Pocket Atlas of Oral Diseases [3rd Edition] 3132417874, 9783132417878, 9783132417885

Table of contents :
Introduction to Oral Medicine
Schematic Classification of Oral Diseases
1 White Lesions
2 Red Lesions
3 Black and Brown Lesions
4 Vesiculobullous Lesions
5 Ulcerative Lesions
6 Papillary Lesions
7 Gingival Enlargement
8 Soft-Tissue Tumors
9 Soft-Tissue Cysts
10 Bone Swellings
11 Neck Swellings
12 Lip Disorders
13 Tongue Disorders

Citation preview

Pocket Atlas of Oral Diseases

Third Edition

George Laskaris, MD, DDS, PhD Associate Professor of Oral Medicine Medical School, University of Athens Athens, Greece; Former Head of Oral Medicine Department of Dermatology “A. Sygros” Hospital Athens, Greece; Visiting Professor University of London London, UK

418 illustrations

Thieme Stuttgart • New York • Delhi • Rio de Janeiro

Library of Congress Cataloging-in-Publication Data is available from the publisher.

© 2020. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstrasse 14, 70469 Stuttgart, Germany +49 [0]711 8931 421, [email protected] Thieme Publishers New York 333 Seventh Avenue, New York, NY 10001 USA +1 800 782 3488, [email protected]

Important note: Medicine is an ever-changing science undergoing continual development. Research and clinical experience are continually expanding our knowledge, in particular our knowledge of proper treatment and drug therapy. Insofar as this book mentions any dosage or application, readers may rest assured that the authors, editors, and publishers have made every effort to ensure that such references are in accordance with the state of knowledge at the time of production of the book. Nevertheless, this does not involve, imply, or express any guarantee or responsibility on the part of the publishers in respect to any dosage instructions and forms of applications stated in the book. Every user is requested to examine carefully the manufacturers’ leaflets accompanying each drug and to check, if necessary in consultation with a physician or specialist, whether the dosage schedules mentioned therein or the contraindications stated by the manufacturers differ from the statementsmadein the present book. Such examination is particularly important with drugs that are either rarely used or have been newly released on the market. Every dosage schedule or every form of application used is entirely at the user’s own risk and responsibility. The authors and publishers requestevery user to report to the publishers any discrepancies or inaccuracies noticed. If errors in this work are found after publication, errata will be posted at www.thieme.com on the product description page. Some of the product names, patents, and registered designs referred to in this book are in fact registered trademarks or proprietary names even though specific reference to this fact is not always made in the text. Therefore, the appearance of a name without designation as proprietary is not to be construed as a representation by the publisher that it is in the public domain.

Thieme Publishers Delhi A-12, Second Floor, Sector-2, Noida-201301 Uttar Pradesh, India +91 120 45 566 00, [email protected] Thieme Publishers Rio de Janeiro, Thieme Publicações Ltda. Edifício Rodolpho de Paoli, 25º andar Av. Nilo Peçanha, 50 – Sala 2508 Rio de Janeiro 20020-906 Brasil +55 21 3172 2297 Cover design: Thieme Publishing Group Typesetting by Thomson Digital, India Printed in Germany by CPI Books GmbH ISBN 978-3-13-241787-8 Also available as an e-book: eISBN 978-3-13-241788-5

54321

This book, including all parts thereof, is legally protected by copyright. Any use, exploitation, or commercialization outside the narrow limits set by copyright legislation without the publisher’s consent is illegal and liable to prosecution. This applies in particular to photostat reproduction, copying, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage.

To my wife Vivi, for her love and her continuous support

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Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

xvii

Introduction to Oral Medicine . . . . . . . . . . . . . . . . . . . . .

xviii

Schematic Classification of Oral Diseases

........

xix

1

White Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1

1.1

Leukoplakia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2

1.2

Hairy Leukoplakia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6

1.3

Lichen Planus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6

1.4

Lichenoid Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12

1.5

Linea Alba . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

14

1.6

Nicotinic Stomatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

14

1.7

Cigarette Smoker’s Lip Lesions . . . . . . . . . . . . . . . . . . . . . . . . . .

16

1.8

Uremic Stomatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16

1.9

Cinnamon Contact Stomatitis . . . . . . . . . . . . . . . . . . . . . . . . . . .

18

1.10

Chemical Burn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

20

1.11

Candidiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

22

1.12

Chronic Biting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

26

1.13

Materia Alba of the Gingiva . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

26

1.14

Fordyce’s Granules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

28

1.15

Leukoedema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

30

1.16

White Sponge Nevus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

30

vii

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Contents 1.17

Dyskeratosis Congenita . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

32

1.18

Pachyonychia Congenita . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

34

1.19

Focal Palmoplantar and Oral Mucosa Hyperkeratosis Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

36

1.20

Mucosal Horn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

36

1.21

Papilloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

38

1.22

Verrucous Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

40

1.23

Squamous Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

40

1.24

Skin and Mucosal Grafts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

42

1.25

Epithelial Peeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

42

2

Red Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

45

2.1

Traumatic Hematoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

46

2.2

Thermal Burn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

46

2.3

Radiation Oral Mucositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

48

2.4

Oral Lesions Secondary to Fellatio and Cunnilingus . . . . . . .

48

2.5

Geographic Tongue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

50

2.6

Denture Stomatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

52

2.7

Candidiasis Erythematous. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

52

2.8

Erythroplakia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

54

2.9

Squamous Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

56

2.10

Plasma Cell Gingivitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

56

2.11

Granulomatous Gingivitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

58

2.12

Desquamative Gingivitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

60

viii

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Contents 2.13

Linear Gingival Erythema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

62

2.14

Contact Allergic Stomatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

62

2.15

Gonococcal Stomatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

64

2.16

Hemangioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

66

2.17

Angiolymphoid Hyperplasia with Eosinophilia . . . . . . . . . . . .

66

2.18

Lupus Erythematosus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

68

2.19

Hereditary Hemorrhagic Telangiectasia . . . . . . . . . . . . . . . . . .

72

2.20

Iron Deficiency Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

74

2.21

Thrombocytopenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

76

2.22

Infectious Mononucleosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

78

2.23

Reactive Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

80

2.24

Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

82

2.25

Sturge–Weber Angiomatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . .

84

2.26

Peripheral Ameloblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

84

3

Black and Brown Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . .

87

3.1

Racial Pigmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

88

3.2

Amalgam Tattoo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

88

3.3

Heavy Metal Deposition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

90

3.4

Drug-Induced Pigmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

90

3.5

Smoker’s Melanosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

94

3.6

Black Hairy Tongue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

94

3.7

Oral Melanoacanthoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

96

ix

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Contents

x

3.8

Ephelides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

98

3.9

Lentigo Simplex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

98

3.10

Lentigo Maligna . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

100

3.11

Melanocytic Nevi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

100

3.12

Nevus of Ota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

104

3.13

Malignant Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

106

3.14

Addison’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

108

3.15

Peutz–Jeghers Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

110

4

Vesiculobullous Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . .

115

4.1

Primary Herpetic Gingivostomatitis . . . . . . . . . . . . . . . . . . . . .

116

4.2

Secondary Herpetic Stomatitis . . . . . . . . . . . . . . . . . . . . . . . . . .

116

4.3

Herpes Zoster . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

118

4.4

Herpangina . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

120

4.5

Hand, Foot, and Mouth Disease . . . . . . . . . . . . . . . . . . . . . . . . .

122

4.6

Erythema Multiforme. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

124

4.7

Stevens–Johnson Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

126

4.8

Toxic Epidermal Necrolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

128

4.9

Pemphigus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

130

4.10

Mucous Membrane Pemphigoid . . . . . . . . . . . . . . . . . . . . . . . . .

132

4.11

Bullous Pemphigoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

136

4.12

Pemphigoid Gestationis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

138

4.13

Linear IgA Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

140

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Contents 4.14

Dermatitis Herpetiformis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

142

4.15

Bullous Lichen Planus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

144

4.16

Epidermolysis Bullosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

146

4.17

Epidermolysis Bullosa Acquisita. . . . . . . . . . . . . . . . . . . . . . . . . .

148

4.18

Angina Bullosa Hemorrhagica . . . . . . . . . . . . . . . . . . . . . . . . . . .

150

4.19

Primary Systemic Amyloidosis . . . . . . . . . . . . . . . . . . . . . . . . . . .

152

4.20

Traumatic Bulla . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

152

4.21

Pyostomatitis Vegetans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

154

5

Ulcerative Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

157

5.1

Traumatic Ulcer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

158

5.2

Eosinophilic Ulcer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

160

5.3

Necrotizing Sialadenometaplasia . . . . . . . . . . . . . . . . . . . . . . . .

162

5.4

Necrotizing Ulcerative Gingivitis . . . . . . . . . . . . . . . . . . . . . . . . .

164

5.5

Noma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

166

5.6

Chronic Ulcerative Stomatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . .

168

5.7

Syphilis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

170

5.8

Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

172

5.9

Systemic Mycoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

174

5.10

Aphthous Ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

178

5.11

Adamantiades–Behçet’s Disease . . . . . . . . . . . . . . . . . . . . . . . . .

180

5.12

Graft Versus Host Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

184

5.13

Wegener’s Granulomatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

186

xi

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Contents 5.14

Nasal Type-Extranodal NK/T-Cell Lymphoma . . . . . . . . . . . . .

188

5.15

Non-Hodgkin’s Lymphomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

190

5.16

Squamous Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

192

5.17

Neutropenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

194

5.18

Cyclic Neutropenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

196

5.19

Congenital Neutropenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

198

5.20

Agranulocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

200

5.21

Bone Marrow Aplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

202

5.22

Myelodysplastic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

204

5.23

Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

206

5.24

Langerhans Cell Histiocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . .

208

5.25

Glycogen Storage Disease, Type 1b . . . . . . . . . . . . . . . . . . . . . .

212

5.26

PFAPA Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

214

5.27

Sweet’s Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

216

5.28

Staphylococcal Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

216

5.29

Pseudomonas Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

218

5.30

Klebsiella Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

220

5.31

Cytomegalovirus Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

220

6

Papillary Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

223

6.1

Papilloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

224

6.2

Condyloma Acuminatum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

224

6.3

Verruca Vulgaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

226

xii

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Contents 6.4

Verruciform Xanthoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

228

6.5

Verrucous Leukoplakia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

228

6.6

Verrucous Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

230

6.7

Squamous Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

230

6.8

Denture Fibrous Hyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . .

232

6.9

Crohn’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

232

6.10

Malignancy-Associated Acanthosis Nigricans . . . . . . . . . . . . .

234

6.11

Benign Acanthosis Nigricans . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

236

6.12

Darier’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

238

6.13

Papillary Palatal Hyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . .

240

6.14

Focal Dermal Hypoplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

242

7

Gingival Enlargement

..............................

245

7.1

Generalized Enlargement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

246

7.2

Localized Enlargement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

258

8

Soft-Tissue Tumors

.................................

265

8.1

Benign . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

266

8.2

Malignant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

296

8.3

Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

316

9

Soft-Τissue Cysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

321

9.1

Mucocele . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

322

9.2

Ranula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

324

9.3

Dermoid Cyst. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

324

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Contents 9.4

Lymphoepithelial Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

326

9.5

Eruption Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

326

9.6

Gingival Cysts of the Newborn . . . . . . . . . . . . . . . . . . . . . . . . . .

328

9.7

Gingival Cyst of the Adult . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

330

9.8

Thyroglossal Duct Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

330

9.9

Nasolabial Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

332

9.10

Incisive Papilla Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

332

10

Bone Swellings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

335

10.1

Torus Mandibularis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

336

10.2

Torus Palatinus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

336

10.3

Multiple Exostoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

338

10.4

Osteoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

338

10.5

Osteosarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

340

10.6

Chondrosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

340

10.7

Burkitt’s Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

342

10.8

Multiple Myeloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

344

10.9

Ewing’s Sarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

344

10.10

Cherubism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

346

10.11

Fibrous Dysplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

346

10.12

Gardner's Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

348

10.13

Paget’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

350

10.14

Odontogenic Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

352

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Contents

11

Neck Swellings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

355

11.1

Cervical Lymphoepithelial Cyst . . . . . . . . . . . . . . . . . . . . . . . . . .

356

11.2

Thyroglossal Duct Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

356

11.3

Dermoid Cyst. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

358

11.4

Cystic Hygroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

358

11.5

Nonspecific Lymphadenitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

360

11.6

Submandibular Sialadenitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

360

11.7

Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

362

11.8

Heerfordt’s Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

362

11.9

Sjögren’s Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

364

11.10

Hodgkin’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

366

11.11

Metastatic Carcinoma in the Cervical Lymph Nodes . . . . . . .

368

12

Lip Disorders

........................................

371

12.1

Cheilitis Glandularis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

372

12.2

Cheilitis Granulomatosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

372

12.3

Melkersson–Rosenthal Syndrome . . . . . . . . . . . . . . . . . . . . . . . .

374

12.4

Exfoliative Cheilitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

374

12.5

Contact Cheilitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

376

12.6

Actinic Cheilitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

376

12.7

Angular Cheilitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

378

12.8

Lip-Licking Cheilitis and Dermatitis . . . . . . . . . . . . . . . . . . . . . .

380

12.9

Median Lip Fissure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

380

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Contents 12.10

Angioedema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

382

12.11

Lymphedema due to Radiation . . . . . . . . . . . . . . . . . . . . . . . . . .

382

12.12

Systemic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

384

13

Tongue Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

389

13.1

Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

390

13.2

Normal Elements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

400

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

405

xvi

Preface Twenty years have passed since the publication of the first edition and twelve years since the second edition of the Pocket Atlas of Oral Diseases. The enthusiastic acceptance by dentists, physicians, and dental and medical students has exceeded all expectations. For the third edition, the clinical orientation of the book remains unchanged. The visual approach is the most powerful tool at the disposal of the oral physician. Acquisition of the skill to “see” lesions in a particular way requires extensive and intensive clinical training and is rewarded with a high degree of diagnostic accuracy. From this point of view, I felt that the format of juxtaposition of text and color images is ideal and was, therefore, chosen for the presentation of the disease entities. For practical purposes the diseases that are included in this pocket book are classified according to three main criteria: (a) the morphology of the lesions, (b) the color of the lesions, and (c) anatomical regions.

This classification leads to the goal of the oral examiners to reach the precise diagnosis, which is a prerequisite for correct and successful treatment. The diagnosis of each disease is based on three fundamental principles: (a) patient's medical history, (b) clinical assessment of signs and symptoms, and (c) laboratory tests, if necessary. In the present edition, the text of the book has been rewritten and adapted to contemporary scientific and publishing demands. Information on more than 40 new diseases and one more chapter have been added. Over 95% of the pictorial color material has been renewed and enriched with high-standard color images. All of these changes guarantee improvement of oral health care, from disease prevention to accurate diagnosis and treatment. For more clinical information, readers may refer to my major book Color Atlas of Oral Diseases: Diagnosis and Treatment, 4th edition; Thieme, 2017. George Laskaris, MD, DDS, PhD

xvii

Introduction to Oral Medicine Oral medicine (stomatology) is an important, rapidly developing dental specialty in several countries of the world that recognizes and cultivates the close interplay between oral and systemic health. The spectrum of diseases of oral medicine is wide and includes diseases of the oral mucosa and the gingiva, lip disorders, salivary gland and jaw diseases, temporomandibular joint disorders, malodor, taste changes, orofacial pain, and oral manifestations of systemic diseases (see the schematic classification on the next page). Oral diseases may be local or systemic, acute or chronic, innocent or serious, painful or not, and life-changing or life-threatening. The oral medicine specialist (stomatologist or oral physician) should collaborate with several medical specialties (dermatology, gastroenterology, otorhinolaryngology, hematology, infectiology, immunology, oncology, pediatrics, neurology, psychiatry, internal medicine, pathology, imaging, and head and neck surgery) and with the dental specialties (general dentistry, oral surgery, periodontology, implantology, pediatric dentistry, oral pathology, and radiology). The oral medicine specialist should have a dental and a basic medical background, particularly in internal medicine, dermatology, otorhinolaryngology, pediatrics, clinical

xviii

pharmacology, therapeutics, histopathology, and others. The general dentist and the medical physician should also have the basic knowledge of oral diseases in order to recognize the primary lesions in the oral cavity and to direct the patient to the oral medicine specialist. The oral cavity, as an examination field, offers important clinical advantages: (a) it is an open cavity readily accessible to inspection and palpation, (b) it is easy to perform a biopsy here, (c) it is regularly examined by the dentist for tooth and gingival problems, and (d) it is accessible to self-examination by the patient. Several diagnostic difficulties exist due to: (a) the plethora of local and systemic diseases with similar lesions and (b) local factors, such as tooth, dentures, foodstuffs, or saliva, which may alter the morphology of the elementary lesions. Clinical diagnostic methodology should follow fundamental principles that we must adhere to in order to arrive at a correct diagnosis. Laboratory tests are a tool that must follow the clinical evaluation. Laboratory results should always be evaluated by the clinician in relation to the clinical features of the disease. The goal of the oral medicine specialist should be the prevention, diagnosis, and treatment of oral diseases.

Schematic Classification of Oral Diseases

A guide, in the form of a tree, for students, residents, and specialists in oral medicine that offers a basic framework for the classification of oral diseases into four major groups: systemic, local, infectious, and neoplasms.

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1 White Lesions White lesions of the oral mucosa are a multifactorial group of disorders, the color of which is produced by the scattering of light through an altered epithelial surface. These lesions are classified into two groups: (1) attached to the oral mucosa and (2) scraped off from the oral mucosa. The diagnosis and differential diagnosis of oral white lesions should be made on the basis of the medical history, clinical features, and laboratory tests.

●

Leukoplakia

●

Fordyce’s Granules

●

Hairy Leukoplakia

●

Leukoedema

●

Lichen Planus

●

White Sponge Nevus

●

Lichenoid Reactions

●

Dyskeratosis Congenita

●

Linea Alba

●

Pachyonychia Congenita

●

Nicotinic Stomatitis

●

●

Cigarette Smoker’s Lip Lesions

Focal Palmoplantar and Oral Mucosa Hyperkeratosis Syndrome

●

Uremic Stomatitis

●

Mucosal Horn

●

Papilloma

●

Verrucous Carcinoma

●

Squamous Cell Carcinoma

●

Skin and Mucosal Grafts

●

Epithelial Peeling

● ● ● ● ●

Cinnamon Contact Stomatitis Chemical Burn Candidiasis Chronic Biting Material Alba of the Gingiva

1

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White Lesions

1.1 Leukoplakia Definition: Leukoplakia is a clinical term without any histologic significance. It is defined as a white patch or plaque that cannot be scrapped off and cannot be characterized, clinically and histologically, as any other disease entity. Leukoplakia is the most common potentially malignant disorder (precancerous lesion) and is characterized by biological heterogenicity. Etiology: The exact etiology remains unknown. Smoking and alcohol consumption are the main environmental causative factors, followed by human papillomavirus (HPV) types 16 and 18, Candida species, chronic local friction, etc. Clinical features: Based on the clinical criteria, leukoplakia is classified into two main groups: (1) homogeneous (common-low risk) and (2) nonhomogeneous, which is subdivided into speckled or nodular (less common-high risk) and verrucous (rare-high risk) forms. Clinically, homogeneous form is characterized by a thin, flat uniform white plaque (▶ Fig. 1.1 and ▶ Fig. 1.2). The speckled form is characterized by a red surface with multiple, small, white macules or nodules (▶ Fig. 1.3 and ▶ Fig. 1.4). Verrucous form presents as an exophytic, irregular, wrinkled or corrugated white plaque (▶ Fig. 1.5). Proliferative verrucous leukoplakia is a subtype of verrucous form, which is characterized by multifocal location, tendency to recur, is usually HPV positive, and has a high rate of malignant transformation. The total risk of malignant transformation of leukoplakia varies between 3 and 6% independent of the form. The buccal mucosa and commissures, tongue, floor of the mouth, gingiva, and lower lip are more frequently affected. The lateral border of the tongue and the floor of the mouth represent areas of high risk for malignant transformation. Laboratory tests: Biopsy and histopathologic examination must be done to determine the risk of malignant transformation of oral leukoplakia. The oral clinicians should remember that the histologic results represent exclusively the site of biopsy taken in a specific time frame and do not have a long-term value.

2

| 24.09.19 - 16:33

1.1 Leukoplakia

Fig. 1.1 Homogeneous leukoplakia on the upper gingiva.

Fig. 1.2 Homogenous leukoplakia on the floor of the mouth.

3

| 24.09.19 - 16:33

White Lesions

Fig. 1.3 Speckled leukoplakia on the buccal mucosa.

Differential diagnosis: Lichen planus, lichenoid reaction, hairy leukoplakia, cinnamon contact stomatitis, nicotinic stomatitis, candidiasis, chronic biting, chemical burn, leukoedema, uremic stomatitis, lupus erythematosus, white sponge nevus, dyskeratosis congenita, pachyonychia congenita, skin, and mucosal grafts. Treatment: The treatment of choice is surgical excision and smoking cessation. Electrosurgery and laser may also be used as alternative procedures. A followup program every 6 months for 3 to 5 years is recommended.

4

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1.1 Leukoplakia

Fig. 1.4 Speckled leukoplakia on the buccal mucosa.

Fig. 1.5 Verrucous leukoplakia on the dorsum of the tongue.

5

| 24.09.19 - 16:33

White Lesions

1.2 Hairy Leukoplakia Definition: Hairy leukoplakia was, during the pre-ART (antiretroviral therapy) era, one of the most common (20–30%) and characteristic lesions of human immunodeficiency virus (HIV) infection, while currently it appears less often. In HIV-infected patients, hairy leukoplakia develops when the CD4 count is less than 500 cells/mm3. In addition, it can also appear in immunosuppressed patients mainly after organ transplantation. Etiology: The lesion is caused by Epstein–Barr virus. Clinical features: Clinically, hairy leukoplakia presents as a white, asymptomatic, often elevated and unremovable patch. The lesion is almost always found bilaterally on the lateral margins of the tongue, and may spread to the dorsum and the ventral surface (▶ Fig. 1.6). Characteristically, the surface of the lesion is corrugated with a vertical orientation to the long axis of the tongue. However, smooth and flat lesions may also be seen. The lesion is not potentially malignant (precancerous). Laboratory tests: Histologic examination, in situ hybridization, polymerase chain reaction, and electron microscopy are useful diagnostic tests. Differential diagnosis: Leukoplakia, cinnamon contact stomatitis, uremic stomatitis, lichen planus, candidiasis, chemical burn, frictional keratosis, leukoedema, and lupus erythematosus. Treatment: Usually, no treatment is required. However, in extent and severe cases acyclovir or valaciclovir or famciclovir can be used with success.

1.3 Lichen Planus Definition: Lichen planus is a relatively common, chronic inflammatory disease of the oral mucosa, skin, genital mucosa, nails, and hair. Etiology: The exact etiology is not well known. However, T-cell-mediated immune reaction against components of epithelial basal cells may be involved. Clinical features: Clinically, oral lichen planus classically presents with small white papules that coalesce, forming a network of lines usually in a symmetrical pattern (Wickman’s striae). Six forms of oral lichen planus are recognized: the reticular and erosive or ulcerative that are common (▶ Fig. 1.7 and ▶ Fig. 1.8), the atrophic and hypertrophic that are less common (▶ Fig. 1.9 and ▶ Fig. 1.10), and the bullous and pigmented (▶ Fig. 1.11 and ▶ Fig. 1.12) that are rare. Frequently, the erosive and atrophic forms involve the gingiva in the pattern of desquamative gingivitis.

6

| 24.09.19 - 16:33

1.3 Lichen Planus

Fig. 1.6 Oral hairy leukoplakia.

Fig. 1.7 Lichen planus, reticular type on the buccal mucosa.

7

| 24.09.19 - 16:33

White Lesions

Fig. 1.8 Lichen planus, erosive type on the dorsum of the tongue.

Fig. 1.9 Lichen planus, atrophic type on the dorsum of the tongue.

8

| 24.09.19 - 16:33

1.3 Lichen Planus

Fig. 1.10 Lichen planus, hypertrophic lesions with a central erosion on the buccal mucosa.

Fig. 1.11 Lichen planus, bullous type on the buccal mucosa.

9

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White Lesions Clinically, the cutaneous lichen planus appears as small, flat, polygonal, shiny papules with characteristic violaceous color, associated by pruritus (▶ Fig. 1.13). The lesions are distributed in a symmetrical pattern, more frequently on the flexor surfaces of the forearms and wrists, the neck, the back, and the sacral area. Linear lesions may develop after scratching the skin (Koebner’s phenomenon). Genitalia and nails may also be affected. Oral lichen planus may follow a course of remissions and exacerbations. The buccal mucosa, tongue, gingiva, and lips are most commonly affected. Middle-aged individuals are more frequently affected, with a female-to-male ratio of 2:1. The diagnosis usually is based on clinical grounds alone. The prognosis of oral lichen planus is usually good, as possibility of malignant transformation is very rare and controversial. Laboratory tests: Biopsy and histologic examination are helpful. Direct immunofluorescence can also be used. Differential diagnosis: Fordyce’s spots, chemical burn, candidiasis, lichenoid reaction to drug or dental material, cinnamon contact stomatitis, geographic tongue, leukoplakia, erythroplakia, graft versus host disease, discoid lupus erythematosus, secondary syphilis, mucous membrane pemphigoid, other chronic bullous diseases, and chronic ulcerative stomatitis. Treatment: Mild, asymptomatic forms of lichen planus do not need therapy. Systemic corticosteroids (e.g., prednisolone 20–40 mg/day) are the drugs of choice in severe, symptomatic cases, particularly in the erosive form. Topical corticosteroids and/or tacrolimus in a 0.5% adhesive ointment form are suggested in less severe cases. The topical use of antiseptic mouthwashes should be avoided.

10

| 24.09.19 - 16:33

1.3 Lichen Planus

Fig. 1.12 Lichen planus, pigmented lesion on the buccal mucosa.

Fig. 1.13 Lichen planus, typical lesions on the forearm.

11

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White Lesions

1.4 Lichenoid Reactions Definition: Lichenoid reactions are a heterogeneous group of lesions of the oral mucosa that exhibit clinical and histopathological similarities to oral lichen planus, but have a different clinical course. Etiology: Persistent, chronic contact of the oral mucosa with amalgam restorations that have been oxidized, may lead to hypersensitivity or toxic reaction, usually due to mercury and rarely to other trace metals (zinc, copper, silver, and tin). Similar reactions may appear after contact with composite resin, dental plaque accumulation, and systemic drug administration. Clinical features: Clinically, lichenoid reaction appears as white and/or erythematous lesions, usually associated with peripheral, irregular delicate white striae (▶ Fig. 1.14 and ▶ Fig. 1.15). Occasionally, erythema and erosions may develop, associated with pain and a burning sensation, particularly to certain foods and spices. Characteristically, the lesions develop exactly at the sites of contact of the oral mucosa with the restorative material, and do not migrate to other sites. The clinical and histopathological features are similar to lichen planus. The buccal mucosa and the lateral margins of the tongue are the most frequently affected. Classically, the lesions disappear after removal of the responsible restorative material. The diagnosis is usually based on the history and clinical features. Laboratory tests: Histopathologic examination is useful. In addition, a skin punch biopsy to detect the suspicious material may be helpful. Differential diagnosis: Lichen planus, discoid lupus erythematosus, druginduced lesions, graft versus host disease, cinnamon contact stomatitis, chronic biting, leukoplakia, and mucous membrane pemphigoid. Treatment: Replacement or polishing of old restorative material is recommended. In serious cases topical or systemic steroids in low dose for 2 to 3 weeks can be helpful.

12

| 24.09.19 - 16:33

1.4 Lichenoid Reactions

Fig. 1.14 Lichenoid reaction of the buccal mucosa caused by contact with an amalgam restoration.

Fig. 1.15 Erosion and white areas of the tongue caused by contact with amalgam restorations.

13

| 24.09.19 - 16:33

White Lesions

1.5 Linea Alba Definition: Linea alba is a relatively common alteration of the buccal mucosa, and is usually bilateral. Etiology: Mechanical pressure or irritation from the buccal surface of the teeth along with sucking is the etiologic factor. Clinical features: Clinically, linea alba presents as unilateral or usually bilateral linear elevation of normal or slightly whitish color and normal consistency on palpation (▶ Fig. 1.16). Characteristically, it appears on the buccal mucosa along the occlusal level of the teeth. Linea alba, occasionally, may be scalloped and is often seen in obese individuals. The diagnosis is based exclusively on the clinical features. Differential diagnosis: Chronic biting, leukoedema, candidiasis, leukoplakia, and cinnamon contact stomatitis. Treatment: No treatment is required.

1.6 Nicotinic Stomatitis Definition: Nicotinic stomatitis or smoker’s palate is a relatively common tobacco-related type of hyperkeratosis that occurs exclusively on the hard palate, and is classically associated with heavy pipe, cigar, or cigarette smoking. Etiology: Mainly the elevated temperature and lesser the tobacco chemicals are the etiologic factors. Clinical features: Clinically, nicotinic stomatitis appears with redness of the palatal mucosa, which later assumes a grayish-white color. It presents with numerous small nodules with characteristic red dots 1 to 5 mm in diameter. They represent the inflamed and dilated orifices of the minor salivary grand ducts (▶ Fig. 1.17). In heavy smokers, fissures, furrows, and mucosal elevation may occur forming an irregular wrinkled surface. The palatal lesions are not potentially malignant. The diagnosis is based on the history and clinical features. Biopsy only rarely may be necessary. Laboratory tests: Usually not required. However, a histopathologic examination is occasionally useful. Differential diagnosis: Reverse smoker’s palate, thermal burn, chemical burn, leukoplakia, Darier’s disease, discoid lupus erythematosus, and candidiasis. Treatment: Cessation of smoking.

14

| 24.09.19 - 16:33

1.6 Nicotinic Stomatitis

Fig. 1.16 Linea alba.

Fig. 1.17 Typical nicotine stomatitis.

15

| 24.09.19 - 16:33

White Lesions

1.7 Cigarette Smoker’s Lip Lesions Definition: Cigarette smoker’s lip lesions are common in heavy smokers (over of 40 cigarettes daily) of nonfiltered cigarettes. Etiology: The lesions are due to high temperature that develops in the area during smoking. Clinical features: Characteristically, the lesions appear on the mucosal surface of the lower lip corresponding to the site at which the cigarette is held. Clinically, the lesions appear as flat or slightly elevated, asymptomatic whitish wide lines intermixed with red striations (▶ Fig. 1.18). The lesions are not premalignant. The diagnosis is exclusively based on the history and clinical features. Differential diagnosis: Chronic biting, chemical and thermal burn, cinnamon contact stomatitis, candidiasis, lichen planus, leukoplakia, and discoid lupus erythematosus. Treatment: The lesions usually disappear after smoking cessation in 1 to 2 months.

1.8 Uremic Stomatitis Definition: Uremic stomatitis is a relatively rare complication of acute or chronic renal failure. Etiology: It is caused by increased levels of urea and other nitrogen-containing products in the peripheral blood and saliva. Uremic stomatitis usually occurs when the urea levels in the blood exceed 300 mg/100 mL. The degradation of oral urea by the enzyme urease forms free ammonia, which may damage the oral mucosa. Clinical features: Two main forms of uremic stomatitis are recognized: (1) the ulcerative and (2) the nonulcerative. The ulcerative form is characterized by painful, superficial, and irregular ulcers of different sizes. These ulcers are covered by a white-brown or black pseudomembrane (▶ Fig. 1.19). The nonulcerative form presents with creased, thick, white projections or plaques that are

16

| 24.09.19 - 16:33

1.8 Uremic Stomatitis

Fig. 1.18 White lines of the lower lip due to heavy smoking.

Fig. 1.19 Uremic stomatitis, ulceration covered by a necrotic black pseudomembrane on the buccal mucosa.

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White Lesions painful and develop on an inflammatory base (▶ Fig. 1.20). The floor of the mouth and the tongue are more frequently affected. Hemorrhage and hematomas may also be observed. Candidiasis and other opportunistic viral and bacterial infections are common oral complications. Unpleasant taste, xerostomia, characteristic uriniferous breath odor, and a burning sensation are common symptoms. The diagnosis of uremic stomatitis is based on the medical history and clinical features, but should be confirmed by laboratory tests. Laboratory tests: The blood and urine levels of urea should be determined for accurate diagnosis. Differential diagnosis: Pseudomembranous candidiasis, cinnamon contact stomatitis, hairy leukoplakia, verrucous hyperplasia, verrucous leukoplakia, necrotizing ulcerative stomatitis, drug-induced stomatitis, and white sponge nevus. Treatment: The oral lesions usually improve after 2 to 4 weeks after hemodialysis and improvement of renal function. A high level of oral hygiene, oxygen-releasing mouthwashes, and artificial saliva are recommended.

1.9 Cinnamon Contact Stomatitis Definition: Cinnamon contact stomatitis is a relatively common oral mucosal reaction in individuals that consume artificially flavored cinnamon-containing products. Etiology: Thereleaseof thecinnamonetherealoilsandtheirconstantcontact with the oral mucosa, usually in the form of chewing gums, candies, toothpaste, dental floss, and mouthwashes maycausehypersensitivity reactionsand oral lesions. Clinical features: Clinically, erythema of the oral mucosa, white hyperkeratotic projections or plaques, and superficial erosions are the prominent features (▶ Fig. 1.21 and ▶ Fig. 1.22). A burning sensation and mild pain are common symptoms. The lateral border and the ventral surface of the tongue, the buccal mucosa, and the gingiva are more frequently affected. Exfoliative cheilitis and perioral dermatitis have also been described. The lesions may be localized or diffuse and mimic hairy leukoplakia, particularly, when they develop on the lateral aspect of the tongue, and lichen planus when they occur on the buccal mucosa. The diagnosis is mainly based on the history and clinical features. Laboratory tests: Usually not required. In rare cases, biopsy and histopathologic examination may be needed.

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1.9 Cinnamon Contact Stomatitis

Fig. 1.20 Uremic stomatitis, white, elevated, creased plaques on the lateral border of the tongue.

Fig. 1.21 Cinnamon contact stomatitis of the lateral border of the tongue.

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White Lesions

Fig. 1.22 Cinnamon contact stomatitis of the buccal mucosa.

Differential diagnosis: Candidiasis, lichen planus, hairy leukoplakia, leukoplakia chemical burn, chronic biting, leukoedema, amalgam contact reaction, plasma cell stomatitis, uremic stomatitis, and discoid lupus erythematosus. Treatment: Discontinuation of any cinnamon product is the first step. This improves the signs and symptoms in approximately 2 weeks’ time. In severe and extended lesions with erosions, systemic corticosteroids in low dose (e.g., 10–20 mg/d prednisolone) for 5 to 7 days help the lesions to heal sooner.

1.10 Chemical Burn Definition: Chemical burn of the oral mucosa is a relatively common lesion. Etiology: It is caused by careless or inappropriate use of a large number of caustic chemical agents and local drugs in dental practice or by the patients. The most common causative agents include locally applied hydrogen peroxide, phenol, alcohol, iodine, silver nitrate, trichloroacetic acid, sodium perborate, eugenol, paraformaldehyde, household chemicals, etc. Clinical features: Clinically, the affected oral mucosa is covered with pseudomembrane, usually white or whitish gray or black, due to epithelial necrosis (▶ Fig. 1.23, ▶ Fig. 1.24, and ▶ Fig. 1.25). The necrotic epithelium can easily be

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1.10 Chemical Burn

Fig. 1.23 Chemical burn of the buccal mucosa due to acetylsalicylic acid (aspirin).

Fig. 1.24 Trichloroacetic acid burn.

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White Lesions scraped off, leaving a red surface with or without bleeding, and occasionally erosions. The lesions are usual painful and heal within 4 to 6 days. The diagnosis is, exclusively, based on the history and clinical features. Differential diagnosis: Thermal burn, mechanical trauma, chronic biting, candidiasis, cinnamon contact stomatitis, necrotizing ulcerative stomatitis and gingivitis, secondary herpetic oral lesions, lichen planus, and leukoplakia. Treatment: It is symptomatic, as the lesions heal spontaneously within 4 to 6 days. Topically, oxygen-releasing mouthwashes are helpful. In severe cases, systemic corticosteroids in a low dose (10–15 mg/d prednisolone for 3–6 days) improve the symptoms soon.

1.11 Candidiasis Definition: Candidiasis is the most frequent oral fungal infection. Over the last four decades, the disease has taken on major importance. Etiology: Oral candidiasis is usually caused by Candida albicans, a fungus found in 20 to 50% of the normal oral flora of healthy people, and is rarely caused by other Candida strains (C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, C. guilliermodii, etc.). The predisposing factors for oral candidiasis may be local (poor oral hygiene, xerostomia, chronic mucosal trauma, dentures, antibiotic mouthwashes, chronic use of inhalational or topical corticosteroids, and radiotherapy of the head and neck) and systemic (iron deficiency anemia, diabetes mellitus, primary immunodeficiency, HIV infection, hematological malignancies, neutropenia, aplastic anemia, systemic corticosteroids and immunosuppressive drugs, systemic antibiotics, hypoparathyroidism, and other endocrine diseases). Clinical features: Oral candidiasis is classified into primary, including lesions exclusively in the mouth and the perioral skin, and secondary, including the oral lesions of mucocutaneous candidiasis. The primary oral candidiasis is classified into five clinical varieties: (1) pseudomembranous, (2) erythematous, (3) nodular or plaque-like, (4) papillary hyperplasia of palate, and (5) lesions contaminated with candida (angular cheilitis, median rhomboid glossitis, and denture stomatitis). The main forms of oral candidiasis that produce white lesions are: (1) pseudomembranous candidiasis, which is the most common form of the disease and may be acute or chronic (rare). Clinically, it is characterized by creamy white or whitish-yellow, slightly elevated spots or plaques which are easily detached, leaving a raw reddish or normal surface (▶ Fig. 1.26). The lesions may be localized or generalized, and more frequently

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1.11 Candidiasis

Fig. 1.25 Chemical burn caused by hydrogen peroxide.

Fig. 1.26 Pseudomembranous candidiasis on the palate.

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White Lesions appear on the buccal mucosa, tongue, palate, lips, and gingiva. Xerostomia, a burning sensation, unpleasant taste, and difficulty in swallowing are the most common symptoms. The diagnosis is usually based on the clinical features. (2) Nodular candidiasis, characterized by white, firm, and raised plaques that usually do not detach (▶ Fig. 1.27). The lesions may persist for a longer time and are usually located on the dorsum of the tongue and the commissures. (3) Mucocutaneous candidiasis, which is a heterogeneous and rare group of clinical syndromes, that are characterized by chronic lesions of the skin, nails, and mucosae, and are usually accompanied with immunological defects. Clinically, the oral lesions appear as white, multiple, plaques, which cannot be removed (▶ Fig. 1.28). Characteristically, the lesions are generalized, with a predilection for the tongue, buccal mucosa, commissures, and palate. Cutaneous and nail involvement are associated with the oral lesions. Laboratory tests: Direct microscopic examination of smears and microbiological culture are suggested. In chronic forms biopsy and histopathologic examination with periodic acid-Schiff stain is indicated. Differential diagnosis: Leukoplakia, hairy leukoplakia, cinnamon contact stomatitis, uremic stomatitis, lichen planus, lupus erythematosus, chronic biting, oral epitheliolysis, chemical and thermal burns, syphilitic mucous patches, and white sponge nevus. Treatment: Systemic triazoles (fluconazole, itraconazole, and ketoconazole) are the drugs of choice. The dosage and duration of treatment depends on the form of candidiasis and the presence of predisposing factors. Meticulous oral hygiene and resolution of any local or systemic predisposing factor is also suggested. Topical treatment with nystatin or miconazole may also be used particularly for infants and children.

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1.11 Candidiasis

Fig. 1.27 Hyperplastic candidiasis on the lateral border of the tongue.

Fig. 1.28 Candida endocrinopathy syndrome, multifocal lesions on the tongue.

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White Lesions

1.12 Chronic Biting Definition: Chronic biting of the oral mucosa or maceration can be a relatively common chronic habit with a psychological background. Etiology: The patients repeatedly bite the oral mucosa, pull it between the teeth, and detach the superficial epithelial layers. Clinical features: Clinically, chronic biting appears as a localized or diffused irregular whitish lesion of small furrows, with desquamation of the epithelium (▶ Fig. 1.29 and ▶ Fig. 1.30). Rarely, petechiae and superficial erosions may be seen. The buccal mucosa, the lateral margins of the tongue, and the labial mucosa are the sites of predilection. Usually, the lesions are bilateral. The diagnosis is exclusively based on the history and clinical features. Differential diagnosis: Leukoedema, candidiasis, cinnamon contact stomatitis, uremic stomatitis, chemical burn, leukoplakia, hairy leukoplakia, lichen planus, and white sponge nevus. Treatment: Usually no treatment is required. However, patients should be recommended to stop the habit.

1.13 Materia Alba of the Gingiva Definition: Materia alba may be seen along the vestibular surface of the attached gingiva in patients with poor oral hygiene and is common along the dentogingival margin. Etiology: It is caused by the accumulation of food debris, dead epithelial cells, and bacteria. Clinical features: Materia alba appears as a soft, whitish plaque that is easily detached after slight pressure (▶ Fig. 1.31). The diagnosis is exclusively made clinically. Differential diagnosis: Candidiasis, leukoplakia, cinnamon contact stomatitis, and chemical burn. Treatment: Good oral hygiene.

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1.13 Materia Alba of the Gingiva

Fig. 1.29 Extensive chronic biting of the lateral border of the tongue.

Fig. 1.30 Localized chronic biting of the lateral border of the tongue.

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White Lesions

Fig. 1.31 Materia alba deposition on the alveolar mucosa of the maxilla.

1.14 Fordyce’s Granules Definition: Fordyce’s granules are ectopic sebaceous glands in the oral mucosa. Etiology: Developmental. It is a normal anatomical variation. Clinical features: Clinically, Fordyce’s granules appear as multiple small, asymptomatic, slightly raised, whitish-yellow well-circumscribed spots that rarely coalesce, forming plaques (▶ Fig. 1.32 and ▶ Fig. 1.33). The vermilion border of the upper lip, commissures, buccal mucosa, and the retromolar region, usually in a symmetrical bilateral pattern, are the sites of predilection. Characteristically, the granules become more evident when the mucosa is stretched. The diagnosis is exclusively based on the clinical features. Differential diagnosis: Candidiasis, lichen planus, and leukoplakia. Treatment: No treatment is required.

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1.14 Fordyce’s Granules

Fig. 1.32 Fordyce’s granules in the buccal mucosa.

Fig. 1.33 Sizeable Fordyce’s granule of the upper lip.

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1.15 Leukoedema Definition: Leukoedema is a common normal anatomical variation. Etiology: It is caused by the increased thickness of the epithelium and intracellular edema of the spinous layer cells. Clinical features: Clinically, the oral mucosa presents as opalescent or grayishwhite with a slightly wrinkled surface, which characteristically disappears when the mucosa is everted and stretched (▶ Fig. 1.34 and ▶ Fig. 1.35). Leukoedema has a normal consistency on palpation. It usually occurs bilaterally on the buccal mucosa, and rarely on the lateral aspects of the tongue and lips. The diagnosis is exclusively made on clinical grounds. Differential diagnosis: Chronic biting, candidiasis, lichen planus, leukoplakia, hairy leukoplakia, cinnamon contact stomatitis, white sponge nevus, and hereditary benign intraepithelial dyskeratosis. Treatment: No treatment is required.

1.16 White Sponge Nevus Definition: White sponge nevus or Cannon’s disease is a relatively rare genetic disease. Etiology: Genetic. It is inherited as an autosomal dominant trait and mutation in the genes encoding keratin 4 and 13. Clinical features: Clinically, it appears as bilateral asymptomatic, white or gray-white thick, lesions with multiple furrows and a spongy texture (▶ Fig. 1.36). The buccal mucosa, tongue, floor of the mouth, soft palate, and labial mucosa are the most commonly affected sites, although lesions may also develop in the vaginal, rectal, nasal, and laryngeal mucosa. The diagnosis is based on the history, clinical features, and histologic examination. Laboratory tests: Biopsy and histologic examination. Differential diagnosis: Leukoedema, chronic biting, leukoplakia, dyskeratosis congenita, pachyonychia congenita, focal palmoplantar and oral mucosa hyperkeratosis syndrome, and hereditary benign intraepithelial dyskeratosis. Treatment: No treatment is required.

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1.16 White Sponge Nevus

Fig. 1.34 Leukoedema of the buccal mucosa.

Fig. 1.35 Leukoedema of the tongue.

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Fig. 1.36 White sponge nevus, lesions on the buccal mucosa.

1.17 Dyskeratosis Congenita Definition: Dyskeratosis congenita, or Zinsser–Engman–Cole, syndrome is an uncommon disorder with great genetic heterogeneity. Etiology: Genetic. It is usually transmitted via an X-linked trait and rarely via an autosomal dominant and autosomal recessive trait. Clinical features: Clinically, dyskeratosis congenita is characterized by hyperpigmentation, telangiectasias, and atrophic skin areas, primarily on the neck, chest, and upper arms (▶ Fig. 1.37). Dystrophic nails, hyperhidrosis of palms and soles, skin and mucosal bullae, chronic blepharitis, continuous lacrimation, anemia, leukopenia, thrombopenia, pulmonary and gastrointestinal disorders, mental retardation, and oral lesions may occur. The oral lesions consist of recurrent blisters, epithelial atrophy, and leukoplakia (▶ Fig. 1.38). Malignant transformation of leukoplakia may occur. Dental anomalies may be observed. Increased risk for malignancies is possible. The diagnosis is based on the history and clinical features.

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1.17 Dyskeratosis Congenita

Fig. 1.37 Dyskeratosis congenita, pigmentation, and atrophy of the skin.

Fig. 1.38 Dyskeratosis congenita, leukoplakia on the dorsum of the tongue.

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White Lesions

Laboratory tests: Histopathologic examination if complications are suspected. Differential diagnosis: White sponge nevus, pachyonychia congenita, epidermolysis bullosa, graft versus host disease, leukoplakia, and lichen planus. Treatment: Supportive. The management of the disease requires multidisciplinary care.

1.18 Pachyonychia Congenita Definition: Pachyonychia congenita is an uncommon genodermatosis. Etiology: Genetic. The disorder is inherited in an autosomal dominant pattern. It is classified into two major types: type I (Jadassohn–Lewandowsky) and type II (Jackson–Lawler), depending on the affected gene. Clinical features: Clinically, the disorder is characterized by symmetrical nail thickening (▶ Fig. 1.39), palmoplantar hyperkeratosis, hyperhidrosis, blister formation on the soles, follicular keratosis, hoarseness, dyspnea, and oral lesions. The oral lesions appear at birth or shortly thereafter and only in type I of the disorder. The oral mucosa appears as thick, white or grayish-white asymptomatic plaques, usually on the buccal mucosa, tongue, palate, and gingiva (▶ Fig. 1.40). The diagnosis is based on the history and clinical features. Differential diagnosis: Dyskeratosis congenita, focal palmoplantar and oral mucosa hyperkeratosis syndrome, white sponge nevus, hereditary benign intraepithelial dyskeratosis, and leukoplakia. Treatment: The treatment is symptomatic.

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1.18 Pachyonychia Congenita

Fig. 1.39 Pachyonychia congenita, thickening of the toe nails.

Fig. 1.40 Pachyonychia congenita, hyperkeratosis of the buccal mucosa.

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1.19 Focal Palmoplantar and Oral Mucosa Hyperkeratosis Syndrome Definition: It is a rare mucocutaneous disorder. Etiology: Genetic. It is inherited in an autosomal dominant trait. Clinical features: Clinically, the disorder is characterized by focal hyperkeratosis at the weight-bearing and pressure-related areas of the palms and soles (▶ Fig. 1.41) and the oral mucosa, mainly the attached gingiva (▶ Fig. 1.42), and less frequently at other oral regions (e.g., palate, lateral border of the tongue, and retromolar area). The oral manifestations present as white hyperkeratotic plaques (leukoplakia). Nail thickening and hyperhidrosis may occur. The lesions usually develop in early childhood and the diagnosis is based on the history and clinical features. Differential diagnosis: Pachyonychia congenita, dyskeratosis congenita, white sponge nevus, focal palmoplantar hyperkeratosis, and leukoplakia. Treatment: The treatment is symptomatic. Systemic retinoids may be helpful for skin lesions.

1.20 Mucosal Horn Definition: Mucosal horn is a rare benign lesion of the oral mucosa analogous to cutaneous horn. Etiology: The cause is keratin accumulation. Clinical features: Clinically, mucosal horn appears as straight or slightly convex keratin projection of few millimeters to 1 cm or more in length with characteristic white color (▶ Fig. 1.43). Similar lesions can be observed on the glans penis and the skin. The cutaneous horn usually occurs on the face (▶ Fig. 1.44). The diagnosis is based on the clinical features and should rarely be confirmed histologically. Laboratory tests: Histopathologic examination.

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1.20 Mucosal Horn

Fig. 1.41 Focal palmoplantar and oral mucosa hyperkeratosis syndrome, hyperkeratosis of the fingers, and thickening of the nails.

Fig. 1.42 Focal palmoplantar and oral mucosa hyperkeratosis syndrome, leukoplakia of the maxillary attached gingiva.

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Fig. 1.43 Mucosal horn on the lingual mucosa.

Differential diagnosis: Papilloma, verruca vulgaris, condyloma accuminatum, leukoplakia, and squamous cell carcinoma. Treatment: The treatment of choice is conservative surgical excision.

1.21 Papilloma See also sections 6.1 and 8.1.1. Definition: It is a benign tumor of the oral mucosa. Etiology: The exact etiology is unknown. In 50 to 60% of papillomas, HPV types 6 and 11 are detected within the lesion. Clinical features: Clinically, papilloma presents as an asymptomatic exophytic, well-circumscribed, pedunculated or sessile tumor with multiple, small finger-like projections that give it a cauliflower-like pattern with white or pale pick or even normal mucosal color (▶ Fig. 1.45). The papilloma is usually solitary, with a size of 0.5 to 1 cm. The soft palate, tongue, and buccal mucosa are the sites of predilection. The clinical diagnosis should be confirmed by histologic examination. Laboratory tests: Histopathologic examination.

