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Morphological patterns:
Neoplasms with basaloid cells:
-basal cell adenoma / carcinoma
-adenoid cystic carcinoma
-cellular pleomorphic adenoma
-primary lymphoepithelioma-like carcinoma
-metastatic small cell carcinoma, Merkel cell carcinoma
-eccrine tumours, pilomatrixoma, basal cell carcinoma from overlying skin
-metastatic basaloid squamous cell carcinoma
-lymphoma
ADEQUACY: Sufficient diagnostic material. At least 2 passes (one dedicated for cell
block if likely to require immunostains e.g. difficult morphology, metastatic tumour,
lymphoma)
Crystalloids:
-crystallised amylase common in cystic lesions of the parotid, appearing as rods,
squares, rectangles, needles, polyhedral shapes; non-birefringent (dark blue on Diff-
Quik, orange on Pap)
-collagenous crystalloids: usually seen in pleomorphic adenoma, appear as radially
arranged, needle shaped crystals (yellow or green with Pap)
-tyrosine-rich crystalloids may be seen in stromal component of pleomorphic
adenoma, adenoid cystic carcinoma, acinic cell carcinoma, low grade polymorphous
adenocarcinoma (flower-petal crystalline structures, often with 'sun-burst' appearance;
yellow-tan with Pap, blue with Diff-Quik; refractile; non-birefringent)
-cholesterol crystals
-calcium oxalate crystals
Specific entities:
Non-neoplastic cysts:
-water-like or viscous mucoid aspirate
-complete collapse of the cyst after aspiration
-histiocytes and other inflammatory cells
-epithelial cells - cuboidal and squamoid
Lymphoepithelial cyst:
-clear or turbid fluid (almost caseous-like material)
-inflammatory cells, macrophages, lymphocytes, immunoblasts, tingible body
macrophages, lympho-histiocytic aggregates, squamous cells, ciliated or mucinous
cells
-recognition of a nonlymphoid, epithelial squamous component is important
-squamous component consists of intermediate to superficial cells and numerous
anucleate squames
-multinucleated giant cells and cholesterol crystals are often present
-lack of oncocytes is a clue (present in Warthin's)
-wide maturational spectrum of lymphocytes seen (predominantly small and mature in
Warthin's)
Acute sialadenitis:
-may be bacterial / viral in aetiology or secondary to duct obstruction by calculi
-numerous neutrophils
-may see bacteria in the background
Chronic sialadenitis:
-scarcely cellular
-ductal epithelium in clusters and sheets
-scanty acinar groups with atrophy
-occasional fibroblasts, lymphocytes, neutrophils and macrophages
-beware squamous metaplastic cells which may show reactive atypia
Necrotising sialometaplasia:
-pools of mucus, inflammatory cells, metaplastic squamous cells showing moderate
reactive atypia
Warthin's tumour:
-precipitate of thin-to-mucoid material containing a granular amorphous substance
and cellular debris
-monolayered sheets of oncocytic cells with distinct cell borders
-mixed population of lymphocytes often in aggregates
-the diagnosis of Warthins may be missed if the inflammatory cells predominate and
the oncocytes are difficult to see
-mast cells are seen within oncocytic clusters
Pleomorphic adenoma:
-aspirates have a thick, gelatinous consistency
-needs 3 components for the diagnosis: epithelial cells, myoepithelial cells, stroma
-ductal cells dispersed and in loosely cohesive groups, flat sheets, glands
-ductal cells are rounded, small, cuboidal with well-defined, sometimes eccentric
cytoplasm
-myoepithelial cells spindled or plasmacytoid; oval to round nuclei; moderate
amounts of cytoplasm or as bare nuclei
-clusters and single cells gradually merging with the mesenchymal elements
-fibrillary, myxoid stromal substance. May also show chondroid matrix.
