotting time

Prothrombin levels below 35% result in gingival bleeding after tooth brushing Spontaneous gingival hemorrhages occur, when the prothrombin levels fail below 20%

Vitamin C (Ascorbic acid )

Deficiency may result in scurvy. It is characterized by spongy and sore gums, loose teeth, anemia, swollen joints, delayed wound healing, hemorrhage, osteoporosis, etc. Defective collagen synthesis “Cork – screw” hair pattern, “Wody legs” with large spontaneous bruises in lower extremities are other features “Trummer field zone” is the classic histologic picture of bone in scurvy

The pathogenic sign is the swollen and spongy gums, particularly the interdental papillae are involved producing the appearance of scurvy buds. In severe cases, hemorrhages to periodontal membranes followed by loss of blood and loosening of teeth occur

Vitamin B1 B1 deficiency is seen in populations consuming (anti-beriberi or anti- polised rice as a staple food neuritic vitamin) Dry beriberi or peripheral neuritis; wet beriberi or cardiac manifestations, and cerebral or wernickes encephalopathy with korsakoff’s psychosis are features of B1 deficiency

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Contd...

Nutrition and Oral Cavity

Contd... Vitamin

General manifestations of deficiency

Oral manifestations of deficiency

Vitamin B2 (Riboflavin) Nasolabial seborrhea or dyssabacea. Vascularization of cornea Scrotal dermatitis

Glossitis: The filiform papillae become atrophic while the fungiform papillae becomes-gorged and mushroom shaped, resulting in magenta colored tongue. Cheilosis, ocular lesions. (Non-specific bilateral angular cheilosis may be seen in association with faulty dentures or in patients with reduced vertical dimension due attrition.)

Niacin

Pellagra (the symptoms of pellagra are referred to Bald tongue of sandwith. as three ‘D’s, i.e. dermatisis, diarrhea, dementia ‘Raw beefy’ tongue. and if not treated may lead 4th, i.e. death) The mucosa becomes fiery red and painful. Salivation is profuse.

Vitamin B5 Pathothenic acid or chick anti-dermatisis factor

Burning feet syndrome Pain and numbness in the toes, sleeplessness and fatigue are features. Pathothenic acid is one of the water-soluble vitamins that is synthesized in the body.

Vitamin B6 (Pyridoxine)

Peripheral neuropathy (due to decreased synthesis of serotonin catecholamine) and demyelination of neurons. Isoniazid (drug use in treatment of TB) is a antagonist of vitamin B6.

Biotin (Vitamin B7 or Biotin deficiency is uncommon since it is well Vitamin H or anti-egg distributed to foods and also supplied by the white injury factor) intestinal bacteria. Folic acid

Macrocytic anemia, glossitis Aminopterin and methotrexate are structural analogs of folic acid use din treatments of many cancers including leukemia. These drugs block the formation of THF and hence DNA synthesis is impaired.

Glossitis: The filiform papillae disappear first, but in advanced cases the fungiform papillae are lost and the tongue becomes smooth and fiery red in color.

Vitamin B12 (antipernicious vitamin or extrinsic factor of castle)

Pernicious anemia Neurological manifestations due to degeneration of posterior and lateral tracts of spinal cord. Degeneration of myelin sheath and peripheral nerves also occurs.

Beefy and tongue with glossopyrosis, glossitis and glossodynia. Hunter’s glossitis or Moeller’s glossitis, which is similar to “bald tongue of sandwith” seen in pellagra.

Sign and symptoms: Other sign and symptoms are abdominal pain, anorexia, and fatigue.

Management It jaundice occur at birth, child should be placed under the special lights.

BIBLIOGRAPHY 1. Archard HO, Witkop CJ. Herediatary hypophosphatemia (vitamin D resistant rickets) presenting primary dental manifestation. Oral Surg Oral Med Oral Pathol. 1966;22:184-93. 2. Bartnick A, Friedrich RE, Roeser K, et al. Oral langerhans cells histiocytosis. J Craniomaxillofac Surg. 2002;30:91-6.

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3. Batra P, Tejani Z, Mars M. X-linked hypophosphatemia dental and histologic finding. J Can Dent Assoc. 2006;72:69-72. 4. Beltes C, Zachou E. Endodontic management in a patient with vitamin D-resistant Rickets. J Endod. 2012;38(2):2558. Epub 2011 Dec 10. 5. Cleveland DB, Goldberg KM, Greenspan JS, et al. Langerhans cell histiocytosis: a report of three cases with unusual oral soft tissue involvement. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82:541-8. 6. Crook MA. Zinc deficiency, Nutrition. 2011;27(10):1085-6. 7. Fay JT. An early case of Hurler’s syndrome (Hunter-HurlerPfaundler syndrome, mucopolysaccharidosis I, dysostosis multiplex): report of a case. J Oral Med. 1972;27(3):64-6. 8. Fayle SA, Pollard MA. Congenital erythropoietic porphyria, oral manifestations and dental treatment in childhood: a case report Quintessence Int. 1994;25(8):551-4. 9. Halligan TJ, Russel NG, Dunn WJ, et al. Identification and treatment of scurvy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100:688-92. 10. Hicks J, Flaitz CM. Langerhans cell histiocytosis: current insight in the molecular age with emphasis on clinical oral and maxillofacial pathology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100:S42-S66. 11. HU C-C, King DL, Thomas HF, et al. A clinical and research protocols characterizing patients with hypophosphatasia: pediatr Dent. 1996;18:17-23. 12. Key SJ, O’Brian CJ, Silvester KC, et al. Eosinophilic granuloma resolution of maxillofacial bony lesion following minimal intervention: a report of three cases and review of literature: J Craniomaxillofac Surg. 2004;32:170-5. 13. Khadim MI. Oral manifestations of malnutrition III. The effect of proteins. J Pak Med Assoc. 1983;33(5):119-22. 14. Kooijman MM, Brand HS. Oral aspects of porphyria, Int Dent J. 2005;55(2):61-6. 15. Lustmann J, Ben-Yehuda D, Somer, et al. Gaucher disease affecting mandible and maxilla: a report of case. Int J Oral Maxillofac Surg. 1991;20:7-8. 16. MacLeod SP, Macintyre DR. Bilateral hypoplasia of mandibular condyles in Hurler’s syndrome. Oral Surg Oral Med Oral Pathol. 1993;75(5):659-60. 17. McGovern MM, Aron A, Brodie SE, et al. Natural history of type A Niemann Pick disease: possible endpoint at therapeutic trials. Neurology. 2006;66:228-32.

18. Myoken Y, Fujita Y, Sugata T, et al. Unilateral cheek swelling in an infant: case report of an unusual presentation of internal bleeding caused by vitamin K deficiency. J Oral Maxillofac Surg. 2010;68(10):2583-5. 19. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edn. Saunders Elsevier, 2009. 20. Nitzan DW, Marmary Y, Azaz B. Mandibular tumorinduced muscular weakness and osteomalacia. Oral Surg Oral Med Oral Pathol. 1981;52(3):253-6. 21. Olsson A, Matsson L, Blomquist HK, et al. Hypophosphatasis affecting permanent dentition: J Oral Pathol Med. 1996;25:343-7. 22. Penner CR, Muller S. Head and neck amyloidosis a clinicopathological study of 15 cases: Oral Oncol. 2006;42:421-9. 23. Pontes HA, Neto NC, Ferreira KB, et al. Oral manifestations of vitamin B12 deficiency: a case report. J Can Dent Assoc. 2009;75(7):533-7. 24. Rashid M, ZarkadaS M, Anca A. Oral manifestations of celiac disease: a clinical guide for dentists, Limeback H. J Can Dent Assoc. 2011;77:b39. 25. Schlosser BJ, Pirigyi M, Mirowski GW. Oral manifestations of hematologic and nutritional diseases. Otolaryngol Clin North Am. 2011;44(1):183-203. 26. Spoelstra MN, Mari A, Mendel M, et al. Kwashiorkor and marasmus are both associated with impaired glucose clearance related to pancreatic b-cell dysfunction, Metabolism. 2012. 27. Stopper ET, Alwai F, Laudenbach JM, et al. Bullous amyloidosis of the roal cavity: a rare clinical presentation and review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:734. 28. Stopper ET, Sollecito TP, Chen SY. Amyloid deposition in the oral cavity: a retrospective study and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95:674-80. 29. Touyz LZG: oral scurvy and periodontal disease: J Can Dent Assoc. 1997;63:837-45. 30. Zambrano M, Nikitakis NG, Sanchez-Quevedo MC, et al. Oral and dental manifestation of vitamin D dependent rickets type I: a report of a pediatric case: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95:705-9.

Nutrition and Oral Cavity

MULTIPLE CHOICE QUESTIONS 1. Marasmus and kwashiorkar is cause due to deficiency of: a. Carbohydrate b. Protein c. Vitamins d. Water 2. Bright reddening of tongue, papillary atrophy and bilateral angular cheilosis seen in: a. Marasmus b. Kwashiorkar c. Amyloidosis d. Both a and b 3. Stain used for detection of amyloid: a. Congo red b. Crystal violet c. Alizarin d. Alician blue 4. Excretion of red color urine seen in: a. Amyloidosis b. Letterer Siwe disease c. Porphyria d. Both a and b 5. Red or brownish color of teeth seen in: a. Porphyria b. Marasmus c. Tay-Sachs disease d. Gaucher’s disease

6. A classic triad of bone destruction in skull, exopthalmos, diabetes insipidus seen in: a. Hand-Schuller-Christian disease b. Letterer Siwe disease c. Hypoglycemia d. Pellagra 7. Shortening of mandible and clear gargoyle cells seen in: a. Niemann-Pick disease b. Hurler’s disease c. Gaucher’s disease d. Both a and c 8. Which one is also refer as ‘antibiotic vitamin’: a. Vitamin C b. Vitamin B c. Vitamin D d. Vitamin A 9. ‘Scorbutic lattice’ is the histopathologic feature seen in: a. Retinol b. Beriberi c. Scurvy d. Zinc deficiency 10. Large pulp chamber, high pulp horns and delayed closure of root apices seen in: a. Hypervitaminosis A b. Rickets c. Pellagra d. None.

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33

Neuromuscular Disorders and Orofacial Pain Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline  Muscle disorders • Muscular dystrophy • Myotonias • Myasthenia gravis • Dermatomyositis  Neuromuscular disorders • Auriculotemporal syndrome • Bell’s palsy • Motor neuron disease • Multiple sclerosis • Myositis ossificans

MUSCLE DISORDERS Muscular Dystrophy There are mainly two types of muscular dystrophy: 1. Severe generalized familial muscular dystrophy 2. Mild restricted muscular dystrophy.

Severe Generalized Muscular Dystrophy It is described as a rapidly progressive muscle disease, usually beginning in early childhood and presenting a strong familial transmission.

Clinical Features Age and sex distribution: It is the most common form of muscular dystrophy and predominately affects males. It

 Facial pain • Trigeminal neuralgia • Glossopharyngeal neuralgia • Geniculate neuralgia • Atypical facial pain • Neuralgia inducing cavitational osteonecrosis • Cluster headache • Paroxysmal hemicranias • Migraine • Temporal arteritis • Burning mouth syndrome

begins in childhood, usually before the age of 6 years and rarely after 15 years. Symptoms: The earliest symptom is inability to walk or run change to which, the children fall readily and associate with muscular enlargement and weakness. Waddling gait: The muscular enlargement ultimately proceeds to atrophy and the limbs appear flaccid. It is the atrophy which is responsible for the postural and ambulatory defects, such as waddling gait.

Oral Manifestations The muscles of mastication, facial, ocular, laryngeal and the pharyngeal muscles are usually involved, only late in the course of disease.

Neuromuscular Disorders and Orofacial Pain

Due to lack of muscle tension, teeth can not be kept properly aligned in the arch. Locking and clicking of the jaw occur.

Management Some patients undergo temporary periods of remission or even complete arrest.

Histopathological Features

Points to Remember

There is gradual disappearance of muscle fibers, as the disease progresses until ultimately no fibers may be recognized. Persistent fibers show variation in size in the earlier stages of disease, some being hypertrophic but others atrophic.

Inability to walk, waddling gait, locking and clicking of the jaw, disappearance of muscle fibers, cardiomegaly, tapir­lips, individual fibers become atrophic, infiltration of fiber bundles, elevated serum creatinine phosphokinase levels.

Lab Findings Serum creatinine phosphokinase levels are elevated in all males.

Myotonias

Management

Types

There is no treatment for this disease. Physical therapy may help prolong the use of specific muscle group.

∙ ∙ ∙

Mild Restricted Muscular Dystrophy It is a slowly progressive proximal myopathy which pri­ marily involves the muscles of shoulder and face and has a weak familial incidence. It is transmitted as an autosomal dominant trait.

Clinical Features Age: The disease begins at any age from 2 years to 60 years, although onset is in the first two decades of life. Symptoms: The earliest symptoms are inability to raise the arms above the head and inability to close the eyes, even during sleep as a result of weakness of the facial muscles. Signs: Scapular muscles become atrophic and weak with subsequent alteration in the posture. Cardiac abnormalities including cardiomegaly and tachycardia are often present and many patients die of sudden cardiac failure.

Oral Manifestations The lips develop a characteristic looseness and protrusion, which have been described as tapir-lips. The patient is unable to whistle or smile. There may be severe open bite and development of diastema.

Histopathological Features There is some variation in size of muscle fibers and moderate infiltration of fiber bundles by connective tissue. Individual fibers ultimately become atrophic.

Dystrophic Congenital Acquired.

Dystrophic Myotonia It is also called myotonic dystrophy or dystrophic myotonica. It is inherited as an autosomal dominant trait.

Clinical Features Age: It does not appear until the 3rd decade of life, but may be seen earlier, i.e. even in childhood. Site: Atrophy of the muscles is seen usually in the hands and forearms. It can be seen in muscles of face, jaws, neck and levators of eyelids. Sign and symptoms: There is associated weakness of the muscles. There is alteration in the facial muscles, which consist of ptosis of the eyelids and atrophy of the masseter and sternocleidomastoid muscles. Myopathic facies and swan neck: The masseteric atrophy produces a narrowing of the lower half of the face which, with ptosis and generalized weakness of the facial musculature gives the patient a characteristic ‘myopathic facies’ and ‘swan neck’. Pharyngeal and laryngeal myotonia also exhibit weakness manifested by a weak, monotonous nasal type of voice and subsequent dysphagia. Recurrent dislocations of the jaw are also reported in this disease. Other features are testicular atrophy, cataract, hypothyroidism with cold extremities, slow pulse, loss of hair and functional cardiac changes.

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There is enlargement of scattered muscle fibers and the presence of centrally placed muscle nuclei in long rows. True hypertrophy in some fibers, is found, as well as in isolated fibers which show extreme degenerative changes including nuclear proliferation, intense basophilic cytoplasmic staining and phagocytosis. Points to Remember Myotonic dystrophy, atrophy of the muscles, ptosis, myopathic facies and swan neck, pharyngeal and laryngeal myotonia, recurrent dislocations of the jaw, scattered muscle fibers, centrally placed muscle nuclei, phagocytosis, basophilic cytoplasmic staining.

Congenital Myotonia It is transmitted as an autosomal dominant trait with incomplete penetrance in some families. It is also called Thomson’s disease.

Clinical Features Age: It commences early in the childhood and may be first noticed because of difficulties in learning to stand and walk.

Clonus: If these spasms are intermittent, it is called ‘clonus’ (myoclonic contraction). Trismus: If spasms are constant, it is called ‘trismus’ (myotonic contractions).

Myasthenia Gravis It is an autoimmune disease characterized by progressive weakness of the skeletal muscles, particularly those innervated by the cranial nerves.

Etiopathogenesis Effect on AChR: This disease affects acetylcholine receptor of muscle fibers which results in fatigability of skeletal muscle. Motor end organs of acetycholine mechanism is normal that is reason smooth and cardiac muscle are not affected. Defective neuromuscular transmission: Defect in the neuromuscular transmission occur secondary to coating of the AChR by circulating antibodies to receptors. Thymus hyperplasia or thymoma: It may occur due to thymus hyperplasia or tumors of the thymus. Other factors: In some cases myasthenia gravis can be related to pregnancy, menstruation and hyperthyroidism.

Clinical Features

Sites: The muscles of the thighs, forearm and shoulders are especially affected as well as are the muscles of the neck, masseter and facial muscles.

Age and sex predilection: It occurs in adults in the middle age group with a predilection for women.

Muscular contraction induces a severe, painless muscular spasm, and an actually delay in relaxation.

Symptoms: It is characterized by a rapidly developing weakness in voluntary muscles, following even minute activities.

Percussion contraction: Electrical and physical stimul­ ation of a muscle produces the characteristic prolonged contraction or percussion contraction. Blinking with strong closure of the eyes will sometimes produce a prolonged contraction of the lids.

Management There is no specific treatment for this disease.

Signs: Repeated muscular contraction will results in weaker contracting muscle. This will lead to loss of weight. Soon patients become exhausted, may eventually become bedfast. Eye: There is diplopia (double vision) and ptosis (drooping eyelids) (Fig. 33.1). The neck muscles may be so weak that the head can not be held up without support.

Points to Remember

Respiratory failure: Death frequently occurs from respiratory failure.

Muscular contraction, painless muscular spasm, Percus­ sion contraction.

Orofacial Manifestations

Acquired Myotonia It refers to spasm of muscles which are more intense than typical myotonia.

Mastication problems: The patient’s chief complains may be difficulty in mastication, deglutition. This occur due to weakness in muscle of mastication. In some cases regurgitation of food are common.

Neuromuscular Disorders and Orofacial Pain

Thymectomy: In patient where there is evidence of thymoma and elevated AChR antibody, thymectomy is indicated. 833

Points to Remember Rapidly developing weakness in voluntary muscles, muscular contraction, diplopia, ptosis, respiratory failure, difficulty in mastication, hang open jaw or dropping of the jaw, sorrowful appearance, dysarthria, weakness of the tongue and palatal muscles, Lymphorrhages, foci of atrophy or necrosis of muscle, elevated serum AChR antibody level, anticholinesterases. Figure 33.1 Ptosis in patient of myasthenia gravis

Dropping of jaw: In some cases muscle of mastication becomes very weak. So after having meal of patient this will results in hang open jaw or dropping of the jaw. Sorrowful appearance: Dropping of the face, leads a sorrowful appearance of the patient with myasthenia gravis. Speech: Speech is often slow and slurred (dysarthria). Tongue: There is disturbance in taste sensation. There may be weakness of the tongue and palatal muscles. Protrusive movements of the tongue may become weak leading, at times to posterior collapse of the organ with airway obstruction.

Histopathological Features Lymphorrhages: Focal collection of small lymphocytes or lymphorrhages is found surrounding small blood vessels in the interstitial tissue of the affected muscles.

Dermatomyositis It is also called polymyositis. It is an acute or a chronic disease of unknown etiology and is characterized by a gradual onset with vague and indefinite prodromata, followed by edema, dermatitis, myositis and sometimes neuritis and mucositis.

Clinical Features Age: It may occur in patients of any age ranging from very young children to elderly, but majority occur in the 5th decade of life. Symptoms: It begins with erythematous skin eruptions, edema, tenderness, swelling and weakness of the proximal muscles of limbs. Fever may be associated with it. Signs: The weakness of muscle is progressive and characteristically spread to the face, neck, larynx, pharynx and heart.

Management

Heliotrope: The skin becomes the seat of violaceous erythema and edema with a predilection for the eyelids, malar area and dorsa of hands. The typical skin lesions include heliotrope (lilac­colored) changes around the face and fingers. The edema which gives the skin a puffy consistency including the face, leaves a reticulated telangiectatic erythema when it subsides.

Anticholinesterases: Cholinesterase inhibitor like edro­ phonium, neostigmine, administered intra­muscularly im­ proves the strength of the affected muscles.

Calcinosis cutis: The skin lesions frequently calcify and form calcium carbonate nodules with a foreign body reaction which is known as calcinosis cutis.

Combination therapy: In some cases anticholinesterase can be combined with intermittent corticosteroids therapy. This will give good results in many cases.

Calcinosis universalis: The term calcinosis universalis is applied when these calcified masses are found generalized throughout the soft tissues.

Foci of atrophy or necrosis of muscle: Foci of atrophy or necrosis of muscle fibers have been described. There is also loss of rounded cross­sectional appearance. Elevated serum AChR antibody level: As this antibody is not found commonly in human being, it is diagnostic indicator of myasthenia gravis.

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Points to Remember

The oral lesions consist of diffuse stomatitis and pharyngitis and are extremely common. Involvement of the muscles of jaw, tongue and pharynx may pose problems in eating and phonation. The oral mucosa may show dark red or bluish erythema. In the early stages, tongue is swollen and later becomes harder and gradually it becomes atrophic. The tongue may become rigid owing to severe calcinosis. Telangiectatic lesions of vermilion border of lips and cheeks may also occur. There is purplish black intrinsic staining of teeth.

NEUROMUSCULAR DISORDERS

Histopathological Features

Auriculotemporal Syndrome

The muscle fibers in dermatomyositis exhibit widespread degeneration and hyalinization (Fig. 33.2). In advanced cases, the muscle fibers disappear leaving only the fibrous stroma. Many fibers show vacuolization, granulation and fragmentation with phagocytosis of disintegrating fibers.

It is also called Frey’s syndrome or gustatory sweating and flushing. It is described in 1853 by Baillarger and is characterized by facial flushing and sweating along the distribution of auriculotemporal nerve.

Lab Findings It manifests as a mild anemia or leukocytosis. In addition, creatinuria is a constant finding as well as elevated levels of serum transaminase and aldolase.

Management Prognosis: Muscle involvement may become severe enough to confine the patient to bed or cause death owing to failure of respiratory muscle.

Polymyositis, heliotrope, weakness of muscle, puffy consistency edema of skin, calcinosis cutis, calcinosis universalis, diffuse stomatitis and pharyngitis, show dark red or bluish erythema on oral mucosa, rigid tongue, purplish black intrinsic staining of teeth, widespread degeneration, hyalinization, vacuolization, granulation fragmentation with phagocytosis, mild anemia.

Pathogenesis It is an unusual phenomenon which arises as a result of damage to the auriculotemporal nerve. Auriculotemporal nerve, in addition to sensory function, also supplies parasympathetic fibers to parotid gland. The fibers regenerate, become misdirected and follow the course of sympathetic fibers to the skin and sweat gland. Parasympathetic fibers would therefore induce sali­ vation; inadvertently stimulate the preauricular­dermal sweat gland and arterioles, causing hydrosis and vasodi­ lation.

Etiology It follows surgical operations such as removal of a parotid tumor or ramus of mandible. It may follow superficial parotidectomy. It may occur due to birth trauma.

Clinical Features Symptoms: The patient exhibits preauricular flushing and sweating of the involved side of face, following ingestion of food or visual stimulation by foods. Patient may sometimes feel pain while eating. The severity of sweating is increased by tart food. Profuse sweating may be evoked by parenteral administration of pilocarpine or eliminated by the administration of atropine. Figure 33.2 Dermatomyositis histopathological features

Sign: Local skin temperature is raised without sweating. Temperature may rise to 100°F. Presence of cutaneous

Neuromuscular Disorders and Orofacial Pain

hyperaesthesia in front and above the ear, area supplied by the auriculotemporal nerve. Crocodile tears: In it patient exhibits profuse lacrimation when food is eaten particularly hot and spicy food. Minor Starch-Iodine test: 1 percent iodine solution is painted on affected area. After the solution is dried, area is coated with layer of starch. After patient having taken food, moisture of sweat will mixed with iodine on the skin. It will results in blue color.

Management Intracranial division of auriculotemporal nerve has been reported to be successful. To control gustatory sweating, may be maintained for up to 3 days, by topical application to the affected skin by 1 percent glycolpyrrolate lotion or cream. Other treatment modalities which can be use are injection of atropine, botulinum toxin. You can also go for topical application of scopolamine cream and systemic use of oxybutynin chloride, an antimuscarinic agent. Points to Remember Frey’s syndrome, preauricular flushing and sweating, raised local skin temperature, Crocodile tears, Minor Starch­Iodine test, intracranial division of auriculotem­ poral nerve.

Bell’s Palsy It is also called 7th nerve paralysis or facial paralysis.

Surgical procedures, such as removal of parotid gland tumor in which the facial nerve is sectioned can also cause facial paralysis. It may cause by ischemia of the nerve near the stylomastoid foramen, resulting in edema of the nerve, its compression in the bony canal and finally, paralysis. Familial and hereditary occurrence is also reported in cases of Bell’s palsy. Tumors of cranial base, parapharyngeal space and infratemporal fossa often cause 7th nerve palsy. Others causes of Bell’s palsy are Melkersson­Rosenthal syndrome, acute otitis media and atmospheric pressure changes.

Clinical Features Age and sex distribution: Women are more commonly affected than men and usually, it occurs in the middle age group. Onset: It arises more frequently in spring and fall, than at any other time of the year. It begins abruptly as paralysis of the facial musculature, usually unilaterally. Symptoms: In some cases, it is preceded by pain on the side of the face which is ultimately involved, particularly within the ear, temple, and mastoid area or at the angle of the jaw. On the affected side, eye can not be closed and wrinkles are absent on that side. There is watering of eye, which leads to infection. It is associated with Melkersson-Rosenthal syndrome. When the patient smiles, the paralysis becomes obvious since the corner of the mouth does not rise nor does the skin of the forehead wrinkles or the eyebrows raise (Fig. 33.3).

Pathogenesis The cortical tract communicating with the motor nucleus ambiguous of facial nerve crosses over to get innervated into the lower face musculature. Upper face fibers are ipsilateral proximal to the nucleus. A cortical lesion will cause contralateral lower face palsy; lesions of brain stem, main trunk or peripheral fibers will result in total hemifacial paralysis.

Etiology It usually occurs after exposure to cold. But many workers believe that it is a chance finding. It may be a causative factor as Bell’s palsy occurs after extraction of teeth and after injection of local anesthetic. Extraction and injection may cause damage to the nerve and subsequent paralysis.

Figure 33.3 Patient having facial paralysis

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The muscular paralysis manifests itself by dropping of the corner of mouth, from which saliva may dribble. The patient has a typical masklike or expressionless appearance. Speech and eating is difficult and occasionally, taste sensation on the anterior portion of tongue is lost or altered. Food is retained in the upper and lower buccal and labial folds due to weakness of buccinator.

Management The use of vasodilator drug like histamine has been proved beneficial in some cases. Other treatment modalities which are used are systemic corticosteroid, hyperbaric oxygen therapy, surgical decompression of intratemporal facial nerve can be given. Points to Remember 7th nerve paralysis, arises in spring, pain on the side of the face, Melkersson Rosenthal syndrome, on the affected side, eye cannot be closed, wrinkles are absent, masklike or expressionless appearance, lost taste sensation, histamine.

Motor Neuron Disease It is described by Charcot in 1870. It is characterized by weakness and wasting of muscles.

Etiopathogenesis Degeneration: There is progressive degeneration of motor neurons of cranial nerves, pyramidal tract and anterior horn cells of spinal cords. Genetic: Many cases seem that it occur due to genetic defect. It can be transmitted as autosomal dominant trait. Types • Progressive muscular atrophy • Amyotrophic lateral sclerosis • Progressive bulbar palsy.

Symptoms: It is characterized by progressive weakness of limbs with associated muscular atrophy, reflex loss and sensory disturbances. The initial symptoms usually consist of difficulty in walking with leg pain and paresthesia. Signs: Atrophy of foot, leg and hand muscles ultimately occurs with the appearance of a typical foot­drop, steppage gait and stork­legs. Amyotrophic lateral sclerosis Synonym: It is also called Lou Gehrig disease (he is famous baseball player who died of these disease) Age and sex distribution: It generally occurs between the ages of 40 to 50 years and affects males more frequently. Precipitating factors include fatigue, alcohol intoxi­ cation and trauma. Infections like syphilis, influenza, typhus and epidemic encephalitis can also lead to amyotrophic lateral sclerosis. Symptoms: The initial symptoms consist of weakness and spasticity of limbs, difficulty in swallowing and talking with indistinct speech and hoarseness. Atrophy, flaccidity, symmetric weakness, slowness of movements and impairment or loss of palatal movements may also occur. Fasciculation: Fasciculation of shoulder and thigh are early symptom. Bulbar paralysis: Dysfunction of muscle controlled by medulla oblongata can be present in the later stage of disease.

Oral Manifestations Stage I: In earlier stages, the tongue is slightly weakened, leaving articulation relatively unaffected. Stage II: In the middle stages, a gradual and generalized weakening of tongue occurs, accompanied by spasticity which results in reduced rate, range and force of articulatory tongue movements. Stage III: In the later stages, there is virtually unintelligible articulation.

Clinical Features

Progressive bulbar palsy

Progressive muscular atrophy

Age and sex distribution: It generally in children and young adults. There is no sex predilection.

Age and sex distribution: It usually occurs in childhood with some reported case at birth. As there incidence of occurrence is same in case male and females.

Symptoms: It is characterized by difficulty in swallowing and phonation, hoarseness.

Neuromuscular Disorders and Orofacial Pain

Palatal paralysis: Paralysis of palatal muscle will results in regurgitation of food in the nasophayrnx and nasal sinuses. 837

Facial involvement: There is weakens of facial muscle which ultimately results in mastication problems. Chewing is difficult as facial muscles become weakened. Signs: Atrophy of facial, masseter, temporal muscles and tongue, with fasciculation of the face and tongue.

Management Fatal course: Course of this disease is fatal. Death usually occurs within 2 years in case of progressive muscular atrophy and progressive bulbar palsy. In case of ALS it can occur within 5 years. Antiglutamate agent: Riluzole has shown some improvement but cure is not possible with this drug also. Points to Remember Types, degeneration of neuron, stork leg, progressive weakness, tongue involvement, bulbar paralysis, palatal paralysis, fatal course.

Multiple Sclerosis It is also called disseminated scleroses.

Etiology The lesions are allergic hypersensitivity manifestations of the nervous tissue due to antigen­antibody reactions. The lesions are due to scattered venous thrombosis in the nervous system associated with altered coagulation of blood. The lesions are due to repeated, transitory localized vasoconstriction in various portions of the nervous system, precipitated by emotional disturbances or fatigue.

Clinical Features Age and sex distribution: It occurs chiefly in younger age group with an onset of symptoms between the ages of 20 and 40 years. There is slight female predilection with familial occurrences. Symptoms: There is fatigability, weakness and stiffness of the extremities with ataxia or gait difficulty, involving one or both leg (Fig. 33.4). Other symptoms includes are area of superficial or deep paresthesia, personality and mood deviation

Figure 33.4 Hand stiffness in patient with multiple sclerosis

towards friendliness and cheerfulness, variety of ocular disturbances including visual impairment as a manife­ station of retrobulbar neuritis, nystagmus and diplopia. Charcot’s triad: It consist of intentional tremors, nysta­ gmus, dysarthria and scanning speech.

Oral Manifestations Facial and jaw weakness occur in some patients. Staccato (a series of short, detached sound or words) type of speech is interesting feature of this disease. In some cases both trigeminal neuralgia and Bell’s palsy have been reported.

Management Patient should be referred to neurologist for further management.

Myositis Ossificans It is a condition in which fibrous tissue and heterotopic bone form within the interstitial tissue or muscle, as well as in associated tendons and ligaments. Secondary destruction and atrophy of the muscle occurs, as this fibrous tissue and bone interdigitate and separate the muscle fibers. Types • L ocalized myositis ossificans or traumatic myositis ossificans. • Progressive myositis ossificans or generalized myositis ossificans.

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It is also called post-traumatic myositis ossificans or solitary myositis. Etiology It is caused by acute or chronic trauma or heavy muscular strains caused by certain occupation or sports. Traumatization of the periosteum of an adjacent bone with the displacement of osteoblasts into the muscle and subsequent formation of bone occurs. Activation of periosteal implants already present in muscle by trauma or hemorrhage. Metaplasia of the pluripotential intermuscular connective tissue into the bone and metaplasia of fibrocartilage can also be causative factors. Pathogenesis Injury → hemorrhage into the muscle or associated tendon or fascia → the hemorrhage organized and undergoes scarring → during healing process cartilage is formed → calcification of cartilage → ossification of cartilage. Clinical features Age and sex distribution: It can occur at any age, sex and more often in young persons. Sites: The most commonly involved muscles are the masseter and sterno­cleidomastoid but in some cases lateral pterygoid muscle can be involved. Symptoms: Site of trauma remains swollen, tender and painful much longer than expected. In some cases there is a mild discomfort associated with a progressive limitation of motion. Signs: The overlying skin may be red and inflamed. Intramuscular mass is palpated at 2 to 3 weeks. The lesion may appear fixed or it may be freely movable on palpation. Oral Manifestations It involves the muscles of face particularly masseter and temporal following single traumatic injury. Some difficulty in opening of the mouth occurs. Histopathological features It exhibits varying stages from hemorrhage, degeneration of muscle and connective tissue hyperplasia to chondrification and ossification. The osteoid and bone trabeculae formed often trap viable muscle fibers but these may ultimately disappear. The trabecular pattern is often extremely bizarre with the cartilage and myxomatous tissue present which may

resemble callus formation. The more mature tissue is usually found on the periphery of the lesion. Management Sufficient rest should be given with limitation of use. Excision after process becomes stationary. Points to Remember Solitary myositis, swollen tender painful at site of trauma, overlying skin is red, difficulty in opening of the mouth, hemorrhage, degeneration of muscle, ossification, chondrification and connective tissue hyperplasia.

Progressive Myositis Ossificans It is characterized by formation of bone in tendons and fascia with subsequent replacement of adjacent muscle by expanded bony mass. In some cases there is history of hereditary and familial pattern. Clinical features Age and sex distribution: It usually affects children before 6 years of age. It is seen more in males as compared to females. It may advance rapidly or there may be long period of relative inactivity with intermittent bursts of activity. Sites: Starts in muscles of neck and upper back and moves to extremities. Soft tissue swelling that is tender and painful and may show redness and heat. Signs: Gradual increase in stiffness and limitation of motion of neck, chest and back and extremities occurs. Ultimately entire groups of muscles become transformed into bone resulting in limitation of movements. It is associated with congenital shortness of first meta­ tarsal and metacarpal bones, shortness of little bone. Interphalangeal joint may be fused. The masseter muscle is frequently involved so that fixation of jaw occurs. Petrified man: The patient becomes transformed into a rigid organism called ‘petrified man’. Patient dies during 3rd or 4th decades. Premature death is usually results from respiratory embarrassment. Histopathological features The muscle in this disease is gradually replaced by connective tissue which undergoes osteoid formation and subsequently ossification. In some cases cartilage formation may become evident.

Neuromuscular Disorders and Orofacial Pain

Management Surgical approach can be considered for the management of progressive myositis ossificans. Points to Remember Tender soft tissue swelling, increase in stiffness of muscles, petrified man, muscle replaced by connective tissue, osteoid formation.

FACIAL PAIN Trigeminal Neuralgia It is also called Tic Douloureux, trifacial neuralgia or fothergill’s disease. Tic douloureux’ is only used when the patient suffers from spasmodic contractions of the facial muscles. Trigeminal neuralgia is an extremely painful condition as it is unique to humans. It is a syndrome in which symptoms are sufficiently distinctive to permit a reliable diagnosis solely on the basis of history.

Etiology Idiopathic trigeminal neuralgia Dental pathosis is believed by some investigators to be involved with the onset of trigeminal neuralgia. It may occur secondary to excessive traction on the various divisions of the fifth nerve, being influenced by maxillo­mandibular relationship, allergic and hypersensitivity reaction causing edema of the trigeminal nerve root. Wolf thought that ischemia at various portions of the trigeminal pathway might be responsible for the paroxysms of pain. Jannetta and others have shown subtle changes of a compression-distortion phenomenon which is usually caused by arterial loops of atherosclerotic vessels. Vessels become elongated with advancing age and with atherosclerotic involvement gain abnormal positions­by wedging into the space between the pons and trigeminal nerve. It is postulated that with progressive material elongation, fascicles of adjacent nerves later suffer myelin injury and pain results. Secondary trigeminal neuralgia Conditions such as carcinoma of the maxillary antrum, nasopharyngeal carcinoma and tumors of peripheral nerve root can cause secondary trigeminal neuralgia. Benign tumors, as well as intracranial vascular anomalies may present trigeminal pain.

Multiple sclerosis is usually associated with trigeminal neuralgia.

Clinical Features Age and sex distribution: It usually occurs in middle and old age, the disease seldom occurs before 35 years of age. Incidence increases with age due to degenerative changes of the nerve fibers. It most frequently occurs in women. Site: It is more common on the right side and the lower portion of the face is more frequently affected. The pain is confined to the trigeminal zone, nearly always unilateral and, if bilateral, is successive rather than concomitant. The mandibular and maxillary divisions are more commonly involved than the ophthalmic; in some instances these two divisions may be simultaneously affected. The pain never crosses the midline. Pretrigeminal neuralgia: There is dull, continuous, aching type of jaw pain which may persist for days prior to onset of characteristic occurrence of paroxysmal pain in the same region of the jaw. This is called pretrigeminal neuralgia. This can show dramatic response to carbamazepine. Nature of pain: The pain is paroxysmal, lasting only a few seconds to a few minutes and is usually of extreme intensity. It may be described by the patient as resembling knife like stabs lightening, electric shock, stabbing or lancinating type of pain. During the intervals between these violent experiences, there is usually no pain or a mild or dull ache. Aggravating factors: The pain is provoked by obvious stimuli to the face. A touch, a draft of air, any movement of the face as in talking, chewing, yawning or swallowing may evoke a lancinating attack. Later the pain may be so severe that the patient lives in constant fear of an attack. Often there is a transitory refractory period after the attack. As the attack occurs, the patient may clutch his face as if in terror of the dreaded pain. Triggers zones: Trigger zones which precipitate an attack when touched, are common on the vermilion border of the lips, the ala of the nose, the cheeks, and around the eyes. The patient learns to avoid touching the skin over the trigger zones which frequently makes him go unwashed or unshaven for days. The neurological examination findings are normal with no objective sensory loss along the trigeminal nerve.

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Histopathological Features

Glossopharyngeal Neuralgia

Trigger point may show fibrosis and infiltration by chronic inflammatory cells. In some cases, there is focal area of myelin degeneration are seen along the course of cranial nerves.

It is also called vagoglossopharyngeal neuralgia. It is a variant of tic douloureux that can mimic oral pathologic condition in which pain is confined to the distribution of the ninth cranial nerve.

Diagnostic Criteria • • • • •

Abrupt onset of attack initiated by light touch Pain is paroxysmal, extreme and lancinating Duration of spasm is less than 2 minutes After attacks refractory periods occur Pain is limited to known distribution of trigeminal nerve branch • Pain is diminished dramatically initially by the use of carbamazepine.

Management Topical capsaicin cream (a nociceptive substance­P suppressor) over the skin may be effective. Carbamazepine (tegretol) has a special effect on the paroxysmal pain. The use of this drug causes paroxysms to become separated by intervals of freedom for weeks, months or even years. This is considered to be the best conservative treatment for trigeminal neuralgia. As an initial dose, 100 mg is given twice daily until relief is established. At no time the daily dose should exceed 1200 mg. Side effects include dizziness, unsteady gait, gastrointestinal distress, skin rashes and aplastic anemia. Recently, baclofen an antispastic drug is also being used. Anticonvulsant like, phenytoin, gabapentin are effec­ tive in pain control as they decrease conductance of Na+ channels and inhibit ectopic discharges. Nonsurgical procedure like microvascular decompression, radiofrequency rhizotomy, and gamma knife radiosurgery of gasserian ganglion are also effective in younger patient. After surgery patient can have complication like facial dysesthesia (distorted sensation of facial skin) and anesthesia dolorosa (combination of anesthesia and spontaneous pain. Points to Remember Tic Douloureux, common on the right side, pretrigeminal neuralgia, knife like stabs’ ‘lightening’, ‘electric shock’, ‘stabbing’ or ‘lancinating’, triggers zones, trigger point may show fibrosis, infiltration by chronic inflammatory cells, topical capsaicin cream, carbamazepine, phenytoin, gabapentin, microvascular decompression, radiofrequency rhizotomy.

Clinical Features Age and sex distribution: This neuralgia occurs without any sex predilection in the middle aged or older persons. Nature of pain: It manifests as sharp excruciating, electric like, lancinating paroxysms of pain in the ear, pharynx, nasopharynx, tonsils or the posterior portion of the tongue. The pain is generally unilateral. Pain often radiates to ear due to involvement of tympanic branch of glossopharyngeal nerve. Attacks have abrupt onset with short duration of 30 to 60 seconds which can be repeated. Glossopharyngeal neuralgia has a tendency towards remissions and exacerbations. Pain free intervals of seconds, minutes, hours, days, and years are common. Trigger zones: The patient usually has a trigger zone in the posterior oro­pharynx or tonsillar fossa. An important and frequent trigger is the initiation of the act of swallowing. Rarely patient may have syncope, seizure, hypotension, arrhythmia and excessive salivation.

Management Topical anesthetic agent: Maximum patient may get instant relief when anesthetic agent applied to the tonsil and pharynx on the side of pain. But this is only last fo one hour so this is used as diagnostic test. Drug treatment: Drugs which can be given in this case are carabamazepine, oxcarbazepine, baclofen, phenytoin and lamotrigine. But these drugs are less effective in glossopharyngeal neuralgia as compare to trigeminal neuralgia. Surgical management: Microvascular decompression or surgical sectioning of glossopharyngeal nerve can be carried out. Points to Remember Vagoglossopharyngeal neuralgia, sharp excruciating, electric like, lancinating paroxysms of pain in the ear, pharynx, trigger zone in the posterior oro­pharynx, topical anesthetic agent, carabamazepine, microvascular decompression.

Neuromuscular Disorders and Orofacial Pain

Geniculate Neuralgia It involves the intermediate nerve of Wrisberg, an important component of the facial (VII) nerve. It is caused pathological involvement of the sensory intermediate nerve root of the VIIth cranial nerve due to neuroma; vascular malformations etc are the cause.

Causes Neuroma and vascular malformation: Pathological involvement of the sensory intermediate nerve root of the VIIth cranial nerve due to neuroma; vascular malformations etc are the cause. Zoster infection: Zoster infection of geniculate ganglion canal also cause this type of neuralgia. This is also called Ramsay Hunt syndrome.

Clinical Features When the triggering is caused by touching the ear, topical anesthesia of the external auditory canal may arrest it. Age and sex: Females are affected more commonly than males. It occurs more commonly in old aged persons.

does not have characteristic of the cranial neuralgias and is not associated with physical signs or demonstrable organic causes. Diagnosis of atypical facial pain is not easy diagnosis for the doctor to make. Patient usually travels from one doctor to another for the relief from the pain. To make diagnosis disease like cracked tooth syndrome, allergic sinus, referred pain to face, myofascial pain impingement of bone on nerve and TMD disorders and tumors should be rule out.

Clinical Features Age and sex distribution: It is usually seen 4th to 6th decade of life with more common in women as compare to men. Location: It more commonly affects one quadrant and may extend to temple, neck or occipital area. Nature of pain: Pain is continuous, deep, diffuse, gnawing and sharp. Patient may called it as drawing, aching or pulling. Signs: Area of pain may contain zone of increase temperature, tenderness and increase bone marrow activity.

Location of pain: Ear, anterior tongue, soft palate. Nature of pain: The pain may be felt in front and deeply in the ear with occasional pain in the palate and the tongue and deeply in the facial musculature. Trigger zone: Triggering is caused by touching the ear.

Management Topical anesthesia: Topical anesthesia of the external auditory canal may arrest pain in some cases. Steroid: Short course of high dose steroids therapy is useful. Acyclovir: This is helpful in case of geniculate neuralgia associated with zoster infection.

Management Gabapentin: This anti­convulsant drug can give dramatic relief in many cases. Opioid analgesic: Opioid analgesic like codeine, fentanyl, hydrocodone, morphine can give relief initially. But their continuous use may lead to addiction. Tricyclic anti­depressant like amitriptyline, nortriptyline can also be used. Other therapy like topical capsaicin for area of localized pain, psychotherapy, behavioral modification, TENS and removal of affected trigeminal nerve gland can also be used.

Points to Remember

Points to Remember

Ramsay Hunt syndrome, pain in ear, anterior tongue, soft palate, trigger by touching the ear, topical anes­ thesia, steroid, acyclovir.

Idiopathic facial pain, continuous, deep, diffuse, gnawing and sharp, pain, zone of increase temperature, gabapentin, opioid analgesic, tricyclic anti­depressant.

Atypical Facial Pain It is also called atypical facial neuralgia, idiopathic facial pain, atypical trigeminal neuralgia and trigeminal neuropathic pain. The international headache society defines atypical facial pain as persistent facial pain that

Neuralgia-inducing Cavitational Osteonecrosis It is also called NICO, alveolar cavitational osteopathosis bone marrow edema. It is controversial topic in the diagnosis of orofacial pain.

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Ischemic osteonecrosis can be cause by degeneration and death of marrow which results in decrease in bone marrow flow resulting in necrosis of bone. This type of osteonecrosis typically results in neuropathic type of pain and that is reason this is included in this chapter.

Clinical Features Age and sex distribution: It is usually seen in women and 3rd to 6th decade of life. Site: Third molar are is most frequently affected. Other site which are involved are walls of sinus and mandibular condyle. Nature of pain: Pain is described as deep ache or sharp bone pain. It begins as initially mild and vague which increase in intensity over the time. Pain can be referred to some distance from affected bone (Fig. 33.5).

Radiological Features

Ischemic myelofibrosis: There is wispy fibrous streaming between fat cells. Intramedullary fibrous scar: There are of dense fibrosis. Cavitations: These are extracellular cystic space which then coalesces to form large space which extent from cortex to cortex. Microinfarction: There is focal areas of marrow hemorr­ hage. There is also calcific necrotic detritus which smudged globular dark masses which represent destroyed trabe­ culae.

Management Antibiotics: This will combat infection and decrease pain. Decortications and curettage: This can be done to remove dead marrow and bone. Points to Remember

It appears as area of regional osteoporosis with ill defined radiolucency. There are also vertical remnants of lamina dura. In some cases there mixed sclerotic and radiolucent area. Bulls eye lesion: Faint centrals sclerotic oval surrounded by thick radiolucent circle which again surrounded by thick and faint sclerotic ring. This is called bull’s eye lesion. Technetium-99m scan show hot spot with increase uptake.