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1.21 Papilloma

Fig. 1.44 Cutaneous horn on the skin of the cheek.

Fig. 1.45 Papilloma on the lateral aspect of the tongue.

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Differential diagnosis: Verruca vulgaris, condyloma accuminatum, sialadenoma papilliferum, verruciform xanthoma, verrucous carcinoma, focal epithelial hyperplasia, and focal dermal hypoplasia syndrome. Treatment: The treatment of choice is surgical excision.

1.22 Verrucous Carcinoma Definition: Verrucous carcinoma is a low-grade variant of squamous cell carcinoma. Etiology: The exact etiology is unknown. Smoking and HPV types 16, 18, and 33 are involved in the pathogenesis. Clinical features: Clinically, verrucous carcinoma presents as a slowly growing, painless, exophytic mass with a characteristic cauliflower-like whitish surface (▶ Fig. 1.46). The size ranges from 1 cm to several centimeters if left untreated. The buccal mucosa, tongue, palate, and alveoral mucosa are the most common sites of involvement. The tumor more frequently affects males than females (ratio 2:1) older than 60 years of age. The clinical diagnosis should be confirmed histologically. Laboratory tests: Histopathologic examination. Differential diagnosis: Papilloma, verrucous hyperplasia, verrucous leukoplakia, verruciform xanthoma, squamous cell carcinoma, and white sponge nevus. Treatment: The treatment of choice is surgical excision.

1.23 Squamous Cell Carcinoma See also sections 2.9, 5.16, 6.7, and 8.2.1. Definition: It is the most common malignant neoplasm of the oral cavity and accounts for 95% of oral malignancies. Etiology: The exact etiology remains unknown. However, many intrinsic and extrinsic factors have been implicated. The most important are smoking, alcohol consumption, chemicals, HPV types 16 and 18, diet, sunlight exposure (lips), immunodeficiency, oncogenes, and tumor suppressor genes. Clinical features: Squamous cell carcinoma presents with a great clinical polymorphism. In about 5 to 8% of cases, it appears in the early stages as an asymptomatic white irregular plaque similar to leukoplakia (▶ Fig. 1.47). The clinical diagnosis should be confirmed by biopsy and histologic examination.

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1.23 Squamous Cell Carcinoma

Fig. 1.46 Early verrucous carcinoma on the dorsum of the tongue.

Fig. 1.47 Early squamous cell carcinoma, mimicking leukoplakia, on the lower gingiva.

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Laboratory tests: Histopathologic examination. Differential diagnosis: Verrucous carcinoma, leukoplakia, papilloma, verruca vulgaris, and verruciform xanthoma. Treatment: Surgical excision with or without radiotherapy and/or chemotherapy.

1.24 Skin and Mucosal Grafts Definition: Skin and mucosal grafts are often utilized in the mouth to cover mucosal defects after extensive surgery for benign and more frequently for malignant tumors, or as free gingival graft. Clinical features: Clinically, both skin and mucosal grafts usually present as a whitish or gray-white plaque (▶ Fig. 1.48). Occasionally, the color of the skin graft is black, due to melanin overproduction. If the skin graft contains hair follicles, it may develop hair in the oral cavity. The tongue, buccal mucosa, palate, gingiva, and alveoral mucosa are the most common sites where either grafts are placed. The diagnosis is based on the history and clinical features. Differential diagnosis: Leukoplakia, traumatic scar, epidermolysis bullosa, and benign tumors. Treatment: No treatment is required.

1.25 Epithelial Peeling Definition: Epithelial peeling or epitheliolysis is a relatively common superficial desquamation of the oral mucosa. Etiology: It is usually caused by the direct irritating effect of toothpastes that contain sodium lauryl sulfate or pyrophosphates. The same phenomenon may be associated with chlorhexidine mouthwash, while, occasionally, the lesions are idiopathic. Clinical features: Clinically, epithelial peeling appears as a superficial, asymptomatic white membrane or plaque or dots that can be easily detached from the oral mucosa (▶ Fig. 1.49 and ▶ Fig. 1.50). The buccal mucosa and the mucobuccal folds are more frequently affected. The lesions usually disappear when patients stop using the causative mouthwash or toothpaste. The diagnosis is based on the history and clinical features.

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1.25 Epithelial Peeling

Fig. 1.48 Skin graft on the lateral border of the tongue.

Fig. 1.49 Epithelial peeling.

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Differential diagnosis: Chronic biting, candidiasis, cinnamon contact stomatitis, thermal or chemical burn, and leukoedema. Treatment: No treatment is necessary other than cessation of the causative agents.

Fig. 1.50 Epithelial peeling.

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2 Red Lesions Red lesions are a large, heterogeneous group of disorders of the oral mucosa. Traumatic lesions, infections, developmental anomalies, allergic reactions, immunologically mediated diseases, premalignant lesions, malignant neoplasms, and systemic diseases are included in this group. The red color of the lesions may be due to thin epithelium, inflammation, dilatation of blood vessels or increased numbers of blood vessels and extravasation of blood into the oral soft tissues.

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Traumatic Hematoma

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Contact Allergic Stomatitis

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Thermal Burn

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Gonococcal Stomatitis

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Radiation Oral Mucositis

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Hemangioma

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Oral Lesions Secondary to Fellatio and Cunnilingus

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Angiolymphoid Hyperplasia with Eosinophilia

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Geographic Tongue

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Lupus Erythematosus

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Denture Stomatitis

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Hereditary Hemorrhagic Telangiectasia

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Candidiasis Erythematous

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Iron Deficiency Anemia

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Erythroplakia

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Thrombocytopenia

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Squamous Cell Carcinoma

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Infectious Mononucleosis

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Plasma Cell Gingivitis

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Reactive Arthritis

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Granulomatous Gingivitis

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Psoriasis

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Desquamative Gingivitis

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Sturge–Weber Angiomatosis

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Linear Gingival Erythema

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Peripheral Ameloblastoma

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2.1 Traumatic Hematoma Definition: Traumatic hematoma occurs when a mechanical injury results in hemorrhage within the oral tissues. Etiology: Mechanical forces, usually biting of the oral mucosa or careless use of dental and surgical instruments. Clinical features: Clinically, traumatic hematoma appears as an irregular, usually flat and painless area, with a bright or deep red color (▶ Fig. 2.1). The size may vary from 1 cm to several centimeters. The lips, tongue, and buccal mucosa are the most commonly affected areas. Patients under anticoagulant therapy can be at risk of developing hematomas. The diagnosis is exclusively based on the history and clinical features. Differential diagnosis: Hematoma due to anticoagulants, thrombocytopenia, thrombasthenia, and vascular malformations. Treatment: Usually no treatment is required as the lesion resolves spontaneously. However, in large hematomas, high doses of ascorbic acid (e.g., 2–3 g/d for about 1 week) may reduce the time of resolution.

2.2 Thermal Burn Definition: Thermal burn to the oral mucosa is a relatively common incident. Etiology: Contact with very hot foods, particularly melted cheese, hot liquids, and metal objects are the most common causes. Clinical features: Clinically, thermal oral burn appears as a painful erythematous area that may undergo desquamation, leaving superficial erosions (▶ Fig. 2.2). The lesions heal spontaneously in about 1-week time. The diagnosis is exclusively based on the history and clinical features. Differential diagnosis: Chemical burn, traumatic lesions, drug reactions, secondary herpes simplex, aphthous ulcers, erosive lichen planus, and mucous membrane pemphigoid. Treatment: No treatment is required as the lesion heals spontaneously in about 4 to 6 days.

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2.2 Thermal Burn

Fig. 2.1 Traumatic hematoma of the lower lip.

Fig. 2.2 Thermal burn of the palate caused by pizza.

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2.3 Radiation Oral Mucositis Definition: Oral radiation mucositis is a common complication of radiation therapy usually for head and neck tumors. Etiology: Radiation for the therapeutic purpose may also cause changes or damage of the normal tissues, particularly those with a high cellular turnover such as oral mucosa, salivary glands, and bone. Clinical features: Oral mucositis is the most common complication during or after radiation therapy of the head and neck area. The oral lesions are classified as acute (early) and chronic (late). Acute mucositis usually occurs at the end of the first week of therapy and clinically presents as diffuse erythema and edema of the oral mucosa associated with a burning sensation or pain (▶ Fig. 2.3). Soon after, erosions or ulcerations may develop, covered by a whitish-yellow exudate. Dry mouth, loss of taste, burning sensation, and pain are common symptoms. The diagnosis is based on the history and clinical features. Differential diagnosis: Mucositis due to chemotherapy, mucositis following stem cell transplant, drug reactions, bisphosphonates and monoclonal antibodies, erythema multiforme, herpetic stomatitis, erosive lichen planus, mucous membrane pemphigoid, pemphigus, and leukemia. Treatment: Prevention of the oral complication to radiation therapy includes high level of oral hygiene, dental and periodontal care, and cessation of smoking and alcohol. The treatment of oral mucositis includes local use of anesthetics, topical corticosteroids and tacrolimus, oxygen-releasing mouthwashes, and saliva substitutes. Systemic corticosteroids in a low dose (e.g., 20–30 mg/d prednisolone) for 2 to 3 weeks in combination with high doses of B-complex vitamins relieve the signs and symptoms.

2.4 Oral Lesions Secondary to Fellatio and Cunnilingus Definition: Fellatio and cunnilingus are ways of practicing oral sex. Etiology: Orogenital sex, sucking, negative pressure, and mechanical irritation from the teeth are the causes of fellatio and cunnilingus. Clinical features: Clinically, the lesions due to fellatio appear as asymptomatic petechiae, erythema, and ecchymoses at the junction of the hard and soft palate and the uvula (▶ Fig. 2.4). The oral lesions due to cunnilingus appear as a

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2.4 Oral Lesions Secondary to Fellatio and Cunnilingus

Fig. 2.3 Radiation mucositis, severe erythema of the gingiva, and the alveolar mucosa.

Fig. 2.4 Fellatio, erythema of the palate.

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Red Lesions superficial erosion and erythema at the lingual frenum (▶ Fig. 2.5). The lesions from both practices disappear spontaneously in 5 to 8 days. The diagnosis is based on the history and clinical features. Differential diagnosis: Traumatic lesions, thermal burn, erythematous candidiasis, infectious mononucleosis, thrombocytopenic purpura, secondary herpetic lesions, and leukemia. Treatment: Usually no treatment is required as the lesions resolve spontaneously.

2.5 Geographic Tongue See also section 13.2. Definition: It is a relatively common benign disorder, affecting the tongue and rarely other sites of the mouth. Etiology: The exact etiology is unknown, but an inherited gene pattern is possible. Clinical features: It presents, usually, as multiple, and rarely as solitary, welldemarcated patches of erythema surrounded by a thin raised, whitish border (▶ Fig. 2.6). Characteristically, the lesions persist for a few days or weeks and disappear, and then develop in another or the same area. The dorsum and the lateral borders of the tongue are the sites of predilection, but rarely lesions may appear at other mucosal sites (geographic stomatitis). The diagnosis is based on the history and on clinical features. Differential diagnosis: Oral psoriasis, reactive arthritis, candidiasis, plasma cell stomatitis, idiopathic dipapillation of filiform papillae, mucous patches of secondary syphilis, drug reactions, and cinnamon contact stomatitis. Treatment: No treatment is required.

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2.5 Geographic Tongue

Fig. 2.5 Cunnilingus, erosions on the frenum of the tongue.

Fig. 2.6 Geographic tongue.

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2.6 Denture Stomatitis Definition: Denture stomatitis is a common benign disorder in people who wear dentures for a long period of time. Etiology: Mechanical irritation from ill-fitting dentures, Candida albicans, or/ and other microorganisms living beneath the dentures, and poor denture hygiene are the causes. Clinical features: Clinically, the mucosa beneath the denture is edematous and erythematous with or without whitish spots that represent accumulation of food remnants or/and hyphae of Candida (▶ Fig. 2.7). The mucosal surface may be smooth, granular, or nodular and it is almost always confined in the denture bearing area, usually, of the maxilla. The disorder is usually asymptomatic, but rarely a burning sensation may occur. The diagnosis is based on the clinical features. Differential diagnosis: Allergic contact reaction due to acrylic monomer, candidiasis, and papillary palatal hyperplasia. Treatment: Improvement of denture fit, good oral and denture hygiene, and antifungal drugs if a C. albicans infection exists.

2.7 Candidiasis Erythematous See also section 1.11. Definition: It is a relatively common type of candidiasis. Etiology: C. albicans and rarely other Candida species. Clinical features: Erythematous candidiasis is classified as acute and chronic. It is highly prevalent in human immunodeficiency virus (HIV)-infected people, usually not receiving antiretroviral therapy (ART), but may, less frequently, develop in patients receiving broad-spectrum antibiotics, systemic corticosteroids, or other immunosuppressive agents for long time. Clinically, erythematous candidiasis appears as erythematous patches that have a predilection for the dorsum of the tongue and palate (▶ Fig. 2.8). The patients may complain of a burning sensation and dry mouth. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination and microbiological examination and culture.

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2.7 Candidiasis Erythematous

Fig. 2.7 Denture stomatitis, erythema, and edema of the palate with C. albicans infection.

Fig. 2.8 Erythematous candidiasis on the dorsum of the tongue.

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Differential diagnosis: Erythroplakia, fellatio, median rhomboid glossitis, denture stomatitis, cinnamon contact stomatitis, mucous patches of secondary syphilis, and thermal and chemical burn. Treatment: Systemic fluconazole or itraconazole 100 mg/d for 15 to 30 days or more.

2.8 Erythroplakia Definition: Erythroplakia is a high risk, potentially malignant disorder (precancerous lesion) of the oral mucosa. Etiology: The exact etiology is not well known. However, the factors that relate to leukoplakia (e.g., tobacco, alcohol, human papillomavirus [HPV] types 16 and 18, and others) are also involved in the pathogenesis of erythroplakia. Clinical features: Clinically, erythroplakia presents as an asymptomatic, fiery red, patch or plaque, with a smooth and velvety surface (▶ Fig. 2.9 and ▶ Fig. 2.10). The red lesions may be associated with white spots or small plaques. The most commonly affected sites are the buccal mucosa, palate, floor of the mouth, lateral aspects of the tongue, and retromolar area. Erythroplakia mainly involves the glans penis and rarely the oral mucosa. The lesion equally affects both sexes from 50 to 70 years. Over 90% of erythroplakias, histologically, demonstrate severe epithelial dysplasia, or carcinoma in situ, or early invasive squamous cell carcinoma at the time of diagnosis. The clinical diagnosis should be confirmed by a biopsy and histologic examination. Laboratory tests: Histopathologic examination. Differential diagnosis: Erythematous candidiasis, cinnamon contact stomatitis, early squamous cell carcinoma, erosive lichen planus, discoid lupus erythematosus, plasma cell stomatitis, plasmacytoma, reactive arthritis, and media rhomboid glossitis. Treatment: The treatment of choice is surgical excision. Smoking and alcohol cessation is strongly recommended.

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2.8 Erythroplakia

Fig. 2.9 Erythroplakia on the palate.

Fig. 2.10 Erythroplakia in conjunction with leukoplakia on the lateral border of the tongue.

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2.9 Squamous Cell Carcinoma See also sections 1.23, 5.16, 6.7, and 8.21. Definition: Squamous cell carcinoma is the most common malignancy of the mouth. Etiology: The exact etiology is unknown. However, smoking, alcohol, oncogenic viruses, mainly HPV 16 and 18, oncogenes and tumor suppressor genes are the most important factors that may be involved in the pathogenesis. Clinical features: Clinically, squamous cell carcinoma appears with a wide polymorphism. In the early stage, it may appear as an asymptomatic, atypical red patch frequently associated with white lesions (▶ Fig. 2.11 and ▶ Fig. 2.12). The clinical diagnosis should be confirmed by a biopsy and laboratory test. Laboratory tests: Histopathologic examination. Differential diagnosis: In the red pattern of the disease, the differential diagnosis includes erythroplakia, erythematous candidiasis, traumatic irritation, cinnamon contact stomatitis, contact reactions to dental material, secondary syphilis, and plasma cell stomatitis. Treatment: The treatment of choice is radical surgical excision.

2.10 Plasma Cell Gingivitis Definition: Plasma cell gingivitis is a rare, specific gingival disorder, histopathologically, characterized by dense plasma cell infiltration of the lamina propria. Etiology: The exact cause is unknown. However, it is believed the disorder to represent a hypersensitivity reaction to local allergens (e.g., chewing gum, ingredients in toothpastes, foods, mint, cinnamon flavoring, and pepper) and plasma cell dyscrasias. Clinical features: Clinically, both free and attached gingiva are bright red and edematous with loss of normal stippling. The lesions can be localized or generalized and are usually accompanied by a burning and itching sensation (▶ Fig. 2.13). Similar lesions have been described on edentulous areas, tongue, and lips. The disease equally affects both sexes, usually from 20 to 40 years of age. It can last for several months or even years, resists to treatment, and tends to relapse. The clinical diagnosis should be confirmed by a biopsy and laboratory tests.

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2.10 Plasma Cell Gingivitis

Fig. 2.11 Early squamous cell carcinoma on the dorsum of the tongue with leukoplakia at the periphery.

Fig. 2.12 Early squamous cell carcinoma on the lateral border of the tongue.

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Laboratory tests: Histopathologic and histochemic examination, and immunoelectrophoresis. Differential diagnosis: Desquamative gingivitis, granulomatous gingivitis, chronic plaque-related gingivitis, linear gingival erythema, gingival plasmacytoma, erythematous candidiasis, erythroplakia, oral psoriasis, and leukemia. Treatment: There is no specific therapy. Topical or systemic corticosteroids are the first line of treatment. Patients should be instructed to keep a dietary history that records any food intake.

2.11 Granulomatous Gingivitis Definition: Granulomatous gingivitis is a rare and unique form of gingivitis with a specific histopathologic pattern. Etiology: The exact etiology remains unknown. Foreign body reaction, local bacterial or fungal infection, and reactions to food additives may be the cause. In several occasions, it represents a local manifestation of a systemic granulomatous disease such as Crohn’s disease, Melkersson–Rosenthal syndrome, sarcoidosis, and tuberculosis. However, cases without association with local or systemic disease may occur (idiopathic). Clinical features: Clinically, granulomatous gingivitis appears as a diffuse erythematous and edematous area of the free and attached gingiva including the interdental papillae (▶ Fig. 2.14). The lesions may be localized or generalized and are associated with tenderness during mastication and tooth brushing. In cases of systemic granulomatous disease, other areas of the mouth may be involved. The disorder can affect both sexes at any age although it is more frequent in adulthood. The clinical diagnosis should be confirmed by biopsy and laboratory tests. Laboratory tests: Histopathologic examination. Specific stains for microorganisms are negative. Differential diagnosis: Orofacial granulomatosis, plaque-related gingivitis, linear gingival erythema, candidiasis, erythroplakia, non-Hodgkin’s lymphoma, gingival plasmacytoma, and cinnamon contact stomatitis. Treatment: Local or systemic corticosteroids are the first line of treatment. If granulomatous gingivitis is part of systemic granulomatous disease, the treatment is the same. If a foreign body is detected, local excision is recommended.

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2.11 Granulomatous Gingivitis

Fig. 2.13 Plasma cell gingivitis, localized.

Fig. 2.14 Granulomatous gingivitis, localized.

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2.12 Desquamative Gingivitis Definition: Desquamative gingivitis is not an independent disease entity, but is a clinical descriptive term used for nonspecific gingival manifestation of several chronic mucocutaneous diseases. Etiology: In the majority of cases, an autoimmune mechanism is responsible. Mucous membrane pemphigoid and lichen planus are frequently related to it. Less frequently, bullous pemphigoid, pemphigus vulgaris, linear lgA disease, epidermolysis bullosa acquisita, chronic ulcerative stomatitis, erythema multiforme, discoid lupus erythematosus, and oral psoriasis may be the underlying disease entity. Clinical features: Clinically, desquamative gingivitis is characterized by erythema, edema, and painful erosions of the marginal and attached gingiva, predominantly labially and buccally (▶ Fig. 2.15 and ▶ Fig. 2.16). Spontaneous desquamation of the gingival epithelium and blister formation are common. A characteristic sign is peeling of the epithelium or hemorrhagic blister formation after mild friction of the gingiva. The gingival lesions may be either localized or generalized. Desquamative gingivitis may be the only oral manifestation, or may be associated with additional oral lesions of the underlying chronic mucocutaneous disease. Females over 40 years of age are more frequently affected. The disorder does not have a direct impact on the periodontal tissues. However, indirectly, poor oral and gingiva hygiene due to discomfort and pain may be the background for the development of periodontal disease. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic immunofluorescences.

examination,

direct

and

indirect

Differential diagnosis: Includes all the mucocutaneous diseases that may be the underlying entities, granulomatous gingivitis, plasma cell gingivitis, necrotizing ulcerative gingivitis, drug-induced gingivitis and stomatitis, and plaquerelated gingivitis. Treatment: Good oral hygiene, avoidance of any mechanical pressure on the gingiva. Topical or systemic corticosteroids or other immunosuppressants are the drugs of choice.

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2.12 Desquamative Gingivitis

Fig. 2.15 Desquamative gingivitis as a manifestation of lichen planus.

Fig. 2.16 Desquamative gingivitis as a manifestation of lichen planus.

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2.13 Linear Gingival Erythema Definition: Linear gingival erythema is a rare gingival disorder usually following HIV infection. Etiology: The exact etiology remains unclear. However, an association with Candida infection is common. Clinical features: Clinically, linear gingival erythema presents as a fiery red band (2–4 mm) along the margin of the gingiva and a punctate or diffuse erythema of the attached gingiva (▶ Fig. 2.17). The disorder may be localized or generalized. Gingival bleeding may, rarely, occur spontaneously or on probing. The disorder does not respond to plaque control measures or root planing and scaling. In the pre-ART era, it was diagnosed in 5 to 10% of HIV-infected patients, while nowadays it seems to be rare. The diagnosis is mainly based on the history, clinical features, and laboratory tests for HIV infection. Laboratory tests: There is no specific diagnostic test for the gingival disorder. Differential diagnosis: Plaque-related gingivitis, plasma cell gingivitis, granulomatous gingivitis, desquamative gingivitis, cinnamon contact gingivitis, and candidiasis. Treatment: High level of oral hygiene and plaque control measures. Systemic antifungals drugs such as fluconazole or itraconazole are, usually, helpful.

2.14 Contact Allergic Stomatitis Definition: Contact allergic stomatitis is a relatively rare, acute, or chronic condition compared to the analogous skin reactions. Etiology: Denture base materials, restorative dental materials, mouthwashes, dentifrices, chewing gums, sweets, foods, drinks, and other substances may be the cause. Clinical features: Clinically, a burning sensation or pain, associated with erythema and edema are the most common symptoms and signs (▶ Fig. 2.18). Rarely, small vesicles, superficial erosions, and hyperkeratotic white lesions are present. The disorder may be acute or chronic. The diagnosis is based on the history, clinical features, and laboratory tests. Laboratory tests: Mucosal and skin patch tests.

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2.14 Contact Allergic Stomatitis

Fig. 2.17 Linear gingival erythema.

Fig. 2.18 Allergic stomatitis following contact with mint-containing chewing gum.

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Differential diagnosis: Denture stomatitis, cinnamon contact stomatitis, erythematous candidiasis, erythroplakia, plasma cell stomatitis, and druginduced oral lesions. Treatment: Removal of suspected allergens, topical or systemic corticosteroids in low dose (e.g., prednisolone 10–20 mg/d for about 7–10 days) are helpful.

2.15 Gonococcal Stomatitis Definition: Gonococcal stomatitis is a rare manifestation of gonococcal infection. Etiology: It is caused by the gram-negative diplococcus Neisseria gonorhoeae. The microorganism is transmitted after direct orogenital sex (e.g., fellatio and cunnilingus). Clinical features: Gonorrhea is the most common sexually transmitted disease. Primarily involves the mucous membranes of genital tract, anus, rectum, and rarely the pharynx and the oral mucosa. Gonococcal stomatitis presents without specific clinical signs. Clinically, the oral mucosa is fiery red and edematous with or without superficial erosions covered with a grayish or yellowish pseudomembrane (▶ Fig. 2.19 and ▶ Fig. 2.20). The patient usually complains of burning, itching, and sore throat, while asymptomatic cases may also occur. The pharyngeal area, tonsils, uvula, and soft and hard palate are the most frequently affected areas. Rarely, lesions may appear on the buccal mucosa, tongue, and gingiva. Submandibular and cervical lymph node enlargement may occur. The diagnosis is based on the history and clinical features, but should be confirmed by microbiological examination. Laboratory tests: Identification of microorganisms by Gram’s stain, or culture, or molecular biological techniques. Differential diagnosis: Streptococcal stomatitis, herpetic stomatitis, herpangina, erythematous candidiasis, cinnamon contact stomatitis, infectious mononucleosis, and erythroplakia. Treatment: The oral lesions are frequently self-limited, and the colonization usually disappears within 2 to 3 months. Third-generation cephalosporins are the drugs of choice.

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2.15 Gonococcal Stomatitis

Fig. 2.19 Gonococcal stomatitis, intense redness of the mucous membrane of the palate and the uvula.

Fig. 2.20 Gonococcal stomatitis, redness, and erosions on the gingival and the alveolar mucosa.

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2.16 Hemangioma Definition: Hemangioma is a relatively common, benign, vascular tumor of infancy and childhood classified in the spectrum of vascular tissue anomalies. Etiology: It is due to endothelial cell proliferation. Clinical features: Clinically and histologically, hemangiomas are divided into three forms: superficial (capillary), deep (cavernous), and mixed. The superficial form consists of multiple, small capillaries and clinically presents as a flat or slightly elevated red macule or plaque (▶ Fig. 2.21). The deep cavernous form consists of large vascular, blood-filled spaces and clinically presents as an elevated tumor of deep red or brown-red color (▶ Fig. 2.22). The size varies between a few to many centimeters and may grow to cause organ deformity. A characteristic clinical sign of hemangioma is that the red color, usually, disappears on pressure and reappears when the pressure is released. The most frequently affected oral sites are the lips, tongue, palate, and gingiva. The diagnosis is mainly based on the history and clinical features. Laboratory test: Histopathologic examination. Because of high risk for bleeding, biopsy is suggested only at a hospital environment. Differential diagnosis: Vascular malformations, pyogenic granuloma, lymphangioma, traumatic hematoma, leiomyoma, hemangioendothelioma, hemangiopericytoma, Kaposi’s sarcoma, and pigmented lesions. Treatment: Surgical excision, laser, cryotherapy, embolization, and sclerotherapy. Some superficial hemangiomas regress spontaneously, particularly on the skin, but rarely on the mouth.

2.17 Angiolymphoid Hyperplasia with Eosinophilia Definition: Angiolymphoid hyperplasia with eosinophilia or epithelioid hemangioma is a rare, benign, reactive, vascular anomaly described in 1969. Etiology: The exact etiology is unknown, although trauma is believed to be the cause.

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2.17 Angiolymphoid Hyperplasia with Eosinophilia

Fig. 2.21 Capillary hemangioma on the gingiva.

Fig. 2.22 Cavernous hemangioma on the lower lip.

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Clinical features: Clinically, the disorder appears as a red or red-brown, usually painless, small nodule or plaque (▶ Fig. 2.23). Intraoral lesions are rare and may develop on the lips, buccal mucosa, tongue, palate, and gingiva. The lesion is common on the skin of the head and neck, more frequently in females from 30 to 50 years of age. Other, rare, locations include the muscles, salivary glands, and bones. The diagnosis is exclusively based on the histologic pattern. Laboratory test: Histopathologic examination. Differential diagnosis: Superficial hemangioma, benign lymphoid hyperplasia, pyogenic granuloma, early Kaposi’s sarcoma, angiosarcoma, hemangioendothelioma, Kimura’s disease, non-Hodgkin’s lymphoma, and early squamous cell carcinoma. Treatment: The treatment of choice is conservative surgical excision.

2.18 Lupus Erythematosus Definition: Lupus erythematosus is an autoimmune disease affecting multiple systems. Etiology: Genetic and environmental factors have been implicated in initiating and establishing the pathogenesis. Clinical features: The disease has a very broad spectrum of clinical manifestations with the cutaneous form at one side, the systemic form at the other side and multiple variants between the two. Cutaneous lupus is classified into three major forms: acute, subacute, and chronic. The chronic type is the most common and includes discoid lupus erythematosus and four further subtypes. The oral mucosa is mainly involved in the discoid (15–25%) and systemic (30–50%) forms. Clinically, in discoid form the oral lesions appear as a well-defined, erythematous, central area surrounded by a sharp elevated border of irradiating whitish striae (▶ Fig. 2.24). Telangiectasias, petechiae, erosions or ulcers, white hyperkeratotic dots or plaques, and atrophic scarring may be seen (▶ Fig. 2.25). The buccal mucosa, lips, palate, gingiva, and tongue are the most frequently affected sites. The oral lesions may be associated with arthralgias

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2.18 Lupus Erythematosus

Fig. 2.23 Angiolymphoid hyperplasia with eosinophilia presenting as a red plaque on the lower gingiva.

Fig. 2.24 Discoid lupus erythematosus, erythematous plaque on the maxillary gingiva and alveolar mucosa.

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Red Lesions and skin lesions including the characteristic butterfly rash on the face (▶ Fig. 2.26). In the systemic form, the oral lesions usually present as extensive painful erosions or ulcers surrounded by a reddish or whitish zone or as red plaques (▶ Fig. 2.27). Petechiae, edema, hemorrhage, bullous eruption, xerostomia, and parotid enlargement, particularly in case of secondary Sjögren's syndrome and conjunctivitis are common clinical findings. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, direct immunofluorescence, serologic tests for anti-double stranded DNA, antinuclear (anti Smith antibodies). In addition, autoantibodies to Ro, La, U1 ribonucleoprotein, and singlestranded DNA are necessary to be positive for final diagnosis. Differential diagnosis: Lichen planus, erythroplakia, leukoplakia, mucous membrane pemphigoid, graft versus host disease, geographic glossitis and stomatitis, and secondary syphilis. Treatment: Topical or systemic steroids, antimalarians, immunosuppressants, dapsone, thalidomide, and monoclonal antibodies are the drugs of choice.

Fig. 2.25 Systemic lupus erythematosus, erythema, and ulceration on the palate.

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2.18 Lupus Erythematosus

Fig. 2.26 Discoid lupus erythematosus, facial lesions forming the characteristic “butterfly rash.”

Fig. 2.27 Systemic lupus erythematosus, lower lip enlargement accompanied by red and white lesions, and erosions.

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2.19 Hereditary Hemorrhagic Telangiectasia Definition: Hereditary hemorrhagic telangiectasia, or Osler–Weber–Rendu disease, is a relatively, rare, genetic disorder characterized by capillaries and small vessel dysplasia. Etiology: Inherited as an autosomal dominant trait. Mutations in two different genes are responsible for the disorder: ENG (endoglin), HHT1, and ALK1 (activin receptor-like kinase). These proteins seem to play a role in blood vessel maturation and vascular smooth muscle development. Clinical features: The cardinal manifestations of the disease are cutaneous, mucosal, and visceral telangiectasias. Clinically, three varieties of telangiectasias have been described: (1) microscopic lesions of less than 2 mm in diameter, (2) nodules, and (3) spider-like lesions. These lesions are round and slightly elevated, with a bright red, purple, or violet color and disappear on pressure with a glass slide and reappear straight after. The oral mucosa is frequently involved with multiple lesions, usually, on the tip and dorsum of the tongue and lips (▶ Fig. 2.28). Less frequently, the palate, buccal mucosa, and gingiva are involved (▶ Fig. 2.29). Hemorrhage from oral lesions may be spontaneous or after minimal mechanical friction and can be vigorous. Epistaxis and gastrointestinal bleeding are early and occasionally serious complications. Cutaneous telangiectasias are more common on the face and less frequent on the fingers and toes. Arteriovenous malformations and fistulas may develop in the lungs, liver, and brain. The diagnosis is mainly based on the history and clinical features. Laboratory test: Histopathologic examination is not pathognomonic. Differential diagnosis: Varicosities, multiple hemangiomas, CREST syndrome, Maffucci’s syndrome, Sturge–Weber syndrome, and Klippel–Trenaunay–Weber syndrome. Treatment: Supportive. There is no specific treatment.

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2.19 Hereditary Hemorrhagic Telangiectasia

Fig. 2.28 Hereditary hemorrhagic telangiectasia, multiple telangiectasias on the tongue.

Fig. 2.29 Hereditary hemorrhagic telangiectasia, multiple telangiectasias on the gingiva.

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2.20 Iron Deficiency Anemia Definition: Iron deficiency anemia is the most common form of anemia. Etiology: It is caused by blood loss, decreased iron intake, decreased iron absorption, disorders in the iron incorporation into the hemoglobin molecule, and increased iron demand or hemolysis. Clinical features: The spectrum of clinical manifestations is very wide and depends on the degree of the anemia. Fatigue, loss of appetite, headaches, arrythmias, pallor of the skin and mucosae, koilonychia, and neurologic disorders are the most common symptoms and signs. The oral mucosa appears atrophic, smooth, and pale or red (▶ Fig. 2.30). Angular cheilitis, glossodynia, and candidiasis are common. Rarely, leukoplakia and erosions may develop. Plummer–Vinson syndrome is a form of iron deficiency anemia. Clinically, it is characterized by anemia, dysphagia, difficulty in swallowing, and atrophy of the dorsum of the tongue. Occasionally, the tongue mucosa appears red (▶ Fig. 2.31). Plummer–Vinson syndrome is classified as a potentially malignant disorder (precancerous condition) of the oral mucosa, which predisposes the development of leukoplakia and squamous cell carcinoma. The clinical diagnosis of anemia should be confirmed by laboratory tests. Laboratory tests: Full blood count, serum ferritin of less than 12 μg/l, serum iron values decline to less than 30 μg/dL. Differential diagnosis: Other types of anemia, lichen planus, geographic tongue, avitaminoses, malnutrition disorders, myelodysplastic syndromes, and syphilitic tertiary glossitis. Treatment: The first step of treatment is identification of the cause. Ferrous sulfate or ferrous fumarate together with vitamin C is the first line of treatment.

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2.20 Iron Deficiency Anemia

Fig. 2.30 Iron deficiency anemia, atrophy, and erythema on the dorsum of the tongue.

Fig. 2.31 Plummer–Vinson syndrome, erythematous and smooth tongue, and angular cheilitis.

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2.21 Thrombocytopenia Definition: Thrombocytopenia is a hematologic disorder characterized by a reduction of the platelet count to less than 20,000 to 30,000/mm3. Etiology: The causes of thrombocytopenia are classified into four major categories: (1) decreased platelet production, (2) increased platelet destruction, (3) increased retention and inactivation of platelets, and (4) other conditions causing thrombocytopenia. Clinical features: Clinically, thrombocytopenia is characterized by spontaneous hemorrhage, petechiae, ecchymoses, and hematomas on the skin, mucosa, and other tissues and organs. The oral manifestations include gingival bleeding, petechiae, ecchymoses, and even hematomas and hemorrhagic bullae, mainly on the palate, buccal mucosa, and gingiva (▶ Fig. 2.32 and ▶ Fig. 2.33). Any teeth extraction or dental procedure with bleeding risk should be postponed until the platelet level is improved. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Bone marrow aspiration and clotting time. The level of platelets in the peripheral blood is usually less than 20,000 to 30,000/mm3. Differential diagnosis: Aplastic anemia, leukemia, agranulocytosis, myelodysplastic syndromes, polycythemia vera, and drug reactions. Treatment: The mainstay of treatment includes blood transfusion, systemic corticosteroids, intravenous immunoglobulin, and splenectomy.

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2.21 Thrombocytopenia

Fig. 2.32 Thrombocytopenia, hemorrhagic bullae on the buccal mucosa.

Fig. 2.33 Thrombocytopenia, petechiae on the maxillary gingiva and alveolar mucosa.

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2.22 Infectious Mononucleosis Definition: Infectious mononucleosis is an acute, self-limited, infectious disease that primarily affects children and young adults. Etiology: The cause is Epstein–Barr virus (or human herpesvirus 4) that is transmitted via saliva. Clinical features: Clinically, infectious mononucleosis is characterized by lowgrade fever (which persists for 1–2 weeks), headache, sore throat, malaise, generalized lymphadenopathy (mostly cervical and auricular), splenomegaly, and hepatomegaly. A maculopapular eruption, usually located on the trunk, head and neck, and the extremities appears on day 4 to 6 and last for about 1 week (▶ Fig. 2.34). The oral manifestations are common and consist of palatal petechiae, uvular edema, tonsillar exudate, gingivitis, and rarely ulcers (▶ Fig. 2.35). The signs and symptoms subside in 3 to 4 weeks. The diagnosis is usually based on the history and clinical features, but should be confirmed by laboratory tests. Laboratory tests: Monospot test (identification of serum heterophile antibodies), increased titers of Epstein–Barr virus DNA in serum. Differential diagnosis: Leukemia, secondary syphilis, diphtheria, cytomegalovirus infection, herpetic stomatitis, HIV infection, palatal erythema from fellatio, and traumatic palatal hematoma. Treatment: Symptomatic. The disease is self-limited.

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2.22 Infectious Mononucleosis

Fig. 2.34 Infectious mononucleosis. Characteristic skin lesions on the cheek associated with auricular and cervical lymphadenopathy.

Fig. 2.35 Infectious mononucleosis. Characteristic petechiae located at the border between hard and soft palate.

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2.23 Reactive Arthritis Definition: Reactive arthritis or Reiter’s syndrome is a rare multisystemic condition in response to infection that primarily affects young individuals, aged 20 to 30 years. Etiology: The exact etiology remains unknown. However, the pathogenesis is mediated by an immunological mechanism. The disease may be triggered by an infectious agent in a genetically susceptible individual, particularly those with (human leukocyte antigen) HLA-B27. Clinical features: Clinically, the classical triad is nongonococcal urethritis, arthritis, and conjunctivitis, in addition to mucocutaneous lesions. Oral lesions occur in 20 to 30% of the patients and appear as diffuse, erythematous, areas intermixed with thin whitish dots or lines and painful superficial erosions. The tongue, palate, gingiva, buccal mucosa, and lips are the most frequently affected sites. Characteristically, on the dorsum of the tongue there is prominent erythema and loss of the filiform papillae, giving a pattern similar to that of geographic tongue (▶ Fig. 2.36). Conjunctivitis, iritis, uveitis, and keratitis may also occur. The genital lesions include balanitis circinata, urethritis, and prostatitis. The cutaneous lesions begin as vesicles and pustules to evolve in scales and hyperkeratosis (keratoderma blenorrhagicum) and most commonly affect the palms and soles (▶ Fig. 2.37). Psoriasis-like skin lesions, and onychodystrophy are common. Rare manifestations are renal, cardiac, and neurologic disorders. The diagnosis is mainly based on the clinical features as there are no specific diagnostic tests. Laboratory tests: Histopathologic examination of the mucocutaneous lesion. A blood test for HLA-B27 may also be helpful. Differential diagnosis: Psoriasis, geographic tongue and stomatitis, erythema multiforme, Adamantiades–Behçet disease, and Sneddon–Wilkinson disease. Treatment: It is symptomatic. Systemic corticosteroids, nonsteroidal anti-inflammatory agents, and sulfasalazine are the drugs of choice.

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2.23 Reactive Arthritis

Fig. 2.36 Reactive arthritis, erythema, and loss of the filiform papillae.

Fig. 2.37 Reactive arthritis, hyperkeratotic plaques on the sole.

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2.24 Psoriasis Definition: Psoriasis is a common chronic, inflammatory dermatosis. Etiology: Multifactorial with genetic, immune-mediated mechanism and several environmental factors playing an important role to the pathogenesis. Clinical features: Clinically, psoriasis appears with great polymorphism but the most common types are psoriasis vulgaris or chronic plaque, which is the most common (90%), guttate, inverse, pustular, and erythrodermic. The classical figures of psoriasis vulgaris are characterized by a symmetrical distribution of well-circumscribed, erythematous, thickening, and scaly plaques in a circular, oval, or polycircular pattern. The oral mucosa is affected in about 2 to 4% of the cases following the skin lesions, mainly in the pustular type of the disease (▶ Fig. 2.38). Clinically, oral lesions are characterized by erythema, white plaques, and circular or semicircular, white, raised lesions similar to geographic tongue. The tongue, palate, gingiva, buccal, and mucosa are most frequently affected (▶ Fig. 2.39). The clinical diagnosis of oral psoriasis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Geographic tongue and stomatitis, cinnamon contact stomatitis, candidiasis, lichen planus, reactive arthritis, and leukoplakia. Treatment: Numerous topical and systemic agents and other therapies have been tried in the treatment of psoriasis, but all of them belong to dermatologist. The treatment of oral lesions is symptomatic.

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2.24 Psoriasis

Fig. 2.38 Psoriasis, pustular type, lesions on the palm.

Fig. 2.39 Psoriasis, white lesions on the tongue similar to geographic tongue.

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2.25 Sturge–Weber Angiomatosis Definition: Sturge–Weber angiomatosis or encephalotrigeminal angiomatosis is a rare, sporadic, congenital, capillary vascular malformation typically involving areas innervated by the trigeminal nerve. Etiology: Development abnormality. Clinical features: Clinically, Sturge–Weber angiomatosis is characterized by (1) great capillary hyperplasia of the face and oral mucosa, (2) hemangiomas of the leptomeninges, (3) calcification of the brain, (4) ocular disorders, and (5) neurologic disorders (epilepsy, seizures, migraine headaches, contralateral hemiparesis, development motor delays, and mild mental retardation). Oral hemangiomas have a bright red or purple color and are usually flat but may also be raised, causing tissue enlargement (▶ Fig. 2.40). They occur in the ipsilateral side with the skin lesions. The gingiva, buccal mucosa, lips, and tongue are most frequently affected. Dentists and oral surgeons must be careful during tooth extraction and periodontal surgery in order to avoid bleeding complications. The facial hemangioma is usually unilateral, has a bright red or purple color, and characteristically, involves the trigeminal nerve region (▶ Fig. 2.41). The facial and oral hemangiomas are usually obvious at birth. The diagnosis is usually based on the history and clinical features. Laboratory tests: Histopathologic examination, MRI, MR arteriography, positron emission tomography, and single-photon emission CT are useful diagnostic tools. Differential diagnosis: Solitary hemangioma, Klippel–Trenaunay–Weber syndrome, hereditary hemorrhagic telangiectasia, and Proteus syndrome. Treatment: There is no specific treatment. Improvement of skin and oral lesions can be achieved with the use of laser.

2.26 Peripheral Ameloblastoma Definition: The peripheral or extraosseous ameloblastoma is a rare variety of the ameloblastoma that arises always in the posterior tooth-bearing mucosa. Etiology: The exact etiology is unknown. The peripheral ameloblastoma probably arises from dental lamina rests or from basal epithelial cells.

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2.26 Peripheral Ameloblastoma

Fig. 2.40 Sturge–Weber angiomatosis, hemangioma affecting the labial and buccal sulcus.

Fig. 2.41 Sturge–Weber angiomatosis, unilateral facial hemangioma.

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Clinical features: Ameloblastoma is the second more common odontogenic tumor after odontoma. Depending on the affected site, it is classified into intraosseous or central and extraosseous or peripheral. The peripheral type is rare (1–2% of all cases). Clinically, it usually appears as a painless, slowly growing, erythematous mass, with a smooth or papillary surface that rarely ulcerates (▶ Fig. 2.42). Most frequently, there are no radiographic findings, as the tumor may cause mild or no osseous destruction. The posterior mucosa and the gingiva of the mandible are more commonly affected. It can cause clinical diagnostic problems and the final diagnosis should be confirmed by histologic examination. Laboratory tests: Histopathologic examination, radiographs, CT, and MRI. Differential diagnosis: Pyogenic granuloma, peripheral giant cell granuloma, peripheral calcifying odontogenic tumor, squamous cell carcinoma, and nonHodgkin’s lymphoma. Treatment: The treatment of choice is conservative surgical excision.

Fig. 2.42 Peripheral ameloblastoma, ulcerated erythematous mass on the retromolar area.

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3 Black and Brown Lesions Pigmented oral lesions are a large group of disorders in which the dark or brown color is the essential clinical characteristic. Usually, the dark color of the lesions is due to melanin production by either melanocytes or nevus cells. In addition, exogenous deposits and pigment-producing bacteria can also produce pigmented lesions. Benign disorders, deposits, benign and malignant neoplasms, and systemic diseases are included in the group of pigmented lesions.

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Racial Pigmentation

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Lentigo Simplex

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Amalgam Tattoo

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Lentigo Maligna

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Heavy Metal Deposition

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Melanocytic Nevi

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Drug-Induced Pigmentation

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Nevus of Ota

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Smoker’s Melanosis

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Malignant Melanoma

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Black Hairy Tongue

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Addison’s Disease

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Oral Melanoacanthoma

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Peutz–Jeghers Syndrome

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Ephelides

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3.1 Racial Pigmentation Definition: Dark discoloration of the oral mucosa may occasionally be a normal finding in dark-skinned healthy individuals. Etiology: Increased melanin production and deposition in the oral mucosa. Clinical features: Clinically, in healthy people, it appears as asymptomatic black or brown flat areas of varying size. The gingiva and buccal mucosa are the most frequently affected sites, followed by the palate and lips (▶ Fig. 3.1). The pigmentation is more prominent in areas of pressure or friction and becomes more intense with aging. The diagnosis is based on the history and clinical features and only rarely a biopsy is needed. Laboratory tests: Histopathologic examination, only in cases of diagnostic dilemma. Differential diagnosis: Smoking-associated melanosis, pigmentation due to drugs, amalgam tattoo, lentigo simplex, pigmented nevi, malignant melanoma, Addison’s disease, and Peutz–Jeghers syndrome. Treatment: No treatment is needed.

3.2 Amalgam Tattoo Definition: Amalgam tattoo is the most common cause of pigmentation of the oral mucosa. Etiology: Implantation of dental amalgam into the oral mucosa during dental procedures. The use of the rubber dam has decreased the risk of amalgam tattoo. Clinical features: Clinically, the condition appears as a solitary or multiple well-defined bluish or black, usually flat, irregular discoloration of varying size (▶ Fig. 3.2). The gingiva, alveolar mucosa, floor of the mouth, and buccal mucosa are more frequently affected sites. The diagnosis is usually based on the history and clinical features and only rarely a biopsy is needed. Laboratory tests: Histopathologic examination. Occasionally, metallic fragments are visible radiographically. Differential diagnosis: Ephelides, lentigo simplex, melanoacanthoma, silver and graphite implantation, cosmetic tattooing, lentigo maligna, and malignant melanoma.

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3.2 Amalgam Tattoo

Fig. 3.1 Racial pigmentation of the gingiva.

Fig. 3.2 Amalgam tattoo on the lower buccal sulcus.

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Treatment: Usually no treatment is required. Conservative surgical excision may be needed only to rule out other benign or malignant melanocytic lesions.

3.3 Heavy Metal Deposition Definition: Heavy metal deposition is a rare phenomenon in the oral mucosa. Etiology: It is caused by ingestion or exposure or implantation of silver, lead, bismuth, mercury, graphite, and other heavy metals. Clinical features: Clinically, the most common and characteristic pattern is a bluish-black linear deposition on the marginal gingiva, especially from bismuth (bismuth line) or from lead (lead line) (▶ Fig. 3.3 and ▶ Fig. 3.4). In the case of silver discoloration of the oral mucosa, as a result of endodontic procedure with silver cones, a brownish-black or gray-brown, asymptomatic macule or small plaque may develop (▶ Fig. 3.5). Graphite discoloration appears as bluish-brown small plaque and usually occurs on the gingiva, palate, and tongue (▶ Fig. 3.6). The diagnosis is based on the history and clinical features. Laboratory tests: Usually not required. Differential diagnosis: Amalgam tattoo, phlebolith, racial pigmentation, Addison’s disease, drug-induced pigmentation, ephilides, lentigo simplex, melanoacanthoma, and melanoma. Treatment: No treatment is required for oral lesions. Conservative surgical excision may occasionally be needed.

3.4 Drug-Induced Pigmentation Definition: Drug-induced oral pigmentation is a relatively common condition. Etiology: Several drugs such as antimalarials, tranquilizers, minocycline, ketoconazole, clofazimine, various chemotherapeutic agents, anti-human immunodeficiency virus medication, hormones, and others may induce oral pigmentation because of increased melanin production or drug metabolite deposition.

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3.4 Drug-Induced Pigmentation

Fig. 3.3 Blue-black linear bismuth deposition on the gingiva (bismuth line).

Fig. 3.4 Blue-black lead deposition on the marginal gingiva (lead line)

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Fig. 3.5 Melanotic silver deposit.

Clinical features: Clinically, oral pigmentation appears as irregular, asymptomatic macules or plaques or diffuse brown or black-brown lesions (▶ Fig. 3.7). The buccal mucosa, tongue, soft palate, and gingiva are the most frequently affected areas. The diagnosis is mainly based on the history and clinical features. Laboratory tests: Usually not required. Histopathologic examination only in cases that are difficult to diagnose. Differential diagnosis: Racial pigmentation, Addison’s disease, Peutz–Jeghers syndrome, smoking pigmentation. Treatment: No treatment is required.

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3.4 Drug-Induced Pigmentation

Fig. 3.6 Graphite fragments in the gingival crevice of the right central incisor.

Fig. 3.7 Pigmentation of the buccal mucosa caused by ketoconazole.

