Color Atlas of Fine Needle Aspiration Cytology [1 ed.] 9789811580321, 9789811580338

This color atlas covers etiology, incidence, clinical features, diagnostic features, immunochemistry, molecular biology

165 15 107MB

English Pages 495 [488] Year 2020

Report DMCA / Copyright

DOWNLOAD FILE

Polecaj historie

Color Atlas of Fine Needle Aspiration Cytology [1 ed.]
 9789811580321, 9789811580338

Table of contents :
Contents
About the Author
1: Introduction and Basic Techniques of Aspiration Cytology in Superficial and Deep Lesions
1.1 Advantages [1–5]
1.2 Needle Tract Seeding
1.3 The Basic Technique of FNAC
1.4 Post FNAC
1.4.1 Fine-Needle Sampling Technique
1.4.2 Fixatives
1.4.3 Staining
1.5 Deep-Seated FNAC
1.5.1 Indications of Deep-Seated Lesions
1.6 USG Guided FNAC (Fig. 1.5)
1.7 CT Guided FNAC
1.8 Endoscopic Ultrasound Guided
1.9 Magnetic Resonance Image Guided
1.10 Mammographic Guided
References
2: Interpretation of Fine Needle Aspiration Cytology Smear
2.1 Malignant Cells
2.1.1 Cell
2.1.2 Nucleus
2.2 Interpretation of FNAC Smear
2.3 Evaluation of the Cytological Features
2.3.1 Cellular Arrangement
2.4 Individual Cells
2.4.1 Cell Shape
2.4.2 Cytoplasm
2.4.3 Cytoplasmic Area
2.4.4 Vacuolation in Cytoplasm
2.5 Nucleus
2.5.1 Nuclear Pleomorphism
2.5.2 Nuclear Margin
2.5.3 Nucleoli
2.5.4 Background of the Smear
2.5.5 False-Positive Cases
2.6 False-Negative Smear
References
3: Aspiration Cytology of Head, Neck and Orbital Lesions
3.1 Cysts in the Neck Region
3.1.1 Branchial Cyst [1–4]
3.1.2 Thyroglossal Cyst [5, 6]
3.1.3 Cystic Hygroma [7]
3.1.4 Acquired Cyst
3.1.4.1 Non-neoplastic
3.1.5 Mucocele [9]
3.2 Lymph Node Lesion in Head–Neck Region
3.2.1 Difficulties
3.3 Paraganglioma [10–12]
3.3.1 Carotid Body Tumour [11, 13]
3.3.2 Differential Diagnosis (Figs. 3.34, 3.35, and 3.36)
3.3.3 Nasopharyngeal Carcinoma (NPC) [14–16]
3.3.4 Parathyroid Neoplasm [17–20]
3.3.5 Meningioma [21–27]
3.3.6 Olfactory Neuroblastoma [28, 29]
3.4 Lesions in the Base of the Skull
3.4.1 Orbital lesion
3.4.2 Lesions of the Eyelid
3.4.3 Tumours of the Eyelid
3.4.3.1 Basal Cell Carcinoma (BCC) [30, 31]
3.4.3.2 Sebaceous Carcinoma [32–34]
3.5 Lacrimal gland
3.5.1 Pleomorphic Adenoma [35]
3.5.2 Adenoid Cystic Carcinoma (ADC)
3.5.3 Mucoepidermoid Carcinoma
3.5.4 Intraorbital Tumours
3.5.4.1 Retinoblastoma [36–38]
3.5.5 Malignant melanoma [39–41]
3.5.6 Rhabdomyosarcoma
3.5.7 Acute Leukaemia Infiltration
3.5.8 Lymphoma [35, 42–44]
3.5.9 Metastatic Malignancy [35, 45–49]
References
4: Aspiration Cytology of Salivary Gland
4.1 The Major Advantages of FNAC [1–4]
4.1.1 Complications of FNAC
4.1.2 Anatomy and Histology of the Salivary Glands
4.1.3 Parotid Gland
4.1.4 Submandibular Gland
4.1.5 Sublingual Gland
4.1.5.1 Histology of the Salivary Gland
4.1.6 Cytology of the Salivary Gland (Figs. 4.1, 4.2, 4.3, 4.4 and 4.5)
4.2 Diagnostic Accuracy
4.2.1 Causes of False-Positive FNAC
4.2.2 Causes of False-Negative FNAC [10]
4.2.3 The Major Difficulties in the Diagnosis [10]
4.2.4 FNAC Techniques and Special Consideration
4.3 Non-neoplastic Lesions
4.3.1 Other Lesions
4.3.1.1 Sialadenosis
4.3.2 Sialadenitis
4.3.2.1 Acute Sialadenitis
4.3.3 Chronic Sialadenitis [11]
4.3.3.1 Common Association
4.3.4 Lymphoepithelial Sialadenitis [12–14]
4.3.5 Clinical Features
4.3.6 Granulomatous Sialadenitis [15]
4.3.6.1 Causes
4.4 Neoplastic Lesions
4.5 The Milan System of Reporting the Salivary Gland Tumours
4.6 Benign Neoplasm
4.6.1 Pleomorphic Adenoma [18, 19]
4.7 Basal Cell Adenoma (BCA) [20, 21]
4.7.1 Histopathology
4.7.2 Differential Diagnosis
4.8 Warthin Tumour [22, 23]
4.8.1 Oncocytoma [24]
4.8.2 Histopathology
4.8.3 Myoepithelioma [25]
4.8.4 Localization
4.8.5 Histopathology
4.8.6 Cell Types
4.8.6.1 Plasmacytoid (Hyaline) Myoepithelial Cells
4.8.6.2 Spindle Cell Type
4.8.6.3 Epithelial Cells
4.8.6.4 Clear Cells
4.9 Myoepithelial Carcinoma
4.9.1 Adenoid Cystic Carcinoma (ADC) [26, 27]
4.9.2 Molecular Genetics
4.9.3 Histopathology
4.9.4 Immunocytochemistry (Fig. 4.65)
4.9.5 Molecular Pathology
4.10 Acinic Cell Carcinoma [28]
4.10.1 Histopathology
4.10.2 Differential Diagnosis
4.10.3 Mucoepidermoid Carcinoma [29, 30]
4.10.4 Histopathology
4.11 Immunocytochemistry
4.11.1 Differential Diagnosis (Fig. 4.80)
4.12 Epithelial Myoepithelial Carcinoma [31]
4.12.1 Epidemiology
4.12.2 Histopathology
4.13 Polymorphous Low-Grade Adenocarcinoma [32]
4.13.1 Epidemiology
4.13.2 Histopathology
4.14 Salivary Duct Carcinoma [33]
4.14.1 Epidemiology
4.14.1.1 Localization
4.14.1.2 Clinical Features
4.14.2 Histopathology
4.15 Adenocarcinoma, Not Otherwise Specified
4.15.1 Epidemiology
4.15.1.1 Localization
4.15.2 Histopathology
4.16 Carcinoma ex-Pleomorphic Adenoma [34]
4.16.1 Epidemiology
4.16.2 Histopathology
4.17 Mammary Analogue Secretory Carcinoma [35]
4.17.1 Histopathology
4.18 Essential Features of Primary NHL in the Salivary Gland (Figs. 4.111 and 4.112)
4.18.1 Differential Diagnosis
4.19 Metastatic Tumours
References
5: Fine Needle Aspiration Cytology of Thyroid
5.1 Indications of Thyroid FNAC
5.1.1 Indications for USG Guided FNAC (Box 5.1)
5.1.2 Complications of FNAC
5.2 Essential Investigations Needed for Effective Interpretation
5.3 Anatomy and Histology of Thyroid
5.3.1 Histology
5.3.2 Thyroid FNAC: Approach
5.4 Thyroid Lesions
5.4.1 Non-neoplastic Conditions
5.4.1.1 Colloid Goitre
5.4.2 Differential Diagnosis
5.4.3 Graves’ Disease
5.5 Thyroiditis
5.5.1 Acute Thyroiditis
5.5.2 Subacute Thyroiditis
5.5.3 Differential Diagnosis
5.6 Lymphocytic Thyroiditis (LT)
5.7 Neoplastic Lesions of Thyroid
5.8 Follicular Neoplasm
5.8.1 Follicular Adenoma
5.8.2 Follicular Carcinoma
5.8.3 Differential Diagnosis (Fig. 5.45)
5.9 Hurthle Cell Neoplasm (Oncocytic Neoplasm)
5.9.1 Differential Diagnosis (Figs. 5.51 and 5.52)
5.10 Hyalinizing Trabecular Tumour
5.10.1 Differential Diagnosis
5.11 Papillary Carcinoma of the Thyroid
5.11.1 Molecular Genetics
5.12 Variants of Papillary Carcinoma [21, 22]
5.12.1 Follicular Variant of Papillary Thyroid Carcinoma
5.12.2 Differential Diagnosis
5.13 Cystic Papillary Thyroid Carcinoma
5.13.1 Tall Cell Variant [23]
5.14 Hurthle Cell Variant
5.14.1 Differential Diagnosis of PTC
5.15 Medullary Carcinoma
5.15.1 Differential Diagnosis (Fig. 5.79a and b)
5.15.2 Variants of Medullary Carcinoma
5.16 Insular Carcinoma
5.16.1 Histopathology
5.16.2 Differential Diagnosis
5.17 Anaplastic Carcinoma
5.17.1 Differential Diagnosis
5.18 Non-Hodgkin Lymphoma [30, 31]
5.18.1 Differential Diagnosis
References
6: Fine Needle Aspiration Cytology of the Breast
6.1 False-Negative Breast FNAC
6.1.1 Triple test [2–4]
6.1.2 Diagnostic Accuracy of Breast FNAC [5–7]
6.1.3 Core Needle biopsy [8, 9]
6.1.3.1 Advantages of Core Needle Biopsy
6.1.3.2 Disadvantages
6.1.4 Mammography
6.1.5 Histopathology of the Breast
6.1.6 Cytology of the Normal Breast
6.1.7 Diagnostic Terminology
6.1.8 Reporting Format of Breast Lesion
6.2 Benign Lesions of the Breast
6.2.1 Mastitis
6.2.1.1 Acute
6.2.2 Key Cytological Features
6.2.3 Chronic
6.2.4 Idiopathic Granulomatous mastitis [11]
6.2.5 Key Cytological Features
6.2.6 Granulomatous mastitis [12]
6.3 Fat Necrosis
6.3.1 Key Cytological Features (Figs. 6.16 and 6.17)
6.3.2 Differential Diagnosis
6.3.3 Galactocele
6.3.4 Key Cytological Features (Figs. 6.18 and 6.19)
6.4 Lactating Adenoma
6.4.1 Key Cytological features [13] (Figs. 6.20 and 6.21)
6.4.2 Differential Diagnosis
6.5 Mucocele
6.5.1 Key Cytological Features
6.5.2 Fibroadenoma
6.5.3 Histopathology
6.5.4 Key Cytological features [14, 15] (Figs. 6.22, 6.23, 6.24, 6.25, 6.26, 6.27, 6.28, and 6.29)
6.5.5 Differential Diagnosis (Fig. 6.30)
6.5.6 Carcinoma
6.6 Fibrocystic Disease
6.6.1 Histopathology
6.6.2 Key Cytological Features (Figs. 6.31, 6.32,6.33, and 6.34)
6.6.3 Differential Diagnosis
6.7 Phyllodes Tumour
6.7.1 Histopathology
6.7.2 Key Cytological features [16–18] (Figs. 6.35, 6.36, 6.37, 6.38, 6.39, 6.40, 6.41, and 6.42)
6.7.3 Differential Diagnosis (Fig. 6.43)
6.8 Papillary Neoplasm
6.8.1 Histopathology
6.8.2 Features of Malignancy
6.8.3 Key Cytological features [19, 20] (Figs. 6.44, 6.45, 6.46, 6.47, 6.48, 6.49, and 6.50)
6.8.4 Cytological Indicators of Malignancy
6.9 Differential Diagnosis
6.9.1 Fibroadenoma
6.9.2 Intraductal Proliferative Lesions of the Breast
6.9.3 Usual Ductal Hyperplasia
6.9.3.1 Histopathology
6.10 Atypical Ductal Hyperplasia
6.10.1 Histopathology
6.10.2 Salient Cytological features [22–24] (Figs. 6.52, 6.53, 6.54, 6.55, 6.56, 6.57, 6.58, 6.59, 6.60, 6.61, 6.62, 6.63 and 6.64)
6.10.3 Differential Diagnosis
6.11 Ductal Carcinoma In Situ
6.11.1 Histopathology
6.11.2 Cytological features [25] (Figs. 6.65, 6.66, and 6.67)
6.11.2.1 Low-Grade DCIS
6.11.3 Differential Diagnosis
6.12 Carcinoma of Breast
6.12.1 Invasive Carcinoma, Not Otherwise Specified
6.12.2 Histopathology
6.12.3 Key Cytological features [27, 28] (Figs. 6.69, 6.70, 6.71,6.72, 6.73, 6.74, 6.75, 6.76, 6.77, 6.78, 6.79, and 6.80)
6.12.4 Differential Diagnosis
6.13 Mucinous Carcinoma
6.13.1 Histopathology
6.13.2 Key Cytological features [29, 30] (Figs. 6.81, 6.82, 6.83, 6.84, 6.85, 6.86, and 6.87)
6.13.3 Differential Diagnosis
6.14 Medullary carcinoma [29, 31]
6.14.1 Key Histopathological Features
6.14.2 Key Cytological Features (Figs. 6.88, 6.89, 6.90, 6.91, 6.92, and 6.93)
6.14.3 Differential Diagnosis
6.15 Apocrine carcinoma [29]
6.15.1 Histopathology
6.15.2 Key Cytological Features (Figs. 6.94, 6.95, and 6.96)
6.15.3 Differential Diagnosis
6.16 Metaplastic carcinoma [32, 33]
6.16.1 Key Histopathological Features
6.16.2 Key Cytological Features (Figs. 6.97, 6.98, 6.99, 6.100, 6.101, 6.102, and 6.103)
6.16.3 Differential Diagnosis
6.17 Tubular Carcinoma
6.17.1 Histology
6.17.2 Key Cytological features [34]
6.17.3 Differential Diagnosis
6.18 Lobular Carcinoma
6.18.1 Histology Key Features
6.18.2 Key Cytological features [35, 36] (Figs. 6.104, 6.105, and 6.106)
6.18.3 Differential Diagnosis
6.19 Carcinoma with Neuroendocrine Differentiation
6.19.1 Histopathology
6.19.2 Key Cytological Features (Figs. 6.107, 6.108, and 6.109)
6.19.3 Differential Diagnosis
6.19.4 Metastatic tumors [37, 38]
6.20 Non-Hodgkin lymphoma [39, 40]
6.20.1 Acute Leukemic deposit [41]
6.21 Male Breast Lesions
6.21.1 Gynaecomastia [42]
6.21.2 Key Cytological Features (Figs. 6.119 and 6.120)
6.21.3 Differential Diagnosis
6.22 Carcinoma in Male Breast
6.23 Nipple Discharge
6.23.1 Key Cytological features [43] (Figs. 6.123 and 6.124)
6.24 Ancillary Investigations on Breast Aspiration material [44–47]
6.24.1 Flow Cytometry
References
7: Fine Needle Aspiration Cytology of the Lung
7.1 Different Techniques of FNAC
7.1.1 Transthoracic Needle Aspirate (TTNA)
7.1.2 TTNA Technique
7.1.3 Transbronchial FNAC
7.1.3.1 Indications to Do Transbronchial FNAC (TBNA)
7.2 Anatomy and Histopathology of the Lung
7.2.1 Cytology (Figs. 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, and 7.7)
7.2.1.1 Lining Cells
7.3 The Cells Simulating Malignancy
7.3.1 Reactive Bronchial Cells
7.3.2 Vegetable Cell
7.4 Inflammatory Lung Lesions
7.4.1 Acute Inflammation
7.4.1.1 Key Cytological Features (Fig. 7.16)
7.4.2 Differential Diagnosis
7.5 Specific Infections
7.5.1 Tuberculosis
7.5.2 Diagnostic Modalities
7.5.3 Key Cytological Features [4–6] (Figs. 7.17, 7.18, 7.19, 7.20, and 7.21)
7.5.4 Differential Diagnosis
7.5.5 Actinomycosis
7.5.6 Nocardia
7.6 Fungal Infections [10–12]
7.6.1 Aspergillus
7.6.2 Key Cytological Features (Figs. 7.27, 7.28, 7.29, and 7.30)
7.6.3 Mucormycosis
7.6.4 Key Cytological Features (Figs. 7.31, 7.32, 7.33, and 7.34)
7.7 Pulmonary Cryptococcosis
7.8 Histoplasma
7.8.1 Clinical Features
7.8.2 Key Cytological Features (Figs. 7.37, 7.38, 7.39, 7.40, and 7.41)
7.9 Pneumocystis Pneumonia [13, 14]
7.9.1 Key Cytological Features (Figs. 7.43, 7.44, and 7.45)
7.9.2 Differential Diagnosis (Fig. 7.46)
7.10 Candidiasis
7.10.1 Key Cytological Features
7.11 Parasites
7.11.1 Hydatid Cyst
7.11.2 Life Cycle
7.11.3 Key Cytological Features [15] (Figs. 7.47, 7.48, and 7.49)
7.11.4 Neoplastic Lesions of the Lung
7.12 Lung Carcinoma
7.12.1 Incidence
7.12.2 Etiological Factors
7.13 Squamous Cell Carcinoma [17–20]
7.13.1 Incidence
7.13.2 Key Cytological Features (Figs. 7.51, 7.52, 7.53, 7.54, 7.55, 7.56, 7.57, 7.58, 7.59, and 7.60)
7.13.3 Types
7.13.3.1 Keratinizing
7.13.3.2 Non-keratinizing
7.13.3.3 Immunocytochemistry (Fig. 7.61)
7.13.3.4 Molecular Genetics
7.13.4 Differential Diagnosis (Fig. 7.62)
7.14 Adenocarcinoma [21, 22]
7.14.1 Key Cytological Features (Figs. 7.63, 7.64, 7.65, and 7.66)
7.14.2 Molecular Cytogenetics (Fig. 7.68)
7.14.3 Differential Diagnosis
7.15 Carcinoid
7.15.1 Key Cytological Features (Figs. 7.69, 7.70, and 7.71)
7.15.2 Differential Diagnosis
7.16 Small Cell Carcinoma
7.16.1 Clinical Features
7.16.2 Key Cytological Features [23, 24] (Figs. 7.73, 7.74, 7.75, 7.76, 7.77, 7.78, and 7.79)
7.16.3 Immunocytochemistry (Fig. 7.80)
7.16.4 Differential Diagnosis
7.17 Large Cell Neuroendocrine Carcinoma
7.17.1 Clinical Features
7.17.2 Key Cytological Features [25]
7.17.3 Differential Diagnosis
7.18 Large Cell Carcinoma
7.18.1 Key Cytological Features (Figs. 7.81, 7.82, 7.83 and 7.84)
7.18.2 Differential Diagnosis
7.19 Other Tumours of Lung
7.19.1 Adenoid Cystic Carcinoma
7.19.2 Key Cytological Features [26, 27] (Figs. 7.85, 7.86, and 7.87)
7.20 Carcinosarcoma
7.20.1 Key Cytological Features (Figs. 7.88, 7.89, 7.90, 7.91, 7.92, and 7.93)
7.21 Pleuropulmonary Blastoma
7.21.1 Clinical Features
7.21.2 Key Cytological Features [28] (Figs. 7.94, 7.95, 7.96, and 7.97)
7.21.3 Differential Diagnosis
7.22 Lymphoma of Lung [29, 30]
7.22.1 Clinical Features
7.22.2 Key Cytological Features (Figs. 7.98, 7.99, and 7.100)
7.23 Metastatic Tumours in the Lung
References
8: Fine Needle Aspiration Cytology of the Mediastinum
8.1 Different Anatomical Compartments (Fig. 8.1)
8.1.1 Techniques to Approach the Mediastinum
8.2 Lesions in the Mediastinum
8.2.1 Thymoma
8.2.2 Clinical Features
8.2.3 Histopathology
8.2.4 Key Cytology Features [2–5] (Figs. 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, and 8.10)
8.2.5 Type A (Medullary Thymoma/Spindle Cell Thymoma)
8.2.6 Type B (Cortical Thymoma)
8.2.7 Differential Diagnosis (Fig. 8.11)
8.3 Malignant Thymoma
8.3.1 Invasive Thymoma
8.3.2 Thymic Carcinoma
8.3.3 Thymic Neuroendocrine Tumours
8.3.4 Typical Thymic Carcinoid
8.3.4.1 Atypical Thymic Carcinoid
8.3.4.2 Cytology
8.4 Germ Cell Tumors [7–9]
8.4.1 Germinomas
8.4.2 Key Cytological Features (Figs. 8.18, 8.19, 8.20, and 8.21)
8.4.3 Differential Diagnosis
8.5 Embryonal Carcinoma
8.5.1 Key Cytology Features (Figs. 8.22, 8.23, and 8.24)
8.6 Lymphomas [10–12]
8.6.1 Non-Hodgkin’s Lymphoma
8.6.2 Primary Mediastinal Large B Cell Lymphoma (PMLBCL)
8.6.3 Key Cytological Features (Fig. 8.25)
8.7 T Lymphoblastic Lymphoma
8.7.1 Key Cytological Features (Fig. 8.26)
8.8 Anaplastic Large Cell Lymphomas
8.8.1 Key Cytological Features (Figs. 8.27 and 8.28)
8.9 Hodgkin Lymphoma
8.9.1 Key Cytological Features (Figs. 8.29 and 8.30)
8.10 Neurogenic Tumour
8.10.1 Ganglioneuroblastoma
8.10.2 Key Cytological Features (Figs. 8.31 and 8.32)
8.10.3 Neurofibroma and Schwannoma
8.10.3.1 Key Cytological Features (Figs. 8.33 and 8.34)
8.11 Malignant Peripheral Nerve Sheath Tumours
References
9: Fine Needle Aspiration Cytology of the Lymph Node
9.1 Indications of FNAC
9.1.1 Contraindication
9.1.2 Limitations of FNAC of Lymph Node
9.1.3 Diagnostic Accuracy [2–5]
9.1.4 Diagnostic Accuracy of FNAC of Lymph Node Depends on
9.2 Normal Anatomy and Histology of the Lymph Node
9.2.1 The Normal Components of the Lymph Node
9.2.2 Follicular Centre Cells (Fig. 9.2)
9.3 Benign Lesions of the Lymph Node
9.3.1 Reactive Lymphoid Hyperplasia
9.3.2 Differential Diagnosis
9.4 Acute Lymphadenitis
9.5 Granulomatous Lymphadenitis
9.5.1 Tuberculosis
9.5.2 Key Cytological Features [ 6–9] (Figs. 9.12, 9.13, 9.14 and 9.15)
9.5.3 Differential Diagnosis
9.6 Lepromatous Lymphadenitis
9.6.1 Key Cytological Features [10, 11] (Figs. 9.18, 9.19, and 9.20)
9.7 Leishminia Lymphadenitis
9.7.1 Key Cytological Features [12] (Fig. 9.21)
9.8 Filarial Lymphadenitis
9.8.1 Key Cytological Features [13, 14] (Fig. 9.22)
9.9 Toxoplasma Lymphadenitis
9.9.1 Key Cytological Features [15]
9.10 Cat Scratch Disease
9.10.1 Key Cytological Features [16]
9.11 Viral Infections
9.11.1 Infectious Mononucleosis (IM)
9.11.2 Key Cytological Features [17] (Fig. 9.23)
9.11.3 Differential Diagnosis
9.12 Kimura’s Disease
9.12.1 Key Cytological Features [18]
9.13 Kikuchi’s Disease
9.13.1 Key Cytological Features [19]
9.13.2 Differential Diagnosis
9.14 HIV Lymphadenopathy [20, 21]
9.14.1 Persistent Generalized Lymphadenopathy (PGL)
9.15 Kaposi’s Sarcoma [22, 23]
9.15.1 Association
9.15.2 Key Cytological Features
9.15.3 Differential Diagnosis of Kaposi’s Sarcoma
9.16 Rosai–Dorfman Disease
9.16.1 Key Cytological Features [24, 25] (Figs. 9.32, 9.33, 9.34, 9.35, and 9.36)
9.16.2 Differential Diagnosis
9.17 Dermatopathic Lymphadenitis
9.17.1 Clinical Features
9.17.2 Key Cytological Features (Figs. 9.39 and 9.40)
9.17.3 Differential Diagnosis
9.18 Castleman’s Disease
9.18.1 Key Cytological Features [26] (Figs. 9.41, 9.42, and 9.43)
9.18.2 Differential Diagnosis
9.18.3 Metastatic Malignant Tumour [27–32]
9.18.4 Squamous Cell Carcinoma (Figs. 9.44, 9.45, 9.46, 9.47, and 9.48)
9.18.5 Adenocarcinoma (Figs. 9.50, 9.51, and 9.52)
9.18.6 Small Cell Carcinoma (Figs. 9.53, 9.54, and 9.55)
9.18.7 Germ Cell Tumour (Figs. 9.56 and 9.57)
9.18.8 Immunocytochemistry
9.19 Lymphoma
9.20 B Cell Non-Hodgkin Lymphoma (NHL)
9.20.1 Small Lymphocytic Lymphoma [39, 40]
9.20.2 Clinical Features
9.20.3 Key Cytological Features (Figs. 9.68, 9.69, 9.70, 9.71, 9.72, and 9.73)
9.20.4 Immunophenotype (Fig. 9.74)
9.21 Mantle Cell Lymphoma
9.21.1 Abbreviation: MCL
9.21.2 Clinical Features
9.21.3 Key Cytological Features [41, 42] (Figs. 9.75, 9.76, 9.77, and 9.78)
9.21.4 Immunophenotype (Fig. 9.79, 9.80, 9.81, 9.82, 9.83, and 9.84)
9.22 Follicular Lymphoma
9.22.1 Abbreviation
9.22.2 Clinical Features
9.22.3 Key Cytological Features [41, 43] (Figs. 9.85, 9.86, 9.87, and 9.88)
9.22.4 Immunophenotype (Fig. 9.89)
9.23 Lymphoplasmacytic Lymphoma
9.23.1 Epidemiology
9.23.2 Clinical Features
9.23.3 Key Cytological Features (Figs. 9.90 and 9.91)
9.24 Marginal Zone Lymphoma (MZL)
9.24.1 Nodal Marginal Zone Lymphoma
9.24.2 Key Cytological Features
9.24.3 Immunophenotype
9.24.4 Chromosomal Abnormality
9.25 Extranodal Marginal Zone Lymphoma
9.25.1 Key Cytological Features (Figs. 9.92 and 9.93)
9.25.2 Immunophenotype
9.25.3 Chromosomal Abnormality
9.26 Hairy Cell Leukaemia
9.26.1 Epidemiology
9.26.2 Clinical Features
9.26.3 Key Cytological Features
9.26.4 Immunophenotype
9.27 Diffuse Large B Cell Lymphoma
9.27.1 Synonym
9.27.2 Epidemiology
9.27.3 Key Cytological Features (Figs. 9.94, 9.95, 9.96, and 9.97)
9.27.4 Immunophenotype (Fig. 9.98)
9.27.5 Chromosomal Abnormality
9.28 Burkitt’s Lymphoma
9.28.1 Epidemiology
9.28.2 Clinical Features
9.28.3 Key Cytological Features [46–48] (Figs. 9.99, 9.100, 9.101 and 9.102)
9.28.4 Immunophenotype (Fig. 9.103)
9.28.5 Chromosomal Abnormality: Characteristic Chromosomal Translocation
9.29 B Lymphoblastic Lymphoma
9.29.1 Epidemiology
9.29.2 Clinical Features
9.29.3 Key Cytological Features [49] (Figs. 9.104 and 9.105)
9.29.4 Chromosomal Abnormality
9.30 T Cell Lymphoma
9.30.1 T Lymphoblastic Lymphoma
9.30.2 Epidemiology
9.30.3 Clinical Features
9.30.4 Key Cytological Features: Same as B Lymphoblastic Lymphoma
9.30.4.1 Immunophenotype
9.30.4.2 Chromosomal Abnormality
9.31 Anaplastic Large Cell Lymphoma
9.31.1 Epidemiology
9.31.2 Clinical Features
9.31.3 Key Cytological Features [50, 51] (Figs. 9.106, 9.107, 9.108, and 9.109)
9.31.4 Immunophenotype
9.32 Peripheral T Cell Lymphoma, Unspecified
9.32.1 Epidemiology
9.32.2 Key Cytological Feature
9.33 Angioimmunoblastic T Cell Lymphoma
9.33.1 Epidemiology
9.33.2 Clinical Features
9.33.3 Key Cytological Features [52, 53]
9.34 Mycosis Fungoides and Sezary Syndrome
9.34.1 Epidemiology
9.34.2 Clinical Features
9.34.3 Key Cytological Features [54] (Figs. 9.110 and 9.111)
9.35 Hodgkin’s Lymphoma [55–58]
9.35.1 Classification
9.36 Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)
9.36.1 Epidemiology
9.36.2 Clinical Features
9.36.3 Classical Hodgkin’s Lymphoma (CHL)
9.36.3.1 Key Cytological Features (Figs. 9.112, 9.113, 9.114, 9.115, 9.116, 9.117, 9.118, 9.119, 9.120, and 9.121)
9.36.3.2 Immunophenotype of R–S Cell (Figs. 9.122 and 9.123)
9.36.3.3 Nodular Lymphocyte Predominant Hodgkin Lymphoma
9.37 Histiocytic and Dendritic Neoplasms
9.37.1 Follicular Dendritic Cell Sarcoma
9.37.1.1 Epidemiology
9.37.1.2 Clinical Features
9.37.2 Key Cytological Features [59, 60]
9.37.3 Immunophenotype
9.38 Langerhans Cell Histiocytosis
9.38.1 Epidemiology
9.38.2 Clinical Features
9.38.3 Key Cytological Features [61, 62] (Figs. 9.125, 9.126, 9.127, and 9.128)
9.39 Leukaemic Infiltration [63, 64]
9.39.1 Acute Lymphoblastic Leukaemia
9.39.1.1 Key Cytological Features (Figs. 9.129 and 9.130)
9.39.2 Acute Myeloid Leukaemia
9.39.2.1 Key Cytological Features
9.40 Chronic Myeloid Leukaemic Infiltration
9.40.1 Key Cytological Features (Figs. 9.131, 9.132, and 9.133)
References
10: Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen
10.1 Intestine
10.1.1 Endoscopic FNAC
10.1.1.1 Technique
10.1.2 Endoscopic Ultrasound-Guided (EUS) FNAC [1]
10.2 Oesophagus
10.2.1 Normal Histology and Cytology
10.2.2 Cytology
10.3 Infection
10.4 Dysplasia in Barrett’s Oesophagus
10.5 Squamous Cell Carcinoma
10.5.1 Epidemiology
10.5.2 Clinical Features
10.5.3 Key Cytological Features (Figs. 10.1 and 10.2)
10.6 Adenocarcinoma
10.6.1 Epidemiology
10.6.2 Clinical Features
10.6.3 Key Cytological Features (Figs. 10.3, 10.4, and 10.5)
10.7 Stomach
10.7.1 Anatomy and Histology
10.7.1.1 Anatomy
10.7.2 Histology
10.7.3 Cytology
10.7.4 Benign Tumours
10.8 Gastric Adenocarcinoma
10.8.1 Epidemiology
10.8.2 Clinical Features
10.8.3 Key Cytological Features
10.8.4 Intestinal Type (Figs. 10.6, 10.7, 10.8, 10.9, 10.10, 10.11, 10.12, and 10.13)
10.8.5 Diffuse or Gastric Type (Figs. 10.14, 10.15, and 10.16)
10.9 Gastrointestinal Stromal Tumour
10.9.1 Epidemiology
10.9.2 Localization
10.9.3 Molecular Pathology
10.9.4 Clinical Features
10.9.5 Key Cytological Features [3, 4] (Figs. 10.17, 10.18, 10.19, 10.20, 10.21, and 10.22)
10.10 Neuroendocrine Tumors [5]
10.10.1 Epidemiology
10.10.2 Clinical Features
10.10.3 Key Cytological Features (Figs. 10.26 and 10.27)
10.11 Non-Hodgkin Lymphoma [6]
10.11.1 Epidemiology
10.11.2 Clinical Features
10.11.3 Type of Lymphomas
10.11.4 Key Cytological Features (Figs. 10.29 and 10.30)
10.12 The Small and Large Intestine
10.12.1 Anatomy, Histology and Cytology
10.12.1.1 Anatomy
10.12.2 Histology
10.12.3 Histology
10.12.4 Cytology
10.13 Infections
10.13.1 Tuberculosis
10.14 Adenocarcinoma
10.14.1 Epidemiology
10.14.2 Clinical Features
10.14.3 Key Cytology Features
10.14.4 Lymphoma [6]
10.15 Large Intestine
10.15.1 Colorectal Adenocarcinoma [7]
10.15.1.1 Epidemiology
10.15.2 Clinical Features
10.15.3 Key Cytological Features (Figs. 10.31 and 10.32)
10.16 Liver
10.16.1 Contraindications of FNAC of Liver
10.16.2 Sampling Technique
10.16.3 Ancillary Tests
10.16.4 Anatomy, Histology and Cytology
10.16.5 Cytology
10.17 Non-neoplastic Lesions
10.17.1 Diffuse Parenchymal Lesions of the Liver
10.17.2 Cirrhosis
10.17.3 Differential Diagnosis
10.17.4 Chronic Hepatitis
10.17.5 Acute Hepatitis
10.17.6 Fatty Change
10.17.7 Pyogenic Abscess
10.17.8 Granulomatous Hepatitis
10.18 Amoebic Abscess
10.18.1 Cytology
10.18.2 Cystic Lesions
10.19 Benign Tumours in the Liver
10.19.1 Focal Nodular Hyperplasia
10.19.2 Epidemiology
10.19.3 Clinical Features
10.20 Hepatocellular Adenomas
10.20.1 Epidemiology
10.20.2 Clinical Features
10.20.3 Cytology [12] (Figs. 10.41, 10.42, and 10.43)
10.20.4 Haemangioma of Liver
10.20.5 Biliary Cystadenoma
10.20.6 Hepatic Angiomyolipoma [13]
10.20.7 Cytology
10.21 Mesenchymal Hamartoma of Liver
10.21.1 Cytology [14]
10.21.2 Differential Diagnosis
10.22 Malignant Tumour
10.22.1 Hepatocellular Carcinoma (HCC) [15–17]
10.22.2 Epidemiology
10.22.3 Clinical Features
10.22.4 Aetiology
10.22.5 Key Cytology Features (Figs. 10.44, 10.45, 10.46, 10.47, 10.48, 10.49, 10.50, 10.51, 10.52, and 10.53)
10.23 Variants of HCC
10.23.1 Fibrolamellar Variant of HCC
10.23.2 Key Cytology Features
10.23.3 Clear Cell Variant
10.24 Giant Cell Variant of HCC
10.24.1 HCC with Fatty Change
10.25 Intrahepatic Cholangiocarcinoma
10.25.1 Epidemiology
10.25.2 Clinical Features
10.25.3 Key Cytology Features [18] (Figs. 10.54, 10.55, 10.56, and 10.57)
10.25.4 Differential Diagnosis
10.26 Hepatoblastoma
10.26.1 Epidemiology
10.26.2 Clinical Features
10.26.3 Key Cytological Feature [19, 20] (Figs. 10.60, 10.61, 10.62, 10.63, 10.64, 10.65, and 10.66)
10.26.4 Fetal
10.27 Primary Sarcomas of Liver
10.27.1 Angiosarcoma
10.27.2 Clinical Features
10.27.3 Key Cytology Features
10.27.4 Differential Diagnosis
10.28 Embryonal Sarcoma of the Liver
10.28.1 Epidemiology
10.28.2 Clinical Features
10.28.3 Key Cytology Features [21, 22] (Figs. 10.67, 10.68, 10.69, 10.70 and 10.71)
10.28.4 Metastatic Lesions in Liver [23]
10.28.5 Key Cytology Features (Figs. 10.72, 10.73, 10.74, 10.75, 10.76, 10.77, 10.78, 10.79, 10.80, 10.81, 10.82, 10.83, 10.84, 10.85, 10.86, 10.87, 10.88 and 10.89)
10.28.6 Malignant Lymphoma of the Liver
10.28.7 Spleen
10.28.8 Normal Cytology
10.29 Non-neoplastic Process of the Spleen
10.30 Accumulation of Abnormal Material and Storage Disease
10.31 Neoplasm [24]
10.31.1 Lymphoma
10.31.2 Epidemiology
10.31.3 Key Cytological Features (Fig. 10.96)
10.31.4 Metastatic Tumour
References
11: Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas
11.1 Gall Bladder
11.1.1 Anatomy and Histology
11.1.2 Cytology
11.1.3 Neoplasms
11.2 Gall Bladder Carcinomas
11.2.1 Epidemiology
11.2.2 Clinical Features
11.2.3 Adenocarcinoma
11.2.4 Squamous Cell Carcinoma
11.2.4.1 Key Cytological Features
11.2.5 Adenosquamous Carcinoma [2]
11.2.5.1 Key Cytological Features
11.3 Neuroendocrine Tumours
11.3.1 Epidemiology
11.3.2 Clinical Features
11.3.3 Key Cytological Features [2, 3] (Figs. 11.6 and 11.7)
11.3.3.1 Immunocytochemistry
11.3.4 Neuroendocrine Carcinoma
11.3.5 Small Cell Neuroendocrine Carcinoma
11.3.5.1 Key Cytological Features
11.3.5.2 Immunocytochemistry
11.3.6 Large Cell Neuroendocrine Carcinoma
11.3.6.1 Key Cytological Features
11.3.6.2 Immunocytochemistry
11.3.7 Pancreas
11.3.8 Sampling Technique
11.3.9 Diagnostic Accuracy [4–7]
11.4 Normal Anatomy and Histology of Pancreas
11.4.1 Histology
11.4.2 Cytology
11.4.2.1 Pancreatic Acinar Cells (Fig. 11.8)
11.4.2.2 Pancreatic Ductal Cells (Fig. 11.9)
11.4.3 Cysts in Pancreas [8]
11.4.4 Congenital Cyst
11.5 Acquired Cyst
11.5.1 Pancreatic Pseudocyst
11.6 Pancreatic True Cyst
11.6.1 Differential Diagnosis
11.6.2 Pancreatitis
11.6.3 Key Cytology Features (Fig. 11.11)
11.7 Chronic Pancreatitis
11.7.1 Key Cytology Features
11.7.2 Differential Diagnosis
11.8 Neoplasms of Pancreas
11.8.1 Serous Cystadenoma
11.8.2 Clinical Features
11.8.3 Key Cytology Features
11.9 Mucinous Cystic Neoplasia [10, 11]
11.9.1 Epidemiology
11.9.2 Clinical Features
11.9.3 Key Cytology Features (Figs. 11.13, 11.14, and 11.15)
11.9.4 Differential Diagnosis
11.10 Malignant Epithelial Neoplasms
11.10.1 Ductal Adenocarcinoma
11.10.2 Epidemiology
11.10.3 Clinical Features
11.10.4 Key Cytological Features [12, 13] (Figs. 11.16, 11.17, 11.18, 11.19, and 11.20)
11.10.5 Differential Diagnosis
11.11 Variants of Ductal Carcinoma
11.11.1 Adenosquamous Carcinoma [14]
11.11.2 Key Cytological Features
11.11.3 Signet Ring Carcinoma [15]
11.11.4 Key Cytological Features
11.11.5 Undifferentiated Carcinoma with Osteoclastic Giant Cell
11.12 Anaplastic Carcinoma
11.12.1 Epidemiology
11.12.2 Key Cytological Features (Figs. 11.21 and 11.22)
11.13 Small Cell Carcinoma [17]
11.13.1 Key Cytological Features (Figs. 11.23 and 11.24)
11.14 Pancreatic Acinar Carcinoma
11.14.1 Epidemiology
11.14.2 Clinical Features
11.14.3 Key Cytological Features [18, 19] (Figs. 11.25, 11.26, 11.27, and 11.28)
11.14.4 Differential Diagnosis
11.15 Solid Pseudopapillary Neoplasm of the Pancreas
11.15.1 Epidemiology
11.15.2 Clinical Features
11.15.3 Key Cytological Features [20, 21] (Figs. 11.29, 11.30, 11.31, 11.32, 11.33, 11.34, and 11.35)
11.15.4 Differential Diagnosis
11.15.5 Pancreaticoblastoma
11.15.6 Key Cytological Features
11.16 Neuroendocrine Tumour
11.16.1 Pancreatic Endocrine Tumour (Islet Cell Tumour of Pancreas)
11.16.1.1 Epidemiology
11.16.2 Clinical Features
11.16.3 Key Cytological Features [22–24] (Figs. 11.36, 11.37, 11.38, 11.39, and 11.40)
11.16.4 Differential Diagnosis
11.17 Metastatic Tumours in the Pancreas
11.17.1 Detection
11.18 Pancreatic Lymphoma [25] (Fig. 11.42)
References
12: Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland
12.1 Normal Cells
12.1.1 Renal Tubular Cells (Fig. 12.1)
12.1.2 Glomeruli
12.2 Renal Cyst
12.2.1 Occurrence
12.2.2 Clinical Features
12.2.3 Key Cytological Features (Fig. 12.2)
12.2.3.1 Differential Diagnosis
12.3 Xanthogranulomatous Inflammation
12.3.1 Clinical Features
12.3.2 Key Cytological Features (Figs. 12.3 and 12.4)
12.3.3 Differential Diagnosis
12.3.4 Renal Tumours
12.4 Benign Tumours of the Kidney
12.4.1 Angiomyolipoma
12.4.2 Epidemiology
12.4.3 Clinical Features
12.4.4 Key Cytological Features [6, 7] (Figs. 12.6, 12.7, 12.8, 12.9, and 12.10)
12.4.5 Immunocytochemistry (Figs. 12.11 and 12.12)
12.4.6 Differential Diagnosis
12.5 Metanephric Adenoma
12.5.1 Epidemiology
12.5.2 Clinical Features
12.5.3 Key Cytological Features [8]
12.5.4 Differential Diagnosis
12.6 Renal Oncocytoma [9]
12.6.1 Epidemiology
12.6.2 Clinical Features
12.6.3 Key Cytological Features (Figs. 12.13 and 12.14)
12.6.4 Differential Diagnosis (Fig. 12.15)
12.7 Renal Cell Carcinoma [ 10–13]
12.7.1 Epidemiology
12.7.2 Clinical Features
12.7.3 Key Cytological Features (Figs. 12.16, 12.17, 12.18, 12.19, and 12.20)
12.7.3.1 Clear Cell RCC
12.7.4 Immunocytochemistry (Figs. 12.21 and 12.22)
12.7.5 Differential Diagnosis
12.7.6 Papillary Carcinoma
12.8 Chromophobe Type
12.8.1 Sarcomatoid Type
12.8.2 Collecting Duct Type
12.8.3 Differential Diagnosis of RCC
12.9 Urothelial Carcinoma
12.9.1 Epidemiology
12.9.2 Clinical Features
12.9.3 Key Cytological Features (Figs. 12.23, 12.24, and 12.25)
12.9.4 Differential Diagnosis
12.9.5 Medullary Carcinoma
12.9.6 Epidemiology
12.9.7 Clinical Features
12.9.8 Key Cytological Features
12.9.9 Differential Diagnosis
12.10 Metastatic Tumours in Kidney [14]
12.10.1 Diagnosis
12.10.2 Renal Lymphoma
12.11 Paediatric Kidney Tumours
12.11.1 Nephroblastoma
12.11.2 Epidemiology
12.11.3 Clinical Features
12.11.4 Key Cytological Features [15, 16] (Figs. 12.26, 12.27, 12.28, and 12.29)
12.11.5 Blastemal Cells
12.11.6 Epithelial Cells
12.11.7 Mesenchymal Cells
12.11.8 Anaplastic Wilms’ Tumour
12.11.9 Differential Diagnosis
12.12 Congenital Mesoblastic Nephroma (CMN)
12.12.1 Epidemiology
12.12.2 Clinical Features
12.12.3 Key Cytological Features [17] (Figs. 12.30, 12.31, and 12.32)
12.12.4 Differential Diagnosis
12.13 Rhabdoid Tumor [18]
12.13.1 Epidemiology
12.13.2 Clinical Features
12.13.3 Key Cytological Features (Figs. 12.33 and 12.34)
12.13.4 Differential Diagnosis
12.14 Clear Cell Sarcoma
12.14.1 Epidemiology
12.14.2 Clinical Features
12.14.3 Key Cytological Features [19] (Figs. 12.35, 12.36, and 12.37)
12.15 Adrenal Gland
12.15.1 Indications
12.15.2 Technical Issue
12.15.3 Complications
12.15.4 Anatomy of the Adrenal Gland
12.15.5 Histology of Adrenal Gland
12.16 Benign Lesions of the Adrenal Gland
12.16.1 Adrenal Cyst
12.16.2 Pseudocyst
12.16.3 Epithelial Cyst
12.16.4 Endothelial Cyst
12.16.5 Parasitic Cyst
12.16.6 Key Cytological Features
12.17 Adrenal Myelolipoma
12.17.1 Epidemiology
12.17.2 Clinical Features
12.17.3 Key Cytological Features [23]
12.17.4 Differential Diagnosis
12.18 Adrenocortical Adenoma
12.18.1 Epidemiology
12.18.2 Clinical Features
12.18.3 Key Cytological Features
12.19 Adrenocortical Carcinoma
12.19.1 Epidemiology
12.19.2 Clinical Features
12.19.3 Adrenal Adenoma Versus Adrenal Cortical Carcinoma
12.19.4 Key Cytological Features [24] (Figs. 12.38, 12.39, and 12.40)
12.19.5 Differential Diagnosis
12.20 Pheochromocytoma
12.20.1 Epidemiology
12.20.2 Clinical Features
12.20.3 Key Cytological Features [20, 25] (Figs. 12.41, 12.42, 12.43, 12.44, and 12.45)
12.20.4 Differential Diagnosis
12.21 Neuroblastoma of the Adrenal Gland
12.21.1 Epidemiology
12.21.2 Clinical Features
12.21.3 Key Cytological Features [26] (Figs. 12.46, 12.47, 12.48, and 12.49)
12.22 Metastatic Tumors [22] (Fig. 12.51)
12.22.1 Diagnosis
12.22.2 Differential Diagnosis
References
13: Fine Needle Aspiration Cytology of the Gonads
13.1 Ovary
13.1.1 Indications of Ovarian FNAC
13.1.1.1 Complications
13.1.1.2 Procurement of Sample
13.2 Benign Lesions of the Ovary
13.2.1 Non-neoplastic Cyst [1]
13.2.2 Key Cytological Features
13.2.3 Differential Diagnosis
13.2.4 Corpus Luteal Cyst
13.2.5 Key Cytological Features
13.2.6 Endometriotic Cyst
13.2.7 Key Cytological Features (Figs. 13.1, 13.2, 13.3, and 13.4)
13.3 Serous Adenoma and Adenocarcinoma of Ovary [2, 3]
13.3.1 Serous Cystadenoma of Ovary
13.3.1.1 Epidemiology
13.3.2 Clinical Features
13.3.3 Key Cytological Features
13.4 Serous Adenocarcinoma
13.4.1 Epidemiology
13.4.2 Genetic Profile
13.4.3 Clinical Features
13.4.4 Key Cytological Features (Figs. 13.5, 13.6, 13.7, 13.8, and 13.9)
13.5 Mucinous Cystadenoma and Cystadenocarcinoma [3, 4]
13.5.1 Mucinous Cystadenoma
13.5.1.1 Epidemiology
13.5.2 Clinical Features
13.5.3 Key Cytological Features
13.6 Mucinous Cystadenocarcinoma
13.6.1 Epidemiology
13.6.2 Clinical Features
13.6.3 Key Cytological Features (Figs. 13.14, 13.15, 13.16, and 13.17)
13.6.4 Differential Diagnosis
13.7 Endometrioid Carcinoma [3]
13.7.1 Epidemiology
13.7.2 Clinical Features
13.7.3 Key Cytological Features
13.8 Clear Cell Carcinoma
13.8.1 Epidemiology
13.8.2 Clinical Features
13.8.3 Key Cytological Features (Figs. 13.18, 13.19, 13.20, and 13.21)
13.8.4 Differential Diagnosis
13.8.5 Germ Cell Tumour
13.9 Mature Teratoma
13.9.1 Epidemiology
13.9.2 Clinical Features
13.9.3 Key Cytological Features
13.10 Immature Teratoma
13.10.1 Epidemiology
13.10.2 Clinical Features
13.10.3 Key Cytological Features (Figs. 13.22 and 13.23)
13.11 Carcinoid Tumours of the Ovary
13.11.1 Epidemiology
13.11.2 Clinical Features
13.11.3 Key Cytological Features [5] (Figs. 13.24 and 13.25)
13.11.4 Differential Diagnosis
13.12 Dysgerminoma
13.12.1 Epidemiology
13.12.2 Clinical Features
13.12.3 Key Cytological features [6] (Figs. 13.26, 13.27, 13.28, 13.29, 13.30, and 13.31)
13.12.4 Differential Diagnosis
13.13 Yolk Sac Tumour
13.13.1 Epidemiology
13.13.2 Clinical Features
13.13.3 Key Cytological Features
13.14 Sex Cord-Stromal Tumour
13.14.1 Granulosa Cell Tumour [3]
13.14.1.1 Epidemiology
13.14.2 Molecular Genetics
13.14.3 Clinical Features
13.14.4 Key Cytological Features (Figs. 13.32, 13.33, 13.34, and 13.35)
13.14.5 Differential Diagnosis
13.15 Sertoli Cell Tumour
13.15.1 Clinical Features
13.15.2 Key Cytological Features [3, 7] (Figs. 13.36 and 13.37)
13.16 Fibroma and Thecoma
13.16.1 Key Cytological Features
13.17 Metastatic Tumours in the Ovary
13.17.1 Key Cytological Features
13.17.2 Indicators of Metastasis
13.18 Testis
13.18.1 Indications of FNAC
13.19 Anatomy and Histology of Testis
13.19.1 Histology
13.19.2 Normal Cells of Testis FNAC (Fig. 13.38)
13.19.2.1 Sertoli Cells
13.19.3 Primary Spermatocytes
13.19.4 Peritesticular Lesions
13.19.5 Hydrocele
13.19.6 Key Cytological Features (Fig. 13.39)
13.20 Inflammation
13.20.1 Acute Epididymitis
13.20.2 Key Cytological Features
13.21 Chronic Epididymitis
13.21.1 Clinical Features
13.21.2 Key Cytological Features
13.22 Tuberculous Epididymitis [8]
13.22.1 Key Cytological Features (Fig. 13.40)
13.22.2 Filarial Inflammation
13.22.2.1 Cytology (Fig. 13.41)
13.23 Adenomatoid Tumour [8, 9]
13.23.1 Epidemiology
13.23.2 Clinical Features
13.23.3 Key Cytological Features
13.24 Spermatocytic Granuloma [8]
13.24.1 Clinical Features
13.24.2 Key Cytological Features (Figs. 13.42 and 13.43)
13.24.3 Male Infertility [10–12]
13.24.4 Sertoli Cell-Only Syndrome (Fig. 13.44)
13.25 Neoplasm of Testis
13.25.1 Seminoma [14, 15]
13.25.2 Epidemiology
13.25.3 Clinical Features
13.25.4 Key Cytological Features of Classical Seminoma (Figs. 13.46, 13.47, 13.48, 13.49, and 13.50)
13.26 Spermatocytic Seminoma [16]
13.26.1 Key Cytological Features of Spermatocytic Seminoma
13.26.2 Differential Diagnosis
13.27 Embryonal Carcinoma
13.27.1 Epidemiology
13.27.2 Clinical Features
13.27.3 Key Cytological Features [17] (Figs. 13.51, 13.52, and 13.53)
13.28 Choriocarcinoma
13.28.1 Epidemiology
13.28.2 Clinical Feature
13.28.3 Key Cytological Features
13.29 Other Tumours of the Testis
13.29.1 Leydig Cell Tumour
13.29.1.1 Epidemiology
13.29.2 Clinical Features
13.29.3 Key Cytological Features
13.30 Non-Hodgkin Lymphoma [18]
13.30.1 Leukemic Infiltration [19]
References
14: Fine Needle Aspiration Cytology of the Soft Tissue Lesions
14.1 Specimen Collection and Ancillary Techniques
14.2 Ancillary Techniques
14.2.1 Immunocytochemistry
14.2.2 Flow Cytometry
14.2.3 Molecular Genetics
14.2.4 Electron Microscopy
14.2.5 Reporting Terminology
14.2.6 Malignancy
14.3 Classification of Soft Tissue Tumours
14.4 Tumours of Adipocytes [10]
14.4.1 Benign Tumours
14.4.1.1 Lipoma
14.4.2 Clinical Feature
14.4.3 Key Cytological Features (Fig. 14.2)
14.5 Angiolipoma
14.5.1 Epidemiology
14.5.2 Clinical Features
14.5.3 Key Cytological Features (Fig. 14.3)
14.6 Spindle Cell Lipoma
14.6.1 Epidemiology
14.6.2 Clinical Features
14.6.3 Key Cytological Features
14.7 Pleomorphic Lipoma
14.7.1 Key Cytological Features (Figs. 14.4 and 14.5)
14.7.2 Differential Diagnosis
14.8 Hibernoma
14.8.1 Epidemiology
14.8.2 Clinical Features
14.8.3 Key Cytological Features
14.8.4 Differential Diagnosis
14.9 Myelolipoma
14.9.1 Key Cytological Features
14.10 Liposarcomas
14.10.1 Epidemiology
14.10.2 Clinical Features
14.10.3 Key Cytological Features [11] (Figs. 14.6 and 14.7)
14.10.4 Differential Diagnosis
14.11 Myxoid Liposarcoma
14.11.1 Epidemiology
14.11.2 Clinical Features
14.11.3 Key Cytological Features [12] (Figs. 14.8,14.9, and 14.10)
14.11.4 Differential Diagnosis
14.12 Pleomorphic Liposarcoma
14.12.1 Epidemiology
14.12.2 Clinical Features
14.12.3 Key Cytological Features [10] (Figs. 14.11 and 14.12)
14.12.4 Differential Diagnosis
14.13 Round Cell Liposarcoma
14.13.1 Key Cytological Features
14.14 Fibroblastic/Myofibroblastic Tumours
14.14.1 Benign
14.14.1.1 Nodular Fasciitis
14.14.2 Clinical Features
14.14.3 Key Cytological Features [13] (Fig. 14.13)
14.15 Myositis Ossificans
14.15.1 Epidemiology
14.15.2 Clinical Features
14.15.3 Key Cytological Features [14] (Figs. 14.14, 14.15, and 14.16)
14.16 Solitary Fibrous Tumour
14.16.1 Epidemiology
14.16.2 Clinical Features
14.16.3 Key Cytological Features [15] (Figs. 14.17, 14.18, and 14.19)
14.16.4 Malignant Solitary Fibrous Tumour
14.17 Dermatofibrosarcoma Protuberans
14.17.1 Key Cytological Features (Figs. 14.20 and 14.21)
14.18 Myofibroblastoma
14.18.1 Epidemiology
14.18.2 Clinical Features
14.18.3 Key Cytological Features [16]
14.19 Fibrosarcoma
14.19.1 Epidemiology
14.19.2 Clinical Features
14.19.3 Key Cytological Features (Figs. 14.22, 14.23, and 14.24)
14.20 So-Called “Fibrohistiocytic Tumours”
14.20.1 Giant Cell Tumour of Tendon Sheath
14.20.2 Epidemiology
14.20.3 Clinical Features
14.20.4 Key Cytological Features [17] (Figs. 14.25, 14.26, 14.27, and 14.28)
14.21 Pleomorphic Malignant Fibrous Histiocytoma
14.21.1 Epidemiology
14.21.2 Clinical Features
14.21.3 Key Cytological Features
14.21.4 Differential Diagnosis
14.22 Tumours of Nerve Sheath
14.22.1 Benign Peripheral Nerve Sheath Tumour
14.22.1.1 Schwannoma and Neurofibroma
14.22.2 Key Cytological Feature [18] (Figs. 14.29, 14.30, and 14.31)
14.23 Malignant Peripheral Nerve Sheath Tumour
14.23.1 Epidemiology
14.23.2 Clinical Features
14.23.3 Key Cytological Feature [19] (Figs. 14.32, 14.33, 14.34, 14.35, and 14.36)
14.24 Tumours of Muscle Origin
14.24.1 Rhabdomyoma
14.24.2 Epidemiology
14.24.3 Clinical Features
14.24.4 Key Cytological Feature [20] (Figs. 14.37 and 14.38)
14.25 Rhabdomyosarcoma [21, 22]
14.25.1 Embryonal Rhabdomyosarcoma
14.25.1.1 Epidemiology
14.25.2 Clinical Features
14.25.3 Key Cytological Feature (Figs. 14.39, 14.40, 14.41, 14.42, and 14.43)
14.26 Alveolar Rhabdomyosarcoma
14.26.1 Epidemiology
14.26.2 Clinical Features
14.26.3 Key Cytological Features
14.27 Pleomorphic Rhabdomyosarcoma
14.27.1 Epidemiology
14.27.2 Clinical Features
14.27.3 Key Cytological Features
14.28 Leiomyosarcomas
14.28.1 Epidemiology
14.28.2 Clinical Features
14.28.3 Key Cytological Feature [23, 24] (Figs. 14.44 and 14.45)
14.29 Tumour of Vascular Origin
14.29.1 Glomus Tumour [25]
14.29.2 Epidemiology
14.29.3 Clinical Features
14.29.4 Key Cytological Feature
14.30 Haemangioma
14.30.1 Clinical Features
14.30.2 Key Cytological Features
14.31 Angiosarcoma [26]
14.31.1 Epidemiology
14.31.2 Clinical Features
14.31.3 Key Cytological Features
14.32 Tumours of Uncertain Histogenesis
14.32.1 Synovial Sarcoma
14.32.2 Epidemiology
14.32.3 Clinical Features
14.32.4 Key Cytological Features [27] (Figs. 14.46, 14.47, 14.48, 14.49, 14.50, 14.51, and 14.52)
14.33 Clear Cell Sarcoma (CCS)
14.33.1 Epidemiology
14.33.2 Clinical Features
14.33.3 Key Cytological Features [28, 29] (Figs. 14.53, 14.54, 14.55, 14.56, and 14.57)
14.34 Epithelioid Sarcoma
14.34.1 Epidemiology
14.34.2 Clinical Features
14.34.3 Key Cytological Features [30] (Figs. 14.58, 14.59, 14.60, and 14.61)
14.35 Alveolar Soft Part Sarcoma
14.35.1 Epidemiology
14.35.2 Clinical Features
14.35.3 Key Cytological Features [31]
14.36 Granular Cell Tumour
14.36.1 Epidemiology
14.36.2 Clinical Features
14.36.3 Key Cytological Features [32]
References
15: Fine Needle Aspiration Cytology of the Bone
15.1 Infection
15.1.1 Osteomyelitis
15.2 Neoplastic Lesions of Bone
15.2.1 Bone Forming Tumour
15.2.1.1 Osteoblastoma
15.2.2 Key Cytological Features [6]
15.2.3 Osteoid Osteoma
15.2.4 Clinical Feature
15.2.5 Key Cytological Features
15.3 Osteosarcoma
15.3.1 Epidemiology
15.3.2 Clinical Features
15.3.3 Key Cytological Features [6, 7] (Figs. 15.5, 15.6, 15.7, 15.8, 15.9, 15.10, and 15.11)
15.3.4 Conventional Osteosarcomas Are of Three Types
15.3.5 Differential Diagnosis
15.4 Cartilage Forming Tumour
15.4.1 Chondroma
15.4.2 Epidemiology
15.4.3 Clinical Features
15.4.4 Key Cytology Features (Figs. 15.12 and 15.13)
15.5 Chondroblastoma
15.5.1 Epidemiology
15.5.2 Clinical Features
15.5.3 Key Cytology Features [8, 9] (Figs. 15.14, 15.15, 15.16, 15.17, 15.18, 15.19, and 15.20)
15.5.4 Differential Diagnosis
15.6 Chondromyxoid Fibroma
15.6.1 Epidemiology
15.6.2 Clinical Features
15.6.3 Key Cytology Features
15.6.4 Differential Diagnosis
15.7 Chondrosarcoma
15.7.1 Epidemiology
15.7.2 Clinical Features
15.7.3 Key Cytology Features [10–15] (Figs. 15.21, 15.22, 15.23, and 15.24)
15.7.4 Differential Diagnosis
15.8 Variants of CHS
15.8.1 Mesenchymal Chondrosarcoma
15.8.1.1 Epidemiology
15.8.2 Clinical Features
15.9 Clear Cell Chondrosarcoma
15.9.1 Epidemiology
15.9.2 Clinical Features
15.9.3 Key Cytology Features
15.10 Dedifferentiated Chondrosarcoma
15.10.1 Epidemiology
15.10.2 Clinical Features
15.10.3 Key Cytology Features
15.11 Giant Cell Tumour of Bone
15.11.1 Epidemiology
15.11.2 Clinical Features
15.11.3 Key Cytology Features [16] (Figs. 15.26, 15.27, 15.28, and 15.29)
15.11.4 Differential Diagnosis
15.12 Chordoma
15.12.1 Epidemiology
15.12.2 Clinical Features
15.12.3 Key Cytology Features [17, 18] (Figs. 15.30, 15.31, 15.32, and 15.33)
15.12.4 Differential Diagnosis
15.13 Ewing’s Sarcoma (EWS)/Peripheral Neuroectodermal Tumour (PNET) [19–22]
15.13.1 Epidemiology
15.13.2 Clinical Features
15.13.3 Key Cytology Features (Figs. 15.34, 15.35, 15.36, and 15.37)
15.13.4 Differential Diagnosis
15.14 Non-Hodgkin Lymphoma [23]
15.14.1 Epidemiology
15.14.2 Types (Figs. 15.39 and 15.40)
15.15 Plasma Cell Neoplasm [24, 25]
15.15.1 Epidemiology
15.15.2 Clinical Features
15.15.3 Key Cytology Features (Figs. 15.42, 15.43, and 15.44)
15.15.4 Differential Diagnosis
15.16 Langerhans Cell Histiocytosis
15.16.1 Epidemiology
15.16.2 Key Cytology Features [27, 28] (Figs. 15.45, 15.46, 15.47, and 15.48)
15.16.3 Differential Diagnosis
15.17 Metastatic Carcinoma
15.17.1 Epidemiology
15.17.2 Clinical Features
15.17.3 Key Cytological Features [29] (Figs. 15.49, 15.50, 15.51, 15.52, 15.53, 15.54, and 15.55)
15.18 Other Bone Lesions
15.18.1 Aneurysmal Bone Cyst [30]
15.18.2 Key Cytological Features (Fig. 15.56)
15.19 Adamantinoma
15.19.1 Epidemiology
15.19.2 Key Cytological Features [31] (Figs. 15.57, 15.58, 15.59, and 15.60)
15.19.3 Differential Diagnosis
References
16: Fine Needle Aspiration Cytology of the Skin Lesions
16.1 Non-neoplastic Lesions of the Skin
16.1.1 Inflammation
16.1.1.1 Viral Infection
16.1.2 Fungal Infection
16.1.3 Bacterial Infection
16.1.3.1 Parasitic Infection
16.1.4 Dermal Leishmaniasis [3]
16.1.5 Cysticercosis [4]
16.1.6 Microfilariae Infection [5]
16.2 Non-neoplastic Benign Lesions of the Skin
16.2.1 Tumoral Calcinosis [6]
16.2.2 Sarcoidosis
16.2.3 Ganglionic Cyst
16.2.4 Cytology Smear (Fig. 16.10)
16.3 Endometriosis
16.3.1 Amyloidosis
16.3.2 Cytology [8]
16.4 Epidermal Inclusion Cyst
16.4.1 Cytology (Figs. 16.15, 16.16, and 16.17)
16.5 Neoplastic Lesions of the Skin
16.5.1 Benign Tumour of Skin Adnexa
16.5.1.1 Pilomatrixoma [9, 10]
16.5.2 Epidemiology
16.5.3 Key Cytological Features (Figs. 16.18, 16.19, 16.20, 16.21, and 16.22)
16.5.4 Differential Diagnosis
16.6 Chondroid Syringoma
16.6.1 Epidemiology
16.6.2 Key Cytological Features [11] (Figs. 16.23, 16.24, 16.25, 16.26, and 16.27)
16.7 Cylindroma
16.7.1 Epidemiology
16.7.2 Location
16.7.3 Clinical Features
16.7.4 Key Cytological Features [12] (Figs. 16.28, 16.29, 16.30, 16.31, 16.32, and 16.33)
16.8 Eccrine Spiradenoma
16.8.1 Epidemiology
16.8.2 Clinical Features
16.8.3 Key Cytological Features [13]
16.9 Hidradenoma
16.9.1 Epidemiology
16.9.2 Key Cytological Features [10, 14] (Figs. 16.34, 16.35, 16.36, and 16.37)
16.10 Syringocystadenoma Papilliferum
16.10.1 Epidemiology
16.10.2 Clinical Features
16.10.3 Key Cytological Features [15] (Figs. 16.38, 16.39, and 16.40)
16.11 Malignant Tumours of the Skin
16.11.1 Basal Cell Carcinoma
16.11.2 Epidemiology
16.11.3 Clinical Features
16.11.4 Key Cytological Features [10, 14] (Figs. 16.41, 16.42, and 16.43)
16.12 Sebaceous Carcinoma
16.12.1 Epidemiology
16.12.2 Key Cytological Features [16] (Figs. 16.44, 16.45, 16.46, and 16.47)
16.13 Malignant Melanoma
16.13.1 Epidemiology
16.13.2 Key Cytological Features [17] (Figs. 16.48, 16.49, and 16.50)
16.14 Squamous Cell Carcinoma
16.14.1 Epidemiology
16.14.2 Clinical Features
16.14.3 Key Cytological Features (Figs. 16.51, 16.52, 16.53, and 16.54)
16.15 Malignant Sweat Gland Tumour
16.15.1 Key Cytological Features [10]
16.16 Merkel Cell Carcinoma
16.16.1 Epidemiology
16.16.2 Clinical Features
16.16.3 Key Cytological Features [18, 19] (Figs. 16.55, 16.56, 16.57, and 16.58)
16.17 Metastasis
16.17.1 Key Cytological Features (Figs. 16.59, 16.60, 16.61, 16.62, and 16.63)
16.17.2 Hematopoietic Malignancy
References
17: Review of the Cases and Self-Assessment
17.1 Answers

Citation preview

Pranab Dey

Color Atlas of Fine Needle Aspiration Cytology

123

Color Atlas of Fine Needle Aspiration Cytology

Pranab Dey

Color Atlas of Fine Needle Aspiration Cytology

Pranab Dey Department of Cytology and Gynecologic Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

ISBN 978-981-15-8032-1    ISBN 978-981-15-8033-8 (eBook) https://doi.org/10.1007/978-981-15-8033-8 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore

Contents

1 Introduction and Basic Techniques of Aspiration Cytology in Superficial and Deep Lesions��������������������������������������������������������������������������������������������������������   1 1.1 Advantages�����������������������������������������������������������������������������������������������������������   1 1.2 Needle Tract Seeding�������������������������������������������������������������������������������������������   1 1.3 The Basic Technique of FNAC ���������������������������������������������������������������������������   1 1.4 Post FNAC�����������������������������������������������������������������������������������������������������������   3 1.4.1 Fine-Needle Sampling Technique�����������������������������������������������������������   3 1.4.2 Fixatives���������������������������������������������������������������������������������������������������   4 1.4.3 Staining ���������������������������������������������������������������������������������������������������   4 1.5 Deep-Seated FNAC���������������������������������������������������������������������������������������������   4 1.5.1 Indications of Deep-Seated Lesions��������������������������������������������������������   4 1.6 USG Guided FNAC���������������������������������������������������������������������������������������������   5 1.7 CT Guided FNAC �����������������������������������������������������������������������������������������������   5 1.8 Endoscopic Ultrasound Guided���������������������������������������������������������������������������   5 1.9 Magnetic Resonance Image Guided �������������������������������������������������������������������   5 1.10 Mammographic Guided���������������������������������������������������������������������������������������   6 References���������������������������������������������������������������������������������������������������������������������   6 2 Interpretation of Fine Needle Aspiration Cytology Smear�������������������������������������   7 2.1 Malignant Cells���������������������������������������������������������������������������������������������������   7 2.1.1 Cell�����������������������������������������������������������������������������������������������������������   7 2.1.2 Nucleus ���������������������������������������������������������������������������������������������������   7 2.2 Interpretation of FNAC Smear�����������������������������������������������������������������������������   9 2.3 Evaluation of the Cytological Features���������������������������������������������������������������   9 2.3.1 Cellular Arrangement�������������������������������������������������������������������������������  10 2.4 Individual Cells ���������������������������������������������������������������������������������������������������  12 2.4.1 Cell Shape �����������������������������������������������������������������������������������������������  12 2.4.2 Cytoplasm �����������������������������������������������������������������������������������������������  14 2.4.3 Cytoplasmic Area�������������������������������������������������������������������������������������  15 2.4.4 Vacuolation in Cytoplasm �����������������������������������������������������������������������  15 2.5 Nucleus ���������������������������������������������������������������������������������������������������������������  17 2.5.1 Nuclear Pleomorphism����������������������������������������������������������������������������  17 2.5.2 Nuclear Margin ���������������������������������������������������������������������������������������  18 2.5.3 Nucleoli���������������������������������������������������������������������������������������������������  18 2.5.4 Background of the Smear������������������������������������������������������������������������  19 2.5.5 False-Positive Cases���������������������������������������������������������������������������������  23 2.6 False-Negative Smear �����������������������������������������������������������������������������������������  25 References���������������������������������������������������������������������������������������������������������������������  25 3 Aspiration Cytology of Head, Neck and Orbital Lesions���������������������������������������  27 3.1 Cysts in the Neck Region�������������������������������������������������������������������������������������  27 3.1.1 Branchial Cyst�����������������������������������������������������������������������������������������  27 3.1.2 Thyroglossal Cyst �����������������������������������������������������������������������������������  28 v

vi

Contents

3.1.3 Cystic Hygroma���������������������������������������������������������������������������������������  28 3.1.4 Acquired Cyst �����������������������������������������������������������������������������������������  29 3.1.5 Mucocele�������������������������������������������������������������������������������������������������  30 3.2 Lymph Node Lesion in Head–Neck Region �������������������������������������������������������  31 3.2.1 Difficulties�����������������������������������������������������������������������������������������������  31 3.3 Paraganglioma�����������������������������������������������������������������������������������������������������  33 3.3.1 Carotid Body Tumour �����������������������������������������������������������������������������  34 3.3.2 Differential Diagnosis �����������������������������������������������������������������������������  35 3.3.3 Nasopharyngeal Carcinoma (NPC) ��������������������������������������������������������  35 3.3.4 Parathyroid Neoplasm�����������������������������������������������������������������������������  38 3.3.5 Meningioma���������������������������������������������������������������������������������������������  40 3.3.6 Olfactory Neuroblastoma�������������������������������������������������������������������������  40 3.4 Lesions in the Base of the Skull���������������������������������������������������������������������������  42 3.4.1 Orbital lesion�������������������������������������������������������������������������������������������  43 3.4.2 Lesions of the Eyelid�������������������������������������������������������������������������������  43 3.4.3 Tumours of the Eyelid�����������������������������������������������������������������������������  44 3.5 Lacrimal gland�����������������������������������������������������������������������������������������������������  46 3.5.1 Pleomorphic Adenoma�����������������������������������������������������������������������������  46 3.5.2 Adenoid Cystic Carcinoma (ADC)���������������������������������������������������������  46 3.5.3 Mucoepidermoid Carcinoma�������������������������������������������������������������������  48 3.5.4 Intraorbital Tumours �������������������������������������������������������������������������������  48 3.5.5 Malignant melanoma�������������������������������������������������������������������������������  49 3.5.6 Rhabdomyosarcoma���������������������������������������������������������������������������������  49 3.5.7 Acute Leukaemia Infiltration�������������������������������������������������������������������  50 3.5.8 Lymphoma�����������������������������������������������������������������������������������������������  51 3.5.9 Metastatic Malignancy�����������������������������������������������������������������������������  51 References���������������������������������������������������������������������������������������������������������������������  52 4 Aspiration Cytology of Salivary Gland���������������������������������������������������������������������  55 4.1 The Major Advantages of FNAC�������������������������������������������������������������������������  55 4.1.1 Complications of FNAC �������������������������������������������������������������������������  55 4.1.2 Anatomy and Histology of the Salivary Glands �������������������������������������  55 4.1.3 Parotid Gland�������������������������������������������������������������������������������������������  55 4.1.4 Submandibular Gland �����������������������������������������������������������������������������  55 4.1.5 Sublingual Gland�������������������������������������������������������������������������������������  55 4.1.6 Cytology of the Salivary Gland���������������������������������������������������������������  56 4.2 Diagnostic Accuracy �������������������������������������������������������������������������������������������  57 4.2.1 Causes of False-Positive FNAC���������������������������������������������������������������  57 4.2.2 Causes of False-Negative FNAC�������������������������������������������������������������  57 4.2.3 The Major Difficulties in the Diagnosis��������������������������������������������������  58 4.2.4 FNAC Techniques and Special Consideration�����������������������������������������  58 4.3 Non-neoplastic Lesions���������������������������������������������������������������������������������������  58 4.3.1 Other Lesions�������������������������������������������������������������������������������������������  59 4.3.2 Sialadenitis�����������������������������������������������������������������������������������������������  60 4.3.3 Chronic Sialadenitis���������������������������������������������������������������������������������  60 4.3.4 Lymphoepithelial Sialadenitis�����������������������������������������������������������������  60 4.3.5 Clinical Features �������������������������������������������������������������������������������������  61 4.3.6 Granulomatous Sialadenitis���������������������������������������������������������������������  62 4.4 Neoplastic Lesions�����������������������������������������������������������������������������������������������  63 4.5 The Milan System of Reporting the Salivary Gland Tumours�����������������������������  63 4.6 Benign Neoplasm�������������������������������������������������������������������������������������������������  63 4.6.1 Pleomorphic Adenoma�����������������������������������������������������������������������������  63

Contents

vii

4.7 Basal Cell Adenoma (BCA) �������������������������������������������������������������������������������  66 4.7.1 Histopathology�����������������������������������������������������������������������������������������  67 4.7.2 Differential Diagnosis �����������������������������������������������������������������������������  70 4.8 Warthin’s Tumour �����������������������������������������������������������������������������������������������  70 4.8.1 Oncocytoma���������������������������������������������������������������������������������������������  72 4.8.2 Histopathology�����������������������������������������������������������������������������������������  72 4.8.3 Myoepithelioma���������������������������������������������������������������������������������������  74 4.8.4 Localization���������������������������������������������������������������������������������������������  75 4.8.5 Histopathology�����������������������������������������������������������������������������������������  75 4.8.6 Cell Types �����������������������������������������������������������������������������������������������  75 4.9 Myoepithelial Carcinoma�������������������������������������������������������������������������������������  76 4.9.1 Adenoid Cystic Carcinoma (ADC) ���������������������������������������������������������  76 4.9.2 Molecular Genetics ���������������������������������������������������������������������������������  77 4.9.3 Histopathology�����������������������������������������������������������������������������������������  77 4.9.4 Immunocytochemistry�����������������������������������������������������������������������������  80 4.9.5 Molecular Pathology�������������������������������������������������������������������������������  80 4.10 Acinic Cell Carcinoma�����������������������������������������������������������������������������������������  80 4.10.1 Histopathology�����������������������������������������������������������������������������������������  80 4.10.2 Differential Diagnosis �����������������������������������������������������������������������������  81 4.10.3 Mucoepidermoid Carcinoma�������������������������������������������������������������������  82 4.10.4 Histopathology�����������������������������������������������������������������������������������������  83 4.11 Immunocytochemistry�����������������������������������������������������������������������������������������  85 4.11.1 Differential Diagnosis �����������������������������������������������������������������������������  85 4.12 Epithelial Myoepithelial Carcinoma �������������������������������������������������������������������  85 4.12.1 Epidemiology�������������������������������������������������������������������������������������������  85 4.12.2 Histopathology�����������������������������������������������������������������������������������������  85 4.13 Polymorphous Low-Grade Adenocarcinoma�������������������������������������������������������  88 4.13.1 Epidemiology�������������������������������������������������������������������������������������������  88 4.13.2 Histopathology�����������������������������������������������������������������������������������������  88 4.14 Salivary Duct Carcinoma�������������������������������������������������������������������������������������  89 4.14.1 Epidemiology�������������������������������������������������������������������������������������������  89 4.14.2 Histopathology�����������������������������������������������������������������������������������������  89 4.15 Adenocarcinoma, Not Otherwise Specified���������������������������������������������������������  90 4.15.1 Epidemiology�������������������������������������������������������������������������������������������  90 4.15.2 Histopathology�����������������������������������������������������������������������������������������  90 4.16 Carcinoma ex-Pleomorphic Adenoma�����������������������������������������������������������������  90 4.16.1 Epidemiology�������������������������������������������������������������������������������������������  90 4.16.2 Histopathology�����������������������������������������������������������������������������������������  90 4.17 Mammary Analogue Secretory Carcinoma���������������������������������������������������������  91 4.17.1 Histopathology�����������������������������������������������������������������������������������������  91 4.18 Essential Features of Primary NHL in the Salivary Gland ���������������������������������  94 4.18.1 Differential Diagnosis �����������������������������������������������������������������������������  94 4.19 Metastatic Tumours���������������������������������������������������������������������������������������������  95 References���������������������������������������������������������������������������������������������������������������������  95 5 Fine Needle Aspiration Cytology of Thyroid �����������������������������������������������������������  97 5.1 Indications of Thyroid FNAC �����������������������������������������������������������������������������  97 5.1.1 Indications for USG Guided FNAC���������������������������������������������������������  97 5.1.2 Complications of FNAC �������������������������������������������������������������������������  97 5.2 Essential Investigations Needed for Effective Interpretation�������������������������������  97 5.3 Anatomy and Histology of Thyroid���������������������������������������������������������������������  98 5.3.1 Histology�������������������������������������������������������������������������������������������������  98 5.3.2 Thyroid FNAC: Approach�����������������������������������������������������������������������  98

viii

Contents

5.4 Thyroid Lesions��������������������������������������������������������������������������������������������������� 102 5.4.1 Non-neoplastic Conditions���������������������������������������������������������������������� 102 5.4.2 Differential Diagnosis ����������������������������������������������������������������������������� 103 5.4.3 Graves’ Disease��������������������������������������������������������������������������������������� 103 5.5 Thyroiditis����������������������������������������������������������������������������������������������������������� 104 5.5.1 Acute Thyroiditis������������������������������������������������������������������������������������� 104 5.5.2 Subacute Thyroiditis ������������������������������������������������������������������������������� 104 5.5.3 Differential Diagnosis ����������������������������������������������������������������������������� 106 5.6 Lymphocytic Thyroiditis (LT)����������������������������������������������������������������������������� 106 5.7 Neoplastic Lesions of Thyroid����������������������������������������������������������������������������� 107 5.8 Follicular Neoplasm��������������������������������������������������������������������������������������������� 107 5.8.1 Follicular Adenoma��������������������������������������������������������������������������������� 107 5.8.2 Follicular Carcinoma������������������������������������������������������������������������������� 108 5.8.3 Differential Diagnosis ����������������������������������������������������������������������������� 109 5.9 Hurthle Cell Neoplasm (Oncocytic Neoplasm)��������������������������������������������������� 112 5.9.1 Differential Diagnosis ����������������������������������������������������������������������������� 115 5.10 Hyalinizing Trabecular Tumour��������������������������������������������������������������������������� 116 5.10.1 Differential Diagnosis ����������������������������������������������������������������������������� 117 5.11 Papillary Carcinoma of the Thyroid��������������������������������������������������������������������� 117 5.11.1 Molecular Genetics ��������������������������������������������������������������������������������� 117 5.12 Variants of Papillary Carcinoma ������������������������������������������������������������������������� 119 5.12.1 Follicular Variant of Papillary Thyroid Carcinoma��������������������������������� 119 5.12.2 Differential Diagnosis ����������������������������������������������������������������������������� 121 5.13 Cystic Papillary Thyroid Carcinoma������������������������������������������������������������������� 121 5.13.1 Tall Cell Variant��������������������������������������������������������������������������������������� 121 5.14 Hurthle Cell Variant��������������������������������������������������������������������������������������������� 121 5.14.1 Differential Diagnosis of PTC����������������������������������������������������������������� 121 5.15 Medullary Carcinoma ����������������������������������������������������������������������������������������� 122 5.15.1 Differential Diagnosis ����������������������������������������������������������������������������� 124 5.15.2 Variants of Medullary Carcinoma����������������������������������������������������������� 126 5.16 Insular Carcinoma����������������������������������������������������������������������������������������������� 126 5.16.1 Histopathology����������������������������������������������������������������������������������������� 127 5.16.2 Differential Diagnosis ����������������������������������������������������������������������������� 127 5.17 Anaplastic Carcinoma����������������������������������������������������������������������������������������� 128 5.17.1 Differential Diagnosis ����������������������������������������������������������������������������� 129 5.18 Non-Hodgkin Lymphoma ����������������������������������������������������������������������������������� 129 5.18.1 Differential Diagnosis ����������������������������������������������������������������������������� 130 References��������������������������������������������������������������������������������������������������������������������� 130 6 Fine Needle Aspiration Cytology of the Breast ������������������������������������������������������� 133 6.1 False-Negative Breast FNAC������������������������������������������������������������������������������� 133 6.1.1 Triple test������������������������������������������������������������������������������������������������� 135 6.1.2 Diagnostic Accuracy of Breast FNAC ��������������������������������������������������� 135 6.1.3 Core Needle biopsy��������������������������������������������������������������������������������� 136 6.1.4 Mammography����������������������������������������������������������������������������������������� 136 6.1.5 Histopathology of the Breast������������������������������������������������������������������� 136 6.1.6 Cytology of the Normal Breast ��������������������������������������������������������������� 136 6.1.7 Diagnostic Terminology��������������������������������������������������������������������������� 136 6.1.8 Reporting Format of Breast Lesion��������������������������������������������������������� 137 6.2 Benign Lesions of the Breast������������������������������������������������������������������������������� 137 6.2.1 Mastitis����������������������������������������������������������������������������������������������������� 137 6.2.2 Key Cytological Features������������������������������������������������������������������������� 137 6.2.3 Chronic����������������������������������������������������������������������������������������������������� 137