Histopathological Features Bone marrow edema show dilated marrow capillaries, sinusoids. Plasmostasis: There is serous ooze around blood vessels.

NICO, deep ache or sharp bone pain, Bulls eye lesion, hot spot on Technetium­99m scan, Plasmostasis, ischemic myelofibrosis, intramedullary fibrous scar, cavitations, microinfarction, calcific necrotic detritus, antibiotics, decortications and curettage.

Cluster Headache It is also called migrainous neuralgia, sphenopalatine neuralgia, histamine cephalgia and Horton syndrome. This is not common and has been called ‘the most pain syndrome known to human’. This can be cause by abnormal hypothalamic function and abnormal release histamine from mast cells.

Figure 33.5 Referred pain pattern of NICO

Neuromuscular Disorders and Orofacial Pain

Precipitating factors of headache are alcohol, cocaine, smoking and nitroglycerine.

Clinical Features Age and sex distribution: Can occur at any age with male predilection in the ratio of 6:1. Location: It is unilateral pain which follows the course of ophthalmic division of trigeminal nerve.

Paroxysmal Hemicranias The clinical features of this disease are similar to cluster headache. This can be differentiated from cluster headache by shorter duration of attacks with high frequency. Paroxys­ mal hemicranias also respond dramatically to indomethacin.

Clinical Features Age and sex distribution: This is more common women.

Nature of pain: It is deep felt in or behind the orbit. It can radiate to temporal and upper cheek region. Pain is paroxysmal and interns with burning or lancinating quality. Attacks last for 15 minutes to 3 hours (Fig. 33.6).

Site: Pain is unilateral and present on ocular, maxillary, temporal and frontal region.

Alarm clock headache: The pain begins at the same time in given 24 hours period with attack occurring in midnight.

Other features: There is lacrimation, conjunctival infec­ tion and rhinorrhea.

Other features: Other features like nasal stuffness, tear­ ing, facial flush congestion conjunctival blood vessel.

Management

Management Drugs which can be use in cluster headache are prednisone, ergotamine, lithium carbonate, indomethacin, methysergide maleate, verapamil and sumatriptan shows some relief in the patient. Neurosurgical intervention also can give relief in some patient. Points to Remember Migrainous neuralgia, deep felt pain in the orbit, Alarm clock headache, neurosurgical intervention.

Nature of pain: Pain last for 2 to 30 minutes. Pain is of boring nature. Attacks occur 2 to 40 in a day.

Indomethacin is drug used in this disease. There is resolution of symptoms within 2 days. It should be given 25 mg TDS for 10 days. If dose is not sufficient it can be increase to 50 mg TDS. Points to Remember Boring pain, indomethacin, lacrimation, conjucntival infection and rhinorrhea.

Migraine It is also called migraine syndrome or migraine headache. It is a syndrome presenting manifestations of diffuse disturbances in body functions occurring during or after stress, characterized by severe periodic headache, irritability and nausea.

Cause

Figure 33.6 Cluster headache showing alarm clock pattern

The cause of the disease is unknown but has seen postulated to be a discharge of autonomic centers in the forebrain leading to constriction in portions of the cerebral arterial tree. In susceptible patients this may become manifest in the preheadache phenomenon. Then, as part of an attempt to maintain cranial homeostasis there is decrease in constrictor in certain other cranial arteries, particularly branches of the external carotid. These secondary effects, possibly hormonal as well as neurogenic in origin are the source of the headache. Reduce activity of serotonin lead to vasoconstriction which leads to cerebral ischemia, which is followed by compensating vasodilatation with pain and cerebral edema.

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Trigger

Temporal Arteritis

Oral contraceptive, stress, alcohol, chocolate, missing a meal, flashing light, odors, lack of sleep, head trauma, physical exertion, fatigue, weather changes, fluorescent lights, aged cheese and menstruation.

It is also called giant cell arteritis, cranial arteritis. It is multifocal vasculitis of cranial arteries usually temporal artery. It is caused by autoimmunity to elastic lamina of the artery.

Clinical Features Age and sex distribution: It is usually seen in third decade of life. Women are more frequently affected than men. Site: The headache pain consists of severe pain in the temporal, frontal and retro orbital areas although other sites such as parietal, post auricular, occipital or sub occipital are also occasionally involved. The pain is usually unilateral but may become bilateral and generalized. Nature of pain: The frequency of attacks in extremely variable as they may occur at frequent intervals over period of year or on only a few occasions during the lifetime of patient. The pain is described as a deep aching, throbbing type. Other features: Other features like nausea vomiting, diarrhea, photophobia and phonophobia can occur. A prodromal stage (preheadache phenomena is noted by some patients consisting of lethargy and dejection several hours before the headache. Visual phenomena such as scintillation (seeing sparks), hallucinations or scotoma (partial or complete loss of light perception), aphasia (loss of ability to express thought) and temporal or partial blindness are often described.

Clinical Features Age and sex distribution: It is seen in old age above 50 years of age. Women are affected more commonly than family. Nature of pain: There is unilateral throbbing headache which later on intense, aching, burning and lancinating pain. Pain coincides with heartbeat (Fig. 33.7). Signs: Superficial temporal artery is sensitive to palpation and may become erythematous, swollen, and tortuous. Jaw claudication: There is pain while mastication. This is called jaw claudication. Eye involvement: There is loss of vision and retro­orbital pain. There may be blindness which is cause by involvement of posterior cilliary artery. This artery supplies optic disc which results ischemic papillopathy. Polymyalgia rheumatica: There is generalized muscle aching and stiffness. Other features: There is fever, malaise, nausea, anorexia, vomiting sore throat and earache.

Management The treatment of migraine includes a wide variety of drugs ranging from acetylsalicylic acid and codeine to ergotamine, methyl salicylic and nor epinephrine. Cognitive behavioral therapy—volitional modulation of stress response should be done. The prognosis of the disease is good, since the condition is not dangerous, and may undergo complete and permanent remission. Points to Remember Severe pain in the temporal, frontal and retro orbital areas, deep aching, throbbing type pain, nauseas vomiting, scintillation, scotoma, aphasia, acetylsalicylic acid, cognitive behavioral therapy.

Figure 33.7 Temporal arteritis pattern of pain

Neuromuscular Disorders and Orofacial Pain

Histopathological Features There is chronic inflammation of tunica intima and tunica media of the temporal artery. There is also narrowing of lumen from edema and proliferation of the tunica intima. There is also multinucleated giant cells which are mixed with macrophages, plasma cells and lymphocytes.

Management Corticosteroid: This disease respond well systemic and topical corticosteroid. Points to Remember Giant cell arteritis, unilateral throbbing headache, aching, burning and lancinating pain, Jaw claudication, polymyalgia rheumatica, chronic inflammation of tunica intima and tunica media of the temporal artery, multinucleated giant cells, corticosteroid.

Burning Mouth Syndrome It is also called stomatopyrosis, stomatodynia, burning tongue syndrome and glossopyrosis. Burning Mouth Syndrome (BMS), is condition characterized by a sensation described by the patient as stinging, burning that affects the oral mucosa, in the absence of clinical or laboratory data to justify these symptoms. There is burning and pain of the mouth or of the tongue, without any visible changes is common with many causes. When the tongue is involved, it is called glossopyrosis. When mucosal surface is involved, it is called stomatopyrosis. It is a chronic orofacial pain, unaccompanied by mucosal lesions or other evident clinical signs upon examination. Careful clinical histories, a general physical examination, a detailed examination of the oral cavity are mandatory to avoid misdiagnosis and inaccuracies in treatment of BMS.

Definition It is defined as “an intraoral burning sensation for which no medical or dental cause can be found” (Headache Classification Committee of the International Headache Society, 2004).

Epidemiology The actual prevalence of BMS is difficult to ascertain however, vary widely, with prevalence varying between

0.7 and 4.5 percent. It is considerably more common in women than men the peak prevalence in the fourth to sixth decades of life. Burning mouth also often coexists with other chronic pain disorders.

Cause There are various local and systemic factors which can cause burning mouth syndrome. Systemic factors: As it is found more common in postmenopausal women, estrogen deficiency is thought to be causative factors. Other systemic factors which can be associated are vitamin deficiency, diabetes mellitus, gastritis, hypothyroidism, mercurlism and Parkinson disease. Local factor: Local factors like temporomandibular dysfunction, OSMF, oral candidiasis, trigeminal neuralgia and xerostomia can be responsible for burning mouth syndrome. Autoimmune: Abnormal level of antinuclear antibodies and rheumatoid factors are found in serum of patient of burning mouth syndrome. Psychological factors: It include anxiety, depression, compulsive disorders, psychological stress and cancero­ phobia. Idiopathic factor: Most times there was no cause found for BMS.

Classification and Subtypes Different classification types have been proposed based on the daily fluctuations of the symptoms (Table 33.1).

Table 33.1 Classification of BMS subtype

Clinical findings

Association

Type 1 Daily pain, not present upon awakening, worsens as the day progresses

Nonpsychiatric

Type 2 Constant pain

Psychiatric, chronic anxiety

Type 3 Intermittent pain in unusual sites (floor of mouth)

Allergic contact anxiety due to preserving agents and additives

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Textbook of Oral Pathology Fundamental inclusion criteria for BMS (Scala et al)

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• Burning sensation located in some area of the oral mucosa; • Persistence of the manifestations for at least 4 to 6 months; • Continuous burning sensation throughout the day, or with increased intensity towards the afternoon­evening; • Infrequent associated sleep disturbances; and • Symptoms relief upon eating or drinking Additional inclusion criteria • Dysgeusia/or Xerostomia • Sensory or chemosensory alteration • Mood changes or psychopathological alterations.

In 1994, Lamey et al, divided the syndrome into three types based on different types of patients •

Type 1: Characterized by progressive pain, patients wake up without pain, which then increases throughout the day, affects approximately 35 percent of patients. This type may be associated with systemic diseases, such as nutritional deficiencies. • Type 2: The symptoms are constant throughout the day and patients find it difficult to get to sleep, represents 55 percent. These patients usually present associated psychological disorders. • Type 3: Symptoms are intermittent, with atypical location and pain. Constitutes 10 percent of patients. It seems that contact with oral allergens could play an important etiologic role in this group.

Types (Cerchiari et al classified BMS according to the associated risk factors:) • • • •

Idiopathic Psychogenic Local and Systemic.

Scala et al proposed two clinical forms of BMS as • ‘ Primary’ or essential/idiopathic BMS, in which the causes cannot be identified. • ‘Secondary’ BMS, resulting from local factors or systemic conditions.

Clinical Features Age and sex distribution: Burning mouth syndrome is most common in middle aged women especially around the time of menopause.

Usually the onset is spontaneous but at times there is a precipitating event such as trauma or dental treatment. There can be an associated xerostomia, dysesthesia and/or dysgeusia. Nature of pain: The patient complains of intense and unbearable pain that interferes with eating, sleeping and virtually every other body function. Usually, there is continuous and spontaneous with an intense burning sensation reported by the patient as if the mouth or tongue were scalded or burnt. Tongue: The tongue may appear as red or atrophic or the mucosa may appear entirely normal. The complaints are usually limited to tongue but may involve the entire mucosa. Psychological dysfunction: Patient who suffers from burning mouth syndrome may be having depression, anxiety, or irritability.

Diagnosis The diagnosis of burning mouth syndrome depends on ex­ clusion of a detectable organic basis for the complaint. The diagnosis of BMS requires careful evaluation of the symp­ toms, with due consideration of a series of inclusion criteria.

Management Removal of causative factors: Removal of factor which is causing the burning mouth syndrome should be done. Mood altering drug: Mood altering drug like chlordia­ zepoxide may be beneficial in some patient. Other drug like clonazepam, amitriptyline, TENS, vitamin B complex and psychological counseling should be given. Points to Remember Stomatopyrosis, intense and unbearable pain, red tongue, psychological dysfunction, clonazepam, Mood altering drug.

BIBLIOGRAPHY 1. Adams WR, Spolnick KJ, Bouquot JE. Maxillofacial osteonecrosis in a patient with multiple facial pain: J Oral Pathol Med. 1999;28:423­32. 2. Benoliel R, Sharav Y. Paroxysmal hemicranias: a case studies and review of litertature: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85:285­92.

Neuromuscular Disorders and Orofacial Pain 3. Benoliel R, Zadik Y, Eliav E Peripheral, et al. Painful traumatic trigeminal neuropathy: clinical features in 91 cases and proposal of novel diagnostic criteria, J Orofac Pain. 2012;26(1):49­58. 4. Bergdahl M, Bergdahl J. Burning mouth syndrome: a prevalence and associated factors: J Oral Pathol Med. 1999;28:350­4. 5. Boes CJ, Doddick DW. Redefining the clinical spectrum of chronic paroxysmal hemicranias: J Headache Pain. 2002;42(8):699­708. 6. Bouquot JE, McMahon RE. Neuropathic pain in maxillofcail osteonecrosis: (NICO) J Oral Pathol Med. 2000;29:345. 7. Chevalier V, Arbab­Chirani R, Tea SH, et al. Facial palsy after inferior alveolar nerve block: case report and review of the literature. Int J Oral Maxillofac Surg. 2010;39(11):1139­42. 8. Chikazu D, Mori Y, Saijo HA, et al. Case of tumoural calcinosis in the temporomandibular joint associated with systemic sclerosis, Int J Oral Maxillofac Surg. 2008;37(2):190­3. 9. Cologne D, Torelli P, Manzoni GC. Migraine with aura: a review of 81 patient with 20­year follow­up: Cephalagia. 1998;18:690­6. 10. DeNucci DJ, Chen CC, Sobiski C, et al. The use of SPECT bone scan to evaluate patient with idiopathic jaw pain: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90:750­7. 11. Evans RW, Graff­Radford SB, Bassiur JP. Pretrigeminal neuralgia: headache. 2005;45:1204­7. 12. Fridrich KL, Taylor RW, Olson RA. Dermatomyositis presenting with Ludwig’s angina. Oral Surg Oral Med Oral Pathol. 1987;63(1):21­4. 13. Friedman RD, Joe J, Bodak LZ. Myotonic dystrophy: report of a case. Oral Surg Oral Med Oral Pathol. 1980;50(3):229­32. 14. Godhi SS, Singh A, Kukreja P, et al. Myositis ossificans circumscripta involving bilateral masticatory muscles. J Craniofac Surg. 2011;22(6):e11­3. 15. Gonçalves LM, Bezerra­Júnior JR, Gordón­Núñez MA, et al. Oral manifestations as important symptoms for juvenile dermatomyositis early diagnosis: a case report. Int J Paediatr Dent. 2011;21(1):77­80. 16. Guarda­Nardini L, Piccotti F, Ferronato G, et al. Myositis ossificans traumatica of the temporalis muscle: a case report and diagnostic considerations. Oral Maxillofac Surg. 2012;16(2):221­5. 17. Horowitz M, Horowitz M, Ochs M, et al. Trigeminal neuralgia and glossopharyngeal neuralgia: two orofacial pain syndromes encountered by dentists. J Am Dent Assoc. 2004;135(10):1427­33. 18. Hungerford Rw, Munsat Tl. Mandibular Fracture and Myotonic Dystrophy; Report of a Case. Oral Surg Oral Med Oral Pathol. 1964;18:121­5. 19. Johansson B. Traumatic myositis ossificans. Oral Surg Oral Med Oral Pathol. 1984;58(6):742.

20. Khan OA. Gabapentin relives trigeminal neuralgia in multiple sclerosis patients: Neurology. 1998;51:611­4. 21. Kleineggar CL, Lilly GE. Cranial arteritis a medical emergency with orofacial manifestation: J AM Dent Assoc. 1999;130:1203­9. 22. Laskawi R, Drobik C, Schonebeck C. Up to date report of botulinum toxin type A treatment in paeitn with gustatory sweating (Frey’s syndrome): Laryngscope. 1998;108:381­4. 23. Laskawi R Ellies M, Rodel R, et al. Gustatory sweating: a clinical implication and etiologic aspect: J Oral Maxillofac Surg. 1999;57:642­9. 24. Lloyd JM, Mitchell RG. Myasthenia gravis as a cause of facial pain, Oral Surg Oral Med Oral Pathol. 1988;66(1):45­6. 25. Marbach JJ, Lavigne GJ, Dubner R, et al. Incidence of phantom tooth pain: an atypical facial neuralgia: Oral Surg Oral Med Oral Pathol. 1982;53:190­3. 26. Martínez­González JM, Martínez­Rodríguez N, Calvo­ Guirado JL, et al. Glossopharyngeal neuralgia: a presentation of 14 cases. J Oral Maxillofac Surg. 2011;69(6):e38­41. 27. Muzyka BC, De Rossi SS. A review of burning mouth syndrome: Cutis. 1999;64:29­35. 28. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology, 3rd edn, Saunder Elsevier, 2009. 29. Parkash H, Goyal MM. Myositis ossificans of medial pterygoid muscle. A cause for temporomandibular joint ankylosis. Oral Surg Oral Med Oral Pathol. 1992;73(1):27­8. 30. Penarrocha M, Bagan JV, Penarrocha MA, et al. Cluster headache and cocaine use: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90:271­4. 31. Ramsey MJ, Der Simonian R, Holtel MR, et al. Corticosteodi treatment for idiopathic facial nerve paralysis: a meta analysis : Laryngoscope. 2000;110:335­41. 32. Roller NW, Garfunkel A, Nichols C, et al. Amyotrophic lateral sclerosis, Oral Surg Oral Med Oral Pathol. 1974;37(1):46­52. 33. Sanger RG, Kirby JW. Report of a case, Oral Surg Oral Med Oral Pathol. 1973;35(4):476­88. 34. Santos Rde F, Brasileiro BF. Diagnosis and management of Bell’s palsy. Gen Dent. 2011;59(4):266­71. 35. SasakUra Y, Kumasaka S, Takashi T, et al. Myasthenia gravis associated with reduced masticatory function: Int J Oral Maxillofac Surg. 2000;29:381­3. 36. Schwartz AH. Trigeminal neuralgia in patient with multiple sclerosis and chronic inflammatory demyelinating polyneuropathy: J Am Dent Assoc. 2005;136:469­76. 37. Shuaib A, Lee MA. Recurrent peripheral facial nerve palsy after dental procedures. Oral Surg Oral Med Oral Pathol. 1990;70(6):738­40. 38. Sun WL, Yan JL, Chen LL. Ramsay Hunt syndrome with unilateral polyneuropathy involving cranial nerves V, VII, VIII, and XII in a diabetic patient. Quintessence Int. 2011;42(10):873­7.

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39. Talacko AA, Reade PC. Progressive bulbar palsy: a case report of a type of motor neuron disease presenting with oral symptoms. Oral Surg Oral Med Oral Pathol. 1990;69(2):182­4. 40. Von Lindern JJ, Niederhagen B, Berge S, et al. Frey syndrome: Cancer. 2000;89:1659­63. 41. Weitzner S. Pathosis of the tongue in oculopharyngeal

muscular dystrophy. Report of two cases. Oral Surg Oral Med Oral Pathol. 1969;28(4):613­7 42. Woke JH. Disease that masquerade as motor neuron disease: Lancet. 1996;347:1347­8. 43. Zakrzewska JM, Patsalos PN. Drugs used in the management of trigeminal neuralgia. Oral Surg Oral Med Oral Pathol. 1992;74(4):439­50.

MULTIPLE CHOICE QUESTIONS



1. Trigeminal neuralgia is also called: a. Tic douloureux b. Trifacial neuralgia c. Fothergill’s disease d. All

7. Myopathic facies and swan neck seen in: a. Myasthenia gravis b. Bell’s palsy c. Dystrophic myotonia d. Motor system disease

2. Following are the trigger zones for trigeminal neuralgia except: a. Tongue b. Lips c. Ala of nose d. Cheeks

8. Purplish black intrinsic staining of teeth seen in: a. Dermatomyositis b. Congenital myotonia c. Both d. None

3. Bell’s palsy affects: a. V cranial nerve c. VIII cranial nerve

b. d.

VII cranial nerve X cranial nerve

4. Syndrome associated with cranial nerve is: a. Bowen syndrome b. Book’s syndrome c. Melkersson­Rosenthal syndrome d. Mohr’s syndrome 5. ‘Crocodile tears’ seen in: a. Frey’s syndrome b. c. Motor system disease d.

Trigeminal neuralgia Bell’s palsy

6. Minor starch iodine test is perform to diagnose: a. Bell’s palsy b. Frey’s syndrome c. Trigeminal neuralgia d. Muscle dystrophy

9. Minor Starch-Iodine test is done for: a. Bell’s palsy b. Frey’s syndrome c. Both a and b d. None of the above 10. Staccato type of speech is an interesting feature of: a. Multiple sclerosis b. Pretrigeminal neuralgia c. Fothergill’s disease d. Dental pathosis 11. Ramsay Hunt syndrome is associated with: a. Vascular malformations b. Overdose of phenytoin c. Zoster infection of geniculate ganglion canal d. Glossopharyngeal neuralgia 12. Alarm clock headache is the characteristic feature of: a. Gustatory sweating b. Cluster headache c. Tic douloureux d. Multiple sclerosis

34

Forensic Odontology

Anil Govindrao Ghom, Savita Ghom Chapter Outline     Â

Record management Identification Dental evaluation Personal recognition Fingerprinting

INTRODUCTION Forensic odontology is the subject concerned with the application of medical and paramedical science knowledge to certain branches of law, both civil and criminal. The medicolegal information obtained from the examination of teeth and jaws falls in the preview of forensic odontology. Upon exposure to physical injury and putrefaction, the human dentition, the enamel of which is the hardest substance in the body outlasts all other tissues. The material used in restoration is also extremely resistant to destruction by chemical and physical elements. The fundamental principles of dental identification are those of comparison (when antemortem records of the proposed deceased are available) and exclusion (when antemortem records of other persons are available). In the absence of the antemortem records attempt to elicit dental information is made by interrogating the relatives and friends of the deceased, which may frequently prove unreliable. Definition Forensic odontology may be defined as the application of dental science to the administration of the law and the furtherance of justice.

    Â

Physical anthropologic examination of bones and teeth Postmortem serology and DNA profiling Bite marks Human abuse Dentist as expert witness

Treatment plan which is given to the patient should be Role of Forensic Odontology updated in the record. All the letter of reference, letter of • Record preparation: The correct handling and be examconsent, insurance and financial statement should store ination and the proper preparation and presentation in the record of the patient. of dental evidence and should criminalcontain legal The progress note inofboth the civil patient procedures. information about the restorative and therapeutic procedure • Identification: identification, either indiwhich is carried out Personal on to the patient. vidually or in context of mass Summaries of the telephonic disasters. conversation with the • Bite mark investigation: Investigation of criminal patient, consultant, insurance company representative and cases where bite marks are involved and the legal authorities should be maintained in the record. interpretation of bite marks. Record should be signed by the personnel. Any change • H uman abuse: Recognition of domestic, childbe made in the record should not erase but a lineand should abuse. crossed on it, so that it is readable. This will help to remove • Legal aspect: Legal aspect of dental traumatology. any fraud intention to alter record. • Others: Forensic odontology also deals with age assessment of patient and comparison and identification of lip print.

RECORD MANAGEMENT The dental record is a legal document of dentist which contains information about subjective and objective finding of the patient. It also includes pathological report, radiographs, and clinical photographs of the patient.

Textbook of Oral Pathology

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Treatment plan which is given to the patient should be updated in the record. All the letter of reference, letter of consent, insurance and financial statement should be store in the record of the patient. The progress note of the patient should contain information about the restorative and therapeutic procedure which is carried out on to the patient. Summaries of the telephonic conversation with the patient, consultant, insurance company representative and legal authorities should be maintained in the record. Record should be signed by the personnel. Any change made in the record should not erase but a line should be crossed on it, so that it is readable. This will help to remove any fraud intention to alter record. It is common now a day that dental record to be maintained electronically. New software programs are developed to maintain patient dental information. This is advantageous as it can be easily networked and transferred. Record should be kept minimum of 7 to 10 years. In the case of pediatric patient record should be maintain until the patient reaches the age to maturity.

Method • • • • •

Dental evaluation Personal recognition Fingerprinting (friction ridge analysis) Physical anthropological examination of bones Serologic and genetic comparison technique.

Results • P ositive identification: No major difference found between antemortem and postmortem data. • Presumptive (possible identification): Some information is missing form antemortem or postmortem records to have positive identification. There is lot of similarities between ante and postmortem record • Insufficient identification evidence: There is less supportive evidence to come at the conclusion on scientific principle. • Exclusion of identification evidence: There are discrepancies seen between antemortem and postmortem data. Exclusion is as important as positive identification.

IDENTIFICATION

DENTAL EVALUATION

Forensic odontology is concerned with the identification of both living and deceased person.

Dental Comparison

Issues of Death Investigation • C ause of death: The sequence which initiated the death of person like physical, chemical injury or disease of person. • Mechanism of death: The pathological process which results in death. • Mode or manner of death: Whether it is natural, accidental, suicidal or homicide. • Undetermined death: The manner of death is not established due to decomposition, dismemberment or postmortem destruction of remains by insect or feral animals. The death certificate is required for probation of will, life insurance claim, and resolution of affairs associated with settlement of an estate.

Dental comparison affords a potentially straightforward and simple means of establishing identity. The method of dental identification depends upon: ∙ The relative resistance of the mineralized dental tissues and dental restoration to changes resulting from decomposition or harsh environment extremes such as conditions of temperature and violent physical forces. ∙ The unique individual characteristic of the dentition and dental restoration. ∙ The availability of documentation of the antemortem status of the dentition in the form of dental treatment records and diagnostic radiographs. Each individual has 32 teeth with 5 surfaces each with their own character of size, shape, position and spacing with the result that no 2 sets of teeth are alike. Teeth extracted after death leave a completely different socket from those removed during life. When the tooth is removed or dental work of any sort is carried out the

Forensic Odontology

teeth pattern is changed and its record may exist with the dentist. In natural decomposition, teeth are practically indestructible. They are not easily destroyed by fire. Being sheltered in the oral cavity, they are generally not damaged. Teeth as well as dentures made of acrylic resin are generally resistant to the action of corrosive acids. The identification from data of authenticated teeth depends entirely upon the accuracy and completeness of authenticated records made during life. Composition of Dental Records • T he number and situation of teeth present and number and situation of teeth lost. • Arrangement, irregularities, erosion, caries, fillings, bridge crown work and dentures. • Exact shape of edentulous arch. • Some of the common identifying features of teeth pertain to faulty development, faulty alignment, presence of stains, localized wear on certain teeth and missing teeth. Faulty development: Teeth may be undersized, oversized, notched or present some other irregularity as a result of faulty development and malformation. Hutchinson’s teeth constitute a classical example of malformation of the incisor in congenital syphilis. These changes are most conspicuous in central incisors which are usually small, widely spaced, notched and less broad at the cutting edge than at the gum margin giving them the appearance of tip of screw driver. Faulty alignment: The defect in the alignment may be in the space between teeth, e.g. widely spaced teeth or overriding teeth. Between the teeth of the upper and lower jaw when there is protrusion of upper incisors resulting in overlap of lateral incisors the bite pattern is known as overbite and the reverse pattern is known as cross-bite. Stains: Pan (betel leaf, tobacco) chewing habit stains the teeth with dark brown or black deposits. Yellowish or dark brown stain on the back of incisor teeth is common in cigarette smokers. Chalky white or yellowish brown areas of discoloration are found in fluorosis. Metal poisoning may cause pigmentation of gums and there by suggest a cause of death. Copper causes green and mercury and lead a blue black line on the gums. Gum hyperplasia induced by phenytoin may aid in identification and suggest epileptic seizure as a cause of death.

Localized wear on certain teeth: A pipe smoker may have localized wear of teeth either on incisors or at angle of mouth due to position of pipe. Notched incisors from holding thread, pins, nail, between teeth on day-to-day basis may suggest the occupation of tailor or hairdresser or cobbler. Missing teeth: The missing tooth may have been lost ante mortem or postmortem. Antemortem loss of teeth due to trauma at or near the time of death if frequently associated with fracture of thin bony plate surrounding the alveolus. In loose tooth which has fallen out, it is not so. Extraction or tooth loss in living person is followed by bleeding from its socket which stops in about 24 hr or sometimes 2 to 3 days when the clot forms in the raw socket. By about 14 days, the clot is obliterated by fibrous tissue and the alveolar rim is smoothened by resorption of bone. By about 5 to 6 months, gradual new bone formation fills the socket but its outline is still visible on X-ray examination. By about 6 months to 1 year, remodeling of new bone completely obliterates the socket leaving a slight depression and the socket outline is not visible on X-ray examination. In recently recovered remains, postmortem tooth loss discloses a clean socket devoid of blood clot. In skeleton in which postmortem loss of teeth is common, the bony rim of alveolus is sharp and feathered.

Procedure or Guideline for Dental Identification It should include not only the oral cavity of the victim but when applicable, the surrounding scene as well, especially in case of conflagration or when only the remnants of the dental arches may remain scattered and rubble and debris.

Postmortem Examination Recovery of dental structure: The task of dental identification begins at the site of discovery of the body. When the gross postmortem changes affecting the teeth have occurred, such as charring, disintegration and fragmentation in fires and high impact accident, meticulous care in their recovery and conveyance to the mortuary are of utmost important. Displaced teeth in decomposed bodies or skeletal remains should be saved, labeled and later secured to the intraoral position using adhesive cement. Most open alveoli are the result of postmortem tooth loss. In recently recovered remains, postmortem tooth loss disclose a clean socket devoid of blood clots.

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Instrument: Instruments used for dental examination includes explorer, mirror, tissue forceps, heavy duty autopsy scalpel, handle and blades, tissue clamps, irrigating syringe, rubber autopsy gloves, polythene specimen bags, gauze sponges (for tooth cleansing) and a source of illumination (flash light or battery operated head lamps); and dental examination form should be used. Photography: It should be taken of full head and face views. Images of occlusal plane of maxillary and mandibular arch should be taken. Reconstruction and examination: Examination should be performed by two persons thoroughly familiar with dental terminology, one actually performing the examination and one recording the data. The recorder should view the actual teeth in order to record the basic morphological pattern of the restoration or cavities. In some cases, it is necessary to remove the jaw from the body for more detailed examination and future reference. Radiography: The use of double pack intraoral radiograph should be used. When placement of intraoral film is not possible occlusal film or lateral oblique film should be used. Charting of dental records (odontogram): The point to be considered while charting are missing teeth, unerupted teeth, supernumerary teeth, restoration, prosthesis, dentures, decayed, broken teeth, mal position, overlapping, crowding and spacing, peculiar shape of teeth. Identification of edentulous bodies: Frequently dentures are present in the mouth of unknown bodies or may be found elsewhere. If the denture can be identified and it can be shown to fit the mouth of the deceased, a reliable identification can be made. The most reliable means of identification of denture is for them to be permanently marked with the name of the patient or some code during manufacture. Problems in identification: It depends upon the circumstances surrounding the death and the care exists in its collection and transport. Incineration produces damage to teeth ranging from mild scorching of the surface to severe charring of the enamel and dentine with crumbling of the crown. Sustained very high temperature will result in calcinations of the teeth with considerable overall shrinkage. Burnt teeth are usually very fragile and suffer separation of the enamel and often gross disintegration of the crowns. In high impact accidents such as aircraft and high speed road crashes much mechanical damage can occur and teeth and jaws may fracture and disintegrate.

Failure to recover significant material may result in failure to identify a body.

Antemortem Record Examination Acquiring antemortem data: This data can be obtained from police, medical examiner. Forensic dentist should determine that records indicate name of person to be identified, and name and address of submitting dentist. Inadequate antemortem data: Errors in charting teeth treated and insufficient descriptive details about the treatment provided are common. Other difficulty arises when a dentist has retired and destroyed his records.

Comparison of Antemortem and Postmortem Record After all the records are collected, it is compared to similarities and discrepancies. Forensic dentist must rely on antemortem records given to him are truly of those person that are purported to represent. Acceptable discrepancies: In some cases, acceptable discrepancies are allowed. For example, if an antemortem record shows deciduous teeth and postmortem records shows no deciduous teeth. In this case as tooth is exfoliated this is allowed. Problems in comparison: Many time postmortem dental materials is compromised due to fractured, avulsed, melting at high fire. When antemortem records radiographs are of poor quality then also there are problems in comparison. Written conclusion: It should be based on objective analysis of data presented and it should be supportable or defensible in court of law.

Role of Dentist in Multiple (Mass) Fatality Incident Identification Mass fatality incidence (MFI) can occur due to natural, accidental and criminal (serial homicide, mass suicide and acts of terrorism). Natural: It include earthquakes, tornadoes, hurricanes, volcanic eruption, fire storms, tsunamis and floods. Victims in natural disaster are scattered throughout broad area. Many of the victims are unknown to areas as they may be tourist. Another problem occur in natural disaster, there is difficulty in retrieval of information and as dental records may be destroyed in natural disaster. Accident: It is cause by transportation accident, fires, industrial and mining accidents. Many times in industrial

Forensic Odontology

and mining accidents as people wear same short of cloths, it is very difficult to identify these bodies Criminal disasters: The rise in national and international terrorism in 21st century has lead to more participation of forensic dentist in identification. Age: Age can be established by radiography of bones and teeth (for root calcification). Calcification of costal cartilage and osteoarthritic changes in large joints and the spine also help. Sex and race: May be deduced by radiography in some cases. Occupation: This can sometimes be deduced from X-ray. The whole range of pulmonary occupational diseases such as silicosis, asbestosis may show specific radiographic findings. The radial artery in laborer’s using pneumatic drill may show calcification; coal carriers and professional wrestlers are liable to calcified lesions of the ligamentum nuchae. Football players may show calcified hematoma of the thigh muscle. Identification: To is possible by comparison of postmortem and antemortem X-ray. Cause of death: Fracture of bones seen on X-ray may indicate their antemortem origin and these include depressed fracture of skull, fracture of hyoid, fracture dislocation of cervical vertebrae, severe injury to bones by cutting instrument or fracture of several ribs which are incompatible with life. Foreign bodies in the upper respiratory tract provide valuable clue. Evidence of poisoning by heavy metals and signs of diseases such as malignant growth may be apparent. Technologic aids in multiple fatality incident analysis: These include X-ray, UV light, postmortem serology and DNA profiling. X-ray: All bodies which are found under suspicious circumstances and which are rendered unrecognizable due to prolonged immersion in water, burning by fire and acid or by any other destructive means such as explosion should be routinely X-rayed. A dental radiograph when available constitutes one of the most valuable pieces of evidence for identification purpose. Panoramic X-ray technique provides excellent pictorial dental record. Computer software technology: The CAPMI (computer assisted postmortem identification) system compares dental record of victims of mass disaster and enables rapid identification of air crash, flood and explosion victims.

Radiography can provide information in relation to age, sex, race, and occupation, diagnosis of certain conditions and identification and cause of death. UV rays: An ultraviolet lamp can be used to locate and define tattoo marks and scars on burned and decomposed remains, and to segregate bones in cases of mix-up. When examined by UV light washed blood stains are readily seen and seminal stains give a bluish white fluorescence. Digital photography: The camera used should be LSR digital camera with interchangeable lenses. Direct digital radiography: This device creates direct image of on the pixels of its CCD or CMOS. This will save time so it is recommended for clinical and forensics casework. Cone beam computed tomography CBCT: It pro vide 3D imaging modality to collect complete maxillamandibular facial anatomic volume of data. X-ray fluorescence (XRF) methodology: Analysis of dental material in cremation and difficult forensic identification case may be facilitated by this technique.

PERSONAL RECOGNITION It is least reliable method used to identify the individual. This is done by visual identification by family member, friend or acquaintance. Many time there is misidentification of the body by this way.

FINGERPRINTING It is analysis of epidermal friction ridges of the finger, palms and feet. This pattern is unique for each person. These fingerprint are genetically determined and even fingerprint of twins are not identical.

PHYSICAL ANTHROPOLOGIC EXAMINATION OF BONES AND TEETH It is analysis of calcified structure of body bone and teeth. Chronological age assessment may be an important factor in establishing the identity of the living or deceased person. It is also important in legal proceedings when specific charge for particular offence may depend on whether the alleged offender is a juvenile. Stage of eruption of the teeth and evidence of changes due to function such as attrition can give an approximate estimate of age. Radiography can provide a great detail, the gross stage of dental development of the dentition.

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Histological: It requires preparation of the tissue for detailed microscopic examination, which can determine more accurately the stage of development of the dentition. 854

Physical and chemical analysis: It is done to determine alterations in ion levels with age have been proposed.

POSTMORTEM SEROLOGY AND DNA PROFILING A known postmortem grouping of an individual serves to narrow the range of possible identities. Even in putrefied bodies, blood group antigen may be detectable for serological studies. The bone marrow in skeletal remains may still retain serologically detectable antigens. This is useful if suitable tissue (blood, semen stored in bank) is available. If such tissue is available, a DNA profiling or autopsy derived tissue should be compared by single probe analysis with that of parent, children, sibling and if be necessary other relatives. This is now used worldwide in aircraft and other major accidents. The techniques which are used for DNA profiling are restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR). The RFLP results in splitting source DNA into thousands of fragment. The PCR can do evaluation of denture DNA or minute quantity of DNA.

Figure 34.2 Bite marks on inmate subject

BITE MARKS (FIGS 34.1 TO 34.3) One of the two major interests of the forensic odontologist is one that has direct relevance to the pathologist, in that it concerns the interpretation of trauma to the body surface.

Figure 34.3 Sexual bite mark

Dental evidence is used to identify the perpetrators of a crime who happened to have left their teeth marks in some substances left at the scene. Generally, it is easier to exclude a certain person than to identify one conclusively from the bite mark.

Definition A bite mark is a patterned injury produced by teeth on animate or inanimate objects, is caused by small enamel defects on the incisal edge of incisor teeth creating individual characteristics during biting procedures. It can be: Tooth mark: Mark left by a tooth (human or non-human). Figure 34.1 Bite marks seen on animate subjects

Arch mark: Mark produce by four or five adjacent teeth in the same arch.

Forensic Odontology

Causes of Bite Marks • C hild abuse: It can be found anywhere on the body, favorite sites being the arms, hands, shoulders, cheeks, buttocks and trunk. Most of the time it is inflicted by the mother. • Sexual assaults: It usually occurs in cases of rape. Most common site of it is breast and nipples but neck, shoulders, thighs, abdomen, pubis and even vulva may be attacked. • It may also be inflicted on police officers when attempting to arrest resisting offenders. • Sports: Bites can occur in sporting events especially football and some forms of wrestling. In this, it can occur anywhere but hands, fingers, nose, forearms, ears and even lips may be target. • Self inflicted: Falls onto the face or a fit may cause the tongue and lips to be badly bitten. Some persons deliberately bite themselves, sometime to fabricate injuries for a variety of motives ranging from gain to psychiatric disorders.

Importance of Bite Marks (Figs 34.4 and 34.5) It can permit precise identification because the alignment of teeth is peculiar to each individual. The mark may be on the article of food found at the scene of crime or on human being to realize that a bite on human flesh can have marks

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Figure 34.5 Human dentition consist of 32 teeth with 5 surface

not necessarily due to break in the continuity of the skin but due to a small subdermal or thin deep hemorrhage. Bite marks are always contaminated by saliva and therefore contain amylase, ptyalin and blood group which can be determined by the cast of suspect of mouth is made and transparency of his bite compared to that of the unknown bite. It should be remembered that bite marks on skin are modified by its elasticity when the teeth are withdrawn. Self-inflicted bite marks are seen in Lesch-Nyhan syndrome. This syndrome is X-linked manifesting insensitivity to pain and self-mutilation by chewing away of lip.

Method of Preservation of Bite Marks

Figure 34.4 Bite mark is represented distorted image of

human dentition

The doctor should be asked how the bite mark may be best preserved. When the substance is plastic such as butter, cheese, lard, or chocolate, it should be stored in a refrigerator to prevent melting or gradual flowing. It should not be deep frozen as this may cause brittleness and cracking. Fruits should be preserved in Campden solution, a metabisulphite fluid used for fruit bottling. If it is not there then 5 percent acetic acid in 40 percent aqueous formaldehyde solution can be used. Whatever preservation is recommended, the object should be adequately photographed with film plane at right angles to the bite and a scale placed in the focal plane. Death freezes a bite mark but a subdermal hemorrhage in living person disappears within 20 minutes hence it is important to take an immediate photograph of the bite mark.

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Classification of Bite Marks 856

• Non human (animals) • Human – In foodstuffs (in a part eaten foodstuff abandoned by offenders at the scene of crime). – On non biological object (on pencils, pipe stems and detonators) – In human skin – Non criminal (erotic bite) – Criminal—it can be offensive (upon victim by assailant) and defensive (upon assailant by victim).

Bite Marks on Foodstuff Foodstuff bite marks can be classified in to 3 types: Type I: Bites that are found in material such as chocolate, which fracture readily with limited depth of tooth penetration. Type II: Bites formed in foods where teeth obtain a good grip and then bitten piece is removed by fracturing it from main material, e.g. apples. Type III: Bites in which teeth bite right through the bitten material, e.g. cheese. These bite exhibits extensive scrape marks and may give and indication of the relative position of upper and lower incisor teeth in centric occlusion. Depth of penetration of the teeth: Where there is only minimum penetration of teeth into the food, the record is of biting edges and where there is greater penetration the record is of the labial aspect of the teeth. Time and temperature: Bite mark in foodstuff may produce the exact mesial-distal dimension of the teeth provided the record is taken immediately after the bite was made. Dimensional and color changes are expected to occur in the foodstuffs due to effect of temperature.

Bite Marks in Human Skin Human tissue has been described as one of the least dependable substances for the registration of bite marks as the bite marks in the tissue is affected by several variables.

Status of the Tissue Site: Type of tissue/condition of skin. For example, loose skin or excessive subcutaneous fat commonly demonstrated easy and extensive brushing leading to a poor bite mark definition. Areas of fibrous tissue or high muscle content

tend to bruise less easily and thus are more likely to demonstrate a bite mark. Age: Infants and elderly individual tend to bruise more easily than other age groups marking the detection of bite marks more difficult. Sex: Females tend to bruise easier than males. Once produced a bite mark will be evident for a longer period of time on females as compared to males. In human, bite mark can be sexual or assault type.

Influencing Factor Bite mark can be influenced by time elapsed between the actual biting and when the impression is made. Depression of the skin as occurs in most bite marks will recover within 10 to 20 minutes after the bite, although discoloration and swelling may be present 24 to 72 hours on a living object. The force exerted: The skin appearance of bite mark may vary from bruising, abrasion, and indentation to actual lacerations. The number of teeth: In general, the more teeth marks present in the bite marks, the better is the likehood of identification utilizing that bite mark. The type of teeth: In many cases, the bite mark is seen to be comprised of the upper anterior teeth. The investigator should take note of the width of teeth. The reaction of the surrounding tissue: Bite marks made hours or days before the event will show inflammatory changes and signs of healing microscopically.

Types of Bite Mark ∙ ∙ ∙ ∙ ∙

Definite bite mark Amorous bite mark Moderately aggressive bite mark Aggressive bite mark Very aggressive bite mark.

Nature of Bite Marks Though called bite marks, but some times it may not be from actual teeth. The lips can transiently mark the skin, if forcibly nipped, especially on children. Suction can produce a crop of punctate hemorrhages, either small petechiae or larger ecchymoses merging into a confluent central bruise. It is caused by front teeth from canine to canine with a gap at either side representing the separation of upper and lower jaw.

Forensic Odontology

A human bite is near circular or a shallow oval. A deep parabolic arch or ‘U-shaped’ can only be animal in origin. The teeth may cause clear, separate marks or they may run into each other to form a continuous or intermittently broken line. As the time progresses, original teeth marks spread out and blur. Teeth marks may be abrasion, bruises or laceration or a combination of any two of three. The clarity of bite marks depends on a number of factors: ∙ If the contour of the part bitten is irregular or markedly curved, then only part of dental arch is in contact with the tissues. ∙ If the bite is forcible, then extensive subcutaneous bruising may spread and blur the outline. ∙ If the bite is inflicted many days before, then healing of abrasion and lacerations and absorption of bruising will leave progressively less detail. ∙ When the teeth are forcibly applied the typical appearance is of two ‘bows’ with their concavities facing each other and a gap at each end. Love bites: They are caused by firm application of the lips, which form an airtight seal against the skin, and then sucking action reduces the air pressure over the centre. This causes shower petechial hemorrhage to appear from rupture of small venules in the superficial layer of the subcutaneous tissue. If forcible the petechiae are confluent and a frank bruise or even hematoma develops.

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Figure 34.7 Impression is taken of the bite and cast is made

Investigations of a Bite Mark (Figs 34.6 to 34.12) Firstly, the bite mark should be carefully and fully photographed. The photograph should be taken from different angles, but especially from directly perpendicular

Figure 34.8 Study case is made

Figure 34.6 Sample bite taken on apple

Figure 34.9 Bite mark of suspect is taken

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Figure 34.10 Positive replica of bite mark is made

viewpoint, with the plane of film at right angle to that of the lesions. An accurate scale should always be held near the lesion, as close as possible. The lesion should almost fill the camera frame in some shots to capture as much detail as possible. When photography is completed, swabs of the bite should be taken to try to recover saliva. Plane cottonwool swab are gently rubbed onto the bite. They should be then deep frozen unless send straight to the serology laboratory. After this, impression of the bite can be taken. It is done by laying a plastic substance over the bite mark, which then hardens, so as to produce negative cast of the lesion. It is usually made with a rubber-or silicon based medium containing catalytic hardeners. Less satisfactory substances are water based pastes, such as plaster of Paris, which are put on wet and allowed to dry before removal. But they have a disadvantage of potential damage to the actual bite. After autopsy, it is also possible for the whole area of the skin carrying the bite to be removed and preserved in formalin for future examination.