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3.5 Smoker’s Melanosis Definition: Smoker’s melanosis is a benign focal pigmentation of the oral mucosa more frequently encountered in women smokers, usually after the third decade of life. Etiology: The cause of the disorder is the increased melanin production as a result of oral mucosal melanocytes stimulation by the prolonged elevated temperature in the mouth and by nicotine and benzopyrene products. Clinical features: Clinically, the pigmentation usually presents as asymptomatic multiple brown pigmented areas, mainly localized at the attached labial anterior gingiva of the mandible (▶ Fig. 3.8). The buccal mucosa, tongue, palate, and lips are less frequently affected. The intensity of pigmentation is related to the number of cigarettes consumed per day and the time of smoking. The diagnosis is based on the history and clinical features, and only rarely a biopsy is needed. Laboratory tests: Rarely, histopathologic examination. Differential diagnosis: Racial pigmentation, traumatic pigmentation, druginduced pigmentation, amalgam tattoo, lentigo simplex, freckles, pigmented nevi, malignant melanoma, Addison’s disease, endocrine disturbances, and hemochromatosis. Treatment: No treatment is required. The pigmentation can gradually diminish after smoking cessation.

3.6 Black Hairy Tongue See also sections 13.1.3 and 13.1.4. Definition: Black hairy tongue is a relatively rare form of hairy tongue. Etiology: The black color is the result of growth of pigment-producing bacteria that colonize the elongated filiform papillae, foods, and tobacco. Clinical features: Clinically, black hairy tongue is characterized by extensive hypertrophy and elongation of the filiform papillae with a characteristic black color (▶ Fig. 3.9 and ▶ Fig. 3.10). The disorder may cause an unpleasant feeling

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3.6 Black Hairy Tongue

Fig. 3.8 Gingival melanosis due to smoking.

Fig. 3.9 Black hairy tongue.

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Black and Brown Lesions of gagging, bad taste, discomfort, and malodor. In addition, black hairy tongue usually causes significant distress to the patients. The diagnosis is based exclusively on the clinical features. Differential diagnosis: Other forms of hairy tongue, furred tongue. Treatment: Topical use of keratolytic agents. Good oral hygiene.

3.7 Oral Melanoacanthoma Definition: Oral melanoacanthoma is a rare, benign, acquired disorder of pigmentation, usually of the skin of black people. Etiology: It is caused by an increased number of dendritic melanocytes dispersed throughout the epithelium, and melanin production as well. Clinical features: Clinically, oral melanoacanthoma presents as a flat, slightly raised asymptomatic black or brown-black macule or plaque (▶ Fig. 3.11). The size varies from a few to many centimeters. The most frequently affected oral sites are the buccal mucosa followed by the palate, gingiva, and lips. The diagnosis is exclusively based on the histologic pattern. Laboratory tests: Histopathologic examination. Differential diagnosis: Melanocytic nevi, lentigo simplex, lentigo maligna, malignant melanoma, ephilides, amalgam tattoo, and smoker’s melanosis. Treatment: The treatment of choice is conservative surgical excision.

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3.7 Oral Melanoacanthoma

Fig. 3.10 Black hairy tongue.

Fig. 3.11 Melanoacanthoma on the palatal gingiva in the canine–premolar area.

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3.8 Ephelides Definition: Ephelides or freckles are benign, multiple discrete brown disorders that commonly appear on sun-exposed skin and rarely in the mouth and lower lip. Etiology: They are caused by increased melanocyte activity and deposition of melanin particularly in the basal cells. Clinical features: Clinically, ephelides appear as multiple, usually brown or red-brown, asymptomatic, discrete round or oval macules, less than 5 mm in diameter, on sun-exposed skin. Rarely, ephelides may appear on the vermilion border of the lower lip and intraorally as well (▶ Fig. 3.12). The clinical diagnosis should be confirmed by histologic examination. Laboratory tests: Histopathologic examination. Differential diagnosis: Lentigo simplex, melanocytic nevi, oral melanoacanthoma, Peutz–Jeghers syndrome, amalgam tattoo, malignant melanoma, and McCune–Albright syndrome. Treatment: Usually no treatment is required. However, for esthetic reasons or diagnostic consideration, conservative surgical excision can be recommended.

3.9 Lentigo Simplex Definition: Lentigo simplex is a benign, rare disorder of pigmentation that primarily occurs on the skin and rarely on the oral mucosa, and it is not related to sunlight exposure. Etiology: It is caused by an increased number of melanocytes in the basal layer and melanin production. Clinical features: Clinically, oral lentigo simplex appears as shortly demarcated, flat round, asymptomatic, macule or small plaque of brown or black-brown color, usually less than 5 mm in diameter (▶ Fig. 3.13). The most commonly affected oral sites are the lower lip, palate, buccal mucosa, and gingiva. The clinical diagnosis should be confirmed by a biopsy and histologic examination. Laboratory tests: Histopathologic examination. Differential diagnosis: Amalgam tattoo, ephelides, melanocytic nevi, oral melanoacanthoma, lentigo maligna, malignant melanoma, Peutz–Jeghers syndrome, and McCune–Albright syndrome. Treatment: Conservative surgical excision, only for oral lesions under constant mechanical friction, is recommended.

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3.9 Lentigo Simplex

Fig. 3.12 Ephelis on the lower lip.

Fig. 3.13 Lentigo simplex on the lower lip.

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3.10 Lentigo Maligna Definition: Lentigo maligna or Hutchinson’s freckle is a premalignant lesion, in situ melanoma, of melanocytes that primarily develops on sun-damaged skin, frequently on the face. Etiology: The exact etiology remains unknown. However, genetic factors and ultraviolet radiation (UVR) may be involved in the pathogenesis of the disease. Clinical features: Lentigo maligna is uncommon in the oral mucosa. Clinically, the oral lesion appears as a black or black-brown plaque of variable size with smooth surface and irregular border (▶ Fig. 3.14). The lower lip, buccal mucosa, palate, and floor of the mouth are the sites of predilection. It has a slow progression, but in 5 to 15 years may transform into malignant melanoma with better prognosis than the other types of melanomas. The final diagnosis is based on histopathologic criteria. Laboratory tests: Histopathologic examination. Differential diagnosis: Malignant melanoma, melanocytic nevi, oral melanoacanthoma, lentigo simplex, ephelides, and amalgam tattoo. Treatment: Surgical excision or radiotherapy.

3.11 Melanocytic Nevi Definition: Melanocytic nevi are common, benign malformations of melanocytes. Etiology: Developmental malformation that are caused by proliferation of modified melanocytes or nevus cells in the epidermis, dermis, or both. Genetic factors seem to play a role in the development of nevi. Additional factors such as environmental, hormonal, and immunologic may be involved in the pathogenesis. Clinical features: Clinically, almost all the types of nevi appear as an asymptomatic, well-demarcated flat or slightly elevated, brown, black, or blue spot or plaque (▶ Fig. 3.15, ▶ Fig. 3.16, ▶ Fig. 3.17, and ▶ Fig. 3.18). The lesions are usually solitary, with a diameter less than 1 cm. The palate, buccal mucosa, gingiva, and lips are the sites of predilection. The clinical features, all the four types of nevi, are identical and not pathognomonic, and the diagnosis is based exclusively on the histologic pattern. There are two main forms of nevi: congenital and acquired. Intraoral acquired nevi are histologically classified into four types: (1) intradermal (intramucosal), (2) junctional,(3) compound, and (4) blue, depending on the location of nevus cells. The intradermal (intramucosal) nevus is the most common type (55%) and histologically is characterized by several

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3.11 Melanocytic Nevi

Fig. 3.14 Lentigo maligna on the lower lip.

Fig. 3.15 Intradermal nevus on the floor of the mouth.

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Fig. 3.16 Junctional nevus on the retromolar area.

nevus cells within the lamina propria that are separated from the epithelium by a band of collagen. The junctional nevus is uncommon, accounting for 3 to 5.5% of oral nevi and histologically is characterized by nests of nevus cells along the basal layer of the epithelium. This type of nevus has an increased risk for malignant transformation to melanoma. The compound nevus is rare (6–8.5%) and histologically is characterized by clusters of nevus cells located both along the epithelial–connective tissue junction and deeper into the lamina propria. The blue nevus is the second more common type (30.5–36%) and histologically is characterized by clusters of melanocytes that are filled with melanin, located in a parallel pattern deep within the lamina propria. Laboratory tests: Histopathologic examination. Differential diagnosis: Amalgam tattoo, ephelides, lentigo simplex, melanoacanthoma, lentigo maligna, and early malignant melanoma. Treatment: The treatment of choice is conservative surgical excision.

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3.11 Melanocytic Nevi

Fig. 3.17 Compound nevus on the palate.

Fig. 3.18 Blue nevus on the buccal mucosa.

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3.12 Nevus of Ota Definition: Nevus of Ota is a developmental pigmentation disorder of the melanocytes that predominantly involves areas of the face that are innervated by the first and second branches of the trigeminal nerve (skin, eyes, and mucous membranes). Etiology: Developmental. The hyperpigmentation is due to melanin-producing melanocytes in the lamina propria, such as the blue nevus, that have failed to reach the epidermis or epithelium during fetal life. Clinical features: Nevus of Ota, appears predominately during childhood, is more common in females (ratio 5:1) and usually occurs in Japanese, Africans, and African-Caribbean and rarely in other ethnologic groups. Characteristically, the pigmentation appears on the eyeball, the skin of the face, and less frequently the nasal, pharyngeal, and oral mucosa. Clinically, the skin lesions present as multiple flat or slightly raised mottled black or brown macules (▶ Fig. 3.19). Hyperpigmentation of ipsilateral sclera is a common sign, while involvement of the cornea, iris, fundus, oculi, and retina is rare (▶ Fig. 3.20). The oral lesions appear as asymptomatic blue or blue-black dots or patches that usually involve the palate and buccal mucosa (▶ Fig. 3.21). The lesions are usually unilateral. Fig. 3.19 Nevus of Ota, black-brown macules on the skin of the face.

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3.12 Nevus of Ota

Fig. 3.20 Nevus of Ota, pigmentation in the eye.

Fig. 3.21 Nevus of Ota, blue nevus in the palatal midline.

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Black and Brown Lesions Malignant transformation of nevus of Ota is very rare. The diagnosis is based on the history and clinical features but has to be confirmed by a biopsy and histologic examination. Laboratory tests: Histopathologic examination. Differential diagnosis: Blue nevus, other melanocytic nevi, Sturge–Weber syndrome, lentigo maligna, malignant melanoma, and amalgam tattoo. Treatment: Q-switched laser and camouflage of face lesions.

3.13 Malignant Melanoma Definition: Melanoma is a malignant skin and mucosae neoplasm, arising either de novo from melanocytes or from a benign melanocytic lesion, with poor prognosis. Etiology: The exact etiology remains unknown. However, three major risk factors are recognized: genetic, environmental, and phenotypic factors reflecting gene and environmental interaction. The prolonged sunlight exposure is important factor for the development of skin melanoma. Clinical features: The skin malignant melanoma is classified, by clinical and histologic criteria, into four basic types: (1) nodular melanoma, (2) superficial spreading melanoma, (3) lentigo maligna melanoma, and (4) acral lentiginous melanoma. Amelanotic melanoma is a rare variant of melanoma without pigmented element that can be classified under one of the four basic types. Primary melanoma of the oral mucosa accounts for 0.5 to 1% of total melanomas, it affects both sexes equally, usually between age 50 and 60. Clinically, oral melanoma appears as a black or black-brown macule, plaque, or nodule that may be ulcerated. The lesions are usually characterized by irregular magins and have a tendency to spread. The nodular and superficial spreading are the most common types in the oral mucosa, whereas lentigo maligna melanoma is very rare (▶ Fig. 3.22, ▶ Fig. 3.23, and ▶ Fig. 3.24). In the mouth, over 80% of the melanomas develop in the hard palate, maxillary gingiva, and alveolar mucosa. The remaining 20% is distributed in the mandibular gingiva, buccal mucosa, tongue, floor of the mouth, and lips. The tumor can also affect other mucosae. The prognosis of skin melanoma depends on the clinical types and the depth of invasion histologically (Breslow’s depth). The clinical diagnosis should be confirmed by histologic examination.

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3.13 Malignant Melanoma

Fig. 3.22 Malignant melanoma, early, nodular type, on the alveolar mucosa.

Fig. 3.23 Malignant melanoma, early, superficial spreading.

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Laboratory tests: Histopathologic examination (Clark’s and Breslow’s scale), immunohistochemical markers. Differential diagnosis: Lentigo maligna, melanocytic nevi, ephelides, lentigo simplex, melanoacanthoma, Kaposi’s sarcoma, pyogenic granuloma, bacterial angiomatosis, and amalgam tattoo. Treatment: Radical surgical excision is the first line of treatment. Adjuvant therapy includes chemotherapy, immunotherapy, hormonal, and molecularly targeted therapy.

3.14 Addison’s Disease Definition: Addison’s disease is a form of chronic adrenal insufficiency classified as primary and secondary. Etiology: Adrenal cortex destruction or dysfunction usually caused by autoimmunity, infection, amyloidosis, hemochromatosis, and adrenal malignancies are the causes. Clinical features: Clinically, Addison’s disease is characterized by weakness, fatigue, weight loss, nausea, loss of appetite, hypotension, tachycardia, gastrointestinal disorders, joint pains, amenorrhea, and mental irritability. A classic sign is increased cutaneous and mucosal pigmentation, especially in areas that are subject to friction and pressure. Dark brown pigmentation of the oral mucosa is an early and common sign (▶ Fig. 3.25 and ▶ Fig. 3.26). The pigmentation may be spotty or diffuse and involves the buccal mucosa, palate, lips, and gingiva. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Adrenocorticotropic hormone stimulation test, serum cortisol levels, serum anti-adrenal antibodies, radiographic examination, biopsy, and histopathologic examination. Differential diagnosis: Racial pigmentation, smoker’s pigmentation, druginduced pigmentation, and Peutz–Jeghers syndrome. Treatment: Hormone replacement therapy. Supportive treatment is also performed.

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3.14 Addison’s Disease

Fig. 3.24 Lentigo malignant melanoma on the buccal mucosa.

Fig. 3.25 Addison’s disease, pigmentation of the buccal mucosa.

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Fig. 3.26 Addison’s disease, pigmentation of the sulcus and the buccal mucosa.

3.15 Peutz–Jeghers Syndrome Definition: Peutz–Jeghers syndrome is a rare, genetic disorder, characterized by mucocutaneous pigmentation and hamartomatous polyps in the gastrointestinal tract. Etiology: Genetic, transmitted by an autosomal dominant trait in 70% of the cases, while 30% are caused by new mutations. Clinical features: Clinically, multiple hamartomatous intestinal polyps are the most important finding (▶ Fig. 3.27). They may be symptomatic (intestinal bleeding, abdominal pain, and rarely ischemic necrosis) or asymptomatic. An increased risk for malignant neoplasms in the gastrointestinal tract and other organs may occur. The oral and cutaneous manifestations are the most characteristic diagnostic findings, and present as multiple, small, round, ovoid, or irregularly-shaped brown or black-brown asymptomatic macules or spots, 1 to 10 mm in diameter (▶ Fig. 3.28, ▶ Fig. 3.29 and ▶ Fig. 3.30). The perioral skin, nose, eyes, lips, buccal mucosa, and tongue are the sites of predilection. These lesions are the most early and classic signs and usually appear after the first year of life. The clinical diagnosis should be confirmed by laboratory tests.

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Fig. 3.27 Peutz–Jeghers syndrome, intestinal polyps.

Fig. 3.28 Peutz–Jeghers syndrome, multiple brown-black macules on lower lip and the skin.

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Black and Brown Lesions

Laboratory tests: Histopathologic examination, intestinal endoscopy, and radiographic examination of the gastrointestinal tract. Treatment: Treatment is not required for the mucocutaneous lesions, surgical excision of polyps if they cause symptoms. Regular follow-up is recommended because of the increased risk of malignancies.

Fig. 3.29 Peutz–Jeghers syndrome, multiple brown-black macules on the skin.

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3.15 Peutz–Jeghers Syndrome

Fig. 3.30 Legend: Peutz–Jeghers syndrome multiple brown-black macules on the buccal mucosa.

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4 Vesiculobullous Lesions Vesiculobullous diseases are a distinct group of oral disorders characterized by the formation of vesicles or bullae. Clinicians must bear in mind that it is uncommon to see intact vesicles or bullae intraorally, since they rupture quickly, leaving erosions or ulcers. This group includes viral diseases, autoimmune and other mucocutaneous diseases, diseases that probably have an immunologically mediated mechanism, mechanical lesions, and genetic diseases. The diagnosis of vesiculobullous diseases is based on clinical, histopathologic, and immunologic grounds.

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Primary Herpetic Gingivostomatitis

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Bullous Pemphigoid

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Secondary Herpetic Stomatitis

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Pemphigoid Gestationis

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Herpes Zoster

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Linear IgA Disease

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Herpangina

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Dermatitis Herpetiformis

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Hand, Foot, and Mouth Disease

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Bullous Lichen Planus

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Erythema Multiforme

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Epidermolysis Bullosa

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Stevens–Johnson Syndrome

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Epidermolysis Bullosa Acquisita

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Toxic Epidermal Necrolysis

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Angina Bullosa Hemorrhagica

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Pemphigus

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Primary Systemic Amyloidosis

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Mucous Membrane Pemphigoid

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Traumatic Bulla

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Pyostomatitis Vegetans

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4.1 Primary Herpetic Gingivostomatitis Definition: Primary herpetic gingivostomatitis is a common, acute, viral infection of the oral mucosa mainly affecting children, adolescents, and rarely adults. Etiology: It is caused by herpes simplex virus type 1 (HSV-1) and less often HSV-2. HSV-1 is transmitted through direct contact with saliva or other secretions. The pathogenesis of herpetic infection follows the course: primary infection–latent phase–reactivation. Clinical features: The onset of the disease is abrupt and is characterized by high fever (38–39oC), headache, malaise, loss of appetite, irritability, characteristic bilateral, sensitive regional lymphadenopathy, burning mouth sensation, and difficulty in swallowing that precede the oral lesions by 1 to 2 days. Clinically, the oral mucosa and the gingiva are red and edematous, with numerous coalescing vesicles that rapidly rupture, leaving painful small, round, shallow ulcers, covered with a yellowish-gray pseudomembrane (▶ Fig. 4.1 and ▶ Fig. 4.2). New vesicles continue to develop over a period of 3 to 5 days. The ulcers gradually heal within 10 to 14 days without scarring. Both the movable and attached oral mucosa can be affected. Involvement of the lips and perioral skin may occur. Serious complications are rare, and include eye involvement, pharyngitis, esophagitis, pneumonitis, meningitis, and encephalitis. In immunocompromised patients, clinical presentation of herpetic stomatitis is distinct, characterized by larger ulcers that spread laterally and are surrounded by a circinate, raised, white-yellow border. The diagnosis is usually based on clinical grounds. Laboratory tests: They are rarely necessary. Histopathologic and cytologic examination, direct and indirect immunofluorescences, and viral culture may be helpful. Differential diagnosis: Aphthous ulcers (herpetiform variety), herpangina, hand, foot, and mouth disease (HFMD), acute necrotizing ulcerative gingivitis, erythema multiforme, early oral pemphigus, and drug-induced stomatitis. Treatment: Systemic antiviral agents (acyclovir, valacyclovir, and famciclovir) are the first-line therapy.

4.2 Secondary Herpetic Stomatitis Definition: Secondary or recurrent herpetic stomatitis is a common oral and perioral viral disease. Etiology: It is caused by reactivation of HSV-1, following primary herpetic infection. Predisposing factors include emotional or physical stress, febrile illness, cold, sunlight, minor trauma, tooth extraction, and local anesthesia.

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4.2 Secondary Herpetic Stomatitis

Fig. 4.1 Primary herpetic gingivostomatitis. Extensive erosions on the tongue.

Fig. 4.2 Primary herpetic gingivostomatitis. Marked erythema, edema, and erosions on the gingiva.

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Clinical features: Clinically, localized, multiple, small vesicles arranged in clusters develop (▶ Fig. 4.3). The vesicles soon rapture, leaving small ulcers that heal spontaneously within 1 week. Prodromal symptoms are burning, itching, tingling, and erythema. The lesions usually develop on the palate, gingiva, and lips. Characteristically, high fever, generalized regional lymphadenopathy, and constitutional symptoms are absent or mild. The diagnosis is exclusively based on the history and clinical features. Laboratory tests: Not required. Differential diagnosis: Primary herpetic gingivostomatitis, early herpes zoster, herpangina, aphthous ulcers, HFMD, streptococcal stomatitis, traumatic erosions, and primary and secondary syphilis. Treatment: It is symptomatic. The lesions heal spontaneously in 4 to 6 days.

4.3 Herpes Zoster Definition: Herpes zoster is an acute self-limiting, vesicular, viral infection that usually affects sensory nerves, more often a single dermatome. Etiology: Reactivation of later varicella-zoster virus (VZV) or herpesvirus type 3 in the partially immune host. The most common predisposing factors for the reactivation of virus are human immunodeficiency virus (HIV) infection, leukemias, lymphomas and other malignancies, radiation, immunosuppressive and cytotoxic drugs, long-term corticosteroid therapy, and old age. Clinical features: The thoracic, lumbosacral, cervical, and trigeminal dermatomes are most frequently affected. The unilateral distribution of the lesions is the most characteristic clinical feature. Clinically, tenderness and pain in the involved dermatome are the first symptoms, followed with fever, headache, and malaise. After 2 to 4 days, the eruptive phase follows characterized by clusters of vesicles in an erythematous base, which within 2 or 3 days evolve into pustules and ulcers, covered by crusts. The lesions persist for 10 to 20 days. The regional lymph nodes are usually tender and enlarged. Oral manifestations occur when the second and third branches of the trigeminal nerve are involved. Frequently, intraoral lesions are associated with unilateral skin lesions on the face (▶ Fig. 4.4 and ▶ Fig. 4.5). The oral mucosa lesions are identical to the skin lesions. Frequently, itching sensation and pain, simulating pulpitis precede the oral lesions. Postherpetic trigeminal neuralgia is a common complication, whereas osteomyelitis, jaw bone necrosis, and loss of teeth are rare. The diagnosis is mainly based on the history and clinical features.

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Fig. 4.3 Secondary herpes. Grouped vesicles on the mucosa of the lower lip.

Fig. 4.4 Herpes zoster, unilateral cluster of vesicles on the right aspect of palate.

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Laboratory tests: Cytologic and histopathologic examination, antibody titters to VZV. Differential diagnosis: Herpes simplex, herpangina, erythema multiforme, and varicella. Treatment: Antivirals (brivudine, valacyclovir, and famciclovir) are the first line of treatment. Analgesics and sedatives to control the pain. Prednisolone (20–30 mg for about 8–10 days) reduces the risk for postherpetic neuralgia.

4.4 Herpangina Definition: Herpangina is an acute self-limiting viral infection that affects children and young adults more frequently. Etiology: It is caused by coxsackievirus (group A) types 1 to 6, 8, 10, 22, and occasionally other types. Clinical features: Clinically, the disease has an acute onset and is characterized by sudden fever (38–40oC), headache, malaise, nausea, dysphagia, and sore throat. Within 24 to 48 hours, an acute inflammation of the posterior oral mucosa and oropharynx develops, associated with numerous, small vesicles (2–5 mm in diameter) that soon rapture, leaving painful shallow ulcers that heal within 7 to 10 days (▶ Fig. 4.6). Characteristically, the lesions involve the soft palate and uvula, tonsillar pillars, and posterior pharyngeal wall. The disease has a peak incidence during summer and autumn. The diagnosis is exclusively based on the history and clinical features. Laboratory tests: Usually not required. Histopathologic and serologic examination, PCR assay, and viral culture only in questionable cases. Differential diagnosis: Primary herpetic gingivostomatitis, herpetiform ulcers, acute lymphonodular pharyngitis, HFMD, RFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome, erythema multiforme, and gonococcal stomatitis. Treatment: It is symptomatic.

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4.4 Herpangina

Fig. 4.5 Herpes zoster, typical facial skin lesions in unilateral distribution.

Fig. 4.6 Herpangina, numerous vesicles and shallow ulcers on the soft palate.

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4.5 Hand, Foot, and Mouth Disease Definition: HFMD is an acute, self-limiting, contagious, viral infection, which may occur in epidemics or isolated cases. Etiology: It is caused by coxsackieviruses, mainly type A16. Clinical features: The disease usually affects children and young adults. Clinically, small vesicles appear on the oral mucosa, 5 to 30 in number, that soon rapture, leaving slightly painful shallow ulcers (2–6 mm in diameter), surrounded by a red halo (▶ Fig. 4.7). The buccal mucosa, tongue, soft palate, and labial mucosa are the most frequently affected sites. The skin lesions consist of small vesicles, 1 to 50 in number, surrounded by a narrow, red halo. The lateral borders and the dorsal surfaces of the fingers and toes, palms, soles, and buttocks are the most common areas involved (▶ Fig. 4.8). Low-grade fever and mild general symptoms may be present. The disease lasts for 5 to 8 days and resolves spontaneously without treatment. The diagnosis is based on clinical criteria. Laboratory tests: They are not necessary. Viral isolation from oral and skin lesion, and PCR assay, only in doubtful cases. Differential diagnosis: Aphthous ulcers, herpes simplex infection, herpangina erythema multiforme, and erythema multiforme. Treatment: It is symptomatic.

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Fig. 4.7 Hand, foot, and mouth disease, shallow ulcers on the lateral margin of the tongue.

Fig. 4.8 Hand, foot, and mouth disease, multiple vesicles on the sole and the lateral aspect of the foot.

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4.6 Erythema Multiforme Definition: Erythema multiforme is an acute or subacute, self-limited, disease that mainly involves the skin and mucous membranes. Etiology: The exact etiology remains unknown. The most important factors implicated in the pathogenesis are HSV types 1 and 2 and less frequently other infections, drugs, radiation, and malignancies. Clinical features: Erythema multiforme, predominantly, affects young adults from 20 to 40 years of age. Clinically, the disease is divided into two forms: (1) minor, with and/or atypical papular target-like lesions with minimal or no mucosal involvement and systemic symptoms and (2) major, which is more severe, with typical and/or atypical papular target-like lesions with severe mucosal involvement and systemic features. Clinically, the primary oral lesions are erythema and multiple, small vesicles that coalesce and then rupture, leaving painful erosions covered by a necrotic pseudomembrane (▶ Fig. 4.9). The lips, soft palate, buccal mucosa, and tongue are most frequently affected. The skin lesions consist of erythematous, flat, round macules, papules, or plaques in a symmetrical pattern. The characteristic skin patterns are target-like or irislike lesions (▶ Fig. 4.10). Conjunctivitis, balanitis, and vaginitis may be followed by fever, coughing, malaise, difficulty of swallowing, and arthralgias. Recurrences are common. The diagnosis is primarily based on clinical criteria, but should be confirmed by a biopsy and histologic examination. Laboratory tests: Histopathologic examination, direct immunofluorescence. Differential diagnosis: Stevens–Johnson syndrome, toxic epidermal necrolysis, primary herpetic gingivostomatitis, herpetiform ulcers, drug reactions, mucous membrane pemphigoid, pemphigus, Kawasaki’s disease, and graft versus host disease. Treatment: Systemic corticosteroids. Antiviral agents (valacyclovir, famciclovir, and acyclovir) for about 4 to 6 months, particularly for patients with frequent recurrences.

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Fig. 4.9 Erythema multiforme, erosions on the dorsum of the tongue.

Fig. 4.10 Erythema multiforme, typical target-like lesions on the finger.

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4.7 Stevens–Johnson Syndrome Definition: Stevens–Johnson syndrome is a relatively rare, acute, life-threatening mucocutaneous disease, characterized by epidermal and mucosal necrosis and detachment. Etiology: The cause is an immune complex-mediated hypersensitivity reaction which is, nearly always, drug-related. In addition, genetic predisposition is involved in the pathogenesis. Clinical features: The disease is unrelated to erythema multiforme and is considered as a milder form of toxic epidermal necrolysis. It begins with prodromal symptoms such as fever, cough, fatigue, malaise, sore throat, arthralgia, myalgias, diarrhea, and photophobia that usually precede the mucocutaneous manifestations by 1 to 3 days. Clinically, the oral mucosa is almost always involved, with extensive vesicles formation that rapture quickly, leaving painful erosions covered by grayish-white or hemorrhagic pseudomembranes (▶ Fig. 4.11). The lesions may extend to the pharynx, larynx, and esophagus. The ocular lesions consist of conjunctivitis, uveitis, corneal ulcerations, or even panopthalmitis. The genital lesions are balanitis, vulvovaginitis, and scrotal erosions (▶ Fig. 4.12). The cutaneous lesions are variable in both gravity and extend. At the beginning, erythematous dusky red, or purpuric macules that tend to coalesce may be present. As the epidermal lesions progress toward necrosis, detachment of epidermis from dermis occurs (▶ Fig. 4.13). The Nikolsky’s sign may be positive. The diagnosis is mainly based on the history and clinical features. Laboratory tests: Histopathologic examination, immunofluorescence. Differential diagnosis: Toxic epidermal necrolysis, erythema multiforme, pemphigus, pemphigoid, drug eruption, Sweet’s syndrome, primary herpetic gingivostomatitis, and graft versus host disease (acute form). Treatment: It is performed in intensive care units or burn units by a team of specialists. Systemic corticosteroids, immunosuppressants, thalidomide, intravenous immunoglobulin, tumor necrosis factor-alpha antagonists are the firstline drugs.

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4.7 Stevens–Johnson Syndrome

Fig. 4.11 Stevens–Johnson syndrome, severe lesions on the lips.

Fig. 4.12 Stevens–Johnson syndrome, erosions on the glans penis.

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Fig. 4.13 Stevens–Johnson syndrome, macular rash, and erosions covered by hemorrhagic crust on the skin.

4.8 Toxic Epidermal Necrolysis Definition: Toxic epidermal necrolysis or Lyell’s disease is a rare, acute, lifethreatening mucocutaneous disease with severe prognosis. Etiology: In more than 95% of the cases, it represents a form of severe drug reaction. More than 100 different medications have been associated with toxic epidermal necrolysis. HIV infection, autoimmune diseases, and malignancies may also be involved in the pathogenesis. Clinical features: The disease is characterized by detachment of the epidermis in over 30% of the whole-body surface. Clinically, it presents with prodromal symptoms such as malaise, low-grade fever, conjunctival burning sensation, coughing, and arthralgias that precede the mucocutaneous manifestations by 1 to 3 days. Following this, painful rush appears that coalesces forming flaccid bullae and eventually causing the characteristic sheet-like epidermal detachment, resembling scalding (▶ Fig. 4.14). The Nikolsky’s sign is positive. The oral mucosa is involved in 85 to 95% with severe inflammation and painful erosions, which predominantly affect the lips, buccal mucosa, tongue, palate, and gingiva (▶ Fig. 4.15). Lesions may be seen on the pharyngeal mucosa,

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Fig. 4.14 Toxic epidermal necrolysis, characteristic detachment of the epidermis.

Fig. 4.15 Toxic epidermal necrolysis, erosions on the gingiva.

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Vesiculobullous Lesions conjunctival, genitals, and anus. The prognosis is poor with a mortality rate ranging from 25 to 35%. The diagnosis is mainly based on the history and clinical features. Laboratory tests: Histopathologic examination, immunofluorescences. Differential diagnosis: Stevens–Johnson syndrome, staphylococcal scalded skin syndrome, drug eruption, pemphigus, pemphigoid, systemic lupus erythematosus, Sweet’s syndrome, and graft versus host disease. Treatment: Hospitalization in intensive care units is mandatory. Intravenous immunoglobulin is currently the recommended treatment. Corticosteroids and immunosuppressants are the first-line drugs. Prevention and treatment of any secondary infection is important.

4.9 Pemphigus Definition: Pemphigus is a group of chronic, blistering, autoimmune mucocutaneous disease. Etiology: Autoimmunity. It is caused by autoantibodies against desmoglein 3 and 1. When the autoantibodies target is desmoglein 3, the lesions present in the oral mucosa; when the target is desmoglein 1, the lesions develop on the skin. Clinical features: Pemphigus is classified into three major types: pemphigus vulgaris, pemphigus foliaceus,and paraneoplastic pemphigus and several subtypes (pemphigus vegetans, drug-induced pemphigus,and IgA [Immunoglobulin A] pemphigus). Pemphigus vulgaris is the most common (90–95% of the cases) and severe type of the disease. Using clinical criteria, pemphigus vulgaris is classified into three types: (1) the mucosal dominant, with mucosal lesions but minimal or no skin lesions, (2) the mucocutaneous, with extensive skin lesions besides the mucosal involvement, and (3) the cutaneous, with only skin lesions, which is rare (1–2%). In over 70%, the oral mucosa is the region of onset, but finally, almost all patients develop oral lesions. Clinically, oral lesions present as bullae, which rapidly rupture, leaving painful erosions with a tendency to extend peripherally (▶ Fig. 4.16). A characteristic feature is the presence of small linear discontinuities of the epithelium, surrounding active erosions, resulting in epithelial disintegration (▶ Fig. 4.17). The buccal mucosa, palate, tongue, floor of the mouth, gingiva, and lips are often involved. Lesions may develop on other mucosae (conjunctival, nose, larynx, pharynx, genitals, and

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4.9 Pemphigus

Fig. 4.16 Pemphigus vulgaris, erythema and erosions on the gingiva in the form of desquamative gingivitis.

Fig. 4.17 Pemphigus vulgaris, extensive erosions on the palate.

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Vesiculobullous Lesions anus) (▶ Fig. 4.18). The skin lesions appear as flaccid bullae that rupture quickly, leaving eroded areas with a tendency to expand centrifugally (▶ Fig. 4.19). The erosions are soon partially covered with crusts. The trunk, axillae, scalp, ears, genital areas, and umbilicus are the most commonly affected areas. Nikolsky’s sign is positive. The course of pemphigus vulgaris is chronic and the prognosis has improved greatly in the past three decades. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, direct and indirect immunofluorescences, detection of anti-desmogleins 1 and 3, IgG autoantibodies by ELISA, immunoprecipitation, and immunobloting. Differential diagnosis: Bullous pemphigoid, mucous membrane pemphigoid, linear IgA disease, pemphigoid gestationis, dermatitis herpetiformis, epidermolysis bullosa acquisita, erythema multiforme, toxic epidermal necrolysis, erosive lichen planus, aphthous ulcers, drug-induced oral ulcerations, Hailey– Hailey disease, and herpetic gingivostomatitis. Treatment: Systemic corticosteroids are the drugs of choice, immunosuppressive drugs in association with corticosteroids. Recently, rituximab, a potent B-cell-depleting chimeric anti-CD20 monoclonal antibody is used in severe, resistant cases.

4.10 Mucous Membrane Pemphigoid Definition: Mucous membrane pemphigoid or cicatricial pemphigoid is a chronic, autoimmune, blistering disease that primarily affects the mucous membranes and rarely the skin, with a tendency for scarring. Etiology: Autoimmunity. Laminin 5, laminin 6, type XVII collagen, bullous pemphigoid antigen 180, b4 integrin subunit, and other antigens with unknown identities are the main target antigen. These are located at the hemidesmosomes and the basement membrane of the epithelium. Clinical features: Four variants of mucous membrane pemphigoid are currently recognized based on the clinical expression and the antigenic target. The disease should not be regarded as a single clinical entity, but rather a disease phenotype with clinical and antigenic heterogeneity. The four phenotype variants are (1) oral pemphigoid, (2) ocular pemphigoid, (3) anti-laminin pemphigoid, and (4) pemphigoid with bullous pemphigoid antigens. The disease

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4.10 Mucous Membrane Pemphigoid

Fig. 4.18 Pemphigus vulgaris, erosions of the conjunctiva.

Fig. 4.19 Pemphigus vulgaris, multiple, crust-covered erosions on the skin.

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Vesiculobullous Lesions predominantly affects females than males, ratio 1.5–2:1, with a mean age of onset of 66 years. The oral mucosa is affected in over 95% and may be the first and only manifestation. Clinically, the oral lesions appear as recurrent vesicles or bullae that rapture, leaving painful erosions (▶ Fig. 4.20). Repeated recurrences may lead to epithelial atrophy or scarring. The buccal mucosa soft palate, tongue, alveolar mucosa, and gingival in the form of desquamative gingivitis are the most frequently affected sites (▶ Fig. 4.21). Ocular lesions consist of conjunctivitis, symblepharon, entropion, dryness, trichiasis, and corneal perforation that may result in blindness (▶ Fig. 4.22). Less commonly, other mucosae (genitals, anus, nose, pharynx, larynx, and esophagus) and rarely the skin may be involved. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, direct and indirect immunofluorescences, immunoblotting, immunoprecipitation, and immunoelectron microscopy. Differential diagnosis: Linear IgA disease, erosive lichen planus, pemphigus, bullous pemphigoid, epidermolysis bullosa acquisita, dermatitis herpetiformis, chronic ulcerative stomatitis, angina bullosa hemorrhagica, lupus erythematosus, and erythema multiforme. Treatment: Systemic corticosteroids are the first-line drugs. Azathioprine, mycophenolate acid or mofetil, cyclophosphamide, dapsone, and rituximab may be used as adjuvant therapy. Topical corticosteroids and tacrolimus ointments are useful for localized mild oral lesions.

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4.10 Mucous Membrane Pemphigoid

Fig. 4.20 Mucous membrane pemphigoid, superficial ulceration on the buccal mucosa.

Fig. 4.21 Mucous membrane pemphigoid, hemorrhagic bulla on the gingiva, and desquamative gingivitis.

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Fig. 4.22 Mucous membrane pemphigoid, symblepharon, fibrotic sequels, and the beginning of corneal opacity.

4.11 Bullous Pemphigoid Definition: Bullous pemphigoid is the most common, chronic autoimmune bullous disease, mainly affecting the skin, and less often the mucous membranes. Etiology: Autoimmunity. Bullous pemphigoid antigens (BP180 and BP230), components of hemidesmosomes of the epidermal basal cells, are the main target. Clinical features: Bullous pemphigoid is a disease of the elderly with mean onset age 65 years, and males are more frequently affected than females, ratio 1.7:1. The oral mucosa is affected in 30 to 40% of the cases, usually after skin, but in about 6% the oral mucosa is the first site of involvement. Clinically, oral lesions begin as bullae that soon rupture, leaving painful shallow superficial ulcerations (▶ Fig. 4.23). Gingival involvement in the pattern of desquamative gingivitis may occur in about 15%. Rarely, other mucosae may also be affected. Cutaneous lesions are always present, and usually begin as a nonspecific, pruritic, erythematous urticarial-like plaque followed by large, tense bullae that rupture, leaving demuded areas without a tendency to extend peripherally (▶ Fig. 4.24). The trunk, arms, and legs in a symmetrical distribution are the

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4.11 Bullous Pemphigoid

Fig. 4.23 Bullous pemphigoid, hemorrhagic blisters on the buccal mucosa.

Fig. 4.24 Bullous pemphigoid, skin blisters of different stage of evolution.

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Vesiculobullous Lesions sites of predilections. The prognosis is usually good. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, direct and indirect immunofluorescence, immunohistochemistry, and ELISA assay to detect the antigenic target. Differential diagnosis: Pemphigus, mucous membrane pemphigoid, dermatitis herpetiformis, linear IgA disease, epidermolysis bullosa aquisita, lichen planus (erosive and bullous type), and lupus erythematosus. Treatment: Systemic corticosteroids are the drugs of choice. Second-line therapy includes azathioprine, cyclophosphamide, mycophenolate acid, and rituximab. Topical corticosteroids and tacrolimus ointments are useful for local, mild lesions.

4.12 Pemphigoid Gestationis Definition: Pemphigoid gestationis, formerly known as herpes gestationis, is a rare, distinctive, self-limited, autoimmune bullous disease that usually develops during the last trimester of pregnancy or in the early postpartum period. Etiology: Autoimmune. The autoimmune response is mainly directed to hemidesmosomal proteins, BPAG2 and collagen XVII, and less frequently to BP230. A genetic background of HLA-DR3 and DR4 may also be involved in the pathogenesis. Clinical features: Pemphigoid gestationis usually affects the skin and less frequently the mucous membranes. Clinically, the cutaneous lesions present abruptly as intensely pruritic, papulobulous eruption and erythema (▶ Fig. 4.25). The bullae are numerous and often coalesce and soon rupture, leaving painful ulcerations. The trunk, face, abdomen, axillae, extremities, palms, and soles are affected. The oral mucosa is rarely involved with hemorrhagic bullae that soon rupture, leaving painful ulcerations (▶ Fig. 4.26). The buccal mucosa, palate, tongue, and gingiva are the most commonly affected sites. The oral lesions follow the cutaneous manifestations and quickly respond to the treatment. Other mucosae may rarely be affected. The clinical diagnosis should be confirmed by laboratory tests.

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4.12 Pemphigoid Gestationis

Fig. 4.25 Pemphigoid gestationis, coalescent vesicles on the axilla.

Fig. 4.26 Pemphigoid gestationis, hemorrhagic bullae on the alveolar mucosa.

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Laboratory tests: Histopathologic examination, direct and indirect immunofluorescence tests. Differential diagnosis: Bullous pemphigoid, pemphigus, linear IgA disease, and mucous membrane pemphigoid, dermatitis herpetiformis, lupus erythematosus, erythema multiforme, and drug eruptions. Treatment: Systemic corticosteroids are the cornerstone of treatment. Azathioprine, mycophenolate acid, methotrexate, dapsone, and cyclosporine may also be used as adjuvant therapies.

4.13 Linear IgA Disease Definition: Linear IgA disease is a rare, chronic, autoimmune subepithelial blistering disorder, characterized by linear IgA deposits along the basement membrane zone of the epidermis/epithelium. Etiology: Autoimmune. Based on the region of IgA deposition, the disease is classified into two forms: (1) a lamina lucida form and (2) a sublamina densa form. In the first form the IgA antibodies react against a97-kDa antigen, while in the second form IgA antibodies bind VII collagen in anchoring fibrils. Clinical features: Depending on the age group, two clinical forms are recognized: the adult form (over 60 years) and the childhood form (usually below 6 years). The disease predominantly affects the skin, while the oral mucosa is involved in 25 to 30% of the cases. Clinically, oral lesions are characterized by bullae formation that rapidly evolves into painful, superficial ulcerations (▶ Fig. 4.27). The gingival involvement may present in the form of desquamative gingivitis (▶ Fig. 4.28). The skin lesions are characterized by sudden onset of vesicles or bullae which affect, in a symmetrical annular pattern, the face, trunk, buttons, and extremities (▶ Fig. 4.29). The blisters soon rapture, leaving superficial ulcerations that heal without scarring. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, direct and indirect immunofluorescence tests.

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4.13 Linear IgA Disease

Fig. 4.27 Linear IgA disease, hemorrhagic bulla on the buccal mucosa.

Fig. 4.28 Linear IgA disease, mild desquamative gingivitis, and erosion of the gingiva.

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Differential diagnosis: Mucous membrane pemphigoid, bullous pemphigoid, pemphigus, dermatitis herpetiformis, epidermolysis bullosa aquisita, and erythema multiforme. Treatment: The first line of treatment is dapsone, second line being corticosteroids, and other immunosuppressive agents.

4.14 Dermatitis Herpetiformis Definition: Dermatitis herpetiformis or Duhring’s disease is a chronic autoimmune bullous dermatosis usually associated with a gluten-sensitive enteropathy. Etiology: Genetic disorder strongly associated with the HLA-DQ2 genotype and HLA-A1, B8, and DR3 in which IgA antiendomysial antibodies are directed against epidermal transglutaminase. Clinical features: The disease is more common from ages 15 to 50, and males are more frequently affected (ratio 1.5–2:1). Clinically, it is characterized by pruritic, erythematous papules, or plaques and vesicles that coalesce in a herpetiform pattern. The lesions exhibit exacerbations and remissions and are commonly located on the extensor surfaces symmetrically (▶ Fig. 4.30). The oral mucosa is affected in 5 to 10% of the cases. Clinically, erythema maculopapular lesions and vesicles are observed in a centrifugal or semicircular pattern (▶ Fig. 4.31). The vesicles rupture rapidly leaving superficial, painful erosions resembling small aphthous ulcers. The palate, buccal mucosa, tongue, and alveolar mucosa are more frequently affected. Dermatitis herpetiformis may be associated with Hashimoto’s thyroiditis, insulin-dependent diabetes mellitus, and rarely other autoimmune diseases. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, direct and indirect immunofluorescence tests.

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4.14 Dermatitis Herpetiformis

Fig. 4.29 Linear IgA disease, small bullae in an herpetiform pattern on the buttock area.

Fig. 4.30 Dermatitis herpetiformis, multiple vesicles, and crusting on the trunk.

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Differential diagnosis: Bullous pemphigoid, mucous membrane pemphigoid, linear IgA disease, pemphigus, herpetiform ulcers, erythema multiforme, and primary herpetic gingivostomatitis. Treatment: Dapsone is the first-line treatment. Sulfapyridine is the secondline choice. Long-term adherence to a gluten-free diet is recommended.

4.15 Bullous Lichen Planus See also section 1.3. Definition: Lichen planus is a common, chronic, inflammatory mucocutaneous disease, and the bullous form is a rare variety of oral lichen planus. Etiology: It represents a T-cell-mediated immune reaction of unknown etiology. Clinical features: Clinically, six types of oral lichen planus have been described. The bullous form is rare and is characterized by formation of bullae of varying size that rapidly rupture, leaving painful ulcerations (▶ Fig. 4.32). The bullae usually arise on a background of papules or striae with the typical pattern of lichen planus. The diagnosis is mainly based on the clinical features, but occasionally should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, direct immunofluorescence. Differential diagnosis: Mucous membrane pemphigoid, epidermolysis bullosa acquisita, bullous pemphigoid, pemphigus, linear IgA disease, lupus erythematosus, graft versus host disease, and angina bullosa hemorrhagica. Treatment: Corticosteroids, topical or systemic.

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4.15 Bullous Lichen Planus

Fig. 4.31 Dermatitis herpetiformis, vesicles in a hemicircular pattern on the alveolar mucosa.

Fig. 4.32 Lichen planus, bullous type on the buccal mucosa.

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4.16 Epidermolysis Bullosa Definition: Epidermolysis bullosa is a heterogeneous group of disorders that share three major features: genetic inheritance, bullae formation,and cutaneous and mucosal fragility under minor pressure. Etiology: Genetic. Over 300 mutations have been implicated, involving at least 18 genes that encode structural epidermal, dermoepidermal, and upper papillary dermis proteins. Clinical features: Based on the anatomical level of the skin where the bullae occur, the pattern of inheritance, and the clinical features, epidermolysis bullosa is classified into three main types: (1) simplex (inherited in an autosomal dominant pattern), (2) junctional (inherited in an autosomal recessive pattern), and (3) dystrophic (inherited in an autosomal dominant or autosomal recessive pattern), and over 30 clinical phenotypes. The clinical spectrum and the degree of severity may range from mild to severe or fatal and the lesions appear at birth or early in infancy. Oral lesions are more common in the junctional and dystrophic types. Clinically, they present as bullae, usually in areas of friction, which soon rupture, leaving painful erosions or ulcers, leading to atrophic scarring, tongue dyskinesia, microstomia, and dystrophic lesions of the dental tissues depending on the type of the disease (▶ Fig. 4.33, ▶ Fig. 4.34, ▶ Fig. 4.35). Leukoplakia and squamous cell carcinoma may develop on the atrophic lesions, mainly in the dystrophic type. The cutaneous lesions are characterized by bullae formation, followed by ulceration and scarring or disfigurement depending on the type (▶ Fig. 4.36). In all types, skin friability occurs under even mild mechanical pressure. Nail involvement, milia, deformities of hand and feet, involvement of the larynx, pharynx, and esophagus are common in the recessive dystrophic type. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. More reliable tests are electron microscopy examination, immunofluorescent antigen mapping, mutation analysis, and molecular genetics. Differential diagnosis: Hailey–Hailey disease, pemphigus, mucous membrane pemphigoid, bullous pemphigoid, linear IgA disease, bullous dermatoses of childhood, epidermolysis bullosa acquisita, and pachyonychia congenita. Treatment: Supportive. Systemic corticosteroids, thalidomide, retinoids, and recently recombinant protein therapy, gene therapy, and others.

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4.16 Epidermolysis Bullosa

Fig. 4.33 Dystrophic epidermolysis bullosa, atrophy and bulla formation on the tongue.

Fig. 4.34 Dystrophic epidermolysis bullosa, scarring on the tongue and lips, and microstomia.

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Fig. 4.35 Dystrophic epidermolysis bullosa, dystrophy and premature damage of the teeth.

4.17 Epidermolysis Bullosa Acquisita Definition: Epidermolysis bullosa acquisita is a rare, noninherited, chronic, autoimmune blistering disease. Etiology: Autoimmune. Type VII collagen, the major component of anchoring fibrils of the dermal–epidermal junction, is the main target antigen. Clinical features: The disease may occur at any age in both sexes and mainly affects the skin and less frequently the oral mucosa and other mucosae. Clinically, the skin lesions are characterized by the formation of tense, recurrent bullae, and ulcerations, usually at the sites of mechanical friction (elbows, knees, joints, dorsal aspect of the hands, feet, toes, and scalp), thereafter the lesions heal with scarring and milia (▶ Fig. 4.37). Atrophic skin areas, hyperpigmentation, alopecia, and nail dystrophy may occur. The oral mucosa is involved in 30 to 50% of the cases. Clinically, a few hemorrhagic bullae may appear, usually following mild trauma, then rupture, leaving painful ulcerations that may

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4.17 Epidermolysis Bullosa Acquisita

Fig. 4.36 Dystrophic epidermolysis bullosa, severe lesions with deformity of the palm and fingers.

Fig. 4.37 Epidermolysis bullosa acquisita, milia, and scarring on the fingers.

