22.03.2013 Views

Dr Alpha Tsui Royal Melbourne Hospital 2008 - RCPA

Dr Alpha Tsui Royal Melbourne Hospital 2008 - RCPA

Dr Alpha Tsui Royal Melbourne Hospital 2008 - RCPA

SHOW MORE
SHOW LESS

You also want an ePaper? Increase the reach of your titles

YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.

Salivary gland cytology<br />

<strong>Dr</strong> <strong>Alpha</strong> <strong>Tsui</strong> <strong>Royal</strong> <strong>Melbourne</strong> <strong>Hospital</strong> <strong>2008</strong><br />

Approach to salivary gland lesions:<br />

1. determine whether the lesion is indeed from the salivary gland. It may be from a<br />

lymph node, skin lesion, soft tissue tumour, thyroid, etc<br />

2. is it non-neoplastic or neoplastic ?<br />

3. 1 cell or 2 cell population (epithelial, myoepithelial cells) ?<br />

4. identify the predominant cell type: Basaloid, squamoid, oncocytic, clear cell,<br />

sebaceous, spindled<br />

5. identify background change and whether stroma-rich or stroma-poor: Lymphoid<br />

background, mucin, hyaline globules / stromal matrix, cystic change<br />

6. if neoplastic, is it benign, low grade or high grade malignancy ? (look at cellularity;<br />

cohesiveness of the cells; degree of nuclear pleomorphism; chromatin pattern; N/C<br />

ratio; nucleoli; cytoplasmic differentiation; stroma to cell ratio; mitoses; necrosis)<br />

7. determine specific diagnostic features (precise subtyping of benign or malignant<br />

lesions is usually not critical as there is little influence on subsequent management)<br />

8. is the lesion primary or metastatic ? (requires clinical history; may need to do<br />

immunostains on the cell block)<br />

Morphological patterns:<br />

Neoplasms with basaloid cells:<br />

-basal cell adenoma / carcinoma<br />

-adenoid cystic carcinoma<br />

-cellular pleomorphic adenoma<br />

-primary lymphoepithelioma-like carcinoma<br />

-metastatic small cell carcinoma, Merkel cell carcinoma<br />

-eccrine tumours, pilomatrixoma, basal cell carcinoma from overlying skin<br />

-metastatic basaloid squamous cell carcinoma<br />

-lymphoma<br />

Neoplasms with squamoid cells:<br />

-low grade mucoepidermoid carcinoma<br />

-salivary duct carcinoma<br />

-metastatic squamous cell carcinoma<br />

-squamous metaplasia in Warthin's tumour and pleomorphic adenoma<br />

Neoplasms with oncocytic cells:<br />

-Warthin's tumour<br />

-oncocytoma<br />

-oncocytic carcinoma<br />

-salivary duct carcinoma<br />

-acinic cell carcinoma<br />

-metastatic Hurthle cell carcinoma from the thyroid<br />

-mucoepidermoid carcinoma (rarely)


