Salivary gland cytology. Salivary gland cytology. Triage helps the clinician. Salivary gland tumors. Diagnostic difficulties

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1 Salivary gland cytology Salivary Gland Cytology Pınar Fırat, MD Professor of Pathology İ.U. İstanbul Faculty of Medicine Çapa, İstanbul 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 adenoma, low for basal cell adenocarcinoma) Diagnostic accuracy is higher for neoplastic vs non-neoplastic lesions for low-grade vs high-grade tumors Sensitivity 77-97%, specificity % Salivary gland cytology Triage Is it a salivary gland lesion? Or arising in the adjacent tissues, lymph node? skin? soft tissue? Is the lesion neoplastic? Benign or malignant? If possible, type of neoplasm? Triage helps the clinician Non-neoplastic lesions: Surgery may not be required Systemic diseases: Different therapeutic modalities Benign tumors, low-grade malignancies: Limited surgery (superficial parotidectomy) 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 Some are extremely rare Some are diagnosed by architecture only-invasion Overlaps in different conditions Cystic lesions (neoplasic/ non-neoplasitic) Squamous cells Hyaline stromal globules Basaloid morphology Spindle cell lesions Benign Pleomorphic adenoma Myoepithelioma Basal cell adenoma Warthin tumor Oncocytoma Malignant Acinic cell carcinoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma Polymorphous low grade adenocarcinoma Salivary duct carcinoma 1

2 Tükrük bezi tümörleri Benign Pleomorfik adenom Myoepitelyoma Malign Adenoid kistik karsinom Epitelyal-myoepitelyal Bazal hücreli Myoepithelial adenom karsinom Warthin tümörü Basaloid Polimorfik düşük dereceli OnkositomOncocytic adenokarsinom Others with poligonal/cuboidal Asinik hücreli cells karsinom Cystic (squamous, mucinous) High grade Mukoepidermoid karsinom Tükrük bezi duktus karsinomu Pleomorphic adenoma Myoepithelial cells, often plasmacytoid or spindled Cohesive epithelial cells Chondromyxoid matrix - fibrillary and bright magenta (Romanowsky stains) with indistinct margins Myoepithelial cells embedded into the fibrillary matrix Fibrillary matrix 2

3 Pleomorphic adenoma Adenoid cystic carcinoma Globuler matrix 3

4 Cystic change Metaplasias: squamous / sebaceous Mucin in the background Atypia in pleomorphic adenoma Pitfalls in diagnosing pleomorphic adenomas : 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

5 67y F 2cm nodular mass in the hard palate Myoepithelioma Myoepithelial cells Epitheloid, plasmacytoid, spindle cell, clear cell patterns Plasmacytoid cells NO matrix Elongated spindle cells Differential dx Pleomorphic adenoma Soft tissue lesions Leiomyoma, schwannoma, noduler fascitis Clear cell tumors If nuclear atypia, necrosis and invasion is present: Myoepithelial carcinoma Myoepitelioma - Collagenous crystals 5

6 Spindle cell myoepithelioma Schwannom Irving Dardick, Sudha Kini, Salivary Gland Tumor Cytopathology, Pathology Images Inc., Canada, 2006 Myoepitehlial l 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

7 Basal cell adenoma Basal cell adenoma Differential diagnosis: Pleomorphic adenoma (Polymorphic, fibrillary matrix) Basal cell adenocarcinoma (nuclear atypia, mitosis, necrosis) Adenoid cystic carcinoma (Hyperchromatic irregular nucleus, coarse chromatin) Adenoid cystic carcinoma Basal cell Adenocarcinoma 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 May be identical to BA Nuclear atypia Mitotic figures Invasion Hyaline matrix Nuclear atypia is not always present 7

8 Naked nuclei are seen in the background Solid variant of adenoid cystic carcinoma do not show abundant matrix May closely mimic basal cell tumors as the number of hyaline globules and their size increases, the diagnosis gets closer to adenoid cystic carcinoma Epitelyal-myoepitelyal karsinom Adenoid kistik karsinom 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. 8

9 Dual cell population Epitelyal - myoepitelyal Epitelyal - myoepitelyal karsinom Polymorphous Low Grade Adenocarcinoma Minor salivary glands Branching papilla Larger amount of cytoplasm Matrix hyaline / myxoid Irving Dardick, Sudha Kini, Salivary Gland Tumor Cytopathology, Pathology Images Inc., Canada,