Contents

ix

6.2.4 Idiopathic Granulomatous mastitis ��������������������������������������������������������� 138 6.2.5 Key Cytological Features������������������������������������������������������������������������� 139 6.2.6 Granulomatous mastitis��������������������������������������������������������������������������� 139 6.3 Fat Necrosis��������������������������������������������������������������������������������������������������������� 140 6.3.1 Key Cytological Features������������������������������������������������������������������������� 140 6.3.2 Differential Diagnosis ����������������������������������������������������������������������������� 141 6.3.3 Galactocele����������������������������������������������������������������������������������������������� 141 6.3.4 Key Cytological Features������������������������������������������������������������������������� 141 6.4 Lactating Adenoma ��������������������������������������������������������������������������������������������� 141 6.4.1 Key Cytological features ������������������������������������������������������������������������� 141 6.4.2 Differential Diagnosis ����������������������������������������������������������������������������� 142 6.5 Mucocele������������������������������������������������������������������������������������������������������������� 142 6.5.1 Key Cytological Features������������������������������������������������������������������������� 142 6.5.2 Fibroadenoma ����������������������������������������������������������������������������������������� 142 6.5.3 Histopathology����������������������������������������������������������������������������������������� 142 6.5.4 Key Cytological features������������������������������������������������������������������������� 142 6.5.5 Differential Diagnosis ����������������������������������������������������������������������������� 144 6.5.6 Carcinoma ����������������������������������������������������������������������������������������������� 144 6.6 Fibrocystic Disease ��������������������������������������������������������������������������������������������� 144 6.6.1 Histopathology����������������������������������������������������������������������������������������� 144 6.6.2 Key Cytological Features������������������������������������������������������������������������� 145 6.6.3 Differential Diagnosis ����������������������������������������������������������������������������� 146 6.7 Phyllodes Tumour ����������������������������������������������������������������������������������������������� 146 6.7.1 Histopathology����������������������������������������������������������������������������������������� 147 6.7.2 Key Cytological features������������������������������������������������������������������������� 147 6.7.3 Differential Diagnosis ����������������������������������������������������������������������������� 147 6.8 Papillary Neoplasm��������������������������������������������������������������������������������������������� 149 6.8.1 Histopathology����������������������������������������������������������������������������������������� 150 6.8.2 Features of Malignancy��������������������������������������������������������������������������� 150 6.8.3 Key Cytological features������������������������������������������������������������������������� 150 6.8.4 Cytological Indicators of Malignancy����������������������������������������������������� 151 6.9 Differential Diagnosis ����������������������������������������������������������������������������������������� 151 6.9.1 Fibroadenoma ����������������������������������������������������������������������������������������� 151 6.9.2 Intraductal Proliferative Lesions of the Breast ��������������������������������������� 151 6.9.3 Usual Ductal Hyperplasia ����������������������������������������������������������������������� 152 6.10 Atypical Ductal Hyperplasia������������������������������������������������������������������������������� 152 6.10.1 Histopathology����������������������������������������������������������������������������������������� 152 6.10.2 Salient Cytological features��������������������������������������������������������������������� 152 6.10.3 Differential Diagnosis ����������������������������������������������������������������������������� 152 6.11 Ductal Carcinoma In Situ������������������������������������������������������������������������������������� 155 6.11.1 Histopathology����������������������������������������������������������������������������������������� 155 6.11.2 Cytological features��������������������������������������������������������������������������������� 155 6.11.3 Differential Diagnosis ����������������������������������������������������������������������������� 155 6.12 Carcinoma of Breast ������������������������������������������������������������������������������������������� 156 6.12.1 Invasive Carcinoma, Not Otherwise Specified ��������������������������������������� 156 6.12.2 Histopathology����������������������������������������������������������������������������������������� 156 6.12.3 Key Cytological features������������������������������������������������������������������������� 156 6.12.4 Differential Diagnosis ����������������������������������������������������������������������������� 157 6.13 Mucinous Carcinoma������������������������������������������������������������������������������������������� 159 6.13.1 Histopathology����������������������������������������������������������������������������������������� 159 6.13.2 Key Cytological features������������������������������������������������������������������������� 160 6.13.3 Differential Diagnosis ����������������������������������������������������������������������������� 160

x

Contents

6.14 Medullary carcinoma������������������������������������������������������������������������������������������� 160 6.14.1 Key Histopathological Features��������������������������������������������������������������� 162 6.14.2 Key Cytological Features������������������������������������������������������������������������� 162 6.14.3 Differential Diagnosis ����������������������������������������������������������������������������� 163 6.15 Apocrine carcinoma��������������������������������������������������������������������������������������������� 163 6.15.1 Histopathology����������������������������������������������������������������������������������������� 163 6.15.2 Key Cytological Features������������������������������������������������������������������������� 163 6.15.3 Differential Diagnosis ����������������������������������������������������������������������������� 164 6.16 Metaplastic carcinoma����������������������������������������������������������������������������������������� 164 6.16.1 Key Histopathological Features��������������������������������������������������������������� 164 6.16.2 Key Cytological Features������������������������������������������������������������������������� 164 6.16.3 Differential Diagnosis ����������������������������������������������������������������������������� 166 6.17 Tubular Carcinoma����������������������������������������������������������������������������������������������� 166 6.17.1 Histology������������������������������������������������������������������������������������������������� 166 6.17.2 Key Cytological features������������������������������������������������������������������������� 166 6.17.3 Differential Diagnosis ����������������������������������������������������������������������������� 166 6.18 Lobular Carcinoma ��������������������������������������������������������������������������������������������� 166 6.18.1 Histology Key Features��������������������������������������������������������������������������� 167 6.18.2 Key Cytological features������������������������������������������������������������������������� 167 6.18.3 Differential Diagnosis ����������������������������������������������������������������������������� 167 6.19 Carcinoma with Neuroendocrine Differentiation ����������������������������������������������� 168 6.19.1 Histopathology����������������������������������������������������������������������������������������� 168 6.19.2 Key Cytological Features������������������������������������������������������������������������� 168 6.19.3 Differential Diagnosis ����������������������������������������������������������������������������� 168 6.19.4 Metastatic tumors������������������������������������������������������������������������������������� 168 6.20 Non-Hodgkin lymphoma������������������������������������������������������������������������������������� 169 6.20.1 Acute Leukemic deposit ������������������������������������������������������������������������� 170 6.21 Male Breast Lesions��������������������������������������������������������������������������������������������� 170 6.21.1 Gynaecomastia����������������������������������������������������������������������������������������� 170 6.21.2 Key Cytological Features������������������������������������������������������������������������� 171 6.21.3 Differential Diagnosis ����������������������������������������������������������������������������� 171 6.22 Carcinoma in Male Breast����������������������������������������������������������������������������������� 171 6.23 Nipple Discharge������������������������������������������������������������������������������������������������� 171 6.23.1 Key Cytological features������������������������������������������������������������������������� 172 6.24 Ancillary Investigations on Breast Aspiration material��������������������������������������� 172 6.24.1 Flow Cytometry��������������������������������������������������������������������������������������� 173 References��������������������������������������������������������������������������������������������������������������������� 173 7 Fine Needle Aspiration Cytology of the Lung ��������������������������������������������������������� 175 7.1 Different Techniques of FNAC ��������������������������������������������������������������������������� 175 7.1.1 Transthoracic Needle Aspirate����������������������������������������������������������������� 175 7.1.2 TTNA Technique������������������������������������������������������������������������������������� 175 7.1.3 Transbronchial FNAC ����������������������������������������������������������������������������� 175 7.2 Anatomy and Histopathology of the Lung����������������������������������������������������������� 176 7.2.1 Cytology��������������������������������������������������������������������������������������������������� 176 7.3 The Cells Simulating Malignancy����������������������������������������������������������������������� 177 7.3.1 Reactive Bronchial Cells������������������������������������������������������������������������� 177 7.3.2 Vegetable Cell ����������������������������������������������������������������������������������������� 179 7.4 Inflammatory Lung Lesions��������������������������������������������������������������������������������� 180 7.4.1 Acute Inflammation��������������������������������������������������������������������������������� 180 7.4.2 Differential Diagnosis ����������������������������������������������������������������������������� 180 7.5 Specific Infections����������������������������������������������������������������������������������������������� 180 7.5.1 Tuberculosis��������������������������������������������������������������������������������������������� 180 7.5.2 Diagnostic Modalities ����������������������������������������������������������������������������� 181

Contents

xi

7.5.3 Key Cytological Features������������������������������������������������������������������������� 181 7.5.4 Differential Diagnosis ����������������������������������������������������������������������������� 182 7.5.5 Actinomycosis����������������������������������������������������������������������������������������� 182 7.5.6 Nocardia��������������������������������������������������������������������������������������������������� 182 7.6 Fungal Infections������������������������������������������������������������������������������������������������� 183 7.6.1 Aspergillus����������������������������������������������������������������������������������������������� 183 7.6.2 Key Cytological Features������������������������������������������������������������������������� 184 7.6.3 Mucormycosis����������������������������������������������������������������������������������������� 184 7.6.4 Key Cytological Features������������������������������������������������������������������������� 185 7.7 Pulmonary Cryptococcosis ��������������������������������������������������������������������������������� 185 7.8 Histoplasma��������������������������������������������������������������������������������������������������������� 186 7.8.1 Clinical Features ������������������������������������������������������������������������������������� 186 7.8.2 Key Cytological Features������������������������������������������������������������������������� 186 7.9 Pneumocystis Pneumonia ����������������������������������������������������������������������������������� 187 7.9.1 Key Cytological Features������������������������������������������������������������������������� 187 7.9.2 Differential Diagnosis ����������������������������������������������������������������������������� 187 7.10 Candidiasis����������������������������������������������������������������������������������������������������������� 188 7.10.1 Key Cytological Features������������������������������������������������������������������������� 189 7.11 Parasites��������������������������������������������������������������������������������������������������������������� 189 7.11.1 Hydatid Cyst ������������������������������������������������������������������������������������������� 189 7.11.2 Life Cycle������������������������������������������������������������������������������������������������ 189 7.11.3 Key Cytological Features������������������������������������������������������������������������� 190 7.11.4 Neoplastic Lesions of the Lung��������������������������������������������������������������� 190 7.12 Lung Carcinoma��������������������������������������������������������������������������������������������������� 190 7.12.1 Incidence ������������������������������������������������������������������������������������������������� 190 7.12.2 Etiological Factors����������������������������������������������������������������������������������� 190 7.13 Squamous Cell Carcinoma����������������������������������������������������������������������������������� 191 7.13.1 Incidence ������������������������������������������������������������������������������������������������� 191 7.13.2 Key Cytological Features������������������������������������������������������������������������� 191 7.13.3 Types ������������������������������������������������������������������������������������������������������� 193 7.13.4 Differential Diagnosis ����������������������������������������������������������������������������� 193 7.14 Adenocarcinoma ������������������������������������������������������������������������������������������������� 194 7.14.1 Key Cytological Features������������������������������������������������������������������������� 194 7.14.2 Molecular Cytogenetics��������������������������������������������������������������������������� 196 7.14.3 Differential Diagnosis ����������������������������������������������������������������������������� 196 7.15 Carcinoid������������������������������������������������������������������������������������������������������������� 197 7.15.1 Key Cytological Features������������������������������������������������������������������������� 198 7.15.2 Differential Diagnosis ����������������������������������������������������������������������������� 198 7.16 Small Cell Carcinoma ����������������������������������������������������������������������������������������� 199 7.16.1 Clinical Features ������������������������������������������������������������������������������������� 199 7.16.2 Key Cytological Features������������������������������������������������������������������������� 199 7.16.3 Immunocytochemistry����������������������������������������������������������������������������� 200 7.16.4 Differential Diagnosis ����������������������������������������������������������������������������� 200 7.17 Large Cell Neuroendocrine Carcinoma��������������������������������������������������������������� 201 7.17.1 Clinical Features ������������������������������������������������������������������������������������� 201 7.17.2 Key Cytological Features������������������������������������������������������������������������� 202 7.17.3 Differential Diagnosis ����������������������������������������������������������������������������� 202 7.18 Large Cell Carcinoma ����������������������������������������������������������������������������������������� 202 7.18.1 Key Cytological Features������������������������������������������������������������������������� 202 7.18.2 Differential Diagnosis ����������������������������������������������������������������������������� 202 7.19 Other Tumours of Lung��������������������������������������������������������������������������������������� 203 7.19.1 Adenoid Cystic Carcinoma ��������������������������������������������������������������������� 203 7.19.2 Key Cytological Features������������������������������������������������������������������������� 203

xii

Contents

7.20 Carcinosarcoma��������������������������������������������������������������������������������������������������� 203 7.20.1 Key Cytological Features������������������������������������������������������������������������� 204 7.21 Pleuropulmonary Blastoma��������������������������������������������������������������������������������� 205 7.21.1 Clinical Features ������������������������������������������������������������������������������������� 205 7.21.2 Key Cytological Features������������������������������������������������������������������������� 205 7.21.3 Differential Diagnosis ����������������������������������������������������������������������������� 206 7.22 Lymphoma of Lung��������������������������������������������������������������������������������������������� 206 7.22.1 Clinical Features ������������������������������������������������������������������������������������� 206 7.22.2 Key Cytological Features������������������������������������������������������������������������� 206 7.23 Metastatic Tumours in the Lung ������������������������������������������������������������������������� 207 References��������������������������������������������������������������������������������������������������������������������� 209 8 Fine Needle Aspiration Cytology of the Mediastinum��������������������������������������������� 211 8.1 Different Anatomical Compartments������������������������������������������������������������������� 211 8.1.1 Techniques to Approach the Mediastinum����������������������������������������������� 211 8.2 Lesions in the Mediastinum��������������������������������������������������������������������������������� 212 8.2.1 Thymoma������������������������������������������������������������������������������������������������� 212 8.2.2 Clinical Features ������������������������������������������������������������������������������������� 212 8.2.3 Histopathology����������������������������������������������������������������������������������������� 212 8.2.4 Key Cytology Features����������������������������������������������������������������������������� 213 8.2.5 Type A (Medullary Thymoma/Spindle Cell Thymoma)������������������������� 214 8.2.6 Type B (Cortical Thymoma) ������������������������������������������������������������������� 214 8.2.7 Differential Diagnosis ����������������������������������������������������������������������������� 214 8.3 Malignant Thymoma������������������������������������������������������������������������������������������� 216 8.3.1 Invasive Thymoma����������������������������������������������������������������������������������� 216 8.3.2 Thymic Carcinoma���������������������������������������������������������������������������������� 216 8.3.3 Thymic Neuroendocrine Tumours����������������������������������������������������������� 216 8.3.4 Typical Thymic Carcinoid����������������������������������������������������������������������� 216 8.4 Germ Cell Tumors����������������������������������������������������������������������������������������������� 217 8.4.1 Germinomas��������������������������������������������������������������������������������������������� 217 8.4.2 Key Cytological Features������������������������������������������������������������������������� 218 8.4.3 Differential Diagnosis ����������������������������������������������������������������������������� 218 8.5 Embryonal Carcinoma����������������������������������������������������������������������������������������� 219 8.5.1 Key Cytology Features����������������������������������������������������������������������������� 219 8.6 Lymphomas��������������������������������������������������������������������������������������������������������� 219 8.6.1 Non-Hodgkin’s Lymphoma��������������������������������������������������������������������� 219 8.6.2 Primary Mediastinal Large B Cell Lymphoma (PMLBCL) ������������������� 219 8.6.3 Key Cytological Features������������������������������������������������������������������������� 219 8.7 T Lymphoblastic Lymphoma������������������������������������������������������������������������������� 220 8.7.1 Key Cytological Features������������������������������������������������������������������������� 220 8.8 Anaplastic Large Cell Lymphomas��������������������������������������������������������������������� 220 8.8.1 Key Cytological Features������������������������������������������������������������������������� 220 8.9 Hodgkin Lymphoma ������������������������������������������������������������������������������������������� 221 8.9.1 Key Cytological Features������������������������������������������������������������������������� 221 8.10 Neurogenic Tumour��������������������������������������������������������������������������������������������� 221 8.10.1 Ganglioneuroblastoma����������������������������������������������������������������������������� 221 8.10.2 Key Cytological Features������������������������������������������������������������������������� 221 8.10.3 Neurofibroma and Schwannoma������������������������������������������������������������� 221 8.11 Malignant Peripheral Nerve Sheath Tumours����������������������������������������������������� 222 References��������������������������������������������������������������������������������������������������������������������� 222 9 Fine Needle Aspiration Cytology of the Lymph Node��������������������������������������������� 225 9.1 Indications of FNAC ������������������������������������������������������������������������������������������� 225 9.1.1 Contraindication��������������������������������������������������������������������������������������� 225 9.1.2 Limitations of FNAC of Lymph Node����������������������������������������������������� 225

Contents

xiii

9.1.3 Diagnostic Accuracy ������������������������������������������������������������������������������� 225 9.1.4 Diagnostic Accuracy of FNAC of Lymph Node Depends on ����������������� 225 9.2 Normal Anatomy and Histology of the Lymph Node����������������������������������������� 226 9.2.1 The Normal Components of the Lymph Node����������������������������������������� 226 9.2.2 Follicular Centre Cells����������������������������������������������������������������������������� 227 9.3 Benign Lesions of the Lymph Node ������������������������������������������������������������������� 228 9.3.1 Reactive Lymphoid Hyperplasia������������������������������������������������������������� 228 9.3.2 Differential Diagnosis ����������������������������������������������������������������������������� 229 9.4 Acute Lymphadenitis������������������������������������������������������������������������������������������� 230 9.5 Granulomatous Lymphadenitis ��������������������������������������������������������������������������� 231 9.5.1 Tuberculosis��������������������������������������������������������������������������������������������� 231 9.5.2 Key Cytological Features ����������������������������������������������������������������������� 231 9.5.3 Differential Diagnosis ����������������������������������������������������������������������������� 232 9.6 Lepromatous Lymphadenitis������������������������������������������������������������������������������� 232 9.6.1 Key Cytological Features ����������������������������������������������������������������������� 232 9.7 Leishminia Lymphadenitis����������������������������������������������������������������������������������� 232 9.7.1 Key Cytological Features������������������������������������������������������������������������� 234 9.8 Filarial Lymphadenitis����������������������������������������������������������������������������������������� 234 9.8.1 Key Cytological Features ����������������������������������������������������������������������� 234 9.9 Toxoplasma Lymphadenitis��������������������������������������������������������������������������������� 234 9.9.1 Key Cytological Features������������������������������������������������������������������������� 235 9.10 Cat Scratch Disease��������������������������������������������������������������������������������������������� 235 9.10.1 Key Cytological Features������������������������������������������������������������������������� 235 9.11 Viral Infections����������������������������������������������������������������������������������������������������� 235 9.11.1 Infectious Mononucleosis (IM)��������������������������������������������������������������� 235 9.11.2 Key Cytological Features������������������������������������������������������������������������� 235 9.11.3 Differential Diagnosis ����������������������������������������������������������������������������� 235 9.12 Kimura’s Disease������������������������������������������������������������������������������������������������� 236 9.12.1 Key Cytological Features������������������������������������������������������������������������� 236 9.13 Kikuchi’s Disease������������������������������������������������������������������������������������������������� 236 9.13.1 Key Cytological Features������������������������������������������������������������������������� 236 9.13.2 Differential Diagnosis ����������������������������������������������������������������������������� 236 9.14 HIV Lymphadenopathy��������������������������������������������������������������������������������������� 236 9.14.1 Persistent Generalized Lymphadenopathy (PGL)����������������������������������� 238 9.15 Kaposi’s Sarcoma������������������������������������������������������������������������������������������������� 238 9.15.1 Association����������������������������������������������������������������������������������������������� 238 9.15.2 Key Cytological Features������������������������������������������������������������������������� 238 9.15.3 Differential Diagnosis of Kaposi’s Sarcoma������������������������������������������� 238 9.16 Rosai–Dorfman Disease��������������������������������������������������������������������������������������� 238 9.16.1 Key Cytological Features������������������������������������������������������������������������� 238 9.16.2 Differential Diagnosis ����������������������������������������������������������������������������� 239 9.17 Dermatopathic Lymphadenitis����������������������������������������������������������������������������� 240 9.17.1 Clinical Features ������������������������������������������������������������������������������������� 240 9.17.2 Key Cytological Features������������������������������������������������������������������������� 240 9.17.3 Differential Diagnosis ����������������������������������������������������������������������������� 240 9.18 Castleman’s Disease��������������������������������������������������������������������������������������������� 242 9.18.1 Key Cytological Features������������������������������������������������������������������������� 242 9.18.2 Differential Diagnosis ����������������������������������������������������������������������������� 242 9.18.3 Metastatic Malignant Tumour����������������������������������������������������������������� 242 9.18.4 Squamous Cell Carcinoma����������������������������������������������������������������������� 243 9.18.5 Adenocarcinoma ������������������������������������������������������������������������������������� 244 9.18.6 Small Cell Carcinoma ����������������������������������������������������������������������������� 244 9.18.7 Germ Cell Tumour ��������������������������������������������������������������������������������� 245 9.18.8 Immunocytochemistry����������������������������������������������������������������������������� 247

xiv

Contents

9.19 Lymphoma����������������������������������������������������������������������������������������������������������� 247 9.20 B Cell Non-Hodgkin Lymphoma (NHL)������������������������������������������������������������� 248 9.20.1 Small Lymphocytic Lymphoma ������������������������������������������������������������� 248 9.20.2 Clinical Features ������������������������������������������������������������������������������������� 248 9.20.3 Key Cytological Features������������������������������������������������������������������������� 248 9.20.4 Immunophenotype����������������������������������������������������������������������������������� 252 9.21 Mantle Cell Lymphoma��������������������������������������������������������������������������������������� 252 9.21.1 Abbreviation: MCL��������������������������������������������������������������������������������� 252 9.21.2 Clinical Features ������������������������������������������������������������������������������������� 252 9.21.3 Key Cytological Features ����������������������������������������������������������������������� 252 9.21.4 Immunophenotype����������������������������������������������������������������������������������� 252 9.22 Follicular Lymphoma������������������������������������������������������������������������������������������� 256 9.22.1 Abbreviation ������������������������������������������������������������������������������������������� 256 9.22.2 Clinical Features ������������������������������������������������������������������������������������� 256 9.22.3 Key Cytological Features������������������������������������������������������������������������� 256 9.22.4 Immunophenotype ��������������������������������������������������������������������������������� 257 9.23 Lymphoplasmacytic Lymphoma������������������������������������������������������������������������� 257 9.23.1 Epidemiology������������������������������������������������������������������������������������������� 257 9.23.2 Clinical Features ������������������������������������������������������������������������������������� 258 9.23.3 Key Cytological Features������������������������������������������������������������������������� 258 9.24 Marginal Zone Lymphoma (MZL) ��������������������������������������������������������������������� 258 9.24.1 Nodal Marginal Zone Lymphoma����������������������������������������������������������� 258 9.24.2 Key Cytological Features������������������������������������������������������������������������� 258 9.24.3 Immunophenotype����������������������������������������������������������������������������������� 259 9.24.4 Chromosomal Abnormality��������������������������������������������������������������������� 259 9.25 Extranodal Marginal Zone Lymphoma ��������������������������������������������������������������� 259 9.25.1 Key Cytological Features������������������������������������������������������������������������� 259 9.25.2 Immunophenotype����������������������������������������������������������������������������������� 259 9.25.3 Chromosomal Abnormality��������������������������������������������������������������������� 259 9.26 Hairy Cell Leukaemia ����������������������������������������������������������������������������������������� 260 9.26.1 Epidemiology������������������������������������������������������������������������������������������� 260 9.26.2 Clinical Features ������������������������������������������������������������������������������������� 260 9.26.3 Key Cytological Features������������������������������������������������������������������������� 260 9.26.4 Immunophenotype����������������������������������������������������������������������������������� 260 9.27 Diffuse Large B Cell Lymphoma������������������������������������������������������������������������� 260 9.27.1 Synonym ������������������������������������������������������������������������������������������������� 260 9.27.2 Epidemiology������������������������������������������������������������������������������������������� 260 9.27.3 Key Cytological Features ����������������������������������������������������������������������� 260 9.27.4 Immunophenotype����������������������������������������������������������������������������������� 261 9.27.5 Chromosomal Abnormality��������������������������������������������������������������������� 261 9.28 Burkitt’s Lymphoma ������������������������������������������������������������������������������������������� 262 9.28.1 Epidemiology������������������������������������������������������������������������������������������� 262 9.28.2 Clinical Features ������������������������������������������������������������������������������������� 262 9.28.3 Key Cytological Features������������������������������������������������������������������������� 263 9.28.4 Immunophenotype����������������������������������������������������������������������������������� 263 9.28.5 Chromosomal Abnormality: Characteristic Chromosomal Translocation������������������������������������������������������������������������������������������� 263 9.29 B Lymphoblastic Lymphoma������������������������������������������������������������������������������� 264 9.29.1 Epidemiology������������������������������������������������������������������������������������������� 264 9.29.2 Clinical Features ������������������������������������������������������������������������������������� 264 9.29.3 Key Cytological Features������������������������������������������������������������������������� 265 9.29.4 Chromosomal Abnormality��������������������������������������������������������������������� 265 9.30 T Cell Lymphoma ����������������������������������������������������������������������������������������������� 265 9.30.1 T Lymphoblastic Lymphoma������������������������������������������������������������������� 265

Contents

xv

9.30.2 Epidemiology������������������������������������������������������������������������������������������� 265 9.30.3 Clinical Features ������������������������������������������������������������������������������������� 265 9.30.4 Key Cytological Features: Same as B Lymphoblastic Lymphoma��������� 265 9.31 Anaplastic Large Cell Lymphoma����������������������������������������������������������������������� 266 9.31.1 Epidemiology������������������������������������������������������������������������������������������� 266 9.31.2 Clinical Features ������������������������������������������������������������������������������������� 266 9.31.3 Key Cytological Features������������������������������������������������������������������������� 266 9.31.4 Immunophenotype����������������������������������������������������������������������������������� 267 9.32 Peripheral T Cell Lymphoma, Unspecified��������������������������������������������������������� 267 9.32.1 Epidemiology������������������������������������������������������������������������������������������� 267 9.32.2 Key Cytological Feature ������������������������������������������������������������������������� 267 9.33 Angioimmunoblastic T Cell Lymphoma������������������������������������������������������������� 267 9.33.1 Epidemiology������������������������������������������������������������������������������������������� 267 9.33.2 Clinical Features ������������������������������������������������������������������������������������� 267 9.33.3 Key Cytological Features������������������������������������������������������������������������� 267 9.34 Mycosis Fungoides and Sezary Syndrome ��������������������������������������������������������� 267 9.34.1 Epidemiology������������������������������������������������������������������������������������������� 267 9.34.2 Clinical Features ������������������������������������������������������������������������������������� 267 9.34.3 Key Cytological Features������������������������������������������������������������������������� 267 9.35 Hodgkin’s Lymphoma����������������������������������������������������������������������������������������� 268 9.35.1 Classification������������������������������������������������������������������������������������������� 268 9.36 Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)������������������� 268 9.36.1 Epidemiology������������������������������������������������������������������������������������������� 268 9.36.2 Clinical Features ������������������������������������������������������������������������������������� 268 9.36.3 Classical Hodgkin’s Lymphoma (CHL)�������������������������������������������������� 268 9.37 Histiocytic and Dendritic Neoplasms ����������������������������������������������������������������� 271 9.37.1 Follicular Dendritic Cell Sarcoma����������������������������������������������������������� 271 9.37.2 Key Cytological Features������������������������������������������������������������������������� 271 9.37.3 Immunophenotype����������������������������������������������������������������������������������� 271 9.38 Langerhans Cell Histiocytosis����������������������������������������������������������������������������� 271 9.38.1 Epidemiology������������������������������������������������������������������������������������������� 271 9.38.2 Clinical Features ������������������������������������������������������������������������������������� 272 9.38.3 Key Cytological Features������������������������������������������������������������������������� 272 9.39 Leukaemic Infiltration����������������������������������������������������������������������������������������� 273 9.39.1 Acute Lymphoblastic Leukaemia ����������������������������������������������������������� 273 9.39.2 Acute Myeloid Leukaemia����������������������������������������������������������������������� 273 9.40 Chronic Myeloid Leukaemic Infiltration������������������������������������������������������������� 273 9.40.1 Key Cytological Features������������������������������������������������������������������������� 273 References��������������������������������������������������������������������������������������������������������������������� 274 10 Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen��������������������� 277 10.1 Intestine ��������������������������������������������������������������������������������������������������������������� 277 10.1.1 Endoscopic FNAC����������������������������������������������������������������������������������� 277 10.1.2 Endoscopic Ultrasound-Guided (EUS) FNAC��������������������������������������� 277 10.2 Oesophagus ��������������������������������������������������������������������������������������������������������� 277 10.2.1 Normal Histology and Cytology������������������������������������������������������������� 277 10.2.2 Cytology ������������������������������������������������������������������������������������������������� 278 10.3 Infection��������������������������������������������������������������������������������������������������������������� 278 10.4 Dysplasia in Barrett’s Oesophagus���������������������������������������������������������������������� 278 10.5 Squamous Cell Carcinoma����������������������������������������������������������������������������������� 278 10.5.1 Epidemiology ����������������������������������������������������������������������������������������� 278 10.5.2 Clinical Features������������������������������������������������������������������������������������� 278 10.5.3 Key Cytological Features ����������������������������������������������������������������������� 278 10.6 Adenocarcinoma ������������������������������������������������������������������������������������������������� 279 10.6.1 Epidemiology ����������������������������������������������������������������������������������������� 279

xvi

Contents

10.6.2 Clinical Features ��������������������������������������������������������������������������������� 279 10.6.3 Key Cytological Features��������������������������������������������������������������������� 279 10.7 Stomach������������������������������������������������������������������������������������������������������������� 279 10.7.1 Anatomy and Histology����������������������������������������������������������������������� 279 10.7.2 Histology��������������������������������������������������������������������������������������������� 280 10.7.3 Cytology ��������������������������������������������������������������������������������������������� 280 10.7.4 Benign Tumours����������������������������������������������������������������������������������� 280 10.8 Gastric Adenocarcinoma����������������������������������������������������������������������������������� 280 10.8.1 Epidemiology��������������������������������������������������������������������������������������� 280 10.8.2 Clinical Features ��������������������������������������������������������������������������������� 280 10.8.3 Key Cytological Features��������������������������������������������������������������������� 280 10.8.4 Intestinal Type������������������������������������������������������������������������������������� 280 10.8.5 Diffuse or Gastric Type����������������������������������������������������������������������� 282 10.9 Gastrointestinal Stromal Tumour����������������������������������������������������������������������� 283 10.9.1 Epidemiology��������������������������������������������������������������������������������������� 283 10.9.2 Localization����������������������������������������������������������������������������������������� 283 10.9.3 Molecular Pathology��������������������������������������������������������������������������� 283 10.9.4 Clinical Features ��������������������������������������������������������������������������������� 283 10.9.5 Key Cytological Features��������������������������������������������������������������������� 283 10.10 Neuroendocrine Tumors������������������������������������������������������������������������������������� 284 10.10.1 Epidemiology��������������������������������������������������������������������������������������� 284 10.10.2 Clinical Features ��������������������������������������������������������������������������������� 284 10.10.3 Key Cytological Features��������������������������������������������������������������������� 284 10.11 Non-Hodgkin Lymphoma ��������������������������������������������������������������������������������� 286 10.11.1 Epidemiology��������������������������������������������������������������������������������������� 286 10.11.2 Clinical Features ��������������������������������������������������������������������������������� 286 10.11.3 Type of Lymphomas ��������������������������������������������������������������������������� 286 10.11.4 Key Cytological Features��������������������������������������������������������������������� 286 10.12 The Small and Large Intestine��������������������������������������������������������������������������� 287 10.12.1 Anatomy, Histology and Cytology ����������������������������������������������������� 287 10.12.2 Histology��������������������������������������������������������������������������������������������� 287 10.12.3 Histology��������������������������������������������������������������������������������������������� 287 10.12.4 Cytology ��������������������������������������������������������������������������������������������� 287 10.13 Infections����������������������������������������������������������������������������������������������������������� 287 10.13.1 Tuberculosis����������������������������������������������������������������������������������������� 287 10.14 Adenocarcinoma ����������������������������������������������������������������������������������������������� 287 10.14.1 Epidemiology��������������������������������������������������������������������������������������� 287 10.14.2 Clinical Features ��������������������������������������������������������������������������������� 287 10.14.3 Key Cytology Features ����������������������������������������������������������������������� 287 10.14.4 Lymphoma������������������������������������������������������������������������������������������� 288 10.15 Large Intestine��������������������������������������������������������������������������������������������������� 288 10.15.1 Colorectal Adenocarcinoma����������������������������������������������������������������� 288 10.15.2 Clinical Features ��������������������������������������������������������������������������������� 288 10.15.3 Key Cytological Features��������������������������������������������������������������������� 288 10.16 Liver������������������������������������������������������������������������������������������������������������������� 288 10.16.1 Contraindications of FNAC of Liver��������������������������������������������������� 288 10.16.2 Sampling Technique ��������������������������������������������������������������������������� 289 10.16.3 Ancillary Tests������������������������������������������������������������������������������������� 289 10.16.4 Anatomy, Histology and Cytology ����������������������������������������������������� 289 10.16.5 Cytology ��������������������������������������������������������������������������������������������� 289 10.17 Non-neoplastic Lesions������������������������������������������������������������������������������������� 290 10.17.1 Diffuse Parenchymal Lesions of the Liver ����������������������������������������� 290 10.17.2 Cirrhosis����������������������������������������������������������������������������������������������� 290

Contents

xvii

10.17.3 Differential Diagnosis������������������������������������������������������������������������� 290 10.17.4 Chronic Hepatitis��������������������������������������������������������������������������������� 290 10.17.5 Acute Hepatitis ����������������������������������������������������������������������������������� 290 10.17.6 Fatty Change ��������������������������������������������������������������������������������������� 290 10.17.7 Pyogenic Abscess��������������������������������������������������������������������������������� 290 10.17.8 Granulomatous Hepatitis��������������������������������������������������������������������� 291 10.18 Amoebic Abscess����������������������������������������������������������������������������������������������� 291 10.18.1 Cytology ��������������������������������������������������������������������������������������������� 291 10.18.2 Cystic Lesions������������������������������������������������������������������������������������� 291 10.19 Benign Tumours in the Liver����������������������������������������������������������������������������� 292 10.19.1 Focal Nodular Hyperplasia ����������������������������������������������������������������� 292 10.19.2 Epidemiology��������������������������������������������������������������������������������������� 292 10.19.3 Clinical Features ��������������������������������������������������������������������������������� 292 10.20 Hepatocellular Adenomas ��������������������������������������������������������������������������������� 292 10.20.1 Epidemiology��������������������������������������������������������������������������������������� 292 10.20.2 Clinical Features ��������������������������������������������������������������������������������� 292 10.20.3 Cytology ��������������������������������������������������������������������������������������������� 293 10.20.4 Haemangioma of Liver ����������������������������������������������������������������������� 293 10.20.5 Biliary Cystadenoma��������������������������������������������������������������������������� 293 10.20.6 Hepatic Angiomyolipoma������������������������������������������������������������������� 293 10.20.7 Cytology ��������������������������������������������������������������������������������������������� 294 10.21 Mesenchymal Hamartoma of Liver������������������������������������������������������������������� 294 10.21.1 Cytology ��������������������������������������������������������������������������������������������� 294 10.21.2 Differential Diagnosis������������������������������������������������������������������������� 294 10.22 Malignant Tumour��������������������������������������������������������������������������������������������� 294 10.22.1 Hepatocellular Carcinoma (HCC) ����������������������������������������������������� 294 10.22.2 Epidemiology��������������������������������������������������������������������������������������� 294 10.22.3 Clinical Features ��������������������������������������������������������������������������������� 294 10.22.4 Aetiology��������������������������������������������������������������������������������������������� 294 10.22.5 Key Cytology Features ����������������������������������������������������������������������� 294 10.23 Variants of HCC������������������������������������������������������������������������������������������������� 296 10.23.1 Fibrolamellar Variant of HCC������������������������������������������������������������� 296 10.23.2 Key Cytology Features ����������������������������������������������������������������������� 296 10.23.3 Clear Cell Variant��������������������������������������������������������������������������������� 296 10.24 Giant Cell Variant of HCC��������������������������������������������������������������������������������� 297 10.24.1 HCC with Fatty Change����������������������������������������������������������������������� 297 10.25 Intrahepatic Cholangiocarcinoma ��������������������������������������������������������������������� 297 10.25.1 Epidemiology��������������������������������������������������������������������������������������� 297 10.25.2 Clinical Features ��������������������������������������������������������������������������������� 298 10.25.3 Key Cytology Features ����������������������������������������������������������������������� 298 10.25.4 Differential Diagnosis������������������������������������������������������������������������� 298 10.26 Hepatoblastoma������������������������������������������������������������������������������������������������� 299 10.26.1 Epidemiology��������������������������������������������������������������������������������������� 299 10.26.2 Clinical Features ��������������������������������������������������������������������������������� 299 10.26.3 Key Cytological Feature ��������������������������������������������������������������������� 299 10.26.4 Fetal����������������������������������������������������������������������������������������������������� 301 10.27 Primary Sarcomas of Liver ������������������������������������������������������������������������������� 301 10.27.1 Angiosarcoma ������������������������������������������������������������������������������������� 301 10.27.2 Clinical Features ��������������������������������������������������������������������������������� 301 10.27.3 Key Cytology Features ����������������������������������������������������������������������� 301 10.27.4 Differential Diagnosis������������������������������������������������������������������������� 301 10.28 Embryonal Sarcoma of the Liver����������������������������������������������������������������������� 301 10.28.1 Epidemiology��������������������������������������������������������������������������������������� 301

xviii

Contents

10.28.2 Clinical Features ��������������������������������������������������������������������������������� 301 10.28.3 Key Cytology Features ����������������������������������������������������������������������� 301 10.28.4 Metastatic Lesions in Liver����������������������������������������������������������������� 302 10.28.5 Key Cytology Features ����������������������������������������������������������������������� 303 10.28.6 Malignant Lymphoma of the Liver ����������������������������������������������������� 306 10.28.7 Spleen ������������������������������������������������������������������������������������������������� 306 10.28.8 Normal Cytology��������������������������������������������������������������������������������� 306 10.29 Non-neoplastic Process of the Spleen��������������������������������������������������������������� 306 10.30 Accumulation of Abnormal Material and Storage Disease������������������������������� 307 10.31 Neoplasm����������������������������������������������������������������������������������������������������������� 308 10.31.1 Lymphoma������������������������������������������������������������������������������������������� 308 10.31.2 Epidemiology��������������������������������������������������������������������������������������� 308 10.31.3 Key Cytological Features��������������������������������������������������������������������� 308 10.31.4 Metastatic Tumour������������������������������������������������������������������������������� 309 References��������������������������������������������������������������������������������������������������������������������� 309 11 Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas��������������������� 311 11.1 Gall Bladder������������������������������������������������������������������������������������������������������� 311 11.1.1 Anatomy and Histology����������������������������������������������������������������������� 311 11.1.2 Cytology ��������������������������������������������������������������������������������������������� 311 11.1.3 Neoplasms������������������������������������������������������������������������������������������� 311 11.2 Gall Bladder Carcinomas����������������������������������������������������������������������������������� 311 11.2.1 Epidemiology��������������������������������������������������������������������������������������� 311 11.2.2 Clinical Features ��������������������������������������������������������������������������������� 311 11.2.3 Adenocarcinoma ��������������������������������������������������������������������������������� 311 11.2.4 Squamous Cell Carcinoma ����������������������������������������������������������������� 312 11.2.5 Adenosquamous Carcinoma ��������������������������������������������������������������� 312 11.3 Neuroendocrine Tumours����������������������������������������������������������������������������������� 313 11.3.1 Epidemiology��������������������������������������������������������������������������������������� 313 11.3.2 Clinical Features ��������������������������������������������������������������������������������� 313 11.3.3 Key Cytological Features��������������������������������������������������������������������� 313 11.3.4 Neuroendocrine Carcinoma����������������������������������������������������������������� 314 11.3.5 Small Cell Neuroendocrine Carcinoma����������������������������������������������� 314 11.3.6 Large Cell Neuroendocrine Carcinoma����������������������������������������������� 314 11.3.7 Pancreas����������������������������������������������������������������������������������������������� 314 11.3.8 Sampling Technique ��������������������������������������������������������������������������� 314 11.3.9 Diagnostic Accuracy ��������������������������������������������������������������������������� 314 11.4 Normal Anatomy and Histology of Pancreas����������������������������������������������������� 314 11.4.1 Histology��������������������������������������������������������������������������������������������� 315 11.4.2 Cytology ��������������������������������������������������������������������������������������������� 315 11.4.3 Cysts in Pancreas��������������������������������������������������������������������������������� 315 11.4.4 Congenital Cyst����������������������������������������������������������������������������������� 315 11.5 Acquired Cyst ��������������������������������������������������������������������������������������������������� 316 11.5.1 Pancreatic Pseudocyst������������������������������������������������������������������������� 316 11.6 Pancreatic True Cyst ����������������������������������������������������������������������������������������� 316 11.6.1 Differential Diagnosis������������������������������������������������������������������������� 316 11.6.2 Pancreatitis������������������������������������������������������������������������������������������� 316 11.6.3 Key Cytology Features ����������������������������������������������������������������������� 316 11.7 Chronic Pancreatitis������������������������������������������������������������������������������������������� 316 11.7.1 Key Cytology Features ����������������������������������������������������������������������� 316 11.7.2 Differential Diagnosis������������������������������������������������������������������������� 317 11.8 Neoplasms of Pancreas ������������������������������������������������������������������������������������� 317 11.8.1 Serous Cystadenoma��������������������������������������������������������������������������� 317

Contents

xix

11.8.2 Clinical Features ��������������������������������������������������������������������������������� 317 11.8.3 Key Cytology Features ����������������������������������������������������������������������� 317 11.9 Mucinous Cystic Neoplasia������������������������������������������������������������������������������� 317 11.9.1 Epidemiology��������������������������������������������������������������������������������������� 317 11.9.2 Clinical Features ��������������������������������������������������������������������������������� 318 11.9.3 Key Cytology Features ����������������������������������������������������������������������� 318 11.9.4 Differential Diagnosis������������������������������������������������������������������������� 318 11.10 Malignant Epithelial Neoplasms����������������������������������������������������������������������� 318 11.10.1 Ductal Adenocarcinoma����������������������������������������������������������������������� 318 11.10.2 Epidemiology��������������������������������������������������������������������������������������� 318 11.10.3 Clinical Features ��������������������������������������������������������������������������������� 319 11.10.4 Key Cytological Features��������������������������������������������������������������������� 319 11.10.5 Differential Diagnosis������������������������������������������������������������������������� 320 11.11 Variants of Ductal Carcinoma��������������������������������������������������������������������������� 320 11.11.1 Adenosquamous Carcinoma ��������������������������������������������������������������� 320 11.11.2 Key Cytological Features��������������������������������������������������������������������� 320 11.11.3 Signet Ring Carcinoma����������������������������������������������������������������������� 320 11.11.4 Key Cytological Features��������������������������������������������������������������������� 320 11.11.5 Undifferentiated Carcinoma with Osteoclastic Giant Cell ����������������� 320 11.12 Anaplastic Carcinoma��������������������������������������������������������������������������������������� 321 11.12.1 Epidemiology��������������������������������������������������������������������������������������� 321 11.12.2 Key Cytological Features��������������������������������������������������������������������� 321 11.13 Small Cell Carcinoma ��������������������������������������������������������������������������������������� 321 11.13.1 Key Cytological Features��������������������������������������������������������������������� 321 11.14 Pancreatic Acinar Carcinoma����������������������������������������������������������������������������� 321 11.14.1 Epidemiology��������������������������������������������������������������������������������������� 321 11.14.2 Clinical Features ��������������������������������������������������������������������������������� 322 11.14.3 Key Cytological Features��������������������������������������������������������������������� 322 11.14.4 Differential Diagnosis������������������������������������������������������������������������� 323 11.15 Solid Pseudopapillary Neoplasm of the Pancreas��������������������������������������������� 323 11.15.1 Epidemiology��������������������������������������������������������������������������������������� 323 11.15.2 Clinical Features ��������������������������������������������������������������������������������� 323 11.15.3 Key Cytological Features��������������������������������������������������������������������� 323 11.15.4 Differential Diagnosis������������������������������������������������������������������������� 325 11.15.5 Pancreaticoblastoma ��������������������������������������������������������������������������� 325 11.15.6 Key Cytological Features��������������������������������������������������������������������� 325 11.16 Neuroendocrine Tumour ����������������������������������������������������������������������������������� 325 11.16.1 Pancreatic Endocrine Tumour (Islet Cell Tumour of Pancreas) ��������� 325 11.16.2 Clinical Features ��������������������������������������������������������������������������������� 325 11.16.3 Key Cytological Features��������������������������������������������������������������������� 325 11.16.4 Differential Diagnosis������������������������������������������������������������������������� 326 11.17 Metastatic Tumours in the Pancreas������������������������������������������������������������������ 327 11.17.1 Detection��������������������������������������������������������������������������������������������� 327 11.18 Pancreatic Lymphoma��������������������������������������������������������������������������������������� 327 References��������������������������������������������������������������������������������������������������������������������� 327 12 Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland��������������������� 329 12.1 Normal Cells ����������������������������������������������������������������������������������������������������� 329 12.1.1 Renal Tubular Cells����������������������������������������������������������������������������� 329 12.1.2 Glomeruli��������������������������������������������������������������������������������������������� 329 12.2 Renal Cyst��������������������������������������������������������������������������������������������������������� 330 12.2.1 Occurrence������������������������������������������������������������������������������������������� 330 12.2.2 Clinical Features ��������������������������������������������������������������������������������� 330

xx

Contents

12.2.3 Key Cytological Features��������������������������������������������������������������������� 330 12.3 Xanthogranulomatous Inflammation����������������������������������������������������������������� 330 12.3.1 Clinical Features ��������������������������������������������������������������������������������� 330 12.3.2 Key Cytological Features��������������������������������������������������������������������� 330 12.3.3 Differential Diagnosis������������������������������������������������������������������������� 331 12.3.4 Renal Tumours������������������������������������������������������������������������������������� 331 12.4 Benign Tumours of the Kidney������������������������������������������������������������������������� 331 12.4.1 Angiomyolipoma��������������������������������������������������������������������������������� 331 12.4.2 Epidemiology��������������������������������������������������������������������������������������� 331 12.4.3 Clinical Features ��������������������������������������������������������������������������������� 331 12.4.4 Key Cytological Features��������������������������������������������������������������������� 331 12.4.5 Immunocytochemistry������������������������������������������������������������������������� 332 12.4.6 Differential Diagnosis������������������������������������������������������������������������� 333 12.5 Metanephric Adenoma��������������������������������������������������������������������������������������� 333 12.5.1 Epidemiology��������������������������������������������������������������������������������������� 333 12.5.2 Clinical Features ��������������������������������������������������������������������������������� 333 12.5.3 Key Cytological Features��������������������������������������������������������������������� 333 12.5.4 Differential Diagnosis������������������������������������������������������������������������� 333 12.6 Renal Oncocytoma��������������������������������������������������������������������������������������������� 333 12.6.1 Epidemiology��������������������������������������������������������������������������������������� 334 12.6.2 Clinical Features ��������������������������������������������������������������������������������� 334 12.6.3 Key Cytological Features ������������������������������������������������������������������� 334 12.6.4 Differential Diagnosis������������������������������������������������������������������������� 334 12.7 Renal Cell Carcinoma ��������������������������������������������������������������������������������������� 334 12.7.1 Epidemiology��������������������������������������������������������������������������������������� 334 12.7.2 Clinical Features ��������������������������������������������������������������������������������� 334 12.7.3 Key Cytological Features��������������������������������������������������������������������� 335 12.7.4 Immunocytochemistry������������������������������������������������������������������������� 336 12.7.5 Differential Diagnosis������������������������������������������������������������������������� 336 12.7.6 Papillary Carcinoma ��������������������������������������������������������������������������� 337 12.8 Chromophobe Type������������������������������������������������������������������������������������������� 337 12.8.1 Sarcomatoid Type ������������������������������������������������������������������������������� 337 12.8.2 Collecting Duct Type��������������������������������������������������������������������������� 337 12.8.3 Differential Diagnosis of RCC ����������������������������������������������������������� 338 12.9 Urothelial Carcinoma����������������������������������������������������������������������������������������� 338 12.9.1 Epidemiology��������������������������������������������������������������������������������������� 338 12.9.2 Clinical Features ��������������������������������������������������������������������������������� 338 12.9.3 Key Cytological Features��������������������������������������������������������������������� 338 12.9.4 Differential Diagnosis������������������������������������������������������������������������� 339 12.9.5 Medullary Carcinoma ������������������������������������������������������������������������� 339 12.9.6 Epidemiology��������������������������������������������������������������������������������������� 339 12.9.7 Clinical Features ��������������������������������������������������������������������������������� 339 12.9.8 Key Cytological Features��������������������������������������������������������������������� 339 12.9.9 Differential Diagnosis������������������������������������������������������������������������� 339 12.10 Metastatic Tumours in Kidney��������������������������������������������������������������������������� 339 12.10.1 Diagnosis��������������������������������������������������������������������������������������������� 339 12.10.2 Renal Lymphoma��������������������������������������������������������������������������������� 339 12.11 Paediatric Kidney Tumours������������������������������������������������������������������������������� 339 12.11.1 Nephroblastoma����������������������������������������������������������������������������������� 339 12.11.2 Epidemiology��������������������������������������������������������������������������������������� 339 12.11.3 Clinical Features ��������������������������������������������������������������������������������� 340 12.11.4 Key Cytological Features��������������������������������������������������������������������� 340 12.11.5 Blastemal Cells ����������������������������������������������������������������������������������� 340

Contents

xxi

12.11.6 Epithelial Cells������������������������������������������������������������������������������������� 340 12.11.7 Mesenchymal Cells����������������������������������������������������������������������������� 341 12.11.8 Anaplastic Wilms’ Tumour����������������������������������������������������������������� 341 12.11.9 Differential Diagnosis������������������������������������������������������������������������� 341 12.12 Congenital Mesoblastic Nephroma (CMN)������������������������������������������������������� 341 12.12.1 Epidemiology��������������������������������������������������������������������������������������� 341 12.12.2 Clinical Features ��������������������������������������������������������������������������������� 341 12.12.3 Key Cytological Features��������������������������������������������������������������������� 341 12.12.4 Differential Diagnosis������������������������������������������������������������������������� 342 12.13 Rhabdoid Tumor ����������������������������������������������������������������������������������������������� 342 12.13.1 Epidemiology��������������������������������������������������������������������������������������� 342 12.13.2 Clinical Features ��������������������������������������������������������������������������������� 342 12.13.3 Key Cytological Features��������������������������������������������������������������������� 342 12.13.4 Differential Diagnosis������������������������������������������������������������������������� 342 12.14 Clear Cell Sarcoma ������������������������������������������������������������������������������������������� 343 12.14.1 Epidemiology��������������������������������������������������������������������������������������� 343 12.14.2 Clinical Features ��������������������������������������������������������������������������������� 343 12.14.3 Key Cytological Features��������������������������������������������������������������������� 343 12.15 Adrenal Gland��������������������������������������������������������������������������������������������������� 344 12.15.1 Indications������������������������������������������������������������������������������������������� 344 12.15.2 Technical Issue������������������������������������������������������������������������������������� 344 12.15.3 Complications ������������������������������������������������������������������������������������� 344 12.15.4 Anatomy of the Adrenal Gland����������������������������������������������������������� 344 12.15.5 Histology of Adrenal Gland����������������������������������������������������������������� 344 12.16 Benign Lesions of the Adrenal Gland��������������������������������������������������������������� 344 12.16.1 Adrenal Cyst ��������������������������������������������������������������������������������������� 344 12.16.2 Pseudocyst������������������������������������������������������������������������������������������� 345 12.16.3 Epithelial Cyst������������������������������������������������������������������������������������� 345 12.16.4 Endothelial Cyst����������������������������������������������������������������������������������� 345 12.16.5 Parasitic Cyst��������������������������������������������������������������������������������������� 345 12.16.6 Key Cytological Features��������������������������������������������������������������������� 345 12.17 Adrenal Myelolipoma ��������������������������������������������������������������������������������������� 345 12.17.1 Epidemiology��������������������������������������������������������������������������������������� 345 12.17.2 Clinical Features ��������������������������������������������������������������������������������� 345 12.17.3 Key Cytological Features��������������������������������������������������������������������� 345 12.17.4 Differential Diagnosis������������������������������������������������������������������������� 345 12.18 Adrenocortical Adenoma����������������������������������������������������������������������������������� 345 12.18.1 Epidemiology��������������������������������������������������������������������������������������� 345 12.18.2 Clinical Features ��������������������������������������������������������������������������������� 345 12.18.3 Key Cytological Features��������������������������������������������������������������������� 345 12.19 Adrenocortical Carcinoma��������������������������������������������������������������������������������� 346 12.19.1 Epidemiology��������������������������������������������������������������������������������������� 346 12.19.2 Clinical Features ��������������������������������������������������������������������������������� 346 12.19.3 Adrenal Adenoma Versus Adrenal Cortical Carcinoma����������������������� 346 12.19.4 Key Cytological Features��������������������������������������������������������������������� 346 12.19.5 Differential Diagnosis������������������������������������������������������������������������� 347 12.20 Pheochromocytoma������������������������������������������������������������������������������������������� 347 12.20.1 Epidemiology��������������������������������������������������������������������������������������� 347 12.20.2 Clinical Features ��������������������������������������������������������������������������������� 347 12.20.3 Key Cytological Features��������������������������������������������������������������������� 347 12.20.4 Differential Diagnosis������������������������������������������������������������������������� 348 12.21 Neuroblastoma of the Adrenal Gland ��������������������������������������������������������������� 348 12.21.1 Epidemiology��������������������������������������������������������������������������������������� 348

xxii

Contents

12.21.2 Clinical Features ��������������������������������������������������������������������������������� 348 12.21.3 Key Cytological Features��������������������������������������������������������������������� 348 12.22 Metastatic Tumors��������������������������������������������������������������������������������������������� 349 12.22.1 Diagnosis��������������������������������������������������������������������������������������������� 350 12.22.2 Differential Diagnosis������������������������������������������������������������������������� 350 References��������������������������������������������������������������������������������������������������������������������� 350 13 Fine Needle Aspiration Cytology of the Gonads ����������������������������������������������������� 351 13.1 Ovary����������������������������������������������������������������������������������������������������������������� 351 13.1.1 Indications of Ovarian FNAC ������������������������������������������������������������� 351 13.2 Benign Lesions of the Ovary����������������������������������������������������������������������������� 351 13.2.1 Non-neoplastic Cyst����������������������������������������������������������������������������� 351 13.2.2 Key Cytological Features��������������������������������������������������������������������� 351 13.2.3 Differential Diagnosis������������������������������������������������������������������������� 351 13.2.4 Corpus Luteal Cyst ����������������������������������������������������������������������������� 351 13.2.5 Key Cytological Features��������������������������������������������������������������������� 352 13.2.6 Endometriotic Cyst ����������������������������������������������������������������������������� 352 13.2.7 Key Cytological Features��������������������������������������������������������������������� 352 13.3 Serous Adenoma and Adenocarcinoma of Ovary ��������������������������������������������� 353 13.3.1 Serous Cystadenoma of Ovary ����������������������������������������������������������� 353 13.3.2 Clinical Features ��������������������������������������������������������������������������������� 353 13.3.3 Key Cytological Features��������������������������������������������������������������������� 353 13.4 Serous Adenocarcinoma������������������������������������������������������������������������������������� 353 13.4.1 Epidemiology��������������������������������������������������������������������������������������� 353 13.4.2 Genetic Profile������������������������������������������������������������������������������������� 353 13.4.3 Clinical Features ��������������������������������������������������������������������������������� 353 13.4.4 Key Cytological Features��������������������������������������������������������������������� 353 13.5 Mucinous Cystadenoma and Cystadenocarcinoma������������������������������������������� 355 13.5.1 Mucinous Cystadenoma����������������������������������������������������������������������� 355 13.5.2 Clinical Features ��������������������������������������������������������������������������������� 355 13.5.3 Key Cytological Features��������������������������������������������������������������������� 355 13.6 Mucinous Cystadenocarcinoma������������������������������������������������������������������������� 355 13.6.1 Epidemiology��������������������������������������������������������������������������������������� 355 13.6.2 Clinical Features ��������������������������������������������������������������������������������� 355 13.6.3 Key Cytological Features��������������������������������������������������������������������� 355 13.6.4 Differential Diagnosis������������������������������������������������������������������������� 356 13.7 Endometrioid Carcinoma����������������������������������������������������������������������������������� 356 13.7.1 Epidemiology��������������������������������������������������������������������������������������� 356 13.7.2 Clinical Features ��������������������������������������������������������������������������������� 356 13.7.3 Key Cytological Features��������������������������������������������������������������������� 356 13.8 Clear Cell Carcinoma����������������������������������������������������������������������������������������� 356 13.8.1 Epidemiology��������������������������������������������������������������������������������������� 356 13.8.2 Clinical Features ��������������������������������������������������������������������������������� 357 13.8.3 Key Cytological Features��������������������������������������������������������������������� 357 13.8.4 Differential Diagnosis������������������������������������������������������������������������� 357 13.8.5 Germ Cell Tumour������������������������������������������������������������������������������� 357 13.9 Mature Teratoma ����������������������������������������������������������������������������������������������� 358 13.9.1 Epidemiology��������������������������������������������������������������������������������������� 358 13.9.2 Clinical Features ��������������������������������������������������������������������������������� 358 13.9.3 Key Cytological Features��������������������������������������������������������������������� 358 13.10 Immature Teratoma ������������������������������������������������������������������������������������������� 358 13.10.1 Epidemiology��������������������������������������������������������������������������������������� 358 13.10.2 Clinical Features ��������������������������������������������������������������������������������� 358 13.10.3 Key Cytological Features��������������������������������������������������������������������� 358

Contents

xxiii

13.11 Carcinoid Tumours of the Ovary����������������������������������������������������������������������� 358 13.11.1 Epidemiology��������������������������������������������������������������������������������������� 358 13.11.2 Clinical Features ��������������������������������������������������������������������������������� 359 13.11.3 Key Cytological Features��������������������������������������������������������������������� 359 13.11.4 Differential Diagnosis������������������������������������������������������������������������� 359 13.12 Dysgerminoma��������������������������������������������������������������������������������������������������� 359 13.12.1 Epidemiology��������������������������������������������������������������������������������������� 359 13.12.2 Clinical Features ��������������������������������������������������������������������������������� 359 13.12.3 Key Cytological features��������������������������������������������������������������������� 359 13.12.4 Differential Diagnosis������������������������������������������������������������������������� 361 13.13 Yolk Sac Tumour����������������������������������������������������������������������������������������������� 361 13.13.1 Epidemiology��������������������������������������������������������������������������������������� 361 13.13.2 Clinical Features ��������������������������������������������������������������������������������� 361 13.13.3 Key Cytological Features��������������������������������������������������������������������� 361 13.14 Sex Cord-Stromal Tumour��������������������������������������������������������������������������������� 361 13.14.1 Granulosa Cell Tumour����������������������������������������������������������������������� 361 13.14.2 Molecular Genetics����������������������������������������������������������������������������� 361 13.14.3 Clinical Features ��������������������������������������������������������������������������������� 361 13.14.4 Key Cytological Features��������������������������������������������������������������������� 361 13.14.5 Differential Diagnosis������������������������������������������������������������������������� 362 13.15 Sertoli Cell Tumour������������������������������������������������������������������������������������������� 362 13.15.1 Clinical Features ��������������������������������������������������������������������������������� 362 13.15.2 Key Cytological Features��������������������������������������������������������������������� 362 13.16 Fibroma and Thecoma��������������������������������������������������������������������������������������� 363 13.16.1 Key Cytological Features��������������������������������������������������������������������� 363 13.17 Metastatic Tumours in the Ovary����������������������������������������������������������������������� 363 13.17.1 Key Cytological Features��������������������������������������������������������������������� 363 13.17.2 Indicators of Metastasis����������������������������������������������������������������������� 363 13.18 Testis ����������������������������������������������������������������������������������������������������������������� 363 13.18.1 Indications of FNAC��������������������������������������������������������������������������� 363 13.19 Anatomy and Histology of Testis����������������������������������������������������������������������� 363 13.19.1 Histology��������������������������������������������������������������������������������������������� 364 13.19.2 Normal Cells of Testis FNAC ������������������������������������������������������������� 364 13.19.3 Primary Spermatocytes ����������������������������������������������������������������������� 364 13.19.4 Peritesticular Lesions��������������������������������������������������������������������������� 364 13.19.5 Hydrocele��������������������������������������������������������������������������������������������� 364 13.19.6 Key Cytological Features��������������������������������������������������������������������� 365 13.20 Inflammation ����������������������������������������������������������������������������������������������������� 365 13.20.1 Acute Epididymitis ����������������������������������������������������������������������������� 365 13.20.2 Key Cytological Features��������������������������������������������������������������������� 365 13.21 Chronic Epididymitis����������������������������������������������������������������������������������������� 365 13.21.1 Clinical Features ��������������������������������������������������������������������������������� 365 13.21.2 Key Cytological Features��������������������������������������������������������������������� 365 13.22 Tuberculous Epididymitis ��������������������������������������������������������������������������������� 365 13.22.1 Key Cytological Features��������������������������������������������������������������������� 365 13.22.2 Filarial Inflammation��������������������������������������������������������������������������� 365 13.23 Adenomatoid Tumour ��������������������������������������������������������������������������������������� 365 13.23.1 Epidemiology��������������������������������������������������������������������������������������� 366 13.23.2 Clinical Features ��������������������������������������������������������������������������������� 366 13.23.3 Key Cytological Features��������������������������������������������������������������������� 366 13.24 Spermatocytic Granuloma��������������������������������������������������������������������������������� 366 13.24.1 Clinical Features ��������������������������������������������������������������������������������� 366 13.24.2 Key Cytological Features��������������������������������������������������������������������� 366 13.24.3 Male Infertility������������������������������������������������������������������������������������� 366

xxiv

Contents

13.24.4 Sertoli Cell-Only Syndrome ��������������������������������������������������������������� 367 13.25 Neoplasm of Testis��������������������������������������������������������������������������������������������� 367 13.25.1 Seminoma ������������������������������������������������������������������������������������������� 367 13.25.2 Epidemiology��������������������������������������������������������������������������������������� 368 13.25.3 Clinical Features ��������������������������������������������������������������������������������� 368 13.25.4 Key Cytological Features of Classical Seminoma������������������������������� 368 13.26 Spermatocytic Seminoma ��������������������������������������������������������������������������������� 369 13.26.1 Key Cytological Features of Spermatocytic Seminoma ��������������������� 369 13.26.2 Differential Diagnosis������������������������������������������������������������������������� 369 13.27 Embryonal Carcinoma��������������������������������������������������������������������������������������� 369 13.27.1 Epidemiology��������������������������������������������������������������������������������������� 369 13.27.2 Clinical Features ��������������������������������������������������������������������������������� 369 13.27.3 Key Cytological Features��������������������������������������������������������������������� 369 13.28 Choriocarcinoma����������������������������������������������������������������������������������������������� 370 13.28.1 Epidemiology��������������������������������������������������������������������������������������� 370 13.28.2 Clinical Feature����������������������������������������������������������������������������������� 370 13.28.3 Key Cytological Features��������������������������������������������������������������������� 370 13.29 Other Tumours of the Testis������������������������������������������������������������������������������� 370 13.29.1 Leydig Cell Tumour����������������������������������������������������������������������������� 370 13.29.2 Clinical Features ��������������������������������������������������������������������������������� 370 13.29.3 Key Cytological Features��������������������������������������������������������������������� 370 13.30 Non-Hodgkin Lymphoma ��������������������������������������������������������������������������������� 371 13.30.1 Leukemic Infiltration��������������������������������������������������������������������������� 371 References��������������������������������������������������������������������������������������������������������������������� 371 14 Fine Needle Aspiration Cytology of the Soft Tissue Lesions����������������������������������� 373 14.1 Specimen Collection and Ancillary Techniques ����������������������������������������������� 373 14.2 Ancillary Techniques����������������������������������������������������������������������������������������� 374 14.2.1 Immunocytochemistry������������������������������������������������������������������������� 374 14.2.2 Flow Cytometry����������������������������������������������������������������������������������� 374 14.2.3 Molecular Genetics����������������������������������������������������������������������������� 374 14.2.4 Electron Microscopy��������������������������������������������������������������������������� 374 14.2.5 Reporting Terminology����������������������������������������������������������������������� 375 14.2.6 Malignancy ����������������������������������������������������������������������������������������� 375 14.3 Classification of Soft Tissue Tumours��������������������������������������������������������������� 375 14.4 Tumours of Adipocytes ������������������������������������������������������������������������������������� 375 14.4.1 Benign Tumours����������������������������������������������������������������������������������� 375 14.4.2 Clinical Feature����������������������������������������������������������������������������������� 376 14.4.3 Key Cytological Features��������������������������������������������������������������������� 376 14.5 Angiolipoma ����������������������������������������������������������������������������������������������������� 376 14.5.1 Epidemiology��������������������������������������������������������������������������������������� 376 14.5.2 Clinical Features ��������������������������������������������������������������������������������� 376 14.5.3 Key Cytological Features��������������������������������������������������������������������� 376 14.6 Spindle Cell Lipoma ����������������������������������������������������������������������������������������� 376 14.6.1 Epidemiology��������������������������������������������������������������������������������������� 376 14.6.2 Clinical Features ��������������������������������������������������������������������������������� 377 14.6.3 Key Cytological Features��������������������������������������������������������������������� 377 14.7 Pleomorphic Lipoma����������������������������������������������������������������������������������������� 377 14.7.1 Key Cytological Features��������������������������������������������������������������������� 377 14.7.2 Differential Diagnosis������������������������������������������������������������������������� 377 14.8 Hibernoma��������������������������������������������������������������������������������������������������������� 377 14.8.1 Epidemiology��������������������������������������������������������������������������������������� 378 14.8.2 Clinical Features ��������������������������������������������������������������������������������� 378

Contents

xxv

14.8.3 Key Cytological Features��������������������������������������������������������������������� 378 14.8.4 Differential Diagnosis������������������������������������������������������������������������� 378 14.9 Myelolipoma ����������������������������������������������������������������������������������������������������� 378 14.9.1 Key Cytological Features��������������������������������������������������������������������� 378 14.10 Liposarcomas����������������������������������������������������������������������������������������������������� 378 14.10.1 Epidemiology��������������������������������������������������������������������������������������� 378 14.10.2 Clinical Features ��������������������������������������������������������������������������������� 378 14.10.3 Key Cytological Features��������������������������������������������������������������������� 378 14.10.4 Differential Diagnosis������������������������������������������������������������������������� 379 14.11 Myxoid Liposarcoma����������������������������������������������������������������������������������������� 379 14.11.1 Epidemiology��������������������������������������������������������������������������������������� 379 14.11.2 Clinical Features ��������������������������������������������������������������������������������� 379 14.11.3 Key Cytological Features��������������������������������������������������������������������� 379 14.11.4 Differential Diagnosis������������������������������������������������������������������������� 380 14.12 Pleomorphic Liposarcoma��������������������������������������������������������������������������������� 380 14.12.1 Epidemiology��������������������������������������������������������������������������������������� 380 14.12.2 Clinical Features ��������������������������������������������������������������������������������� 380 14.12.3 Key Cytological Features��������������������������������������������������������������������� 380 14.12.4 Differential Diagnosis������������������������������������������������������������������������� 380 14.13 Round Cell Liposarcoma����������������������������������������������������������������������������������� 380 14.13.1 Key Cytological Features��������������������������������������������������������������������� 381 14.14 Fibroblastic/Myofibroblastic Tumours��������������������������������������������������������������� 381 14.14.1 Benign������������������������������������������������������������������������������������������������� 381 14.14.2 Clinical Features ��������������������������������������������������������������������������������� 381 14.14.3 Key Cytological Features��������������������������������������������������������������������� 381 14.15 Myositis Ossificans ������������������������������������������������������������������������������������������� 381 14.15.1 Epidemiology��������������������������������������������������������������������������������������� 381 14.15.2 Clinical Features ��������������������������������������������������������������������������������� 381 14.15.3 Key Cytological Features��������������������������������������������������������������������� 381 14.16 Solitary Fibrous Tumour ����������������������������������������������������������������������������������� 382 14.16.1 Epidemiology��������������������������������������������������������������������������������������� 382 14.16.2 Clinical Features ��������������������������������������������������������������������������������� 382 14.16.3 Key Cytological Features��������������������������������������������������������������������� 382 14.16.4 Malignant Solitary Fibrous Tumour ��������������������������������������������������� 382 14.17 Dermatofibrosarcoma Protuberans��������������������������������������������������������������������� 383 14.17.1 Key Cytological Features��������������������������������������������������������������������� 383 14.18 Myofibroblastoma ��������������������������������������������������������������������������������������������� 384 14.18.1 Epidemiology��������������������������������������������������������������������������������������� 384 14.18.2 Clinical Features ��������������������������������������������������������������������������������� 384 14.18.3 Key Cytological Features��������������������������������������������������������������������� 384 14.19 Fibrosarcoma����������������������������������������������������������������������������������������������������� 384 14.19.1 Epidemiology��������������������������������������������������������������������������������������� 384 14.19.2 Clinical Features ��������������������������������������������������������������������������������� 384 14.19.3 Key Cytological Features��������������������������������������������������������������������� 384 14.20 So-Called “Fibrohistiocytic Tumours”�������������������������������������������������������������� 385 14.20.1 Giant Cell Tumour of Tendon Sheath ������������������������������������������������� 385 14.20.2 Epidemiology��������������������������������������������������������������������������������������� 385 14.20.3 Clinical Features ��������������������������������������������������������������������������������� 385 14.20.4 Key Cytological Features��������������������������������������������������������������������� 385 14.21 Pleomorphic Malignant Fibrous Histiocytoma������������������������������������������������� 386 14.21.1 Epidemiology��������������������������������������������������������������������������������������� 386 14.21.2 Clinical Features ��������������������������������������������������������������������������������� 386 14.21.3 Key Cytological Features��������������������������������������������������������������������� 386

xxvi

Contents

14.21.4 Differential Diagnosis������������������������������������������������������������������������� 386 14.22 Tumours of Nerve Sheath ��������������������������������������������������������������������������������� 386 14.22.1 Benign Peripheral Nerve Sheath Tumour ������������������������������������������� 386 14.22.2 Key Cytological Feature ��������������������������������������������������������������������� 386 14.23 Malignant Peripheral Nerve Sheath Tumour����������������������������������������������������� 387 14.23.1 Epidemiology��������������������������������������������������������������������������������������� 387 14.23.2 Clinical Features ��������������������������������������������������������������������������������� 387 14.23.3 Key Cytological Feature ��������������������������������������������������������������������� 387 14.24 Tumours of Muscle Origin��������������������������������������������������������������������������������� 389 14.24.1 Rhabdomyoma������������������������������������������������������������������������������������� 389 14.24.2 Epidemiology��������������������������������������������������������������������������������������� 389 14.24.3 Clinical Features ��������������������������������������������������������������������������������� 389 14.24.4 Key Cytological Feature ��������������������������������������������������������������������� 389 14.25 Rhabdomyosarcoma������������������������������������������������������������������������������������������� 389 14.25.1 Embryonal Rhabdomyosarcoma��������������������������������������������������������� 389 14.25.2 Clinical Features ��������������������������������������������������������������������������������� 389 14.25.3 Key Cytological Feature ��������������������������������������������������������������������� 389 14.26 Alveolar Rhabdomyosarcoma��������������������������������������������������������������������������� 390 14.26.1 Epidemiology��������������������������������������������������������������������������������������� 390 14.26.2 Clinical Features ��������������������������������������������������������������������������������� 391 14.26.3 Key Cytological Features��������������������������������������������������������������������� 391 14.27 Pleomorphic Rhabdomyosarcoma��������������������������������������������������������������������� 391 14.27.1 Epidemiology��������������������������������������������������������������������������������������� 391 14.27.2 Clinical Features ��������������������������������������������������������������������������������� 391 14.27.3 Key Cytological Features��������������������������������������������������������������������� 391 14.28 Leiomyosarcomas ��������������������������������������������������������������������������������������������� 391 14.28.1 Epidemiology��������������������������������������������������������������������������������������� 391 14.28.2 Clinical Features ��������������������������������������������������������������������������������� 391 14.28.3 Key Cytological Feature ��������������������������������������������������������������������� 391 14.29 Tumour of Vascular Origin ������������������������������������������������������������������������������� 392 14.29.1 Glomus Tumour����������������������������������������������������������������������������������� 392 14.29.2 Epidemiology��������������������������������������������������������������������������������������� 392 14.29.3 Clinical Features ��������������������������������������������������������������������������������� 392 14.29.4 Key Cytological Feature ��������������������������������������������������������������������� 392 14.30 Haemangioma ��������������������������������������������������������������������������������������������������� 392 14.30.1 Clinical Features ��������������������������������������������������������������������������������� 392 14.30.2 Key Cytological Features��������������������������������������������������������������������� 392 14.31 Angiosarcoma ��������������������������������������������������������������������������������������������������� 392 14.31.1 Epidemiology��������������������������������������������������������������������������������������� 392 14.31.2 Clinical Features ��������������������������������������������������������������������������������� 392 14.31.3 Key Cytological Features��������������������������������������������������������������������� 393 14.32 Tumours of Uncertain Histogenesis������������������������������������������������������������������� 393 14.32.1 Synovial Sarcoma ������������������������������������������������������������������������������� 393 14.32.2 Epidemiology��������������������������������������������������������������������������������������� 393 14.32.3 Clinical Features ��������������������������������������������������������������������������������� 393 14.32.4 Key Cytological Features��������������������������������������������������������������������� 393 14.33 Clear Cell Sarcoma (CCS)��������������������������������������������������������������������������������� 394 14.33.1 Epidemiology��������������������������������������������������������������������������������������� 395 14.33.2 Clinical Features ��������������������������������������������������������������������������������� 395 14.33.3 Key Cytological Features��������������������������������������������������������������������� 395 14.34 Epithelioid Sarcoma������������������������������������������������������������������������������������������� 396 14.34.1 Epidemiology��������������������������������������������������������������������������������������� 396 14.34.2 Clinical Features ��������������������������������������������������������������������������������� 396

Contents

xxvii

14.34.3 Key Cytological Features��������������������������������������������������������������������� 396 14.35 Alveolar Soft Part Sarcoma������������������������������������������������������������������������������� 397 14.35.1 Epidemiology��������������������������������������������������������������������������������������� 397 14.35.2 Clinical Features ��������������������������������������������������������������������������������� 397 14.35.3 Key Cytological Features��������������������������������������������������������������������� 397 14.36 Granular Cell Tumour ��������������������������������������������������������������������������������������� 397 14.36.1 Epidemiology��������������������������������������������������������������������������������������� 397 14.36.2 Clinical Features ��������������������������������������������������������������������������������� 398 14.36.3 Key Cytological Features��������������������������������������������������������������������� 398 References��������������������������������������������������������������������������������������������������������������������� 398 15 Fine Needle Aspiration Cytology of the Bone����������������������������������������������������������� 399 15.1 Infection������������������������������������������������������������������������������������������������������������� 400 15.1.1 Osteomyelitis��������������������������������������������������������������������������������������� 400 15.2 Neoplastic Lesions of Bone������������������������������������������������������������������������������� 400 15.2.1 Bone Forming Tumour������������������������������������������������������������������������� 400 15.2.2 Key Cytological Features��������������������������������������������������������������������� 401 15.2.3 Osteoid Osteoma��������������������������������������������������������������������������������� 401 15.2.4 Clinical Feature����������������������������������������������������������������������������������� 401 15.2.5 Key Cytological Features��������������������������������������������������������������������� 401 15.3 Osteosarcoma����������������������������������������������������������������������������������������������������� 402 15.3.1 Epidemiology��������������������������������������������������������������������������������������� 402 15.3.2 Clinical Features ��������������������������������������������������������������������������������� 402 15.3.3 Key Cytological Features��������������������������������������������������������������������� 402 15.3.4 Conventional Osteosarcomas Are of Three Types������������������������������� 403 15.3.5 Differential Diagnosis������������������������������������������������������������������������� 404 15.4 Cartilage Forming Tumour�������������������������������������������������������������������������������� 404 15.4.1 Chondroma ����������������������������������������������������������������������������������������� 404 15.4.2 Epidemiology��������������������������������������������������������������������������������������� 404 15.4.3 Clinical Features ��������������������������������������������������������������������������������� 404 15.4.4 Key Cytology Features ����������������������������������������������������������������������� 404 15.5 Chondroblastoma����������������������������������������������������������������������������������������������� 405 15.5.1 Epidemiology��������������������������������������������������������������������������������������� 405 15.5.2 Clinical Features ��������������������������������������������������������������������������������� 405 15.5.3 Key Cytology Features ����������������������������������������������������������������������� 405 15.5.4 Differential Diagnosis������������������������������������������������������������������������� 406 15.6 Chondromyxoid Fibroma����������������������������������������������������������������������������������� 406 15.6.1 Epidemiology��������������������������������������������������������������������������������������� 406 15.6.2 Clinical Features ��������������������������������������������������������������������������������� 406 15.6.3 Key Cytology Features ����������������������������������������������������������������������� 407 15.6.4 Differential Diagnosis������������������������������������������������������������������������� 407 15.7 Chondrosarcoma ����������������������������������������������������������������������������������������������� 407 15.7.1 Epidemiology��������������������������������������������������������������������������������������� 407 15.7.2 Clinical Features ��������������������������������������������������������������������������������� 407 15.7.3 Key Cytology Features ����������������������������������������������������������������������� 407 15.7.4 Differential Diagnosis������������������������������������������������������������������������� 408 15.8 Variants of CHS������������������������������������������������������������������������������������������������� 408 15.8.1 Mesenchymal Chondrosarcoma����������������������������������������������������������� 408 15.8.2 Clinical Features ��������������������������������������������������������������������������������� 408 15.9 Clear Cell Chondrosarcoma������������������������������������������������������������������������������� 408 15.9.1 Epidemiology��������������������������������������������������������������������������������������� 408 15.9.2 Clinical Features ��������������������������������������������������������������������������������� 409 15.9.3 Key Cytology Features ����������������������������������������������������������������������� 409

xxviii

Contents

15.10 Dedifferentiated Chondrosarcoma��������������������������������������������������������������������� 409 15.10.1 Epidemiology��������������������������������������������������������������������������������������� 409 15.10.2 Clinical Features ��������������������������������������������������������������������������������� 409 15.10.3 Key Cytology Features ����������������������������������������������������������������������� 409 15.11 Giant Cell Tumour of Bone������������������������������������������������������������������������������� 409 15.11.1 Epidemiology��������������������������������������������������������������������������������������� 409 15.11.2 Clinical Features ��������������������������������������������������������������������������������� 409 15.11.3 Key Cytology Features ����������������������������������������������������������������������� 409 15.11.4 Differential Diagnosis������������������������������������������������������������������������� 410 15.12 Chordoma����������������������������������������������������������������������������������������������������������� 410 15.12.1 Epidemiology��������������������������������������������������������������������������������������� 410 15.12.2 Clinical Features ��������������������������������������������������������������������������������� 410 15.12.3 Key Cytology Features ����������������������������������������������������������������������� 411 15.12.4 Differential Diagnosis������������������������������������������������������������������������� 411 15.13 Ewing’s Sarcoma (EWS)/Peripheral Neuroectodermal Tumour (PNET) ��������� 412 15.13.1 Epidemiology��������������������������������������������������������������������������������������� 412 15.13.2 Clinical Features ��������������������������������������������������������������������������������� 412 15.13.3 Key Cytology Features ����������������������������������������������������������������������� 412 15.13.4 Differential Diagnosis������������������������������������������������������������������������� 413 15.14 Non-Hodgkin Lymphoma ��������������������������������������������������������������������������������� 413 15.14.1 Epidemiology��������������������������������������������������������������������������������������� 413 15.14.2 Types��������������������������������������������������������������������������������������������������� 413 15.15 Plasma Cell Neoplasm��������������������������������������������������������������������������������������� 414 15.15.1 Epidemiology��������������������������������������������������������������������������������������� 414 15.15.2 Clinical Features ��������������������������������������������������������������������������������� 414 15.15.3 Key Cytology Features ����������������������������������������������������������������������� 414 15.15.4 Differential Diagnosis������������������������������������������������������������������������� 415 15.16 Langerhans Cell Histiocytosis��������������������������������������������������������������������������� 415 15.16.1 Epidemiology��������������������������������������������������������������������������������������� 415 15.16.2 Key Cytology Features ����������������������������������������������������������������������� 415 15.16.3 Differential Diagnosis������������������������������������������������������������������������� 416 15.17 Metastatic Carcinoma ��������������������������������������������������������������������������������������� 416 15.17.1 Epidemiology��������������������������������������������������������������������������������������� 416 15.17.2 Clinical Features ��������������������������������������������������������������������������������� 416 15.17.3 Key Cytological Features��������������������������������������������������������������������� 416 15.18 Other Bone Lesions������������������������������������������������������������������������������������������� 418 15.18.1 Aneurysmal Bone Cyst ����������������������������������������������������������������������� 418 15.18.2 Key Cytological Features��������������������������������������������������������������������� 418 15.19 Adamantinoma��������������������������������������������������������������������������������������������������� 418 15.19.1 Epidemiology��������������������������������������������������������������������������������������� 418 15.19.2 Key Cytological Features��������������������������������������������������������������������� 418 15.19.3 Differential Diagnosis������������������������������������������������������������������������� 419 References��������������������������������������������������������������������������������������������������������������������� 419 16 Fine Needle Aspiration Cytology of the Skin Lesions��������������������������������������������� 421 16.1 Non-neoplastic Lesions of the Skin������������������������������������������������������������������� 421 16.1.1 Inflammation��������������������������������������������������������������������������������������� 421 16.1.2 Fungal Infection����������������������������������������������������������������������������������� 421 16.1.3 Bacterial Infection������������������������������������������������������������������������������� 421 16.1.4 Dermal Leishmaniasis������������������������������������������������������������������������� 422 16.1.5 Cysticercosis ��������������������������������������������������������������������������������������� 422 16.1.6 Microfilariae Infection������������������������������������������������������������������������� 423

Contents

xxix

16.2 Non-neoplastic Benign Lesions of the Skin������������������������������������������������������� 423 16.2.1 Tumoral Calcinosis ����������������������������������������������������������������������������� 423 16.2.2 Sarcoidosis������������������������������������������������������������������������������������������� 423 16.2.3 Ganglionic Cyst����������������������������������������������������������������������������������� 424 16.2.4 Cytology Smear����������������������������������������������������������������������������������� 424 16.3 Endometriosis ��������������������������������������������������������������������������������������������������� 424 16.3.1 Amyloidosis����������������������������������������������������������������������������������������� 424 16.3.2 Cytology ��������������������������������������������������������������������������������������������� 425 16.4 Epidermal Inclusion Cyst����������������������������������������������������������������������������������� 425 16.4.1 Cytology ��������������������������������������������������������������������������������������������� 425 16.5 Neoplastic Lesions of the Skin ������������������������������������������������������������������������� 425 16.5.1 Benign Tumour of Skin Adnexa ��������������������������������������������������������� 425 16.5.2 Epidemiology��������������������������������������������������������������������������������������� 425 16.5.3 Key Cytological Features��������������������������������������������������������������������� 426 16.5.4 Differential Diagnosis������������������������������������������������������������������������� 426 16.6 Chondroid Syringoma��������������������������������������������������������������������������������������� 427 16.6.1 Epidemiology��������������������������������������������������������������������������������������� 427 16.6.2 Key Cytological Features��������������������������������������������������������������������� 427 16.7 Cylindroma ������������������������������������������������������������������������������������������������������� 428 16.7.1 Epidemiology��������������������������������������������������������������������������������������� 428 16.7.2 Location����������������������������������������������������������������������������������������������� 428 16.7.3 Clinical Features ��������������������������������������������������������������������������������� 428 16.7.4 Key Cytological Features��������������������������������������������������������������������� 428 16.8 Eccrine Spiradenoma����������������������������������������������������������������������������������������� 429 16.8.1 Epidemiology��������������������������������������������������������������������������������������� 429 16.8.2 Clinical Features ��������������������������������������������������������������������������������� 429 16.8.3 Key Cytological Features��������������������������������������������������������������������� 430 16.9 Hidradenoma����������������������������������������������������������������������������������������������������� 430 16.9.1 Epidemiology��������������������������������������������������������������������������������������� 430 16.9.2 Key Cytological Features��������������������������������������������������������������������� 430 16.10 Syringocystadenoma Papilliferum��������������������������������������������������������������������� 431 16.10.1 Epidemiology��������������������������������������������������������������������������������������� 431 16.10.2 Clinical Features ��������������������������������������������������������������������������������� 431 16.10.3 Key Cytological Features��������������������������������������������������������������������� 431 16.11 Malignant Tumours of the Skin������������������������������������������������������������������������� 431 16.11.1 Basal Cell Carcinoma ������������������������������������������������������������������������� 431 16.11.2 Epidemiology��������������������������������������������������������������������������������������� 432 16.11.3 Clinical Features ��������������������������������������������������������������������������������� 432 16.11.4 Key Cytological Features��������������������������������������������������������������������� 432 16.12 Sebaceous Carcinoma ��������������������������������������������������������������������������������������� 433 16.12.1 Epidemiology��������������������������������������������������������������������������������������� 433 16.12.2 Key Cytological Features��������������������������������������������������������������������� 433 16.13 Malignant Melanoma����������������������������������������������������������������������������������������� 434 16.13.1 Epidemiology��������������������������������������������������������������������������������������� 434 16.13.2 Key Cytological Features��������������������������������������������������������������������� 434 16.14 Squamous Cell Carcinoma��������������������������������������������������������������������������������� 435 16.14.1 Epidemiology��������������������������������������������������������������������������������������� 435 16.14.2 Clinical Features ��������������������������������������������������������������������������������� 435 16.14.3 Key Cytological Features��������������������������������������������������������������������� 435 16.15 Malignant Sweat Gland Tumour����������������������������������������������������������������������� 436 16.15.1 Key Cytological Features��������������������������������������������������������������������� 436

xxx

Contents

16.16 Merkel Cell Carcinoma������������������������������������������������������������������������������������� 436 16.16.1 Epidemiology��������������������������������������������������������������������������������������� 436 16.16.2 Clinical Features ��������������������������������������������������������������������������������� 436 16.16.3 Key Cytological Features��������������������������������������������������������������������� 436 16.17 Metastasis����������������������������������������������������������������������������������������������������������� 437 16.17.1 Key Cytological Features��������������������������������������������������������������������� 437 16.17.2 Hematopoietic Malignancy����������������������������������������������������������������� 438 References��������������������������������������������������������������������������������������������������������������������� 438 17 Review of the Cases and Self-Assessment����������������������������������������������������������������� 439 17.1 Answers������������������������������������������������������������������������������������������������������������� 463

About the Author

Pranab Dey  is Professor in the Department of Cytology and Gynecologic Pathology at Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh. Professor Dey completed his M.D. (pathology) from PGIMER, Chandigarh, and FRCPath (cytopathology) from the Royal College of Pathologists, London. He has been a Consultant of cytology and gynecologic pathology in PGIMER for the last 27 years and Professor since the last 9 years. Professor Dey has conducted many research projects and has pioneered works on DNA flow cytometry, image morphometry, mono-layered cytology, and cytomorphologic findings of various lesions on cytology smears. He is a well-published author and has published several books in the field of cytology and gynecologic pathology, 270 publications in international journals. Professor Dey is a member of various societies.

xxxi

1

Introduction and Basic Techniques of Aspiration Cytology in Superficial and Deep Lesions

Presently fine needle aspiration cytology (FNAC) is an easy and useful technique in the diagnosis, management and assessment of prognosis of a lesion.

