Lecture 45- Cytopathology of Epithelial Cells

What are general cytologic features of epithelial cells?

High cellularity, appear in adherent clusters, medium to large size, cuboidal-columnar or polygonal shape, distinct cell borders, round to oval centrally located nuclei, abundant cytoplasm.

Where are epithelial cells normally found in cytology?

Surface epithelium from scrapes, swabs, washes, or normal exfoliation; mature squamous cells may appear individualized with angular cytoplasm; respiratory and GI cells are columnar.

Why can epithelial cells be difficult to interpret on cytology?

They can appear in hyperplasia and neoplasia, and may resemble normal tissue; histopathology is required for specific diagnosis.

What are the naming conventions for epithelial neoplasia?

Benign non-glandular = epithelioma; benign glandular = adenoma; malignant non-glandular = carcinoma; malignant glandular = adenocarcinoma.

What are papillomas?

Benign epithelial tumors, often viral; exophytic, inverted, or plaque-like; squamous papillomas are pedunculated, papillated "cauliflower" warts; cytology shows squamous cells with large eccentric nucleus, reticulated chromatin, stippled/vacuolated cytoplasm; koilocytes indicate viral papillomas.

What are sebaceous adenomas?

Common in dogs (limbs, trunk, eyelids; poodles, beagles), uncommon in cats (dorsal trunk); solitary raised smooth or wartlike masses; cytology shows clusters of well-differentiated sebocytes with abundant vacuolated cytoplasm.

What is sebaceous hyperplasia?

Appears similar to sebaceous adenoma both visually and cytologically; terms often used interchangeably.

What is sebaceous carcinoma?

Uncommon, low-grade, locally invasive, rare metastasis; cytology shows fine vacuoles and criteria of malignancy (COM).

What are perianal gland tumors?

Include adenomas, epitheliomas, and adenocarcinomas; common in older intact male dogs, androgen responsive; occur in perianal region, tail, prepuce, thigh; cytology shows hepatocyte-like cells with abundant granular cytoplasm and smaller reserve cells with dark nuclei.

What is perianal gland adenoma?

Benign circumanal/hepatoid gland tumor, common in intact males.

What is perianal gland epithelioma?

Low-grade malignancy, many reserve cells present.

What is perianal gland adenocarcinoma?

Rare malignant tumor, COM not prominent, requires histopathology.

What is AGASACA?

Apocrine gland adenocarcinoma of the anal sac; common in dogs, rare in cats; malignant, locally invasive, metastasizes to lymph nodes, lungs, bone; associated with paraneoplastic hypercalcemia and renal disease; cytology shows clusters/sheets of moderate epithelial cells with round nuclei, stippled chromatin, pale cytoplasm, indistinct borders.

What are ceruminous gland tumors?

Adenomas and adenocarcinomas of ear canal; most aural neoplasia malignant; ceruminous gland adenocarcinoma (CGAC) is most common malignant type; cytology shows tight clusters of epithelial cells with high N:C ratio, prominent nucleoli, black cytoplasmic granules; locally invasive, spreads to lymph nodes.

What is ceruminous cystomatosis?

Ceruminous hyperplasia in cats, presenting as blue-black cystic lesions at external opening with inspissated cerumen.

What are sweat gland tumors?

Uncommon, occur on head, dorsal neck, limbs; solitary raised ulcerated masses; cytology shows exfoliative cuboidal-columnar cells in sheets, moderate round nuclei, pale granular cytoplasm; COM defines adenocarcinoma.

What are cutaneous follicular cysts and tumors?

Benign lesions such as infundibular keratinizing acanthoma, trichoepithelioma, cholesteatoma; malignant types uncommon; cytology cannot distinguish cyst from tumor.

What is trichoblastoma?

Basal cell tumor of hair germ/follicular origin; common in dogs and cats; firm elevated intradermal mass, often head/neck; usually benign; cytology shows basal-type epithelial cells.

What is basal cell carcinoma?

Uncommon malignant basal cell tumor; cytology shows COM, numerous mitotic figures.

What is squamous cell carcinoma (SCC)?

Common in dogs and cats; occurs on sun-exposed areas (oral, pinnae, ventrum, nailbeds, eyelids); variable presentation (plaque-like, papillary, ulcerated); cytology shows COM, asynchronous N:C ratio, angular keratinized cytoplasm, perinuclear vacuolization, cellular dissociation, neutrophilic inflammation due to keratin.

What are visceral epithelial tumors?

Pulmonary, thymoma, hepatocellular, biliary, pancreatic, GI, urinary tract, mammary gland tumors.

What are pulmonary epithelial tumors?

Primary tumors more common in cats than dogs; feline tumors often metastasize; cytology shows ciliated columnar epithelium (bronchoalveolar origin), papillary formations, eosinophilic adherence; paraneoplastic neutrophilia possible.