Neoplasms with clear cells:<br />

-clear cell oncocytoma<br />

-myoepithelioma<br />

-mucoepidermoid carcinoma<br />

-acinic cell carcinoma<br />

-epithelial-myoepithelial carcinoma<br />

-clear cell adenocarcinoma<br />

-metastatic clear cell carcinoma (e.g. from the kidney)<br />

Neoplasms with sebaceous differentiation:<br />

-sebaceous adenoma / lymphadenoma<br />

-monomorphic adenoma<br />

-pleomorphic adenoma<br />

-Warthin’s tumour<br />

-mucoepidermoid carcinoma<br />

Lesions with spindled cells:<br />

-non-specific fibrosis<br />

-nodular fasciitis<br />

-schwannoma<br />

-myoepithelioma / myoepithelial carcinoma<br />

-primary sarcomatoid carcinoma, sarcoma, carcinosarcoma<br />

-metastatic carcinoma, melanoma<br />

Lesions containing lymphocytes:<br />

-chronic sialadenitis<br />

-benign lymphoepithelial lesion<br />

-lymphoepithelial cyst<br />

-intraparotid lymph node<br />

-Warthin's tumour<br />

-sebaceous lymphadenoma<br />

-acinic cell carcinoma<br />

-mucoepidermoid carcinoma<br />

-primary lymphoepithelioma-like carcinoma<br />

-lymphoma<br />

Lesions with mucin:<br />

-mucocoele (rarely involving the parotid and submandibular glands)<br />

-mucoepidermoid carcinoma<br />

-mucinous adenocarcinoma<br />

-pleomorphic adenoma (rarely)<br />

Neoplasms with hyaline globules or fibrillary stromal matrix:<br />

-pleomorphic adenoma<br />

-basal cell adenoma<br />

-adenoid cystic carcinoma (not seen in solid variant or poorly differentiated tumour)<br />

-epithelial-myoepithelial carcinoma<br />

-polymorphous low grade adenocarcinoma


Neoplasms with cystic change:<br />

-Warthin’s tumour<br />

-pleomorphic adenoma<br />

-cystadenoma<br />

-mucoepidermoid carcinoma<br />

-acinic cell carcinoma<br />

-cystadenocarcinoma<br />

-metastatic e.g. cystic squamous cell carcinoma (commonly from nasopharynx)<br />

Tumours with 2-cell population (epithelial and myoepithelial cells):<br />

-pleomorphic adenoma<br />

-basal cell adenoma / basal cell adenocarcinoma<br />

-adenoid cystic carcinoma<br />

-epithelial-myoepithelial carcinoma<br />

Tumours with 1-cell population (epithelial or myoepithelial cells):<br />

-myoepithelioma<br />

-canalicular adenoma<br />

-acinic cell carcinoma<br />

-oncocytoma, oncocytic carcinoma<br />

-polymorphous low grade adenocarcinoma<br />

-salivary duct carcinoma<br />

-clear cell adenocarcinoma<br />

ADEQUACY: Sufficient diagnostic material. At least 2 passes (one dedicated for cell<br />

block if likely to require immunostains e.g. difficult morphology, metastatic tumour,<br />

lymphoma)<br />

Normal salivary gland components:<br />

-acinar tissue of serous or mucinous type, adipose tissue, ductal epithelium<br />

-serous acinar cells show basophilic granular cytoplasm (Diff-Quik) with PASD<br />

positive cytoplasmic granules; usually in lobulated spherical clusters<br />

-mucinous cells are tall, columnar with abundant, finely granular or vacuolated<br />

cytoplasm and basally located small round nuclei<br />

-ductal cells seen as monolayered, cord-like or 3-D fragments<br />

-ductal cells have scant cytoplasm and round to oval, small and dark nuclei<br />

-myoepithelial cells are rarely seen as an isolated component in normal tissue and<br />

they are closely associated with epithelial structures<br />

-myoepithelial cells have oval to plasmacytoid shape, oval to round nuclei, moderate<br />

amounts of cytoplasm or as bare nuclei<br />

-other variable cell types: oncocytes (increase with age), metaplastic squamous cells,<br />

sebaceous cells, lymphoid cells<br />

Crystalloids:<br />

-crystallised amylase common in cystic lesions of the parotid, appearing as rods,<br />

squares, rectangles, needles, polyhedral shapes; non-birefringent (dark blue on Diff-<br />

Quik, orange on Pap)<br />

-collagenous crystalloids: usually seen in pleomorphic adenoma, appear as radially<br />

arranged, needle shaped crystals (yellow or green with Pap)


-tyrosine-rich crystalloids may be seen in stromal component of pleomorphic<br />

adenoma, adenoid cystic carcinoma, acinic cell carcinoma, low grade polymorphous<br />

adenocarcinoma (flower-petal crystalline structures, often with 'sun-burst' appearance;<br />

yellow-tan with Pap, blue with Diff-Quik; refractile; non-birefringent)<br />

-cholesterol crystals<br />

-calcium oxalate crystals<br />

Specific entities:<br />

Non-neoplastic cysts:<br />

-water-like or viscous mucoid aspirate<br />

-complete collapse of the cyst after aspiration<br />

-histiocytes and other inflammatory cells<br />

-epithelial cells - cuboidal and squamoid<br />

Lymphoepithelial cyst:<br />

-clear or turbid fluid (almost caseous-like material)<br />

-inflammatory cells, macrophages, lymphocytes, immunoblasts, tingible body<br />

macrophages, lympho-histiocytic aggregates, squamous cells, ciliated or mucinous<br />