Table 1.1  Comparison of aspiration cytology and histopathological study

Rapidity

1.1

Advantages [1–5]

FNAC technique has many advantages over the histopathology. These advantages include (Table 1.1): • • • • •

A simple technique. An office technique. Quick and economical. It can eliminate tissue biopsy in many conditions. All the special techniques such as immunocytochemistry, molecular techniques, flow cytometry and bacterial culture are possible from FNAC material. • High sensitivity and specificity. Limitations • Significant loss of the tissue architecture • Difficult to differentiate in situ from invasive carcinoma • Not possible to comment on the capsular and lymphatic invasion Complications • Minor hematoma formation • Anaphylactic shock in case of rupture of the hydatid cyst • Surgical emphysema in case of intrathoracic FNAC • An accidental tear of an aneurysmal vessel • Needle tract seedling [6]: It is a debatable issue, and it rarely occurs if we use fine bore needle

1.2

Needle Tract Seeding

The needle tract seeding is a potential danger of FNAC. There are many contradictory reports in this area [6]. However, the needle tract seeding may not be a mere myth as the exact inci-

Procedure Cost Architecture Ancillary studies

Sensitivity and specificity

Histopathological Fine needle aspiration cytology examination Very fast Takes time, at least 1 day Office procedure Operation theatre needed Cheaper Costly Not maintained Well maintained Possible Possible. Immunocytochemistry, Flow cytometry, microbial culture, the genetic study can be done Good Excellent. It is the “gold standard”

dence of this phenomenon is difficult to ascertain. The FNAC technique is more beneficial than the needle tract seeding. Contraindications • No absolute contraindications of FNAC. • Avoid in case of bleeding diathesis. • Avoid when there is a chance of rupturing the hydatid cyst. • Avoid in case of confirmed aneurysmal cyst.

1.3

The Basic Technique of FNAC

A. Equipment (Fig. 1.1) • Clean glass slides. • Pistol handle: It is a metal “pistol-like handle” to hold the syringe so that one hand of the operator is free. • Syringe: Clean fresh sterile syringe either 20 or 10 ml. • Needle: Ordinary disposable needle from 22 to 27 gauge. It is preferable to use a thin gauge needle except in case of bone and hard swelling. • Spirit swab.

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_1

1

2

1  Introduction and Basic Techniques of Aspiration Cytology in Superficial and Deep Lesions

Fig. 1.1  Basic requirements for FNAC techniques include pistol handle, syringe, needle, cotton swab, fixative (95% ethanol) and forceps

• Other necessary chemicals: –– Neutral buffered formalin 10% for cell block. –– Balanced salt solution for flow cytometry or molecular tests. –– Ethanol (95%) for fixation of the smear. –– Solution for liquid-based cytology. The Essential Requirements of a Good FNAC Clinic • Well ventilated • Well lighted • Preferably near the hospital outdoor • Equipped with an examination bed, working table, and chair • A sink with running water • Rapid staining kit • Microscope Steps of FNAC (Box 1.1) The essential steps of the FNAC procedure include:

Box 1.1: Essential Steps of FNAC

Reassurance: Identify the patient and reassure him Clinical history: Take good clinical history including bleeding disorder Step proper • Clean the lesion by spirit swab • Grasp the swelling by one hand to immobilize it • Insert the needle with syringe and pistol handle attached with it • Pass the needle back and forth by moving the pistol handle • Create negative pressure • Release the suction and withdraw the needle

• Detach the needle from the syringe and fill the syringe with air • Reattach the needle with syringe • Push the material on the slides and make multiple smears Ancillary technique: Take one part of the remaining sample in the syringe hub or re-aspirated material for ancillary study Re-examination: Bleeding or any other complications

Clinical History • Identify the patient • Take proper consent • Note down the chief complaints • Take a relevant past medical history • Examine the patient Aspiration Technique (Fig. 1.2) • Clean the lesion by spirit swab. • Grasp the swelling by one hand to immobilize it. • Insert the needle with syringe and pistol handle attached with it. • Pass the needle back and forth by moving the pistol handle. • Create negative pressure. • Release the handle. • Take out the needle. • Remove the needle from the syringe and take air in the syringe. • Reattach the needle with a syringe. • Push the aspirate out of the syringe to a fresh glass slide.

1.4 Post FNAC

3

a

b

c

d

Fig. 1.2 (a) The area of aspiration is cleaned, (b) needle attached with handle is introduced in the lesion and moved to and fro, (c) Needle is withdrawn, and the material is put on the slide and (d) Smear is made by pressing a clean glass slide on the material

• Spread the material on the slide with the help of a spare glass slide. • Keep few slides in 95% ethanol for wet fixation. • Tell the patient to press the puncture site firmly with a piece of dry cotton for a few minutes. • Re-examine the patient if needed.

1.4

Post FNAC

• Care should be taken so that there is no bleeding or any other significant complications. • Often the patient may have a vasovagal attack, particularly after testicular FNAC. So the cytologists should not hurry, and the patient should relax adequate time in lying position.

1.4.1 Fine-Needle Sampling Technique In recent days fine-needle sampling (FNS) technique is also considered as one of the essential procedures. FNS bears several advantages that include: Advantages • Easy and simple • Free of blood • Suitable for small lesion and thyroid This technique should be avoided in: Avoid FNS • Cystic lesion • Bony and hard swelling • It is better to avoid if you need material for cell block

4

1  Introduction and Basic Techniques of Aspiration Cytology in Superficial and Deep Lesions

• • • • •

Thin Prep: Company made methanol-based fixative SurePath: Company made ethanol-based solution Cellblock: 10% Neutral buffered formalin Flow cytometry: Balanced salt solution Molecular testing (gene sequencing): Balanced salt solution

1.4.3 Staining Air-dried smear: May Grunwald Giemsa stain, Diff–Quick stain Wet fixed smear: Papanicolaou’s stain, Haematoxylin and Eosin stain Fig. 1.3  Fine-needle sampling technique: The area is cleaned, and the lesion is held in between two fingers then the needle (unattached with a syringe) is introduced in the lesion

Safety Precautions of the Operator • The FNAC technique room should have adequate light and ventilation • The operator should take barrier precautions such as wearing apron, gloves, mask etc. • Facilities for the proper disposal of waste material • Avoid needle re-sheathing Causes of Inadequate Material • Faulty FNAC procedure: Too much suction or too little suction, not to move the needle to and fro within the lesion. • Hard swelling where the needle may not penetrate. • Faulty spreading of the material: too much pressure causing crushing artefact, thick smear. • Needle may not have touched the small swelling.

1.5 Fig. 1.4  Fine-needle sampling technique: The syringe filled with air is attached with the needle, and the material is pushed on the clean glass slide

The exact procedure of FNS is described below (Figs. 1.3 and 1.4): • • • • •

Hold the swelling tightly Insert the needle in the swelling Move the needle gently back and forth Withdraw the needle and attach it with a syringe full of air Push the material on the glass slide

1.4.2 Fixatives In most of the time, we prepare a few air-dried smear in FNAC. The common fixatives in FNAC clinic include: • Routine fixatives: 95% ethyl alcohol, denatured alcohol and 100% methanol

Deep-Seated FNAC

1.5.1 Indications of Deep-Seated Lesions • Exact diagnosis and subtyping of the lesions. • Staging of a tumour, e.g. mediastinal involvement of lung carcinoma, • To do ancillary techniques for molecular genetics, flow cytometric immunophenotyping and microbial culture. Advantages of Guided FNAC • Possible to procure a sample from the representative area. • Deep-seated non-palpable lesions are accessible. • Little chance to the injury of the vital structures. • Likely to avoid necrotic or cystic area. Information Needed before Doing Guided FNAC • Location of the needle and therefore the choice of the modality such as intrathoracic lesion is better approached by CT scan.

1.9 Magnetic Resonance Image Guided

5

• Size of the lesion: Sub-centimetre small lesions are better approached by CT scan. • Coagulation disorder. The Ideal Characteristics of the Modality of Guided FNAC • There should not be any radiation hazard. • The smallest lesion should be visualized. • High resolution. • Real-time imagining of the lesion is preferable. The Commonly Used Guided Techniques • Ultrasonography (USG) • Computerized tomographic (CT) scan • Endoscopic ultrasound guidance • Magnetic resonance image (MRI) guidance • Mammographic guidance

1.6

USG Guided FNAC (Fig. 1.5)

Principle: In this technique, high-frequency sound wave is used, which is reflected on the surface of the tissue. The final image is reconstructed from these reflected waves. Advantages • Cheap • Rapid • No radiation hazards • Relatively easy technique • Movable instrument Disadvantages • USG guided FNAC is challenging to perform in air-filled organs such as lung or bone. • Relatively low resolution than CT scan. • The success of the technique largely depends on the operator.

1.7

CT Guided FNAC

Fig. 1.5  Ultrasound of the kidney showing a hypoechoic lesion. Fine needle aspiration cytology was done from this kidney lesion under ultrasound guidance

Disadvantages • Relative costly • Radiation hazards • Time-consuming procedure

1.8

Endoscopic Ultrasound Guided

Principle: In this technique, the lesion is at first detected with the help of the USG probe attached to the endoscope. The localized image is then aspirated by a needle with an internal stylet within the endoscope. Advantages • Small mediastinal nodes or swelling can be aspirated. • Lesion outside the intestinal lumen such as lymph node or pancreatic small mass can be aspirated successfully. • Highly sensitive technique. • Cost-effective.

Principle: In this technique, multiple images are developed based on the different physical density of different tissue. These images are reconstructed with the help of the computer.

1.9

Advantages • Resolution is high. • Small lesion near a vital organ can be approached. • The success of the technique does not depend on the operator.

Advantages • No radiation hazards. • It is applied where CT scan/USG guided FNAC is failed.

Magnetic Resonance Image Guided

Principle: Radiofrequency energy is applied to generate images.

6

1  Introduction and Basic Techniques of Aspiration Cytology in Superficial and Deep Lesions

Disadvantages • Very expensive • It takes time to do • Needs special equipment • Only applicable in selected cases of breast or lung

1.10 Mammographic Guided Principle: Stereotactic localization of the lesion is done with the help of mammography. The needle is inserted in the localized point, and the material is withdrawn. It is a cumbersome technique and is used only in breast lesions.

References 1. Dey P. Role of ancillary techniques in diagnosing and subclassifying non-Hodgkin’s lymphomas on fine needle aspiration cytology. Cytopathology. 2006;17(5):275–87. 2. Field AS, Geddie WR.  Role of fine needle aspiration biopsy cytology in the diagnosis of infections. Diagn Cytopathol. 2016;44(12):1024–38. 3. Qiu T, Guo H, Zhao H, Wang L, Zhang Z. Next-generation sequencing for molecular diagnosis of lung adenocarcinoma specimens obtained by fine needle aspiration cytology. Sci Rep. 2015;5:11317. 4. Narang S, Solanki A, Kashyap S, Rani L. Utility of fine needle aspiration cytology to comprehend the pathogenesis of extrapulmonary tuberculosis. Diagn Cytopathol. 2016;44(2):98–102. 5. Durgapal P, Mathur SR, Kalamuddin M, Datta Gupta S, Parshad R, Julka PK, et al. Assessment of Her-2/neu status using immunocytochemistry and fluorescence in situ hybridization on fine-needle aspiration cytology smears: experience from a tertiary care Centre in India. Diagn Cytopathol. 2014;42(8):726–31. 6. Tyagi R, Dey P.  Needle tract seeding: an avoidable complication. Diagn Cytopathol. 2014;42(7):636–40.

2

Interpretation of Fine Needle Aspiration Cytology Smear

2.1

Malignant Cells

The recognition of malignant cells is a fundamental aspect of the assessment of FNAC smear. The characteristic features of malignant cells [1, 2] are highlighted in box 2.1 and Fig. 2.1.

Box 2.1: Characteristic Features of Malignant Cells

Cell: Enlarged, variable shapes. Nuclei: • • • • • •

Enlarged and pleomorphic nuclei. Irregular nuclear margin. Thickening of nuclear membrane. Nuclear budding and protrusion. Nucleoli: Multiple, prominent and irregular in shape. Chromatin pattern. –– Irregular coarse chromatin. –– Fine chromatin. –– Regular peripherally clumped chromatin. –– Vesicular chromatin. • Micronuclei. Note: There is no single important feature of malignant cell. Possibly a constellation of features are important.

2.1.1 Cell Size: Enlarged cells: The cells are large. Shape: The malignant cells usually have variable shapes and sizes. However, shape and size are not dependable factors in diagnosing a malignant cell.

Fig. 2.1  Malignant cell showing enlarged nuclei, prominent nucleoli and clumped chromatin

2.1.2 Nucleus Enlarged and Pleomorphic Nuclei The nuclei of the malignant cells are enlarged and pleomorphic. The disproportionate enlargement of nuclei compared to cytoplasm causes high nucleocytoplasmic (N: C) ratio. The variation of shape and size is known as pleomorphism. The malignant cells usually show variable nuclear pleomorphism. Irregular Nuclear Margin (Fig. 2.2) Malignant cells show an irregular nuclear margin in the form of: • Nuclear convolution. • Nuclear margin compression causing moulding. • Longitudinal nuclear grooving.

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_2

7

8

Fig. 2.2  Irregular nuclear margin of the malignant cell

2  Interpretation of Fine Needle Aspiration Cytology Smear

Fig. 2.4  Multiple prominent nucleoli in the malignant cell

Fig. 2.5  Irregular coarse chromatin in malignant cell Fig. 2.3 Malignant cell showing enlarged nuclei with thickened nuclear membrane and coarse chromatin

Thickening of the Nuclear Membrane (Fig. 2.3) The malignant cells often show focal thickening of the nuclear membrane. Nucleoli (Fig. 2.4) Nucleoli of the malignant cells are often multiple, prominent, with variable shape and size. Large prominent macro-­ nucleoli are frequently present in malignant melanoma and hepatocellular carcinoma. It is important to note that nucleolar enlargement is related to the metabolic activity of a cell. So it may also be present in chronic inflammation or reparative cells. Chromatin Pattern (Fig. 2.5) The changes in chromatin pattern is the essential feature of a malignant cell [3]. The benign and normal cells show a

smooth and even chromatin pattern. Whereas, the malignant cells have a significant alteration of the chromatin pattern in the form of: • • • •

Irregular coarse chromatin. Fine chromatin. Regular peripherally clumped chromatin. Vesicular chromatin.

Nuclear Budding and protrusion [4] (Fig. 2.6) The cancer cells often show the abrupt extension of the nuclear margin in the form of nuclear budding. Abnormal Mitosis and Metaphase Plate (Figs. 2.7a and b) Abnormal mitotic figures in the form of star-shaped mitosis or the presence of metaphase plate are also the features of a cancer cell.

2.3 Evaluation of the Cytological Features

Fig. 2.6  Nuclear budding in malignancy

a

9

Fig. 2.8  The micronuclei within the cytoplasm of the cell

Micronuclei (Fig. 2.8) Cancer cells often show frequent micronuclei [5]. Micronuclei are the tiny fragmented nuclei within the cytoplasm of the cells. The micronuclei are 2 to 3 micron in diameter and take the same stain as that of nuclei.

2.2

Interpretation of FNAC Smear

Clinical Information The following clinical data is necessary for the interpretation of the FNAC smear:

b

• • • • •

Chief complaints. The site, size and duration of the lesion. Radiological findings. Essential laboratory data. Relevant medical history.

2.3

Evaluation of the Cytological Features

The smears should be screened for various features as mentioned in box 2.2.

Box 2.2: Evaluation of the Cytological Features

Fig. 2.7 (a) Tripolar mitotic figure indicating abnormal mitosis (b) Metaphasic plate connecting the two nuclei

• Cellular arrangement • Individual cell morphology • Cell shape

10

2  Interpretation of Fine Needle Aspiration Cytology Smear

• Cytoplasm –– Vacuolations –– Colour –– Pigment –– Phagocytosed material • Nucleus –– Nuclear pleomorphism –– Nuclear margin –– Nuclear groove –– Chromatin pattern –– Nucleoli –– Intranuclear inclusion • Background of the smear –– Necrosis –– Inflammation –– Cystic changes –– Mucinous material –– Connective tissue material –– Neurofibrillary material

Fig. 2.10  Clusters of tumour cells in carcinoma

Fig. 2.11  Sheet-like arrangement of malignant cells

Fig. 2.9  Discrete cells in lymphoma

2.3.1 Cellular Arrangement Discrete Cells (Fig. 2.9) Singly scattered discrete cells are seen in lymphoma or poorly differentiated carcinoma. Clusters (Fig. 2.10) The malignant cells often present in small and large clusters. The recognition of groups of tumour cells excludes the possibility of lymphoma. Sheets (Fig. 2.11) The sheets of tumour cells are usually present in carcinoma.

Gland (Fig. 2.12) Usually, 10–20 columnar or cuboidal cells take part in the formation of the gland. The gland may not be in a complete circle, and occasionally they may be fragmented. The glandular structure indicates the diagnosis of adenocarcinoma. Follicles (Fig. 2.13) Follicle formation is commonly seen in thyroid FNAC smear. At least 10–15 thyroid follicular cells make a complete follicle. The thyroid follicles may often have colloids within the central lumen. Follicular neoplasms of thyroid commonly show an abundant number of microfollicles. Rosette (Fig. 2.14) In case of pseudorosette, the cells are present around the central fibrillary material. Unlike gland, here the cells are not attached to any basement membrane. The rosettes are present

2.3 Evaluation of the Cytological Features

11

in neuroblastoma, retinoblastoma and peripheral neuroectodermal tumours. Papillary Fragment (Fig. 2.15) In papillae, the finger-like arrangement of cells are present around a central fibrovascular core. The axis of the cell is perpendicular to the long axis of papillae. FNAC smear may not show typical fibrovascular core, and only avascular papillae may be present. The papillae are commonly present in papillary carcinomas of thyroid, lung, ovary, colon etc. Trabecular-Like Pattern (Fig. 2.16) Two or three cells are present in small rows to make the trabecular pattern of arrangement. Cytology smears of the hepatocellular carcinoma often show this pattern. Fig. 2.12  Gland-like arrangement of cells in adenocarcinoma

Fig. 2.13  Follicular arrangement of cells in follicular neoplasm of thyroid

Fig. 2.14  Rosette-like arrangement of cells in neuroblastoma

Fig. 2.15  Papillary arrangement of cells in papillary carcinoma of the thyroid

Fig. 2.16 Trabecular arrangement of cells in a hepatocellular carcinoma

12

Fig. 2.17  Indian file arrangement in lobular carcinoma of the breast in a pleural effusion

2  Interpretation of Fine Needle Aspiration Cytology Smear

Fig. 2.19  Fascicle-like arrangement in a leiomyosarcoma

Palisading Arrangement Here, the peripheral cells in a cluster are arranged in regular rows. This pattern is present in basal cell carcinoma.

2.4

Individual Cells

Individual cell morphology provides vital information for interpreting the FNAC smear.

2.4.1 Cell Shape The shape of the cell provides a critical clue in the subtyping of a malignant tumour. The tumour cell may have the following different forms: Fig. 2.18  Acinar ball surrounded by cell in adenoid cystic carcinoma

Indian File Arrangement (Fig. 2.17) The cells may often present in a single row of cells like Indian file arrangement. It is present in small cell carcinoma and lobular carcinoma of the breast. Central Acellular Ball-like Structure Surrounded by Cells (Fig. 2.18) The ball-like structure surrounded by cells is typically present in adenoid cystic carcinoma, cylindroma and granulosa cell tumour. Fascicular Pattern (Fig. 2.19) The oval to spindle cells may be present in small interlacing bundles to make the fascicles. The fascicular arrangement of cells is often present in fibrosarcoma, leiomyosarcoma etc.

Round (Fig. 2.20) The predominant round cells are present in: • Malignant round cell tumours such as non-Hodgkin lymphoma, neuroblastoma, Ewing’s tumour/peripheral neuroectodermal tumour (PNET), rhabdomyosarcoma, nephroblastoma. • Neuroendocrine tumours. • Small cell carcinoma.

Spindle (Fig. 2.21) The predominantly spindle-shaped cells are present in: • Sarcoma with spindle cell morphology: Malignant peripheral nerve sheath tumour, fibrosarcoma, leiomyosarcoma etc.

2.4 Individual Cells

13

Fig. 2.20  Round cells in acute lymphoblastic leukaemia

Fig. 2.22  Polyhedral shaped cells in squamous cell carcinoma

Fig. 2.21  Spindle-shaped cells in sarcoma

Fig. 2.23  Bizarre pleomorphic cells in an anaplastic carcinoma

• Soft tissue tumours such as neurofibroma, schwannoma and fibroma. • Malignant melanoma. • Mesothelioma. • Thymoma with mainly spindle cell.

Bizarre (Fig. 2.23) Irregular bizarre cells are often present in:

Polygonal Cells (Fig. 2.22) The predominant component of the polyhedral cells may be present in: • • • • • •

Squamous cell carcinoma. Renal cell carcinoma. Hepatoma. Pheochromocytoma. Adrenocortical carcinoma. Certain type of soft part sarcoma: Monophasic synovial sarcoma, alveolar soft part sarcoma.

• Pleomorphic sarcoma such as pleomorphic liposarcoma and rhabdomyosarcoma • Anaplastic carcinoma • Undifferentiated carcinoma • Malignant melanoma

Fibre Cells Elongated fibre-like cells are present in squamous cell carcinoma (Fig. 2.24). Tadpole Cells (Fig. 2.25) Tadpole-like cells with cytoplasmic extension are present in squamous cell carcinoma.

14

2  Interpretation of Fine Needle Aspiration Cytology Smear

Fig. 2.24  Elongated fibre-like cells in squamous cell carcinoma

Fig. 2.26  Cercariform cell in transitional cell carcinoma

Fig. 2.25  Tadpole cells with cytoplasmic extension

Fig. 2.27  Binucleated cells with mirror image-like nuclei of Reed– Sternberg cell

Cercariform Cells (Fig. 2.26) The cell with a long cytoplasmic extension known as cercariform cells are present in urothelial cell carcinoma. Reed Sternberg Cell (Fig. 2.27) These are binucleated cells with mirror image-like nuclei. Doughnut Cell (Fig. 2.28) This is the cell with peculiar Doughnut-shaped nuclei. It is seen in anaplastic large cell lymphoma.

2.4.2 Cytoplasm The cytopathologist should collect various data regarding the cytoplasm of the cells. Fig. 2.28  Doughnut cell in anaplastic large cell lymphoma

2.4 Individual Cells

Fig. 2.29  Cytoplasmic vacuolation in adenocarcinoma

15

Fig. 2.30  Large vacuoles have pushed the nuclei in periphery producing signet ring cell

2.4.3 Cytoplasmic Area Scanty Cytoplasm Malignant cells usually have a small amount of cytoplasm. However, benign cells (e.g. lymphocyte) may also have scant cytoplasm. Moderate Amount The malignant cells may also show a moderate amount of cytoplasm such as adenocarcinoma, squamous cell carcinoma, carcinoid etc. Abundant Amount Abundant amount of cytoplasm is seen in hepatocellular carcinoma, mucinous adenocarcinoma, acinic cell carcinoma and renal cell carcinoma. Fig. 2.31  Multiple small vacuoles in the lipoblast of liposarcoma

2.4.4 Vacuolation in Cytoplasm Cytoplasmic vacuolation is present in adenocarcinoma (Fig.  2.29). The vacuoles usually contain carbohydrates or lipids. At times the vacuoles may be large and push the nucleus at the periphery making a signet ring-like appearance (Fig. 2.30). Fine vacuolated cytoplasm is seen in liposarcoma (Fig.  2.31). In the case of chordoma, large cells (Physaleferous cells) with bubbly cytoplasmic vacuoles are seen (Fig. 2.32). Colour The colour of the cytoplasm may often indicate the type of malignancy. • Orange colour in Papanicolaou’s stain (Fig.  2.33): Squamous cell carcinoma. • Deep blue cytoplasm (Fig. 2.34): Lymphoid cells. • Reddish hue (Fig. 2.35): Neuroendocrine tumour.

Fig. 2.32  Bubbly cytoplasmic vacuoles in the Physaleferous cells

16

2  Interpretation of Fine Needle Aspiration Cytology Smear

Fig. 2.33  Orangeophilic cytoplasm in keratinized squamous cells

Fig. 2.35 Reddish granules in the cytoplasm of neuroendocrine tumour

Fig. 2.34  Deep blue cytoplasm in lymphoid cells of lymphoma

Fig. 2.36  Brownish black melanin pigment in melanoma

Pigment The presence of different pigments is helpful in the identification of various malignancies. • Brown-black melanin pigment (Fig.  2.36): Malignant melanoma. • Deep blue bile pigment in MGG and golden yellow in haematoxylin and eosin stain (Fig. 2.37): Hepatocellular carcinoma. The benign cells may also contain different types of pigment such as: • Alveolar histiocytes (Fig.  2.38): containing carbon pigment. • Histiocytes in the old haemorrhage (Figs. 2.39 and 2.40): Hemosiderin pigment.

Fig. 2.37  Dark blue bile pigment in hepatocellular carcinoma

2.5 Nucleus

Fig. 2.38  Carbon laden alveolar macrophages

17

Fig. 2.41 Phagocytosed (emperipolesis)

lymphocytes

within

the

cytoplasm

Phagocytosis It is important to note the intracytoplasmic cells such as: • Erythrophagocytosis: Engulfed RBC may be present in a viral infection. • Emperipolesis (Fig.  2.41): Engulfed lymphocytes in Rosai Dorfman syndrome.

Intracytoplasmic Lumina The intracytoplasmic lumina are present in lobular carcinoma.

Fig. 2.39  Haemosiderin laden histiocytes in the gastric lavage

Intracytoplasmic Inclusions Certain viral infections may show intracytoplasmic inclusion, e.g. cytomegalovirus.

2.5

Nucleus

The study of nuclei of the cells is the most crucial aspect of the interpretation of the FNAC smear.

2.5.1 Nuclear Pleomorphism Marked pleomorphism: • • • •

Fig. 2.40  Dark blue hemosiderin granules in Pearl’s stain

Undifferentiated carcinoma Anaplastic carcinoma Pleomorphic sarcoma Malignant melanoma

Mild to moderate pleomorphism: The various malignancies show mild-to-moderate nuclear pleomorphism. The nuclear pleomorphism increases with the increased grade of a malignant tumour.

18

2  Interpretation of Fine Needle Aspiration Cytology Smear

Monomorphic nuclei (Fig. 2.42): Deceptively, many malignant tumours may have monomorphic nuclei such as: • • • • •

Follicular carcinoma of the thyroid Acinic cell carcinoma of the parotid gland Mucinous carcinoma Carcinoid Lobular carcinoma of the breast

Benign Tumours with Pleomorphic Nuclei (Fig. 2.43) It is important to note that many benign tumours may often show mild-to-moderate degree of nuclear pleomorphism such as: • • • •

Schwannoma particularly ancient schwannoma. Paraganglioma. Pleomorphic lipoma. Adrenocortical adenoma.

Fig. 2.42  Monomorphic nuclei in follicular carcinoma of the thyroid

2.5.2 Nuclear Margin As mentioned before the irregularity of the nuclear margin is one of the features of malignancy [6]. Deep longitudinal nuclear grooves (Fig. 2.44) are often present in: • • • • • •

Langerhans cell histiocytosis Papillary carcinoma of the thyroid Chondroblastoma Meningioma Brenner tumour Granulosa cell tumour of the ovary

2.5.3 Nucleoli • Inconspicuous nucleoli: The nucleoli may be indistinct to absent in squamous cell carcinoma, certain non-­Hodgkin’s lymphoma, neuroendocrine tumours. • Prominent: Well visible or prominent nucleoli may be present in both neoplastic and non-neoplastic lesions: –– Non-neoplastic: Repairative cell. Post radiation. Chemotherapy induced. –– Neoplastic: Adenocarcinoma. • Large macronucleoli (Fig. 2.45): Prominent large nucleoli are present in: –– Malignant melanoma –– Hepatocellular carcinoma –– Endodermal sinus tumour.

Chromatin Pattern (Fig. 2.46) • Irregular coarse chromatin: Poorly differentiated carcinoma. • Fine chromatin: The various non-Hodgkin’s lymphoma, acute leukaemia. • Regular peripherally clumped chromatin: Plasma cell. • Vesicular chromatin: Adenocarcinoma.

Intranuclear Inclusion (Fig. 2.47) The intranuclear inclusion is the invagination of the cytoplasm within the nucleus. This is quite distinct from the nucleoli as the colour of the inclusion is the same as that of cytoplasm. The following tumours show intranuclear inclusion [7]: • • • • Fig. 2.43  Moderately pleomorphic nuclei in paraganglioma

Papillary carcinoma of the thyroid Meningioma Bronchioloalveolar carcinoma Malignant melanoma

2.5 Nucleus

19

a

b

c

d

Fig. 2.44  Deep longitudinal nuclear grooves in (a) Papillary carcinoma of thyroid, (b) Langerhans cell histiocytosis, (c) Chondroblastoma and (d) Meningioma. Red arrows indicating nuclear grooves

Occasionally nuclear vacuolation may mimic intranuclear inclusion (Figs. 2.48 and 2.49).

2.5.4 Background of the Smear The background of the smear provides vital information in diagnosing a lesion. Necrosis (Fig. 2.50) Necrotic background may be due to degenerated tumour cells or inflammatory cells. In the case of tumour necrosis, the outline of the ghost of tumour cells is present. Whereas, in inflammation, only inflammatory cells and necrotic tissue are present. Fig. 2.45  Punched out large macronuclei in melanoma

20

2  Interpretation of Fine Needle Aspiration Cytology Smear

a

b

c

d

e

f

Fig. 2.46 (a) Fine chromatin pattern in leukaemic blasts, (b) Coarse chromatin in squamous cell carcinoma, (c) Salt and pepper chromatin in a case of neuroendocrine tumour (May Grunwald Giemsa stain), (d)

Haematoxylin and eosin stain of the same, (e) Cartwheel appearance of the chromatin in plasma cells and (f) Optically clear nuclei in the cells of papillary carcinoma of thyroid

2.5 Nucleus

21

Fig. 2.47  Intranuclear inclusions in papillary carcinoma of thyroid

Fig. 2.50  Smear shows a necrotic background

Fig. 2.48  Nuclear vacuolation in a hepatocellular carcinoma in haematoxylin and eosin stain smear

Fig. 2.51  Cyst fluid: Abundant foamy macrophages in cyst

Inflammation Only the inflammatory cells may be present in the smear. In acute inflammation, only polymorphs are seen, whereas, in chronic inflammation, lymphocytes and plasma cells are present. Inflammation may be present in both neoplastic and non-neoplastic lesions. Cystic Changes (Fig. 2.51) In cystic degeneration, the smear shows many foamy histiocytes in a thin fluid background. Many tumours may show cystic degeneration in the central part.

Fig. 2.49  Nuclear vacuolation in a hepatocellular carcinoma

Mucinous Material (Fig. 2.52) Mucinous material may be present in mucinous neoplasm, e.g. mucinous adenocarcinoma. In the case of duct obstruction, there may be mucinous cyst formation that may yield mucinous material.

22

2  Interpretation of Fine Needle Aspiration Cytology Smear

Fig. 2.52  Mucinous background of the smear

Fig. 2.54  Chondroid material in the background

Fig. 2.53  Connective tissue matrix in synovial sarcoma

Fig. 2.55  Osteoid material in the background

Connective Tissue Material (Fig. 2.53) Pinkish connective tissue material may be present in soft tissue tumour. Osteoid material or chondroid material is present in osteosarcoma or chondrosarcoma, respectively (Figs. 2.54 and 2.55). In these cases, one should give attention to the accompanying cells for the exact nature of a tumour. Myxoid degeneration may be present as a process of degeneration or in a myxoid tumour (Fig. 2.56). Colloid Colloid is thin blue in the Giemsa stained smear (Fig. 2.57). Colloid may be confused with proteinaceous plasma from the blood. Occasionally the colloid material may be very thick and inspissated (Fig.  2.58), and this type of chewing gum-like colloid is seen in papillary carcinoma. Synovial fluid: The synovial fluid typically shows a mossy background (Fig. 2.59).

Fig. 2.56  Myxoid background of the smear

2.5 Nucleus

Fig. 2.57  Thin colloid in a case of colloid goitre

23

Fig. 2.60  Neurofibrillary material in the background

Neurofibrillary Material Typical neurofibrillary material are present in the tumour of neuroepithelial origin (Fig. 2.60). Final Reporting Final reporting of any lesion should be given from: • • • • • • • Fig. 2.58  Thick inspissated colloid in papillary carcinoma of thyroid

Clinical details of the patient. Cytology data. Radiological data. Biochemical information. Immunocytochemistry. Molecular genetic. Final diagnosis.

2.5.5 False-Positive Cases The common causes of false-positive reporting in FNAC include: Reparative Atypia (Fig. 2.61) At times, regenerative cells after the injury or inflammation may show significant nuclear pleomorphism. The nucleocytoplasmic ratio of such cells remains unaltered. Moreover, the chromatin pattern of these cells is also not changed. Endothelial Cells (Fig. 2.62) Endothelial cells may show nuclear enlargement and pleomorphism and may be mistaken as malignant cells in FNAC smear.

Fig. 2.59  Synovial fluid shows a typical mossy background

24

2  Interpretation of Fine Needle Aspiration Cytology Smear

Fig. 2.61  Radiation-induced nuclear atypia

Fig. 2.63  Degenerated muscle cells may mimic as cancer cells

Fig. 2.62 Endothelial cells showing nuclear enlargement and pleomorphism

Fig. 2.64  Clusters of endometrial cells in endometriosis may mimic malignant cells

Degenerated Muscle Cells Degenerated muscle cells in the neck region are often bizarre and may be mistaken as metastatic carcinoma (Fig.  2.63). These cells usually have moderate to abundant cytoplasm. Endometrial Cells The clusters of endometrial cells in endometriosis may mimic malignancy (Fig.  2.64). The proper clinical history and associated stromal cells and macrophages are a helpful guide to avoid the mistake. Pleomorphism in Benign Tumours Certain tumours such as schwannoma may show significant nuclear pleomorphism and may be mistaken as malignancy (Fig. 2.65). Fig. 2.65  Pleomorphic cells in schwannoma

References

Radiation and Chemotherapy-Induced Changes Radiation and chemotherapy may cause nuclear enlargement; however, the nucleo-cytoplasmic ratio is not altered here.

2.6

False-Negative Smear

Malignant cells may be mistaken as benign cells due to the following reasons: Monomorphic Cells If the nuclei of the malignant cells are monomorphic then the cells may be misinterpreted as benign cells such as in follicular neoplasm, hurthle cell neoplasm etc. Lookalike (Fig. 2.66) Malignant cells may have similar look like benign cells such as in acinic cell carcinoma of the parotid gland, or case of well-differentiated renal cell carcinoma.

Fig. 2.66  Acinic cell carcinoma of the parotid gland mimicking benign acinar cells

25

References 1. Dey P. Cancer nucleus: morphology and beyond. Diagn Cytopathol. 2010;38(5):382–90. 2. Zink D, Fischer AH, Nickerson JA.  Nuclear structure in cancer cells. Nat Rev Cancer. 2004;4(9):677–87. 3. Dey P. Chromatin pattern alteration in malignant cells: an enigma. Diagn Cytopathol. 2005;32(1):25–30. 4. Verma S, Dey P. Correlation of morphological markers of chromosomal instability in fine needle aspiration cytology with grade of breast cancer. Cytopathology. 2014 Aug;25(4):259–63. 5. Samanta S, Dey P.  Micronucleus and its applications. Diagn Cytopathol. 2012 Jan;40(1):84–90. 6. Dey P. Nuclear margin irregularity and cancer: a review. Anal Quant Cytol Histol. 2009;31(5):345–52. 7. Arora SK, Dey P. Intranuclear pseudoinclusions: morphology, pathogenesis, and significance. Diagn Cytopathol. 2012;40(8):741–4.

3

Aspiration Cytology of Head, Neck and Orbital Lesions

There are miscellaneous lesions in the head and neck region. There are large varieties of metastatic and primary tumours in these regions, which primarily involve the lymph nodes, soft tissue, salivary glands, thyroid etc. This chapter mainly discusses the cytology of these lesions other than salivary gland and thyroid.

3.1

Cysts in the Neck Region

Figure 3.1 highlights the different types of cysts in the head– neck area.

3.1.1 Branchial Cyst [1–4] Type: Congenital cyst. Behaviour: Benign.

Common locations: Medial border of the sternocleidomastoid muscle. Clinical feature: Usually asymptomatic, however, infected cyst may enlarge rapidly and produces pressure symptoms. Key Cytological Features (Figs. 3.2 and 3.3) • FNAC yields fluid. • Foamy macrophages. • Benign squamous cells, columnar cells. • Cholesterol crystals. Differential Diagnosis • Metastatic squamous cell carcinoma: –– Higher age group. –– Careful observation always shows discrete malignant cells. • Cystic papillary carcinoma of the thyroid.

Fig. 3.1  The classification of cyst of the head and neck region

Cysts in the neck region

Acquired

Congenital

-Branchial cyst -Thyroglossal cyst -Diffuse lymphangioma/cystic hygroma

Neoplastic

-Squamous cell carcinoma -Warthin tumour -Acinic cell carcinoma

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_3

Non-neoplastic

-Mucocele -Dermoid cyst -Retention cysy of the salivary gland

27

28

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Fig. 3.2  Foamy macrophages and squamous epithelial cells in a branchial cyst

Fig. 3.3  Macrophages with attached squamous cells in branchial cyst

–– Fragments of papillae. –– Intranuclear inclusions and longitudinal grooving of nuclei.

3.1.2 Thyroglossal Cyst [5, 6] Type: Congenital cyst. Age: Common in childhood period. Behaviour: Benign. Location: Midline neck swelling above the level of the hyoid bone. Embryogenic Development Thyroid comes down from the foramen cecum of the tongue. The thyroglossal duct in that region may persist and form the thyroglossal cyst.

Fig. 3.4  Thin colloid with foamy macrophages in a thyroglossal cyst

Fig. 3.5  Clusters of thyroid follicular cells in a thyroglossal cyst

Key Cytological Features (Figs. 3.4, 3.5 and 3.6) • Colloid in the background. • Thyroid follicular cells. • Columnar cells. • Occasional squamous cells. Differential Diagnosis • Branchial cyst. • Epidermal inclusion cyst. • Colloid goitre.

3.1.3 Cystic Hygroma [7] Age: Commonly in infant and childhood period. Behaviour: Benign.

3.1 Cysts in the Neck Region

29

Fig. 3.6  Foamy macrophages and squamous cells in a thyroglossal cyst

Fig. 3.8  Many mature squamous cells both nucleated and anucleated

Fig. 3.7  Mature lymphocytes in a thin fluid background

Fig. 3.9  Calcification in epidermal inclusion cyst

Clinical Presentation • Large diffuse cystic lesion. • Soft and compressible. • Overlying skin gives a reddish colour. Gross material: Clear fluid. Key Cytological Features (Fig. 3.7) • Mature lymphocytes. • Thin fluidy background.

3.1.4 Acquired Cyst 3.1.4.1 Non-neoplastic Epidermal Inclusion Cyst [8] Type: Acquired cyst. Behaviour: Benign.

Age: Any age group. Location: Anywhere in the head–neck region. Clinical Presentation • Subcutaneous swelling. • Elevated small puncta in the middle. Gross material: Thick whitish material. Key Cytological Features (Figs. 3.8, 3.9, 3.10, and 3.11) • Mature squamous cells present, both nucleated and anucleated. • Rarely multinucleated giant cells. • Calcified material. Differential Diagnosis • Metastatic squamous cell carcinoma (SQCC): The differentiating features:

30

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Fig. 3.10 Cystic degeneration in a metastatic squamous cell carcinoma

Fig. 3.12  Thick mucinous material and scattered histiocytes and columnar cells in mucocele

Fig. 3.11  In case of cystic degeneration in metastatic squamous cell carcinoma

Fig. 3.13  A case of mucoepidermoid carcinoma. Discrete tumour cells in a mucinous background resembling mucocele

–– Recent onset in squamous cell carcinoma. –– Most of the time the primary lesion is known. –– At least a few cells show moderate to marked pleomorphism.

3.1.5 Mucocele [9] Type: Acquired cyst. Behaviour: Benign. Age: Any age group. Aetiology: Obstruction of the duct of the salivary gland with pent up secretion. It is, therefore, a pseudocyst. Location: Upper part of neck and floor of the mouth.

Gross aspirate: Thick mucinous material. Key Cytological Features (Fig. 3.12) • Histiocytes and columnar cells. • Thick mucinous background. Differential Diagnosis • Mucoepidermoid carcinoma (Figs. 3.13 and 3.14: FNAC often yields mucinous material with low cellularity in the mucoepidermoid carcinomas and therefore, the tumour may be mistaken as a mucocele. The individual cell morphology of the tumour cells may be an important distinguishing point. In case of doubt, a repeat FNAC from multiple sites is mandatory.

3.2 Lymph Node Lesion in Head–Neck Region

Fig. 3.14  Mucoepidermoid carcinoma showing discrete tumour cells in a mucinous background. The careful observation of the individual cells helps to distinguish from mucous cyst

3.2

31

Fig. 3.15  Cystic degeneration in the metastatic squamous cell carcinoma showing occasional mature looking squamous cells in a thin fluidy background

 ymph Node Lesion in Head–Neck L Region

Lymph nodes are the frequent targets of FNAC in the head– neck regions. Both non-neoplastic and neoplastic processes affect the lymph nodes. Many malignancies of the head–neck region first time present as enlarged lymph nodal mass. The various primary sites of the metastatic tumours are: • Oropharyngeal carcinoma (Figs.  3.15, 3.16, and 3.17): Predominantly squamous cell carcinoma arises in the oropharyngeal region. The tumour may often show significant cystic degeneration and scanty tumour cells to make the diagnosis difficult. • Salivary gland tumours. • Thyroid Carcinomas: Any thyroid malignancy may metastasize in the local cervical lymph node. However, metastatic papillary carcinoma may often show cystic changes and FNAC yields turbid thin fluid. It may be the initial presentation of the tumour, and only careful observation reveals tiny papillary fragments with nuclear inclusion and grooving (Figs.  3.18, 3.19, and 3.20). Occasionally medullary carcinoma of thyroid may present at first times as metastatic lymph node (Fig. 3.21). • Lung, breast and stomach (Figs. 3.22 and 3.23). • Other: Distant sites and also uncommon sites (Figs. 3.24 and 3.25).

Fig. 3.16  A case of cystic degeneration in squamous cell carcinoma showing occasional large pleomorphic malignant cells

3.2.1 Difficulties • Cystic squamous cell carcinoma may mimic benign cyst and vice versa.

Fig. 3.17  Abundant discrete and clusters of malignant cells in a metastatic squamous cell carcinoma

32

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Fig. 3.18 Metastatic papillary carcinoma: Papillary fragments in lymph node FNAC

Fig. 3.21  Metastatic medullary carcinoma of the thyroid in a cervical lymph node

Fig. 3.19  Metastatic papillary carcinoma: Scatters macrophages and occasional thyroid follicular cells in a cystic papillary carcinoma

Fig. 3.22  Metastatic small cell carcinoma in a supraclavicular lymph node. The discrete and loosely arranged cells with chromatin threading

Fig. 3.20  Metastatic papillary carcinoma: Higher magnification showing cells with nuclear grooves

Fig. 3.23  Metastatic small cell carcinoma in a supraclavicular lymph node. Higher magnification showing round cells with scanty cytoplasm having hyperchromatic nuclei

3.3 Paraganglioma

Fig. 3.24  Metastatic medulloblastoma in the upper cervical lymph node. The discrete small round cells

33

Fig. 3.26  Benign salivary acinar and ductal cells in the upper cervical swelling in a known primary carcinoma of the tongue

Fig. 3.27  The benign salivary ductal cells may mimic metastatic carcinoma Fig. 3.25  Metastatic medulloblastoma in the upper cervical lymph node. Higher magnification showing round monomorphic cells with hyperchromatic nuclei

• Cystic papillary carcinoma may show scanty cellularity and may mislead. • At times salivary ductal cells may mimic metastasis in a known case of squamous cell carcinoma for the evaluation of metastasis (Figs. 3.26 and 3.27).

3.3

Paraganglioma [10–12]

Origin Paraganglioma develops from the sympathetic and parasympathetic ganglions of the autonomic nervous system (Fig. 3.28).

Sympathetic Paraganglia Mostly located in the abdomen. Parasympathetic Paraganglia In the neck region form the divisions of the glossopharyngeal and vagus nerve. Locations • Paragangliomas are often present on either side of the vertebral bodies. They may occur from the base of the skull near the middle ear to the pelvis. • Paraganglioma in the neck region. –– Carotid body tumour: At the level of division of the carotid artery. –– At the base of the skull near the middle ear.

34

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Fig. 3.28  Schematic diagram showing the origin of paraganglioma from the different autonomic ganglion

Extra-adrenal paraganglia

Sympathetic

Secretion

Para sympathetic

Secretion

Location

Nor-adrenaline

Abdominal

Malignancy: 15 to 50%

Dopamine

Location

Neck

Malignancy: 2 to 13%

Behaviour Benign in course and only 2 to 19% tumours may have malignant changes.

3.3.1 Carotid Body Tumour [11, 13] Origin and Location Parasympathetic ganglion located in the branching of the common carotid artery. Clinical Features • Slowly growing. • Painless. • Usually asymptomatic rarely pain and hoarseness of voice. • Size: 2 to 8 cm in diameter, average 3.8-cm diameter. Age Distribution In adults, mainly fourth to fifth decade, females are frequently affected. Histopathology (Fig. 3.29) • Tumour is composed of the chief cells and sustentacular cells. • Zellabellan pattern: Clusters of chief cells surrounded by vascularized septae. • Chief cells: The cells have a large amount of vacuolated cytoplasm with central round nuclei. • Sustentacular cells: These cells are around the nests of chief cells.

Fig. 3.29  Histopathology section of carotid body tumour showing nests of tumour cells

Criteria of Malignancy The distant metastasis is the hallmark of malignancy. Local invasion or nuclear pleomorphism is not the criteria of malignancy. Key Cytological Features (Figs. 3.30, 3.31, 3.32, and 3.33) • Syncytial arrangement of cells. • Cells with moderate cytoplasm having oval to spindle-­ shaped nuclei. • Relatively monomorphic nuclei. • Bland chromatin. • Abrupt pleomorphic nuclei. • Intranuclear inclusion. • Vague rosettes.

3.3 Paraganglioma

35

Fig. 3.30  Paraganglioma: Predominant syncytial arrangement of the cells

Fig. 3.33  Paraganglioma: Cells with bland chromatin pattern

Immunocytochemistry Positive: NSE, Chromogranin, synaptophysin, S 100 and CAM 5.2.

3.3.2 Differential Diagnosis (Figs. 3.34, 3.35, and 3.36) Medullary Carcinoma (Fig. 3.34) • Immunostaining: Calcitonin positive in medullary carcinoma is the most helpful features. Metastatic Neuroendocrine Tumour (Fig. 3.35) • Clinical history of the primary tumour may be helpful in such a case. Fig. 3.31 Paraganglioma: pleomorphism

Round

to

oval

cells

with

mild

3.3.3 N  asopharyngeal Carcinoma (NPC) [14–16] Definition NPC is a squamous cell carcinoma that originates from the mucosa of the nasopharynx. Synonym Lymphoepithelioma and squamous cell carcinoma. Age and Sex Distribution • The bimodal age distribution. • Increased incidence in 30 years. • Peak incidence in 55 to 60 years. • Equal occurrence in both male and female.

Fig. 3.32  Paraganglioma: Occasional cell show nuclear enlargement and pleomorphism

Aetiology • Epstein-Barr virus (EBV): EBV is possibly one of the contributory factors of NPC. EBV DNA is often present

36

3  Aspiration Cytology of Head, Neck and Orbital Lesions

a

b

c

d

e

f

Fig. 3.34  A 35-year-old female presented with upper cervical lymph node for 6  months. Initial FNAC diagnosis was paraganglioma. However, histopathology of the swelling revealed metastatic medullary carcinoma.(a) Oval to spindle cells in clusters in the upper cervical lymph node. (b) Higher magnification of the same showing salt and

pepper chromatin in the upper cervical lymph node. (c) Loose clusters of tumour cells in a metastatic medullary carcinoma in the upper cervical lymph node. (d) Higher magnification of the same. (e) Histopathology section revealed features of medullary carcinoma. (f) The tumour cells are positive for calcitonin

3.3 Paraganglioma

37

in NPC and its precursor lesion but not in the normal mucosal epithelium of the nasopharynx. Besides, high serum IgA antibodies level against EBV in the patient is also an indicator of association of EBV and NPC. • Diet: Food containing nitrosamines. • Other: Cigarette smoking and formalin vapour exposure. Clinical Presentation • Majority of the patients present with cervical lymph nodal enlargement.

• Occasionally post-nasal blood-tinged drip and pressure symptoms in the Eustachian tube (e.g. otitis media). Histopathology • Non-keratinizing SQC. • Sheets and trabeculae of tumour cells. • Lymphocyte and plasma cell infiltration in the tumour. Key Cytological Features (Figs. 3.37, 3.38, 3.39, and 3.40) • Discrete and loose clusters of cells. • Round to oval cells having an indistinct cytoplasmic margin. • A moderate amount of cytoplasm. • Moderate nuclear pleomorphism. • Fine chromatin. • Prominent nucleoli. • Abundant lymphocyte and plasma cells in the background. Immunocytochemistry • Strongly positive for pan-cytokeratin and p63. • Positive for EBV encoded early RNA. • Negative for CK 7 and CK 20.

Fig. 3.35  Cytology smear of a case of metastatic neuroendocrine tumour showing syncytial clusters of cells Fig. 3.36 Differential diagnosis of paraganglioma of neck (carotid body tumour)

Metastatic neuroendocrine tumour

Cytoplasmic reddish granules

Salt and pepper chrmatin

Differential Diagnosis • Hodgkin lymphoma (Fig.  3.41): The large binucleated tumour cell may resemble Reed-Sternberg cells.

Paraganlioma

Medullary carcinoma

Syncytial arrangement of cells Sudden nuclear pleomorphism

Discrete monomorphic tumour cells

Bland chromatin

Granular chromatin

38

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Fig. 3.37  Nasopharyngeal carcinoma: Syncytial and discrete arrangement of tumour cells

Fig. 3.40  Nasopharyngeal carcinoma: The cells have fine chromatin with prominent nucleoli

Fig. 3.38  Nasopharyngeal carcinoma: Large round cells with moderate amount of cytoplasm. The tumour cells are admixed with lymphocytes

Fig. 3.41 Hodgkin carcinoma

lymphoma

may

simulate

nasopharyngeal

• Non-Hodgkin lymphoma (NHL): Discrete large tumour cells admixed with reactive lymphoid cells may simulate NHL.  CD 45 and pan-cytokeratin immunostaining are helpful in this context. • Metastatic small cell carcinoma(Fig. 3.42): Small tumour cells with scattered background lymphocytes of metastatic small cell carcinoma may simulate NPC.

3.3.4 Parathyroid Neoplasm [17–20]

Fig. 3.39  Nasopharyngeal carcinoma: Large round cells with moderate nuclear pleomorphism

Normal Parathyroid Glands • Total four in number. • Located posterior to the thyroid glands. • Each gland is less than 30 mg in weight. • Secretes parathormone.

3.3 Paraganglioma

Fig. 3.42  Round discrete tumour cells with admixed lymphocytes of metastatic small cell carcinoma

39

Fig. 3.43  Parathyroid adenoma. Loose aggregates and discrete tumour cells

Clinical Features of a Parathyroid Tumour • Usually asymptomatic: 15 to 50%. • Renal stone. • Skeletal involvement. • Hypercalcemia. • Rarely Neck swelling: Only 2%. Age Incidence At any age, the mean age is 55 to 60 years. Sex Female: male ratio is 3:1. Histopathology • Parathyroid adenoma is well circumscribed. • Tumour cells are in follicle, sheets, acini and trabeculae. • Thin fibrovascular septae often traverse the tumour. • Cell population: Oxyphil cell, chief cells and clear cells. • Polygonal with a clear or eosinophilic cytoplasm. • Monomorphic nuclei, however, there may be mild nuclear pleomorphism in the cells.

Fig. 3.44  Parathyroid adenoma. The vague follicular pattern of the cells

Key Cytology Features (Figs. 3.43, 3.44, 3.45, and 3.46) Predominant pattern: Small collection of cells with the occasional microfollicular pattern. • • • • • • •

A moderate amount of clear cytoplasm. Relatively regular nucleus. Occasionally enlarged pleomorphic nuclei. Absence of any colloid in the aspirate. Absence of any macrophages. Lack of any papillae to suggest papillary carcinoma. Background is clean.

Immunocytochemistry Parathormone positive.

Fig. 3.45  Parathyroid adenoma. Discrete monomorphic tumour cells

40

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Fig. 3.46  Parathyroid adenoma. The cells have a moderate amount of clear cytoplasm

Fig. 3.47  Meningioma. Oval to spindle cells in small fascicles in a nasal meningioma

Note The clinical features, hypercalcemia and radiological abnormality are the only indicators of suspicion of parathyroid neoplasms.

3.3.5 Meningioma [21–27] Location Nasal and orbital region. Presenting Features Protruding mass as nasal polyp or exophthalmos if located in the orbital region. Key Cytological Features (Figs. 3.47, 3.48, 3.49, 3.50, 3.51, and 3.52) • Cohesive clusters and discrete cells. • The concentric arrangement of the cells may produce whorl-like arrangement. • Oval to elongated cells with spindle-shaped nuclei. • Cytoplasm: Moderate. • Often longitudinal nuclear grooves. • Intranuclear cytoplasmic inclusions. • Psammoma body.

Fig. 3.48  Meningioma. Concentrically arranged cells

3.3.6 Olfactory Neuroblastoma [28, 29] Definition It is a malignant tumour of neuroectodermal derivation and is developed from the olfactory mucous membrane of the nasal cavity. Synonym Esthesioneuroblastoma, or esthesio neuroepithelioma.

Differential Diagnosis: Metastatic Carcinoma Nuclei have bland chromatin.

Incidence Uncommon tumour, It represents only 2–3% of the sinonasal tract malignancy.

3.3 Paraganglioma

Fig. 3.49  Meningioma. The cells with moderate amount of cytoplasm and oval to spindly nuclei

41

Fig. 3.52  Meningioma. Intranuclear pseudo-inclusion

Age and Sex Distribution • It may occur at any age. • Bimodal peak: Second and sixth decade. • Males and females are affected equally. Location Upper part of the nasal cavity near the cribriform plate. Clinical Feature • Unilateral nasal obstruction. • Epistaxis. • Slowly growing soft polypoid nasal polyp.

Fig. 3.50  Meningioma. Occasional cells show nuclear groove

Histopathology • Nest of tumour cells surrounded by fibrous stroma rich in blood vessels. • Multiple Homer-Wright rosette type of pseudorosette. • True Flexner-Wintersteiner-type rosette. • Round monomorphic tumour cells. • “Salt and pepper” like chromatin. Key Cytological Features (Figs. 3.53, 3.54, and 3.55) Predominant pattern: Small clusters and discrete cells. • The cells containing scanty cytoplasm with minimally pleomorphic round nuclei. • Salt and pepper chromatin and inconspicuous nucleoli. • Pseudorosette. • Neurofibrillary material with entangled cells. Immunocytochemistry • Positive: NSE, chromogranin. • Negative: CK, LCA (CD 45) and CD 99.

Fig. 3.51  Meningioma. The nuclear groove in higher magnification

42

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Differential Diagnosis Malignant round cell tumour (e.g. peripheral neuroectodermal tumour, rhabdomyosarcoma).

3.4

Lesions in the Base of the Skull

The common lesions in the base of the skull include:

Fig. 3.53  Olfactory neuroblastoma. Discrete round tumour cells

• Nerve sheath tumours (neurofibroma and schwannoma): These tumours are often noted in the region of the base of the skull (Figs. 3.56 and 3.57). • Chordoma: Occasionally chordoma may also be present in this location. The typical physaliferous cells in the bluish chondromyxoid background are the characteristic of chordoma (Figs. 3.58, 3.59, 3.60, and 3.61).

Fig. 3.56  Schwannoma. Cluster of oval to spindle cells Fig. 3.54  Olfactory neuroblastoma. Pseudorosette

Fig. 3.55  Olfactory neuroblastoma. Higher magnification of the same

Fig. 3.57  Schwannoma. The cells have elongated spindle-shaped nuclei with pointed ends

3.4 Lesions in the Base of the Skull

Fig. 3.58 Chordoma. background

Tumour

cells

43

in

the

chondromyxoid

Fig. 3.61  Chordoma. Higher magnification of the physaliferous cell

• Various metastatic carcinomas, particularly nasopharyngeal carcinoma may be seen in this location.

3.4.1 Orbital lesion FNAC of the orbital lesion is a relatively safe and straightforward technique. A team of cytologist, ophthalmologist and radiologist should be present at the time of performing FNAC of the orbital lesion.

Fig. 3.59  Chordoma. Large physaliferous cell with abundant bubbly cytoplasm having central nuclei

Indications of Orbital FNAC • Recurrent neoplasm. • Non-resectable tumour. • Confirmation of metastasis. • Lymphoma and leukemic infiltration. • Inflammatory swelling. Complications • Eyeball perforation. • Haemorrhage. • Infection. • Brain injury.

3.4.2 Lesions of the Eyelid Inflammatory Lesions Granulomatous lesions may be seen in the eyelids. The causes of granulomatous inflammation include: The common granulomatous lesions:

Fig. 3.60  Chordoma. Many scattered physaliferous cells

• Tuberculosis (Fig. 3.62): The characteristic features are: necrosis, epithelioid cell granulomas, and multinucleated giant cells. Ziehl-Neelsen stain for acid-fast bacilli or bacterial culture is positive for mycobacterial tuberculosis.

44

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Fig. 3.62  Epithelioid cell granulomas in tuberculosis of the eyelid

Fig. 3.64  Cysticercosis: Higher magnification of the tegument layer of cysticercous

Fig. 3.63  Cysticercosis: Inflammatory cells along with the tegument layer of cysticercous

Fig. 3.65  Aspergillus surrounded by lymphocytes

• Fungal and parasitic disease (Figs. 3.63, 3.64, and 3.65): Cytology smears show the fungal profile or the parasites. Also, the smears show multinucleated giant cells, epithelioid cell granulomas and eosinophils. • Rarely sarcoidosis: Sarcoid uncommonly affects the eyelid. Epithelioid cell granulomas in the absence of necrosis are the hallmark of sarcoidosis.

3.4.3.1 Basal Cell Carcinoma (BCC) [30, 31] BCC is a carcinoma of the epithelium of the skin that resembles normal basal cells. Incidence It constitutes 90% of the eyelid carcinomas.

3.4.3 Tumours of the Eyelid

Age It may occur at any age. However, it is more frequent in middle-­aged and elderly people.

Eyelids may show both benign and malignant tumours. The tumours of the eyelid that needs special attention are described here.

Clinical Features Slowly growing ulcerated lesions.

3.4 Lesions in the Base of the Skull

45

Key Cytological Features (Figs. 3.66, 3.67, 3.68, and 3.69) • Cohesive aggregates of cells. • Palisading arrangement: The peripheral cells are arranged perpendicularly to the inner layer of cells. • Cytoplasm: The cell morphology is better recognized in the peripheral cells. The tumour cells are round with less amount of cytoplasm. • Nucleus: Hyperchromatic with inconspicuous nucleoli.

3.4.3.2 Sebaceous Carcinoma [32–34] Sebaceous carcinoma develops from the meibomian gland. Incidence 1 to 5% of malignant tumours of the eyelid and third most common carcinoma of eyelid. Cell of origin: Sebaceous cells.

Fig. 3.68  Basal cell carcinoma. The cells with peripheral pallisading arrangement

Fig. 3.66  Basal cell carcinoma: Clusters and discrete tumour cells Fig. 3.69  Basal cell carcinoma: Round cells with scanty cytoplasm having hyperchromatic nuclei

Age incidence: Any age group of people may be affected, the mean age is 65 years. Clinical Feature • Commonly present as swelling in the upper eyelid. • It may simulate as chalazion or keratoconjunctivitis. Histopathology • Lobules of tumour cells with cytoplasm. • Central large pleomorphic nuclei.

Fig. 3.67  Basal cell carcinoma. Multiple cohesive clusters of tumour cells

abundant

foamy

Key Cytological Features (Figs. 3.70, 3.71, and 3.72) Predominant pattern: Dissociated and infrequent clusters of cells

46

3  Aspiration Cytology of Head, Neck and Orbital Lesions

• • • • •

Large cells. Abundant foamy cytoplasm. Centrally placed nuclei. Moderately nuclear pleomorphism. Prominent nucleoli. Special stain: The cells are strongly positive for oil red O.

3.5

Lacrimal gland

The common tumours of the lacrimal gland are described below:

Fig. 3.70  Sebaceous carcinoma: Multiple clusters of cells

3.5.1 Pleomorphic Adenoma [35] Incidence The most frequent tumours of the lacrimal gland. Cytomorphology The cytology features are similar to that of the salivary gland (Figs. 3.73, 3.74, 3.75, and 3.76).

3.5.2 Adenoid Cystic Carcinoma (ADC) ADC is also frequently seen in the lacrimal gland.

Fig. 3.71  Sebaceous carcinoma: Large cells with moderate amount of vacuolated cytoplasm

Fig. 3.72  Sebaceous carcinoma: The moderately pleomorphic nuclei

Cytology (Figs. 3.77, 3.78, 3.79, and 3.80) • Solid clusters. • Hyaline globules surrounded by tumour cells. • Round cells with scanty cytoplasm. • Minimally pleomorphic and hyperchromatic nuclei.

Fig. 3.73  Pleomorphic adenoma of the lacrimal gland. Chondromyxoid stromal material and discrete tumour cells

3.5 Lacrimal gland

47

Fig. 3.74  Pleomorphic adenoma of the lacrimal gland. The round to oval cells with moderate amount of cytoplasm in the background of deep pink stromal material

Fig. 3.77  Adenoid cystic carcinoma of the lacrimal gland. Pinkish hyaline globules along with tumour cells

Fig. 3.75  Pleomorphic adenoma of the lacrimal gland. The cells show moderate cytoplasm with mildly pleomorphic nuclei

Fig. 3.78  Adenoid cystic carcinoma of the lacrimal gland. The tumour cells have scanty cytoplasm with monomorphic round nuclei

Fig. 3.76  Pleomorphic adenoma of the lacrimal gland. The oval to round cells in chondromyxoid stroma

Fig. 3.79  Adenoid cystic carcinoma of the lacrimal gland. The round cells with hyperchromatic nuclei

48

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Fig. 3.80  Adenoid cystic carcinoma of the lacrimal gland. Higher magnification of the same

Fig. 3.81  Retinoblastoma. Discrete monomorphic round cells

3.5.3 Mucoepidermoid Carcinoma Rarely this tumour may affect the lacrimal gland.

3.5.4 Intraorbital Tumours 3.5.4.1 Retinoblastoma [36–38] Incidence: • The most frequent malignant intraocular neoplasm. • Sporadic: 60%, inherited: 40%. Origin: Primitive neuroectodermal tissue. Age: Mean age is 24 months. Clinical Features • The progressive loss of visual acuity. • White pupillary reflex (leukocoria). • Red and painful eye. • Glaucoma. Histopathology • Diffuse sheets of tumour cells. • Multiple rosettes: Classical rosettes. • Small round cells. • High nucleo-cytoplasmic ratio. • Hyperchromatic nuclei. • Necrosis and calcification.

Fig. 3.82  Retinoblastoma. Discrete and loose clusters of cells

Flexner–Wintersteiner

Key Cytological Features (Figs. 3.81, 3.82, 3.83, and 3.84) • Arrangement of the cells: Clusters and discrete cells, many rosettes.

Fig. 3.83  Retinoblastoma. The cells show scanty cytoplasm having round mildly pleomorphic nuclei

3.5 Lacrimal gland

Fig. 3.84  Retinoblastoma. Rosettes-like arrangement

49

Fig. 3.85  Melanoma in orbit: The loose clusters of tumour cells with blackish melanin pigment

• • • •

Small round cells with scanty cytoplasm. Round mildly pleomorphic hyperchromatic nuclei. Nucleoli indistinct. Occasional cells are large having more cytoplasm with cytoplasmic processes. • Rosettes: Central lumen surrounded by the cells with cytoplasmic processes towards the central canal. Immunocytochemistry Positive: NSE, S 100 and Rb. Note: Detailed clinical history and physical findings along with the above-mentioned cytology are the characteristics of retinoblastoma. Differential Diagnosis • Malignant small blue tumours (neuroblastoma, rhabdomyosarcoma, peripheral neuroectodermal tumour etc.). Immunocytochemistry is required for the diagnosis.

3.5.5 Malignant melanoma [39–41] Origin: Intraocular melanoma develops from the uveal tract. Incidence: The most frequent primary malignant tumour of the eye. In Asia, the incidence of ocular melanoma is 0.2 per million cases. Clinical Features • One-fourth of the cases are asymptomatic. • Rest may present with flashing, decreased vision, floaters in the eye. Key Cytological Features (Figs. 3.85 and 3.86) • Cohesive aggregates and dissociated large cells.

Fig. 3.86  Melanoma in orbit: Higher magnification of the same showing large cells with fine chromatin and cytoplasmic melanin pigment

• Cytoplasm containing melanin pigment. • Moderate nuclear pleomorphism. • Macronucleoli. Immunocytochemistry: Strongly positive HMB 45.

3.5.6 Rhabdomyosarcoma Rhabdomyosarcoma is the most frequent soft tissue tumours in orbit. Key Cytology Features (Figs. 3.87, 3.88, 3.89, and 3.90) The cytology features have been described in detail in soft tissue tumour section.

50

Fig. 3.87  Rhabdomyosarcoma of eye: Discrete and cohesive clusters of malignant round cells

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Fig. 3.90  Rhabdomyosarcoma of eye: Myogenin positive tumour cells

• Smears show round monomorphic cells. • The tigroid background may be noted. • Tumour cells. –– Small cells: Scanty cytoplasm with round minimally pleomorphic nuclei. –– Larger and intermediate cell: Relatively more amount of cytoplasm. The nuclei are enlarged with moderate pleomorphism. Nucleoli are prominent. • Frequent bi-nucleation. • Occasionally strap cells are seen. Immunocytochemistry Positive: SMA, desmin, caldesmon. Negative: LCA (CD 45), CD 99, NSE, Chromogranin. Fig. 3.88  Rhabdomyosarcoma of eye: Round cells with scant cytoplasm having fine chromatin

3.5.7 Acute Leukaemia Infiltration Incidence: Nearly about 2 to 8% of acute leukaemia may have infiltration in eye. Common type: Acute myeloid leukaemia more commonly infiltrate in eye. Clinical features: Unilateral or bilateral proptosis. Key Cytological Features In myeloid leukaemic deposit (Fig. 3.91, 3.92, and 3.93): • • • • •

Fig. 3.89  Rhabdomyosarcoma of eye: Desmin positive tumour cells

Discrete round cells. Scanty deep blue cytoplasm. Fine nuclear chromatin with 1–2 prominent nucleoli. Cytoplasmic Auer rods. Associated myelocytes, metamyelocytes or promyelocytes cells.

3.5 Lacrimal gland

51

3.5.8 Lymphoma [35, 42–44] Incidence: –– It occurs in 2% of systemic non-Hodgkin lymphoma (NHL). –– NHL in orbit constitutes 10% orbital tumours. –– Primary intraocular NHL is very rare. Types of NHL • Predominantly B cell NHL (97%). –– Extranodal marginal zone lymphoma (59%). –– Diffuse large B cell lymphoma (23%). –– Follicular lymphoma (9%). –– Mantle cell lymphoma (5%). Fig. 3.91  Discrete leukemic blasts in acute myeloid leukaemia of the eye

Key Cytological Features The cytological features depend on the types of NHL. However, all the subtypes of NHL of the eye show the following common characteristics (Figs. 3.94, and 3.95): • The tumour cells are discretely arranged. • The background shows abundant lymphoglandular bodies. • The tumour cells are positive for CD 45. • On cell block/flow cytometry: Light chain restriction in B NHL.

3.5.9 Metastatic Malignancy [35, 45–49] Common Primary Sites of Malignancy • Head and neck region. • Lung. Fig. 3.92  Occasional blasts show cytoplasmic granularity

Fig. 3.93  Occasional blasts show Auer rod in leukaemic deposit

Fig. 3.94  Non-Hodgkin lymphoma. Discrete tumour cells with lymphoglandular bodies in the background

52

Fig. 3.95  Non-Hodgkin lymphoma. The cells are round with deep blue

3  Aspiration Cytology of Head, Neck and Orbital Lesions

Fig. 3.97  Metastatic carcinoma in the orbit: Higher magnification of the same

References

Fig. 3.96  Metastatic carcinoma in the orbit: The clusters of malignant cells in the FNAC smears in a case of known colonic carcinoma

• Breast. • Large intestine. Types of Malignancy (Fig. 3.96, and 3.97) • Adenocarcinoma. • Squamous cell carcinoma. • Sarcoma.

1. Koch EM, Fazel A, Hoffmann M. Cystic masses of the lateral neck– Proposition of an algorithm for increased treatment efficiency. J Craniomaxillofac Surg. 2018;46(9):1664–8. 2. Daoud FS.  Branchial cyst: an often forgotten diagnosis. Asian J Surg. 2005;28(3):174–8. 3. Papadogeorgakis N, Petsinis V, Parara E, Papaspyrou K, Goutzanis L, Alexandridis C. Branchial cleft cysts in adults. Diagnostic procedures and treatment in a series of 18 cases. Oral Maxillofac Surg. 2009;13(2):79–85. 4. Warson F, Blommaert D, De Roy G. Inflamed branchial cyst: a potential pitfall in aspiration cytology. Acta Cytol. 1986;30(2):201–2. 5. Persaud R, Short M, Kothari P, Robinson A.  Thyroglossal duct cyst masquerading as a haematoma. J Laryngol Otol. 2004;118(3):240–1. 6. Chang TJ, Chang TC, Hsiao YL.  Fine needle aspiration cytology of thyroglossal duct cyst: an analysis of 10 cases. Acta Cytol. 1999;43(2):321–2. 7. Henke AC, Cooley ML, Hughes JH, Timmerman TG. Fine-needle aspiration cytology of lymphangioma of the parotid gland in an adult. Diagn Cytopathol. 2001;24(2):126–8. 8. Phukan JP, Sinha A, Pal S, Sinha R. Cytological diagnosis of epidermal inclusion cyst of breast: A rare benign lesion. J Nat Sci Biol Med. 2014;5(2):460–2. 9. Bardales RH, Baker SJ, Mukunyadzi P.  Fine-needle aspiration cytology findings in 214 cases of nonparotid lesions of the head. Diagn Cytopathol. 2000;22(4):211–7. 10. Rana RS, Dey P, Das A. Fine needle aspiration (FNA) cytology of extra-adrenal paragangliomas. Cytopathology. 1997;8(2):108–13.

References 11. Zaharopoulos P.  Diagnostic challenges in the fine-needle aspiration diagnosis of carotid body paragangliomas: report of two cases. Diagn Cytopathol. 2000;23(3):202–7. 12. Ntanasis-Stathopoulos I, Tsilimigras DI, Klapsinou E, Daskalopoulou D, Vaida S, Arnogiannaki N, et al. Challenging differential diagnosis of an extra-adrenal paraganglioma; the role of fine needle aspiration cytology. Diagn Cytopathol. 2017;45(6):565–8. 13. Naniwadekar MR, Jagtap SV, Kshirsagar AY, Shinagare SA, Tata HR, Sahoo K.  Fine needle aspiration diagnosis of carotid body tumor in a case of multiple paragangliomas presenting with facial palsy: a case report. Acta Cytol. 2010;54(4):635–9. 14. Jayaram G, Swain M, Khanijow V, Jalaludin MA. Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma. Diagn Cytopathol. 1998;19(3):168–72. 15. Kollur SM, El Hag IA.  Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma in cervical lymph nodes: comparison with metastatic squamous-cell carcinoma, and Hodgkin's and non-Hodgkin’s lymphoma. Diagn Cytopathol. 2003;28(1):18–22. 16. Viguer JM, Jimenez-Heffernan JA, Lopez-Ferrer P, Banaclocha M, Vicandi B. Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma. Diagn Cytopathol. 2005;32(4):233–7. 17. Mincione GP, Borrelli D, Cicchi P, Ipponi PL, Fiorini A. Fine needle aspiration cytology of parathyroid adenoma. A review of seven cases. Acta Cytol. 1986;30(1):65–9. 18. Heo I, Park S, Jung CW, Koh JS, Lee SS, Seol H, et al. Fine needle aspiration cytology of parathyroid lesions. Korean J Pathol. 2013;47(5):466–71. 19. You Q, Wang X, Zou Y, Yang C, Teng X.  Fine needle aspiration cytology of parathyroid lesions. Zhonghua Bing Li Xue Za Zhi. 2015;44(9):655–6. 20. Sriphrapradang C, Sornmayura P, Chanplakorn N, Trachoo O, Sae-­ Chew P, Aroonroch R.  Fine-needle aspiration cytology of parathyroid carcinoma mimic hurthle cell thyroid neoplasm. Case Rep Endocrinol. 2014;2014:680876. 21. Deshmukh SD, Rokade VV, Pathak GS, Nemade SV, Ashturkar AV. Primary extra-cranial meningioma in the right submandibular region of an 18-year-old woman: a case report. J Med Case Rep. 2011;5:271. 22. Gupta AP, Parate RC.  Fine-needle aspiration cytology of jugular foramen meningioma presenting as parapharyngeal mass. Indian J Pathol Microbiol. 2011;54(2):398–9. 23. Agrawal P, Dey P, Saikia UN, Gupta N, Radhika S, Nijhawan R, et  al. Fine-needle aspiration cytology of orbital meningiomas. Diagn Cytopathol. 2012;40(11):967–9. 24. Gupta N, Kaur J, Srinivasan R, Das A, Mohindra S, Rajwanshi A, et al. Fine needle aspiration cytology in lesions of the nose, nasal cavity and paranasal sinuses. Acta Cytol. 2011;55(2):135–41. 25. Qutub MF, Haider A, Jawad HA, Khalbuss WE.  Fine needle aspiration cytology of ectopic meningioma presenting as a neck mass: a case report and a review of the literature. Cytopathology. 2012;23(1):61–4. 26. Rorat E, Yang W, DeLaTorre R. Fine needle aspiration cytology of parapharyngeal meningioma. Acta Cytol. 1991;35(5):497–500. 27. Bose S, Kapila K, Sarkar C, Verma K. Fine-needle aspiration cytology of meningiomas with unusual presentations. Diagn Cytopathol. 1988;4(3):258–61. 28. Logrono R, Futoran RM, Hartig G, Inhorn SL.  Olfactory neuroblastoma (esthesioneuroblastoma): appearance on fine-needle aspiration: report of a case. Diagn Cytopathol. 1997;17(3):205–8.

53 29. Chung J, Park ST, Jang J.  Fine needle aspiration cytology of metastatic olfactory neuroblastoma: a case report. Acta Cytol. 2002;46(1):40–5. 30. Bharani V, Kumar R, Gupta N, Srinivasan R, Rajwanshi A, Nahar U, et  al. Fine-needle aspiration cytology in primary cutaneous tumors. Diagn Cytopathol. 2017;45(8):681–8. 31. Dey P, Das A, Radhika S, Nijhawan R. Cytology of primary skin tumors. Acta Cytol. 1996;40(4):708–13. 32. Garbyal RS, Gupta P, Kumar M, Bohra A, Chaube A.  A cytologic perspective on meibomian gland carcinoma. Acta Cytol. 2007;51(2):171–7. 33. Das DK, Das J, Bhatt NC, Chachra KL, Natarajan R.  Orbital lesions. Diagnosis by fine needle aspiration cytology. Acta Cytol. 1994;38(2):158–64. 34. Das DK, Das J, Natarajan R, Lal Chachra K, Bhambhani S.  Meibomian gland carcinoma initially identified by cytology. Diagn Cytopathol. 1986;2(2):154–6. 35. Gupta N, Kaur J, Rajwanshi A, Nijhawan R, Srinivasan R, Dey P, et  al. Spectrum of orbital and ocular adnexal lesions: an analysis of 389 cases diagnosed by fine needle aspiration cytology. Diagn Cytopathol. 2012;40(7):582–5. 36. Akhtar M, Ali MA, Sabbah R, Sackey K, Bakry M.  Aspiration cytology of retinoblastoma: light and electron microscopic correlations. Diagn Cytopathol. 1988;4(4):306–11. 37. Das DK, Das J, Chachra KL, Natarajan R.  Diagnosis of retinoblastoma by fine-needle aspiration and aqueous cytology. Diagn Cytopathol. 1989;5(2):203–6. 38. Karcioglu ZA.  Fine needle aspiration biopsy (FNAB) for retinoblastoma. Retina. 2002;22(6):707–10. 39. Czerniak B, Woyke S, Domagala W, Krzysztolik Z.  Fine needle aspiration cytology of intraocular malignant melanoma. Acta Cytol. 1983;27(2):157–65. 40. Kishore M, Kumar V, Kaushal M. Malignant melanoma of conjunctiva: Diagnosis on fine-needle aspiration cytology. J Lab Physicians. 2018;10(4):453–6. 41. Singh P, Singh A.  Choroidal melanoma. Oman J Ophthalmol. 2012;5(1):3–9. 42. Wolska-Szmidt E, Jakubowska A, Krzystolik K, Chosia M.  Fine needle aspiration biopsy and molecular analysis in differential diagnosis of lymphoproliferative diseases of the orbit and eye adnexa. Pol J Pathol. 2004;55(2):51–7. 43. Nassar DL, Raab SS, Silverman JF, Kennerdell JS, Sturgis CD. Fine-needle aspiration for the diagnosis of orbital hematolymphoid lesions. Diagn Cytopathol. 2000;23(5):314–7. 44. Subramanian R, Solo S, Mishra MM, Murugan P, Siddaraju N, Basu D, et al. Fine needle aspiration cytology of primary lymphoid lesions of the orbit: report of four cases. Acta Cytol. 2007;51(3):417–20. 45. Char DH, Schwartz A, Miller TR, Abele JS.  Ocular metastases from systemic melanoma. Am J Ophthalmol. 1980;90(5):702–7. 46. Logrono R, Inhorn SL, Dortzbach RK, Kurtycz DF. Leiomyosarcoma metastatic to the orbit: diagnosis of fine-needle aspiration. Diagn Cytopathol. 1997;17(5):369–73. 47. Srinivasan R, Krishnanand G.  Cytologic diagnosis of metastatic hepatocellular carcinoma presenting as an orbital mass. A case report. Acta Cytol. 2007;51(1):83–5. 48. Kim CY, Ha CW, Lee SC. Vitreous and retinal metastasis from gastric cancer. Eur J Ophthalmol. 2010;20(3):615–7. 49. Singh AD, Biscotti CV. Fine needle aspiration biopsy of ophthalmic tumors. Saudi J Ophthalmol. 2012;26(2):117–23.

4

Aspiration Cytology of Salivary Gland

Fine needle aspiration cytology (FNAC) is a useful technique in the salivary gland lesions. It primarily helps in recognition of the neoplastic lesions from the non-neoplastic lesions and selection of the cases for surgical management.

The minor salivary glands: Located in the oral mucous membrane, larynx and bronchi.

4.1

• The largest salivary gland: 25 gm weight. • Below the external ear and on the mandible. • The secretion flows through the Stenson’s duct, which ends within the mouth opposite the second molar tooth. • Compound tubuloalveolar serous gland.

The Major Advantages of FNAC [1–4]

• Incisional biopsy of the salivary gland is usually avoided due to the fear of the development of fistula. So FNAC is the best alternative procedure to diagnose and manage the salivary gland swellings. • The diagnostic accuracy of FNAC is high. • FNAC helps to avoid the unnecessary surgical exploration of the non-tumorous of the salivary gland. • FNAC helps in the better surgical management of the neoplastic lesions. • The other essential investigations such as microbial culture, flow cytometry, molecular testing etc. can be done on the FNAC sample.

