04.05.2017

Salivary cytology

• It is a reliable diagnostic test – However, definitive subclassification may be difficult for some lesions • Diagnostic accuracy differs according to the entity (e.g. high for pleomorphic , low for basal Cytology cell ) Pınar Fırat, MD • Diagnostic accuracy is higher Professor of Pathology – for neoplastic vs non-neoplastic lesions İ.U. İstanbul Faculty of Medicine Çapa, İstanbul – for low-grade vs high-grade tumors • Sensitivity 77-97%, specificity 86-100%

Salivary gland cytology Triage helps the clinician Triage • Is it a salivary gland lesion? • Non-neoplastic lesions: Surgery may not be – Or arising in the adjacent tissues, lymph required node? skin? soft tissue? • Systemic diseases: Different therapeutic • Is the lesion neoplastic? modalities • Benign tumors, low-grade : Limited • Benign or malignant ? surgery (superficial parotidectomy) • If possible, type of ? • High-grade malignancies: Extensive surgery (Facial nerve sacrifice, lymph node neck dissection may be necessary; neo-adjuvant therapy may be indicated) • Inoperable patients

Diagnostic difficulties Salivary gland tumors

• Wide spectrum of benign and malignant tumors • Benign • Malignant – Some are extremely rare – – Acinic cell – Some are diagnosed by architecture only-invasion – Myoepithelioma – • Overlaps in different conditions – – – Cystic lesions (neoplasic/ non-neoplasitic) – Warthin tumor – Epithelial-myoepithelial – Squamous cells – carcinoma – Hyaline stromal globules – Polymorphous low grade – adenocarcinoma – Basaloid morphology – – – Spindle cell lesions – – – – –

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Tükrük bezi tümörleri Pleomorphic adenoma

• Benign • Malign – Pleomorfik adenom – Adenoid kistik karsinom • Myoepithelial cells, often plasmacytoid or – Myoepitelyoma – Epitelyal-myoepitelyal spindled – Bazal hücreliMyoepithelial adenom karsinom • Cohesive epithelial cells BlidBasaloid – Polimorfik düşük dereceli – Warthin tümörü • Chondromyxoid matrix - fibrillary and bright – OnkositomOncocytic adenokarsinom Others with poligonal/cuboidal cells magenta (Romanowsky stains) with indistinct – – Asinik hücreli karsinom Cystic (squamous, mucinous) margins – – Mukoepidermoid karsinom High grade • Myoepithelial cells embedded into the fibrillary – – Tükrük bezi duktus karsinomu matrix – –

Fibrillary matrix

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Pleomorphic Adenoid cystic adenoma carcinoma Globuler matrix

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Cystic change

Metaplasias: squamous / sebaceous

Mucin in the background Atypia in pleomorphic adenoma

Pitfalls in diagnosing pleomorphic : • Cellular specimens with sparse or absent matrix material • Lesions with focal hyaline globules/adenoid cystic-like areas • Lesions with cytologic atypia • Lesions with metaplastic changes, especially squamous or mucinous features

Cellularity with scanty matrix

4 04.05.2017

67y F 2cm nodular mass in the hard palate

Myoepithelioma

• Myoepithelial cells – Epitheloid, plasmacytoid, spindle cell, clear cell patterns

Differential dx – Pleomorphic adenoma – Soft tissue lesions • Leiomyoma, schwannoma, noduler fascitis – Clear cell tumors Plasmacytoid cells Elongated spindle cells • If nuclear atypia, necrosis and invasion is NO matrix present: Myoepithelial carcinoma

Myoepitelioma - Collagenous crystals

5 04.05.2017

Spindle cell myoepithelioma

Schwannom

Irving Dardick, Sudha Kini, Salivary Gland Tumor Cytopathology, Pathology Images Inc., Canada, 2006

MithlilMyoepitehlial tumors

Bazaloid tumors

Histology: Myoepithelial carcinoma

Basal cell adenoma

• Basaloid cells – Round-oval uniform nuclei, scanty cytoplasm, regular chromatin • Varied cellularity • Peripheral palisading • Hyaline stroma – Stick to cells, globules, basement-memb.like material • Squamous metaplasia