Matching the Bite Mark with the Suspect Dentition

Figure 34.11 Cast of suspect is made

The teeth of those who are either suspected by the police or who had access to the victims should be examined. In most jurisdictions, it is vital that fully informed consent should be obtained from the persons beforehand. Any refusal must be a bar to any further action. When children are concerned, usually in the setting of child abuse, the consent of fully informed parents or guardian must be obtained. Then dentition is examined for number of teeth, missing teeth, complete or partial denture, occlusion, broken teeth, irregular teeth and abnormalities of the teeth. Photographs of dentition of the patient can be taken. After that impression of bite of suspect should be taken. Tracing can be made from the positive cast of a bite impression, inking the cutting edge of front teeth and transferring these to transparent sheets, which can then be laid over the photograph to determine correspondence.

HUMAN ABUSE

Figure 34.12 Cast is matched with previous mark

Dental professional are likely to encountered more victims of physical, neglective sexual and psychological abuse. Child abuse is nonaccidental, physical, mental, emotional and sexual trauma before 18 years of age. This abuse is done by parents, teacher, babysitter and person is acting as parent.

Forensic Odontology

Elder abuse is done for the patients who are physically or mentally ill.

Personal injury: TMJ damage, dental trauma in vehicular, home, sports, recreational and work related accident.

Intimate partner violence: This abuse are differ from child and elder abuse as they have choice of circumstance and place.

Dental fraud: Charging for material or procedure that were not used.

Sign and symptoms of human abuse: There is laceration in labial or lingual frenum which can occur due to forceful feeding or blow. There may be fracture of zygomatic bone, nasal bone, and teeth. There may be bilateral periorbital ecchymoses (raccoon mask), bilateral contusion of the lip commissures. There may be traumatic alopecia secondary to grabbing of head hair of victim.

Identification of multiple fatality incident victims: dental expert is requested in identification of homicide victims and in bite mark and human abuse cases.

BIBLIOGRAPHY

1. Arany S, Ohtani S, Yosioka N, et al. Age estimation from aspartic racemization of root dentin by internal standard method. Forensic Sci Int. 2004;141:127-30. Dentist role in reporting human abuse: When the dentist 2. Austin-Smith D, Maples WR. The reliability of skull/ determines to report child or elder abuse, documentation of photographs superimposition individual identification. J the physical evidence to support the charge is must. Forensic Sci. 1994;39:446-55. 3. Jakush J. Forensic dentistry: J AM Dent Assoc. 1989;119: 355-68. DENTIST AS EXPERT WITNESS 4. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Dentist act as ‘witness of fact’ i.e. they only testify the facts maxillofacial pathology, 3rd edition, Saunder Elsevier, that are known to them. Dentists are qualified to testify 2009. by the judge, who bases his or her opinion on education 5. Pretty IA. A web based surface of odontologist opinion concerning bite mark analysis. J Forensic Sci. 2003;48: background, dental and forensic expertise, publication and 1117-20. other professional qualifications. Dentist is required to 6. Standish SM, Stimson PG. Forensic dentistry: legal testify in following situation. obligation and methods of identification for the practitioner. Malpractice based on negligence: It includes battery Dent Clinic North AM. 1977;21:1-196.

(extraction of the wrong tooth), misdiagnosis, and failure to diagnose.

MULTIPLE CHOICE QUESTIONS 3. The techniques which are used for DNA profiling are: a. RFLP b. PCR c. Both d. None

1. Copper causes discoloration of gums which can be seen as: a. Green line b. Blue line c. Black line d. Reddish line 2. Wasted blood stains and seminal stains can be easily seen by: a. Infrared lights b. UV rays c. X-rays d. Both a and b



4. Bite mark on fruits are preserved in: a. Deep freezed b. Campden solution c. Alcohol d. Water 5. Bite mark which fracture readily with limited depth of tooth penetration: a. Type I b. Type II c. Type III d. None

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Syndromes of the Orofacial Region Shubhangi Mhaske (Jedhe) Chapter Outline

 Classification of syndrome  Syndromes associated with craniofacial anomalies of genetic origin  Cleidocranial dysplasia  Apert’s syndrome  Ellis-van Creveld syndrome  Crouzon syndrome  Trisomy 21 syndrome  Trisomy 18 syndrome  Trisomy 13 syndrome  Cerebrohepatorenal syndrome  Cerebrocostomandibular syndrome  Hajdu–Cheney syndrome  Anderson syndrome  Caffey–Silverman syndrome  Median cleft face syndrome  Melnick Needles syndrome  Mohr syndrome (OFD II)  Treacher Collins syndrome  Pierre-Robin syndrome  Marfan syndrome  Ehlers-Danlos syndrome  Hereditary hypohydrotic ectodermal dysplasia  Stevens-Johnson syndrome  Mucocutaneous lymph node syndrome  Incontinentia pigmenti  Broad groups of pigmentary disorders  Peutz-Jeghers syndrome  Albright’s syndrome  Sjögren’s syndrome  Heerfordt’s syndrome  Riley-Day syndrome  Gardner’s syndrome  Trichodento-osseous syndrome  Naegali-Franceschetti-Jadassohn syndrome

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Johanson-blizzard syndrome Oculodentodigital dysplasia Fanconi’s syndrome Lacrimo-auriculo-dento-digital syndrome Nevoid basal cell carcinoma syndrome Ascher’s syndrome Melkersson-Rosenthal syndrome van der Woude syndrome Hereditary hemorrhagic telangiectasia Cowden syndrome Zinsser-Engman-Cole syndrome Winchester syndrome Anhydrotic ectodermal dysplasia/Christ-SiemensTouraine syndrome Zellweger syndrome Beckwith-Wiedemann syndrome Orofacial digital (OFD) syndrome Hurler syndrome Mobius syndrome Aglossia-Adactylia syndrome Burning mouth syndrome Tuberous sclerosis Zimmerman Laband syndrome Rutherford syndrome Ramon syndrome Papillon-Lefevre syndrome Klippel-Trenaunay-Weber syndrome Auriculotemporal syndrome Paratrigeminal syndrome Horton’s syndrome Migraine syndrome Horner’s syndrome Jaw-Winking syndrome Plummer-Vinson syndrome Chediak-Higashi syndrome

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Syndromes of the Orofacial Region

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Sweet’s syndrome Lazy leukocyte syndrome Maffucci’s syndrome Blue rubber bleb naevus syndrome Diffuse neonatal haemangiomatoses Sturge-Weber syndrome Reiter’s syndrome Behçet’s syndrome Cushing syndrome Adrenogenital syndrome

INTRODUCTION The heritage of the term syndrome is ancient. It was used by Hippocrates to denote a group of regularly concurrent symptoms which resulted from several causes. The word syndrome has its origin from the Greek literature which means, “running together” (syn—together and dromos— running). The word syndrome has been used in English language since 1541. At this time there is neither complete agreement concerning what constitutes a syndrome nor there is a uniform method of nomenclature. Syndrome is defined as “A group of signs and symptoms or a set of symptoms usually three or more, which occur together characteristic of a morbid condition”. Or “It is the aggregate of signs and symptoms associated with any morbid process and constituting together the picture of the disease.” Syndromes being a multisystem disease are difficult to classify in a specific pattern. It is a grouped together symptom complex which is of varied etiology and clinical presentation.

Classification of Syndromes Many syndromes are classified according to: ∙ Eponym—For example, Morquio-Brailsford syndrome ∙ Cause—For example, Crush syndrome ∙ Pathogenesis—For example, Dumping syndrome ∙ Anatomic location—For example, oculo-dento-digital syndrome ∙ Main symptoms—For example, progressive hemifacial atrophy

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General adaptation syndrome Progeria Waterhouse-Frederichsen syndrome von Recklinghausen’s neurofibromatosis Basal cell nevus or nevoid basal cell carcinoma syndrome Multiple endocrine neoplasia syndromes Tuberous sclerosis Klippel-Trenaunay syndrome von Hippel-Lindau syndrome Parkes-Weber syndrome

Eponyms: Eponyms are used to describe syndromes and diseases since the middle of the nineteenth century when they were employed by neurologists to separate groups of similar clinical entities—one of the most obvious merits is the honor bestowed upon several keen observers who have dotted the medical and dental history. The etiological factors for the occurrence of the syndromes are not definite. Many times it occurs due to genetic influence or genetic disposition. Racial predominance is also seen as a causative factor. Offsprings of an affected individual usually have chance of acquiring the disorder if inherited. The syndrome sometimes becomes progressively more severe in succeeding generations. Syndromes may also occur due to immunodysfunction or an abnormal immune response to microbial antigen– dysfunction of certain glands and vascular anomalies can also result in form of syndromes. Diagnosis of a syndrome is problematic because of the extreme variability of its clinical expression. Although the prognosis in some of the conditions is extremely poor, mortality is drastically reduced with early diagnosis and recent advanced treatment modalities available. Treatment can be directed at correction or reconstruction of the existing deformities. During infancy and childhood the patient should be examined frequently to rule out suspicious conditions. Growth and development should be observed closely for evidence of mental impairment or abnormalities of sexual development. This will facilitate early identification of potentially dangerous syndromes.

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Syndromes as already stated are difficult to classify in a specific pattern as it is a grouped together multisystem complex of signs and symptoms. For sake of convenience, orofacial syndromes are compiled together under the following headings: ∙ Syndromes associated with craniofacial anomalies of genetic origin ∙ Syndromes associated with skin and pigmentation ∙ Syndromes associated with salivary and lacrimal glands ∙ Syndromes associated with teeth ∙ Syndromes associated with oral mucous membrane, lips and cheek, gingiva, tongue ∙ Syndromes associated with nerves ∙ Syndromes associated with blood and vascular malformations ∙ Syndromes associated with immunodeficiency ∙ Syndromes associated with hormonal disturbances ∙ Syndromes with benign oral neoplastic or hamartomatous components.

SYNDROMES ASSOCIATED WITH CRANIOFACIAL ANOMALIES OF GENETIC ORIGIN Genetic Factors Genetic information in humans is carried by 23 pairs (46) of chromosomes, known as autosomes which carry information regarding the structure and functions of the body one pair (2) is known as the sex chromosome, determines the sex of the individual (XY in male and XX in female). Genetically derived-disorders can be considered under three major groups: 1. Chromosomal disorders 2. Single gene (monogenic) disorders 3. Multifactorial disorders.

Chromosomal Disorders The disorder in this group is due to errors in number and/or structure of the chromosomes. For example, Down syndrome (Trisomy 21) results from an additional autosomal chromosome, while Klinefelter syndrome is associated with an additional X chromosome in male, i.e. XXY. Deletion of part of chromosome 5 results in the Cri–Du–Chat syndrome.

Single Gene Disorders The disorders in this group are due to defects in a single gene which refers to the primary error in the DNA code. These disorders are inherited following Mendelian laws and are subdivided according to the chromosome on which the abnormal (mutant) gene is situated and by the nature of the trait. The inheritance is known as autosomal when the abnormal gene is situated on an autosome and the trait is said to be X-linked when such a gene is situated on the X chromosome. These traits may either be “dominant” or “recessive” (autosomal dominant or recessive, and X-linked dominant or recessive). Autosomal dominant inheritance has the following characteristics: ∙ Every affected person has at least one affected parent. ∙ Both males and females are likely to be affected and are capable of transmitting the disease ∙ Transmission is generally seen (father to son or daughter and mother to son/daughter) with no skipping of generation ∙ Affected persons typically transmit the trait to half their offspring These general rules however are modified by: ∙ Penetrance—carrier of abnormal genes may be so mildly affected to be entirely indistinguishable from normal persons. A gene is said to be “penetrant” if it is expressed in a given carrier ∙ Expressivity—a mildly affected parent may have severely affected child or vice versa. There is variation in the expression ∙ New mutation—an individual who does not carry a gene for a particular inherited condition may rarely have an affected infant. Autosomal recessive inheritance The characteristic are: ∙ The trait usually appears only in sibs and not in their parents ∙ On average one in four of the sibs are affected ∙ Consanguinity is generally seen among the parents of the affected individual ∙ Males and females tend to be equally affected ∙ Affected individuals will generally have normal children but all of the children will be carrier of the condition.

Syndromes of the Orofacial Region

Sex-linked inheritance When the X chromosome carries the abnormal gene, the disorder is said to be X-linked and when the Y chromosome carries it, the condition is said to be X-linked dominant disorders, e.g. (the hypoplastic form of amelogenesis, e.g. hypohidrotic ectodermal dysplasia).

Multifactorial Inheritance This involves interaction between both environmental and genetic factors. The environmental factors include: (1) trauma; (2) neoplastic disease; (3) toxic drugs; (4) metabolic factors and (5) infections.

Genetics of Craniofacial Malformation Causes of congenital malformation ∙ Genetic factors – Chromosomal disorders – Single gene disorders – Multifactorial disorders (polygenic and environmental) at birth and disorders of later life ∙ Nongenetic factors – Maternal infections – Maternal metabolic derangements and genetic diseases. (Diabetes, hypertension, thyroid disorders) – Maternal exposure to radiation – Disturbances of embryonic differentiation and fetal growth. Some craniofacial malformation syndromes with autosomal dominant inheritance: ∙ Blepharophimosis syndrome ∙ Waardenburg’s syndrome ∙ Treacher Collins syndrome ∙ Van der-Woudes syndrome ∙ Popliteal pterygium syndrome ∙ Oculo-dento-digital syndrome ∙ Ectrodactyly-ectodermal dysplasia clefting (EEC) ∙ Craniosynostosis syndromes: – Crouzon syndrome – Saethre-Chotzen syndrome – Pfeiffer’s syndrome – Apert syndrome. Some craniofacial syndromes with recessive inheritance: ∙ Cryptophthalmos syndrome ∙ Orofacial digital syndrome ∙ Roberts syndrome ∙ Carpenter’s syndrome.

X-linked Inheritance Syndromes ∙ ∙ ∙ ∙ ∙ ∙ ∙ ∙ ∙

Albinism—Deafness syndrome Amelogenesis imperfecta (two types) Coffin—Lowry syndrome Aarskog syndrome Focal dermal hypoplasia X-linked hydrocephaly Lowe syndrome Mucopolysaccharide II (Hunter) Orofacial-digital syndrome.

Multifactorial (MFR) ∙ ∙ ∙ ∙ ∙ ∙ ∙

Sturge-Weber syndrome Mobius syndrome Frontonasal dysplasia syndrome Goldenhar syndrome Aglossia–adactylia syndrome Cleft lip–cleft palate malformations Craniosynostosis.

Cleidocranial Dysplasia Cleidocranial dysplasia is an autosomal dominant condition although in less than half the cases it occurs spontaneously. The condition is characterized by the defects in the clavicles, cranial vault and occasionally with other selected and dental findings. As the name suggest, the frequent changes seen in the syndrome are in the clavicles and the cranium. The clavicles are unilaterally or bilaterally hypoplastic or aplastic. When hypoplastic the deficiency is seen at the acromial end allowing the individual to approximate their shoulders in front of the chest. X-ray of the chest reveal the exact defect. The skull is large with frontal, parietal and occipital bossing. Delayed mineralization of the sutures is a constant finding of the syndrome. There is usually a midfacial hypoplasia present resulting in relative prognathism of the mandible. Essential oral features include high arched vault of the palate with or without clefts, delayed eruption of teeth, malformed roots, supernumerary teeth and frequent impactions. A skull X-ray reveals the features together with the obtuse mandibular angle which is increasingly reported in these patients. Impacted teeth in affected individuals are reported to be lacking cellular cementum.

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Apert’s Syndrome (Acrocephalosyndactyly)

Trisomy Syndromes

Acrocephalysyndactyly is believed to be transmitted by an autosomal dominant gene occurring sporadically in about 1 to 2000,000 of the general population. Clinical features include ovoid skull, brachycephalic and often presents a horizontal supraorbital groove. Premature closure of the sutures occurs and often the anterior fontanelle is open due to late closure. Features of hand and feet include syndactylism. Osseous or cutaneous fusion of fingers is usually present. Oral features include a high palatal vault and the presence of posterior palatal and uvular clefts. Dental malocclusion is consistent. Other oral features include mandibular prognathism, malocclusion and retarded eruption.

Trisomy syndromes represent autosomal chromosome disorders. Several disorders in this group have been discovered. Only those with craniofacial and associated dental anomalies will be dealt with in the following discussion. They are: ∙ Trisomy 21 syndrome (Down’s syndrome) ∙ Trisomy 18 syndrome (Edward syndrome) ∙ Trisomy 13 syndrome (Patau syndrome).

Ellis-van Creveld Syndrome Synonym: Chondroectodermal dysplasia Ellis-van Creveld syndrome consists of anomalies derived from the ectodermal mesodermal germ layers. The disorder is believed to be inherited as an autosomal recessive trait. The disorder is congenital. Defects are seen in the extremities, teeth, nails and hair. Rarely cardiac anomalies also have been noted. Person is of short stature from birth. Polydactyly with or without syndactyly is present. Nails are dystrophic and hairs are sparse. Oral manifestations—deciduous teeth show hypoplasia occasionally and partial anodontia of permanent dentition is seen. Prognathism of lower jaw is present. There is obliteration of labial suture due to gingival frenal attachments.

Crouzon Syndrome Synonym: Craniofacial dysostosis Craniofacial dysostosis is an autosomal dominant condition, characterized by cranial synostosis, ocular proptosis and hypoplastic maxilla. The appearance is quite characteristic because of exophthalmos, hypertelorism and the under development of the maxilla. Exophthalmos is due to shallow orbits. Maxillary hypoplasia is responsible for the relative mandibular prognathism which is a consistent feature of this syndrome. The upper lip is usually short and the nose is parrot like. The cranium is brachycephalic. Oral features include, malocclusion, cleft lip and palate with V shaped palate. Some of the occasional findings include peg shaped teeth and partial anodontia.

Trisomy 21 Synonym: Down’s syndrome Trisomy 21 occurs in one in about 650 births. This syndrome is characterized by several features involving almost all organs of the body. The affected individual is mentally retarded, short stature and exhibits brachycephaly with a relatively flat occiput. Fontanelles close later and frontal sinuses are hypoplastic. The ears are small and the iris shows speckling (Brushfield’s spots). Disorders involving the pelvis, skin hair and genital occur with variable frequency. Facial features include a small head and an open mouth. Oral manifestation—short mouth, large tongue and tongue thrust beyond the lips. Maxillary lateral incisors show abnormality. They are either conical or missing developmentally. Microdontia is often present. Delayed eruption and malocclusion are other findings. The palate is high arched and narrow, the usual may be bifid. Necrotizing ulcerative gingivitis is reported to be common in these individuals. In about 95 percent of the affected individual’s condition arises as the result of the failure of paired chromosomes to disjoin and enter separate daughter cells during meiosis. Both chromosomes (number 21) from parental cell enter the gamete destined for fertilization and at fertilization a third chromosome (number 2) is added from the normal gamete of the other parent. The result is a zygote with three chromosomes (number 21) which is known as trisomy 21.

Trisomy 18 Syndrome Synonym: Edward syndrome Children with trisomy 18 are quite striking at birth with intrauterine retardation of growth and characteristic facial appearance. Trisomy 21 and trisomy 13, nondysfunction is the cause of this syndrome. Increased maternal age is an important factor in its causation.

Syndromes of the Orofacial Region

The affected individuals are mentally retarded and show hypertonicity. The index finger overlapping the third finger and the fifth over fourth are the striking features. Oral features—small mandible high arched palate and occasional cleft palate.

Trisomy 13 Syndrome Synonym: Patau syndrome In the trisomy 13 syndromes, affected individuals show 46 normal chromosomes but a portion of chromosome 13 is attached to another chromosome or is present as a fragment. The majority of cases are due to nondisjunction. The physical features are characteristic. They include microcephaly, microphthalmia, ocular hypertelorism, malformed ear, deafness, polydactyly and heart anomalies. Oral features include a small mandible, high arched palate and occasional cleft palate and bifid uvula. As with all trisomy syndromes. Chromosomal counts confirm the diagnosis.

Cerebrohepatorenal Syndrome Synonym: Bowen syndrome The cerebrohepatorenal syndrome is believed to be having an autosomal recessive inheritance. The condition is characterized by craniofacial anomalies, renal cortical cysts, hypoprothrombinemia and several other occasional findings involving genitals, spleen and pancreas. Oral features include micrognathia, protruding tongue and high arched palate.

Cerebrocostomandibular Syndrome The cerebrocostomandibular syndrome is an autosomal recessive condition. This disorder is characterized by mental retardation, thoracic deformities and mandibular and facial anomalies. Clinical features include microcephaly, long trunk, rib anomalies producing gaps and tracheal cartilage malformation producing a barking cough. Oral features include micrognathia, palate defects and absence of hard and often the soft palate.

Hajdu-Cheney Syndrome Synonym: Acro-osteolysis Acro-osteolysis is a rare autosomal disorder characterized by short stature, disintegration of the terminal phalanges of fingers and toes, premature loss of teeth and abnormal shape of skull.

The affected individual is generally short. A long nose, low frontal hairline and flared ears are the characteristic facial features. The phalanges of fingers and toes exhibit acro-osteoses and clubbing of nails present. The skull is dolicocephalic. Sutures are usually open. Oral features include premature loss of teeth.

Anderson Syndrome Synonym: Familial osteodysplasia The recently reported syndrome of familial osteodysplasia is an autosomal recessive disorder, characterized by craniofacial and skeletal anomalies, presence of hyperuricemia and diastolic hypertension. Oral features include mandibular prognathism, hypoplastic maxilla and resultant malocclusion. The mandible without wide angle, increased body length and reduced ramus and body height is an essential features of the syndrome.

Caffey-Silverman Syndrome Synonym: Infantile cortical hyperostosis Infantile cortical hyperostosis is characterized by the bilateral mandibular swellings, hyperirritability and fever occurring in infants. The bilaterally symmetrical swellings which occur over the ramus, angle and the body of the mandible are very striking. The soft tissue is tender and edematous, often undergoing remission and exacerbations. Similar bony and soft tissues changes may be seen in ribs, ulna, femur, clavicle, tibia and irritability are seen as preceding symptoms in about 70 percent of the affected infants. Hematological and biochemical findings include raised erythrocyte sedimentation rate, leukocytosis anemia and increased alkaline phosphatase levels. This disorder is characteristically seen in the infants, the onset being usually between the second to sixth months after birth, although a few cases have been reported in utero. Disorders to be considered in differential diagnosis include osteomyelitis and parotid gland inflammation or tumors.

Median Cleft Face Syndrome Synonym: Frontonasal dysplasia Frontonasal dysplasia is a disorder of unknown genetic causes (possibly multifactorial) characterized by facial disorders such as nasal clefts and notches, preauricular tags and ocular hypertelorism. Extracranial anomalies are usually not found in this syndrome. Oral features may include cleft lip and malocclusion.

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Synonym: Osteodysplasty Melnick Needles syndrome is an autosomal dominant condition characterized by the generalized bone dysplasia and abnormal faces. The facial appearance is quite typical with marked exophthalmos, full cheeks, large ears, micrognathia and a transversely long mouth. Radiographically the skull exhibits delayed closure of the basic of the skull and mastoid process. There are also skeletal deformities involving clavicle, vertebrae, radius, tibia, fibula and humerus, micrognathia and malocclusion. Facies are quite striking in that two unrelated patients look like siblings. X-rays and blood chemistry help in the diagnosis as serum alkaline phosphatase is elevated.

Mohr Syndrome (OFD II) Synonym: OFD orofacial digital syndrome II The Mohr syndrome is an autosomal recessive disorder characterized by oral, facial and digital defects. The affected individual is moderately short, exhibiting digital deformities such as brachydactyly, syndactyly or polydactyly. Facial features include the midline cleft lip and the broad and bifid tip of the nose. Oral features include the lobate tongue, high arched palate, hypoplastic body of mandible, and the absence of mandibular incisors. The syndrome resembles the orofacial digital I syndrome, which is X-linked and occurs only in females.

Treacher Collins Syndrome Synonym: Mandibulofacial dysostosis Treacher Collins syndrome primarily affects structures developing from the first branchial arch but it also involves the second branchial arch, to a minor degree. The persons affected have a convex facial profile with a prominent nose and retrusive chin. It is generally a bilateral anomaly with a characteristic faces including downward sloping of the palpebral fissures, coloboma of the lower eyelid, mandibular and midface hypoplasia and deformed pinnas.

Etiology and Pathogenesis It is transmitted by an autosomal dominant mode of inheritance although about half the cases are due to spontaneous mutation. Affected siblings are remarkably similar and the syndrome becomes progressively more severe in succeeding generations.

This disorder is relatively rare with an incidence between 0.5 and 10.6 cases per 10,000 births. Stapedial artery dysfunction results in the defects of the stapes and incus and first arch vessels supplying the maxilla. The expression begins as early as the sixth to seventh embryonic week. Mandibular abnormalities such as improper orientation and hypoplasia of the mandibular elevater muscles result due to failure of developments of ancillary vascular supply by inferior alveolar artery.

Clinical Findings Treacher Collins syndrome is a combined development anomaly of first and second branchial arch. Varying degrees of hypoplasia of the mandible, maxilla, and zygoma is seen. Abnormalities of medial pterygoid plates and hypoplasia of lateral pterygoid plates are common. Notched or linear colobomas of the outer third of the lower eyelid are found in 75 percent of patients. The facial appearance is characteristic and described as bird like or as fish like. Microdontia or underdeveloped ear and a narrow extension of the hair over the preauricular region known as “hair like” are common in this syndrome. Oral findings include cleft palate in about 30 percent of the patients and macrostomia in 15 percent of the patients. Cleft palate and malocclusion is present. The underdeveloped zygomatico-maxillary complex leads to a clinically severe midface deficiency. Radiographic findings include downward sloping floors of the orbits, peaked long nasal contor, aplastic or hypoplastic zygomatic process of the temporal bone and obtuse mandibular angle. Lateral cephalograms demonstrate antegonial notching and broad concave nature of the inferior border of the mandible helps to distinguish the condition from other syndromes involving the mandible.

Treatment and Prognosis It is directed at correction or reconstruction of the existing deformities. Neutralization of conductive hearing loss through surgery and hearing aids is helpful. Ophthalmic surgery is done to correct eye defects.

Pierre-Robin Syndrome The Pierre-Robin syndrome manifest clinically as microganthia, glossoptosis and high arched or cleft palate in the neonate. It can occur as an isolated finding or as a component of various syndrome or development anomalies.

Syndromes of the Orofacial Region

Primary findings are retrognathia and hypoplasia of mandible. Respiratory and feeding problems are prevalent and may result in episodic airway obstruction, infant hypoxia, malnutrition and failure to thrive.

Etiology and Pathogenesis Incidence is 5.3 to 22.7 percent per 100,000 births with 39 percent of the infants exhibiting no additional abnormalities 25 percent have known syndromes and 36 percent have one or more anomalies that are not a part of a known syndrome. Fetal malposition and interposition of the tongue between the palatal shelves have long been considered the etiologic catalysts for palatal deformity and micrognathia. Recent evidence suggest that the primary defect may be due to genetically influenced metabolic growth disturbances of the maxilla and mandible rather than to mechanical obstruction by the tongue during embryogenesis.

Clinical Features Infants present without severe micrognathia and mandibular hypoplasia. A ‘U’ shaped high arched palate is usually present. Glossoptosis is the result of the retro positional attachment of genioglossus muscle because of the retrognathic mandible. The geniohyoid muscle is fore shortened so that support to the hyoid bone and strap muscles of the larynx is also compromised.

Treatment and Prognosis Treatment is supportive to overcome feeding problems and the patient should be monitored for airway obstruction.

Marfan’s Syndrome It is a heritable disorder of connective tissue characterized by abnormalities of the skeletal, cardiovascular and ocular systems. Diagnosis is problematic because of the extreme variability of clinical expression. The syndrome is notable for a number of cases of sudden catastrophic death occurred in affected athletes (undiagnosed).

Etiology and Pathogenesis It is an autosomal dominant inherited in 1 in 100,000 individuals. There are no ethnic, racial or gender predictions. The Marfan’s gene is believed to produce a change in one of the proteins that provide strength to a complete connective tissues probably collagen. The gene has been located on chromosomes 15 and will provide for diagnostic testing in pairs at risk. Diagnosis is based on

characteristic abnormalities of the musculoskeletal ocular and cardiovascular systems and a positive family history.

Clinical Features Patients characteristically present with a tall slender stature with relatively long legs and arms, large hands with long fingers and loose joints. The arms, legs and digits are disproportionately long compared to the patient trunk. Chest deformities present with a protrusion or indentation of the breast bone. Even the normal thoracic kyphosis is absent and the back is straight. Oral findings include high arched palate with dental crowding. The face appears long and narrow. The cardiovascular system shows mitral valve prolapsed in 75 to 85 percent of the cases. Aortic dilatation is there of the ascending aorta leading to aortic regurgitation. Ocular findings include dislocation of the lens (ectopic lentis). Retinal detachment is infrequent but myopia (short sightedness) is a common finding.

Treatment and Prognosis Subluxation of the lens of the eye, chest cavity deformities potential for pneumothorax are serious prognostic indicators. Treatment consists of annual medical examination with a cardiovascular, emphasis frequent ophthalmologic examination, scoliosis screening and echocardiography. Mortality has been drastically reduced with the use of composite grafts to replace the aortic value and region containing the aortic aneurysm.

Ehlers-Danlos Syndrome The Ehlers-Danlos syndrome is an uncommon inherited disorder of connective tissue, clinically characterized by joint hypermobility and skull hyperextensibility. There are inherited defect in collagen metabolism. In addition to the skin and joint anomalies, severe gastrointestinal and cardiovascular complications may occur and coexist. The condition has been classified into eight variants. The periodontal form (EDS type VIII) is characteristic by rapidly progressing periodontal disease resulting in complete tooth loss in second or third decade of life.

Etiology and Pathogenesis Various subtypes of Ehlers-Danlos syndrome are inherited as autosomal dominant, autosomal recessive and X-linked traits. There is defect in the synthesis and structure of type III collagen. A deficiency of the enzyme lysyl hydroxylase

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resulting in decreased amounts of collagen hydroxylsine has also been reported. The conversion of precollagen to collagen is prevented. 868

Clinical Features There is marked hyper elasticity of skin and extreme laxity of the joints. The skin can be stretched for several centimeters and when released it resumes its contor. Skin has velvety appearance with high degree of fragility and bruisability. Minor trauma may produce ecchymosis, bleeding and large gaping wounds with poor healing tendencies and “cigarette paper” scar formation especially on the forehead and lower legs and over pressure points. Articular hypermobility is variable. Extreme joint laxity leads to spontaneous dislocation of joints (back knee) flat feet, etc. Cardiovascular anomalies include mitral valve prolapsed and rupture of major blood vessels. Pulmonary problems include spontaneous pneumothorax and respiratory impairment secondary to chest wall deformities. Orofacial features include a narrow maxilla flattened midface and wide nasal bridge. Fragility of gingival and mucosal tissues may be problematic. Marked extensibility of the tongue enabling contact with the tip of the nose has been described. Dental findings include deep anatomic grooves and excessive cuspal height of the molars and premolars. Maceration of roots and pulpal calcified structures have been noted.

Treatment and Prognosis Prognosis depends on severity of the systemic manifestation. The cardiovascular status of all patients should be

evaluated and monitored. Sudden death can occur. surgical intervention must be tempered in light of connective tissue fragility unsuccessful owing to suture failure. Wound healing is delayed and prolong bleeding may occur following injury.

SYNDROMES ASSOCIATED WITH SKIN AND PIGMENTATION Hereditary Ectodermal Dysplasia In order to be considered an ectodermal dysplasia, the disorder should meet the following criteria suggested by Solomon et al. ∙ The disease must be congenital ∙ The disease must be diffuse (not localized) and must involve the epidermis as well as at least one of its appendages (hair, sebaceous glands, nails, mucosa, mucosal glands and teeth) ∙ The epidermal component may involve keratinocytes, melanocytes or Langerhans cells or any combination there of ∙ The disease is not progressive, infact patients often improve somewhat over a period of years ∙ Increased delineation of syndromes with ectodermal defects has led to considerable difficulty in developing a coherent classification of this disorder ∙ The ectodermal dysplasia are classified by Freire-Maia and Pinheiro for the purpose of delimiting the field as conditions with at least one of the following four features: 1. Trichodysplasia 2. Dental defects 3. Onychoysplasia 4. Dyshidrosis.

Classification of the Ectodermal Dysplasis Disorder

Inheritance

Subgroup 1-2-3-4 Anhidrotic X-linked ED

X-linked semidominant

Hypohidrotic ED (autosomal recessive)

Autosomal recessive

Xeroderma, talipes, and enamel defect

Autosomal dominant

Rosselli-Gulienetti syndrome

Autosomal recessive

Rapp-Hodgkin hypohidrotic ED

Autosomal dominant

Ectrodactyly-ED-clefting syndrome

Autosomal dominant

Contd...

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Contd... Disorder

Inheritance

Subgroup 1-2-3

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Hidrotic ED(Clouston’s syndrome)

Autosomal dominant

Trichodento-osseous syndrome

Autosomal dominant

Trichorhinophalangeal syndrome

Heterogeneous recessive

Ellis-van Creveld syndrome

Autosomal recessive

Schöpf-Schulz Passarge syndrome

Autosomal recessive

Dento-oculocutaneous syndrome

Autosomal dominant ?

Odontotrichomelic dysplasia

Autosomal recessive ?

Tooth and nail syndrome

Autosomal recessive

Subgroup 1-3-4 Freire-Maia syndrome

?

Subgroup 2-3-4 Hypoplastic enamel - onycholysis

Autosomal dominant

hypohidrosis Tooth and Nail syndrome

Autosomal recessive

Gorlin’s syndrome

Autosomal recessive ?

Oculodentodigital syndrome

?

Monilethrix and anodontia

Autosomal dominant

Oral-facial digital syndrome (type I)

X- linked dominant ?

Subgroup 1-3 Curly hair-ankyloble pharon-nail dysplasia

Autosomal dominant

Palmoplantar hyperkeratosis and alopecia

Heterogeneous

Onychotrichodysplasia with neutropenia

Autosomal recessive

Subgroup 1-4 Congenital ED of the face

Heterogeneous ?

Subgroup 2-3 Nail dystrophy-deafness syndrome

Autosomal dominant

Triphalangeal thumbs-hypoplastic distal Phalanges-onychodystrophy

Autosomal recessive

Subgroup 2-4 Marshall’s ED with ocular and hearing defects

Autosomal dominant

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A large number of further ectodermal dysplasias are associated with alterations of the oral mucosa or of the teeth. They are listed in the following: Syndrome

Oral manifestations

Other features

Cranioectodermal dysplasia; dolichocephaly

Small decidous teeth; hypodontia; taurodonitism

Hypoplastic enamel; shortened arms, finger toes; hair anomalies

Trichodento-osseous syndrome

Amelogenesis imperfecta enamel Curly hair, sclerotic bone hypoplasia, unerupted teeth; taurodontism

Tricho-onychodental syndrome

Hypodontia: conical teeth

Fine short hair; thining of the lateral ends of the eyebrows

Tricho-onychodental syndrome

Taurodontism, enamel defects

Fine curly hair; thin dysplastic nails

Curry-Hall syndrome

Small and conical deciduous teeth; retained incisors; small permanent teeth

Short limbs; polydactyly, nail dysplasia

Otodental dysplasia

Globodontia; taurodontism; microdontia; hypodontia

Sensorineural hearing loss

GAPO: (growth retardation alopecia pseudoanodontia and optic atrophy)

Failure of both dentitions to erupt

Frontal bossing midface hypoplasia

Johanson-Blizzard syndrome

Hypodontia in both dentitions. Roots of deciduous teeth are short and deformed, crowns are conical

Hearing loss panceratic dysfunction mental retardation microcephaly; hypoplastic ala nasi

Waardenburg’s syndrome

Cleft lip/palate

Deafness; hair depigmentation

LEOPARD syndrome (lentigines, electrocardiographic anomalies, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retarded growth, deafness)

No mucosal lentigines but there may be grandular cell myoblastomas

Triangular face with hypertelorism and ptosis

Congenital erythrokeratoderma

Hyperkeratosis occasional carcinoma

Deafness erythrokeratoderma

with sensorineural hearing loss

Hereditary Hypohydrotic (Anhydrotic) Ectodermal Dysplasia Hereditary hypohydrotic (anhydrotic) ectodermal dysplasia is a specific syndrome characterized by a congenital dysplasia of one or more ectodermal structures and their accessory appendages, manifested primarily by: ∙ Hypohydrosis ∙ Hypotrichosis ∙ Hypodontia. It affects skin, hair, nails, eyes, teeth, facies, sensorineural apparatus and adnexal glandular structures in various combinations and of varying severity.

Clinical Features The patients exhibit a soft, smooth, thin, dry skin with partial or complete absence of sweat glands. Such

persons cannot perspire and they consequently suffer from hyper- pyrexia and an inability to endure warm temperatures. The hair of the scalp, a eyebrow are fine scanty and blond.

Oral Manifestation They manifest anodontia or oligodontia. Complete or partial absence of teeth with frequent malformation of any teeth present. Where some teeth are present, they are commonly truncated or cone shaped when complete anodontia exists, the growth of the jaw is not impaired.

Stevens-Johnson Syndrome At one time considered to be a separate disease, StevensJohnson syndrome is now recognized as simply a severe bullous form of erythema multiforme with widespread

Syndromes of the Orofacial Region

involvement typically including the skin, oral cavity, eyes and genitalia. It commences with the abrupt occurrence of fever, malaise, photophobia and eruption of the oral mucosa, genitalia and the skin. The cutaneous lesions in this mucocutaneous-ocular disease are similar to those of erythema multiforme, although they are commonly hemorrhagic and are often vesicular or bullous.

Mucocutaneous Lymph Node Syndrome Synonym: Kawasaki disease This syndrome was first described by Kawasaki in 1967 in the Japanese children. The etiology of this disease is still unknown but is suggested to be of viral disease or a “collagen-vascular” disease.

Clinical Features The diseases have been reported to occur in children of age 3 to 12 years. The most frequent symptoms as determined by the epidemiological study group of the Japanese MCLS research committee are: ∙ Fever for 5 or more days with no response to antibiotics ∙ Bilateral congestion of ocular conjunction ∙ Changes in the extremities peripherally including indurative edema, erythematous palms and soles and membranous desquamation of fingers and toes ∙ Lips and mouth show dryness, cracking and swelling of tongue papilla ∙ Polymorphous exanthema of torso without vesicles or crust ∙ Acute purulent swelling of cervical lymph nodes. Other findings include diarrhea, proteinuria leukocytosis and increased sedimentation rate. Cardiac abnormality may occur .While the vast majority of the cases are self-limiting and nonfatal, occasional deaths may occur as a result of cardiac complications.

Incontinentia Pigmenti Incontinentia pigmenti, also known as Bloch-Sulzberger syndrome, is an uncommon genetic disease with an Xlinked dominant mode of inheritance. This distinctive multisystem disorder is characterized by abnormalities of skin pigmentation. Linear rows of blisters on the extremities are seen at birth. Occasionally the trunk is also involved. Later on the blisters are replaced by warty lesions that may persist until first year of age. In the final stage, there is hyperpigmentation, caused by melanin deposition in the upper dermis. Mental

retardation, seizures, microcephaly, and other CNS disorders and ocular and skeletal anomalies occur in about 30 percent of the patients. In 90 percent of patients major dental anomalies such as partial or complete anodontia, pegshaped or conical deformities of the teeth, enamel disorders, and delayed eruption are found (Bjellerup, Carrney, Milam et al; Vogte and Matheson). The oral mucosa is not involved.

BROAD GROUPS OF PIGMENTARY DISORDERS A multitude of factors, genetic and/or acquired related to melanin and/or some other histologic substrates needs to be considered in properly understanding the etiopatho-genesis in a particular case and its management. Disease of hypoand hyperpigmentation can for all practical purposes be grouped into two broad divisions: 1. Cause showing cutaneous pigmentary alteration as the most significant and predominant sign if not the only exclusive clinical feature, representing in most instances a relative lack of excess of melanin pigmentation. 2. Those cases showing these disorders as one of the clinical features in associations with other cutaneous and/or extracutaneous manifestation which often appear more significant. That is the pigmentary disorders may be either: ∙ Depigmentary and hypopigmentary or ∙ Hyperpigmentary of various shades.

Peutz-Jeghers Syndrome Synonym: Periorificial lentiginosis This is an autosomal dominant disorder showing pigmented macules on the oral mucosa and skin associated with gastrointestinal polyposis. There is no sex or racial preponderance. A family history is found in 60 percent of cases. Pigmented macules show an increased amount of melanin in the basal layer of the epidermis without any associated increase in the number of melanocytes. Macules are present at birth, infancy or early childhood. The oral mucosa is always involved with affection of buccal mucosa, gums hard palate and lower lips. Lesions are irregularly distributed round, oval or irregularly patch brown or black in color and 1 to 5 mm in diameters. Also present on the face, hands, feet and nails. Gastrointestinal polyps are benign hamartoma with relatively less potential for malignant transformation. They may occur throughout the gastrointestinal tract but are commonly observed in the small intestine. The symptoms

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of GI polyps are repeated abdominal colic, rectal bleeding, hematoma, anemia usually start between 10 and 30 years of age. Apart from an increased risk of malignancy life expectancy is normal.

Albrights Syndrome Albrights syndrome consists of fibrous dysplasia, large pigmented cutaneous macules endocrine dysfunction with precocious puberty and somatic over growth. Cutaneous pigmented macules are usually present or appear soon after birth and are usually light brown in color. They have irregular serrated margins and are asymmetrically distributed, (with in the midline). Bony lesions usually first present during the first decade with pain, pathological fractures, swellings and deformities. In females precocious puberty at the age of 5 years may occur in the form of pubic hairs, vaginal bleeding and breast enlargement. Biochemical raised serum alkaline phosphatase level may be observed in the presence of widespread bone involvement. Histopathologically hyperpigmented macules and normal skin show a normal number of melanocytes with absent or occasional macromelanosomes in the melanocytes and keratinocytes. The disease is not usually lethal. Pathological fractures normally unite easily.

SYNDROMES ASSOCIATED WITH SALIVARY AND LACRIMAL GLANDS • • • •

Sjögren’s syndrome Heerford’s syndrome Riley-Day syndrome Felty’s syndrome.

Sjögren’s Syndrome Synonyms: Sicca syndrome, Gougerat-Sjögren’s syndrome, rheumatoid sialadenitis. Sjögren’s has described this syndrome in 1933. Sjögren’s syndrome is a condition originally described as a triad consisting of keratoconjunctivitis sicca, xerostomia and rheumatoid arthritis. Primary Sjögren’s syndrome is so called when patients present only with dry eyes and dry mouth (Sicca complex). The secondary Sjögren’s syndrome involves or develops systemic lupus erythematosus, polyarteritis nodosa , polymyositis or scleroderma as well as rheumatoid arthritis.

Etiology Various causes of this disease have been suggested, genetic, hormonal, infections and immunologic among others. It is generally assumed that the antigen-antibody reaction is not the sole cause of this disease. As majority of those affected are women, hormonal deregulation plays a role. Laboratory findings support the autoimmune etiologic role. Bertram has reported that 75 percent of a series of 35 patients with Sjögren’s syndrome had in their sera antisalivary duct antibody. In addition the sicca complex and Sjögren’s syndrome have been found to be associated with the HLA system, specifically HLA - DR3 and DR4.

Clinical Features The disease occurs predominantly in women over 40 years of age, although children or young adults may be affected. The female:male ratio is 10:1. The typical features are dryness of mouth and eyes as a result of hypofunction of the salivary and lacrimal glands. This often results in painful, burning sensations of the oral mucosa. In addition various secretory glands of the nose, larynx, pharynx and tracheobronchial tree (buccopharyngolaryngitis sicca) as well as of the vagina are involved with this dryness. Sialochemistry studies have demonstrated significantly elevated levels of IgA, potassium and sodium in the patients of sicca complex. Rheumatoid arthritis is an integral part of the secondary Sjögren’s syndrome. It has been shown that patients with rheumatoid arthritis have certain different clinical manifestations than patients with sicca complex, despite similar histologic findings and some laboratory findings. In this regard patients without rheumatoid arthritis that is sicca complex more frequently manifest parotid gland enlargements, lymphadenopathy, purpura, Raynaud’s phenomenon, kidney involvement and myositis.

Histologic Features Three types of histologic alterations have been described: • In one case there may be intense lymphocytic infiltration of the gland replacing all the acinar structures although the lobular architecture is preserved, there may be proliferation of the ductal epithelium and myoepithelium to form “epimyoepithelial islands”. Both of these histologic changes are identical with those occurring in the benign lymphoepithelial lesion (Mikulicz’s disease).

Syndromes of the Orofacial Region

• The third alteration may be simply an atrophy of the Riley-Day Syndrome glands sequential to the lymphocytic infiltration. Riley-Day syndrome is characterized by sialorrhea, excessive perspiration, defective lacrimation and erythematous Laboratory Findings blotching of the skin. Primary Sjögren’s syndrome have shown a polyclonal hyperglobulinemia and may develop cryoglobulins. Other Features Multiple organ or tissue specific antibodies are found, Wide fluctuance in blood pressure, emotional instability including antisalivary duct antibodies, rheumatoid factor cold hands and feet and hyporeflexia. It is manifested first and antinuclear antibodies. in infancy by impaired swallowing and sucking and by An increased sedimentation rate is present in 80 percent absence of tears, growth is retarded and the ability to walk of these cases. The antisalivary duct antibody present is and sit and speech is delayed. There is marked absence of three times more common in secondary Sjögren’s syndrome fungi form papillae on the tongue. Occurs commonly or than the sicca complex. almost inclusively in Jews and is inherited as an autosomal Treatment and prognosis: There is no satisfactory recessive trait. Sialorrhea is especially marked during treatment for Sjögren’s syndrome. Patients are treated excitement. The syndrome is thought to result from an symptomatically. Keratoconjunctivitis is treated with inborn error in catecholamine metabolism. lubrication with artificial tears containing methyl cellulose. Xerostomia is treated with the saliva substitutes. SYNDROMES AFFECTING TEETH

Heerfordt’s Syndrome Synonym: Uveoparotid fever. Uveoparotitis: Uveoparotitis is considered to be a form of sarcoidosis in which characteristically there is firm, painless usually bilateral enlargement of parotid glands, accompanied by the inflammation of the uveal tracts of the eye and cranial nerve involvement. The submaxillary and sublingual glands may be similarly involved and even the lacrimal glands may be swollen, all features suggestive of Mikulicz’s disease or Sjögren’s syndrome. A chronic low grade fever is often present and the patient may complain of lassitude, malaise and vague gastrointestinal disturbances or even nausea and vomiting. Xerostomia is common. The most common eye lesion in uveoparotitis and often the earliest symptoms is uveitis, but conjunctivitis, keratitis and corneal herpes among others also have been reported. Although the uveitis may begin unilaterally, it eventually becomes bilateral and in most cases result in some permanent visual impairment. The most common nerve paralysis is of seventh nerve which may be unilateral or bilateral, which is said to occur in 1/3rd to 1/2 of the cases. The signs and symptoms of this syndrome disappear within time, although some swellings of the parotid glands and visual disturbance may persists.