10 Neoplasms with basaloid cells Neoplasms producing matrix Basal cell adenoma Basal cell adenoca. Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma Pleomorphic adenoma Neoplasms of the skin basal cell carcinoma pilomatrixoma Small cell carcinoma Basal cell adenoma Basal cell adenoca. Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma Polymorphous low-grade adenocarcinoma Pleomorphic adenoma PA Basal cell Ad Basal cell adenoma Basal cell adenocarcinoma ACC Ep-Myo Ca Pleomorphic adenoma Adenoid cystic ca. Matrix producing, basaloid looking tumors Pattern PA BCA BCAC ACC sheets and syncytia, cells embedded in matrix cohesive clusters; + peripheral palisading; cohesive clusters; + peripheral palisading; 3-D cylinders and branching groups Cells Nuclear atypia Matrix Clinical features plasmacytoid & spindled myoepithelial cells and cuboidal epithelial cells Fibrillar chondromyxoid matrix-irregular edges Basaloid cells, round to oval or elongated nuclei Intercellular hyaline matrix; circumferential hyaline bands Basaloid cells, round to oval or elongated nuclei; +atypia Intercellular hyaline matrix; circumferential hyaline bands Background Myoepithelial cells naked nuclei naked nuclei; + necrosis Basaloid cells, maybe some myoepithelial cells, oval to angulated nuclei; mild to moderate atypia large acellular cylinders and globules of hyaline matrix surrounded by cells- sharp edges naked nuclei; + necrosis Adenoid cystic carcinoma Ki-67 Modified from William C. Faquin s hand out, USCAP,

11 Histology: Basal cell adenoma 70 y, F CT: 1cm spiculated mass in the right upper lobe of the lung. PET/CT: increased FDG up-take in left parotid gland (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 Cystic background looking like necrosis Warthin Tümörü May present only by one or two components 11

12 Mast cell Onkositler Cystic lesions of the salivary glands Non-neoplastic Lenfoepitelhial cyst Retantion cyst Mucocel Branchial cyst Dermoid cyst Epidermoid cyst Neoplastic Benign Warthin tumor Pleomorphic adenoma Cystadenoma Malign Mucoepidermoid carcinoma Acinic cell carcinoma Gabrijela Kocjan, Clinical Cytopathology of the Head and Neck, cases with histopathologic follow up FNAC correctly diagnosed 25 of 36 neoplasms however..., 5 Warthin s tumors 2 squamous cell carcinomas 2 mucoepidermoid carcinomas 2 schwannomas yielded non-representative aspirates Sensitivity 70% Specificity 96% 12

13 Branchial cyst Well differentiated squamous cell carcinoma 62y, F 2 cm mass in the left parotid Oncocytoma Cellularity, isolated oncocytes 3-dimentional oncocytic groups Round uniform nucleus, prominent nucleoli, large granuler eosinophilic cytoplasm Capillary fragments within the groups NO cystic background, NO lymphocytes Oncocytoma Differential diagnosis: Noduler oncocytic hyperplasia Hypocellularity Warthin tumor Monolayers, cystic background, lymphocytes y Oncocytic carcinoma Warthin Dyscohesion, large nucleus, pleomorphism, mitosis, necrosis Acinic cell carcinoma Prominent asiner structures 13

14 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 PAS+D resistant t cytoplasmic zymogen granules Bland nuclear cytologic features Background naked nuclei + lymphocytes Acinic cell Oncocytoma 14

15 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 epithelium Adipose tissue 15

16 Acinic cell carcinoma Differential diagnosis: Salivary gland tissue Oncocytic tumors Clear cell tumors Mucoepidermoid carcinoma Cytomorphology depends on the grade of the tumor Mucus-secreting cells 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 16

17 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 Prominent nucleoli Sheets, clusters, papillae, and cribriform groups Background necrosis 17

18 Salivary gland tumors Epithelial cells What type? Basaloid, clear, oncocytic? Nuclear atypia? Overt malignancy? Myoepithelial l cells ( plasmocytoid/ spindle cells) Matrix production Fibrillary? Hyaline? Background Cyst content, mucin, necrosis? Main differential diagnosis. Matrix-containing lesions: Pleomorphic adenoma vs adenoid cystic carcinomaprimary Basaloid neoplasms: salivary gland Basal cell adenoma vs basal cell adenocarcinoma neoplasm! vs adenoid cystic carcinoma Oncocytic lesions: Warthin s tumor vs oncocytoma vs acinic cell carcinoma Mucinous cysts: Low-grade mucoepidermoid carcinoma vs mucocele High-grade carcinomas: Clinical Mucoepidermoid carcinoma vs salivary duct carcinoma features vs! metastatic carcinoma Spindle cell lesions: Immuno! Myoepithelial tumors vs soft tissue tumors 18

19 MILAN REPORTING SYSTEM William Faquin, MD, PhD q,, 19