Bazal cell adenoma

6 04.05.2017

Basal cell adenoma

Differential diagnosis: • Pleomorphic adenoma (Polymorphic, fibrillary matrix) • Basal cell adenocarcinoma (nuclear atypia, mitosis, necrosis) • Adenoid cystic carcinoma (Hyperchromatic irregular Basal cell adenoma nucleus, coarse chromatin)

Adenoid cystic carcinoma

• Painful mass or pain during the FNA • Basaloid cells with dark angulated nuclei (variable nuclear atypia) • Acellular hyaline matrix with sharp borders • Variably sized, often large, three-dimensional hyaline spheres Basal cell Adenocarcinoma

May be identical to BA Nuclear atypia Mitotic figures Invasion

Hyaline matrix

Nuclear atypia is not always present

7 04.05.2017

Solid variant of adenoid cystic carcinoma do not show abundant matrix Naked nuclei are seen in the background May closely mimic basal cell tumors

Epitelyal-myoepitelyal karsinom Adenoid kistik karsinom as the number of hyaline globules and their size increases, the diagnosis gets closer to adenoid cystic carcinoma

Epithelial-myoepithelial carcinoma

• Matrix producing basaloid looking tumor – Hyaline globules / myxoid matrix • Cellular smears, naked nuclei in the background • Dual cell population – One component may dominate

Epitelyal myoepitelyal Ca.

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Dual cell population

Epitelyal - myoepitelyal

Epitelyal - myoepitelyal karsinom

Polymorphous Low Grade Adenocarcinoma

Minor salivary Branching papilla Larger amount of cytoplasm Irving Dardick, Sudha Kini, Salivary Gland Tumor Cytopathology, Matrix – hyaline / myxoid Pathology Images Inc., Canada, 2006

9 04.05.2017

Neoplasms with basaloid cells producing matrix

. Basal cell adenoma . Basal cell adenoma . Basal cell adenoca. . Basal cell adenoca. . Adenoid cystic carcinoma . Adenoid cystic carcinoma . Epithelial-myoepithelial . Epithelial-myoepithelial carcinoma carcinoma . Pleomorphic adenoma . Polymorphous low-grade . Neoplasms of the skin adenocarcinoma – basal cell carcinoma . Pleomorphic adenoma – pilomatrixoma . Small cell carcinoma

PA Basal cell Ad

Basal cell adenoma Basal cell adenocarcinoma ACC Ep-Myo Ca

Pleomorphic adenoma Adenoid cystic ca.

Matrix producing, basaloid looking tumors

PA BCA BCAC ACC Pattern sheets and cohesive clusters; cohesive clusters; 3-D cylinders and syncytia, cells + peripheral + peripheral branching groups embedded in matrix palisading; palisading;

Cells plasmacytoid & Basaloid cells, Basaloid cells, Basaloid cells, spindled round to oval or round to oval or maybe some Nuclear myoepithelial cells elongated nuclei elongated nuclei; myoepithelial cells, and cuboidal +atypia oval to angulated atypia epithelial cells nuclei; mild to moderate atypia Matrix Fibrillar Intercellular hyaline Intercellular hyaline large acellular chondromyxoid matrix; matrix; cylinders and Clinical matrix-irregular circumferential circumferential globules of hyaline features edges hyaline bands hyaline bands matrix surrounded by cells- sharp edges Background Myoepithelial cells naked nuclei naked nuclei; naked nuclei; Adenoid cystic carcinoma + necrosis + necrosis Ki-67

Modified from William C. Faquin’s hand out, USCAP, 2005

10 04.05.2017

Histology: Basal cell adenoma

.70 y, F .CT: 1cm spiculated mass in the right upper lobe of the . .PET/CT: increased FDG up-take in left (Well circumscribed mass, 1.5cm in diameter)

Never trust globules Ask the clinical features, see the nuclear atypia

PET scan for salivary gland : .Limited value .Warthin’s tumors, pleomorphic adenomas, basal cell adenomas show increased FDG uptake

Warthin’s tumor

• Oncocytes with large polygonal granular cytoplasm forming clusters/ monolayers • Lymphocytes, like a lymph node Warthin Tümörü • Cystic background looking like necrosis