cells<br />

-recognition of a nonlymphoid, epithelial squamous component is important<br />

-squamous component consists of intermediate to superficial cells and numerous<br />

anucleate squames<br />

-multinucleated giant cells and cholesterol crystals are often present<br />

-lack of oncocytes is a clue (present in Warthin's)<br />

-wide maturational spectrum of lymphocytes seen (predominantly small and mature in<br />

Warthin's)<br />

Acute sialadenitis:<br />

-may be bacterial / viral in aetiology or secondary to duct obstruction by calculi<br />

-numerous neutrophils<br />

-may see bacteria in the background<br />

Chronic sialadenitis:<br />

-scarcely cellular<br />

-ductal epithelium in clusters and sheets<br />

-scanty acinar groups with atrophy<br />

-occasional fibroblasts, lymphocytes, neutrophils and macrophages<br />

-beware squamous metaplastic cells which may show reactive atypia<br />

Necrotising sialometaplasia:<br />

-pools of mucus, inflammatory cells, metaplastic squamous cells showing moderate<br />

reactive atypia<br />

Features favouring necrotising sialometaplasia: necrosis, squamous cells,<br />

typical site: palate, history of trauma.<br />

Features against necrotising sialometaplasia: keratin debris, intermediate<br />

cells, mucous-secreting cells, oncocytes.


Duct obstruction (by calculi):<br />

-fibrosis and chronic inflammation<br />

-squamous, mucinous and ciliated metaplasia<br />

-may have abundant extracellular mucus, mimicking a mucoepidermoid carcinoma<br />

-foreign body reaction with giant cells if duct rupture<br />

Lymphoepithelial sialadenitis (benign lymphoepithelial lesion):<br />

-cellular smears with lymphocytes, follicular centre cells, tingible body macrophages,<br />

plasma cells and lympho-histiocytic aggregates<br />

-tight groups of ductal and basal epithelial cells (rarely seen)<br />

-may be mistaken for a lymph node if no epithelial cells are present<br />

Intraparenchymal lymph node:<br />

-reactive pattern with polymorphous population of lymphoid cells<br />

-scant to absent epithelial component<br />

Warthin's tumour:<br />

-precipitate of thin-to-mucoid material containing a granular amorphous substance<br />

and cellular debris<br />

-monolayered sheets of oncocytic cells with distinct cell borders<br />

-mixed population of lymphocytes often in aggregates<br />

-the diagnosis of Warthin’s may be missed if the inflammatory cells predominate and<br />

the oncocytes are difficult to see<br />

-mast cells are seen within oncocytic clusters<br />

Features favouring Warthin’s tumour: oncocytes, necrosis-like granular<br />

background, lymphocytes, mast cells.<br />

Features against Warthin’s tumour: intermediate cells; malignant<br />

squamous cells; mucous-secreting cells.<br />

Pleomorphic adenoma:<br />

-aspirates have a thick, gelatinous consistency<br />

-needs 3 components for the diagnosis: epithelial cells, myoepithelial cells, stroma<br />

-ductal cells dispersed and in loosely cohesive groups, flat sheets, glands<br />

-ductal cells are rounded, small, cuboidal with well-defined, sometimes eccentric<br />

cytoplasm<br />

-myoepithelial cells spindled or plasmacytoid; oval to round nuclei; moderate<br />

amounts of cytoplasm or as bare nuclei<br />

-clusters and single cells gradually merging with the mesenchymal elements<br />

-fibrillary, myxoid stromal substance. May also show chondroid matrix.<br />

-hyaline globules, tyrosine crystalloids and oxalate crystals may be present<br />