-hyaline globules, tyrosine crystalloids and oxalate crystals may be present
-admixture of cellular and stromal components shows a characteristic blending, not
seen in other salivary gland tumours
-cystic change may occur: containing cellular debris, squamous as well as mucus-
producing cells
-oncocytic and squamous metaplasia can occur as potential pitfall
-beware occasional large stromal cells with multiple or multilobated bizarre nuclei,
probably representing a degenerative change
Problems with pleomorphic adenoma:
-matrix mistaken for mucus misdiagnosing as mucoepidermoid carcinoma
-cell-poor stroma-rich variant is a problem
-desmoplasia from other lesions may be mistaken for myxoid matrix
-squamous metaplasia, foam cells and cystic change may suggest mucoepidermoid
carcinoma
-morphology of pleomorphic adenoma (hyaline globules, basaloid cells) is quite
similar to that in polymorphous low grade adenocarcinoma or adenoid cystic
carcinoma
-atypical epithelial or myoepithelial cells
-predominantly spindled myoepithelial cells may suggest a sarcoma
-plasmacytoid myoepithelial cells may mimic a lymphoma or plasmacytoma
-cellular or matrix-deficient variant may resemble small blue cell tumours
Myoepithelioma:
-single cells or loosely cohesive sheets with slightly elongated spindled-shaped or
plasmacytoid cells, eccentric nuclei and inconspicuous nucleoli
-malignant myoepithelioma: marked atypia, necrosis, mitoses, intranuclear or
intracytoplasmic inclusions
Oncocytoma:
-clean or slightly bloody background
-cellular smear with oncocytes in 3D groups, sheets (multi-layered) and micro-acinar
structures
-round nuclei usually centrally located and containing distinct nucleoli
-cells show abundant granular, dense, non-vacuolated cytoplasm, sharp cytoplasmic
borders and cytoplasmic granules (blue on Diff-Quik; pink-orange on Pap)
-nuclear atypia may be prominent in benign cases
-absent lymphocytes and background debris
Oncocytic carcinoma:
-can be difficult to distinguish from oncocytoma with nuclear atypia
-more nuclear pleomorphism is seen
-mitoses, necrosis usually present
Clear-cut malignant nuclear features are not seen in all the cases of
adenoid cystic carcinomas.
Features favouring adenoid cystic carcinoma: tubular, cylindrical and
cribriform structures, finger-like or cup-shaped cellular fragments.
Features against adenoid cystic carcinoma: chondromyxoid stroma, 3-D
basaloid clusters, clear cells.
Mucoepidermoid carcinoma:
-grading depends on cyst formation, ratio of stroma to epithelial cells and degree of
nuclear atypia
Low-grade:
-some tumours may only yield cyst fluid with a few mucous cells that are bland
-mixture of mucus-producing glandular cells with finely vacuolated cytoplasm,
intermediate and epidermoid (squamoid) cells in a mucoid background characteristic
-mucous cells may be histiocyte-like or resemble goblet cells
-intermediate cells have higher N/C ratio than epidermoid cells with darker ovoid
nuclei, small nucleoli and small amounts of cytoplasm (important component for the
diagnosis)
-epidermoid cells are non-keratinising with abundant cytoplasm
-background of mucus (stringy, not fibrillary), muciphages, lymphocytes, cholesterol
crystals. Keratinous debris is not a feature.
High grade:
-semisolid aspirate with numerous markedly atypical cells
-predominance of epidermoid cells and intermediate cells with scant mucus-producing
cells
Any thick mucoid aspirate, even if sparsely cellular, should be suspicious for
mucoepidermoid carcinoma.
Features favouring mucoepidermoid carcinoma: intermediate cells, mucin-
secreting cells, mucoid background.
Features against mucoepidermoid carcinoma: plasmacytoid cells,
chondromyxoid stroma, marked keratinisation in the squamous cells and oncocytes.
Polymorphous low-grade adenocarcinoma (PLGA):
-site (minor salivary glands, esp. palate) and clinical history very important
-sheets, tight clusters, pseudopapillary and acinar structures
-small to medium-sized cells with scant to moderate cytoplasm
-uniform, finely granular nuclei with inconspicuous nucleoli and occasional nuclear
overlap
-dense and hyalinised stromal spheres an important component
-nuclei of adenoid cystic carcinoma show greater atypia than PLGA
-absent myoepithelial cells
Epithelial-myoepithelial carcinoma:
-characteristic bimodal population of large, clear, myoepithelial cells and small
cuboidal, hyperchromatic ductal cells, forming tubular, trabecular, pseudopapillary
structures
-background of stripped myoepithelial cell nuclei
-acellular, homogeneous, extracellular material surrounding cellular aggregates
-specific diagnosis is difficult if there is no biphasic pattern
-nuclear atypia is mild with most cells having enlarged oval nuclei and small nucleoli
-mitoses, apoptosis, necrosis uncommon
Features favouring epithelial-myoepithelial carcinoma: biphasic pattern
with darker central ductal cells and clear peripheral myoepithelial cells.
Features against epithelial-myoepithelial carcinoma: squamous cells,
chondromyxoid stroma, finger-like cellular fragments.
