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Salivary Gland Cytology
Pınar Fırat, MDProfessor of Pathology
İ.U. İstanbul Faculty of MedicineÇapa, İstanbul
Salivary gland 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 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 86-100%
Salivary gland cytology
• Is it a salivary gland lesion?– Or arising in the adjacent tissues, lymph
node? skin? soft tissue?
• Is the lesion neoplastic?
Triage
• 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
• 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
Salivary gland tumors
• Benign– Pleomorphic adenoma
– Myoepithelioma
– Basal cell adenoma
• Malignant– Acinic cell carcinoma
– Mucoepidermoid carcinoma
– Adenoid cystic carcinoma– Warthin tumor
– Oncocytoma
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– Epithelial-myoepithelial carcinoma
– Polymorphous low grade adenocarcinoma
– Salivary duct carcinoma
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Tükrük bezi tümörleri
• Benign– Pleomorfik adenom
– Myoepitelyoma
– Bazal hücreli adenom
• Malign– Adenoid kistik karsinom
– Epitelyal-myoepitelyal karsinomMyoepithelial
B l id– Warthin tümörü
– Onkositom
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– Polimorfik düşük dereceli adenokarsinom
– Asinik hücreli karsinom
– Mukoepidermoid karsinom
– Tükrük bezi duktus karsinomu
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BasaloidOncocyticOthers with poligonal/cuboidal cellsCystic (squamous, mucinous)
High grade
Pleomorphic adenoma
• Myoepithelial cells, often plasmacytoid or spindled
• Cohesive epithelial cells p
• Chondromyxoid matrix - fibrillary and bright magenta (Romanowsky stains) with indistinct margins
• Myoepithelial cells embedded into the fibrillary matrix
Fibrillary matrix
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Adenoid cysticcarcinoma
Pleomorphicadenoma
Globuler matrix
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Metaplasias: squamous / sebaceous
Cystic change
Mucin in the background Atypia in pleomorphic adenoma
Cellularity with scanty matrix
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
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67y F2cm nodularmass in thehard palate
NO matrix
Plasmacytoid cells Elongated spindle cells
Myoepithelioma
• Myoepithelial cells– Epitheloid, plasmacytoid, spindle cell, clear cell
patterns
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
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Irving Dardick, Sudha Kini, Salivary Gland Tumor Cytopathology, Pathology Images Inc., Canada, 2006
Spindle cell myoepithelioma
Schwannom
Histology: Myoepithelial carcinoma
M it hli l tMyoepitehlial tumors
Bazaloid tumors
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
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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)
Basal cell Adenocarcinoma
May be identical to BANuclear atypiaMitotic figuresInvasion
Adenoid cystic carcinoma
• Painful mass or pain during the FNA
• Basaloid cells with dark angulated nuclei(variable nuclear atypia)
• Acellular hyaline matrix with sharp bordersAcellular hyaline matrix with sharp borders
• Variably sized, often large, three-dimensional hyaline spheres
Hyaline matrixHyaline matrix
Nuclear atypia is not always present
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Naked nuclei are seen in the background
Solid variant of adenoid cystic carcinomado not show abundant matrixMay closely mimic basal cell tumors
as the number of hyaline globules and their size increases, the diagnosis gets closer to adenoid cystic carcinoma
Adenoid kistik karsinomEpitelyal-myoepitelyal karsinom
Epithelial-myoepithelial carcinoma
• Matrix producing basaloid looking tumor
– Hyaline globules / myxoid matrix
• Cellular smears, naked nuclei in the background
• Dual cell population• 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 glandsBranching papillaLarger amount of cytoplasmMatrix – hyaline / myxoid Irving Dardick, Sudha Kini, Salivary Gland Tumor Cytopathology,
Pathology Images Inc., Canada, 2006
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Neoplasms with basaloid cells
Basal cell adenoma
Basal cell adenoca.
Adenoid cystic carcinoma
Epithelial-myoepitheliali
Basal cell adenoma
Basal cell adenoca.
Adenoid cystic carcinoma
Epithelial-myoepithelial i
Neoplasms producing matrix
carcinoma
Pleomorphic adenoma
Neoplasms of the skin
– basal cell carcinoma
– pilomatrixoma
Small cell carcinoma
carcinoma
Polymorphous low-grade adenocarcinoma
Pleomorphic adenoma
Basal cell adenoma Basal cell adenocarcinoma
Pleomorphic adenoma Adenoid cystic ca.