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Vesiculobullous Lesions heal with scarring (▶ Fig. 4.38). The lesions mainly affect the buccal mucosa, palate, tongue, and gingiva in the pattern of desquamative gingivitis. Other mucosae may also be involved, including the larynx, esophagus, and conjunctiva. The diagnosis is based on the history and clinical features, but should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, direct and indirect immunofluorescence, and immunoelectron microscopy. Differential diagnosis: Inherited epidermolysis bullosa, mucous membrane pemphigoid, bullous pemphigoid, linear IgA disease, pemphigus, bullous lichen planus, angina bullosa hemorrhagica, systemic lupus erythematosus, and porphyria cutanea tarda. Treatment: Systemic and/or topical corticosteroids are the first line of treatment. Immunosuppressive drugs, colchicine, dapsone, and rituximab can also be used.

4.18 Angina Bullosa Hemorrhagica Definition: Angina bullosa hemorrhagica is a benign, principally, subepithelial, blood blistering oral disorder. Etiology: The exact etiology remains unknown. Predisposing factors are mild trauma, long-term use of steroid inhalers, increased vascular fragility, and probably a genetic predisposition. Clinical features: Clinically, the characteristic lesion consists of asymptomatic, single or multiple hemorrhagic bullae that mostly occur on the soft palate and the buccal mucosa (▶ Fig. 4.39). The bullae then rupture spontaneously, leaving superficial, mild, painful ulcerations that heal without scarring in 4 to 6 days. The disorder is more common in middle-aged women. The diagnosis is mainly based on the history and clinical features. However, laboratory tests should be performed if a vesiculobullous disease is suspected. Laboratory tests: Histopathologic examination, direct and indirect immunofluorescent tests. Differential diagnosis: Traumatic bulla, epidermolysis bullosa acquisita, mucous membrane pemphigoid, bullous pemphigoid, linear IgA disease, pemphigus, pemphigoid gestationis, bullous lichen planus, primary systemic amyloidosis, and idiopathic thrombocytopenic purpura.

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4.18 Angina Bullosa Hemorrhagica

Fig. 4.38 Epidermolysis bullosa acquisita, bulla, and erosion on the buccal mucosa.

Fig. 4.39 Angina bullosa hemorrhagica, multiple hemorrhagic bullae on the buccal mucosa.

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Treatment: Usually, the bullae regress spontaneously within 4 to 6 days. In the case of multiple lesions, a short regimen of systemic corticosteroids in low dose for 6 to 8 days shortens the healing period of ulcers.

4.19 Primary Systemic Amyloidosis See also section 8.3.1. Definition: Amyloidosis is a relatively rare, heterogenous group of metabolic disorder that is characterized by abnormal extracellular deposition of amyloid within the tissues. Etiology: The etiology is not exactly known. Clinical features: Clinically, amyloidosis is classified into two major types: the systemic and the localized, and several subtypes. Primary systemic amyloidosis is the most severe type of the disease, affecting individuals older than 50 years. Oral lesions are common, and present as multiple, red papules, nodules or tumors, petechiae, ecchymoses, ulcers, macroglossia, salivary glands infiltration. Rarely, asymptomatic, hemorrhagic, bullae formation may occur, particularly on the tongue and buccal mucosa mimicking bullous disease (▶ Fig. 4.40). The diagnosis is based on the clinical features and laboratory tests. Laboratory tests: Histopathologic examination with Congo red staining, methyl violet, and thioflavin-T are necessary. Differential diagnosis: Bullous pemphigoid, mucous membrane pemphigoid, pemphigus, epidermolysis bullosa acquisita, and angina bullosa hemorrhagica. Treatment: Symptomatic.

4.20 Traumatic Bulla Definition: A relatively common benign disorder in the oral cavity. Etiology: The cause is a sharp mechanical injury (biting, teeth, and prosthetic appliances) of the oral mucosa, which may form abrupt subepithelial hemorrhage that may detach the epithelium forming a hemorrhagic bulla. Clinical features: Clinically, the lesion appears usually as a single asymptomatic bulla containing blood, and usually disappears within 2 to 3 days without treatment (▶ Fig. 4.41). The bulla is tense, well defined, with a size of few

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4.20 Traumatic Bulla

Fig. 4.40 Amyloidosis, hemorrhagic bullae, and ecchymoses on the tongue.

Fig. 4.41 Traumatic hemorrhagic bulla of the buccal mucosa.

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Vesiculobullous Lesions millimeters to 1 cm. The buccal mucosa is the site of predilection and rarely other oral sites. The diagnosis is usually based on the history and clinical features. Laboratory tests: Usually not required. Histopathologic examination. Differential diagnosis: Angina bullosa hemorrhagica, epidermolysis bullosa acquisita, bullous lichen planus, mucous membrane pemphigoid, linear IgA disease, pemphigoid gestationis, pemphigus, and amyloidosis. Treatment: No treatment is needed.

4.21 Pyostomatitis Vegetans Definition: Pyostomatitis vegetans is a rare, benign, oral mucosal pustular disease that usually coexists with ulcerative colitis and Crohn’s disease. Etiology: The etiology is unknown. Clinical features: The disease affects most frequently males than females (ratio 3:1) with a preference for young and middle-aged individuals. Clinically, it is characterized by multiple, small, gray to yellow pustules, in a linear pattern, that coalesce and develop on an erythematous surface (▶ Fig. 4.42). The pustules then rupture, leaving painful shallow snail-track ulcerations. The buccal mucosa, palate, uvula, and gingiva are the most frequently affected sites. The oral lesions, usually, appear at the same time or after the intestinal symptoms and rarely may precede them. Similar lesions may develop on the skin characterized as pyodermatitis vegetans and pyoderma gangrenosum. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, direct immunofluorescence. Differential diagnosis: Primary herpetic gingivostomatitis, herpetiform aphthous ulcerations, Adamantiades–Behçet disease, dermatitis herpetiformis, pemphigoid, pemphigus, and drug reactions. Treatment: The control of the underlying intestinal disease is of great importance. Systemic corticosteroids are the first line of treatment for the oral lesions. Azathioprine and dapsone can be used in parallel with corticosteroids.

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4.21 Pyostomatitis Vegetans

Fig. 4.42 Pyostomatitis vegetans, multiple coalescing pustules on the gingiva and alveolar mucosa.

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5 Ulcerative Lesions Ulcerative lesions are a heterogeneous, wide group of common and rare oral mucosal disorders. The most common causes of these lesions are mechanical and reactive factors, infectious diseases and neoplasms, as well as autoimmune and hematologic disorders. The main clinical feature in all these conditions is an ulcer, which is defined as loss of all epithelial layers. In addition, the term “erosion” is used to define a superficial loss of epithelium. However, at the clinical level, the terms “ulcer” and “erosion” are usually used interchangeably. In this chapter, only primary ulcerative lesions are discussed and not the lesions that arise secondarily from the ruptured bullae.

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Traumatic Ulcer

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Neutropenia

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Eosinophilic Ulcer

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Cyclic Neutropenia

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Necrotizing Sialadenometaplasia

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Congenital Neutropenia

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Necrotizing Ulcerative Gingivitis

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Agranulocytosis

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Noma

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Bone Marrow Aplasia

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Chronic Ulcerative Stomatitis

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Myelodysplastic Syndrome

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Syphilis

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Leukemia

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Tuberculosis

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Langerhans Cell Histiocytosis

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Systemic Mycoses

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Glycogen Storage Disease, Type 1b

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Aphthous Ulcers

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PFAPA Syndrome

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Adamantiades–Behçet’s Disease

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Sweet’s Syndrome

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Graft Versus Host Disease

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Staphylococcal Infection

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Wegener’s Granulomatosis

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Pseudomonas Infection

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Nasal Type-Extranodal NK/T-Cell Lymphoma

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Klebsiella Infection

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Non-Hodgkin’s Lymphomas

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Cytomegalovirus Infection

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Squamous Cell Carcinoma

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5.1 Traumatic Ulcer Definition: Traumatic ulcer is one of the most common ulcerations of the oral mucosa. Etiology: The most common causes are a sharp or broken tooth, rough fillings, sharp parts of full or partial dentures, dental instruments, sharp foodstuff, biting, sharp foreign bodies, overzealous tooth brushing, etc. Clinical features: Clinically, the presentation is variable, but usually traumatic ulcers appear as solitary, painful lesions with a smooth red or whitish-yellow surface and thin erythematous or whitish halo (▶ Fig. 5.1 and ▶ Fig. 5.2). They are usually soft on palpation and heal spontaneously without scarring, within 6 to 10 days after removal of the cause. However, chronic traumatic ulcers may, clinically, mimic oral squamous cell carcinoma. A close relationship between an ulcerogenic factor (mechanical damage) and the ulcer is necessary for the diagnosis. The lateral borders of the tongue, buccal mucosa, lips, palate, and gingiva are the sites of predilection. The diagnosis is mainly based on the history and clinical features. However, if an ulcer persists over 10 to 12 days a biopsy must be performed to rule out cancer or other severe diseases. Laboratory tests: Histopathologic examination. Differential diagnosis: Squamous cell carcinoma and other malignancies, aphthous ulcer, eosinophilic ulcer, Riga Fede ulceration, syphilitic ulcer (chancre), oral tuberculosis, oral systemic mycoses, microbial ulcerations, non-Hodgkin’s lymphoma, necrotizing sialadenometaplasia, and several other oral ulcerations. Treatment: Removal of the causative agent. Topical corticosteroid ointments in Orabase or gel improve the symptoms and help healing, oxygen-releasing mouthwashes.

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5.1 Traumatic Ulcer

Fig. 5.1 Traumatic ulcer of the tongue.

Fig. 5.2 Traumatic ulcer of the upper gingiva.

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5.2 Eosinophilic Ulcer Definition: Eosinophilic ulcer is a rare, benign, often self-limited, inflammatory lesion of the oral mucosa unrelated to Langerhans cell histiocytosis. Etiology: The exact etiology remains unknown, although a traumatic injury has been suggested as the causative agent. Clinical features: Clinically, eosinophilic ulcer appears acutely as a painful ulcer with an irregular surface, covered with a whitish-yellow membrane, raised inflammatory and slightly indurated border (▶ Fig. 5.3 and ▶ Fig. 5.4). The tongue is the site of predilection (> 74%), followed by the lips, buccal mucosa, and rarely the gingiva. Usually, the ulcer is solitary but multiple lesions may occur. The clinical diagnosis should be confirmed by a biopsy and laboratory tests. Laboratory tests: Histopathologic examination. Immunohistochemical and molecular studies with polymerase chain reaction (PCR) should be performed in some cases. Differential diagnosis: Traumatic ulcer, major aphthous ulcers, histiocytic eosinophilic granuloma, Riga Fede ulceration, Wegener’s granulomatosis, nonHodgkin’s lymphoma, syphilitic ulcer (chancre), oral tuberculosis, necrotizing sialadenometaplasia, squamous cell carcinoma, and hematological disorders. Treatment: Spontaneous healing in several weeks or months may occur. However, the healing time can be shortened (8–12 days) by systemic corticosteroids in low dose (prednisolone 20–30 mg/d for 1–2 weeks).

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5.2 Eosinophilic Ulcer

Fig. 5.3 Eosinophilic ulcer of the dorsum of the tongue, early stage.

Fig. 5.4 Eosinophilic ulcer on the tongue, late stage.

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5.3 Necrotizing Sialadenometaplasia Definition: Necrotizing sialadenometaplasia is a relatively rare, benign, selfhealing inflammatory disorder of the salivary glands. Etiology: The cause is unknown, but the dominant theory suggests a vascular damage (obstruction) and necrosis of the involved salivary glands. Clinical features: Clinically, the lesion appears acutely, as a painless nodular, inflammatory swelling that leads to a painful crater-like ulcer, with raised, irregular border, and diameter of 0.5 to 5 cm (▶ Fig. 5.5 and ▶ Fig. 5.6). It is usually unilateral, but more than one lesion may develop in a bilateral pattern. The posterior part of the hard palate is the site of predilection (75–80%) and less frequently, the lower lip, buccal mucosa, and retromolar area. Clinically and histologically, the disorder mimics squamous cell carcinoma and adenocarcinoma. The diagnosis is based on the history, clinical features, and laboratory tests. Laboratory tests: Histopathologic examination. The microscopic findings resemble squamous cell carcinoma or mucoepidermoid carcinoma. Differential diagnosis: Squamous cell carcinoma, salivary gland adenocarcinomas, nasal type-extranodal natural killer (NK)/T-cell non-Hodgkin’s lymphoma, syphilitic ulcer (chancre), systemic mycoses, eosinophilic ulcer, and traumatic ulcer. Treatment: The lesion is usually self-healing and heals within 4 to 6 weeks. Systemic corticosteroids in low dose (prednisolone 10–20 mg/d for 1–2 weeks) reduce the healing time and prevent possible bone destruction.

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5.3 Necrotizing Sialadenometaplasia

Fig. 5.5 Necrotizing sialadenometaplasia, early lesion presenting as a small enlargement.

Fig. 5.6 Necrotizing sialadenometaplasia, large, crater-like ulceration on the posterior part of the hard palate.

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5.4 Necrotizing Ulcerative Gingivitis Definition: Necrotizing ulcerative gingivitis is an acute, painful, inflammatory, infectious gingival disease of young individuals. Etiology: Anaerobic bacteria, spirochetes, and other bacteria play an important causative role. Predisposing factors include physical and psychological stress, poor oral hygiene, smoking and mainly HIV infection, and other forms of immunosuppression. Clinical features: Clinically, it is characterized by dense inflammation and ulcerations with painful crater-like necrosis of the interdental papillae and the marginal gingiva, which are covered by a yellow-grayish pseudomembrane (▶ Fig. 5.7 and ▶ Fig. 5.8). Spontaneous bleeding, halitosis, and intense salivation are common. Regional lymphadenopathy, mild fever, and malaise may also occur. The lesions may be localized or generalized. If the disease is left untreated and the tissue destruction is great it can progress to necrotizing ulcerative periodontitis or may spread to the adjacent soft tissues, as necrotizing ulcerative stomatitis. The diagnosis is based on the history and clinical features. Laboratory tests: Usually it is not needed. Histopathologic examination is not pathognomonic. Differential diagnosis: Primary herpetic gingivostomatitis, desquamative gingivitis, granulomatous gingivitis, agranulocytosis, neutropenia, acute leukemia, Langerhan’s cell histiocytosis, scurvy, pyostomatitis vegetans. Treatment: Systemic metronidazole (500 mg three times daily for 6–7 days) in association with oxygen-releasing mouthwashes is the treatment of choice, particularly in severe cases. Plaque control measures, scaling, and root planing after acute stage are necessary.

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5.4 Necrotizing Ulcerative Gingivitis

Fig. 5.7 Necrotizing ulcerative gingivitis, early stage.

Fig. 5.8 Necrotizing ulcerative gingivitis with extensive destruction of the interdental papillae.

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5.5 Noma Definition: Noma or cancrum oris is a rare, rapidly progressive and severe destructive disorder, usually involving the oral tissues. Etiology: Anaerobic bacteria and spirochetes along with local and systemic predisposing factors (poor oral hygiene, systemic infections and parasitic diseases, severe malnutrition, diabetes mellitus, leukemia, HIV infection, malignancies, and immune defects) are the cause. The disease usually affects children and rarely adults, particularly in socioeconomically deprived areas of Africa, Asia, and South America. Clinical features: Clinically, the disease usually begins as acute necrotizing ulcerative gingivitis that quickly spreads to the adjacent soft tissues, forming abnormal necrotic ulcerations (▶ Fig. 5.9). The gangrenous necrosis progressively involves the buccal mucosa, lips, and the underlying bone, producing catastrophic lesions (▶ Fig. 5.10). The gangrenous ulcers have an irregular border and are covered with whitish-yellow or brown fibrin and debris. Salivation, halitosis, fever, malaise, and regional lymphadenopathy are always present. The diagnosis is based on the history and clinical features. Laboratory tests: Microbiological culture may be necessary to determine the choice of antibiotics. Differential diagnosis: Nasal type-extranodal NK/T-cell lymphoma, Burkitt’s lymphoma, leukemia, aplastic anemia, agranulocytosis, tuberculosis, and systemic mycoses. Treatment: Appropriate antibiotics, hydration, and a nutritious diet as soon as possible. Surgical reconstruction should follow after stabilization of tissue destruction.

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5.5 Noma

Fig. 5.9 Noma, early mucosal ulceration of the lower lip.

Fig. 5.10 Noma, perforation of the lower lip with extension to the skin and scarring at a late stage.

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5.6 Chronic Ulcerative Stomatitis Definition: Chronic ulcerative stomatitis is a rare, chronic, oral disease with characteristic immunofluorescent pattern. Etiology: Autoimmune, with specific tissue-bound and circulating autoantibodies, targeting Delta Np63a nuclear epithelial cells protein. Clinical features: The disease involves almost exclusively the oral mucosa and has a chronic course with recurrences. Clinically, it presents as erythema and painful erosions of the gingiva, usually localized, in the form of desquamative gingivitis (▶ Fig. 5.11). Painful erosions, associated with white striations, similar to those of lichen planus and discoid lupus erythematosus may occur on the buccal mucosa and the tongue (▶ Fig. 5.12). Rarely, skin lesions similar to lichen planus may be seen. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination and mainly direct and indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) tests. Differential diagnosis: Lichen planus, discoid lupus erythematosus, mucous membrane pemphigoid, linear IgA disease, epidermolysis bullosa acquisita, pemphigus, and oral psoriasis. Treatment: Hydroxychloroquine is the drug of choice. Systemic corticosteroids may also be used. Topical corticosteroids in the form of ointment or gel in mild cases.

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5.6 Chronic Ulcerative Stomatitis

Fig. 5.11 Chronic ulcerative stomatitis, desquamative gingivitis.

Fig. 5.12 Chronic ulcerative stomatitis, erosions interspersed with white striated lesions on the buccal mucosa.

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5.7 Syphilis Definition: Syphilis is a sexually transmitted chronic, systemic, infection that is characterized by a variety of clinical manifestations. Etiology: Treponema pallidum, a member of the genus Treponema, is the cause which was identified by Schaudinn and Hoffmann in 1905. Clinical features: The disease may be congenital (rare) or acquired (common). Acquired syphilis, on epidemiologic, clinical, and therapeutic criteria, is classified as: (1) early syphilis, which includes primary and secondary stages and clinical relapses, due to incomplete treatment, and lasts for less than 1 year, (2) latent syphilis, which is subclassified into early stage (lasts for a year or less) and late stage (lasts for more than a year), and (3) late syphilis,also called tertiary syphilis. Oral manifestations are common and may develop in all stages of syphilis. The classic lesion in the primary stage is the chancre that appears at the site of inoculation of T. pallidum, usually 3 weeks after the infection. Oral chancre appears in about 5 to 10% of the cases, and clinically presents as a round or oval, painless, ulcer with a smooth surface, raised border, and indurated base. It is often surrounded by a narrow red border and is covered by a grayish or whitish serous exudate teeming with T. pallidum (▶ Fig. 5.13 and ▶ Fig. 5.14). The size varies from a few millimeters to 3 cm in diameter. The tongue, lips, palate, and tonsillar area are the sites of predilection. Without treatment the chancre heals spontaneously within 3 to 8 weeks. Regional lymphadenopathy is a constant sign. The secondary stage begins 6 to 8 weeks after the appearance of the chancre, and lasts for 2 to 10 weeks. Oral lesions are mucous patches (common) (▶ Fig. 5.15), macular syphilides, and condylomata lata (rare) (▶ Fig. 5.16). Clinically, mucous patches present as flat or slightly raised, painless, oval or round papules or patches with erosions covered by a grayish-white membrane teeming with T. pallidum. Constitutional symptoms and signs, generalized lumphadenopathy, as well as cutaneous manifestations (macular syphilides, papules, condylomata lata, nails involvement, hair loss, atypical rash, etc.) are constant findings. Tertiary syphilis begins after a period of 2 to 10 years or more. Oral lesions are gumma (▶ Fig. 5.17), atrophic glossitis, and interstitial glossitis. The clinical diagnosis of syphilis should be confirmed by laboratory tests.

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5.7 Syphilis

Fig. 5.13 Chancre on the sulcus of the penis.

Fig. 5.14 Chancre on the ventrum of the tongue.

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Fig. 5.15 Syphilitic mucous patches on the lateral border of the tongue.

Laboratory tests: Dark-field microscopic examination, serologic tests (VDRL, FTA-ABS, RPR, TPI, TPHA, and others). Differential diagnosis: Aphthous ulcer, herpes simplex, angular cheilitis, traumatic ulcer, infectious mononucleosis, erythema multiforme, candidiasis, oral tuberculosis, and plethora of other oral lesions and diseases. Treatment: Penicillin G is the golden choice of treatment of all stages of syphilis. Erythomycin or cephalosporins may be used as alternative drugs.

5.8 Tuberculosis Definition: Tuberculosis is one of the world’s most widespread, chronic, granulomatous, infectious disease that primarily affects the lungs. Etiology: Mycobacterium tuberculosis.

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5.8 Tuberculosis

Fig. 5.16 Condyloma lata on the dorsum of the tongue.

Fig. 5.17 Perforation of the palate by syphilitic gumma.

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Clinical features: The oral lesions are rare, and usually secondary to pulmonary tuberculosis. Clinically, oral tuberculosis appears as a painless or painful ulcer, usually single and rarely multiple. The ulcer is irregular at the periphery with thin margin, vegetating surface covered by a gray-yellowish exudate, and soft base (▶ Fig. 5.18). The surrounding tissues are inflamed. The size of ulcer ranges from 1 to 5 cm. The dorsum of the tongue is most commonly affected, followed by the lips, soft palate, buccal mucosa, and gingiva. Osteomyelitis of the jaws, periapical granuloma, regional lymphadenopathy and scrofula are less common oral manifestations. The diagnosis of oral tuberculosis is based on the clinical features and laboratory tests. Laboratory tests: Histopathologic examination, sputum culture, chest radiography, tuberculin skin test, and nucleic acid amplification (DNA and RNA) tests for mycobacterium tuberculosis. Differential diagnosis: Chancre, aphthous ulcer, eosinophilic ulcer, necrotizing sialadenometaplasia, non-Hodgkin’s lymphoma, squamous cell carcinoma, systemic mycoses, actinomycosis, sarcoidosis, and Wegener’s granulomatosis. Treatment: Tuberculosis requires management by appropriate medical team. Streptomycin, isoniazid, ethambutol, rifampin, pyrazinamide, and others are the drugs of choice.

5.9 Systemic Mycoses Definition: Systemic mycoses are relatively, rare, chronic fungal infections. Etiology: The most common systemic mycoses are: (1) histoplasmosis, caused by Histoplasma capsulatum, (2) aspergilosis, caused by Aspergillus species, (3) mucormycosis caused by Mucor–Rhizopus, (4) cryptococcosis, caused by Cryptococcus neoformas, (5) blastomycosis, caused by Blastomyces dermatitidis, (6) paracoccidioidomycosis, caused by Paracoccidioides brasiliensis. Some of them are endemic in certain geographic parts of the world while others affect individuals with predisposing conditions such as: HIV infection, immunocompromised status, neutropenia, aplastic anemia, leukemia, lymphomas, organ transplantation, diabetes mellitus, and malignancies. Clinical features: Oral involvement in systemic mycoses is characterized by an atypical chronic, irregular, and vegetating ulcer, usually painful, with a tendency to spread (▶ Fig. 5.19 and ▶ Fig. 5.20). The surface of the ulcers is

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5.9 Systemic Mycoses

Fig. 5.18 Tuberculosis, ulcer on the lateral edge of the tongue.

Fig. 5.19 Histoplasmosis on the palate, two small ulcers are noticed.

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Fig. 5.20 Paracoccidioidomycosis, enlargement and ulceration on the gingiva.

characteristically necrotic and black in mycormycosis and aspergillosis (▶ Fig. 5.21 and ▶ Fig. 5.22) while in the other mycoses is usually red. Systemic signs and symptoms are always present depending on the organ involved. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, microbiologic culture, and CT. Differential diagnosis: Tuberculosis, syphilis, squamous cell carcinoma, nonHodgkin’s lymphomas, necrotizing sialadenometaplasia, agranulocytosis, myelodysplastic syndrome, mucocutaneous leishmaniasis, and Wegener’s granulomatosis. Treatment: Intravenous liposomal amphotericin B, itraconazole, fluconazole, posaconazole, and voriconazole are the drugs of choice.

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5.9 Systemic Mycoses

Fig. 5.21 Mucormycosis, early lesion on the upper lip.

Fig. 5.22 Aspergillosis, ulceration on the palate.

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5.10 Aphthous Ulcers Definition: Aphthous ulcers or recurrent aphthous stomatitis are one of the most common diseases of the oral mucosa, affecting 10 to 30% of the population. Etiology: The exact etiology remains unknown. Recent opinion is that impaired cell-mediated immune response plays primary role in the pathogenesis. Several predisposing factors have been implicated in the development of aphthous ulcers, including genetic predisposition, trauma, allergy, stress, iron deficiency, low levels of vitamin B12 and folic acid, hormonal disturbances, etc. Clinical features: On clinical criteria, based on the size, number, depth of ulcer, duration, and scarring, aphthous ulcers are classified into minor, major, and herpetiform types. Minor aphthae is the most common type and clinically appear as small, painful round ulcers (3–6 mm in diameter) with a whitishyellow bottom and thin red areaola (▶ Fig. 5.23). The lesions may be single or multiple (2–6) lasting for 7 to 12 days and heal, without scarring. The major type is characterized by deep, painful ulcers (1–3 cm in diameter) with whiteyellow surface and red inflammatory halo (▶ Fig. 5.24). The herpetiform type is characterized by multiple small (1–3 mm in diameter), painful, shallow ulcers, with a tendency to coalesce into irregular ulcers (▶ Fig. 5.25). The ulcers are typically multiple (10–100), last for 1 to 2 weeks and heal without scarring. The nonkeratinized movable mucosa (tongue, buccal mucosa, soft palate, and lips) is most frequently affected in all three clinical types. Recurrences are common, with variable intervals of quiescence between attacks. The oral clinicians should remember that aphthous ulcers may represent a manifestation of systemic disease. The diagnosis is based on the history and clinical features. Laboratory tests: There are no specific laboratory tests. Differential diagnosis: Traumatic ulcer, herpes simplex, herpangina, hand, foot, and mouth disease (HFMD), Adamantiades–Behçet’s disease, chancre, PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome, Sweet’s syndrome, cyclic neutropenia, leukemia, Crohn’s disease, ulcerative colitis, and early erythema multiforme.

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5.10 Aphthous Ulcers

Fig. 5.23 Minor aphthous ulcer on the lower lip.

Fig. 5.24 Major aphthous ulcer on the tip of the tongue.

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Treatment: There is no effective treatment for aphthae. The treatment is local or systemic. Topical corticosteroids in the form of triamcinolone 0.1% in orabase, clobetasole propionate, tacrolimus 0.1% or 0.03%, amplexanox 5%, and diclofenac 3% have been used with partial success. For major aphthae and herpetiform type, systemic corticosteroids in low doses (e.g., prednisolone 20–30 mg/d for 7–10 days) are recommended. In severe cases thalidomide (it is contraindicated in women of reproductive age and of course during pregnancy), dapsone, colchicine, pentoxifylline, and azathioprine have been used with uncertain results.

5.11 Adamantiades–Behçet’s Disease Definition: Adamantiades–Behçet’s disease is a chronic multisystemic and polysymptomatic inflammatory disorder. Etiology: Probably autoimmune. Humoral and cellular type responses against one or more endogenous antigens are possibly playing a major role in the pathogenesis. Clinical features: The disease affects more often males than females (ratio 5:1–10:1), usually between 20 and 30 years, but it may occur at any age. Clinically, the major diagnostic criteria are: (1) recurrent (three episodes per year), aphthous ulcers in the oral mucosa (▶ Fig. 5.26); (2) ocular lesions: conjunctivitis, iritis with hypopyon, uveitis, and retinal vasculitis, which can cause blindness (▶ Fig. 5.27); (3) recurrent genital ulcers, valanitis, and perianal ulcers (▶ Fig. 5.28); (4) cutaneous lesions: papules, pustules, folliculitis, erythema nodosum, ulcers, and rarely necrotic lesions (▶ Fig. 5.29); (5) positive pathergy test (positive 50–60%). Less frequently, secondary criteria may also be present such as: arthritis, arthralgias, thrombophlebitis and phlebothrombosis, arterial occlusions and aneurysms, pericarditis, endocarditis, epididymitis, pulmonary, renal, gastrointestinal, and central nervous system (CNS) manifestations. For the diagnosis the required criteria are: recurrent aphthous ulcers and two other major criteria. However, the disease cannot be excluded when one major and more than two secondary criteria are present. The oral mucosa is almost always affected (95–100%) and frequently the aphthous ulcers precede other manifestations and may present in all clinical subtypes (minor–major–herpetiform). The diagnosis is mainly based on the clinical grounds.

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5.11 Adamantiades–Behçet’s Disease

Fig. 5.25 Herpetiform ulcers, multiple lesions on the soft and hard palate.

Fig. 5.26 Adamantiades–Behçet’s disease, aphthous ulcers on the tongue.

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Fig. 5.27 Adamantiades–Behçet’s disease, conjunctivitis.

Laboratory tests: There are no pathognomonic tests. Differential diagnosis: Aphthous ulcers, reactive arthritis (Reiter’s syndrome), erythema multiforme, Sweet’s syndrome, PFAPA syndrome, pyostomatitis vegetans, ulcerative colitis, and Crohn’s disease. Treatment: Systemic corticosteroids, immunosuppressants, colchicine, dapsone, thalidomide and monoclonal antitumor necrosis factor alpha antibodies have been used either alone or in combination.

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5.11 Adamantiades–Behçet’s Disease

Fig. 5.28 Adamantiades–Behçet’s disease, small ulcer on the scrotum.

Fig. 5.29 Adamantiades–Behçet’s disease, mild necrotic ulcers on the skin of the palm.

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5.12 Graft Versus Host Disease Definition: Graft versus host disease is a complex multisystemic immune disorder, and one of the major complications in patients who have undergone allogeneic bone marrow or stem cells transplantation to treat leukemia, myelodysplastic syndrome, myelic aplasia, immunodeficiency disorders, and solid tumors. Etiology: It is the result of the immune reaction caused by the allogeneic lymphoid cells of the donor against the host who lacks the donor’s antigens. Clinical features: The disorder manifests with a plethora of signs and symptoms from multiple tissues and organs. It is classified into (1) acute, which occurs the first week following the transplant and up to 3 months after and develops in 20 to 40% of the patients, and (2) chronic, which begins 100 days after the transplantation and develops in 40% of the patients. Clinically, the acute form is characterized by fever, diffuse erythematous and maculopapular skin rash, gastrointestinal and liver involvement, and rarely mucosal manifestations (conjunctivitis and erythema, atypical ulcerations, and lichenoid lesions of the oral mucosa). The chronic form is characterized by liver dysfunction, pulmonary insufficiency, scleroderma and lichen planus-like skin lesions, eye disorders, gastrointestinal disorders, and oral lesions. Clinically, the oral lesions are common (70–90%) and include: erythema, lichenoid lesions, and painful ulcerations that mainly affect the tongue, buccal mucosa, gingiva, and lips. Xerostomia, salivary glands involvement, and restriction of mouth opening may also occur (▶ Fig. 5.30 and ▶ Fig. 5.31). The diagnosis is mainly based on the history and clinical features. Laboratory tests: Histopathologic examination. Differential diagnosis: Lichen planus, drug related stomatitis, Sjögren's syndrome, systemic sclerosis, lupus erythematosus, and oral mucositis due to radiation or chemotherapy. Treatment: Systemic corticosteroids with or without immunosuppressives are the first line of treatment. Topical oral treatment with artificial saliva, topical steroids, antiseptic mouthwashes, anesthetics, and mouthwashes, with granulocyte-macrophage colony-stimulating factor, are suggested.

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5.12 Graft Versus Host Disease

Fig. 5.30 Graft versus host disease, chronic form. Lichenoid lesions on the tongue.

Fig. 5.31 Graft versus host disease, chronic form. Edema and lichenoid lesions on the lower lip.

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5.13 Wegener’s Granulomatosis Definition: Wegener’s granulomatosis is a rare, chronic granulomatous vasculitis, with questionable prognosis. Etiology: The exact etiology remains unknown. However, genetic, immunologic and environmental factors may be involved in the pathogenesis. Clinical features: The disease is classified into localized and generalized forms. Clinically, the classic triad is (1) granulomatous inflammation of the upper and lower respiratory system, (2) glomerulonephritis, and (3) systemic vasculitis that affects the skin, oral mucosa, and other organs. The oral lesions present as multiple or solitary, irregular ulcerations with inflammatory features. The tongue, soft palate, buccal mucosa, and gingiva are the most frequently affected areas (▶ Fig. 5.32 and ▶ Fig. 5.33). The oral lesions may rarely be the only, early, manifestations (localized form) or part of systemic (generalized form) disease. The skin lesions appear as palpable purpura, nodules, ulcers, and necrotic papules. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Serum autoantibodies against neutrophils cytoplasm (C-ANCA) are positive in 80% of patients with generalized form and 60% with localized form. Increase of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are common findings. Differential diagnosis: Non-Hodgkin’s lymphoma, nasal-NK–T-cell lymphoma, leukemia, myelodysplastic syndrome, systemic mycoses, tuberculosis, necrotizing sialadenometaplasia, major aphthous ulcer, and squamous cell carcinoma. Treatment: The treatment of choice is the combination of corticosteroids and cyclophosphamide. Azathioprine, mycophenolate acid, and recent biologic agents (e.g., rituximab and infliximab) have been used with success.

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5.13 Wegener’s Granulomatosis

Fig. 5.32 Wegener’s granulomatosis, early ulcer on the upper alveolar sulcus.

Fig. 5.33 Wegener’s granulomatosis, large ulcers on the alveolar mucosa, palate, and buccal mucosa.

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5.14 Nasal Type-Extranodal NK/T-Cell Lymphoma Definition: Nasal type-extranodal NK/T-cell lymphoma or angiocentric T-cell lymphoma or midline lethal granuloma is a very aggressive specific type of nonHodgkin’s lymphoma that derives from NK/T-cells and characteristically affects the nasopharynx, palate, skin, and rarely gastrointestinal tract and testis. Etiology: The etiology is unclear, although it is CD56 + positive and EBV is detected in cases out of the nasal cavity. Clinical features: The disease is more common in males (ratio 3:1) of 55 to 65 years of age. Clinically, it is characterized by prodromal signs and symptoms such as fever, weight loss, weakness, epistaxis, nasal stuffiness, foul-odor, nasal discharge and obstruction, edema and erythema of the palate, trismus, and visual disturbances. As the disease progress, deep necrotic ulcers develop that spread both peripherally and in depth (▶ Fig. 5.34 and ▶ Fig. 5.35). The lesions deteriorate rapidly, causing destruction and perforation of soft and hard tissues, resulting in severe disfiguration. Bleeding and secondary infections are common complications. The prognosis is unfavorable, with a high fatality rate. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination and immunohistochemical and molecular examinations. Differential diagnosis: Other types of non-Hodgkin’s lymphoma, Wegener’s granulomatosis, necrotizing sialadenometaplasia, minor salivary glands adenocarcinoma, squamous cell carcinoma, tuberculosis, aspergillosis, mucormycosis, and gumma. Treatment: The first line of treatment is systemic CHOP chemotherapy combined with radiation.

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5.14 Nasal Type-Extranodal NK/T-Cell Lymphoma

Fig. 5.34 Extranodal NK/T-cell lymphoma, ulceration with inflammatory reaction on the center of the palate.

Fig. 5.35 Extranodal NK/T-cell lymphoma, great ulceration, and destruction of the palate.

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5.15 Non-Hodgkin’s Lymphomas Definition: Non-Hodgkin’s lymphomas comprise a heterogeneous group of lymphoid tissue malignancies that account for 70 to 80% of all lymphomas. Over 90% of the cases derive from B-lymphocytes and 10% from T-lymphocytes. Etiology: The exact etiology remains unknown. However, genetic and environmental factors (viruses, helicobacter Pylori, radiation, medications, autoimmune conditions, and immunodeficiencies) seem to play a significant causative role. Clinical features: Based on the disease progression, and the degree of cellular aggression, non-Hodgkin’s lymphomas are classified into three categories: (1) low, (2) intermediate, and (3) high grade. However, the most recent classification is that by WHO (2008) that divides lymphomas into two major groups: B-cell derived, and T-cells derived, and over 30 subtypes. Clinically, the disease is characterized by persistent peripheral lymphadenopathy, lymphoid organ involvement, and up to 40% extranodal manifestations. The oral cavity is rarely the first and only manifestation, or more often is part of systemic disease. Clinically, oral non-Hodgkin’s lymphoma presents as a diffuse, usually, painless swelling, which may or may not be ulcerated (▶ Fig. 5.36 and ▶ Fig. 5.37). The surface of the ulcer is irregular with surrounding inflammation and firm on palpation. The soft palate, posterior gingiva, base of the tongue, floor of the mouth, and the tonsillar area are most frequently affected. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination and immunohistochemical and cytogenetic examinations. Differential diagnosis: Hodgkin’s disease, Wegener’s granulomatosis, eosinophilic ulcer, necrotizing sialadenometaplasia, tuberculosis, systemic mycoses, squamous cell carcinoma, and minor salivary gland adenocarcinoma. Treatment: The treatment of choice is chemotherapy, monoclonal antibodies against CD20 antigen (rituximab), and radiotherapy.

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5.15 Non-Hodgkin’s Lymphomas

Fig. 5.36 Non-Hodgkin’s lymphoma, localized enlargement on the lower gingiva.

Fig. 5.37 Non-Hodgkin’s lymphoma, vegetative enlargement on the lateral border of the tongue.

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5.16 Squamous Cell Carcinoma See also sections 1.23, 2.9, 6.7, and 8.2.1. Definition: Squamous cell carcinoma is the most common malignant neoplasm of the oral cavity and accounts for 93 to 95% of oral malignancies. Etiology: Despite the fact the exact etiology remains unknown, many intrinsic and extrinsic factors have been implicated. Among them the most important are smoking, alcohol consumption, oncogenic viruses (mainly human papillomavirus types 16 and 18), immunodeficiency, oncogenes, and tumor suppressor genes. Human cancer share properties, referred to as hallmarks, among which sustained proliferation, escape from apoptosis, and genomic instability are the most common. All of them are associated with DNA replication stress and cancer development. Clinical features: Squamous cell carcinoma of the oral mucosa presents with great clinical polymorphism. At an early stage, it appears as an asymptomatic white or red small plaque, or combination of both, erosion or small module (▶ Fig. 5.38 and ▶ Fig. 5.39). In the advanced stage, it appears as a painful deep ulcer, with irregular, vegetating surface and elevated hard edges or as an exophytic ulcerated irregular mass (▶ Fig. 5.40 and ▶ Fig. 5.41). The lateral border and the ventral surface of the tongue are the most frequently affected sites (> 50%), followed by the lips, buccal mucosa, palate, floor of the mouth, gingiva, and alveolar mucosa. As a rule, any oral lesion that persists for more than 10 days, in the absence of a clear etiologic factor, has to raise suspicion for carcinoma. The clinical diagnosis should be confirmed by a biopsy. Laboratory tests: Histopathologic examination. Differential diagnosis: Traumatic ulcer, leukoplakia, erythroplakia, tuberculous ulcer, eosinophilic ulcer, necrotizing sialadenometaplasia, minor salivary glands adenocarcinoma, Wegener’s granulomatosis, non-Hodgkin’s lymphoma, and any atypical oral lesion that persists for more than 10 days. Treatment: Radical surgical excision, with or without radiotherapy and/or chemotherapy. Recently, targeted treatments using monoclonal antibodies have been tried.

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5.16 Squamous Cell Carcinoma

Fig. 5.38 Early squamous cell carcinoma on the lateral border of the tongue.

Fig. 5.39 Early squamous cell carcinoma on the lateral border of the tongue.

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Fig. 5.40 Late squamous cell carcinoma on the lateral border of the tongue.

5.17 Neutropenia Definition: Neutropenia is a hematologic disorder characterized by a low neutrophil count (< 1800/μL). Etiology: The causes of neutropenia may be hereditary or acquired. Acquired causes may include bone marrow disorders or peripheral disorders. Clinical features: Patients with neutropenia are susceptible to infections, mainly by gram-positive or gram-negative bacteria and by fungi. The risk of infection is related to the severity of neutropenia. It is high, when neutrophil count is less than 500/μL. Clinically, systemic symptoms include high fever, malaise, loss of appetite, and other signs and symptoms mainly from respiratory and uropoietic systems, the inner ear, the skin, and the oral mucosa. The oral manifestations are common and include multiple ulcers primarily on the tongue, palate, gingiva and lips, soft-tissue abscesses, advanced periodontal disease, and bacterial and fungal infections (▶ Fig. 5.42 and ▶ Fig. 5.43). The clinical diagnosis should be confirmed by hematologic tests.

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5.17 Neutropenia

Fig. 5.41 Late, exophytic, squamous cell carcinoma on the palate.

Fig. 5.42 Neutropenia, multiple ulcers on the tongue.

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Laboratory tests: Peripheral blood examination and bone marrow aspiration. Differential diagnosis: Different specific forms of neutropenia, myelodysplastic syndrome, agranulocytosis, aplastic anemia, and leukemia. Treatment: The responsibility of treatment falls on the hematologist. Systemic antibiotics, antifungal medication, and granulocyte colony-stimulating factor (G-CSF) are the drugs of choice.

5.18 Cyclic Neutropenia Definition: Cyclic neutropenia is a rare form of neutropenia characterized by a cyclic, repeated reduction of the neutrophilic leukocytes. Etiology: Genetic. In many of the cases, the disease is transmitted as an autosomal dominant trait with variable expression, but several isolated cases may occur. Clinical features: The disease is usually manifested in infancy or childhood. The reduction of neutrophils occurs regularly at 3-week intervals and may last for 1 to 3 days. A recovery phase of 5 to 8 days follows when the number of neutrophils returns to normal. Typically, patients may complain of low-grade fever, headache, malaise, anorexia, dysphagia, arthralgias, cervical lymphadenopathy, gastrointestinal disorders, skin and oral manifestations. Clinically, the oral lesions present as a painful, irregular ulcer covered by a whitish membrane and surrounded by an erythematous halo (▶ Fig. 5.44). The lower lip, tongue, buccal mucosa, and soft palate are the most frequently affected sites. Gingivitis, characteristically, deteriorates during the phase of neutropenia (▶ Fig. 5.45). The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Hematologic examination should be performed three times per week for 6 to 8 weeks and bone marrow aspiration. Differential diagnosis: Aphthous ulcers, congenital neutropenia, oral herpetic lesions, agranulocytosis, Mediterranean fever, and leukemia. Treatment: Supportive care. High level of oral hygiene and topical application of steroid ointments or tacrolimus on the ulcer is needed. The systemic treatment is performed by the pediatrician or the hematologist.

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5.18 Cyclic Neutropenia

Fig. 5.43 Neutropenia, ulceration on the soft palate.

Fig. 5.44 Cyclic neutropenia, atypical ulceration of the lower lip mucosa.

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Fig. 5.45 Cyclic neutropenia, gingivitis.

5.19 Congenital Neutropenia Definition: Congenital neutropenia or infantile agranulocytosis is a rare genetic form of neutropenia, characterized by a quantitative, persistent, decrease in circulating neutrophils, associated with life-threating bacterial infections. Etiology: Genetic. The disorder is inherited by an autosomal dominant or autosomal recessive pattern, but some cases appear to be sporadic. Clinical features: Multiple, recurrent, bacterial infections characterize the clinical feature of the disease, which is, usually, present at birth. The most common infections involve the respiratory and urinary tracts, middle ear, skin, and oral mucosa, and these may be life threatening. Oral manifestations are common and include persistent and recurrent ulcerations, gingivitis and periodontitis, bacterial infections, and candidiasis (▶ Fig. 5.46 and ▶ Fig. 5.47). The periodontal disease is characterized by extensive bone destruction, tooth mobility, and loss. The marginal and attached gingiva are fiery red and edematous, while the interdental papillae are hyperplastic. Fever, malaise, fatigue, and lymphadenopathy are common. The disease is gradually improving with age. The clinical diagnosis should be confirmed by laboratory tests.

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5.19 Congenital Neutropenia

Fig. 5.46 Congenital neutropenia, gingivitis, and early periodontitis in the maxilla of a 6-year-old child.

Fig. 5.47 Congenital neutropenia, scars from recurrent ulceration, and edema of the lower lip.

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Laboratory tests: Complete blood count and radiographic examination of the jaws. Differential diagnosis: Cyclic neutropenia, agranulocytosis, aplastic anemia, leukemia, Shwachman–Diamond syndrome, aggressive periodontitis, glycogen storage disease type 1b, Chediak–Higashi syndrome, hypophosphatasia, acatalasia, and Papillon–Lefèvre syndrome. Treatment: High level of oral hygiene and periodontal treatment. Systemic treatment is the responsibility of the pediatrician or hematologist.

5.20 Agranulocytosis Definition: Agranulocytosis is an acute hematologic disorder characterized by a severe reduction or complete absence of the granulocyte series, especially neutrophils, both in the peripheral blood and the bone marrow. Etiology: It can be caused by either a reduction in production or increase in destruction of granulocytes. Agranulocytosis is classified into idiopathic (of unknown etiology), secondary (usually caused by medication and infections), and genetic (caused by cytokine G-CSF insufficiency). Clinical features: Clinically, the disease has a sudden onset and is characterized by chills, fever, malaise, dysphagia, and arthralgias. Within 12 to 24 hours, oral, pharyngeal, respiratory, gastrointestinal, and skin infections, usually, develop. Pneumonia, related to death, may occur within a few days. The oral lesions are common and early. Clinically, multiple necrotic ulcers appear covered by gray-white or dark and dirty pseudomembranes without an inflammatory red halo (▶ Fig. 5.48). The buccal mucosa, tongue, lips, palate, and tonsils are the most common sites of involvement. Severe necrotizing gingivitis with periodontal tissue destruction occurs (▶ Fig. 5.49). The oral lesions are frequently associated with increased salivation, painful mastication, and difficulty in swallowing. The clinical diagnosis should be confirmed by the laboratory tests. Laboratory tests: Hematologic examination of the peripheral blood and bone marrow aspiration. Differential diagnosis: Neutropenias, aplastic anemia, acute leukemia, infectious mononucleosis, Wegener’s granulomatosis, acute necrotizing ulcerative gingivitis, and periodontitis.

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5.20 Agranulocytosis

Fig. 5.48 Agranulocytosis, early ulceration on the mucosa of the lower lip.

Fig. 5.49 Agranulocytosis, early manifestations with gingival ulceration and inflammation.

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Treatment: If medication is responsible, it should be discontinued immediately. Hematopoiesis growth factors (G-CSF, GM-CSF) and antibiotics are administered. The treatment of the disease is the responsibility of the hematologist and requires hospital admission.

5.21 Bone Marrow Aplasia Definition: Bone marrow aplasia is a rare hematologic disorder that is characterized by bone marrow failure of all stem cells lines. Etiology: The disease may be idiopathic (possibly of autoimmune nature), secondary (due to medication, radiotherapy, chemicals, viruses, etc.), and rarely congenital (dyskeratosis congenital, Fanconi’s anemia). Clinical features: The onset of the disease is usually insidious and the signs and symptoms are present within a great spectrum and are related to one or more hematologic cell lines deficiencies. Clinically, weakness, fatigue, headache, tachycardia, and dyspnea due to reduction of red blood cells may occur. Bacterial infections and mycoses due to neutropenia and hemorrhage of various organs due to thrombocytopenia are common findings. The oral manifestations are usually related to the degree of the coexisting neutropenia and thrombocytopenia. Clinically, the oral mucosa appears pale with petechiae, ecchymoses, hematomas, and spontaneous bleeding, particularly from the gingiva (▶ Fig. 5.50). Multiple, necrotic ulcerations, with characteristic absence of surrounding inflammation may be present (▶ Fig. 5.51). Additionally, there is hemorrhage, petechiae, and ecchymoses on the skin and other mucosae. The prognosis is poor if the disease left untreated. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Full blood cell counts and bone marrow aspiration. Differential diagnosis: Agranolocytosis, neutropenias, thrombocytopenia, myelodysplastic syndrome, leukemia, infectious mononucleosis, HIV infection, and systemic lupus erythematosus. Treatment: The hematologist is responsible for the treatment that requires hospital admission. Red blood and platelet transfusions, bone marrow transplantations, corticosteroids, immunosuppressive medication, and antibiotics are suggested.

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5.21 Bone Marrow Aplasia

Fig. 5.50 Aplastic anemia, early hemorrhagic ulceration of the maxillary gingiva.

Fig. 5.51 Aplastic anemia, large hemorrhagic ulceration on the upper lip.

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5.22 Myelodysplastic Syndrome Definition: Myelodysplastic syndrome is a heterogeneous group of acquired clonal disorder of the hematopoietic stem cells. Etiology: It is unknown. In most cases the disorder is idiopathic, although it may develop secondary to radiotherapy, chemotherapy, infections, drugs, and immunological disorders. Clinical features: Myelodysplastic syndrome is classified into seven groups by WHO (2008) depending on (1) cell lines criteria in the peripheral blood and the bone marrow, and (2) the clinical features. Clinically, the groups are characterized by systemic symptoms (fever, fatigue, muscular weakness, etc.), anemia, multiple recurrent bacterial infections, and hemorrhage caused by the neutropenia and thrombopenia. The oral manifestations include persistent and recurrent ulcerations, hemorrhage, usually gingival bleeding, periodontitis, and candidiasis (▶ Fig. 5.52 and ▶ Fig. 5.53). Splenomegaly and lymphadenopathy may be present. The course may be indolent, and the disease may present as a wasting illness, but ultimately may be fatal. The diagnosis is based on clinical and laboratory criteria. Laboratory tests: Bone marrow aspiration, biopsy, and peripheral blood examination. Differential diagnosis: Myeloblastic leukemia, myelic aplasia, agranulocytosis, neutropenias, thrombocytopenia, and Sweet’s syndrome. Treatment: It includes growth factors (G-CSF, GM-CSF), erythropoietin, corticosteroids, immunosuppressive and chemotherapeutic agents, and allogenic stem cells transplantation. The treatment is the responsibility of the hematologist.