Cystic lesions containing squamous cells in the head and neck region:
-differential diagnosis:
-skin, subcutaneous lesions including epidermal, dermoid, sebaceous cysts, etc
-branchial cysts
-cystic squamous cell carcinoma (primary and metastatic)
-cystic salivary gland lesions with squamous cells e.g. mucoepidermoid carcinoma,
Warthins
-branchial cysts are generally seen in young patients and should never be diagnosed in
the elderly unless cystic squamous cell carcinoma has been excluded (usually
requiring excisional biopsy)
-malignant cells from a cystic squamous cell carcinoma can look relatively bland and
the aspirate is commonly hypocellular.
-in the fluid medium, the squamous cells are generally more rounded and appearing
less pleomorphic although neoplastic squamous cells often have aberrant shapes.
-features that favour malignancy include large tissue fragments, nuclear
pleomorphism, hyperchromasia and background necrosis. p53 staining in significant
numbers of cells favours a malignant process.
-the other potential problem is reactive squamous atypia in an actively inflamed
background. The chromatin pattern is open, vesicular and often with a central
nucleolus. The pyknotic nucleus of a parakeratotic squamous cell may also appear
dark but the overall size of the cell is very small.
FALSE POSITIVES:
-atypical features in pleomorphic adenoma
-reparative atypia in chronic or necrotising sialadenitis
-inflammation with reactive atypia, mucin strands and squamous metaplasia,
mimicking a mucoepidermoid carcinoma
-radiation atypia
FALSE NEGATIVES:
-cystic lesions e.g. mucoepidermoid carcinoma with predominantly mucin and scanty
tumour cells
-well-differentiated tumours e.g. acinic cell carcinoma, low grade mucoepidermoid
carcinoma
-only the benign component is sampled in a carcinoma ex pleomorphic adenoma
-low grade lymphoma
-lymphoepithelial sialadenitis transforming to lymphoma
PRACTICAL TIPS:
2. Hyaline globules are not specific for adenoid cystic carcinoma. May be seen in
other tumour types. Solid or high grade adenoid cystic carcinoma does not contain
significant matrix material, making diagnosis difficult.
8. Beware cystic lesion with squamous cells in the elderly, look carefully for features
of squamous cell carcinoma (may represent a metastasis in a lymph node with
cystic necrotic change). Branchial cysts are rare in the elderly. Recommend
excision, even if the squamous cells look bland.
Fig 1. Normal acinar cells in a lobule.
Fig 6. Oncocytic carcinoma. Tumour cells have malignant nuclear features and
granular cytoplasm.
Fig 7. Pleomorphic adenoma with epithelial and stromal components.
Fig 14. Basal cell adenoma. Thickened basement membrane material around a nest.
Fig 15. Basal cell adenoma. Note: Bland tumour cells.
Fig 18. Mucoepidermoid carcinoma. Intermediate cells with higher N/C ratio (red
arrow). Epidermoid cells with lower N/C ratio (yellow arrow).
Fig 19. Adenoid cystic carcinoma with elongated groups and single cells.
Fig 20. Adenoid cystic carcinoma. Finger-like and bowl-shaped cell groups.
Fig 21. Adenoid cystic carcinoma with a cribriform structure.
Fig 24. Adenoid cystic carcinoma with basophilic mucoid matrix material.
Fig 25. Adenoid cystic carcinoma. Note tumour cells with angulated nuclei.
Fig 28. Acinic cell carcinoma. Tumour cells with enlarged round nuclei, granular and
vacuolated cytoplasm.
Fig 29. Salivary duct carcinoma.
Fig 30. Branchial cyst with squamous cells and marked inflammation in a young
patient.
Fig 31. Metastatic squamous cell carcinoma to a parotid lymph node. This degree of
keratinisation is not seen in a mucoepidermoid carcinoma. Also the tumour cells can
look rather bland.
Fig 32. Pilomatrixoma with basaloid cells, resembling a basaloid salivary gland
neoplasm.
Fig 33. Pilomatrixoma with shadow squamous cells - important diagnostic feature.
References
Klijanienkp J, Vielh P. Monographs in clinical cytology vol 15. Salivary gland
tumours. Karger. 2000.
Tsui A. Difficult problems in head and neck cytology. Cytoletter. 2005 Dec:7-13
Miliauskas JR, Orell SR. Fine-needle aspiration cytological findings in five cases of
epithelial-myoepithelial carcinoma of salivary glands. Diagn Cytopathol
2003;28:163-167