May present only by one or two components

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Mast cell

Onkositler

Cystic lesions of the salivary glands

Non-neoplastic Neoplastic • Lenfoepitelhial Benign • Retantion cyst • Warthin’ tumor . 63 cases with histopathologic follow up • Mucocel • Pleomorphic adenoma . FNAC correctly diagnosed 25 of 36 neoplasms • Branchial cyst • however...., •Dermoid cyst Malign . 5 Warthin’s tumors • Epidermoid cyst • Mucoepidermoid carcinoma . 2 squamous cell • . 2 mucoepidermoid carcinomas . 2 schwannomas yielded non-representative aspirates Sensitivity 70% Specificity 96% Gabrijela Kocjan, Clinical Cytopathology of the Head and Neck, 2001

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Well differentiated Branchial cyst

62y, F 2 cm mass in the left parotid

Oncocytoma Oncocytoma

Differential diagnosis: • Noduler oncocytic hyperplasia • Cellularity, isolated oncocytes – Hypocellularity • 3-dimentional oncocytic groups • Warthin tumor – Round uniform nucleus, prominent nucleoli, – Monolayyyers, cystic backg round, l ypyymphocytes Warthin large granuler eosinophilic cytoplasm • Oncocytic carcinoma – Dyscohesion, large nucleus, pleomorphism, mitosis, necrosis • Capillary fragments within the groups • Acinic cell carcinoma • NO cystic background, NO lymphocytes – Prominent asiner structures

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Oncocytic carcinoma

Irving Dardick, Sudha Kini, Salivary Gland Tumor Cytopathology, Pathology Images Inc., Canada, 2006

Acinic cell carcinoma

• Cellular smears of acinar cells • Sheets and dyshesive crowded 3-D clusters • Large polygonal cells with abundant finely vacuolated to granular cytoplasm • PASDitttlPAS+D resistant cytoplasm ic zymogen granu les • Bland nuclear cytologic features • Background naked nuclei + lymphocytes

Acinic cell Oncocytoma

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Epithelial-myoepithelial carcinoma Acinic cell carcinoma

Salivary gland tissue

• Serous and mucinous acinar cells in grapelike clusters • Admixed small tubules and/or sheets of ductal • Adipose tissue

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Acinic cell carcinoma Mucoepidermoid carcinoma

Differential diagnosis: • Cytomorphology depends on the grade of the • Salivary gland tissue tumor • Oncocytic tumors • Mucus-secreting cells • Clear cell tumors • Squamous cells • Intermediate cells (low N/C ratio) • Mucoid background

Mucoepidermoid carcinoma

Low grade MEC

• Common cause of false-negative cytologic diagnosis, the aspirate may yield only cyst contents • The epithelial cells are bland, easily be misinterpreted as histiocytes

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Warthin High grade MEC

Onkositom

Acinic cell MEC

MEC Warthin

Metastatic carcinomas

Salivary duct carcinoma

• Overtly malignant cytology • Polygonal cells with abundant cytoplasm • Large hyperchromatic, pleomorphic nuclei • Prominent nucleoli • Sheets, clusters, papillae, and cribriform groups • Background necrosis

17 04.05.2017

Salivary gland tumors Main differential diagnosis ….

• Matrix-containing lesions: • Epithelial cells – Pleomorphic adenoma vs adenoid cystic carcinomaPrimary – What type? Basaloid, clear, oncocytic? • Basaloid neoplasms: salivary gland – Nuclear atypia? Overt ? – Basal cell adenoma vs basal cell adenocarcinomaneoplasm! vs adenoid cystic carcinoma • MithlilllMyoepithelial cells ( plasmocytoid/ spindle cells) • Oncocytic lesions: • Matrix production – Warthin’s tumor vs oncocytoma vs acinic cell carcinoma • Mucinous : – Fibrillary? Hyaline? – Low-grade mucoepidermoid carcinoma vs mucocele • Background • High-grade carcinomas: Clinical – Mucoepidermoid carcinoma vs salivary duct carcinomafeatures vs ! – Cyst content, mucin, necrosis? metastatic carcinoma • Spindle cell lesions: Immuno! – Myoepithelial tumors vs soft tissue tumors

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MILAN REPORTING SYSTEM

William Faquin,,, MD, PhD http://www.youtube.com/watch?v=LvyD1_LIR4E&feature=youtu.be&t=24s

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