• • • • • • • • • •

Gardner’s syndrome Trichodento-osseous syndrome Naegeli-Franceschetti-Jadassohn syndrome Johanson-Blizzard syndrome Oculodentodigital dysplasia Fanconi’s syndrome Lacrimo-auriculo-dento-digital syndrome Cleidocranial dysplasia Hereditary ectodermal dysplasia Nevoid basal cell carcinoma syndrome.

Gardner’s Syndrome Gardner’s syndrome is an autosomal dominantly inherited disorder with variable penetrance, characterized by multiple supernumerary teeth, multiple osteomas of bony skeleton, intestinal polyposis, and various skin and soft tissue tumors. Multiple sebaceous cyst are also associated.

Etiology Manifestation of Gardner’s syndrome is thought to be due to abnormal growth of all three primordial germ layers.

Clinical Features Multiple polyps of the colon appear in the second decade of life. Although asymptomatic, malignant changes or

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risk of colonic cancer is almost 100 percent by the age of fifty. Skeletal abnormalities are localized cortical skeletal thickening of long tubular bones and osteomas of the mandibular rami are characteristic of this syndrome. Dental anomalies noted are supernumerary teeth, odontomas, multiple unerupted teeth and multiple caries. Sebaceous or epidermoid cyst appear later in life over the face, scalp and extremities. Lipoma are frequently noted in the subcutaneous tissue. Fibromas are also reported.

Diagnosis Family history of colonic malignancy. Osteomas of the mandible and cutaneous lesions are indicators of the possible symptomatic colonic polyps.

Trichodento-osseous Syndrome This autosomal dominantly inherited familial syndrome affects the hair, teeth and bones. Approximately 50 percent of the affected patients complain of brittle nails that peel frequently. Dental manifestations are enamel hypoplasia, impacted teeth, taurodont teeth and multiple dentoalveolar abscesses, a thickened cortical bone enamel is thin with normal dentin.

Naegeli-Franceschetti-Jadassohn Syndrome This is a rare autosomal dominant inherited syndrome characterized by the development of reticulate brown or slate-gray pigmentation, yellowish discoloration of teeth palmoplantar hyperkeratosis and hypohydrosis with heat intolerance.

Johanson-Blizzard Syndrome This syndrome is characterized by hypoplasia of the nasal alae: • Oligodontia • Scalp and hair defects • Sensory neural defects • Short stature • Psychomotor retardation and malabsorption. The nose is beak like and the teeth are peg shaped and hair is sparse. Height, weight and head circumference are all subnormal and osseous development is delayed.

Oculodentodigital Dysplasia Oculodentodigital dysplasia is an autosomal dominantly inherited syndrome that affects the eyes, teeth, digits, skeleton and the nervous system.

Features A characteristic face in which the nose is thin and also hypoplastic microphthalmia or microcornia. Enamel hypoplasia and syndactyly and camptodactyly of the fourth and fifth fingers.

Fanconi’s Syndrome Synonym: Familial pancytopenia. Familial panmyelophthisis: It is inherited disorder of childhood characterized by diffuse cutaneous pigmentation, skeletal and dental changes, hematological anomalies, mental retardation and hypogonadism. There is enamel hypoplasia reported with this syndrome. Cutaneous pigmentation is present with 85 percent of the cases characterized by generalized dusky or olive brown pigmentation on lower trunk and neck. Hematological abnormalities include progressive hypoplastic anemia, neutropenia and thrombocytopenia. Skeletal anomalies are short and broad hands with tapering fingers, absence of thumbs, aplasia of the radius and microcephaly.

Lacrimo-auriculo-dento-digital Syndrome Lacrimo-auriculo-dento-digital syndrome is an autosomal dominant malformation complex that affects craniofacial structures including teeth and salivary glands. The first case of lacrimo-auriculo-dento-digital syndrome was first reported by Levey in 1967. The features are: Lacrimal—absence of the lacrimal puncta nasolacrimal ducts and lacrimal sacs. Dental—dental dysplasia hypodontia, hypoplasia, amelogenesis imperfecta, high narrow palate. Digital—arachnodactyly, radioulnar synostosis, hypoplasia of the first digit. Ears—protuberant ears that are cup shaped. Sensory hearing loss.

Nevoid Basal Cell Carcinoma Syndrome (Bifid Rib Syndrome Or Gorlin-Goltz Syndrome) The dental/oral manifestation The developing teeth may get displaced because of the odontogenic keratocysts associated with this syndrome. There is deformity of teeth and may not develop till middle age of life.

Syndromes of the Orofacial Region

SYNDROMES ASSOCIATED WITH LIPS AND CHEEK • • • • • •

Ascher’s syndrome Melkersson-Rosenthal syndrome van der Woude syndrome Hereditary hemorrhagic telangiectasia Cowden syndrome Zinsser-Engman-Cole syndrome.

Ascher’s Syndrome Ascher’s syndrome, first described in 1920, is the combination of a progressive enlargement of the upper lip (double lip) lid laxity (blepharochalasis) and goiter. The lip abnormality may be identical to the acquired double lip or it may be the result of chronic recurrent then persistent lip swelling. Thus, Ascher’s syndrome does have some parallels with Melkersson-Rosenthal syndrome, but only the upper lip is involved and the horizontal ford is almost always seen. The lips feel soft and lobulated. Excessive salivation may be present—it is considered a localized disorder of elastic tissue because both the eyelids and upper lip seem to be deficient in this structural component. There may also be endocrine problems including thryoid goiter acromegaly and menstrual irregularities.

Melkersson-Rosenthal Syndrome Synonym: Miescher’s disease This condition is characterized by recurring spontaneous swelling of one or both lips (which may become permanent) has no cause. The manifestation of this syndrome is facial swelling, facial neural paresis and plicated tongue. The syndrome generally appears in adults. Many cases reveal possible additional involvement of areas away from the face such as hands and chest. Additional symptoms include secretary disturbances of the salivary and lacrimal glands.

van der Woude Syndrome The van der Woude syndrome was first described by Demarquay Rischet. It is also called Demarquay-Rischet syndrome. Its manifestations are: • Congenital lip fistulas, especially of the lower lip • Cleft lip and cleft palate • Hypodontia • Flattened nose and • Skeletal and cardiac abnormalities.

Hereditary Hemorrhagic Telangiectasia Synonym: Osler’s disease, Osler-Weber-Rendu disease. This is a relatively common autosomal dominant disorder. It was first described by Bird, Garland and Aiming. HHT is characterized by widespread vascular involvement with recurrent episode of spontaneous bleeding with multiple telangiectasia of the skin and mucous membranes.

Clinical Features The first and the most common clinical sign is persistent nose bleeds which begins in childhood. Tiny red macules and papules are seen around the mouth. The lesions blanch readily on diascopy. These are telangiectasia throughout the gastrointestinal system and lungs. CNS manifestation is migraines and epilepsy. Recurrent GIT bleeding may occur. There may be associated liver spleen vascular anomalies.

Oral Manifestations The oral mucosa has telangiectasia on the vermilion border of the lip, the lip mucosa, tongue a buccal, mucosa and palate and less oftenly gingiva. Oral bleeding in observed as a frequent complaint after tooth brushing. Multiple telangiectasias have been reported in the CREST syndrome. C — Calcinosis cutis R — Raynauds phenomenon E — Esophageal dysfunction S — Sclerodactyly T — Telangiectasia.

Cowden Syndrome Synonym: Multiple hamartoma syndrome. Cowden syndrome is a rare inherited genodermatose. The major features include: • Multiple hamartomatous papules and nodules of the skin and oral mucosa • Together with thyroid and breast anomalies • Polyposis of the gastrointestinal tract. This syndrome was named after the first patient reported. Almost all patients have mucocutaneous abnormalities, typically facial papules or nodules (usually hair follicle hamartoma with histologic features of trichilemmomas). Or nodules on neck, hands and forearms and of the palms and soles.

Zinsser-Engman-Cole Syndrome Synonym: Dyskeratosis congenita This extremely rare syndrome is characterized by keratinization of the oral mucosa, reticular cutaneous

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hyperpigmentation, nail dystrophy and pancytopenia. There is sex linked recessive inheritance pattern. The initial lesions may be noted as early as fourth or fifth year as a reticulated hyperpigmentation on the face neck and trunk. Purpuric lesions can be seen as the hematology abnormalities develop. The most commonly observed involvement of the oral mucous membrane (sites being tongue and buccal mucosa) is characterized by extensive keratinization, primary lesion that consists of a bulla that eventually ruptures apparently leads to eventual keratinization. The likelihood of squamous cell carcinoma developing is well documented and all cases should be followed very carefully for such occurrence.

SYNDROMES ASSOCIATED WITH TONGUE • • • • • • • • •

Orofacial digital syndrome Meckel syndrome Mobius syndrome Hurler syndrome Maroteaux-Lamy syndrome Beckwith hypoglycemic syndrome Aglossia-adactylia syndrome Melkersson-Rosenthal syndrome Burning mouth syndrome. Many syndromes associated with tongue are characterized by macroglossia. They include the following:

Winchester Syndrome Winchester syndrome clinically resembles a storage disorder but lacks the metabolic defects. Patients have joint deformities, corneal opacities, a coarse facies, thickened skin and macroglossia.

Anhydrotic Ectodermal Dysplasia/ChristSiemens-Touraine Syndrome It is characterized by skin anomalies, alopecia, dental abnormalities and in some cases by an enlarged tongue.

Zellweger Syndrome Its features are dwarfism, cardiac defects, facial anomalies, cutis laxa and macroglossia.

Beckwith-Wiedemann Syndrome Patients have an omphalocele, microglossia and hypertrophy of various organs or even gigantism. Often during

pregnancy hydrominon develops because of difficulty in swallowing caused by enlarged fetal tongue. Many of the metabolic storage or lysosomes disorders are characterized by macroglossia; the patients usually have so many other problems that the macroglossia almost never is the presenting complaint. Included in this group are: • Mucopolysaccharidosis • Hurler syndrome • Hunter syndrome • Sanfilippo’s syndrome • Sulfatidoses • Austin syndrome • Gangliosidoses • GMI or landing syndrome • Cornelia de Lange syndrome II with muscle and tongue hyperplasia, abnormal ears and CNS abnormalities • Leroy syndrome • Mannosidoses • Glycogen storage diseases mainly type II or Pompe’s disease.

Orofacial Digital (OFD) Syndrome OFD Type 1 Orofacial digital syndrome has been subdivided into several disorders but the classic or type 1 OFD is of primary interest. It is inherited as an X-linked dominant triat so that only females are affected because the gene is lethal in males. The first case was described by Papillon Leage and Psaume in 1954.

Features of OFD Type 1 Clefts of the jaw and tongue in canine region. Others features are syndacyly, brachydactyly and polydactyly), small nostril, a lobulated tongue with hamartoma. Aberrant hyperplastic oral frenula which appears to lead to the clefting of jaws, tongue and upper lip.

Hurler Syndrome Synonym: Mucopolysaccharidosis Hurler syndrome is a disturbance of mucopolysaccharide metabolism exhibiting a variety of classical clinical features. It is characterized by an elevated mucopolysaccharide excretion level in the urine.

Clinical Features The disease usually becomes apparent at the age of two, progresses during early childhood and adolescence and terminates in death usually before puberty.

Syndromes of the Orofacial Region

Facies—large head with prominent forehead, broad saddle nose and wide nostrils, thick lips and large tongue, open mouth and nasal congestion. Progressive corneal clouding is classic feature with hepatosplenomegaly. Flexion contraction results in “claw hand”. The individuals are dwarf and mentally retarded.

Aglossia-Adactylia Syndrome

Oral Manifestation

Extremities involvement may be severe, from complete peromelia to absence of single digit.

Short and broad mandible with prominent gonions. Delayed eruption of teeth, localized areas of bone destruction in the jaws may be found which appear to be representing hyperplastic dental follicles with large pools of metachromatic material, probably mucopolysaccharide. Gingival hyperplasia is almost always present. Enlarged tongue is present.

Histopathology Excessive accumulation of intracellular mucopolysaccharide in many tissues and organs and throughout the body. There is elevated level of mucopolysaccharide in the urine.

Mobius Syndrome Synonym: Congenital facial diplegia Congenital facial diplegia is a nonfamilial deficient development of cranial muscles consisting of facial diplegia with bilateral paralysis of the ocular muscles, particularly the abducens. The cause of the disease is now recognized as degeneration of the 6th and 7th cranial nerve muscles although it was originally thought to be a primary nuclear hypoplasia with secondary muscle atrophy.

Clinical Features

This syndrome in which absence of the tongue is associated with failure of digits to develop is extremely rare. It was first described by De Jussier.

Systemic Manifestations

Oral Manifestation The tongue is absent in majority of the cases. The sublingual muscular ridge may be enlarged. The mandible is usually small and poorly developed.

Burning Mouth Syndrome Clinical Features Burning mouth syndrome [burning and pain of the mouth or of the tongue, painful tongue. Glossodynia] without any visible changes is common with many causes. The patient complains of intense and unbearable pain that interferes with eating, sleeping and virtually every other body function. The tongue may appear as red or atrophic or the mucosa may appear entirely normal. The complaints are usually limited to tongue but may involve the entire mucosa. Burning mouth syndrome is most common in middle aged women especially around the time of menopause. Neurologic disorders may also present with mouth or tongue symptoms, most often unilateral. If the pain seems localized to one side of the tongue, a microbiologic evaluation may be indicated.

It is manifested in the first few days of life by failure to close the eyes during sleep. Because of the partial or complete facial paralysis, the infant exhibits no change in the facial expression even when crying or laughing. There is difficulty in mastication, saliva frequently drools from the corners of the mouth and speech is severely impaired. The majority of patients have other associated congenital defects, including external ophthalmoplegia, deafness, paresis of the tongue, soft palate or jaw muscles, clubfoot, mental defects and epilepsy.

• • • • • • • •

Treatment and Prognosis

Tuberous Sclerosis

There is no treatment for the disease but the prognosis appears to be good, barring complications.

(Described under syndromes with benign oral neoplastic and hamartomatous components). There is gingival fibromatosis

SYNDROMES ASSOCIATED WITH GINGIVA Tuberous sclerosis Zimmerman - Laband syndrome Rutherford syndrome Ramon syndrome Cowden syndrome Papillon-Lefevre syndrome Klippel trenaunay-Weber syndrome Melkersson-Rosenthal syndrome.

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or there may be single or multiple fibromas of the gingiva, oral mucosa and skin. 878

Zimmerman-Laband Syndrome

• Premature loss of deciduous teeth by the age of 4 or 5 years • Deep periodontal abscess may be present • Permanent teeth are also lost in the same manner.

Synonym: Laband syndrome Laband syndrome (LS) is a rare disorder characterized by gingival fibromatosis, abnormalities of the nose and /or ears and absence and /or hypoplasia of the nails or terminal phalanges of the hands and feet. Other more variable features include hyperextensibility of joints, hepatosplenomegaly, mild hirsutism and mental retardation. The first case was described by Zimmerman in 1928; Lanband et al described the first familial occurrences in 1964.

Klippel-Trenaunay-Weber Syndrome (KTW)

Rutherford Syndrome

Oral Manifestation

This syndrome has autosomal dominant inheritance: the manifestations are: • Congenially enlarged gingiva • Delayed tooth eruption • “Curtain like” corneal opacities • Associated features are: mental retardation and dentigerous cysts.

Angiomatous involvement of lips, buccal mucosa, tongue, palate, gingiva and oropharynx. In addition, enlarged maxilla, premature eruption of teeth and marked displacement of teeth on the affected side producing dental malocclusion have also been reported.

Ramon Syndrome The characteristic features of this syndrome are: Gingival fibromatosis. Hypertrichosis, cherubism, mental retardation and epilepsy. There is characteristic perivascular fibrosis in gingival biopsies. Other associated features include juvenile rheumatoid arthritis; the gingival fibromatosis usually always precedes cherubism.

Papillon-Lefevre Syndrome This is an inherited disorder transmitted as an autosomal recessive trait. The disease usually manifests during early childhood as circumscribed erythematous hyperkeratotic plaques on the palms and soles. Hyperkeratosis may extend to the sides of hands and feet, knees and elbows. Transverse grooves of nails occur. Dental changes are: • Gingivitis • Periodontitis

Klippel-Trenaunay-Weber syndrome was reported by Klippel and Trenaunay in 1900. It consists of a classical triad of clinical features and angioma formation. The predominant features of the KTW syndrome are asymmetric limb hypertrophy. Cutaneous hemangiomas and pigmenta. Varicose veins located on the legs, abdomen and trunk. Other abnormalities include macrodactyly hyperpigmented nevi on skin, telangiectasia, macrocephaly and enlarged genitalia.

SYNDROMES ASSOCIATED WITH NERVES • • • • • •

Auriculotemporal syndrome (Frey’s syndrome) Reader’s syndrome (Paratrigeminal syndrome) Horton’s syndrome (cluster headache) Migrainous syndrome (migraine) Horner’s syndrome Jaw-Winking syndrome (Marcus-Gunn Phenomenon).

Auriculotemporal Syndrome Synonyms: Frey’s syndrome, Gustatory sweating The auriculotemporal syndrome is an unusual phenomenon which arises as a result of damage to the auriculotemporal nerve and subsequent reinnervation of the sweat glands by parasympathetic salivary fibers.

Etiology The syndrome follows some surgical operation such as removal of parotid tumor or the ramus of mandible or parotids of some type that has damaged the auriculotemporal nerve.

Syndromes of the Orofacial Region

After a considerable amount of time following surgery during which the damaged nerve develops, innervating sweat glands which then function after salivary, gustatory or psychic stimulation.

Clinical Features The patient typically exhibits flushing and sweating of the involved side of the face, chiefly in the temporal area during eating. The profuse sweating may be evoked by the parenteral administration of pilocarpine or eliminated by the administration of atropine or a procaine block of the auriculotemporal nerve. The auriculotemporal syndrome is not a common condition. Nevertheless the possibility of its occurrence must always be considered.

Treatment Treatment of the auriculotemporal syndrome by the intracranial division of the auriculotemporal nerve has been reported to be successful.

Reader’s Syndrome (Paratrigeminal Syndrome) The paratrigeminal syndrome is a disease characterized by severe headache or pain in the area of trigeminal distribution with signs of ocular sympathetic paralysis. The sympathetic symptoms and homolateral pain in the head or eye occur without vasomotor or trophic disturbances. These signs and symptoms usually appear suddenly. The disease appears to be the most common in males, chiefly those of middle age. Paratrigeminal syndrome presents some of the signs of the Homer’s syndrome but can be differentiated from it by the presence of pain and little or no change in sweating activity on the affected side of face. The cause of this disease is unknown but dramatic improvement has been found after elimination of dental infection.

Horton’s Syndrome Synonyms: Sphenopalatine neuralgia, cluster headache, periodic migrainous neuralgia. Sphenopalatine neuralgia is a pain syndrome originally described by sluder as a symptom complex referable to the nasal ganglion. Vial described a similar syndrome but believed it involved the vidian nerve and concluded that the condition reported by sluder should be termed “vidian neuralgia”. It is considered to be a variant of migraine.

Etiology The suggested etiology is that it is caused by vasodilatation involving the internal maxillary artery a branch supplying the sphenopalatine region. The theory of deviation of nasal septum being one of the causes is also questioned.

Clinical Features This syndrome is characterized by unilateral paroxysm of intense pain in the region of the eyes, maxilla, ear and the mastoid, base of the nose and beneath the zygoma. Sometimes the pain extends into the occipital area as well. The paroxysm of pain has a rapid onset, persists for about 15 minutes to several hours and then disappears as rapidly as they began. There is no “trigger zone”. The pain occurs atleast once in a day regularly. This disappears after some weeks or months and the period of freedom may be for months or years. In addition to pain sensation, other complaints may be sneezing, swelling of the nasal mucosa, severe nasal discharge may be there after painful attacks. Also accompanied are epiphora or watering of the eyes, bloodshot eyes and paresthesia. Men are more commonly affected than women.

Treatment Cocainization of the sphenopalatine ganglion or alcohol injection of this structure is one of the widely used therapies. Surgical resection of the ganglion is done in some cases.

Migraine Syndrome (Migraine) Migraine is a syndrome presenting manifestations of diffuse disturbances in body functions occurring during or after stress, characterized by severe periodic headache, irritability and nausea. The cause of the disease is unknown but has been postulated to be a discharge of autonomic centers in the forebrain leading to constriction in portions of the cerebral arterial tree. In susceptible patients it may become manifest in the preheadache phenomenon. Then, as part of an attempt to maintain cranial homeostasis there is decrease in constrictor in certain other cranial arteries, particularly branches of the external carotid. These secondary effects, possibly harmonal as well as neurogenic in origin are the source of the headache.

Clinical Features Usually seen in second decade of life. The frequency of attacks is extremely variable as they may occur at

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frequent intervals over period of year or on only a few occasions during the lifetime of patient. A prodromal stage (preheadache phenomena) is noted by some patients consisting of lethargy and dejection several hours before the headache. Visual phenomena such as scintillation hallucinations or scotomas are often described. The headache pain consists of severe pain in the temporal, frontal and retro-orbital areas although other sites such as parietal, postauricular, occipital or suboccipital are also occasionally involved. The pain is usually unilateral but may become bilateral and generalized. The pain is described as a deep aching, throbbing type.

Treatment and Prognosis The treatment of migraine includes a wide variety of drugs ranging from acetylsalicylic acid and codeine to ergotamine, methyl salicylic and nor epinephrine. The prognosis of the disease is good, since the condition is not dangerous, and may undergo complete and permanent remission.

Horner’s Syndrome Synonym: Sympathetic ophthalmoplegia Horner’s syndrome is a condition characterized by: miosis or contraction of the pupil of the eye due to paresis of the dilator of the pupil. Ptosis: drooping of the eyelid due to paresis of the smooth muscle elevator of the upper eyelid. Anhidrosis and vasodilatation over the face due to interruption of pseudomotor and vasomotor control. Its chief significance lies in the fact that it indicates the presence of a primary disease. The lesions in the brain-stem, chiefly tumors or infections in the cervical or high thoracic vertebrae will occasionally produce this syndrome. Preganglionic fibers in the anterior spinal roots to the sympathetic chain in the low cervical and high thoracic area are rather commonly involved by infection, trauma or pressure as by aneurysm or tumor to produce Horner’s syndrome.

Jaw-Winking Syndrome (Marcus-Gunn Phenomenon; Pterygoid-Levators Synkinesis) This interesting condition consists of congenital unilateral ptosis with rapid elevation of ptotic eyelid occurring on movement of the mandible to the contralateral side. It is commonly recognized in the infant by the mother, when breast feeding her baby she notices one of its eyelids shoot up. As in the case reported by Smith and Gans.

The syndrome may be later in life but also is seen to be as hereditary in some cases. Males are more commonly affected than females. The left upper eyelid is more frequently involved than the right. It is also thought that about 2 percent of all cases of congenital ptosis are due to this condition. There are numerous theories concerning the etiology of this disease and these have been reviewed by Simpson. The most widely accepted is that the levators palpebral muscle is connected not only with the third nucleus, but also with the external pterygoid portion of the fifth nucleus. However, there is some evidence of supranuclear involvement. An interesting condition Marin Amat Syndrome or “inverted Marcus-Gunn phenomenon” is usually seen after the peripheral facial paralysis. In this condition, the eye closes automatically when the patient opens his mouth forcefully and fully as in chewing and tears may flow.

SYNDROMES ASSOCIATED WITH BLOOD • Plummer-Vinson syndrome • Chediak-Higashi syndrome • Sweets syndrome (Acute febrile neutrophilic dermatosis) • Lazy leukocyte syndrome.

Plummer-Vinson Syndrome Synonym: Iron deficiency anemia The Plummer-Vinson syndrome is one manifestation of iron-deficiency anemia and was first described by Plummer in 1914 and by Vinson in 1922 under the term “hysterical dysphagia” not until 1936; however was the full clinical significance of this condition was recognized. Ahlbom then defined it as a predisposition for the development of carcinoma in the upper alimentary tract. It is in fact one of the few known predisposing factors in oral cancer.

Clinical Features While an iron deficiency anemia can occur at any age Plummer-Vinson syndrome occurs chiefly in women and in the fourth-fifth decade of life. Presenting symptoms of the anemia and the syndrome are cracks or fissures at the corners of the mouth; a lemon tinted pallor of the skin, a smooth red, painful tongue with the atrophy of filiform and later fungiform papillae and resulting from esophageal

Syndromes of the Orofacial Region

stricture of the web. Koilonychias or spoon shaped finger nails which are brittle and break easily have been reported in many patients. Splenomegaly has also been reported in 20 to 30 percent of the cases. The depletion of iron stores in the body, manifested as iron deficiency anemia may be the direct cause of the mucous membrane atrophy, since the integrity of epithelium is dependant upon adequate serum iron levels. The atrophy of the epithelium predisposes to the development of carcinoma in these tissues. This relationship was first noted by Albom in the patients suffering from carcinoma of pharynx and upper part of esophagus.

Laboratory Finding Blood examination reveals a hypochromic microcytic anemia of varying degree while megaloblasts typical of pernicious anemia. The red blood cell count is generally between 3,000,000 and 4,000,000 cells per cubic mm; and the hemoglobin is invariably low. The anemia of the iron deficiency type can be confirmed by lack of a reticulocyte response following administration of vitamin B12. Serum iron is low and there is an absence of free hydrochloric acid in the stomach. The achlorhydria is generally the cause of the faulty absorption of iron since the absence of hydrochloric acid prevents the conversion of unabsorbable dietary ferric iron to the absorbable ferrous state. The exfoliated squamous epithelial cells also showed changes such as deficiency of keratinized cells, a reduced cytoplasmic diameter of cells with a paradoxical enlargement of the nucleus, an increase in the nucleoli, presence of double nucleus and karyohexis.

Chediak-Higashi Syndrome Chediak-Higashi syndrome is an uncommon genetic disease which is often fatal in early life as result of a lymphoma like terminal phase, hemorrhage or infection. It is transmitted as an autosomal recessive trait.

Clinical Features The characteristic clinical features of this disease consist of oculocutaneous albinism, photophobia, nystagmus and recurrent infections. The degree of albinism and the structures involved are quite variable as is pigmentary dilutions of structures. Recurrent infections usually involve the respiratory tract and skin. Occasional other findings include neurologic problems, a variety of gastrointestinal disturbances,

generalized lymphadenopathy and hepatosplenomegaly. The disease has been sometimes associated with the malignant lymphomas.

Oral Manifestations Ulcerations of the oral mucosa, severe gingivitis and glossitis are the commonly described oral lesion.

Laboratory Findings Hematological studies show that the patients classically exhibit giant abnormal granules in the peripheral circulating leukocytes in their marrow precursors and in many other cells of the body as well. These granules are the hallmark of the syndrome and are invariably present. They are thought to represent abnormal lysosomes and bear resemblance to toxic granulations and Dohle bodies. Pancytopenia is sometimes presents.

Treatment and Prognosis There is no specific treatment for this disease and death usually occurs within first few years of life as a result of secondary infection or hemorrhage.

Sweet’s Syndrome Synonym: Acute febrile neutrophilic dermatosis Sweet’s syndrome was first described by sweet in 1964. He identified young women who had sudden development of erythematous nodules associated with fever and malaise. Typically the skin lesions consists of coleasing, plague forming papules which at first sight give the illusion of vesiculation but are solid on palpation. Histopathologically the lesion show papillary dermal edema and an intense neutrophilic infiltrate, but do not represent an infection or leukemic infiltrate. In majority of the cases a febrile infection of the upper respiratory tract, tonsillitis or influenza like disease precedes the clinical symptoms by 1 to 3 weeks. Twenty percent of the acute myelogenous leukemia patients have documented this manifestation as an early sign.

Lazy Leukocyte Syndrome First described by Miller, Oski and Harris in 1971. Lazy leukocyte syndrome is caused by loss of the chemotactic functions of the neutrophils. The bone marrow contains normal numbers of mature neutrophils, but the patients have severe neutropenia because the cells are unable to migrate from the marrow to the peripheral blood.

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Clinical Manifestations

Diffuse Neonatal Hemangiomatoses

The infections complications are apparent at age 1 to 2 years. The most common infections noted are gingivitis, stomatitis, otitis media and bronchitis. The total WBC count is in the low normal range. But the absolute neutrophil count is as low as 100/mm3 to 200 mm3. Erythrocytes and platelets are normal. The diagnosis is based on neutrophil mobilization tests showing lack of normal response.

This term encompasses a benign form in which the child may have hundreds of small cutaneous hemangiomas without visceral involvement and a disseminated form in which organ involvement is present. The latter group is prone to complications like hemorrhage, disseminated intravascular coagulation. Cardiac failure and compression of vital structures. Systemic corticosteroids are usually indicated.

SYNDROMES ASSOCIATED WITH VASCULAR MALFORMATIONS Syndromes associated with hemangiomas: • Maffucci’s syndrome • Blue-Rubber bleb nevus syndrome • Diffuse neonatal hemangiomatoses Syndromes associated with Ports wine stain • Sturge-Weber syndrome • Klippel-Trenaunay syndrome • Von Hippel-Lindau syndrome • Parkes-Weber syndrome • Beckwith-Wiedemann syndrome.

Maffucci’s Syndrome Cutaneous hemangiomas appearing in infancy are associated with hard nodules of the bones, especially distal, which are enchondroma on histology. Abnormal bone growth, interference with epiphyseal cartilage and pathology fractures can cause gross deformity which is added to by enlargement of the vascular swellings into large masses. Maffucci’s syndrome is associated with an increased risk of malignancies like chondrosarcoma, fibrosarcoma, angiosarcoma, lymphangiosarcoma, osteosarcoma and ovarian tumors.

Blue Rubber Bleb Nevus Syndrome Synonym: Blans syndrome Blue-Rubber bleb nevus syndrome is seen as an association of multiple cutaneous and gastrointestinal tract hemangiomas, the skin lesions are typically bluish, rubbery, nipple like compressible angioma, along with smaller blue marks and larger cavernous hemangiomas. Gastrointestinal bleeding, hematuria, menorrhagia and epistaxis may be the presenting features if other visceral angioma are present. Cases may be sporadic or familial with autosomal dominant inheritance.

Sturge-Weber Syndrome Synonym: Encephalofacial angiomatoses A facial portwine stain in the distribution of the first branch of the trigeminal nerve is associated with homolateral leptomeningeal angiomatosis, usually over the posterior parietal and occipital lobes of the cerebral cortex. It is postulated to be a developmental defect of certain ectodermal and mesodermal elements closely approximated in the brain and meninges at 4 to 8 weeks of gestational age. The port wine stain is present at birth and is unilateral, but may cross the midline and also involve mucosae. Patients with additional involvement of in the distribution of the second branch of the trigeminal nerve have a high risk of ocular complications, some patients also have bilateral facial lesions or involvement of the trunk or extremities. Convulsions of the grand mal type generally appear during the first year of life and behavioral problems, subnormal intelligence, contralateral hemiparesis and EEG abnormalities (usually unilateral or focal) may be seen. Ocular involvement (40%) is in the form of ipsilateral glaucoma, congestion strabismus and loss of vision. Characteristic S-shaped intracranial calcifications are found in the leptomeninges within the first few months of life, on CT scans and on X-rays after the age of 2 years. They increase in density until the end of second decade when 50 to 60 percent of patients show this on radiography. They are thought to be due to anoxic injury from vascular stasis and increased vascular permeability in the areas of the angioma.

SYNDROMES ASSOCIATED WITH IMMUNODEFICIENCY • Acquired immunodeficiency syndrome • Reiter’s syndrome • Behçet’s syndrome.

Syndromes of the Orofacial Region

Reiter’s Syndrome The underlying cause of this disease syndrome is unknown although there appears some genetic influence in some cases. An abnormal immune response to microbial antigens is now considered to be a likely mechanism for the multiple manifestations of this disease. (Syndrome)

Clinical Features Arthritis, nongonococcal urethritis, and conjunctivitis or uveitis. The urethritis and conjunctivitis or uveitis. The urethritis generally precedes the appearance of other lesions. Mucocutaneous lesions may be seen in up to half of the patients. Orally the lesions have been described as relatively painless aphthous type lesions (ulcers) occurring almost anywhere in the mouth. Tongue lesions are like that of the geographic tongue. The duration of the disease varies from weeks to months and recurrences are not common. Nonsteroidal anti-inflammatory drugs are used for the treatment of this disease.

Behçet’s Syndrome Exact etiology of this syndrome is unknown although the underlying disease mechanism may be very similar to the one associated the aphthous ulcers. Genetic predisposition and viral etiology has also been suggested.

Clinical Features The lesions of this syndrome typically affect the oral cavity, the eye, and the genitalia. Recurrent arthritis of the wrists, ankles and knees may be seen. Cardiovascular manifestations are usually of thrombotic type and neurologic manifestations are in the form of headaches. Oral manifestations of this syndrome appear identical to the ulcers of the aphthous stomatitis. The ulcers are usually of the minor aphthous type and are found in the typical aphthous distribution. Ocular changes are found in most of Bechetix patients. Uveitis, conjunctivitis and retinitis are more common inflammatory processes. Genital lesions are ulcerative in nature and may be the cause of significant pain and discomfort. Inflammatory bowel disease has also been reported. Histopathology—T lymphocytes are predominant. Neutrophilic infiltrates in which the cells appear within the vessel walls have also been described. Treatment—consist of systemic steroid therapy.

SYNDROMES ASSOCIATED WITH HORMONAL DISTURBANCES • • • • •

Cushing syndrome Adrenogenital syndrome General adaptation syndrome Hutchinson-Gilford syndrome Waterhouse-Friderichsen syndrome.

Cushing Syndrome Cushing syndrome is a result of hormonal excess resulting from any of the following: • Hyperplastic adrenal cortices without any other clinically evident endocrine lesion. • Adrenal cortical adenoma or carcinoma • Ectopically located adrenal like tumor for, e.g. of an ovary • ACTH secreting tumor of the anterior pituitary • Nonpituitary carcinoma for, e.g. of a lung or pancreas. When this syndrome is associated with spontaneous bilateral adrenal hyperplasia, it is referred to as Cushing disease. This syndrome is characterized by a rapidly acquired adiposity about the upper portion of the body, moon like appearance of the face. A tendency to become round shouldered and develop a “buffalo-hump” at the base of the neck. Other features include muscle weakness, vascular hypertension, glycosuria not controlled by insulin and albuminuria. The oral pathologist’s primary concern with this peculiar disease state lies in the bone changes. In children there may be osteoporosis and premature cessation of the epiphyseal growth, while in adults there is a severe osteoporosis. The pathogenesis suggested is based on the SFN (sugarfat-Nitrogen) hormone group of steroids. The ‘N’ hormone stimulates osteogenesis and closing of the epiphysis and ‘S’ hormone leads to a retardation of osteoblastic activity and reduction in matrix formation.

Adrenogenital Syndrome This condition results when there is hyperplasia of the adrenal cortex. Depending on the age at onset and the sex of the person affected the clinical signs occur. These manifestations are pseudohermaphroditism, sexual precocity and virilism in women or feminization in men. If the disease begins early, premature eruption of the teeth may occur.

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General Adaptation Syndrome 884

General adaptation syndrome (GAS) represents the signs and symptoms occurring due to prolonged “stress” as a part of individual adaptation mechanism. The adrenal gland and stress has a close relationship. This theory was proposed by Hans Selye. Adrenal changes result due to prolonged stress leading to mobilization of lipids and ultimate exhaustion atrophy of the cortical cells. The hormones of the adrenal cortex are necessary for cellular enzymes to catalyze the energy producing processes of cells. All ‘stresses’ agents stimulate adrenal function through stimulation of pituitary to secrete ACTH. If excessive amounts of hormones are produced, eventually pathologic changes occur in those tissues which respond to the stimulation and the diseases of adaptation, (hypertension, periarteritis nodosa and others) result. The stages are: • Ist “Alarm reaction” which consists of a shock phase and then a counter shock phase • IInd “Adaptation stage” in which a person’s resistance to original stressor is greater but his resistance to other stressor agents is lowered • IIIrd—if the stressor is continued. He eventually enters a stage of exhaustion and dies. If the stressor is removed, he enters a stage of convalescence and recovers.

Progeria (Hutchinson-Gilford Syndrome) Progeria is a very rare disease originally described by Hutchinson in 1886. It is of unknown etiology and is characterized by dwarfism and premature senility. It is thought to be transmitted as an autosomal recessive trait.

Clinical Features Affected infants appear normal at birth, but the typical clinical features become manifest within the first few years. The patients all have amazing resemblance to each other, exhibiting alopecia, pigmented areas of the trunk, atrophic veins and loss of subcutaneous fat. The individuals have a squeaky voice, a beak nose and a hypoplastic mandible. The intelligence these individuals is either normal or above normal. Even at an early age person resembles a wizened little old person.

Oral Manifestations As described by Gardner’s, there is accelerated formation of irregular secondary dentin, apparently a manifestation

of the premature ageing process. Delayed eruption is also reported.

Waterhouse-Friderichsen Syndrome Acute adrenal cortical insufficiency is relatively rare and it occurs in connection with waterhouse-Friderickson syndrome. This disease primarily occurs in children but also occurs in adults. It is characterized by a rapidly fulminating septic course, a pronounced purpose and death within 48 to 72 hours—Meningococci, streptococci and pneumococci are the organisms most responsible for the disease. At autopsy, the conspicuous change is bilateral adrenal hemorrhage. The use of antibiotics and cortisone has changed the course of the disease from its usual fatal termination to recovery in some cases.

SYNDROMES WITH BENIGN ORAL NEOPLASTIC OR HAMARTOMATOUS COMPONENTS • von Recklinghausen’s neurofibromatosis • Nevoid basal cell carcinoma syndrome • Multiple mucosal neuroma syndrome (multiple endocrine neoplasia type III) • Tuberous sclerosis • Acanthosis nigricans • Albright’s syndrome.

von Recklinghausen’s Neurofibromatosis Two distinct varieties of this classic syndrome are now recognized: • Neurofibromatosis 1: which is often associated with oral lesions. • Neurofibromatosis 2: (bilateral acoustic neurofibromatosis) which is caused by a gene on a different chromosome is much less common, and while often accompanied by other central nervous system tumors is less frequently associated with obvious peripheral neurofibromatosis or oral lesions. Neurofibromatosis 1 is inherited as an autosomal dominant condition. But only half the cases exhibit a family history. The syndrome is characterized by the simultaneous occurrence usually on the trunk, axilla and pelvic area of light brown pigmentation (cafe au lait spot, light brown macules with a smooth outline “like the coast of California”). The finding of six or more macules

Syndromes of the Orofacial Region

with a diameter of 1.5 cm or greater is diagnostic of neurofibromatosis. Cafe au lait spots are also found in 10 percent of the normal population, especially in fair skinned persons. Similar skin lesions with the same name occur in Albright’s syndrome. Other findings are axillary freckling (Crowe’s sign) and a wide variety of nerve and nerve sheath tumors in both central and peripheral nervous systems. The peripheral lesions are often indistinguishable from those called neurilemmoma (tumors of the nerve sheath: schwannoma). Both neurofibroma and neurilemmoma are encapsulated S-100 positive tumors that show patterns of whorled connective tissue elements histologically with readily recognizable axons with or without myelin sheath. The central lesions because of their location within a bony cavity often in association with various nerve roots lead to neurologic symptoms, mental retardation and vertebral anomalies large infiltrating lesions that occur both peripherally and centrally and lead to severe deformity and are referred to as ‘plexiform neuroma’. Pheochromo cystomas (tumors of the adrenal medulla and paraganglia). Approximately 5 percent of the patients with neurofibromatosis have well developed oral lesions and macroglossia. The tongue being the most common oral location for neurofibroma both in this syndrome and in solitary oral neurofibroma.

Basal Cell Nevus or Nevoid Basal Cell Carcinoma Syndrome Synonym: Gorlin-Goltz syndrome, Jaw-cyst-bifid rib syndrome. This syndrome was first described by Binkely and Johansson in 1951. This has been thoroughly reviewed by Gorlin and his co-workers.

Clinical Features This syndrome has the following variable manifestations: Cutaneous anomalies: Basal cell carcinoma, other benign cyst and tumors, palmar pitting, palmar and plantar keratosis and dermal calcinosis

Neurologic anomalies: Mental retardation, dural calcification, agenesis of corpus callosum. Sexual abnormalities: Hypogonadism in males and ovarian tumors. Oral manifestations: The keratocyst may displace the developing teeth and result in their deformity.

Multiple Endocrine Neoplasia Syndromes (MEN Syndromes) This is a group of syndromes characterized by tumors of various endocrine organs occurring in association with a variety of other pathologic features. Steiner and his associates have classified these syndromes into: MEN I — type I MEN II — type II Khairi and associates have decribed type III (MEN III) other workers have subdivided type II into II A (synonymous with original type II) and II B (synonymous with type III).

Clinical Features MEN I: Consists of tumors of hyperplasia’s of the pituitary, parathyroid, adrenal cortex and the pancreatic islets occurring in association with peptic ulcers and gastric hypersecretion. MEN II: (Sipples syndrome, II A) is characterized by parathyroid hyperplasia or adenoma but no tumors of pancreas. However, in addition these patients have pheochromocytomas of the adrenal medulla and medullary carcinoma of the thyroid gland. There is no peptic ulcer. MEN III: (II B) it is characterized by mucocutaneous neuroma, pheochromocytomas of the adrenal medulla, medullary carcinoma of the thyroid. Other abnormalities include hypertrophied corneal nerves, other skeletal defects and gastrointestinal difficulties, oral manifestations. MEN III: Is particularly having the constant component of multiple oral neuroma. The neuroma are most common on the lips tongue and buccal mucosa. They produce “Bumpy Lips” since the neuroma present at birth or may develop later appear as small elevated sessile nodules on the vermilion producing puffy lips. On the tongue they are commonly present on the anterior third.

Dental osseous anomalies: Multiple odontogenic keratocyst, jaw prognathism, rib anomalies (often bifid) and vertebral anomalies.

Tuberous Sclerosis

Ophthalmologic abnormalities: Hypertelorism with wide nasal bridges, congenital blindness and strabismus

Synonyms: Pringle-Bourneville syndrome adenoma sebaceum.

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The key skin findings are hypopigmented macules (ashleaf macules) connective tissue nevi, (shagreen patch) and multiple angiofibroma. Red brown macules and papules are seen about the mouth in the nasolabial folds. CNS findings include epilepsy mental retardation.

papillomatous lesions can be found on the lips, especially at the commissures. The tongue shows elongated filiform papillae, deeper folds and may appear enlarged. The buccal mucosa may be also thickened and show increased folds. there may also be gingival hyperplasia. In contrast to skin lesions, the oral lesions are usually not pigmented. The papillomatous lip changes resembling angular cheilitis are limited almost exclusively to tumor, related AN. The course of the disease is chronic and there is no satisfactory treatment for this disease.

Oral Features

Klippel-Trenaunay Syndrome

The oral cavity frequently shows distinctive changes. Angiofibroma, fibromas or papillomas are found on the gingiva, hard and soft palate, buccal mucosa and tongue. They may be white or yellow although they lack any distinctive tint. Both dentitions have tiny pits arising from enamel defects. The pits are often an early diagnostic clue. A high palate, macroglossia, cleft lip and palate and hemangiomas have been described.

Classically, a port wine stain usually of the lower limb is associated with limb hypertrophy, lymphoedema, venous varicosities and obstructed, absent or deeper vessels. The cutaneous lesions be angioma or angiokeratomas. The bone and soft tissue hypertrophy may be both linear (almost 100% of patients) and circumferential (75%) and develops gradually. Varicose veins are present which may be obscured clinically by edema.

Tuberous sclerosis (TS) is an autosomal dominant disorder with marked variability of expression in a given family. 886

Clinical Features

Acanthosis Nigricans Acanthosis nigricans (AN) is a misnomer. Patients develop velvety dark patches particularly in flexural areas, but also in the mouth. There is papillomatosis and hyperkeratosis but no acanthosis and no increase in pigment, it appears that the deranged epithelial growth is directed through epidermal growth factor receptors. Several type of AN can be identified. • Tumor-related: In many cases, when tumor is removed AN disappears. • Endocrine: In a variety of endocrine syndromes AN is a frequent finding. • Juvenile or familial AN: Reported in some families • Drug induced: A variety of drug, primarily nicotinic acid can produce presumably by acting on growth factor receptors.

Oral Features The perioral lesions may be velvety brown patches particularly at the corners of the mouth. Multiple

Von Hippel-Lindau Syndrome An autosomal dominant condition is classically present as bilateral retinal angiomatosis leading to visceral impairment and blindness and cerebellar or medullary hemangioblastoma. Renal angioma and/or renal cell carcinoma, hepatic angioma and pheochromocytoma may occur. Port wine stains and café au lait spots are seen in 5 percent of patients.

Parkes-Weber Syndrome Arteriovenous fistulas are seen with features of the Klippel-Trenaunay syndrome, viz. Port wine stain, venous varicosities and limb hypertrophy. They may be suspected by a thrill or continuous bruit at the involved site. Their diagnosis should be confirmed by arteriography for large fistulae or by diagnostic methods using isotopes.