-admixture of cellular and stromal components shows a characteristic blending, not<br />

seen in other salivary gland tumours<br />

-cystic change may occur: containing cellular debris, squamous as well as mucusproducing<br />

cells<br />

-oncocytic and squamous metaplasia can occur as potential pitfall<br />

-beware occasional large stromal cells with multiple or multilobated bizarre nuclei,<br />

probably representing a degenerative change


Problems with pleomorphic adenoma:<br />

-matrix mistaken for mucus misdiagnosing as mucoepidermoid carcinoma<br />

-cell-poor stroma-rich variant is a problem<br />

-desmoplasia from other lesions may be mistaken for myxoid matrix<br />

-squamous metaplasia, foam cells and cystic change may suggest mucoepidermoid<br />

carcinoma<br />

-morphology of pleomorphic adenoma (hyaline globules, basaloid cells) is quite<br />

similar to that in polymorphous low grade adenocarcinoma or adenoid cystic<br />

carcinoma<br />

-atypical epithelial or myoepithelial cells<br />

-predominantly spindled myoepithelial cells may suggest a sarcoma<br />

-plasmacytoid myoepithelial cells may mimic a lymphoma or plasmacytoma<br />

-cellular or matrix-deficient variant may resemble small blue cell tumours<br />

Features favouring pleomorphic adenoma: ductal cells, myoepithelial<br />

cells and chondromyxoid stroma all present.<br />

Features against pleomorphic adenoma: mucous-secreting and/or<br />

intermediate cells; lack of myoepithelial cells or chondromyxoid stroma.<br />

Basal cell adenoma:<br />

-cellular smear<br />

-small clusters of branching cords, thick trabeculae, acini, single cells<br />

-2 types of basaloid cells:<br />

-larger oval to polygonal cells with round or oval nuclei, moderate amounts of<br />

delicate pale cytoplasm (light cells – ductal)<br />

-small oval cells with bland hyperchromatic nuclei and scanty cytoplasm; often<br />

show palisading at the periphery of the groups (dark cells – myoepithelial)<br />

-basosquamous whorling, keratin debris, keratinising squamous cells may be present<br />

(absent in adenoid cystic carcinoma)<br />

-may have extracellular homogeneous, hyaline, nonfibrillary and metachromatic<br />

material at the edge of cell clusters<br />

-thick bands of hyaline membrane outline individual nests<br />

-collagenous stroma contains fibroblasts and capillaries<br />

Features favouring basal cell adenoma: 2 types of basaloid cells, bare<br />

nuclei, bland nuclear features.<br />

Features against basal cell adenoma: necrosis, mitoses, tubular and fingerlike<br />

structures, coarse chromatin.<br />

Basal cell adenocarcinoma:<br />

-marked cytological atypia including prominent nucleoli, mitoses, necrosis<br />

-cells arranged in more 3-D multi-layered clusters<br />

-diagnosis on cytology often difficult in low grade tumours, requiring demonstration<br />

of local invasion on histology<br />

Myoepithelioma:<br />

-single cells or loosely cohesive sheets with slightly elongated spindled-shaped or<br />

plasmacytoid cells, eccentric nuclei and inconspicuous nucleoli


-malignant myoepithelioma: marked atypia, necrosis, mitoses, intranuclear or<br />

intracytoplasmic inclusions<br />

Features favouring myoepithelioma: a pure population of plasmacytoid<br />

or spindled cells; no chondroid matrix; no hyaline globules.<br />

Features against myoepithelioma: mitoses; marked atypia; intranuclear<br />

or intracytoplasmic inclusions.<br />

Oncocytoma:<br />

-clean or slightly bloody background<br />

-cellular smear with oncocytes in 3D groups, sheets (multi-layered) and micro-acinar<br />

structures<br />

-round nuclei usually centrally located and containing distinct nucleoli<br />

-cells show abundant granular, dense, non-vacuolated cytoplasm, sharp cytoplasmic<br />