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5.22 Myelodysplastic Syndrome

Fig. 5.52 Myelodysplastic syndrome, ulceration on the lateral border of the tongue.

Fig. 5.53 Myelodysplastic syndrome, ulceration and bleeding of upper gingiva.

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5.23 Leukemia Definition: Leukemia is a heterogeneous group of neoplastic disorders of the blood-forming tissues, characterized by abnormal stem cell proliferation and maturation of bone marrow and the peripheral blood. Etiology: A combination of genetic and environmental factors (viruses, radiation, chemicals, etc.) plays a great role in the etiology of leukemia. Clinical features: Depending on the clinical course and the degree of maturation of the neoplastic cells, leukemias are classified into acute and chronic types. Depending on the affected cell line that dominates and also its origin, they are subclassified into myelogenous, lymphocytic, hairy cell, monocytic, eosinophilic, basophilic, megacaryoblastic, and erythroleukemia. The main clinical signs and symptoms of leukemias are: weakness, fatigue, fever, weight loss, chills, headache, night sweats, skin pallor, bleeding, infections, bone pain, lymphadenopathy, splenomegaly, hepatomegaly, salivary glands enlargement, and oral mucosa lesions. All types of leukemia may cause oral manifestations to a different degree (50–80%), during their course. The lesions are more common in monocytic leukemia, followed by the myelogenous and less often the lymphocytic. Clinically, petechiae, ecchymoses, spontaneous gingival bleeding and enlargement, ulcerations, necrosis, delayed wound healing, and submandibular and cervical lymph node enlargement are included in the spectrum of oral features (▶ Fig. 5.54 and ▶ Fig. 5.55). A characteristic early and common finding, mainly in the monocytic and myelomonocytic types, is localized or generalized gingival enlargement (▶ Fig. 5.56). Oral candidiasis and herpes simplex are common complications. The clinical diagnosis of leukemia should be confirmed by laboratory tests. Laboratory tests: Peripheral blood counts and bone marrow examination. The histopathologic examination of oral lesions can only be indicative of the disease. Differential diagnosis: Neutropenias, agranulocytosis, asplastic anemia, thrombocytopenia, myelodysplastic syndrome, acute necrotizing ulcerative gingivitis and stomatitis, gingival overgrowth due to drugs, and scurvy. Treatment: The treatment of leukemia lies with the hematologist. Multiagent chemotherapy, peripheral blood stem cells or bone marrow transplantation, cytostatic medication, radiotherapy, and monoclonal antibodies are used in various combinations.

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5.23 Leukemia

Fig. 5.54 Chronic myelogenous leukemia, ulcerations and ecchymoses of the tongue.

Fig. 5.55 Acute myelogenous leukemia ulcerations of the tongue.

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Fig. 5.56 Acute monocytic leukemia, pronounced swelling of the gums.

5.24 Langerhans Cell Histiocytosis Definition: Langerhans cell histiocytosis is a heterogeneous group of clonal proliferative disorder of Langerhans cells that express a positive immunophenotype for S100, CD1a, and CD207. Etiology: It is unclear. A genetic link exists between the two cell lines. The presence of clonal CD1a histiocytes within the lesions is an indication that the disease may be a clonal neoplastic disorder. WHO classifies Langerhans cell histiocytosis under dendritic and histiocytic cell neoplasms. Clinical features: The spectrum of the disease includes four clinical types: (1) Letterer–Siwe (rare and severe ▶ Fig. 5.57), (2) Hand–Schüller–Christian (relatively rare and severe ▶ Fig. 5.58 and ▶ Fig. 5.59), (3) Eosinophilic granuloma (common and less severe ▶ Fig. 5.60 and ▶ Fig. 5.61), and (4) Hashimoto– Pritzker or congenital (rare and self-healing). Oral lesions may occur in all four types but are more common in the first three. Letterer–Siwe disease is the acute multisystemic type that manifests prior to second year of life and has poor prognosis. Clinically, the oral lesions present as ecchymoses, ulcerations, gingivitis, periodontitis, and loose teeth (▶ Fig. 5.57). Skin rash, onycholysis, lymphadenopathy, otitis

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5.24 Langerhans Cell Histiocytosis

Fig. 5.57 Letterer–Siwe disease, palatal ulcerations, and periodontal disease with tooth displacement.

Fig. 5.58 Hand–Schüller–Christian disease, exophthalmos.

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Fig. 5.59 Hand–Schüller–Christian disease, enlargement and ulcerations of the gingiva.

media, involvement of liver, spleen, bones, lungs, and hematologic disorders are common findings. Hand–Schüller–Christian disease is the chronic, multifocal type with a milder course and generally of better prognosis. It occurs between 2 and 6 years of life. Clinically, the classic triad is osteolytic lesions, exophthalmos (▶ Fig. 5.58), and diabetes insipidus. In addition, chronic otitis, media and externa, and skin rash are common, while liver, spleen, lungs, and lymph nodes involvement are less common. Clinically, the oral lesions present as ulcerations, edema, gingival enlargement and ulcerations, halitosis, taste disturbances, tooth mobility, and loss (▶ Fig. 5.59). Eosinophilic granuloma is the localized type of the disease that does not affect the viscera and has good prognosis. It usually occurs between 7 to 15 years of age. Clinically, it is characterized by solitary or multiple osseous lesions. The jaw bones may be affected and result in osseous destruction and tooth mobility and loss. Gingival enlargement, gingival, and palatal ulcerations are common (▶ Fig. 5.60 and ▶ Fig. 5.61). Hashimoto–Pritzker disease is limited to the skin and starts at birth or soon after. The oral mucosa is not involved. The clinical diagnosis of Langerhans cell histiocytosis should be confirmed by laboratory tests.

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5.24 Langerhans Cell Histiocytosis

Fig. 5.60 Eosinophilic granuloma, localized gingival enlargement with periodontal osseous destruction.

Fig. 5.61 Eosinophilic granuloma, palatal ulceration, and osseous destruction of the maxilla.

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Laboratory tests: Histopathologic examination, histochemical examination, radiographic examination, and CT-MRI scans. Differential diagnosis: Leukemia, multiple myeloma, non-Hodgkin’s lymphoma, mycosis fungoides, squamous cell carcinoma, agranulocytosis, necrotizing ulcerative gingivitis and periodontitis, and aggressive periodontitis. Treatment: Surgical curettage with or without radiotherapy is the treatment of choice for eosinophilic granuloma. Systemic corticosteroids may also be used. For the two systemic types of the disease, corticosteroids and chemotherapy are suggested.

5.25 Glycogen Storage Disease, Type 1b Definition: Glycogen storage disease is a rare group of disorders involving the metabolic pathways of glycogen. Etiology: Genetic. It is classified into 11 types, depending on the type of enzyme deficiency. Type 1b is caused by a transport deficiency of the glucose6-phosphatase and is transmitted by an autosomal recessive pattern of inheritance. Clinical features: Clinically, the main features are hypoglycemia, hyperlipidemia, hepatomegaly, enlarged kidneys, delayed physical development, short stature and bleeding diathesis, characteristic facial appearance known as doll’s face, neutropenia, and functional disorders of the peripheral neutrophils (▶ Fig. 5.62). Chronic pangreatitis, ulcerative colitis, and Crohn’s disease may also occur. Oral manifestations include gingivitis, aggressive periodontitis, and recurrent painful ulcerations (▶ Fig. 5.63). Macroglossia, deep arched palate (▶ Fig. 5.64), and oral infections may also occur. The clinical diagnosis should be confirmed by laboratory tests.

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5.25 Glycogen Storage Disease, Type 1b

Fig. 5.62 Glycogen storage disease type 1b, characteristic “doll’s face.”

Fig. 5.63 Glycogen storage disease type 1b, large ulceration on the lateral border of the tongue.

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Laboratory tests: Histopathologic and biochemical examinations. Differential diagnosis: Congenital neutropenia, cyclic neutropenia, agranulocytosis, Chediak–Higashi syndrome, Mediterranean fever, diabetes mellitus, hypophosphatasia, and acatalasia. Treatment: High levels of oral hygiene and antiseptic mouthwashes are recommended. The systemic treatment must be left to pediatricians.

5.26 PFAPA Syndrome Definition: PFAPA is a rare, recurrent disease. Etiology: Defective overexpression of interleukin 1β (IL-1β). Clinical features: Clinically, the disease is characterized by periodic fever (38–40oC) that lasts for 4 to 6 days and is accompanied by chills and fatigue. Aphthous-like ulcers in major or minor form commonly develop with a preference to the soft palate and uvula (▶ Fig. 5.65). Pharyngitis, tonsillitis, and bilateral cervical adenitis complete the clinical features. Headache, abdominal pain, and arthralgia are less common symptoms. The disease usually recurs every 4 to 8 weeks for 1 to 2 years and then resolves spontaneously. Children and young individuals are more frequently affected. The diagnosis is made on the history and clinical features. Laboratory tests: No definitive diagnostic tests are available. Differential diagnosis: Aphthous ulcer, Adamantiades–Behçet’s disease, HFMD, herpetic gingivostomatitis, infectious mononucleosis, cyclic neutropenia, leukemia, myelodysplastic syndrome, HIV infection, and Sweet’s syndrome. Treatment: Treatment is symptomatic. Cimetidine is the drug of choice, systemic corticosteroids in low dose for 6 to 10 days is the second-choice drug.

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5.26 PFAPA Syndrome

Fig. 5.64 Glycogen storage disease type 1b, high-arched palate.

Fig. 5.65 PFAPA syndrome, ulcers on the soft palate close to the uvula.

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5.27 Sweet’s Syndrome Definition: Sweet’s syndrome or acute febrile neutrophilic dermatosis is an uncommon acute dermatosis associated with systemic manifestations. Etiology: Unknown. However, a hypersensitivity reaction to different factors is possible. On the basis of possible etiology, five forms of the syndrome are recognized: (1) idiopathic (> 50%), (2) malignancy-associated, (3) drug-induced, (4) bowel disease-associated, and (5) pregnancy-related. Clinical features: Clinically, it is characterized by constitutional signs and symptoms, cutaneous lesions, ocular lesions, and oral lesions. The oral lesions are rare and present as deep, large ulcers, similar to major aphthous ulcers, 1 to 5 cm or more in diameter (▶ Fig. 5.66). The lips, tongue, buccal mucosa, and palate are more frequently affected. The cutaneous lesions first appear abruptly, as nonpruritic edematous and erythematous papules or plaques that coalesce and have a tendency to spread. Vesiculobullous lesions that progress to ulcerations are common (▶ Fig. 5.67). The ocular lesions include conjunctivitis, episcleritis, sclerites, periorbital, and orbital inflammation. Sudden high fever (38–39oC), malaise, fatigue, arthralgias, and myalgias are common and early symptoms. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, blood examination with characteristic neutrophilic domination (60–80%), and elevated ESR and CRP. Differential diagnosis: Adamantiades–Behçet’s disease, aphthous ulcers, PFAPA syndrome, erythema multiforme, pyostomatitis vegetans, leukemia, non-Hodgkin’s lymphoma, Wegener’s granulomatosis, and systemic lupus erythematosus. Treatment: Systemic corticosteroids are the drug of choice. Dapsone, colchicine, thalidomide, cyclosporine, and tacrolimus are the main alternative drugs.

5.28 Staphylococcal Infection Definition: Staphylococcal infection is rare in the oral mucosa. Etiology: Staphylococcus aureus and staphylococcus epidermidis are the most causative strains. Predisposing factors are trauma of the oral mucosa, poor oral hygiene, and various systemic diseases (diabetes mellitus, tuberculosis, neutropenia, leukemia, other malignancies, and immunodeficiencies).

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5.28 Staphylococcal Infection

Fig. 5.66 Sweet’s syndrome, deep ulceration on the lower labial mucosa.

Fig. 5.67 Sweet’s syndrome, edema, pustules, and ulceration on the fingers.

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Clinical features: Clinically, staphylococcal oral infection appears as a round or oval, abnormal, solitary ulcer with raised inflammatory border. The surface of the ulcer is covered by a whitish or yellow-white necrotic exudate (▶ Fig. 5.68). Low fever, malaise, headache, and regional lymphadenopathy may be present. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Gram staining and microbiological culture. Differential diagnosis: Traumatic ulcer, aphthous ulcer, chancre, tuberculus ulcer, other infectious ulcers, non-Hodgkin’s lymphoma, neutropenia, myelodysplastic syndrome, and Wegener’s granulomatosis. Treatment: Systemic antibiotics such as clarithromycin 500 mg every 8 hours for 4 to 6 days.

5.29 Pseudomonas Infection Definition: Pseudomonas infection is rare in the oral mucosa. Etiology: It is mainly due to strain Pseudomonas aeruginosa, a gram-negative aerobic bacillus, which is an opportunistic pathogen and it mostly affects immunosuppressed individuals. Clinical features: The respiratory and urinary tract, eyes, ears, sinus, nails, skin, and subcutaneous tissues are more frequently involved, while it is rare in the mouth, lips, and perioral region. Clinically, oral infection presents as an irregular necrotic painful, deep ulcer, which tends to expand and is accompanied by intense inflammation (▶ Fig. 5.69). The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Microbiologic examination and isolation of the microbe is necessary for final diagnosis. Differential diagnosis: Oral ulcerations from other bacteria, neutropenia, agranulocytosis, tuberculosis, and systemic mycoses. Treatment: First-choice drugs are ciprofloxacin 500 mg twice daily for 6 days or piperacillin-tazobactam or cefepime.

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5.29 Pseudomonas Infection

Fig. 5.68 Staphylococcal ulceration of the lower lip.

Fig. 5.69 Extensive necrotic lesions on the gingiva and palate due to Pseudomonas aeruginosa.

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5.30 Klebsiella Infection Definition: Klebsiella oral infection is a rare phenomenon and may occur in patients with diabetes mellitus, HIV infection, and patients undergoing chemotherapy. Etiology: It is due to the strain Klebsiella pneumoniae. Clinical features: Respiratory and urinary tracts are mainly involved, while the mouth is rarely affected. Clinically, oral infection presents as an irregular, painful, deep ulcer with a necrotic center covered by a thick gray-whitish pseudomembrane (▶ Fig. 5.70). Fever and lymphadenopathy may occur. The clinical features are not diagnostic and microbiological confirmation is necessary. Laboratory tests: microorganism.

Microbiologic

examination

and

isolation

of

the

Differential diagnosis: Oral ulcerations from other bacteria, major aphthous ulcer, tuberculosis, chancre, eosinophilic ulcer, non-Hodgkin’s lymphoma, and neutropenia. Treatment: Drugs of choice are ciprofloxacin and tetracycline. Alternative drugs are second- and third-generation cephalosporins or aminoglycosides.

5.31 Cytomegalovirus Infection Definition: Oral infection with cytomegalovirus is rare and usually occurs in immunosuppressed individuals. Etiology: Cytomegalovirus or herpes simplex virus type 5 is the cause of the infection. Predisposing conditions for cytomegalovirus infection are HIV infection, immunosuppression, and transplant recipients. Clinical features: By the age of 70 years, 90 to 100% of the population is infected. In immunocompetent individuals, the infection is asymptomatic in more than 95% of the cases, and only 5% may present signs and symptoms, similar to those of infectious mononucleosis. Clinically, it presents as atypical, usually painful ulcer (0.5–1 cm in diameter) that persists for a long time (▶ Fig. 5.71). The gingiva and the tongue are the most frequently affected areas. Painful enlargement of the major and minor salivary glands leading to dry mouth may occur. Fever, sore throat, cough, pharyngitis, malaise, myalgia, joint

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5.31 Cytomegalovirus Infection

Fig. 5.70 Oral ulcerations on the floor of the mouth caused by Klebsiella.

Fig. 5.71 Cytomegalovirus infection. Atypical ulcer of the gingiva.

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Ulcerative Lesions pain, abdominal pain, diarrhea, lymphadenopathy, hepatosplenomegaly, meningeal irritation, and less frequently maculopapular and pruritic cutaneous eruptions may be seen. Oral lesions are rare and occur mainly in patients with AIDS, immunocompromised transplant patients and other immunosuppressed individuals. Rarely, complications include eye disorders, pneumonia, myocarditis, gastrointestinal and hematologic disorders, and CNS involvement. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Monoclonal antibodies against cytomegalovirus antigen, PCR, ELISA, and histopathologic examination. Differential diagnosis: Infectious mononucleosis, herpes simplex, traumatic ulcer, chancre, aphthous ulcer, and drug-induced ulceration. Treatment: The main agents used are intravenous ganciclovir and oral valaciclovir.

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6 Papillary Lesions Papillary lesions of the oral mucosa are a relatively small group, appearing clinically as exophytic growths with a verrucous or cauliflower-like surface. Reactive lesions, benign tumors, malignancies, and systemic diseases are included in this group. Etiologically, traumatic, viral, neoplastic, and other factors may cause these lesions. The diagnosis is based on clinical and histopathologic criteria.

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Papilloma

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Denture Fibrous Hyperplasia

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Condyloma Acuminatum

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Crohn’s Disease

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Verruca Vulgaris

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Verruciform Xanthoma

Malignancy-Associated Acanthosis Nigricans

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Verrucous Leukoplakia

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Benign Acanthosis Nigricans

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Darier’s Disease

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Papillary Palatal Hyperplasia

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Focal Dermal Hypoplasia

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Verrucous Carcinoma Squamous Cell Carcinoma

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6.1 Papilloma See also sections 1.21 and 8.1.1. Definition: Papilloma is a relatively common benign tumor of the stratified squamous epithelium. Etiology: In 50 to 60% of papillomas, human papilloma virus (HPV) types 6 and 11 are detected within the tumor. Clinical features: Oral papilloma affects, equally, both sexes, most commonly from 30 to 50 years of age. Clinically, it presents as an exophytic, wellcircumscribed, pedunculated or sessile tumor, consisting of multiple, small projections that give the tumor a cauliflower-like appearance (▶ Fig. 6.1). The color varies between white, pale pink, and even normal mucosal, depending on the degree of keratinization. The size ranges from 3 to 6 mm and rarely grows above 1 cm. The lesion is usually solitary, occurring more frequently on the soft palate, tongue, buccal mucosa, and less commonly in other sites. The clinical diagnosis should be confirmed histologically. Laboratory tests: Histopathologic examination. Differential diagnosis: Condyloma acuminatum, verruca vulgaris, verruciform xanthoma, early verrucous carcinoma, sialadenoma papilliferum, focal epithelial hyperplasia, and focal dermal hypoplasia syndrome. Treatment: The treatment of choice is conservative surgical excision.

6.2 Condyloma Acuminatum Definition: Condyloma acuminatum is a common, sexually transmitted tumor, mainly occurring in the anogenital region and rarely in the oral mucosa. Etiology: HPV, mainly the low-risk types 6 and 11 are the cause. Clinical features: Clinically, oral condyloma acuminatum appears as single, or more often multiple, sessile, painless, well-circumscribed, exophytic mass with a cauliflower-like surface (▶ Fig. 6.2 and ▶ Fig. 6.3). The lesions have a whitish or normal color and a size that ranges from 0.5 to 2 cm. The labial mucosa, buccal mucosa, palate, and tongue are more frequently affected. The clinical diagnosis should be confirmed by laboratory tests.

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6.2 Condyloma Acuminatum

Fig. 6.1 Papilloma of black color on the palate due to increased melanin production.

Fig. 6.2 Condyloma acuminatum on the palate.

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Laboratory tests: Histopathologic examination, in situ hybridization, and polymerase chain reaction tests. Differential diagnosis: Papilloma, verruca vulgaris, verruciform xanthoma, early verrucous carcinoma, sialadenoma papilliferum, focal epithelial hyperplasia, and focal dermal hypoplasia syndrome. Treatment: The treatment of choice is conservative surgical excision and electrosurgery.

6.3 Verruca Vulgaris Definition: Verruca vulgaris is a common, benign, mainly cutaneous lesion that may, rarely, appear in the oral mucosa. Etiology: HPV, mainly types 1, 2, and 4 are the cause. Clinical features: Verruca vulgaris usually develops on the fingers of children, from where it can potentially be autoinoculated in the oral mucosa. Clinically, the oral lesion presents as a painless, small, exophytic growth with a cauliflower-like surface and whitish or pink-white color (▶ Fig. 6.4). The lesions may be single or multiple and sessile or pedunculated. The lips, commissures, and tongue are more frequently affected. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Papilloma, condyloma acuminatum, verruciform xanthoma, focal epithelial hyperplasia, and mucosal horn. Treatment: The treatment of choice is conservative surgical excision and electrosurgery.

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6.3 Verruca Vulgaris

Fig. 6.3 Multiple condylomata acuminate on the lower lip mucosa.

Fig. 6.4 Multiple verruca vulgaris on the gingiva.

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6.4 Verruciform Xanthoma Definition: Verruciform xanthoma is a rare oral mucosal lesion that was first described by Shafer in 1971. Etiology: The exact etiology is unknown. Clinical features: Clinically, verruciform xanthoma presents as a painless, sessile, well-demarcated, usually elevated lesion with a papillary surface and normal or whitish-yellowish color (▶ Fig. 6.5). The size ranges from 0.5 to 2 cm in diameter. It most frequently develops on the alveolar mucosa and gingiva and less often on the labial mucosa, buccal mucosa, palate and floor of the mouth. The lesion is not associated with systemic metabolic disorders. The clinical diagnosis should be confirmed by laboratory examinations. Laboratory tests: Histopathologic and immunohistochemical examinations. Differential diagnosis: Papilloma, condyloma acuminatum, verruca vulgaris, early verrucous carcinoma, and sialadenoma papilliferum. Treatment: The treatment of choice is conservative surgical excision.

6.5 Verrucous Leukoplakia See also section 1.1. Definition: Verrucous leukoplakia is a rare clinical form (0, 2–1%) of leukoplakia with a great risk for malignant transformation. Etiology: The exact etiology is unknown. Clinical features: Clinically, it presents as an irregular, white, exophytic, wrinkled or corrugated plaque. Proliferative verrucous leukoplakia is a subtype of verrucous leukoplakia, which is presented with multifocal location, tendency to recur after surgical excision, and a high rate of malignant transformation (▶ Fig. 6.6). Laboratory tests: Biopsy and histopathologic examination must always be performed. Differential diagnosis: Verrucous hyperplasia, verrucous carcinoma, verruciform xanthoma, condyloma acuminatum, papilloma. Treatment: The treatment of choice is surgical excision and the patients have to be followed up every 4 to 6 months for 3 to 5 years.

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6.5 Verrucous Leukoplakia

Fig. 6.5 Exophytic verruciform xanthoma with unusual presentation on the lower gingiva.

Fig. 6.6 Verrucous leukoplakia on the buccal mucosa and the commissure.

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6.6 Verrucous Carcinoma See also sections 1.22 and 8.2.2. Definition: Verrucous carcinoma, is a low-grade variant of squamous cell carcinoma, with a good biological behavior. Tobacco use and HPV types 16, 18, 30 seem to play important role in the pathogenesis. Etiology: Smoking and HPV types 16, 18, and 33 are involved in the pathogenesis. Clinical features: Clinically, it presents as a slowly growing, painless, whitish exophytic mass with a papillary or verruciform surface (▶ Fig. 6.7). Along with the characteristic clinical features, biopsy and histopathologic examination should be performed to rule out other papillary growths and squamous cell carcinoma. Characteristically, verrucous carcinoma develops slowly, has a good biological behavior, characteristic histopathologic pattern, rarely metastasizes, and has a good prognosis. Differential diagnosis: Verrucous hyperplasia, verrucous leukoplakia, squamous cell carcinoma, papilloma, verruciform xanthoma, and white sponge nevus. Laboratory tests: Biopsy and histopathologic examination should be performed. The clinical diagnosis should be confirmed histologically. Treatment: Treatment of choice is surgical excision.

6.7 Squamous Cell Carcinoma See also sections 1.23, 2.9, 5.16, and 8.2.1. Squamous cell carcinoma has a wide spectrum of clinical presentations. A relatively common clinical feature is an exophytic mass. It may have a papillary or verruciform surface and red, whitish or normal color, and a tendency to grow (▶ Fig. 6.8). The surface is usually ulcerated, and the base indurated on palpation. The tongue, buccal mucosa, floor of the mouth, and gingiva are the most common sites affected by this clinical form of carcinoma. A biopsy and histopathologic examination are necessary to rule out verrucous carcinoma.

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6.7 Squamous Cell Carcinoma

Fig. 6.7 Early verrucous carcinoma on the lateral border of the tongue.

Fig. 6.8 Squamous cell carcinoma on the buccal mucosa with lobulated surface.

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6.8 Denture Fibrous Hyperplasia Definition: Denture fibrous hyperplasia is a common mucosal reaction of the fibrous connective tissue. Etiology: Poor fitting of partial, or complete dentures in individuals who have been wearing the dentures for a long period of time. Clinical features: Clinically, denture fibrous hyperplasia presents as multiple or solitary, inflamed and elongated mucosal papillary folds, usually on the facial aspect of the mucolabial or mucobuccal grooves (▶ Fig. 6.9). The lesions are mobile, painful, and usually ulcerated at the base of the folds. The size may vary from 1 to 5 cm or more and it may affect the maxilla or mandible or both. The diagnosis is based on the history and clinical features and rarely a biopsy is necessary to rule out other oral lesions. Laboratory tests: Histopathologic examination. Differential diagnosis: Multiple fibromas, neurofibromatosis, verrucous hyperplasia, verrucous carcinoma, squamous cell carcinoma, non-Hodgkin’s lymphoma, and Crohn’s disease. Treatment: The treatment of choice is conservative surgical excision and construction of a new denture.

6.9 Crohn’s Disease Definition: Crohn’s disease is a chronic, inflammatory, bowel disease characterized by granulomatous reaction, mainly in the ileum, colon, and upper intestinal tract. Etiology: The exact etiology remains unknown. However, immunologic reaction against microbial antigens may be involved in the pathogenesis, combined with genetic, psychogenic, and dietary factors. Clinical features: The disease, usually, affects young individuals (15–30 years old). Clinically, it presents with abdominal pain, nausea, diarrhea, weight loss, low-grade fever, and rectal hemorrhage. More than 50% of the patients have extraintestinal manifestations such as arthralgias, arthritis, spondylitis, iritis or uveitis, liver and spleen involvement, and cutaneous and oral manifestations. The oral lesions may either precede or follow the bowel involvement and occur in 10 to 20% or more of the patients. Clinically presents as nodular swellings, which may be ulcerated, and usually coalesce resulting in a cobblestone appearance of the mucosa (▶ Fig. 6.10). Granulomatous lip swelling, gingival enlargement, erythema, exfoliation, and taste disturbances may also occur

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6.9 Crohn’s Disease

Fig. 6.9 Denture fibrous hyperplasia.

Fig. 6.10 Crohn’s disease, ulcerated nodule on the lower vestibule.

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Papillary Lesions (▶ Fig. 6.11). The cutaneous manifestations include erythema nodosum, pyoderma gangrenosum, and manifestations of Sweet’s syndrome. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, colonoscopy, bowel radiology, erythrocyte sedimentation rate and C-reactive protein tests, immunologic test for perinuclear antineutrophil cytoplasmic antibodies. Differential diagnosis: Orofacial granulomatosis, cheilitis granulomatosa, denture fibrous hyperplasia, Melkersson–Rosenthal syndrome, ulcerative colitis, celiac disease, tuberculosis, and sarcoidosis. Treatment: The treatment is the responsibility of the gastroenterologist. It may include exclusion diet and symptomatic and specific treatment. Systemic corticosteroids, immunosuppressive agents, antibiotics, 5-aminosalicylic acid agents, antitumor necrosis factor-alpha.

6.10 Malignancy-Associated Acanthosis Nigricans Definition: Malignancy-associated acanthosis nigricans is a type of acanthosis nigricans that affects adults and is always accompanied by a malignancy (paraneoplastic mucocutaneous disease), usually stomach adenocarcinoma, viscera adenocarcinoma, and less commonly non-Hodgkin’s lymphoma and others. Etiology: The exact etiology remains unknown. However, it is believed that the development of the lesions is driven by factors (insulin-like growth factor 1), secreted by the neoplastic cells, that stimulate the epithelial and epidermal cells causing hyperplasia. Clinical features: Acanthosis nigricans is classified into two major types: The benign form (genetic and acquired) and the malignancy-associated form. Oral manifestations are more common in the malignancy-associated form. Clinically, the oral lesions appear as multiple, painless, verrucous, or papillomatous growths that most often involve the lips, tongue, palate, and gingiva (▶ Fig. 6.12 and ▶ Fig. 6.13). Similar lesions may develop in other mucosae (conjunctiva, pharynx, esophagus, anus, vagina, and intestine). The skin is rough with pigmentation, while multiple papillomatous lesions or tags occur on the axillae, inguinal area, neck, and less often on the palms and soles (▶ Fig. 6.14). The diagnosis is based on clinical criteria and laboratory tests. Laboratory tests: Histopathologic examination, investigation for the detection of malignancy.

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6.10 Malignancy-Associated Acanthosis Nigricans

Fig. 6.11 Crohn’s disease, cheilitis granulomatosa.

Fig. 6.12 Malignancy-associated acanthosis nigricans, papillomatous lesions on the palate.

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Fig. 6.13 Malignancy-associated acanthosis nigricans, papillomatous lesions on the commissure and the buccal mucosa.

Differential diagnosis: Benign acanthosis nigricans, pyostomatitis vegetans, focal epithelial hyperplasia, focal dermal hypoplasia syndrome, lipoid proteinosis, and pemphigus vegetans. Treatment: The treatment of oral and skin lesions is symptomatic.

6.11 Benign Acanthosis Nigricans Definition: Benign acanthosis nigricans is a rare mucocutaneous disorder, which is subdivided into (1) familiar, (2) secondary, and (3) pseudoacanthosis. Etiology: The familiar or genetic form is inherited in an autosomal dominant pattern, and rarely involves the oral mucosa. The secondary form occurs as part of other syndromes and various endocrinopathies and does not involve the oral mucosa. The pseudoacanthosis form affects obese and dark-skinned people and involves the skin only. The familial form of benign acanthosis nigricans involves the oral mucosa in approximately 10 to 15% of the cases. Clinically, there is hypertrophy and elongation of the filiform papillary resulting in a shaggy appearance of the tongue. The lips, palate, and the gingiva may be covered by asymptomatic, papillomatous, growths with normal color (▶ Fig. 6.15). The

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6.11 Benign Acanthosis Nigricans

Fig. 6.14 Malignancy-associated acanthosis nigricans, black-brown papillomatous lesions on the axilla.

Fig. 6.15 Benign acanthosis nigricans, papillomatous enlargement of the interdental papillae.

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Papillary Lesions skin is thick with small, velvety, papillary growths (tags) and dark discoloration (▶ Fig. 6.16). The disorder, usually, begins during childhood or at puberty. The diagnosis is mainly based on the history and the clinical features. Laboratory tests: Histopathologic examination. Differential diagnosis: Other benign forms of acanthosis nigricans, malignancy-associated acanthosis nigricans, focal dermal hypoplasia syndrome, and Darier’s disease. Treatment: Symptomatic. The treatment of choice is good oral hygiene, electrosurgery, and conservative surgical excision of oral lesions.

6.12 Darier’s Disease Definition: Darier’s disease or dyskeratosis follicularis is an uncommon mucocutaneous genodermatosis. Etiology: Genetic. It is inherited as an autosomal dominant trait. Clinical features: Darier’s disease affects mainly the skin and nails and less often the oral, ocular, pharyngeal, vaginal, vulval, and rectal mucosae. Clinically, multiple, painless, brownish-red skin papules, which usually coalesce into plaques, are seen (▶ Fig. 6.17). The forehead, ears, scalp, chest, and back are more frequently affected. The nails present with subungual keratosis and longitudinal white or red ridges and lines. The cutaneous lesions may be accompanied by pruritus and odor and usually deteriorate during the summer. The oral mucosa is affected in 20 to 40% of cases and the severity follows the activity of skin lesions. Clinically, the typical oral lesions are small whitish, confluent, papules that may coalesce, giving a micropapillomatous appearance or may become hypertrophic, assuming a cobblestone pattern (▶ Fig. 6.18). The palate, gingiva, buccal mucosa, and tongue are more frequently affected. Salivary glands obstruction and painful swelling may occasionally occur. The clinical diagnosis should be confirmed by laboratory test. Laboratory tests: Histopathologic examination is unique and diagnostic. Differential diagnosis: Acanthosis nigricans, Hailey–Hailey disease, pemphigus, papillary hyperplasia of the palate, nicotinic stomatitis, Grover’s disease, and seborrheic dermatitis. Treatment: The treatment of oral lesions is symptomatic. The treatment of cutaneous lesions is performed by the dermatologist. Moisturizers, dermabrasion, systemic retinoid, cyclosporine, and methotrexate among others have been tried.

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6.12 Darier’s Disease

Fig. 6.16 Benign acanthosis nigricans, small cutaneous nodules.

Fig. 6.17 Darier’s disease, coalescing cutaneous papules.

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Fig. 6.18 Darier’s disease, coalescing hypertrophic papules of the gingiva.

6.13 Papillary Palatal Hyperplasia Definition: Papillary palatal hyperplasia is a benign, clinical form of denture stomatitis, and rarely may develop in edentulous people with high-arched palate. Etiology: The causative factor is primarily mechanical irritation, mouth breathing and secondary Candida albicans infection. Clinical features: Clinically, papillary palatal hyperplasia appears with multiple coalescing, small, edematous, and reddish, papillary projections 1 to 2 mm in diameter (▶ Fig. 6.19). The lesions are usually asymptomatic, confluent, and may occupy part or all of the hard palate, giving a cauliflower-like pattern (▶ Fig. 6.20). The diagnosis is based on clinical criteria. Laboratory tests: It is not necessary.

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6.13 Papillary Palatal Hyperplasia

Fig. 6.19 Papillary palatal hyperplasia.

Fig. 6.20 Papillary palatal hyperplasia and ulceration caused by negative pressure from the denture.

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Differential diagnosis: Denture stomatitis, candidiasis, acanthosis nigricans, Darier’s disease, and focal dermal hypoplasia. Treatment: The treatment of choice is good oral and denture hygiene. In severe cases electrosurgery or CO2 laser.

6.14 Focal Dermal Hypoplasia Definition: Focal dermal hypoplasia or Coltz’s syndrome is a rare multisystemic genodermatosis. Etiology: Genetic. It is inherited in an X-linked dominant pattern. It is caused by mutations of the PORCN gene. Clinical features: Clinically, the cutaneous manifestations include linear hypoplastic streaks, which follow the Blaschko’s lines, atrophy, telangiectasias, multiple, soft raspberry-like papillomas, and hypo- and hyperpigmentation. Nail dystrophy, brittle and sparse hair, syndactyly, polydactyly or oligodactyly, microcephaly, ocular abnormalities, mental retardation, and oral lesions may also occur. The oral manifestations are multiple papillomas (40–50%) on the tongue, buccal mucosa, palate, gingiva, and lips (▶ Fig. 6.21). Oligodontia, small teeth, enamel hypoplasia, delayed eruption, malocclusion, cleft lip, or cleft palate can also be observed (▶ Fig. 6.22). The diagnosis is based on the clinical criteria and laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Multiple papillomas, multiple condylomas acuminatum, focal epithelial hyperplasia, orofacial-digital syndrome, and acanthosis nigricans. Treatment: Symptomatic. The treatment of choice is conservative surgical excision or electrosurgery of oral papillomas.

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6.14 Focal Dermal Hypoplasia

Fig. 6.21 Focal dermal hypoplasia, multiple papillomas on the tongue.

Fig. 6.22 Focal dermal hypoplasia, oligodontia, and small teeth.

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7 Gingival Enlargement A common characteristic of this group of lesions is that they are located on the gingiva and present as a submucosal enlargement covered by normal epithelium. The lesions can be either generalized or localized. Local diseases, druginduced lesions, systemic diseases, and tumors are included in this particular group of disorders.

Generalized Enlargement

Localized Enlargement

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Plaque-Related Hyperplastic Gingivitis

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Pyogenic Granuloma

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Mouth Breathing Gingivitis

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Peripheral Giant Cell Granuloma

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Drug-Induced Gingival Overgrowth

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Granular Cell Tumor of the Newborn

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Gingival Overgrowth in Pregnancy

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Periodontal Abscess

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Gingival Overgrowth due to Leukemia

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Parulis

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Hereditary Gingival Fibromatosis

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Multiple Exostoses

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Zimmermann–Laband Syndrome

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Scurvy

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7.1 Generalized Enlargement 7.1.1 Plaque-Related Hyperplastic Gingivitis Definition: Plaque-related gingivitis is the most common form of gingival disease, characterized by chronic inflammatory reaction. However, in cases with intense, chronic, inflammation marked gingival hyperplasia may develop. Etiology: Accumulation of microbial plaque (biofilm), poor oral hygiene, calculus, smoking, mouth breathing, food impaction, and systemic factors such as diabetes mellitus, metabolic diseases, and immunological disorders are the causes. Clinical features: Clinically, the interdental papillae and the marginal gingiva are erythematous, edematous, and significantly increased in size due to lamina propria fibromatosis, intense inflammation, and edema (▶ Fig. 7.1). In cases with great gingival hyperplasia, pseudopockets may develop. If left untreated it may progress to periodontitis. The diagnosis is usually based on the clinical features. Laboratory tests: Histopathologic and radiographic examinations. Differential diagnosis: Linear gingival erythema, periodontitis, mouth breathing gingivitis, leukemia, drug-induced gingival enlargement, and pregnancyassociated gingivitis. Treatment: High level of oral hygiene, plaque control, elimination of causative factors, surgical reconstruction in advanced cases, and antimicrobial mouthwashes as an adjunct.

7.1.2 Mouth Breathing Gingivitis Definition: Mouth breathing gingivitis is a unique form of gingivitis, with specific clinical features. Etiology: Mouth breathing is usually the result of nasal septum defects, or large adenoids in the nasopharynx. This form of gingivitis, usually, occurs in young individuals and affects mainly the upper anterior gingiva. Clinically, the gingiva and predominantly the interdental papillae are enlarged, dry, erythematous, and shiny, covering part of the crown of the teeth (▶ Fig. 7.2). The disorder is deteriorated by the presence of a considerable amount of dental plaque. The diagnosis is based on the history and the clinical features. Laboratory tests: The histopathologic examination in not specific.

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7.1 Generalized Enlargement

Fig. 7.1 Plaque-related gingivitis with prominent gingival hyperplasia.

Fig. 7.2 Gingivitis caused by mouth breathing with dental plaque deposits dominating.

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Gingival Enlargement

Differential diagnosis: Drug-induced gingival enlargement, hyperplastic gingivitis, leukemia, and mucopolysaccharidoses. Treatment: Restoration of nasal breathing, plaque control, and gingivectomy if required.

7.1.3 Drug-Induced Gingival Overgrowth Definition: Drug-induced gingival overgrowth is a relatively common disorder of the gingiva. Etiology: Phenytoin, cyclosporine, and calcium channel blockers are the main medications causing gingival enlargement in about of 30 to 70% of patients as a side effect. Less frequently other medication can also be implicated in gingival overgrowth such as contraceptives and erythromycin. Clinical features: The frequency and degree of gingival enlargement depends on the treatment regime and its duration. In addition, important risk factors are the oral hygiene level and the presence of dental plaque. Clinically, marginal gingiva, interdental papillae, and attached gingiva appear enlarged and firm, lobulated or smooth, normal or red in color, and painless with little or no tendency to bleed (▶ Fig. 7.3, ▶ Fig. 7.4, ▶ Fig. 7.5, ▶ Fig. 7.6, ▶ Fig. 7.7, and ▶ Fig. 7.8). The overgrowth is usually generalized but may be localized to a few teeth, is more prominent in the anterior part of the jaws, and can partially or entirely cover the crown of the teeth. In severe cases, difficulties in mastication or speech may occur. The diagnosis is based on the history and clinical features. Laboratory tests: Histopathologic examination, but it is not specific. Differential diagnosis: Plaque-related hyperplastic gingivitis, mouth breathing gingivitis, pregnancy-associated gingivitis, hereditary gingival fibromatosis, leukemia, amyloidosis, Hurler’s syndrome, Zimmermann–Laband syndrome, Wegener’s granulomatosis, and Crohn’s disease. Treatment: Surgical excision and high level of oral hygiene is the first line of treatment. Discontinuation of the offending drugs often results is cessation of the gingival enlargement, but this should be decided by the attending physician.

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Fig. 7.3 Gingival enlargement caused by phenytoin.

Fig. 7.4 Gingival enlargement caused by cyclosporine.

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Fig. 7.5 Gingival enlargement caused by cyclosporine.

Fig. 7.6 Gingival enlargement caused by nifedipine.

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Fig. 7.7 Gingival enlargement caused by felodipine.

Fig. 7.8 Gingival enlargement caused by felodipine.

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7.1.4 Gingival Overgrowth in Pregnancy Definition: Gingival overgrowth in pregnancy or pregnancy gingivitis is a relatively rare form of gingival hyperplasia that occurs usually during pregnancy or during the menstrual cycle. Etiology: Increased levels of estrogen and progesterone in association with poor oral hygiene. Clinical features: Clinically, the disorder appears as significant gingival enlargement, localized or generalized. The gingiva and the interdental papillae are edematous, soft, bright red, with dense inflammation, and enlargement covering the crown of the teeth (▶ Fig. 7.9). Gingival hemorrhage and sensitivity are common. Glossodynia, dysgeusia, and bad breath are common symptoms during pregnancy. The diagnosis is, exclusively, based on the history and clinical features. Laboratory tests: Histopathologic examination, but it is not specific. Differential diagnosis: Plaque-related gingivitis, scurvy, diabetes mellitus, leukemia, and drug-induced gingival overgrowth. Treatment: High level of oral hygiene. The gingivitis may regress after pregnancy.

7.1.5 Gingival Overgrowth due to Leukemia See also section 5.23. Gingival overgrowth is a common and early finding in leukemias. However, gingival overgrowth occurs, more frequently, in patients with monocytic or myelomonocytic types of leukemia. The enlargement may be localized or generalized, and it is due to gingival infiltration by leukemic cells. The gingiva bleeds spontaneously, is enlarged, edematous, and inflamed, covering the crowns of the teeth (▶ Fig. 7.10, and ▶ Fig. 7.11). The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Peripheral blood count and bone marrow examination. Histopathologic examination of gingiva is indicative.

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Fig. 7.9 Hyperplastic gingivitis and granulomas during pregnancy.

Fig. 7.10 Acute myelomonocytic leukemia, hemorrhagic swelling of the gums.

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Differential diagnosis: Drug-induced gingival overgrowth, pregnancy gingivitis, hereditary gingival fibromatosis, Zimmermann–Laband syndrome, agranulocytosis, and scurvy. Treatment: Treatment lies upon the hematologist.

7.1.6 Hereditary Gingival Fibromatosis Definition: Hereditary gingival fibromatosis is a rare gingival overgrowth, characterized by fibrous connective tissue hyperplasia. Etiology: It may be genetic or idiopathic. The mutation of son of sevenless (SOS1) gene is responsible. The disease is usually transmitted as an autosomal dominant or rarely autosomal recessive trait. Clinical features: The disorder, usually, begins before the 15th year of age, in both sexes. Clinically, the gingiva overgrowth may be generalized or localized to one or more quadrants. The gingiva is firm, smooth, or nodular with no or minimal inflammation and normal color (▶ Fig. 7.12). The teeth may be partially or completely covered by the enlarged gingiva. Either jaw may be affected but the enlargement tends to be more prominent in the maxilla and can cause delayed teeth eruption and malocclusion. The diagnosis is mainly based on the history and clinical features. Laboratory tests: Histopathologic examination and molecular tests could be performed to identify the specific mutations. Differential diagnosis: Drug-related gingival overgrowth, mouth breathing gingivitis, Zimmermann–Laband syndrome, other genetic syndromes associated with gingival overgrowth, mucopolysaccharidoses (Hurler’s syndrome), leukemia, and amyloidosis. Treatment: The treatment of choice is surgical excision (gingivectomy) and high levels of oral hygiene.

7.1.7 Zimmermann–Laband Syndrome Definition: Zimmermann–Laband syndrome is a very rare genothermatosis with one of the main clinical characteristics being the great gingival enlargement. Etiology: Genetic. It is inherited in an autosomal dominant pattern. The cause is mutations of the KCNH1 gene, on chromosome 1q32 and ATP6V1B2 gene, on chromosome 8p21.

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Fig. 7.11 Erythroleukemia, hemorrhagic enlargement of the lower gingiva.

Fig. 7.12 Hereditary gingival fibromatosis, prominent gingival enlargement that covers the crowns of the teeth.

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Clinical features: Clinically, it is characterized by hypertrichosis, facial dysmorphism, joint hyperextensibility, macrosomia at birth, hepatosplenomegaly, mental retardation, and gingival enlargement. The gingival enlargement is one of the prominent features and is usually observed during the second or third month of life. Clinically, the gingiva appear enlarged and lobular covering partially or fully the crown of the teeth (▶ Fig. 7.13). Rarely, macroglossia and macrocheilia may also be observed. The diagnosis is mainly based on the history and clinical features. Laboratory tests: Histopathologic examination and molecular tests to identify the specific mutations. Differential diagnosis: Hereditary gingival fibromatosis, Murray–Puretic– Drescher syndrome, Rutherford syndrome, Cross syndrome, Ramon’s syndrome, and drug-related gingival overgrowth. Treatment: There is no specific treatment. Gingivectomy along with a program of high level of oral hygiene is suggested.

7.1.8 Scurvy Definition: Scurvy is a rare systemic nutritional disorder that primarily affects the gingiva, skin, hair, nails, muscles, and joints. Etiology: It is caused by the deficiency of vitamin C (ascorbic acid). Most cases are due to dietary deficiency in patients with chronic alcoholism or chronic illnesses. Vitamin C plays an important role in collagen composition, folic acid metabolism, iron absorption, and immune stimulation. Clinical features: Clinically, early manifestations of scurvy include malaise and weakness, followed by perifollicular hyperkeratotic papules, petechiae, hematomas, hemorrhages, susceptibility to infections, delayed wound healing, and oral lesions. The oral manifestations consist of generalized swelling and redness of the interdental and marginal gingiva, followed by spontaneous gingival bleeding, ulcerations, and tooth mobility (▶ Fig. 7.14). Petechiae, ecchymoses, and hemorrhages are commonly seen in other oral mucosal sites. The diagnosis is based on the history, clinical features, and laboratory examination.

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Fig. 7.13 Zimmermann–Laband syndrome, great gingival enlargement with a lobular pattern.

Fig. 7.14 Scurvy, prominent gingival enlargement, and erythema.

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Laboratory tests: The diagnosis can be confirmed by low plasma levels of vitamin C, typically below 0.1 mg/dL. Differential diagnosis: Leukemia, neutropenia, agranulocytosis, protein deficiency, and necrotizing ulcerative gingivitis. Treatment: Ascorbic acid orally 1 to 2 gr/d and a diet rich in fresh fruits and vegetables is recommended, with high level of oral hygiene.

7.2 Localized Enlargement 7.2.1 Pyogenic Granuloma Definition: Pyogenic granuloma is a common reactive, tumor-like granular tissue overgrowth of vascular tissue (capillary microangiogenesis). Etiology: Topical mild irritation or trauma. Clinical features: Clinically, pyogenic granuloma appears as a painless, sessile, or pedunculated exophytic mass with smooth or slightly lobulated surface and deep red color (▶ Fig. 7.15 and ▶ Fig. 7.16). The surface is often ulcerated and covered by a whitish-yellowish fibrinous membrane. It has elastic consistency and bleeds easily, either spontaneously or under light pressure. The lesion, usually, grows rapidly and the size varies between a few millimeters up to 1 to 2 cm or more. In over 70% of the cases, it develops on the gingiva followed by the tongue, buccal mucosa, lips, and palate. Children and young individuals are more frequently affected, and the female–male ratio is 2:1. Pregnancy granuloma and post extraction granuloma are a variety of pyogenic granulomas. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Peripheral giant cell granuloma, pregnancy granuloma, peripheral ossifying fibroma, peripheral brown tumor, hemangioma, leiomyoma, bacillary angiomatosis, Kaposi’s sarcoma, hemangioendothelioma, and hemangiopericytoma. Treatment: The treatment of choice is conservative surgical excision.

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Fig. 7.15 Pyogenic granulomas on the upper anterior gingiva.

Fig. 7.16 Pyogenic granuloma on the palatal gingiva.

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7.2.2 Peripheral Giant Cell Granuloma Definition: Peripheral giant cell granuloma is a relatively common, reactive tumor-like lesion that typically occurs exclusively on the gingiva or the edentulous alveolar ridge. Etiology: A tissue reaction to mechanical irritation, mild trauma, or dental plaque. The dominant belief is that it originates from mononuclear phagocytes or osteoclasts of the periodontal ligament or the periosteum. Clinical features: Clinically, peripheral giant cell granuloma presents as a wellcircumscribed pedunculated or sessile mass, with deep red color, elastic consistency and size that ranges from 0.5 to 2 cm or more. It can easily bleed and is often ulcerated (▶ Fig. 7.17). It occurs at any age group, with a peak from 30 to 40 years of life, and is more common in females (ratio 2:1). The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Pyogenic granuloma, pregnancy granuloma, peripheral ossifying fibroma, peripheral brown tumor, bacillary angiomatosis, Kaposi’s sarcoma, leiomyoma, and hemangioma. Treatment. The treatment of choice is conservative surgical excision.