Syndromes of the Orofacial Region

MULTIPLE CHOICE QUESTIONS 1. Defects in clavicle is characteristics feature of: a. Cleidocranial dysplasia b. Edward syndrome c. Pierre-Robin syndrome d. Mobius syndrome 2. Trisomy 18 syndrome refers to: a. Down’s syndrome b. Patau syndrome c. Edward syndrome d. Crouzon syndrome 3. An autosomal recessive disorder characterized by oral, facial and digital defects is: a. Anderson syndrome b. Mohr syndrome c. Heerfordt’s syndrome d. Sjögren’s syndrome 4. A connective tissue disorder characterized by abnormalities of skeletal, cardiovascular and ocular system is: a. Marfan’s syndrome b. Ehlers-Danlos syndrome c. Albright’s syndrome d. Both a and b 5. A triad consisting of keratoconjunctivitis sicca, xerostomia and rheumatoid arthritis is: a. Heerfordt’s syndrome b. Sjögren’s syndrome c. Riley-Day syndrome d. Fanconi’s syndrome 6. Flushing and sweating of the involved side of face, chiefly in the temporal area seen in: a. Horton’s syndrome b. Rutherford syndrome c. Frey’s syndrome d. Ramon syndrome

7. Buffalo hump development at the base of neck refer to: a. Beçhet’s syndrome b. Reiter’s syndrome c. Adrenogenital syndrome d. Cushing’s syndrome

8. A syndrome characterized by dwarfism and premature senility: a. Progeria b. Hutchinson-Gilford syndrome c. Both d. MEN syndrome 9. A lemon tinted pallor of the skin, esophageal stricture of web, koilonychias is the clinical feature of: a. Plummer-Vinson syndrome b. Horner’s syndrome c. Parkes-Weber syndrome d. None 10. Multiple odontogenic keratocyst, jaw prognathism, bifid rib and vertebral anomalies seen in: a. MEN syndrome b. Gorlin-Goltz syndrome c. Progeria d. Both a and b 11. Treacher Collins Syndrome primarily affects structures developing from: a. First brachial arch b. Second brachial arch c. Both first and second brachial arch d. None of the above 12. Ehlers–Danlos syndrome is characterized by except: a. Skull hyperextensibilty b. Joint hypermobility c. Hyperelasticity of skin d. Ectopic lentis 13 Multiple sebaceous cyst are often associated with: a. Gardner’s Syndrome b. Kawasaki’s Syndrome c. Fanconi’s Syndrome d. All of the above

887

Appendices

890

Pituitary dwarfism, Down’s syndrome, congenital heart disease, progeria

Pituitary gigantism, facial hemi-hypertrophy, angioma of face, and genetic component

Hereditary

Traumatic injury, crowding of teeth, hypercementosis

Trauma during development

Microdontia

Macrodontia (megadontia)

Fusion

Concrescence

Dilaceration

Etiology True generalized— all the teeth are smaller than normal. Relative generalized— normal or slightly smaller than normal teeth; are present in jaws that are somewhat larger than normal. Localized—it involves only single tooth. True generalized— all the teeth are larger than normal. Relative generalized —normal teeth present in smaller jaw Localized—one or more large teeth exist Complete (before calcification) Incomplete (after calcification) Union with cementum, extraction of teeth should be done carefully Sharp bend in root, may cause problems during extraction

Types

Esthetic recovery

Esthetic problems, periodontal complication

Crown and bridge should be given

Management

Orthodontic treatment

Pathological features

Crowding, malocclusion, impaction of teeth

Clinical/Radiological features Affected teeth are maxillary lateral incisors and 3rd molars. Peg shaped laterals (mesial and distal sides converges or taper incisally).

Aparna Thombre

APPENDIX I: DIFFERENTIAL DIAGNOSIS OF MOST COMMON LESIONS OF ORAL CAVITY

Textbook of Oral Pathology

Failure of Hertwig root sheath to invaginate

Defect in morphological development

Taurodontism

Dens in dente (dens invaginatus)

Talon cusp

Hereditary and familial tendency

Gemination

Etiology

Mild type (accenuted lingual pit area), intermediated form (small pear shaped invagination) producing tooth in tooth appearance Extreme form (it extends beyond pulp chamber)

Coronal type (occur in crown) Radicular type (occur in root)

T shaped projection called eagle Talon. Associated with Rubinstein-Taybi syndrome

Bull like teeth, elongated pulp chamber, associated with Klinefelter syndrome

Clinical/Radiological features

Hypotaurodont Mesotaurodont Hypertaurodont

Bifid crown on single root. Common pulp canals and either single or partially divided pulp chambers. Crown is wider. Enamel or dentin of crown hypoplastic or hypocalcified

Types

Pathological features

Preventive care taken by performing endodontic treatment

Restoration of defect

No treatment is required

Management

Appendices

891

Hereditary, involves only ectodermal component

Autosomal dominant mode

Autosomal dominant

Dentinogenesis imperfecta

Dentin dysplasia (root less teeth)

Radicular coronal

Type I (with osteogenesis imperfecta) Type II (without osteogenesis imperfecta) Type III (brandywine type)

Hypoplastic Hypomaturation Hypocalcification

Types

Metal and ceramic crown

Enamel is normal, mantle dentin (narrow zone of dentin beneath enamel), less dentinal tubules, large area of a tubular dentin, pulp chamber are obliterated with a tubular dentin.

Amber like appearance, translucent teeth, multiple pulp exposure, teeth not sensitive

Coronal and radicular dentin comprised of tubular and osteodentin, appear as lava flowing around the boulders. Normal and abnormal dentin is well demarcated

Composite veneer crown should be given

Hypoplastic (lack of differentiation of ameloblasts, no matrix formation), Hypocalcification (defective matrix formation and subnormal mineral deposition), Hypomaturation (alteration in enamel rod and rod sheath structure)

Chalky white color teeth, open contact point, severe abrasion, cheesy enamel, snow capped teeth

Mobility of teeth, bluish or brownish translucency at cervical area, enamel does not chip off

Management

Pathological features

Clinical/Radiological features

892

Amelogenesis imperfecta

Etiology

Textbook of Oral Pathology

Local ischemic changes during odontogenesis

Congenital

Congenital

Congenital heart disease, Pierre Robin syndrome, in acquired mouth breathing, ankylosis Paget’s disease, fibrous dysplasia, pituitary gigantism

Hormonal imbalance, incomplete twinning and lymphatic abnormalities

Regional odontodysplasia (ghost teeth)

Agnathia (hypognathous)

Agenesis of jaws

Micrognathia

Macrognathia (megagnathia)

Facial hemihypertrophy

Etiology

Apparent type, True type (congenital or acquired)

Types Extraction of teeth followed by fabrication of prosthesis

Dentin is thin and globular, irregular tubules, and wide predentin layer, tiny droplet calcification

Resection followed by orthodontic treatment

No treatment Thick skin, hypertrichosis, excessive secretion, unilateral enlargement

Surgical approach to correct micrognathia

Management

Pathological features

Gummy smile Mandibular prognathisms, prominent chin button, steep mandibular angle

Midfacial deformity, interference in feeding, speech problems, malocclusion

Absence of some part of mandible or maxilla, absence of condyle

Absence of mandible or maxilla, rudimentary tongue, absence of ear

Abnormal pulp, teeth deformed, soft leathery appearance and yellowish brown in color

Clinical/Radiological features

Appendices

893

Trauma, heredity, infection peripheral nerve dysfunction Hereditary, nutritional factors, defective vascular supply, traumatic stress, Streeter’s fetal dysplasia Hereditary

Autosomal dominant trait

Allergic origin. Hypersensitivity to bacterial toxins

Hereditary, normal variation

Facial hemiatrophy

Cleft lip and cleft palate

Double lip

Peutz-Jeghers syndrome

Cheilitis granulomatosa

Fordyce granules

Etiology

Multiple, small, discrete milia like yellowish lesion. Confluent plaque are also present

Diffuse, nodular, painless, firm growth of lip. Associated with MelkerssonRosenthal syndrome

Café au lait spot, intestinal polyposis, and intussusceptions

Cupid bow, associated with Ascher’s syndrome

Surgical treatment for intestinal polyps, steroid injection

Surgical treatment

No treatment is required

Oral macular lesion exhibits excessive accumulation of melanin granules in basal cell layer Granulomatous inflammation with chronic inflammatory cells, Langhans types of multinucleated giant cells The peripheral cells are flat and darkly stained and inner cells are lipid rich and pale. The duct may show keratin plugging

Excision for cosmetic reason

Obturators, surgical correction

Difficult breastfeeding, upper anterior misplaced, middle ear infection, difficulty in speech

Management No effective treatment

Pathological features

Vertical furrow or line in midline, howling of cheek, delayed tooth eruption

Clinical/Radiological features

894

Congenital or acquired

Unilateral incomplete, unilateral complete, bilateral complete cleft

Types

Textbook of Oral Pathology

HPV type 13 and 32

Autosomal dominant with incomplete penetrance

Congenital, genetic defect, vitamin deficiency

Persistence of tubercular impar, infection due Candida albicans

Heck disease (focal epithelial hyperplasia)

White sponge nevus

Fissured tongue

Median rhomboid glossitis

Etiology

Types

Elongated erythematous patch, diamond shaped area devoid papillae

Mild to severe parakeratosis, thinning of suprapapillary epithelium, acanthosis, elongation of rete pegs, neutrophilic infiltration

No treatment is required

Marked thickening of epithelium with hyperparakeratinization, acanthosis and spongiosis. Intracellular edema, pyknotic nuclei. Basket wave appearance

Bilateral, asymptomatic, deeply folded white or gray lesion. Spongy consistency, sometimes ragged white area

Antifungal agents, antiseptic gargles.

No treatment is required. Cleaning of tongue after consumption of food thoroughly

Self-regressing lesion

Hyperparakeratosis with extensive acanthosis, koilocytes, fusion of rete pegs, increase mitotic activity Degeneration of the basal layer

Small pedunculated, polypoid or nodular soft tissue growth. Size 1 to 5 mm

Small furrows or grooves on the dorsal surface of tongue. Discomfort due to food accumulation. Associated with MelkerssonRosenthal syndrome

Management

Pathological features

Clinical/Radiological features

Appendices

895

Sun exposed Superficial epithelium of the sebaceous ducts

Keratoacanthoma

Well circumscribed, elevated umblicated crater like lesion with central depression, margin rolled and sharply delineated

Slow growing, cauliflower like growth with finger like projection. Base is sessile. White color and firm in consistency, it can occur in Down’s syndrome or Cowden’s syndrome

HPV can be responsible

Asymptomatic mobile swelling in midline of neck, dome shaped, compressible

Papilloma

Remnant of embryonic thyroglossal tract

Thyroglossal duct cyst

Nodular exophytic mass, smooth cystic swelling, dysphonia, dysphagia and dyspnea

Lingual mandibular salivary gland depression, gingival salivary gland choristoma

Endodermal down growth at the site of foramina cecum

Lingual thyroid nodule

Multiple irregular, well demarcated patchy erythematous areas with desquamation of filiform papillae. Periphery surrounded by yellowish-white serpiginous line

Clinical/Radiological features

Aberrancy

Family history, associated with emotional stress

Types Heavy dose of vitamins should be given

Hyperparakeratinization of epithelium, with loss of filiform papillae. Intercellular edema, spongiotic abscess (neutrophil polymorphs

Surgical excision of the lesion

Surgical excision along with tract

Surgical excision Thick hyperkeratinized should be carried with parakeratin out plugging, pseudoepitheliomatous hyperplasia, spinous cell layer is thick

Multiple finger like projection, vascular connective tissue, few inflammatory cells, hyperkeratosis and acanthosis

It exhibits normal salivary gland lobules and ducts

Linear stratified squamous epithelium or transitional epithelium

It is composed of normal Surgical excision mature thyroid tissue. should be done Colloid degeneration

Management

Pathological features

896

Geographic tongue

Etiology

Textbook of Oral Pathology

Excessive proliferation of fibroblast cells, with synthesis of collagen

Surgical excision should be carried out Proliferation of fibroblasts cells, cells are spindle shaped, bundles of collagen, thin epithelium and flattening of rete pegs Small, well circumscribed, slow growing, nodular growth, pedunculated, surface smooth, soft to firm in consistency

Fibroma

Surgical excision with histopathological evaluation

Cells are elongated bipolar, and spindle shaped. Fusiform dendritic cells

Dome shaped dark blue papule, flat pigmented macule over the skin of mucous membrane

Blue nevus

Surgical excision should be carried out

Pigmented papule or macules over the hard palate or the gingiva

Compound nevus

Surgical excision should be done

Management

Surgical excision Focal areas of proliferating nevus cells, should be carried out cluster of cells present at apex of epithelial rete pegs

Clusters or nests of nevus cells confined to connective tissue, spindle shaped cells, multinucleated giant cells, some cells are pigmented

Pathological features

Presence of nevus cells distributed in basal layer of epithelium as well as adjacent connective tissue

Asymptomatic brown or black macule

Junctional nevus

Clinical/Radiological features Raised flat area on skin, with dark brown color, asymptomatic

Types

Intradermal (intramucosal) nevus common mole

Etiology

Appendices

897

Reactive proliferation of periodontal or periosteal tissue

Connective tissue of the periosteum of jaw bone or from periodontal ligament tissue

Reactive lesion

It is origin from primitive mesenchyme

Peripheral giant cell granuloma

Central giant cell granuloma

Myxoma

Peripheral type Central type

Types

Surgical excision Epithelium should be done ulcerated with areas of hemorrhage, proliferating fibroblasts, multinucleated giant cells, spindle shape cells, intercellular edema with inflammatory cell infiltrate

Small, exophytic, well circumscribed pedunculated lesion, painless, firm lobulated dark red color, bleeding from surface

Rare lesion and firm and nodular growth of varying size

Radical surgery is Loose textured tissue recommended as it containing delicate is aggressive lesion reticulin fiber and mucoid material, stellate shaped cells

Surgical excision Fibrovascular should be carried connective tissue out stroma, proliferating spindle shaped stromal cells and interlacing collagen fibers, multiple multinucleated giant cells which contain 5 to 20 nuclei, small foci of osteoids of oven bone is present

Surgical excision should be carried out

Peripheral diffuse sheets of proliferating fibroblast with plump monomorphic nuclei, hypercellular reactive tissue, osteoids may be present Central—whorled pattern of fibroblastic stroma with presence of collagen fiber. Irregular calcified masses seen in later stage

Peripheral—small painless, lobulated swelling, sessile, hard to firm on palpation Central—bony hard swelling, expansion and distortion of the cortical plate. Disfigurement of face

Small bony hard swelling, expansion of cortical plate, vital teeth, some lesion may cause perforation of cortical plate

Management

Pathological features

Clinical/Radiological features

898

Ossifying fibroma

Etiology

Textbook of Oral Pathology

Origin from adipose tissue

Vascular tissue origin

Proliferation of lymphocytes

Neoplasms of osseous tissue

Lipoma

Hemangioma

Lymphangioma

Osteoma

Etiology

Compact osteoma cancellous osteoma

Cavernous Capillary Portwine stain central

Types

Nodular, exophytic, bony hard growth, expansion of cortical plate, Gardners syndrome present with osteoma

Painless nodule, may be diffuse with lighter color, crepitant sound, may produce macroglossia

Raised, multinodular, red, blue or purple lesion, blanches on compression, compressibility test positive Central type – painful expansile jaw swelling, affected bone pulsatile, loosening of teeth and anesthesia of skin and mucous membrane

Well defined, soft movable lump, painless, yellow in color and smooth overlying surface

Clinical/Radiological features

Management Surgical excision should be carried out

Injection of sclerosing agent should be given

May regress spontaneously, persistent lesion should undergo surgical excision

Surgical excision

Pathological features Proliferating mature fat cells with loose areolar tissue stroma, round cells, vacuolated with centrally placed nuclei, lobules of fat cells separated by fibrous tissue Capillary – small endothelial line capillaries in the lesion, cells are single layered, cells spindle shaped, plump Cavernous – large irregularly shaped dilated endothelial sinuses contain large aggregates of erythrocytes, single layer of flattened endothelial cells line, area of hemorrhage Proliferating, thin walled, lymphatic vessels, lined by plump endothelial cells, multiple papillomatous nodule on the surface Dense cortical bone with distinct lamellar pattern, cortical bone sclerotic and avascular, reduce marrow spaces

Appendices

899

Neoplasm of smooth muscle cells

Neoplasm of striated muscles

Leiomyoma

Rhabdomyoma

Slow growing, Well circumscribed, painless mass, deep seated

Slow growing, painless, submucosal nodules, surface is smooth, yellowish in color, firm, encapsulated

Slow enhancing pain bony hard swelling, expansion and distortion of the cortical plate

Cartilaginous tissue origin

Chondroma

Clinical/Radiological features Painful, small in size, expansion and distortion of cortical plates

Types Surgical excision

Surgical excision

Surgical excision done with surrounding normal tissue

Surgical excision is done

Well defined lobules of hyaline cartilage, mature chondrocytes, cells are round or oval in shape Spindle shaped smooth muscle cells, cells arranged in fascicle or stream line fashion, cigar shaped appearance Sharply outline, Unencapsulated mass of round or oval striated muscle cells, multiple vacuoles in the cell neoplasm, irregular cross striation, cell nuclei are vesicular

Management

Small area of osteoblastic activity followed by mature osteoid calcified, nidus consist of interlacing meshwork of bony trabeculae, vascular connective tissue stroma, numerous osteoblasts are present

Pathological features

900

Osteoblastoma

Etiology

Textbook of Oral Pathology

Derived from Schwann cells, neuroectodermal origin

Autosomal dominant hereditary condition

Derived from primitive neural crest

Neurilemmoma (Schwannoma)

Neurofibroma

Neuroectodermal tumor of infancy

Etiology

Types

Management Surgical excision

Surgical excision should be done

Surgical excision with through curettage

Pathological features Proliferating spindle shaped neoplastic Schwann cells with elongated nuclei, Antoni A tissue (parallel rows of palisading nuclei of Schwann cells) Antoni B tissue (disorderly arranged cells and fibers band) Verocay bodies Numerous proliferating spindle shaped cells resembling fibroblast, haphazard arrangement, delicate collagen fiber, café au lait spot revels basilar melanosis Pigmented cells and nonpigmented cells, open nucleus, flattened or cubical in shape with pale nuclei, unpigmented cells occur in cluster, and surrounded by pigmented cells

Slow enlarging, Well circumscribed, painless nodule, smooth firm, exophytic, tender to palpation, central lesion present, well demarcated bony hard lesion

Submucosal mass, Multilobulated surface, expansion, pain, paresthesia, soft tissue lesion present as freely movable nodule, flabby masses, café au lait spot Swelling, expansion, distortion, facial asymmetry, surface is brown or black pigmentation, slow growing

Clinical/Radiological features

Appendices

901

Consist of oncocytes

Warthins tumor (oncocytoma)

Slow enlarging, Well circumscribed, soft painless swelling, well encapsulated movable lesion, compressible and doughy feeling

Basal cell— encapsulated, movable lesion less than 3 cm lesion are firm Canalicular—small painless, movable encapsulated. Lesion covered by smooth intact epithelium

Basal cell adenoma Canalicular adenoma

Proliferation of single epithelial cell type

Monomorphic adenoma

Clinical/Radiological features Slow growing, well delineated exophytic growth, surface smooth, lobulated, painless, soft and rubbery consistency

Types

Management Surgical excision should be carried out

Surgical excision of the lesion

Simple surgical excision is done

Pathological features Proliferation of glandular, basophilic, epithelial cells in the form of diffuse sheets or clusters, polygonal shape glandular epithelium cells arranged in clumps or interlacing strand, squamous metaplasia, myxoid and chondroid areas are present Basal type— granular epithelial cells in the forms of oval shaped nests, outer layer is cubiodal and inner layer is uniform Canalicular— anatomizing network of cuboidal and columnar cells which give impression of multiple interconnecting canals, connective tissue stroma is myxomatous and composed of eosinophilic hypocellular mucoid matrix Multiple cystic spaces lined by pseudostratified columnar epithelial cells, cells are arranged in double layer pattern, cystic lumen filled with homogeneous eosinophilic material

902

Pleomorphic adenoma

Etiology

Textbook of Oral Pathology

Slow growing exophytic papillary growth with white pebbly surface. Multiple rugae like folds with deep clefts, regional lymph nodes enlarged and tender

Tobacco chewing and snuff dipping habits

Verrucous carcinoma

Laser therapy Papillary surface covered by thick layer of parakeratin, acanthotic rete ridges, parakeratin plugging, pushing margin, connective tissue intense inflammatory infiltration

Surgical excision or electrocautery along with radiotherapy Neoplastic proliferation of baseloid epithelial cells in solid island, cells are columnar in shape, palisaded arrangement, intercellular bridge absent,

Slow growing, elevated lesion which develops central crust, with rolled border, it invades and destroys the adjacent tissue

Exposure to sunlight

Basal cell carcinoma (rodent ulcer)

Surgical treatment and radiotherapy in some cases should be given

Well differentiated (resembles the cells of squamous epithelium, keratin pearls), moderately differentiated (more dysplastic little or no keratin and greater number of mitotic cell division), poorly differentiated (no keratin, no resemblance to cells of stratified squamous epithelium, mitotic division rate is high)

White or red variegated path, exophytic invasive ulcer, induration around periphery, painful due to secondary infection, pathological fracture can occur in extensive cases

Management

Pathological features

Clinical/Radiological features

Tobacco, betel nut, alcohol, actinic radiation, herpes simplex, immunosuppressant and genetic factors

Types

Sq cell carcinoma (epidermoid carcinoma)

Etiology

Appendices

903

Arises from undifferentiated mesenchymal cells

Malignant fibrous histiocytoma

Enlarging, exophytic lobulated and ulcerated, fleshy appearance, pain, hemorrhage, paresthesia, gross facial disfigurement

Fast enlarging, large, painful, bulky, lobulated fleshy mass, surface ulcerated due to trauma

Neoplasm of fibroblast

Fibrosarcoma

Surgical excisions is the most effective treatment

Radical surgical excision and chemotherapy should be given

Wide surgical excision with radiotherapy and chemotherapy

Spindle shape epithelial cells, nuclear hyperchromatism, Cellular pleomorphism, increased mitosis, tumor giant cells, little or no keratin formation, inflammatory cell infiltration Proliferation of spindle shaped, malignant fibroblast cells. It has tadpole like appearance, streaming fashion arrangement, abnormal mitotic activity Proliferating polyhedral or oval shaped, malignant histiocytes, cart wheel or storiform pattern, increased mitotic activity, cellular pleomorphism, giant cells are present

Radical surgery with prophylactic neck dissection

Excessive proliferation of neoplastic melanocytes, extensive cellular pleomorphism, cells are round, polyhedral and multinucleated, numerous mitotic activity

Macular pigmented focal lesion which grow rapidly to results in large painful diffuse mass, surface ulceration is common, small satellite lesion

Pain, ulceration, swelling, fleshy and polypoid growth pattern

Hutchinson’s freckle type superficial spreading type Invasive type

Management

Pathological features

Clinical/Radiological features

Spindle cell carcinoma

Arises from melanocytes

Types

904

Malignant melanoma

Etiology

Textbook of Oral Pathology

Cell along the adipose tissue line

Mesenchymal tissue origin

Arises from endothelial cells of the blood capillaries, triggering factors are HIV infection, immunosuppressant and environmental factors

Lesion arise from endothelial cells or undifferentiated reticuloendothelial cells

Liposarcoma

Hemangioendothelioma

Kaposi’s sarcoma

Ewing’s sarcoma

Etiology

It can be endemic Rarely can be epidemic

Types Surgery and radiotherapy

Surgical exicision and radiotherapy should be done

Treated by radiotherapy and chemotherapy

Radiotherapy, chemotherapy and surgery is recommended

Cellular lesion contain foamy, fat containing malignant lipoblasts cells, signet appearance (vacuolated cytoplasm) cells poorly differentiated round cells, irregularly shaped giant cells Neoplastic proliferation of malignant endothelial cells. The cells are pleomorphic, large polyhedral or slightly flattened, nuclei are round, increased abnormal mitosis Patch stage (dilated, irregular, blood vessels, lined by normal endothelial cells), plaque stage (dilated jagged vascular channels lined by spindle type cells) nodular stage (slit like spacing containing RBCs) Proliferating, packed round cells which have monotonous round or oval nuclei, hyperchromatic cells arranged in diffuse pattern, cells are round, increased mitotic activity

Fast enlarging, localized, painful, nodular swelling, surface ulceration, paresthesia, anesthesia, bleeding upon slight trauma, expansile lesion It can be presented in patch, plaque, nodular form. Nodule can be multiple

Moderate fever, leukocytosis, rapid swelling severe pain, paresthesia, surface ulceration

Rapidly growing, painful, submucosal masses, lobulated lesion, firm in consistency

Management

Pathological features

Clinical/Radiological features

Appendices

905

Neoplasm of cartilage tissue, may be caused by Paget’s disease

Arises from bone, may arise from pre-existing Paget’s diease, fibrous dysplasia, osteochondroma and chronic osteomyelitis

Neoplasm of cells of lymphoid tissue

Osteosarcoma

Non-Hodgkins lymphoma

Combination therapy is given in the form of radiotherapy and chemotherapy

Chemotherapy should be given

Actively proliferating spindle shaped, oval angular malignant osteoblast cells with cellular stroma, cellular pleomorphism, increased mitosis, multiple area of osteoid bone within fibrous stroma

Proliferation of Malignant lymphocytes, Cellular pleomorphism, cells small in size, Nodular pattern— tend to aggregate in large cluster Diffuse pattern— monotonous proliferating tumor cells within connective tissue

Fast enlarging painful swelling causing expansion, and distortion, facial deformity, displacement of teeth, numbness of lip, overlying skin inflamed, ulceration, hemorrhage, pathological fracture

Medullary osteosarcoma, Periosteal osteosarcoma, Parosteal osteosarcoma, Soft tissue osteosarcoma

Fever, night sweats, malaise, anorexia, weight loss, generalized lymphadenopathy, abdominal pain, fast enlarging exophytic growth, lymph nodes firm, rubbery, overlying surface is red and inflamed

Wide surgical excision should be done

Can be well differentiated like benign or poorly differentiated, spindle shaped malignant cells, binuclear cells

Management

Pathological features

Painless facial asymmetry, later pain, tenderness, anesthesia or paresthesia in the region, extensive local tissue destruction, expansion of bone, nasal obstruction

Clinical/Radiological features

Primary Secondary

Types

906

Chondrosarcoma

Etiology

Textbook of Oral Pathology

Cause by EpsteinBarr virus

Neoplasm of lymphocytes

Neoplasm of Plasma cell

Burkitt’s lymphoma

Hodgkin lymphoma

Multiple myeloma

Etiology

Types

Severe deep bone pain, gradual bone loss, increased susceptibility to infection, nausea, vomiting, anemia, jaw lesion fast enlarging, painful swelling, egg shell cracking, perforation of cortex

Persistent generalized lymphadenopathy, lymph nodes are firm rubbery, generalized weakness, pain low grade fever, edema of extremities, hepatosplenomegaly, oral lesion present as submucosal swelling with ulceration

Rapid painless, loosening of teeth, fast enlarging large expansile swelling, overlying mucosa is ulcerated, paraplegia, perforation of cortical plate

Clinical/Radiological features

Management Chemotherapy should be given

Chemotherapy should be given

Chemotherapy

Pathological features Proliferation of lymphocytes, syncytial appearance (nucleus surrounded by cytoplasm), mitotic activity is abundant, starry sky appearance (macrophages with clear cytoplasm scatter uniformly throughout the tumor) Malignant lymphoid cells, non-neoplastic inflammatory cells, Reed-Sternberg giant cells (mirror image nuclei), Owl eye appearance. It can be of lymphocyte prominent, mixed cellularity, lymphocytes depletion and nodular sclerosis Sheets of closely packed, round or oval cells, resemble plasma cells, cartwheel or checkerboard pattern (eccentrically placed nuclei exhibits chromatin), mitotic figure may be high, binucleated or multinucleated cells

Appendices

907

Arises from glandular epithelium of salivary gland

Adenoid cystic carcinoma (cylindroma)

Mucoepidermoid tumor

Striated muscle origin

Embryonal Alveolar Pleomorphic

Types

Slow growing, painless swelling having cystic feeling, in some cases rapid growth, pain hemorrhage, ulceration, paresthesia occurs. Bony expansion, facial nerve paralysis

Slow enlarging growth, surface ulceration, mass below the ear, pain is seen fixation and induration of tumor paresthesia may be seen

Rapidly growing lesion, swelling, pain, extensive damage, indurated, fixed and ulcerated

Clinical/Radiological features

Management Surgery, radiotherapy and chemotherapy should be given

Wide surgical excision should be carried out

Surgical excision

Pathological features Embryonal (small round cells with monotonous hyperchromatic nuclei) Alveolar (round cells pattern similar to lung alveoli) Pleomorphic (primitive muscle formation, prominent nuclei) Small darkly staining, polygonal or cuboidal cells of uniform size, Swiss cheese pattern (double layer of tumor cells arranged in duct like pattern, containing eosinophilic coagulum at center), cribriform pattern, neurotrophism (spread via perineural or intranueral spaces) It contain mucus secreting, epidermoid and intermediate types of cells, it can be well differentiated (no cellular pleomorphism) Poorly differentiated (cellular pleomorphism, pushing front)

908

Rhabdomyosarcoma

Etiology

Textbook of Oral Pathology

Tobacco, alcohol, candidiasis, dietary deficiency, syphilis, viral, hormonal imbalance, chronic irritation, actinic radiation, galvanism

Severe stage of epithelial dysplasia

Heavy use of tobacco, alcohol

Normal variant

Leukoplakia

Carcinoma in situ

Erythroplakia

Leukoedema

Etiology

Homogeneous Erythroleukoplakia Speckled

Diffuse translucent, grayish, white area, filmy appearance, wrinkled appearance, when stretched mucosal condition disappear

Small, extensive, red velvety lesion with well defined margin

Deep and wide surgical excision

No treatment

Features of invasive Epidermoid carcinoma, chronic inflammatory cell infiltration, reduction in keratin production and increase in vascularity Thickening of epithelium with mild parakeratosis, enlarged spinous cells with pyknotic nuclei, rete peg are broad,

Surgical excision Hyperkeratosis, on surface of lesion, keratin should be carried out pearl formation, loss of orientation, loss of polarity, basement membrane intact

Stoppage of habit, cryosurgery, vitamin A, antioxidant therapy

Hyperorthokeratinization, hyperparakeratinization, acanthosis, nuclear hyperchromatism, cellular pleomorphism, poikilocarynosis, dyskeratosis, enlarged nucleoli, dropshaped rete pegs, basoloid appearance, presence of candidial hyphae

Homogeneous (white patch having smooth or corrugated surface with irregular margin) Ulcerative (mixed red and white lesion with small keratotic nodules) Nodular (maximum risk for malignant transformation)

Homogeneous Non-homogeneous Cryptogenic Speckled or nodular ulcerative

White plaque, ulcerated, eroded, or reddened area, resemble leukoplakia or erythroplakia

Management

Pathological features

Clinical/Radiological features

Types

Appendices

909

Tobacco

Betel nut, red chillies, nutritional deficiency, immunological factors, genetic factors

Psychological stress, autoimmune reaction

Oral submucous fibrosis

Lichen planus

Reticular Erosive Plaque Atrophic Bullous

Types

Management Complete stoppage of oral habits

Intralesional injection of steroid, enzyme, systemic steroid, injection of placental extract

Steroids, dapsone therapy

Pathological features Hyperparakeratosis, acanthosis, ductal epithelium exhibits squamous metaplasia, atrophic changes, inflammatory cell infiltration Hyperkeratanized Atrophic epithelium, flattening and shortening of rete pegs, cellular atypia, nuclear pleomorphism, increases mitosis, basilar hyperplasia, blood vessels dilated and congested, perivascular fibrosis Hyperorthokeratinization, hyperparakeratinization, thickening of granular cell layer, saw tooth appearance, liquefaction degeneration, civatte bodies (round ovoid amorphous eosinophilic bodies) are seen

Red palatal mucosa, few red and dot like areas surrounded by white keratotic ring, ulceration can be seen

Burning sensation, vesicle inflammatory reaction. Xerostomia or excessive salivation, stiffening of oral mucosa, leathery feeling, trismus, blanched mucosa, difficulty in deglutition Wickham striae present Reticular – raised thin white radiating line, non-elevated, burning sensation erosive – mixture of erythematous ulcerated and white pseudomembranous area, pain and burning sensation plaque – raises or flattened white area, atrophic – smooth poorly defined erythematous area. Bullous – large vesicles are seen

Clinical/Radiological features

910

Stomatitis nicotina

Etiology

Textbook of Oral Pathology

Unknown stimuli

Unknown etiology, infarction of tissue

Streptococcus pyogenes, Staphylococcus aureus

Caused by paramyxovirus

Autoimmune disease, defective cell-mediated immunity

Sialolithiasis

Necrotizing sialometaplasia

Bacterial sialadenitis

Mumps (endemic parotitis)

Mikulicz’s disease

Etiology

Acute chronic

Types Can be removed by digital manipulation, lithotripsy

Lesion heal spontaneously

Stone is acellular, amorphous, outer margin aggregates microbial colonies, ductal lining changed into stratified squamous epithelium Absence of epithelium, necrotic debris, coagulation of necrosis, distended cells, basophilic nuclei, accumulation of mucin in zone of necrosis

Steroid should be given Unilateral or bilateral diffuse swelling. Soft swelling, movable, fever, URI, xerostomia

Benign infiltration of lymphocytes, myoepithelial islands. Obliteration of lumen of duct due to proliferating epithelial cells, eosinophilic material

Antiviral drugs

Chronic—acinar atrophy Antibiotics therapy of salivary gland with subsequent fibrosis, dilatation of the ductal system, hyperplasia of the ductal epithelium, periductal fibrosis, chronic inflammatory cell infiltration

Management

Pathological features

Parotid gland is affected, eversion of ear lobe, acute pain during salivation, recurrent exudation

Acute—sudden onset of painful swelling, fever, redness of overlying skin, trismus, difficulty in swallowing, parotid papilla inflamed Chronic—recurrent tendered swelling, duct orifice inflamed, decreased salivary flow

Deep seated punched out ulceration on hard or soft palate, presence of gray granular lobules, numbness or burning pain

Submandibular gland more involved, intermittent pain which can be severe. Affected gland enlarged, stone can be palpated

Clinical/Radiological features

Appendices

911

Immune mediated chronic inflammatory response, presence of serum antinuclear antibodies

Hormonal disturbance, malnutrition, liver cirrhosis, chronic alcoholism, diabetes Arises from odontogenic epithelium. It may be predispose by trauma, infection, previous inflammation

Sialosis

Ameloblastoma

Hypertrophy of serous acinar cells, secretory granules in cytoplasm and lipomatosis may occur

Plexiform—continuous Enucleation should be carried out anastomosing strands, fish net pattern, columnar cell. Follicular—discrete follicle, island of fibrous continuous strand, microcyst formation. Acanthomatous— keratin pearls, squamous metaplasia. Granular cell—stellate reticulum like cells swollen with coarse eosinophilic granules. Basal cell—cuboidal shaped in narrow strand

Parotid gland involved little pain, discomfort

Slow growing, painless, ovoid, fusiform bony hard swelling, expansion and distortion of cortex, gross facial asymmetry, egg shell cracking, pathological fracture

Peripheral type damantinoma of long bone mural ameloblastoma

Steroids, antibiotics, antifungal

Infiltration of lymphocytes in intralobular ducts of salivary gland, atrophy of salivary gland acini, hyperplasia of ductal epithelium, myoepithelial islands

Xerostomia, Xerophthalmia and arthralgia. Severe tiredness, disturbed taste sensation, dry mucosa, red and atrophic tongue mucosa, cobble stone appearance (fissuring and lobulation of the surface)

Primary (sicca syndrome) – no other disease Secondary – with arthritis

Elimination of causative organism

Management

Pathological features

Clinical/Radiological features

Types

912

Sjögren’s syndrome

Etiology

Textbook of Oral Pathology

Cells of stratum intermedium

Remnants of dental lamina, cells rests of Malassez, and basal layer of oral epithelium

Calcifying epithelial odontogenic tumor (pindborg tumor)

Squamous odontogenic tumor

Ameloblastic fibroma

Reduce enamel epithelium

Adenomatoid odontogenic tumors

Etiology

Types

Surgical enucleation should be done

Surgical enucleation should be done

Closely packed, polyhedral cells, cribriform arrangement, hyalinized stroma ,oval shaped nuclei, hyperchromatic nuclei, prominent intercellular bridges and distinct cell boundaries, Lisegang ring (calcified masses), clear cells Irregularly shaped, islands of well differentiated squamous epithelium in fibrous connective tissue stroma, round or oval shaped islands, microcyst formation, calcification is seen

Mandible > maxilla, Slow enlarging painless swelling, expansion, distortion of cortical plate, displacement of teeth

Maxillary incisor canine area, painless swelling, mobility of teeth, local tenderness

Mandibular premolar-molar area, slow growing, painless, distortion of cortical plate, displacement of teeth, facial asymmetry

Surgical excision Epithelial and should be carried mesenchymal cells are present, multiple sharply out defined strands or islands bordered by tall columnar cells, cell free zone of hyaline connective tissue in epithelial component

Surgical enucleation should be done

Odontogenic cells in duct like pattern within stroma giving adenomatoid appearance, small foci of calcification is seen, solid nests or rosette patterns

Maxillary anterior region, slow enlarging, bony hard swelling, elevation of upper lip, expansion of jaw

Management

Pathological features

Clinical/Radiological features

Appendices

913

Derived from connective tissue of odontogenic epithelium

Derived from dental papilla or follicular mesenchymal

Odontogenic fibroma

Odontogenic myxoma

Periapical cemental dysplasia

Occur after histodifferentiation but before morphodifferentiation

Peripheral type— extra-osseous Central—arises within the jawbone

Complex— disorganized dental tissue. Compound— Discrete tooth like structure

Types

No treatment is Initial stage - cemental required tissue at apex of involved and replaced by fibrous connective tissue, Cementoblastic stage— small amorphous masses Immature cementum Mature stage—entire fibrous tissue replaced by mature cemental tissue

Surgical excision should Widely separated undifferentiated spindle be carried out or angular or stellate shaped cells. Focal areas of delicate immature collagen fibrilar strands, blood vessels exhibits hyalinization at periphery Slow growing, painless swelling, displacement of regional teeth, expansion of bone

Mandibular anterior teeth, females are affected, asymptomatic small and multiple, teeth are vital, radiologically detected

Surgical excision Peripheral—mass of dense connective tissue should be carried out with spindle shaped fibroblast, surface epithelium slender rete pegs project in CT, clear cells Central—thin strands odontogenic, clear cells, areas of spherical or diffuse calcification and contain giant cells

Surgical enucleation should be done

Presence of encapsulated mass of denticles, complex odontome presented as irregularly arranged dental tissue

Complex—anterior maxilla. Compound—posterior mandible, small asymptomatic lesion, expansion of cortex, displaced teeth Peripheral—slow growing, exophytic, well circumscribed growth, firm in consistency, painless, interdental lesion cause separation of teeth Central—slow growing, painless swelling, displacement of teeth, cortical expansion

Management

Pathological features

Clinical/Radiological features

914

Odontoma

Etiology

Textbook of Oral Pathology

Hamartomatous malformation of cementum forming tissue autosomal dominant trait Arises from cementoblast

Intraosseous lesion

Arises from remnant of the dental lamina, developing tooth germ, basal layer of oral epithelium

Familial gigantiform cementoma

Cementoblastoma

Odontogenic carcinoma

Odontogenic keratocyst

Etiology

Types

Surgical excision should be carried out

Radical surgical excision should be carried out

Surgical enucleation or marsupialization of the cyst can be carried out

Islands or strands of clear cells, cells are glycogen rich, non-clear cells resembles dental lamina, epithelial tissue surrounded by zone of myxomatous tissue Cystic cavity lined by keratinized stratified epithelium, lining epithelium is flat, para-keratinization, daughter cyst or satellite cyst present (multiple small micro cyst) present

Large swelling with expansion of cortical plate, mobility of teeth

Islands or strands of clear cells, cells are glycogen rich, nonclear cells resembles dental lamina, epithelial tissue surrounded by zone of myxomatous tissue

Mandible > maxilla, slow growing bony hard swelling, expansion of cortical plate, intermittent pain, dull sound when tooth percussed

Large mass of amorphous cemental tissue with presence of reversel line, soft and vascular connective tissue stroma, cementoblasts or cementoclast are present, multinucleated cells are present

Surgical osseous Loose vascular tissue stroma, delicate collagen recontouring fiber, monomorphic fibroblasts, acellular cementum, ovoid calcification

Slow growing painless expansile jaw swelling, multiple lesion seen, facial asymmetry can also occur

Management

Pathological features

Clinical/Radiological features

Appendices

915

Inflammatory origin

Accumulation of fluid in follicular space

Radicular cyst

Eruption cyst

Lateral periodontal cyst

Cells of reduced enamel epithelium

Types

Management

Small cystic cavity lined Surgical excision should be carried out by connective tissue wall, on inner aspect by nonkeratinized stratified Squamous epithelium. Thickening of lining epithelium, cells have pyknotic nuclei

No treatment is needed

Ghost cells within the lumen of cyst Small fluctuant swelling on alveolar ridge, eruption hematoma occur due to mastication Asymptomatic, small painless soft tissue swelling can occur, mucosa is pale in color, vital tooth

Root canal treatment with apical curettage can be done. In larger lesion excision should be done Cystic cavity line by non-keratinized Stratified squamous epithelium, localized area of increased cell proliferation, cholesterol cleft (small ribbon shaped cleft like space) arcading pattern can be seen. Inflammatory cell infiltration

Marsupialization Cystic cavity line of odontogenic epithelium, should be carried out stroma contain young fibroblast cells separated by ground substance rich in collagen bundles, cystic epithelium is flat, low columnar, some cases bud like proliferation called mural proliferation is seen

Pathological features

Non-vital tooth, asymptomatic and detected on radiograph, expansion occur in larger lesion, pain if secondarily infected

Mandible > maxilla, asymptomatic, slowly enlarging bony hard swelling occur, expansion of bone, Crepitus sensation, facial asymmetry, paresthesia and pathological fracture may occur

Clinical/Radiological features

916

Dentigerous cyst

Etiology

Textbook of Oral Pathology

Bony hard extensive swelling of the jaw, expansion and distortion of cortical pates, tooth vital, perforation of the cortex

Calcifying epithelial odontogenic cyst

Slow enlarging asymptomatic growth in mandibular anterior region

Surgical excision should be carried out

Surgical excisions should be carried out Cystic cavity lined by odontogenic keratinized epithelium, cells are columnar or cuboidal, ghost cells are eosinophilic, satellite microcyst

Surgical enucleation should be carried out

Multiple cystic cavities separated from one another by fibrous septa. Lined by cuboidal or squamous epithelium

Lined by thin squamous epithelium with focal area of thickening, microcyst is also found, organization of glandular elements may results in acinar like cluster

Surgical excision should be carried out

Cystic cavity lined by a thin epithelium made up of flat or cuboidal cells. pyknotic nuclei with perinuclear cytoplastic vacuoles

Firm compressible, fluid filled swelling, well circumscribed, smooth surface and bluish or normal in color

Not needed

Small keratin fill cystic cavity lined by flattened epithelium

Multiple asymptomatic, small discrete white nodule. It undergoes spontaneous regression

Management

Pathological features

Clinical/Radiological features

Well defined, painless expansile jaw lesion

Remnant of dental lamina

Sialo-odontogenic cyst

Cyst of dental lamina (along alveolar ridge, odontogenic origin) Epstein pearls (along midpalatine raphe) Bohn’s nodule (at junction of hard and soft palate)

Types

Botyroid odontogenic cyst

Arises from gingival soft tissue, cell rest of dental lamina

Gingival cyst of adult

Gingival cyst of newborn

Etiology

Appendices

917

Inflammatory in origin, cell rests of Malassez or reduced enamel epithelium Proliferation of epithelium along the line of fusion between maxilla and premaxilla

Lower part of embryonic nasolacrimal duct

Proliferation and cystic degeneration of epithelial remnants after closure of embryonic nasopalatine duct

Pseudocyst

Globulomaxillary cyst

Nasolabial cyst (Kelstadt’s cyst)

Nasopalatine duct cyst

Traumatic bone cyst

Types

Surgical removal should be done

Painful bony hard swelling, paresthesia of lip, expansion of cortical plate, displacement of teeth, vital teeth

Surgical excision

Small painful swelling in midline of anterior part of hard palate, pressure sensation on floor of the nose, displacement of root of central incisor, salty discharged, fluctuation can be done

Cystic cavity surrounded Surgical exploration should by loose vascular be done connective tissue wall, no epithelial lining, CT stroma is made of fibrous tissue

Cystic lined ciliated columnar or nonkeratinized stratified Squamous epithelium, mucus secretory cells, presence of pigment, presence of neurovascular bundles

Cystic lumen supported Surgical excision should be done by connective tissue wall, lined by pseudostratified ciliated columnar epithelium, infolding of cystic lining

Small painless swelling of upper lip, obliteration of nasolabial fold, can project into floor of nose

Asymptomatic, pain when secondary infected, small swelling in canine region and tooth is vital

Cystic cavity lined by stratified or pseudostratified ciliated columnar epithelium chronic inflammatory cell infiltration

Management Surgical excision should be carried out

Pathological features

Seen in mandibular third Cystic cavity lined by molar and tooth has hyperplastic, nonhistory of pericoronitis keratinized squamous epithelium, intense inflammatory reaction

Clinical/Radiological features

918

Paradental cyst

Etiology

Textbook of Oral Pathology

Surgical excision should be carried out

Surgical excision should be carried out

Large mucous filled area surrounded by connective tissue wall, mucous filled area

Cystic cavity lined by orthrokeratinized stratified squamous epithelium exhibiting hair follicle, sebaceous gland, desquamated keratin, cyst capsule consist of narrow zone of compressed connective tissue

Soft fluctuant unilateral swelling in floor of mouth, bluish translucent appearance like frog belly

Obstruction of the duct, compression of duct, perforation of duct

Remnant of embryonic skin

Ranula

Dermoid cyst

Painless swelling with doughy consistency, elevation of tongue, midline location

Surgical excision should be carried out

Mucous retention— small cystic cavity filled with mucous lined by flattened epithelial cells Mucous extravasation— cystic cavity surrounded by compressed connective tissue wall. Mucous stroma

Lower lip involved, small raised lesion and bluish swelling, round to oval shaped smooth fluctuant