4.1.1 Complications of FNAC Usually free of any significant complications. However, FNAC may cause the following complications • • • •

Mild haemorrhage. Injury to the facial nerve. Infection. FNAC induced changes such as infraction and squamous metaplasia.

4.1.2 A  natomy and Histology of the Salivary Glands The major salivary glands: Parotid, submandibular and sublingual glands.

4.1.3 Parotid Gland

4.1.4 Submandibular Gland • Lighter than the parotid gland: 8 to 10 gm weight. • Located in between the two bellies of the digastric muscle. • The duct of the submandibular gland (Wharton’s duct) opens in the mouth behind the lower incisor tooth. • Compound tubuloalveolar seromucinous gland.

4.1.5 Sublingual Gland • The smallest among the three major glands: 0nly 4 gm. • Location: Sublingual. • Secretion passes through multiple ducts in the floor of the mouth. • Compound tubuloalveolar seromucinous gland.

4.1.5.1 Histology of the Salivary Gland • Numerous acini that open into the duct. • Acini: –– Triangular shaped cells with the apex in the luminal side. –– Mucous secreting cells. –– Myoepithelial cells surrounding the basal lamina. • Duct: Lined by small cuboidal cells.

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_4

55

56

4  Aspiration Cytology of Salivary Gland

4.1.6 C  ytology of the Salivary Gland (Figs. 4.1, 4.2, 4.3, 4.4 and 4.5) Ductal cells • Small clusters. • The cells with scanty cytoplasm. • Round monomorphic nucleus. Acinar cells • • • •

Ball-like clusters. Abundant cytoplasm. The foamy vacuolated appearance of the cell. Monomorphic round nucleus. Myoepithelial cells

• Spindle-shaped cells. • Spindle-shaped nuclei. • Often plasmacytoid appearance.

Fig. 4.1  Salivary ductal cells: Cohesive cluster of cells with scanty cytoplasm and monomorphic nuclei

Fig. 4.2  Ball-like clusters of acini

Fig. 4.3  Benign salivary acinar cells and ductal cells

Fig. 4.4  Acinar cells show abundant vacuolated cytoplasm and monomorphic nuclei

Fig. 4.5  Acinar cells with bare nuclei may mimic lymphocytes

4.2 Diagnostic Accuracy

Note At times, the acinar cell may contain only bare nuclei due to cytoplasmic fragility and may mimic lymphocytes (Fig. 4.5).

4.2

Diagnostic Accuracy

FNAC has high diagnostic sensitivity and specificity [5–9]. Sensitivity: Variable from 52 to 98%. Specificity: Very high overall specificity 87 to 98%. The sensitivity and specificity regarding the identification of the neoplasm of the salivary gland is nearly 100%.

4.2.1 Causes of False-Positive FNAC • Pleomorphic adenoma (PA) may simulate adenoid cystic carcinoma (ADC) and vice versa.

57

• Oncocytic changes in chronic inflammation may mimic Warthin tumour. • Benign acinar cells often mimic acinic cell carcinoma (ACC). • Reactive atypia in the inflammatory lesion may simulate neoplasm.

4.2.2 Causes of False-Negative FNAC [10] • ACC often simulates as benign salivary acinar cells (Fig. 4.6). • Minimal nuclear pleomorphism and cystic changes in the low-grade mucoepidermoid carcinoma may resemble as a non-neoplastic cyst (Figs. 4.7 and 4.8). • Mucosa-associated lymphoma (MALTOMA) in the salivary gland may mimic as chronic inflammation in FNAC smear (Figs. 4.9 and 4.10). • Warthin tumour may also resemble as an inflammatory lesion.

Fig. 4.6 (a) and (b) are from acinic cell carcinoma, whereas (c) and (d) are from the benign salivary gland. At times it is difficult to distinguish them

58

4  Aspiration Cytology of Salivary Gland

Fig. 4.9  MALTOMA of the parotid may mimic chronic sialadenitis Fig. 4.7  Cystic mucoepidermoid carcinoma may mimic as benign cyst. Only higher magnification may reveal the nature of the cells (inset)

Fig. 4.10  Chronic sialadenitis showing extensive lymphoid cells

Fig. 4.8  Benign cystic lesion in the upper neck

4.2.3 T  he Major Difficulties in the Diagnosis [10] • The extreme heterogeneity of the different SGTs. • Both benign and malignant tumours have almost similar features such as myoepithelioma versus malignant myoepithelioma. • Overlapping cytological features in different tumours: –– Hyaline globules: Noted both in ADC and in basal cell adenoma. –– Squamous metaplasia: Seen both in PA and in mucoepidermoid carcinoma. –– Oncocytic changes: Both in Warthin tumour and in oncocytoma.

4.2.4 FNAC Techniques and Special Consideration The FNAC technique is the same as we do in other areas. However, one should take care of: • To do FNAC from the different sites. • In case of a cystic lesion, re-aspiration after the initial drainage of the cyst fluid. • Along with MGG stain, always have a Papanicolaou’s stain (for squamous cell confirmation). • Material to take for cell block and flow cytometry. • Microbial culture to do in case of necrosis.

4.3

Non-neoplastic Lesions

Cystic Lesions Described in Chap. 3.

4.3 Non-neoplastic Lesions

59

4.3.1 Other Lesions 4.3.1.1 Sialadenosis Sialadenosis is a benign and non-inflammatory lesion. There is diffuse hypertrophy of the acini without any inflammatory changes. Clinical Feature • Mostly asymptomatic. • Slowly growing. • Progressive. • Bilateral diffuse enlargement of the parotid glands. • Diffuse swelling with an ill-defined margin. Aetiology Unknown and less understood. Often associated with: • • • • •

Chronic alcoholics. Cirrhosis. Obese person. Diabetes mellitus. Drug intake: Phenylbutazone and adrenergic drugs.

Fig. 4.12  Sialadenosis. Higher magnification of the same showing the benign acinar cells

Key Cytological Features (Figs. 4.11, 4.12, 4.13, and 4.14) • Abundant benign groups of acinar cells. • Mild nuclear enlargement. • No inflammatory cells in the background. Diagnostic Points As cytology findings are non-specific so the cases should be correlated clinically also for the diagnosis of sialadenosis. Fig. 4.13  Sialadenosis. Ball-like clusters of acinar cells

Fig. 4.11  Sialadenosis. Abundant salivary acinar cells in a clean background

Fig. 4.14  Sialadenosis. Higher magnification of the same showing acinar cells with vacuolated cytoplasm and round mildly enlarged nuclei

60

4  Aspiration Cytology of Salivary Gland

4.3.2 Sialadenitis 4.3.2.1 Acute Sialadenitis FNAC is usually avoided in such cases because the diagnosis is clinically evident in the majority of the patients. Common Causes • Poor oral conditions. • Obstruction of the salivary duct due to stone (sialolithiasis). • Mumps affecting the salivary glands. • Immunocompromised patients. Clinical Features • Pain and tenderness. • Fever. • Diffuse bilateral swelling of the salivary glands.

Fig. 4.15  Chronic sialadenitis. Abundant lymphocytes and salivary ductal cells

Key Cytological Features • A large number of polymorphs. • Necrotic debris. • Benign ductular cells: The cell may show mild nuclear atypia. Note Necrosis may be present in the malignant tumour. In case of any such suspicion, one should do multiple FNAC from the different areas of the salivary gland.

4.3.3 Chronic Sialadenitis [11] 4.3.3.1 Common Association • Obstruction of the salivary duct due to stone. • The various autoimmune disease particularly Sjögren syndrome. • Radiation exposure.

Fig. 4.16  Chronic sialadenitis. Higher magnification of the same

Common Involvement of the Glands • Submandibular glands: 80% cases. • Parotid glands: 20%. • Sublingual glands: Uncommon. Key Cytological Features (Figs. 4.15, 4.16, and 4.17) • Abundant lymphocytes in the background. • Salivary ductal cells. • Sparse acinar cells due to destruction of the acini. • Infrequently metaplastic squamous cells.

4.3.4 Lymphoepithelial Sialadenitis [12–14] Synonyms: Mikulicz’s disease, benign lymphoepithelial lesion. The preferable terminology is lymphoepithelial sialadenitis (LESA).

Fig. 4.17  Chronic sialadenitis. Abundant discrete lymphocytes

4.3 Non-neoplastic Lesions

61

Age incidence: May occur in any age. However, it is more frequent in fourth to seventh decade. Sex incidence: Three times more common in female. Association • About 50% of LESA is associated with Sjogren’s syndrome. • Various autoimmune lesions (e.g. Rheumatoid arthritis).

4.3.5 Clinical Features • Painful parotid gland (submandibular glands are infrequently affected). • Usually bilateral and diffuse. Risk of Malignancy More than 40 times risk to develop NHL.

Fig. 4.19  Lymphoepithelial sialadenitis. Higher magnification of the same showing ductal cells with lymphocytic infiltration

Key Cytological Features (Figs. 4.18,4.19, and 4.20) • A large number of reactive lymphoid cells: Mature lymphocytes, follicular centre cells, immunoblasts and plasma cells. • Clusters of salivary duct cells infiltrated by lymphocytes. • Frayed margins of the ductal cell clusters. Diagnostic Hallmark Lymphoepithelial islands with lymphocytic destruction of the acini in the background of abundant reactive lymphoid cells. Differential Diagnosis • NHL: The FNAC smears of LESA may mimic NHL and vice versa. It is often challenging to distinguish these two

Fig. 4.20  Lymphoepithelial sialadenitis. The irregular fraying margin of the ductal cells

entities. However, the following features may be helpful:

Fig. 4.18  Lymphoepithelial sialadenitis. Abundant reactive lymphoid cells and occasional clusters of ductular cells

–– Monomorphic cells in NHL. –– Light chain restriction in B-NHL on flow cytometry. • Warthin tumour: Abundant lymphoid cells may also be present in Warthin tumour and mislead the cytologists (Fig. 4.21). The clues to the diagnosis of Warthin tumour are: –– Abundant oncocytes. –– Dirty background. –– Usually Unilateral involvement of the gland. • Lymph node within the parotid or submandibular glands (Fig.  4.22): Intraparotid lymph node may also simulate LESA and difficult to distinguish on cytology smear. However, the lymph node is well-circumscribed nodular swelling.

62

4  Aspiration Cytology of Salivary Gland

a

b NHL: Monomorphic lymphoid cells

c Chronic sialadenitis: Abundant lymphoid cells

Warthin tumour : Oncocytes

d LESA: Duct cells and lymphocytes

Fig. 4.21  Differential diagnosis of lymphoepithelial sialadenitis. (a). NHL: Monomorphic lymphoid cells, (b). Warthin tumour: abundant oncocytes, (c) Chronic sialadenitis is characterized by abundant lymphoid cells and (d) LESA: Both ductal cells and lymphocytes present

• Chronic sialadenitis: The amount of reactive lymphoid cells is less in chronic sialadenitis compare to LESA (Fig. 4.21).

4.3.6 Granulomatous Sialadenitis [15] 4.3.6.1 Causes • Chronic bacterial infection: Tuberculosis. • Fungal infection. • Sialolithiasis. • Sarcoidosis.

Fig. 4.22  FNAC smear of an intraparotid lymph node. It is difficult to distinguish this entity from LESA

Key Cytological Features (Figs. 4.23 and 4.24) • Epithelioid cell granulomas. • Langhans giant cells. • Lymphocytes.

4.6 Benign Neoplasm

Fig. 4.23  Sarcoid granuloma. Well circumscribed epithelioid cells granulomas. The smear is free of any necrosis

63

Fig. 4.25  Aspergillosis of the parotid gland: FNAC smear showing thin slender acute angle branched aspergillus along with inflammatory cells (Periodic acid Schiff stain)

4.5

 he Milan System of Reporting T the Salivary Gland Tumours

The group of expert cytologists proposed “The Milan System for Reporting Salivary Gland Cytopathology” to avoid problems of labelling of cytology of the salivary gland swellings. It is an evidence-based and practical approach of reporting of FNAC of the salivary gland [17]. There are six categories in this reporting system (Table  4.1), and each group carries its own risk of malignancy that ranges from 5% to more than 90%. It is expected that the Milan system of reporting will help to standardize uniform approach in FNAC of the SGTs. Fig. 4.24  Sarcoid granuloma. Higher magnification of the same showing granuloma

4.6

Benign Neoplasm

• Eosinophils: In fungal infections. • Absence of necrosis in sarcoidosis. • Also, the presence of definitive organisms is often noted (Fig. 4.25).

4.6.1 Pleomorphic Adenoma [18, 19]

4.4

Synonym Mixed tumour of the salivary gland.

Neoplastic Lesions

Salivary gland neoplasms are composed of a diverse collection of tumours. Figure 4.26 shows the classification of the tumours of the salivary gland according to World health organization [16].

PA is the benign SGT that shows epithelial and myoepithelial components together. The cells of both the components are monoclonal in origin.

Origin The tumour possibly develops from the reserve cells of the intercalated duct.

64

4  Aspiration Cytology of Salivary Gland

Fig. 4.26  Classification of the salivary gland by World Health Organization in 2017

Table 4.1  The Milan system for reporting salivary gland lesions Risk of malignancy 25%

Category Definition I Non-diagnostic

Description Inadequate material

II III

Non-neoplastic Atypia of undetermined significance

Benign lesions (sialadenitis, sialadenosis, infections) Atypia is present. No definite opinion on malignancy can be given. Possibly inadequate sample from the neoplasm

10% 20%

IV

Neoplasm Benign Salivary gland neoplasm of uncertain malignant potential (SUMP) Suspicious of malignancy Malignancy

This category includes benign tumours Predominantly benign neoplasm, however, atypical cells present

2 cm) gives more sensitivity. • Specificity: Near about 100%. • False-positive rate: 0.1 to 0.2%. • False-negative rate: 0.1 to 0.7%.

7.1.3 Transbronchial FNAC 7.1.3.1 Indications to Do Transbronchial FNAC (TBNA) • In case of sub-centimetre tiny mucosal lesion. • Tumour underneath the mucosa with an intact layer of the mucous membrane. • To stage the carcinoma of the lung by taking a sample of hilar lymph nodes. • Unknown cause of enlarged mediastinal node. • Conventional: –– Simple fibreoptic bronchoscope helps to procure the sample. –– Peribronchial hilar lymph node located near the bronchus is sampled. • Endoscopic ultrasound-guided FNA (EUS-FNA) [1]: –– An ultrasound probe is used to get a real-time image. –– EUS-FNA provides better visualization of the lesion. –– Much more sensitive than conventional transbronchial FNAC. –– It needs good training. Table 7.1 highlights the comparison of TTNA and EUS-FNA. Contraindications of FNAC • Respiratory failure. • Uncontrolled cough reflex or no cough reflex. • Bleeding disorder or patient under the treatment of anticoagulant. • Known case of hydatid cyst.

Complications of FNAC • Pneumothorax is the main complication. It may occur in 5 to 50% cases. The severity of the pneumothorax depends on the length of the needle track and the number of passes.

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_7

175

176

7  Fine Needle Aspiration Cytology of the Lung

Table 7.1  Conventional TBNA versus EUS-FNA Conventional TBNA Relatively less cellular than EUS-TBNA Real-time visualization not possible Difficult to have material from the tiny lesions Rare chance to puncture small vessels

EUS-FNA More cellular smear Real-time visualization of the lesion possible Possible to have material from tiny sub-centimetre lesions Very rare chance to puncture small vessels

The majority of the cases are treated by conservative therapy [2]. • Haemorrhage in the lung parenchyma. • Cardiac tamponade, air embolism and lung torsion are very rare events.

7.2

• Type I pneumocytes: Represents 95%: Slender and flat cells. • Type II pneumocytes: Represents 5%: Round cells, central nuclei, prominent nucleoli.

7.2.1 Cytology (Figs. 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, and 7.7) 7.2.1.1 Lining Cells • Ciliated columnar cells: –– Single and loose clusters. –– Tall columnar cells with basal plate and tufts of cilia in one end. –– Regular round basally placed nuclei. –– Moderate amount of cytoplasm. • Alveolar pneumocytes:

Anatomy and Histopathology of the Lung

Upper respiratory tract: • • • •

Nose. Paranasal sinus. Pharynx. Larynx. Lower respiratory tract

• • • •

Trachea. Bronchi. Bronchioles. Lung alveoli.

The Lung Is Made of • Bronchioles: Bronchus enters in the lung and divides into lobar bronchi, segmental bronchi, subsegmental bronchi and bronchioles. • Alveolar ducts: Smallest bronchioles end into the alveolar ducts. • Alveolar sac: Alveolar ducts open into the alveolar sacs. • Alveoli: Alveolar sacs contain the air spaces known as alveoli. Histology of Alveoli • Alveoli are lined by the epithelial cells situated on the basement membrane made, which is surrounded by the thin-walled blood capillaries. • The cells lying on the basement membrane are type I and type II pneumocytes and alveolar macrophages. • The other side of the basement membrane has endothelial cells of the blood vessels situated on the basement membrane of the capillaries.

Fig. 7.1  Respiratory epithelial cells. Cells in a cluster with tufts of cilia

Fig. 7.2  Respiratory epithelial cells. Single and binucleated cells

7.3 The Cells Simulating Malignancy

Fig. 7.3  Histiocytes. Histiocytes with carbon particles. Many respiratory epithelial cells and polymorphs are also seen

Fig. 7.4  Goblet cell: Cell with vacuolated cytoplasm having peripherally pushed nucleus

177

Fig. 7.6  Mesothelial cells: Higher magnifications showing monomorphic cells

–– Flattened squamous epithelial cells (type I pneumocytes). –– Columnar looking cells (type II pneumocytes). • Alveolar macrophages: –– Present as discrete singly scattered. –– Cells are round. –– Cytoplasm: Abundant, contain brownish coloured carbon particles. –– Nuclei: Central, bean shaped, fine chromatin. • Goblet cells: –– Moderate amount of cytoplasm. –– Single to multiple vacuoles. –– Regular round nuclei. • Mesothelial cells: –– Monolayer collection of cells. –– Gaps in between the cells mimic window pattern. –– Well-defined cytoplasmic margin. –– Round nuclei located centrally or eccentrically. –– Fine chromatin and prominent nucleoli.

7.3

The Cells Simulating Malignancy

7.3.1 Reactive Bronchial Cells Aetiology: Chronic irritation due to various infections in the lung, chronic bronchitis or asthma.

Fig. 7.5  Mesothelial cells: Monolayer sheet of monomorphic cells

Cytomorphology (Figs. 7.8, 7.9, 7.10, 7.11, and 7.12) • Large clusters. • Enlarged and pleomorphic nuclei. • Prominent nucleoli. • Smooth nuclear margin.

178

7  Fine Needle Aspiration Cytology of the Lung

Mesothelial cells

Malignant cells

Fig. 7.7  Cytomorphology of mesothelial cells and malignant cells

Fig. 7.8  Reactive bronchial cell showing multinucleation

Fig. 7.9  Hyperplastic bronchial cells showing nuclear enlargement and small prominent nucleoli

7.3 The Cells Simulating Malignancy

179

• Often multinucleated. • However, the cells maintain terminal plate and cilia. Note: The following features help to distinguish reactive bronchial cells from malignant cells [3]: • The transition between the completely normal looking bronchial cells and atypical cells is detectable in malignancy. • The presence of the terminal plate and cilia in reactive bronchial cells. Table 7.2 highlights the differentiating features of reactive bronchial cells and carcinoma.

7.3.2 Vegetable Cell Fig. 7.10  Hyperplastic bronchial cells with preserved cilia

At times the contaminant vegetable cells may simulate malignancy. It may occur in sputum or bronchoalveolar lavage and not seen in FNAC. The Characteristic Features of Vegetable Cells Are (Fig. 7.13) • Large cell. Table 7.2  Reactive bronchial cells versus carcinoma Reactive bronchial cells Absent two cell population as there is a gradual transition of reactive bronchial cells to atypical cells Terminal plate and cilia are preserved No significant nuclear enlargement

Fig. 7.11  Carcinoma. Tumour cells in a cluster along with normal respiratory cells

Fig. 7.12  carcinoma: Clusters of cells showing nuclear overlapping, and pleomorphism

Regular nuclear margin Coarse chromatin

Fig. 7.13  Vegetable cells in sputum

Adenocarcinoma Presence of two cell population

Terminal plate and cilia are detached from the cell Significant nuclear enlargement (at least six times that of normal bronchial cells) Irregular nuclear margin Irregular coarse chromatin

180

7  Fine Needle Aspiration Cytology of the Lung

a

b

Fig. 7.14 (a) Occasional atypical squamous cells in necrotic tissue. (b) Large atypical cells of squamous cell carcinoma in higher magnification

• Abundant cytoplasm. • Thick cytoplasmic margin. • The cytoplasm may be mistaken as nuclei.

The golden rules in diagnosis of malignancy

Necrosis • Occasionally squamous cell carcinoma shows a large amount of necrosis, and a careful search is needed to get malignant squamous cells (Figs. 7.14 a and b).

1. Never diagnose malignancy in absence of any space occupying lesion. 2. Avoid diagnosis of malignancy in scanty cellularity. 3. Be cautious to diagnose malignancy in a clean background. 4. Avoid diagnosis of malignancy when there are overlapping cytological features

The golden rules in diagnosis of malignancy in the cytology smears of lung lesions are highlighted in Fig. 7.15.

7.4

Inflammatory Lung Lesions

7.4.1 Acute Inflammation 7.4.1.1 Key Cytological Features (Fig. 7.16) • Abundant neutrophils. • Histiocytes. • Often background necrotic material. • Thin-walled capillaries.

7.4.2 Differential Diagnosis • Squamous cell carcinoma. –– Among the necrotic tissue, there may be occasional viable squamous cells. –– The cells have dark hyperchromatic nuclei. –– In case of clinical suspicion for malignancy, one should do repeat FNAC. • Other infections: Tuberculosis and fungal infection may also cause predominantly acute inflammatory cells. Ziehl Neelsen stain for acid-fast bacilli and special stain for fungi are needed.

Fig. 7.15  The golden rules in the diagnosis of malignancy

7.5

Specific Infections

7.5.1 Tuberculosis Causative agents: Mycobacteria are responsible for tuberculosis. • Mycobacterium tuberculosis: Aerobic, non-motile and non-capsulated bacterium. • Also: M. bovis, M. pinnipedii, M. africanum, M. microti, M. caprae and M. canetti. Spread: Droplet inhalation.

7.5 Specific Infections

Fig. 7.16  Acute inflammation: Abundant polymorphs

181

Fig. 7.17  Tuberculosis: Necrosis along with many polymorphs and respiratory epithelial cell

7.5.2 Diagnostic Modalities • Sputum examination. • Bronchoalveolar lavage. • FNAC from the space-occupying lesion of the lung.

7.5.3 K  ey Cytological Features [4–6] (Figs. 7.17, 7.18, 7.19, 7.20, and 7.21) • Necrotic material. • Epithelioid cell granulomas: The epithelioid cells have an ample amount of cytoplasm with elongated nuclei. The cells are present in syncytium and loose aggregates. • Many multinucleated Langhan’s types of giant cells: These are large cells about 250 microns in size having multiple nuclei. The nuclei are arranged peripherally as “horse shoe” shaped manner. • Background lymphocytes.

Fig. 7.18  Tuberculosis: Multinucleated giant cells

Special Stains • Ziehl Neelsen stain: –– The overall acid-fast bacilli (AFB) positivity ranges from 25 to 60%. –– Highest AFB positivity in necrosis: 70%. –– Epithelioid cell granuloma with necrosis: 60%. –– Only epithelioid cell granuloma: 20%. • Auramine Rhodamine fluorescent stain. Culture of Aspirated Material • Culture in Lowenstein-Jensen media: For 8–12 weeks. • BACTEC culture: 3 weeks. Polymerase chain reaction (PCR) such as Multiplex PCR, allele-specific PCR, PCR restriction analysis, real-time PCR:

Fig. 7.19 Tuberculosis: Necrosis, along with epithelioid cell granuloma

182

7  Fine Needle Aspiration Cytology of the Lung

7.5.5 Actinomycosis Incidence: Rare infection of the lung. Pulmonary actinomycosis represent 15% of the total burden of infections. Mean age: Usually middle age to elderly patients. The mean age is 57 years. Causative organism: Actinomyces israelii. Actinomyces are filamentous Gram-positive, non-acid fast organism. Occurrence: The infection primarily occurs in the tonsillar fossa and gingival crevices. Secretions from these sites contaminate the respiratory tract. Symptoms: Chest pain, fever, cough and dyspnea.

Fig. 7.20  Tuberculosis: Epithelioid cell granuloma

Cytomorphology [7, 8] (Fig. 7.22) • Cotton ball-like clusters of the organisms. • Filamentous branching organisms. • The background shows abundant polymorphs and necrosis.

7.5.6 Nocardia Causative organism: Nocardia asteroides, and Nocardia brasiliensis. Gram-positive, weakly acid-fast filamentous aerobic organism. Infection • Infection in the lung occurs due to direct inhalation of Nocardia species. • It mainly occurs in immunosuppressed patients. Fig. 7.21  Tuberculosis: Epithelioid cell granuloma is composed of epithelioid cells and lymphocytes

Symptoms: Cough and high-grade fever.

• Sensitivity: 78–96%. • Specificity: 85–100%. Xpert MTB/RIF: Automated semi-nested polymerase chain reaction (PCR) technique. • Sensitivity: 97%. • Specificity: 99%. • Turnover time: 2 hour.

7.5.4 Differential Diagnosis • Other causes of granulomas: Sarcoidosis, fungal infection etc. • Carcinoma: Squamous cell carcinoma often produces granuloma in response to keratin. However, the identification of malignant squamous cell confirm the diagnosis of malignancy.

Fig. 7.22  Actinomycosis: Cotton ball-like cluster with radiating filamentous branching organisms

7.6 Fungal Infections

183

Fig. 7.23  Nocardia: Thin filamentous organism in abundant inflammatory cells

Fig. 7.25  Nocardia: Faintly stained long filamentous organism in haematoxylin and eosin stain

Fig. 7.24 Nocardia: Higher magnification showing long slender organism

Fig. 7.26 Nocardia: Modified Ziehl Neelsen stain showing the organism

Cytomorphology [ 7, 9] (Figs. 7.23, 7.24, 7.25, and 7.26) • Long thin, filamentous, branching organisms. • They are Gram-positive and weak acid-fast positive organism. • Positive in modified Ziehl-Neelsen stain.

• • • •

7.6

Fungal Infections [10–12]

7.6.1 Aspergillus Causative organisms: Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. Risk Factors • Long-standing neutropenia.

Prolonged use of Corticosteroid therapy. Acquired immunodeficiency disease. Transplant patients. Patients taking chemotherapeutic drugs.

The spread of infection: By droplet inhalation. Type of infection in the lung: The effects of inhalation of the spore depends on the immunity of the host: • Normal host: No effect. • Immunocompromised host: Invasive pulmonary aspergillosis. • Chronic lung disease: Chronic, necrotizing aspergillosis. • Cavitary lung disease: Aspergilloma. • Asthma: Allergic bronchopulmonary aspergillosis.

184

7  Fine Needle Aspiration Cytology of the Lung

7.6.2 K  ey Cytological Features (Figs. 7.27, 7.28, 7.29, and 7.30) • Organism: –– Aspergillus is long, thick, regularly septate, with acute angle (45°-angle) branching. • Necrosis. • Inflammation. • Calcium oxalate crystals and Charcot-Leyden crystals. • Eosinophils. • Atypia of squamous cells: Squamous cells with nuclear atypia may often mimic malignant cells.

Fig. 7.29  Aspergillus: Clusters of Aspergillus organisms in inflammation in Papanicolaou’s stained smear

Fig. 7.27  Aspergillus: Organisms in clusters among a large number of inflammatory cells

Fig. 7.30  Aspergillus: Note the atypical squamous cells in the smear

7.6.3 Mucormycosis Infection: Inhalation of conidia of mucor. Risk Factors • Immunocompromised patients. • Transplant patients. • Diabetes mellitus. • Chronic renal failure. • Various hematologic malignancies. Fig. 7.28  Aspergillus: Higher magnification showing better morphology. The organisms are long, uniformly septated with acute angle branching

Clinical feature: The clinical features are non-specific and clinically ambiguous to identify the infection.

7.7 Pulmonary Cryptococcosis

• • • •

185

Refractory fever even after antibiotics. Dry cough. Dyspnea. Pleuritic pain.

7.6.4 K  ey Cytological Features (Figs. 7.31, 7.32, 7.33, and 7.34) • Necrosis. • Inflammation. • Organism. –– Broad-based. –– Non-septate and looks like a long ribbon. –– The fungal hyphae are 6–50 micron in diameter. Fig. 7.33  Mucormycosis: Periodic acid Schiff’s stain highlights the fungi

Wide angle branching

Thick broad and

a

Fig. 7.31 Mucormycosis: Thick broad fungi with wide-angled branching Thin, septate and acute angle branching

b Fig. 7.34  Differential diagnosis of a) mucormycosis and b) Aspergillus fungi

–– Wide angled branching. –– Special stains: Periodic acid-Schiff (PAS), Grocott-­ Gomori methenamine-silver.

7.7

Fig. 7.32  Mucormycosis: Bunch of fungi. Note the broad fungi with wide-angle branching

Pulmonary Cryptococcosis

Causative organisms: Cryptococcus neoformans or Cryptococcus gattii. The spread of infection: Inhalation of the desiccated yeast cells or spores. The organisms are frequently noted in the soil contaminated with pigeon droppings.

186

7  Fine Needle Aspiration Cytology of the Lung

Clinical Features • Asymptomatic. • Chronic cough. • Fever. • Chest pain.

7.8

Histoplasma

Cytomorphology (Figs. 7.35 and 7.36) • Necrosis. • Inflammation. • Histiocytes containing the organism. • Organism. –– Budding yeast. –– Round shape 6–10 micron diameter. –– Thick outer capsule. –– Within the histiocytes, it appears as a clear halo. –– Special stain: PAS, mucicarmine or alcian blue, India ink.

Risk Factor

Causative Organism Histoplasma capsulatum. Infection: Inhalation of conidia.

• Immunocompromised patient. • Debilitated person.

7.8.1 Clinical Features • Mostly asymptomatic patients. • Acute histoplasmosis. • Mimic pulmonary tuberculosis: Lung nodule and mediastinal lymphadenopathy. • Pneumonia leading to respiratory failure. • Chronic pulmonary histoplasmosis. • Disseminated histoplasmosis.

7.8.2 K  ey Cytological Features (Figs. 7.37, 7.38, 7.39, 7.40, and 7.41) • • • •

Fig. 7.35  Cryptococci: A large number of round shaped cryptococci in necrotic material

Fig. 7.36  Cryptococci: PAS stained organism

Acute or chronic inflammatory cells. Necrosis. Often epithelioid cell granulomas. Organism: –– Mostly intracellular within the macrophages. –– Small round 2–4 micron diameter organism. –– Stain: Visible in May Grunwald Giemsa stain, methenamine silver.

Fig. 7.37  Histoplasma: Abundant histiocytes and inflammatory cells. The histiocytes containing histoplasma organisms

7.9 Pneumocystis Pneumonia

187

Fig. 7.38  Histoplasma: Macrophage loaded with histoplasma

Fig. 7.40  Histoplasma: Histoplasma in higher magnification

Fig. 7.39  Histoplasma: Many small round shaped organisms in PAS stain

Fig. 7.41  Histoplasma: Epithelioid cell granuloma

Differential Diagnosis Leishmania (Fig. 7.42). Table 7.3 highlights the essential information on different fungal infections in the lung.

7.9.1 K  ey Cytological Features (Figs. 7.43, 7.44, and 7.45)

7.9

Pneumocystis Pneumonia [13, 14]

Causative organism: Pneumocystis jirovecii pneumonia. Previous name: Pneumocystis carinii. Risk factors: Acquired immunodeficiency syndrome, immunosuppression, corticosteroid therapy, renal transplantation. Clinical Features • Acute sudden onset of respiratory failure. • Radiograph: Bilateral perihilar diffuse opacity.

• Inflammation. • Eosinophilic amorphous and frothy material. • Careful examination shows 1–2 micron round-shaped organism. • Difficult to identify by Papanicolaou’s stain as the organisms remain unstained. • Special stain: Methanamine silver.

7.9.2 Differential Diagnosis (Fig. 7.46) • Collections of RBCs: RBCs as an artefact may mimic pneumocystis.

188

7  Fine Needle Aspiration Cytology of the Lung

• Mucus plug: Mucus plugs are usually homogenous. • Bacterial clump: Occasionally bacterial clumps may mimic pneumocystis.

7.10 Candidiasis Causative organism: Candida albicans. Part of the flora of the oral cavity in a healthy person. Risk factor: Opportunistic infection and occurs in an immunocompromised patient. Clinical features: Fever, cough and dyspnea. Conclusive evidence of infection: The presence of these fungi in FNAC of lung lesion. Fig. 7.43  Pneumocystis jirovecii: Amorphous material along with respiratory epithelial cells and inflammatory cells

Small 3 micron round shaped

a Small 2 micron with kinetoplast in one end

b Fig. 7.42 Differential diagnosis between a) histoplasma and b) leishmania

Fig. 7.44  Pneumocystis jirovecii: Frothy material containing many small round trophozoites

Table 7.3  Essential information on different fungi Organism Cryptococcus

Morphology of the fungi Round shaped 6–10 μ diameter Thick outer capsule. Budding yeast

Aspergillus

Slender, thick (3–6 micron width), regularly septate, with acute angle branching

Mucormycetes

Broad based, non-septate long ribbon like with wide angled branching. The fungal hyphae are 6–50 micron in width Small, oval budding yeasts with 2–4 micron. Often long pseudohyphae Small round 2–4 micron diameter narrow budding organism

Candida Histoplasma

Stains PAS, mucicarmine, alcian blue, India ink The capsule is stained by PAS PAS, Mucicarmine, Methanamine silver

Risk factors Usually immunocompromised patient but may occur in non-immunocompromised patients also

PAS, methenamine-silver

Long-standing neutropenia, prolonged use of corticosteroid therapy, Acquired immunodeficiency disease Immunocompromised patients, transplant patients, diabetes mellitus, chronic renal failure

PAS

Immunocompromised patients

Methenamine silver

Immunocompromised patient, debilitated person

7.11 Parasites

189

7.10.1 Key Cytological Features • Budding yeast: 2–4 micron in size. • Candidal pseudohyphae. • Inflammatory cells in the background.

7.11 Parasites 7.11.1 Hydatid Cyst Causative organism: Echinococcus granulosus.

7.11.2 Life Cycle Fig. 7.45  Pneumocystis jirovecii: Trophozoites of P. jirovecii appear as frothy material

Definitive host: Dogs. Intermediate host: Ship, goat and pigs.

Mucus globules

Pneumocystis Jiroveci

a

c

RBCs in aggregation

b Fig. 7.46  Differential diagnosis of Pneumocystis jirovecii infection

190

7  Fine Needle Aspiration Cytology of the Lung

Accidental Host: Humans • Adult worm remains in the intestine. • Adult worm releases numerous eggs that come out through faeces. • The intermediate host ingests eggs. • Embryos are released in the intestine of the intermediate host. • Embryos pierce the intestinal capillaries and come to the portal circulation. • They grow into cystic metacestodes in lung and liver. • The cyst contains a large number of protoscolices that may have the capability to develop into an adult worm. Common Organs Involvement Lung: 10 to 30%. Liver: 70%. Other organs: Spleen, kidney, brain etc.

Fig. 7.48  Hydatid cyst: Scolex

7.11.3 Key Cytological Features [15] (Figs. 7.47, 7.48, and 7.49) • Turbid fluid aspirated and smear show background. • Hooklets of the hydatid cyst. • Acellular laminated membranous fragments. • Sparse inflammatory cells.

dirty

7.11.4 Neoplastic Lesions of the Lung Figure 7.50 shows the recent classification of lung neoplasms by World Health Organization [16] in 2015.

Fig. 7.49  Hydatid cyst: Typical hooklets

7.12 Lung Carcinoma 7.12.1 Incidence • It is the most frequent carcinoma. • The most common cause of death due to cancer. • The carcinoma of lung represents about 13 to 14% of new cancers in the United States.

7.12.2 Etiological Factors

Fig. 7.47  Hydatid cyst: Membranous fragment

• Cigarette smoking: About 80% of the lung carcinoma are attributed by cigarette smoking. • Environmental risk factors: Exposure to radon, asbestos, air pollution. • Genetic risk factor: Higher cancer risk (2.5 times) in first-­ degree relatives of the cancer patients.

7.13 Squamous Cell Carcinoma

191

Tumours of lung

Epithelial tumours

Adenocarcinoma Squamous cell carcinoma -Keratinizing -Non –keratinizing -Basaloid Neuroendocrine tumours - Small cell carcinoma

Metastatic Tumours

Mesenchymal tumors

Pulmonary hamaroma Chondroma

Lymphohistiocytic tumours

PEComa Pleuropulmonary blastoma

MALT lymphoma diffuse large cell lymphoma Langerhans cell histiocytosis

Synovial asrcoma Others

-Large cell neuroendocrine carcinoma -Carcinoid tumours -Typical carcinoid

Tumours of ectopic origin

-Atypical carcinoid Large cell carcinoma Adenosquamous carcinoma Giant cell carcinoma Carcinosarcoma Pulmonary blastoma Salivary gland type tumours

Germ cell tumours Intrapulmonary thymoma Melanoma

Fig. 7.50  World Health Organization classification of lung tumour

Clinical Features • Pain chest. • Cough. • Dyspnoea. • Haemoptysis. Classification of lung tumour: WHO classification of lung tumours is highlighted in Fig. 7.50.

7.13 Squamous Cell Carcinoma [17–20] 7.13.1 Incidence • Squamous cell carcinoma (SQCC) is the second most frequent type of lung carcinoma. • It represents 20% of cases of lung cancer. Aetiology: Tobacco smoking is the primary cause of SQCC.

7.13.2 Key Cytological Features (Figs. 7.51, 7.52, 7.53, 7.54, 7.55, 7.56, 7.57, 7.58, 7.59, and 7.60) Predominant pattern: Large clusters of epithelial tissue, dispersed cells, keratinized epithelial cells and necrosis. • Oval to polygonal cells. • Deep eosinophilic cytoplasm in haematoxylin and eosin stain smear. • Orangeophilic cytoplasm in Papanicolaou’s stain representing intracellular keratin. • Nuclei are enlarged round to oval. • Mild-to-moderate nuclear pleomorphism. • Hyperchromatic nucleus. • Nucleoli not prominent. • Many elongated fibre cells and also tadpole cells with one-sided nucleus and extended tail-like cytoplasm are seen. • Necrotic and inflammatory background.

192

7  Fine Needle Aspiration Cytology of the Lung

Fig. 7.51 Squamous cell carcinoma: Small clusters and discrete malignant cells in the background of inflammation

Fig. 7.54  Squamous cell carcinoma: Cell to cell junction is evident in these tumour cells

Fig. 7.52  Squamous cell carcinoma: The tumour cells are polygonal with centrally placed enlarged, pleomorphic nuclei

Fig. 7.55  Squamous cell carcinoma: A large amount of inflammation and necrosis are often seen in this tumour

Fig. 7.53  Squamous cell carcinoma: The polygonal tumour cells with well-defined cell border. Nucleoli are inconspicuous

Fig. 7.56  Squamous cell carcinoma: Orangeophilic cells indicates intracellular keratinization

7.13 Squamous Cell Carcinoma

193

Fig. 7.57  Non-Keratinizing squamous cell carcinoma: Tumour cells in an inflammatory background

Fig. 7.59  Non-Keratinizing squamous cell carcinoma: The cells with high nucleocytoplasmic ratio and moderate pleomorphism

Fig. 7.58  Non-Keratinizing squamous cell carcinoma: The oval cells with enlarged nuclei having prominent nucleoli

Fig. 7.60  Squamous cell carcinoma: Fibre cell

7.13.3 Types 7.13.3.1 Keratinizing • Orangeophilic cytoplasm. • Usually low Nucleo-cytoplasmic ratio. • Inconspicuous nucleoli. • Many fibre and tadpole cells present. 7.13.3.2 Non-keratinizing • Cytoplasm is basophilic. • High nucleo-cytoplasmic ratio. • Prominent nucleoli. • Relatively less number of fibre and tadpole cells. 7.13.3.3 Immunocytochemistry (Fig. 7.61) Positive: P63, P40and CK 5/6. Negative: TTF 1 and napsin.

7.13.3.4 Molecular Genetics • Amplification. –– Chromosome 3q of TP63. –– Chromosome 7p of EGFR. • Mutation: –– P53 (80%). –– Rb (15%). –– PIK3CA (15%).

7.13.4 Differential Diagnosis (Fig. 7.62) Table 7.4 highlights the differential diagnosis of squamous cell carcinoma. • Squamous metaplasia: –– Usually in a single layer. –– The nucleo-cytoplasmic ratio is low.

194

7  Fine Needle Aspiration Cytology of the Lung

a

p40

c

b

d

e

TTF 1

Napsin

f

Fig. 7.61  Cytology smear (a, b) and cell block (c) of a squamous cell carcinoma case. The tumour cells show a strong nuclear positivity of p40 (d) and negative TTF 1 (e) and napsin (f) stain

Enlarged nuclei, However, nucleocytoplasmic ratio is not altered

a

–– –– –– –– –– ––

Discrete and small groups of cells. Small cells, scanty cytoplasm. Hyperchromatic nuclei. Rows of cells compressed to each other. Nuclear moulding. Crushing artefact.

7.14 Adenocarcinoma [21, 22]

Enlarged nuclei, with high nucleocytoplasmic ratio

b

Incidence: It represents 38% of all lung carcinomas. Aetiology: Tobacco smoking.

7.14.1 Key Cytological Features (Figs. 7.63, 7.64, 7.65, and 7.66)

Fig. 7.62  differential diagnosis of (a) metaplastic cells and (b) malignant squamous cells

Predominant pattern: The clusters of epithelial cells, glands, tight three-dimensional ball, papillae with necrosis or mucinous background.

–– Nuclear pleomorphism is minimum. • Adenocarcinoma. –– Gland pattern. –– 3-D ball-like clusters –– Pseudopapillary clusters. –– Basophilic cytoplasm. –– Vacuoles in the cytoplasm. • Small cell carcinoma.

• Round to columnar. • Cytoplasm: –– Moderate amount. –– Often vacuolated and the large vacuoles may push the cells to periphery giving a signet ring-like appearance. • Nuclei: –– Enlarged with a high nucleocytoplasmic ratio. –– Moderately pleomorphic.

7.14 Adenocarcinoma

195

Table 7.4  Differential diagnosis of squamous cell carcinoma Features Cell arrangement

Squamous metaplasia Monolayer sheets

Small cell carcinoma Discrete

Background

Clean

Nuclei

No significant pleomorphism

Chromatin thread and crushing artefact Mild pleomorphism Often nuclear moulding

Cytoplasm

Moderate, orangeophilic in Papanicoalou’s stain P63 positive. Immunostain does not help to differentiate it from malignant cells

Immunostaining

Scanty Chromogranin, synaptophysin and pan-cytokeratin

Adenocarcinoma Glandular arrangement Mucous material

Squamous cell carcinoma Discrete and clusters

Moderate pleomorphism Fine to vesicular chromatin Abundant vacuolated TTF-1, napsin and CK7 positive

Moderate pleomorphism. Hyperchromatic and pleomorphic

Necrotic or dirty

Moderate, orangeophilic in Papanicoalou’s stain P63, CK5/6 positive

Fig. 7.63  Adenocarcinoma: Individual cells with a moderate amount of vacuolated cytoplasm

Fig. 7.65  Adenocarcinoma: Higher magnification showing cells with central to eccentric nuclei

Fig. 7.64  Adenocarcinoma: Ball-like tight clusters of tumour cells

Fig. 7.66  Adenocarcinoma: Discrete and loos clusters of tumour cells with moderate nuclear pleomorphism and vacuolated cytoplasm

196

7  Fine Needle Aspiration Cytology of the Lung

–– Prominent nucleoli. –– Fine chromatin. • The background may show mucinous secretion. The mucin within the cytoplasm may show cytoplasmic vacuolation. • Psammoma bodies and papillae in papillary adenocarcinoma. • Uncommon variants: Mucinous carcinoma, signet ring adenocarcinoma, clear cell adenocarcinoma and fetal adenocarcinoma.

• EGFR tyrosine kinase resistant cases: Mutation in exon 20 and T790M mutation. • ALK gene fusion: –– It represents 5% of adenocarcinomas. –– EML4-ALK fusion is the most common ALK arrangement. –– More common in non-smokers. • Others: –– ROS 1, RET gene arrangement (1–2%). –– MYC and ERBB2 amplification (5%).

Immunocytochemistry (Fig. 7.67) Positive: TTF 1, napsin, CK 7. Negative: p40 and p63.

7.14.3 Differential Diagnosis

7.14.2 Molecular Cytogenetics (Fig. 7.68) • EGFR mutation. –– Nearly about 40% of adenocarcinomas in the Asian population. –– More common in females and never smokers. –– Mutation: • A point mutation in exon 18. • Major bulk (90%): Deletions in exon 19 and point mutation of codon L858R in exon 21. • Insertion in exon 20.

a

d

Table 7.5 highlights adenocarcinoma.

e

differential

diagnosis

of

• Poorly differentiated squamous cell carcinoma: –– Immunocytochemistry is needed to distinguish poorly differentiated adenocarcinoma and poorly differentiated squamous cell carcinoma (SQCC). • Metastatic adenocarcinoma: –– History of other primary carcinomas. –– TTF 1 is positive in lung adenocarcinoma. • Reactive mesothelial cells: –– Mesothelial cells are present as monolayer sheets whereas adenocarcinoma cells are usually present in three-dimensional clusters.

b

Napsin

the

CK 7

c

TTF 1

f

P40

Fig. 7.67  Cytology smear (a), cell block (b) and panel of immunocytochemistry including TTF 1 (c), napsin (d), CK 7 (e) and p40 (f) in a case of adenocarcinoma of lung

7.15 Carcinoid

197

Fig. 7.68  Schematic diagram of EGFR mutation in lung carcinoma

Mutation

Exon 18

Tyrosine kinase domain of EGFR gene

5%

Exon 19 45%

Exon 20

Point mutation of G719C

In-frame deletion of E 746-A750

T790M

1%

Exon 21 40%

Acquired resistance of tyrosine kinase inhibitor

90%

L858R substitution

Table 7.5  The differential diagnosis of adenocarcinoma Atypical alveolar hyperplasia Clean background

Squamous cell carcinoma (Poorly differentiated) Mesothelial cells Necrotic background Clean background

Usually in monolayer

Discrete and clusters

Low nucleocytoplasmic ratio and no significant nuclear enlargement Regular nuclear margin Nuclear pleomorphism is less

High nucleocytoplasmic ratio and significant nuclear enlargement Irregular nuclear margin Moderate nuclear pleomorphism

• Viral inclusions: –– Intranuclear viral inclusions may simulate as macronucleoli. However, there may be a halo around the inclusion.

7.15 Carcinoid Carcinoid tumours are low-grade neuroendocrine tumours. Types: They are divided into: Typical carcinoid: Less than two mitosis/2 square mm area, no necrosis. Atypical carcinoid: More than two mitosis/2 square mm area [2–10].

Monolayer cells with a window-­ like gap Low nucleocytoplasmic ratio and no significant nuclear enlargement Regular nuclear margin Nuclear pleomorphism is less

Adenocarcinoma Mucous secretion may be present Glandular arrangement High nucleocytoplasmic ratio and significant nuclear enlargement Irregular nuclear margin Moderate nuclear pleomorphism

On cytology smear, it may not be possible to distinguish typical from atypical carcinoid. However, atypical carcinoid may be diagnosed in the presence of necrosis with other morphological features of carcinoid. Incidence: Less than 1% of all lung carcinomas. Almost 80 to 90% of carcinoid tumours are typical carcinoid. Location: Almost two-third of the carcinoid tumours are central in location, and one-third of tumours are peripheral in location. Clinical Features Central carcinoid may present with the features of airway obstruction, and peripheral carcinoid may be often asymptomatic.

198

7  Fine Needle Aspiration Cytology of the Lung

7.15.1 Key Cytological Features (Figs. 7.69, 7.70, and 7.71) Predominant pattern: Small loose clusters and dissociated cells • • • • • • • •

Hypercellular smear. The cells are mainly discrete. Many pseudorosettes and small rows of cells. Individual cells are monomorphic. Cytoplasm is moderate having reddish granularity. Minimally pleomorphic nuclei. Chromatin shows “salt and pepper” appearance. Infrequent mitosis. Atypical carcinoid: Frequent mitosis and necrosis. Fig. 7.71  Carcinoid: the cells show a moderate amount of reddish granular cytoplasm

Fig. 7.69  Carcinoid: Discrete small round cell with minimal nuclear pleomorphism Fig. 7.72 Carcinoid: The tumour cells are strongly positive for chromogranin

Immunocytochemistry (Fig. 7.72) • Positive: Chromogranin, synaptophysin and CD56. –– Often positive for cytokeratin.

7.15.2 Differential Diagnosis

Fig. 7.70  Carcinoid: Small clusters and discrete cell

Small Cell Carcinoma • Scanty cytoplasm. • Small hyperchromatic nuclei. • Nuclear moulding. • Small rows of cells with nuclear moulding. • Nuclear crushing artefact.

7.16 Small Cell Carcinoma

199

7.16 Small Cell Carcinoma Incidence: Small cell carcinoma (SCC) represents 13% of lung cancer. Aetiology: Cigarette smoking. Sex ratio: Male to female ratio is 2:1. Age: Median age is 60 years.

7.16.1 Clinical Features • Same as other lung carcinomas. • Paraneoplastic syndrome: –– Hyponatremia, hypercalcemia, Cushing’s syndrome, Gynaecomastia etc.,

7.16.2 Key Cytological Features [23, 24] (Figs. 7.73, 7.74, 7.75, 7.76, 7.77, 7.78, and 7.79)

Fig. 7.74  Small cell carcinoma: The tumour cells are almost twice the size of small lymphocytes

Predominant pattern: Abundant discrete and occasional loose clusters of epithelial cells • • • • • • • • • •

Usually discrete and small clusters of cells. Often small rows of cells. Frequent crushing artefact present. The cells are oval to teardrop shaped and one and half times bigger than small lymphocytes. Cytoplasm is scanty. Nuclei are oval to “carrot-shaped” shaped. Chromatin gives “salt and pepper” appearance. Inconspicuous nucleoli. Two nuclei compress to each other and produce nuclear moulding. Blue bodies around the nuclei.

Fig. 7.73  Small cell carcinoma: Many discrete small round cells

Fig. 7.75  Small cell carcinoma: Occasional small clusters of cells

Fig. 7.76  Small cell carcinoma: Abundant discrete tumour cells. Nuclear threading is present

200

7  Fine Needle Aspiration Cytology of the Lung

7.16.3 Immunocytochemistry (Fig. 7.80) Positive: • Strongly positive for neuroendocrine markers such as CD 56, chromogranin and synaptophysin. • Also positive for cytokeratin and TTF-1. Molecular Genetics • Inactivation of p 53 and RB1. • Mutation: CREBBP, EP300 and MLL. • Amplification: FGFR1, MYCL and E2F2.

7.16.4 Differential Diagnosis

Fig. 7.77  Small cell carcinoma: These cells have scanty cytoplasm and nuclear moulding

Table 7.6 highlights the differential diagnosis of small cell carcinoma of the lung. Reserve cell hyperplasia: –– Reserve cells are much smaller cells with normal chromatin. Lymphocytes: • Small lymphocytes may mimic small cell carcinoma (SCC). • The cells are smaller than SCC and usually discrete. • Lymphoglandular bodies are present. Poorly differentiated carcinoma: –– At times it may be challenging to differentiate poorly differentiated carcinoma from SCC based on morphology alone. –– Frequent nuclear moulding is present in SCC. Carcinoid tumour:

Fig. 7.78  Small cell carcinoma: Rows of cells with nuclear moulding

• Abundant cytoplasm with reddish granulation. • Salt and pepper chromatin. Lymphomas: –– The presence of lymphoglandular bodies is characteristic of NHL. Non-keratinizing SQC: • This tumour is difficult to differentiate from SCC. • Nuclear moulding is present in SCC. • Nuclear threading and small rows of cells are often seen in SCC.

Fig. 7.79  Small cell carcinoma: The tumour cells are in loose clusters with nuclear crushing artefact

7.17 Large Cell Neuroendocrine Carcinoma

201

b

a

c

Chromogranin

d

CD 56

Fig. 7.80  A case of small cell carcinoma of lung showing cytology smear (a), cell block section (b), chromogranin positivity (c), and CD 56 positivity (d) Table 7.6  Differential diagnosis of small cell carcinoma Small cell carcinoma Cells are discrete and in loose clusters Lymphoglandular bodies are absent Nuclear threading is present Mildly pleomorphic nuclei with nuclear moulding Salt and pepper chromatin Cytoplasmic granules absent Chromogranin, synaptophysin, CD56 positive

Squamous cell carcinoma Discrete and tight clusters

Nuclear threading is absent

Carcinoid Cells are discrete and in loose clusters Lymphoglandular bodies are absent Nuclear threading is absent

Moderate nuclear pleomorphism

Mildly pleomorphic nuclei

Hyperchromatic Cytoplasmic granules absent. Orangeophilia in Papanicolaou’s stain P63, p40 and CK 5/6 positive

Salt and pepper chromatin Reddish cytoplasmic granules present Chromogranin, synaptophysin, CD56 positive

Lymphoglandular bodies are absent

Lymphoma Only discrete cells Lymphoglandular bodies are present Nuclear threading is absent Mildly pleomorphic nuclei Fine chromatin Cytoplasmic granules absent CD45 positive

7.17 Large Cell Neuroendocrine Carcinoma

7.17.1 Clinical Features

Large cell neuroendocrine carcinoma (LCNC) consists of large pleomorphic cells with neuroendocrine morphology. Aetiology: Same as SCC.

• Peripherally located. • Cough, chest pain and hemoptysis. • Paraneoplastic syndrome: Usually absent.

202

7  Fine Needle Aspiration Cytology of the Lung

7.17.2 Key Cytological Features [25] Predominant pattern: Abundant discrete cells with occasional small clusters of tumour cells. • Abundant cellularity. • Discrete, small clusters, sheets and occasional rosette-like structures are present. • Large cells with moderate nuclear pleomorphism. • Prominent nucleoli. • Nuclear moulding may be present.

Immunocytochemistry • Positive: CD 56, chromogranin and synaptophysin. Fig. 7.81  Large cell carcinoma: Loose cluster of tumour cells

7.17.3 Differential Diagnosis Large cell carcinoma: Large pleomorphic cells in LCNC may simulate large cell carcinoma. Immunocytochemistry is helpful in this situation.

7.18 Large Cell Carcinoma Incidence: Large cell carcinoma (LCC) represents 10% of lung carcinomas. Age: Elderly male, mean age 60 years. Aetiology: Same as that of other lung carcinomas. Clinical features: Same as that of other lung carcinomas.

7.18.1 Key Cytological Features (Figs. 7.81, 7.82, 7.83 and 7.84)

Fig. 7.82  Large cell carcinoma: The tumour cells are moderately pleomorphic with large prominent nucleoli

• Syncytial and discrete arrangement of cells. • Individual cells are large with moderate nuclear pleomorphism. • A moderate amount of cytoplasm. • Markedly pleomorphic nuclei. • Multinucleated tumour giant cells. • Many prominent nucleoli. • Necrosis in the background. • Often neutrophils adhere to the tumour cells.

7.18.2 Differential Diagnosis • Adenocarcinoma: Following features are helpful in the diagnosis of adenocarcinoma. –– Gland pattern. –– Mucinous material.

Fig. 7.83  Large cell carcinoma: Higher magnification showing better morphology of the tumour cells

7.20 Carcinosarcoma

Fig. 7.84  Large cell carcinoma: Bizarre looking tumour cells with multiple prominent nucleoli

203

Fig. 7.85  Adenoid cystic carcinoma: The multiple globules and discrete tumour cells

• Sarcomas: –– Immunocytochemistry: Vimentin is helpful for the diagnosis of sarcoma. • Amelanotic melanoma: –– HMB45 positivity in melanoma. • Squamous cell carcinoma (SQCC), poorly differentiated: –– Occasional orangeophilic cells indicate SQCC.

7.19 Other Tumours of Lung 7.19.1 Adenoid Cystic Carcinoma Incidence: Less than 1% of lung carcinoma. Typical locations: It occurs around the central airways. It is an endobronchial tumour. Clinical features: Airway obstruction features: Breathlessness, cough, hemoptysis.

Fig. 7.86  Adenoid cystic carcinoma: The globules are surrounded by the tumour cells

7.19.2 Key Cytological Features [26, 27] (Figs. 7.85, 7.86, and 7.87) • Many magenta coloured globules. • These globules are surrounded by the tumour cells. • The cells are round having scanty cytoplasm with central mildly pleomorphic and hyperchromatic nuclei.

7.20 Carcinosarcoma Carcinosarcoma is a malignant neoplasm of the lung that consists of both components of malignant non-small cell epithelial tumour and sarcoma.

Fig. 7.87  Adenoid cystic carcinoma: The tumour cells have scanty cytoplasm and round monomorphic nuclei

204

7  Fine Needle Aspiration Cytology of the Lung

Incidence: Uncommon tumour, less than 0.1% of all lung cancers. Age: Elderly patient, median age 65 years. Sex: Male are commonly affected. Male: female is 8:1. Clinical features: Same as other lung tumours.

7.20.1 Key Cytological Features (Figs. 7.88, 7.89, 7.90, 7.91, 7.92, and 7.93) Predominant pattern: Both clusters of epithelial and stromal fragments with many spindle cell components • Epithelial component: Predominantly squamous cell carcinoma, occasionally adenocarcinoma. • Sarcoma component: –– Spindle cells: Discrete and small clusters.

Fig. 7.90  Carcinosarcoma: Cellblock section showing many spindle cells

Fig. 7.88  Carcinosarcoma: Abundant discrete and loose clusters of tumour cells

Fig. 7.91  Carcinosarcoma: Cells are strongly positive for vimentin

Fig. 7.89  Carcinosarcoma: Oval to spindle cells with elongated nuclei

Fig. 7.92  Carcinosarcoma: Strong cytoplasmic positivity of desmin

7.21 Pleuropulmonary Blastoma

Fig. 7.93  Carcinosarcoma: Many tumour cells are also positive for pan-cytokeratin

205

Fig. 7.94  Pleuropulmonary blastoma: Abundant discrete tumour cells

–– Malignant cartilaginous element, osteoid element. –– Malignant cells with rhabdomyosarcoma differentiation. Note It is challenging to diagnose carcinosarcoma purely on morphology basis. Immunocytochemistry is needed in such cases.

7.21 Pleuropulmonary Blastoma Pleuropulmonary blastoma is a malignant tumour of children, which consists of solid or cystic sarcomatoid component. Incidence: Very rare, only a few hundred cases have been reported. Age: Less than 2 years of age, Median age is 10 months.

Fig. 7.95  Pleuropulmonary blastoma: Loose clusters of tumour cells

7.21.1 Clinical Features • Breathlessness. • Chest pain. • Hemoptysis.

7.21.2 Key Cytological Features [28] (Figs. 7.94, 7.95, 7.96, and 7.97) • Abundant discrete round cells. • The cells have scanty cytoplasm and round relatively monomorphic nuclei.

Fig. 7.96  Pleuropulmonary blastoma: The individual cells have scanty cytoplasm and mildly pleomorphic nuclei with inconspicuous nucleoli

206

7  Fine Needle Aspiration Cytology of the Lung

7.22.2 Key Cytological Features (Figs. 7.98, 7.99, and 7.100) MALTOMA: • Discrete immature lymphoid cells. • Smear consists of relatively small immature lymphoid cells, plasma cells and cells with the plasmacytoid appearance. • The small lymphoid cells have scanty cytoplasm, regular nuclear outline and condensed chromatin with inconspicuous nucleoli. • Immunological markers: The cells are positive for CD 45, CD 20 and negative for CD 5, CD 23 and CD 10. Fig. 7.97  Pleuropulmonary blastoma: Higher magnification of the cell showing fine chromatin

• Occasional large polygonal cells present. These cells have enlarged moderately pleomorphic nuclei. • Spindle cells with stromal material. Immunocytochemistry • Positive: Vimentin, desmin and smooth muscle actin.

7.21.3 Differential Diagnosis Synovial sarcoma: Positive for CK and EMA. Ewing’s sarcoma: Positive for CD 99. Fig. 7.98  Non-Hodgkin lymphoma: Discrete immature lymphoid cells

7.22 Lymphoma of Lung [29, 30] Incidence: Lymphoma of lung represents only 1% of all lung tumours. Approximately 10% of extranodal NHL occurs in lung. Types of Lymphoma • Mucosa-associated lymphoid tissue (MALTOMA) (70 to 90%). • Diffuse B cell lymphoma (5 to 20%). • Peripheral T cell lymphoma and lymphomatoid granulomatosis: rare.

7.22.1 Clinical Features • Asymptomatic. • Symptomatic: Cough, chest pain and breathlessness.

Fig. 7.99  Non-Hodgkin lymphoma: Higher magnification showing large cells with scanty cytoplasm

7.23 Metastatic Tumours in the Lung

Fig. 7.100  Non-Hodgkin lymphoma: Large cells with scanty cytoplasm having an irregular nuclear outline

207

Fig. 7.101  Metastatic urothelial cell carcinoma: Clusters of malignant cells

Diffuse B cell lymphoma • • • • •

Discrete large lymphoid cells with scanty cytoplasm. Irregular nuclear membrane. Vesicular chromatin. Prominent nucleoli. Immunological markers: The cells are positive for CD 45, CD 20, CD 79a and CD 10 (variable). Negative for CD 5 and CD 23.

7.23 Metastatic Tumours in the Lung The lung is the most common site of metastasis of different carcinomas. The common primary sites are breast, colon and kidney. However, any primary tumours may metastasize in the lung (Figs.  7.101, 7.102, 7.103, 7.104, 7.105, 7.106, 7.107, 7.108, 7.109, and 7.110). The possible primary sites can be detected by: • • • •

Fig. 7.102  Metastatic urothelial cell carcinoma: Elongated columnar looking cells

A good clinical history. Radiological examination. Detailed cytological features. Immunocytochemistry on the cell block section.

Fig. 7.103  Metastatic fibrosarcoma: Discrete oval to elongated tumour cells

208

7  Fine Needle Aspiration Cytology of the Lung

Fig. 7.104 Metastatic fibrosarcoma: At places small fascicular arrangement of the tumour cells

Fig. 7.107  Metastatic osteosarcoma: The cells with moderately pleomorphic nuclei and coarse, irregular chromatin

Fig. 7.105  Metastatic fibrosarcoma: Individual tumour cells have moderately pleomorphic nuclei and blunt ends

Fig. 7.108  Metastatic osteosarcoma: Occasional cells have abundant cytoplasm and eccentric nuclei

Fig. 7.106  Metastatic osteosarcoma: Loose clusters of tumour cells

Fig. 7.109  Metastatic endometrioid carcinoma: Loose clusters of tumour cells

References

Fig. 7.110  Metastatic endometrioid carcinoma: Higher magnification showing nuclear morphology of the individual cells

References 1. Inoue T, Kurimoto N, Furuya N, et  al. New technique for endobronchial ultrasound-guided transbronchial needle aspiration to improve diagnostic yield. J Bronchology Interv Pulmonol. 2013;20(1):28–32. 2. Jackson R, Coffin LH, DeMeules JE, Miller DB, Dietrich P, Fairbank J. Percutaneous needle biopsy of pulmonary lesions. Am J Surg. 1980;139(4):586–90. 3. Naryshkin S, Bedrossian CW.  Selected mimics of malignancy in sputum and bronchoscopic cytology specimens. Diagn Cytopathol. 1995;13(5):443–7. 4. Abraham AE, Suresh PK, Sridevi HB, Sahu KK, Adiga D, Minal J, Rai S, Acharya V. Image-guided fine needle aspiration cytology of Intrathoracic lesions. J Cytol. 2019 Apr-Jun;36(2):106–10. 5. Ghildiyal S, Acharya S, Thakur B, Rawat J, Kumar R. Cytopathology of pulmonary lesions: a tertiary care center experience. J Cytol. 2018 Oct-Dec;35(4):212–6. 6. Chatterjee D, Dey P.  Tuberculosis revisited: cytological perspective. Diagn Cytopathol. 2014 Nov;42(11):993–1001. 7. McHugh KE, Sturgis CD, Procop GW, Rhoads DD.  The cytopathology of Actinomyces, Nocardia, and their mimickers. Diagn Cytopathol. 2017 Dec;45(12):1105–15. 8. Higashi Y, Nakamura S, Ashizawa N, Oshima K, Tanaka A, Miyazaki T, Izumikawa K, Yanagihara K, Yamamoto Y, Miyazaki Y, Mukae H, Kohno S.  Pulmonary Actinomycosis mimicking ­pulmonary Aspergilloma and a brief review of the literature. Intern Med. 2017;56(4):449–53. 9. Sharma S, Singh P, Garg R, Dey P. Pulmonary nocardiosis in fine-­ needle aspiration cytology smears: report of four cases. Diagn Cytopathol. 2016 Apr;44(4):347–50. 10. George B, Rivera Rolon MDM, Clement CG. Role of fine-needle aspiration cytology in early diagnosis of fungal infections. Diagn Cytopathol. 2020 Apr 30. 11. Gochhait D, Dey P, Rajwanshi A, Nijhawan R, Radhika S, Gupta N. Spectrum of fungal and parasitic infections on fine needle aspiration cytology. Diagn Cytopathol. 2015 Jun;43(6):450–5. 12. Das R, Dey P, Chakrabarti A, Ray P. Fine-needle aspiration biopsy in fungal infections. Diagn Cytopathol. 1997 Jan;16(1):31–4.

209 13. Chandra P, Delaney MD, Tuazon CU. Role of special stains in the diagnosis of pneumocystis carinii infection from bronchial washing specimens in patients with the acquired immune deficiency syndrome. Acta Cytol. 1988;32(1):105–8. 14. Jacobs JA, Dieleman MM, Cornelissen EI, Groen EA, Wagenaar SS, Drent M.  Bronchoalveolar lavage fluid cytology in patients with pneumocystis carinii pneumonia. Acta Cytol. 2001;45(3):317–26. 15. Kapatia G, Tom JP, Rohilla M, Gupta P, Gupta N, Srinivasan R, Rajwanshi A, Dey P. The clinical and cytomorphological spectrum of hydatid disease. Diagn Cytopathol. 2020 Feb 13. 16. Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, Chirieac LR, Dacic S, Duhig E, Flieder DB, Geisinger K, Hirsch FR, Ishikawa Y, Kerr KM, Noguchi M, Pelosi G, Powell CA, Tsao MS, Wistuba I.  WHO panel. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015 Sep;10(9):1243–60. 17. Patel TS, Shah MG, Gandhi JS, Patel P. Accuracy of cytology in sub typing non small cell lung carcinomas. Diagn Cytopathol. 2017 Jul;45(7):598–603. 18. da Cunha SG, Lai SW, Saieg MA, Geddie WR, Pintilie M, Tsao MS, Boerner SL, Hwang D.  Cyto-histologic agreement in pathologic subtyping of non small cell lung carcinoma: review of 602 fine needle aspirates with follow-up surgical specimens over a nine year period and analysis of factors underlying failure to subtype. Lung Cancer. 2012 Sep;77(3):501–6. 19. Fassina A, Cappellesso R, Simonato F, Lanza C, Marzari A, Fassan M.  Fine needle aspiration of non-small cell lung cancer: current state and future perspective. Cytopathology. 2012 Aug;23(4):213–9. 20. Dey P, Ghosh RK.  Fine-needle aspiration cytology of non-small cell lung carcinoma: a paradigm shift. Diagn Cytopathol. 2019 Apr;47(4):351–8. 21. Fine-needle aspiration cytology of non-small cell lung carcinoma: A paradigm shift. 22. Shukla S, Malhotra KP, Husain N, Gupta A, Anand N. The utility of cytology in the diagnosis of adenocarcinoma lung: a tertiary care center study. J Cytol. 2015 Jul-Sep;32(3):159–64. 23. Boucher LD, Yoneda K.  Cytologic characterization of bronchial epithelial changes in small cell carcinoma of the lung. Acta Cytol. 1995;39(1):69–72. 24. Zaharopoulos P, Wong JY, Stewart GD.  Cytomorphology of the variants of small-cell carcinoma of the lung. Acta Cytol. 1982 Nov-Dec;26(6):800–8. 25. Jimenez-Heffernan JA, Lopez-Ferrer P, Vicandi B, Mariño A, Tejerina E, Nistal M, Viguer JM. Fine-needle aspiration cytology of large cell neuroendocrine carcinoma of the lung: a cytohistologic correlation study of 11 cases. Cancer. 2008 Jun 25;114(3):180–6. 26. Radhika S, Dey P, Rajwanshi A, Guleria R, Bhusnurmath B. Adenoid cystic carcinoma in a bronchial washing. A case report. Acta Cytol. 1993;37(1):97–9. 27. Kaur G, Mitra S, Dey P.  Fine-needle aspiration cytology of an adenoid cystic carcinoma of trachea: common tumor in uncommon location. Diagn Cytopathol. 2019 Aug;47(8):808–12. 28. Nicol KK, Geisinger KR. The cytomorphology of pleuropulmonary blastoma. Arch Pathol Lab Med. 2000;124(3):416–8. 29. Ko HM, Geddie WR, Boerner SL, Rogalla P, da Cunha Santos G. Cytomorphological and clinicopathological spectrum of pulmonary marginal zone lymphoma: the utility of immunophenotyping. Cytopathology: PCR and FISH studies; 2013. 30. Sprague RI. deBlois GG.  Small lymphocytic pulmonary lym phoma. Diagnosis by transthoracic fine needle aspiration. Chest. 1989;96(4):929–30.

8

Fine Needle Aspiration Cytology of the Mediastinum

The mediastinum contains the vital structures of the body. It is surrounded laterally by lungs, anteriorly by sternum and posteriorly by the vertebral column.

8.1

 ifferent Anatomical Compartments D (Fig. 8.1)

Anterior mediastinum: It is located in between sternum and pericardium. • Common tumours: Thymoma, Germ cell tumour, lymphoma, Paraganglioma and thyroid lesions. Posterior mediastinum: It is situated in between the thoracic vertebra and pericardium. • Common tumours: Neurofibroma, Schwannoma and Paraganglioma. Superior mediastinum: It is bounded by the superior thoracic aperture above and inferiorly through the plane of sternal angle and lower border of thoracic fourth vertebra.

Vertebral column

Anterior mediastinum Thymoma, Germ cell tumour Middle mediastinum Lymphoma, metastasis

Common tumours: Lymphoma and various metastatic tumours.

8.1.1 Techniques to Approach the Mediastinum • Transbronchial fibreoptic endoscopic guided FNAC. • Transesophageal endoscopic guided FNAC. • CT scan and USG guided FNAC.

Posterior mediastinum Neurogenic tumour

Diaphagram

Fig. 8.1  Schematic diagram of the mediastinum

Transbronchial and transesophageal fibreoptic endoscopic guided FNAC: The most popular techniques: • • • •

• Common tumours: Thymoma, thymic carcinoid and lymphoma. Middle mediastinum: It is bounded anteriorly and posteriorly by the anterior and posterior borders of the pericardium, laterally in between the mediastinal pleura of the lungs.

Superior mediastinum Thymoma, lymphoma

Sternum

Usually done in the central lesions around the bronchi. The smaller lesion can be sampled. Real-time imaging possible. No radiation exposure. CT scan guided FNAC:

• • • •

Excellent resolution. Smaller lesions can be sampled. Lesions near the vital organs can be sampled. Radiation exposure. USG guided FNAC

• Real-time monitoring of the needle is possible. • No radiation hazards. Contraindications • No absolute contraindication. • Bleeding disorders: Haemophilia, therapy.

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_8

anticoagulation

211

212

8  Fine Needle Aspiration Cytology of the Mediastinum

8.2.3 Histopathology

Complications • Bleeding. • Pneumothorax. • Haemoptysis.

8.2

Lesions in the Mediastinum

8.2.1 Thymoma Incidence: Relatively uncommon tumour. Incidence rate is 2.2/million/year. Age: Mainly occurs in adults. Rarely seen in children. Location: It is most common in the anterior mediastinum. Sex preponderance: No sex preponderance.

8.2.2 Clinical Features • Pressure symptoms: Superior vena cava syndrome and dyspnea. • Metastasis causing pleural effusion. • Systemic features: Fever and cachexia. • Autoimmune diseases: • Myasthenia gravis is the most commonly seen. • Others: Pure red cell aplasia, pernicious anaemia, Addison’s disease, Graves’ disease etc.

Fig. 8.2  WHO classification of thymoma

Type A

Type AB

Thymoma

Type B1

WHO classification of thymoma [1] is shown in Fig. 8.2. The tumour is well enclosed by a thick capsule that often divides it into multiple lobules. The tumour shows multiple microcysts, rosettes-like structures and glandular components. Type A thymoma: It consists of spindle-shaped cells. The tumour is well enclosed by a thick capsule that often divides it into multiple lobules. The tumour shows multiple micro cysts, rosettes-like structures and glandular components. Type AB thymomas: It shows a variable amount of lymphocytes. These lymphocytes are immature T lymphocytes and positive for TdT. Type B1 thymoma: It strongly resembles normal cortical part of the thymus. The epithelial tumour cells are scattered within the dense lymphocytic component. Type B2 thymoma: It is rich in lymphocytes along with scattered and islands of pale-coloured epithelial cells. The cells are polyhedral with round vesicular nuclei. Type B3 thymoma: It shows multiple tumour lobules that are mainly composed of polygonal epithelial cells with clear cytoplasm.

Spindle shaped epithlial cells

• Spindle shaped epithelial cells • Abundant T lymphocytes • CD20+epithelial cells

MImics cortical areas of thymus

Type B2

• Large amount of lymphocytes • Scattered neoplastic epithelial cells

Type B3

• Abundant round to polygonal epithelial cells • Scattered lymphocytes

Metaplastic

Solid areas of epithelial cells Spindle cells Scanty lymphoid cells

8.2 Lesions in the Mediastinum

213

8.2.4 K  ey Cytology Features [2–5] (Figs. 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, and 8.10) Predominant pattern: Dispersed lymphoid cells with cohesive clusters of epithelial cells. Overall Features of Thymoma • Biphasic pattern: Both epithelial and lymphoid cells. • Epithelial cells: –– Usually in small clusters. –– Oval to polyhedral cells. –– A moderate amount of cytoplasm. –– Vesicular nucleus. –– Fine chromatin and inconspicuous nucleoli. • Background lymphoid cells. • Squamous cells may be present. • Hassal’s corpuscles are rarely noted.

Fig. 8.5  Medullary thymoma/Type A: The individual cells have scanty indistinct cytoplasm and monomorphic spindly nuclei

Fig. 8.3  Medullary thymoma /Type A: Abundant clusters and small bundles of cells

Fig. 8.6  Medullary thymoma/Type A: Higher magnification showing better cell morphology

Fig. 8.4  Medullary thymoma/Type A: The cells are oval to spindle shaped

Fig. 8.7  Type B (cortical thymoma): Epithelial cells in the abundant lymphoid cells

214

8  Fine Needle Aspiration Cytology of the Mediastinum

8.2.5 Type A (Medullary Thymoma/Spindle Cell Thymoma) • Many clusters and small fascicles of spindle cells. • Scattered scanty lymphocytes are admixed with epithelial cells. • Spindle cells: –– Cytoplasm: Scanty. –– Nuclei: Spindle-shaped with blunt ends. –– Chromatin: Fine. –– Nucleoli: Inconspicuous. • Mitosis: Absent. • Scanty lymphocytes in the background. • Hassal’s corpuscles: Absent. Fig. 8.8  Type B (cortical thymoma): Scattered epithelial cells among the lymphocytes

8.2.6 Type B (Cortical Thymoma) • Predominantly reactive lymphoid cells: These cells are positive for TdT, CD1a, CD4, CD8, CD5 and CD99. • Background lymphoglandular bodies and tingible body macrophages are present. • Scattered discrete or small islands of epithelial cells. • Epithelial cells: –– Round to oval. –– Monomorphic. –– Pale cytoplasm. –– Nuclei around with finely stippled chromatin.

Fig. 8.9  Type B (cortical thymoma): The epithelial cells have a moderate amount of pale cytoplasm and centrally placed round nuclei

Immunocytochemistry • Type A thymoma: –– Positive for AE 1, p63 and PAX 8. –– Negative for TdT positive T cells. • Type AB thymoma. –– Positive for CK14, CK19 and p63. –– T lymphocytes are positive for TdT. • Type B1 thymoma: –– Positive for CK19 and p63 and PAX8. –– T lymphocytes are positive for TdT, CD 1a, CD 4 and CD 8. • Type B2 thymoma: –– Same as B1. • Type B3 thymoma: –– Epithelial cells are positive for CK19, CK 5/6, p63 and PAX8. The cells are negative for TTF 1 and CD 20. –– T lymphocytes are positive for TdT.

8.2.7 Differential Diagnosis (Fig. 8.11) Table 8.1 highlights the differential diagnosis of thymoma. Fig. 8.10  Type B (cortical thymoma): Clusters of epithelial cells among the lymphocytes

• Non-Hodgkin’s lymphoma. –– Immature lymphoid cells.

8.2 Lesions in the Mediastinum

215

Discrete immature lymphoid cells

a Non Hodgkin lymphoma

c Thymoma

Tigroid background

Island of monomorphic epithelial cells

b Seminoma

Fig. 8.11  Differential diagnosis of thymoma includes A) non-Hodgkin lymphoma, and B) seminoma Table 8.1  Differential diagnosis of predominant round cell morphology in mediastinal mass Seminoma / dysgerminoma Anterior mediastinum

Metastatic small cell Non-Hodgkin’s lymphoma carcinoma Middle mediastinum Anterior and mediastinum mediastinum Discrete Discrete and loose clusters Scanty Scanty

Thymoma Location

Thymoma Anterior and superior mediastinum

Cell arrangement

Clusters

Discrete

Cytoplasm

Moderate amount

Background

The reactive lymphoid cell may produce lymphoglandular bodies Positive: CK 7, EMA

The moderate amount and prominent nucleoli Trigroid background

Lymphoglandular bodies

Positive: PLAP, OCT4

Positive: LCA (CD45)

Immunocytochemistry

–– Morphology depending on the Type of NHL. –– Monoclonal cells: Light chain restriction in B NHL or aberrant expression of T markers. • Metastatic squamous cell carcinoma. –– Clinical history and lung shadow.

Chromatin threading and crushing artefact Positive Chromogranin, synaptophysin, CD56

–– P40 positive cells. • Germinoma. –– Tigroid background. –– Nuclei: Large vesicular with prominent nucleoli. –– PLAP 1 positive.

216

8.3

8  Fine Needle Aspiration Cytology of the Mediastinum

Malignant Thymoma

• Invasive thymoma. • Thymic carcinomas.

8.3.1 Invasive Thymoma • Cytology: On cytology smear, it is not possible to detect an invasive thymoma. –– A biphasic population of cells: Scattered or aggregated epithelial cells and background lymphoid cells. –– Cells with high nucleocytoplasmic ratio having prominent nucleoli.

8.3.2 Thymic Carcinoma

Fig. 8.12  Carcinoid. Loose clusters and discrete tumour cells

Clinical • Invasive in nature. • Not related with Myasthenia Gravis. • At the time of presentation, the tumours are not resectable. • Relatively rare. Cytological Feature [6] • Epithelial cells: Enlarged and pleomorphic nuclei. • Nuclei are hyperchromatic. • Mitotic activities are seen. • Necrosis present. Immunocytochemistry • Aberrant expression of CD 5. • Positive for CD 70, CD117.

8.3.3 Thymic Neuroendocrine Tumours

Fig. 8.13  Carcinoid. Oval to elongated cells with reddish granular cytoplasm

Location: Anterior mediastinum. Types: • Typical and atypical carcinoid. • Large cell neuroendocrine carcinoma. • Small cell carcinoma.

8.3.4 Typical Thymic Carcinoid Incidence: About 2–4% of all thymic tumours. Cytology (Figs. 8.12, 8.13 and 8.14): • • • • •

Discrete cells. Small round cells. Scanty cytoplasm. Large cells also admixed with the small cells. Round nuclei, minimal pleomorphism.

Fig. 8.14  Carcinoid. Mildly pleomorphic nuclei with salt and pepper chromatin

8.4 Germ Cell Tumors

217

• Typical granular chromatin resembles “salt and pepper chromatin”. • Absent nucleoli. • Spindle cells.

8.3.4.1 Atypical Thymic Carcinoid It is not possible to confirm the diagnosis of atypical thymic carcinoid tumour on FNAC smear. The characteristic histopathological features of this lesion are: • The presence of necrosis. • High mitosis: 2–10 per sq. mm area in the histopathology section. Large cell neuroendocrine carcinoma.

8.3.4.2 Cytology • Necrosis present. • More than ten mitoses per 2 sq. mm area. • Large cells. • Moderately pleomorphic nuclei. • Granular chromatin. • Immunocytochemistry: Strongly positive for CD 56, NSE, chromogranin synaptophysin.

Fig. 8.16  Thymic small cell carcinoma. Tumour cells show scanty cytoplasm having monomorphic nuclei

Small Cell Carcinoma (Figs. 8.15, 8.16, and 8.17) • Discrete small cells. • Scanty cytoplasm. • Granular chromatin. • Inconspicuous nucleoli. • Immunocytochemistry: Positive for CK and also neuroendocrine markers.

Fig. 8.17  Thymic small cell carcinoma. The higher magnification showing granular chromatin

8.4

Germ Cell Tumors [7–9]

8.4.1 Germinomas

Fig. 8.15  Thymic small cell carcinoma. The discrete small round cells

Incidence: About 8% of total extranodal germ cell neoplasms. Peak age: 33 years. Location: Anterior mediastinum.

218

8.4.2 K  ey Cytological Features (Figs. 8.18, 8.19, 8.20, and 8.21)

8  Fine Needle Aspiration Cytology of the Mediastinum

• PLAP is presently not a useful germ cell marker, and OCT4/SALL 4 is preferable. • Focal weak positivity for cytokeratin.

Predominant pattern: Discrete tumour cells • Discrete and occasional clusters of cells. • Many lymphocytes in the background. • Round cells with moderate to abundant vacuolated cytoplasm. • Moderate nuclear pleomorphism. • Single to multiple prominent nucleoli. • Typical tigroid background. • Frequent mitotic figures. • Occasional ill-formed granulomas.

8.4.3 Differential Diagnosis

• PLAP, OCT 4, SALL 4. About 70% cases are positive for CD117.

• Non-Hodgkin’s lymphoma: –– Lymphoglandular bodies. –– relatively less amount cytoplasm. –– The absence of characteristic tigroid background. • Poorly differentiated carcinoma: –– Absent of unique tigroid background. –– Immunocytochemistry is helpful. • Other germ cell tumour such as embryonal carcinoma: –– The clusters of cells. –– Moderate to marked nuclear pleomorphism. –– Macronucleoli.

Fig. 8.18  Seminoma. Discrete tumour cells in a tigroid background

Fig. 8.20  Seminoma. Round mildly pleomorphic cells having scanty cytoplasm and prominent nucleoli

Fig. 8.19  Seminoma. Frequent nuclear threading present

Fig. 8.21  Seminoma. Epithelioid granuloma in seminoma

Immunocytochemistry Positive:

8.6 Lymphomas

8.5

219

Embryonal Carcinoma

Incidence: About 12% of all the mediastinal germ cell tumours. Mean age: 27 years.