7.2.3 Granular Cell Tumor of the Newborn Definition: Granular cell tumor of the newborn or congenital epulis of the newborn is an uncommon, benign, soft-tissue tumor of the oral cavity, exclusively seen in newborns on the alveolar ridges. Etiology: It probably originates from primitive mesenchymal cells. Clinical diagnosis: Clinically, it appears at birth as an asymptomatic, solitary, pedunculated tumor of normal or red color, with a smooth or slightly lobulated surface (▶ Fig. 7.18). The size varies from 0.5 to 2 cm. The maxilla is affected twice as often as the mandible and it has a female predilection (9:1). The diagnosis is based on the history and clinical features but should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, immunohistochemical analysis demonstrates that the cells are negative for S100 protein.

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Fig. 7.17 Peripheral giant-cell granuloma on the palatal gingiva.

Fig. 7.18 Granular cell tumor of the newborn.

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Differential diagnosis: Melanotic neuroectodermal tumor of infancy, hamartomas, fibroma, and gingival cyst of the newborn. Treatment: The treatment of choice is conservative surgical excision.

7.2.4 Periodontal Abscess Definition: Periodontal abscess is an accumulation of pus within a preexisting deep periodontal pocket. Etiology: Changes in the subgingival microflora and the host’s response in combination with local factors (e.g., stenosis or complete obliteration at the pocket opening). Clinical features: Clinically, periodontal abscess appears as a painful, soft, red gingival swelling (▶ Fig. 7.19). On pressure, pus exudes from the cervical area of the tooth. The involved teeth are tender to percussion and occasionally mobile. Other symptoms and signs include bleeding, halitosis, and in more severe cases fever, malaise and regional lymphadenopathy. A characteristic finding is that the adjacent teeth are vital. However, a periodontal abscess can be associated with endodontic pathology. The diagnosis is mainly based on clinical criteria. Laboratory tests: Radiographic examination. Differential diagnosis: Dental abscess, gingival cyst of adults, lateral periodontal cyst, incisive papilla cyst, nasolabial cyst, and actinomycosis. Treatment: Drainage and debridement of the periodontal pocket, systemic antibiotics, and periodontal treatment.

7.2.5 Parulis Definition: Parulis or fistula granuloma is a common lesion that develops, exclusively, on the gingiva. It is characteristically found at the opening of the sinus tract of a periodontal or periapical fistula. Clinical features: Clinically, the lesion presents as a painless, exophytic, granulomatous mass, identical to pyogenic granuloma (▶ Fig. 7.20).

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Fig. 7.19 Periodontal abscess on a background of periodontitis.

Fig. 7.20 Periodontal fistula on a background of advanced periodontitis.

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7.2.6 Multiple Exostoses Definition: Multiple exostoses are a relatively rare type of bony exostoses that occur on the buccal aspect of the maxilla and less often the mandible, usually bilateral. Etiology: Developmental, genetic and environmental factors may be involved. Clinical features: Clinically, multiple exostoses present as multiple, asymptomatic, nodular bony elevations along the buccal aspect of the alveolar bone of the jaws, covered by normal mucosa (▶ Fig. 7.21). The diagnosis is, exclusively, based on the clinical features. Laboratory tests: Not required. Differential diagnosis: Multiple osteomas, Gardner’s syndrome, Paget’s disease of the bone, and fibrous dysplasia. Treatment: No treatment is required.

Fig. 7.21 Multiple exostoses of the maxilla.

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8 Soft-Tissue Tumors “Tumor” is a loose, descriptive term to characterize a firm or solid, raised, usually, asymptomatic swelling that is larger than 0.5 cm in diameter. Both epithelial and mesenchymal lesions can represent a “tumor.” Benign and malignant neoplasms, reactive lesions, infections, and systemic diseases are included in this group of lesions. The location, consistency, surface, inflammation, and presence or absence of pain are important clinical signs and symptoms for the differential diagnosis of a given tumor. However, clinicians should make the final diagnosis exclusively on the basis of a biopsy and the histopathologic pattern.

Benign

Malignant

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Papilloma

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Squamous Cell Carcinoma

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Focal Epithelial Hyperplasia

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Verrucous Carcinoma

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Fibroma

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Kaposi’s Sarcoma

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Fibrous Developmental Malformation

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Peripheral Ossifying Fibroma

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Malignant Fibrous Histiocytoma

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Fibrosarcoma

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Lipoma

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Myxoma

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Chondrosarcoma

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Fibrous Histiocytoma

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Leiomyosarcoma

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Focal Oral Mucinosis

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Hemangioendothelioma

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Neurofibroma

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Hemangiopericytoma

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Schwannoma

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Mucoepidermoid Carcinoma

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Traumatic Neuroma

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Adenoid Cystic Carcinoma

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Granular Cell Tumor

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Leiomyoma

Polymorphous Low-Grade Adenocarcinoma

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Soft-Tissue Chondroma

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Other Malignant Salivary Gland Tumors

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Non-Hodgkin’s Lymphoma

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Malignant Melanoma

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Soft-Tissue Osteoma

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Melanotic Neuroectodermal Tumor of Infancy

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Lymphangioma

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Keratoacanthoma

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Amyloidosis

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Pleomorphic Adenoma

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Actinomycosis

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Myoepithelioma

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Cystadenoma

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Papillary Cystadenoma Lymphomatosum

Miscellaneous

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8.1 Benign 8.1.1 Papilloma See also sections 1.21 and 6.1. Definition: Papilloma is a relatively common benign tumor of the stratified squamous epithelium. Etiology: In 50 to 60% of papillomas, human papilloma virus (HPV) types 6 and 11 are detected within the tumor. Clinical features: Oral papilloma affects, equally, both sexes, most commonly from 30 to 50 years of age. Clinically, it presents as an exophytic, wellcircumscribed, pedunculated or sessile tumor, consisting of multiple, small projections that give the tumor a cauliflower-like appearance (▶ Fig. 8.1). The color varies between white, pale pink, and even normal mucosal, depending on the degree of keratinization. The size ranges from 3 to 6 mm and rarely grows over 1 cm. The lesion is usually solitary, occurring more frequently on the soft palate, tongue, buccal mucosa, and less commonly in other sites. The clinical diagnosis should be confirmed histologically. Laboratory tests: Histopathologic examination. Differential diagnosis: Condyloma accuminatum, verruca vulgaris, verruciform xanthoma, early verrucous carcinoma, sialadenoma papilliferum, focal epithelial hyperplasia, and focal dermal hypoplasia syndrome. Treatment: The treatment of choice is conservative surgical excision.

8.1.2 Focal Epithelial Hyperplasia Definition: Focal epithelial hyperplasia or Heck’s disease is a benign hyperplastic disorder of the oral mucosa, first described by Archard et al in 1965. Etiology: HPV types 13 and 32. Clinical features: The disease is predominantly observed in Eskimos, American Indians, South Africans, and sporadic in Europe and other ethnic groups. Clinically, focal epithelial hyperplasia presents as multiple, sessile, painless, and slightly elevated nodules of 1 to 10 mm in diameter, with a whitish or pale pink color (▶ Fig. 8.2 and ▶ Fig. 8.3). The surface of the lesions is smooth or mildly granular. Characteristically, when the mucosa is stretched, the lesions tend to disappear. The buccal mucosa, lips, and tongue are most frequently affected.

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Fig. 8.1 Papilloma on the palate.

Fig. 8.2 Focal epithelial hyperplasia, multiple white-pink nodules on the buccal mucosa.

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Soft-Tissue Tumors Rarely, conjunctival involvement may occur. The diagnosis is based on the clinical features but has to be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, in situ hybridization, and polymerase chain reaction techniques. Differential diagnosis: Multiple condylomas acuminatum, multiple verouca vulgaris, multiple papillomas, focal dermal hypoplasia syndrome, and Cowden’s syndrome. Treatment: The lesions may spontaneously reverse after a few months and up to 2 years. For lesions that cause esthetic problem, conservative surgical excision, electrosurgery, or laser CO2 may be suggested.

8.1.3 Fibroma Definition: Fibroma is the most common, benign, intraoral tumor that originates from the connective tissue. Etiology: In most cases, it is not a true neoplasm, but a reactive hyperplasia in response to chronic local irritation or trauma. Clinical features: Fibroma affects both sexes equally, usually from 30 to 50 years of age. Clinically, it presents as a well-circumscribed, usually sessile or with broad base, asymptomatic tumor with a smooth surface, normal epithelium, and a firm consistency (▶ Fig. 8.4). Not uncommonly, the surface has a whitish color and is rarely ulcerated by a continuous mechanical irritation. The tumor is usually solitary with a diameter of approximately 0.5 to 1 cm or more. The buccal mucosa, tongue, palate, gingiva, and lips are more often affected. Giant cell fibroma is a variation of fibroma with specific histopathologic pattern (▶ Fig. 8.5). The diagnosis is mainly based on the clinical features, but it should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Giant cell fibroma, peripheral ossifying fibroma, neurofibroma, schwannoma, lipoma, myxoma, fibrous histiocytoma, fibrous developmental malformation, and oral focal mucinosis. Treatment: The treatment of choice is conservative surgical excision.

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Fig. 8.3 Focal epithelial hyperplasia, multiple white-pink nodules on the mucosa of the lower lip and the tongue.

Fig. 8.4 Fibroma on the lower lip.

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Fig. 8.5 Giant cell fibroma on the dorsum of the tongue.

8.1.4 Fibrous Developmental Malformation Definition: Fibrous developmental malformation is a rare, benign, fibrous overgrowth, which usually occurs in the maxillary tuberosity region. Etiology: The exact etiology is unknown. Probably developmental. Clinical features: Clinically, fibrous developmental malformation appears as a painless, fibrous overgrowth that classically develops bilaterally, in a symmetrical pattern, in the maxillary tuberosity region and rarely in the retromolar region of the mandible (▶ Fig. 8.6 and ▶ Fig. 8.7). The surface of the lesion is smooth and covered by normal mucosa with pale color. It is firm on palpation and the fibrous mass is usually attached to the underlying bone, but rarely may be mobile. The size may extend to several centimeters, but occasionally may touch each other causing speech, mastication, and swallowing problems. The diagnosis is mainly based on the history and clinical features.

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Fig. 8.6 Fibrous developmental hyperplasia of the maxillary tuberosities on the right.

Fig. 8.7 Fibrous developmental hyperplasia of the maxillary tuberosities on the left.

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Laboratory tests: Histopathologic examination. Differential diagnosis: Fibroma, hereditary gingival fibromatosis, and neurofibromas. Treatment: The treatment of choice is conservative surgical excision.

8.1.5 Peripheral Ossifying Fibroma See also chapter 7. Definition: Peripheral ossifying fibroma, or peripheral fibroma, is a relatively common benign tumor with specific clinical and histologic features. It occurs exclusively on the gingiva. Etiology: The exact etiology is unknown. It is believed to derive from either the periodontal membrane or the periosteum. Clinical features: The peripheral ossifying fibroma is usually seen in teenagers and young adults. Females are more frequently affected to a ratio 2:1. Clinically, the tumor presents as a circumscribed gingival growth, sessile or pendiculated, that is covered by normal mucosa (▶ Fig. 8.8). However, frequently the surface can be erythematous or even ulcerated (▶ Fig. 8.9). The size varies between 0.5 to 2 cm. It develops more often in the incisor-cuspid region. The clinical diagnosis should be confirmed histologically. Laboratory tests: Histopathologic examination. Differential diagnosis: Fibroma, pyogenic granuloma, peripheral giant cell granuloma, peripheral odontogenic tumors. Treatment: Conservative surgical excision.

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Fig. 8.8 Peripheral ossifying fibroma on the lower gingiva.

Fig. 8.9 Peripheral ossifying fibroma with an erythematous surface, on the upper gingiva.

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8.1.6 Lipoma Definition: Lipoma is a benign tumor of adipose tissue, relatively rare in the oral cavity. Etiology: The exact etiology is unknown. Clinical features: Oral lipoma equally affects both sexes, usually from 40 to 50 years of age. Clinically, it presents as a well-defined, painless, tumor, sessile or pedunculated, of yellowish or pink-yellow color and a size from 0.5 to 3 cm (▶ Fig. 8.10 and ▶ Fig. 8.11). It is covered by a thin mucosal layer with visible blood capillaries. On palpation, it is, usually, soft and occasionally fluctuant, mimicking a cyst. The buccal mucosa and vestibule and less often the tongue, palate, and lips are the most common sites affected. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Myxoma, oral focal mucinosis, fibroma, mucocele, dermoid cyst, and cystadenoma. Treatment: The treatment of choice is conservative surgical excision.

8.1.7 Myxoma Definition: Myxoma is a very rare, benign tumor of the oral cavity of mesenchymal origin. Etiology: The exact etiology is unknown. Most of the tumors represent a myxoid degeneration of the connective tissue, rather than a true neoplasm.

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Fig. 8.10 Bilobular lipoma on the buccal mucosa.

Fig. 8.11 Lipoma on the buccal mucosa.

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Clinical features: Clinically, oral myxoma presents as a well-circumscribed tumor covered by normal mucosa and soft on palpation (▶ Fig. 8.12), on the buccal mucosa and less often on the floor of the mouth, and palate. The diagnosis is based exclusively on the histologic pattern. Laboratory tests: Histopathologic examination. Differential diagnosis: Lipoma, oral focal mucinosis, fibroma, mucocele, and cystadenoma. Treatment: The treatment of choice is conservative surgical excision.

8.1.8 Fibrous Histiocytoma Definition: Fibrous histiocytoma is a benign cellular tumor, primarily composed of histiocytes and fibroblasts. It is very rare on the oral mucosa. Etiology: The exact etiology is unknown. Clinical features: Fibrous histiocytoma equally affects both sexes, usually from 50 to 70 years of age. Clinically, it presents as a painless, firm tumor, covered by normal or whitish epithelium, which may be ulcerated (▶ Fig. 8.13). The size ranges from 0.5 to 2 cm. The buccal mucosa, tongue, and gingiva are most frequently affected. The clinical features are not diagnostic and the final diagnosis is mainly based on the histologic pattern. Laboratory tests: Histopathologic examination. Differential diagnosis: Granular cell tumor, fibroma, neurofibroma, schwannoma, myxoma, lipoma, and leiomyoma. Treatment: The treatment of choice is conservative surgical excision.

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8.1 Benign

Fig. 8.12 Myxoma on the buccal mucosa.

Fig. 8.13 Fibrous histiocytoma on the buccal mucosa.

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8.1.9 Focal Oral Mucinosis Definition: Mucinoses are a heterogeneous group of lesions that affect the production and deposition of mucous, mainly on the skin and rarely on the oral mucosa. Etiology: The exact etiology is unknown. However, it is believed to be caused by a functional disorder that leads to increased production of hyaluronic acid from fibroblasts. Clinical features: Mucinoses are classified into primary and secondary. The primary group is divided into two types: the degenerative-inflammatory, and the hamartomatous–neoplastic. Focal dermal and oral mucinosis belong to the primary degenerative–inflammatory type. Clinically, it presents as a circumscribed, painless tumor that might be sessile or pedunculated and is covered by smooth, normal mucosa (▶ Fig. 8.14). On palpation the tumor is soft and the size varies from 0.5 to 2 cm. The gingiva is the site of predelection (over 70%), followed by the palate, buccal mucosa, and tongue. The clinical features are not pathognomonic and the diagnosis is based on the histologic pattern. Laboratory tests: Histopathologic examination and histochemical stains. Differential diagnosis: Lipoma, myxoma, fibroma, peripheral ossifying fibroma, cystadenoma, and mucocele. Treatment: The treatment of choice is conservative surgical excision.

8.1.10 Neurofibroma Definition: Neurofibroma is a, relatively rare, benign tumor of the oral mucosa, originating from Schwann cells, the perineural fibroblasts, or the endoneurium. Etiology: The exact etiology is unknown. Clinical features: Oral neurofibroma can be either solitary or multiple, as part of von Recklinghausen’s disease. Clinically, it presents as a slowly developing, well-circumscribed, usually pedunculated, and painless tumor of relatively firm consistency that is covered by normal mucosa (▶ Fig. 8.15).

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8.1 Benign

Fig. 8.14 Oral focal mucinosis, circumscribed tumor on the palatal gingiva.

Fig. 8.15 Solitary neurofibromas in the side of the tongue.

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Soft-Tissue Tumors The size varies from 0.5 to 2 cm. The buccal mucosa, tongue, palate, and alveolar mucosa are most commonly affected. Multiple skin and oral neurofibromas are a common finding of von Recklinghausen’s disease (▶ Fig. 8.16). The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination and immunohistochemical examination. Differential diagnosis: Neurofibromatosis type 1, schwannoma, fibroma, leiomyoma, granular cell tumor, fibrous histiocytoma. Treatment: The treatment of choice is conservative surgical excision.

8.1.11 Schwannoma Definition: Schwannoma or neurilemoma is a relatively rare, benign tumor of the nervous tissue that derives from the Schwann cells. Etiology: The exact etiology is unknown. Clinical features: Oral schwannoma may be solitary or part of neurofibromatosis, type 2. Clinically, it appears as a slowly growing, solitary, wellcircumscribed, sessile tumor that is covered by normal mucosa (▶ Fig. 8.17). It is usually painless and firm and the size can range from 0.5 to 2 cm in diameter. The tongue is the most affected site, followed by palate, buccal mucosa, gingiva, and lips. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Neurofibroma, fibroma, fibrous histiocytoma, leiomyoma, granular cell tumor, and pleomorphic adenoma. Treatment: The treatment of choice is conservative surgical excision.

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8.1 Benign

Fig. 8.16 Neurofibromatosis, multiple neurofibromas of the skin, as part of von Recklinghausen’s disease.

Fig. 8.17 Schwannoma of the tongue.

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8.1.12 Traumatic Neuroma Definition: Traumatic neuroma or amputation neuroma is a reactive hyperplasia of nerve fibers and surrounding tissue. Etiology: Incision or injury of a nerve bundle. Clinical features: Clinically, traumatic neuroma appears as a small, usually mobile tumor covered by normal mucosa (▶ Fig. 8.18). It grows slowly and rarely exceeds 1 cm in diameter, and is accompanied by pain in about 50% of the cases, particularly on palpation. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Schwannoma, meurofibroma, granular cell tumor, fibroma, lipoma, multiple endocrine neoplasia syndrome, type 2b, salivary gland disorders, and foreign body reaction. Treatment: The treatment of choice is conservative surgical excision.

8.1.13 Granular Cell Tumor Definition: Granular cell tumor is a relatively rare benign tumor. It is believed to derive from Schwann cells or undifferentiated mesenchymal cells. Etiology: Unknown. Clinical features: The granular cell tumor, usually, affects females (ratio 2:1), from 40 to 60 years of age. Clinically, it appears as a small, asymptomatic, firm, sessile, well-circumscribed, slightly elevated tumor, with a pale or erythematous or whitish or normal color and 1 to 2 cm in size (▶ Fig. 8.19 and ▶ Fig. 8.20). The dorsum and the lateral borders of the tongue are the sites of predilection, followed by the buccal mucosa and palate. The tumor is, usually, solitary and may also be found on the skin, breast, and very rarely in viscera. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination; histochemically the cells are positive for the S100 protein. Differential diagnosis: Schwannoma, neurofibroma, fibrous histiocytoma, leiomyoma, rhabdomyoma, granular cell tumor of infancy, fibroma, pleomorphic adenoma, and cystadenoma. Treatment: The treatment of choice is conservative surgical excision.

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Fig. 8.18 Traumatic neuroma on the dorsum of the tongue.

Fig. 8.19 Granular cell tumor on the dorsum of the tongue.

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Fig. 8.20 Granular cell tumor on the lateral border of the tongue.

8.1.14 Leiomyoma Definition: Leiomyoma is a benign tumor of smooth muscle that usually develops in the uterus, gastrointestinal tract, and the skin. Oral lesion is rare and originates from the smooth muscles of blood vessels walls or the circumvallate papillae of the tongue. Etiology: The exact etiology is unknown. Clinical features: Oral leiomyoma affects both sexes equally, usually over 30 years of age. Clinically, it appears as a slowly growing, painless, firm and wellcircumscribed tumor with a reddish or normal color (▶ Fig. 8.21 and ▶ Fig. 8.22). The tongue is most commonly affected, followed by buccal mucosa, palate, and lower lip. Histologically, it is classified into three types: solid–vascular– epithelioid. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic and immunohistochemical examinations. Differential diagnosis: Hemangioma, granular cell tumor, schwannoma, myofibroma, hemangioendothelioma, hemangiopericytoma, and squamous cell carcinoma. Treatment: The treatment of choice is conservative surgical excision.

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Fig. 8.21 Leiomyoma on the dorsum of the tongue.

Fig. 8.22 Ulcerated leiomyoma on the dorsum of the tongue.

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8.1.15 Soft-Tissue Chondroma Definition: Soft-tissue chondroma is a benign tumor of chondroid tissue that may, rarely, develop in the oral soft tissues. The tumor is believed to derive from remnants of ectopic chondroid tissue or from polyvalent mesenchyme cells. Etiology: The exact etiology is unknown. Clinical features: Clinically, oral soft-tissue chondroma appears as a painless, usually sessile, spherical and firm tumor that is covered by normal mucosa (▶ Fig. 8.23). It varies in size from 0.5 to 1 cm in diameter. The dorsum and the lateral borders of the tongue are the most frequently affected sites (80–90%), followed by buccal mucosa, palate, and gingiva. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Neurofibroma, schwannoma, fibroma, lipoma, focal oral mucinosis, and granular cell tumor. Treatment: The treatment of choice is conservative surgical excision.

8.1.16 Soft-Tissue Osteoma Definition: Soft-tissue osteoma is a very rare, benign tumor caused by proliferation of osseous cells in the oral soft tissues (choristoma). Etiology: The exact etiology is unknown. Clinical features: Clinically, oral soft-tissue osteoma appears as a painless, well-circumscribed, hard tumor, covered by thin and smooth epithelium of whitish or pale color (▶ Fig. 8.24). The size ranges from 0.5 to 2 cm in diameter. The palate, alveolarmucosa,andlessoftentongueandbuccalmucosaarethesitesofpredilection. Theclinicaldiagnosisshouldbeconfirmedbylaboratorytests. Laboratory tests: Histopathologic examination. Differential diagnosis: Torus palatinus, torus mandibularis, other exostoses, chondroma, fibroma, and Gardner’s syndrome. Treatment: The treatment of choice is conservative surgical excision.

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Fig. 8.23 Chondroma, the palatal gingiva respectively with the premolars.

Fig. 8.24 Soft-tissue osteoma on the alveolar mucosa.

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8.1.17 Melanotic Neuroectodermal Tumor of Infancy Definition: Melatonic neuroectodermal tumor of infancy is a rare, benign tumor of neural crest origin, which usually develops in tooth-bearing areas, only in infants, less than 6 months of age. Etiology: The exact etiology is unknown. Clinical features: Clinically, it presents as a rapidly growing, painless mass of erythematous-brown or normal color and elastic consistency that is covered by normal mucosa (▶ Fig. 8.25). The tumor may lead to osseous destruction which together with the rapid development can give the impression of malignancy. The tumor mostly appears on the maxilla (75–80%) and less often in the mandible. Cases have been also reported in the skull, skin, brain, epididymis, testicles, and uterus. The diagnosis is based on the history and clinical features, but should be confirmed by laboratory tests. Laboratory tests: Histopathologic and immunohistochemical examinations. Differential diagnosis: Granular cell tumor of the newborn, hamartomas, osteosarcoma, chondrosarcoma, neuroblastoma, and odontogenic tumors. Treatment: The treatment of choice is conservative surgical excision.

8.1.18 Lymphangioma Definition: Lymphangioma is relatively common oral disorder caused by hyperplasia of the lymphatic tissue. Etiology: Developmental malformation. Clinical features: Depending on the size and the lymphatic spaces, lymphangiomas are classified into three types: (1) capillary or microcystic, (2) cavernous or macrocystic, and (3) mixed or micro–macrocystic. A specific type of macrocystic type is the cystic hygroma. Clinically, oral lymphangioma appears as small, soft, irregular nodule similar to small cyst or vesicle, with a yellowbrown or red color (▶ Fig. 8.26). The size ranges from a few millimeters to several centimeters or it can be a very extensive lesion that may cause generalized enlargement and organ deformity. The tongue is the most frequently affected site and less often the soft palate, buccal mucosa, lips, and rarely the gingiva. The diagnosis is based on the clinical and histopathologic features.

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Fig. 8.25 Melanotic neuroectodermal tumor of infancy on the maxilla.

Fig. 8.26 Small lymphangioma on the dorsum of the tongue.

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Laboratory tests: Histopathologic examination. Differential diagnosis: Vascular malformations, hemangioma, papillary hyperplasia of the palate, median rhomboid glossitis, lymphoepithelial cyst, and lingual thyroid. Treatment: The treatment of choice is conservative surgical excision for small and medium lesions.

8.1.19 Keratoacanthoma Definition: Keratoacanthoma is a fairly common, benign, skin tumor that occurs, usually, on sunlight exposed skin and arises from the hair follicles. Etiology: The exact etiology remains uncertain. Sunlight and HPV seem to play an important role in the pathogenesis. Clinical features: It is more common in males than females (ratio 1.8:1) older than 50 years. Clinically, keratoacanthoma appears as a painless, wellcircumscribed dome-shaped or bud-shaped tumor of 1 to 2 cm in diameter, with a characteristic keratin crater at the center (▶ Fig. 8.27, ▶ Fig. 8.28). Classically, the tumor grows rapidly and within 4 to 8 weeks reaches the final size. For a period of 1 to 2 months, it persists without change and may then undergo spontaneous regression. Based on histogenesis and biological behavior, two types of keratoacanthoma are recognized: type 1 (bud shaped)and type 2 (dome shaped). About 10% of keratoacanthomas are located on the lips, whereas very few cases have been reported intraorally. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Squamous cell carcinoma, basal cell carcinoma, warty dyskeratoma, papillary syringadenoma, and cutaneous horn. Treatment: The treatment of choice is conservative surgical excision or radiation or electrosurgery or cryotherapy.

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Fig. 8.27 Keratoacanthoma on the vermilion border of the lower lip.

Fig. 8.28 Keratoacanthoma on the skin of the nose.

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8.1.20 Pleomorphic Adenoma Definition: Pleomorphic adenoma is the most common benign neoplasm of the major and minor salivary glands. It is derived from the myoepithelial and glandular cells of the salivary duct. Etiology: The exact etiology is unknown. Clinical features: Pleomorphic adenoma of minor salivary glands, most commonly develops on the posterior aspect of the palate (60–65%), followed by the upper lip, retromolar region, buccal mucosa, and rarely on tongue. Clinically, it presents as an asymptomatic, slowly growing, firm swelling, with a size of 2 to 3 cm in diameter (▶ Fig. 8.29). The tumor is covered by normal mucosa and it is rarely ulcerated. The diagnosis is based on the clinical features but must be confirmed by a biopsy. Laboratory tests: Histopathologic examination. Differential diagnosis: Monomorphic adenomas, malignant tumors of salivary glands, necrotizing sialadenometaplasia, fibroma, lipoma, non-Hodgkin’s lymphoma, and chronic abscess. Treatment: The treatment of choice is surgical excision.

8.1.21 Myoepithelioma Definition: Myoepithelioma is a relatively rare, benign tumor of salivary glands, originating from the myoepithelial cells. Etiology: The exact etiology is unknown. Clinical features: It most frequently affects the parotid gland and the minor salivary glands of the palate, usually from 30 to 50 years of age, with no sex predilection. Clinically, myoepithelioma of minor salivary glands presents as a painless, slowly growing, well-circumscribed, firm enlargement that is usually covered by normal epithelium (▶ Fig. 8.30). The clinical features are nondiagnostic; therefore, the final diagnosis is based on the histologic pattern. Laboratory tests: Histopathologic examination. Differential diagnosis: Pleomorphic adenoma, other monomorphic adenomas, cystadenoma, malignant salivary gland tumors, necrotizing sialadenometaplasia, fibroma, lipoma, and non-Hodgkin’s lymphoma. Treatment: The treatment of choice is surgical excision.

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Fig. 8.29 Pleomorphic adenoma, swelling on the palate.

Fig. 8.30 Myoepithelioma on the palate.

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8.1.22 Cystadenoma Definition: Cystadenoma is a rare benign, salivary gland tumor, characterized by predominantly multicystic growth. Etiology: The exact etiology is unknown. Clinical features: It represents 3 to 5% of benign tumors of minor salivary glands and is more common is females. Clinically, cystadenoma appears as a well-circumscribed, slightly elevated, soft tumor, covered by normal mucosa and a size that varies from 0.5 to 2 cm in diameter (▶ Fig. 8.31). The tumor is more common in the minor salivary glands, particularly in the buccal mucosa, floor of the mouth, and lips. As the clinical features are not characteristic the final diagnosis should be based exclusively on the specific histologic pattern. Laboratory tests: Histopathologic examination. Differential diagnosis: Mucocele, ranula, duct ectasia, chronic sialadenitis, lymphoepithelial cyst, early papillary cystadenoma lymphomatosum, mucoepidermoid carcinoma, and acinic cell carcinoma. Treatment: The treatment of choice is conservative surgical removal.

8.1.23 Papillary Cystadenoma Lymphomatosum Definition: Papillary cystadenoma lymphomatosum or adenolymphoma or Warthin’s tumor is a relatively common, benign tumor of the salivary glands. Etiology: The exact etiology is unknown. Clinical features: It mainly affects the parotid gland, and rarely the minor salivary grands. The tumor is more common in males than females (ratio 5:1–7:1) predominantly from 50 to 70 years of age. Clinically, it appears as a painless, firm or soft swelling, covered by normal mucosa (▶ Fig. 8.32). The tumor develops slowly and can reach 1 to 4 cm in diameter. The clinical diagnosis should be confirmed by the histologic examination. Laboratory tests: Histopathologic examination. Differential diagnosis: Other benign tumors of the salivary glands, malignant tumors of salivary glands, cystadenoma, mucocele, lymphoepithelial cyst, sialadenosis, and non-Hodgkin’s lymphoma. Treatment: The treatment of choice is conservative surgical excision.

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Fig. 8.31 Cystadenoma.

Fig. 8.32 Papillary cystadenoma lymphomatosum, swelling with unclear borders on the buccal mucosa.

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8.2 Malignant 8.2.1 Squamous Cell Carcinoma See also sections 1.23, 2.9, 5.16, and 6.7. Squamous cell carcinoma of the oral cavity has a variety of clinical features and may mimic several oral diseases, leading to diagnostic dilemmas. A relatively common clinical pattern for the malignancy is an exophytic, irregular mass or tumor (▶ Fig. 8.33). The surface of the tumor is usually ulcerated, and the base is indurated on palpation. Biopsy and histologic examination must be performed for final, accurate diagnosis.

8.2.2 Verrucous Carcinoma See also sections 1.22 and 6.6. Verrucous carcinoma is a low-grade variant of squamous cell carcinoma, characterized by slow, persistent growth, good biological behavior, and prognosis. Clinically, it presents as a slowly growing, painless, exophytic tumor with a characteristic verrucous whitish surface (▶ Fig. 8.34). Early lesions may mimic several other verrucous lesions, so that the final diagnosis is based on the histologic pattern.

8.2.3 Kaposi’s Sarcoma Definition: Kaposi’s sarcoma is a malignant tumor, originating from endothelial cells with relatively good biological behavior and slow development. Etiology: The main etiologic factor is human herpesvirus type 8. Clinical features: Kaposi’s sarcoma is classified into four groups: 1. Classic: It is more common in Jewish, Balcans, Greeks, and other Mediterranean individuals, and primarily involves the skin and rarely the oral mucosa and other mucosae. Males are more commonly affected (ratio 3:1 and 8:1), from the age of 50 to 70 years, and has a slow development. 2. African endemic: It is common in Uganda and other African countries, and primarily involves the skin and lymph nodes, rarely the oral mucosa, and usually has an indolent course.

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Fig. 8.33 Exophytic squamous cell carcinoma on the lower lip.

Fig. 8.34 Coexistence of verrucous carcinoma (white exophytic lesion on the buccal mucosa) and squamous cell carcinoma (ulceration on the lingual aspect of the retromolar area).

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Soft-Tissue Tumors 3. Iatrogenic immunosuppression-related: It is observed in patients with kidney transplantation and other organ transplants, as well as those having received immunosuppressive drugs for long time for a variety of diseases. This form usually has an indolent clinical course, but sometimes can be aggressive, involving the viscera, but rarely the oral mucosa. 4. Epidemic AIDS-related: It is without race predilection and of high incidence among AIDS patients. However, after antiretroviral therapy the prevalence of AIDS-related Kaposi’s sarcoma has dramatically reduced. It usually involves the skin, lymph nodes, viscera, and frequently the oral mucosa with a rapid course. Clinically, the oral lesions appear as single or multiple macules, tumors or elevated plaques that might ulcerate and are of bright red or brown-red color (▶ Fig. 8.35, ▶ Fig. 8.36, ▶ Fig. 8.37). The most commonly affected sites are the palate and gingiva, followed by tongue, buccal mucosa, and lips. The clinical diagnosis should be confirmed by the histologic examination. Laboratory tests: Histopathologic and immunohistochemical examinations. Differential diagnosis: Pyogenic granuloma, peripheral giant cell granuloma, bacillary angiomatosis, hemangioma, leiomyosarcoma, hemangioendothelioma, hemangiopericytoma, malignant melanoma, and non-Hodgkin’s lymphoma.

Fig. 8.35 Kaposi’s sarcoma on the hard palate.

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Fig. 8.36 Ulcerated Kaposi’s sarcoma on the palate.

Fig. 8.37 Classic Kaposi’s sarcoma, multiple tumors on the skin of the foot.

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Treatment: The first line of therapy is chemotherapy with or without radiation or surgical excision for localized lesions.

8.2.4 Malignant Fibrous Histiocytoma Definition: Malignant fibrous histiocytoma is one of the most common softtissue sarcomas in adults. It derives from fibroblasts and histiocytes. Etiology: The exact etiology is unknown. Clinical features: It is very rare in the mouth and usually develops in the jaw bones or the oral soft tissues. Clinically, the tumor presents as a rapidly developing and painless or painful, exophytic mass, of red-brown color, with or without ulceration (▶ Fig. 8.38). The size ranges from 2 to 6 cm in diameter. The gingiva and alveolar mucosa are most frequently affected. The clinical features are not characteristic, and the final diagnosis is exclusively based on histologic criteria. Laboratory tests: Histopathologic examination. Differential diagnosis: Chondrosarcoma, fibrosarcoma, Kaposi’s sarcoma, leiomyosarcoma, squamous cell carcinoma, and peripheral giant cell granuloma. Treatment: The treatment of choice is radical surgical excision. Radiotherapy and chemotherapy may also be used as adjunctive therapy.

8.2.5 Fibrosarcoma Definition: Fibrosarcoma is a rare malignant neoplasm of mesenchymal origin, deriving from fibroblasts. It is most common in the limbs and trunk and very rare in the mouth. Etiology: The exact etiology is unknown. Clinical features: Clinically, oral fibrosarcoma presents as an exophytic, slowly growing, usually painless, mass of soft or slightly firm consistency that may or may not be ulcerated (▶ Fig. 8.39). The tongue, gingiva, buccal mucosa, and palate are the sites of predilection. The clinical features are not diagnostic and the final diagnosis is based on the histologic criteria. Laboratory tests: Histopathologic and immunohistochemical examinations. Differential diagnosis: Malignant fibrous histiocytoma, angiosarcoma, Kaposi’s sarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, and peripheral giant cell granuloma.

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Fig. 8.38 Malignant fibrous histiocytoma on the lower gingiva.

Fig. 8.39 Fibrosarcoma on the palate.

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Treatment: The treatment of choice is radical surgical excision. Radiotherapy and chemotherapy may also be used as adjunctive therapy.

8.2.6 Chondrosarcoma Definition: Chondrosarcoma is a malignant neoplasm that is characterized by cartilage formation by the tumor cells. Etiology: The exact etiology is unknown. Clinical features: It is classified into primary, when it develops de novo and secondary, when it develops from a preexisting benign cartilage tumor. The tumor is rare in the jaws. Clinically, oral chondrosarcoma presents as a hard swelling that develops rapidly, causing extensive osseous destructions with pain and loosening and displacement of the teeth. Occasionally, a large, erythematous, lobulated and ulcerated, exophytic mass may occur (▶ Fig. 8.40). The clinical diagnosis should be confirmed by the histologic examination. Laboratory tests: Histopathologic and immunohistochemical examinations. Differential diagnosis: Osteosarcoma, Ewing’s sarcoma, malignant fibrous histiocytoma, squamous cell carcinoma, peripheral giant cell granuloma, and odontogenic tumors. Treatment: The treatment of choice is radical surgical excision. Radiotherapy and chemotherapy can also be used.

8.2.7 Leiomyosarcoma Definition: Leiomyosarcoma is a malignant neoplasm of the smooth muscle tissue that most commonly occurs in the uterus, gastrointestinal tract, skin, while it is rare in the mouth. Etiology: The exact etiology is unknown. Primary oral leiomyosarcoma may derive from smooth muscle cells of the blood vessels or the circumvallate papillae of the tongue or from pluripontent remnants of embryonic mesenchyme. Clinical features: Clinically, it presents as a slowly growing, painless or painful, raised firm mass with a smooth red surface, which may or may not exhibit ulceration (▶ Fig. 8.41). The gingiva, tongue, and palate are the most common affected sites. Females are more frequently affected usually from 50 to 70 years. The clinical features are not characteristic and the diagnosis is exclusively based on the histologic criteria.

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Fig. 8.40 Chondrosarcoma on the lingual aspect of the mandible.

Fig. 8.41 Leiomyosarcoma on the lower gingiva, in the canine area.

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Laboratory tests: Histopathologic examination and immunohistochemical markers. Differential diagnosis: Leiomyoma, peripheral ossifying fibroma, Kaposi’s sarcoma, angiosarcoma, other soft-tissue sarcomas, and squamous cell carcinoma. Treatment: The treatment of choice is radical surgical excision. Radiotherapy and chemotherapy may also be used.

8.2.8 Hemangioendothelioma Definition: Hemangioendothelioma is a rare malignant neoplasm of the vascular wall of endothelial cells. It usually occurs on the skin of the head and neck and is very rare in the mouth. Etiology: The exact etiology is unknown. Clinical features: Clinically, oral hemangioendothelioma presents as an elevated, painless, firm mass, with a characteristic deep red or brown-red color, with or without ulceration (▶ Fig. 8.42). The tongue, palate, buccal mucosa, and gingiva are the sites of predilection. The clinical diagnosis has to be confirmed by histologic examination. Laboratory tests: Histopathologic examination and immunohistochemical markers. Differential diagnosis: Kaposi’s sarcoma, hemangiopericytoma, malignant fibrous histiocytoma, leiomyoma, squamous cell carcinoma, and pyogenic granuloma. Treatment: The treatment of choice is radical surgical excision with or without radiotherapy and chemotherapy.

8.2.9 Hemangiopericytoma Definition: Hemangiopericytoma is a rare neoplasm of vascular tissue that arises from the pericytes of the vascular wall and it is very rare in the mouth. Etiology: The exact etiology is unknown. Clinical features: Clinically, oral hemangiopericytoma usually presents as a well-circumscribed, painless, elevated mass of red or normal color and firm consistency (▶ Fig. 8.43). The tumor, usually, progresses quickly and may ulcerate. The tongue, buccal mucosa, and palate are the most frequently affected sites. The clinical features are not diagnostic, and the final diagnosis is exclusively based on the histologic pattern.

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Fig. 8.42 Hemangioendothelioma on the buccal mucosa.

Fig. 8.43 Hemangiopericytoma on the lateral border of the tongue.

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Laboratory tests: Histopathologic examination and immunohistochemical markers. Differential diagnosis: Hemangioendothelioma, Kaposi’s sarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and squamous cell carcinoma. Treatment: The treatment of choice is radical surgical excision, with or without radiotherapy and chemotherapy.

8.2.10 Mucoepidermoid Carcinoma Definition: Mucoepidermoid carcinoma is one of the most common minor salivary gland malignancy in children and adults, which comprises of three, histologically different, cellular populations (mucous secreting cells, squamous cells, and intermediate), with a broad spectrum of biological behavior. Etiology: The exact etiology is unknown. Clinical features: Clinically, intraoral tumors present as a slowly growing, painless enlargement that can have soft or firm consistency and could be ulcerated (▶ Fig. 8.44). The soft palate and retromolar pad are the sites of predilection, followed by buccal mucosa, tongue, and upper lip. In the parotid gland the tumor presents as a slowly growing, painless mass, which progressively develops tenderness, pain, trismus, and facial nerve paresis. The 5-year overall survival is about 80%. The clinical diagnosis should be confirmed by the histologic examination. Laboratory tests: Histopathologic examination, molecular genetics, and specific gene expression. Differential diagnosis: Pleomorphic adenoma, monomorphic adenomas, cystadenoma, necrotizing sialadenometaplasia, acinic cell adenocarcinoma, polymorphous low-grade adenocarcinoma, and other salivary gland malignancies. Treatment: The treatment of choice is radical surgical excision. Postoperative radiotherapy may be used for aggressive tumors.

8.2.11 Adenoid Cystic Carcinoma Definition: Adenoid cystic carcinoma is one of the most common malignant neoplasms of the salivary glands, with characteristic histologic pattern. Etiology: The exact etiology is unknown. Clinical features: It is common neoplasm of minor salivary grands (> 50%). Clinically, intraoral adenoid cystic carcinoma presents as a slightly painful, slowly growing, swelling that often ulcerates (▶ Fig. 8.45). Along with the

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Fig. 8.44 Ulcerated mucoepidermoid carcinoma on the palate.

Fig. 8.45 Ulcerated adenoid cystic carcinoma on the palate.

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Soft-Tissue Tumors gradual swelling, tenderness, pain, and facial nerve palsy are common in patients with parotid tumor. It metastasizes usually through the perineural spaces, in 30 to 40% of the cases and is usually of poor prognosis. It mainly occurs in the palate and less often in upper lip, buccal mucosa, and tongue. The tumor, equally, affects both sexes, most commonly from the age of 40 to 60 years. The clinical features are not specific, and the final diagnosis is based on the histologic examination. Laboratory tests: Histopathologic and immunohistochemical examinations. Differential diagnosis: Pleomorphic adenoma, monomorphic adenomas, mucoepidermoid carcinoma, polymorphous low-grade adenocarcinoma, other malignant tumors of salivary glands, squamous cell carcinoma, and necrotizing sialadenometaplasia. Treatment: The treatment of choice is radical surgical excision. Radiotherapy is commonly used as adjunctive therapy.

8.2.12 Polymorphous Low-Grade Adenocarcinoma Definition: Polymorphous low-grade adenocarcinoma is a separate, malignant, clinicopathologic entity, which almost exclusively affects the minor salivary glands, with a low metastatic potential. It is the second most common malignant neoplasm of the minor salivary glands, after mucoepidermoid carcinoma. Etiology: The exact etiology is unknown. Clinical features: Clinically, polymorphous low-grade adenocarcinoma appears as a painless, firm, slowly growing mass with or without ulceration (▶ Fig. 8.46 and ▶ Fig. 8.47). The size varies from 1 to many centimeters. The palate is the site of predilection (60–70%), followed by upper lip, buccal mucosa, and retromolar pad. The overall prognosis is excellent with more than 90 to 95% of patients being alive after a 10-year follow-up. The final diagnosis is exclusively based on the histologic criteria. Laboratory tests: Histopathologic examination and immunohistochemical markers. Differential diagnosis: Pleomorphic adenoma, acinic cell carcinoma, mucoepidermoid carcinoma, other salivary gland adenocarcinomas, and necrotizing sialanenometaplasia. Treatment: The treatment of choice is surgical excision.

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Fig. 8.46 Polymorphous low-grade adenocarcinoma on the palate.

Fig. 8.47 Polymorphous low-grade carcinoma ulcerated, on the palate.

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8.2.13 Other Malignant Salivary Gland Tumors Acinic cell adenocarcinoma, carcinoma ex pleomorphic adenoma, clear-cell adenocarcinoma, adenocarcinoma not otherwise specified, are included in the category of minor salivary gland malignant neoplasms. Clinically, almost all of them appear as a firm, painless or not, swelling or tumor that may or not be ulcerated (▶ Fig. 8.48, ▶ Fig. 8.49, ▶ Fig. 8.50, and ▶ Fig. 8.51). The oral clinicians should remember that the clinical features are not characteristic and diagnostic, and the final diagnosis is exclusively based on the basis of the biopsy and histopathologic and other specific examinations.

8.2.14 Non-Hodgkin’s Lymphoma Definition: Non-Hodgkin’s lymphoma is a heterogeneous group of lymphoid tissue malignancies that account for 70 to 80% of all lymphomas. Etiology: The exact etiology remains unclear. Genetic and environmental factors (e.g., Epstein–Barr virus, human T-cell leukemia virus type 1, medications, radiation, HIV infection, Sjögren’s syndrome, etc.) seem to play a significant role in the pathogenesis. Clinical features: Based on the disease progression and the degree of cellular aggression, non-Hodgkin’s lymphomas are classified into three categories: (1) low grade, (2) intermediate, and (3) high grade. The WHO (2008) divided the disorder into two major groups: (1) B-cell derived and (2) T-cell derived. In addition, more than 30 subtypes have been described. Oral non-Hodgkin’s lymphoma is the third most frequently malignancy of the mouth but rarely is the first and only manifestation of the disease. Clinically, oral lesions, present as a diffuse, painless, swelling that may be ulcerated (▶ Fig. 8.52 and ▶ Fig. 8.53). The ulcer’s surface appears irregular with surrounding inflammation and slightly firm on palpation. The soft palate, tongue, gingiva, buccal mucosa, and floor of the mouth are most commonly affected. Regional and systemic lymphadenopathy are common. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic and immunohistochemical examinations. Differential diagnosis: Eosinophilic ulcer, Wegener’s granulomatosis, Hodgkin’s disease, soft-tissue sarcomas, squamous cell carcinoma, necrotizing sialadenometaplasia, systemic mycoses, and amyloidosis. Treatment: The treatment of choice is chemotherapy and radiotherapy.

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Fig. 8.48 Acinic cell adenocarcinoma of the palate.

Fig. 8.49 Malignant pleomorphic adenoma on the buccal mucosa.

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Fig. 8.50 Ulcerated clear cell adenocarcinoma on the palate.

Fig. 8.51 Adenocarcinoma not otherwise specified on the palate.

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Fig. 8.52 Non-Hodgkin’s lymphoma, multiple enlargements on the buccal mucosa.

Fig. 8.53 Non-Hodgkin’s lymphoma, ulcerated nodule on the skin.

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8.2.15 Malignant Melanoma See also section 3.13. Definition: Melanoma is a malignant skin and mucosae neoplasm, arising either de novo from melanocytes or from a benign melanocytic lesion, with poor prognosis. Etiology: The exact etiology remains unknown. However, three major risk factors are recognized: genetic, environmental, and phenotypic factors reflecting gene and environmental interaction. The prolonged sunlight exposure is important factor for the development of skin melanoma. Clinical features: The skin malignant melanoma is classified, by clinical and histologic criteria, into four basic types: (1) nodular melanoma, (2) superficial spreading melanoma, (3) lentigo maligna melanoma, and (4) acral lentiginous melanoma (▶ Fig. 8.54). Amelanotic melanoma is a rare variant of melanoma without pigmented element that can be classified under one of the four basic types. Primary melanoma of the oral mucosa accounts for 0.5 to 1% of total melanomas, it affects both sexes equally, usually from age 50 to 60. Clinically, oral melanoma appears as a black or black-brown macule, plaque, or nodule that may be ulcerated (▶ Fig. 8.55). The lesions are usually characterized by irregular margin and have a tendency to spread. The nodular and superficial spreading are the most common types in the oral mucosa and rarely the lentigo maligna melanoma. In the mouth, over 80% of the melanomas develop on the hard palate, maxillary gingiva, and alveolar mucosa. The remaining 20% is distributed on the mandibular gingiva, buccal mucosa, tongue, floor of the mouth, and lips. The tumor can also affect other mucosae. The prognosis of skin melanoma depends on the clinical types and the depth of invasion histologically (Breslow’s depth). The clinical diagnosis should be confirmed by histologic examination. Laboratory tests: Histopathologic examination (Clark’s and Breslow’s scale), immunohistochemical markers. Differential diagnosis: Lentigo maligna, melanocytic nevi, ephelides, lentigo simplex, melanoacanthoma, Kaposi’s sarcoma, pyogenic granuloma, bacterial angiomatosis, and amalgam tattoo. Treatment: Radical surgical excision is the first line of treatment. Adjuvant therapy includes chemotherapy, immunotherapy, hormonal, and molecularly targeted therapy.

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8.2 Malignant

Fig. 8.54 Malignant melanoma, multiple lesions on the skin of the trunk.

Fig. 8.55 Malignant melanoma, nodular type, multiple lesions on the gingiva.

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Soft-Tissue Tumors

8.3 Miscellaneous 8.3.1 Amyloidosis Definition: Amyloidosis is a relatively rare, heterogeneous group of metabolic disorders characterized by abnormal extracellular deposition of amyloid, an amorphous fibrillar proteinaceous material, within various tissues and organs. Etiology: The exact etiology is unknown. Genetic and environmental factors (viruses and radiations) may be responsible. Clinical features: Clinically, amyloidosis is classified into two major forms: the systemic and the localized and several subtypes. Primary systemic amyloid light-chain amyloidosis is the most severe and common form of the disease, which in about 10 to 20% of the cases is associated with multiple myeloma. The prognosis is poor because of renal or heart failure. Oral involvement may be the only manifestation or it may be part (30–50%) of a disseminated disease. Clinically, the most frequent oral lesions are: petechiae, ecchymoses, papules, nodules or tumors, macroglossia, ulcers, minor and major salivary gland infiltration, xerostomia, and rarely hemorrhagic bullae formation (▶ Fig. 8.56 and ▶ Fig. 8.57). The most common cutaneous lesions are: purpura, petechiae, papules, nodules, bullous eruptions, ulcers, alopecia, and waxy skin discoloration. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Specific staining with Congo red, methyl violet, and thioflavin-T should be done. Immunohistochemical examination can also be used. Differential diagnosis: Crohn’s disease, lipoid proteinosis, multiple neurofibromatosis, mucopolysaccharidosis, sarcoidosis, Kaposi’s sarcoma, bullous pemphigoid, and pemphigus. Treatment: It is mainly symptomatic. The types of treatment that have been used include: systemic corticosteroids, colchicine, melfalan, anthracycline, chlorambucil, dimethyl sulfoxide, autologous hematopoietic stem cell transplantation, and others, but with poor results.

