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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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–

–

y

– 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

–

–

–

– Polimorfik düşük dereceli adenokarsinom

– Asinik hücreli karsinom

– Mukoepidermoid karsinom

– Tükrük bezi duktus karsinomu

––

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