Mucous retention cyst, mucous extravasations cyst

Surgical curettage should be done

Multiple blood filled spaces lined by spindle shaped cells or flat endothelial cells, epithelial absent, cystic spaces separated by loose connective tissue wall, multiple multinucleated giant cells

Accumulation of saliva due to obstruction

Management

Pathological features

Mucocele

Clinical/Radiological features Enlarging diffuse, firm swelling, facial asymmetry, swelling pulsatile, egg shell cracking, pathological fracture, profuse bleeding, paresthesia, difficulty in opening mouth

Types

Aneurysmal bone cyst

Etiology

Appendices

919

Chronic carious lesion, stimuli of short duration, chemical irritation, severe attrition or abrasion

Caries reaching pulp, pulp exposure by cavity preparation, trauma to teeth, chemical irritation, cracked tooth syndrome

Same as acute pulpitis

Intense proliferation of pulpal connective tissue due to low grade infection

Results of extension of pulpal inflammation

Acute pulpitis

Chronic pulpitis

Pulp polyp (chronic hyperplastic pulpitis)

Acute apical periodontitis

Types

Direct pulp capping, drainages of pus, root canal treatment should be done

Extraction of tooth or root canal treatment should be done

Root canal treatment

Severe edema with vasodilatation, dense infiltration of polymorphonuclear leukocytes, destruction of odontoblasts cells at pulp dentin border, microabscess formation Cellular infiltration by lymphocytes, plasma cells and macrophages, blood capillaries are prominent, fibroblastic activity, formation of collagen bundles Numerous proliferating fibroblasts and young blood capillaries, inflammatory cell infiltration, by plasma cells and lymphocytes, stratified squamous epithelial lining

Tooth is extremely sensitive, lacinating pain, percussion test positive, history of night pain, pain subsided after drainage established

Moderate pain, sensitivity, extrusion of tooth, severe pain, tenderness positive

Small pinkish red, lobulated mass protruding from pulp chamber. Large open carious cavity, lesion bleeds profusely upon provocation, tooth is painless

Restoration of tooth with proper antibiotics coverage

Elimination of causative factor, pulp capping should be done

Acute inflammatory reaction in odontoblastic regions, dilatation of pulpal blood vessels, edema in pulp with infiltration by polymorphonuclear leukocytes, thrombosis of pulpal blood vessels

Tooth sensitive to thermal changes, pain of short duration, vitality test is positive

Intermittent dull or throbbing pain, tooth is less sensitive to pain as compared to acute pulpitis

Management

Pathological features

Clinical/Radiological features

920

Focal reversible pulpitis

Etiology

Textbook of Oral Pathology

Response to infection, occlusal trauma

Infection of dental pulp, infected granuloma, infected cyst, compound fracture, postradiation secondary infection

Periapical granuloma

Osteomyelitis

Etiology

Acute suppurative, Acute subperiosteal, Chronic suppurative, Chronic diffuse sclerosing, Chronic focal sclerosing

Types Root canal treatment with apicoectomy

Antibiotics, sequestrectomy, analgesic, hyperbaric oxygen therapy should be given

Acute suppurative– bone marrow undergo liquefaction, thrombosis of blood vessels. Acute inflammatory cell infiltration, Brodie’s abscess can be seen. Chronic suppurative – accumulation of exudates and pus, lymphocytes, plasma cells, macrophages, osteoblastic and osteoclastic activity producing reversal line. Focal sclerosing— presence of dense mass, without marrow tissue, fibrotic marrow. Diffuse sclerosing— formation of dense irregular bone with hypocellular fibrous stroma, reversal line and resting line is seen Acute suppurative— severe pain, diffuse large swelling, excessive salivation, bad breath, multiple sinus, paresthesia of lip. Chronic suppurative— pain is mild and dull, jaw swelling, sinus formation. Focal sclerosing— asymptomatic, tooth with large carious lesion. Diffuse sclerosing— asymptomatic, vague pain, foul taste, acute exacerbation may occur producing mild pain and fistula tract formation

Management

Granulation tissue mass consist of proliferating fibroblasts, endothelial cells, immature blood capillaries, chronic inflammatory cells, cholesterol cleft, foam cells

Pathological features

Percussion test positive, mild pain, discomfort

Clinical/Radiological features

Appendices

921

Virulent bacteria like Streptococcus pyogenes and Bacteroides, osteomyelitis, infected postextraction wound Causative organism Hemolytic Streptococci periapical, pericoronal or periodontal infection, gunshot injury, osteomyelitis Replacement of marrow by macrophages

Cellulitis

Ludwig’s angina

Hand-SchullerChristian disease

Eosinophilic granuloma

Low-grade infection or trauma

Types Elimination of causative agents with extraction of involved tooth

Antibiotics and Fibrin and serum removal of fluid in tissue, separation of periosteum primary factors and muscle, acute inflammatory cell infiltration High dose of antibiotics

Surgery and chemotherapy should be given

Surgical curettage

Multiple osteoid, primitive bony tissue, osteoblastic activity is prominent, marrow spaces contain patchy area of chronic inflammatory cell infiltration

Acute inflammatory cell infiltration

Multiple large vacuolated foam cells, small nonvacuolated cells

Numerous proliferating histiocytes, in diffuse sheets, eosinophils is seen, multinucleated giant cell present

Carious non-vital tooth (lower first molar), slight tenderness or vague pain can be present

Large diffuse, painful swelling over the face or neck with facial osteomyelitis, infected postextraction wound Large diffuse board like swelling in floor with brawny induration, elevation of tongue, no pitting on pressure, speech difficulty Exophthalmos, diabetes insipidus, skins rashes, otitis media, facial asymmetry, ulceration and necrosis of oral mucosa, loosing of teeth and halitosis Fever malaise, headache and anorexia, localized pain, tenderness, gingival soft tissue swelling

Management

Pathological features

Clinical/Radiological features

922

Garre’s osteomyelitis

Etiology

Textbook of Oral Pathology

Inflammatory reaction, circulatory disturbance, defective connective tissue mechanism, autoimmune disorders

Paget’s disease

Deep aching bone with bilateral symmetrical swelling, deformity of bone in stress bearing area, headache, deafness, blindness occur due to narrowing of skull foramina, bowing of leg, waddling gait, diastema, loosening of teeth, difficulty in lip closure, pathological fracture of bone

Fatigue, weakness, polyuria, thirst, depression, loss of memory, peptic ulcer, bone pain, loosening of teeth and fracture of jaw bone

Primary Secondary

Adenoma hyperplasia of parathyroid gland

Hyperparathyroidism

Clinical/Radiological features Hepatosplenomegaly, lymphadenopathy, ecchymosis of skin, mucosal ulceration, gingival hyperplasia

Types

Letterer-Siwe disease

Etiology

Management

Osteoclastic bone resorption, bone replaced by highly vascularized cellular connective tissue, bone marrow replaced by fibrous stroma, reversal and resting line, mosaic pattern seen in the bone, chronic inflammatory cells and dilated blood capillaries

Administration of calcitonin, surgery in severe cases

Excision of Osteoclastic resorption of bony trabeculae, areas parathyroid tumor of excessive hemorrhage and hemosiderin pigmentation, brown tumor (tissue takes brown color), multiple multinucleated giant cells

Marked proliferation of Poor prognosis non-lipidized histiocytes

Pathological features

Appendices

923

Can be developmental or caused by liver damage, glandular dysfunctions, trauma

It can occur due to latent hyperparathyroidism, hormone dependent neoplasm, trauma, familial pattern

Defective matrix formation, cross linking of adjacent molecule

Cherubism

Osteogenesis imperfecta

Neonatal lethal type Sever non-lethal type moderate and deforming type Mild and nondeforming type

Monostotic Polyostotic (Jaffe’s type and Albright’s syndrome)

Types

Management Growth ceases after puberty, surgical recontouring

Self limiting disease

No treatment is possible

Pathological features Highly cellular, proliferating, well vascularized fibrilar connective tissue, spindle shaped fibroblasts arranged in whorled pattern. Chinese latter pattern seen, spheroidal areas of calcification, lesion blends with surrounding normal bone. Remodeling of woven bone to lamellar bone Whorled pattern cellular connective tissue stroma, proliferating fibroblasts, multinucleated giant cells, eosinophilic perivascular cuffing of collagen fibers, extravasated RBC, hemosiderin pigments Thinning of cortex, immature woven bone, short, thin, fragile bony trabeculae, increased osteoblasts, osteoclasts

Slow enlarging, painless, unilateral swelling, facial asymmetry, expansion and gradual distortion of cortical plate, displacement of teeth, malocclusion, in Albright’s syndrome café-au lait spot, and other endocrine abnormalities can be seen

Bilateral painless Symmetric swelling, giving rise to chubby face, eyes raised to heaven look, increases cheek fullness, widening of alveolar ridge, lymphadenopathy, premature exfoliation of teeth Multiple fracture of bone, generalized body deformity, dwarfed stature, blue sclera, deafness, defective heart valves

Clinical/Radiological features

924

Fibrous dysplasia

Etiology

Textbook of Oral Pathology

Progress rapidly, pain in bone, pathological fracture occur, facial asymmetry

Replacement of bone by fibrous tissue

Increased tendency of development severe osteomyelitis, anemia, thrombocytopenia, leukopenia, deafness, blindness, facial paralysis, frontal bossing, long bones shortened, spontaneous hematoma

Massive osteolysis

Autosomal dominant Autosomal recessive

Absence of clavicle, shoulder can meet in midline, nose is flat, wide, hypoplastic maxilla, delayed closure of fontanels, high and narrow arched palate

Clinical/Radiological features

Rapidly bilateral symmetrical mandibular swelling, deep seated tendered soft tissue swelling, dysphagia, pseudoparalysis anemia occurs.

Genetic defect

Osteopetrosis (marble bone disease)

Types

Infantile cortical hyperostosis

Hereditary autosomal dominant trait

Cleidocranial dysplasia

Etiology

No treatment is required

No treatment is required

Radiation therapy can be given

Edema and thickening of periosteum with apposition of many thin bony trabeculae parallel to each other

Foci of resorption, bone is replaced by fibrovascular connective tissue showing chronic inflammatory cell infiltration

No treatment is possible

Management

Dense and sclerotic bone with compensatory remodeling. Medullary cavity is small and little amount of marrow tissue. Osteoblasts are present

Pathological features

Appendices

925

Degenerative disease, aging process or trauma

Genetically determined

Can be precipitated by tuberculosis, herpes simplex, infectious mononucleosis, hyperimmune reaction

Hereditary

Psoriasis

Erythema multiforme

White sponge nevus

Types

Not specific

Topical and systemic steroid therapy is given

Atrophy with Hyperparakeratosis, absence of granular cell layer, clubbing of rete pegs, intraepithelial microabscess formation (monro abscess), increased mitotic activity, mild lymphocyte cell infiltration Acanthosis, intra or intercellular edema and necrosis of the epithelium, subepithelial connective tissue shows edema and perivascular infiltration of lymphocytes and macrophages

Painless, dry white scaly patches, patch are well circumscribed, erythematous, sterile pustule, Auspitz’s sign (tiny bleeding point) oral cavity lesion are well defined, grayish white or yellowish patches Rapidly developing Erythematous macules, papules, bulls eye or target lesion (concentric erythematous rings separated by ring of near normal color on skin), vesicle are eroded or ulcerated bleed profusely, foul smell in mouth Asymptomatic white folded areas in the mucosa, oral lesion are soft and spongy and peculiar opalescent hue, surface show area of desquamation

Self regression Mild to moderate Self regressing hyperparakeratosis, acanthosis, Intercellular edema, vacuolated cells in the spinous cell layer having pyknotic nuclei, mild inflammatory cell infiltration

Analgesics, antiinflammatory drugs should be given

Vertical or horizontal crack on the articular cartilage, cartilage less elastic, elevation of disc surface called lipping, degeneration of chondrocytes

Clicking sounds while opening and closing movements. Limitation of movement. Pain

Management

Pathological features

Clinical/Radiological features

926

Osteoarthritis

Etiology

Textbook of Oral Pathology

Ulceration and heal without scarring, skin lesion as red eczematous plaque

P. vulgaris – rapidly Developing vesicle, rupture bullae are painful, bleeds profusely Nikolsky’s sign positive, orally bleb like blister are seen P. vegetans – papillomatous hyperplasia following rupture, cerebriform tongue

Bullous pemphigoid

P. vulgaris P. vegetans P. foliaceous P. erythematosus

Clinical/Radiological features

Mild erosion or desquamation gingival tissue, erythematous lesion, mucosal bullae are tense, tough, after rupture painful eroded or ulcerated area Nikolsky’s sign is positive. Heal by scar formation, corneal ulceration, scaring results in adhesion in conjunctiva

Autoimmune mechanism

Types

Cicatricial pemphigoid

Pemphigus

Etiology

Systemic steroid therapy Extracellular edema, vacuolation in basement membrane zone, formation of subepithelial vesicles or bullae, inflammatory cell infiltration present, blood vessels dilated

Systemic steroid therapy

Steroid antibiotics to control infection

Suprabasilar split occur due to formation of vesicle or bullae, basal layer of row of tomb stones, loss of intercellular bridges, disruption of prickle cells, Tzank cells are found, acanthosis in spinous cell layer

Same as cicatricial type

Management

Pathological features

Appendices

927

Acquired type is caused by multiple myeloma, diabetes mellitus, TB, amyloidosis

Autoantibodies and immune complex

Lupus erythematosus

SLE—skin lesion in butterfly configuration over malar region, itching, burning, hyperpigmentation, loss of hair, xerostomia, mucosal petechiae DLE—elevated red purple macule, covered by yellow or gray scale, butterfly distribution, carpet track appearance, enlarge at periphery pain and burning of oral mucosa

Multiple vesicle and bullae on pressure area, after rupture raw painful ulcers which heal with scarring, nail sheds, decreased mouth opening due to scarring, delayed eruption and increased periodontal disease

EB simplex EB dystrophic Junctional EB EB acquista

Systemic LE Discoid LE

Clinical/Radiological features

Types Systemic steroid therapy

Destruction of basal or suprabasal layers of the oral epithelium, resulting in formation of vesicle or bullae

Systemic steroid SLE—atrophy with therapy should be hyperkeratinization, given liquefactive degeneration, edema of subepithelial connective tissue, lymphocyte infiltration fibrinoid degeneration DLE— hyperparakeratinization, Atrophic epithelium, keratin plugging, acanthosis, pseudoepitheliomatous hyperplasia, perivascular lymphocytes infiltration

Management

Pathological features

928

Epidermolysis bullosa

Etiology

Textbook of Oral Pathology

Loss by wear of dental tissue caused by abrasion by foreign substance Usually located at cervical areas of teeth. (e.g. toothbrush, dentifrice) Lesions are more wide than deep. Premolars and cuspids are commonly affected. Broad concavities within smooth surface enamel.

Progressive loss of hard dental tissue by chemical processes not involving bacterial action

Loss of tooth surface at the cervical areas of teeth caused by tensile and compressive forces during tooth flexure

Abrasion

Erosion

Abfraction

Affects buccal/labial cervical areas of teeth. • Deep, narrow V-shaped notch. • Commonly affects single tooth with excursive interferences or eccentric occlusal loads.

Cupping of occlusal surfaces, (incisal grooving) with dentin exposure. Increased incisal translucency, wear on non-occluding surfaces and raised amalgam restorations. Clean, non-tarnished appearance of amalgams. Loss of surface characteristics of enamel in young children. Preservation of enamel “cuff” in gingival crevice is common. Hypersensitivity and pulp exposure in deciduous teeth.

Loss by wear of surface of tooth or restoration caused by tooth-to-tooth Matching wear on occluding surfaces. contact during mastication or parafunction Shiny facets on amalgam contact. Enamel and dentin wear at the same rate. Possible fracture of cusps or restorations

Attrition

Clinical Appearance

Definition

Term

Tabular presentation of tooth tissue loss

Appendices

929

Actinomycosis Actinomycosis israeli, naeslundi, viscosus, odontolyticus and proprionica

Cervicofacial is most common. It involves face, neck, tongue and mandible. Organisms may enter oral mucosa producing swelling and induration of the tissues. It produces abscess which opens onto skin surface. Other areas involved are pulmonary and abdominal cavity

Lepromatous nodules tongue lips and It affects skin, peripheral nerves upper respiratory tract. Hypopigmented patches hard palate. Gingival hyperplasia with loosening of tooth with partial or complete loss of sensation. Two types tuberculoid (Skin) and lepromatous (Nerves) type-It produces disfigurement like loss of fingers, toes, (claw toe) Nasal depression. May cause sudden death.

Leprosy Mycobacterium leprae

Involvement of maxilla and mandible may lead to osteomyelitis. Pus contains sulfur granules. When stained with gram stain they show “sun ray appearance”.

Grams staining, culture of sulfur granules

Slit skin smears stained with Z-N stain. Lepromin test

Staining by Ziehl-Neelsen stain Culture by Lowenstein-Jensen media, Loeffler’s serum slope. Tuberculin test (Mantoux test)

Oral tuberculous ulcers, more commonly found on tongue, are irregular superficial or deep painful ulcers which tend to increase in size. TuberculomaTuberculous periapical granuloma

Persistent cough with or without hemoptysis, gradual weight loss, cervical, axillary and mediastinal lymphadenopathy. Tuberculous lymphadenitis (Scrofula), painful lymph nodes, with perforations and crustations, Cold abscess. Lupus vulgaris is primary tuberculosis of skin especially of face leading to formation of papular nodules which may ulcerate. Miliary tuberculosis occurs due to lymphatic dissemination

Tuberculosis Mycobacterium tuberculosis Acid fast bacilli

Staining by Alberts stain, Ponder’s stain and Neisser’s stain. Culture on Loeffler’s serum. Tellurite agar is selective media. Eleck’s test Schick test

Leathery, grayish white “pseudomembrane”. It is formed by dead epithelial cells, coagulated fibrin and purulent exudates. “Bull neck” Swelling of neck due to striking cervical lymphadenopathy.

Skin and mucous membrane lesions. Mucous membrane lesions are found on larynx, pharynx and tonsils.,conjunctiva. Hoarseness of voice, respiratory stridor and dyspnea may lead to airway obstruction in children

Diphtheria Corynebacterium diphtheriae

Culture Dick test

Diagnosis

930

Stomatitis scarletina Tonsillitis with grayish exudates “Strawberry tongue” and “raspberry tongue”

Tonsillitis, Pharyngitis, fever, vomiting, skin rash, bright scarlet on 2nd or 3rd day due to injury to endothelium and dilatation of blood capillaries

Scarlet fever B-hemolytic streptococci

Patognomic/Characteristic oral Diagnosis features

Clinical features

Lesion and causative organism

Important bacterial infections

Textbook of Oral Pathology

Clinical features It enters the wound and produce toxins. Tetanospasmin in anaerobic conditions. It affects the synapse of motor interneurons causing sever muscle spasms. Opisthotonus-Arched back due to contraction of back muscles. Primary- (3 day to 3 months) Chancre. A lesion that develops at site of inoculation. Secondary- (6 weeks after primary) Skin-Macular popular painless lesions Painless macules and papules TertiaryGumma is focal granulomatous lesion with central necrosis. CVS and CNS involvement is seen Congenital-Transmission of infection to child by mother Frontal bossing, saddle nose, irregular thickening of supraclavicular joint (Hegoumenaki’s Sign) Saber shin

Lesion and causative organism

Tetanus Clostridium tetani

Syphilis Treponema pallidum

Diagnosis Grams staining Culture in Robertsons’s cooked meat medium and blood agar. Direct immunofluorescence

Direct examination by dark field microscopy. Culture not possible Wasserman’s test, VDRL test, Kahn test, Fluorescent treponemal antibody absorption test and T. pallidum hemagglutination assay.

Patognomic/Characteristic oral Diagnosis features Lock jaw-Spasm of masseter muscle leads to trismus. Dysphagia, laryngeal spasms may lead to asphyxia. Risus sardonicus or Grimace-sustained contraction of facial muscles. Primary-Chancre on lips, palate, gingival and tonsils. Secondary-Mucous patches (Snail track ulcers)-Multiple grayish white plaques overlying over an ulcerated surface. Seen on tongue, gingival and buccal mucosa. Tertiary syphilis-Gumma of tongue and palate and produce a deep painless ulcer and palatal perforation. Syphilitic glossitis Congenital: Short maxilla high arched palate, Hutchinson’s triad-Hypoplasia of incisor and molar teeth (Mulberry molar, Moon’s molar, Fournier teeth, Screw driver shaped incisors) Eighth nerve deafness, and interstitial keratitis of eye

Appendices

931

Incubation 2–26 days

2–10 days

8–12 days

2 weeks

Reactivation of chickenpox is called zoster 14–18 days

Infection

Herpes simplex Primary and secondary

Herpangina Coxsackie group A virus

Measles

Chickenpox Varicella zoster

Varicella Zoster

Mumps epidemic parotitis

Clinical features

Duct of parotid gland becomes puffy and red.

Extremely painful, unilateral vesicles which form ulcers are found on buccal mucosa tongue uvula and pharynx and larynx.

Extremely painful lesion due to inflammation of dorsal root ganglia. Fever pain tenderness along the course of involved sensory nerves. It is characteristically dermatomic and unilateral in distribution. It is an acute contagious viral infection of children. Unilateral and bilateral swellings of the salivary glands usually parotid glands. Swellings are usually rubbery in consistency producing pain on mastication. Fever, pain below the ear.

Small blister like lesions on buccal mucosa tongue gingival and palate. Lesions rupture to form eroded ulcers.

Koplick’s spots: These occur 2–3 days of cutaneous rashes. They are small irregular spots bluish white specks surrounded by bright margins. Palatal pharyngeal petechiae, gingival ulceration congestion of throat may occur.

Tonsillar small vesicles that rupture to form crops of ulcers. Causes dysphagia

It is a primary varicella zoster infection. It is acute, extremely contagious disease occurring in children. It is characterized by exanthematous vesicular rash with headache, fever anorexia. Lesions occur on trunk face and extremities. Lesion rupture to form a superficial crust and heal by desquamation.

Acute contagious dermatropic infection affecting children. Fever, cough, conjunctivitis, photophobia, lacrymation and eruptive lesions of skin and mucous membranes. Lesions are tiny red macules or papules which coalesce to form large lesions

Sore throat cough, low-grade fever, rhinorrhea

Oral manifestations Herpetic stomatitis herpes labialis, vesicular lesions rupture and form shallow ragged extremely painful ulcer covered by gray membrane surrounded by erythematous halo. Heal spontaneously within 7–14 days without scar.

932

Herpetic eczema, herpetic conjunctivits, herpetic meningoencephalitis and disseminated herpes simplex of the newborn. Herpetic whitlow. Prodromal symptoms include fever headache. Bodyache

Important viral infections

Textbook of Oral Pathology

Evidence of inflammation persist following eliminations of plaque and calculus, as well as improved hygiene

Indistinguishable from hyperplastic gingivitis, Pregnancy, puberty, hormonal except that then erythematous enlargement is fluctuation may be contributory generalized and the patient history

Pregnancy gingivitis

Idiopathic gingivitis

Severe pain, fetid odor, punched out papilla, pseudomembranous ulceration, exudate and erythema; usually most sever in anterior region

ANUG

Painful, erythematous gingiva as well as odor of ammonia and excessive salivation

Erythematous and atrophic appearance without enlargement; pain and sloughing of surface epithelium are characteristic

Desquamative gingivitis

Uremic gingivitis

Pale, fibrotic appearance of gingiva, loss of stippling, edema, exudate and hemorrhage from the sulcular surface on probing, increase pocket depth

Chronic gingivitis

Edematous enlargement and erythema may be dramatic, but the consistent feature is dramatic hemorrhage after even slight pressure on the tissue

Bulbous, edematous enlargement of gingiva, may be focal or generalized; ‘boggy’ and pocket depth is increase

Hyperplastic gingivitis

Hemorrhagic gingivitis

Erythema, edema, tenderness limited to the marginal gingiva and interdental papillae, younger patient

Significance

Failure to respond to normally effective treatment usually suggest diminished host resistance or other contributory systemic disease that has not been diagnosed

Associated with renal failure

Associate with bleeding disorders, scurvy, leukemia and hemopoietic suppression; may become severe

Indicates the need for additional diagnostic evaluation to identify the underlying contributory condition

Often persist to some degree despite local plaque control

Diagnostic sign of the causative condition; improvement is usually dramatic following resolution of systemic condition

Improved hygiene and oral prophylaxis usually yields significant improvement by minimizing the inflammatory component of the process

Rapid response to improved status of the host, antibiotics therapy and superficial debridment of the tissue

Topical corticosteroid application during episode of increase severity usually required to maintain symptomatic control

Autoimmune conditions such as lichen planus and cicatrical pemphigoid

Compromise host resistance to infection

Inflammation of the crevicular pockets can be controlled by plaque removal if pockets can be kept clean

Deeper, hyperplastic response resolve with plaque removal but enlargement persist

Superficial, resolve quickly with plaque formation with no permanent defect

Chronic inflammation produce a recurring cycle of active inflammation and reparative fibrosis

Caused by poor oral hygiene, hormonal or medication

Contributory factors None beyond the poor oral hygiene and relatively short duration of the process

Form of gingivitis Clinical features

Marginal gingivitis

Comparison of different forms of gingivitis

Appendices

933

Textbook of Oral Pathology Enamel pathology

934

A. Developmental • Amelogenesis imperfecta • Dens invaginatus • Enameloma B. Environmental pathology • Attrition • Abrasion • Erosion

C. Enamel caries • Pit and fissure • Smooth surface • Caries at cementoenamel junction D. Pigmentation • Endogenous • Exogenous E. Enameloma

Dentin pathology

A. Developmental • Dentinogenesis imperfecta • Dentinal dysplasia • Regional odontodysplasia • Dentin hypocalcification B. Dentinal caries

C. Neoplastic • Dentinoma • Odontoma D. Regressive changes • Secondary dentin • Dentinal sclerosis

Leukopenia

I. Infections A. Bacterial • Typhoid • Paratyphoid fever • Brucellosis • Tularemia (early) B. Viral and rickettsial • Influenza • Measles • Rubella • Chickenpox • Infectious hepatitis • Colorado tick fever • Dengue • Yellow fever C. Protozoal • Malaria • Relapsing fever • Kala-azar D. Any overwhelming infection • Miliary tuberculosis • Septicemia II. Hemopoietic disorders • Gaucher’s disease • Pernicious anemia • Aplastic anemia • Chronic hypochromic anemia

• Aleukemic leukemia • Agranulocytosis III. Chemical agent A. Agents commonly producing leukopenia in all patient if given in sufficient dose • Mustards (sulfur and nitrogen mustards) • Urethane • Busulfan • Benzene • Antimetabolites B. Agents occasionally associated with leukopenia apparently as result of individual sensitivity • Analgesics, sedative and anti-inflammatory • Antithyroid drug • Anticonvulsant • Sulfonamides • Antihistamine • Antimicrobial agents • Tranquilizers IV. Physical agents • X-ray radiation and radioactive substance V. Anaphylactic shock and early stages reaction of foreign protein VI. Disease of unknown etiology • Liver cirrhosis • Disseminated erythematosus • Cyclic neutropenia

Appendices Basophilia

I. Blood disorders • Chronic myelocytic leukemia • Chronic anemia • Hodgkin’s disease II. Splenectomy

III. Infection • Chronic inflammation of accessory tissue • Smallpox • Chickenpox IV. Myxedema V. After injection of foreign proteins VI. Some cases of nephrosis

Neutrophilia

A. Acute infection • Coccal • Bacilli • Fungi • Spirochetes • Virus • Rheumatic fever • Diphtheria • Small pox B. Inflammatory • Coronary thrombosis • Gout • Collagen vascular disease • Burns • Hypersensitivity reaction C. Intoxication • Uremia • Diabetes acidosis • Poisoning by chemical and drugs like lead, mercury, digitalis, insect venoms, black widow spider

D. Acute hemorrhage E. Acute hemolysis F. Malignant tumor of • Gastrointestinal tract • Liver • Bone marrow G. Blood disorders • Myelocytic leukemia • Polycythemia • Myelofibrosis • Myeloid metaplasia • Chronic idiopathic neutropenia • Hereditary neutrophilia H. Miscellaneous • Physiologic in the newborn • During labor • After repeated vomiting • Convulsion • Paroxysmal tachycardia • After epinephrine injection

Eosinophilia

A. Allergic • Bronchial asthma • Urticaria • Angioneurotic edema • Hay fever • Allergic rhinitis • Drug sensitivity B. Skin disease • Pemphigus • Demits herpetiformis • Bullous pemphigoid C. Parasitic infection • Trichinosis • Echinococcosis disease D. Blood disorders • Chronic myelocytic leukemia • Polycythemia vera

E.

F. G. H.

I. J.

• Hodgkin’s disease • Pernicious anemia Infection • Scarlet fever • Chorea • Erythema multiforme Malignant disease of any type Following irradiation Miscellaneous • Pulmonary infiltration with eosinophilia • Tropical eosinophilia • Polyarteritis nodosa • Rheumatoid arthritis • Sarcoidosis • Certain poison Inherited Idiopathic

935

Textbook of Oral Pathology Lymphocytosis

936

A. Acute infection • Infectious mononucleosis • Acute infectious lymphocytosis • Infectious hepatitis B. Chronic infection • Tuberculosis • Secondary and congenital syphilis • Undulant fever

C. D. E. F.

Lymphocytic leukemia Lymphosarcoma Heavy chain disease Hemopoietic disorders • Neutropenia • Exanthema

Monocytosis

A. Bacterial infection • Tuberculosis • Subacute bacterial endocarditis • Syphilis • Brucellosis • Typhoid B. Protozoan and rickettsial infection • Malaria • Rocky Mountain spotted fever • Typhus • Kala azar • Trypanosomiasis • Oriental sore C. Blood disorders • Lymphoma • Leukemia

D. E. F.

G.

H.

• Hodgkin’s disease • Multiple myeloma Lipid storage disease • Gaucher disease Malignant neoplasm • Carcinoma of ovary, breast and stomach Collagen vascular disease • Lupus erythematosus • Rheumatoid arthritis Granulomatous disease • Sarcoidosis • Ulcerative colitis • Regional arteritis Chronic high dose steroid therapy

Peripheral plasmocytosis

I. Infection A. Viral • Rubella • Rubeola • Varicella • Infectious mononucleosis B. Bacterial • Streptococcal • Diplococcal • Syphilis • Tuberculosis C. Protozoal • Malaria • Trichinosis II. Serum sickness A. Drugs • Penicillin • Sulfisoxazole

B. Antitoxins • Equine tetanus • Equine diphtheria III. Neoplasm A. Hematological • Plasma cell leukemia • Chronic lymphocytic leukemia B. Non-hematological • Breast • Prostate IV. Miscellaneous • Transfusion • Hyper-immunization • Trauma

Appendices Causes and mechanism of vitamin D deficiency

Predisposing factors

Mechanism

Dietary lack of meat and dairy product Lack of adequate exposure to ultraviolet light Gastric intestinal disease or chronic liver disease Aluminum toxicity and biphosphonates Administration of anticonvulsant drug like phenobarbitone result in increase Chronic renal failure Hypophosphatemia rickets (X linked dominant)

Low levels of vitamin D in the diet Failure of vitamin D precursor synthesis in the skin Malabsorption of vitamin D and calcium Direct inhibition of bone mineralization These drug enhance liver enzyme activity which breakdown of vitamin D to biological inert product Reduced conversion of 25(OH)D3 to 1,25 (OH)2 D3 Inherited defect in renal tubular phosphate reabsorption leading to hypophosphatemia Defect mutation in bone alkaline phosphatase which cause inhibition of bone mineralization at the calcification front

Hypophosphatasia (autosomal recessive)

Differentiating features of ossifying fibroma of fibrous dysplasia

Features

Ossifying fibroma

Fibrous dysplasia

Age

3rd and 4th decade

1st and 2nd decade

Gender predilection

Females

Equal

Location

Body of mandible

Maxilla

Radiography

Well defined margin

Poorly defined margin

Lesion shape Roughly

Nodular or spherical

Fusiform or elliptical

937

Textbook of Oral Pathology

APPENDIX II: GLOSSARY Rashmi Ekka Aberration: It is a variation from the normal form or course . Aberrancy: It is defined as that situation in which a tissue develops at a site where it is not normally found. Ablation : It is removal of a part by excision or amputation. Abnormal: It is not normal , deviating in some from the usual structure, position or state . Abrasion : It is the wearing away of a structure or substance by mechanical means such as scrubbing or grinding . Abrasive: It is a substance which contains an abrasive which tends to erode the surface . Abfraction : Loss of tooth surface at the cervical areas of teeth, caused by tensile and compressive forces during tooth flexure ; cervical erosive lesions that cannot be attributed to any particular cause . Abscess: An abscess is a localized collection of pus surrounded by an area of inflamed tissue in which hyperemia and infiltration of leukocytes is marked . Actinic keratosis: It is a premahgnant squamous cell lesion resulting from long-term exposure to solar radiation and may be found on the vermilion border of lip as well as other sun exposed skin surfaces . Actinic clastosis: It is a lesion on the labial mucosa exposed to sun . A white area of atrophic epithelium develops with underlying scarring of the lamina propria . Actinic cheilitis: When this atrophic tissue abrades to ulcer, it is called actinic cheilitis . Acanthosis: This condition is characterized by widening and thickening of stratum spmosum . Acantholysis: It is the pathological separation of epidermal or epithelial cells by breakdown of desmosomes in stratum spmosum (seen in pemphigus) . Acquired : Relating to something not of genetic origin but resulting from outside influence . Acrocephalic : It is a highly arched or pointed skull . Acute: Having severe symptoms and a short course . Adduction : Drawing in towards the center or to median line , as opposed to abduction . Adenomatosis oris : It is the swelling of the mucous glands of the lips with no inflammation or secretion . Adrenodontia: It is a morphological indication of over activity of adrenal glands characterized by large pointed canines and teeth with occlusal surfaces showing brown discoloration . Aerodontia: It is that branch of dentistry concerned with the care and treatment of dental conditions caused by high altitude flying . Afferent nerve : It refers to any nerve transmitting impulse from the periphery to the center . Ageusia: It is the loss or absence of sense of taste .

Aglossostomia: It is the congenital absence of the tongue and of mouth opemng . Agranulocytosis: A marked decrease in the number of granulocytes, particularly neutrophils . Allelograft: A graft using material not derived from a donor or from animal sources, e . g . synthetic resins , stainless steel alloy . Allergen: A substance capable of inducing hypersensitivity or an allergic reaction. Allergy: It is hypersensitivity to any normally harmless substance resulting in an exaggerated or abnormal reaction . Allograft: It is a graft derived from a donor of the same species but genetically dissimilar . Amniocentesis : It is diagnostic procedure in which a small amount of amniotic fluid is withdrawn from amniotic sac, a membrane surrounding the fetus in uterus , to detect fetal defects . Amalgam tattoo : Oral soft tissue discolorations due to amalgam ; most common pigmentation of the oral cavity . Amelogenes is: The formation of the enamel portion of the tooth . Analgesia: It is relief from pain or insensitibilty to pain . Analogous : Having similar properties . Anesthesia: It is the general loss of all sensations or feelings . Anemia: It is an abnormal reduction in the number of circulating red blood cells, the quantity of hemoglobin and the volume of packed red cells in a given unit of blood . Anaphylaxis : It is an antigen-antibody reaction produced by the parenteral injection of an antigen causing hypersensitivity . Anastomosis : It is a communication between two vessels . Anachoresis: If the bacteria circulating in the bloodstream settle in areas of inflammation or of lowered resistance in the pulp and produce pulpitis, abscess or necrosis, the phenomenon is referred to as anachoresis . Anomaly: Deviation or irregularity as compared with the normal . Anorexia: It is the lack of appetite . Anomalad : It is a malformation together with its subsequently derived structural changes; the primary defect setting off a series of secondary or even tertiary events resulting in multiple anomalies . Anosmia: It is the absence of sense of smell . Antagonist: It is any tissue that acts against or in opposition to another tissue . Anaplasia: It is the reversion of the same type of cells from a more highly differentiated to a less highly differentiated type . Antibody: It is any one of the class of substances produced in the body as a reaction to a specific antigen and with which, it reacts in some observable way to produce a specific effect such as inactivation, agglutination, and/or flocculation .

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Antibiotics: These are substances produced by microorganisms which suppress the growth or kill other microorganisms at a very low concentration. Antidote: It is an agent used to counteract or prevent the action of poisons. Antigen: It is any substance that when introduced into the body, excites the formation of specific antibodies. Angioma:A tumor made up of blood or lymph vessels. Ankyloglossia: Extensive adhesion of the tongue to the floor of the mouth or the lingual aspect of the anterior portion of the mandible caused by a short lingual frenum. Apertognathia (open bite): A condition in which the anterior or the posterior teeth of the mandible cannot be brought into occlusion with antagonist teeth of maxilla. Aponeuroses: These are collagenous sheets or ribbons that resemble flat, broad tendons. It may cover the surface of the muscle and assist in attaching superficial muscles or separate the structures. Aplasia: Absence of an organ or organ’s part due to failure of development of the embryonic tissue of origin. Arteriosclerosis: A condition characterized by loss of elasticity and thickening of artery walls. Atrophy: It is a reduction in size of tissue or of an organ due to decrease in the size or number of its constituent cells. Atresia: It is the congenital occlusion or absence of one or two major salivary gland ducts. Atypical: Irregular, not conformable to the type. Attrition: It is the physiologic wearing away of tooth material as a result of tooth to tooth contact. Auscultation: Listening to the sound produced within the body with the help of a stethoscope. Autogenous: It is produced within the body itself. It is self generated. Autograft: It is a graft taken from one of the patient’s body and transplanted to another part in the same individual. Autoantibody: An antibody that reacts against an antigenic constituent of the person’s own tissues. Autoimmune disease: A disease characterized by tissue injury caused by a humoral or cell-mediated immune response against constituents of the body’s own tissues. Autoimmunity: Immune-mediated destruction of the body’s own cells and tissues; immunity against self. Autosomes: The non-sex chromosomes that are identical for men and women. Autoinoculation: To inoculate with a pathogen such as a virus from one’s own body. Bacteremia: It refers to the circulation of bacteria in the blood. Bacteria: These are microscopic unicellular vegetative organisms having a single chromosome, no nuclear envelope and a rigid cell wall. They may be seen as rods, cocci or filaments and divide by binary fission. Bacteriostatic: It is any agent that inhibits the growth and multiplication of bacteria.

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Baelz’s disease: It is a disease characterized by the presence of painless papules on the labial mucous membrane. (Cheilitis glandularis-superficial suppurative type). Ballooning degeneration: It is characterized by the isolation of a cell from its neighbors, especially in the lower layers of the epidermis, the withdrawing of its prickles after intracytoplasmic edema and vacuolization and the amitotic division of its nucleus so as to form multinucleated giant cells. Bay cyst: Apical cyst which have a direct connection with apical foramen have been termed as ‘bay cyst’. Bednar aphthae: Two ulcers appearing symmetrically one on either side of the midline of the hard palate in infants, thought to be caused by the nipple or by thumb sucking or sucking hard object. Benign: Not malignant; favorable for recovery. Bicameral abscess: It is an abscess which contains two chambers. Biopsy: It is the gross and microscopic examination of tissue or cells removed from living patients for the purpose of diagnosis or prognosis of the disease or the confirmation of the normal condition. Blanching: To take the color out of and make white. Bleb: It is a bulla or other skin blister filled with blood or serous fluid. Blind abscess: It is the one having no fistulous tracts. Blister: It is a vesicle caused by localized accumulation of fluid beneath the skin. Blood: It is the red fluid in the vessels of the circulating system which conveys oxygen and nutritive materials to the tissue and removes carbon dioxide and waste matter. Blood pressure: It is the pressure exerted by the blood on the artery walls and is dependent on the force of heart action, the elasticity of the vessel walls, capillary resistance and the volume and viscosity of blood. Blood transfusion: The intravenous administration of blood to help replenish excess blood loss due to hemorrhage or other wise, is known as blood transfusion. Boil: It is a localized skin abscess usually at the site of a hair follicle. Bosselated: Having a knob like protrusion or bosses. Bowen’s disease: It is a localized intraepidermoid carcinoma that may progress to invasive carcinoma over many years. Bradycardia: It is an abnormal slowness of the heart and pulse rate. Bradyglossia: It is an abnormal slowness of speech, due to difficulty in tongue movements. Bradypnea: It is an abnormal slowness of respiration. Bruise: It is a superficial injury, caused by a blow with no laceration but with discoloration of the skin and subcutaneous tissue produced by an accumulation of blood. Bruxism: It can be defined as the involuntary, unconscious, and excessive grinding, tapping or clenching of teeth or it is defined as non-functional grinding or gnashing of the teeth, usually during sleep.

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Buccal bifurcation cyst: A cyst of uncertain origin found primarily on the distal or facial aspect of a vital mandibular third molar, consisting of intensely inflamed connective tissue and epithelial lining. Bullae: It is an elevated blister like lesion containing clear fluid and is bigger than 1 cm in diameter. Burrows: These are short, linear, straight or sinuous lines in the skin. Burn: It is the injury resulting from the application of excessive heat, electric current, friction and caustics to skin or mucous membrane. Carcinogenesis: Carcinogenesis or oncogenesis or tumorogenesis means induction of a tumor agent which can induce tumor. The tumor agents are called carcinogens. Carabelli’s cusp: It is an accessory lingual cusp located on mesiopalatine cusp of maxillary second primary molars and 1st, 2nd and 3rd permanent molars. Capsule: Compressed fibrous connective tissue around a benign neoplasm separating it from surrounding tissues. Carcinoma: A malignant growth made up of epithelial cells that are capable of infiltration and metastasis. Caries: Demineralization of inorganic and dissolution of organic part of the tooth surface caused by bacteria. Carcinoma in situ: It is a histopathological diagnosis defined as a proliferation of basal epithelial cells from the basement membrane to the surface, with almost all of the cells manifesting cytologic atypia. Immediate maturation into a superficial keratin layer is possible, but no invasion into the underlying connective tissues can be seen. Calcareous: Relating to or containing calcium or calcium salts; chalky. Calcification: It is the deposition in organic tissue of calcium salts causing hardening. Calcinosis: It is a condition characterized by either localized or generalized deposition of calcium salts in nodules in the soft tissues. Callus: The mesh of fibrous bony tissue surrounding and uniting the bone ends after fracture. It is later replaced by hard bone. Camper’s line: It is the line extending from the external auditory meatus to a point below the nasal point and is also called facial line. Cancellous: Having a lattice like spongy structure; applied to bone tissue. Canker: It is an ulceration especially of the mouth and lips and it is also called aphthous stomatitis. Capillary: These are one of the very fine thread like blood vessels connecting the veins and arteries. Carbuncle: It is a staphylococcal infection of the sweat glands or hair follicles causing inflammation of the surrounding subcutaneous tissue and discharging pus through several openings, finally sloughing away. Carcinosarcoma: It is a mixed tumor containing characteristics of both carcinoma and sarcoma.

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Cariology: It is the scientific study of dental caries, its causes, prevention and treatment. Carrier: The individual who continues to harbor infectious agent either following recovery from the illness it induced. Cartilage: It is a form of elastic, nonvascular connective tissue attached to articular bone surfaces and also forming some parts of the skeleton. Catabolism: It is the process of breakdown of complex compounds by the body. Catarrh: It is the inflammation of the mucous membranes, especially those of nose and throat, with discharge of mucus. Causalgia: It is a burning sensation arising after trauma to a sensory nerve. Cellulitis: Cellulitis may be defined as a non-suppurative inflammation of the subcutaneous tissue extending along the connective tissue planes and across the intercellular spaces. Cell: It is one of the minute masses of protoplasm, containing a nucleus which forms the basis of all animal and plant structure. Cementicle: It is a small calcareous body developing in the periodontal membrane. Cell mediated immunity: It is the type of immunity in which the predominant role is played by T lymphocytes. Central: In oral pathology, it is the lesion occurring within bone. Centromere: The constricted portion of the chromosome that divides the short arms from the long arms. Chief complaint: It is the patient’s response to the dentist’s question. Cheilitis: It is the inflammation of lip. Chemoprophylaxis: It is the use of chemical drugs in the prevention of disease. Chemotherapy: It is the treatment of a disease by chemicals which affect pathogenic organisms without harming the patient or it is the treatment of malignant neoplasia by chemical means. Cheesy: Lesion’s texture is similar to curd of cheese. Chemotaxis: Taxis or movement in response to chemical stimulation. Chromatin: A general term used to refer to the material (DNA) that forms the chromosomes. Chronic: Persisting over a long time; when applied to a disease, chronic means that there has been little change or extremely slow progression over a long period. Chills: It is cold sensation with shivering, often characteristic of onset of fever. Chloroma: It is a condition characterized by multiple myeloid tumors of greenish color, affecting particularly the face and skull, and associated with blood picture of leukemia. Choriostoma: It refers to excessive amount of normal tissue that is present in abnormal location. Chondromalacia: It is a condition characterized by abnormal softness of the cartilage. Ciliated: Having hair like processes or fringe of hair.

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Circulation: It is the movement or flow in a circle, retracing its course repeatedly, applied especially to the flow of blood through the body. Cleft lip: It is a birth defect that results in a unilateral or bilateral opening in the upper lip between the mouth and the nose. Cleft palate: Cleft palate is a birth defect characterized by an opening in the roof of the mouth caused by lack of tissue development. Coagulation: When blood is shed, it loses its fluidity in few minutes and sets into a semisolid jelly. This is called coagulation or clotting. Cold abscess: It is a slow developing tuberculous abscess generally about a bone or joint and with little inflammation. Collar stud abscess: It is a superficial abscess connected by a sinus tract to a larger deep abscess. Complement system: This consists of a group of serum proteins which by series of reactions produce and release by products whose functions are to initiate an inflammatory reaction, to regulate and enhance phagocytic function and attack the bacterial cell membrane. Congenital: Present at or before birth but not necessarily inherited. Coalesce: It is a term used to denote to fusion or union of separated parts. Consanguinity: Blood relationship. In genetics, the term is generally used to describe marriages among close relatives. Corrugated: Having a surface that appears wrinkled. Cotton wool: Confluent radiopacities. Coarctation: It is narrowing or constriction, applied especially to blood vessels. Col: It is a depression in an interdental papilla between the two peaks, one on each side of the contact area. Coma: It is a state of complete unconsciousness from which a patient cannot be aroused, even by determined external stimulation. Commensal: It is an organism that lives on or within another organism, to its own advantage and without being detrimental to the host. Commissure: It is the point of union between similar parts or bodies. Concretion: It refers to any hardened or solidified mass in the tissue. Counter irritation: It refers to the deliberate production of superficial irritation in order to mask or relive an existing irritation or pain. Concrescence: It is a form of fusion that occurs after the root and other major parts of the involved teeth are formed or when the roots of two or more teeth are united by cementum, below the cementoenamel junction. Craniomalacia: It refers to a condition characterized by softness of bones of the skull, usually seen in infants. Crater: It is a localized depression, usually circular, with raised edge or rim.