PA Basal cell Ad
Ep-Myo CaACC
Matrix producing, basaloid looking tumorsPA BCA BCAC ACC
Pattern sheets and syncytia, cellsembedded in matrix
cohesive clusters;+ peripheral palisading;
cohesive clusters;+ peripheral palisading;
3-D cylinders and branching groups
Cells plasmacytoid & spindled myoepithelial cells
Basaloid cells, round to oval or elongated nuclei
Basaloid cells, round to oval or elongated nuclei;
Basaloid cells, maybe somemyoepithelial cellsNuclear myoepithelial cells
and cuboidal epithelial cells
elongated nuclei elongated nuclei; +atypia
myoepithelial cells, oval to angulatednuclei; mild to moderate atypia
Matrix Fibrillarchondromyxoidmatrix-irregularedges
Intercellular hyaline matrix; circumferential hyaline bands
Intercellular hyaline matrix; circumferential hyaline bands
large acellularcylinders and globules of hyaline matrix surrounded by cells- sharpedges
Background Myoepithelial cells naked nuclei naked nuclei;+ necrosis
naked nuclei;+ necrosis
Modified from William C. Faquin’s hand out, USCAP, 2005
Nuclearatypia
Clinicalfeatures
Ki-67Adenoid cystic carcinoma
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70 y, FCT: 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)
Histology: Basal cell adenoma
Never trust globulesAsk the clinical features, see the nuclear atypia
PET scan for salivary gland :Limited valueWarthin’s tumors, pleomorphic adenomas, basal cell adenomasshow increased FDG uptake
Warthin’s tumor
• Oncocytes with large polygonal granular cytoplasm forming clusters/ monolayers
• Lymphocytes, like a lymph nodeLymphocytes, like a lymph node
• Cystic background looking like necrosis
May present only by one ortwo components
May present only by one ortwo components
Warthin TümörüWarthin Tümörü
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Onkositler
Mast cell
Cystic lesions of the salivary glands
Non-neoplastic
• Lenfoepitelhial cyst
• Retantion cyst
• Mucocel
Neoplastic
Benign
• Warthin’ tumor
• Pleomorphic adenoma
• Branchial cyst
• Dermoid cyst
• Epidermoid cyst
p
• Cystadenoma
Malign
• Mucoepidermoid carcinoma
• Acinic cell carcinoma
Gabrijela Kocjan, Clinical Cytopathology of the Head and Neck, 2001
63 cases with histopathologic follow up
FNAC correctly diagnosed 25 of 36 neoplasms 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%
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Branchial cyst
Well differentiated squamous cell carcinoma
62y, F2 cm mass in theleft parotid
Oncocytoma
• Cellularity, isolated oncocytes
• 3-dimentional oncocytic groups
– Round uniform nucleus prominent nucleoli– 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 Warthiny y g y p y
• Oncocytic carcinoma– Dyscohesion, large nucleus, pleomorphism, mitosis, necrosis
• Acinic cell carcinoma– Prominent asiner structures
Warthin
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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
PAS D i t t t l i l• PAS+D resistant cytoplasmic zymogen granules
• Bland nuclear cytologic features
• Background naked nuclei + lymphocytes
Acinic cell Oncocytoma
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Acinic cell carcinomaEpithelial-myoepithelial carcinoma
Salivary gland tissue
• Serous and mucinous acinar cells in grapelike clusters
• Admixed small tubules and/or sheets of ductal epithelium
• Adipose tissue
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Acinic cell carcinoma
Differential diagnosis:
• Salivary gland tissue
• Oncocytic tumors
• Clear cell tumors• Clear cell tumors
Mucoepidermoid carcinoma
• Cytomorphology depends on the grade of the tumor
• Mucus-secreting cells
• Squamous cellsSquamous cells
• Intermediate cells (low N/C ratio)
• Mucoid background
Mucoepidermoid carcinoma
Low grade MEC
• Common cause of false-negative cytologic diagnosis, theaspirate may yield only cyst contents
• The epithelial cells are bland, easily be misinterpreted as histiocytes
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Onkositom
Warthin
MEC
MEC Warthin
Acinic cell
High grade MEC
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
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Salivary gland tumors
• Epithelial cells– What type? Basaloid, clear, oncocytic?
– Nuclear atypia? Overt malignancy?
M ith li l ll• Myoepithelial cells ( plasmocytoid/ spindle cells)
• Matrix production– Fibrillary? Hyaline?
• Background– Cyst content, mucin, necrosis?
Main differential diagnosis ….
• Matrix-containing lesions: – Pleomorphic adenoma vs adenoid cystic carcinoma
• Basaloid neoplasms: – Basal cell adenoma vs basal cell adenocarcinoma vs adenoid
cystic carcinoma
Primary salivary gland
neoplasm!
• Oncocytic lesions: – Warthin’s tumor vs oncocytoma vs acinic cell carcinoma
• Mucinous cysts: – Low-grade mucoepidermoid carcinoma vs mucocele
• High-grade carcinomas: – Mucoepidermoid carcinoma vs salivary duct carcinoma vs
metastatic carcinoma
• Spindle cell lesions: – Myoepithelial tumors vs soft tissue tumors
Clinicalfeatures !
Immuno!
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MILAN REPORTING SYSTEM
William Faquin, MD, PhDq , ,http://www.youtube.com/watch?v=LvyD1_LIR4E&feature=youtu.be&t=24s