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Salivary Glands Basic Morphology and Diagnostic Clues on FNA

Pınar Fırat Professor of Pathology

İ.U. İstanbul Faculty of Medicine

Çapa, 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

• Goal: TRIAGE of the patient

• Is it salivary gland?

– Or a lesion arising in the adjacent tissues,

lymph node? skin? soft tissue?

• Is the lesion neoplastic?

• Is the neoplasm benign or malignant?

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

Salivary gland tumors

• Uncommon,

• <3% of the H&N tumours

• Most swellings are due to non-neoplastic

disease

• Most tumors are seen in the parotid gland

~1 in 6 parotid tm,

~1 in 3 submandibular tm,

~3 in 4 minor salivary gland tm are malignant

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

– Clear cell pattern

– Spindle cell lesions

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Salivary gland tumors

• 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

–

–

–

–

Pleomorphic adenoma

• Cohesive epithelial cells

• Myoepithelial cells, often plasmacytoid or

spindled

• 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

cystic

carcinoma

Pleomorphic

adenoma

Globuler matrix

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Metaplasias: squamous / sebaceous

Cystic change

Mucin in the background Atypia in pleomorphic adenoma

Giant cells

Cellularity with scanty matrix

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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

67y F

2cm nodular

mass in the

hard 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

Irving Dardick, Sudha Kini, Salivary Gland Tumor Cytopathology,

Pathology Images Inc., Canada, 2006

Spindle cell myoepithelioma

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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

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 BA

Nuclear atypia

Mitotic figures

Invasion

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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

Hyaline matrix

Adenoid cystic carcinoma

Nuclear atypia is not always present

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

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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

Epithelial myoepithelial ca.

Dual cell population

Epithelial - myoepithelial

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, 2006

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Neoplasms with

basaloid cells

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

Neoplasms

producing matrix

Basal cell adenoma

Pleomorphic adenoma Adenoid cystic ca.

Basal cell adenocarcinoma

PA

Ep-Myo Ca ACC

Basal cell Ad

Matrix producing, basaloid looking tumors

PA BCA BCAC ACC

Pattern sheets and syncytia

with ductal

arrangement,

embedded cells in

matrix

cohesive clusters;

+ peripheral

palisading;

cohesive clusters;

+ peripheral

palisading;

3-D cylinders and

branching groups

Cells plasmacytoid &

spindled

myoepithelial cells

and cuboidal

epithelial cells

Basaloid cells,

round to oval or

elongated nuclei

Basaloid cells,

round to oval or

elongated nuclei;

+atypia

Basaloid cells,

maybe some

myoepithelial, oval

to angulated nuclei;

mild to moderate

atypia

Matrix Fibrillar

chondromyxoid

matrix-irregular

edges

Intercellular hyaline

matrix;

circumferential

hyaline bands

Intercellular hyaline

matrix;

circumferential

hyaline bands

large acellular

cylinders and

globules of hyaline

matrix surrounded

by cells- sharp

edges

Background Myoepithelial cells naked nuclei naked nuclei;

+ necrosis

naked nuclei;

+ necrosis

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

Nuclear

atypia

Clinical

features

Ki-67 Adenoid cystic carcinoma

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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)

Histology: Basal cell adenoma

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’s Tumor

Oncocytes

Mast

cell

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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

• Oncocytic carcinoma – Dyscohesion, large nucleus, pleomorphism, mitosis, necrosis

• Acinic cell carcinoma – Prominent asiner structures

Warthin

Oncocytic carcinoma / Oncocytic neoplasia

Irving Dardick, Sudha Kini, Salivary Gland Tumor Cytopathology,

Pathology Images Inc., Canada, 2006

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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 cytoplasmic zymogen granules

• Indistinct cell borders

• Bland nuclear cytologic features

• Background naked nuclei + lymphocytes

Irving Dardick, Sudha Kini, Salivary Gland Tumor Cytopathology,

Pathology Images Inc., Canada, 2006

Acinic cell carcinoma

Differential diagnosis:

• Salivary gland tissue

• Oncocytic tumors

• Clear cell tumors

Epithelial-myoepthelial 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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Mucoepidermoid carcinoma

• Most common salivary gland malignancy in

children and adults

• 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

High grade MEC

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

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Salivary gland tumors

• Epithelial cells

– What type? Basaloid, clear, oncocytic?

– Nuclear atypia? Overt malignancy?

• 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

• 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

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Salivary gland cytology

If the lesion could not be classified, final report

should include all the differential diagnosis