8.5.1 K  ey Cytology Features (Figs. 8.22, 8.23, and 8.24) • The tumour cells arranged discretely, small tight clusters and papillae. • The large cells. • Cytoplasm: Moderate amount. • Nuclear pleomorphism: Moderate. • Nucleoli: Multiple, large. • The FNAC smears resemble a poorly differentiated carcinoma.

Fig. 8.24  Embryonal carcinoma. The tumour cells show scanty cytoplasm and large prominent nucleoli

Immunocytochemistry Positive: CD 30, CK, OCT 4, NANOG and SALL 4.

8.6

Lymphomas [10–12]

8.6.1 Non-Hodgkin’s Lymphoma The common types of NHL in mediastinum: • Diffuse sclerosing large B cell lymphoma. • Lymphoblastic lymphoma.

8.6.2 P  rimary Mediastinal Large B Cell Lymphoma (PMLBCL) Fig. 8.22  Embryonal carcinoma. Discrete large tumour cells

Incidence: 2–3% of all NHL. Age: Young age. Location: Anterior-superior mediastinum. Clinical symptoms: Superior vena cava syndrome.

8.6.3 Key Cytological Features (Fig. 8.25) • Singly scattered large lymphoid cells. • Nuclei are enlarged and 2–3 times larger than mature lymphocytes. • Scanty to moderate cytoplasm. • Vesicular chromatin. • Prominent nucleoli. • Background shows many lymphoglandular bodies.

Fig. 8.23  Embryonal carcinoma. Discrete large tumour cells

Immunocytochemistry Positive: CD19, CD20, CD22 and CD 79a positive. The lymphoid cells show weak CD 30 positivity. Negative: CD 10.

220

8  Fine Needle Aspiration Cytology of the Mediastinum

Fig. 8.25  Primary mediastinal large B cell lymphoma: Discrete large lymphoid cells with large nuclei having prominent nucleoli

Fig. 8.26  Lymphoblastic lymphoma: Discrete monomorphic lymphoid cells with fine chromatin and inconspicuous nucleoli

Molecular Genetics • Amplified 9p24.1 chromosomal region. • Amplification and rearrangement of PDL1 and PDL2. • Mutation of BCL6. Differential Diagnosis • Diffuse B cell NHL with mediastinal involvement: Associated with peripheral lymph nodal involvement and bone marrow infiltration.

8.7

T Lymphoblastic Lymphoma

Incidence: It accounts for 25% of all adult lymphoblastic leukaemia. Age: Young adults.

8.7.1 Key Cytological Features (Fig. 8.26) • The cells are two times larger than the mature lymphocyte. • The thin outer rim of cytoplasm. • Convoluted nuclear margin. • Finely dispersed chromatin. • Indistinct nucleoli.

Immunocytochemistry Positive: TdT, CD 34, CD 1a, CD3 and CD5.

8.8

Anaplastic Large Cell Lymphomas

Incidence: 3% of NHL in adult and uncommon in the mediastinum.

Fig. 8.27  Anaplastic large cell lymphoma: Discrete large pleomorphic population of lymphoid cells

8.8.1 K  ey Cytological Features (Figs. 8.27 and 8.28) • Typical “hallmark” cells: –– Large cells. –– Abundant cytoplasm. –– Convoluted nuclei. –– Large mononuclear cells: Moderate cytoplasm, pleomorphic nuclei with prominent nucleoli. Immunocytochemistry • Positive: CD 3, CD 5, CD 30 and anaplastic lymphoma kinase (ALK). Molecular Genetics • T-cell receptor gene rearrangement. • ALK gene fusion to NPM1 gene t(2;5) (p23;q35).

8.10 Neurogenic Tumour

Fig. 8.28  Anaplastic large cell lymphoma: The individual cells are large having irregular nuclear margin

8.9

221

Fig. 8.29  Hodgkin lymphoma: Polymorphic population of lymphoid cells with scattered large atypical cells

Hodgkin Lymphoma

Incidence: 10% of all mediastinal mass and 70% of all mediastinal lymphomas. Age: It occurs in 15 to 35 years age period. Sex: Common in females. Localization: Anterior mediastinum in thymus or lymph node. Common Type: Nodular sclerosing Hodgkin’s lymphoma.

8.9.1 K  ey Cytological Features (Figs. 8.29 and 8.30) • Polymorphic population consisting of lymphocytes, plasma cells and eosinophils. • Classical Reed–Sternberg (R–S) cell: Large binucleated cell with prominent nucleoli. • Mononuclear Hodgkin’s cells. Immunocytochemistry Positive: • R–S cells are positive for CD 15 and CD 30. • Weakly positive for PAX-5. Differential Diagnosis • Primary mediastinal large B cell lymphoma.

8.10 Neurogenic Tumour

Fig. 8.30  Hodgkin lymphoma: Reed–Sternberg cell with binucleated nuclei having prominent nucleoli

8.10.2 Key Cytological Features (Figs. 8.31 and 8.32) • • • •

Dissociated small round cell. Scanty cytoplasm. Round hyperchromatic and monomorphic nuclei. Also, many ganglionic cells with polygonal shape and abundant cytoplasm having vesicular chromatin and prominent nucleoli.

8.10.1 Ganglioneuroblastoma

8.10.3 Neurofibroma and Schwannoma

Incidence: 1 in one lakh population. Age: Less than 5 years. Sex: No sex preponderance. Location: Posterior mediastinum.

8.10.3.1 K  ey Cytological Features (Figs. 8.33 and 8.34) • Fascicles of the oval to spindle-shaped cells. • Cytoplasm: Scanty indistinct.

222

Fig. 8.31  Ganglioneuroma: Abundant ganglionic cells

8  Fine Needle Aspiration Cytology of the Mediastinum

Fig. 8.34  Neurofibroma: Discrete elongated spindle cells

• Nuclei: Long spindle-shaped with thin pointed ends. • Kinking of nuclei.

8.11 M  alignant Peripheral Nerve Sheath Tumours • Fascicles of spindle cells with scant cytoplasm. • Marked nuclear pleomorphism. • Frequent mitosis.

References Fig. 8.32  Ganglioneuroma: The ganglionic cells have abundant cytoplasm with central to eccentric round nuclei

Fig. 8.33  Neuroblastoma: Abundant round cells with scanty cytoplasm and monomorphic round nuclei

1. Travis WDBE, Muller-Hermelink HK, et  al. World Health Organization classification of Tumours. Pathology and genetics of Tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004. 2. Dahlgren S, Sandstedt B, Sundstrom C.  Fine needle aspiration cytology of thymic tumors. Acta Cytol. 1983;27(1):1–6. 3. Wakely PE Jr. Fine needle aspiration in the diagnosis of thymic epithelial neoplasms. Hematol Oncol Clin North Am. 2008;22(3):433–42. 4. Mondal A, Ray BN, Mukherjee PK.  Cytologic diagnosis of thymoma by fine needle aspiration. Indian J Pathol Microbiol. 1989;32(3):237–9. 5. Ryu HS, Koh JS, Park S, Kim MS, Cho SY, Lee SS. Classification of thymoma by fine needle aspiration biopsy according to WHO classification: a cytological algorithm for stepwise analysis in the classification of thymoma. Acta Cytol. 2012;56(5):487–94. 6. Kuo TT, Chan JK. Thymic carcinoma arising in thymoma is associated with alterations in immunohistochemical profile. Am J Surg Pathol. 1998;22(12):1474–81. 7. Dehner LP.  Germ cell tumors of the mediastinum. Semin Diagn Pathol. 1990;7(4):266–84. Epub 1990/11/01 8. Knapp RH, Hurt RD, Payne WS, et al. Malignant germ cell tumors of the mediastinum. J Thorac Cardiovasc Surg. 1985;89(1):82–9. Epub 1985/01/01 9. Weidner N.  Germ-cell tumors of the mediastinum. Semin Diagn Pathol. 1999;16(1):42–50. Epub 1999/06/04

References 10. Hoda RS, Picklesimer L, Green KM, Self S. Fine-needle aspiration of a primary mediastinal large B cell lymphoma: a case report with cytologic, histologic, and flow cytometric considerations. Diagn Cytopathol. 2005;32(6):370–3. Epub 2005/05/10 11. Suster S, Moran CA.  Pleomorphic large cell lymphomas of the mediastinum. Am J Surg Pathol. 1996;20(2):224–32. Epub 1996/02/01

223 12. Nakagawa A, Nakamura S, Koshikawa T, et al. Clinicopathologic study of primary mediastinal non-lymphoblastic non-Hodgkin's lymphomas among the Japanese. Acta Pathol Jpn. 1993;43(1– 2):44–54. Epub 1993/01/01

9

Fine Needle Aspiration Cytology of the Lymph Node

The fine needle aspiration cytology (FNAC) technique in the nodal lymph lesion is presently well accepted. The various infective lesions can be quickly separated from the lymphoma and metastatic tumours. FNAC is very useful in the diagnosis of metastatic tumours in the lymph node. The primary diagnosis and the sub-classifications of lymphoma are possible with the help of FNAC, immunocytochemistry and flow cytometry (FCM) [1].

9.1 • • • • • • •

Indications of FNAC

Identification of reactive lymphoid hyperplasia (RLH). Diagnosis of infective lymphadenopathy. Diagnosis of various metastatic tumours. Primary diagnosis of lymphomas. Sub-classifications of lymphoma. Staging of lymphoma. Detection of the confirmation of low to the high grade of lymphoma at the time of follow up.

9.1.1 Contraindication • No contraindication.

9.1.2 Limitations of FNAC of Lymph Node • Non-diagnostic material. –– Tiny lymph node. –– Fibrosed node. –– Necrotic node. –– Small deep-seated node. • No architectural information. –– Subtypes of Hodgkin lymphoma (HL). –– Grading of follicular lymphoma (FL). –– Some specific lesions such as Castleman’s disease.

• No archival material for further research: Cellblock can be kept only for the tiny amount of tissue, and it is not possible to preserve a large amount of archival material for future research.

9.1.3 Diagnostic Accuracy [2–5] The overall diagnostic accuracy: 90% to 95% in metastatic tumour • A false-positive report is rare. • False-positive report. –– Over interpretation of benign cells inclusion in the lymph node, mesothelial cells, endothelial cells and regenerative muscle fragments. –– The diagnostic accuracy of lymphomas: 90% in diagnosis particularly in high-grade NHL and Hodgkin lymphoma. –– FNAC diagnosis of low-grade NHL may be difficult at times. –– Limited accuracy: T cell-rich B cell lymphoma, grading of FL, peripheral T cell lymphoma and nodular lymphocyte-predominant HL.

9.1.4 D  iagnostic Accuracy of FNAC of Lymph Node Depends on • Location and size: –– FNAC of the small lymph node may yield suboptimal material. –– Deep-seated retroperitoneal lymph node or para hilar lymph nodes are difficult to approach. • Necrotic and sclerotic node: –– Necrotic or sclerotic lymph node yields non-­ representative material. • Focal involvement: –– Focal involvement may not yield representative material.

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_9

225

226

9  Fine Needle Aspiration Cytology of the Lymph Node

• The skill of the cytologist: –– A thorough examination and interpretation are vital to an accurate diagnosis. The skill and experience of the cytologists play an important role here. • Ancillary test: –– Immunocytochemistry (ICC): ICC in the cell block section increases diagnostic accuracy. –– Flow cytometry: Exact sub-classification of NHL is possible if flow cytometry is done on the FNAC sample. –– Molecular genetics: Polymerase chain reaction and fluorescent in situ hybridization may increase the diagnostic rate much higher.

9.2

 ormal Anatomy and Histology N of the Lymph Node

Bean shaped structure with three parts: Cortex, paracortex and medulla (Fig. 9.1). Cortex • This is located in the outer convex region of the lymph node. • Composed of many lymphoid follicles: primary and secondary lymphoid follicles. • Primary lymphoid follicles: Spherical collections of lymphocytes (B). • Secondary lymphoid follicles: –– The pale germinal centre develops within the primary follicle when B cells undergo antigenic stimulation. –– The germinal centre has three zones: (1) dark zone, (2) basal light zone and (3) and an apical light zone.

Fig. 9.1  Schematic diagram of the anatomy of the lymph node

–– Dark zone: The B cells enter the lymph node through afferent vessels and aggregates in the dark zone. Here, the B cells are changed to centroblasts due to antigenic stimulation. –– Basal light zone: The centroblasts differentiates into centrocytes and migrate to the basal light zone. –– Apical light zone: Finally, the centrocytes migrate into the apical light zone and become B memory cells or plasma cells. Mantle zone: It is the outer circumferential ring of germinal centre composed of small lymphocytes. Paracortex: It is located in between the cortex and medulla. The paracortex contains mainly T lymphocytes. This region also contains many high endothelial venules. Medulla • The medulla is composed of large blood vessels, tortuous lymphatic sinuses and medullary cords. • Medullary cords: The closely packed lymphocytes, plasma cells and macrophages around the lymphatic sinuses form the medullary cords. • The lymphocytes travel out from the cortex and then migrates into the medullary sinuses. Subsequently, they leave the lymph node by entering through the efferent lymphatic vessels.

9.2.1 T  he Normal Components of the Lymph Node B lymphocytes • Lymph node contains 20 to 30% B lymphocytes. • Small round cells. • Scanty deep blue cytoplasm. • A round nucleus with condensed nuclear chromatin. • Origin: The pluripotential stem cells of bone marrow. • In the bone marrow: It is converted from the stem cell to Pro-B cell to pre-B cell and finally immature B cell. • Immature B cell to mature B cell differentiates and comes to the circulation. • Mature B lymphocytes aggregate in the lymph node as a primary follicle. • After antigenic stimulation, the B lymphocytes form the germinal centre and differentiates into centroblast to centrocytes to memory B cell or plasma cells. • Each B lymphocyte is predestined to only one type of specific immunoglobulin. • V, D, J gene rearrangement occurs during the development of specific immunoglobulin producing B cells.

9.2 Normal Anatomy and Histology of the Lymph Node

227

T Lymphocytes • Lymph node contains 70 to 80% T lymphocytes. • These are round cells with scanty cytoplasm and indistinguishable from B lymphocytes by morphology alone. –– Origin: T cell is originated from bone marrow stem cells and processed in the thymus. Germline mutation of T cell receptor gene occurs in the thymus. –– Each T lymphocytes contain T cell receptor (TCR). –– TCR has two parts: Constant part is attached with the cell membrane and variable part containing the amino acid terminal region is out of the membrane. This variable part of the receptor binds with the antigen. –– TCR complex: A complex formed by TCR along with CD4, CD8 and CD3 markers. Natural Killer Cells • Natural killer (NK) cells are large cells with granular cytoplasm. • These cells express CD 16 and CD 56. NK cells are negative for CD 4 and 50% of NK cell express CD 8. Immunoblasts • Relatively large cells, three times larger than mature lymphocytes. • Moderate to abundant deep blue cytoplasm. • Round nuclei with large prominent nucleoli that are located on the nuclear membrane. Plasma Cells • Round small cells with scanty cytoplasm. • Eccentric nuclei. • Peripherally clumped chromatin known as cart-wheel chromatin. • Perinuclear Hauff: Circumferential clear halo around the nucleus. Histiocytes • Relatively large cells. • Moderate to abundant cytoplasm. • Kidney shaped convoluted nuclei. • Phagocytosed nuclear fragments in the cytoplasm. • The histiocytes with phagocytosed debris are also known as tangible body macrophages.

9.2.2 Follicular Centre Cells (Fig. 9.2) • Small non-cleaved cell (lymphoblast): –– Small lymphocytes. –– Regular nuclear margin.

Fig. 9.2  Schematic diagram of follicular centre cells

–– Chromatin is fine. –– No nucleoli. • Large non-cleaved cell (centroblast). –– Larger than small lymphocytes. –– Chromatin is fine. –– Many nucleoli. • Large cleaved cell (centrocytes): –– Larger than mature lymphocytes. –– Cleaved nuclei. –– Chromatin is coarse. –– Nucleoli are small. • Small cleaved cell (centrocytes): –– Small lymphocytes. –– Cleaved nuclear margin is cleaved. –– Chromatin is coarse. The CD markers of different cells of the lymph node are highlighted in Fig. 9.3. Lymphoglandular Bodies (Fig. 9.4) • Small bluish fragments of the cytoplasm. • Usually found in association of the lymphoid cells. • LG bodies are not entirely specific for lymphoid cells, and many small round cell tumours may also show scanty LG bodies.

228

9  Fine Needle Aspiration Cytology of the Lymph Node

Fig. 9.3  CD markers in lymphoid cell population

Fig. 9.4  Lymphoglandular body in the reactive lymph node: Deep

Fig. 9.5  Reactive lymphoid hyperplasia: Abundant discrete lymphoid cells

9.3

9.3.1 Reactive Lymphoid Hyperplasia

Key Cytological Features (Fig. 9.5, 9.6, 9.7, and 9.8) Predominant pattern: Abundant discrete polymorphic population of cells

Incidence: Reactive lymphoid hyperplasia (RLH) is the most frequent lesions in the lymph node. Age: Usually seen in children and young adults. Typical locations: Cervical, axilla and inguinal regions. Aetiology: Any type of antigenic stimulation, viral infection, bacterial infection, the drainage area of cancer sites.

• Hypercellular smear. • A Polymorphic population of lymphoid cells. • Lympho-histiocytic tangles: Lymphocytes admixed with many histiocytes. • Abundant tingible body macrophages. • Scattered lymphoglandular bodies.

Benign Lesions of the Lymph Node

9.3 Benign Lesions of the Lymph Node

Fig. 9.6  Reactive lymphoid hyperplasia: Polymorphic population of cells

229

Fig. 9.9  Viral infection: The presence of many immunoblasts may mislead the cytologist

• • • • • • •

Mature lymphocytes. Centrocytes. Centroblasts. Immunoblasts. Plasma cells. Occasional neutrophils, eosinophils and mast cells. Many capillary fragments.

Note: The presence of mitosis has no value as it is commonly seen in the reactive lymphoid cells.

9.3.2 Differential Diagnosis

Fig. 9.7  Reactive lymphoid hyperplasia: Lympho-histiocytic tangle

Fig. 9.8  Reactive lymphoid hyperplasia: Higher magnification of the lympho-histiocytic tangle

• Viral infection (Fig. 9.9): –– Large atypical cells with enlarge nuclei having prominent nucleoli. –– The atypical cells are associated with transformed lymphocytes. –– A thorough clinical history: Fever and multiple tiny lymph nodes, short duration, sore throat etc. • Non-Hodgkin lymphoma (Fig. 9.10): –– Clinical history: Multiple nodes, more than 5 cm, rapidly enlarging node favour Non-Hodgkin lymphoma (NHL). –– The monomorphic population of cells. –– Absence of lymphohistiocytic tangles. –– Ancillary tests: Light chain restriction in B-NHL, and demonstration of aberrant T cell markers expression in FCM. • Hodgkin lymphoma (Fig. 9.11): –– Large rubbery lymph node. –– The polymorphic population of cells containing follicullar centre cells along with many eosinophils. –– Reed–Sternberg cells.

230

9  Fine Needle Aspiration Cytology of the Lymph Node

• Other cases of lymphadenopathy: –– Castleman’s disease: May be diagnosed as reactive hyperplasia. –– HIV-induced lymphadenopathy: Not possible to diagnose on cytology and may be interpreted as RLN.

9.4

Acute Lymphadenitis

Common occurrence: Drainage area of acute infection. Clinical Features • Tender, red and inflamed lymph node. • Fever. Fig. 9.10  Differential diagnosis of chronic lymphocytic lymphoma (a) and reactive lymphoid hyperplasia (b)

Fig. 9.11 (a) Polymorphic population of cells in Hodgkin lymphoma along with discrete Reed–Sternberg cell, (a) Polymorphic population of cells with occasional immunoblasts

Key Cytologic Features • Abundant neutrophils. • Background necrosis.

9.5 Granulomatous Lymphadenitis

9.5

231

Granulomatous Lymphadenitis

Common Occurrence • Infection: Chronic bacterial infection, fungal infection etc. • Foreign body reaction. • Autoimmune diseases: Rheumatoid arthritis, giant cell arteritis etc. • Miscellaneous: Sarcoidosis.

9.5.1 Tuberculosis Infective Organism • Mainly by Mycobacterium tubercle. • M. bovis and Mycobacterium africanum. • Non-tuberculous mycobacteria (NTM) infection.

Fig. 9.12  Tuberculous lymphadenitis: Granuloma with reactive lymphoid cells

Sites of Involvement • Pulmonary. • Extra-pulmonary: Lymph node commonly involved (35%). Clinical Feature of Tuberculous Lymphadenitis • Enlarged lymph node. • Non-tender. • Fever. The spread of infection: Lymphatic spread from the lung.

9.5.2 K  ey Cytological Features [ 6–9] (Figs. 9.12, 9.13, 9.14 and 9.15) • Multiple epithelioid cell granulomas: –– Well circumscribed round-shaped structure. –– Oval to elongated cells with a moderate amount of pale cytoplasm. –– Elongated nuclei with blunt ends. –– Admixed with lymphocytes. • Many multinucleated Langhan’s type of giant cell: –– The large cells with peripherally placed multiple nuclei like a horseshoe-shaped manner. –– Overall 15–30 nuclei. –– Nuclear morphology is often similar to epithelioid cells. • Background necrosis. • Reactive lymphoid cells.

Fig. 9.13  Tuberculous lymphadenitis: Higher magnification of the epithelioid cell granuloma

Four patterns: • Epithelioid cell granulomas and multinucleated giant cells in a necrotic background: It is easy to identify these cases.

Fig. 9.14  Tuberculous lymphadenitis: Multinucleated giant cells in the background of reactive lymphoid cells

232

9  Fine Needle Aspiration Cytology of the Lymph Node

Fig. 9.15  Tuberculous lymphadenitis: Epithelioid cell granulomas in the necrotic material

Fig. 9.16 Epithelioid cell granuloma in the case of Hodgkin’s lymphoma

• Only necrosis: A careful search for acid-fast bacilli is needed in such smears. • Reactive lymphoid cells and occasional epithelioid cell granulomas. • Only reactive lymphoid cells.

–– Connective tissue fragments of spindle: Connective tissue matrix present.

Ancillary Tests • Ziehl Neelsen stain: The sensitivity 33 to 59%, and specificity is 100%. • PCR: Sensitivity and specificity of PCR. • Bacterial culture: The sensitivity is 35 to 49% and specificity is 85 to 100%.

9.5.3 Differential Diagnosis • Hodgkin lymphoma (Fig. 9.16): –– The presence of typical Reed–Sternberg cell. –– The epithelioid cell granulomas are not well-formed. • NHL: –– NHL such as T cell-rich B cell lymphoma may show epithelioid cell granulomas. –– Immature lymphoid cells are present in NHL. • Granulomas in various malignancies: –– Seminoma. –– Keratinizing squamous cell carcinoma. –– T cell-rich B cell lymphoma. –– HL. • Mimickers of epithelioid cells (Fig. 9.17): –– Fibroblasts: The nuclei have more pointed ends. –– Endothelial cells: Often arranged around lumen and linear arrangement.

9.6

Lepromatous Lymphadenitis

Incidence: Granulomatous lymphadenitis is also seen in leprosy. It is an uncommon cause of granuloma.

9.6.1 K  ey Cytological Features [10, 11] (Figs. 9.18, 9.19, and 9.20) • • • • • • • •

Many foamy cells with vacuolated cytoplasm. The cytoplasm gives soap bubble-like appearance. Central nuclei. Fine chromatin and conspicuous nucleoli. Multinucleated giant cells. Epithelioid cell granulomas. Occasional Scattered spindle cells. Careful observation may show intracellular and extracellular negative images. • Modified Z-N stain: Large clusters of lepra bacilli within the cytoplasm.

9.7

Leishminia Lymphadenitis

Occurrence: Predominantly seen in the Indian subcontinent and Mediterranean countries. Causative organism: Leishmania donovani.

9.7 Leishminia Lymphadenitis

233

Fig. 9.17 (a) Epithelioid cell granuloma showing both elongated epithelioid cells and lymphocytes, (b) Endothelial cells mimicking epithelioid cell granuloma

Fig. 9.18  Lepromatous lymphadenitis: Many foamy cells along with lymphocytes

Fig. 9.19  Lepromatous lymphadenitis: The foam cells have abundant cytoplasm and centrally placed nuclei

234

9  Fine Needle Aspiration Cytology of the Lymph Node

• Reactive lymphoid cells, plasma cells and histiocytes. • Histocytes contain the Leishmania Donovan (LD) bodies. –– Membrane-bound small 1 to 3 micron. –– Round to oval-shaped structure. –– kinetoplast: Rod-shaped structure near nucleus, • Extracellular LD bodies may be present. • Occasionally multinucleated giant cells. • Epithelioid cell granulomas may be present.

9.8

Filarial Lymphadenitis

Causative organism: Wuchereria bancrofti. Fig. 9.20  Lepromatous lymphadenitis: Lepra stain showing a bunch of leprae bacilli within the foam cells

Pathogenesis • Circulating microfilaria may infiltrate the lymph node. • Adult filarial larva may also remain within the lymph node. • The parasites evoke granulomatous response in the node.

9.8.1 K  ey Cytological Features [13, 14] (Fig. 9.22) • Smears show reactive lymphoid cells and a large number of eosinophils. • Epithelioid cell granulomas. • Microfilaria or adult worm: Elongated long sheathed structure having pointed tail. No nuclei in the tail region. Fig. 9.21  Leishmania lymphadenitis: Reactive lymphoid cells along with many histiocytes containing Leishmania donovani bodies

Spread to Man • Sandfly inoculates the promastigote form of Leishmania into the skin. • Histiocytes phagocytose these promastigotes. These are transformed into amastigotes. • Asmastigotes come out from the histiocytes by rupturing the cells. • Amastigotes proliferate into the reticuloendothelial cells of skin and spleen.

9.7.1 Key Cytological Features [12] (Fig. 9.21) • The smears show a polymorphic population of lymphoid cells.

Note: A low power screening is needed in such case to identify the microfilaria.

9.9

Toxoplasma Lymphadenitis

Causative organism: Toxoplasma gondii. Infection Transmission • Definitive host: Cat. • Intermediate host: Human, usually occult infection. Clinical Features • Malaise. • Weakness. • Fever and cough. • Cervical lymphadenopathy. • Generalized lymphadenopathy.

9.11 Viral Infections

235

9.11 Viral Infections 9.11.1 Infectious Mononucleosis (IM) Causative organism: Epstein-Barr virus infection. Clinical Features • Common in young adults. • Fever and pharyngitis. • Physical examination: splenomagaly.

Lymphadenopathy

and

Prognosis: The disease is self-limiting.

Fig. 9.22  Microfilaria: Microfilaria of W. bancrofti in the lymph node aspirate. The long slender organisms with round ends and no nuclei at the tail end

9.9.1 Key Cytological Features [15] • • • •

Reactive lymphoid population. Background necrosis. Histiocytes with granular cytoplasm. Numerous small and crescent-shaped organism inside the histiocytes that may look like as karyorrhectic debris.

9.10 Cat Scratch Disease Causative organism: Bartonella henselae. Clinical Feature • Skin rash and fever. • Enlarged inguinal, auxiliary or cervical lymph.

9.11.2 Key Cytological Features [17] (Fig. 9.23) • Polymorphic population of reactive lymphoid cells with many immunoblots. • Atypical lymphoid cells: Large cells containing moderate-­ to-­ abundant basophilic cytoplasm, paranuclear “hof”, large nuclei, fine chromatin and prominent nucleoli. • Many tingible body macrophages.

9.11.3 Differential Diagnosis • HL: Typical Reed–Sternberg cells are present in Hodgkin lymphoma. • Large cell lymphoma: Monoclonal cells in FCM.  IM shows predominant CD8-positive cells. • Reactive lymphoid hyperplasia: Initial stage of IM may simulate reactive hyperplasia.

Prognosis: Self-limiting disorder. Patient heals spontaneously within a few weeks.

9.10.1 Key Cytological Features [16] • • • • • •

Smears shows a large number of polymorphs. Occasional epithelioid cell granulomas. Reactive lymphoid cells, histiocytes. Many tingible body macrophages. Histiocytes with engulfed neutrophils. Bartonella henselae are demonstrated by Steiner and Steiner method.

Differential Diagnosis • Suppurative granulomatous Lymphadenitis. Fig. 9.23  Viral infection: reactive lymphoid cells with many scattered immunoblasts

236

9.12 Kimura’s Disease Aetiology: Unknown. Common occurrence: Young Asians. Clinical features: Lymphadenopathy, salivary gland enlargement.

9.12.1 Key Cytological Features [18] Non-specific findings • • • •

Reactive lymphoid cells. Eosinophils. Reactive lymphoid cells. Occasional multinucleated giant cells.

9  Fine Needle Aspiration Cytology of the Lymph Node

–– The presence of crescent-shaped nuclei of the histiocytes. • Reactive lymphoid hyperplasia.

9.14 HIV Lymphadenopathy [20, 21] The lesions seen: • Persistent generalized lymphadenopathy (Fig. 9.24). • Neoplastic lesions. –– Non-Hodgkin lymphoma. –– Hodgkin lymphoma. –– Kaposi sarcoma. • Infections (Figs.  9.25, 9.26, 9.27, 9.28, 9.29, 9.30, and 9.31): Cryptococcosis, Histoplasma and tuberculosis.

Differential Diagnosis • Parasitic infection: Here parasites are present in the smear. • HL: Classical Reed–Sternberg’s (RS) cells seen.

9.13 Kikuchi’s Disease Distribution: Japan and other Asian countries. Aetiology: Unknown. Clinical Features • Young woman. • Fever. • Painless cervical lymphadenopathy. • Blood examination: Atypical peripheral lymphocytosis. Prognosis: Self-limited disease.

Fig. 9.24  Florid lymphadenopathy

reactive

lymphoid

hyperplasia

in

HIV

9.13.1 Key Cytological Features [19] • Necrotic with abundant karyorrhectic debris. • Histiocytes showing peripherally placed angulated crescent-­shaped nuclei. • Characteristically absent polymorphs and plasma cells. • Immunoblasts and monocytes.

9.13.2 Differential Diagnosis • Necrotizing granulomatous Lymphadenitis: –– The complete absence of polymorphs. Fig. 9.25  Cryptococcal lymph node: Reactive lymphoid cells and many Cryptococci

9.14 HIV Lymphadenopathy

237

Fig. 9.26  Cryptococcal lymph node: Round-shaped cryptococci with the prominent capsule

Fig. 9.29  Mucormycosis in the lymph node: Aseptate broad fungal structures

Fig. 9.27  Cryptococcal lymph node: The organism better highlighted in this microphotograph

Fig. 9.30  Histoplasma: Reactive lymphoid cells with histiocytes containing many round fungal structures

Fig. 9.28  Mucormycosis in the lymph node: Broad right-angled branched mucormycosis

Fig. 9.31  Histoplasma: Abundant 4–5 micron round structures identified in the Ziehl Neelsen stain

238

9  Fine Needle Aspiration Cytology of the Lymph Node

9.14.1 Persistent Generalized Lymphadenopathy (PGL)

9.15.3 Differential Diagnosis of Kaposi’s Sarcoma

• Florid reactive lymphoid cells:

• Granulation tissue: –– Capillary endothelial cells mimic Kaposi’s sarcoma. –– Inflammatory cells present. –– Minimal to absent nuclear atypia. • Spindle cell lesions: Nodular fasciitis, leiomyoma and angiosarcoma.

Early stage –– Polymorphic population of lymphoid cells. –– Follicular centre cells, immunoblasts and monocytoid B cells. –– Monocytoid B cells: Abundant, clear cytoplasm. –– Predominantly CD19-positive B cell: polyclonal in nature. –– Impossible to differentiate from reactive lymphoid hyperplasia without HIV infection. Advanced stage: • Abundant plasma cells. • Occasional tingible body macrophages. • Follicular centre cells. Neoplasms: • • • • • •

Diffuse large B cell lymphoma. Burkitt’s lymphoma. Primary effusion lymphomas. Plasmablastic lymphoma. Extranodal marginal zone lymphoma. Hodgkin lymphoma.

9.15 Kaposi’s Sarcoma [22, 23] 9.15.1 Association • HIV patients. • Immunosuppressive patients. • Classic form: With skin involvement. Infections: Human herpesvirus 8 (100%). Lymph node involvement: Rare.

9.15.2 Key Cytological Features • • • •

Usually low cellularity. Scattered and loosely aggregated cells. Spindle shaped and blunt-ended nuclei. Background of reactive lymphoid cells.

9.16 Rosai–Dorfman Disease Synonym: Sinus histiocytosis with massive lymphadenopathy (SHML). Age distribution: Frequently present in the first two decades of life. Clinical Features • Enlarged lymph nodes. • Fever. • Pain in the joint. • High ESR. • Polyclonal hypergammagloubulinaemia. Extranodal involvement: Salivary glands, ocular adnexa, bone and skin. Prognosis: Spontaneous regression.

9.16.1 Key Cytological Features [24, 25] (Figs. 9.32, 9.33, 9.34, 9.35, and 9.36) Predominant pattern: Polymorphic population of lymphoid cells with emperipolesis • Emperipolesis: Histiocytes engulf many lymphocytes. In addition, plasma cells and even neutrophils are also phagocytosed by histiocytes. • Histiocytes have abundant pale cytoplasm with central nuclei. Immunostaining: • Histiocytes are positive for CD 68 and S-100, CD11c, CD14 and CD33. • Negative for CD 1a.

9.16 Rosai–Dorfman Disease

239

Fig. 9.32  Rosai–Dorfman disease: Reactive lymphoid cells and abundant histiocytes showing emperipolesis

Fig. 9.35  Rosai–Dorfman disease: Scattered histiocytes with moderate cytoplasm and enlarged nuclei

Fig. 9.33  Rosai–Dorfman emperipolesis

Fig. 9.36 Rosai–Dorfman disease: Occasional histiocytes with a comma-shaped nucleus

disease:

Histiocytes

showing

9.16.2 Differential Diagnosis

Fig. 9.34 Rosai–Dorfman disease: Higher magnification of emperipolesis showing histiocytes with phagocytosed lymphocytes

• Reactive lymphoid hyperplasia (Fig. 9.37): –– The presence of characteristics emperipolesis. –– Superimposed lymphocytes on the histiocytes are the mimickers of emperipolesis. These cells remain in a different plane and so the change of focus of the microscope identifies these mimickers. • Malignant histiocytosis: –– Abundant histiocytes with enlarged nuclei. –– The nuclear atypia is relatively less in Rosai–Dorfman disease. • Langerhans cell histiocytosis (Fig. 9.38): –– Frequent nuclear grooves in the histiocytes. –– Many eosinophils. –– Histiocytes are positive for both S-100 and CD1a.

240

9  Fine Needle Aspiration Cytology of the Lymph Node

Fig. 9.37 Differential diagnosis of Rosai–Dorfman disease and reactive lymphoid hyperplasia

• Haemophagocytosis syndrome: –– Frequent phagocytosis of red blood cells and platelets instead of lymphocytes and plasma cells.

9.17 Dermatopathic Lymphadenitis Aetiology: Chronic irritation of the lymph node from the drainage area of the inflammatory skin lesion or mycosis fungoides. This commonly occurs in the drainage lymph node of chronic inflammatory skin lesions such as psoriatic erythroderma, exfoliative dermatitis and also mycosis fungoides. Common sites: Axillary and inguinal lymph nodes.

9.17.1 Clinical Features • Enlarged firm lymph node. • Associated skin lesions. Prognosis: Usually benign condition, however, the prognosis is bad in case of association with mycosis fungoides.

9.17.2 Key Cytological Features (Figs. 9.39 and 9.40) Predominant pattern: Polymorphic population of lymphoid cells with pigment containing histiocyte. • Reactive lymphoid cell population. • Many scattered histiocytes containing melanin pigments. • The nuclei of the histiocytes often show grooving and intranuclear pseudoinclusions. Immunocytochemistry: The histiocytes are positive for S 100 and CD 1a.

9.17.3 Differential Diagnosis • Metastatic melanoma: –– The nuclei of metastatic melanoma are enlarged and pleomorphic with large prominent nucleoli. • Langerhans cell histiocytosis: –– Background excess eosinophils. –– Frequent nuclear groves. –– Absence of melanin-containing histiocytes.

9.17 Dermatopathic Lymphadenitis

241

Fig. 9.38  Differential diagnosis of Rosai–Dorfman disease and Langerhans cell histiocytosis

Fig. 9.39  Dermatopathic lymphadenitis: Reactive lymphoid cells with melanin-containing histiocytes

Fig. 9.40  Dermatopathic lymphadenitis: Higher magnification showing cells with abundant melanin

242

9  Fine Needle Aspiration Cytology of the Lymph Node

9.18 Castleman’s Disease Aetiology: Unknown. Clinical presentation: • Localized: Enlarged lymph node. Commonly mediastinal lymphadenopathy. • Systemic: Fever and generalized lymphadenopathy, often pleural effusion. Types: • Hyaline vascular type: Many small atretic follicles with central hyalinized vessels. These follicles are surrounded by multiple concentric layers of small lymphocytes. • Plasma cell type. Abundant interfollicular plasma cells.

Fig. 9.42  Castleman’s disease: Many plasma cells present

9.18.1 Key Cytological Features [26] (Figs. 9.41, 9.42, and 9.43) Predominant pattern: Polymorphic population of lymphoid cells • • • •

No characteristic cytological features. Reactive lymphoid cells with lymphohistiocytic tangles. Many follicular dendritic cells. Convoluted nuclei of the histiocytes with coarse nuclear chromatin. • At times large atypical cells may mimic Reed–Sternberg cell. • Eosinophilic granular debris. • Hyalinized capillaries.

Fig. 9.43  Castleman’s disease: Large atypical histiocytes

9.18.2 Differential Diagnosis • Reactive lymphoid hyperplasia: Not possible to differentiate from Castleman’s disease on cytology.

9.18.3 Metastatic Malignant Tumour [27–32] The common primary sites of the lymph node:

Fig. 9.41  Castleman’s disease: Reactive lymphoid cells

• The lymph node serving the drainage area of the body part. • Supraclavicular lymph node: Lung, oesophagus and stomach. • Cervical lymph node: Oropharynx, Larynx, salivary gland and thyroid. • Inguinal lymph node: Lower limbs and external genitalia.

9.18 Castleman’s Disease

243

• Para-aortic: Cervix and lung. • Axillary lymph node: Lung and breast. Diagnostic accuracy: 96%. The diagnostic approach for the source of the metastatic tumour in lymph node 1. Clinical history: • Chief complaints: It may help to the localization of the primary such as: –– Lung: Cough and chest pain indicates. –– Oesophagus: Dysphagia indicates. –– Larynx: Hoarseness of voice. • Past history: Histopathology report of any previous biopsy or surgical resection. • Histopathology of the tumour, if any. 2. Complete physical examination: Simple physical ­examination of the patient may help to find out the primary source of the tumour. • Intra-abdominal examination: Any palpable mass. • Head neck region: Oropharynx, salivary glands and thyroid. • intra-oral examination: Buccal cavity and tongue. • External genitalia. 3. Serum tumour markers: Prostate-specific antigen, human chorionic gonadotrophic hormone, alpha-fetoprotein etc. 4. Blood and urine examination. 5. Radiological imaging: Ultrasonogram, chest X-ray etc. 6. Cytological examination: • Polymorphic population of cells. • Usually multiple clusters of foreign cells and occasionally discrete cells.

9.18.4 Squamous Cell Carcinoma (Figs. 9.44, 9.45, 9.46, 9.47, and 9.48)

Fig. 9.44  Metastatic squamous cell carcinoma: Multiple clusters of malignant cells

Fig. 9.45  Metastatic squamous cell carcinoma: Scattered oval to polyhedral cells with hyperchromatic nuclei

• • • •

Often shows cystic changes and turbid fluid is aspirated. Re-aspirate the cyst fluid. Polyhedral cells with the squamoid appearance. Organophilic cytoplasm in Papanicolaou’s stain indicates intracellular keratin. • Tadpole and fibre cells. • Enlarged, pleomorphic nuclei. • Hyperchromasia. Immunostaining (Fig. 9.49,a and b): Positive: p63, EMA and CK 5/6.

Fig. 9.46  Metastatic squamous cell carcinoma: Higher magnification showing large polyhedral cells with moderately enlarged nuclei

244

9  Fine Needle Aspiration Cytology of the Lymph Node

a

Fig. 9.47  Metastatic squamous cell carcinoma: Occasional organophilic cells in Papanicolao’s stain confirm intracellular keratin

b

Fig. 9.49 (a)Metastatic squamous cell carcinoma: The tumour cells showing nuclear positivity of p63. (b) Metastatic squamous cell carcinoma: The tumour cells showing membranous positivity of CK 5/6 Fig. 9.48  Metastatic squamous cell carcinoma: Oval to spindle cells are often seen

9.18.5 Adenocarcinoma (Figs. 9.50, 9.51, and 9.52) • • • • •

Glandular arrangement. Cells with moderate amount cytoplasm. The cytoplasm is often of vacuolated. Central to eccentric nuclei with prominent nucleoli. Mucus material in the background.

9.18.6 Small Cell Carcinoma (Figs. 9.53, 9.54, and 9.55) • • • •

Predominantly dissociated cells. Occasional cohesive groups of cells. Small cell with scanty cytoplasm. Hyperchromatic nuclei.

Fig. 9.50  Metastatic adenocarcinoma: Gland-like structure

• Chromatin threading. • Convoluted nuclei.

9.18 Castleman’s Disease

245

Fig. 9.51  Metastatic adenocarcinoma: Clusters of malignant cells with eccentric nuclei

Fig. 9.54  Metastatic small cell carcinoma: Discrete cells with hyperchromatic nuclei

Fig. 9.52  Metastatic adenocarcinoma: Clusters and discrete tumour cells with eccentric nuclei giving signet ring appearance

Fig. 9.55  Metastatic small cell carcinoma: Smear showing nuclear moulding and chromatin threading

9.18.7 Germ Cell Tumour (Figs. 9.56 and 9.57) • Characteristic vacuolated and tigroid-like background smear. • Dissociated round cells having enlarged moderately pleomorphic nuclei. Nuclear pleomorphism is marked in endodermal sinus tumour. • Large single-to-multiple prominent nucleoli. • Opened up chromatin.

Fig. 9.53  Metastatic small cell carcinoma: Discrete and loose clusters of cells with small round cells having scanty cytoplasm

Sarcoma (Fig. 9.58) • Only 2 to 5% soft-tissue sarcomas metastasize in lymph node. • Cytomorphology depends on the type of sarcoma. The correct subtyping of sarcoma is difficult from the cytology smear alone. The prior knowledge of the primary tumour is needed for the exact diagnosis of such cases.

246

9  Fine Needle Aspiration Cytology of the Lymph Node

• The cells are usually moderate to markedly pleomorphic. • Large bizarre nuclei with multiple large prominent nucleoli. • Occasionally clusters of spindle cells in the connective tissue stroma. Melanoma (Figs. 9.59 and 9.60) • Usually, primary sites are known, and the diagnosis is easy. • Markedly pleomorphic cells. • Macronucleoli. • Cytoplasmic melanin pigment.

Fig. 9.56  Metastatic germ cell tumour: Dissociated round cells in a foamy vacuolated background

Neuroendocrine Tumours (Figs. 9.61, 9.62, and 9.63) • Discrete oval cells. • The characteristic rosette. • Scanty cytoplasm. • Salt and pepper chromatin.

Fig. 9.57  Metastatic germ cell tumour: Higher magnification showing cells with moderate pleomorphism and prominent nucleoli. Note the tigroid background

Fig. 9.59  Metastatic melanoma: Clusters of round moderately pleomorphic cells

Fig. 9.58  Metastatic sarcoma in the lymph node: Multiple large clusters of spindle cells

Fig. 9.60  Metastatic melanoma: The cells showing melanin pigment in the cytoplasm

9.19 Lymphoma

247

9.18.8 Immunocytochemistry

Fig. 9.61  Metastatic neuroendocrine tumour: Discrete oval to spindle cells

Immunocytochemistry (ICC) is a beneficial technique to detect the type and the primary site of malignancy. ICC can be done stepwise (Fig. 9.64): Step 1: To detect a broad type of malignancy: carcinoma, lymphoma, melanoma, sarcoma and germ cell tumour (Table 9.1). Step 2: The exact typing of carcinoma and primary site. Stepwise approach. Step 1: The primary type of malignancy: Only a few selected antibodies may help here: CK, LCA, vimentin, chromogranin, Melan A and PLAP. Step 2: To detect the exact typing and the primary site, the selective panel of antibody is used (Table 9.2). There is no specific marker/s of adenocarcinoma. CK 7 and CK 20 combination can broadly differentiate many carcinomas and should be used to guess the possible primary site/s [33–36] (Fig. 9.65).

9.19 Lymphoma Cytology is becoming popular in diagnosing sub-classifying lymphoma after the introduction of the World Health Organization Classification (WHO) [37]. WHO kept the homogenous entities in the same group based on three factors: • Cytomorphology. • Immunophenotyping. • Molecular genetics. Fig. 9.62  Metastatic neuroendocrine tumour: The cells show elongated nuclei

Fortunately, all this information are possible to get from the FNAC material of the lymph node. Therefore, after the initial smear preparation end examination, one should re-­ aspirate for cell block/flow cytometry and molecular genetics. The overall technical approach of the lymphoma on FNAC has been highlighted in Fig. 9.66. WHO group classification of lymphoma is predominantly based on the type of cells from which the lymphoma develops: • Mature and immature B cells. • Mature and immature T and NK cells. The brief WHO classification [38] is shown in Fig. 9.67. FL: Follicular lymphoma, DLBCL: Diffuse large B cell lymphoma. The current 2016 WHO classification of lymphoma included many changes, and these are briefly mentioned in Table 9.3.

Fig. 9.63  Metastatic neuroendocrine tumour: Higher magnification showing mildly pleomorphic nuclei with stippled chromatin

248

9  Fine Needle Aspiration Cytology of the Lymph Node

Fig. 9.64  Stepwise approach to detect the primary site of malignancy in a metastatic tumour in the lymph node

Table 9.1  The basic panel of antibody to detect the broad type of tumour Type of tumour Carcinoma Lymphoma Sarcoma Melanoma Neuroendocrine carcinoma Germ cell tumour

Antibody positivity Cytokeratin, EMA CD 45(LCA) Vimentin Melan A/ HMB-45 Chromogranin/synaptophysin PLAP

Table 9.2  Antibody to detect the specific type of tumour Types of tumour Squamous cell carcinoma Adenocarcinoma Renal cell carcinoma Hepatocellular carcinoma Neuroendocrine carcinoma Prostatic carcinoma Thyroid carcinoma Adrenocortical carcinoma Lung adenocarcinoma

Antibody positivity CK 5/6, p63 CK 7/ CK 20 CD 10, PAX 8 Heper 1, pCEA Chromogranin/synaptophysin PSA TTF1, thyroglobulin Melan A, inhibin TTF 1

9.20 B Cell Non-Hodgkin Lymphoma (NHL) 9.20.1 Small Lymphocytic Lymphoma [39, 40] Synonym: Chronic lymphocytic leukaemia, B cell type.

Epidemiology • It represents 7% of all NHL. • Elderly patients, the median age is 70 years. • Male: female ratio is 2: 1. The cell of origin: Mature B cell. Prognosis: Indolent and incurable. However, less aggressive lesions.

9.20.2 Clinical Features • Mostly asymptomatic and detected during the routine haematological investigation. • Occasionally weakness, lymphadenopathy and hepatosplenomegaly. • At times detected during the investigation of haemolytic anaemia and thrombocytopenia.

9.20.3 Key Cytological Features (Figs. 9.68, 9.69, 9.70, 9.71, 9.72, and 9.73) Predominant pattern: Hypercellular smear with monomorphic discrete cells • The monomorphic population of small lymphoid cells. • Cells are small with scanty cytoplasm.

9.20 B Cell Non-Hodgkin Lymphoma (NHL) Fig. 9.65  The possible primary sites on the basis of CK 7 and CK 20 positivity. Figure showing the algorithmic approach to detect the type and metastatic sites

Fig. 9.66  Technical approach in lymphoma (PBS: Phosphate buffer solution, FISH: Fluorescent in situ hybridization, NGS: Next-generation sequencing)

249

250

9  Fine Needle Aspiration Cytology of the Lymph Node

Fig. 9.67  Brief overview of the WHO classification of Non-Hodgkin lymphoma (NHL) Table 9.3  Overview of the changes in 2016 WHO classification of lymphoma Entity B-cell leukaemia/lymphoma Monoclonal B cell lymphocytosis (MBL) Chronic lymphocytic leukaemia (CLL)

Hairy cell leukaemia Lymphoplasmacytic lymphoma In situ follicular neoplasia Paediatric-type FL Duodenal FL Large B cell lymphoma with IRF-4 rearrangement Predominantly diffuse FL with 1p36 deletion Mantle cell lymphoma

In situ mantle cell neoplasia Diffuse large B cell lymphoma (DLBCL) EBV positive DLBCL, not otherwise specified (NOS) EBV+ mucocutaneous ulcer Burkitt lymphoma (BL) with 11q aberration High-grade B cell lymphoma, NOS High-grade B cell lymphoma with MYC, BCl2 and BCl6 rearrangement T cell leukaemia/lymphoma

Remarks Separated low count MBL (0.5 X 109/L) • No option to diagnose CLL with 95% cases).

9.30 T Cell Lymphoma 9.30.1 T Lymphoblastic Lymphoma Synonym • Precursor T lymphoblastic leukaemia or lymphoma. • T acute lymphoblastic leukaemia.

9.30.2 Epidemiology • Common in adolescents. • Males are commonly affected. Cell of Origin • Clonal proliferation of premature T cell. • 95% of lymphoblastic lymphoma are T cell type.

9.30.3 Clinical Features Fig. 9.104  Acute lymphoblastic lymphoma: Discrete immature lymphoid cells

• Mediastinal mass is the frequent presentation. • Lymphadenopathy. • High leucocyte count.

9.30.4 Key Cytological Features: Same as B Lymphoblastic Lymphoma 9.30.4.1 Immunophenotype Positive: TdT, CD1a, CD2, CD3,CD5, CD7, CD4 and CD8. Blast cells may co-express CD4 and CD8. Negative: CD19 and CD20. 9.30.4.2 Chromosomal Abnormality • Translocation of t(10;14)(q24;q11.2) causing TLX1 (HOX11) gene overexpression. • Translocation of t(1;14)(p32;q11.2) causing overexpression of TAL1. Fig. 9.105 Acute lymphoblastic lymphoma: Higher magnification showing cells with scanty cytoplasm and condensed nuclear chromatin

Prognosis: Higher risk than B-LBL.

266

9  Fine Needle Aspiration Cytology of the Lymph Node

9.31 Anaplastic Large Cell Lymphoma Synonym: Ki 1 lymphoma.

9.31.1 Epidemiology • 3% of adult NHL • 30% of childhood lymphoma. Cell of origin: T cell origin.

9.31.2 Clinical Features • Lymphadenopathy. • Systemic symptoms. • Extranodal involvement is common at the time of presentation. • Bone, skin and soft tissue are involved as extranodal site.

Fig. 9.107  Anaplastic large cell lymphoma: Small lymphoid cells admixed with many scattered large atypical cells

9.31.3 Key Cytological Features [50, 51] (Figs. 9.106, 9.107, 9.108, and 9.109) • • • •

Discrete large pleomorphic lymphoid cells. Atypical large cells with bizarre irregular nuclei. Many cells with multilobated nuclei. “Hallmark” cells: Large cell with horseshoe-shaped convoluted nucleus containing multiple nulceoli. • Doughnut cells: Multinucleated cells with garland-like multiple nuclei. Fig. 9.108  Anaplastic large cell lymphoma: Higher magnification of the large pleomorphic cells

Fig. 9.106  Anaplastic large cell lymphoma: Discrete lymphoid cells showing many large pleomorphic cells Fig. 9.109  Anaplastic large cell lymphoma: Bizarre cell with multilobed nuclei

9.34 Mycosis Fungoides and Sezary Syndrome

267

9.31.4 Immunophenotype

9.33.2 Clinical Features

• • • • •

• Lymphadenopathy. • Hepatosplenomegaly. • Systemic symptoms.

CD3, CD30, occasional cells are positive for CD45. ALK positive in majority of the cases. EMA positive. CD3 is mostly negative (75% cases). CD2,CD5 and CD4 are positive.

Chromosomal abnormality: Translocation of t (2:5) (p23;q35) resulting in the fusion of ALK and NPM genes. Prognosis: ALK positive tumours show better prognosis than ALK negative tumours.

9.32 P  eripheral T Cell Lymphoma, Unspecified 9.32.1 Epidemiology • Rare T-NHL. • Adults are mainly affected.

9.32.2 Key Cytological Feature • • • • •

Medium-to-large lymphoid cells. Enlarged nuclei. Moderately pleomorphic. Irregular nuclear contour with convolution. Coarse clumped chromatin.

Immunophenotyping Prognosis: Aggressive course, Five-year survival 20%. Positive: CD 3, CD7, CD4/CD8.

9.33.3 Key Cytological Features [52, 53] • • • •

Polymorphic population of cells. Lymphocytes, many immunoblasts and plasma cells. Large atypical cells simulating Reed–Sternberg cells. Large cells with clear cytoplasm having centrally placed atypical nuclei. • Large amount of capillaries. Immunophenotype Positive: CD3, CD2, CD5. CD4 are often positive and CD8 is variably expressed. Chromosomal Abnormality • Triosomy of chromosomes 3, 5, and 21. • Gain of X chromosome. • Loss of 6q.

9.34 M  ycosis Fungoides and Sezary Syndrome 9.34.1 Epidemiology • Mycosis Fungoides represents 0.5% of all NHL. • It represents 50% of all primary cutaneous NHL. • Male:Female ratio is 2:1. Cell of origin: T cell origin.

9.33 Angioimmunoblastic T Cell Lymphoma Abbreviation: AITL Synonym: Peripheral T cell lymphoma, Angioimmunoblastic lymphadenopathy

9.33.1 Epidemiology • 1–2% of all NHL • Elderly patients. • Males are commonly affected. Cell of origin: T cell origin.

9.34.2 Clinical Features • Plaque-like patches in the skin. • Advanced stage: Lymph nodal involvement.

9.34.3 Key Cytological Features [54] (Figs. 9.110 and 9.111) • Polymorphic population of cells. • Reactive lymphoid cells. • Many intermediate-sized cells with deep blue cytoplasm having enlarged irregular convoluted nuclei giving “cerebriform appearance”. • Melanin pigment within the histiocytes.

268

9  Fine Needle Aspiration Cytology of the Lymph Node

• Mixed cellularity Hodgkin lymphoma. • Lymphocyte-depleted Hodgkin lymphoma.

9.36 N  odular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) 9.36.1 Epidemiology • CHL represents 90% of all HL. • NLPHL represents 10% of HL. • Bimodal distribution of HL: First peak incidence in15 to 30 years and second peak in elderly patient.

Fig. 9.110  Mycosis fungoides: Cytology smear showing many atypical cells

Localization • Lymph nodal involvement. • Extranodal involvement is rare.

9.36.2 Clinical Features • Lymphadenopathy. • Systemic symptoms like malaise, fever.

9.36.3 Classical Hodgkin’s Lymphoma (CHL)

Fig. 9.111  Mycosis fungoides: The cells are intermediate in size with scanty cytoplasm. Nuclei are pleomorphic with fine chromatin

9.36.3.1 K  ey Cytological Features (Figs. 9.112, 9.113, 9.114, 9.115, 9.116, 9.117, 9.118, 9.119, 9.120, and 9.121) • Polymorphic population of cells: mature lymphocytes, eosinophils, plasma cells and immunoblasts. • Many eosinophils.

Immunophenotype Positive: CD2, CD3, CD4 and CD5. Negative: CD8 and CD7.

9.35 Hodgkin’s Lymphoma [55–58] 9.35.1 Classification WHO classification of Hodgkin’s lymphoma (HL). Classical Hodgkin Lymphoma • Nodular sclerosis Hodgkin lymphoma. • Lymphocyte-rich Hodgkin lymphoma.

Fig. 9.112  Hodgkin lymphoma: Abundant discrete polymorphic population of cells with classical Reed–Sternberg cell

9.36 Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)

269

Fig. 9.113  Hodgkin lymphoma: Smear showing occasional Hodgkin cells

Fig. 9.116  Hodgkin lymphoma: Polymorphic population of cells with occasional atypical looking Hodgkin cell

Fig. 9.114  Hodgkin lymphoma: Classical Reed–Sternberg cell showing binucleation with prominent nucleoli

Fig. 9.117  Hodgkin lymphoma: Higher magnification of the same

Fig. 9.115  Hodgkin lymphoma: Hodgkin cells along with many eosinophils and lymphocytes

Fig. 9.118  Hodgkin lymphoma: Ill formed epithelioid cell granuloma

270

9  Fine Needle Aspiration Cytology of the Lymph Node

• Many scattered Reed–Sternberg (R–S) cells. –– Large cell. –– Abundant cytoplasm. –– Bi-nucleated. –– Coarse chromatin. –– Large prominent nucleoli. • Hodgkin cell: Large cell with single enlarged nuclei with irregular margin, coarsely clumped chromatin having prominent nucleoli. • Ill formed epithelioid cell granulomas. • Nodular sclerosis variant: It shows scanty cellularity, many capillaries, fibroblasts and collagenous substances, lacunar-type R–S cells.

Fig. 9.119  Hodgkin lymphoma with lymphocytic depletion: Abundant atypical cells and occasional mature lymphoid cells

Fig. 9.120  Hodgkin lymphoma with lymphocytic depletion: Higher magnification of the same showing cells with scanty cytoplasm and large nuclei with fine chromatin and prominent nucleoli

Fig. 9.121  Hodgkin lymphoma: Cell block section showing polymorphic cell population along with many eosinophils and occasional Reed Sternberg cell

9.36.3.2 I mmunophenotype of R–S Cell (Figs. 9.122 and 9.123) Positive: CD15, CD30 and PAX5. Negative: CD20 and CD45.

Fig. 9.122  Hodgkin lymphoma: CD15 positive cells

Fig. 9.123  Hodgkin lymphoma: CD30 positive cells

9.38 Langerhans Cell Histiocytosis

9.36.3.3 N  odular Lymphocyte Predominant Hodgkin Lymphoma • Polymorphic population of cells. • Many small lymphoid cells. • Less amount of eosinophils and neutrophils. • L&H cells. –– Large cell. –– Scanty cytoplasm. –– Multilobated nuclei. –– Often there is folding of the nuclei giving a “popcorn” appearance. –– Vesicular chromatin. –– Many small nucleoli. Immunophenotype of L&H Cell (Fig. 9.124) Positive: CD 20, CD 45, CD79a, PAX5 and occasionally EMA. Negative: CD15 and mostly negative (90%) for CD 30.

9.37 Histiocytic and Dendritic Neoplasms 9.37.1 Follicular Dendritic Cell Sarcoma Synonym: Follicular dendritic cell tumour.

9.37.1.1 Epidemiology • Very rare tumour. • Median age: 50 years. • Male and female equally affected. Cell of origin: Follicular dendritic cells.

271

9.37.1.2 Clinical Features • Gradually enlarging lymph node. • Usually no systemic symptoms.

9.37.2 Key Cytological Features [59, 60] • Discrete, small clusters and fascicles like distribution of the cells. • Cells are in oval to spindle shape. • Nuclear contour is regular. • Fine chromatin with prominent nucleoli. • Many bi- and multinucleated cells. • Reed–Sternberg-like cells.

9.37.3 Immunophenotype Positive: Always positive: CD21, CD23, CD35 and D2–40. Variably positive: EMA, CD68 and S-100. Negative: HMB45, CK, CD3 and CD34.

9.38 Langerhans Cell Histiocytosis Abbreviation: LCH  Synonym: Eosinophilic granuloma, Histiocytosis X and Langerhans cell granulomatosis

9.38.1 Epidemiology • Predominantly occurs in children. • Median age: 5.9 years.

Fig. 9.124  Immunocytochemistry pattern of classical Hodgkin lymphoma and nodular Lymphocyte Predominant Hodgkin Lymphoma

272

9  Fine Needle Aspiration Cytology of the Lymph Node

• Men are more affected. • 4.1 per million/year. Cell of origin: Langerhans cell histiocytes. Localization • Usually involves lymph node, bone, skin and lung.

9.38.2 Clinical Features • • • •

Lytic lesion of the bone. Lymph nodal enlargement. Skin or lung may be involved. It may present as solitary involvement or multifocal involvement of bone, lymph node, lung, skin with hepatomegaly.

Fig. 9.126  Langerhans cell histiocytosis: Smear showing a large number of eosinophils and large histiocytes with multilobated nuclei

9.38.3 Key Cytological Features [61, 62] (Figs. 9.125, 9.126, 9.127, and 9.128) Predominant pattern: Discrete mixed population of cells consisting of lymphocytes, polymorphs, many eosinophils and many large atypical histiocytes. • The atypical histiocytes are. –– Mono or multinucleated. –– Multilobated. –– Deep longitudinal nuclear grove. –– The nuclear chromatin is fine. –– Large prominent nucleoli. • Abundant eosinophils in the background. Fig. 9.127  Langerhans cell histiocytosis: Many cells showing deep nuclear convolution

Fig. 9.125  Langerhans cell histiocytosis: Low power magnification showing polymorphs, lymphocytes, eosinophils and many atypical histiocytes

Fig. 9.128  Langerhans cell histiocytosis: Higher magnification showing bi- and multinucleated cells with open chromatin

9.40 Chronic Myeloid Leukaemic Infiltration

273

Immunophenotype Positive: CD1a (CD207), Langerin, S100. The cells are also positive for CD68 and vimentin. Negative: Pan T and pan B cell markers. Electron microscopy: Positive for Tennis racket-shaped Birbeck granules.

9.39 Leukaemic Infiltration [63, 64] 9.39.1 Acute Lymphoblastic Leukaemia 9.39.1.1 K  ey Cytological Features (Figs. 9.129 and 9.130) • A large number of discrete lymphoid blasts. • The background may have reactive lymphoid cells. • The blasts: –– Round cells. –– Scanty deep blue cytoplasm. –– Fine chromatin with prominent nucleoli.

Fig. 9.130  Acute lymphatic leukaemia infiltration: Higher magnification showing cells with scanty cytoplasm having fine chromatin

9.39.2 Acute Myeloid Leukaemia 9.39.2.1 Key Cytological Features • Many myeloblasts, myelocytes and promyelocytes. • Myeloblasts. –– 3–4 times of lymphocytes –– Round nuclei. –– Fine chromatin. –– Multiple prominent nucleoli. –– Auer rods present. • Depending on the type of AML, the number of promyelocytes, myeloblasts and monocytoid cells may vary widely. • Reactive lymphoid cells may be present. • Nucleated RBCs present.

Fig. 9.131  Chronic myeloid leukaemic infiltration: Abundant myelo and metamyelocytes, along with megakaryocytes

Immunophenotype • Myeloblasts: Positive for myeloperoxidase, CD13, CD33 and CD117.

9.40 C  hronic Myeloid Leukaemic Infiltration 9.40.1 Key Cytological Features (Figs. 9.131, 9.132, and 9.133) • The discrete population of myelocytes, metamyelocyte, promyelocyte, blasts and basophils. • Many megakaryocytes. • Nucleated RBCs. Fig. 9.129  Acute lymphatic leukaemia infiltration: Discrete immature lymphoblasts

274

Fig. 9.132  Chronic myeloid leukaemic infiltration: Higher magnification showing better morphology of the cells

Fig. 9.133  Chronic myeloid leukaemic infiltration: Occasional megakaryocytes are present (arrow)

References 1. Dey P. Role of ancillary techniques in diagnosing and subclassifying non-Hodgkin’s lymphomas on fine needle aspiration cytology. Cytopathology. 2006;17(5):275–87. 2. Hehn ST, Grogan TM, Miller TP.  Utility of fine-needle aspiration as a diagnostic technique in lymphoma. J Clin Oncol. 2004;22(15):3046–52. 3. Schafernak KT, Kluskens LF, Ariga R, Reddy VB, Gattuso P. Fine-­ needle aspiration of superficial and deeply seated lymph nodes on patients with and without a history of malignancy: review of 439 cases. Diagn Cytopathol. 2003;29(6):315–9. 4. Gupta RK, Naran S, Lallu S, Fauck R. The diagnostic value of fine needle aspiration cytology (FNAC) in the assessment of palpable supraclavicular lymph nodes: a study of 218 cases. Cytopathology. 2003;14(4):201–7. 5. Nasuti JF, Yu G, Boudousquie A, Gupta P.  Diagnostic value of lymph node fine needle aspiration cytology: an institutional experi-

9  Fine Needle Aspiration Cytology of the Lymph Node ence of 387 cases observed over a 5-year period. Cytopathology. 2000;11(1):18–31. 6. Bezabih M, Mariam DW, Selassie SG.  Fine needle aspiration cytology of suspected tuberculous lymphadenitis. Cytopathology. 2002;13(5):284–90. 7. Nidhi P, Sapna T, Shalini M, Kumud G.  FNAC in tuberculous lymphadenitis: experience from a tertiary level referral Centre. Indian J Tuberc. 2011;58(3):102–7. 8. Mudduwa LK, Nagahawatte AS. Diagnosis of tuberculous lymphadenitis: combining cytomorphology, microbiology and molecular techniques  - a study from Sri Lanka. Indian J Pathol Microbiol. 2008;51(2):195–7. 9. Singh UR, Bhatia A, Gadre DV, Talwar V. Cytologic diagnosis of tuberculous lymphadenitis in children by fine needle aspiration. Indian J Pediatr. 1992;59(1):115–8. 10. Bhake AS, Desikan KV, Jajoo UN.  Cytodiagnosis of histoid leprosy. Lepr Rev. 2001;72(1):78–82. 11. Mehdi G, Maheshwari V, Gaur S, Sharma R.  Histoid lep rosy: diagnosis by fine needle aspiration cytology. Acta Cytol. 2003;47(3):529–31. 12. Dey P, Radhika S, Rajwanshi A, Ray R.  Fine-needle aspira tion cytology of leishmania lymphadenitis. Diagn Cytopathol. 1992;8(5):551–2. 13. Dey P, Radhika S, Jain A. Microfilariae of Wuchereria bancrofti in a lymph node aspirate. A case report. Acta Cytol. 1993;37(5):745–6. 14. Joshi AM, Pangarkar MA, Ballal MM.  Adult female Wuchereria bancrofti nematode in a fine needle aspirate of the lymph node. Acta Cytol. 1995;39(1):138. 15. Ahmad M, Iqbal J, Mansoor A, Khan AH.  Toxoplasmic lymphadenitis--a clinicopathological study. J Pak Med Assoc. 1991;41(12):303–5. 16. Stastny JF, Wakely PE Jr, Frable WJ.  Cytologic features of necrotizing granulomatous inflammation consistent with cat-scratch disease. Diagn Cytopathol. 1996;15(2):108–15. 17. Stanley MW, Steeper TA, Horwitz CA, Burton LG, Strickler JG, Borken S.  Fine-needle aspiration of lymph nodes in patients with acute infectious mononucleosis. Diagn Cytopathol. 1990;6(5):323–9. 18. Jayaram G, Peh KB. Fine-needle aspiration cytology in Kimura’s disease. Diagn Cytopathol. 1995;13(4):295–9. 19. Viguer JM, Jimenez-Heffernan JA, Perez P, Lopez-Ferrer P, Gonzalez-Peramato P, Vicandi B. Fine-needle aspiration cytology of Kikuchi’s lymphadenitis: a report of ten cases. Diagn Cytopathol. 2001;25(4):220–4. 20. Vanisri HR, Nandini NM, Sunila R. Fine-needle aspiration cytology findings in human immunodeficiency virus lymphadenopathy. Indian J Pathol Microbiol. 2008;51(4):481–4. 21. Nayak S, Mani R, Kavatkar AN, Puranik SC, Holla VV.  Fine-­ needle aspiration cytology in lymphadenopathy of HIV-positive patients. Diagn Cytopathol. 2003;29(3):146–8. 22. Gamborino E, Carrilho C, Ferro J, et  al. Fine-needle aspiration diagnosis of Kaposi’s sarcoma in a developing country. Diagn Cytopathol. 2000;23(5):322–5. 23. Al-Rikabi AC, Haidar Z, Arif M, Al-Ajlan AZ, Ramia S.  Fineneedle aspiration cytology of primary Kaposi’s sarcoma of lymph nodes in an immunocompetent man. Diagn Cytopathol. 1998;19(6):451–4. 24. Mallick S, Ghosh R, Iyer VK, Jain D, Mathur SR. Cytomorphological and morphometric analysis of 22 cases of Rosai-Dorfman disease: a large series from a tertiary care Centre. Acta Cytol. 2013;57(6):625–32. 25. Kumar B, Karki S, Paudyal P. Diagnosis of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) by fine needle aspiration cytology. Diagn Cytopathol. 2008;36(10):691–5. 26. Mallik MK, Kapila K, Das DK, Haji BE, Anim JT. Cytomorphology of hyaline-vascular Castleman’s disease: a diagnostic challenge. Cytopathology. 2007;18(3):168–74.

References 27. Mohanty SK, Dey P, Ghoshal S, Saikia UN.  Cytologic features of metastatic nasopharyngeal carcinoma. Diagn Cytopathol. 2002;27(6):340–2. 28. Grenko RT, Shabb NS. Metastatic nasopharyngeal carcinoma: cytologic features of 18 cases. Diagn Cytopathol. 1991;7(6):562–6. 29. Dey P, Amir T, Jogai S, Al JA.  Fine-needle aspiration cytol ogy of metastatic transitional cell carcinoma. Diagn Cytopathol. 2005;32(4):226–8. 30. Khirwadkar N, Dey P, Das A, Gupta SK.  Fine-needle aspiration biopsy of metastatic soft-tissue sarcomas to lymph nodes. Diagn Cytopathol. 2001;24(4):229–32. 31. Loya AC, Prayaga AK, Arora A, et  al. Lymph node metasta sis of soft tissue tumors: a cytomorphologic study. Acta Cytol. 2007;51(2):153–60. 32. Cantley RL, Cimbaluk D, Reddy V, Iacusso C, Gattuso P.  Fine-­ needle aspiration diagnosis of a metastatic adult sclerosing rhabdomyosarcoma in a lymph node. Diagn Cytopathol. 2010;38(10):761–4. 33. Hall PA. Keratin expression in human tissues and neoplasms: other issues. Histopathology. 2003;43(2):196–7. 34. Heatley MK. Keratin expression in human tissues and neoplasms. Histopathology. 2002;41(4):365–6. 35. Chu PG, Weiss LM. Keratin expression in human tissues and neoplasms. Histopathology. 2002;40(5):403–39. 36. Moll R, Divo M, Langbein L.  The human keratins: biology and pathology. Histochem Cell Biol. 2008;129(6):705–33. 3 7. National Cancer Institute sponsored study of classifications of non-Hodgkin’s lymphomas: summary and description of a working formulation for clinical usage. The non-Hodgkin’s lymphoma pathologic classification project. Cancer. 1982;49(10):2112–35. 38. Cazzola M. Introduction to a review series: the 2016 revision of the WHO classification of tumors of hematopoietic and lymphoid tissues. Blood. 2016 May 19;127(20):2361–4. 39. Dey P, Amir T, Al Jassar A, et  al. Combined applications of fine needle aspiration cytology and flow cytometric immunophenotyping for diagnosis and classification of non Hodgkin lymphoma. Cytojournal. 2006;3:24. 40. Shin HJ, Caraway NP, Katz RL.  Cytomorphologic spectrum of small lymphocytic lymphoma in patients with an accelerated clinical course. Cancer. 2003;99(5):293–300. 41. Rassidakis GZ, Tani E, Svedmyr E, Porwit A, Skoog L. Diagnosis and subclassification of follicle center and mantle cell lymphomas on fine-needle aspirates: a cytologic and immunocytochemical approach based on the revised European-American lymphoma (REAL) classification. Cancer. 1999;87(4):216–23. 42. Swerdlow SH, Williams ME. From centrocytic to mantle cell lymphoma: a clinicopathologic and molecular review of 3 decades. Hum Pathol. 2002;33(1):7–20. 43. Oviatt DL, Cousar JB, Collins RD, Flexner JM, Stein RS. Malignant lymphomas of follicular center cell origin in humans. V. Incidence, clinical features, and prognostic implications of transformation of small cleaved cell nodular lymphoma. Cancer. 1984;53(5):1109–14. 44. Lenz G, Wright GW, Emre NC, et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A. 2008;105(36):13520–5. 45. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11. 46. Stastny JF, Almeida MM, Wakely PE Jr, Kornstein MJ, Frable WJ.  Fine-needle aspiration biopsy and imprint cytology of small

275 non-cleaved cell (Burkitt’s) lymphoma. Diagn Cytopathol. 1995;12(3):201–7. 47. Grogan TM, Warnke RA, Kaplan HS.  A comparative study of Burkitt’s and non-Burkitt’s "undifferentiated" malignant lymphoma: immunologic, cytochemical, ultrastructural, cytologic, histopathologic, clinical and cell culture features. Cancer. 1982;49(9):1817–28. 48. Das DK, Gupta SK, Pathak IC, Sharma SC, Datta BN.  Burkitt-­ type lymphoma. Diagnosis by fine needle aspiration cytology. Acta Cytol. 1987;31(1):1–7. 49. Iyer VK.  Pediatric lymphoma diagnosis: role of FNAC, biopsy, immunohistochemistry and molecular diagnostics. Indian J Pediatr. 2013 Sep;80(9):756–63. 50. Ng WK, Ip P, Choy C, Collins RJ.  Cytologic and immunocytochemical findings of anaplastic large cell lymphoma: analysis of ten fine-needle aspiration specimens over a 9-year period. Cancer. 2003;99(1):33–43. 51. Rapkiewicz A, Wen H, Sen F, Das K. Cytomorphologic examination of anaplastic large cell lymphoma by fine-needle aspiration cytology. Cancer. 2007;111(6):499–507. 52. Dey P, Radhika S, Das A.  Fine-needle aspiration biopsy of angio-immunoblastic lymphadenopathy. Diagn Cytopathol. 1996;15(5):412–4. Epub 1996/12/01 53. Ng WK, Ip P, Choy C, Collins RJ. Cytologic findings of angioimmunoblastic T-cell lymphoma: analysis of 16 fine-needle aspirates over 9-year period. Cancer. 2002;96(3):166–73. 54. Pai RK, Mullins FM, Kim YH, Kong CS. Cytologic evaluation of lymphadenopathy associated with mycosis fungoides and Sezary syndrome: role of immunophenotypic and molecular ancillary studies. Cancer. 2008;114(5):323–32. 55. Zhang JR, Raza AS, Greaves TS, Cobb CJ. Fine-needle aspiration diagnosis of Hodgkin lymphoma using current WHO classification-re-evaluation of cases from 1999-2004 with new proposals. Diagn Cytopathol. 2006;34(6):397–402. 56. Jogai S, Al-Jassar A, Dey P, Adesina AO, Amanguno HG, Francis IM.  Fine needle aspiration cytology of Hodgkin’s lymphoma: a cytohistologic correlation study from a cancer center in Kuwait. Acta Cytol. 2006;50(6):656–62. 57. Jogai S, Dey P, Al Jassar A, Amanguno HG, Adesina AO.  Role of fine needle aspiration cytology in nodular sclerosis variant of Hodgkin’s lymphoma. Acta Cytol. 2006;50(5):507–12. 58. Das DK, Francis IM, Sharma PN, et  al. Hodgkin's lymphoma: diagnostic difficulties in fine-needle aspiration cytology. Diagn Cytopathol. 2009;37(8):564–73. 59. Mohanty SK, Dey P, Vashishta RK, Rajwanshi A. Cytologic diagnosis of follicular dendritic cell tumor: a diagnostic dilemma. Diagn Cytopathol. 2003;29(6):368–9. 60. Fan YS, Ng WK, Chan A, et al. Fine needle aspiration cytology in follicular dendritic cell sarcoma: a report of two cases. Acta Cytol. 2007;51(4):642–7. 61. SenGupta SK, Vince JD, Chakravorty P, Sinha SK. Langerhan cell granulomatosis with unusual FNAC findings. Diagn Cytopathol. 1998;18(5):349–51. 62. Ramadas PT, Kattoor J, Mathews A, Abraham EK.  Fine needle aspiration cytology of Langerhans cell thyroid histiocytosis and its draining lymph nodes. Acta Cytol. 2008;52(3):396–8. 63. Dey P, Varma S, Varma N. Fine needle aspiration biopsy of extramedullary leukemia. Acta Cytol. 1996;40(2):252–6. 64. Mourad WA, Sneige N, Huh YO, et al. Fine needle aspiration cytology of extramedullary chronic myelogenous leukemia. Acta Cytol. 1995;39(4):706–12.

Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

10.1 Intestine The various luminal lesions of the gastrointestinal tract are directly sampled by endoscopic biopsy. Therefore, many clinicians prefer to have endoscopic biopsy rather than FNAC. However, FNAC techniques have many added advantages such as the lesion can be sampled from multiple areas, the stenotic area can be approached, rapid techniques and better preserve morphology. The following FNAC sampling techniques are available: • Endoscopic aspiration. • Endoscopic ultrasound-guided aspiration.

10.1.1 Endoscopic FNAC Superficial and also deep seated mucosal lesions are aspirated by endoscopic FNAC.

10.1.1.1 Technique • The lesion is directly visualized by a fibreoptic endoscope. • The needle is introduced through the endoscopic tract to the lesion. • To and fro movement. • Adequate suction is given. • Suction is stopped, and the needle is withdrawn. • Multiple smears (both air-dried and wet smear) are made. Major advantages: • In submucosal lesions. • GIT stenotic areas.

10

10.1.2 Endoscopic Ultrasound-Guided (EUS) FNAC [1] Indications • Submucosal lesion. • Lesions outside the lumen of GIT. • Small lesions. Technique: Same as that of endoscopic guided FNAC except that here USG helps to identify the lesion. Major advantages: • More accurate. • Better visualization.

10.2 Oesophagus 10.2.1 Normal Histology and Cytology Histology. The oesophagus has four layers: • Mucosa. –– Lining: Mainly non-keratinizing stratified squamous epithelium except the terminal 2  cm of the oesophagus, which is lined by simple columnar epithelium. –– Lamina propria: Loose connective tissue and multiple oesophagal cardiac glands. –– Lamina muscularis: Smooth muscle. • Submucosal: Made up of dense collagenous tissue, vessels and glands. • Muscle layer: Outer longitudinal and an inner circular layer. • Adventitia: Loose connective tissue.

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_10

277

278

10.2.2 Cytology • Squamous epithelial cells. –– Polygonal cells. –– Abundant orangeophilic cytoplasm. –– Centrally placed round nuclei. –– Bland chromatin. –– Inconspicuous nucleoli. • Stromal fragment.

10.3 Infection Majority of the infections of the oesophagus is diagnosed by oesophagal brush cytology. FNAC has little role in this area. The cytology is helpful in the diagnosis of Candida, herpes simplex, cytomegalovirus etc. Barrett’s oesophagus [2]: In Barrett’s oesophagus (BE), the lining of the lower oesophagus is replaced by intestinal columnar cells containing goblet cells. This condition is diagnosed by brushing cytology.

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

• Chest pain. • Loss of weight. • Hoarseness of voice.

10.5.3 Key Cytological Features (Figs. 10.1 and 10.2) Predominant pattern: Discrete and cohesive groups of tumour cells • • • • •

Predominantly oval to polygonal in shape. Dense orangeophilic cytoplasm. Central hyperchromatic nuclei. Moderately pleomorphic nuclei. Coarse with irregularly clustered chromatin.

• Cytological feature. –– Tight sheets of epithelial cells. –– The regular margin of the sheets. –– Columnar epithelial cells. –– Goblet cells: Large cytoplasmic vacuoles.

10.4 Dysplasia in Barrett’s Oesophagus • The irregular margin of the cell clusters. • Nuclear overcrowding Nuclear overlapping and loss of polarity. • Columnar cells. –– Enlarged pleomorphic nuclei. –– Focal thickening of the nuclear membrane. –– Nucleoli are prominent.

Fig. 10.1  Squamous cell carcinoma of the oesophagus: Polyhedral cells with well-defined cell margin. Centrally placed enlarged pleomorphic nuclei

10.5 Squamous Cell Carcinoma 10.5.1 Epidemiology • Squamous cell carcinoma (SQCC) of the oesophagus represents 85% of oesophagal malignancies. • The sixth leading cause of death. • SQCC is common in sixth decade. • Male are four times more affected than females.

10.5.2 Clinical Features • Pain during swallowing. • Dysphagia.

Fig. 10.2  Squamous cell carcinoma of the oesophagus: Discrete and loose cluster of tumour cells with a moderate amount cytoplasm and hyperchromatic nuclei

10.7 Stomach

279

• Fibre and tadpole cells. • Necrotic background.

10.6 Adenocarcinoma 10.6.1 Epidemiology • The incidence rate of oesophageal adenocarcinoma (EAD) 0.7 per 100,000 person-years in the globe. • More common in Europe and North America. • Males are four times more affected than females. • EAD occurs mainly in the elderly patient. • The mean age is the seventh decade of life. Localization • EAD arises from the lower part of the oesophagus and oesophagogastric junction.

Fig. 10.4 Adenocarcinoma of oesophagus: Higher magnification showing large clusters of pleomorphic cells

10.6.2 Clinical Features • • • •

Dysphagia. Pain. Weight loss. Reflux.

10.6.3 Key Cytological Features (Figs. 10.3, 10.4, and 10.5) • • • •

Multiple clusters of tumour cells. Frequent glandular arrangement. Sheets of cells with overlapping of nuclei. Groups of cells show outer feathering of cells.

Fig. 10.5  Adenocarcinoma of oesophagus: Haematoxylin and eosin stain smear showing cells with overlapping nuclei and hyperchromasia

• • • •

Tumour cells show cytoplasmic vacuolation. Large and pleomorphic nucleus. Prominent nucleoli. Necrosis and tumour diathesis in the background.

10.7 Stomach 10.7.1 Anatomy and Histology

Fig. 10.3  Adenocarcinoma of oesophagus: Loose clusters of tumour cells with moderate nuclear pleomorphism

10.7.1.1 Anatomy • The stomach lies in the epigastric region. • It connects the oesophagus proximally and distally the duodenum. • The stomach is situated under the diaphragm. • The pancreas lies posterior to the stomach.

280

Parts: Cardiac, fundus, body and pyloric region. Cardiac: Narrow part near the gastroesophageal junction. Funds: This is the curved shaped part which is projected upwards. Body: It is the bulging central part of the stomach. Pylorus: It is the narrow passage that ends from the body to the duodenum.

10.7.2 Histology Mucosal lining cells: Simple columnar lining epithelial cells. Gastric glands:

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

Cytology • Multiple clusters of epithelial cells. • Nuclei show mild pleomorphism.

10.8 Gastric Adenocarcinoma 10.8.1 Epidemiology • Adenocarcinoma of the stomach is one of the most frequent cancers in the GIT. • The second commonest cause of malignancy-related death. • The tumour is the highest in Central Asia and eastern Europe.

• It has three parts: Isthmus, neck and base. • Gland lining: Simple columnar epithelial cells, mucus-­ secreting cells, oxyntic (parietal) cells, chief cells and 10.8.2 Clinical Features enteroendocrine cells. • Parietal or oxyntic: Secretes hydrochloric acid. • In the early stage, the tumour is asymptomatic. • Chief cells (zymogenic): Secretes pepsinogen, renin and • In the advanced stage, the tumour presents as: gastric lipase enzymes. –– Dysphagia. • Mucus-secreting cells: Secretes mucous that protects the –– Vomiting. gastric mucosa. –– Loss of weight. –– Anaemia.