What is thymoma?

Neoplasm of thymic epithelial cells, mostly in older dogs and cats; cytology shows epithelial cells with COM plus abundant small lymphocytes, variable medium/large lymphocytes, low mast cells; paraneoplastic syndromes include myasthenia gravis, hypercalcemia, exfoliative dermatitis (cats).

What is hepatocellular adenoma?

Benign "hepatoma," usually single mass in one lobe.

What is hepatocellular carcinoma (HCC)?

Malignant hepatic tumor, three forms (massive, nodular, diffuse), often left lateral lobe; cytology shows COM if obvious, but well-differentiated HCC may resemble benign tissue; histopath required; rare paraneoplastic hypoglycemia.

What is cholangiocellular carcinoma?

Most common primary hepatic tumor of cats; aggressive with high metastasis; cytology shows cuboidal biliary cells in sheets/tubular/acinar arrays, scant cytoplasm, well-differentiated; compared to cysts (clear/yellow fluid, few cells).

What is biliary adenoma/cystadenoma?

Rare benign biliary tumor; solitary circumscribed lesions with small cysts; cytology shows sheets of biliary cells with blue mucinous extracellular material.

What is exocrine pancreatic adenocarcinoma?

Aggressive malignant tumor; 85% metastasize at diagnosis (thoracic/abdominal LN, mesentery, GI, liver); cytology shows highly cellular samples with high N:C ratio, anisokaryosis, nuclear molding, angular nuclei, stippled chromatin, multiple irregular nucleoli, cytoplasmic vacuoles; paraneoplastic neutrophilia, elevated pancreatic enzymes, ALT/ALP.

What are gastric epithelial tumors?

Polyps and adenomas (pylorus), difficult to distinguish even with histology; gastric adenocarcinoma (dogs) most common in pylorus, metastasizes to lymph nodes, presents as mass, ulcerations, diffuse thickening, severe ulcerations leading to perforation and peritonitis.

What are intestinal epithelial tumors?

Adenomatous polyps (rectum in dogs, intestines in cats), solitary masses; difficult to distinguish from carcinoma in situ; adenocarcinoma (colon in dogs, small intestine in cats) shows COM and clear cytoplasmic vacuoles.

What are renal epithelial tumors?

Primary renal tumors rare; renal cell carcinoma, adenocarcinoma, transitional cell carcinoma; lymphoma most common primary renal tumor in cats.

What is transitional cell carcinoma (urothelial carcinoma)?

Most common bladder tumor; dogs (trigone region), cats (bladder wall opposite trigone); cytology shows COM, Melamed-Wolinska bodies (magenta cytoplasmic inclusions); PCR for BRAF mutation available.

What are mammary gland tumors?

Neoplasia mostly in caudal glands; cytology difficult to distinguish hyperplasia, dysplasia, benign tumors, well-differentiated carcinomas; adenomas show sheets/clusters of uniform epithelial cells; benign mixed mammary tumors may show cartilage/bone cells plus spindle myoepithelial cells; carcinomas show individualized epithelial cells or sheets/clusters with eccentric nuclei, basophilic cytoplasm, clear vacuoles, COM, increased mitotic activity.

What are general cytologic features of neuroendocrine tumors?

Highly cellular, "naked nuclei" from ruptured cells, adherent clusters, round to cuboidal cells, indistinct borders, weak COM even in malignant tumors.

What are examples of neuroendocrine tumors?

Insulinoma, gastrinoma, chemodectoma, thyroid tumors, pheochromocytoma, AGASACA.

What is insulinoma?

Beta-cell tumor of pancreas; adenoma or carcinoma; most common in dogs; secretes insulin causing hypoglycemia (BG <40, clinical signs alleviated with dextrose).

What is pheochromocytoma?

Adrenal medulla tumor; secretes catecholamines; clinical signs variable, often incidental finding.

What is the cytologic difference between epithelial and mesenchymal tumors?

Epithelial tumors exfoliate readily with high cellularity and cohesive clusters, while mesenchymal tumors exfoliate poorly and appear as spindle/stellate cells in loose aggregates.

Where on a cytology slide is epithelial detail easiest to evaluate?

At the edges of clusters or in thinner areas of the smear, where individual cell borders are clearer.

What happens to cell cohesion in malignant epithelial tumors?

Malignant cells may lose cohesion, appearing more individualized compared to benign epithelial clusters.

What are general cytologic features of epithelial malignancy?

High cellularity, medium to large cells, cuboidal/columnar/polygonal shapes, distinct borders, round to oval nuclei, abundant cytoplasm, criteria of malignancy (COM).

What are koilocytes and what do they indicate?