borders and cytoplasmic granules (blue on Diff-Quik; pink-orange on Pap)<br />

-nuclear atypia may be prominent in benign cases<br />

-absent lymphocytes and background debris<br />

Features favouring oncocytoma: numerous isolated or clustered oncocytes.<br />

Features against oncocytoma: lymphocytes, vacuolated cytoplasm,<br />

numerous mitoses, chondromyxoid stroma, myoepithelial cells.<br />

Oncocytic carcinoma:<br />

-can be difficult to distinguish from oncocytoma with nuclear atypia<br />

-more nuclear pleomorphism is seen<br />

-mitoses, necrosis usually present<br />

Adenoid cystic carcinoma:<br />

-cellular smear<br />

-crowded 3-D sheets, cribriform, acinar structures<br />

-finger or cup-shaped groups an important feature<br />

-small uniform cohesive basaloid cells with high N/C ratio, nuclear moulding, small<br />

distinct nucleoli and minimal cytoplasm<br />

-look for significant nuclear abnormalities including prominent nucleoli, enlarged<br />

nuclear size, hyperchromasia and coarse chromatin (all these features may not present<br />

in low grade tumours)<br />

-lack of matrix in poorly differentiated or solid variant with only small cells may<br />

mimic a small cell carcinoma<br />

-presence of necrosis favours adenoid cystic carcinoma (seen in 50% of the cases)<br />

2 types of extracellular material:<br />

A) sheets of basaloid cells with microcystic spaces containing homogeneous acellular<br />

hyaline globules or branching, cylindromatous hyaline material with basaloid cells<br />

arranged around these cores<br />

-these hyaline spheres (reduplicated basement membrane material) have a sharp<br />

interface with the tumour cells<br />

-this material is metachromatic (bright pink on Diff-Quik; light grey-blue with Pap)<br />

-no myoepithelial cells embedded in the matrix


-the matrix can also be mucoid in appearance<br />

B) desmoplastic stroma: does not form spheres or cylinders and interdigitates with the<br />

tumour cells<br />

Clear-cut malignant nuclear features are not seen in all the cases of<br />

adenoid cystic carcinomas.<br />

Features favouring adenoid cystic carcinoma: tubular, cylindrical and<br />

cribriform structures, finger-like or cup-shaped cellular fragments.<br />

Features against adenoid cystic carcinoma: chondromyxoid stroma, 3-D<br />

basaloid clusters, clear cells.<br />

Mucoepidermoid carcinoma:<br />

-grading depends on cyst formation, ratio of stroma to epithelial cells and degree of<br />

nuclear atypia<br />

Low-grade:<br />

-some tumours may only yield cyst fluid with a few mucous cells that are bland<br />

-mixture of mucus-producing glandular cells with finely vacuolated cytoplasm,<br />

intermediate and epidermoid (squamoid) cells in a mucoid background characteristic<br />

-mucous cells may be histiocyte-like or resemble goblet cells<br />

-intermediate cells have higher N/C ratio than epidermoid cells with darker ovoid<br />

nuclei, small nucleoli and small amounts of cytoplasm (important component for the<br />

diagnosis)<br />

-epidermoid cells are non-keratinising with abundant cytoplasm<br />

-background of mucus (stringy, not fibrillary), muciphages, lymphocytes, cholesterol<br />

crystals. Keratinous debris is not a feature.<br />

High grade:<br />

-semisolid aspirate with numerous markedly atypical cells<br />

-predominance of epidermoid cells and intermediate cells with scant mucus-producing<br />

cells<br />

Problems with mucoepidermoid carcinoma:<br />

-can be sparsely cellular<br />

-inflammation may predominate over epithelial cells<br />

-cystic change with only a few “benign-appearing” cells<br />

-low grade nuclear features<br />

-may have sebaceous, clear cell or rarely oncocytic change<br />

-high grade mucoepidermoid carcinomas may look like other high grade malignant<br />

tumours<br />

Any thick mucoid aspirate, even if sparsely cellular, should be suspicious for<br />

mucoepidermoid carcinoma.<br />

Features favouring mucoepidermoid carcinoma: intermediate cells, mucinsecreting<br />

cells, mucoid background.<br />

Features against mucoepidermoid carcinoma: plasmacytoid cells,<br />

chondromyxoid stroma, marked keratinisation in the squamous cells and oncocytes.