10.7.3 Cytology • Mucus-secreting cells: –– Cohesive groups of cells and flat sheets. –– Monolayer. –– Tall columnar cells. –– Abundant vacuolated cytoplasm. –– Centrally place monomorphic nuclei. –– Fine nuclear chromatin and inconspicuous nucleoli. • Chief cells: –– Cuboidal cells. –– Abundant coarse basophilic cytoplasmic granules. –– Monomorphic small round nuclei. • Parietal cells: –– Round cells. –– Vacuolated cytoplasm. –– Eosinophilic granules in the cytoplasm. –– Monomorphic small round nuclei.

10.7.4 Benign Tumours Gastric Polyp • Usually hyperplastic polyp. • No risk for carcinoma. • Brush cytology is more suitable than FNAC.

Association: • • • • •

Helicobacter pylori infection. Smoking. Intake of a large amount of smoked fish. Pickled vegetables. Low socioeconomic setting.

10.8.3 Key Cytological Features Types of gastric adenocarcinoma: • Intestinal. • Diffuse (gastric) type.

10.8.4 Intestinal Type (Figs. 10.6, 10.7, 10.8, 10.9, 10.10, 10.11, 10.12, and 10.13) • The cells are present both dissociated and also in loose clusters. • Considerable nuclear overlapping. • Tumour cells. –– Columnar in shape. –– Cytoplasm scanty to moderate.

10.8  Gastric Adenocarcinoma

281

Fig. 10.6 Adenocarcinoma of the stomach: Multiple clusters of tumour cells with nuclear crowding

Fig. 10.9  Adenocarcinoma of the stomach: Haematoxylin and eosin-­ stained smear showing nuclear pleomorphism and hyperchromasia

Fig. 10.7  Adenocarcinoma of the stomach: The tumour cells are oval with a moderate amount of cytoplasm and nuclear pleomorphism

Fig. 10.10  Adenocarcinoma of the stomach: Tumour cells showing membranous positivity of CK7

Fig. 10.8  Adenocarcinoma of the stomach: Haematoxylin and eosin-­ stained smear showing small clusters of tumour cells

Fig. 10.11  Adenocarcinoma of the stomach: Tumour cells are negative for CK20

282

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

Fig. 10.12  Adenocarcinoma of the stomach: CD117 negativity

Fig. 10.14  Diffuse or gastric type: The clusters of tumours cells in pools of mucin

Fig. 10.13  Adenocarcinoma of the stomach: CD34 negativity

Fig. 10.15  Diffuse or gastric type: Higher magnification showing cells with nuclear enlargement and pleomorphism

–– Enlarged hyperchromatic nuclei. –– The irregular margin of nuclei. –– Prominent nucleoli.

10.8.5 Diffuse or Gastric Type (Figs. 10.14, 10.15, and 10.16) • Discrete cell population. • Tumour cells. –– Round cells. –– Abundant cytoplasmic vacuolation. –– Nucleus pushed to the periphery giving a signet ring-­ like appearance. –– Prominent nucleoli. • Background often shows mucinous material. Differential Diagnosis • Histiocytes may mimic signet ring cells.

Fig. 10.16  Diffuse or gastric type: The cells with abundant cytoplasm. The cytoplasmic vacuoles have pushed the nuclei in the periphery with signet ring-like appearance

10.9  Gastrointestinal Stromal Tumour

10.9 Gastrointestinal Stromal Tumour Gastrointestinal stromal tumour (GIST) is the mesenchymal tumours of GIT that develops from the Interstitial cells of Cajal, the primitive stem cells.

10.9.1 Epidemiology • GIST represents only about 1% neoplasms of the GIT. • The tumour may occur in any age; however, it is commonly seen in elderly person. • Median age is 65 years. • Males are slightly more affected than females.

283

10.9.5 K  ey Cytological Features [3, 4] (Figs. 10.17, 10.18, 10.19, 10.20, 10.21, and 10.22) • Predominant pattern: Multiple small fascicles and occasional dissociated tumour cells. • Predominantly spindle cell population. • Scanty cytoplasm. • Elongated spindle-shaped nuclei. • Mild-to-moderate nuclear pleomorphism. • Chromatin is coarse. • Absent nucleoli. • Many naked nuclei in the background. • Frequent mitosis and necrosis present.

10.9.2 Localization • • • •

Stomach: 60%. Small intestine (duodenum also) 30%. Colon and rectum: 5%. Oesophaus: 1%.

10.9.3 Molecular Pathology • About 85% of GIST shows mutation of receptor tyrosine kinase gene KIT or platelet-derived growth factor receptor alpha (PDGFRA) in chromosome 4. The mutant KIT bears the capability of autonomous activation without ligand binding. • Mutations of KIT predominantly occur. –– Exon 11: 60%. –– Exon 9: 6%. • Mutations of KRAS and BRAF. • Near about 10% of GIST shows mutations of PDGFRA.

Fig. 10.17  Gastrointestinal stromal tumour: Large fascicles and abundant discrete tumour cells

10.9.4 Clinical Features • • • •

Vague discomfort in the abdomen. Mass abdomen. Nausea and vomiting. Blood in the stool.

Behaviour: The following factors are responsible for the behaviour of GIST: • Size of the tumour. • Mitotic activity per 50 high power field.

Fig. 10.18  Gastrointestinal stromal tumour: The oval to elongated tumour cells

284

Fig. 10.19  Gastrointestinal stromal tumour: Predominantly discrete tumour cells with spindle-shaped nuclei

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

Fig. 10.22  Gastrointestinal stromal tumour: Haematoxylin and eosin-­ stained smear, showing abundant eosinophilic cytoplasm. The nuclei are round with mild atypia

Immunocytochemistry (Figs. 10.23, 10.24, and 10.25): Positive for CD117 (C-kit), CD34 and DOG1. Differential Diagnosis • Other spindle cell tumours. –– Leiomyoma. –– Schwannoma. –– Malignant peripheral nerve sheath tumour.

10.10 Neuroendocrine Tumors [5]

Fig. 10.20  Gastrointestinal stromal tumour: Higher magnification showing elongated nuclei with blunt ends having mild nuclear pleomorphism and fine nuclear chromatin

All neuroendocrine tumours (NET) of the GIT are potentially malignant. Synonym: Carcinoid tumour.

10.10.1 Epidemiology • NET of stomach represents 2% of all malignancies of stomach. • NET of stomach accounts for 9% of all NET of GIT. • The tumours commonly occur in middle-aged patients.

10.10.2 Clinical Features • Usually asymptomatic. • A large tumour may produce carcinoma-like features.

10.10.3 K  ey Cytological Features (Figs. 10.26 and 10.27) Fig. 10.21  Gastrointestinal stromal tumour: Epithelioid type showing predominant round cells with a moderate amount of cytoplasm and indistinct cytoplasmic margin

Predominant pattern: Dissociated and loosely clumped of tumour cells

10.10  Neuroendocrine Tumors

285

Fig. 10.23  Gastrointestinal stromal tumour: Tumour cells showing cytoplasmic positivity of CD117

Fig. 10.26  Neuroendocrine tumour of stomach showing oval cells in loose clusters

Fig. 10.24  Gastrointestinal stromal tumour: Higher magnification of the same showing strongly positive CD117

Fig. 10.27  Neuroendocrine tumour of stomach: The nuclei show salt and pepper chromatin

• Tumour cells are round to oval with minimal pleomorphism. • Cytoplasm shows reddish granularity. • Nuclei are eccentrically placed. • The nuclear chromatin is salt and pepper-like. • Tiny inconspicuous nucleoli. Immunocytochemistry (Fig.  Chromogranin, synaptophysin.

Fig. 10.25  Gastrointestinal stromal tumour: Tumour cells showing strong membranous positivity of CD34

10.28):

Positive:

Differential Diagnosis • Adenocarcinoma: –– Nuclear pleomorphism is relatively more. –– Chromatin coarse. –– Prominent nucleoli. –– Immunocytochemistry: Negative for chromogranin and synaptophysin.

286

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

10.11.4 K  ey Cytological Features (Figs. 10.29 and 10.30) • Cytological features depend on the type of lymphoma. • Overall discrete immature lymphoid cells. • Background lymphoglandular bodies. Differential Diagnosis • Poorly differentiated carcinoma:

Fig. 10.28  Neuroendocrine tumour of stomach: Synaptophysin positive tumour cells

10.11 Non-Hodgkin Lymphoma [6] 10.11.1 Epidemiology • The stomach is the most frequent extranodal location of NHL. • About 40% of extranodal lymphoma occurs in the stomach. • Primary gastric lymphoma is rare, and it represents 5% of all gastric cancers. • Gastric lymphoma commonly occurs in the elderly patient. • Males are two times more affected than females.

Fig. 10.29  Follicular NHL of the stomach: Both large and small immature lymphoid cells

10.11.2 Clinical Features • Gastritis and peptic ulcer-like symptoms. • Weakness. • Dysphagia.

10.11.3 Type of Lymphomas • Predominantly B cell lymphoma. • Diffuse large B cell lymphoma. • MALT lymphoma.

Fig. 10.30  Follicular NHL of the stomach: The relatively larger tumour cells with scanty cytoplasm and round nuclei with fine chromatin. The smaller cells have condensed nuclear chromatin

10.14 Adenocarcinoma

–– Cell clustering. –– Moderate cytoplasm. –– Absence of lymphoglandular bodies. • Carcinoid: –– Reddish granular cytoplasm. –– No lymphoglandular bodies. –– Salt and pepper chromatin.

287

10.12.4 Cytology Columnar Cells • Mainly in small sheets with a honeycomb appearance. • Tall columnar cells. • Round, monomorphic nuclei.

10.12 The Small and Large Intestine

Goblet Cells • Round cells with large cytoplasmic vacuolations. • Monomorphic round nuclei.

10.12.1 Anatomy, Histology and Cytology

10.13 Infections

10.12.1.1 Anatomy Small Intestine • The small intestine is 4 to 7 m long. • It starts from the pyloric canal and to the ileocecal junction. • The small intestine consists of duodenum, jejunum and ileum.

10.13.1 Tuberculosis Tuberculosis is commonly diagnosed by FNAC. Cytology Smears • Epithelioid cell granulomas. • Giant cells. • Necrosis.

10.12.2 Histology The small intestine is made of three layers: Mucous membrane, submucosa and muscularis layer (interna and externa). Mucosa: • Mucosal lining cells are simple tall columnar epithelial cells. • The mucosa contains multiple villi with intervillous space. • Mucosal lining cells are simple tall columnar epithelial cells. • Also, absorptive cells, goblet cells and diffuse neuroendocrine system (DNES) cells are present.

Ziehl Neelsen stain: Positive for acid-fast bacilli (AFB).

10.14 Adenocarcinoma 10.14.1 Epidemiology • Adenocarcinoma of the small intestine represents 3% of all malignancies of GIT. • The tumour mainly occurs in the duodenum. • It occurs in the elderly patient. • Median age is 65 years. • Males are frequently affected.

10.14.2 Clinical Features

Large intestine • The large intestine is 1.5 m in length. • It extends from cecum to anal orifice. • It consists of the cecum, colon, rectum and anal canal.

10.12.3 Histology The large intestine has almost similar histology to that of the small intestine. The mucosal membrane of the colon lacks any villi. The main mucosal cells are surface absorptive cells, followed by goblet cells and endocrine cells.

• Usually asymptomatic. • Vague abdominal discomfort.

10.14.3 Key Cytology Features • • • • • •

Multiple clusters and dissociated cells. Gland-like arrangement. Columnar cells. Vacuolated cytoplasm. Moderately pleomorphic nuclei. Prominent nucleoli.

288

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

10.14.4 Lymphoma [6] NHL is more common than carcinoma in the small intestine. A common type of non-Hodgkin lymphoma: B cell • • • •

DLBCL. Marginal zone lymphoma (MALTomas). Follicular lymphoma. Mantle cell lymphoma.

The cytomorphologic features of non-Hodgkin lymphoma have been described in previous chapters.

10.15 Large Intestine

Fig. 10.31  Adenocarcinoma colon: Tumour cells having round cells with a moderate amount of cytoplasm and moderate nuclear pleomorphism

10.15.1 Colorectal Adenocarcinoma [7] 10.15.1.1 Epidemiology • Colorectal adenocarcinoma is one of the most frequent cancers. • It is the third most common cancers. • Males are commonly involved. • The tumour commonly was seen in the adult patients. • The peak incidence of this tumour is seventh decade.

10.15.2 Clinical Features • Altered bowel habit. • Anaemia. • Haematochezia.

10.15.3 K  ey Cytological Features (Figs. 10.31 and 10.32)

Fig. 10.32 Adenocarcinoma colon: Higher magnification showing moderately pleomorphic nuclei having fine chromatin

Indications of FNAC of the liver are: • The cytological features are mainly the same as that of small intestinal adenocarcinoma.

10.16 Liver The liver is one of the richest vascular organ. Therefore, it is prone to have harbouring various metastatic tumours. FNAC of the liver is mainly applied to identify the primary and metastatic tumours in the liver. The parenchymal lesions of the liver are difficult to categorize on FNAC.

• Diagnosis of metastatic tumours of the liver. • Diagnosis of primary malignancies. • The diagnosis of various infective lesions.

10.16.1 Contraindications of FNAC of Liver • Bleeding diathesis. • Hydatid cyst of liver. • Haemangioma of liver.

10.16 Liver

Complications of FNAC of Liver • Relatively safe procedure. • Internal bleeding. • Biliary peritonitis. • Anaphylactic shock in case of ruptured hydatid cyst. Diagnostic Accuracy of FNAC of Liver [8, 9] • The overall sensitivity and specificity to detect metastatic versus primary tumours of the liver are 90% and 100%, respectively. • The false-positive diagnosis of FNAC is almost nil. • The false-negative diagnosis is due to scanty cellularity and small lesion.

10.16.2 Sampling Technique FNAC of the liver is done with the help of following guided technique: Ultrasonography: • • • •

The most simple and popular technique. Cheaper. No radiation hazards. Flexible and rapid. Computerized tomographic (CT) scan:

• It is more sophisticated. • Can detect tiny lesion. • Radiation hazard.

289

10.16.4 Anatomy, Histology and Cytology Anatomy • Location: Right upper abdomen. • Parts: Right, left lobe, quadrate lobe and caudate lobes. • In between two lobes, falciparum ligament is present. • Porta hepatis: Located on the inferior surface of the liver. It is the entry point of blood vessels and lymphatics. Histology • The liver is made up of multiple lobules. • In between the lobules, the portal triads are present. • Portal triad has hepatic artery, bile ductules and tributaries of portal vein. • Lobules are made of hepatocytes, which are in rows. • The hepatic sinusoid is present in between the rows of hepatocytes. The lining of the sinusoids contain Kupffer cells and macrophages.

10.16.5 Cytology Hepatocytes (Figs. 10.33 and 10.34) • The cells are large and polyhedral. • Cytoplasm is abundant. • Centrally placed nuclei. • Nucleoli are prominent. • Cytoplasmic golden yellow coloured bile pigment. • Intranuclear pseudo inclusion may be present.

Endoscopic ultrasound-guided FNAC • • • •

It can detect the smallest lesion. No radiation hazards. No chance of needle seeding. Time-consuming procedure.

10.16.3 Ancillary Tests The following ancillary test must be done: • One part of the sample should be kept for cell block by putting the material in 10% neutral buffered formalin. The cell block section can be used for immunocytochemistry or histochemistry. • If necessary, the sample should be kept for flow cytometry.

Fig. 10.33  Benign hepatocytes: Polygonal hepatocytes with central nuclei

290

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

• Multiple fragments of connective tissue. • Increased number of fibroblasts.

10.17.3 Differential Diagnosis • Hepatocellular carcinoma (HCC): Three critical differentiating features in HCC: 1) Nucleo-cytoplasmic ratio of the cells are high in HCC, 2) Scattered bare nuclei and 3) trabecular pattern of hepatocytes. • Hepatitis. • Regenerative nodules.

10.17.4 Chronic Hepatitis Fig. 10.34  Benign hepatocytes: Bile pigments within the hepatocytes (arrow)

Bile Ductules • A small cohesive group of cells giving “honeycomb-like appearance”. • Round cell. • Scanty cytoplasm. • Monomorphic round nuclei. Kupffer Cells • Scattered isolated cells. • Scant cytoplasm containing ingested material. • Nuclei are “bean-shaped”. • Inconspicuous nucleoli.

10.17 Non-neoplastic Lesions 10.17.1 D  iffuse Parenchymal Lesions of the Liver It is not possible to identify the non-neoplastic lesions of the liver with the help of FNAC.

10.17.2 Cirrhosis Cytology • Many clusters and discrete hepatocytes. • Hepatocytes. –– They may show a completely normal appearance. –– Mild nuclear pleomorphism. –– Irregular nuclear contour. –– Prominent nucleoli. • Many groups of bile duct cells.

FNAC is usually not done in chronic hepatitis. Cytology • Reactive atypia of the hepatocytes. • Excess lymphocytes. • Apoptotic cells. • Fatty changes in the hepatocytes.

10.17.5 Acute Hepatitis Cytology • Many neutrophils. • Histiocytes. • Necrotic material in the background. • Infective organisms may be seen.

10.17.6 Fatty Change Fatty change may be noted in case of malnutrition, alcoholic persons and diabetes mellitus. Cytology • Hepatocytes show vacuoles in the cytoplasm. • Nucleus is located in the periphery of the cells.

10.17.7 Pyogenic Abscess Pyogenic abscess of the liver is caused by bacterial infection such as streptococci or staphylococci. Cytology (Fig. 10.35) • Necrosis. • Neutrophils.

10.18  Amoebic Abscess

291

Fig. 10.35  Pyogenic abscess: Abundant polymorphs in the FNAC smear of the liver

Fig. 10.37  Leishmania: LD bodies within the histiocyte in a leishmanial infection of the liver

Fig. 10.36  Granulomatous inflammation of the liver: FNAC smear showing epithelioid cell granuloma and hepatocytes

Fig. 10.38  Mucormycosis in the liver: Broad-based aseptate fungal hyphae

• Degenerated hepatocytes. • Reactive changes in the hepatocytes.

10.18.1 Cytology

10.17.8 Granulomatous Hepatitis

• • • •

Necrotic material. Occasional polymorphs. Hepatocytes may show degenerative changes. Trophozoites are present: Round cell, moderate cytoplasm, vesicular nuclei with characteristic engulfed RBCs.

Granulomatous hepatitis may be noted in tuberculosis, sarcoidosis, autoimmune hepatitis or drug-induced hepatitis. The cytology smears show epithelioid cell granulomas and multinucleated giant cells (Fig. 10.36).

Other infections (Figs. 10.37 and 10.38): The liver may be involved by various other parasitic and fungal infections.

10.18 Amoebic Abscess

10.18.2 Cystic Lesions

An amoebic abscess is caused by Entamoeba histolytica infection in the liver.

Congenital Cysts • Accidentally detected as the patients are asymptomatic.

292

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

• Predominantly unilocular. • Caused by dilation of the bile duct. • Cytology. –– Scanty cellularity. –– Scattered foamy histiocytes. –– Occasional columnar or cuboidal cells.

10.19.3 Clinical Features

Hydatid Cysts [10] (Figs. 10.39 and 10.40) • The causative organism is Echinococcus granulosus. • Solitary cyst. • Membrane bound. • Cytology. –– Fragments of a laminated membrane. –– Scolices. –– Characteristic hooklets. –– Occasional inflammatory cells. –– Multinucleated giant cells.

Cytology [11] • Benign hepatocytes. • Many clusters of bile ductal cells. • Many fibroblasts in the background.

10.19 Benign Tumours in the Liver

10.20.1 Epidemiology

10.19.1 Focal Nodular Hyperplasia It is not a neoplastic lesion. It is the reaction of the hepatocytes in response to vascular malformation in the liver.

• Predominantly occurs in the females of reproductive age group. • Use of oral contraceptive. • Men using anabolic steroids.

10.19.2 Epidemiology

10.20.2 Clinical Features

• 90% of cases are females. • Mainly in the third and fourth decade of life.

• Pain in the abdomen. • Haemorrhage.

Fig. 10.39  Hydatid cyst: Laminated structure

Fig. 10.40  Hydatid cyst: Hooklet in case of hydatid cyst of the liver

• Asymptomatic. • Incidentally detected during imaging for some other purpose. • Characteristic USG: Hypervascular in the arterial phase, mass with stellate scar having radiated appearance.

10.20 Hepatocellular Adenomas Hepatocellular adenomas (HCA) is the benign neoplastic lesion of hepatocytes.

10.20  Hepatocellular Adenomas

293

• At times the palpable mass. • CT scan: Well defined, circumscribed mass with a prominence of centripetal arrangement in the arterial phase.

10.20.3 Cytology [12] (Figs. 10.41, 10.42, and 10.43) • Abundant 3-D clusters of hepatocytes. • The hepatocytes are normal in appearance: Polygonal, monomorphic round nuclei. • The complete absence of ductular bile cells is the essential features of HCA.

Fig. 10.43  Hepatocellular adenoma: Higher magnification showing the polygonal cells with centrally placed monomorphic round nuclei

There are no specific diagnostic features of HCA. However, the combination of clinical features, CT scan findings and cytology may be the possible clues in the diagnosis of such lesions. Differential diagnosis: Hepatocellular carcinoma and focal nodular hyperplasia.

10.20.4 Haemangioma of Liver

Fig. 10.41  Hepatocellular adenoma: Abundant benign hepatocytes in small and large clusters

Haemangioma is the commonest benign neoplasm of liver. The patients are detected incidentally. Cytology • The aspirate from haemangioma of liver yields blood only. • FNAC smears show mainly RBCs, occasional endothelial cells and fragments of stromal tissue.

10.20.5 Biliary Cystadenoma Biliary cystadenomas are uncommon benign tumours of the liver. The tumour is only seen in females. Cytology • Multiple clusters of epithelial cells. • Columnar cells with regular round nuclei.

10.20.6 Hepatic Angiomyolipoma [13] Fig. 10.42  Hepatocellular adenoma: The cells are looking like normal hepatocytes. There is a striking absence of bile ductular cells

Hepatic angiomyolipoma is a tumour of PECOMA group that expresses HMB45.

294

• • • •

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

Epidemiology and clinical features:

10.22.2 Epidemiology

Median age is 50 years. Age range 9 to 80 years. 80% AML of the liver occurs in female. The liver is the second frequent site after kidney.

• • • •

HCC represents 5% of all cancer. It represents 80 to 85% of all primary cancer of the liver. Commonly occurs in male. Predominantly in 30 to 40 year age group.

10.20.7 Cytology

10.22.3 Clinical Features

• Mature adipose tissue. • Many clusters of cells with thick-walled blood vessels. • The groups of the oval to spindle cells having pale cytoplasm. • Nuclear atypia. • Megakaryocytes, myeloid group of cells and nucleated RBC indicating extramedullary haematopoiesis.

• • • • • •

Immunocytochemistry: Positive: HMB-45 and smooth muscle actin.

10.22.4 Aetiology

Differential Diagnostic • HCC. • Sarcoma. • Granulomatous inflammation. • Metastatic carcinoma.

10.21 Mesenchymal Hamartoma of Liver Mesenchymal Hamartoma is a very rare benign tumour of the liver. It is seen predominantly in children.

10.21.1 Cytology [14] • • • •

Many clusters of spindle cells. Spindle cells: Blunt nuclei and grooved. Small monomorphic round-shaped epithelial cells. Stromal fragments.

10.21.2 Differential Diagnosis • Undifferentiated sarcoma. • Inflammatory pseudotumor. • Leiomyoma and leiomyosarcoma.

10.22 Malignant Tumour 10.22.1 H  epatocellular Carcinoma (HCC) [15–17] HCC is the most frequent primary malignancy of the liver.

Pain. Weight loss. Malaise and weakness. Sudden deteriorating symptoms of cirrhotic patients. Enlarged liver. Jaundice.

• Hepatitis: Chronic HBV and HCV infection: One hundred times riskier in HBV infection. Cirrhosis of the liver: • About 90% of HCC is developed from cirrhosis. • Associated haemochromatosis may enhance further risk. • Growth factors produced from stellate cells of the cirrhotic liver may promote HCC. • Aflatoxin: Aspergillus parasiticus and Aspergillus flavus produce Aflatoxin, which is known as carcinogen. Aflatoxin causes mutation of p53 tumour suppressor protein.

10.22.5 K  ey Cytology Features (Figs. 10.44, 10.45, 10.46, 10.47, 10.48, 10.49, 10.50, 10.51, 10.52, and 10.53) Arrangement of the Cells • Trabecular: Four to five layers of hepatocytes. Long strands of cells and often show branching. More than 85% of HCC shows the trabecular arrangement. • Acinar or glandular: The tumour cells arranged around the central lumen. • Thin cords or microtrabeculae: Only two rows of hepatocytes form microtrabeculae. This pattern is common in well-differentiated HCC. • Tumour cells. –– Tumour cells look like hepatocytes. –– Polygonal cells. –– The cytoplasmic margin is well defined. –– Moderate-to-severe nuclear pleomorphism.

10.22  Malignant Tumour

295

Fig. 10.44 Well-differentiated hepatocellular carcinoma: Multiple clusters of tumour cells

Fig. 10.47  hepatocellular carcinoma: The isolated and loose clusters of tumour cells with many bare nuclei

Fig. 10.45  Well-differentiated hepatocellular carcinoma: The polyhedral shaped tumour cells resembling normal hepatocytes

Fig. 10.48  hepatocellular carcinoma: The higher magnification showing cells with moderate nuclear pleomorphism

Fig. 10.46  Well-differentiated hepatocellular carcinoma: Higher magnification showing cells with abundant cytoplasm and mildly pleomorphic nuclei

Fig. 10.49  hepatocellular carcinoma: The trabecular arrangement of the tumour cells

296

Fig. 10.50  Hepatocellular carcinoma: Acinar arrangement of cells

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

Fig. 10.53  Hepatocellular carcinoma: Macronucleoli

–– Macronucleoli (70% cases). –– Fine to coarse nuclear chromatin. –– Intranuclear cytoplasmic inclusion (15% cases). –– Bile pigments within the tumour cells (35% cases). • Many bare nuclei in the background. • Transgressing thin capillaries within the tumour cell clusters. • Multinucleated tumour giant cells in poorly differentiated HCC.

10.23 Variants of HCC 10.23.1 Fibrolamellar Variant of HCC Fig. 10.51 Hepatocellular carcinoma: The cells with vacuolated cytoplasm

Epidemiology • 1% of all HCC • Common in 20 to 30 years age. • Median age 25 years.

10.23.2 Key Cytology Features • Discrete cells. • Large polygonal cells with eosinophilic cytoplasm simulating oncocytes. • Nuclei are round with minimal pleomorphism. • Coarse chromatin. • Prominent nucleoli. • Intranuclear cytoplasmic inclusions present. • Hyaline cytoplasmic droplets present. • Discrete and small rows of fibroblasts.

10.23.3 Clear Cell Variant Fig. 10.52  Hepatocellular carcinoma: The higher magnification showing cells with large prominent nucleoli

It represents 10% of HCC.

10.25  Intrahepatic Cholangiocarcinoma

297

10.24.1 HCC with Fatty Change

Cytology • Small clusters of cells. • Abundant clear cytoplasm. • Marked nuclear pleomorphism. • Hyperchromatic nuclei. • Irregular nuclear contour.

• Many discrete and sheets of malignant hepatocytes. • Large cells with cytoplasmic vacuoles. • The nucleus is pushed to one corner of the cell giving a “signet ring” appearance. • Hyperchromatic nuclei with prominent nucleoli.

Differential Diagnosis • Metastatic clear cell carcinoma: Renal cell carcinoma, adrenocortical carcinoma and ovarian clear cell carcinoma.

10.24 Giant Cell Variant of HCC Giant cell variant of HCC is a rare tumour. Cytology • Many mono- and multinucleated tumour giant cells present. • The giant cells look like “osteoclastic giant cell”. • The other diagnostic cytological features present. Small Cell Variant • Discrete and loose clusters of cells. • Small cell. • Round nucleus. • Condensed dark chromatin. Differential tumour.

diagnosis:

Metastatic

Differential diagnosis: Fatty liver. Immunocytochemistry • Alpha-fetoprotein: The commonly used marker of HCC. Relatively low sensitivity (65%) and high specificity (96%). • Hepatocyte paraffin 1 antibod (Hep Par1): Hep Par1 is a urea cycle enzyme with high sensitivity (100%) and specificity (90%). • Polyclonal carcinoembryonic antigen (p-CEA):p-CEA stains bile canaliculi and duct, which are present as intercellular canaliculi in HCC. • Glypican-3: Glypican-3 is a relatively better marker than Hep Par 1. It is positive in malignant hepatocytes only. • Arginase 1: Highly sensitive (90%) and specific (100%) marker of HCC. Table 10.1 highlights the comparison of different immunostaining in HCC.

neuroendocrine

Spindle Cell Variant • Multiple small groups of cells. • Scanty cytoplasm. • Spindle-shaped moderately pleomorphic nucleus. • Giant hepatocytes. Differential diagnosis: Metastatic leiomyosarcoma.

Differential Diagnosis • Metastatic adenocarcinoma: Discussed later on.

10.25 Intrahepatic Cholangiocarcinoma 10.25.1 Epidemiology • Intrahepatic Cholangiocarcinoma (ICC) represents 15% of all primary liver malignancies. • ICC occurs in fifth to seventh decade.

Table 10.1  Immunocytochemistry in Hepatocellular carcinoma Antigen Alpha-­ fetoprotein

Hep Par1:

Arginase-1

Glypican-3

Characteristics Oncofetal glycoprotein. It is present in fetal hepatocytes, epithelial cells of the gastrointestinal tract and yolk sac It is a urea cycle enzyme. It is present on the membrane of mitochondria A urea cycle enzyme

It is a heparan sulphate proteoglycan. It is present both in the cell membrane of the fetal hepatocytes

Localization Cytoplasmic

Sensitivity About 65%

Specificity 96%

Cytoplasmic positivity

100% sensitivity in HCC More than 90% sensitive High sensitivity (100%)

90% specific for HCC

Cytoplasmic and membranous Cytoplasmic and membranous

90 to 100% specific for HCC Highly specific for HCC (100%)

Importance High serum alpha-fetoprotein (more than 500 ng/ml) is highly suggestive of hepatocellular carcinoma (HCC) Reliable marker for HCC

Reliable marker for HCC

Adult liver cells do not express glypican-3. So it is helpful in distinguishing HCC from benign reactive hepatocytes

298

10.25.2 Clinical Features • • • •

Pain in the abdomen. Weakness. Malaise. Obstructive jaundice.

10.25.3 K  ey Cytology Features [18] (Figs. 10.54, 10.55, 10.56, and 10.57)

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

Immunocytochemistry (Figs. 10.58 and 10.59) • Positive: CK7, CK19, EMA, CAM 5.2,MOC31,p-CEA, PDX-1 and Claudin. • Negative: Glypican3, arginase1 and Hep Per1.

10.25.4 Differential Diagnosis

Tight clusters of malignant cells. Occasional glandular and papillary pattern. Small columnar cells having scanty cytoplasm. Hyperchromatic round nuclei with prominent nucleoli.

• Metastatic adenocarcinoma: Not always possible to differentiate by morphology. • Hepatocellular carcinoma: –– Polygonal cells. –– Many bare nuclei. –– ICC is positive for CK7, CK17 and CK 19, whereas, HCC is positive for Glypican3, arginase1 and Hep Per1.

Fig. 10.54  Cholangiocarcinoma: Tight clusters and sheets of tumour cells

Fig. 10.56  Cholangiocarcinoma: Round cells with hyperchromatic mildly pleomorphic nuclei

Fig. 10.55  Cholangiocarcinoma: Sheet of tumour cells with scanty cytoplasm and mildly pleomorphic nuclei

Fig. 10.57  Cholangiocarcinoma: Higher magnification of the cells showing mildly pleomorphic nuclei having coarse chromatin

• • • •

10.26 Hepatoblastoma

299

• Majority of the hepatoblastoma occurs under the age of 5 years. • Males are more affected than females.

10.26.2 Clinical Features • • • • • •

Fig. 10.58  Cholangiocarcinoma: CK7 positive tumour cells in a cell block section

Fever. Weight loss. Abdominal pain and discomfort. Abdominal enlargement. Hepatomegaly. In the majority of the cases (>90%), serum alpha-­ fetoprotein is raised.

10.26.3 K  ey Cytological Feature [19, 20] (Figs. 10.60, 10.61, 10.62, 10.63, 10.64, 10.65, and 10.66) Anaplastic • Loose aggregates of cells. • Small cell. • Scanty cytoplasm. • Round monomorphic nuclei. Embryonal • Small clusters and sheets of tumour cells. • Rosette-like structures are present. • Cells are larger than anaplastic type.

Fig. 10.59  Cholangiocarcinoma: The tumour cells are CK19 positive

10.26 Hepatoblastoma Hepatoblastoma is a malignant blastomatous tumour of the hepatocytes.

10.26.1 Epidemiology • The most frequent childhood liver tumour and represents 1% of all paediatric cancers. • The median age is one and a half year.

Fig. 10.60  Hepatoblastoma: Multiple clusters and acinar arrangement of cells

300

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

Fig. 10.61  Hepatoblastoma: Higher magnification of acini

Fig. 10.64  Hepatoblastoma: Thick rows of cells

Fig. 10.62  Hepatoblastoma: The cells are a small round shaped with scanty cytoplasm

Fig. 10.65  Hepatoblastoma: Solid three-dimensional clusters of cells

Fig. 10.63 Hepatoblastoma: Occasional cells in cluster showing polygonal appearance with moderate cytoplasm

Fig. 10.66  Hepatoblastoma: Tumour cells, along with occasional nucleated RBCs

10.28  Embryonal Sarcoma of the Liver

• The cytoplasm is scanty to moderate. • Nuclei are enlarged, moderately pleomorphic and hyperchromatic. • Multiple nucleoli.

301

• • • •

Immunocytochemistry: Positive: CD31, CD 34 and vWF.

10.26.4 Fetal Cellular Component • The cells are in discrete or in small clusters. • Acinar arrangement. • Relatively larger cells. • Polygonal shaped. • Cytoplasmic margin is well-defined. • Round relatively monomorphic nuclei. • Chromatin is fine. • Cytoplasm often contains bile pigment. Mesenchymal components: Spindle cells in small clusters along with osteoid material. Extramedullary haematopoiesis: Many nucleated RBCs, the cells of myeloid series and often megakaryocytes. Differential Diagnosis • HCC. • Malignant small round blue cell tumour.

Spindle-shaped nuclei. Cytoplasmic vacuolation and intracytoplasmic lumina. Moderate nuclear pleomorphism. Large prominent nucleoli.

10.27.4 Differential Diagnosis • Epithelioid Hemangioendothelioma: • Metastatic spindle cell sarcoma: Metastatic GIST and leiomyosarcoma may simulate angiosarcoma. Immunocytochemistry may be helpful for the confirmation of angiosarcoma. • Sarcomatoid HCC: Sarcomatoid HCC is positive for the various markers such as HepPar1, arginase and glypican 3.

10.28 Embryonal Sarcoma of the Liver Embryonal sarcoma is an undifferentiated sarcoma of the liver.

10.28.1 Epidemiology

10.27.1 Angiosarcoma

• Near about 6% of all childhood primary liver malignancy. • Commonly occurs in 5–10 year age group. • Rare in adults.

Angiosarcoma is the malignant tumour of the blood vessels. Epidemiology

10.28.2 Clinical Features

• • • •

• • • •

10.27.2 Clinical Features

10.28.3 K  ey Cytology Features [21, 22] (Figs. 10.67, 10.68, 10.69, 10.70 and 10.71)

• Pain in the upper part of the abdomen. • Weight loss. • Jaundice.

Predominant pattern: Two different types of cell population consisting of round mildly pleomorphic cells and large bizarre cells.

10.27 Primary Sarcomas of Liver

Rare tumour of the liver. It represents only 1% of all primary liver cancer. Mainly occurs in the 6th–seventh decade. Often associated with the radiographic dye Thorostat and anabolic steroid. • Association with cirrhosis.

10.27.3 Key Cytology Features • Multiple small clusters and loosely cohesive cells.

Pain abdomen. Abdominal swelling. Fever. Normal level of alpha-fetoprotein (AFP) level.

• Round to oval cells: Mild nuclear pleomorphism, coarse chromatin and prominent nucleoli. • Large cells: Large severely pleomorphic nuclei. • Many atypical mitoses.

302

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

Fig. 10.67  Embryonal sarcoma: Multiple clusters of tumour cells in a necrotic background

Fig. 10.70  Embryonal sarcoma: Large bizarre nuclei

Fig. 10.68  Embryonal sarcoma: The tumour cells with round moderately pleomorphic nuclei

Fig. 10.71  Embryonal sarcoma: Bizarre nuclei with multiple prominent nucleoli

• Eosinophilic acellular globular material. • Myxoid background. Immunocytochemistry: The hyaline globules are usually weak positive for B72.3 antibody, alpha-l antitrypsin,

10.28.4 Metastatic Lesions in Liver [23] The liver is a very vascular organ, and therefore it is a rich source of metastasis of various malignancies.

Fig. 10.69  Embryonal sarcoma: The cells have moderate cytoplasm and large pleomorphic nuclei

• The secondaries in the liver are many fold commoner than primary liver tumours. • The common primary sites of the metastatic tumours are intestine, gall bladder, pancreas, kidney, lung and breast. • Clinical features: Pain abdomen, hepatomegaly and ascites.

10.28  Embryonal Sarcoma of the Liver

303

10.28.5 K  ey Cytology Features (Figs. 10.72, 10.73, 10.74, 10.75, 10.76, 10.77, 10.78, 10.79, 10.80, 10.81, 10.82, 10.83, 10.84, 10.85, 10.86, 10.87, 10.88 and 10.89) • The cells appear foreign population. • The cytological features depend on the exact type of malignancy. • The tumour cells are often admixed with benign hepatocytes. • The common types of malignancies are: –– Adenocarcinoma. –– Squamous cell carcinoma. –– Malignant melanoma. –– Neuroendocrine tumours. –– Transitional cell carcinoma.

Fig. 10.74 Metastatic carcinoma: Higher magnification showing hepatocytes and tumour cells

Fig. 10.72  Metastatic carcinoma: Clusters and discrete tumour cells admixed with hepatocytes

Fig. 10.75  Metastatic carcinoma: The individual cells showing moderate cytoplasm and large round nuclei having multiple prominent nucleoli

Fig. 10.73  Metastatic carcinoma: Discrete tumour cells with a moderate amount of cytoplasm and pleomorphic nuclei

Fig. 10.76  Metastatic adenocarcinoma from gall bladder: There are many discrete cells with occasional large pleomorphic nuclei

304

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

Fig. 10.77  Metastatic adenocarcinoma from gall bladder: Higher magnification showing large pleomorphic nuclei

Fig. 10.80  Metastatic giant cell tumour: Individual large cells with pleomorphic nuclei

Fig. 10.78  Metastatic giant cell tumour: Tumour cells, along with many multinucleated giant cells

Fig. 10.81  Metastatic neuroendocrine tumour: Discrete tumour cells

Fig. 10.79  Metastatic giant cell tumour: Multinucleated giant cells

Fig. 10.82  Metastatic neuroendocrine tumour: The cells with abundant cytoplasm and monomorphic nuclei

10.28  Embryonal Sarcoma of the Liver

305

Fig. 10.83  Metastatic malignant melanoma: Scattered tumour cells containing melanin

Fig. 10.86  Metastatic Small round cell tumour: The tumour cells are small, with scanty cytoplasm and monomorphic nuclei

Fig. 10.84  Metastatic malignant melanoma: Higher magnification showing better morphology of the tumour cells

Fig. 10.87 Metastatic urothelial cell carcinoma: Many scattered tumour cells

Fig. 10.85  Metastatic Small round cell tumour: Discrete small round cells

Fig. 10.88  Metastatic urothelial cell carcinoma: The tumour cells have moderate cytoplasm with eccentric nuclei

306

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

10.28.7 Spleen FNAC of the spleen is useful in various neoplastic and non-­ neoplastic lesions. The Indications of FNAC of the Spleen include Diagnosis of: • Various infective lesions: tuberculosis. • Staging of lymphoma. • Storage disease. • Metastatic tumour in the spleen. • Amyloidosis. Fig. 10.89  Metastatic urothelial cell carcinoma: The higher magnification showing the cells with abundant cytoplasm, eccentric nuclei and enlarged mildly pleomorphic nuclei

Table 10.2  Differentiating cytological and immunocytochemistry features between Hepatocellular carcinoma and metastatic adenocarcinoma Hepatocellular carcinoma Trabecular, acinar and small clusters of cells Capillaries within the tumour cells are present The cells are polygonal and often resemble hepatocyte Large prominent macronucleoli Bile pigment within the cytoplasm is present Many naked nuclei in the background are present Positive: Hep par 1 Glypican-3, Arginase1 Alpha-fetoprotein

Metastatic adenocarcinoma Frequent glandular arrangement Absent Columnar in appearance Absent Absent

Leishmaniasis

and

Technique • FNAC of the spleen is always done under CT scan or USG. • A team of cytologist, radiologist and surgeon should always be in the team of aspiration. • The sample should be procured for air-dried smear, alcohol fixed smear, cell block and culture if necessary. Complications • Massive bleeding. • Pneumothorax. • Rarely rupture of the spleen. Contraindications • Bleeding diathesis. • Infectious mononucleosis.

Absent Negative: Hep par 1 Glypican-3, Arginase1 Alpha-fetoprotein

Differential diagnosis: Hepatocellular carcinoma: Table 10.2 shows the differentiating features between HCC and metastatic adenocarcinoma.

10.28.6 Malignant Lymphoma of the Liver • Primary lymphoma in the liver is rare. • About 65% of advanced NHL may secondarily involve the liver. • The commonest NHL of the liver are: –– DLBCL. –– Burkitt’s NHL. –– MALTOMA.

10.28.8 Normal Cytology The cell population is the same as that of the aspirates of lymph node. • The polymorphic population of lymphoid cells: Follicular centre cells. • Histiocytes. • Capillaries. • Clusters of platelets.

10.29 Non-neoplastic Process of the Spleen Various Infections • Leishmanial infection (Fig. 10.90): FNAC is often used as a necessary investigative technique to diagnose leishmanial infection.

10.30  Accumulation of Abnormal Material and Storage Disease

307

Fig. 10.90  Leishmaniasis of the spleen: Leishmania donovani bodies in histiocytes (arrow)

Fig. 10.92  Aspergillus infection in the spleen: PAS-positive slender, acute angle branching hyphae of Aspergillus (arrow)

Fig. 10.91  Tuberculosis of spleen: Epithelioid cell granuloma

Fig. 10.93  Hydatid cyst spleen: Smear showing membrane fragment (arrow), granular debris in the background and histiocytes

• Tuberculous infection (Fig.  10.91): Tuberculosis of the spleen can present as space-occupying lesions. FNAC smears show epithelioid cell granulomas, multinucleated giant cells and necrosis. • Other infection (Figs.  10.92, 10.93, 10.94, and 10.95): Various other infections such as aspergillosis, histoplasmosis and hydatid cyst are diagnosed by FNAC.

10.30 A  ccumulation of Abnormal Material and Storage Disease Abnormal Material Amyloidosis: • Reddish coloured. • Acellular.

Fig. 10.94  Hydatid cyst spleen: Membranous fragment of the cyst wall

308

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen

Fig. 10.95 Hydatid cyst spleen: Hooklets of the echinococcus granulosus

Fig. 10.96  Hepatosplenic T-cell lymphoma: Immature medium-sized lymphoid cell with nuclear convolution (see arrow)

• Amorphous. • Positive for Congo red: Apple green birefringence in polarised light.

10.31.2 Epidemiology

Storage Disease Gaucher’s disease: • Large cell. • Abundant crumpled paper-like cytoplasm. • Eccentrically placed round nuclei.

10.31 Neoplasm [24] 10.31.1 Lymphoma Unique Lymphomas of the Spleen • Splenic marginal zone lymphoma. • Hepatosplenic T cell lymphoma. Splenic Marginal Zone Lymphoma • B cell NHL. • Medium-sized immature lymphoid cells. Immunophenotyping: Positive: CD 19 and CD 20. Negative: CD 5, CD10 and CD 23. Hepatosplenic T Cell Lymphoma (HSTCL) [25] HSTCL is an aggressive T cell lymphoma.

• Rare type of lymphoma. • It represents only 1% of all peripheral T cell lymphoma. • Young adults are mainly affected. • Median age 35 years. • Males are commonly affected. Common organ involved: Spleen and also liver. Clinical features: Hepatosplenomegaly, anaemia and thrombocytopenia.

10.31.3 K  ey Cytological Features (Fig. 10.96) • • • •

Discrete medium-sized immature lymphoid cells. Thin rim of cytoplasm. Nuclei are round with frequent convolutions. Fine chromatin.

Immunophenotyping Positive: CD3, and gamma delta T cell receptor. Negative: Alpha-beta receptor, CD3, CD4, and CD5. Sarcomas • Angiosarcoma.

CD8

References

309

References

Fig. 10.97  Metastatic squamous cell carcinoma of spleen showing multiple clusters of malignant cells

Fig. 10.98  Metastatic squamous cell carcinoma of spleen showing polyhedral cells with enlarged pleomorphic nuclei

10.31.4 Metastatic Tumour Primary sources: Lung, skin melanoma, colon ovary, cervix and bladder. Rate: 2 to 30% of patients in autopsy. Presentation • Asymptomatic in the majority of the cases. • Single to multiple solitary space-occupying lesion. Cytology (Figs. 10.97 and 10.98) It depends on the type of primary tumour.

1. Vander Noot MR 3rd, Eloubeidi MA, Chen VK, Eltoum I, Jhala D, Jhala N, Syed S, Chhieng DC.  Diagnosis of gastrointestinal tract lesions by endoscopic ultrasound-guided fine-needle aspiration biopsy. Cancer. 2004 Jun 25;102(3):157–63. 2. Haggitt RC. Barrett’s esophagus, dysplasia, and adenocarcinoma. Hum Pathol. 1994;25(10):982–93. 3. Kapatia G, Gupta N, Saikia UN, et al. Fine needle aspiration cytology of primary and metastatic gastrointestinal stromal tumour. Cytopathology. 2020;31(2):136–43. 4. Pih GY, Kim DH. Endoscopic ultrasound-guided fine needle aspiration and biopsy in gastrointestinal subepithelial tumors. Clin Endosc. 2019;52(4):314–20. 5. Modlin IM, Sandor A.  An analysis of 8305 cases of carcinoid tumors. Cancer. 1997;79(4):813–29. 6. Shirwaikar Thomas A, Schwartz M, Quigley E.  Gastrointestinal lymphoma: the new mimic. BMJ Open Gastroenterol. 2019;6(1):e000320. Published 2019 Sep 13 7. Heriot AG, Kumar D, Thomas V, Young M, Pilcher J, Joseph AE.  Ultrasonographically-guided fine-needle aspiration cytology in the diagnosis of colonic lesions. Br J Surg. 1998;85(12):1713–5. 8. Nazir RT, Sharif MA, Iqbal M, Amin MS. Diagnostic accuracy of fine needle aspiration cytology in hepatic tumours. J Coll Physicians Surg Pak. 2010;20(6):373–6. 9. Swamy MC, Arathi C, Kodandaswamy C. Value of ultrasonography-­ guided fine needle aspiration cytology in the investigative sequence of hepatic lesions with an emphasis on hepatocellular carcinoma. J Cytol. 2011;28(4):178–84. 10. Kapatia G, Tom JP, Rohilla M, et al. The clinical and cytomorphological spectrum of hydatid disease [published online ahead of print, 2020 Feb 13]. Diagn Cytopathol. 2020; https://doi.org/10.1002/ dc.24391. 11. Ruschenburg I, Droese M. Fine needle aspiration cytology of focal nodular hyperplasia of the liver. Acta Cytol. 1989;33(6):857–60. 12. Suen KC. Diagnosis of primary hepatic neoplasms by fine-needle aspiration cytology. Diagn Cytopathol. 1986;2(2):99–109. 13. Cha I, Cartwright D, Guis M, Miller TR, Ferrell LD. Angiomyolipoma of the liver in fine-needle aspiration biopsies: its distinction from hepatocellular carcinoma. Cancer. 1999;87(1):25–30. 14. al-Rikabi AC, Buckai A, al-Sumayer S, al-Damegh S, al-Bassam AR. Fine needle aspiration cytology of mesenchymal Hamartoma of the liver. A case report. Acta Cytol. 2000;44(3):449–53. 15. Wee A. Fine-needle aspiration biopsy of hepatocellular carcinoma and related hepatocellular nodular lesions in cirrhosis: controversies, challenges, and expectations. Pathol Res Int. 2011;2011:587936. 16. Wee A.  Fine needle aspiration biopsy of malignant mass lesions in the liver: a revisit of diagnostic profiles and challenges. J Gastrointest Oncol. 2013;4(1):5–7. 17. Wee A.  Fine needle aspiration biopsy of the liver: algorithmic approach and current issues in the diagnosis of hepatocellular carcinoma. Cytojournal. 2005;2:7. Published 2005 Jun 8 18. Stroescu C, Herlea V, Dragnea A, Popescu I. The diagnostic value of cytokeratins and carcinoembryonic antigen immunostaining in differentiating hepatocellular carcinomas from intrahepatic cholangiocarcinomas. J Gastrointestin Liver Dis. 2006;15(1):9–14. 19. Jain BL, Mathur DR, Vyas MC, Ramdeo IN. Cytologic diagnosis of hepatoblastoma by fine needle aspiration biopsy cytology. Acta Cytol. 1997;41(6):1858–60. 20. Iyer VK, Kapila K, Agarwala S, Verma K. Fine needle aspiration cytology of hepatoblastoma. Recognition of subtypes on cytomorphology. Acta Cytol. 2005;49(4):355–64.

310 21. Pollono DG, Drut R.  Undifferentiated (embryonal) sarcoma of the liver: fine-needle aspiration cytology and preoperative chemotherapy as an approach to diagnosis and initial treatment. A case report. Diagn Cytopathol. 1998;19(2): 102–6. 22. Krishnamurthy SC, Datta S, Jambhekar NA.  Fine needle aspiration cytology of undifferentiated (embryonal) sarcoma of the liver: a case report. Acta Cytol. 1996;40(3):567–70.

10  Fine Needle Aspiration Cytology of the Intestine, Liver and Spleen 23. Gupta N, Kumar V, Dey P, Srinivasan R, Nijhawan R, Rajwanshi A. A study of unusual metastasis in fine needle aspirate of the liver. Cytopathology. 2005;16(3):158–60. 24. Gochhait D, Dey P, Rajwanshi A, et al. Role of fine needle aspiration cytology of spleen. APMIS. 2015;123(3):190–3. 25. Kumar R, Dey P, Das A, Sachdeva MS, Varma S.  Hepatosplenic T-cell lymphoma is a distinct rare entity: diagnosis by fine-needle aspiration cytology. Diagn Cytopathol. 2011;39(9):677–80.

Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas

11.1 Gall Bladder Gall bladder and extrahepatic bile duct are often undergone for cytological examination. The common cytological techniques are: • • • •

Biliary brush cytology. Endoscopic FNAC. Percutaneous FNAC. Retrograde endoscopic cholangiopancreatography.

11.1.1  Anatomy and Histology The gall bladder is situated in the inferior aspect of the liver. It is a pear-shaped organ with three parts: fundus, body and cystic duct. The bile is stored in the body that passes through cystic duct to the common bile duct and ultimately ends in the second part of duodenum. The wall of the gall bladder is composed of epithelium, lamina propria, smooth muscle and serosa. The mucosa is lined by simple columnar epithelium. The right and left hepatic duct join to form the common hepatic duct. The cystic duct joins with the common hepatic duct and forms the common bile duct. The pancreatic duct merges with the common bile duct and forms ampulla of Vater that finally opens into the second part of duodenum.

11.1.2  Cytology Bile Duct Cells • Usually in a small sheet. • Monolayer. • Round cells. • No nuclear pleomorphism. • Scanty cytoplasm.

11

Gall Bladder Lining Cells • Simple columnar epithelial cells. • The cells are mainly in small sheets.

11.1.3  Neoplasms The WHO classification of neoplastic lesions of the gall bladder [1] is mentioned in Fig. 11.1.

11.2 Gall Bladder Carcinomas 11.2.1  Epidemiology • Gall bladder carcinomas are the most frequent malignancies in the biliary tree. • It is most common in Chile. • Male are more frequently affected than females.

11.2.2  Clinical Features • Vague pain in the upper abdomen and discomfort. • Abdominal bloating. • Jaundice.

11.2.3  Adenocarcinoma Key Cytological Features [2] (Figs. 11.2, 11.3, 11.4, and 11.5) • Multiple tight clusters cells. • Significant nuclear crowding. • Cells are columnar in appearance. • A moderate amount of cytoplasm. • An enlarged and pleomorphic nucleus with prominent nucleoli.

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_11

311

312

11  Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas

Fig. 11.1  World Health Organization classification of neoplastic lesions of the gall bladder

Fig. 11.2  Adenocarcinoma of gall bladder: Multiple tight clusters of tumour cells

Fig. 11.3  Adenocarcinoma of gall bladder: The higher magnification showing cells with moderate cytoplasm and enlarged pleomorphic nuclei

11.2.4  Squamous Cell Carcinoma

11.2.5  Adenosquamous Carcinoma [2]

Pure squamous cell carcinoma of the gall bladder is rare.

11.2.5.1 Key Cytological Features • Clusters, dissociated cells and glandular arrangement. • Both adenocarcinoma and squamous cell components are present. • Adenocarcinoma: Tumour cells with the gland-like arrangement, vacuolated cytoplasm, pleomorphic nuclei with prominent nucleoli.

11.2.4.1 Key Cytological Features • Scattered polyhedral squamous cells. • Fibre and tadpole cells. • Intracytoplasmic keratin. • Hyperchromatic nuclei.

11.3 Neuroendocrine Tumours

313

Fig. 11.4  Adenocarcinoma of gall bladder: The haematoxylin and eosin-stained smear showing ball like 3-dimensional clusters of cells

Fig. 11.6  Neuroendocrine tumour of gall bladder: Abundant dissociated tumour cells

Fig. 11.5  Adenocarcinoma of gall bladder: The haematoxylin and eosin-stained smear showing cells with a moderate amount of vacuolated cytoplasm having enlarged hyperchromatic nuclei

Fig. 11.7  Neuroendocrine tumour of gall bladder: The cell has monomorphic nuclei with stippled chromatin

11.3.2  Clinical Features • Squamous cell component: Oval to polyhedral orangeophilic cells with hyperchromatic nuclei.

• Mainly asymptomatic and incidentally detected. • Occasionally vague pain abdomen.

11.3 Neuroendocrine Tumours

11.3.3  Key Cytological Features [2, 3] (Figs. 11.6 and 11.7)

11.3.1  Epidemiology • Neuroendocrine tumours (NET) of the gall bladder is very uncommon. • Only 0.2% of all NET occurs in the gall bladder. • Females are commonly affected.

• Discrete and occasional loose clusters. • Cells are round with often reddish granularity in the cytoplasm. • Nuclei are predominantly monomorphic. • Salt and pepper chromatin.

314

11.3.3.1 Immunocytochemistry Positive: Chromogranin, synaptophysin and CD56.

11.3.4  Neuroendocrine Carcinoma These are extremely uncommon tumours in the gall bladder. The tumour may be: • Small cell neuroendocrine carcinoma. • Large cell neuroendocrine carcinoma.

11.3.5  Small Cell Neuroendocrine Carcinoma 11.3.5.1 Key Cytological Features • Abundant cellularity. • Frequent crushing artefact. • The small discrete cells. • Cells with scanty cytoplasm. • High N:C ratio. • Hyperchromatic nuclei. • Nuclear moulding present. 11.3.5.2 Immunocytochemistry • Positive: Chromogranin, synaptophysin and CD56.

11.3.6  Large Cell Neuroendocrine Carcinoma 11.3.6.1 Key Cytological Features • Hypercellular smear. • Discrete cells. • Large Cells with scanty cytoplasm. • Pleomorphic nucleus. • The nuclear chromatin is coarsely clumped. 11.3.6.2 Immunocytochemistry • Positive: Chromogranin, synaptophysin and CD56.

11.3.7  Pancreas The vast majority of the space-occupying lesions of the pancreas are malignant. The pancreas is rich in enzymes, and incisional biopsy may lead to serious complications. FNAC is a useful technique in the diagnosis of pancreatic lesions. FNAC is therefore preferable in pancreatic space-occupying lesions than any other diagnostic modalities. Indications of FNAC • For the confirmation of early malignancy or resectable malignant tumours. • To avoid unnecessary surgical intervention in case of benign tumours.

11  Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas

• To confirm the advanced unresectable malignant lesions. • To diagnose cystic lesions of the pancreas. Complications Most of the time, there are no severe complications. The overall complications are: Minor complications • Pain abdomen. • Minor haemorrhage. Major complications • Pancreatitis may rarely occur. • Severe bleeding and death. Contraindications • Bleeding diathesis. • Anticoagulant therapy. • If there is any obstruction in the upper gastrointestinal tract, then EUS-FNAC is not possible.

11.3.8  Sampling Technique The following sampling techniques are used to procure material from the pancreatic lesions: 1 . USG guidance: Rapid and easiest technique. 2. CT scan guidance: Small lesions are well visualized. 3. Endoscopic USG guidance (EUS-FNAC): Gaining popularity as it can detect the smaller lesions accurately, without radiation hazards and higher sensitivity. 4. Pancreatic brush by Endoscopic retrograde cholangiopancreatography (ERCP): This technique is useful in the lesions located in the duct of the pancreas. 5. Biliary duct brushing.

11.3.9  Diagnostic Accuracy [4–7] • Due to better sophisticated technical modality, the diagnostic sensitivity of FNAC of pancreas increased from 75% to 95%. • The specificity of FNAC of the pancreas is now as high as 98%. • Positive predictive value: Near about 100%.

11.4 N  ormal Anatomy and Histology of Pancreas The pancreas is a retroperitoneal organ. It extends from the C-shaped curves of the duodenum to the spleen. The pancreas lies behind the stomach and traverses transversely along the posterior abdominal wall.

11.4 Normal Anatomy and Histology of Pancreas

315

Anatomically the pancreas is divided into head, neck, body and tail. It also contains a small part known as a uncinated process, which extends from the inferior and lateral part of the pancreas.

11.4.1  Histology • Pancreas consists of exocrine (80%) and endocrine (20%) glands. • Exocrine part: –– Multiple lobules with bunches of acini. The lining of the acinar cells is made of triangular pyramid-shaped columnar cells. –– The acini drain into small ducts. The lining cells of the duct is cuboidal epithelial cells. –– The multiple smaller ducts join to form the larger ducts and subsequently form the main pancreatic duct. –– The exocrine pancreas liberates various pancreatic enzymes such as pancreatic amylase, pancreatic lipase, trypsinogen, chymotrypsinogen, procarboxypeptidase, elastase etc. • Endocrine part: –– Multiple spherical clusters of endocrine cells called “islets of Langerhans”. –– The cells are arranged as small nests. –– The cells contain endocrine granules within the cytoplasm. –– The pancreatic endocrine cells liberate various types of hormones, such as: α cells: Glucagon, β cells: Insulin, ð cells: Somatostatin, G cell: Gastrin. Enterochromaffin cells: 5-hydroxytryptamine. Pancreatic polypeptide cells: Pancreaticpolypeptide.

11.4.2  Cytology 11.4.2.1 Pancreatic Acinar Cells (Fig. 11.8) • Cells arranged as acini. • Abundant cytoplasm. • Ill-defined cytoplasmic margin. • Small monomorphic nuclei. • Nuclear chromatin bland with inconspicuous nucleoli. 11.4.2.2 Pancreatic Ductal Cells (Fig. 11.9) • Cohesive groups of cells. • Round cells, scanty cytoplasm. • Well-defined cell borders. • Monomorphic small nuclei. • Tiny nucleoli.

Fig. 11.8  Normal acini: The acinar cells have abundant cytoplasm and small monomorphic nuclei

Fig. 11.9  Pancreatic ductal cells: Small round to oval monomorphic cells

11.4.3  Cysts in Pancreas [8] Pancreatic cystic lesions may be congenital or acquired.

11.4.4  Congenital Cyst Congenital pancreatic cysts are rare. FNAC yields clear fluid. Cytology smear • Scanty cellularity. • Occasional clusters of benign columnar cells.

316

11  Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas

11.5 Acquired Cyst

Pancreatic cyst

11.5.1  Pancreatic Pseudocyst Aetiology • Acute pancreatitis. • Trauma at the time of operation, • Reflux of bile from the bile duct to the pancreas. The bile damages the pancreatic cells and may cause leakage of the pancreatic enzymes causing tissue destruction. It may further produce cyst formation. Clinical Feature • Abdominal pain. • Jaundice.

Non-neoplastic cyst

High • Amylase • Lipase

Neoplastic cyst

• • • •

High Cell CEA CA19.9 CA125

Fig. 11.10  Types of pancreatic cyst

Key Cytological Features • FNAC yields straw-coloured fluid. • Often tinged with blood. • Many foamy histiocytes. • Polymorphs and lymphocytes. • The complete absence of epithelial cells is a characteristic findings. • The high content of amylase. • Low level of carcinoembryonic antigen.

11.6 Pancreatic True Cyst • Very rare. • Cytology smears show occasional cuboidal or columnar cells. Fig. 11.11  Acute pancreatitis: Abundant neutrophils

11.6.1  Differential Diagnosis

• Degenerated acinar and ductal cells. • Ductal cells may show nuclear pleomorphism that may • The neoplastic cyst can be distinguished with non-­ simulate malignant cells. neoplastic pseudocyst based on cellularity, and the bio- • Calcified material and necrotic fat. chemical nature (Fig. 11.10).

11.6.2  Pancreatitis FNAC is not indicated in acute pancreatitis. In a clinically known case, one should avoid FNAC.

11.6.3  Key Cytology Features (Fig. 11.11) • Degenerated and necrotic material. • Many neutrophils. • Histiocytes.

11.7 Chronic Pancreatitis It is a sequela of acute pancreatitis. It may often simulate as a malignant tumour in the radiology.

11.7.1  Key Cytology Features • • • •

Scanty cellularity. Both polymorphs and lymphocytes. Occasional clusters of pancreatic duct cells. Minimal nuclear pleomorphism in the ductal cells.

11.9 Mucinous Cystic Neoplasia

317

11.7.2  Differential Diagnosis

11.8.3  Key Cytology Features

• Adenocarcinoma: The degree of nuclear atypia and the number of such cells are more in adenocarcinoma.

• • • • •

11.8 Neoplasms of Pancreas

Immunocytochemistry: Positive for CK7 and CK19.

World Health Organization (WHO) classified the tumours of pancreas [9] predominantly into three groups (Fig. 11.12): • Benign epithelial neoplasms and precursors. • Malignant epithelial neoplasms. • Neuroendocrine tumours of the pancreas.

11.8.1  Serous Cystadenoma Serous cystadenoma is a benign tumour of the pancreas. Epidemiology • One percent of all the tumours of the pancreas. • Female are affected three times more than male. • Mean age: 58 years.

11.8.2  Clinical Features • Pain abdomen, nausea and vomiting. • Radiology detects incidental cystic mass in the pancreas. • CT scan and USG: Multiloculated cyst.

Fig. 11.12 WHO classification of pancreatic neoplasm

FNAC yields clear fluid. Occasional clusters or sheets of cells. Round to polygonal-shaped cells. Monomorphic nuclei, fine chromatin Nucleoli absent.

11.9 Mucinous Cystic Neoplasia [10, 11] Mucinous cystic neoplasia (MCN) is a benign mucin-­ producing tumour of the pancreas. The neoplasm is classified on histopathology as benign, borderline or invasive depending on: • • • • •

Multilayering of the epithelium. Presence of papillae. Stromal invasion. Nuclear enlargement. Nuclear pleomorphism.

11.9.1  Epidemiology • It represents 5 to 8% of all pancreatic tumours. • Mainly occur in female (more than 90%). • Mean age: 50 years.

318

11  Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas

11.9.2  Clinical Features • Mainly asymptomatic and incidentally detected. • A large cyst may show features of compression to an adjacent structure. • Pain abdomen. • Palpable mass. • Mainly seen in the body and tail parts. • CT scan: Thick-walled multiloculated cyst.

11.9.3  Key Cytology Features (Figs. 11.13, 11.14, and 11.15) Predominant pattern: Scattered cells in pools of mucin Fig. 11.15  Mucinous neoplasm of the pancreas: Higher magnification showing round-to-oval epithelial cells with mild pleomorphism

• FNAC yields mucinous material. • The tumour cells are present as sheets or singly scattered. • Round to columnar cells. • Vacuolated cytoplasm. • Eccentric nuclei. • Mild-to-moderate pleomorphic nuclei in borderline and invasive tumours. • Mucinous adenocarcinoma: –– Three-dimensional clusters of tumour cells. –– Enlarged nuclei. –– Moderate nuclear pleomorphism. –– Irregular nuclear margin. Fig. 11.13  Mucinous neoplasm of the pancreas: Loose clusters of tumour cells in the abundant mucinous background

11.9.4  Differential Diagnosis • Pseudocyst: No epithelial cells present.

11.10 Malignant Epithelial Neoplasms 11.10.1  Ductal Adenocarcinoma It is an invasive epithelial malignancy of pancreas that shows glandular differentiation.

11.10.2  Epidemiology

Fig. 11.14  Mucinous neoplasm of the pancreas: The tumour cells are floating in the mucin

• • • •

It represents 90% of all pancreatic neoplasms. Median age: 70 years. Predominantly seen in 60 to 80 years age. Males and females are equally affected.

11.10 Malignant Epithelial Neoplasms

319

11.10.3  Clinical Features • • • •

Triad of symptoms. Unexplained loss of weight. Abdominal pain. Jaundice.

Location: Near about two-third of cases in body and rest one-third cases in the tail of the pancreas. Aetiology • Cigarette smoking is strongly related to this carcinoma. • Alcohol intake. • Radiation and chemical exposure. • Diabetes mellitus. • Low-fibre diet with high meat content.

Fig. 11.17 Ductal adenocarcinoma: The tumour cells in a dirty necrotic background

11.10.4  Key Cytological Features [12, 13] (Figs. 11.16, 11.17, 11.18, 11.19, and 11.20) Predominant pattern: 3-D clusters of cells, glandular arrangement, microacinar structure, monolayered flat sheets of cells and scattered single cells. • The poorly differentiated carcinomas show more dispersed cell population. • Well-differentiated carcinoma shows micro-acini and “drunken honeycomb” appearance of the cells with occasional disarranged cells. • Individual cells are round with variable nuclear pleomorphism. • The nuclear outline is irregular. • Prominent nucleoli.

Fig. 11.16  Ductal adenocarcinoma: Loose clusters of cells showing mild-to-moderate nuclear pleomorphism

Fig. 11.18  Ductal adenocarcinoma: Three-dimensional clusters of tumour cells

Fig. 11.19  Ductal adenocarcinoma: Moderately pleomorphic nuclei with nuclear overcrowding

320

11  Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas

11.11 Variants of Ductal Carcinoma 11.11.1  Adenosquamous Carcinoma [14] • It accounts for 2–4% of exocrine pancreatic malignancies. • At least 30% of the tumour component should contain squamous part.

11.11.2  Key Cytological Features

Fig. 11.20  Ductal adenocarcinoma: Individual cells show moderate nuclear enlargement and pleomorphism. The nuclear chromatin is fine with prominent nucleoli Table 11.1  Differential diagnosis of adenocarcinoma of pancreas Features Nuclear crowding and loss of polarity Microacini Nuclear margin Nucleoli Necrosis and mitosis CA19.9

Adenocarcinoma Yes

Chronic pancreatitis No

Abundant Irregular Prominent Frequent High

Almost nil Smooth Inconspicuous Both absent Low

• The smears show dual differentiation: Squamous and glandular. • Glandular differentiation: –– Gland-like arrangement. –– Cells with a moderate amount of vacuolated cytoplasm. –– Often signet ring type of cells. • Squamous differentiation. –– Polyhedral cells. –– Tadpole and fibre cells. –– Orangeophila in Papanicolaou’s smear. –– Many dyskaryotic cells. • The squamoid differentiation may be focal and so maybe missed in FNAC.

11.11.3  Signet Ring Carcinoma [15]

• No normal duct or acinar cells. • Absence of normal acinar and ductal cells.

• A rare variant of tumour.

Three Important Cytological Criteria 1. Nuclear pleomorphism. 2. Nuclear enlargement. 3. Nuclear contour irregularity.

11.11.4  Key Cytological Features

11.10.5  Differential Diagnosis Table 11.1 highlights the differential diagnosis of ductal adenocarcinoma of the pancreas. • Chronic pancreatitis: –– Absence of significant nuclear pleomorphism, regular nuclear margin and maintained nucleocytoplasmic ratio usually eliminate malignancy. • Normal pancreatic aspirate: Rarely well-differentiated adenocarcinoma may mimic normal cells.

• Many signet ring cells. • The background shows abundant mucin. Note: Possibility of metastatic signet ring carcinoma stomach should be eliminated.

11.11.5  Undifferentiated Carcinoma with Osteoclastic Giant Cell It is a very rare tumour. Key Cytological Features [16] • Many multinucleated tumour giant cells having 20–30 bland-looking nuclei.

11.14 Pancreatic Acinar Carcinoma

321

• Many large mononuclear tumour cells showing moderate nuclear atypia and multiple prominent nucleoli.

Immunocytochemistry • Positive: Alpha-1 antichymotrypsin, and alpha-1 antitrypsin. • Negative: Cytokeratin and carcinoembryonic antigen.

11.12 Anaplastic Carcinoma Synonyms: Pleomorphic carcinoma, sarcomatoid carcinoma or giant cell carcinoma.

11.12.1  Epidemiology

Fig. 11.22  Anaplastic carcinoma: Large multinucleated tumour giant cells

• 2.5% of all ductal carcinoma • Rare and aggressive tumour. • Usually occurs in aged males.

• Many markedly enlarged multinucleated giant cells are present. • Occasional gland-like structures.

• Clinical feature: Abdominal pain, weight loss.

Differential diagnosis: Malignant melanoma and pleomorphic sarcoma.

11.12.2  Key Cytological Features (Figs. 11.21 and 11.22)

11.13 Small Cell Carcinoma [17]

• • • •

Abundant cells. Background necrosis and polymorphs. Many scattered spindle-shaped cells. Large pleomorphic nuclei with many prominent nucleoli.

• A rare tumour. • Near about 1% of all pancreatic cancer.

11.13.1  Key Cytological Features (Figs. 11.23 and 11.24) • Discrete small round cells. • Thin rim of cytoplasm. • Hypechromatic nuclei. Note: It is necessary to eliminate the possibility of metastatic small cell carcinoma before the primary diagnosis of small cell carcinoma of the pancreas.

11.14 Pancreatic Acinar Carcinoma 11.14.1  Epidemiology

Fig. 11.21  Anaplastic carcinoma: The smears show many large pleomorphic cells

• It represents 1–2% of all pancreatic neoplasm. • The mean age: 60 years. • Males are more affected than female (Male:female is 2:1).

322

Fig. 11.23  Small cell carcinoma of the pancreas: Abundant dissociated small cells

Fig. 11.24  Small cell carcinoma of the pancreas: Oval-to-mildly elongated cells with scanty cytoplasm and hyperchromatic nuclei

11  Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas

Fig. 11.25  Acinar cell carcinoma: The loose clusters of tumour cells

Fig. 11.26  Acinar cell carcinoma: The acinar cells in a cluster

11.14.2  Clinical Features • Pain in the abdomen. • Weight loss. • Malaise and jaundice.

11.14.3  Key Cytological Features [18, 19] (Figs. 11.25, 11.26, 11.27, and 11.28) Predominant pattern: Loose clusters of acinar cells • • • •

FNAC smears are hypercellular. Multiple loosely cohesive clusters and discrete cells. The acinar arrangement is frequent. Large cell.

Fig. 11.27  Acinar cell carcinoma: The cells have enlarged nuclei with indistinct cytoplasmic margin

11.15 Solid Pseudopapillary Neoplasm of the Pancreas

Fig. 11.28 Acinar cell carcinoma: Tumor cells with a moderate amount of vacuolated cytoplasm and centrally placed mildly enlarged nuclei

• • • • •

323

Fig. 11.29  Solid pseudopapillary neoplasm of the pancreas: Abundant cells arranged in clusters and papillae

Polygonal in shape. Cytoplasm: Abundant and granular. Centrally placed nuclei. Monomorphic nucleus. Homogenously dark chromatin with prominent nucleoli.

11.14.4  Differential Diagnosis • Normal acinar cells: –– Normal acinar cells maintain the nucleocytoplasmic ratio with normal chromatin pattern. • Pancreatic endocrine tumour: –– Lack of frequent acinar pattern. –– The presence of rosette-like pattern. –– Characteristic granular chromatin.

11.15 S  olid Pseudopapillary Neoplasm of the Pancreas Solid pseudopapillary neoplasm (SPN) is a low-grade malignant tumour with uncertain histogenesis.

11.15.1  Epidemiology • It represents only 1–2% of pancreatic tumours. • All the patients are female. • Mean age 28 years.

11.15.2  Clinical Features • Incidentally detected.

Fig. 11.30  Solid pseudopapillary neoplasm of the pancreas: Papillary structure with a fibrovascular core. The papillae are lined by multilayered epithelial cells

• A large tumour may have abdominal pain and vague discomfort. • USG and CT scan: Multiloculated cystic swelling with solid components. • Most of the tumours are seen in the body and tail of the pancreas.

11.15.3  Key Cytological Features [20, 21] (Figs. 11.29, 11.30, 11.31, 11.32, 11.33, 11.34, and 11.35) Predominant pattern: Multiple papillae and discrete tumour cells with foamy macrophages. • Multiple papillary figures with the fibrovascular core. The papillae are lined by multilayered epithelial cells.

324

Fig. 11.31  Solid pseudopapillary neoplasm of the pancreas: The discrete round to oval tumour cells

Fig. 11.32  Solid pseudopapillary neoplasm of the pancreas: The higher magnification showing cells with oval nuclei having monomorphic nuclei and fine chromatin

11  Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas

Fig. 11.34  Solid pseudopapillary neoplasm of the pancreas: Many macrophages in the background

Fig. 11.35  Solid pseudopapillary neoplasm of the pancreas: Higher magnification of the showing tumour cells and large foamy macrophages

• The background shows many foamy macrophages. • The tumour cells are in small clusters, discrete and pseudorosette. • The tumour cells. –– Small and round cells. –– The cytoplasm is scanty to moderate. –– Round nuclei with eccentric position. –– Bland nuclear chromatin. –– Occasional prominent nucleoli. –– Nuclear infolding and grooves may be present in some cells. • Hyaline droplets or pink cytoplasmic inclusions are seen. The globules are PAS-positive and diastase resistant.

Fig. 11.33  Solid pseudopapillary neoplasm of the pancreas: The cells with nuclear convolution and grooving

Immunohistochemistry Positive: Beta-catenin, CD10, Amylase, NSE, CD56 and Alpha-1 antitrypsin. Negative: Chromogranin and Chymotrypsin.

11.16 Neuroendocrine Tumour

325

11.15.4  Differential Diagnosis • Neuroendocrine tumours: See below. • Papillary carcinoma: –– The morphology of the discrete tumour cells of SPN is different than papillary carcinoma.

11.15.5  Pancreaticoblastoma Pancreatoblastoma is a very rare tumour, and only a few hundred cases have been seen. Tumour mainly occurs in children. The median age is 4 years.

11.15.6  Key Cytological Features • Discrete and acinar arrangement of the cells. • Round to cuboidal cells with reddish granular cytoplasm. • Also, blastemal cells are present. These cells are small, round with scanty cytoplasm having a high nucleocytoplasmic ratio. • Cells with squamoid differentiation are seen. This feature helps to differentiate pancreatoblastoma from acinic cell tumour. Immunocytochemistry: alpha-1-antitrypsin.

CK,

NSE,

CEA

The non-functional NET bears the main bulk of the tumours (more than 60%). Location: Most common in body and tail region.

11.16.3  Key Cytological Features [22–24] (Figs. 11.36, 11.37, 11.38, 11.39, and 11.40) • The tumour cells are predominantly scattered and isolated. • Occasionally small clusters and rosette-like arrangement. • The tumour cells. –– Round shaped. –– Reddish granular cytoplasm. –– Central to eccentric nuclei mimicking plasma cells. –– Round and mildly pleomorphic. –– “Salt and pepper” like chromatin.

and

11.16 Neuroendocrine Tumour 11.16.1  Pancreatic Endocrine Tumour (Islet Cell Tumour of Pancreas) 11.16.1.1 Epidemiology • It represents 1–2% of all pancreatic tumours. • Male and female are equally affected. • Age range: 40 to 60 years. • Children are rarely affected.

Fig. 11.36  Neuroendocrine tumour of the pancreas: Abundant cells in loose clusters and discretely arranged

11.16.2  Clinical Features The symptoms depend on the type of the pancreatic endocrine tumour (PET). There are two types of pancreatic endocrine tumour (PET): • Functional type: The tumour cell secretes a large amount of hormone secretion, causing diarrhoea, pain abdomen etc. • Non-functional type: The tumours are mostly asymptomatic and are detected incidentally.

Fig. 11.37  Neuroendocrine tumour of the pancreas: The acinar-like arrangement of the cells

326

11  Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas

PET is graded on as grade I to III based on Ki67 index (Table 11.2). Immunocytochemistry (Fig. 11.41) Positive: Synaptophysin, Chromogranin, NSE, CD56. Negative: CK20 and CK7.

11.16.4  Differential Diagnosis Table 11.3 shows the differential diagnosis of a neuroendocrine tumour of the pancreas. • Solid and cystic papillary neoplasm: Fig. 11.38  Neuroendocrine tumour of the pancreas: Higher magnification showing acinar arrangement

Table 11.2  Grading of PET Grade I II III

Ki67 index Less than 2% 3–20% More than 20%

Fig. 11.39  Neuroendocrine tumour of the pancreas: Many discrete monomorphic tumour cells

Fig. 11.41  Neuroendocrine tumour of the pancreas: The tumour cells are positive for chromogranin

Table 11.3 Differential diagnosis of pancreatic neuroendocrine tumour versus well-differentiated adenocarcinoma

Fig. 11.40  Neuroendocrine tumour of the pancreas: Higher magnification showing monomorphic nuclei having salt and pepper chromatin

Pancreatic neuroendocrine tumour Usually, the cells are discrete Cytoplasmic reddish granularity present A moderate amount of cytoplasm Relatively monomorphic nuclei Salt and pepper chromatin Positive: Chromogranin and synaptophysin

Pancreatic well-differentiated adenocarcinoma The cells are in small clusters Cytoplasmic vacuolations Scanty amount of cytoplasm Moderate nuclear pleomorphism Irregular coarse chromatin Negative for Chromogranin and synaptophysin

References

–– Young female, and cystic-solid component in radiology. –– Papillary structures. –– Foamy macrophages. • Well-differentiated adenocarcinoma: Points favouring carcinoma are: –– Cells are mainly arranged in clusters. –– Relatively more pleomorphic. –– Chromatin is usually coarse. –– Prominent nucleoli.

11.17 Metastatic Tumours in the Pancreas Incidence: Metastatic tumour in pancreas constitutes only 10 to 15% of pancreatic carcinomas. Common primary sites: Lung, breast and kidney.

11.17.1  Detection • Proper clinical history of the primary tumour. • Comparison with the primary tumour. • Immunocytochemistry in doubtful cases. –– Lung: TTF1. –– Breast: GATA3 and GCDFP. –– Kidney: CD10, PAX8 and RCC.

11.18 Pancreatic Lymphoma [25] (Fig. 11.42) Primary lymphoma of the pancreas is rare. It represents 0.5% of all pancreatic neoplasms. Type of lymphoma: MALTOMA, DLBCL, SLL and follicular lymphoma.

Fig. 11.42  Discrete large immature lymphoid cells with lymphoglandular bodies in a case of diffuse large B cell lymphoma of the pancreas

327

References 1. Klimstara DS, Lam AL, Paradis V, Schimacher P. Tumours of gall bladder and Extrahepatic bile ducts. In: World Health Organization classification of Tumours. Pathology and genetics of Tumours of the digestive system. 5th ed. Lyon: IARCPress; 2019. 2. Kumar R, Srinivasan R, Gupta N, et  al. Spectrum of gallbladder malignancies on fine-needle aspiration cytology: 5 years retrospective single institutional study with emphasis on uncommon variants. Diagn Cytopathol. 2017;45(1):36–42. 3. Yadav R, Jain D, Mathur SR, Iyer VK.  Cytomorphology of neuroendocrine tumours of the gallbladder. Cytopathology. 2016;27(2):97–102. 4. Afify AM, Al-Khafaji BM, Kim B, Scheiman JM.  Endoscopic ultrasound-­guided fine needle aspiration of the pancreas. Diagnostic utility and accuracy. Acta Cytol. 2003;47(3):341–8. 5. Di Stasi M, Lencioni R, Solmi L, et al. Ultrasound-guided fine needle biopsy of pancreatic masses: results of a multicenter study. Am J Gastroenterol. 1998;93(8):1329–33. 6. Lerma E, Musulen E, Cuatrecasas M, Martinez A, Montserrat E, Prat J.  Fine needle aspiration cytology in pancreatic pathology. Acta Cytol. 1996;40(4):683–6. 7. Dey P, Radhika S, Rajwanshi A, Kochhar S. Fine needle aspiration biopsy of pancreas. Indian J Pathol Microbiol. 1994;37(3):269–74. 8. Centeno BA, Warshaw AL, Mayo-Smith W, Southern JF, Lewandrowski K. Cytologic diagnosis of pancreatic cystic lesions. A prospective study of 28 percutaneous aspirates. Acta Cytol. 1997;41(4):972–80. 9. Gill AJ, Klimstara DS, Lam AK, Washington MK. Tumours of pancreas. In: World Health Organization classification of Tumours. Pathology and genetics of Tumours of the digestive system. 5th ed. Lyon: IARCPress; 2019. 10. Dodd LG, Farrell TA, Layfield LJ. Mucinous cystic tumor of the pancreas: an analysis of FNA characteristics with an emphasis on the spectrum of malignancy associated features. Diagn Cytopathol. 1995;12(2):113–9. 11. Gupta RK, Scally J, Stewart RJ. Mucinous cystadenocarcinoma of the pancreas: diagnosis by fine-needle aspiration cytology. Diagn Cytopathol. 1989;5(4):408–11. 12. Lin F, Staerkel G. Cytologic criteria for well differentiated adenocarcinoma of the pancreas in fine-needle aspiration biopsy specimens. Cancer. 2003;99(1):44–50. 13. Cohen MB, Egerter DP, Holly EA, Ahn DK, Miller TR. Pancreatic adenocarcinoma: regression analysis to identify improved cytologic criteria. Diagn Cytopathol. 1991;7(4):341–5. 14. Lozano MD, Panizo A, Sola IJ, Pardo-Mindán FJ.  FNAC guided by computed tomography in the diagnosis of primary pancreatic adenosquamous carcinoma. A report of three cases. Acta Cytol. 1998;42(6):1451–4. 15. El Hussein S, Khader SN. Primary signet ring cell carcinoma of the pancreas: cytopathology review of a rare entity. Diagn Cytopathol. 2019;47(12):1314–20. 16. Shiihara M, Higuchi R, Izumo W, Furukawa T, Yamamoto M.  A comparison of the pathological types of undifferentiated carcinoma of the pancreas. Pancreas. 2020;49(2):230–5. 17. Sannomiya H, Okamoto T, Ryu S, et  al. Gan To Kagaku Ryoho. 2019;46(13):2312–4. 18. Villanueva RR, Nguyen-Ho P, Nguyen GK.  Needle aspiration cytology of acinar-cell carcinoma of the pancreas: report of a case with diagnostic pitfalls and unusual ultrastructural findings. Diagn Cytopathol. 1994;10(4):362–4. 19. Klimstra DS, Heffess CS, Oertel JE, Rosai J. Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases. Am J Surg Pathol. 1992;16(9):815–37. 20. Pettinato G, Di Vizio D, Manivel JC, Pambuccian SE, Somma P, Insabato L.  Solid-pseudopapillary tumor of the pancreas: a neoplasm with distinct and highly characteristic cytological features. Diagn Cytopathol. 2002;27(6):325–34.