Squamous epithelial cells with vacuolated cytoplasm and eccentric nucleus, associated with viral papillomas.

What are cytologic features of sebaceous adenomas?

Clusters of sebocytes with abundant vacuolated cytoplasm, well‑differentiated appearance, usually solitary raised masses.

What cytologic features distinguish sebaceous carcinoma from adenoma?

Carcinomas show finer vacuoles, criteria of malignancy (anisocytosis, anisokaryosis, mitotic figures), and local invasion.

What are reserve cells in perianal gland tumors?

Small epithelial cells with dark nuclei, often seen alongside hepatocyte‑like cells in adenomas and epitheliomas.

What paraneoplastic syndrome is associated with AGASACA?

Hypercalcemia of malignancy, which may cause renal disease.

What cytologic features are typical of AGASACA?

Clusters/sheets of moderate epithelial cells, round nuclei with stippled chromatin, pale cytoplasm, indistinct borders, spindle‑like appearance possible.

What cytologic features are typical of ceruminous gland adenocarcinoma?

Tight clusters of epithelial cells, high N:C ratio, prominent nucleoli, black cytoplasmic granules, locally invasive with LN spread.

What are cytologic features of sweat gland adenomas/carcinomas?

Exfoliative cuboidal‑columnar cells in sheets, moderate round nuclei, pale granular cytoplasm; COM defines adenocarcinoma.

What are cytologic features of basal cell carcinoma?

High cellularity, numerous mitotic figures, criteria of malignancy; uncommon compared to benign trichoblastomas.

What cytologic features are typical of squamous cell carcinoma (SCC)?

Angular keratinized cytoplasm, asynchronous N:C ratio, perinuclear vacuolization, cellular dissociation, neutrophilic inflammation due to keratin debris.

Why can SCC cytology be difficult to interpret?

Neutrophilic inflammation and keratin debris obscure cellular detail, mimicking infection.

What are cytologic features of pulmonary epithelial tumors?

Ciliated columnar epithelium (bronchoalveolar origin), papillary formations, eosinophilic adherence, paraneoplastic neutrophilia; feline tumors often metastasize.

What are cytologic features of thymoma?

Epithelial cells with COM plus abundant small lymphocytes, variable medium/large lymphocytes, low mast cells; paraneoplastic syndromes include myasthenia gravis, hypercalcemia, exfoliative dermatitis in cats.

What are cytologic features of hepatocellular carcinoma (HCC)?

Individualized epithelial cells or sheets/clusters, eccentric nuclei, basophilic cytoplasm with clear vacuoles, COM, increased mitotic activity; well‑differentiated HCC may resemble benign tissue.

What are cytologic features of cholangiocellular carcinoma?

Cuboidal biliary cells in tight sheets, scant cytoplasm, tubular/acinar arrays, aggressive with high metastasis; compared to cysts (clear fluid, few cells).

What are cytologic features of exocrine pancreatic adenocarcinoma?

Highly cellular, high N:C ratio, anisokaryosis, nuclear molding, angular nuclei, stippled chromatin, multiple irregular nucleoli, cytoplasmic vacuoles; paraneoplastic neutrophilia, elevated pancreatic enzymes, ALT/ALP.

What are cytologic features of gastric adenocarcinoma?

Highly cellular aspirates with COM, ulcerated or diffuse thickening masses, metastasis to lymph nodes; severe ulcerations may lead to perforation and peritonitis.

What are cytologic features of intestinal adenocarcinoma?

COM, clear cytoplasmic vacuoles, individualized epithelial cells; difficult to distinguish from adenomatous polyps or carcinoma in situ.

What are cytologic features of transitional cell carcinoma (urothelial carcinoma)?

High cellularity, COM, Melamed‑Wolinska bodies (magenta cytoplasmic inclusions), aggressive behavior; PCR for BRAF mutation available.

What are cytologic features of mammary adenomas?

Sheets/clusters of uniform epithelial cells, benign appearance.

What are cytologic features of benign mixed mammary tumors?

May show cartilage or bone cells, clumps of spindle myoepithelial cells, and epithelial cells; aspiration may miss components, biopsy needed.

What are cytologic features of mammary carcinomas?

Individualized epithelial cells or sheets/clusters, eccentric nuclei, basophilic cytoplasm with clear vacuoles, COM, increased mitotic activity.

What are cytologic features of insulinoma?

Beta‑cell tumor of pancreas; secretes insulin causing hypoglycemia (BG <40, alleviated with dextrose); cytology shows epithelial clusters with naked nuclei.

What are cytologic features of pheochromocytoma?

Adrenal medulla tumor; cytology shows epithelial/neuroendocrine cells with naked nuclei; clinical signs variable due to catecholamine release, often incidental finding.