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Crust: Dry products of exudation from lesions occurring on skin and lips. Crepitations: It refers to a crackling noise occurring in the joint when affected by certain disease. Cryosurgery: It is the use of extreme cold for surgical destruction of tissue. Cryotherapy: It is the treatment of disease with use of extreme cold. Cryptogenic leukoplakia: In a small proportion of cases of leukoplakia, no underlying cause has been found. Such lesions are termed as idiopathic or cryptogenic leukoplakia. Culture: It is the growth of microorganisms in an artificial medium. Curettage: It refers to the removal of foreign matter from the walls of a bony cavity or from the root surface. Cyst: Cyst is a pathological cavity which may or may not be lined by epithelium and consists of fluid, semi-fluid or gaseous content (but not by pus) and surrounded by connective tissue capsule. True cyst is a pathologic cavity always lined by epithelium usually containing fluid or semi-solid material. Cytology: It is the scientific study of cell. Cytopathic: Pertaining to or characterized by pathologic changes in cells. Cyanosis: It is the bluish discoloration of the skin and mucous membranes, often due to deficient oxygenation of the blood. Dental kinesiology: It is the study of motion and function of jaws and oral musculature; the accompanying neurological, vascular and other supporting system network and the impact of those muscle functions and neurological dynamics have on dental and systemic health. Developmental anomalies: Malformation or defects resulting from disturbance of growth and development are known as developmental anomalies. Dens in dente: It is also called dens invaginatus. Infolding of the outer surface of the tooth into interior. It is a developmental variation which is thought to arise as a result of invagination in the surface of tooth crown before calcification occurs. Dens evaginatus: Dens evaginatus is a developmental condition that appears clinically as an accessory cusp or globules of enamel on occlusal surface between buccal and lingual cusp of premolars. Debridment: It is the removal of dead tissue and foreign matter from a wound. Degeneration: It refers to the gradual deterioration of tissue with loss of function and chemical changes within the tissue. Dentistry: It is a branch of medicine concerned with oral and dental diseases and their prevention and treatment and with oral prosthesis. Desmosomes: The term desmosomes refers to the structures forming the site of contact between adjacent cells, especially epithelial cells. Desquamation: It refers to the peeling off of the outer layer of epithelium.

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Dental fluorosis: A condition of enamel hypoplasia characterized by white chalky spots or brown staining and pitting of teeth due to an increased level of fluoride; affecting enamel matrix formation and calcification by impairment of ameloblastic function. Dentigerous cyst: An odontogenic cyst that surrounds the crown of an impacted tooth; caused by fluid accumulation between the reduced enamel epithelium and enamel surface, resulting in a cyst. Deoxyribonucleic acid (DNA): A substance composed of a double chain of polynucleotide; both chains coiled around a central axis form a double helix. DNA is the basic genetic code or template for amino acid formation. Dermoid cyst: A cyst of midline of the upper neck or the anterior floor of the mouth of young patients, derived from remnants of embryonic skin; consisting of a lumen lined by a keratinizing stratified squamous epithelium and containing one or more skin appendages such as hair, sweat or sebaceous glands. Diffuse: Used in the description of a lesion; when borders of the lesion are not well defined and it is not possible to detect the exact parameters of the lesion, then this term is used. Diploid: Having two sets of chromosomes; the normal constitution of somatic cells. Diagnosis: It is the determination of the nature or cause of the disease. Differential diagnosis: The list of similar clinical picture, according to probable identity of condition at hand, is the differential diagnosis. Dimorphic anemia: It is a condition in iron deficiency and folic acid deficiency anemia can occur concomitantly. Diploe: The spongy layer of bone position between the inner and outer layers of compact bone. Diverticuli: They are small pouches or out pocket of the ductal system of one of the major salivary glands. Disinfection: This is the process by which pathogenic microorganisms are removed from the surface, without removing bacterial spores. Dilacerations: It refers to angulations or sharp bends or curves in the root and crown of the teeth. Disease: It is the departure from the average anatomical structure or is an abnormal degree of failure of physiological function or some reduction in psychological efficiency, due to either adversity in the genetic endowment of the individual or misuse of his free will or to adverse factors in the environment in which he lives or some combination of these factors or it is defined as loss of ease. Distomolar: Found in the molar region frequently located distal to 3rd molar. Discrete: Separate. Composed of separate parts, not joined or blended. Dislocation: It is the displacement of any part from its normal position, especially in the cases of bone and joints. Direct fracture: It refers to the fracture that occurs at the site of blow.

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Discoid lupus erythematous (DLE): It is a circumscribed slightly elevated white patch that may be surrounded by a red telangiectic halo. Dose: It is one measured portion of any medicine which is to be taken one at a time. Dominant: In genetics, a trait or characteristic that is manifested when it is carried by only one of a pair of homologous chromosomes. Dorsal: Directed towards or situated on the back surface (opposite of ventral). Dry abscess: It is an abscess that disperses without bursting or coming to a head. Drainage: It is the gradual removal of fluid from a cavity or wound. Dressing: It is a medicament used to promote wound healing or as a covering for a wound, used for protection or to assist healing. Drug: It is any medicinal substance. Dyskinesia: It is defined as an impairment of voluntary motions, causing movements that are incomplete or only partial. Dysesthesia: It refers to the impairment of feeling or sensations; a condition in which a normal stimulus produces disagreeable sensations. Dyskeratosis: This lesion shows abnormal orientation in development of epithelial cells. Dysodontiasis: It refers to the painful, difficult or delayed eruption of the teeth. Dysostosis: It refers to the congenital defective bone formation. Dysphagia: An experience of having great difficulty in swallowing. Dystrophic calcification: Pathologic calcification that occurs in degenerating and dead tissue. Dysplasia: It refers to the abnormal formation or development. Dyspnea: It is a shortness of breath. Ecchymosis: It refers to the diffuse extravasation of blood into the tissues. Larger purpuric lesions are called ecchymoses. Ectoderm: The outermost of the three primary germ layers of the embryo, from which are developed the epidermis, the external sense organs and the oral and anal mucous membranes. Edema: It is accumulation of excess fluid in the intercellular tissue spaces or body cavities. Electrocautery: It is cauterization by low voltage current producing burn like tissue repair, but with no control over the extent or quality of tissue destruction. Electrodesiccation: It refers to the deeply penetrating tissue dehydration produced by the insertion of electrodes into the tissue. Empirical therapy: With serious infections, it is often necessary to begin antibiotic therapy before culture result is available, this is called empirical therapy which is directed towards organisms which are most likely to have caused that infection.

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Embedded teeth: Those teeth which are unerupted usually because of lack of eruptive force. Embolism: It refers to the sudden blockage of blood vessels by a clot or other obstruction within the blood stream, causing failure of circulation. Empyema: It is the accumulation of pus in a body cavity or a hollow organ. Enamel pearls, nodules, or droplets: Pearls or droplets described as small buttons or nodules of enamel usually about 1 mm or 2 mm in diameter that form on the root or at the bifurcation of multi-rooted teeth. Embryonic: Pertaining to the earliest stage of development of an organism. Emigration: The passage of white blood cells through the endothelium and walls of small blood vessels. Endotoxin: They are heat stable phospholipid-polysaccharide-protein complex contained as a structural part of the cell of many gram-negative bacterias and released by disintegration of the cells. Enanthema: It is an eruption occurring on a mucous surface or on any surface within the body as opposed to exanthema. Endemic: Prevalent in a particular region. Endosteal: It is within the bone. Endothelium: It refers to the membrane lining the heart and blood vessels. Engorgement: It refers to the excess of blood in any part of the body or it is the localized congestion or distension. Enostosis: It is a localized morbid bone growth arising within the bone cavity. Enucleate: The word enucleate means to remove an organ or part, or a circumscribed, space filling lesion entirely, i.e. from its outer sheath or covering. Endodermal: Pertaining to the innermost of the three primitive germ layers of an embryo. Endodermal structures include the epithelium pharynx, respiratory tract (except the nose) and digestive tract. Epidemic: Affecting large number of people within an area or region. Epidemiology: It is that branch of science concerned with the study of a disease or condition through its frequency and distribution. Epithelium: It is a thin cellular layer covering or lining the organs and tissues of the body. Eponym: The name of an organ, syndrome, disease, etc. that contains or is derived from a proper name. Epulis: Any tumor of the gums; more especially either a fibrous or a giant cell tumor. Eruption: The act of appearing, or pushing through, as of teeth coming through the gums or a visible skin lesion occurring in disease. Erythema: It is the redness in the skin either diffuse or patchy, caused by congestion of the subcutaneous capillaries. Erythematous: It characterized by a redness of the tissue due to engorgement of the capillaries in the region.

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Erythroplastic: It is characterized by a reddish appearance. This term implies abnormal tissue proliferation in the reddish area. Erythrocyte: One of the red cells found in blood which carries oxygen and is produced by the bone marrow. Erythroplakia: The term is applied to any area of reddened velvety textured mucosa that cannot be identified on the basis of clinical and histopathological examination as a cause of inflammation or any other disease process. Erythrodontia: There is deposition of porphyrins in dentin and to a lesser extent in the enamel which imparts red or brown color to the deciduous and permanent teeth and known as erythrodontia. Erosion: It is a shallow crater in the epithelial surface that appears on clinical examination as a very shallow erythematous area with only superficial changes. Or a moist red lesion often caused by rupture in vesicles and bullae as well as trauma. Erosion (teeth): It is loss of tooth substance due to chemical process that does not involve bacterial activity. Erythroplasia: These are painless erythematous eruptions, popular or macular in nature, affecting the mucous membrane. Eschar: It is a dry slough, the result of burning or due to contact with a corrosive agent. Etiology: The study or theory of the factors that cause disease and their introduction to the host. Eversion: A turning outward or a state being turned outwards. Excrescence: It refers to an abnormal growth protruding from body or plant. Exacerbation: It refers to an increase in the severity of a disease or any symptoms. Examination: It refers to investigations carried out for diagnostic purpose. Exanthema: It is an eruptive fever. Excoriation: It is the superficial loss of surface skin or a graze. Excursion: It refers to any movement of a movable part from a resting position during the performance of some functions. Exfoliation: It is the peeling off in layers or in scales. Exophthalmos: It refers to the abnormal protrusion of the eyeball. Exophytic: It refers to a word relating to something growing outwards, used for tumor projecting above the normal surface contours or it refers to any pathological growth that project above the normal contours of the oral surface. Expansile: Capable of being extended or expanded. Expressivity: In genetics, the degree of clinical manifestation of a trait or characteristic. Exostosis: It is a bony swelling developing on the bone surface or on a tooth root. Exotoxin: It refers to a toxic secretion of bacterial cells which cause damage in sites distant from the focus of infections or they are heat labile proteins which are secreted by certain bacteria and diffuse readily into surrounding tissue.

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Extravasation: It is the escape of fluid from vessels into the surrounding tissue. Extrinsic: Having its origin outside and separated from a body, organ or part. Exudate: The matter that passes out into adjacent tissues through vessel walls in inflammation. Facies: The appearance of the face. Factitial injuries: These are accidentally self induced injuries on the basis of habits with frequent psychological backgrounds. Favorable fracture: If the fracture line runs in such a manner that the associated muscle tends to hold the fragments together, the fracture is described as favorable. Facet: It is a small abraded area on a bone or on tooth surface. Familial: Relating to a family, or affecting several of its members. Fascia: It is the layer of areolar tissue beneath the skin or the layer of areolar tissue investing the muscles, nerves and other organs. Fenestrate: To pierce with one or more holes, sometimes used on the walls of bony defect in an attempt to stimulate repair. Fenestration: It refers to a surgical procedure by which one or more holes are pierced in hard tissue. Fever: It refers to an abnormal increase in body temperature. Final diagnosis: It is statement with which precise diagnosis has been made on the basis of all required observation, identification of definitive symptoms and the pathological report and patient response to therapy. Fibro-cemento-osseous lesions: It is a skeletal disorder in which bone is replaced by fibrous tissue which in turn is replaced by mineralized tissue. Fissure: It is a linear often crusted, tender, painful defect in continuity of the skin, occurring usually at the mucocutaneous junctions and at sites where there is considerable elasticity of the skin. Fistula: It is communicating tract between two epithelial surfaces which is lined by granulation tissue which is subsequently epithelized. Fibrosis: There is an abnormal formation of fibrous tissue. Fluctuant: A wavelike motion felt on palpating a cavity with nonrigid walls, especially one containing fluid. Fluoride mottling: A condition of enamel hypoplasia characterized by white chalky spots or brown staining and pitting of teeth due to an increased level of fluoride affecting enamel matrix formation and calcification by impairment of ameloblastic function. Focus of infection: It refers to a circumscribed area of tissue, which is infected with exogenous pathogenic microorganisms and which is usually located near a mucous or cutaneous surface. Focal infection: It refers to metastasis from the focus of infection of organisms or their products that are capable of injuring tissue.

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Foramen: A small hole in a bone through which passes either blood vessels or nerves or both. Focal osteitis: A condition sometimes occurring after tooth extraction, particularly after traumatic extraction, resulting in a dry appearance of the exposed bone in the socket, due to disintegration or loss of the blood clot. Foreign body granuloma: A reaction to foreign materials that are too large to be ingested by either microphages (PMNs) or macrophages. Frenal tag: A redundant piece of mucosal tissue that projects from the maxillary labial frenum. Fusion: It is also called synodontia. It represents the embryonic union of normally separated tooth germs. Fulguration: It refers to the superficial tissue dehydration produced by a surgical electrode held slightly away from the tissue, causing sparking. Galvanism: The production of an electric current caused when two dissimilar metals used as restorations in the mouth come into contact, this can cause discomfort and even pain. Gangrene: It is the necrosis of tissue due to failure of the arterial blood supply caused by injury or disease. Gelation: The process of change of a colloid from a sol to a gel. Gerodontia: It is that branch of dentistry which deals with the care of old people. Gemination: It refers to the process whereby single tooth germ invaginates resulting in incomplete formation of two teeth that may appear as a bifid crown on a single root. Genetic heterogeneity: Having more than one inheritance pattern. Ghost teeth: A developmental disturbance of several adjacent teeth in which the enamel and dentin are thin and irregular and fail to adequately mineralize; surrounding soft tissue is hyperplastic and contains focal accumulations of spherical calcifications and odontogenic rests. Gingivosis: It refers to the any degenerative condition affecting the gingiva. Gland: An organ that produces secretions. Glossodynia: It refers to the burning or painful condition of the tongue. Gomphosis: It is the firm attachment of two bones without a movable joint. Gorham’s disease: In this condition a large portion of bone disappears without any apparent cause. Granuloma: A tumor composed of granulation tissue. Granulomatosis: It refers to the development of multiple granuloma. Granulation tissue: It is the reparative tissue that is formed on the surface of wound having pink, soft, granular appearance showing histologically new small blood vessel and fibroblast. Green stick bone fracture: It is a fracture in which one side of bone is broken and the other side is bent but intact. Ground glass: Fine radiopaque spots in radiolucent background.

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Gustatory: The sense of taste or the act of tasting. Hamartomas: It is a tumor like malformation of oral tissues, developmental in origin with tissue being native to the site. Habit: It is a tendency toward an act or an act that has become a repeated performance, relatively fixed, constant, easy to perform and almost automatic. Hemoglobinopathies: These are a group of hereditary disorders characterized by the presence of structurally abnormal hemoglobin. Hereditary disease: They are apparent at birth but some may not become evident for years. Hemoptysis: The presence of blood in the sputum caused by bleeding in the upper respiratory tract or the lungs. Hemorrhage: It refers to the internal or external loss of blood due to injury or other damage to blood vessels. Hemidesmosome: It refers to a structure found on the basal surface of an epithelial cell, the attachment site between the cell and the underlying membrane. Heredity: It refers to the transmission of a characteristic from parent to child or to later generation. Heterotrophic: It is a term used relating to organisms which require a complex source of carbon for nourishment and growth. Hematoma: It is large clot resulting from blood released into the tissue from a ruptured or injured blood vessel. Healing: It is repair and replacement of dead or damaged cells by healthy cells. Histology: It refers to the study of the anatomy and physiology of tissue and cells using microscopic technique. Holistic: It refers to an approach to treatment that takes into consideration the whole person, not just the disease or condition. Homologous: Having the same or corresponding structure or position but not necessary similar in function. Horner’s teeth: Incisor teeth with horizontal grooves caused by enamel deficiency. Hypodontia: It refers to the absence of one or more teeth. Hypertrophy: It refers to the enlargement caused by an increase in size of cells. Hydrocyst: It refers to a cyst whose contents are watery in nature. Hyperplasia: It refers to the enlargement caused by increase in number of cells. Hypoplasia: It is the failure of full development of an organ or tissue. Hydrostomia: It refers to a condition characterized by constant dribbling from the mouth. Hygroma: It refers to a swelling caused by fluid surrounding an inflamed bursa, or distending a sac or cyst. Hypertension: Exceptionally high tension especially abnormally high blood pressure. Hypnosis: It refers to a sleep or a trance state, especially one induced artificially by verbal suggestions or concentration upon some object.

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Hypsodont: Having teeth with long crowns and short roots seen in herbivorous animals. Hydropic degeneration: It refers to replacement of the nuclei of stratum basal by clear space due to edema and degeneration of cells. Iatrogenic diseases: Theses are the diseases produced by the action of a doctor or due to medical treatment. Idiopathic: It is any spontaneous or primary disease with no apparent external cause. Idiosyncrasy: It refers to a reaction to a particular drug in therapeutic doses in a manner not necessarily related to its pharmacological properties. Impacted teeth: They are those prevented from erupting by some physical barriers in the eruption path. Immunity: It is the resistance exhibited by the host towards injury caused by microorganisms and their products. Impermeable: Not permitting passage especially of fluids. Implant: The word implant means to insert into the body or to graft as in plastic surgery. Infection: It is a clinicopathological entity-involving invasion of the body by pathologic microorganisms and the reaction of tissues to microorganism and their toxins. Inspection: It refers to an examination of the affected part of the body. Internal derangement: It can be defined as mal-relationship of the meniscus to the condylar head and articular eminence where an alteration of its attachment allows the meniscus to assume an abnormal position. Inflammatory collateral cyst: It is a cyst which arises in the periodontium of an erupted tooth as a result of inflammatory process in the periodontal pocket. Involucrum: Small section of necrotic bone may be completely lysed, while a large one may get localized, and get separated and form shell of new bone called involucrum by a bed of granulation tissue or a sheath particularly new bone sheath that forms about sequestration. Indirect fracture: Fracture site distant from where the actual blow takes place, usually seen on contralateral side. In vitro: Within glass referring to observations made in a test tube or culture dish as opposed to in vivo. In vivo: Within a living organism. Indentation: It refers to the condition of being serrated or notched. Induced: Brought on by an outside agent or is artificially produced. Induration: It refers to the state of being hard or the process of becoming hard. Inflammation: It is the reaction of living tissue to injury. Infarction: It is a localized area of ischemic necrosis in an organ or tissue resulting from sudden reduction of either its arterial supply or venous drainage. Inflation: It refers to the distension with gas especially air. Inostosis: It refers to the process by which bony tissue is reformed to replace tissue that has been destroyed.

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Insidious: Unperceived coming on gradually and stealthily. Intermittent: Occurring at intervals with periods of cessation. Intubation: It refers to the introduction of a tube through the mouth or the nose to allow air, gas or vapor to pass into the lungs. Iontophoresis: It refers to the therapeutic treatment by electrical introduction of ions into the body tissue. Ischemia: It refers to the deficiency in the blood supply to a part or an organ which may be due to constriction, contraction or blocking of the arteries. Isograft: It refers to a graft derived from one member of a pair of monozygotic twins and transplanted to the other. Jaw winking: It refers to a movement of the lower jaw causing an involuntary movement of the eyelids. Joint: The place of connection between two bones, allowing of more or less movement an articulation. Keloid: It refers to a fibrous hyperplastic scar growth on the skin. Kernicterus: Staining of brain tissue cause by accumulation of unconjugated bilirubin in the brain. Knitting: It refers to the process of repair of a bone fracture. Lain’s disease: Burning of the tongue and the soft tissue of the mouth due to electrogalvanism caused by the use of dissimilar metals in dental restoration. Lancinating: It is the term used to describe shooting, tearing or sharply cutting type of pain. Leukoplakia: A white patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease, which is more than 5 mm. Lesion: A wound or injury or a patch of disease on the skin. A morbid change in tissue function. Lichen planus: Relatively common dermatitis occurs on skin and oral mucous membrane and refers to a lace-like pattern produced by symbolic algal and fungal colonies on the surface of rocks in nature. Lipomatosis: It refers to excessive localized accumulation of fats in the tissues. Localized: Lesion or condition happening within one small area. Lateral: Away from midline. Ludwig’s angina: This condition may be defined as an overwhelming rapidly spreading septic cellulitis involving submandibular, submental and sublingual space bilaterally. Lymph: It refers to the clear fluid found in the lymphatics vessels. Lymphadenitis: It refers to the inflammation of the lymph nodes. Macule: Well circumscribed flat lesion that is noticeable due to the change from the normal skin color to red may be due to inflammation or pigmented due to presence of melanin hemosiderin or other drugs. Maceration: It refers to the softening of a substance by soaking in a liquid.

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Malocclusion: It refers to any deviation from the normal occlusion of the teeth resulting in impaired functions. Marrow: It refers to the soft tissue canal and interstices of bones. Marsupialization: It refers to an operation for the evacuation of a cyst and the suturing of its walls to the edges of the wound. Metastasis: It is defined as spread of tumor by invasion in such a way that discontinuous secondary tumor mass/masses arc formed at the site of lodgment. Metaplasia: It is a reversible change in which one adult cell type is replaced by another adult cell type. Mesiodens: It refers to supernumerary tooth located at or near the midline in the incisal region of maxilla between the central incisors. Medicine: It refers to the study and treatment of diseases especially treatment without recourse to surgery or any drug used for the treatment of the disease. Metabolism: It refers to the physical and chemical changes in the tissue by which a living body is maintained and energy generated. Mitosis: It is the indirect division of cells, a typical method of cell reproduction. Mucocele: It is a term used to describe swelling caused by pooling of saliva at the site of injured minor salivary gland. Muscle: It is a contractile organ by means of which movement is produced in an animal organism. Muscle spasm: It refers to a sudden involuntary contraction of the muscle or group of muscles attended by pain and interference with function. Mucus plug: These are incompletely mineralized sialoliths. Natal teeth: These are teeth which are observed in the oral cavities at birth. Narcosis: A state of profound unconsciousness or stupor produced by drugs. Nausea: A feeling of sickness or a tendency to vomit. Necrosis: It the sum of the morphologic changes that follow cell death in a living tissue or organs. Neonatal teeth: These are teeth which erupt during the first 30 days of life. Neoplasia: It is an abnormal mass of tissue, the growth of which exceeds and is un-coordinate with that of normal tissue and persists in the same excessive manner after cessation of stimuli which evoke the changes. Neurotropic: Attracted to or having an affinity for nervous tissue. Nevus: It is circumscribed new growth of skin or oral mucosa of congenital origin, presenting as small, elevated, or flat pigmented lesion. Nodules: This lesion is present deep in the dermis and epidermis and can be moved easily over them. Nociceptive: Relating to any pain producing stimulus, or to pain receptor nerves. Nosology: It refers to the science of classification of disease.

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Numbness: Partial or total loss of sensation which may be deliberately induced as in cases of local anesthesia or it may be pathological. Nutrition: It refers to the process by which food is assimilated. Ointment: It refers to a fatty semisolid substance used as a base for local medicaments for external application. Oligodontia: It is agenesis of a few numbers of teeth. Oncology: It refers to the study of neoplasm. Operation: Anything performed, especially any procedure by a surgeon, either with instruments or by hand. Oroantral opening: The accidental opening in the floor of maxillary sinus during dental extraction is called oroantral opening. Oral submucus fibrosis: An insidious chronic disease affecting any part of the oral cavity and sometimes the pharynx, proceeded by and/or associated with vesicle formation, it is always associated with juxtraepithelial inflammatory reaction followed by fibroelastic change of the lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa and causing trismus and inability to eat. Oral medicine: It is that area of dental practice which deals with diagnosis and treatment of oral disease by nonsurgical means, which may be localized in the oral cavity or which may be oral manifestation of systemic disease and those phases of dental practice concerned with diagnosis and treatment of medically compromised patients. Organ: It refers to any separate part of the body having a specific function. Organism: It refers to any individual plant or animal or an organized body of living cells. Osteomyelitis: It is an inflammation of bone marrow that produce clinically apparent pus and secondarily affect the calcified component Or It is an infection of bone that involves all three components periosteum, cortex, and marrow Or It may be defined as an inflammatory condition of the bone that begins as an infection of medullary cavity and the Haversian system which extends to involve the periosteum of the affected area. Papillary: Describing the tumor or growth exhibiting numerous surface projection. Papules: These are solid lesions raised above the skin surface that are smaller than 1 cm in diameter. Pathogenecity: It is the ability of microbial species to produce disease. Paramolar: It is a supernumerary molar usually small and rudimentary which is situated buccally or lingually to one of maxillary molars or inter-proximally between 1st, 2nd and 3rd maxillary molars. Palpation: It refers to feeling of the affected part by hand. Pain: It refers to the distressing or unpleasant sensation transmitted by a sensory nerve usually indicative of injury or of disease. Palliation: It refers to the act of alleviating or affording relief without curing.

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Paresthesia: The term refers to perverted sensation like burning, prickling or crawling sensation of the skin. Parageusia: It refers to an unpleasant taste in the mouth. Parakeratosis: It refers to any abnormality of the stratum corneum of the epidermis, which may be associated with inflammation of the prickle cell layers causing defective formation of keratin and characterized by the persistence nuclei. Paralysis: It is the loss or impairment of muscle function or of sensation due to nerve injury or destruction of neurons. Pararhizoclasia: It is the inflammatory ulcerative destruction of the deep layers of tissue and the alveolar process about the root of a tooth. Parenteral: Descriptive of methods of drug administration other than by the alimentary canal. Parodontal: Near or next to a tooth sometimes used as synonymous with periodontal. Parrot tongue: A horny, dry tongue which cannot be protruded, seen in typhus and low fever is called parrot tongue. Pathogen: Any agent that produces or is able to produce disease. Parulis: It is mass of granulation tissue which covers the opening of a sinus. Pathogenesis: The development of disease from its inception to the appearance of characteristic symptoms or lesions. Pathognomonic: Characteristic of one specific disease or pathological condition as distinct from any others. Pathology: That branch of medicine which is concerned with the structural and functional changes caused by disease. Pedunculated: Describing the tumor or growth whose base is narrower than the widest part of lesion. Peridens: Supernumerary teeth that are erupted ectopically either buccally or lingually to the normal arch referred to as peridens. Petechiae: Purpuric lesions 1 to 2 cm in diameter. Permeation: The spreading or extension through tissues or organs, used especially of malignant tumors extending by continuous growth through the lymphatics. Pericemental abscess: A parodental abscess not arising from a diseased pulp or an extension of the periodontal pocket. Percussion: Listening to the tapping note with a finger placed on the affected part or in cases of teeth with the help of handle of the probe. Periodontitis: It is name given to periodontal disease when the superficial inflammation in the gingival tissue extends into the underlying alveolar bone and there is loss of attachment. Periodontosis: Chronic noninflammatory destruction of periodontal ligament and the associated alveolar bone. Phoenix abscess: It an acute exacerbation of a chronic or suppurative apical periodontitis. Phlegmon: Acute inflammation of the subcutaneous connective tissue. Pit: It is defined as hollow fovea or indent blind tracts lined with epithelium.

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Pilation: It is a hair like fracture found in cranial bones. Plasmapheresis: It is a method of increasing the number of blood cells in the blood count. From the blood plasma is skimmed out simply on standing and remaining concentrate is reinfused into the patient. Plaque: It is a solid raised lesion that is over 1cm in diameter. Pleomorphic: The word pleomorphic means occurring in several distinct shapes. Pleurodont: Having teeth attached to the side of a bony socket or to the side of the jaw. Plexus: A plexus of nerves or a network of blood or lymphatic vessels. Pocket: It is an abnormal space developing between the tooth root and the gums. Poison: Any substance that when absorbed into the system of a living body is liable to cause injury and to endanger life. Poikiloderma: It refers to a combination of atrophy, telangiectasia and pigmentary changes. Polylophodont: These are teeth with multi-ridged crowns. Pre-cancerous lesion: Morphologically altered tissue in which cancer is more likely to occur than its normal counterpart. Pre-cancerous condition: It is a generalized state associated with a significantly increased risk of cancer. Premedication: The administration of drugs or sedatives before treatment, to help in patient management especially with nervous patient. Prescribe: To write instruction for the preparation, composition and administration of a medicine. Prevalence: The number of cases of a disease at any given time in any given place. Priestley’s mass: A green or brown stain on the anterior teeth of the young or where reduced enamel epithelium remains over the enamel. Procheilia: It is the condition in which one lip protrudes forwards of its normal position. Prognosis: It is the prediction of the course, duration, and termination of the disease and the likelihood of its response to therapy. Prosthesis: The word prosthesis is used for a manufactured appliance used to take the place of a natural part or to correct a congenital abnormality or it may be defined as an appliance which replaces lost or congenitally missing tissue. Proteolysis: The process of digestion of proteins and its conversion by enzymes into peptones, proteoses, etc. Protuberance: The word protuberances refers to a swelling, eminence or knob of the tissue. Pseudomembrane: It refers to a false membrane, a skin like layer formed by fibrinous exudates containing leukocytes and bacteria. Pseudoepitheliomatous hyperplasia: In this conditions the rete pegs extend far downward, usually accompanied by acanthosis. The cells are normal in size, shape and chromaticity.

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Psychosomatic: Relating to the mind and the body; particularly relating to the interdependence of mental processes and bodily function. Pustule: It refers to a raised lesion containing purulent material. Purpura: It refers to reddish to purple flat lesion caused by blood extravasated from a vessel leaking into subcutaneous tissue. Pulsation: It is the rhythmic throb or beating as that of the heart. Pulse: The expansion and contraction of an artery due to increased tension of its walls following contraction of the heart and subsequent relaxation. Pus: It is a liquid usually yellowish in color formed in certain infection and composed of tissue fluid containing bacteria and leukocytes. Putrefaction: The decomposition of organic matter through the action of microorganisms, resulting in the production of various solid and liquid compounds and gases giving off a foul odor. Pyemia: Generalized septicemia caused by pyogenic microorganism in the blood stream and marked by the formation of multiple abscesses. Ranula: The term ranula is used for a mucocele occurring in the floor of mouth in association with ducts of the submandibular or sublingual glands. Radiology: It is that branch of health sciences dealing with radioactive substances and radiant energy and with the diagnosis and treatment of disease by means of both ionizing (X-rays) and non-ionizing (ultrasound) radiations. Radiolucent: Offering little resistance to X-rays in radiography; almost transparent. Rash: It refers to a temporary cutaneous eruption. Recrudescence: The return of symptoms or the recurrence of the disease after a temporary remission. Recurrence: The return of symptoms or of a disease after a period of remission. Regurgitation: The return of undigested or partially digested food from the stomach or esophagus to the mouth or of fluid or semifluid to the nose. Reticular: Relating to net or net like structure. Regeneration: It is replacement of injured tissue by parenchymal cells of the same types. Retrogenia: It refers to a condition in which chin is set back in relation to the rest of the facial skeleton. Rh hump: In the deciduous 1st molar crown a characteristic ring like defect may be seen which is called Rh hump. Rhinorrhea: It refers to any discharge of fluid from the nose. Rhizotomy: A surgical division of either a tooth root or a nerve root. Root dehiscence: It is a pathological condition in which the vestibular surface of the tooth root is exposed to the oral cavity over some or all of the apical two-thirds of its length. Rudiment: It refers to an organ or part either imperfectly developed or at an early stage of development.

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Rubber jaw: In this condition it is possible to mold the shape of the jaw with the fingers, but teeth will resume its position when the pressure is released. Satellite abscess: It is a secondary abscess arising from and situated near a primary abscess. Saburra: It refers to a foul condition of the mouth and teeth or of the stomach due to food debris. Saucerization: It is the wide and shallow depression occurring about a wound or bone cavity as in osteomyelitis. Sclerosis: It refers to hardening of vessels or part applied particularly to arteries and to proliferation of connective tissue in the nervous system as a result of degeneration. Scale: Loosened imperfectly cornified parakeratotic superficial layer of skin that is shed as fine, brawny, dirty white, yellowish keratinous dust or large pearly white flakes. Sequestra: Small pieces of necrotic bone which are avascular and which harbor microorganisms are known as sequestra. Serum: If blood is allowed to clot an amber colored liquid which remains after separation of the clot is known as serum. Septicemia: The word septicemia implies a overwhelming bacterial proliferation and release of toxins in the blood. Sessile: It describe a tumor or growth whose base is the widest part of the lesion. Shock: It is state of inadequate perfusion of all cells and tissues, which at first leads to reversible hypoxic injury, but if sufficiently protracted or grave, to irreversible cell and organ injury and sometimes to the death of the patient. Sickle cell anemia: In homozygous individuals the whole of HbA (hemoglobin A) is replaced by HbS (hemoglobin S, i.e. an abnormal hemoglobin) and this is known as sickle cell disease. Sickle cell trait: In heterozygous individuals only 50% of HbA is replaced by HbS and this is known as sickle cell trait. Sinus: It is a blind tract leading from the surface down to the tissue which is lined by granulation tissue or which may be epithelized. Sialorrhea (ptyalism): An increased salivary secretion is termed as sialorrhea or ptyalism. Sialolithiasis: It is the formation of calcific concretions within parenchyma or ductal system of major or minor salivary glands. Sinusitis: Inflammation of mucosa of paranasal sinuses is referred to as sinusitis. When maxillary sinus is involved it is called maxillary sinusitis. Sialoschesis: It is the suppression of the secretion of the salivary glands. Sign: It defined as any change in the body or its function which is perceptible to a trained observer and may indicate a specific disease. SLE (systemic lupus erythematous): It is characterized by the presence of abnormal serum antibodies and immune complexes. Slough: It refers to the necrotizing tissue that scales or peels off in ulcerative conditions.

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Spongiosis: This term is used to signify intercellular edema of the epithelium, in which intercellular bridges of the stratum spinosum become more prominent. Stagnation: It refers to the cessation of flow of any circulating fluid in the body. Sterilization: It is the process of destruction of the microbial life from an article or surface inclusive of bacterial spores. Sterile abscess: It refers to an abscess containing no microorganisms. Stenosis: It is the constriction or narrowing of an aperture canal or duct. Stimulus: It refers to any agent or impulse that excites or promotes a functional reaction. Stippled: Having a mottled or spotted appearance with light and dark patches. Stomatology: The medical speciality concerned with the mouth and its diseases sometimes used synonymously with dentistry. Striation: It is a stripe or streak or a series of stripes or streaks. Stricture: It is an abnormal contraction of any aperture or vessels. Stridor: It is a harsh whistling sound produced by the respiratory system. Superficially invasive (micro invasive) squamous cell carcinoma: A histopathological diagnosis of a routine squamous cell carcinoma, usually well differentiated, which has invaded only slightly into the underlying connective tissues. Subluxation (hypermobility): It is the unilateral or bilateral positioning of the condyle anterior to the articular eminence, with repositioning to normal to accomplish normal physiologic activity. Subscription: It is a part of a prescription containing direction for the preparation and compounding of the ingredients of a medicine. Suzanne’s gland: An oral mucous gland found in the alveolo-lingual sulcus near the midline. Symbiosis: It is the intimate association of two organism of different species. Symptoms: Any indication of the presence or course of a disease either by functional or other changes occurring in the patient. Syncope: It is a transient loss of consciousness caused by cerebral hypoxia or changes in cerebral blood flow. Syndesmosis: It is the joining of two bone surfaces by the interposition of connective tissue which forms an interosseous membrane. Syndrome: A complex of symptoms, occurring together, which characterize one disease or lesion. Talon’s cusp: It projects lingually from the cingulum area of maxillary and mandibular teeth Or It is anomalous hyperplasia of cingulum on the lingual of maxillary and mandibular incisor resulting in the formation of a supernumerary cusp.

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Taurodontism: Body of tooth is enlarge at the expense of root. It is characterized by clinical and anatomical crown of normal shape and size, an elongated body and short root with a longitudinally enlarged pulp chamber. Tablet: It is a small solid disk containing one dose of a drug. Tapir mouth: It is a condition characterized by loose thickened lips and caused by atrophy of the orbicularis oris muscle. Taste: The perception of flavor, a sensation produced by stimulation of the gustatory nerve endings in the tongue with a soluble substance. Telangiectasia: It is the dilatation of the capillaries and small arteries forming types of angiomas. Teratoma: It is true neoplasm made up of a number of different types of tissue which are not native to the area in which the tumor occurs. Thalassemia: It is an inherited impairment of hemoglobin synthesis in which there is partial or complete failure to synthesize a specific type of globin chain. Therapy: It refers to the treatment of disease. Thermocautery: It is the use of head points for cauterization. Tic: A spasmodic twitching particularly of the facial muscles; a habit spasm. Tinnitus: The term refers to a ringing noise in the ears. Toxin: It is a poisonous substance produced by animal or vegetable cells more particularly by bacteria. Trabeculae: It refers to a septum extending from the outer capsule or envelop into an organ. Trephone: These are substances prepared by leukocytes from the plasma protein which is necessary for nourishment of tissue cell. Transplantation: It is the transfer of tissue either from another donor or from one site to another. Transposition: It is the interchange in position of two adjacent teeth. Treatment: It is the means used to combat or cure a disease. Trignodent: A tooth having three cusps in the form of a triangle. Trismus: It is the inability to open the mouth because of tonic spasm of the jaw muscles. Tropics: It is that portion of the surface of the globe where the sun passes directly overhead. Tumor: It is an autonomous new growth of tissue or it is an abnormal mass of tissue the growth of which exceeds and is uncoordinated with that of normal tissue and persists in the same excessive manner even after the cessation of stimuli which evoked changes. Tubercle: It is a rounded eminence on bone. Tumefaction: It is the state of being or becoming swollen. Twining: It indicates the cleavage of tooth germ into two complete resulting in formation of supernumerary teeth that is mirror image or near image of tooth from which it has developed. Tyndallization: A method of sterilizing culture media by exposure to steam at 100 degree Celsius on three successive days for: About 30 minutes each day.

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Ulcer: Deep craters that extends through the entire thickness of the surface epithelium and involve the underlying connective tissue Or Defect in epithelium, it is a well circumscribed depressed lesion over which epidermal layer is lost. Unfavorable fracture: If the associated muscle tends to pull the fragment of the fracture, it is described an unfavorable. Uvuloptosis: It is a relaxed dropped position of palatine uvula. Vaccine: It is any material used for preventive inoculation against a specific disease. Vallate: Having a surrounding wall or rim. Varicosity: It refers to a distended vein, superficial, bluish and painless. Vasodilator: The term refers to a nerve or some external agent which cause vascular dilatation. Vesicle: These are elevated blisters containing clear fluid that are under 1 cm in diameter. Vertigo: It is a sensation of loss of equilibrium in which sufferers feel either that the world is revolving round them or that they are revolving in space. Verrucous: Describing the tumor or growth exhibiting a rough and warty surface. Virulence: It is a term applied to the properties in a particular strain of microorganism. Vicarious: Relating to a normal process occurring in an abnormal position or under abnormal conditions. Virus: A complex organic particle of submicroscopic dimensions capable of growth and reproduction only within the cells of the host organism it infects. Wasting disease of teeth: It is defined as any gradual loss of tooth substance characterized by the formation of smooth polished surfaces without ragged to the possible mechanism of this loss. Wandering teeth: It is movement of unerupted teeth for no apparent reasons (distal drift). Wandering abscess: An abscess that tracks through the tissue and finally comes to a point some distance form the original site. Weal: It is a reddish, raised and circumscribed lesion on the skin, generally caused by a blow or a bite. Working diagnosis: Following reappraisal of diagnostic data at hand including those of follow-up examination which may be seen necessary and which may provide new relevant finding and indicating result from any additional diagnostic procedure. Wound: It is any injury to the tissues or organs cause by cut, stab or tear, usually going deeper than the outer skin or integument. Wolf’s law: This law states that, the bone structure depends on the strain and stresses to which bone is subjected. Xerostomia: It is a subjective clinical condition of less than normal amount of saliva. Xenograft: It is a type of graft derived from a donor of different species.

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APPENDIX III: NORMAL VALUES OF VARIOUS LABORATORY PARAMETERS Smruti Nanda

HEMATOLOGY Red Blood Cells RBC (Male) RBC (Female) RBC (Child) White Blood Cells WBC (Male) WBC (Female) WBC (Child) Hemoglobin Hb (Male) Hb (Female) Hb (child) Hb (Newborn) Hematocrit Hct (Male) Hct (Female) Hct (Child) MCV MCH MCHC

Neutrophils Bands neutrophils Lymphocytes Monocytes Eosinophils Basophils GENERAL CHEMISTRY Amylase Bilirubin, Direct Bilirubin, Indirect Bilirubin, Total BUN Calcium (Total) Creatine (Male) Creatine (Female) Creatinine Glucose

Iron Iron binding capacity Phosphorus Potassium

4.2-5.6 M/ pL 3.8-5.1 M/ pL 3.5-5.0 M/ pL 3.8-11.0 K/mm cubed 3.8-11.0 K /mm cubed 5.0-10.0 K /mm cubed

14-18 g/dL 12-16 g /dL 10-14 g /dL 15-25 g /dL 39-54% 34-47% 30-42% 78-98 fL 27-35 pg 31-37% 50-70 % 0-6% 20-40 % 2-8% 1-5% 0-1%

50-150 U/dL 0.1-0.3 mg/dL 0.2-0.7 mg/dL 0.3-1.0 mg/dL 8-18 mg/dL 8-11 mg /dL 0.2-0.6 mg/dL 0.6-1.0 mg/dL 0.6-1.5 mg/dL 70-110 mg/dL (diuresis greater than or equal to 180 mg/dL ) 50-150 pg/dL 250-370 pg/dL 2.2-4.8 mg/dL 3.5-5.5 mEq/L

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APPENDIX III: NORMAL VALUES OF VARIOUS LABORATORY PARAMETERS Smruti Nanda 951 HEMATOLOGY Red Blood Cells RBC (Male) RBC (Female) RBC (Child) White Blood Cells WBC (Male) WBC (Female) WBC (Child) Hemoglobin Hb (Male) Hb (Female) Hb (child) Hb (Newborn) Hematocrit Hct (Male) Hct (Female) Hct (Child) MCV MCH MCHC Neutrophils Bands neutrophils Lymphocytes Monocytes Eosinophils Basophils GENERAL CHEMISTRY Amylase Bilirubin, Direct Bilirubin, Indirect Bilirubin, Total BUN Calcium (Total) Creatine (Male) Creatine (Female) Creatinine Glucose

Iron Iron binding capacity Phosphorus Potassium

4.2–5.6 M/µL 3.8–5.1 M/µL 3.5–5.0 M/µL 3.8–11.0 K/mm cubed 3.8–11.0 K/mm cubed 5.0–10.0 K/mm cubed 14–18 g/dL 12–16 g/dL 10–14 g/dL 15–25 g/dL 39–54% 34–47% 30–42% 78–98 fL 27–35 pg 31–37% 50–70% 0–6% 20–40% 2–8% 1–5% 0–1% 50–150 U/dL 0.1–0.3 mg/dL 0.2–0.7 mg/dL 0.3–1.0 mg/dL 8–18 mg/dL 8–11 mg/dL 0.2–0.6 mg/dL 0.6–1.0 mg/dL 0.6–1.5 mg/dL 70–110 mg/dL (diuresis greater than or equal to 180 mg/dL) 50–150 µg/dL 250–370 µg/dL 2.2–4.8 mg/dL 3.5–5.5 mEq/L

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Protein (Total) SGPT Sodium T3 Thyroglobulin Thyroxine (T4) total Urea nitrogen Uric acid (Male) Uric acid (Female) LIPID PANEL (ADULT) Cholesterol (Total) Cholesterol (HDL) Cholesterol (LDL) Triglycerides (Male) Triglycerides (Female) URINE Color Specific Gravity pH Na K Cl Protein Osmolality COAGULATION APTT Platelets Plasminogen PT PTT FSP Fibrinogen Bleeding time Thrombin time

5.5–8 gm/dL 8–32 U/L 135–148 mEq/L 0.8–1.1 µg/dL Less than 55 ng/mL 5–13 µg/dL 8–25 mg/dL 3.5–7.7 mg/dL 6.6 mg/dL Less than 200 mg/dL desirable 30–75 mg/dL Less than 130 mg/dL desirable Greater than 40–170 mg/dL Greater than 35–135 mg/dL Straw 1.003–1.040 4.6–8.0 10–40 mEq/L Less than 8 mEq/L Less than 8 mEq/L 1–15 mg/dL 80–1300 mOsm/L 21–35 seconds 150,000–450,000/mm3 62–130% 10–14 seconds 32–45 seconds Less than 10 µg/dL 200–400 mg/dL 2–6 minutes 9–13.5 seconds

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APPENDIX IV: CLASSIFICATION SYSTEMS OF ODONTOGENIC TUMOR Satish Chhugani

i . Broca ' s Classification (1869) ii . Malassez Classification (1885) hi . Bland-Sutton Classification (1888) lv . Gabell , James, and Payne Classification (1914 ) v . Thoma and Goldman Classification (1946) vi . Pmdborg and Clausen Classification (1958) vii . WHO Classification (1971) viii . WHO Classification (1992) IX . WHO Classification (2002) [ Revised Version] x . WHO Classification (2005) Broca’s Classification [1869 ] In 1869, the French Physician and Professor of pathology and clinical surgery , Pierre Paul Broca proposed a classification of tumor originating from dental tissue . • Coined the term “ Odontome ” . • Classified the lesions according to the stage of development of the tooth when abnormal growth commenced. •

Malassez Classification [1885] • Louis Charles Malassez made minor modifications to Broca’s classification with no major changes in the classification. • Introduced “ Epithelial Rests of Malassez ” . Bland-Sutton Classification [1888 ] • Classification based upon the type of the particular cells of the tooth germ from which the tumor arose . • Included odontogenic cyst and fibrous osteogenic tumors in the classification . • Subdivided the odontome into those arising from : a . Aberrations of the enamel organ . b . Aberrations of the follicle, papillae . c . Aberrations of the whole tooth germ . d . Anomalous odontomes . Gabell , Janies and Payne Classification [1914] • Modified Bland-Sutton classification . • Used the term “ odontome ” for all odontogenic tumors . • Included radicular cyst and dentigerous cyst as odontome . • Recognized 3 mam groups of odontomes : 1. Epithelial odontomes: Included neoplasm known at the time as a ‘ multilocular cyst’ as well as ‘non- neoplastic cysts’ . 2 . Composite odontomes: Lesions derived from epithelium and connective tissue and formed either irregular calcified masses or recognizable tooth - like structures . 3 . Connective tissue odontome: Fibrous and other connective tissue tumors thought to arise from dental mesenchyme only .