328 21. Singh P, Kumar P, Rohilla M, et al. Fine needle aspiration cytology with the aid of immunochemistry on cell block confirms the diagnosis of solid pseudopapillary neoplasm of the pancreas [published online ahead of print, 2020 Apr 22]. Cytopathology. 2020; https:// doi.org/10.1111/cyt.12838. 22. Gu M, Ghafari S, Lin F, Ramzy I.  Cytological diagnosis of endocrine tumors of the pancreas by endoscopic ultrasoundguided fine-­ needle aspiration biopsy. Diagn Cytopathol. 2005;32(4):204–10.

11  Fine Needle Aspiration Cytology of the Gall Bladder and Pancreas 23. Collins BT, Cramer HM.  Fine-needle aspiration cytology of islet cell tumors. Diagn Cytopathol. 1996;15(1):37–45. 24. Jimenez-Heffernan JA, Vicandi B, Lopez-Ferrer P, Gonzalez-­ Peramato P, Perez-Campos A, Viguer JM.  Fine needle aspiration cytology of endocrine neoplasms of the pancreas. Morphologic and immunocytochemical findings in 20 cases. Acta Cytol. 2004;48(3):295–301. 25. Alzerwi NAN. Primary pancreatic lymphoma masquerading as carcinoma. Case Rep Oncol Med. 2020;2020:5160545.

Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

12

In modern times various modern radiological techniques are 12.1 Normal Cells available to diagnose the renal space-occupying lesions. Fine needle aspiration cytology is used in only those cases which 12.1.1  Renal Tubular Cells (Fig. 12.1) are indeterminate in the radiology and advanced non-­ resectable malignancies. The renal tubular cells are the predominant cell population in FNAC of a normal kidney. Indications of FNAC The cytological appearance: • Diagnosing indeterminate cases on radiology. • In surgically non-resectable cases of renal cell • Loose aggregates of round cells. • A moderate amount of granular cytoplasm. carcinoma. • Monomorphic nucleus. • Metastatic tumours in the kidney. • Bland chromatin with a small nucleoli. • The kidney lesions that may need partial nephrectomy. • Infective lesions in kidney. • The malignancies where nephrectomy is not indicated 12.1.2  Glomeruli such as lymphoma. • Therapeutic drainage of cyst fluid. • Densely packed cells. • The round to ovoid clusters of cells. Complications [1] • Minor haemorrhage and hematoma formation. • Haematuria. • Mild pain. • Abscess formation. Diagnostic Accuracy [2–4] The diagnostic accuracy of FNAC of the kidney is high. • The sensitivity of FNAC is 75 to 90%. • Specificity is near about 98%. • False-negative cases are low. The leading cause of false negativity is the sampling error in sub-centimetre lesion. • False positivity is mainly due to misinterpretation of normal kidney tubular cells as well-differentiated renal cell carcinoma (RCC). At times adrenocortical cells and hepatocytes may also be mistaken as RCC. Fig. 12.1  Loose cluster of cells with abundant cytoplasm and monomorphic nuclei having small nucleoli

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_12

329

330

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

• Small round cells. • The cytoplasm is less in amount. • Often encased by thin blood capillaries.

12.2.3.1 Differential Diagnosis • Renal cell carcinoma: Cystic RCC may be mistaken as benign renal.

Endothelial cells: Elongated cells scattered in the background.

12.3 Xanthogranulomatous Inflammation

12.2 Renal Cyst 12.2.1  Occurrence • Renal cysts are the commonest space-occupying lesions in the kidney. • It comprises 80% of the renal lesions.

Xanthogranulomatous inflammation is a chronic inflammatory lesion of the kidney caused by Escherichia coli, Pseudomonas and Proteus.

12.3.1  Clinical Features

12.2.2  Clinical Features

• • • •

• Incidental detection at the time of investigation of some other lesions. • USG shows the cystic structure. • FNAC is rarely indicated for diagnosis.

12.3.2  Key Cytological Features (Figs. 12.3 and 12.4)

12.2.3  Key Cytological Features (Fig. 12.2) • • • • • •

FNAC yields velar fluid. The smears are hypocellular. Scattered foamy histiocytes with monomorphic nuclei. The histiocytes often contain hemosiderin pigments. Ill preserved renal tubular epithelial cells. Scant inflammatory cells.

Fig. 12.2  Renal cyst: Many foamy histiocytes and inflammatory cells

• • • •

Renal pain. Haematuria. Repeated urinary tract infection. USG or intravenous pyelography show space-occupying lesion in the kidney and often simulate RCC.

Abundant lymphocytes and histiocytes. Necrotic tissue. Multinucleated giant cells. Large foamy histiocytes having abundant cytoplasm, centrally located nucleus and single prominent nucleolus. The nucleocytoplasmic ratio of the cell is low.

Fig. 12.3  Xanthogranulomatous inflammation: Many foamy histiocytes and lymphocytes

12.4 Benign Tumours of the Kidney

331

12.3.3  Differential Diagnosis

12.4 Benign Tumours of the Kidney

• Renal cell carcinoma (RCC): Histiocytes may mimic the cells of RCC. Nuclear morphology is helpful in the correct diagnosis.

12.4.1  Angiomyolipoma

12.3.4  Renal Tumours Figure 12.5 highlights the summary of the WHO classification of kidney tumours [5].

Angiomyolipoma (AML) is a benign tumour of the kidney. It belongs to the group of perivascular epithelioid cell tumour (PEComa).

12.4.2  Epidemiology • AML represents 1% of all renal neoplasms. • AML occurs four times more frequent in females.

12.4.3  Clinical Features • Patients with tuberous sclerosis are asymptomatic. • Patients without tuberous sclerosis usually present with large mass and complaint of haematuria, and renal pain. • USG or CT scan is always diagnostic as they indicate a large amount of fat admixed with blood vessels and muscle.

12.4.4  Key Cytological Features [6, 7] (Figs. 12.6, 12.7, 12.8, 12.9, and 12.10) Fig. 12.4  Xanthogranulomatous inflammation: Occasional multinucleated giant cell and foamy histiocytes

Predominant pattern: Abundant cellularity with three types of tissue components: mature adipose tissue, blood vessels and smooth muscle.

Renal tumour

Renal cell tumours • Clear cell renal cell carcinoma • Multilocular clear cell renal cell carcinoma • Papillary renal cell carcinoma • Chromophoberenal cell carcinoma • Carcinoma of the collecting ducts of Bellini • Renal medullary carcinoma • Xp11 translocation carcinomas • Carcinoma associated with neuroblastoma • Mucinous tubular and spindle cell carcinoma • Renal cell carcinoma, unclassified • Papillary adenoma • Oncocytoma • Papillary adenoma

Fig. 12.5  WHO classification of renal tumours

Metanephric tumours • Metanephric adenoma • Metanephric adenofibroma • Metanephric stromal tumor

Mesenchymal tumours in children

Mesenchymal tumours in adult

• Clear cell sarcoma • Rhabdoid tumor • Congenital mesoblastic nephroma

• Leiomyosarcoma • Angiosarcoma • Angiomyolipoma

Nephroblastic tumour of children

Neuroendocrine tumour

• Nephroblastoma • Cystic partially differentiated nephroblastoma • Pediatric cystic nephroma

• Carcinoid • Neuroblastoma Pheochromocytoma

Miscellaneous tumour Metastatic tumour

332

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

Fig. 12.6  Angiomyolipoma: Large cluster of the oval to spindle cells

Fig. 12.9 Angiomyolipoma: Round to oval cells with moderate nuclear pleomorphism

Fig. 12.7  Angiomyolipoma: Spindle cells having elongated nuclei

Fig. 12.10  Angiomyolipoma: Cell block section showing vascular channels and smooth muscle cells

• Multiple capillary channels admixed with fat. • The cells of the adipose tissue are benign in appearance. • There are numerous syncytial like collection and discrete smooth muscle with a moderate amount of fibrillary cytoplasm. • Oval to spindle-shaped nucleus having fine chromatin and prominent nucleolus. • The nuclei may show significant pleomorphism.

12.4.5  Immunocytochemistry (Figs. 12.11 and 12.12)

Fig. 12.8  Angiomyolipoma: Cluster of round to oval cells

Positive: HMB-45, Melan A and SMA. Negative: CD10, PAX8 and RCC.

12.6 Renal Oncocytoma

333

–– Bland nuclear chromatin, admixed fat, capillaries and smooth muscle cells favour AML. –– Radiological findings are helpful in this aspect. Table 12.1 highlights the differential diagnosis between AML and renal cell carcinoma.

12.5 Metanephric Adenoma Metanephric adenoma (MA) is an uncommon benign tumour.

12.5.1  Epidemiology Fig. 12.11  Angiomyolipoma: HMB45 positive tumour cells

• Only a few hundred tumours are reported. • Median age: 50 years. • Common in females.

12.5.2  Clinical Features • • • • •

Often asymptomatic and incidentally detected. Renal pain. Haematuria. Abdominal mass. Polycythemia.

12.5.3  Key Cytological Features [8]

Fig. 12.12  Angiomyolipoma: SMA positive cells

Table 12.1  The differential diagnosis between angiomyolipoma and renal cell carcinoma Angiomyolipoma Radiological evidence of significant components of fat Atypical cells are accompanied with capillaries, smooth muscle fragments and fat Positive: HMB 45, SMA AND Melan A

Renal cell carcinoma No fat component on radiology Large cells with an enlarged nucleus and prominent nucleolus Positive: CD10, PAX8, RCC

• Multiple papillary clusters and loose clusters of tumour cells. • Small round cells. • Scanty cytoplasm. • Round monomorphic nucleus. • Fine nuclear chromatin. • Absent nucleoli.

12.5.4  Differential Diagnosis

12.4.6  Differential Diagnosis

• Renal cell carcinoma: Papillary RCC may simulate mesonephric adenoma. The cells in RCC are large and pleomorphic. • Wilms’ tumour: Wilms’ tumour shows blastemal and epithelial cells.

Table 12.1 highlights the differential diagnosis between AML and renal cell carcinoma.

12.6 Renal Oncocytoma [9]

• Renal cell carcinoma:

It is a benign epithelial tumour of the kidney.

334

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

12.6.1  Epidemiology • It represents 5% of kidney tumours. • Age range: 25–90 years. • Males are twice more affected than females.

12.6.2  Clinical Features • Usually asymptomatic. • Occasionally renal pain, haematuria and dysuria. • CT scan/USG: Non-specific, however, often shows a stellate scar.

12.6.3  Key Cytological Features (Figs. 12.13 and 12.14)

Fig. 12.14  Oncocytoma: Cells showing abundant cytoplasm with central monomorphic nuclei

Predominant pattern: Abundant discrete oncocytes • • • • • • • • • • •

Abundant cellularity. Loose clusters, discrete and sheets of cells. Nest-like cluster in the cell block section. Polygonal-shaped cells. Well-defined cytoplasmic margin. Abundant granular cytoplasm. Central round nuclei. Cells are often binucleated. Nucleoli are prominent. No mitotic activity is noted. Absence of necrosis.

• Hepatocytes: Rarely hepatocytes may simulate oncocytes when the right kidney is aspirated.

12.7 Renal Cell Carcinoma [ 10–13] RCC is the most frequent malignant tumour of the kidney.

12.7.1  Epidemiology 12.6.4  Differential Diagnosis (Fig. 12.15) • Renal cell carcinoma (RCC): Papillary structures and nuclear atypia favours RCC.

• • • • •

It accounts for 2% carcinoma of the body. Near about 90% of malignant renal tumours. Male:female ratio is 2:1. Commonly occurs in elderly males over 50 years. Uncommonly the children may be affected.

Association: RCC is often associated with cigarette smoking, obesity, hypertension, occupational exposure to trichloroethylene, acquired cystic disease.

12.7.2  Clinical Features • The patients commonly present with: –– Renal pain, haematuria and a palpable mass in the abdomen. –– Occasionally the patients may have weight loss and fever. Fig. 12.13  Oncocytoma: Abundant discrete oval to polygonal cells with well-defined cytoplasmic border

Immunocytochemistry and molecular cytogenetics are highlighted in Table 12.2.

12.7 Renal Cell Carcinoma

335

Reddish granular cytoplasm

Polyhedral cell with well defined margin

Oncocytoma

Well differentiated hepatocellular carcinoma

Large cells with vacuolated cytoplasm. Nuclei are moderately plemorphic

Renal cell carcinoma

Fig. 12.15  Differential diagnosis of oncocytoma Table 12.2  Molecular cytogenetics and immunocytochemistry of the various types of renal cell carcinoma Type Clear cell carcinoma

Frequency 70%

Papillary renal carcinoma

15%

Chromophobe renal carcinoma

5%

Collecting duct carcinoma

1%

Xp11 translocation RCC

Very rare

Immunocytochemistry RCC+ CD10+ CK7+ CD10+ CD117+ CK7+ CK7+ P63+ RCC+ CD10+ CK7-

12.7.3  Key Cytological Features (Figs. 12.16, 12.17, 12.18, 12.19, and 12.20) 12.7.3.1 Clear Cell RCC • High cellularity. • Large clusters and occasionally discrete.

Cytogenetics abnormality del 3p • Triosomies of chromosomes 3q, 7, 12, 16, 17 and 20. • Loss of Y. Multiple losses of chromosomes 1, 2, 6, 10, 13, 17 and 21 Deletions 1q,6p,8p,13q,21q t(X;1)(p11.2;q22) Or t(X;17) (p11.2;q22)

• Tumour cells. –– Well-defined cytoplasmic margin. –– Abundant clear cytoplasm. –– Centrally located round nucleus. –– Mild-to-moderately enlarged nuclei depending on the tumour grade.

336

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

Fig. 12.16  Renal cell carcinoma: Multiple papillary clusters and discrete cells

Fig. 12.19  Renal cell carcinoma: Nuclei are enlarged with increased nucleo-cytoplasmic ratio

Fig. 12.17  Renal cell carcinoma: the cells with abundant cytoplasm having eccentric nuclei

Fig. 12.20  Renal cell carcinoma: Haematoxylin eosin-stained smear showing cells with eccentric nuclei. The nuclear chromatin is fine with occasional prominent nucleoli

–– Frequent binucleated cells. –– The nuclear chromatin is coarse. –– Prominent nucleoli.

12.7.4  Immunocytochemistry (Figs. 12.21 and 12.22) Positive: CD10, RCC and EMA. Negative: CK7 and CD117.

12.7.5  Differential Diagnosis Fig. 12.18  Renal cell carcinoma: The nuclei are pleomorphic with prominent nucleoli

The differential diagnosis of RCC is highlighted in Table 12.3.

12.8 Chromophobe Type

337

–– Smaller cuboidal cells: Scanty cytoplasm, round regular nucleus, bland chromatin, inconspicuous nucleoli. Occasional nuclear grooving present. –– Large cells: Abundant granular cytoplasm, enlarged pleomorphic nucleus, multiple prominent nucleoli. • Psammoma bodies are occasionally present. Immunocytochemistry Positive: CK7, CD10. Negative: RCC, CD117.

12.8 Chromophobe Type

Fig. 12.21  Renal cell carcinoma: Tumour cells are positive for PAX8

• • • •

Hypercellular smear. Small clusters and dissociated cells. Tumour cells: Two types. Large cells –– Polyhedral cells. –– Abundant pale, granular cytoplasm. –– Cytoplasmic margin is well defined. –– Enlarged nuclei. –– Wrinkled nuclear margin. –– Moderate nuclear pleomorphism. Small cells

• • • •

Fig. 12.22  Renal cell carcinoma: Membranous positivity of CD10 Table 12.3  The differential diagnosis of renal cell carcinoma Renal cell carcinoma Radiology often helpful to locate the mass in the kidney Clinically no Cushing’s syndrome Predominantly tight clusters, papillary and discrete cells Relatively clean background Positive: Keratin AE1 and AE3, EMA Vimentin, CD10 and PAX8 Negative: Mela A, Inhibin alpha and calretinin

Adrenocortical carcinoma The mass may have clear demarcation from kidney Clinically Cushing’s syndrome may be present Mainly discrete and loose groups of cells Vacuolated fatty background Positive: Mela A, Inhibin alpha and calretinin Negative: AE1 and AE3, EMA Vimentin, CD10 and PAX8

Small cells. Scanty granular cytoplasm. Enlarged round nuclei. Pleomorphism is marked.

Immunocytochemistry Positive: EMA, CK7 and CD117. Negative: RCC.

12.8.1  Sarcomatoid Type • Mainly cohesive groups and dissociated cells. • The cells are spindle shaped. • Nuclei are elongated spindle shaped with moderately pleomorphic, irregular contour and prominent nucleoli. • Also, there are large cells with abundant clear cytoplasm. • Necrotic background. • Occasionally smear may show cartilaginous or osteoid material.

12.7.6  Papillary Carcinoma • Multiple papillae and large clusters of cells. • Many foamy histiocytes that often contain hemosiderin pigment. • The two types of tumour cells:

12.8.2  Collecting Duct Type • Papillary clusters and single discrete cells. • Relatively large cells. • A moderate amount of eosinophilic cytoplasm.

338

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

• Enlarged pleomorphic and hyperchromatic nucleus. • Large prominent nucleolus. Immunocytochemistry: Positive: PAX8, p63 and CK7.

12.8.3  Differential Diagnosis of RCC • Normal renal tubular cells: –– Enlarged nuclei, high nucleocytoplasmic ratio and prominent nucleoli indicate RCC. • Hepatocytes: Polygonal cells with bile pigments in the cytoplasm of the hepatocytes. • Angiomyolipoma: Radiological features, mature adipose tissue, smooth muscle cells and HMB45 positive cells. • Xanthogranulomatous pyelonephritis: Discussed before. • Adrenal tumour: Adrenocortical tumours are positive for Melan A, alpha Inhibin and calretinin.

Fig. 12.23  Urothelial carcinoma: Small clusters of cells with the columnar appearance and peripherally placed nuclei

12.9 Urothelial Carcinoma 12.9.1  Epidemiology • It accounts for 7% of all renal malignancy. • Males are commonly affected. • Age: Common in the seventh decade. Association: Men working in the dye industry particularly benzidine and naphthyl amine.

12.9.2  Clinical Features • painless haematuria, • Renal pain. • Abdominal mass in occasional cases (10%).

Fig. 12.24 Urothelial carcinoma: The cells showing a moderate amount of cytoplasm and moderately pleomorphic nuclei

12.9.3  Key Cytological Features (Figs. 12.23, 12.24, and 12.25) Predominant pattern: Abundant discrete cells and papillary clusters • Discrete, multiple tight groups and papillary arrangement of cells. • Columnar to polygonal cells. • Well-defined cytoplasmic margin. • Dense homogenous cytoplasm. • Enlarge nuclei with a high nucleocytoplasmic ratio. • Moderate to marked pleomorphic nuclei depending on the grade of the tumours. • Large prominent nucleoli in high-grade tumour. • Cercariform cells with a long thin tail like cytoplasm.

Fig. 12.25  Urothelial carcinoma: Higher magnification showing elongated cells with round nuclei having high nucleocytoplasmic ratio

12.11 Paediatric Kidney Tumours

339

12.9.4  Differential Diagnosis

12.10 Metastatic Tumours in Kidney [14]

• Papillary RCC: It shows: –– Macrophages and occasionally psammoma bodies in RCC. –– Positive for RCC antigen and negative for CEA. • Reactive transitional cells: No nuclear pleomorphism and enlargement in benign transitional cells.

Metastasis in kidney constitutes only 7% of renal tumour. These tumours are mostly asymptomatic. Source: Breast, lung, stomach and opposite kidney. Indicators of metastasis:

12.9.5  Medullary Carcinoma

• Bilateral involvement of the kidney. • Medical history of a primary tumour in other organs. • Undifferentiated tumours that are difficult to classify.

12.9.6  Epidemiology

12.10.1  Diagnosis

• Rare tumour and only a few hundred cases have been published. • Male:female ratio is 2:1. • Predominantly occurs in second to third decade. • Associated with sickle cell haemoglobinopathy.

• FNAC smears of kidney lesion may be similar to the smear of the primary site. • Immunocytochemistry may be helpful. –– Lung: TTF1. –– Breast: GCDFP, ER/PR, GATA3. –– Intestine: CDX2.

12.9.7  Clinical Features

12.10.2  Renal Lymphoma

• Flank pain. • Haematuria. • Abdominal mass.

Primary lymphoma of the kidney is very uncommon, and the kidney is usually secondarily involved by lymphoma. Primary lymphoma of the kidney represents 3% of kidney lesions. The most frequent type of NHL of the kidney is diffuse large B cell lymphoma.

12.9.8  Key Cytological Features • The cells are in loose aggregates and dissociated. • Round cells with vacuolated cytoplasm. The vacuoles may be small and multiple or single and large. • Peripherally placed nuclei. • Irregular nuclear contour. • Moderately pleomorphic nuclei. • Nuclei are often grooved with prominent nucleoli. • associated with sickle cell trait. Immunocytochemistry Positive: PAX8, CK7 and CAM5.2.

12.9.9  Differential Diagnosis • Urothelial cell carcinoma: –– UCC often shows cercariform cells. • Renal cell carcinoma: –– Difficult to differentiate from medullary carcinoma. • Collecting duct carcinoma: –– Elderly patient. –– Positive for CK34.

12.11 Paediatric Kidney Tumours 12.11.1  Nephroblastoma Nephroblastoma is the malignant tumour of the kidney that originated from the blastemal cells. Synonym: Wilms’ tumour.

12.11.2  Epidemiology • Wilms’ tumour is the commonest childhood kidney tumour and accounts for 6% of all paediatric tumours. • Near about 90% of Wilms’ tumour occurs before 6 years of age. • 98% of Wilms’ tumour is seen before 10 years. • The highest number of Wilms’ tumour occurs in 2 to 5 year age period. Association: WAGR syndrome, Beckwith–Wiedemann syndrome and Drash syndrome.

340

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

Fig. 12.26  Wilms’ tumour: Abundant discrete blastemal cells

Fig. 12.28  Wilms’ tumour: Deep pink collagenous mesenchymal

Fig. 12.27  Wilms’ tumour: The blastemal cells with scanty cytoplasm and round mildly pleomorphic nuclei with fine chromatin

Fig. 12.29  Wilms’ tumour: Well circumscribed glomeruloid body

12.11.3  Clinical Features • • • • •

Large palpable mass in the abdomen detected by parents. Abdominal distension. Pain in the abdomen. Haematuria. Hypertension.

12.11.5  Blastemal Cells • Predominantly discrete cells. • Small round cells. • Thin rim of scanty bluish cytoplasm (on May–Grunwald– Giemsa smear). • Round nucleus. • Opened up chromatin. • Multiple nucleoli.

12.11.4  Key Cytological Features [15, 16] (Figs. 12.26, 12.27, 12.28, and 12.29)

12.11.6  Epithelial Cells

Predominant pattern: The smears show the three components of Wilms’ tumour consisting of immature round blastemal cells, occasional epithelial cells and fragments of mesenchymal cells.

• The epithelial cells are usually in numerous cohesive groups, tubules and “rosette-like” arrangement. • The cells are relatively large compared to blastemal cells. • A moderate amount of cytoplasm.

12.12 Congenital Mesoblastic Nephroma (CMN)

• • • •

341

Centrally placed nuclei. Fine chromatin. Prominent nucleolus. Tight, cohesive well-circumscribed cells resembling “glomeruloid like bodies”.

12.12 Congenital Mesoblastic Nephroma (CMN) CMN is a low-grade malignant fibrosarcoma of the kidney of the infant.

12.12.1  Epidemiology

12.11.7  Mesenchymal Cells • Clusters of spindle-shaped cells, embedded in the mesenchymal matrix material. • The cells with rhabdoid differentiation.

• It accounts for 3–4% of all childhood kidney tumours. • The commonest kidney tumours under 6 months.

12.12.2  Clinical Features 12.11.8  Anaplastic Wilms’ Tumour

• Large abdominal mass detected by the parents. • Haematuria.

• Many large pleomorphic cells. • Multinucleated cells. • Frequent mitotic activities.

12.12.3  Key Cytological Features [17] (Figs. 12.30, 12.31, and 12.32)

Immunocytochemistry Positive: Vimentin, desmin, cytokeratin and NSE.

Predominant pattern: Multiple fragments of small fascicles of spindle cells.

12.11.9  Differential Diagnosis

• Abundant cellularity. • Scanty cytoplasm, spindle-shaped nucleus.

• Neuroblastoma: –– Many rosettes with neurofibrillary material. –– The complete absence of mesenchymal cells in the FNAC smear. –– Immunocytochemistry: Chromogranin and synaptophysin positive cells. • Rhabdomyosarcoma: –– Many binucleated and multinucleated cells. –– Cell with cross striation. –– Immunocytochemistry: Positive for desmin. • A primitive neuroectodermal tumour (PNET): –– Small cells with vacuolated cytoplasm. –– Many rosettes with central neurophilic material. –– Immunocytochemistry: Positive: synaptophysin and Mic 2. Table 12.4 highlights the differential diagnosis of nephroblastoma.

Fig. 12.30  Mesoblastic nephroma: Clusters of spindle cells

Table 12.4  The differential diagnosis of nephroblastoma (Wilms’ tumour) Features Rosettes Tubules Mesenchymal cells Neurofibrillary material Strap cells CD99 Desmin Synaptophysin

Nephroblastoma (Wilms’ tumour) − + + − − N N P

+ = present, − = absent, N = negative, P = positive

Neuroblastoma + − − + − N N N

Rhabdomyosarcoma − − − − + N P N

Primitive neuroectodermal tumour + − − + − P N P

342

Fig. 12.31  Mesoblastic nephroma: Spindle cells arranged in small bundles

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

Fig. 12.33 Rhabdoid tumour: Discrete round cells with scanty cytoplasm

12.13.1  Epidemiology • • • •

It accounts for 2% of all childhood kidney tumour. Median age: 11 months. Rare after 3 years of age. Male:female ratio is 1.5:1.

12.13.2  Clinical Features • Haematuria. • Abdominal mass. • The patients may have posterior fossa tumour.

Fig. 12.32  Mesoblastic nephroma: Discrete oval to spindle cells

• Fine chromatin. • Absent nucleolus. Immunocytochemistry Positive: Vimentin and SMA.

12.12.4  Differential Diagnosis

12.13.3  Key Cytological Features (Figs. 12.33 and 12.34) • • • • • • •

Many discrete and also small aggregates of cells. Naked nuclei in the background. Large cells with a well-defined outline. Moderate to abundant cytoplasm. Large moderately pleomorphic nuclei. Vesicular chromatin with a single large nucleoli. Characteristic pinkish intracytoplasmic inclusions.

Immunocytochemistry: Positive: vimentin and EMA. Loss of INI1.

• Congenital fibrosarcoma: Nuclear atypia is significant.

12.13 Rhabdoid Tumor [18] Rhabdoid tumour of the kidney (RTK) is a highly fatal malignant renal tumour of the young child.

12.13.4  Differential Diagnosis • Rhabdoid differentiation of Wilms’ tumour: –– Here the cells show cytoplasmic striations. –– No intracytoplasmic inclusions.

12.14 Clear Cell Sarcoma

Fig. 12.34  Rhabdoid tumour: Tumour cells, along with many naked nuclei

343

Fig. 12.35  Clear cell sarcoma: Many discrete cells with abundant clear cytoplasm

12.14 Clear Cell Sarcoma Clear cell sarcoma (CCSK) is a rare malignant childhood renal tumour. Synonym: Bone metastasizing renal tumour of the childhood.

12.14.1  Epidemiology • • • •

It represents 3 to 6% of all childhood kidney tumours. Mean age: 3 years. The tumour occurs mainly in 2 to 3 years of age. Male: female ratio is 2:1.

12.14.2  Clinical Features • • • • •

Fig. 12.36  Clear cell sarcoma: Large cells with abundant clear cytoplasm and centrally placed nuclei with prominent nucleoli

Abdominal distension. Pain in the abdomen. Haematuria. Bone metastasis occurs in 20 to 40% of CCSK. Propensity of bony metastasis is almost ten times than other kidney tumours.

12.14.3  Key Cytological Features [19] (Figs. 12.35, 12.36, and 12.37) • Clusters, and scattered single cells. • Many capillary fragments with attached spindle-shaped septal cells. • Magenta coloured acellular material. • Cord cells. –– Large polyhedral cells.

Fig. 12.37  Clear cell sarcoma: Tumour cell with background pinkish stromal material

344

–– Abundant clear cytoplasm. –– Central nucleus. –– Frequent deep nuclear groove. –– Granular nuclear chromatin. –– Small nucleoli. • Septal cells. –– Spindle-shaped cells. –– Elongated spindly nuclei. –– Vesicular chromatin. –– Grooved nuclei. • Dark apoptotic cells.

Immunocytochemistry Positive: Vimentin, Bcl2 and cyclin D1. Negative: CD34, desmin and S100.

12.15 Adrenal Gland The adrenal gland is a rich source of metastasis from various primary malignancies. FNAC is an effective technique to detect various metastatic lesions. It may also help to identify the various infective lesions.

12.15.1  Indications • To identify the metastatic lesions. • To detect primary tumours of the adrenal. • Identification of the infective lesions.

12.15.2  Technical Issue FNAC is a relatively safe technique that can be done by either USG or CT scan guidance. The diagnostic accuracy of FNAC of the adrenal gland is high [20–22]. Sensitivity: 81 to 85%. Specificity: 90 to 100%. In addition to smear preparation, the FNAC material should be procured for:

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

• Sudden fatal hypertensive crisis in case of pheochromocytoma due to release of catecholamines. • Surgical emphysema. • Minor haematuria. • Hypotension.

12.15.4  Anatomy of the Adrenal Gland • • • • •

Retroperitoneal organ. Located in the upper pole of the kidney. Overall 3–4 cm long. Weight:10–12 gm. The right gland is pyramid-shaped and located in the upper pole of the right kidney. • The left adrenal gland is crescentic and placed in the medial border of the left kidney.

12.15.5  Histology of Adrenal Gland • Outer cortex and an inner medulla. • Cortex: It has three zones from outside to inside: zona glomerulosa, zona fasciculate and zona reticularis. –– Zona glomerulosa: It is a thin zone. It is composed of polyhedral cells with lipid-laden vacuolated cytoplasm. The nuclei are round monomorphic having small prominent nucleoli. The cell liberates aldosterone. –– Zona fasciculate: It is the widest zone. The cells are similar to that of zona glomerulosa. The cell releases glucocorticoids (mainly cortisol). –– Zona reticularis: It is a dense zone and is composed of small cells with scanty dense cytoplasm having small round nuclei. The cell liberates dehydroepiandrosterone. • Medulla: The medulla is composed of elongated cells with eosinophilic cytoplasm and another set of small round cells. The cells of medulla release catecholamines.

12.16 Benign Lesions of the Adrenal Gland 12.16.1  Adrenal Cyst

• Cellblock to do immunocytochemistry. • Material for fungal or bacteriological culture. • Material for flow cytometry.

Adrenal cysts are uncommon benign lesions of the adrenal gland. Most of the cysts are incidentally detected during radiological investigation. Types of cyst:

12.15.3  Complications

• • • •

FNAC is free of any significant complications [20–22]. However, the following complications may arise:

Pseudocyst. Epithelial cyst. Endothelial cyst. Parasitic cyst.

12.18 Adrenocortical Adenoma

345

12.16.2  Pseudocyst

12.17.2  Clinical Features

• Second most common cyst of the adrenal gland. • Caused by the adrenal haemorrhage followed by cyst formation. • They are developed as a sequel to adrenal haemorrhage within the normal adrenal gland or within an adrenal tumour. The cysts do not show any lining epithelium.

• Patients are asymptomatic. • Incidentally detected by CT scan for some other investigations. • Occasionally the tumour becomes large and causes pressure symptoms.

12.16.3  Epithelial Cyst • • • •

Uncommon in the adrenal gland. It accounts for 9% of the adrenal cysts. Retention or embryonal cyst. Layer of epithelial cells line the cyst wall.

12.17.3  Key Cytological Features [23] • Mature adipose tissue. • Myeloid and erythroid series of cells. • Megakaryocytes.

12.17.4  Differential Diagnosis

12.16.4  Endothelial Cyst

• Renal angiomyolipoma.

• The most frequently noted cyst (45%). • Angiomatous or lymphangiomatous cyst.

12.18 Adrenocortical Adenoma

The cyst wall is made by the endothelial cells lining.

12.16.5  Parasitic Cyst • It accounts for 7% of adrenal cyst. • The cyst is caused by parasites such as Echinococcus granulosus (hydatid cyst).

12.16.6  Key Cytological Features

An adrenocortical adenoma is the benign tumour of the adrenal gland. An adrenal adenoma is challenging to differentiate from adrenal hyperplasia. However, the adrenal adenoma is usually unilateral and nodular. Whereas, adrenal hyperplasia is bilateral and diffuse.

12.18.1  Epidemiology

• The clear or haemorrhagic fluid is aspirated. • Foamy histiocytes. • Occasional epithelial cells.

• It represents 5% of all adrenal neoplasms. • About 10% of the general population may have an adrenal adenoma. • Both sexes are equally affected. • Any age group may be affected.

12.17 Adrenal Myelolipoma

12.18.2  Clinical Features

Adrenal myelolipoma is a benign neoplasm of the adrenal gland.

• The tumour may be functioning or non-functioning. • Non-functioning tumours are asymptomatic. • Functioning tumours may have Cushing’s syndrome or Conn’s syndrome.

12.17.1  Epidemiology • It accounts for 2.5% of all adrenal neoplasms. • Adrenal myelolipoma occurs in fifth to seventh decade of life. • Females are affected more than males.

12.18.3  Key Cytological Features • Smears show characteristic bubbly background. • Multiple cohesive clusters of tumour cells.

vacuolated

346

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

• Large cells. • Abundant vacuolated cytoplasm and indistinct cell margin. • Monomorphic mildly enlarged nucleus. • Occasional large pleomorphic cells. • Also, many cells with bare nuclei. • Mitosis and necrosis are absent.

12.19 Adrenocortical Carcinoma Adrenocortical carcinomas (ACCa) is a highly aggressive malignant epithelial neoplasm. Fig. 12.38  Adrenocortical carcinoma: Many discrete and cohesive clusters of tumour cells in a bubbly background

12.19.1  Epidemiology • ACCa accounts for 3% of all adrenal neoplasms. • Common in 40 to 50 year age. • More frequent in females. Female:male ratio is 2.5:1.

12.19.2  Clinical Features • Both functional (80 to 90%) and non-functional (10%). • Functional tumour: They may present with Cushing’s syndrome or virilization. • Non-functional: As there are no symptoms, so the tumour first time presents as large mass in the adrenal gland.

12.19.3  Adrenal Adenoma Versus Adrenal Cortical Carcinoma The following features help to differentiate adrenal adenoma from carcinoma: Features of ACCa are: • • • •

Fig. 12.39  Adrenocortical carcinoma: The scattered tumour cells have vacuolated cytoplasm and moderately pleomorphic nuclei

Size of the tumour: >5 cm in diameter. Weight: >50 gm. Necrosis present. Unencapsulated.

12.19.4  Key Cytological Features [24] (Figs. 12.38, 12.39, and 12.40) Predominant pattern: Abundant discrete round cells in a bubbly vacuolated background • Background of the smear is bubbly vacuolated. • Predominantly discrete tumour cells with cytoplasm.

intact

Fig. 12.40  Adrenocortical carcinoma: Higher magnification showing tumour cells with pleomorphic nuclei and large prominent nucleoli

12.20 Pheochromocytoma

• The tumour cells contain abundant vacuolated cytoplasm. • Central to eccentrically placed hyperchromatic round nuclei. • Moderate to marked nuclear pleomorphism. • Coarsely granular chromatin with large prominent nucleoli. • Many mitotic figures present. • Necrosis.

Immunocytochemistry Positive: HMB45, Melan A, calretinin, inhibin-alpha, SF1 and occasionally synaptophysin. Negative: CK, EMA and CEA.

347

12.20.3  Key Cytological Features [20, 25] (Figs. 12.41, 12.42, 12.43, 12.44, and 12.45) • Cellular smear. • Scattered single cells and loose clusters. • Epithelial cell: –– Discrete. –– Polygonal to plasmacytoid oval cells. –– Reddish granular cytoplasm. –– Moderately pleomorphic nuclei. –– Salt and pepper chromatin. –– Intranuclear pseudoinclusions. • Spindle cells. –– Abundant cytoplasm. –– Spindle-shaped nuclei. –– Coarse chromatin.

12.19.5  Differential Diagnosis • Renal cell carcinoma: –– RCC is positive for PAX8, CD10 and vimentin.

12.20 Pheochromocytoma Pheochromocytoma is a tumour of chromaffin cells of the adrenal gland.

12.20.1  Epidemiology • The incidence rate is two to eight per million person per year. • It is present in 5% of an incidentally detected adrenal mass. • Both males and females are equally affected. • It occurs in third to fifth decade of life. • Mostly sporadic tumours. • Only 10% of cases are part of MEN syndrome.

Fig. 12.41  Pheochromocytoma: Abundant discrete and loosely cohesive tumour cells

12.20.2  Clinical Features • • • •

About 10% of pheochromocytomas are bilateral. 10% extra-adrenal. 10% malignant. Secretion of catecholamines causes the triad of symptoms: paroxysmal hypertension, sweating and tachycardia. This triad of symptoms are characteristic and occur in only 25% of patients. • Less commonly the patients may have pallor, anxiety, panic attack along with postural hypotension.

Fig. 12.42  Pheochromocytoma: The round cell with a moderate amount of cytoplasm and moderate nuclear pleomorphism

348

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

• Ganglionic cells. –– Abundant granular cytoplasm. –– Eccentrically placed nuclei. –– Large nuclei with prominent nucleoli.

Immunocytochemistry Positive: NSE, chromogranin and tyrosine hydroxylase. Negative: CK and EMA.

12.20.4  Differential Diagnosis

Fig. 12.43  Pheochromocytoma: The vacuolated cytoplasm having indistinct cytoplasmic margin

• Adrenocortical carcinoma: The features in favour of pheochromocytoma include: –– Spindle cells. –– Cytoplasmic reddish globular material. –– Chromogranin and S100 positivity. • Metastatic carcinoma: –– Clinical history of the known primary tumour. –– Pheochromocytoma is positive for chromogranin.

12.21 Neuroblastoma of the Adrenal Gland Neuroblastoma develops from the non-chromaffin cells of the adrenal medulla.

12.21.1  Epidemiology • Neuroblastoma is one of the most frequent tumours of childhood. • It is the third most frequent tumour of the children. Fig. 12.44  Pheochromocytoma: Both round and scattered spindle-­ • Majority of the neuroblastoma occurs before 5 years of shaped cells life. • More common in males.

12.21.2  Clinical Features • Abdominal neuroblastoma may cause abdominal discomfort and pain. • Mediastinal neuroblastoma: Dyspnea. • Paraspinal neuroblastoma: Neurological pressure symptoms. • Also, there may be paraneoplastic syndrome such as diarrhoea, hypokalaemia, Horner’s syndrome etc.

12.21.3  Key Cytological Features [26] (Figs. 12.46, 12.47, 12.48, and 12.49) Fig. 12.45  Pheochromocytoma: The higher magnification of the spindle cells

• Abundant discrete and loose aggregates of cells.

12.22 Metastatic Tumors

349

Fig. 12.46  Adrenal neuroblastoma: Abundant discrete and loose clusters of cells

Fig. 12.49  Adrenal neuroblastoma: Occasional rosette-like structures

Fig. 12.47  Adrenal neuroblastoma: The cells are often embedded in neurofibrillary material

Fig. 12.50  Adrenal neuroblastoma: Tumour cells are positive for NSE

• The cells are often entangled with neurofibrillary material. • Frequent rosette formation. • Small round cells with scanty cytoplasm. • Relatively small round regular nucleus. • Granular chromatin. Immunocytochemistry (Fig. 12.50): Positive: NSE, NB84 and CD56. Differential diagnosis: Other malignant round cell tumours.

12.22 Metastatic Tumors [22] (Fig. 12.51) Fig. 12.48  Adrenal neuroblastoma: Higher magnification showing tumour cells having granular chromatin

The adrenal gland is commonly affected by a metastatic malignant tumour.

350

12  Fine Needle Aspiration Cytology of the Kidney and Adrenal Gland

6. Zhou H, Guo M, Gong Y.  Challenge of FNA diagnosis of angiomyolipoma: a study of 33 cases. Cancer Cytopathol. 2017;125(4):257–66. 7. Taavitsainen M, Krogerus L, Rannikko S.  Aspiration biopsy in renal angiomyolipoma. Acta Radiol. 1989;30(4):381–2. 8. Portugal R, Barroca H.  Clear cell sarcoma, cellular mesoblastic nephroma and metanephric adenoma: cytological features and differential diagnosis with Wilms tumour. Cytopathology. 2008;19(2):80–5. 9. Tickoo SK, Reuter VE, Amin MB, et  al. Renal oncocytosis: a morphologic study of fourteen cases. Am J Surg Pathol. 1999;23(9):1094–101. 10. Helpap B, Knupffer J, Essmann S. Nucleolar grading of renal cancer. Correlation of frequency and localization of nucleoli to histologic and cytologic grading and stage of renal cell carcinomas. Mod Pathol. 1990;3(6):671–8. 11. Erdogan F, Demirel A, Polat O.  Prognostic significance of morphologic parameters in renal cell carcinoma. Int J Clin Pract. 2004;58(4):333–6. 1 2. Medeiros LJ, Gelb AB, Weiss LM. Renal cell carcinoma. Prognostic Fig. 12.51  Smear showing clusters of tumour cells with mild-to-­ significance of morphologic parameters in 121 cases. Cancer. moderate nuclear pleomorphism and prominent nucleoli in a case of 1988;61(8):1639–51. metastatic adenocarcinoma of the lung in the adrenal gland 13. Lee CH, Chung SY, Moon KC, Park IA, Chung YR, Ryu HS.  A pilot study evaluating fine-needle aspiration cytology of clear-­ Frequency: Near about 80% of the lesions diagnosed by cell renal cell carcinoma: comparison of ancillary immunocytochemistry and Cytomorphological characteristics of SurePath™ FNAC of the adrenal gland are metastatic tumour. liquid-based preparations with conventional smears. Acta Cytol. Source: Lung, breast, kidney, ovary and stomach. 2015;59(3):239–47. 14. Giashuddin S, Cangiarella J, Elgert P, Levine PH. Metastases to the kidney: eleven cases diagnosed by aspiration biopsy with histological correlation. Diagn Cytopathol. 2005;32(6):325–9. 12.22.1  Diagnosis 15. Dey P, Radhika S, Rajwanshi A, et  al. Aspiration cytology of Wilms’ tumor. Acta Cytol. 1993;37(4):477–82. • Clinical history of the primary tumour. 16. Shet T, Viswanathan S.  The cytological diagnosis of paediatric • Mostly bilateral (50%). renal tumours. J Clin Pathol. 2009;62(11):961–9. 17. Dey P, Srinivasan R, Nijhawan R, et  al. Fine needle aspiration • Cytomorphology on FNAC smear. cytology of mesoblastic nephroma. A case report. Acta Cytol. • Immunocytochemistry: A panel of immunocytochemistry 1992;36(3):404–6. is helpful to confirm the diagnosis. 18. Agrawal P, Srinivasan R, Rajwanshi A, et al. Fine needle aspiration cytology of paediatric soft tissue tumours highlighting challenges in diagnosis of benign lesions and unusual malignant tumours. Cytopathology. 2019;30(3):301–8. 12.22.2  Differential Diagnosis 19. Srinivasan R, Nijhawan R, Dey P, Samujh R. Fine needle aspiration cytology of clear cell sarcoma of the kidney and its distinction from • Adrenocortical carcinoma versus metastatic renal cell Wilms’ tumor. Acta Cytol. 1997;41(3):950–1. 20. Rana C, Krishnani N, Kumari N.  Spectrum of adrenal lesions carcinoma and prostatic adenocarcinoma. on fine needle aspiration cytology. Indian J Pathol Microbiol. • Pheochromocytoma versus metastatic neuroendocrine 2012;55(4):461–6. tumours. 21. Fassina AS, Borsato S, Fedeli U. Fine needle aspiration cytology (FNAC) of adrenal masses. Cytopathology. 2000;11(5):302–11. 22. Gupta RK, Majumdar K, Saran RK, Srivastava S, Sakhuja P, Batra VV. Role of endoscopic ultrasound-guided fine-needle aspiration in adrenal lesions: analysis of 32 patients. J Cytol. 2018;35(2):83–9. References 23. Kumar R, Dey P. Fine-needle aspiration cytology of non-neoplastic adrenal pathology. Diagn Cytopathol. 2016;44(6):472–6. 1. Baert L.  Renal cyst puncture and abscess formation. Urology. 24. Kanjilal B, Ghosh M, Mitra A, et  al. Cytological diagnosis of 1978;11(5):543–4. adrenocortical carcinoma: a report of 2 cases in children. Diagn 2. Renshaw AA, Granter SR, Cibas ES. Fine-needle aspiration of the Cytopathol. 2018;46(12):1064–7. adult kidney. Cancer. 1997;81(2):71–88. Epub 1997/04/25 25. Bhargav P.  Response to "CT-guided fine needle aspiration cytol 3. Kelley CM, Cohen MB, Raab SS. Utility of fine-needle aspiration ogy diagnosis of extra-adrenal pheochromocytoma". J Cytol. biopsy in solid renal masses. Diagn Cytopathol. 1996;14(1):14–9. 2012;29(1):100. Epub 1996/02/01 26. Wadih GE, Nance KV, Silverman JF. Fine-needle aspiration cytol 4. Zardawi IM.  Renal fine needle aspiration cytology. Acta Cytol. ogy of the adrenal gland. Fifty biopsies in 48 patients. Arch Pathol 1999;43(2):184–90. Lab Med. 1992;116(8):841–6. 5. Moch H, Humphrey PA, Ulbright TM, Reuter VE. WHO classification of Tumours of the urinary system and male genital organs. Lyon: IARC Press; 2016.

Fine Needle Aspiration Cytology of the Gonads

13.1 Ovary In recent times, the fine needle aspiration cytology of ovary has gained enough importance because of preoperative neoadjuvant chemotherapy. Based on FNAC, various ovarian malignant tumours are treated, and therefore the accurate diagnosis of the ovarian tumour is essential. Moreover, the FNAC can guide the clinician to treat various benign cystic lesions of ovary.

13.1.1  Indications of Ovarian FNAC • Diagnosis of the malignant ovarian tumour for neoadjuvant chemotherapy. • Diagnosis of malignancy in an advanced inoperable stage. • Diagnosis of benign cysts of the ovary. • Diagnosis of recurrent ovarian malignancy. Contraindications: There are no serious contraindications of FNAC of the ovary.

13.1.1.1 Complications • Almost no complications except minor haemorrhage in the tumour and pain abdomen. • Needle tract seeding does not occur if the fine needle is used during FNAC procedure. 13.1.1.2 Procurement of Sample • The material is collected with the help of USG or CT scan guidance. • One part of the aspirated material should always be kept for cell block.

13

sampling is one of the important causes of false-negative tumours. • False-positive cases are rare.

13.2 Benign Lesions of the Ovary 13.2.1  Non-neoplastic Cyst [1] Follicular Cyst • It is the most frequent cystic lesion in the ovary. • The follicular cyst develops from the continuous enlargement of the graafian follicle. • They are mostly unilocular cyst with thin wall. • FNAC is in general not indicated for diagnosis.

13.2.2  Key Cytological Features • • • • • • • •

Fluid is aspirated. Paucicellular. Multiple aggregates of cells. Small round cell with scanty cytoplasm. Well-defined cytoplasmic margin. Monomorphic round nucleus. Tiny nucleoli. Occasional nuclear grooves.

13.2.3  Differential Diagnosis • Granulosa cell tumour. • Carcinoma.

Diagnostic accuracy: • The sensitivity of ovarian FNAC is 85 to 90%. • The specificity of FNAC of the ovary is 98%. • False-negative cases are mainly in borderline ovarian tumour particularly mucinous neoplasm. Inadequate

13.2.4  Corpus Luteal Cyst The persistently enlarged corpus luteum may present as a cyst. These cysts are seldom aspirated.

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_13

351

352

13  Fine Needle Aspiration Cytology of the Gonads

13.2.5  Key Cytological Features • • • • • • • • •

The haemorrhagic fluid is aspirated. Paucicellular. Loose clusters and dissociated large cells. Abundant vacuolated cytoplasm. Hyaline droplets within the cytoplasm. Round monomorphic centrally placed nuclei. Single prominent nucleoli. Many histiocytes with engulfed hemosiderin pigment. Central round nuclei.

13.2.6  Endometriotic Cyst The endometriosis in the ovary often presents as an endometriotic cyst. It happens due to regular periodic bleeding in the ovarian endometriosis.

Fig. 13.2  Endometriotic cyst: Large cluster of endometrial cells

13.2.7  Key Cytological Features (Figs. 13.1, 13.2, 13.3, and 13.4) • Dark brown material is aspirated. • Many histiocytes filled with golden brown hemosiderin pigments. • Small cohesive clusters of endometrial cells are present. • Small round cells with an ill-defined cytoplasmic margin. • Small hyperchromatic nucleus. • Inconspicuous nucleoli. • Occasional stromal fragments. Fig. 13.3  Endometriotic cyst: Stromal fragments, scattered spindle cells and endometrial cell clusters

Fig. 13.1  Endometriotic cyst: Many foamy histiocytes, polymorphs and endometrial cells

Fig. 13.4  Endometriotic cyst: Higher magnification showing the morphology of the endometrial cells. The cells are round with monomorphic nuclei

13.4 Serous Adenocarcinoma

353

13.3 Serous Adenoma and Adenocarcinoma of Ovary [2, 3]

13.4.4  Key Cytological Features (Figs. 13.5, 13.6, 13.7, 13.8, and 13.9)

13.3.1  Serous Cystadenoma of Ovary

Predominant pattern: Abundant clusters, and glands of tumour cells

13.3.1.1 Epidemiology • Serous cystadenoma of ovary represents 50% of all serous tumours. • The most common epithelial tumour of the ovary. • One-fifth of the serous cystadenomas are bilateral.

13.3.2  Clinical Features • Mostly asymptomatic. • At times abdominal pain. • Occasionally vaginal bleeding.

• • • • • •

Large cells with a moderate amount of cytoplasm. Cytoplasmic vacuolations present. Moderately pleomorphic nucleus. Large nucleoli. Frequent mitosis. Psammoma bodies.

Immunohistochemistry (Figs. 13.10, 13.11, 13.12, and 13.13) Positive: CK7, PAX8, WT1 and p53. Negative: CK20 and CDX2.

13.3.3  Key Cytological Features • • • • • •

Clear fluid is aspirated. Scanty cellularity. Cuboidal or columnar cells with moderate cytoplasm. Round monomorphic nucleus. Absence of nucleoli. Psammoma body may be present.

13.4 Serous Adenocarcinoma 13.4.1  Epidemiology • Serous adenocarcinoma accounts for almost 50% of all ovarian malignancies. • Commonly occurs in the sixth decade. • Mean age: 65 years.

Fig. 13.5  Serous adenocarcinoma of ovary: Multiple clusters and glandular arrangement of cells

13.4.2  Genetic Profile • P53 mutation in high-grade serous carcinoma. • BRCA 1 mutation in 50% of cases. • Infrequently KRAS mutation.

13.4.3  Clinical Features • • • •

Pelvic pain. Ascites. Mass in pelvic. Pressure symptoms such as anorexia and nausea.

Fig. 13.6  Serous adenocarcinoma of ovary: The malignant cells forming glands

354

13  Fine Needle Aspiration Cytology of the Gonads

Fig. 13.7  Serous adenocarcinoma of ovary: The cluster of tumour cells showing nuclear enlargement and pleomorphism

Fig. 13.10  Serous adenocarcinoma of ovary: Strong nuclear positivity of PAX8

Fig. 13.8  Serous adenocarcinoma of ovary: Haematoxylin and eosin-­ stained smear showing many three-dimensional clusters of cells

Fig. 13.11  Serous adenocarcinoma of ovary: Strong nuclear positivity of p53

Fig. 13.9  Serous adenocarcinoma of ovary: The higher magnification showing large cells with clumped chromatin

Fig. 13.12  Serous adenocarcinoma of ovary: Strong nuclear positivity of WT1

13.6 Mucinous Cystadenocarcinoma

355

13.6 Mucinous Cystadenocarcinoma 13.6.1  Epidemiology • It represents 10% of mucinous neoplasm of the ovary and 5% of ovarian carcinomas. • The patients are mainly postmenopausal. • Mean age: 45 to 50 years.

13.6.2  Clinical Features

Fig. 13.13  Serous adenocarcinoma of ovary: Membranous positivity of CK7

13.5 Mucinous Cystadenoma and Cystadenocarcinoma [3, 4] 13.5.1  Mucinous Cystadenoma 13.5.1.1 Epidemiology • Mucinous tumours represent 12% of all mucinous tumour. • Mucinous cystadenoma accounts for 80% mucinous neoplasm of ovary. • Mostly unilateral. • Mean age: 50 years. Genetic Profile • KRAS mutation.

• Mainly asymptomatic. • Occasionally pain abdomen. • Pressure symptoms such as constipation or increased frequency of micturition.

13.6.3  Key Cytological Features (Figs. 13.14, 13.15, 13.16, and 13.17) Predominant pattern: Aggregates of tumour cells in abundant mucinous material • • • • •

FNAC yields mucinous material. Many tight clusters of cells. Vacuolated cytoplasm. Enlarged, pleomorphic nucleus. Prominent nucleoli.

Immunocytochemistry • Positive: CK 7, PAX-8, MUC 5 AC and MUC 2. • Negative: CK 20.

13.5.2  Clinical Features • Mainly asymptomatic. • Lower abdominal pain. • Mass in pelvis.

13.5.3  Key Cytological Features • • • • • •

FNAC yields mucinous material. Multiple clusters and “honeycomb” like sheets of cells. Columnar cells. Vacuolated cytoplasm. Eccentrically placed nuclei. Background mucinous material.

Fig. 13.14  Mucinous adenocarcinoma: The tumour cells are embedded in mucinous material

356

13  Fine Needle Aspiration Cytology of the Gonads

13.6.4  Differential Diagnosis • Metastatic carcinoma: –– Not possible based on FNAC smear. –– Immunocytochemistry: Mucinous carcinomas are positive for CK7 and PAX8 and negative for CK 20. • Borderline malignancy: Not possible to confirm in FNAC smear.

13.7 Endometrioid Carcinoma [3] 13.7.1  Epidemiology

Fig. 13.15  Mucinous adenocarcinoma: The cluster of tumour cells

• Endometrioid carcinoma represents 20% of all carcinoma of the ovary. • It is mainly present in elderly women. • Mean age: 55 years. • Often related to endometriosis (40%). Molecular Genetics • Mutation of CTNNB1 (38%). • PTEN mutation (21% case). • Microsatellite instability (19% cases).

13.7.2  Clinical Features • Mainly asymptomatic. • Occasionally pelvic mass and abdominal pain.

13.7.3  Key Cytological Features Fig. 13.16 Mucinous adenocarcinoma: Haematoxylin and eosin-­ stained smear showing cluster of tumour cells floating in pools of mucin Predominant pattern: Abundant small clusters of tumour

cells

• Small groups of cell. • Columnar shaped cells with moderately pleomorphic nuclei. • Squamous cells. • Macrophages containing hemosiderin. • Background necrosis and haemorrhage. Immunohistochemistry Positive: CK 7, ER and PR. Negative: WT1 and p16.

13.8 Clear Cell Carcinoma 13.8.1  Epidemiology Fig. 13.17 Mucinous adenocarcinoma: The higher magnification showing mildly pleomorphic tumour cells

• It represents 8% of all ovarian carcinoma.

13.8 Clear Cell Carcinoma

357

• Majority of them are related to endometriosis (70%). • Mean age: 55 years.

13.8.2  Clinical Features • Pelvic mass and pain abdomen. • Paraneoplastic syndromes: thromboembolism.

Hypercalcemia

and

13.8.3  Key Cytological Features (Figs. 13.18, 13.19, 13.20, and 13.21) Predominant pattern: Abundant dissociated and small groups of tumour cells with clear cytoplasm • Multiple clusters and discrete cells.

Fig. 13.18  Clear cell carcinoma of the ovary: Multiple clusters and discrete tumour cells

Fig. 13.20  Clear cell carcinoma of the ovary: The sheets of tumour cells with abundant clear cytoplasm and round nuclei

Fig. 13.21  Clear cell carcinoma of the ovary: The tumour cells with Pinkish globular acellular material. The individual cells show centrally placed enlarged nuclei and large vacuolated cytoplasm

• Abundant clear vacuolated cytoplasm. • Centrally located nucleus having pleomorphism. • Fine chromatin with prominent nucleoli. • Pinkish acellular ball-like material.

moderate

13.8.4  Differential Diagnosis • Metastatic renal cell carcinoma: Clinical history and immunocytochemistry.

13.8.5  Germ Cell Tumour Fig. 13.19  Clear cell carcinoma of the ovary: The oval to polyhedral cells with a well-defined margin. The cytoplasm is clear and vacuolated

Germ cell tumour of ovary accounts for 30% of all ovarian neoplasms.

358

13  Fine Needle Aspiration Cytology of the Gonads

13.9 Mature Teratoma Synonym: Dermoid cyst and mature cystic teratoma.

13.9.1  Epidemiology • Mature teratoma accounts for 25% of all ovarian tumours. • It constitutes the main bulk of ovarian germ cell tumour (90%). • Predominantly occurs in 20 to 50 years of age.

13.9.2  Clinical Features • Asymptomatic (50%). • Pain in the lower abdomen and pelvic mass.

Fig. 13.22  Immature teratoma: Multiple clusters and dissociated oval to elongated cell

13.9.3  Key Cytological Features • • • • • •

FNAC yields pultaceous material. Many anucleated squamous cells. Sebaceous cells. Columnar epithelial cells. Mesenchymal cells. Neural components.

13.10 Immature Teratoma 13.10.1  Epidemiology • It represents 1% of malignant ovarian neoplasm. • It constitutes a minor proportion of ovarian teratomas (3%). • Predominantly seen under 30 years of age. • Mean age: 20 years.

13.10.2  Clinical Features • Pelvic swelling. • Abdominal pain.

13.10.3  Key Cytological Features (Figs. 13.22 and 13.23) In addition to the cytological features of mature teratoma, one may also see:

Fig. 13.23  Immature teratoma: The cells are round with mild nuclear enlargement and pleomorphism

• • • •

Many rosettes-like structures. Small cells with thin rim cytoplasm. Round mildly pleomorphic nuclei. Fine chromatin.

13.11 Carcinoid Tumours of the Ovary 13.11.1  Epidemiology • Rare tumour. • It represents about 1% of teratomas of the ovary. • Elderly patients, mean age is 53 years.

13.12 Dysgerminoma

13.11.2  Clinical Features • Asymptomatic. • The patients may have flushing, diarrhoea and hypertension.

13.11.3  Key Cytological Features [5] (Figs. 13.24 and 13.25) Predominant pattern: Discrete and occasional rosette-­ forming small round cells • Discrete tumour cells. • Occasional rosettes are present. • Small round cells.

359

• Monomorphic nuclei. • “Salt and pepper” chromatin. Immunocytochemistry Positive: Chromogranin, synaptophysin and CD 56.

13.11.4  Differential Diagnosis • Sertoli cell tumour: –– Multiple tubular structures. –– Tumour cells usually show moderate cytoplasm. • Granulosa cell tumour: –– Nuclear grooving. –– Call Exner body. • Small cell carcinoma: Nuclear moulding and crushing artefact.

13.12 Dysgerminoma 13.12.1  Epidemiology • Represent less than 1% of all ovarian cancer. • The most frequent malignant germ cell tumours of the ovary. • Common in second to third decade. • Mean age: 22 years.

13.12.2  Clinical Features Fig. 13.24  Carcinoid of the ovary: Loose clusters of oval cells

• Pelvic mass. • Pain abdomen. • Uncommonly patients may have paraneoplastic syndrome. • One-quarter of patients may present during pregnancy.

13.12.3  Key Cytological features [6] (Figs. 13.26, 13.27, 13.28, 13.29, 13.30, and 13.31) Predominant pattern: Dissociated round-shaped tumour cells with an admixture of lymphocytes.

Fig. 13.25  Carcinoid of the ovary: The cells with reddish granular cytoplasm. Nuclei show mildly pleomorphism and salt and pepper chromatin

• Characteristic vacuolated background. • Tumour cells. –– Round cells. –– Scanty cytoplasm, often vacuolated. –– Round nuclei. –– Mild nuclear pleomorphism. –– Fine chromatin. –– Prominent nucleoli.

360

Fig. 13.26  Dysgerminoma: Abundant discrete tumour cells

Fig. 13.27  Dysgerminoma: The tumour cells with moderate cytoplasm and mildly pleomorphic nuclei along with chromatin threading

Fig. 13.28 Dysgerminoma: Higher magnification showing better nuclear morphology. The tumour cells have a moderate amount of cytoplasm and large nuclei with prominent nucleoli

13  Fine Needle Aspiration Cytology of the Gonads

Fig. 13.29  Dysgerminoma: The tumour cells are admixed with many lymphocytes

Fig. 13.30  Dysgerminoma: The cells with indistinct cytoplasmic margin and pleomorphic nuclei

Fig. 13.31 Dysgerminoma: Scattered ill-formed epithelioid cell granuloma

13.14 Sex Cord-Stromal Tumour

• Lymphocytes are admixed with tumour cells. • Frequent epithelioid cell granulomas. Immunohistochemistry • Positive: Placental alkaline phosphatase, CD 117 and OCT-4.

13.12.4  Differential Diagnosis Non-Hodgkin lymphoma: • Many lymphoglandular bodies. • Tumour cells are positive for CD45.

13.13 Yolk Sac Tumour

361

13.14 Sex Cord-Stromal Tumour 13.14.1  Granulosa Cell Tumour [3] 13.14.1.1 Epidemiology • Granulosa cell tumour (GCT) accounts for 1 to 3% of all ovarian tumours. • Patients are mainly postmenopausal. • Mean age of adult granulosa cell tumour: 50 years. • Mean age of juvenile granulosa cell tumour: 15 years.

13.14.2  Molecular Genetics • Point mutation of the FOXL2 gene (90%). • Trisomy 12 and 14.

13.13.1  Epidemiology

13.14.3  Clinical Features

• Yolk sac tumour (YST) accounts for 20% of all malignant germ cell tumours of the ovary. • YST constitutes 1% of all malignant tumours of the ovary. • Mean age: 20 years. • Commonly present in young adults.

• • • •

13.13.2  Clinical Features

13.14.4  Key Cytological Features (Figs. 13.32, 13.33, 13.34, and 13.35)

• Abdominal mass. • Pain in the abdomen.

• Cellular smear. • Dissociated and small groups of cells.

Lower abdominal mass. Pelvic pain. Vaginal bleeding. Virilization and hirsutism.

13.13.3  Key Cytological Features Predominant pattern: Small groups and papillae • Occasional discrete cells. • Tumour cells. –– Large cells. –– Bubbly cytoplasm. –– Large pleomorphic nucleus. –– Multiple large irregular nucleoli. • Long branched vascular channels that are surrounded by malignant cells. The cells often form knobby protrusions. Immunohistochemistry • Positive: Alpha-fetoprotein, CK, PLAP and CD 34. • Negative: CD 117 and EMA.

Fig. 13.32  Granulosa cell tumour: Multiple tight, cohesive tumour cells

362

13  Fine Needle Aspiration Cytology of the Gonads

• Cells often arranged peripherally of spherical pinkish material. • Round cells. • Scanty cytoplasm. • The cytoplasmic border is indistinct. • Monomorphic round nuclei. • Dispersed chromatin. • Longitudinal nuclear groove. Immunohistochemistry • Positive: Inhibin, calretinin, WT1 and FOXL2. • Negative: CK7.

13.14.5  Differential Diagnosis Fig. 13.33  Granulosa cell tumour: The cells have scanty cytoplasm and round nuclei with minimal pleomorphism

• Carcinoid tumour. –– Stippled chromatin. –– Reddish granular cytoplasm. –– No nuclear groove. • Small cell carcinoma. –– Nuclear moulding. –– Hyperchromatic nuclei.

13.15 Sertoli Cell Tumour Incidence • Uncommon ovarian tumour. • It represents 4% of sex cord-stromal tumour. • Most common in the early reproductive age period.

Fig. 13.34 Granulosa cell tumour: Occasional pinkish globules present

13.15.1  Clinical Features • Abdominal pain. • Vaginal bleeding.

13.15.2  Key Cytological Features [3, 7] (Figs. 13.36 and 13.37) Predominant pattern: Discrete and occasional tubules I a fatty background • • • •

Fig. 13.35  Granulosa cell tumour: The cells often show nuclear grooving

Discrete cells. Occasional tubular arrangement. The background is foamy vacuolated. Round cell with monomorphic nuclei.

13.19 Anatomy and Histology of Testis

363

13.17.1  Key Cytological Features • It is not possible to identify the metastatic tumour by morphology alone. • Mucinous background. • Discrete tumour cells with cytoplasmic vacuolations. • Eccentrically placed enlarged nuclei.

13.17.2  Indicators of Metastasis • Clinical history. • Bilateral mass lesions. • Abundant signet ring cells. Fig. 13.36  Sertoli cell tumour; abundant discrete tumour cells in a vacuolated background

13.18 Testis Testicular FNAC is not popular with the clinicians because many think that the testicular mass should have orchiectomy rather than to have FNAC. Moreover, there is a hypothetical risk of needle tract transmission at the time of FNAC of the testis. FNAC is immensely helpful in clinically equivocal cases and also in the suspected infection in the testis that can be treated by medicine. FNAC of the testis is also useful in the management of male infertility cases.

13.18.1  Indications of FNAC • • • • Fig. 13.37  Sertoli cell tumour: Individual cells are round with minimal nuclear pleomorphism

13.16 Fibroma and Thecoma 13.16.1  Key Cytological Features • • • •

Low cellularity. Scattered spindle cells. Spindle-shaped nucleus. Fine nuclear chromatin.

13.17 Metastatic Tumours in the Ovary Metastatic tumours of the ovary are mostly bilateral. Sources: Large intestine, stomach and breast.

Any equivocal tumour in testis. Mass due to infection. Male infertility cases. Follow up the investigation in a leukemic relapse in testis.

Contraindication: There is no contraindication in testicular FNAC. Complications: Except pain and local trauma, there are no significant complications in testicular FNAC. The needle tract seeding is a myth rather than a reality.

13.19 Anatomy and Histology of Testis Location: Both testis are situated in the scrotum. Shape and Dimension • The oval-shaped structure. • Anterior, medial and lateral surface of the testis is convex. • It is 4 cm long, 2.5 cm in breadth and 3 cm in thickness.

364

13  Fine Needle Aspiration Cytology of the Gonads

13.19.1  Histology • It is made of numerous seminiferous tubule. • Germ cells undergo maturation within the tubules. • Seminiferous tubules are surrounded by connective tissue that is rich in vessels, Sertoli cells and Leydig cells. • Seminiferous tubules accumulate in rete testis, and from there ductus efference develops. • The ductus efference further joins in the epididymis. • From the epididymis ductus deferens develops.

13.19.2  Normal Cells of Testis FNAC (Fig. 13.38) 13.19.2.1 Sertoli Cells • Large cells. • Abundant cytoplasm. • Fine cytoplasmic vacuolations. • Indistinct cell border. • A round nucleus with granular chromatin. • Prominent nucleolus.

• Scanty and vacuolated cytoplasm. • A round nucleus with condensed chromatin. • Indistinct nucleolus. Spermatozoa • Triangle-shaped cells. • Peripherally pushed nuclei. • Dark condensed chromatin. • The tip of the cell show clear cytoplasm. • A long tail. Leydig Cells • Large round cells. • Abundant cytoplasm. • Pinkish granules. • Reinke’s crystal. • A round regular nucleus with granular chromatin. • Prominent nucleolus.

13.19.4  Peritesticular Lesions Peritesticular lesions are the commonest targets of FNAC.

13.19.3  Primary Spermatocytes • • • • •

The round cells. Thin rim of deeply basophilic cytoplasm. Round to oval nucleus. Fine chromatin. Indistinct nucleolus. Secondary spermatocytes cannot be identified.

Spermatids • Round cells.

Spermatozoa

Spermatid

Sertoli cell

Spermatocyte

Distribution of Lesions • Cystic lesions (43%). • Inflammatory lesions (25%). • Neoplastic lesions (12%). • Others.

13.19.5  Hydrocele In the case of hydrocele, fluid is accumulated in the tunica vaginalis. Congenital hydrocele: Persistent communication between the peritoneal sac and scrotal sac. Here, the processus vaginalis is present and therefore the fluid accumulates in the scrotal sac. Secondary hydrocele: It is caused by local inflammation, tumour or torsion of the testis. Key Cytological Features • Clear straw coloured fluid. • Scanty cellularity. • Sheets of mesothelial cells. • Monomorphic round nuclei. Spermatocele [8] In case of spermatocele, the epididymis is dilated focally due to blockage of the efferent ducts.

Fig. 13.38  Normal spermatogenesis: Smear showing Sertoli cells, spermatocytes, spermatids and spermatozoa

Cause: Trauma causing inflammation and blockage of the efferent ducts. The cyst contains a lot of spermatozoa.

13.23 Adenomatoid Tumour

Fig. 13.39  Spermatocele: Abundant spermatozoa along with occasional macrophages with ingested sperm head

13.19.6  Key Cytological Features (Fig. 13.39) • • • •

FNAC yields clear/milky fluid. Abundant spermatozoa. Foamy macrophages containing spermatozoa. Mesothelial cells.

365

Fig. 13.40  Tuberculosis: Epithelioid cell granuloma in a necrotic background

13.21.2  Key Cytological Features • Scanty cellularity. • Lymphocytes and histiocytes. • Occasional polymorphs.

13.20 Inflammation

13.22 Tuberculous Epididymitis [8]

13.20.1  Acute Epididymitis

13.22.1  Key Cytological Features (Fig. 13.40)

Clinical Features • Fever. • Pain. • Tenderness. • Associated urinary tract infection.

• • • • • •

13.20.2  Key Cytological Features • • • • • •

Aspiration yields purulent material. The background shows necrotic debris. Abundant polymorphs. Degenerated epithelial cells. Sheets of epithelial cells. Macrophages.

FNAC yields thick caseous material. Necrotic background. Many epithelioid cell granulomas. Multinucleated giant cells. Lymphocytes. Ziehl Neelsen stain: positive for acid-fast bacilli (AFB).

13.22.2  Filarial Inflammation 13.22.2.1 Cytology (Fig. 13.41) • Many microfilariae. • Lymphocytes. • Multinucleated giant cells. • Epithelioid cell granulomas. Low power search is mandatory to detect such parasites.

13.21 Chronic Epididymitis 13.21.1  Clinical Features

13.23 Adenomatoid Tumour [8, 9]

• Pain and discomfort in the scrotum. • Swelling and redness of the scrotum.

The adenomatoid tumour is the benign mesothelial tumour of the paratesticular tissue.

366

Fig. 13.41  Microfilaria in the Para testicular nodule. The long thread-­ like microfilaria

13  Fine Needle Aspiration Cytology of the Gonads

Fig. 13.42  Spermatocytic granuloma: Abundant spermatozoa and foamy histiocytes with ingested sperms

13.23.1  Epidemiology • It is the most frequent tumour paratesticular tissue. • Adenomatoid tumour represents 60% of all benign paratesticular tumour. • It commonly occurs in third and fourth decade of life.

13.23.2  Clinical Features • Asymptomatic and incidentally detected. • Painless swelling.

13.23.3  Key Cytological Features • Rich in cellularity. • Multiple clusters and monolayer cells simulating mesothelial cells. • A round regular nucleus with small nucleolus. Immunocytochemistry: Positive: CK, EMA, calretinin and WT1.

13.24 Spermatocytic Granuloma [8] Location: Head of the epididymitis. Cause: Due to extravasation of sperms through the vasa differentia. The injury to the vas deference occurs mainly due to vasectomy.

Fig. 13.43 Spermatocytic granuloma: Ill formed epithelioid cell granuloma

13.24.2  Key Cytological Features (Figs. 13.42 and 13.43) • • • • • •

Many ill-formed epithelioid cell granuloma. Histiocytes with phagocytosed sperm heads. Lymphocytes. Many spermatozoa. No necrosis. Z-N stain for AFB: Negative.

13.24.3  Male Infertility [10–12]

13.24.1  Clinical Features

Testicular FNAC is superior to testicular biopsy in case of male infertility. This is because of:

• Nodule at the epididymis. • Mostly asymptomatic patient.

• Easy technique. • Safe.

13.25 Neoplasm of Testis

367

Early Maturation Arrest • No maturation of germ cells after the spermatocyte level. • Smears show spermatocytes and Sertoli cells.

• Minimally invasive. • Easy to interpret the smear. Sensitivity and specificity: 100%.

Late Maturation Arrest • No maturation after the spermatid. • Cytology smears show Sertoli cells, spermatocytes and spermatids. • No spermatozoa.

13.24.4  Sertoli Cell-Only Syndrome (Fig. 13.44) • Abundant sertoli cells. • No germ cell. • Variable number of mast cells.

Normal Spermatogenesis • Large number of spermatozoa, spermatozoa. • Sertoli cells.

spermatids

and

Azoospermia with normal spermatogenesis in FNAC: It indicates the possibility of block in the path of semen.

13.25 Neoplasm of Testis The testicular tumour is classified by WHO [13] as (Fig. 13.45):

13.25.1  Seminoma [14, 15] Fig. 13.44 Only Sertoli cells are present in Sertoli cell-only syndrome

Seminoma is a malignant germ cell tumour originated from the primordial germ cells.

Testicular tumour Miscellaneous

Germ cell tumour derived from germ cell neoplasia in situ Non Invasive germ cell neoplasia • Germ cell neoplasia in situ • lntratubular germ cell neoplasia Tumors of one histological type (pur forms) • Seminoma • Embryonal carcinoma • Yolk sac tumour • Trophoblastic tumours • Choriocarcinoma • Trophoblastic neoplasms other than chonocarc noma • Monophaslc choriocarcinoma • Placental site trophoblastic tumour Tumors of more than one histological type (mixed forms)

Germ cell tumour unrelated to germ cell neoplasia In situ • Spermatocytic seminoma • Teratoma • Dermoid cyst • Monodermal teratoma • Teratoma with somatic type malignancies • Mixed teratoma and yolk sac tumour

Fig. 13.45  World Health Organization’s classification of testicular tumour

Sox cord/gonadal stromal tumors • Leydig cell tumour • Mallgnant Leydig cell tumour • Sertoli cell tumour • Malignant Sertoli cell tumour • Granulosa cell tumour Tumours of the thecoma/fibroma group • Thecoma • Fibroma

368

13  Fine Needle Aspiration Cytology of the Gonads

13.25.2  Epidemiology • • • •

Seminoma is the most frequent germ cell tumours. It represents 50% of the testicular germ cell tumours. It develops in 30–50 year age group. Mean age: 40 years.

13.25.3  Clinical Features • Painless mass in the testis. • About 20% of patients may have painful swelling. • Occasionally the patient may present first time as metastatic tumour (3%).

13.25.4  Key Cytological Features of Classical Seminoma (Figs. 13.46, 13.47, 13.48, 13.49, and 13.50)

Fig. 13.47  Seminoma: The tumour cells have a moderate amount of vacuolated cytoplasm. Nuclei are round, pleomorphic with occasional prominent nucleoli

Predominant pattern: Abundant discrete tumour cells admixed with lymphocytes in a tigroid background. • The characteristic lacy vacuolated background, which is due to fragile cytoplasm. This is also called a “tigroid background”. • Round cells with scanty vacuolated cytoplasm. • Mild pleomorphic nucleus. • Fine chromatin. • Chromatin threads are seen. • Prominent nucleoli. • Many scattered lymphocytes in the background. • Occasional epithelioid cell granulomas. Immunocytochemistry: Positive: placental alkaline phosphatase and CD 117.

Fig. 13.48  Seminoma: Smear showing chromatin thread

Fig. 13.46  Seminoma: Abundant discrete tumour cells along with scattered lymphocytes

Fig. 13.49  Seminoma: Higher magnification showing round nuclei, fine chromatin and prominent nucleoli

13.27 Embryonal Carcinoma

369

–– Absence of tigroid background. –– Immunocytochemistry: Positive for CD 45. • Metastatic carcinoma: –– Cohesive clusters. –– Absent “tigroid” background.

13.27 Embryonal Carcinoma 13.27.1  Epidemiology • Embryonal carcinoma constitutes 2 to 15% of germ cell tumours of testis. • Peak age: 35 years. Fig. 13.50  Seminoma: Epithelioid cell granuloma

13.27.2  Clinical Features

13.26 Spermatocytic Seminoma [16]

• Painless mass in testis. • Occasionally painful mass.

• Spermatocytic seminoma constitutes only 4% of all seminoma. • Elderly males are commonly affected.

13.27.3  Key Cytological Features [17] (Figs. 13.51, 13.52, and 13.53)

13.26.1  Key Cytological Features of Spermatocytic Seminoma

Predominant pattern: Abundant 3-dimensional clusters, acinar and papillae of tumour cells.

• The variable population of cells: Small, medium and large cells. • No “tigroid” background. • The medium-sized cells. –– Predominant population. –– Scanty to moderate cytoplasm. –– Large central nuclei. –– Coarse nuclear chromatin. –– Large prominent nucleoli. • Small cells. –– Scanty cytoplasm. –– Irregular nucleus. –– Dense chromatin. • Large cells. –– Abundant cytoplasm. –– Moderately pleomorphic enlarged nucleus. –– Binucleated with multiple prominent nucleoli.

• Necrotic background. • Large cell with a moderate amount of vacuolated cytoplasm. • Large markedly pleomorphic nucleus. • Macronucleoli. • Hyalinized globule.

13.26.2  Differential Diagnosis • Non-seminomatous germ cell tumour. • Non-Hodgkin lymphoma: –– Lymphoglandular bodies.

Fig. 13.51  Embryonal carcinoma: abundant discrete tumour cells

370

13  Fine Needle Aspiration Cytology of the Gonads

13.28.2  Clinical Feature • The patient usually presents with features of metastasis.

13.28.3  Key Cytological Features

Fig. 13.52  Embryonal carcinoma: Severely pleomorphic nuclei with irregular nuclear margin

• Two populations of cells: Syncytiotrophoblast and cytotrophoblasts • The syncytiotrophoblasts. –– Large cells. –– Abundant cytoplasm. –– Markedly pleomorphic nuclei. –– Many prominent nucleoli. • The cytotrophoblastic. –– Small cells. –– Scanty vacuolated cytoplasm. –– Nuclei are mildly pleomorphic. –– Indistinct nucleoli. Immunocytochemistry: Positive: hCG.

13.29 Other Tumours of the Testis 13.29.1  Leydig Cell Tumour 13.29.1.1 Epidemiology • Leydig cell tumour represents 2% of all testicular neoplasms. • The patients may be in any age group.

13.29.2  Clinical Features Fig. 13.53  Embryonal carcinoma: Markedly pleomorphic nuclei with multiple prominent nucleoli

Immunocytochemistry Positive: AFP and CD30. Negative: CD117. Yolk sac tumour: Described before in ovary section.

13.28 Choriocarcinoma 13.28.1  Epidemiology • Choriocarcinoma as a pure form accounts for 0.3% of all testicular tumours. • Patients are mainly 20 to 40 years of age.

• Mostly asymptomatic patients. • The patients may present gynaecomastia, precocious puberty and Cushing’s disease.

13.29.3  Key Cytological Features • Mainly dissociated and occasional loose groups of tumour cells. • Large cells with abundant cytoplasm. • A round nucleus with fine pale chromatin. • Prominent nucleoli. • The characteristic intranuclear and cytoplasmic Reinke’s crystal present.

References

Fig. 13.54  Non-Hodgkin lymphoma of the testis: Discrete immature lymphoid cells with scanty cytoplasm and enlarged nuclei. Background showing abundant lymphoglandular bodies

13.30 Non-Hodgkin Lymphoma [18] Frequency • Non-Hodgkin lymphoma of the testis represents 1% of all lymphomas of the body. • Lymphoma of testis represents 5% of all testicular tumours. Types of Lymphomas • Predominantly diffuse large B cell lymphoma (90%). • Follicular lymphoma. • MALTOMA. • Small lymphocytic lymphoma. Cytology: Similar to other lymphomas in the body (Fig. 13.54).

13.30.1  Leukemic Infiltration [19] • It is important to diagnose the leukaemic infiltration in testis as testicular relapse of acute leukaemia carries bad prognosis. • FNAC is a safe and rapid technique. Cytology: Abundant immature leukemic blasts.

References 1. Ganjei P, Dickinson B, Harrison T, Nassiri M, Lu Y.  Aspiration cytology of neoplastic and non-neoplastic ovarian cysts: is it accurate? Int J Gynecol Pathol. 1996;15(2):94–101.