Polymorphous low-grade adenocarcinoma (PLGA):<br />

-site (minor salivary glands, esp. palate) and clinical history very important<br />

-sheets, tight clusters, pseudopapillary and acinar structures<br />

-small to medium-sized cells with scant to moderate cytoplasm<br />

-uniform, finely granular nuclei with inconspicuous nucleoli and occasional nuclear<br />

overlap<br />

-dense and hyalinised stromal spheres an important component<br />

-nuclei of adenoid cystic carcinoma show greater atypia than PLGA<br />

-absent myoepithelial cells<br />

Features favouring PLGA: polyhedral or oval cells in pseudopapillary<br />

clusters, hyaline globules, typical site e.g. palate.<br />

Features against PLGA: finger-like structures, chondromyxoid stroma.<br />

Acinic cell carcinoma:<br />

-bloody but otherwise 'clean' background<br />

-cohesive 3-D sheets, clusters, sometimes with fibrovascular cores as well as acinarlike<br />

groups and single cells<br />

-tumour cells resembling normal acinar cells with slightly atypical nuclei with small<br />

nucleoli and abundant cytoplasm<br />

-cytoplasm is delicate with small vacuoles and containing larger PASD+ zymogen<br />

granules (oncocytes have smaller granules and denser cytoplasm with no vacuoles)<br />

-occasional bare tumour cell nuclei and single cells important feature<br />

-nuclei stripped of cytoplasm may resemble lymphocytes and may potentially be<br />

misdiagnosed<br />

-features of acinic cell carcinoma as distinguished from normal: hypercellularity; acini<br />

with loss of nuclear polarity; numerous bare nuclei; lack of ductal cells and fat.<br />

-rare psammoma bodies in papillary cystic variant<br />

Features favouring acinic cell carcinoma: cellular clusters of large acinar<br />

cells, vascular cores, monotonous appearance, cytoplasmic vacuoles and zymogen<br />

granules.<br />

Features against acinic cell carcinoma: extensive necrosis, plasmacytoid cells,<br />

oncocytes, squamous cells, chondromyxoid stroma.<br />

Epithelial-myoepithelial carcinoma:<br />

-characteristic bimodal population of large, clear, myoepithelial cells and small<br />

cuboidal, hyperchromatic ductal cells, forming tubular, trabecular, pseudopapillary<br />

structures<br />

-background of stripped myoepithelial cell nuclei<br />

-acellular, homogeneous, extracellular material surrounding cellular aggregates<br />

-specific diagnosis is difficult if there is no biphasic pattern<br />

-nuclear atypia is mild with most cells having enlarged oval nuclei and small nucleoli<br />

-mitoses, apoptosis, necrosis uncommon


Features favouring epithelial-myoepithelial carcinoma: biphasic pattern<br />

with darker central ductal cells and clear peripheral myoepithelial cells.<br />

Features against epithelial-myoepithelial carcinoma: squamous cells,<br />

chondromyxoid stroma, finger-like cellular fragments.<br />

Salivary duct carcinoma:<br />

-cells are arranged singly, in sheets or cohesive clusters<br />

-cribriform areas, rosette-like aggregates, papillary architecture may be present<br />

-large, polygonal, epithelial cells with moderate to abundant eosinophilic, granular<br />

cytoplasm and large, hyperchromatic nuclei with prominent nucleoli (squamoid or<br />

apocrine-like appearance)<br />

-atypia ranges from mild (uncommon) to markedly pleomorphic<br />

-extensive necrotic debris in the background an important clue<br />

-psammoma bodies may be seen<br />

Features favouring salivary duct carcinoma: granular cytoplasm, nuclear<br />

atypia, mitoses, comedo-necrosis.<br />

Features against salivary duct carcinoma: mucous-secreting cells, mucinous<br />

background, squamous cells.<br />

Cystic lesions containing squamous cells in the head and neck region:<br />

-differential diagnosis:<br />

-skin, subcutaneous lesions including epidermal, dermoid, sebaceous cysts, etc<br />

-branchial cysts<br />

-cystic squamous cell carcinoma (primary and metastatic)<br />

-cystic salivary gland lesions with squamous cells e.g. mucoepidermoid carcinoma,<br />