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dontogenic cysts introduced by Bland-Sutton were excluded. O Enamel Pearls being developmental malformations were considered tumors under the name of “Enamelomas”. Classification was amplified by American Academy of Oral Pathology, and ran as follows: I. Epithelial tumors: – Adamantoblastoma – Enameloma II. Mesenchymal tumors: – Odontogenic fibroma – Dentinoma – Cementoma III. Mixed tumors: (Odontomas) – Soft odontoma – Soft and calcified odontoma – Completely formed odontoma with enamel, dentin, pulp, cementum, periodontal mem brane - Compound (many small teeth) - Complex (irregular tooth structure)

Pindborg and Clausen Classification [1958] The classification was based on the characteristic reciprocal epithelial mesenchymal interaction occurring during normal tooth development. Tumors were classified into two main groups: Epithelial tumors: a. Epithelial tumors with no inductive changes in the connective tissue: • Ameloblastoma • Calcifying epithelial odontogenic tumor b. Epithelial tumors that do show inductive changes in the mesenchyme: • Ameloblastic fibroma • Dentinoma • Odontomas Mesodermal tumors: • Odontogenic fibroma • Odontogenic myxoma • Cementifying fibroma

Appendices WHO (World Health Organization) CLASSIFICATION [ 1971] In 1971, the first authoritative and useful guide to the classification of odontogenic tumors was published by WHO, authored by Pindborg and Kramer. Malignant Benign Odontogenic carcinomas: • Ameloblastoma • Malignant Ameloblastoma • Calcifying epithelial odontogenic tumor • Primary intraosseous carcinoma • Ameloblastic fibroma • Other carcinomas arising from odontogenic epithelium, • Adenomatoid odontogenic tumor including those arising from odontogenic cysts. • Calcifying odontogenic cyst Odontogenic sarcomas: • Dentinoma • Ameloblastic fibrosarcoma • Ameloblastic fibro-odontoma • Ameloblastic odontosarcoma • Complex odontoma • Fibroma (odontogenic fibroma) • Myxoma (myxofibroma) • Cementomas: – Benign cementoblastoma – Cementifying fibroma – Periapical cemental dysplasia – Gigantiform cementoma – Melanotic neuroectodermal tumor of infancy

WHO CLASSIFICATION [1992] In 1992, a second edition entitled: “Histological Typing of Odontogenic Tumors” appeared. The authors of the first edition were joined by a third author, Professor Mervyn Shear in this edition. Benign Odontogenic epithelium without odontogenic ectomesenchyme • Ameloblastoma • Squamous odontogenic tumor • Calcifying epithelial odontogenic tumor • Clear cell odontogenic tumor

Malignant Odontogenic carcinomas: • Malignant ameloblastoma • Primary intraosseous carcinoma • Malignant variants of other odontogenic epithelial tumors • Malignant changes in odontogenic cysts

Odontogenic epithelium with odontogenic ectomesenchyme, with or without dental hard tissue formation • Ameloblastic fibroma • Ameloblastic fibrodentinoma and ameloblastic fibro- odontoma. • Odontoameloblastoma • Adenomatoid odontogenic tumor • Calcifying odontogenic cyst • Complex odontoma • Compound odontoma

Odontogenic sarcomas: • Ameloblastic fibrosarcoma • Ameloblastic fibrodentinosarcoma and ameloblastic fibro- odontosarcoma Odontogenic carcinosarcoma

Odontogenic ectomesenchyme with or without included odontogenic epithelium • Odontogenic fibroma • Myxoma (odontogenic myxoma, myxofibroma) • Benign cementoblastoma

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Textbook of Oral Pathology WHO CLASSIFICATION [2002] (Revised Version By Philipsen and Reichart) Revision and updating of the WHO classification was done by Philipsen and Reichart in 2002.

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Benign Odontogenic epithelium with mature, fibrous stroma; odontogenic ectomesenchyme not present • Ameloblastomas – Intraosseous (Infiltrative) – Extraosseous (Peripheral) – Desmoplastic – Unicystic • Squamous odontogenic tumor • Calcifying epithelial odontogenic tumor • Adenomatoid odontogenic tumor. Odontogenic epithelium with odontogenic ectomesenchyme, with or without dental hard tissue formation • Ameloblastic fibroma and fibrodentinoma (neoplastic) • Ameloblastic fibrodentinoma (non-neoplastic) • Ameloblastic fibro-odontoma • Complex odontoma • Compound odontoma • Odontoameloblastoma • Calcifying ghost cell odontogenic tumor Mesenchyme and/or odontogenic ectomesenchyme with or without included odontogenic epithelium • Odontogenic fibroma (simple) • Odontogenic fibroma (WHO-type) • Odontogenic myxoma or myxofibroma • Benign cementoblastoma

Malignant Odontogenic carcinomas: • Malignant (metastasizing) ameloblastoma • Ameloblastic carcinoma: – Primary – Carcinoma in intraosseous ameloblastoma (dedifferentiated) – Carcinoma in peripheral ameloblastoma • Primary intraosseous squamous cell carcinoma: – Solid – Cystogenic: - Non-keratinizing cyst - Odontogenic keratocyst • Calcifying ghost cell odontogenic carcinoma (malignant epithelial odontogenic ghost cell tumor) • Clear cell odontogenic carcinoma Odontogenic sarcomas : • Ameloblastic fibrosarcoma • Ameloblastic fibrodentino- and fibro-odontosarcoma • Odontogenic carcinosarcoma

Appendices WHO CLASSIFICATION [2005] Classification was approved at the Editorial and Consensus Conference held in Lyon, France (WHO/ IARC), in July 2003 in conjunction with the preparation of the new WHO Blue Book Volume “Pathology and Genetics of Tumors of the Head and Neck”. This new WHO Blue Book encompasses both histopathological and genetic criteria for tumor classification. Malignant Benign Odontogenic epithelium with mature, fibrous stroma; odontogenic Odontogenic carcinomas: • Metastasizing , malignant ameloblastoma ectomesenchyme not present • Ameloblastic carcinoma: • Ameloblastomas: – primary – solid/multicystic – secondary (dedifferentiated), intraosseous – extraosseous/peripheral – secondary (dedifferentiated), extraosseous – desmoplastic • Primary intraosseous squamous cell carcinoma (PIOSCC): – unicystic – PIOSCC solid type • Squamous odontogenic tumor – PIOSCC derived from odontogenic cysts • Adenomatoid odontogenic tumor – PIOSCC derived from keratinizing cystic odontogenic • Calcifying epithelial odontogenic tumor tumor • Keratinizing cystic odontogenic tumor • Clear cell odontogenic carcinoma Odontogenic epithelium with odontogenic ectomesenchyme, • Ghost cell odontogenic carcinoma with or without dental hard tissue formation Odontogenic sarcomas: • Ameloblastic fibroma • Ameloblastic fibrosarcoma • Ameloblastic fibrodentinoma • Ameloblastic fibrodentino and fibro-odontosarcoma • Ameloblastic fibro-odontoma • Complex odontoma • Compound odontoma • Odontoameloblastoma • Calcifying cystic odontogenic tumor • Dentinogenic ghost cell tumor Mesenchyme and/or odontogenic ectomesenchyme with or without included odontogenic epithelium • Odontogenic fibroma (epithelium–poor and epithelium–rich types) • Odontogenic myxoma or myxofibroma • Cementoblastoma

CLASSIFICATION OF ODONTOGENIC TUMOR Benign A] Epithelial With inductive changes in the connective tissue AOT Ameloblastofibroma Dentinoma Calcifying odontogenic tumor Odonto-ameloblastoma Odontoma Without inductive changes in the connective tissue ameloblastoma CEOT Epithelial atypia Ameloblastic changes in odontogenic cyst

B] Mesenchymal Odontogenic myxoma Odontogenic fibroma Cementoma Periapical cemental dysplasia Cementifying fibroma Benign cementoblastoma Malignant A] Epithelial With inductive changes in connective tissue Ameloblastic fibrosarcoma Ameloblastic odontosarcoma Without inductive changes in connective tissue Malignant ameloblastoma Primary intraosseous carcinoma Malignant changes in odontogenic cyst

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Textbook of Oral Pathology

NON-ODONTOGENIC NEOPLASMS OF THE JAWS 958

Benign • Ossifying fibroma • Fibrous dysplasia • Osteoblastoma • Osteoid osteoma • Chondroma • Myxoma • Chondroblastoma • Chondromyxoid fibroma • Osteoma • Osteoid osteoma • Central giant cell granuloma • Giant cell tumor • Hemangioma of bone • Idiopathic histiocytes (Langerhans cell disease) • Tori and exostosis • Coronoid hyperplasia • Central Schwannoma

Malignant • Osteosarcoma • Chondrosarcoma • Mesenchymal chondrosarcoma • Ewing sarcoma • Burkitt lymphoma • Multiple myeloma • Solitary plasmacytoma of bone • Metastatic carcinoma • Neurogenic sarcoma • Kaposi sarcoma • Malignant hemangioendothelioma • Primary lymphoma of bone

CLASSIFICATION OF TUMOR Tissue of origin Squamous epithelium Transitional epithelial Basal cell layer Glandular epithelium Hepatocyte Neuroectodermal MesenAdipose tissue chymal Adult fibrous tissue Embryonic fibrous tissue Cartilage Bone Synovium Skeletal muscle Smooth muscle Mesothelium Blood vessels Lymph vessels Glomus cell Meninges Hemopoietic cell Lymphoid tissue Nerve sheath Nerve cell Mixed Salivary gland Tumor of more than Totipotent cells in gonads or in one germ cell layer embryonal rest Epithelial

Benign Squamous cell papilloma Transitional cell papilloma --------Adenoma Liver cell adenoma Nevus Lipoma Fibroma Myxoma Chondroma Osteoma Benign synovioma Rhabdomyoma Leiomyoma -----------Hemangioma Lymphangioma Glomus tumor Meningioma ---------------------Neurilemmoma Ganglioneuroma Pleomorphic adenoma Mature teratoma

Malignant Squamous cell carcinoma Transitional cell carcinoma Basal cell carcinoma Adenocarcinoma Hepatocellular carcinoma Melanoma Liposarcoma Fibrosarcoma Myxomsarcoma Chondrosarcoma Osteosarcoma Synovial sarcoma Rhabdomyosarcoma Leiomyosarcoma Mesothelioma Angiosarcoma Lymphangiosarcoma --------------Invasive meningioma Leukemia Malignant lymphoma Neurogenic sarcoma Neuroblastoma Malignant salivary gland tumor Immature teratoma

Appendices

PRECANCEROUS LESION AND CONDITION Precancerous lesion • Leukoplakia • Erythroplakia • Palatal lesion associated with reverse smoking • Verrucous hyperplasia • Carcinoma in situ

Precancerous condition • Oral submucous fibrosis • Sideropenic anemia • Erosive lichen planus • Discoid lupus erythematosus • Dyskeratosis congenita

Histological Classification of Cancer and precancers of the Oral Mucosa (histological typing of cancer and precancer (WHO 1997) Precancerous lesions (clinical classification) Carcinomas • Leukoplakia • Squamous cell carcinoma • Erythroplakia • Verrucous carcinoma • Palatal keratosis associated with reverse smoking. • Basaloid squamous cell carcinoma • Adenoid squamous cell carcinoma Precancerous lesions (histological classification) • Spindle cell carcinoma • Squamous epithelial dysplasia • Adenosquamous carcinoma • Squamous cell carcinoma in situ • Undifferentiated carcinoma. • Solar keratosis Benign lesions capable of microscopically resembling oral Benign lesions capable of resembling oral precancerous lesions squamous cell carcinoma and oral verrucous carcinoma • White lesions resembling leukoplakia • Papillary hyperplasia • Red lesions resembling erythroplakia • Granular cell tumor • Focal epithelial hyperplasia • Discoid lupus erythematosus • Reactive and regenerative atypia. • Median rhomboid glossitis Precancerous conditions • Keratoacanthoma • Sideropenic dysphagia • Necrotizing sialometaplasia • Lichen planus • Juxtra oral organ of chievitz • Oral submucus fibrosis • Chronic hyperplastic candidiasis • Syphilis • Verruciform xanthoma • Discoid lupus erythematosus • Verruca vulgaris • Xeroderma pigmentosum • Condyloma acuminata. • Epidermolysis bullosa. WHO classification of malignant tumor of oral cavity Malignant epithelial tumor Squamous cell carcinoma Verrucous carcinoma Basaloid squamous cell carcinoma Papillary squamous cell carcinoma Spindle cell carcinoma Acantholytic squamous cell carcinoma Adenosquamous carcinoma Carcinoma cuniculatum Lymphoepithelial carcinoma Epithelial precursor lesions Soft tissue tumors Kaposi sarcoma Lymphangioma Ectomesenchymal chondromyxoid tumor Focal oral mucinosis Congenital granular cell epulis

Hematolymphoid tumors Diffuse large B-cell lymphoma (DLBCL) Mantle cell lymphoma Follicular lymphoma Extranodal marginal zone B-cell lymphoma of MALT type Burkitt lymphoma T-cell lymphoma (including anaplastic large cell lymphoma) Extramedullary plasmacytoma Langerhans cell histiocytosis Extramedullary myeloid sarcoma Follicular dendritic cell sarcoma/tumor Mucosal malignant melanoma Secondary tumors

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960

Epithelial • Squamous cell carcinoma • Metastatic carcinoma • Basal cell carcinoma • Transitional cell carcinoma • Malignant melanoma • Verrucous carcinoma • Spindle cell carcinoma • Primary intra-alveolar carcinoma • Intraepidermoid carcinoma • Adenoid squamous cell carcinoma Fibrous connective tissue • Fibrosarcoma • Malignant fibrous histiocytomas Adipose tissue • Liposarcoma Cartilage • Chondrosarcoma Bone • Osteosarcoma • Osteochondrosarcoma • Ewing sarcoma Vascular • Hemangioendothelioma • Hemangiopericytoma • Angiosarcoma

Neural tissue • Neurosarcoma • Neurofibrosarcoma • Neuroblastoma • Ganglioneuroma Muscle • Leiomyosarcoma • Rhabdomyosarcoma • Malignant granular cell myoblastoma Lymphoid tissue • Hodgkin’s lymphoma • Non-Hodgkin’s lymphoma • Primary reticular cell sarcoma • Burkitt’s lymphoma • Leukemia Myeloma • Multiple myeloma • Plasmacytoma Tumor of salivary gland • Mucoepidermoid carcinoma • Adeno-cystic carcinoma • Adeno-carcinoma • Acinic cell carcinoma • Malignant changes in pleomorphic adenoma

Classifications of cyst By Robinson (1945) From odontogenic tissues • Periodontal cyst – Radicular or dental root apex type – Lateral type – Residual type

– Dentigerous cyst – Primordial cyst From non-dental tissues • Median cyst • Incisive canal cyst • Globulomaxillary cyst

By who Developmental Odontogenic cysts Primordial Gingival cyst of infants Eruption cyst Dentigerous cyst (follicular) Gingival cyst of adults Lateral periodontal cyst Glandular odontogenic cyst , sialo-odontogenic cyst

Non-odontogenic Nasopalatine duct (incisive canal) cyst Globulomaxillary cyst Nasolabial cyst Inflammatory cysts Radicular Apical and lateral Residual Paradental (inflammatory collateral, mandibular infected buccal cyst)

Appendices By Gorlin (1964) Odontogenic cysts • Dentigerous cyst • Eruption cyst • Gingival cyst of newborn infants • Lateral periodontal and gingival cyst • Keratinizing and calcifying cyst • Radicular cyst • Primordial cyst • Multiple cysts of jaws and multiple cutaneous nevoid basal cell carcinoma and skeletal anomalies Non-odontogenic and fissural cysts • Globulomaxillary cyst (premaxilla maxillary cyst) • Nasoalveolar (Nasolabial Klestadt’s) cyst • Nasopalatine (median anterior maxillary) cyst

• Median mandibular cyst • Anterior lingual cyst • Dermoid and epidermoid cyst • Palatal cyst of newborn infants Cysts of neck and oral floor and salivary gland • Thyroglossal duct cyst • Lymphoepithelial (bronchial cleft) cyst • Oral cysts with gastric or intestinal epithelium • Salivary gland cyst • Mucocele and ranula Pseudo-cyst • Aneurysmal bone cyst • Static (developmental latent) bone cyst • Traumatic (hemorrhagic solitary) bone cyst

DEVELOPMENTAL DISTURBANCES OF ORAL AND PARAORAL STRUCTURES Developmental disturbances of jaws • Agnathia • Micrognathia • Macrognathia • Facial hemihypertrophy • Facial hemiatrophy • Abnormalities of dental arch relations Developmental disturbances of lips and palate • Congenital lips and commissural pits and fistula • Double lip • Cleft lip and palate • Cheilitis glandularis • Cheilitis granulomatosis • Labial and oral melanotic macule Developmental disturbances of the tongue • Microglossia • Macroglossia • Ankyloglossia • Cleft tongue • Fissured tongue • Medial rhomboidal glossitis • Benign migratory glossitis • Hairy tongue • Lingual varices • Lingual thyroid nodule

Developmental disturbances of oral mucosa • Fordyce’s granules • Focal epithelial hyperplasia (Heck’s disease) Developmental disturbances of gingiva • Fibromatosis gingivae • Retrocuspid papilla Developmental disturbances of oral lymphoid tissue • Reactive lymphoid aggregates • Lymphoid hamartoma • Angiolymphoid hyperplasia • Lymphoepithelial cyst Developmental disturbances of salivary glands • Aplasia • Xerostomia • Hyperplasia of palatal gland • Atresia • Aberrancy • Developmental mandibular salivary depression Fissural (inclusion, developmental) cyst of oral region • Median anterior maximum cyst • Median palatal cyst • Nasoalveolar cyst • Palatal cyst of the neonate • Thyroglossal tract cyst • Benign cervical lymphoepithelial cyst • Dermoid and epidermoid cyst

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ABNORMALITIES OF TEETH 962

Alteration in size • Microdontia • Macrodontia Alteration in shape • Germination • Fusion • Dilacerations • Dens in dente • Dens evaginatus • Taurodontism • Concrescence • Supernumerary roots • Enamel pearls • Talon cusp • Attrition, abrasion, erosion Alteration in number • Anodontia (total or partial) • Supernumerary teeth • Predeciduous dentition • Postpermanent dentition Defects of enamel • Environmental defects of enamel • Amelogenesis imperfecta

Defect of enamel • Dentinogenesis imperfecta • Dentin dysplasia • Dentine hypocalcification Defect of enamel and dentin • Regional odontodysplasia Abnormalities of dental pulp • Pulp calcification • Internal resorption • External resorption Alteration in color • Exogenous stains • Endogenous stains Disturbances of growth (eruption) of teeth • Premature eruption • Delayed eruption • Multiple unerupted teeth • Embedded and impacted teeth • Ankylosed deciduous teeth

CLASSIFICATION OF CANDIDIASIS Candidiasis of nails and skin • Candidal onychia • Candidal paronychia Candidiasis confined to skin • Interdigital candidiasis • Intertriginous candidiasis • Moniliids Candidiasis confined to mucosae Oral mucosa • Acute oral candidiasis – Acute pseudomembranous candidiasis (thrush) – Acute atrophic candidiasis (antibiotics sore mouth) • Chronic oral candidiasis – Chronic atrophic candidiasis (denture sore mouth) – Chronic hyperplastic candidiasis Gastrointestinal mucosa • Pharyngeal candidiasis • Esophageal candidiasis • Intestinal candidiasis Respiratory mucosa • Bronchial candidiasis Genitourinary mucosae • Candidal vulvovaginitis

Mucocutaneous candidiasis Confined to mucocutaneous surface • In condition with major immunologic defect – Swiss-type agammaglobulinemia – Hereditary thymic dysplasia – DiGeorge syndrome – AIDS • In condition with minor immunological or other systemic defect • Chronic mucocutaneous candidiasis (CMC) syndromes – Familial mucocutaneous candidiasis – Candidiasis endocrinopathy syndrome – Localized chronic mucocutaneous candidiasis – Diffuse chronic mucocutaneous candidiasis – Chronic mucocutaneous candidiasis in association with thymoma Confined to mucocutaneous junctions • Candidal angular cheilitis • Perianal candidiasis Systemic candidiasis • Candidal endocarditis • Candidal septicemia • Candidal meningitis

Appendices

CLASSIFICATION OF SALIVARY GLAND DISORDERS Developmental disorders • Aberrancy • Aplasia and hypoplasia • Hyperplasia • Atresia • Accessory ducts • Diverticuli • Congenital fistula Functional disorders • Sialorrhea • Xerostomia • Allergic • Associated with malnutrition and alcoholism Infection • Viral infection • Bacterial infection • Mycotic infection Autoimmune disorders • Sjogren’s syndrome • Mickulicz’s disease Obstructive disorders • Sialolithiasis • Mucus plug • Stricture and stenosis • Foreign bodies • Extra-ductal causes

Cyst • Mucocele • Ranula Asymptomatic enlargement • Sialosis • Uveoparotid fever • Recurrent non-specific parotitis Neoplasms Benign but seldom recurrent • Warthin’s tumor • Oncocytoma • Monomorphic salivary adenomas Benign but often recurrent • Pleomorphic adenoma • Mucoepidermoid tumor (low grade) • Acinic cell tumor (some) Malignant • Carcinoma in pleomorphic adenoma • Adenoid cystic carcinoma • Mucoepidermoid tumor (high grade) • Acinic cell tumor (some) • Squamous carcinoma • Adenocarcinoma • Undifferentiated carcinoma

SOFT TISSUE TUMORS OF MAJOR SALIVARY GLAND AND PARAGLANDULAR TISSUES Vascular • Primary hemangioma of parotic gland • Lymphangioma • Arteriovenous fistula • Angiosarcoma Lymphoreticular • Lymphoma • Atypical lymphoreticular hyperplasia • Histiocytosis • Lymphoepithelial lesion • Benign reactive hyperplasia Smooth muscle • Leomyoma • Leiomyosarcoma

Skeletal muscle • Rhabdomyosarcoma • Rhabdomyoma • Infantile rhabdomyoma • Massetric hypertrophy Neurogenous • Neurofibroma • Neurofibrosarcoma • Neurilemmoma • Traumatic neuroma • Neuroepithelial sarcoma • Granular cell tumor • Meningoma Fibroblastic and histiocytic • Fibrous scar or Keloid • Fibrosarcoma • Fibromatosis • Histiocytoma

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Textbook of Oral Pathology

OLD WHO CLASSIFICATION OF SALIVARY GLAND TUMOR (THACKERAY AND SOBIN 1972) 964

1. Epithelial tumors A. Adenoma • Pleomorphic adenoma • Monomorphic adenoma • Adenolymphoma (Warthin’s tumor) • Oxyphilic adenoma (Oncocytoma) • Other types – Basal cell adenoma – Canalicular adenoma • Mucoepidermoid tumor • Acinic cell tumor B. Carcinoma • Adenoid cystic carcinoma





• • • •

Adenocarcinoma Epidermoid carcinoma Undifferentiated carcinoma Carcinoma in pleomorphic adenoma (Malignant pleomorphic adenoma) 2. Nonepithelial tumors Unclassified lesions Allied conditions • Benign lymphoepithelial lesion • Sialosis • Oncocytosis

FIBRO-OSSEOUS LESION OF JAW BONE Fibro-osseous lesions of medullary bone origin • Fibrous dysplasia • Fibro-osteoma • Cherubism • Juvenile ossifying fibroma • Giant cell tumor • Aneurysmal bone cyst • Jaw lesions in hyperparathyroidism • Paget’s disease

Fibro-osseous lesions of periodontal origin • Periapical cemental dysplasia • Florid osseous dysplasia • Cemento-ossifying fibroma • Cementifying fibroma • Ossifying fibroma

Appendices

CLASSIFICATION OF TONGUE DISORDERS Congenital and developmental disorders • Aglossia and microglossia • Macroglossia • Ankyloglossia • Cleft tongue • Ankyloglossum superius syndrome • Lingual varices • Lingual thyroid nodule • Variations in tongue movement • Patent thyroglossal duct cyst • Tongue thrusting • Lingual polyp • Reactive lymphoid aggregate • Lingual cyst Local tongue disorders • Fissured tongue • Median rhomboidal glossitis • Benign migratory glossitis • Hairy tongue • Crenated tongue • Foliate papillitis • Leukokeratosis nicotine glossi Depapillation of tongue Local disease • Eosinophilic granuloma • Traumatic injuries • Lesions due to automutilation • Allergic stomatitis • Facial hemiatrophy • Cranial arteritis • Chronic candidiasis Systemic disease • Iron deficiency anemia • Plummer Vinson syndrome • Pernicious anemia • Niacin deficiency • Folic acid deficiency • Peripheral vascular disease

• Dermatomyositis • Diabetes • Syphilis • Zoster infection • Tuberculosis Neurological disease • Glossodynia • Dyskinesia • Paralysis • Oropharyngeal dysphagia Cyst • Anterior median lingual cyst • Bronchogenic cyst • Epidermoid and dermoid cyst • Gastric mucosal cyst • Parasitic cyst • Thyroglossal duct cyst Benign tumor • Fibroma • Glomus tumor • Granular cell tumor • Leiomyoma • Rhabdomyoma • Plasmacytoma Premalignant lesion and conditions • Leukoplakia • Lichen planus • Oral submucus fibrosis Malignant tumor • Squamous cell carcinoma • Malignant lymphoma • Malignant melanoma • Metastatic tumor • Sarcoma Miscellaneous • Pigmentation of tongue • Phlebectasia

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Textbook of Oral Pathology

WHITE LESION OF ORAL CAVITY 966

Scrapable lesion

Non-scrapable lesion

White coated tongue Pseudomembranous candidiasis Morsicatio Thermal burn Sloughing traumatic lesion Toothpaste or mouth wash reaction Chemical burn Secondary syphilis Diphtheria

Linea alba Leukoedema Leukoplakia Tobacco pouch keratosis Actinic cheilosis Lichen planus Nictoine stomatitis Hairy leukoplakia Hyperplastic candidiasis Lupus erythematous Skin graft Submucous fibrosis White sponge nevus Hereditary benign intraepithelial dyskeratosis Pachyonychia congenita Tertiary syphilis Uremic stomatitis

RED AND WHITE LESION Erythema migrans Candidiasis Lichen planus Burns Actinic cheilosis

Nicotine stomatitis Erythroleukoplakia Cinnamon reaction Lupus erythematosus Scarlet fever Verruciform xanthoma

RED LESION OF ORAL CAVITY Pharyngitis Traumatic erythema Denture stomatitis Erythematous candidiasis Erythema migrans Angular cheilitis

Thermal burns Erythroplakia Anemia Hemangioma Lupus erythematous Scarlet fever Plasma cell gingivitis Radiation mucositis

Appendices

BLUE/PURPLE/BROWN/GRAY/BLACK/YELLOW LESION Blue/purple lesion Varicosities Submucosal hemorrhage Amalgam tattoo Mucocele Eruption cyst Salivary duct cyst Hemangioma Ranula Kaposi’s sarcoma Nasopalatine duct cyst Salivary gland tumor Gingival cyst of adults Blue nevus Malignant melanoma

Brown/gray/black lesion Racial pigmentation Amalgam tattoo Black/brown hairy tongue Melanotic macule Smoker’s melanosis Non-amalgam tattoo Melanocytic nevus Malignant melanoma Oral melanoacanthoma Drug ingestion Peutz-Jeghers syndrome Addison’s disease Neurofibromatosis McCune-Albright syndrome Heavy metal poisoning Melanotic ectodermal tumor of infancy

Yellow lesion Fordyce granules Superficial abscess Accessory lymphoid aggregates Lymphoepithelial cyst Lipoma Jaundice Verruciform xanthoma Pyostomatitis vegetans

VESICULOBULLOUS AND ULCERATIVE LESION Acute (short duration) Traumatic ulcer Apthous stomatitis Recurrent herpes labialis Primary herpetic gingivostomamitis Necrotizing ulcerative gingivitis Mucosal burns Recurrent intraoral herpes simplex Allergic reaction Erythema multiforme Herpangina Varicella Herpes zoster Hand foot and mouth disease Necrotizing sialometaplasia Anesthetic necrosis Primary syphilis Behçet syndrome

Chronic (long duration) Erosive lichen planus Squamous cell carcinoma Mucous membrane pemphigoid Traumatic granuloma Lupus erythematous Pemphigus vulgaris Deep fungal infection Tuberculosis Sarcoidosis Epidermolysis bullosa Pyostomatitis vegetans Wegner’s granulomatosis Midline lethal granuloma Noma Tertiary syphilis

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Textbook of Oral Pathology

PAPILLARY LESION OF ORAL CAVITY 968

Giant cell fibroma Verruciform xanthoma Verrucous carcinoma Condyloma acuminatum Multifocal epithelial hyperplasia Darier’s disease Acanthosis nigricans

Hairy tongue Papilloma Inflammatory papillary hyperplasia Verruca vulgaris Leukoplakia (some variant) Squamous cell carcinoma Hairy leukoplakia

CLASSIFICATION OF GIANT CELL Physiological • Osteoblast • Trophoblast • Megakaryocyte

Inflammatory condition • Foreign body type • Langhans type • Aschoff’s cells • Touton type

Neoplastic condition • Osteoclastic • Reed Sternberg • Atypical • Giant cell fibroblast

CLASSIFICATION OF GIANT CELL LESION Physiological • Root resorption of deciduous teeth Traumatic • Traumatic granuloma • Peripheral and central giant cell granuloma • Epulis fissuratum • Pyogenic granuloma • Chronic occlusal trauma • Internal resorption causing periapical granuloma • Root resorption from pressure trauma • Healing of sockets after extraction

Infection • Syphilis • Yaws • Bezel • Tuberculosis • Leprosy • Sarcoidosis • Plasmocytosis • Blastomycosis • Histoplasmosis • Candidiasis • Actinomycosis • Aspergillosis • Sporotrichosis • Mucormycosis • Criptococosis • Rhinosporidiosis • Coccidiomycosis

Appendices

CLASSIFICATION OF GIANT CELL LESIONS BASED ON CAUSES OR LOCATION Physiological conditions • Resorption of deciduous teeth • Healing of extraction teeth • Orthodontic tooth movement • Syncytiotrophoblasts of placenta Non-neoplastic growth • Soft tissue – PGCG – Giant cell fibroma – Epulis fissuratum – Traumatic granuloma • Bone – CGCG – Browns tumor – Fibrous dysplasia – Pagets disease – Osteomalacia – Cherubism Cysts and neoplasms • Cysts – ABC – CEOT – Solitary bone neoplasm • Benign neoplasms – Giant cell tumor – Osteoid osteoma – Osteoblastoma – Central hemangioma • Malignant neoplasms – Osteosarcoma – Hodgkin’s lymphoma – Reticular cell sarcoma – Lymphosarcoma – Oral squamous cell carcinoma

Infections • Bacterial – Tuberculosis – Syphilis – Leprosy – Actinomycosis – Osteomyelitis • Viral – Herpes simplex – Herpes zoster – Mumps – CMV – Measles • Fungal – Histoplasmosis – Candidiasis – Blastomycosis – Coccidioidomycosis – Rhinosporidosis • Protozoal – Leishmoniasis • Chlamydial – Lymphogranuloma venerum Non-infective granuloma • Midline lethal granuloma • Wegener’s granulomatosis • Plasma cell granuloma • Sarcoidosis Periodontal conditions • Periodontitis • Periapical cyst • Periapical granuloma • Chronic periapical abscess Miscellaneous • Internal resorption • External resorption • Massive osteolysis • Spindle or epithelial cell nevus

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Textbook of Oral Pathology

PRIMARY AND SECONDARY SWELLINGS OF HARD AND SOFT PALATE INCLUDING GINGIVAE 970

Traumatic • Hematoma • Postoperative injection swellings • Denture granuloma • Fibrous epulis • Peripheral giant cell granuloma • Traumatic bone cyst Inflammatory • Periapical infections • Gingival abscess • Osteomyelitis • Quinsy (peritonsillar abscess) • Tuberculoma • Gumma Cystic Odontogenic • Primordial (keratocyst) • Dentigerous • Periapical • Gingival cyst of adults and children Non-odontogenic • Nasopalatine duct cyst • Median palatine cyst • Palatine papilla cyst • Mucocele of palatal glands Drugs • Dilantin sodium ‘ • Cyclosporine Systemic • Vitamin deficiency • Leukemia • Pregnancy tumor • Hyperparathyroidism • Fibrous dysplasia • Paget disease • Histiocytosis X Allergic • Angioneurotic edema Miscellaneous • Impaction of misplaced teeth-ectopic eruption • Osteoradionecrosis • Chemical necrosis • Noma

Neoplastic Odontogenic • Ameloblastoma • Adenomatoid odontogenic tumor • Calcifying epithelial odontogenic tumor • Odontogenic myxoma • Odontogenic fibroma • Odontoameloblastoma • Ameloblastic fibro-odontoma • Complex odontome • Compound odontome Non-odontogenic • Torus palatinus • Osteoma • Chondroma • Rhabdomyoma • Chondroma • Neurofibroma • Schwannoma • Hemangioma • Lymphangioma • Pleomorphic adenoma • Fibroma • Ossifying fibroma • Myxoma • Papilloma • Melanoma Malignant • Osteogenic sarcoma/chondrosarcoma • Multiple myeloma • Rhabdomyosarcoma • Malignant hemangioendothelioma • Kaposi’s sarcoma • Ewing’s tumor • Transitional cell carcinoma • Hodgkin’s lymphoma • Malignant pleomorphic adenoma • Adenoid cystic cell carcinoma • Fibrosarcoma • Squamous cell carcinoma • Malignant melanoma • Metastatic carcinoma

Appendices

CAUSES OF TRISMUS Traumatic Extra-articular • Blow or fall • Surgical extractions and fracture mandible • Keloid following burns • Improper inf. Alveolar nerve block injection • Masseter muscle / sphenomandibular ligament calcification Intra-articular • Forceps delivery and followed by ankylosis • TMJ fracture • Upward and backward dislocation • Acute forward dislocation Infections Extra-articular • Pericoronitis • Osteomyelitis • Cellulitis • Parotid infections • Otitis media • Mastoiditis • Tonsillitis • Oral ulcers • Diphtheria • Tetanus • Infected granuloma of bone like (TB, syphilis, actinomycosis) Intra-articular • Osteomyelitis of TMJ (local cause or through blood) • Arthritis (rheumatoid, osteoarthritis, rheumatoid fever)

Neoplastic Any tumor intra/extra-articular/exostosis of condyle and coronoid Osteoradionecrosis (both intra or extra-articular) Systemic • Tetany • Hypothyroidism • Strychnine poisoning • Epilepsy • Hysteria • Physical, chemical, electrical or mental shock or extreme fear • Brain tumors and hemorrhage in medulla oblongata Congenital • Ankylosis of maxilla to mandible Miscellaneous • Fusion of coronoid process to zygoma • Submucous fibrosis • Scleroderma

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Textbook of Oral Pathology

CONDITIONS PRODUCING MACROCHELIA (LIP ENLARGEMENT AND SWELLING) 972

Traumatic • Acute blow or face, friction and surgical interference • Insect bite • Chronic mouth breathing • Self inflicted chronic injuries like lip sucking and biting, glass blowing and pipe smoking, etc. Neoplastic Benign • Papilloma • Melanoma • Monomorphic adenoma • Canalicular adenoma • Pleomorphic adenoma • Mucoepidermoid tumor • Fibroma • Neurofibroma • Lipoma • Hemangioma • Lymphangioma • Granular cell myoblastoma • Solitary myeloma Malignant • Squamous cell carcinoma • Malignant melanoma • Basal cell carcinoma • Malignant pleomorphic adenoma • Mucoepidermoid tumor • Adenocarcinoma • Fibrosarcoma • Neurofibrosarcoma • Lymphosarcoma • Angiosarcoma • Rhabdomyosarcoma • Kaposi sarcoma in AIDS

Inflammatory • Collateral edema from dental infections • Acute furuncle in nose or lip • Carbuncle or abscess due to mucous gland or hair follicle • Infected traumatic lesions • Chronic macrocheilia following repeated attacks of inflammations • Tuberculoma • Sarcoidosis • Syphilis • Actinomycosis • Molluscum contagiosum • Radiation cheilitis • Mucocele Allergic • Giant urticaria • Angioneurotic edema Congenital • Congenital macrocheilia • Congenital double lip Miscellaneous and syndromes • Amyloidosis • Keratoacanthoma • Cheilitis glandularis • Papillomatosis in acanthosis nigricans and adenocarcinoma • Tuberous sclerosis • Hereditary hemorrhagic telangiectasia • Lipoidosis • Idiopathic fibroedema • Melkersson syndrome • Cheilitis granulomatosis • Crohn’s disease (macrocheilia) • Polystomatitis vegetans

Appendices

SWELLINGS OF FLOOR OF THE MOUTH Traumatic • Hematoma • Embedding of foreign body (foreign body granuloma) • Denture granuloma Postradiation swellings Cystic swellings • Sublingual dermoid • Thyroglossal duct cyst • Branchial cyst • Ranula • Plunging ranula Inflammatory • Collateral edema from odontogenic infection • Swellings of Wharton’s duct • Stone in Wharton’s duct • Mikulicz disease • Swelling of sublingual and submandibular salivary gland • Acute infections following trauma Allergic • Angioneurotic edema Syndromes • Hereditary hemorrhagic telangiectasia • Struge-Weber disease

Neoplastic Benign • Papilloma • Melanoma • Monomorphic adenoma • Pleomorphic adenoma • Oxyphilic adenoma • Hemangioma • Hemangiopericytoma • Endothelioma • Lymphangioma • Neurofibroma • Neurilemmoma • Plasmacytoma • Rhabdomyoma • Leiomyoma • Lipoma • Fibroma Malignant • Squamous cell carcinoma • Mucoepidermoid tumor • Adenocarcinoma • Malignant pleomorphic adenoma • Fibrosarcoma • Reticulum cell sarcoma • Lymphosarcoma • Rhabdomyosarcoma • Adenolymphoma • Hemangioendothelioma • Kaposi’s sarcoma (AIDS)

ULCERATION OF ORAL CAVITY Traumatic Physical • Rough and badly fitting restoration • Ulcers due to tooth present at birth and sharp edges • From splints • Force injection ulcers on palate • Electric burn due to live wire • Post filling ulcer on frenum of tongue • Epileptic ulcers Thermal • Hot liquid • Refrigerant local anesthetics Chemical • Drugs like aspirin, arsenic, bismuth, and lead • Actinic cheilosis on lips • Radiation and laser radiation

Infections Nonspecific (Strepto and Staph) • Nonspecific infected ulcers primarily traumatic streptostomatitis Specific (bacilli and cocci) • Aphthous ulcer • Tuberculosis • Diphtheria • Tularemia (rabbit fever) • Granuloma inguinale • Leprosy • Gonorrhea • Pneumococcal • Ulcers of oral cavity in infections with bacillus

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METABOLIC AND GENETIC JAW DISEASES 974

Genetic abnormalities • Cherubism • Osteopetrosis • Osteogenesis imperfecta • Cleidocranial dysplasia • Crouzon syndrome • Treacher Collins syndrome (mandibulofacial dysostosis) • Pierre Robin syndrome • Marfan syndrome • Ehlers Danlos syndrome

Metabolic conditions • Paget’s disease • Hyperthyroidism • Hypophosphatasia • Infantile cortical hyperostosis • Phantom bone disease • Acromegaly • Fibrous dysplasia

VIRUSES CAUSING DISEASE IN ORAL CAVITY Name of virus

Disease cause

Herpes simplex virus I or Human herpes virus I

Herpetic gingivostomatitis (primary and secondary)

Herpes simplex virus II or Human herpes virus II

Genital infection

Varicella-zoster or Human herpes virus III

Chickenpox, shingles

Epstein Barr virus or Human herpes virus IV

Mononucleosis, Burkitt’s lymphoma, hairy leukoplakia, nasopharyngeal carcinoma

Cytomegalovirus or Human herpes virus V

Salivary gland enlargement

Human herpes virus VI

Roseola infantum

Human herpes virus VIII

Kaposi sarcoma

Papilloma viruses

Oral papilloma, wart, heck disease, condyloma acuminatum

Coxsackieviruses

Herpangina, hand, foot and mouth disease

Measles virus

Measles

Mumps virus

Mumps, parotitis

OSTEOLYTIC LESIONS Congenital • Cherubism Traumatic • Solitary bone cyst • Osteoporotic marrow defect • Fractures Radiation induced • Osteoradionecrosis Inflammatory • Acute or chronic osteomyelitis Metabolic • Hyperparathyroidism • Eosinophilic granuloma • Letterer-Siwe disease

Granulomatous disease • Central giant cell granuloma • Giant cell tumor Odontogenic cyst • Dentigerous • Radicular • Odontogenic keratocyst Odontogenic tumor • Ameloblastoma • Odontogenic myxoma Malignant neoplasm • Squamous cell carcinoma • Malignant melanoma • Verrucous carcinoma Others • Aneurysmal bone cyst • Traumatic bone cyst

Appendices

TEETH ANOMALIES AND THEIR CAUSE Anomalies

Cause

Hyperdontia

Idiopathic supernumerary teeth Cleft lip and palate Gardner syndrome Cleidocranial dysplasia

Hypodontia

Idiopathic Cleft lip and palate Hereditary hypohidrotic ectodermal dysplasia Incontinentia pigmenti Radiotherapy during childhood

Macrodontia

Fusion Gemination Idiopathic Facial hemihyperplasia Gigantism

Microdontia

Supernumerary teeth Peg shaped lateral incisor Dens invaginatus Cleft lip and palate Idiopathic Hereditary hypohidrotic ectodermal dysplasia Radiotherapy during childhood Congenital syphilis Hypopituitarism

Malformed crown

Mesiodens Environmental enamel hypoplasia Peg shaped lateral incisor Dens invaginatus Turner’s tooth Fusion Gemination Talon cusp Dens evaginatus Amelogenesis imperfecta Dentinogenesis imperfecta Regional odontodysplasia Congenital syphilis Vitamin D resistant rickets Renal osteodystrophy Hypoparathyroidism Pseudohypoparathyroidism Epidermolysis bullosa Radiotherapy during childhood

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Textbook of Oral Pathology

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976

Anomalies

Cause

Enamel loss

Caries Trauma Attrition Abrasion Erosion Dentinogenesis imperfecta Amelogenesis imperfecta

Extrinsic staining of teeth

Tobacco Coffee, tea, cold drinks Chromogenic bacteria Chlorhexidine

Intrinsic discoloration of teeth

Aging Death of pulp Fluorosis Tetracycline Internal resorption Calcific metamorphosis Dentinogenesis imperfecta Amelogenesis imperfecta Congenital erythropoietic porphyria Erythroblastosis fetalis

Abnormal shaped root

External root resorption Dilacerations Hypercementosis Concrescence Taurodontism Enamel pearl Benign cementoblastoma Radiotherapy during childhood Dentinogenesis imperfecta Dentin dysplasia

Appendices

TYPICAL HISTOLOGICAL FEATURE Typical features

Name of disease

Starry sky

Burkitt’s lymphoma, infective mononucleosis, polycythemia

Rushton bodies

Dentigerous cyst

Reed Stenberg cell

Hodgkin’s disease

Dropping off effect

Junctional nevus

Saw tooth appearance

Lichen planus

Antoni type A and type B tissue

Neurilemmoma

Honey comb or Swiss cheese pattern

Adenoid cystic carcinoma of salivary gland

Picket fence or tombstone

Primordial cyst

Liesegang ring

Calcifying epithelial odontogenic tumor

Safety pin appearance

Granuloma inguinale

Lipschutz bodies

Herpes simples infection

Anitschkow cell

Aphthous ulcer, sickle cell anemia, megaloblastic anemia and iron deficiency anemia

Henderson-Paterson inclusion

Molluscum contagiosum

Dilapidated brick wall effect

Familial benign chronic pemphigus

Cartwheel or checkerboard appearance

Multiple myeloma

Tobacco cells or cell in cells

Hereditary benign intraepithelial dyskeratosis

Lava flowing around boulder

Dentin dysplasia (shield type I)

Signet ring appearance

Liposarcoma

Storiform

Malignant fibrous histiocytoma

Tadpole like

Fibrosarcoma

Cigar like appearance

Leiomyoma

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Textbook of Oral Pathology

APPENDIX V: HISTOLOGY DIAGRAMS OF ORAL TISSUES NORMAL HISTOLOGICAL DIAGRAM Sangamesh Halawar

Oral epithelium

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Dental lamina

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