371 2. Dey P, Dhar KK, Nijhawan R, Karmakar T, Khajuria A. Fine needle aspiration biopsy in gynecologic malignancies. Recurrent and metastatic lesions. Acta Cytol. 1994;38(5):698–701. 3. Gupta N, Rajwanshi A, Dhaliwal LK, et  al. Fine needle aspiration cytology in ovarian lesions: an institutional experience of 584 cases. Cytopathology. 2012;23(5):300–7. 4. Tahir Z, Yusuf NW, Ashraf M, Yusuf AW, Aziz F. Fine needle aspiration of unilocular ovarian cysts--a cytohistological correlation. J Pak Med Assoc. 2004;54(5):266–9. 5. Kumar M, Rajwanshi A, Dey P. Carcinoid of the ovary: diagnostic challenge on fine-needle aspiration cytology. Diagn Cytopathol. 2014;42(7):612–4. 6. Chakrabarti I, Bera P, Gangopadhyay M, De A. Fine needle aspiration diagnosis of bilateral dysgerminoma with syncytiotrophoblastic giant cells. J Cytol. 2009;26(2):86–7. 7. Arora SK, Dey P. Fine needle aspiration cytology of Sertoli-Leydig cell tumors of ovary masquerading as dysgerminoma. Diagn Cytopathol. 2013;41(7):647–9. 8. Gupta N, Rajwanshi A, Srinivasan R, Nijhawan R.  Fine needle aspiration of epididymal nodules in Chandigarh, North India: an audit of 228 cases. Cytopathology. 2006;17(4):195–8. 9. Mondal K, Mandal R, Saha A, Shahabuddin MD, Sarkar R. Fine needle aspiration cytology of epididymal nodules and its corroboration with ultrasonographic-histological findings. Diagn Cytopathol. 2020;48(2):118–27. 10. Qublan HS, Al-Jader KM, Al-Kaisi NS, et al. Fine needle aspiration cytology compared with open biopsy histology for the diagnosis of azoospermia. J Obstet Gynaecol. 2002;22(5):527–31. 11. Verma AK, Basu D, Jayaram G.  Testicular cytology in azoospermia. Diagn Cytopathol. 1993;9(1):37–42. 12. Ali MA, Akhtar M, Woodhouse N, Burgess A, Faulkner C, Huq M.  Role of testicular fine-needle aspiration biopsy in the evaluation of male infertility: cytologic and histologic correlation. Diagn Cytopathol. 1991;7(2):128–31. 13. Eble JNSG, Epstein JI, Sesterhenn IA. World Health Organization classification of Tumours. Pathology and genetics of Tumours of the urinary system and male genital organs. Lyon: IARC Press; 2004. 14. Caraway NP, Fanning CV, Amato RJ, Sneige N. Fine-needle aspiration cytology of seminoma: a review of 16 cases. Diagn Cytopathol. 1995;12(4):327–33. Epub 1995/06/01 15. Assi A, Patetta R, Fava C, Berti GL, Bacchioni AM, Cozzi L. Fine-­ needle aspiration of testicular lesions: report of 17 cases. Diagn Cytopathol. 2000;23(6):388–92. 16. Saran RK, Banerjee AK, Gupta SK, Rajwanshi A. Spermatocytic seminoma: a cytology and histology case report with review of the literature. Diagn Cytopathol. 1999;20(4):233–6. 17. Singh AD, Wani FA, Bhardwaj S.  Diagnostic accuracy of FNAC and cyto-histopathological correlation in testicular and paratesticular mass lesions. Cytopathology. 2017;28(6):542–8. 18. Hayder S, Das DK, Björk O, Löwhagen T. Fine needle aspiration cytology (FNAC) of the testes in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: preliminary report. Pediatr Hematol Oncol. 1988;5(1):29–34. 19. de Almeida MM, Chagas M, de Sousa JV, Mendonca ME.  Fine-­ needle aspiration cytology as a tool for the early detection of testicular relapse of acute lymphoblastic leukemia in children. Diagn Cytopathol. 1994;10(1):44–6.

Fine Needle Aspiration Cytology of the Soft Tissue Lesions

Presently, fine needle aspiration cytology (FNAC) of soft tissue lesions is a reliable and safe technique. It is because FNAC can provide accurate diagnosis and prognostic assessment with the support of multiple additional tests, e.g. immunocytochemistry (ICC), polymerase chain reaction (PCR) and next-generation sequencing (NGS). FNAC is a quick and safe procedure and can avoid unnecessary surgical intervention in many soft tissue lesions. The Indications of FNAC • Diagnosis of soft tissue neoplasms. • Confirmation of recurrence. • Diagnosis of metastasis. Complications • No major Complications. • Only minor haemorrhage. Diagnostic Accuracy [1–4] • Sensitivity: 90%. • Specificity: 98%. • False-negative rate: 15%. • False-positive: 5%. Causes of False-Negative FNAC • Inadequate sample: This may be due to fibrosis, necrosis or increased vascularity of the tumour. The hyalinized tumour may yield hypocellular material. • Non-representative: The FNAC may aspirate the cells from the neighbouring tissue. It is essential to have FNAC from the multiple sites because of tumour heterogeneity. • The error of interpretation: Well-differentiated tumour may simulate like normal tissue and may wrongly be interpreted as benign or normal.

14

False-Positive Diagnosis The causes of false-positive diagnosis are: • Reactive atypia due to inflammation or regenerative tissue. • The ancient schwannoma may be significantly pleomorphic and may be mistaken as a malignant tumour. A complete clinical, radiological and cytological correlation should always be done before any radical surgery. A massive mutilating surgery based on FNAC should be avoided.

14.1 S  pecimen Collection and Ancillary Techniques FNAC of the soft tissue is done in the usual manner. However, certain things to follow in case of soft tissue FNAC: • At the time of FNAC the following history should be taken: –– Age: Many soft tissue tumours occur in the particular age period. –– Chief complaints: Most of the malignant tumours grow rapidly. –– Size: Malignant tumours are usually more than 5 cm of diameter. –– Radiological imaging: CT scan or MRI help in the assessment of local or systemic spread and therefore are helpful to know the nature of the tumour. –– History: History of previous malignancy may help in the recent diagnosis.

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_14

373

374

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

14.2 Ancillary Techniques

14.2.2  Flow Cytometry

14.2.1  Immunocytochemistry

Flow cytometry is helpful in suspected lymphoma cases.

Immunocytochemistry (ICC) on the cell block material helps considerably in the identification of the exact typing of the soft tissue tumours (SFT). Table 14.1 highlights the essential antibody markers in different SFT. Table 14.1  Immunocytochemistry of soft tissue tumours Tumour LS RMS Neurofibroma MPNST Granular cell tumour Haemangioma Angiosarcoma LCH Desmoid tumour Fibrosarcoma Well-differentiated liposarcoma Myxoid liposarcoma EWS/PNET SS Epithelioid sarcoma Clear cell sarcoma DSRT

Immunocytochemistry h-caldesmon, SMA,calponin, desmin, transgelin Desmin, Myogenin, MyoD1 SOX10, CD34, S100, EMA S-100, SOX10 SOX10, S100, NSE, CD56 CD31, CD34, Claudin5, ERG, vWF CD31, CD34, ERG, Claudin5, Fli-1 CD1a, CD207, S100 Beta catenin, Vimentin, Desmin CD68 Vimentin, CD34, MDM2, S100, p16 Vimentin, TLS, MDM2, S100, p16 CD99, FLI-1, Vimentin TLE-1, pan cytokeratin, EMA, CK7, CK19 AE1/AE3, EMA, D2–40, FLI-1, Vimentin S100, Tyrosinase, MITF, Melan A, Vimentin AE1/AE3, EMA, MOC31, BER-EP4, WT1, Vimentin, Desmin

MPNST Malignant peripheral nerve sheath tumour, LCH Langerhans cell histiocytosis, LS Leiomyosarcoma, DSRT Desmoplastic small round cell tumour, EWS Ewing’s sarcoma, PNET Peripheral neuroectodermal tumours, SS Synovial sarcoma, RMS Rhabdomyosarcoma

14.2.3  Molecular Genetics Specific chromosomal changes are often helpful in the diagnosis of many SFT. The chromosomal changes can be detected by PCR, FISH and next-generation sequencing (NGS). Table 14.2 highlights the molecular genetics of different soft tissue tumours [5].

14.2.4  Electron Microscopy Electron microscopy (EM) is a costly and time-consuming technique. However, it is helpful in certain sarcomas such as rhabdomyosarcoma angiosarcomas [6] (Table 14.3). Table 14.3  Electron microscopic features in certain sarcomas Tumour Clear cell sarcoma DSRT

Electron microscopic features Melanosome Intermediate filaments as a whorling pattern around the nucleus EWS Neural differentiation, occasionally epithelial differentiation Epithelioid sarcoma Cell to cell junction Malignant Intermediate filaments located adjacent to rhabdoid tumour nuclei MPNST Interdigitating cell processes, reduplication of the basal lamina RMS Cytoplasmic cross filament Vascular tumours Weibel-Palade bodies SS Cell to cell junction, cytoplasmic intermediate filaments microvilli-like processes

Table 14.2  Chromosomal changes in different soft tissue tumours Tumour Alveolar soft part sarcoma Chondrosarcoma, extraskeletal myxoid type Clear cell sarcoma Dermatofibrosarcoma protuberans DSRT Epithelioid sarcoma EWS Inflammatory myofibroblastic tumour Liposarcoma, myxoid RMS, alveolar RMS, embryonal Schwannoma SS

Chromosomal abnormalities der(X)t(X;17)(p11;q25) t(9;22)(q22;q12) t(12;22)(q13;q12) t(2;22)(q33;q12) Ring form of chromosome 17 and 22 t(11;22)(p13;q12) t(8;22)(q22;q11); +2 t(11;22)(q24;q12) t(21;22)(q12;q12) 2p23 rearrangement t(12;16)(q13;p11) t(2;13)(q37;q14); del [13](q14) t(8;11)(q12;q21); +11 (trisomy); del [11] Deletion of 22q t(X;18)(p11;q11)

FISH probes used TFE3 EWS-R1 EWS-R1 EWS-R1

Gene involved ASPL-TFE3

EWS-R1

WTl-EWS

EWS-R1 EWS-R1 ALK Chop(DDIT3) FKHR(FOX01A)

FLll-EWS

SYT(SS18)

SSX1-SYT

AFT1-EWS

ALK EWSR1/FUS-DDIT3 PAX3-FKHR

14.4 Tumours of Adipocytes

375

Table 14.4  Fédération Nationale des Centers de Lutte Contré le Cancer grading of sarcoma Features Mitotic figures Areas of necrosis

Score 0 Absence of necrosis

Histology of the tumour

1 0 to 9 / 10 HPF More than 50% tumour necrosis Already defined histological category

2 10 to19 / 10 HPF Less than 50% tumour necrosis Already defined Histological category

3 More than 20 / 10 HPF

Undifferentiated sarcomas and a few other sarcomas

HPF High power field

14.2.5  Reporting Terminology

• Grade 3: Tumours other than Grade 1 with necrosis more than 15%.

The soft tissue tumour can be reported as: • General category: –– Non-diagnostic. –– Benign. –– Atypia possibly benign. –– Atypia suspicious for malignancy.

14.2.6  Malignancy • Exact typing of the soft tissue tumour, if possible. Otherwise, the SFT can be labelled in a general type and then the possibility of the tumour. –– Spindle cell types: It includes schwannoma, MPNST, fibrosarcoma, leiomyosarcoma and dermatofibrosarcoma protuberans. –– Round cell type: Various malignant round cell tumours such as soft tissue ES, RMS (Embryonal and alveolar), DSRT and round cell liposarcoma. –– Pleomorphic cell type: Pleomorphic RMS, pleomorphic liposarcoma and malignant fibrous histiocytoma. –– Biphasic pattern: SS. • Grading of soft tissue sarcoma (STS): The prognosis of the various soft tissue tumour largely depends on the grading of SFT. • There are two systems of grading: –– NCI grading system is done by Costa et al. [7]. –– French grading system is done by Guillou et al. [8]. NCI system grading of soft tissue sarcoma [7] (STS): • Grade 1 sarcoma. –– Myxoid and well-differentiated liposarcoma. –– Deep-seated dermatofibrosarcoma protuberans. –– LS. –– Malignant hemangiopericytoma. –– Malignant schwannoma. –– Chondroid sarcoma or myxoid chondrosarcoma. • Grade 2: Tumours other than Grade 1 with necrosis less than 15%.

The French grading system of sarcomas: Tumour is at first scored based on: • Tumour differentiation: Score 1, 2 and 3. This system already does the initial type of tumour and its score. • Mitotic rate: Score 0, 1,2, 3. • Tumour necrosis score 0,1,2. Now, the final grade depends on the total score (see Table 14.4). Total score: Grade 1: Total score 2 to 3, Grade 2: Total score 4 to 5, Grade 3: Total score 6 to 8 • Result of ancillary investigations: The detailed result of the various ancillary techniques should be mentioned in the main report.

14.3 Classification of Soft Tissue Tumours World Health Organization classifies the STS [9] according to the cell of origin and biological behaviour of the tumour (see Fig. 14.1).

14.4 Tumours of Adipocytes [10] 14.4.1  Benign Tumours 14.4.1.1 Lipoma Epidemiology • The lipoma is the commonest SFT and accounts for 50% of all SFT. • In any age group may be affected. However, It commonly occurs in the 30 to 60 year age. • Rare in children.

376

Adipocytic tumours Benign

Lipoma, Myolipoma, Angiolipoma, Spindle cell lipoma, Pleomorphic Lipoma, Intermediate (locally aggressive) Atypical lipomatous tumour/Well differentiated liposarcoma Malignant Dedifferentiated liposarcoma, Myxoid liposarcoma, Round cell liposarcoma Pleomorphic liposarcoma, Mixed-type liposarcoma, Liposarcoma, not otherwise specified

Vascular tumours Benign

Haemangiomas, Epithelioid haemangioma, Lymphangioma Intermediate(locally aggressive) Kaposiform haemangioendothelioma Intermediate(rarely metastasizing) Retiform haemangioendothelioma, Papillary intralymphatic angioendothelioma, Kaposi sarcoma Malignant Epithelioid haemangioendothelioma, Angiosarcoma of soft tissue

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

Soft tissue tumours

Fibroblastic/myofibroblastic tumours Benign

Nodular fascilitis, Proliferative fascilitis, Proliferative myositis, Myositis ossificans Intermediate(locally aggressive) Superficial fibromatoses Desmoid-type fibromatoses, Lipofibromatosis Intermediate(rarely metastasizing) Solitary fibrous tumor, Haemangiopericytoma Infantile fibrosarcoma Malignant Adult fibrosarcoma, Myxofibrosarcoma Low grade fibromyxoid sarcoma So called Fibrohistiocytic tumors Benign Giant cell tumour of tendon sheath, Diffusetype giant cell tumour, Intermediate(rarely metastasizing) Plexiform fibrohistiocytic tumour Giant cell tumour of soft tissues Malignant Pleomorphic MFH, Giant cell MFH Inflammatory MFH

CHONDRO-OSSEOUS TUMORS Soft tissue chondroma, Mesenchymal chondrosarcoma, Extraskeletal osteosarcoma

Smooth muscle tumors Leiomyoma Leiomyosarcoma Pericytic (perivascular) tumours Glomus tumour malignant glomus tumour Skeletal muscle tumours Benign Rhabdomyoma Malignant Embryonal rhabdomyosarcoma, Alveolar rhabdomyosarcoma, Pleomorphic rhabdomyosarcoma Tumors of uncertain differentiation Benign Myxoma Intermediate(rarely metastasizing) Mixed tumor, Myoepithelioma Malignant Synovialsarcoma, Epithelioid sarcoma, Alveolar soft part sarcoma, clear cell sarcoma of soft tissue, PNET/Extraskeletal Ewing tumor, Desmoplastic small round cell tumour, Neoplasma with perivascular epithelioid cell differentiation (PEComa)

Fig. 14.1  World Health Organization classifies the soft tissue sarcoma

14.5 Angiolipoma 14.5.1  Epidemiology The tumour is common in the late second decade. Children and elderly persons are rarely affected.

14.5.2  Clinical Features • Multiple small reddish subcutaneous swelling. • Mainly occurs in the forearm.

14.5.3  Key Cytological Features (Fig. 14.3) Fig. 14.2  Lipoma: Large clusters of mature adipocyte

14.4.2  Clinical Feature • Usually presents as painless slow-growing tumours. • The tumour may occur in any anatomical locations.

• Smears show multiple branched blood capillaries. • Many clusters of mature adipocytes.

14.6 Spindle Cell Lipoma 14.6.1  Epidemiology

14.4.3  Key Cytological Features (Fig. 14.2) • Smears show multiple clusters of mature fat. • The fat cells contain abundant cytoplasm. • Centrally placed small regular nucleus.

• It is mainly noted in 50 to 70 years of age. • Median age: 55 years.

14.8 Hibernoma

Fig. 14.3 Angiolipoma: Fat cells along with many thin-walled capillaries

377

Fig. 14.4  Pleomorphic lipoma: Loose cluster and discrete fat cells with nuclear atypia

14.6.2  Clinical Features • Single mobile subcutaneous swelling. • Slow growing nodules. • Predominantly seen in the back of the neck, and back.

14.6.3  Key Cytological Features • • • • • • • •

Multiple clusters of mature adipocytes. Multiple clusters and small fascicles of spindle cells. Oval to elongated nucleus. Bland nuclear chromatin. Inconspicuous nucleoli. Nuclear grooves present. Acellular collagenous material. Many mast cells.

Immunocytochemistry: Positive: CD34, actin and desmin. Occasionally cells show S-100 positivity. Differential Diagnosis • Various other spindle cell lesions such as Schwannoma, Myxoid sarcoma and well-differentiated liposarcoma.

14.7 Pleomorphic Lipoma 14.7.1  K  ey Cytological Features (Figs. 14.4 and 14.5) • Multiple clusters of mature fat cells. • The fat cells have enlarged nuclei. • Nuclei are hyperchromatic.

Fig. 14.5  Pleomorphic lipoma: The cells show vacuolated cytoplasm and centrally placed pleomorphic nuclei

• Floret cells: Multiple nuclei arranged semicircularly like the petal of a flower. • Absence of lipoblasts.

14.7.2  Differential Diagnosis • Liposarcoma: –– Rapidly growing mass. –– usually deep-seated, –– No floret cells.

14.8 Hibernoma Hibernoma is an uncommon benign adipocytic tumour made of brown fat cells.

378

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

14.8.1  Epidemiology

14.10 Liposarcomas

• It represents only 1% of all lipomatous tumour. • Commonly present in young persons. • Mean age of 38 years.

Atypical lipomatous liposarcoma.

tumor

(ALT)/well-differentiated

14.10.1  Epidemiology 14.8.2  Clinical Features • Slowly growing mass for many years. • Common location: Thigh, trunk, scapular and head-neck region.

• ALT accounts for 45% of all liposarcomas. • It is seen mostly in the older adult and peak incidence is in the sixth decade.

14.10.2  Clinical Features 14.8.3  Key Cytological Features • Multiple clusters of mature adipocytes and hibernoma cells. • Hibernoma cells. –– Large cell with pale cytoplasm. –– Multiple small vacuolations in the cytoplasm. –– Centrally located small nuclei. • Abundant blood capillaries.

14.8.4  Differential Diagnosis • Granular cell tumour: NSE and S-100 protein positivity in ICC. • Well-differentiated liposarcoma. • Adult rhabdomyoma: –– Relatively large cells. –– Characteristic fibrillary cytoplasm. –– Positive for myoglobin. • Lipoma: Absence of hibernoma cells.

• Deep-seated slowly developing mass. • The typical location is in the extremities followed by the retroperitoneal region.

14.10.3  K  ey Cytological Features [11] (Figs. 14.6 and 14.7) • • • • • •

Multiple loose aggregates of fat cells. A large cell having vacuolated cytoplasm. Enlarged and moderately pleomorphic nucleus. Large round to polygonal fat cells. Occasional floret cells present. Lipoblasts are characteristic of liposarcoma: –– Round cell. –– Multiple small vacuoles around the nuclei. –– The vacuoles give compression to the nuclei. –– Occasionally compressed nuclei simulate “signet ring” cells.

14.9 Myelolipoma Myelolipoma is mainly noted in the adrenal gland. Occasionally it may be present in the pelvic and retroperitoneal area.

14.9.1  Key Cytological Features • Mature fat tissue. • The variable admixture of immature granulocytic series of cell. • Megakaryocytes. • Nucleated red blood cells.

Fig. 14.6  Well-differentiated liposarcoma: Scattered large atypical cells

14.11 Myxoid Liposarcoma

Fig. 14.7  Well-differentiated liposarcoma: Large tumour cell with many enlarged nuclei

379

Fig. 14.8  Myxoid liposarcoma: Discrete tumour cells with a myxoid background

14.10.4  Differential Diagnosis • Pleomorphic lipoma: –– The typical floret cells present. –– Slow growing tumour. –– Well circumscribed. • Fat necrosis: Fat necrosis, along with lipophages may simulate ALT. –– Absence of lipoblasts in fat necrosis. • Lipoma: Rarely lipoma may simulate ALT. However, the atypical cells in lipoma are focally present.

14.11 Myxoid Liposarcoma 14.11.1  Epidemiology • Myxoid liposarcoma (MLS) represents 10% of all sarcomas in adults. • It represents more than 30% of all liposarcomas. • Commonly occurs in 40 to 50 years of age.

Fig. 14.9  Myxoid liposarcoma: The tumour cells are oval with a moderate amount of vacuolated cytoplasm and enlarged nuclei

14.11.2  Clinical Features • Painless large swelling. • Mainly extremities are affected.

14.11.3  K  ey Cytological Features [12] (Figs. 14.8,14.9, and 14.10) • • • •

The smear shows the granular myxoid background. Many arborizing complex thin-walled capillaries. Characteristic lipoblasts. Many scattered round to oval cells.

Fig. 14.10  Myxoid liposarcoma: Lipoblast (arrow) with central nuclei surrounded by the vacuoles

380

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

• Enlarged nuclei with the high nucleocytoplasmic ratio. • The cells are often vacuolated.

14.11.4  Differential Diagnosis • Other myxoid tumours: Intramuscular myxoma, or tumours with myxoid degeneration. The presence of arborizing capillaries is the characteristic feature of MLS. • Spindle cell lipoma with myxoid change: Absence of lipoblasts or branching capillaries. • The myxoid variant of malignant fibrous histiocytoma (MFH). • Mucinous adenocarcinoma: –– Highly cellular. –– No capillaries. –– No lipoblast. –– CK positive.

Fig. 14.11  Pleomorphic sarcoma: Cluster of tumour cells showing marked nuclear pleomorphism

14.12 Pleomorphic Liposarcoma 14.12.1  Epidemiology • • • •

It represents 5% of all liposarcomas. It constitutes one-fifth of all pleomorphic sarcomas. Elderly patients. Both sexes are equally affected.

14.12.2  Clinical Features • Rapidly growing mass. • Predominantly in the extremities. Fig. 14.12  Pleomorphic sarcoma: Large cells with vacuolated cytoplasm and centrally placed bizarre nuclei

14.12.3  K  ey Cytological Features [10] (Figs. 14.11 and 14.12) Predominant pattern: Dissociated and loosely aggregated cells • • • • • • • •

Large cell with enlarged nucleus. Marked nuclear pleomorphism. Irregular nuclear outline. Coarse chromatin. Multiple prominent nucleoli. Lipoblast. Background necrosis. Many mitotic figures.

Note: The presence of lipoblast is the most important indicator of pleomorphic liposarcoma.

14.12.4  Differential Diagnosis • Other pleomorphic sarcomas: Pleomorphic RMS and malignant fibrous histiocytoma.

14.13 Round Cell Liposarcoma It is a very uncommon tumour.

14.15 Myositis Ossificans

14.13.1  Key Cytological Features • • • • • •

Many discrete and small groups of cells. Small round cells. Vacuolated cytoplasm. Pleomorphic nucleus. Prominent nucleoli. No myxoid material.

14.14 Fibroblastic/Myofibroblastic Tumours 14.14.1  Benign 14.14.1.1 Nodular Fasciitis Epidemiology • Relatively common SFT. • Any age group may be affected; however, it is common in young patients.

14.14.2  Clinical Features • Painful swelling. • Rapidly growing nodule. • Predominantly located in the extremities and trunk.

14.14.3  K  ey Cytological Features [13] (Fig. 14.13) • • • •

Hypercellular smear. The discrete and tight cluster of cells. The cells are often arranged around thin capillaries. Round and spindle cells.

Fig. 14.13  Nodular fasciitis: Loosely cohesive oval to spindle cells

381

• • • •

The spindle-shaped nuclei with the blunt end. Fine chromatin. Inconspicuous nucleolus. Mitotic figures are often present.

Differential Diagnosis • Sarcoma.

14.15 Myositis Ossificans Myositis ossificans (MO) is a reparative lesion that heals spontaneously.

14.15.1  Epidemiology • MO may affect in the age group. • Young adults are commonly affected.

14.15.2  Clinical Features • History of trauma is often present. • Usually occur in the buttock, thigh or elbow. • At first, the swelling is painful, and slowly it becomes painless firm nodule.

14.15.3  K  ey Cytological Features [14] (Figs. 14.14, 14.15, and 14.16) • Smears are hypocellular. • Dirty granular material in the background.

Fig. 14.14  Myositis ossificans: Osteoid material and osteoblasts

382

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

14.16.1  Epidemiology • Uncommon tumour. • It may occur in second to seventh decade. • Median age: 50 years.

14.16.2  Clinical Features • Usually located in the extremities, thoracic wall, peritoneum, mediastinum and head neck region. • The painless slowly growing mass. • About 90% of the tumours are benign.

Fig. 14.15  Myositis ossificans: Connective tissue fragment

14.16.3  K  ey Cytological Features [15] (Figs. 14.17, 14.18, and 14.19) • Smears are moderately cellular. • Small fascicles and discrete cells. • The background shows collagenous material and bare nuclei. • The individual cells are: –– Oval to spindle shaped. –– Thin cytoplasm. –– Nuclei are spindle shaped with both ends blunt. –– The nuclear chromatin is granular with absent nucleoli.

14.16.4  Malignant Solitary Fibrous Tumour

Fig. 14.16  Myositis ossificans: Scattered osteoblasts

• Hypercellular smear. • High mitosis. • Nuclear pleomorphism.

• Many multinucleated osteoclastic giant cells. • Osteoblast. • Myofibroblast are present. –– These are round to oval cells. –– Abundant basophilic cytoplasm. • Nuclei are peripherally located.

Differential Diagnosis Osteosarcoma • Clinical history of trauma in MO. • Correct identification of myofibroblasts.

14.16 Solitary Fibrous Tumour The solitary fibrous tumour is the benign tumour with possible origin form the fibroblasts.

Fig. 14.17  Solitary fibrous tumour: Discrete and small fascicles of tumour cells

14.17 Dermatofibrosarcoma Protuberans

383

14.17.1  K  ey Cytological Features (Figs. 14.20 and 14.21) • Multiple fascicles of cells. • Long spindle-shaped nucleus with mild pleomorphism. • Small nucleolus.

Differential Diagnosis • Fibrous histiocytoma. • Nodular fasciitis.

Fig. 14.18  Solitary fibrous tumour: Oval to spindle cells embedded in pinkish material

Fig. 14.20  Dermatofibrosarcoma protuberans: Cluster of oval to spindle cells

Fig. 14.19  Solitary fibrous tumour: Round to oval cells with scanty cytoplasm. Nuclei are monomorphic with granular chromatin

Differential Diagnosis • Other SFT with spindle-shaped nuclei such as MPNST, monophasic SS, fibromatosis, LS.

14.17 Dermatofibrosarcoma Protuberans Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignancy. • Adult males are commonly affected. • DFSP presents as a skin nodule.

Fig. 14.21  Dermatofibrosarcoma protuberans: Discrete cells showing oval to spindle-shaped nuclei having granular chromatin

384

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

14.18 Myofibroblastoma Myofibroblastoma is a benign mesenchymal neoplastic lesion due to proliferation of myofibroblasts.

14.18.1  Epidemiology • Mainly adults are affected. • Mean age: 55 years.

14.18.2  Clinical Features • Breast is mainly affected. • Rarely buttock, abdominal wall. • Painless swelling.

Fig. 14.22  Fibrosarcoma: Multiple tight clusters of oval to spindle cells

14.18.3  Key Cytological Features [16] • • • • •

Multiple clusters and dissociated spindle cells. Vacuolated cytoplasm. Spindly nuclei. Granular chromatin. Large multinucleated cells. Immunocytochemistry: Positive: Desmin and CD34.

14.19 Fibrosarcoma Fibrosarcoma is a malignant tumour of fibroblasts. Fig. 14.23  Fibrosarcoma: Small fascicles of spindle cells

14.19.1  Epidemiology • Fibrosarcoma accounts for 2–3% of all sarcoma. • It is more frequent in 30 to 55 years of age. • Both sexes are equally affected.

14.19.2  Clinical Features • The painless rapidly growing mass. • Typical locations: Extremities, trunk, head-neck area.

14.19.3  K  ey Cytological Features (Figs. 14.22, 14.23, and 14.24) • Small clusters and fascicles of cells. • “Herring bone pattern” in the cell block section

Fig. 14.24  Fibrosarcoma: The scattered cells with spindle-shaped nuclei. The nuclei show mild-to-moderate pleomorphism

14.20 So-Called “Fibrohistiocytic Tumours”

• • • • •

385

The spindle-shaped nucleus with pointed ends. The irregular contour of the nuclei. Moderate nuclear pleomorphism. Fine chromatin. Background shows necrosis.

Differential Diagnosis • Sarcomas with predominant spindle-shaped nuclei: –– Leiomyosarcoma. –– SS. –– MPNST.

14.20 So-Called “Fibrohistiocytic Tumours” 14.20.1  Giant Cell Tumour of Tendon Sheath

Fig. 14.25  Giant cell tumour of tendon sheath: Many multinucleated giant cells, round stromal cells and pigment laden macrophages

Giant cell tumour of tendon sheath (GCTTS) is a benign lesion of the synovial cells. Two forms: • Localized form: Nodular tenosynovitis. Predominantly occurs in the hand, and also in the arm and leg. • Diffuse form: pigmented villonodular tenosynovitis. Pigmented villonodular tenosynovitis usually affects near the knee joint and also ankle joint.

14.20.2  Epidemiology • GCTTS may occur at any age. • Frequently seen in 30 to 50 years of age.

14.20.3  Clinical Features

Fig. 14.26  Giant cell tumour of tendon sheath: Giant cell surrounded by many pigment laden histiocytes

• GCTTS presents as slowly growing painless mass. • Common locations: Finger (85%), near ankle and knee joint.

14.20.4  K  ey Cytological Features [17] (Figs. 14.25, 14.26, 14.27, and 14.28) Predominant pattern: Abundant osteoclast-like giant cells, pigment laden macrophages and stromal cells. • Good cellularity. • Numerous scattered homogenously admixed osteoclast-­ like giant cells. • Each cell contains 30 to 40 nuclei. Fig. 14.27  Giant cell tumour of tendon sheath: Multinucleated giant • The morphology of the nuclei is similar to stromal cells. cell contains many small nuclei • Round nuclei.

386

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

14.21.2  Clinical Features • The large painless slow-growing mass. • Common locations: Extremities and trunk.

14.21.3  Key Cytological Features • • • • • • Fig. 14.28  Giant cell tumour of tendon sheath: The higher magnification showing round stromal cells

• • • •

Fine chromatin. Prominent nucleoli. Infrequently nuclear groove. Discrete stromal cells: –– Polygonal cells. –– Abundant cytoplasm. –– Regular round nucleus. –– Occasional nuclear groove. –– Intranuclear inclusions. • No atypical mitosis. • Hemosiderin laden macrophages.

Many clusters of spindle cells. Moderate cytoplasm. Pleomorphic nucleus. Coarse chromatin. Prominent nucleolus. Also, many large bizarre pleomorphic cell and tumour giant cells with markedly pleomorphic nuclei are seen.

14.21.4  Differential Diagnosis • Pleomorphic liposarcoma: Lipoblasts present. • Pleomorphic rhabdomyosarcoma: Striated Myogenin and Myo D positive cells. • Anaplastic carcinoma: Positive for CK. • Anaplastic large cell lymphoma: –– Discrete cells. –– Absent stromal material. –– CD30 and ALK1 positive cells.

cells,

14.22 Tumours of Nerve Sheath Immunocytochemistry Stromal cells. Positive: CD 68 and SMA. Multinucleated giant cells. Positive for CD 68, and phosphatase.

14.22.1  B  enign Peripheral Nerve Sheath Tumour tartrate-resistant

acid

Differential Diagnosis • Giant cell tumour of bone: Bone is involved.

14.21 P  leomorphic Malignant Fibrous Histiocytoma Pleomorphic MFH is a tiny subset of pleomorphic sarcoma. Synonyms: Malignant fibrous histiocytoma, fibroxanthosarcoma.

14.21.1  Epidemiology • The tumour is usually present in elderly patients. • Male: female ratio is 1.2:1.

14.22.1.1 Schwannoma and Neurofibroma • Common in elderly patients. • The common locations: Head and neck region, extremities and cerebellopontine angle. • Mainly sporadic tumour.

14.22.2  K  ey Cytological Feature [18] (Figs. 14.29, 14.30, and 14.31) Predominant pattern: Multiple small fascicles of spindle cells. The cytological features of schwannoma and neurofibromas are grossly overlapping: • • • • •

Multiple fascicles of cells. Spindle-shaped nuclei. Pointed nuclear ends. Wavy kinked nuclei. Myxoid changes or cystic degeneration may be present.

14.23 Malignant Peripheral Nerve Sheath Tumour

387

• The cells of ancient schwannoma often show significant nuclear pleomorphism. • Besides, the palisading arrangement of cells is also seen in schwannoma.

Differential Diagnosis • Sarcoma: Nuclear pleomorphism in ancient schwannoma may mimic as sarcoma.

14.23 M  alignant Peripheral Nerve Sheath Tumour Fig. 14.29  Schwannoma: Multiple clusters of oval to spindle cells

Malignant peripheral nerve sheath tumour (MPNST) develops from the peripheral nerves or an already existing neurofibroma. Synonym: Neurofibrosarcoma.

14.23.1  Epidemiology • It represents 5 to 10% of all sarcomas. • The tumour is commonly present in 20 to 60 year age.

14.23.2  Clinical Features

Fig. 14.30  Schwannoma: The tumour cells are embedded in neurofibrillary stroma

• Tumour involves proximal part of the extremities, pelvis and retroperitoneum. • The patient often complaints of rapidly developing mass. • The tumour may present as quickly growing neurofibromatous nodule. • In case of the development from peripheral nerve sheath, the patient may have radicular pain and paresthesia.

14.23.3  K  ey Cytological Feature [19] (Figs. 14.32, 14.33, 14.34, 14.35, and 14.36) Predominant pattern: Multiple tiny fascicles of spindle cells having pleomorphic nuclei • • • • • • • Fig. 14.31  Schwannoma: The tumour cells have spindle-shaped nuclei with pointed ends

Hypercellular smear. Often the background is fibrillary. Nuclei are elongated spindle-shaped with both ends pointed. Nuclear kinking or wavy nuclei. Moderate nuclear pleomorphism. Frequent mitotic figures. Predominantly polygonal cells are present in the epithelioid type of MPNST. • Background necrosis may be present.

388

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

Fig. 14.32  Malignant peripheral nerve sheath tumour: Many discrete spindle cells

Fig. 14.35  Malignant peripheral nerve sheath tumour: Higher magnification showing fine chromatin

Fig. 14.33  Malignant peripheral nerve sheath tumour: The cells have moderately pleomorphic spindle-shaped nuclei

Fig. 14.36  Malignant peripheral nerve sheath tumour: Cells with moderate nuclear pleomorphism and pointed ends

Immunocytochemistry: Positive: S100, Myelin basic protein and SOX10. Differential Diagnosis • Fibrosarcoma. • Leiomyosarcomas. • Monophasic synovial sarcoma. Immunocytochemistry is needed to diagnose these tumours.

Fig. 14.34  Malignant peripheral nerve sheath tumour: Spindle-shaped nuclei with kinking

14.25 Rhabdomyosarcoma

389

14.24 Tumours of Muscle Origin 14.24.1  Rhabdomyoma Rhabdomyoma (RM) is a rare benign tumour of skeletal muscle.

14.24.2  Epidemiology • • • •

Rare tumour. RM may occur from 30 to 80 years. Median age: 60 years. Male: female ratio is 3:1.

14.24.3  Clinical Features • Common location: Head and neck area (90%). • Features of the upper airway obstruction.

14.24.4  K  ey Cytological Feature [20] (Figs. 14.37 and 14.38) • • • • •

Many discrete tumour cells. The cell is large. The cytoplasm is abundant and vacuolated. Cytoplasmic cross striation. Small round nuclei having a single prominent nucleoli.

Fig. 14.38  Rhabdomyoma: Higher magnification showing cells with abundant bluish cytoplasm with central round monomorphic nuclei

Types of rhabdomyosarcoma: 1) pleomorphic, 2) embryonal and 3) alveolar.

14.25.1  Embryonal Rhabdomyosarcoma 14.25.1.1 Epidemiology • The most frequent type of RMS. • It accounts for 50% of all RMS. • Embryonal RMS occurs mainly below ten years of age.

14.25.2  Clinical Features

14.25 Rhabdomyosarcoma [21, 22] Rhabdomyosarcoma (RMS) is a malignant tumour of the skeletal muscle.

Location: Head and neck, and genitourinary region such as urinary bladder and vagina. Symptoms: Rapidly developing mass and various signs of obstruction such as proptosis, sinusitis and urinary obstruction.

14.25.3  K  ey Cytological Feature (Figs. 14.39, 14.40, 14.41, 14.42, and 14.43) Predominant pattern: Abundant small round tumour cells

Fig. 14.37  Rhabdomyoma: Multiple clusters of skeletal muscle cells

• Abundant cellularity. • Two types of cells. –– Small cells: Round mildly pleomorphic nucleus, fine chromatin and prominent nucleolus. –– Large cells: Abundant cytoplasm and round, or spindle-­ shaped nuclei. These are the intermediate to late rhabdomyoblasts. • Frequent bi- and multinucleation. • Multinucleated giant cells.

390

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

Fig. 14.39  Rhabdomyosarcoma: Abundant cells in loose clusters and discretely

Fig. 14.42  Rhabdomyosarcoma: The tumour cells are positive for myogenin

Fig. 14.40  Rhabdomyosarcoma: The cells are round with scanty cytoplasm. The nuclei are round and monomorphic

Fig. 14.43  Rhabdomyosarcoma: The tumour cells are positive for desmin

• Strap cells. • The tigroid background may be present.

14.26 Alveolar Rhabdomyosarcoma 14.26.1  Epidemiology • • • •

Alveolar rhabdomyosarcoma represents 20% of all RMS. Any age group may be affected. Common in adolescent and young age. Both sexes are equally affected. Molecular cytogenetics:

Fig. 14.41 Rhabdomyosarcoma: Haematoxylin and eosin-stained smear showing round cells with hyperchromatic nuclei

• Majority: Translocation (2; 13) (q35; q14). • Small subset: translocation t (1; 13)(p36; q14).

14.28 Leiomyosarcomas

391

14.26.2  Clinical Features

14.28 Leiomyosarcomas

• They are rapidly developing swelling in the extremities, paraspinal and perineal region. • Often pressure symptoms due to the compression of the neighbouring structures.

Leiomyosarcomas (LS) is the benign tumour of smooth muscle.

14.26.3  Key Cytological Features

• Common in the middle aged and elderly persons. • Other than uterine origin a significant percentage of LS is of retroperitoneal origin. • LS uncommonly occurs in the extremities.

• • • • •

Hypercellular smear. Uniform population of tumour cells. Small round cells. Deep blue cytoplasm with small vacuolations. The round moderately pleomorphic nucleus with fine chromatin. • Prominent nucleolus. • Multinucleated giant cells.

14.27 Pleomorphic Rhabdomyosarcoma 14.27.1  Epidemiology • Rare tumour. • It occurs in the adult person. • Median age: sixth decade.

14.27.2  Clinical Features

14.28.1  Epidemiology

14.28.2  Clinical Features • The retroperitoneal tumour presents as the symptoms of compression such as jaundice or Budd Chiari syndrome if the LS occurs in the inferior vena cava.

14.28.3  K  ey Cytological Feature [23, 24] (Figs. 14.44 and 14.45) • • • • • • •

Multiple fascicles of cells. Also, the dissociated cells are seen. The cells have cigar-shaped elongated nuclei. Both ends of the nuclei are blunt. A moderate degree of nuclear atypia. Many multinucleated tumour giant cells. High mitotic activity.

• The deep soft tissue of the thigh region. • Rapidly growing mass.

14.27.3  Key Cytological Features • • • • • • •

Hypercellular smear. Abundant dissociated and loosely cohesive cells. large cells with moderate cytoplasm, Markedly pleomorphic nuclei. Multiple prominent nucleoli. Multinucleated tumour giant cells. Many mitotic figures.

Immunocytochemistry: Positive: Desmin, myogenin and myo D1. Differential Diagnosis • Various small blue round cell tumour.

Fig. 14.44  Leiomyosarcoma: Abundant oval to elongated tumour cells with blunt-ended nuclei

392

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

14.29.4  Key Cytological Feature • FNAC is usually not done in glomus tumours. • Dissociated round cells. • The cells are entangled within the myxoid fibrillary background. • Ill-defined cell margin. • Abundant cytoplasm. • Monomorphic round nuclei. • Bland chromatin. • Inconspicuous to absent nucleoli. Immunocytochemistry: Positive: CD 31, CD 34 and SMA.

Fig. 14.45  Leiomyosarcoma: Haematoxylin and eosin stain showing mildly pleomorphic spindle-shaped nuclei

14.30 Haemangioma Haemangioma is a benign vascular tumour.

Note: Mitotic count may not be helpful to distinguish LS from the leiomyoma. However, the following factors indicate LS such as many discrete cells, nuclear atypia and frequent mitotic figures. Immunocytochemistry: Positive: Desmin and caldesmon. Differential Diagnosis • Other spindle cell tumour: MPNST, fibrosarcoma, schwannoma etc.

14.29 Tumour of Vascular Origin 14.29.1  Glomus Tumour [25] Glomus tumour is a benign tumour of the modified smooth muscle cells of the glomus body.

14.30.1  Clinical Features • Children are commonly affected. • Soft compressible swelling in the head-neck area and in the extremities.

14.30.2  Key Cytological Features • • • • •

FNAC usually yield blood. Scant cellularity. Scattered cells with elongated spindly nuclei. Fragments of blood capillaries. Occasional histiocytes.

14.31 Angiosarcoma [26] Angiosarcoma is the malignant tumours of endothelial cells.

14.29.2  Epidemiology • Glomus tumour accounts for 2% of all SFT. • It predominantly occurs in young adults. • The equal incidence in both sexes.

14.29.3  Clinical Features • Common location: Peripheral part of the extremity such as fingers, the wrist and foot. • Complaints: Painful reddish swelling.

14.31.1  Epidemiology • A very rare tumour. • Angiosarcoma commonly occurs in elderly persons.

14.31.2  Clinical Features Location: The deeper tissue of the lower extremities, arm, trunk and head-neck area. Symptoms: Rapidly enlarging mass, anaemia, persistent haematoma formation.

14.32 Tumours of Uncertain Histogenesis

393

14.31.3  Key Cytological Features • • • • •

FNAC usually yields blood. Paucicellular smear. Discrete oval to spindle cells. Nuclei are hyperchromatic and moderately pleomorphic. Occasional tumour cells are signet ring type with intracytoplasmic RBC. Immunocytochemistry: Positive: CD34 and CD31.

14.32 Tumours of Uncertain Histogenesis 14.32.1  Synovial Sarcoma Synovial sarcoma (SS) is an aggressive malignancy of uncertain histogenesis. The term “Synovial sarcoma” is a complete misnomer as the tumour is unrelated with synovial lining cells.

Fig. 14.46  Synovial sarcoma: The small fascicles and discrete spindle cells

14.32.2  Epidemiology • SS represents 5 to 10% of all SFT. • The tumour is seen in any age group; however, it commonly occurs in 15 to 40 years.

Molecular Genetics • Translocation of t(x;18) (p11;q11).

14.32.3  Clinical Features Fig. 14.47  Synovial sarcoma: Large cluster of oval to spindle cells

• Painless mass. • Rapidly growing. • Tumour predominantly occur around knee joints or deep tissue of the extremities.

14.32.4  K  ey Cytological Features [27] (Figs. 14.46, 14.47, 14.48, 14.49, 14.50, 14.51, and 14.52) Prdominant pattern: Abundant spindle and epithelial looking cells with occasional gland. Biphasic synovial cell sarcoma • The dual population of cells: Epithelial and spindle cells. • Epithelial cells: –– Often arranged as glands, tubules and papillae like. –– Round to oval cells.

Fig. 14.48 Synovial sarcoma: Both spindle cells and scattered epithelial-­like cells

394

Fig. 14.49  Synovial sarcoma: The polyhedral cells have a moderate amount of cytoplasm with enlarged nuclei

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

Fig. 14.52  Synovial sarcoma: The cells showing TLE1 positivity

–– Moderate to abundant cytoplasm. –– Regular round nucleus. –– Fine chromatin. –– Occasional prominent nucleolus. • Spindle cells: –– Predominantly arranged as small fascicles and discretely. –– Nuclei are elongated. –– Hyperchromatic. –– Irregular nuclear contour. –– Prominent nucleoli. Monophasic synovial cell sarcoma

Fig. 14.50  Synovial sarcoma: Haematoxylin and eosin-stained smear showing epithelial-like cells

• • • • •

Epithelial cells are absent. Predominantly spindle cells. Many mitotic figures. Necrosis. Mast cells.

Immunocytochemistry Epithelial cells. Positive: TLE-1, Pan cytokeratin, EMA and CK7. Spindle cells. Positive: TLE-1, Vimentin, Calponin and CD99. Differential Diagnosis • Fibrosarcoma. • Leiomyosarcoma.

14.33 Clear Cell Sarcoma (CCS) Fig. 14.51  Synovial sarcoma: Higher magnification showing both spindle and epithelial cells having fine chromatin

Synonym: Malignant melanoma of the soft part.

14.33 Clear Cell Sarcoma (CCS)

395

14.33.1  Epidemiology • CCS represents 1% of all SFT. • It occurs in 10 to 50 years of age, and young adults are commonly affected. Molecular cytogenetics: Characteristic translocation of t(l2;22)(q13;q12) causing fusion of ATF1 gene on chromosome 12 and the EWS gene on chromosome 22.

14.33.2  Clinical Features Location: Legs, hand and wrist. The tumour is deep-seated attached with the aponeurosis. Chief complaints: • Slowly growing swelling for years. • Usually painless.

Fig. 14.54  Clear cell sarcoma: Polyhedral cells with well-defined cytoplasmic margin and a moderate amount of cytoplasm

14.33.3  K  ey Cytological Features [28, 29] (Figs. 14.53, 14.54, 14.55, 14.56, and 14.57) Predominant pattern: Clusters and loosely cohesive tumour cells with clear cytoplasm. • • • • • • • •

Polygonal or spindle-shaped cells. Cytoplasm is abundant. Cytoplasmic melanin pigmentation. Eccentrically placed nuclei. Moderately pleomorphic nuclei. Prominent nucleoli. Intranuclear pseudo inclusions. Many bi- and multinucleated tumour giant cells.

Fig. 14.53  Clear cell sarcoma: Abundant discrete tumour cells

Fig. 14.55  Clear cell sarcoma: The nuclei are enlarged with a single prominent nucleolus

Fig. 14.56  Clear cell sarcoma: Haematoxylin and eosin-stained smear showing better nuclear morphology

396

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions

14.34.3  K  ey Cytological Features [30] (Figs. 14.58, 14.59, 14.60, and 14.61) Predominant pattern: Discrete spindle and polyhedral cell • • • • • • • •

Hypercellular smear. Predominantly discrete cell. Polyhedral and spindle-shaped cells. Dense eosinophilic cytoplasm. Eccentrically placed enlarged nuclei. Vesicular chromatin with prominent macronucleoli. Epithelioid granuloma like structures may be noted. Inflammatory cells along with necrotic tissue in the background.

Fig. 14.57  Clear cell sarcoma: The tumour cells are positive for HMB45

Immunocytochemistry: Positive: S-100, HMB-45 and Melan A. Differential Diagnosis • Epithelioid sarcoma: Positive for CK and negative for HMB-45 and S-100 protein. • Synovial sarcoma: Nuclear character of SS is different. It has fine chromatin and indistinct nucleoli. • Metastatic carcinoma: –– Clinical history of the primary carcinoma. –– Positive for CK and negative for HMB-45. Fig. 14.58  Epithelioid sarcoma: Multiple loose clusters and discrete tumour cells

14.34 Epithelioid Sarcoma 14.34.1  Epidemiology • It is a rare tumour. • It occurs in 10 to 40 years of age. • Median age: 25 years.

14.34.2  Clinical Features Location: Finger, hand, wrist and forearm. Symptoms • Single or multiple nodular swelling. • Slowly growing swelling.

Fig. 14.59  Epithelioid sarcoma: The cluster of oval to polyhedral tumour cells. Occasional spindle cells are also noted

14.36 Granular Cell Tumour

397

14.35.1  Epidemiology • It accounts for 1% of sarcomas. • Predominantly the tumour is noted in 15 to 35  years of age.

14.35.2  Clinical Features Location: Extremities of the body particularly in buttock and thigh. Symptoms: Usually asymptomatic for many months as the tumour is slow-growing and painless.

Fig. 14.60  Epithelioid sarcoma: Higher magnification showing moderately pleomorphic nuclei and prominent nucleoli

14.35.3  Key Cytological Features [31] • • • • • • • • • • •

Abundant cellularity. Discrete and loose groups of cells. Pseudoacinar arrangement. Large cells with well-defined margin. Polygonal in shape. Abundant granular cytoplasm. Centrally placed nuclei. Enlarged nuclei with stippled chromatin. Large prominent nucleoli. Intranuclear cytoplasmic inclusions. Many bare nuclei. Immunostaining: Positive: Vimentin, SMA and desmin.

Fig. 14.61  Epithelioid sarcoma: Higher magnification showing moderately pleomorphic nuclei and prominent nucleoli

Differential Diagnosis • Metastatic renal cell carcinoma: PAX8 and CD10 positive. • Granular cell tumour: S-100 positive and negative for desmin and SMA.

Immunocytochemistry: Positive: AE1/AE3, EMA, D2–40, FLI-1 and Vimentin. Differential Diagnosis • Clear cell sarcoma: Positive for HMB-45. • Poorly differentiated metastatic carcinoma.

14.36 Granular Cell Tumour Granular cell tumour is a rare SFT.

14.35 Alveolar Soft Part Sarcoma

14.36.1  Epidemiology

Alveolar soft part sarcoma (ASPS) is a rare malignant sarcoma of uncertain histogenesis.

• A rare tumour. • It is noted in any age group.

398

14.36.2  Clinical Features • The tumour is common in tongue, vulva, breast and bronchus. • Slowly growing mass.

14.36.3  Key Cytological Features [32] • • • •

Discrete and loose groups of cells. Large cells with abundant granular cytoplasm. Small monomorphic round nuclei. Bare naked nuclei present. Immunocytochemistry: Positive: S 100 and NSE.

References 1. Sapi Z, Antal I, Papai Z, et al. Diagnosis of soft tissue tumours by fine-needle aspiration with combined cytopathology and ancillary techniques. Diagn Cytopathol. 2002;26(4):232–42. 2. Dey P, Mallik MK, Gupta SK, Vasishta RK.  Role of fine needle aspiration cytology in the diagnosis of soft tissue tumours and tumour-like lesions. Cytopathology. 2004;15(1):32–7. 3. Nagira K, Yamamoto T, Akisue T, et al. Reliability of fine-needle aspiration biopsy in the initial diagnosis of soft-tissue lesions. Diagn Cytopathol. 2002;27(6):354–61. 4. Bezabih M.  Cytological diagnosis of soft tissue tumours. Cytopathology. 2001;12(3):177–83. 5. Sreekantaiah C.  The cytogenetic and molecular characterization of benign and malignant soft tissue tumors. Cytogenet Cell Genet. 1998;82(1–2):13–29. 6. Brahmi U, Srinivasan R, Komal HS, Joshi K, Gupta SK, Rajwanshi A. Comparative analysis of electron microscopy and immunocytochemistry in the cytologic diagnosis of malignant small round cell tumors. Acta Cytol. 2003;47(3):443–9. 7. Costa J, Wesley RA, Glatstein E, Rosenberg SA.  The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases. Cancer. 1984;53(3):530–41. 8. Guillou L, Coindre JM, Bonichon F, et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol. 1997;15(1):350–62. 9. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F.  World Health Organization classification of Tumours. Pathology and genetics of Tumours of soft tissue and bone, vol. 5. 4th ed. Lyon: IARC press; 2013. 10. Kapila K, Ghosal N, Gill SS, Verma K. Cytomorphology of lipomatous tumors of soft tissue. Acta Cytol. 2003;47(4):555–62. 11. Dey P. Fine needle aspiration cytology of well-differentiated liposarcoma. A report of two cases. Acta Cytol. 2000;44(3):459–62. 12. Szadowska A, Lasota J.  Fine needle aspiration cytology of myxoid liposarcoma; a study of 18 tumours. Cytopathology. 1993;4(2):99–106. 13. Silvanto AM, Melly L, Hannan SA, Kocjan G. FNAC of nodular fasciitis mimicking a pleomorphic adenoma: another diagnostic pitfall. Cytopathology. 2010;21(4):276–7.

14  Fine Needle Aspiration Cytology of the Soft Tissue Lesions 14. Barwad A, Banik T, Gorsi U, Dey P. Fine needle aspiration cytology of myositis ossificans. Diagn Cytopathol. 2011;39(6):432–4. 15. Gupta N, Barwad A, Katamuthu K, et al. Solitary fibrous tumour: a diagnostic challenge for the cytopathologist. Cytopathology. 2012;23(4):250–5. 16. Hannah CD, Oliver DH, Liu J.  Fine needle aspiration biopsy and immunostaining findings in an aggressive inflammatory myofibroblastic tumor of the lung: a case report. Acta Cytol. 2007;51(2):239–43. 17. Gupta K, Dey P, Goldsmith R, Vasishta RK. Comparison of cytologic features of giant-cell tumor and giant-cell tumor of tendon sheath. Diagn Cytopathol. 2004;30(1):14–8. 18. Domanski HA, Akerman M, Engellau J, Gustafson P, Mertens F, Rydholm A. Fine-needle aspiration of neurilemoma (schwannoma). A clinicocytopathologic study of 116 patients. Diagn Cytopathol. 2006;34(6):403–12. 19. Gupta K, Dey P, Vashisht R.  Fine-needle aspiration cytology of malignant peripheral nerve sheath tumors. Diagn Cytopathol. 2004;31(1):1–4. 20. Gupta N, Rajwanshi A, Mohindra S, Vasishta RK, Batra C, Gupta AK.  Diagnosis of adult rhabdomyoma by fine needle aspiration cytology: a report of 2 cases. Acta Cytol. 2010;54(5 Suppl):968–72. 21. de Almeida M, Stastny JF, Wakely PE Jr, Frable WJ. Fine-needle aspiration biopsy of childhood rhabdomyosarcoma: reevaluation of the cytologic criteria for diagnosis. Diagn Cytopathol. 1994;11(3):231–6. Epub 1994/01/01 22. Atahan S, Aksu O, Ekinci C. Cytologic diagnosis and subtyping of rhabdomyosarcoma. Cytopathology. 1998;9(6):389–97. 23. Val-Bernal JF, Martino M, Terán A, Yllera E, Castro-Senosiain B.  Endoscopic ultrasound-guided fine-needle aspiration cytology in the diagnosis of leiomyomas of the gastrointestinal tract. Rev Esp Patol. 2019;52(3):154–62. 24. Mittal N, Gupta N, Nijhawan R, Kang M, Joshi K.  FNAC diagnosis of metastatic leiomyosarcoma causing SVC obstruction. Cytopathology. 2010;21(6):416–8. 25. Pérez-Guillermo M, Sola Pérez J, García Rojo B, Hernández GA. Fine needle aspiration cytology of cutaneous vascular tumours. Cytopathology. 1992;3(4):231–44. 26. Fulciniti F, Di Mattia D, Bove P, et  al. Fine needle aspiration of metastatic epithelioid angiosarcoma: a report of 2 cases. Acta Cytol. 2008;52(5):612–8. 27. Klijanienko J, Caillaud JM, Lagace R, Vielh P. Cytohistologic correlations in 56 synovial sarcomas in 36 patients: the Institut curie experience. Diagn Cytopathol. 2002;27(2):96–102. 28. Creager AJ, Pitman MB, Geisinger KR.  Cytologic features of clear cell sarcoma (malignant melanoma) of soft parts: a study of fine-needle aspirates and exfoliative specimens. Am J Clin Pathol. 2002;117(2):217–24. 29. Vidya R, Rekhi B. Cytomorphological spectrum, including immunohistochemical results of 16 cases of Clear Cell Sarcoma of Soft Tissue, along with positive EWSR1 gene rearrangement result in two cases [published online ahead of print, 2020 Apr 30]. Cytopathology. 2020; https://doi.org/10.1111/cyt.12845. 30. Barwad A, Dey P, Das A. Fine needle aspiration cytology of epithelioid sarcoma. Diagn Cytopathol. 2011;39(7):517–20. 31. Min KW, Na W, Oh YH, Park YW, Park MH. Fine needle aspiration cytology of alveolar soft part sarcoma of the cheek. Cytopathology. 2010;21(3):205–7. 32. Choudhary Z, Gupta P, Malhotra P, Bhardwaj M, Sharma PK. Granular cell tumour of the Chest Wall: FNA diagnosis with a review of literature and elaboration of cytological mimickers. J Clin Diagn Res. 2017;11(8):ED01–3.

15

Fine Needle Aspiration Cytology of the Bone

Fine needle aspiration cytology (FNAC) of the bony lesion has a variable response to the clinicians. FNAC of the malignant tumours of bone yields good diagnostic material and high accuracy rate. However, FNAC of benign bony lesion often provides suboptimal content because it is difficult to pierce the cortical bone. Many clinicians prefer core needle biopsy of the bony lesion over FNAC as it gives adequate material, particularly in the benign bony lesion. The core needle biopsy needs local anaesthesia, and the processing of the bone tissue requires time. The indications of FNAC of bony lesions are:

Table 15.1  Immunocytochemistry of bone lesions

• • • •

• The diagnostic accuracy depends on the following factors: –– Thick sclerotic bone. –– Calcified tissue. –– Necrotic tissue. –– Mainly cartilaginous tissue. –– Cystic bony lesion.

Suspected primary malignancy. Metastatic tumour in the bone. Systemic disease involving bone. Infection such as tuberculosis or fungal lesion.

Complications • No significant complications. • Mild local haemorrhage. • Rarely infection. Techniques • Simple percutaneous FNAC is done in case of visible and superficial bony lesion by seeing the X-ray picture. • Deep-seated FNAC is done by CT scan guidance or fluoroscopic guidance. • In addition, to routine air-dried and alcohol fixed smear, the material must be procured for cell block to do immunocytochemistry [1] (Table  15.1), microbial culture and molecular genetics. Diagnostic Accuracy [2–4] • The diagnostic accuracy rate is 95%. • Sensitivity rate of FNAC of the bone lesion is 93 to 96%. • Specificity rate is 94 to 98%. • Positive predictive value is 99%. • Negative predictive value is 92%.

Lesion Osteosarcoma Chondroblastoma Chondrosarcoma Chordoma Ewing’s sarcoma Langerhans cell histiocytosis Plasmacytoma

Immunocytochemistry Osteocalcin and osteonectin S100 protein and SOX9 S100 protein Brachyury, NSE, pan CK, EMA, CEA and S100 CD99, FLI-1 and vimentin CD1a, CD207(Langerin) and S100 CD38 and CD138

Normal Cells (Figs. 15.1 and 15.2) • Osteoblasts. –– Single scattered cells. –– Round cells. –– Abundant cytoplasm. –– Reddish granularity in cytoplasm. –– Eccentrically placed nuclei. –– Small nucleoli. • Osteoclasts. –– Discrete cells. –– Large cells. –– Abundant cytoplasm. –– Multiple nuclei: 15 to 45 in number. • Chondrocytes. –– Usually present as a loose cluster. –– Small round cells. –– Small monomorphic nuclei. –– The cells are embedded in the reddish-blue chondroid material (MGG stain).

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 P. Dey, Color Atlas of Fine Needle Aspiration Cytology, https://doi.org/10.1007/978-981-15-8033-8_15

399

400

Fig. 15.1  Cytology smear showing osteoblast and osteoclastic giant cell (see arrow)

15  Fine Needle Aspiration Cytology of the Bone

Fig. 15.3  Epithelioid cell granuloma in tuberculosis of the bone

• A large number of lymphocytes. • Plasma cells. • Histiocytes. Tuberculous Osteomyelitis Cytology (Fig. 15.3) • • • •

Multiple epithelioid cell granulomas. Langhans-type giant cells. Necrosis. Along with scattered osteoclasts and osteoblasts.

Ziehl-Neelsen stain: Positive for mycobacteria. Mycobacterial culture: Positive for Mycobacterial tuberculosis. Fig. 15.2  Benign chondrocytes having abundant cytoplasm with centrally placed nuclei

15.1 Infection

15.2 Neoplastic Lesions of Bone World Health Organization (WHO) classified bone tumors [5], as mentioned in the Fig. 15.4.

15.1.1 Osteomyelitis Infection of the bone is labelled as “osteomyelitis”.

15.2.1 Bone Forming Tumour

Acute Osteomyelitis It is the acute inflammation of the bone. Cytology:

15.2.1.1 Osteoblastoma Epidemiology

• A large number of polymorphs. • Necrotic tissue fragments. • Osteoblasts. Chronic Osteomyelitis Cytology

• It accounts for only 1% of bone tumours. • They are commonly seen in 10 to 30  years. Mean age: 20 years. Clinical Features Typical location: Spine, sacrum, femur and proximal part of the tibia.

15.2 Neoplastic Lesions of Bone

401

Bone tumors

Marrow tumor

Cartilage forming

Osteogenic tumor

• • • • •

• Osteoid osteoma • Osteoblastoma • Osteosarcoma • Conventional • Chondroblastic • Fibroblastic • Osteoblastic • Telangiectatic • Small cell • Low grade central • Secondary • Parosteal • Periosteal

Osteochondroma Chondroma Chondromyxoid Fibroma Chondrobastoma Chondrosarcoma • Central, primary, and secondary • Peripheral • Dedifferentiated • Mesenchymal • Clear cell

Fibrogenic tumor: Desmoblatic fibroma, fibrosarcoma

Smooth muscle tumor: Leiomyoma, Leiomyosarcoma

• Plasma cell tumor • Lymphoma

Giant cell tumor • Lymphoma • Malignancy in giant cell tumor Ewing’s tumor/peripheral neuroectoderma tumor Miscellaneous lesions: Aneurysmal bone cyst, Langerhan’s cell histocytosis, Fibrous dysplasia, simple cyst

Vascular tumor: Hemangioma, angiosarcoma

Notochodal tumor: Chordoma

Fig. 15.4  World Health Organization classification of bone tumour

Symptoms: • Pain and swelling. • Scoliosis and back pain in case of spinal osteoblastoma. Radiography: • A lytic lesion with a periosteal shell. • Well-circumscribed oval or round defect.

15.2.2 Key Cytological Features [6] • Multiple clusters and discrete cells. • Osteoblasts: –– Plasmacytoid appearance with eccentric nuclei. –– Reddish granularity in the cytoplasm. –– Cytoplasmic clear “hof.” –– Fine chromatin. –– Often bi nucleated. • Osteoclasts. • Spindle cells in small fascicles often entangled on pink stromal material. • Osteoid material. Differential diagnosis: Osteosarcoma.

15.2.3 Osteoid Osteoma Osteoid osteoma is a benign neoplasm of bone. Epidemiology • Children and adolescents are commonly affected.

15.2.4 Clinical Feature Location: Common in long bone. Symptoms: • Mild-to-severe pain. • Often nocturnal. • Relieved by salicylates. Radiology: A central bone-forming nidus that is encircled by a dense cortical sclerotic rim of bone.

15.2.5 Key Cytological Features • Hypocellular. • osteoblasts and osteoclastic giant cells.

402

15  Fine Needle Aspiration Cytology of the Bone

15.3 Osteosarcoma Osteosarcoma is the aggressive malignant neoplasm of the bone.

15.3.1 Epidemiology • It is the most frequent primary malignant bone tumour (after the exclusion of multiple myeloma). • Incidence: 2.5 per million populations per year. • Osteosarcoma commonly occurs in the second decade. • More than 50% of osteosarcoma occurs under 25 year. • Another surge of the tumour occurs after 30 years. • Male: female ratio is 3:2. Fig. 15.5  Osteosarcoma: Abundant discrete tumour cells

15.3.2 Clinical Features Location: • Metaphysis of a long bone. The proximal end of tibia, the distal end of the femur, upper end of the humerus. • Jaw, pelvic bone, spine and skull bone. Symptoms: • Non-specific pain. • Tender bony swelling. Radiology: • • • •

Osteolytic lesion. Osteoblastic. Mixed. Destruction of the cortical bone with invasion in the neighbouring tissue.

Fig. 15.6  Osteosarcoma: The round cells with a moderate amount of cytoplasm having pleomorphic round nuclei

15.3.3 Key Cytological Features [6, 7] (Figs. 15.5, 15.6, 15.7, 15.8, 15.9, 15.10, and 15.11) Predominant pattern: Hypercellular smear showing moderately pleomorphic cells with osteoid material • Abundant cellularity. • The predominantly discrete and also loose group of tumour cells. • Round cells. • The cytoplasm contains abundant reddish granularity. • Markedly pleomorphic nuclei. • Many binucleated cells. • Variable number of osteoclastic multinucleated giant cells.

Fig. 15.7  Osteosarcoma: The large, moderately pleomorphic cells and reddish osteoid material

15.3 Osteosarcoma

403

Fig. 15.8 Osteosarcoma: Haematoxylin and eosin-stained smear showing loose clusters of tumour cells

Fig. 15.10  Osteosarcoma: Haematoxylin and eosin-stained smear showing individual tumour cell having eccentrically placed enlarged nuclei and with coarse chromatin

Fig. 15.9 Osteosarcoma: Haematoxylin and eosin-stained smear showing cells with a well-defined margin. The cells have central to eccentric nuclei

Fig. 15.11  Osteosarcoma: Haematoxylin and eosin-stained smear showing discrete malignant cells with coarsely granular chromatin

• The background shows dense acellular osteoid material. • Necrotic tissue. • Many mitotic figures.

• Fibroblastic osteosarcoma. –– Abundant spindle cells. –– Less number of osteoblasts.

15.3.4 Conventional Osteosarcomas Are of Three Types

Small Cell Osteosarcoma Small cell osteosarcoma accounts for 1.5% of all osteosarcomas.

• Osteoblastic: Predominantly osteoid matrix material in the background. • Chrondroblastic: –– Mainly background chondroid material. –– Many chondroblasts. –– Mature chondrocytes.

Cytology • Small round cells with a thin rim of cytoplasm. • The cells are larger than lymphocytes. • Mild nuclear pleomorphism. • Coarse chromatin.

404

15  Fine Needle Aspiration Cytology of the Bone

Telangiectatic Osteosarcoma Telangiectatic osteosarcoma represents about 4% of all osteosarcomas. Cytology

Symptoms • Usually asymptomatic. • Involvement of the short tubular bone. • The patient may complain of swelling and pain.

• • • • • •

X-ray of enchondroma: Well-marginated radiolucent swelling. A punctate or ring pattern of mineralization is noted.

Background is bloody. Paucicellular smear. Spindle-shaped cells. Hyperchromatic and pleomorphic nucleus. Many multinucleated giant cells. Small epithelioid-like cells.

Immunocytochemistry • Osteocalcin, osteonectin and CD99.

15.3.5 Differential Diagnosis

15.4.4 Key Cytology Features (Figs. 15.12 and 15.13) • The smear shows thick hyaline cartilage. • Metachromatic material in the background. • Loose clusters and dissociated cells that are often entangled in the cartilage material. • Round cells with bland nuclei.

• Reactive osteoblasts: No abnormality of the nuclear chromatin. • Malignant fibrous histiocytoma (MFH): Radiological features of osteosarcoma are characteristic. • Ewing’s sarcoma: Discrete cells with “salt and pepper” chromatin. • Giant cell tumour of bone: The stromal cells in Giant cell tumour (GCT) are usually monomorphic round cells. • Chondrosarcoma: Difficult to distinguish on cytology alone.

15.4 Cartilage Forming Tumour 15.4.1 Chondroma Chondroma is a benign cartilaginous neoplasm.

Fig. 15.12  Chondroma: Multiple cartilaginous fragments

15.4.2 Epidemiology • It is one of the most frequent bone tumours. • Chondroma represent 25% of all bone tumours. • It may occur in age; however, the chondroma is common in 20 to 40 year age. • Both sexes are equally affected.

15.4.3 Clinical Features Location • Most common in the bones of hand and foot particularly short tubular bone. • Next commonly occurs in the long bone: Proximal part of humerus and femur.

Fig. 15.13  Chondroma: Higher magnification showing better morphology of the cartilage cells

15.5 Chondroblastoma

405

15.5 Chondroblastoma Chondroblastoma is a benign cartilaginous neoplasm of bone.

15.5.1 Epidemiology • Chondroblastoma represents 1% of all bone tumours. • Tumour is commonly seen in the second decade of life. • Males are more affected.

15.5.2 Clinical Features Location:

Fig. 15.14  Chondroblastoma: Abundant discrete tumour cells

• Epiphyseal and epimetaphyseal regions of the proximal and distal end of the femur and tibia. • Infrequently it involves flat bone of acetabulum and ilium.

Symptoms • Localized pain and swelling. • The restricted joint movement if the tumour occurs near the joint. Radiology • Always present as a lytic lesion. • Well-demarcated lesion with a thin rim of sclerotic bone.

15.5.3 Key Cytology Features [8, 9] (Figs. 15.14, 15.15, 15.16, 15.17, 15.18, 15.19, and 15.20)

Fig. 15.15  Chondroblastoma: The tumour cells with a well-defined margin. The cells are round with moderate cytoplasm

Predominant pattern: Abundant discrete round cells and osteocleoclast-like giant cells along with chondroid material in the background. • The smear shows multiple small fragments cartilaginous material. • Many discrete chondroblasts are present: –– Round to polygonal cells. –– Round monomorphic nuclei. –– Fine chromatin with 1–2 small nucleoli. –– Characteristic longitudinal nuclear groove. • Many osteoclastic giant cells containing 10 to 20 nuclei. • Woolly calcification may be present.

Fig. 15.16  Chondroblastoma: Tumour cells with multinucleated giant cells

406

Fig. 15.17  Chondroblastoma: Haematoxylin and eosin-stained smear showing loose clusters and discrete tumour cells

Fig. 15.18  Chondroblastoma: Haematoxylin and eosin-stained smear showing multinucleated osteoclastic giant cells and discrete osteoblasts

15  Fine Needle Aspiration Cytology of the Bone

Fig. 15.19  Chondroblastoma: Haematoxylin and eosin-stained smear showing discrete tumour cells. The cells have well-defined cytoplasmic margin, moderate cytoplasm and mildly pleomorphic nuclei with nuclear grooving

Fig. 15.20  Chondroblastoma: Higher magnification showing deep longitudinal groves

15.5.4 Differential Diagnosis

15.6.1 Epidemiology

• Langerhans cell histiocytosis: Many eosinophils present, cartilaginous material is absent, an X-ray of chondroblastoma is characteristic.

• • • •

15.6 Chondromyxoid Fibroma

15.6.2 Clinical Features

Chondromyxoid fibroma is a rare benign cartilaginous neoplasm of bone.

Location • Proximal tibia and distal femur.

It accounts for 1% of all tumours of bone. It comprises 2.5% of benign tumours of bone. The tumour is common in the second and third decade. The tumour is more common in males.

15.7 Chondrosarcoma

• Flat bones such as ilium or ribs.

407

• Often cortical erosion or destruction. • Ring-like mineralization.

Symptoms: Pain and swelling.

15.6.3 Key Cytology Features • Smears show scattered chondrocytes, myxoid cells and fibroblasts. • The background shows chondromyxoid stromal substances. • The chondrocytes are often entangled in the reddish-­ purple stroma material. • Chondrocyte. –– Variable sized ovoid cells. –– Mildly pleomorphic nuclei. –– Small indistinct nucleoli. • Stellate cells with thin elongated nuclei. • Fibroblasts. • Osteoclastic giant cells.

15.7.3 Key Cytology Features [10–15] (Figs. 15.21, 15.22, 15.23, and 15.24) Predominant pattern: Abundant chondrocytes cells are embedded within the chondroid material • Abundant reddish-purple chondroid or myxoid element. • Isolated chondroid cells embedded in the chondromyxoid material. • The cells have well-defined cytoplasmic margin. • Pale vacuolated cytoplasm.

15.6.4 Differential Diagnosis Various other cartilaginous tumours: Enchondroma, chondroblastoma and chondrosarcoma.

15.7 Chondrosarcoma Chondrosarcoma (CHS) is a malignant cartilaginous neoplasm.

15.7.1 Epidemiology

Fig. 15.21 Chondrosarcoma: Multiple fragments of cartilaginous material

• CHS represents 20% of malignant bone tumours. • It is the third common primary malignant bone tumour. • The primary CHS commonly occurs in fourth to fifth decades of life. • Slightly more common in males than females. • More than 90% of CHS is the conventional type.

15.7.2 Clinical Features Location: Flat bones of the pelvis, proximal femur, proximal humerus, distal femur and ribs. Symptoms: Chronic pain and swelling. Radiology • CHS is seen in the diaphysis or metaphysis of the bone. • Fusiform expanded bone with a cortical thickening.

Fig. 15.22  Chondrosarcoma: The tumour cells are embedded in cartilaginous material

408

15  Fine Needle Aspiration Cytology of the Bone

15.7.4 Differential Diagnosis • Enchondroma: –– Radiological features of cortical destruction. –– Rich cellularity. –– Binucleation. • Chondroblastic osteosarcoma. • Chordoma: –– Characteristic physaliphorous cells in chordoma.

15.8 Variants of CHS 15.8.1 Mesenchymal Chondrosarcoma Fig. 15.23  Chondrosarcoma: Haematoxylin and eosin-stained smear showing malignant chondrocytes embedded in the cartilaginous material

15.8.1.1 Epidemiology • A rare malignant tumour. • It accounts for less than 10% of all primary CHS. • The tumour occurs in any age. • It is common in the second and third decades of life.

15.8.2 Clinical Features Location: The tumour occurs in craniofacial bone, ribs, pelvic bones and vertebra. Symptoms: Pain and swelling. Radiological Examination • Osteolytic lesion and destruction of cortical bone. • Spreading of the tumour in the adjacent soft tissue.

Fig. 15.24  Chondrosarcoma: Haematoxylin and eosin-stained smear showing chondroid cells with vacuolated cytoplasm and central large Grading of Chondrosarcoma

Grade 1 • Moderate cellularity • No nuclear pleomorphism • Mild hyperchromasia

Grade 2 • Abundant cellularity • Moderate nuclear pleomorphism • Moderate hyperchromasia

Grade3 • Abundant cellularity • Severe nuclear pleomorphism • Severe hyperchromasia

Fig. 15.25  Grading of chondrosarcoma

• Moderately enlarged central hyperchromatic nuclei. • Frequent binucleation. The CHS is graded from 1 to 3 depending on the cellularity, nuclear pleomorphism and hyperchromasia (Fig. 15.25).

Key Cytology Features • Hypercellular smear. • Undifferentiated round cells material. • Background necrosis. • Tumour cells are small. • Round monomorphic nuclei. • Enlarged nuclei. • Nuclear chromatin is coarse. • Prominent nucleoli. • Many osteoclast-like giant cells.

and

cartilaginous

15.9 Clear Cell Chondrosarcoma 15.9.1 Epidemiology • • • •

Clear cell CHS accounts for 2% of all CHS. Males are commonly affected. The tumour may be seen at any age. It commonly occurs in 25 to 50 years of age.

15.11 Giant Cell Tumour of Bone

409

15.9.2 Clinical Features

15.11.1  Epidemiology

Location:

• • • •

• Clear cell CHS may involve any bone. • Head of humerus and femur (more than two-third cases). • Skull, spine, hands and feet.

GCT accounts for 5% of all bone tumours. It accounts for 25% of all benign bone tumours. The tumour is most common in 25 to 45 years. Male and female are almost equally affected with slightly more female predominance.

Symptoms: Pain for several years.

15.11.2  Clinical Features 15.9.3 Key Cytology Features

Location:

• • • • •

• Long bones are commonly affected. • Flat bone particularly pelvis is also affected.

Discrete large cells. Abundant clear cytoplasm. Centrally located large hyperchromatic nucleus. Many multinucleated giant cells. Background cartilaginous material.

15.10 Dedifferentiated Chondrosarcoma 15.10.1  Epidemiology • Dedifferentiated chondrosarcoma represents 10% of all CHS. • It may occur 25 to 85 years of age. • However, the tumour commonly occurs in 40 to 50 years period.

15.10.2  Clinical Features Location: Pelvis, femur and humerus. Symptoms: Pain, swelling and pathological fracture.

Symptoms: Pain, swelling and difficulties of movement. Radiology • The tumour is epiphyseal in location. It is an expanding lytic lesion with thinned out or destroyed the cortical cover. • A “soap-bubble” like appearance is often seen.

15.11.3  K  ey Cytology Features [16] (Figs. 15.26, 15.27, 15.28, and 15.29) Predominant pattern: Abundant osteoclasts-like giant cells and stromal cells. • A large number of osteoclastic giant cells admixed with stromal cells. • Multinucleated osteoclastic giant cells.

15.10.3  Key Cytology Features • Many chondrocytes embedded in the cartilaginous material. • The chondrocyte is round to polygonal with pale vacuolated cytoplasm and enlarged nucleus. • Frequent binucleation. • The other component is undifferentiated sarcoma element. The tumour cells have spindle-shaped nuclei with moderate pleomorphism.

15.11 Giant Cell Tumour of Bone Giant cell tumour (GCT) is a benign neoplasm of bone. However, the tumour is locally infiltrating in nature.

Fig. 15.26  Giant cell tumour of bone: Multinucleated giant cells and stromal cells

410

Fig. 15.27  Giant cell tumour of bone: The osteoclastic giant cell containing 12 to 20 nuclei

15  Fine Needle Aspiration Cytology of the Bone

Fig. 15.29  Giant cell tumour of bone: The stromal cells with well-­ defined cytoplasm having central to eccentric nuclei. The nuclei are round to oval with minimal nuclear pleomorphism

–– Chondroblastoma: Round monomorphic nuclei with a longitudinal groove. –– Aneurysmal bone cyst: Many haemosiderin laden macrophages. –– Brown tumour of hyperparathyroidism: Multiloculated cystic lesion in X-ray, history of hyperparathyroidism, Many pigment laden foamy macrophages and monomorphic stromal cells.

15.12 Chordoma Chordoma is a low-grade malignant tumour originated from the remnants of notochordal rest. Fig. 15.28  Giant cell tumour of bone: High powered view of the giant cells

–– Abundant cytoplasm. –– Almost 50 to 100 nuclei. • Stromal cells. –– Round to spindle cells. –– A moderate amount of cytoplasm. –– Round to spindle-shaped nuclei. –– Chromatin is granular. –– Prominent nucleoli. • Giant cells are intimately attached to spindle cell clusters.

15.11.4  Differential Diagnosis • Bone lesions rich in osteoclastic giant cells: –– Osteosarcoma: Markedly pleomorphic mononuclear cells.

15.12.1  Epidemiology • It represents 1 to 4% of all malignant bone tumours. • Frequent in the sixth decade. • Males are commonly affected.

15.12.2  Clinical Features Location: Axial spinal region particularly sacral (60%) and spheno-occipital region (25%). Symptoms: It depends on the location of the tumour. Usually, it presents as a slow-growing tumour. • Sacral: Back pain, constipation, paresthesis. • Spheno-occipital region: Chronic headache.

15.12 Chordoma

411

15.12.3  K  ey Cytology Features [17, 18] (Figs. 15.30, 15.31, 15.32, and 15.33) Predominant pattern: Many large physaliphorous cells in a chondromyxoid material. • FNAC yields thick mucoid material. • Background of the smear shows abundant chondromyxoid material. • Many scattered large cells labelled as “physaliphorous cells”. –– Abundant bubbly vacuolated cytoplasm. –– Centrally placed round nuclei. –– Monomorphic nuclei. –– Granular chromatin with prominent nucleoli. Fig. 15.32  Chordoma: Haematoxylin and eosin-stained smear showing many physaliferous cells and mononuclear cells

Fig. 15.30  Chordoma: The scattered cells in abundant chondromyxoid material

Fig. 15.33  Chordoma: Haematoxylin and physaliferous cells showing physaliferous cell

• Small round cells. –– Small monomorphic nuclei. –– Granular chromatin and single prominent nucleoli. • Immunocytochemistry: Positive: Brachyury, NSE, Pan CK, EMA, CEA, S100 and Vimentin.

15.12.4  Differential Diagnosis

Fig. 15.31  Chordoma: Large physaliferous cells with abundant bubbly vacuolated cytoplasm

• Chondrosarcoma: –– Absence of classical physaliphorous cells. –– background myxoid material. –– Chondrosarcoma negative for CK. • Metastatic adenocarcinoma: –– Clinical history. –– The nuclei are enlarged and pleomorphic. –– No typical myxoid background.

412

15  Fine Needle Aspiration Cytology of the Bone

15.13 E  wing’s Sarcoma (EWS)/Peripheral Neuroectodermal Tumour (PNET) [19–22] Ewing’s sarcoma (EWS)/peripheral neuroectodermal tumour (PNET) are the malignant round cell tumour. These tumours show frequent neuroectodermal differentiation.

15.13.1  Epidemiology • EWS/PNET represents 8% of all primary malignant bone tumours. • The second commonest childhood malignant bone tumour. • The tumour commonly occurs in 5 to 20 years. • Male: female ratio is 1.4:1.

Fig. 15.34  Ewing’s tumour: Abundant discrete round cells

Chromosomal changes: Specific chromosomal translocation t [10, 21] (q24;q12) (95% case) causing EWS-FLI-1 fusion gene.

15.13.2  Clinical Features Location: • The diaphysis or metaphyseal-diaphyseal part of the long bone, particularly from femur and tibia. • Pelvis and ribs are also affected. Radiology • An osteolytic lesion and long bone. • Moth eaten look of the bone. • Multiple layers of periosteal reaction resembling onion skin-like arrangement.

Fig. 15.35  Ewing’s tumour: The tumour cells have a scanty thin rim of cytoplasm and round monomorphic nuclei

Symptoms: • Pain. • Swelling. • Infrequently pathological fracture.

15.13.3  K  ey Cytology Features (Figs. 15.34, 15.35, 15.36, and 15.37) Predominant pattern: Abundant discrete small round cells • • • •

Abundant cellularity. Dissociated small round cells. Rosette-like structures. Two types of cell population: Light and dark cells.

Fig. 15.36  Ewing’s tumour: Haematoxylin and eosin-stained smear showing dark cells and light cells

15.14 Non-Hodgkin Lymphoma

413

15.13.4  Differential Diagnosis Neuroblastoma: Positive for NB84. Non-Hodgkin lymphoma: Lymphoglandular bodies and CD45 positive cells. Small cell type of osteosarcoma: Osteoid material. Multiple myeloma: Cartwheel chromatin pattern, CD138 and CD38.

15.14 Non-Hodgkin Lymphoma [23] 15.14.1  Epidemiology

Fig. 15.37  Ewing’s tumour: Haematoxylin and eosin-stained smear showing dark cells with hyperchromatic nuclei and cells with comparatively pale nuclei

• Non-Hodgkin lymphoma (NHL) constitutes 7% of all bone malignancies. • Approximately 5% of extranodal NHL affects the bone. Location: It commonly involves femur, spine and pelvic bones. Symptoms: Pain and swelling.

15.14.2  Types (Figs. 15.39 and 15.40) • DLBCL (90%). • Follicular centre cell lymphoma. • Anaplastic large cell lymphoma.

Fig. 15.38  Ewing’s tumour: CD99 positive tumour cells

• Dark cells: –– Round cells. –– Thin rim of cytoplasm. –– Dark condensed nucleus. • Light cells. –– A moderate amount of vacuolated cytoplasm. –– Round monomorphic nucleus. –– Fine granular chromatin. –– Inconspicuous to absent nucleoli. Immunocytochemistry (Fig. 15.38): Positive: CD99, NSE, CK and vimentin.

Fig. 15.39  Secondarily involved known case of anaplastic large cell lymphoma in ilium of pelvic bone: Abundant immature lymphoid cells

414

15  Fine Needle Aspiration Cytology of the Bone

Criteria of Multiple myeloma

Major criteria • Plasmacytoma on biopsy • Marrow plasmacytosis: more than 30% plasma cells • Presence of M component: • Serum IgG>3.5g/dl, IgA>2g/dl • Urine : Bence jones protein without amyloidosis

Minor criteria Marrow • Plasmacytosis (10-30% plasma cells) • M component present but less than listed above) • Lytic bone lesions • Reduced normal levels of immunoglobulins(