Warthin’s<br />

-branchial cysts are generally seen in young patients and should never be diagnosed in<br />

the elderly unless cystic squamous cell carcinoma has been excluded (usually<br />

requiring excisional biopsy)<br />

-malignant cells from a cystic squamous cell carcinoma can look relatively bland and<br />

the aspirate is commonly hypocellular.<br />

-in the fluid medium, the squamous cells are generally more rounded and appearing<br />

“less pleomorphic” although neoplastic squamous cells often have aberrant shapes.<br />

-features that favour malignancy include large tissue fragments, nuclear<br />

pleomorphism, hyperchromasia and background necrosis. p53 staining in significant<br />

numbers of cells favours a malignant process.<br />

-the other potential problem is reactive squamous atypia in an actively inflamed<br />

background. The chromatin pattern is open, vesicular and often with a central<br />

nucleolus. The pyknotic nucleus of a parakeratotic squamous cell may also appear<br />

“dark” but the overall size of the cell is very small.


FALSE POSITIVES:<br />

-atypical features in pleomorphic adenoma<br />

-reparative atypia in chronic or necrotising sialadenitis<br />

-inflammation with reactive atypia, mucin strands and squamous metaplasia,<br />

mimicking a mucoepidermoid carcinoma<br />

-radiation atypia<br />

FALSE NEGATIVES:<br />

-cystic lesions e.g. mucoepidermoid carcinoma with predominantly mucin and scanty<br />

tumour cells<br />

-well-differentiated tumours e.g. acinic cell carcinoma, low grade mucoepidermoid<br />

carcinoma<br />

-only the benign component is sampled in a carcinoma ex pleomorphic adenoma<br />

-low grade lymphoma<br />

-lymphoepithelial sialadenitis transforming to lymphoma<br />

PRACTICAL TIPS:<br />

1. Many lesions may be complicated by cystic degeneration, inflammation, clear cell<br />

change or metaplasia.<br />

2. Hyaline globules are not specific for adenoid cystic carcinoma. May be seen in<br />

other tumour types. Solid or high grade adenoid cystic carcinoma does not contain<br />

significant matrix material, making diagnosis difficult.<br />

3. Fibrous stroma from chronic sialadenitis can mimic myxoid matrix of a<br />

pleomorphic adenoma. The former is a pauci-cellular lesion with scattered<br />

inflammatory cells. There are no ductal or myoepithelial cells as in pleomorphic<br />

adenoma.<br />

4. If a cystic lesion contains mucin, always suspect low-grade mucoepidermoid<br />

carcinoma.<br />

5. If well-differentiated keratinised malignant squamous cells predominate, beware<br />

metastatic squamous cell carcinoma (from ENT sites). Mucoepidermoid<br />

carcinoma does not usually contain well-keratinised neoplastic squamous cells.<br />

6. Loss of normal lobulated arrangement in acinar cells may raise suspicion of<br />

malignancy (well-differentiated acinic cell carcinoma).<br />

7. Enlargement of a few epithelial cells in an otherwise typical pleomorphic<br />

adenoma does not indicate malignancy. However, if the atypical cells are<br />

numerous forming substantial aggregates and are adjacent to bland epithelial cells


typical of pleomorphic adenoma, a carcinoma ex pleomorphic adenoma should be<br />

suspected.<br />

8. Beware cystic lesion with squamous cells in the elderly, look carefully for features<br />

of squamous cell carcinoma (may represent a metastasis in a lymph node with<br />

cystic necrotic change). Branchial cysts are rare in the elderly. Recommend<br />

excision, even if the squamous cells look “bland”.


Fig 1. Normal acinar cells in a lobule.<br />

Fig 2. Lymphoepithelial sialadenitis with a small cluster of epithelial cells and a<br />

background of mature lymphocytes.


Fig 3. Warthin’s tumour with oncocytes.<br />

Fig 4. Warthin’s tumour with oncocytes.


Fig 5. Oncocytoma. Tumour cells have granular cytoplasm. No lymphocytes in the<br />

background.<br />

Fig 6. Oncocytic carcinoma. Tumour cells have malignant nuclear features and<br />

granular cytoplasm.