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8.3 Miscellaneous

Fig. 8.56 Amyloidosis, two red-brown nodules on the tip of the tongue.

Fig. 8.57 Amyloidosis, macroglossia.

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8.3.2 Actinomycosis Definition: Antinomycosis is a subacute or chronic granulomatous infectious disease. Etiology: It is caused by actinomyces israelii, a gram-positive anaerobic bacterium and a normal inhabitant of the oral cavity. Clinical features: On anatomical criteria the disease is classified into three forms: (1) cervicofacial, (2) pulmonary, and (3) abdominal. The cervicofacial form is the most common (50–60% of cases) and is associated with oral lesions. Clinically, it presents as a painless, inflammatory swelling that grows slowly and characteristically hard on palpation (▶ Fig. 8.58). As the lesion progresses, multiple abscesses and draining sinuses form, intraorally and on the skin (▶ Fig. 8.59 and ▶ Fig. 8.60). Yellow, purulent material that represents colonies of Actinomyces (sulfur granules) may discharge from the sinuses. Healing of old lesions results in scar formation, but new abscesses and sinuses develop. The tongue, buccal mucosa, lips, submandibular and submental areas, jaws, and salivary glands are the most common sites affected. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic and bacteriologic examinations. Differential diagnosis: Tuberculosis, systemic mycoses, oral soft-tissue abscess, periapical and periodontal abscess, and benign and malignant oral tumors. Treatment: Penicillin G is the treatment of choice, while amoxicillin and erythromycine are second-line choices. In addition, surgery is indicated in some cases.

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8.3 Miscellaneous

Fig. 8.58 Actinomycosis, swelling in the alveolar mucosa between canine and premolar.

Fig. 8.59 Actinomycosis, abscesses, and fistulae on the alveolar mucosa.

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Fig. 8.60 Actinomycosis, skin abscess, and fistula on the cheek.

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9 Soft-Τissue Cysts Cysts are epithelium-lined, pathological cavities, usually filled with fluid, semisolid material, or cellular debris. Cysts of the oral cavity are a histologically and genetically heterogenous group of disorders. They are located in the soft tissues of the oral cavity. Clinically, they present as a soft or fluctuant swelling. The cysts that are included in this group may be developmental, odontogenic, and traumatic in origin.

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Mucocele

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Gingival Cyst of the Newborn

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Ranula

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Gingival Cyst of the Adult

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Dermoid Cyst

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Thyroglossal Duct Cyst

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Lymphoepithelial Cyst

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Nasolabial Cyst

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Eruption Cyst

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Incisive Papilla Cyst

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9.1 Mucocele Definition: Mucoceles, or mucous cysts, are common lesions of the oral mucosa, originating from minor salivary glands and their ducts. Etiology: Local minor trauma and duct rupture or ductal obstruction probably due to a mucous plug. Clinical features: Depending on the pathogenesis, three types of mucoceles are recognized: (1) extravasation mucocele (common), which results from duct rupture due to trauma and spillage of mucin into the surrounding soft tissues, (2) mucous retention cyst (uncommon), which usually results from ductal dilatation due to partial ductal obstruction, and (3) superficial mucocele, which is a variant of the extravasation type, common on the soft palate and is caused by accumulation of mucus at the epithelial–connective tissue junction, causing epithelial detachment and formation of a small vesicle of 1 to 3 mm in diameter. Clinically, mucocele presents as a painless, dome-shaped, solitary, bluish or translucent, fluctuant swelling that ranges in size from a few millimeters to several centimeters in diameter (▶ Fig. 9.1 and ▶ Fig. 9.2). A common finding is that the cyst partially empties and then reforms due to the accumulation of new fluid. The lower lip is the most common site of involvement, usually laterally, at the level of the bicuspids. Less common sites are the buccal mucosa, tongue, floor of the mouth, retromolar area, and soft palate. Extravasation mucoceles display a peak incidence during the second and third decades, while the mucous retention types are more common in older age groups. The diagnosis is, usually, based on clinical criteria, but should be confirmed by laboratory test. Laboratory tests: Histopathologic examination. Differential diagnosis: Lymphangioma, hemangioma, pyogenic granuloma, cystadenoma, lipoma, myxoma, mucoepidermoid carcinoma, Sjögren’s syndrome, and lymphoepithelial cyst. Treatment: The treatment of choice is conservative surgical excision. Occasionally, the lesion may recur after surgery.

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9.1 Mucocele

Fig. 9.1 Mucocele on the lower lip.

Fig. 9.2 Mucocele on the buccal sulcus.

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9.2 Ranula Definition: Ranula is a form of mucocele that occurs exclusively on the floor of the mouth. Etiology: Trauma or ductal obstruction. Clinical features: Clinically, it presents as a smooth, fluctuant, painless swelling on the floor of the mouth, lateral to the midline (▶ Fig. 9.3). The color ranges from normal to a translucent bluish, and the size is usually in the range of 1 to 3 cm, or larger. The diagnosis is, usually, based on clinical criteria. Laboratory tests: Histopathologic examination. Differential diagnosis: Dermoid cyst, abscess, hemangioma, lymphangioma, and lymphoepithelial cyst. Treatment: The treatment of choice is conservative surgical removal or marsupialization but recurrences are relatively common.

9.3 Dermoid Cyst Definition: Dermoid cyst is an uncommon cystic lesion arising from embryonic epithelial remnants. Etiology: Developmental. Clinical features: Clinically, it presents as a slowly growing, painless, swelling with a normal or yellowish-red color and a characteristic soft dough-like consistency on palpation. The size varies from a few millimeters to 10 cm in diameter, and the lesion usually occurs in the midline of the floor of the mouth (▶ Fig. 9.4). If the cyst is located above the geniohyoid muscle, it can displace the tongue upward and create difficulty in mastication, speech, and swallowing. When the cyst occurs below the geniohyoid muscle, it may protrude submentally. Rarely, dermoid or epidermoid cysts may develop in the lips. The cyst frequently appears in early adulthood. The clinical diagnosis should be confirmed by histologic examination. Laboratory tests: Histopathologic examination. Histologically, three types are recognized: epidermoid–dermoid–teratoma. Differential diagnosis: Ranula, abscess, lymphoepithelial cyst, cystic hygroma, and lymph nodes enlargement. Treatment: The treatment of choice is conservative surgical removal.

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9.3 Dermoid Cyst

Fig. 9.3 Ranula.

Fig. 9.4 Dermoid cyst protruding on the floor of the mouth.

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9.4 Lymphoepithelial Cyst Definition: Lymphoepithelial cyst is an uncommon developmental lesion of the oral mucosa. Etiology: It is caused by cystic degeneration of glandular or surface epithelium entrapped in lymphoid tissue during embryogenesis. Clinical features: Clinically, it presents as an asymptomatic, mobile, welldefined nodule, usually firm on palpation and elevated, with a yellowish or whitish color. The size ranges from 0.5 to 2 cm in diameter. The floor of the mouth is the most frequent location, followed by the posterior lateral border and the ventral surface of the tongue (▶ Fig. 9.5 and ▶ Fig. 9.6). Lymphoepithelial cysts are histologically similar to the branchial cleft cysts that develop in the lateral neck. The clinical diagnosis should be confirmed by histologic examination. Laboratory tests: Histopathologic examination. Differential diagnosis: Lymphoid tissue aggregation, lymphangioma, dermoid cyst, mucocele, cystadenoma, lipoma, and fibroma and other benign tumors. Treatment: The treatment of choice is conservative surgical removal.

9.5 Eruption Cyst Definition: Eruption cyst is a soft-tissue form of dentigerous cyst and is associated with an erupting deciduous or permanent tooth. Etiology: Separation of the dental follicle from around the crown of the tooth. Mechanical trauma may result in hemorrhage, forming the bluish color. Clinical features: Clinically, it presents as a well-demarcated, fluctuant, and soft swelling directly overlying the crown of an erupting tooth. Usually, the color is blue or dark red, depending on the amount of blood in the cystic fluid (▶ Fig. 9.7 and ▶ Fig. 9.8). The diagnosis is usually made on the basis of clinical criteria, but should be confirmed by histologic examination. Laboratory tests: Histopathologic examination. Differential diagnosis: Hematoma, hemangioma, amalgam tattoo, pigmented nevi, melanoma, and melanotic neuroectodermal tumor of infancy. Treatment: Usually no treatment is required, as the cyst often ruptures spontaneously. However, in cases with symptoms or secondary infection, a simple excision of the roof of the cyst is recommended.

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9.5 Eruption Cyst

Fig. 9.5 Lymphoepithelial cyst between the foliate papillae of the tongue.

Fig. 9.6 Lymphoepithelial cyst on the floor of the mouth.

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Fig. 9.7 Eruption cyst.

9.6 Gingival Cysts of the Newborn Definition: Gingival cysts of the newborn are small, keratin-filled, cysts on the alveolar mucosa of infants that appear at birth or soon thereafter. Etiology: They arise from remnants of the dental lamina. Clinical features: Clinically, they appear as multiple or solitary, asymptomatic, whitish nodules 1 to 3 mm in diameter, usually on the maxillary alveolus (▶ Fig. 9.9). The cysts contain keratin and regress spontaneously within a few weeks. The diagnosis is made at the clinical level, but should be confirmed by laboratory test. Laboratory tests: Histopathologic examination. Differential diagnosis: Lymphangioma, granular cell tumor of the newborn, and various hamartomas. Treatment: No treatment is required, as the lesions regress spontaneously.

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9.6 Gingival Cysts of the Newborn

Fig. 9.8 Eruption cyst.

Fig. 9.9 Gingival cysts of the newborn, multiple white nodules on the upper alveolar mucosa.

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9.7 Gingival Cyst of the Adult Definition: Gingival cyst of the adult is a rare lesion located on the free or the attached gingiva. Etiology: It originates from remnants of the dental lamina. Clinical features: Clinically, it appears as a painless, well-circumscribed swelling, 0.5 to 1 cm in diameter (▶ Fig. 9.10). The mandibular premolar and canine areas are the sites of predilection (70–80%). The condition is more frequent in patients over 40 years of age. The clinical diagnosis should be confirmed by laboratory test. Laboratory tests: Histopathologic examination. Differential diagnosis: Lateral periodontal cyst, dental or periodontal abscess, mucocele, fibroma, peripheral ossifying fibroma, and neurofibroma. Treatment: The treatment of choice is conservative surgical removal.

9.8 Thyroglossal Duct Cyst Definition: Thyroglossal duct cyst is a rare developmental lesion that may form along the thyroglossal tract. Etiology: Remnants of thyroglossal duct epithelium. Clinical features: The cyst is usually located under the hyoid bone but can be located anywhere from the suprasternal notch to the foramen cecum of the dorsal tongue. Intraorally, it appears as a painless, fluctuant, swelling usually 1 to 3 cm in diameter at the midline of the dorsum of the tongue close to the foramen cecum (▶ Fig. 9.11). The cyst is most often diagnosed in patients under 20 years of age. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, 99mTc or 125I, CT, and MRI scans. Differential diagnosis: Median rhomboid glossitis, lymphoepithelial cyst, fibroma, lipoma, myxoma, leiomyoma, and squamous cell carcinoma. Treatment: The treatment of choice is surgical removal, known as Sistrunk procedure.

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9.8 Thyroglossal Duct Cyst

Fig. 9.10 Gingival cyst of the adult between the lower lateral incisor and canine.

Fig. 9.11 Thyroglossal duct cyst on the midline of the dorsum of the tongue.

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9.9 Nasolabial Cyst Definition: Nasolabial cyst is a rare developmental soft-tissue cyst that develops in the upper lip in the canine region. Etiology: Unclear. Presumably, it develops from epithelial remnants of the nasolacrimal duct. Clinical features: Clinically, it appears as a soft-tissue swelling in the mucobuccal fold of the maxilla, lateral to the midline (▶ Fig. 9.12). Occasionally, the patient may complain of nasal obstruction, discomfort, or difficulty in wearing dentures. The cyst is more common in women, usually from 40 to 50 years of age. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Soft-tissue abscess, tooth abscess, mucocele, radicular cyst, salivary gland neoplasms, and mesenchymal neoplasms. Treatment: The treatment of choice is conservative surgical excision.

9.10 Incisive Papilla Cyst Definition: Incisive papilla cyst is a variety of the nasopalatine cyst. Etiology: It arises from epithelial rests of the nasopalatine foramen. Clinical features: Clinically, it appears as a slowly growing soft swelling of the incisive papilla, covered with normal mucosa (▶ Fig. 9.13). The cysts, after mechanical irritation, may inflame and become painful due to local infection. The clinical diagnosis should be confirmed by histologic examination. Laboratory tests: Histopathologic examination. Differential diagnosis: Tooth and periodontal abscesses, mechanical trauma of the palatine papilla, fibroma, and lipoma. Treatment: The treatment of choice is conservative surgical removal.

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9.10 Incisive Papilla Cyst

Fig. 9.12 Nasolabial cyst, swelling at the nasolabial area.

Fig. 9.13 Incisive papilla cyst.

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10 Bone Swellings Bone swellings are lesions that characteristically present as asymptomatic or symptomatic hard lumps, covered by normal epithelium. Developmental disorders and benign and malignant tumors are included in this group of lesions.

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Torus Mandibularis

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Multiple Myeloma

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Torus Palatinus

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Ewing’s Sarcoma

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Multiple Exostoses

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Cherubism

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Osteoma

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Fibrous Dysplasia

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Osteosarcoma

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Gardner’s Syndrome

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Chondrosarcoma

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Paget’s Disease

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Burkitt’s Lymphoma

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Odontogenic Tumors

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10.1 Torus Mandibularis Definition: Torus mandibularis is a relatively common bony exostosis that characteristically occurs along the lingual aspect of the mandible. Etiology: Developmental malformation. Clinical features: Clinically, it presents as an asymptomatic, bony swelling, covered by normal mucosa. The lesion displays slow growth during the second and third decades of life. Characteristically, the disorder appears bilaterally on the lingual surface of the mandible, usually in the areas adjacent to the bicuspids (▶ Fig. 10.1). The diagnosis is exclusively based on clinical criteria. Laboratory test: Usually not required. Differential diagnosis: Osteoma, osteosarcoma, and Gardner’s syndrome. Treatment: Unnecessary unless full or partial denture construction is required.

10.2 Torus Palatinus Definition: Torus palatinus is a relatively common, bony exostosis that occurs along the middle line of the hard palate. Etiology: Developmental malformation. Clinical features: Clinically, it presents as a slowly growing, nodular, lobular or spindled, asymptomatic bony swelling covered by normal mucosa. Characteristically, the lesion appears along the midline of the hard palate (▶ Fig. 10.2). It occurs more often in women, and usually appears during the third decade of life. The diagnosis is based on the clinical findings. Laboratory tests: Usually not required. Differential diagnosis: Osteoma, osteosarcoma, and Gardner’s syndrome. Treatment: Unnecessary unless full denture construction is required.

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10.2 Torus Palatinus

Fig. 10.1 Torus mandibularis.

Fig. 10.2 Torus palatinus on the center of the hard palate superficially ulcerated.

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Bone Swellings

10.3 Multiple Exostoses See also section 7.2.6. Definition: Multiple exostoses are multiple bony hard masses along the buccal aspect of the alveolar ridges of the jaws. Clinical features: Multiple exostoses may occur on the buccal and labial surface of the maxilla, and rarely on the mandible. Clinically, the lesions appear as multiple, asymptomatic, bony swellings (▶ Fig. 10.3). The diagnosis is based on the clinical findings. Etiology: Developmental malformation. Laboratory test: Not required. Differential diagnosis: Multiple osteomas, Gardner’s syndrome, fibrous dysplasia, and Paget’s disease. Treatment: Unnecessary unless full denture preparation is required.

10.4 Osteoma Definition: Osteoma is a benign neoplasm that consists of mature compact or cancellous bone. Etiology: The exact etiology is unknown. Clinical features: Clinically, it presents as an asymptomatic, slowly growing bony swelling of the jaws. The size ranges from a few millimeters to several centimeters. Multiple jaw osteomas are a common feature of Gardner’s syndrome (▶ Fig. 10.4). The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination and radiography. Differential diagnosis: Exostoses, Gardner’s syndrome, osteosarcoma, and odontogenic tumors. Treatment: The treatment of choice is conservative surgical excision.

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10.4 Osteoma

Fig. 10.3 Multiple exostoses of the maxilla.

Fig. 10.4 Gardner’s syndrome, multiple osteomas of the mandible.

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Bone Swellings

10.5 Osteosarcoma Definition: Osteosarcoma is the most common primary malignant neoplasm of bones, but relatively rare on the jaws. Etiology: The exact etiology is unknown. Clinical features: The jaws are affected in 6 to 7% of cases, and usually during the third decade of life. Both jaws are affected equally and it is more common in men. Clinically, the lesion presents as a rapidly growing, hard swelling, which progressively produces facial deformity (▶ Fig. 10.5). Pain, paresthesia, tooth loosening, and nasal obstruction may also occur. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, radiography, and CT scans. Differential diagnosis: Chondrosarcoma, Ewing’s sarcoma, metastatic tumors, odontogenic tumors and cysts, giant cell tumor, and cherubism. Treatment: The treatment of choice is radical surgical excision, supplementary radiotherapy, and chemotherapy.

10.6 Chondrosarcoma See also section 8.2.6. Chondrosarcoma is more common in men than in women, from 30 to 60 years of age. Clinically, it appears as a painless hard swelling that progressively enlarges, causing extensive bone destruction with pain and loosening of the teeth (▶ Fig. 10.6).

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10.6 Chondrosarcoma

Fig. 10.5 Osteosarcoma on the anterior part of the maxilla.

Fig. 10.6 Chondrosarcoma, lingual and buccal enlargement of the mandible.

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10.7 Burkitt’s Lymphoma Definition: Burkitt’s lymphoma is a high-grade non-Hodgkin’s B-cell lymphoma, which was first described by Dennis Burkitt in 1956 in central Africa. Etiology: Epstein–Barr virus is strongly associated. Clinical features: Burkitt’s lymphoma is classified into two basic forms: (1) the classic African or endemic, and (2) the non-African or sporadic. The malignancy is prevalent in central Africa (the endemic form), and usually affects children from 2 to 12 years of age. Cases have also been observed in other countries (the sporadic form), and in the last decades, in patients with acquired immunodeficiency syndrome. The jaws are the most common site of Burkitt’s lymphoma (60–70%). Clinically, it presents as a rapidly growing, hard swelling that causes bone destruction, tooth loss, and facial deformity (▶ Fig. 10.7 and ▶ Fig. 10.8). Pain, paresthesia, and large ulcerating or nonulcerating masses may also be seen. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, radiography, and histochemical markers. Differential diagnosis: Central giant cell granuloma, ossifying fibroma, other non-Hodgkin’s lymphomas, odontogenic tumors, cherubism, melanotic neuroectodermal tumor of infancy, multiple mueloma, and osteosarcoma. Treatment: Chemotherapy is the treatment of choice in various combinations. The CHOP (cyclophosphamide, hydroxyldaunomycin [doxorubicin], oncovin [vincristine], and prednisone) regimen is one of the most successful treatments alone or in combination with radiotherapy and surgery. Surgical excision has a place in early, localized lesions.

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10.7 Burkitt’s Lymphoma

Fig. 10.7 Burkitt’s lymphoma, enlargement on the lower gingiva.

Fig. 10.8 Burkitt’s lymphoma, jaw enlargement with mild facial palsy.

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10.8 Multiple Myeloma Definition: Multiple myeloma is a relatively rare, malignant plasma-cell disorder. Etiology: The exact etiology is unknown. Clinical features. The malignancy is more common in men over 50 years of age, and the jaws are affected in about 20 to 30% of cases. Clinically, it presents with bone swelling, tooth mobility, pain, and paresthesia. A painless, soft swelling, usually on the alveolar mucosa and gingiva, may develop as part of the overall disease spectrum (▶ Fig. 10.9). The final diagnosis is based on the laboratory tests. Laboratory tests: Complete blood count, bone-marrow biopsy, radiography, CT, MRI, PET, and serum and urine protein electrophoresis. Differential diagnosis: Plasmacytoma, non-Hodgkin’s lymphoma, Ewing’s sarcoma, leukemia, Langerhans cell histiocytosis, osteosarcoma, and odontogenic tumors. Treatment: The treatment of choice is chemotherapy, radiotherapy, and autologous stem cell transplant.

10.9 Ewing’s Sarcoma Definition: Ewing’s sarcoma is a distinctive primary, malignant neoplasm of the bones originating from undifferentiated mesenchymal cells of bone and is characterized by the presence of small round cells. Etiology: The exact etiology is unknown. However, over 90% of the tumor cells demonstrate translocation between chromosomes 11 and 22. Clinical features: It mainly affects children and young adults. The long bones, pelvis, and ribs are more commonly involved, while it is uncommon in the jaws. Clinically, jaw expansion associated with pain are the most common signs and symptoms. It progresses to osseous destruction and teeth mobility while there is often an ulcerated soft mass, originating from the bone lesion (▶ Fig. 10.10). Facial disfigurement, paresthesia, and fever may occur. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic and immunohistochemical examinations, radiographic examination, and cytogenetics. Differential diagnosis: Osteosarcoma, chondrosarcoma, non-Hodgkin’s lymphoma, giant cell tumor, odontogenic tumors, and osteomyelitis. Treatment: The treatment of choice is radical surgical excision, in combination with radiotherapy and chemotherapy.

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10.9 Ewing’s Sarcoma

Fig. 10.9 Multiple myeloma, localized gingival enlargement.

Fig. 10.10 Ewing’s sarcoma, enlargement on the mandible.

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10.10 Cherubism Definition: Cherubism is a rare benign, genetic, fibro-osseous disorder with high penetrance and variable expressivity which exclusively affects the jaws. Etiology: Genetic. It is caused by SH3BP2 gene mutation of chromosomes 4p16.3. Clinical features: The first symptoms and signs, usually, appear during the first decade of life and progress until puberty, when they stabilize and often regress. Clinically, the disease appears as a painless, symmetrical, bilateral, expansion of the jaw bones and cheeks, producing a chubby facial appearance (▶ Fig. 10.11). Premature exfoliation of deciduous teeth, tooth displacements, and unerupted permanent teeth are common findings. In severe cases, extensive maxillary involvement causes stretching of the skin of the upper face, exposing the sclerae of the eyes, creating the cherubism pattern. The diagnosis is based on the history, clinical features and laboratory tests. Laboratory tests: Histopathologic examination and radiography. Differential diagnosis: Fibrous dysplasia, odontogenic tumors, odontogenic cysts, central giant cell granuloma, Langerhan’s cell histiocytosis, osteosarcoma, and Ewing’s sarcoma. Treatment: The treatment of choice is conservative surgical excision. Orthodontic intervention may be required. Spontaneous resolution of the lesions, after puberty, may occur in most cases.

10.11 Fibrous Dysplasia Definition: Fibrous dysplasia is a benign, developmental disorder, which is characterized by the replacement of normal bone by immature, cellular fibrous tissue, containing irregular trabeculae of woven bone. Etiology: Genetic. It is a sporadic disorders caused by GNAS1 gene mutation. Clinical features: Two forms of the disease are recognized: (1) the monostotic, which is limited to a single bone and accounts for 80 to 90% of the cases, and (2) the polyostotic or McCune–Albright syndrome. Clinically, in the monostotic form the jaw lesions present as painless, slowly growing, bone swellings (▶ Fig. 10.12). The swelling may be firm, elastic or hard on palpation and may cause intraolar bone deformity, and tooth displacement or facial asymmetry. The maxilla is more often affected, commonly unilateral and rarely bilateral. The ribs, femur, and shin are most frequently affected. The polyostotic form is characterized by multiple bone involvement, skin pigmentation or

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10.11 Fibrous Dysplasia

Fig. 10.11 Cherubism, bilateral facial enlargement.

Fig. 10.12 Fibrous dysplasia, osseous enlargement of the maxilla.

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Bone Swellings

Fig. 10.13 Fibrous dysplasia, café au lait macules on the skin of the cheek.

café au lait macules, and endocrine disorders (▶ Fig. 10.13). The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, CT, and radiography. Differential diagnosis: Cherubism, odontogenic tumors, ossifying fibroma, central giant cell granuloma, Paget’s disease, exostoses, osteosarcoma, chondrosarcoma, and Ewing’s sarcoma. Treatment: The treatment of choice is conservative surgical excision, systemic bisphosphonates. However, small, inactive jaw bone lesions do not require treatment.

10.12 Gardner's Syndrome Definition: Gardner's syndrome is a rare genodermatosis. Etiology: Genetic. It is usually inherited in an autosomal dominant pattern. About 30% of the cases represent spontaneous, new gene mutations. Clinical features: Clinically, the oral manifestations are common and include multiple impacted teeth, supernumerary teeth, multiple odontomas, jaw osteomas, and benign soft tissue tumors (▶ Fig. 10.14). The cutaneous lesions are: epidermoid and sebaceous cysts, subcutaneous fibromas and rarely skin pigmentation (▶ Fig. 10.15). The main feature of the syndrome is the presence

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10.12 Gardner's Syndrome

Fig. 10.14 Gardner's syndrome, multiple osteomas of the mandible.

Fig. 10.15 Gardner's syndrome, pigmentation of the neck.

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Bone Swellings of multiple intestinal tumors (colon and rectum), that usually appear before puberty and have a high rate of malignant transformation into adenocarcinomas. Rarely, benign or malignant neoplasms may occur in other organs. It is important to know that congenital hyperpigmentation of the retinal epithelium is an early diagnostic sign. For final diagnosis four or more lesions are necessary to be identified. Laboratory test: Histopathologic examination. Differential diagnosis: Jaw and other bone exostoses, Peutz-Jeghers syndrome, Cowden syndrome, juvenile polyposis syndromes, cleidocranial dysplasia. Treatment: Supportive. Prophylactic surgical excision of the intestinal polyps.

10.13 Paget’s Disease Definition: Paget’s disease or osteitis deformans is a chronic, relatively common disorder characterized by uncoordinated bone resorption and deposition. Etiology: The exact etiology is unknown. However, genetic mutation, viral infection and hormonal disorders may be involved. Clinical features: Clinically, the signs and symptoms develop gradually and are characterized by bone pain, headache, deafness, visual disorders, dizziness, and progressive bone enlargement. Progressive expansion of the maxilla and the mandible leads to symmetrical thickening of the alveolar ridges (▶ Fig. 10.16). Edentulous patients may complain that their dentures do not fit due to alveolar enlargement (▶ Fig. 10.17). Delayed wound healing, bleeding, and osteomyelitis, after tooth extraction, may occur. The maxilla is more frequently affected than the mandible. Males are more often affected than females. Two major forms of the disease are recognized: (1) the monostotic, and (2) the polyostotic. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic and radiographic examinations. Elevations of serum alkaline phosphatase and urinary hydroxyproline levels are common findings. Differential diagnosis: Fibrous dysplasia, multiple exostoses, fibro-osseous lesions, osteosarcoma, and multiple myeloma. Treatment: Most cases require no treatment. Calcitonin and bisphosphonates may slow the pathological process.

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10.13 Paget’s Disease

Fig. 10.16 Paget’s disease, enlargement of the maxilla, and expansion into the sulcus.

Fig. 10.17 Paget’s disease, enlargement of an edentulous maxilla.

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10.14 Odontogenic Tumors Definition: Odontogenic tumors are a heterogonous group of lesions that originate from tooth germ tissues. Etiology: The exact etiology is unknown. Some are neoplasms and others hamartomas. Classification: On the basis of the tissue of origin, three major varieties are recognized: (1) tumors of odontogenic epithelium, (2) tumors of odontogenic mesenchyme, and (3) mixed odontogenic tumors. Every odontogenic tumor has a different biological behavior and histologic features. Depending on the affected site, they are classified into: (1) intaosseous or central that account for 99% of all cases, and (2) extraosseous or peripheral that are very rare. Clinical features: Most odontogenic tumors are, usually asymptomatic for long time and are discovered only during a routine radiographic examination. However, with time they may form a usually painless, slowly growing swelling or expansion of the mandible or the maxilla (▶ Fig. 10.18, ▶ Fig. 10.19, ▶ Fig. 10.20). The clinical signs and symptoms are not diagnostic and the final diagnosis should be made by laboratory tests. Laboratory tests: Histopathologic and radiographic examinations. Differential diagnosis: Different varieties of odontogenic tumors, odontogenic cysts, osteosarcomas, chondrosarcomas, multiple myeloma, Gorlin’s syndrome, cherubism, and fibrous dysplasia. Treatment: The treatment of choice is conservative surgical excision.

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10.14 Odontogenic Tumors

Fig. 10.18 Central ameloblastoma, enlargement of the maxilla with teeth displacement.

Fig. 10.19 Calcifying epithelial odontogenic tumor, peripheral type. Tumor of the lower gingivae on the buccal aspect.

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Fig. 10.20 Odontogenic myxoma, enlargement of the mandible.

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11 Neck Swellings This is a heterogeneous group of lesions, presenting clinically as fluctuant, soft or firm, lateral or midline neck swellings. The lesions may be asymptomatic, sensitive or painful, mobile or fixed, solitary or multiple. Cysts, infectious diseases, autoimmune and systemic diseases, and neoplasms are included in this group of disorders which usually cause diagnostic problems.

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Cervical Lymphoepithelial Cyst

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Tuberculosis

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Thyroglossal Duct Cyst

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Heerfordt’s Syndrome

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Dermoid Cyst

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Sjögren’s Syndrome

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Cystic Hygroma

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Hodgkin’s Disease

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Nonspecific Lymphadenitis

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Submandibular Sialadenitis

Metastatic Carcinoma to the Cervical Lymph Nodes

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11.1 Cervical Lymphoepithelial Cyst Definition: Cervical lymphoepithelial cyst or branchial cleft cyst is a relatively rare lesion, located in the upper lateral neck, along the anterior border of the sternocleidomastoid muscle. It is a variant of lymphoepithelial cyst. Etiology: Developmental. The pathogenesis remains unclear. There are two aspects regarding the origin: (1) remnants from branchial clefts, particularly from the second, and (2) cystic alteration of embryologic or tonsillar epithelium within cervical lymphoid tissues. Clinical features: Clinically, it appears as an asymptomatic, soft, fluctuant swelling (2–10 cm in diameter), usually lateral (▶ Fig. 11.1). It usually becomes apparent between the second and third decade of life. The cyst is usually painless, but the patients may complain of tension or mild pain, if secondary infection occurs. The diagnosis is based on the clinical and laboratory criteria. Laboratory tests: Histopathologic examination. Differential diagnosis: Dermoid cyst, thyroglossal duct cyst, lymph node enlargement, sialadenitis, salivary gland tumors, soft tissue benign tumors, non-Hodgkin’s lymphoma, and lymph node metastases. Treatment: The treatment of choice is conservative surgical removal.

11.2 Thyroglossal Duct Cyst See also section 9.8. Definition: Thyroglossal duct cyst is a rare disorder that may form along the thyroglossal track. Etiology: Developmental dysplasia. It derives from the remnants of thyroglossal duct epithelium. Clinical Features: Thyroglossal duct cysts often appear in the midline of the neck, usually below the hyoid bone and submentally. Clinically, the lesion presents as a painless, fluctuant, movable swelling, a few millimeters to several centimeters in diameter on the anterior neck (▶ Fig. 11.2). A fistula may form opening on the skin. Rarely, thyroid carcinoma may originate in a thyroglossal duct cyst. The diagnosis is based on clinical criteria but has to be confirmed by laboratory tests.

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11.2 Thyroglossal Duct Cyst

Fig. 11.1 Cervical lymphoepithelial cyst.

Fig. 11.2 Thyroglossal duct cyst, enlargement close to the thyroid gland.

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Laboratory tests: 99mTc or 125I, CT, and MRI scans. Differential diagnosis: Cervical lymphoepithelial cyst, lymph node enlargement, and non-Hodgkin’s lymphoma. Treatment: The treatment of choice is surgical removal.

11.3 Dermoid Cyst See also section 9.3. When dermoid cysts develop below the geniohyoid muscle, protrude submentally as a painless, doughy swelling (▶ Fig. 11.3). In such cases, the differential diagnosis should include thyroglossal duct cyst, periapical and soft-tissue abscesses, and sublingual sialadenitis.

11.4 Cystic Hygroma Definition: Cystic hygroma is a form of macrocystic lymphangioma that consists of large cystic spaces, which primarily develops on the side of the neck, and may be unilateral or bilateral. Etiology: Developmental. Clinical features: Clinically, it appears as a large, soft swelling of the neck, extending to the submandibular or submental area, and occasionally to the buccal and the parotid area (▶ Fig. 11.4). It usually appears at birth or upto 3 years of age, and may cause aesthetic or respiratory problems. The diagnosis is based on clinical and histopathologic features. Laboratory tests: Histopathologic examinations. Differential diagnosis: Cervical lymphoepithelial cyst, diffuse lymphadenopathy, parotitis, submandibular sialadenitis, hemangioma, thyroid cyst, Hodgkin’s disease, Sjögren’s syndrome, and Heerfordt’s syndrome. Treatment. The treatment of choice is surgical removal.

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11.4 Cystic Hygroma

Fig. 11.3 Dermoid cyst, submental swelling, with a double-chin appearance.

Fig. 11.4 Cystic hygroma, enlargement in the submandibular area and the neck.

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11.5 Nonspecific Lymphadenitis Definition: Lymphadenitis is a lymphoid hyperplasia and inflammation of the lymph nodes. Etiology: Bacterial, viral, or fungal infections. Clinical features: Lymph nodes in the neck area (submandibular, subdigastric, midjugular, low jugular, and cervical) may produce neck swellings (▶ Fig. 11.5). Clinically, in acute infections, the lymph nodes appear enlarged, tender, soft, and movable, while in chronic conditions they are enlarged, not tender, firm, and occasionally fixed. Enlarged lymph nodes may be single or multiple. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Fine needle aspiration test and histopathologic examination. Differential diagnosis: Submandibular sialadenitis, non-Hodgkin’s lymphoma, Hodgkin’s disease, human immunodeficiency virus (HIV) infection, and bacterial infections. Treatment: Treatment of the specific infection is required.

11.6 Submandibular Sialadenitis Definition: Submandibular sialadenitis is an inflammatory disorder of the submandibular salivary glands. Etiology: Infections and rarely sialoliths or trauma. Clinical features: Clinically, it presents as a tender swelling, usually unilateral, at the angle and the body of the mandible (▶ Fig. 11.6). The overlying skin is usually erythematous, and the duct orifice is red intraorally. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Fine needle aspiration test and microbiologic and histopathologic examinations. Differential diagnosis: Lymph node enlargement, buccal cellulitis, nonHodgkin’s, lymphomas, tuberculosis, sarcoidosis, and Sjögren’s syndrome. Treatment: Antibiotics.

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11.6 Submandibular Sialadenitis

Fig. 11.5 Submandibular and cervical lymph node enlargement due to herpetic oral infection.

Fig. 11.6 Submandibular sialadenitis, bilateral swelling of submandibular region.

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11.7 Tuberculosis See also section 5.8. Definition: Tuberculosis is one of the world’s most widespread chronic infectious disease that primarily affects the lungs. Etiology: It is due to the bacillus Mycobacterium tuberculosis. Clinical features: The morbidity of the disease has increased the last four decades with the emergence of HIV infection, the movement of populations, increased frequency of immunosuppressive treatments, and relaxation of preventive vigilance. Oral manifestations of tuberculosis are uncommon (0.05– 1.4%) and present as a wide spectrum of lesions, usually secondary to pulmonary infection. The most common oral lesion is the tuberculous ulcer. Regional lymphadenopathy usually accompanies the oral lesions. A particular form of cervical lymph node tuberculosis is known as scrofula. Clinically, it presents as a swelling of numerous cervical lymph nodes that occasionally leads to the formation of numerous fistulas though the overlying skin (▶ Fig. 11.7 and ▶ Fig. 11.8). The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, culture of sputum, chest radiology, Mantoux test, and nucleic acid amplification (DNA and RNA) tests for M. tuberculosis are necessary for final diagnosis. Differential diagnosis: Actinomycosis, submandibular sialadenitis, nonHodgkin’s lymphoma, cat scratch disease, and dental abscess. Treatment: The management of tuberculosis requires an appropriate medical team. The basic drugs are streptomycin, isoniazid, ethambutol, rifampin, pyrazinamide, and others.

11.8 Heerfordt’s Syndrome Definition: Heerfordt’s syndrome or uveoparotid fever or uveoparotitis is a rare clinical form of sarcoidosis. Etiology: The exact etiology is unknown. It is presumably related to an infectious agent. Clinical features: Clinically, the disorder is characterized by a bilateral, firm, painless, swelling of the parotid glands, ocular lesions (uveitis, conjunctivitis,

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11.8 Heerfordt’s Syndrome

Fig. 11.7 Tuberculosis, swollen cervical and submandibular lymph nodes.

Fig. 11.8 Tuberculosis, submandibular lymph node swelling and fistula creation.

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Neck Swellings and keratitis), facial paralysis, skin lesions, and low-grade fever. Submandibular, sublingual salivary gland, and lacrimal gland enlargement may also occur (▶ Fig. 11.9). The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, Kveim–Siltzbach skin test, and radiography. Differential diagnosis: Sjögren’s syndrome, Mikulicz’s syndrome, orofacial granulomatosis, and sialadenitis. Treatment: Corticosteroids and other drugs that are used for the treatment of sarcoidosis. Often the symptoms resolve spontaneously, within 2 or 3 years.

11.9 Sjögren’s Syndrome Definition: Sjögren’s syndrome is a chronic multisystemic, autoimmune exocrinopathy that predominantly involves lacrimal, salivary, and other exocrine glands. Etiology: The exact etiology is unknown. However, genetic (increased HLA-B8, DR3, DQ2, and DRw52A) and immunologic factors seem to play an important role in the pathogenesis. Clinical features: Using clinical, serologic, and genetic criteria two forms of the disease are recognized: primary and secondary, when it is associated with collagen diseases. The cardinal clinical manifestations include a recurrent enlargement of the parotid, submandibular (▶ Fig. 11.10) and lacrimal glands, lymphadenopathy, purpura, Raynaud’s phenomenon, myositis, and renal and pulmonary manifestations. Keratoconjunctivitis sicca, xerostomia, cheilitis, dental caries, and candidiasis are common findings (▶ Fig. 11.11 and ▶ Fig. 11.12). Finally, there is increased risk of B-cell non-Hodgkin’s lymphoma development. These B-cells lymphomas are often extranodal and can originate from salivary and lacrimal glands. The disease most frequently affects women from 40 to 60 years of age. New classification criteria for Sjögren’s syndrome were defined in 2012 by the American College of Rheumatology. For diagnosis of the disease at least two of the following three objective criteria should be present: (1) positive serum anti-SSA and/or anti-SSB antibodies or positive rheumatoid factor and ANA titer greater than 1:320, (2) focal lymphocytic sialadenitis with a focus score greater than or equal to 1 focus/4 mm2 in labial salivary gland biopsy specimen, and (3) keratoconjunctivitis sicca with ocular staining score greater than or equal to 3.

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11.9 Sjögren’s Syndrome

Fig. 11.9 Heerfordt’s syndrome, swelling of submandibular and sublingual glands, and sarcoidosis of skin nodules.

Fig. 11.10 Sjögren’s syndrome, enlargement of the parotid and the neck region.

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Fig. 11.11 Sjögren’s syndrome, conjunctivitis, and edema of the eyelids.

Laboratory tests: Histopathologic examination and serological tests (antinuclear antibodies [ANA], anti-DNA, anti-SSA [Ro], and anti-SSB [La] antibodies). Differential diagnosis: Heerfordt’s syndrome, Mikulicz’s syndrome, collagen diseases, graft versus host disease, HIV infection, and amyloidosis. Treatment: The treatment of choice is corticosteroids, immunosuppressives, and antimalariar drugs as well as artificial saliva and tears.

11.10 Hodgkin’s Disease Definition: Hodgkin’s disease is a malignant lymphoproliferative disorder, characterized by the presence of the Reed–Sternberg cells and their variants. Etiology: The exact etiology is unknown. However, genetic and environmental factors and mainly Epstein–Barr virus, seems to play a role in the pathogenesis. Clinical features: Clinically, painless and persistent swelling, usually of the cervical and supraclavicular lymph nodes or other lymph node groups, is the common presenting sign (▶ Fig. 11.13). In the early stages the lymph nodes are

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11.10 Hodgkin’s Disease

Fig. 11.12 Sjögren’s syndrome, dry and lobulated tongue.

Fig. 11.13 Hodgkin’s disease, cervical lymph node enlargement.

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Neck Swellings often movable, and later they become fixed to the surrounding tissues. Anorexia, weight loss, fever, night sweats, and pruritus may accompany lymphadenopathy. Oral ulceration may also occur. Laboratory tests: Histopathologic examination and immunologic and molecular markers. Differential diagnosis: Non-Hodgkin’s lymphoma, tuberculosis, infectious mononucleosis, Heerfordt’s syndrome, and cat scratch disease. Treatment. The treatment of choice is chemotherapy and radiotherapy.

11.11 Metastatic Carcinoma to the Cervical Lymph Nodes Definition: Metastases from primary oral malignancy to regional lymph nodes. Etiology: Infiltration of malignant cells to regional lymph nodes. Clinical Features: Metastases of oral squamous cell carcinoma are a relatively common phenomenon and mainly occur in the regional cervical lymph nodes, usually via the lymphatic or vascular vessels. It has been estimated that approximately 30 to 50% of patients with oral carcinoma present at diagnosis with cervical metastases. The submandibular and jugular nodes are more frequently affected. Clinically, the metastases may be tender or not, and are usually firm, fixed, and present as swellings (▶ Fig. 11.14 and ▶ Fig. 11.15). The metastatic deposits are usually lateral, and rarely bilateral. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination, magnetic resonance tomography (MRT), and positron emission tomography (PET) scan. Differential diagnosis: Submandibular sialadenitis, Hodgkin’s disease, nonHodgkin’s lymphoma, Heerfordt’s syndrome, leukemia, tuberculosis, syphilis, infectious mononucleosis, and cat scratch disease. Treatment: Surgical excision, radiotherapy, and chemotherapy.

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11.11 Metastatic Carcinoma to the Cervical Lymph Nodes

Fig. 11.14 Late squamous cell carcinoma on the lower lip with enlargement of the right submandibular and cervical areas due to metastases.

Fig. 11.15 Metastatic cervical lymph node swelling.

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12 Lip Disorders Disorders that exclusively affect the lips (specific cheilitides), systemic diseases that produce characteristic lip lesions, and some other entities are included in this group. In some of them, the diagnosis can be made on the basis of clinical criteria, but histopathologic confirmation of the clinical diagnosis is always necessary.

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Cheilitis Glandularis

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Cheilitis Granulomatosa

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Lip-Licking Cheilitis and Dermatitis

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Melkersson–Rosenthal Syndrome

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Median Lip Fissure

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Exfoliative Cheilitis

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Angioedema

Contact Cheilitis

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Actinic Cheilitis

Lymphedema due to Radiation

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Angular Cheilitis

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Systemic Diseases

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12.1 Cheilitis Glandularis Definition: Cheilitis glandularis is a rare, chronic inflammatory disorder of the minor salivary glands, characteristically affecting the lower lip. Etiology: The exact etiology is unknown, although several factors such as chronic irritation, sun exposure, smoking, and heredity have been implicated. Clinical features: Clinically, it presents as a swelling of the lower lip due to hyperplasia or hypertrophy and inflammation of the minor salivary glands (▶ Fig. 12.1). Characteristically, the orifices of the minor salivary glands are dilated, and pressure on the lip may cause expression of mucous or mucopustular fluid from the ductal openings. Crusting, erosions, and microabscesses may also occur. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Cheilitis granulomatosa, Melkersson–Rosenthal syndrome, Crohn’s disease, sarcoidosis, cystic fibrosis, and lymphangioma. Treatment: The treatment of choice is topical steroids and antibiotics in case of infection. Vermilionectomy is indicated only in severe cases.

12.2 Cheilitis Granulomatosa Definition: Cheilitis granulomatosa is a rare, chronic disorder of the lips, which is considered to be a localized form of orofacial granulomatosis, or part of Crohn’s disease. Etiology: The exact etiology is unknown, although dietary or other allergens have been implicated. Clinical features: Clinically, it presents as a painless, persistent, and diffuse swelling of one or both lips (▶ Fig. 12.2). Small vesicles, erosions, and scaling may occur. It is thought that cheilitis granulomatosa is a monosymptomatic form of Melkersson–Rosenthal syndrome or orofacial granulomatosis. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic examination. Differential diagnosis: Melkersson–Rosenthal syndrome, cheilitis glandularis, Crohn’s disease, sarcoidosis, cystic fibrosis, lymphangioma, and angioedema.

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12.2 Cheilitis Granulomatosa

Fig. 12.1 Cheilitis glandularis.

Fig. 12.2 Cheilitis granulomatosa of the lower lip.

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Treatment: The treatment of choice is topical or systemic corticosteroids, along with tetracyclines. Plastic surgery in severe cases.

12.3 Melkersson–Rosenthal Syndrome Melkersson–Rosenthal syndrome is a rare disorder characterized by cheilitis granulomatosa, facial paralysis, fissured tongue, and less often intraoral and facial edema (▶ Fig. 12.3). The term orofacial granulomatosis has been proposed to include conditions and diseases characterized by granulomatous inflammation in the oral and facial area (cheilitis granulomatosa, Melkersson–Rosenthal syndrome, Crohn’s disease, and sarcoidosis). The clinical diagnosis should be confirmed by histologic examination. The differential diagnosis and treatment are identical to those of cheilitis granulomatosa.

12.4 Exfoliative Cheilitis Definition: Exfoliative cheilitis is a, relatively, common chronic inflammatory disorder of the vermilion border of the lips. Etiology: The exact etiology is unknown. However, emotional stress, topical agents, cold or hot weather, prolonged sun exposure, etc. have been implicated Clinical features: Clinically, it is characterized by persistent scaling, crusting, and erythema of the vermilion border of the lips. This pattern is repetitive, resulting in yellowish, hyperkeratotic, thickening crusting, and fissuring (▶ Fig. 12.4). Candida albicans superinfection is common. The lesions are more common in young individuals, usually persist, with variable severity, for months or years, and may cause cosmetic problems. The diagnosis is mainly based on the clinical features. Laboratory tests: Histopathologic examination. Differential diagnosis: Contact cheilitis, actinic cheilitis, lip-licking cheilitis, and retinoid-associated cheilitis. Treatment: Symptomatic. Topical moistening agents, corticosteroids, and antifungals may be helpful. Topical ointment of tacrolimus (0.1 or 0.03%) twice a day for 1 or 2 weeks, followed for 2 to 3 weeks once a day seems to have the best results.

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12.4 Exfoliative Cheilitis

Fig. 12.3 Cheilitis granulomatosa affecting both upper and lower lips in a patient with Melkersson Rosenthal Syndrome.

Fig. 12.4 Exfoliative cheilitis.

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12.5 Contact Cheilitis Definition: Contact cheilitis is an acute inflammatory disorder of the lips that is attributed to allergy. Etiology: The most common causes include lipsticks, lip balms, tooth paste, mouthwashes, spices, aromatic substances, and foods. Clinical features: Clinically, it is characterized by mild edema and erythema, followed by irritation and thick whitish-brown scaling (▶ Fig. 12.5). A burning sensation and mild pain are common. It is usually confined to the vermilion border of both lips. The diagnosis is based on the history, clinical features, and laboratory tests. Laboratory tests: Skin patch test can be useful to identify the causative agent. Differential diagnosis: Exfoliative cheilitis, plasma cell cheilitis, and lip-licking cheilitis. Treatment: Discontinuation of all substances that might cause it. Topical or systemic corticosteroids can be useful.

12.6 Actinic Cheilitis Definition: Actinic cheilitis is a chronic degenerative disorder of the lower lip. Etiology: Long-term exposure to sunlight (i.e., farmers, sailors, outdoor workers, etc.). Clinical features: Clinically, in the early stage, mild erythema and edema, followed by dryness and fine scaling of the lower lip vermilion border are the presenting signs. As the lesion progresses, the epithelium becomes thin and smooth, with small whitish-gray areas intermingled with red regions and scaly formations (▶ Fig. 12.6). Erosions and tiny nodules may develop. The lesion is premalignant, and usually occurs in men over 50 years of age. The clinical diagnosis must be confirmed by laboratory tests. Laboratory tests: Histopathologic examination.

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12.6 Actinic Cheilitis

Fig. 12.5 Contact cheilitis caused by contact with an aromatic agent (cinnamon).

Fig. 12.6 Actinic cheilitis.

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Differential diagnosis: Exfoliative cheilitis, leukoplakia, lichen planus, lupus erythematosus, early squamous cell carcinoma, and cheilitis due to radiation. Treatment: Protection of lips from sunlight. Vermilionectomy in severe cases. Regular monitoring of the patients is suggested.

12.7 Angular Cheilitis Definition. Angular cheilitis, or perlèche, is a common disorder of the lips that manifests on the corner of the mouth, unilaterally or bilaterally. Etiology: Multifactorial etiology. Reduced vertical dimension, mechanical trauma, salivation, C. albicans, staphylococci, streptococci,iron deficiency anemia, riboflavin deficiency, Crohn’s disease, sarcoidosis, and human immunodeficiency virus (HIV) infection may be involved in the pathogenesis. Clinical features: Clinically, the disorder is characterized by erythema, maceration, fissuring, erosions, and crusting at the commissures (▶ Fig. 12.7 and ▶ Fig. 12.8). Classically, the lesions do not extend beyond the mucocutaneous border. A burning sensation, Candida infection, and dryness may occur. Remissions and exacerbations are common. The diagnosis is mainly based on the clinical findings and rarely on laboratory tests. Laboratory tests: Special tests are not required unless a possible underlying disease is suspected. Differential diagnosis: Iron deficiency anemia, megaloblastic anemia, riboflavin deficiency, and Crohn’s disease. Treatment: Correction of the occlusal vertical dimension, topical steroid ointments along with antifungals and antibiotics.

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12.7 Angular Cheilitis

Fig. 12.7 Angular cheilitis.

Fig. 12.8 Angular cheilitis.

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12.8 Lip-Licking Cheilitis and Dermatitis Definition: Lip-licking cheilitis and dermatitis is a chronic inflammatory reaction that almost exclusively occurs in children or young adults that have a habit of continuously licking the area. Etiology: Constant licking of the lips and the perioral skin. Clinical features: Clinically, the vermilion border of the lips and the perioral skin are erythematous, associated with scaling, crusting, and fissuring of variable severity (▶ Fig. 12.9). A burning sensation is a common symptom. The diagnosis is based exclusively on the history and clinical features. Differential diagnosis: Perioral dermatitis, contact cheilitis and dermatitis, exfoliative cheilitis, and retinoid-associated cheilitis. Treatment: Discontinuation of the licking habit is the key to treatment. Topical steroids and tacrolimus ointment, associated with antimycotic agents.

12.9 Median Lip Fissure Definition: Median lip fissure is a relatively rare disorder that may appear in the lower or upper lip, and is more common in males. Etiology: The exact etiology is not clear, although mechanical irritation, maceration, cold, wind, and other factors in association with a hereditary predisposition have been implicated. Clinical features: Clinically, it presents as a deep, inflammatory, persistent vertical fissure at the middle of the lip, usually infected by C. albicans and bacteria (▶ Fig. 12.10). Spontaneous bleeding, discomfort, and pain are common. The diagnosis is based exclusively on the history and clinical features. Laboratory tests: Not required. Differential diagnosis: Mechanical or thermal trauma, cleft lip, Crohn’s disease, metabolic disorders, and HIV infection. Treatment: Topical steroids with or without antifungal agents and antibiotics. Plastic reconstruction in severe cases.

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12.9 Median Lip Fissure

Fig. 12.9 Prominent licking cheilitis and dermatitis.

Fig. 12.10 Median lip fissure of the lower lip.

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12.10 Angioedema Definition: Angioedema is a relatively common allergic disorder that is characterized by transient edema that involves the dermis, subcutaneous tissues, and submucosa. Etiology: The disorder is classified into (1) hereditary, transmitted via the autosomal dominant trait, and (2) acquired, which may be caused by food, medications, infections, local anesthetics, malignancies, immune antigenantibody complexes, and other substances. Clinical features: Clinically, angioedema of all forms is characterized by edema of the skin, the mucous membranes, and the subcutaneous tissues. It has sudden onset and usually lasts 24 to 72 hours. There is a predilection for loose tissue areas, such as the periocular area, oral mucosa, genitals, hands and feet in a symmetrical pattern. Clinically, oral lesions present as a sudden, painless, smooth swelling, mainly involving the lips, tongue, and soft palate (▶ Fig. 12.11). Involvement of respiratory system may lead to edema of the larynx, blocking of the upper airways and occasionally death. In some cases, angioedema may start within a few minutes after drug administration and usually lasts for 24 to 48 hours. The diagnosis is mainly based on the history, clinical features and laboratory tests. Laboratory tests: Skin patch tests, serum immunologic tests, and molecular analysis, particularly for the hereditary type. Differential diagnosis: Cheilitis granulomatosa, cheilitis glandularis, cellulitis, surgical emphysema, lymphedema, and lymphangioma. Treatment: The management starts with the withdrawal of the suspected allergen as soon as possible. Systemic corticosteroids or intramuscular epinephrine should be administered in acute severe cases and antihistamines as well. Hospital admission should be considered in severe life-threatening cases.

12.11 Lymphedema due to Radiation Radiation therapy for oral and other head and neck malignancies is common. The side effects on the oral mucosa after radiation mainly depend on the dose and duration of the treatment. Lymphedema of the lips may occur. Clinically, it presents as a painless, erythematous swelling (▶ Fig. 12.12). The diagnosis is exclusively based on the history and clinical features.

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12.11 Lymphedema due to Radiation

Fig. 12.11 Angioedema, swelling of the lips.

Fig. 12.12 Radiation-induced mucositis, lesions on the lower lip.

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Lip Disorders

12.12 Systemic Diseases Some systemic diseases with oral manifestations may produce lip swelling. Crohn’s disease, sarcoidosis, tuberculosis, and cystic fibrosis are the more common in this group. Crohn’s disease is a chronic inflammatory, probably immunologically mediated, condition primarily involving the ileum and other parts of the gastrointestinal tract. Lip swelling is one of the most common oral manifestations of the disease (▶ Fig. 12.13). Nodular or diffuse soft swelling, a cobblestone appearance of the mucosa, mucosal tag lesions, ulcers, angular cheilitis, and aphthous like ulcerations may also occur (see also section 6.9). Sarcoidosis is a systemic granulomatous disease affecting the lungs, lymph nodes, spleen, liver, central nervous system, bones, oral mucosa, and salivary glands (see also section 11.8). The mouth is rarely involved. Lip swelling may occur (▶ Fig. 12.14). Red oral mucosal nodules with or without ulceration may also be seen. Tuberculosis (see also sections 5.8 and 11.7) may rarely produce inflammatory lip swelling (▶ Fig. 12.15). Cystic fibrosis is a relatively common multisystemic, life-threatening, inherited disorder (1 in 2,000 births) caused by a defective gene on chromosome 7.

Fig. 12.13 Crohn’s disease, cheilitis granulomatosa.

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Fig. 12.14 Sarcoidosis, multiple redviolet nodules of the upper lip.

Fig. 12.15 Lupus vulgaris, swelling and edema of the lower lip.

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Clinical features: Clinically, cystic fibrosis is characterized by dysfunction of the exocrine glands (pancreas, bronchial, tracheal, gastrointestinal tract, and sweat glands). The salivary glands may also be affected. Lip swelling, gingivitis, and dryness are the more frequent oral findings (▶ Fig. 12.16 and ▶ Fig. 12.17). The principal manifestations are chronic pulmonary infections, pancreatic insufficiency, cirrhosis, malabsorption, abdominal pain, skeletal disorders, finger clubbing, skin wrinkling, and sweating with characteristic salty taste (▶ Fig. 12.18). The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Increased chloride and sodium ion levels in sweat, absence of pancreatic enzymes in the intestinal fluid, chest radiography, and histopathologic examination of the minor salivary glands. Differential diagnosis: Lipoid proteinosis, mucopolysaccharidosis, cheilitis granulomatosa, and cheilitis glandularis. Treatment: Treatment should be left to the specialist pediatrician.

Fig. 12.16 Cystic fibrosis, lower lip enlargement.

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Fig. 12.17 Cystic fibrosis, lower lip enlargement.

Fig. 12.18 Cystic fibrosis, finger clubbing.

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13 Tongue Disorders Disorders that almost exclusively affect the tongue are included in this group. Some of them are normal variants and not disease entities. In the great majority of them the diagnosis should be based on the history and clinical features and rarely laboratory tests are needed.

Disorders

Normal Elements

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Fissured Tongue

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Filiform Papillae

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Geographic Tongue

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Fungiform Papillae

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Hairy Tongue

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Foliate Papillae

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Furred Tongue

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Circumvallate Papillae

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Median Romboid Glossitis

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Plasma Cell Glossitis

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Crenated Tongue

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Tongue Varices

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13.1 Disorders 13.1.1 Fissured Tongue Definition: Fissured tongue or plicated tongue is a common, benign, normal tongue variant with a prevalence rate ranging from 2 to 7% of the population. Etiology: Developmental, with possible involvement of a hereditary pattern with a polygenic trait of transmission or an autosomal dominant trait with incomplete penetration. Clinical features: Clinically, fissured tongue is characterized by multiple fissures or grooves on the dorsal surface of the tongue and occasionally on the lateral borders as well (▶ Fig. 13.1). Some individuals exhibit a deep and wide central fissure and several minor transverse fissures that stem from the central one. The fissures may vary in depth, size, number, and usually have a symmetrical distribution. The condition is usually asymptomatic, although food debris, microorganisms, and fungi may be retained in the deeper fissures, causing mild burning or soreness. Fissured tongue is often associated with geographic tongue (20–30%). The diagnosis is exclusively based on clinical features. Differential diagnosis: Melkersson–Rosenthal syndrome, Sjögren’s syndrome, and interstitial syphilitic glossitis. Treatment: No treatment is required.

13.1.2 Geographic Tongue See also section 2.5. Definition: Geographic tongue is a relatively common benign disorder, primarily affecting the tongue and rarely the rest of the oral mucosa. Etiology: The exact etiology remains unknown, although an inherited gene pattern has been suggested. Clinical features: Clinically, geographic tongue is characterized by multiple or rarely solitary, usually asymptomatic, circinate, erythematous, depapillated patches, typically surrounded by a slightly elevated whitish border, usually restricted to the dorsum and the lateral borders of the tongue (▶ Fig. 13.2). Rarely, similar lesions may develop on the buccal mucosa, floor of the mouth,

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13.1 Disorders

Fig. 13.1 Fissured tongue.

Fig. 13.2 Geographic tongue, multiple lesions.

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Tongue Disorders palate, and labial mucosa (geographic stomatitis) (▶ Fig. 13.3). Classically, the lesions persist for a few days or weeks and then disappear completely and reappear on another or the same area. The lesions vary in size from several mm to several cm and often coexist with fissured tongue. In addition, the disorder may occur in association with psoriasis and reactive arthritis. The diagnosis is made clinically. Differential diagnosis: Candidiasis, oral psoriasis, reactive arthritis (Reiter’s syndrome), mucous patches of secondary syphilis, cinnamon contact stomatitis, plasma cell stomatitis, and drug reactions. Treatment: No treatment is required but the patients should be reassured.

13.1.3 Hairy Tongue See also section 3.6. Definition: Hairy tongue is a relatively common disorder due to elongation of the filiform papillae and marked accumulation of keratin. Etiology: The exact etiology is unknown. Predisposing factors are emotional stress, radiation of the head and neck, heavy smoking, mouthwashes, systemic antibiotics, bacterial and Candida species infection, and poor oral hygiene. Clinical features: Clinically, hairy tongue is characterized by hypertrophy and elongation of the filiform papillae of the tongue, resulting in a hair-like appearance. The color may range from whitish to brown (▶ Fig. 13.4) or black. The disorder is usually asymptomatic, although occasionally may cause an unpleasant feeling of gagging, bad taste, malodor, discomfort, and distress to the patients. The diagnosis is based, exclusively, on the clinical features. Differential diagnosis: Furred tongue, candidiasis, and acanthosis nigricans. Treatment: Elimination of predisposing factors, brushing of the dorsum of the tongue by a tongue cleaner, and topical use of keratolytic agents (e.g., trichloroacetic acid 30%, salicylic acid, and podophyllin in alcohol) applied by the physician.

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Fig. 13.3 Geographic stomatitis. Geographic tongue-like lesions on the floor of the mouth.

Fig. 13.4 Hairy tongue.

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13.1.4 Furred Tongue Definition: Furred or coated tongue is a relatively uncommon disorder in healthy individuals. It is common in patients with febrile illnesses, usually associated with painful oral lesions. Etiology: The cause is accumulation of debris, bacteria, and desquamated epithelial cells, along with poor oral hygiene and dehydration. Clinical features: Clinically, furred tongue presents as a white or whitishyellow, asymptomatic, thick coating on the dorsal surface of the tongue (▶ Fig. 13.5). In contrast to hairy tongue, the length of the filiform papillae is almost normal. Characteristically, furred tongue appears and disappears within a short period. The diagnosis is exclusively based on the clinical features. Differential diagnosis: Hairy tongue, hairy leukoplakia, and candidiasis. Treatment: Treatment of the underlying illnesses, good oral hygiene, and brushing with a tongue cleaner.

13.1.5 Median Rhomboid Glossitis See also section 13.6. Definition: Median rhomboid glossitis is a benign, rare disorder that occurs exclusively on the dorsum of the tongue. Etiology: Presumably developmental, associated with Candida albicans infection. Clinical features: Clinically, median rhomboid glossitis appears as a welldemarcated, asymptomatic, erythematous rhomboid or oval area along the midline of the dorsum of the tongue, immediately anteriorly to the foramen cecum (▶ Fig. 13.6 and ▶ Fig. 13.7). The surface of the lesion may be flat or multinodular and usually is secondarily infected by C. albicans. The diagnosis is, usually, based on the clinical features. Laboratory tests: Usually not required. Histopathologic examination is rarely needed.

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13.1 Disorders

Fig. 13.5 Furred tongue.

Fig. 13.6 Median rhomboid glossitis, flat type.

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Differential diagnosis: Candidiasis, geographic tongue, hemangioma, lymphangioma, thyroglossal duct cyst, interstitial syphilitic glossitis, and nonHodgkin’s lymphoma. Treatment: Usually no treatment is required. In cases with C. albicans infection, systemic fluconazole or itraconazole is necessary.

13.1.6 Plasma Cell Glossitis Definition: Plasma cell glossitis is a rare, benign disorder of the tongue with characteristic histologic pattern. Etiology: The exact etiology remains unknown, although several predisposing factors such as cinnamon, mint, peppers, dentifrices, mouthwashes, foods, medications, and others have been implicated. Clinical features: Clinically, plasma cell glossitis has a rapid onset and appears as a localized or diffuse bright erythema with loss of filiform papillae, associated with a burning sensation, usually on the dorsum and the lateral border, and less often the ventral surface of the tongue (▶ Fig. 13.8). Rarely, similar lesions may appear on the lips, gingiva, buccal mucosa, and palate. Typically, edentulous areas are usually free of lesions. The disorder, usually, persists for a prolonged period of time. The clinical diagnosis should be confirmed by laboratory tests. Laboratory tests: Histopathologic and immunohistochemical examination. Differential diagnosis: Geographic tongue, median rhomboid glossitis, granulomatous glossitis, cinnamon contact stomatitis, allergic reaction, erythematous candidiasis, plasmacytoma, and reactive arthritis. Treatment: Symptomatic. In severe cases systemic corticosteroids in low doses are the first line of treatment (e.g., prednisolone 20–30 mg/d for 1–2 weeks, then tapered for 2–4 weeks). It is suggested to patients to keep a dietary history to identify and avoid possible allergens.

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Fig. 13.7 Median rhomboid glossitis, nodular type.

Fig. 13.8 Plasma cell glossitis

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13.1.7 Crenated Tongue Definition: Crenated tongue is a normal phenomenon on the lateral borders of the tongue. Etiology: Misarranged teeth, the habit of strong pressing the tongue against the teeth or pathologic edema of the tongue may be the cause. Clinical features: Clinically, crenated tongue consists of shallow asymptomatic impressions, covered by normal mucosa, on the lateral border of tongue due to the neighboring teeth (▶ Fig. 13.9). Systemic diseases such as myxedema, acromegaly, primary systemic amyloidosis, angioedema, and lipoid proteinosis may cause megaloglossia and subsequently a crenated tongue. The diagnosis is based exclusively on the clinical features. Treatment: No therapy, except reassurance is required.

13.1.8 Tongue Varices Definition–Etiology: Tongue varices are an abnormal dilation of veins and are a common finding in individuals over 60 years. The disorder is usually not related with any other systemic vascular disease. Clinical features: Clinically, tongue varices, typically, appear as multiple, tortuous, sublingual, widened and elevated, nodule-like, blue-purple asymptomatic lesions. They occur, usually bilaterally, on the ventral surface and the lateral borders of the tongue, and less frequently on the floor of the mouth (▶ Fig. 13.10). The diagnosis is exclusively based on the clinical features. Differential diagnosis: Hemangioma, other vascular malformations, pigmented nevi, and congenital telangiectasia. Treatment: No treatment is required.

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Fig. 13.9 Crenated tongue.

Fig. 13.10 Globular expansion (varice) of the sublingual tuberculum.

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13.2 Normal Elements Normal anatomical elements and mildly abnormal and innocent conditions of the tongue are included in this group.

13.2.1 Filiform Papillae The filiform papillae are normal elements that cover the anterior two-thirds of the dorsum, including the tip of the tongue (▶ Fig. 13.11). They form an abrasive surface to control the food bolus as it is pressed to the palate. Marked hypertrophy and elongation of filiform papillae due to accumulation of keratin, form the hairy tongue. In such cases individual filiform papillae can become 15 to 20 mm long and 2 mm thick.

13.2.2 Fungiform Papillae Fungiform papillae are normal, multiple, small, round, and slightly elevated red nodules, scattered between the filiform papillae, along the anterior portion of the dorsum of the tongue. They consist of vessels and connective tissue and multiple thin neural ends (taste buds). Fungiform papillae may sometimes become inflamed and enlarged (papillitis) (▶ Fig. 13.12) and may cause a burning sensation or mild pain, mainly at the tip of the tongue (glossodynia).

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Fig. 13.11 Filiform papillae, slightly marked.

Fig. 13.12 Hypertrophic fungiform papillae on the center of the dorsum of the tongue.

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Tongue Disorders

13.2.3 Foliate Papillae Foliate papillae are a normal anatomical element at the base of the posterior, lateral borders, of the tongue, bilateral and symmetrical, which also have taste buds. The size varies from few millimeters to 1 to 2 cm and they are 4 to 6 in number. Hypertrophy of the foliate papillae, usually results from chronic or acute irritation, as the substratum of them is lymphoid tissue (▶ Fig. 13.13). Patients with hypertrophic foliate papillae may develop cancerophobia and dentists may clinically confuse them with squamous cell carcinoma or non-Hodgkin’s lymphoma. Reassurance is the best course of action.

13.2.4 Circumvallate Papillae Circumvallate papillae are normal anatomical elements at the posterior dorsal surface of the tongue. They are 10 to 15 in number arranged in a V-shaped pattern. In the deep groove surrounding the papillae, numerous taste buds are present. Clinically, they appear as flattened nodules of 1 to 3 mm in diameter. Hypertrophy of the papillae results in red, well-circumscribed, raised, asymptomatic nodules (▶ Fig. 13.14), which when discovered by the patient may cause fear of a malignancy. Reassurance is the best action.

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13.2 Normal Elements

Fig. 13.13 Hypertrophic foliate papillae of the tongue.

Fig. 13.14 Hypertrophic circumvallate papillae of tongue.

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Index Note: Page numbers set bold or italic indicate headings or figures, respectively.

A Acanthosis nigricans – as differential diagnosis 237, 238, 242, 392 – benign 236, 237, 239 –– as differential diagnosis 236 – malignancy-associated 234, 235–236 –– as differential diagnosis 238 Acatalasia 200, 214 Acinic cell adenocarcinoma 306, 307 Acinic cell carcinoma 294, 308 Acral lentiginous melanoma 106 Actinomycosis 262, 317, 318, 319–320, 362 Acute lymphonodular pharyngitis 120 Acyclovir 6, 116, 124 Adamantiades-Behçet disease 180, 181–183 – as differential diagnosis 80, 154, 178, 214, 216 Addison’s disease 108, 109– 110 – as differential diagnosis 88, 90, 92, 94 Adenoid cystic carcinoma 305, 306 Agranulocytosis 200, 201 – as differential diagnosis 76, 164, 166, 176, 196, 200, 202, 204, 206, 212, 214, 218, 258 Amalgam contact reaction 13 – as differential diagnosis 20 Amalgam tattoo 88, 89 – as differential diagnosis 88, 90, 94, 96, 98, 100, 102, 106, 108, 314, 326 Amelanotic melanoma 106, 314

Amphotericin B 176 Amyloidosis 152, 153, 313, 316 – as differential diagnosis 154, 248, 254, 366 Anemia – aplastic 76 – iron deficiency 74, 75, 378 – megaloblastic 378 Angina bullosa hemorrhagica 150, 151 – as differential diagnosis 134, 150, 152, 154 Angioedema 372, 382, 383 Angiolymphoid hyperplasia with eosinophilia 66, 69 Angiosarcoma 68, 304 Angular cheilitis 172 Aphthous ulcers 178, 179 – as differential diagnosis 46, 116, 118, 158, 160, 172, 182, 196, 214, 216, 218, 220, 222 Aplastic anemia 76, 166, 196, 200, 203, 206 Arthritis, reactive 80, 81 – as differential diagnosis 50, 54, 82, 182, 392, 396 Ascorbic acid 46, 258 Aspergillosis 174, 177, 188 Avitaminoses 74 Azathioprine 154

B Bacillary angiomatosis 258, 260, 298, 314 Bacterial angiomatosis 108 Basal cell carcinoma 290 Benign lymphoid hyperplasia 68 Biting, chronic 26, 27 Black hairy tongue 94, 95 Blastomycosis 174 Blue nevus 102, 103, 106 – See also Melanocytic nevus Bone marrow aplasia 202

Breslow’s depth 106 Brivudine 120 Buccal cellulitis 360 Bullous lichen planus 144 – as differential diagnosis 145, 150, 154 Bullous pemphigoid 136, 137 – as differential diagnosis 132, 134, 140, 142, 144, 146, 150, 152, 316 – desquamative gingivitis in 60 Burn – chemical 20, 23 –– as differential diagnosis 54 – thermal 46, 47 –– as differential diagnosis 50, 54 Butterfly rash 68

C Calcium channel blockers 248 Candidiasis 22, 23, 25 – as differential diagnosis 4, 6, 10, 14, 16, 20, 22, 26, 28, 30, 44, 50, 52, 58, 62, 82, 242, 392, 394, 396 – erythematous 396 – pseudomembranous 18 Candidiasis erythematous 52, 53 – as differential diagnosis 54, 56, 58, 64 Cat scratch disease 362, 368 Celiac disease 234 Central ameloblastoma 353 Chediak-HIgashi syndrome 200, 214 Cheilitis – actinic 374, 376, 377 – angular 378, 379 – contact 374, 376, 377 – exfoliative 374, 375, 376, 378, 380

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Index – lip-licking 374, 376, 380, 381 – plasma cell 376 – radiation 378 – retinoid-associated 374, 380 Cheilitis glandularis 372, 372, 373, 382, 386 Cheilitis granulomatosa 372, 373, 375, 384, 386 – as differential diagnosis 234, 372, 382 Chemical burn 20, 23 – as differential diagnosis 54 Cherubism 346, 347 – as differential diagnosis 340, 342, 348, 352 Chondroma, soft-tissue 285, 286, 286 Chondrosarcoma 301, 302, 340, 341 – as differential diagnosis 288, 300, 340, 344, 348, 352 Chronic biting 26, 27 Cigarette smoker’s lip lesions 16, 17 Cinnamon contact stomatitis 18, 19–20 – as differential diagnosis 4, 6, 12, 14, 16, 18, 22, 24, 26, 30, 44, 54, 56, 58, 62, 64, 82, 392, 396 Ciprofloxacin 220 Circumvallate papillae 402, 403 Clear cell adenocarcinoma 310, 311 Cleft lip 380 Cleidocranial dysplasia 350 Colchicine 182, 216 Compound nevus 100 – See also Melanocytic nevus Condyloma accuminatum 224, 225 – as differential diagnosis 38, 40, 224, 226, 228, 242, 266, 268 Condyloma lata 173 Contact allergic stomatitis 62, 63

406

Cowden’s syndrome 268, 350 CREST syndrome 72 Crohn’s disease 232, 233, 235, 378, 384, 384 – as differential diagnosis 182, 248, 316, 372, 380 Cross syndrome 256 Cryptococcosis 174 Cunnilingus, oral lesions secondary to 48, 51 Cutaneous horn 39, 290 Cyclophosphamide 342 Cyclosporine 216, 248, 249– 250 Cystadenoma 293, 294 – as differential diagnosis 274, 276, 278, 282, 292, 294, 306, 322, 326 Cystic fibrosis 372, 384, 386, 387 Cystic hygroma 324, 358, 359 Cytomegalovirus 78, 220, 221

D Dapsone 144, 154, 182, 216 Darier’s disease 238, 239–240 – as differential diagnosis 238, 242 Dental abscess 262, 330, 362 Denture fibrous hyperplasia 232, 233 – as differential diagnosis 234 Denture stomatitis 52, 53 – as differential diagnosis 54, 64, 242 Dermatitis – lip licking 380 – perioral 380 Dermatitis herpetiformis 142, 143, 145 – as differential diagnosis 132, 134, 138, 142, 154 Dermoid cyst 324, 325, 358, 359 – as differential diagnosis 274, 324, 326, 356 Desquamative gingivitis 60, 61

– as differential diagnosis 6, 58, 62 – in epidermolysis acquisita 150 – in lichen planus 61 Diabetes mellitus 214, 252 Diphtheria 78 Drug-induced gingival overgrowth 248, 249–251, 252 Drug-induced gingivitis, as differential diagnosis 60 Drug-induced pigmentation 90, 93, 94, 108 Duct ectasia 294 Dyskeratosis congenita 32, 33 – as differential diagnosis 4, 30, 34, 36

E Emphysema, surgical 382 Eosinophilic granuloma 210, 211 Eosinophilic ulcer 160, 161, 310 – as differential diagnosis 158, 162, 190, 192, 220 Ephelides 98, 99, 314 – as differential diagnosis 88, 90, 96, 98, 100, 102, 108 Epidermolysis bullosa 34, 42, 146, 147–149 – as differential diagnosis 150 – desquamative gingivitis in 60 Epidermolysis bullosa acquisita 148, 149, 151 – as differential diagnosis 132, 134, 138, 142, 144, 146, 150, 152, 154, 168 Epithelial peeling 42, 43–44 Epstein-Barr virus 6 Eruption cyst 326, 328–329 Erythema multiforme 124, 125

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Index – as differential diagnosis 48, 80, 116, 120, 126, 132, 134, 142, 144, 172, 182, 216 –– desquamative gingivitis in 60 Erythroleukemia 255 Erythromycin 172 Erythroplakia 54, 55 – as differential diagnosis 10, 54, 56, 58, 64, 70, 192 Ewing’s sarcoma 344, 345 – as differential diagnosis 302, 340, 344, 346, 348 Exostoses, multiple 264, 264, 338, 339 – as differential diagnosis 338, 348, 350 Extravasation mucocele 322

F Famciclovir 6, 116, 120 Fellatio, oral lesions secondary to 48, 49, 54, 78 Felodipine 251 Fibroma 268, 269 – as differential diagnosis 262, 272, 276, 278, 280, 282, 286, 292, 326, 330, 332 – giant cell 268, 270 – ossifying 348 – peripheral ossifying 272, 273 –– as differential diagnosis 258, 260, 268, 278, 304, 330 Fibrosarcoma 299, 300, 300 Fibrous developmental hyperplasia 271 Fibrous developmental malformation 268, 270 Fibrous dysplasia 346, 347– 348 – as differential diagnosis 264, 338, 346, 350, 352 Fibrous histiocytoma 275, 276, 300

– as differential diagnosis 268, 280, 282, 302, 304, 306 Filiform papillae 400, 401 Fluconazole 176, 396 Focal dermal hypoplasia syndrome 242, 243 – as differential diagnosis 40, 224, 226, 236, 238, 242, 266, 268 Focal epithelial hyperplasia 266, 267, 269 – as differential diagnosis 40, 224, 226, 236, 242, 266 Focal oral mucinosis 278, 286 Focal palmoplantar and oral mucosa hyperkeratosis syndrome 36, 37 – as differential diagnosis 30, 34 Foliate papillae 402, 403 Fordyce’s granules 10, 28, 29 Fungiform papillae 400, 401 Furred tongue 392, 394

G Ganciclovir 222 Gardner’s syndrome 339, 348, 349 – as differential diagnosis 264, 286, 336, 338 Geographic stomatitis 393 Geographic tongue 50, 51, 390, 391 – as differential diagnosis 10, 70, 74, 80, 82, 396 Giant cell fibroma 239, 270 Giant cell granuloma 342, 346, 348 Giant cell tumor 340, 344 Gingival cyst of adults 262, 330, 331 Gingival cyst of newborn 262, 328, 329 Gingival plasmacytoma 58 Gingivitis – desquamative 60, 61 –– as differential diagnosis 6, 58, 62

–– in lichen planus 61 – drug-induced, as differential diagnosis 60 – granulomatous 58, 59 –– as differential diagnosis 60, 62, 164 – in leukemia 252 – mouth breathing 246, 247, 248, 254 – necrotizing ulcerative 116, 164, 165 –– as differential diagnosis 60 – plaque-related 58, 246, 247 –– as differential diagnosis 60, 62 – plasma cell 56, 59 –– as differential diagnosis 60 – pregnancy-associated 248, 252, 253, 254 Glycogen storage disease type 1b 200, 212, 213, 215 Gonococcal stomatitis 64, 65, 120 Gorlin’s syndrome 352 Graft versus host disease 124, 126, 130, 184, 185, 366 – as differential diagnosis 10, 12, 34, 70 Grafts 42 Granular cell tumor 276, 280, 281, 282, 282, 283, 284, 286 Granular cell tumor of the newborn 260, 261 – as differential diagnosis 282, 288, 328 Granulomatous gingivitis 58, 59 – as differential diagnosis 60, 62, 164 Granulomatous glossitis 396 Graphite implantation 88, 93 Grover’s disease 238 Gumma 173, 188

H Hailey-Hailey disease 132, 146, 238 Hairy leukoplakia 6, 7

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Index – as differential diagnosis 4, 18, 20, 24, 394 Hairy tongue 392, 393 – as differential diagnosis 394 Hamartoma 262, 288, 328 Hand, foot, and mouth disease (HFMD) 122, 123 – as differential diagnosis 116, 118, 120, 178, 214 Hand-Schüller-Christian disease 209, 210, 210 Hashimoto-Pritzker disease 210 Heavy metal deposition 90, 91–92 Heerfordt’s syndrome 358, 362, 365, 366, 368 Hemangioendothelioma 303, 304 – as differential diagnosis 66, 68, 258, 284, 298, 306 Hemangioma 66, 67 – as differential diagnosis 68, 72, 84, 258, 260, 284, 290, 298, 322, 324, 326, 396, 398 – cervical 358 Hemangiopericytoma 303, 304 – as differential diagnosis 66, 258, 284, 298, 304 Hematoma, traumatic 46, 47, 66, 78, 326 Hematopoiesis growth factors 202 Hemochromatosis 94 Hereditary benign intraepithelial dyskeratosis 30, 34 – as differential diagnosis 30 Hereditary gingival fibromatosis 254, 255 – as differential diagnosis 248, 254, 256, 272 Hereditary hemorrhagic telangiectasia 72, 73 – as differential diagnosis 84 Herpangina 120, 121, 178 – as differential diagnosis 64, 116, 118

408

Herpes simplex 172, 178, 196, 222 Herpes zoster 118, 118, 119, 121 Herpetic gingivostomatitis 116, 117 – as differential diagnosis 118, 120, 124, 126, 132, 144, 154, 164, 214 Herpetic stomatitis 116 – as differential diagnosis 48, 64, 78 Herpetiform ulcers 120, 124, 144, 154, 181 Histiocytic eosinophilic granuloma 160 Histoplasmosis 174, 175 Hodgkin’s disease 190, 310, 361, 366, 368 Human immunodeficiency virus (HIV) – as differential diagnosis 78, 202, 214, 360, 366, 380 – candidiasis erythematous in 52 – hairy leukoplakia in 6 Human papillomavirus (HPV) 2, 40 Hurler’s syndrome 248 Hydroxychloroquine 168 Hydroxyldaunomycin 342 Hypophosphatasia 200, 214

I Idiopathic dipapillation of filiform papillae 50 Incisive papilla cyst 262, 332, 333 Intradermal nevus 100, 101 – See also Melanocytic nevus Iron deficiency anemia 74, 75, 378 Itraconazole 396

J Jackson-Lawler syndrome 34

Jadassohn-Lewandowky syndrome 34 Junctional nevus 100, 102 – See also Melanocytic nevus

K Kaposi’s sarcoma 296, 297– 298 – as differential diagnosis 66, 68, 108, 258, 260, 300, 304, 306, 314, 316 Kawasaki’s disease 124 Keratoacanthoma 289, 290 Keratolytics 392 Kimura’s disease 68 Klebsiella infection 220, 221 Klippel-Trenaunay-Weber syndrome 72, 84 Koebner’s phenomenon 10

L Langerhan’s cell histiocytosis 208 – as differential diagnosis 164, 344, 346 Lateral periodontal cyst 262, 330 Leiomyoma 283–284, 284 – as differential diagnosis 66, 258, 260, 276, 280, 282, 304, 330 Leiomyosarcoma 301, 302 – as differential diagnosis 298, 300, 306 Leishmaniasis, mucocutaneous 176 Lentigo maligna 100, 101 – as differential diagnosis 88, 96, 98, 102, 106, 108, 314 Lentigo maligna melanoma 106, 109, 314 Lentigo simplex 98, 99, 314 – as differential diagnosis 88, 90, 94, 96, 98, 100, 102, 108 Letterer-Siwe disease 208, 209 Leukemia 206 – acute monocytic 208

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Index – acute myelogenous 207 – acute myelomoncytic 253 – as differential diagnosis 48, 50, 58, 76, 78, 164, 166, 196, 200, 202, 212, 214, 216, 248, 254, 258, 344, 368 – chronic myelogenous 207 – gingival overgrowth in 252 – myeloblastic, as differential diagnosis 204 Leukoedema 30, 31 – as differential diagnosis 4, 6, 14, 20, 30, 44 Leukoplakia 2, 3–5 – as differential diagnosis 10, 12, 14, 16, 22, 24, 26, 28, 30, 34, 36, 38, 40, 42, 70, 82, 192, 378 – hairy 6, 7 –– as differential diagnosis 4, 18, 20, 24, 394 – verrucous 228, 229 Lichen planus 6, 7–9, 11 – as differential diagnosis 4, 6, 12, 16, 20, 22, 24, 28, 34, 54, 70, 74, 134, 138, 168, 184, 378 – bullous 144, 145 –– as differential diagnosis 150, 154 – desquamative gingivitis in 61 – erosive 46, 48 Lichenoid reaction 12, 13 – as differential diagnosis 4, 10 Linea alba 14, 15 Linear gingival erythema 62, 63 – as differential diagnosis 58 Linear IgA disease 140, 141, 143 – as differential diagnosis 132, 134, 138, 144, 146, 150, 154, 168 – desquamative gingivitis in 60 Lingual thyroid 290 Lip fissure, median 380, 381

Lipoid proteinosis 236, 316, 386 Lipoma, as differential diagnosis 268, 276, 278, 282, 286, 292, 322, 326, 330, 332 Lupus erythematosus 68, 70– 71 – as differential diagnosis 4, 6, 24, 130, 134, 138, 150, 184, 202, 216, 378 – discoid 54, 69, 71 –– as differential diagnosis 10, 12, 16, 20, 168 –– desquamative gingivitis in 60 Lupus vulgaris 385 Lymphadenitis 360, 361 Lymphangioma 287, 288 – as differential diagnosis 66, 322, 324, 326, 328, 372, 382, 396 Lymphedema 382 – from radiation 382 Lymphoepithelial cyst 326, 327 – as differential diagnosis 290, 294, 322, 324, 330 – cervical 356, 357, 358 Lymphoid tissue aggregation 326 Lymphoma 68 – Burkitt’s 166, 342, 343 – Hodgkin’s 190, 310, 366, 368 – non-Hodgkin’s 190, 191, 310, 312 –– as differential diagnosis 58, 68, 86, 160, 176, 192, 212, 216, 218, 220, 292, 294, 298, 342, 344, 356, 358, 360, 362, 368, 396 –– nasal type-extranodal natural killer/T-cell 188, 189 ––– as differential diagnosis 162, 166

M Maffucci’s syndrome 72 Malnutrition 74 Materia alba of gingiva 26, 28 McCune-Albright syndrome 98 Median lip fissure 380, 381 Median rhomboid glossitis 394, 395, 397 – as differential diagnosis 54, 290, 330, 396 Mediterranean fever 196, 214 Megaloblastic anemia 378 Melanoacanthoma 96, 97, 314 – as differential diagnosis 88, 90, 98, 102, 108 Melanocytic nevus 100, 314 – as differential diagnosis 96, 98, 100, 106, 108 Melanoma, malignant 106, 107, 314, 315 – as differential diagnosis 88, 90, 94, 96, 98, 100, 102, 106, 298, 326 Melanotic neuroectodermal tumor of infancy 262, 287, 288, 326, 342 Melkersson-Rosenthal syndrome 374 – as differential diagnosis 234, 372, 390 Metastatic carcinoma in cervical nodes 368 Metronidazole 164 Mikulicz’s syndrome 364, 366 Monomorphic adenoma 292, 306 Mononucleosis, infectious 78, 79 – as differential diagnosis 50, 64, 172, 202, 214, 222, 368 Mucocele 322, 323 – as differential diagnosis 274, 276, 278, 294, 326, 330, 332 –– extravasation 322 –– superficial 322 Mucoepidermoid carcinoma 305, 306

409

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Index – as differential diagnosis 294, 308, 322 Mucopolysaccharidoses 248, 254, 316, 386 Mucormycosis 174, 177, 188 Mucosal grafts 42 Mucosal horn 36, 38 – as differential diagnosis 226 Mucositis, radiation oral 48, 49 Mucous retention cyst 322 Multiple condylomata 227 Multiple endocrine neoplasia syndrome 282 Multiple exostoses 264, 264, 338, 339 – as differential diagnosis 338, 348, 350 Multiple myeloma 344, 345 – as differential diagnosis 212, 342, 350, 352 Multiple osteoma 264 Murray-Puretic-Drescher syndrome 256 Mycoses, systemic 174, 318 – as differential diagnosis 212, 218 Myelodysplastic syndrome 204, 205 – as differential diagnosis 176, 196, 202, 206, 214, 218 Myoepithelioma 291, 292 Myofibroma 284 Myxoma 268, 274, 274, 275, 278, 354 – as differential diagnosis 322, 330

N Nasal type-extranodal natural killer/T-cell non Hodgkin’s lymphoma 162, 166, 188 Nasolabial cyst 262, 332, 333 Necrotizing sialadenometaplasia 162, 163 – as differential diagnosis 160, 176, 188, 190, 192, 292, 306, 308

410

Necrotizing ulcerative gingivitis 164, 165, 258 – as differential diagnosis 116, 206, 212 Necrotizing ulcerative stomatitis, as differential diagnosis 18, 22 Neuroblastoma 288 Neurofibroma 277, 278 – as differential diagnosis 268, 272, 276, 280, 282, 286, 330 Neurofibromatosis 279 – multiple 316 Neurofibromatosis type 1 280 Neurofibromatosis type 2 280 Neuroma, traumatic 281, 282 Neutropenia 194, 195, 197 – as differential diagnosis 164, 202, 204, 206, 218, 220, 258 – congenital 196, 198, 199, 214 – cyclic 197–198 –– as differential diagnosis 200, 214 Nevus – blue 102, 103, 106 – compound 100 – intradermal 100, 101 – junctional 100, 102 – melanocytic 100, 314 –– as differential diagnosis 96, 98, 100, 106, 108 – of Ota 104, 104, 105 – pigmented 88, 94, 326, 398 – white sponge 30, 32 –– as differential diagnosis 4, 18, 24, 30, 34, 36, 40 Nicotinic stomatitis 14, 15 – as differential diagnosis 4, 238 Nifedipine 250 Nodular melanoma 106, 107, 314 Noma 166, 167

O Odontogenic cyst 352

Odontogenic tumors 352, 353– 354 – as differential diagnosis 272, 288, 302, 338, 340, 342, 344, 346, 348 Oncovin 342 Oral epitheliolysis 24 Oral focal mucinosis 268, 274, 276, 277 Oral sex 48 Orofacial granulomatosis 58, 234, 364 Orofacial-digital syndrome 242 Osteoma 338 – as differential diagnosis 336, 338 Osteomyelitis 344 Osteosarcoma 341 – as differential diagnosis 288, 302, 336, 338, 342, 344, 346, 348, 350, 352

P Pachyonychia congenita 34, 35 – as differential diagnosis 4, 30, 34, 36, 146 Paget’s disease of bone 350, 351 – as differential diagnosis 264, 338, 348 Papillae – circumvallate 402, 403 – filiform 400, 401 – foliate 402, 403 – fungiform 400, 401 Papillary cystadenoma lymphomatosum 293, 294, 294 Papillary palatal hyperplasia 240, 241 – as differential diagnosis 52, 238, 290 Papillary syringadenoma 290 Papilloma 38, 39, 224, 225, 266, 267 – as differential diagnosis 38, 40, 42, 226, 228, 242, 268

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Index Papillon-Lefèvre syndrome 200 Paracoccidioidomycosis 174, 176 Parotitis 358 Parulis 262 Pemphigoid – as differential diagnosis 10, 12, 46, 48, 116, 124, 126, 130, 132, 154 – bullous 136, 137 –– as differential diagnosis 132, 134, 140, 142, 144, 146, 150, 152, 316 –– desquamative gingivitis in 60 – desquamative gingivitis in 60 – mucous membrane 132, 135–136, 138 –– as differential diagnosis 70, 142, 144, 146, 150, 154, 168 Pemphigoid gestationis 132, 139, 154 Pemphigus 48, 130 – as differential diagnosis 124, 126, 130, 138, 142, 144, 146, 150, 152, 154, 168, 316 Pemphigus vegetans 236 Pemphigus vulgaris 130, 131, 133 – desquamative gingivitis in 60 Penicillin G 172, 318 Periapical abscess 318 Periodontal abscess 262, 263, 318, 330, 332 Periodontal fistula 263 Periodontitis, aggressive 200, 212 Perioral dermatitis 380 Peripheral ameloblastoma 84, 86 Peripheral brown tumor 258, 260 Peripheral calcifying odontogenic tumor 86

Peripheral giant cell granuloma 260, 261 – as differential diagnosis 86, 258, 272, 298, 300, 302 Peripheral odontogenic tumors 272 Peripheral ossifying fibroma 272, 273 – as differential diagnosis 258, 260, 268, 278, 304, 330 Peutz-Jeghers syndrome 110, 111–112 – as differential diagnosis 88, 92, 98, 108, 350 PFAPA 120, 214, 215 – as differential diagnosis 178, 182, 216 Phenytoin 248, 249 Phlebolith 90 Pigmented nevi 88, 94, 326, 398 Plasma cell gingivitis 56, 59 – as differential diagnosis 60, 62 Plasma cell glossitis 396, 397 Plasma cell stomatitis, as differential diagnosis 20, 50, 54, 56, 64, 392 Plasmacytoma 54, 344 – as differential diagnosis 396 – gingival 58 Pleomorphic adenoma 289, 292, 309 – as differential diagnosis 280, 282, 292, 306, 308 Plummer-Vinson syndrome 74, 75 Polycythemia vera 76 Polymorphous low-grade adenocarcinoma 307, 308 – as differential diagnosis 306, 308 Porphyria cutanea tarda 150 Posaconazole 176 Pregnancy gingival overgrowth 252, 253, 254 Pregnancy granuloma 258, 260

Proliferative verrucous leukoplakia 2 Protein deficiency 258 Proteus syndrome 84 Pseudomonas infection 218, 219 Psoriasis 82, 83 – as differential diagnosis 50, 58, 80, 168 – desquamative gingivitis in 60 Pyogenic granuloma 258, 259 – as differential diagnosis 66, 68, 86, 108, 260, 272, 298, 304, 314, 322 Pyostomatitis vegetans 154, 155 – as differential diagnosis 164, 182, 216, 236

R Racial pigmentation 89 – as differential diagnosis 90, 92, 94, 108 Radiation lymphedema 382 Radiation oral mucositis 48, 49 Radiation-induced mucositis 383 Radicular cyst 332 Ramon’s syndrome 256 Ranula 294, 324, 324, 325 Reiter’s syndrome 182, 392 Rhabdomyoma 282 Riboflavin deficiency 378 Riga Fede ulceration 158, 160 Rituximab 132 Rutherford syndrome 256

S Salivary gland adenocarcinoma 162, 188, 190, 192, 292 Salivary gland tumors 356 Sarcoidosis 234, 316, 360, 372, 384, 385 Schwannoma 279, 280

411

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Index – as differential diagnosis 268, 276, 280, 282, 284, 286 Scurvy 164, 252, 254, 256, 257 Seborrheic dermatitis 238 Sex, oral 48 Shwachman-Diamond syndrome 200 Sialadenitis 364 – chronic 294, 356 – submandibular 358, 360, 360, 361, 368 Sialadenoma papilliferum 40, 224, 226, 228, 266 Silver implantation 88, 92 Sjögren’s syndrome 364, 365– 367 – as differential diagnosis 184, 322, 358, 360, 364, 390 Skin grafts 42 Smoker’s melanosis 94, 95, 96, 108 Smoking pigmentation 92 Smoking-associated melanosis 88 Sneddon-Wilkinson disease 80 Soft-tissue chondroma 286 Soft-tissue osteoma 285, 286 Soft-tissue sarcoma 310 Squamous cell carcinoma 41, 57, 193–195, 231, 295, 369 – as differential diagnosis 38, 40, 54, 68, 86, 158, 160, 162, 176, 188, 190, 212, 284, 290, 300, 302, 304, 306, 308, 310, 330, 378 – as papillary lesion 230 – as red lesion 56 – as soft tissue tumor 296 – as ulcerative lesion 192 – as white lesion 40 Staphylococcal infection 216, 219 Staphylococcal scalded skin syndrome 130 Stevens-Johnson syndrome 126, 127–128 – as differential diagnosis 124, 130

412

Stomatitis – cinnamon contact 18, 19–20 –– as differential diagnosis 4, 6, 12, 14, 16, 22, 24, 26, 30, 44, 54, 56, 58, 64, 82, 392, 396 – contact allergic 62, 63 – denture 52, 53 –– as differential diagnosis 54, 64, 242 – drug-induced 18 – gonococcal 64, 65, 120 – herpetic 48, 64, 78 – necrotizing ulcerative, as differential diagnosis 18, 22 – nicotinic 14, 15 –– as differential diagnosis 4, 238 – plasma cell, as differential diagnosis 20, 50, 54, 56, 64, 392 – streptococcal 64, 118 – ulcerative 134, 168, 169 –– desquamative gingivitis in 60 – uremic 16, 17, 19 –– as differential diagnosis 4, 6, 20, 24 Streptococcal stomatitis 64, 118 Sturge-Weber angiomatosis 84, 85 Sturge-Weber syndrome 72, 106 Sulfapyridine 144 Superficial spreading melanoma 106, 107, 314 Sweet’s syndrome 216, 217 – as differential diagnosis 126, 130, 182, 204, 214 Syphilis 118, 158, 160, 162, 170, 171–172 – as differential diagnosis 10, 24, 54, 56, 70, 74, 78, 176, 368, 390, 392, 396 Systemic sclerosis 184

T Tacrolimus 216 Telangiectasia, congenital 398 Tetracycline 220 Thalidomide 182, 216 Thermal burn 46, 47 – as differential diagnosis 50, 54 Thrombasthenia 46 Thrombocytopenia 76, 77 – as differential diagnosis 46, 204, 206 Thrombocytopenic purpura 50 Thyroglossal duct cyst 330, 331, 356, 357 – as differential diagnosis 356, 396 Thyroid cyst 358 Thyroid, lingual 290 Tongue – black hairy 94 – crenated 398, 399 – fissured 390, 391 – furred 392, 394, 395 – geographic 50, 51, 390, 391 –– as differential diagnosis 10, 70, 74, 80, 82, 396 – hairy 392, 393 –– as differential diagnosis 394 – varices 398, 399 Tooth abscess 332 Torus mandibularis 286, 336, 337 Torus palatinus 286, 336, 337 Toxic epidermal necrolysis 128, 129 – as differential diagnosis 124, 126 Traumatic bulla 150, 152, 153 Traumatic hematoma 46, 47, 66, 78 Traumatic neuroma 281, 282 Traumatic pigmentation 94 Traumatic ulcer 158, 159 – as differential diagnosis 160, 162, 172, 178, 192, 218, 222 Triazoles, for candidiasis 24

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Index Tuberculosis 172, 175, 362, 363, 384 – as differential diagnosis 160, 166, 172, 176, 188, 190, 192, 218, 220, 234, 318, 360, 368

U Ulcerative colitis 182, 234 Ulcerative stomatitis 134, 168, 169 – desquamative gingivitis in 60 Uremic stomatitis 16, 17, 19 – as differential diagnosis 4, 6, 20, 24

V Valaciclovir 6, 116, 120, 124, 222

Verruca vulgaris 226, 227 – as differential diagnosis 38, 40, 42, 224, 226, 228, 266, 268 Verruciform xanthoma 228, 229, 266 – as differential diagnosis 40, 42, 224, 226, 228, 266 Verrucous carcinoma 40, 41, 230, 231, 295, 296 – as differential diagnosis 40, 42, 224, 226, 228, 266 Verrucous hyperplasia 18, 40, 228 Verrucous leukoplakia 228, 229 von Recklinghausen’s disease 279 Voriconazole 176

W Warty dyskeratoma 290 Wegener’s granulomatosis 186, 187 – as differential diagnosis 160, 176, 188, 190, 192, 216, 218, 248, 310 White sponge nevus 30, 32 – as differential diagnosis 4, 18, 24, 30, 34, 36, 40 Wickman’s striae 6

Z Zimmerrmann-Laband syndrome 248, 254, 254, 257

413

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