Fig 7. Pleomorphic adenoma with epithelial and stromal components.<br />

Fig 8. Pleomorphic adenoma with epithelial cells, forming ductal structures.


Fig 9. Pleomorphic adenoma. Fibrillary myxoid stroma.<br />

Fig 10. Spindled myoepithelial cells in the myxoid stroma.


Fig 11. Carcinoma ex pleomorphic adenoma. Note tumour cells with malignant<br />

nuclear features.<br />

Fig 12. Basal cell adenoma, forming intersecting thick trabeculae.


Fig 13. Basal cell adenoma. Peripheral palisading of the cells.<br />

Fig 14. Basal cell adenoma. Thickened basement membrane material around a nest.


Fig 15. Basal cell adenoma. Note: Bland tumour cells.<br />

Fig 16. Mucoepidermoid carcinoma. Note mucous cells (Arrow).


Fig 17. Mucoepidermoid carcinoma with abundant epidermoid cells.<br />

Fig 18. Mucoepidermoid carcinoma. Intermediate cells with higher N/C ratio (red<br />

arrow). Epidermoid cells with lower N/C ratio (yellow arrow).


Fig 19. Adenoid cystic carcinoma with elongated groups and single cells.<br />

Fig 20. Adenoid cystic carcinoma. Finger-like and bowl-shaped cell groups.


Fig 21. Adenoid cystic carcinoma with a cribriform structure.<br />

Fig 22. Adenoid cystic carcinoma. Note hyaline globules.


Fig 23. Adenoid cystic carcinoma with cylindromatous hyaline material, surrounded<br />

by tumour cells.<br />

Fig 24. Adenoid cystic carcinoma with basophilic mucoid matrix material.


Fig 25. Adenoid cystic carcinoma. Note tumour cells with angulated nuclei.<br />

Fig 26. Acinic cell carcinoma.


Fig 27. Acinic cell carcinoma with papillary groups and single cells.<br />

Fig 28. Acinic cell carcinoma. Tumour cells with enlarged round nuclei, granular and<br />

vacuolated cytoplasm.


Fig 29. Salivary duct carcinoma.<br />

Fig 30. Branchial cyst with squamous cells and marked inflammation in a young<br />

patient.


Fig 31. Metastatic squamous cell carcinoma to a parotid lymph node. This degree of<br />

keratinisation is not seen in a mucoepidermoid carcinoma. Also the tumour cells can<br />

look rather bland.<br />

Fig 32. Pilomatrixoma with basaloid cells, resembling a basaloid salivary gland<br />

neoplasm.


Fig 33. Pilomatrixoma with shadow squamous cells - important diagnostic feature.


References<br />

Klijanienkp J, Vielh P. Monographs in clinical cytology vol 15. Salivary gland<br />

tumours. Karger. 2000.<br />

Hughes JH et al. Pitfalls in salivary gland fine-needle aspiration cytology. Arch<br />

Pathol Lab Med 2005;129:26-31<br />

Mukunyadzi P. Review of fine-needle aspiration cytology of salivary gland<br />

neoplasms, with emphasis on differential diagnosis. Am J Clin Pathol<br />

2002;118(Supp1):S100-S115<br />

Schindler S et al. Diagnostic challenges in aspiration cytology of the salivary glands.<br />

Sem Diag Pathol 2001;18(2):124-146<br />

<strong>Tsui</strong> A. Difficult problems in head and neck cytology. Cytoletter. 2005 Dec:7-13<br />

Miliauskas JR, Orell SR. Fine-needle aspiration cytological findings in five cases of<br />

epithelial-myoepithelial carcinoma of salivary glands. Diagn Cytopathol<br />

2003;28:163-167<br />

Nasuti JF et al. Utility of cytomorphologic criteria and p53 immunolocalisation in<br />

distinguishing benign from malignant cystic squamous-lined lesions of the neck on<br />

fine-needle aspiration. Diagn Cytopathol 2002;27:10-14<br />

David O et al. Parotid gland fine-needle aspiration cytology: An approach to<br />

differential diagnosis. Diagn Cytopathol 2007;35:47-56

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!