JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2025

I-N12B

Slide A

Signalment: (JPC #2147443): Age and breed unspecified dog

HISTORY: Small dermal mass from the perianal region

HISTOPATHOLOGIC DESCRIPTION: Haired skin, perianal region: Expanding the dermis, elevating the epidermis, and compressing surrounding adnexa and perianal (hepatoid) glands is a 1 cm diameter, well-circumscribed, unencapsulated, densely cellular neoplasm composed of uniform broad trabeculae and islands of polygonal cells surrounded by a single layer of attenuated basaloid reserve cells and supported by a delicate fibrovascular stroma. Polygonal cells have distinct cell borders with abundant granular eosinophilic cytoplasm and one central, round nucleus with finely stippled chromatin and one prominent magenta nucleolus. Basaloid cells have indistinct cell borders, scant eosinophilic cytoplasm, and one ovoid to elongate nucleus with coarsely stippled chromatin and 1-3 nucleoli. Anisocytosis and anisokaryosis are mild. Mitotic figures are confined to the basaloid cells and are less than 1 per 2.37mm². Diffusely the adjacent perianal glands are hyperplastic. There is focally extensive collagen mineralization in the compressed overlying superficial dermis.

MORPHOLOGIC DIAGNOSIS: Haired skin, perianal region: Perianal gland (hepatoid gland) adenoma, breed unspecified, canine.

Slide B

Signalment: (JPC #2647025): Age and breed unspecified dog

HISTORY: Large perianal dermal mass in a dog with inguinal lymphadenomegaly

HISTOPATHOLOGIC DESCRIPTION: Haired skin, perianal region: Expanding and infiltrating the dermis, compressing adnexa, and elevating the focally ulcerated epidermis is a 1 cm diameter, partially encapsulated, infiltrative, densely cellular neoplasm composed of polygonal cells arranged in cords, trabeculae, and solidly cellular areas on a fine fibrovascular stroma. Neoplastic cells have distinct cell borders and moderate amounts of eosinophilic granular cytoplasm that is often microvacuolated (sebaceous differentiation). Nuclei are round to ovoid with finely stippled chromatin and 1-4 distinct nucleoli. The mitoses average 3 per individual 40x HPF with few atypical mitoses. There is marked anisocytosis and anisokaryosis and frequent individual cell necrosis. Focally within the neoplasm there is necrosis and cavitation with replacement by abundant fibrin, hemorrhage, necrotic debris, degenerate neutrophils, and large colonies of cocci. Islands of neoplastic cells occasionally infiltrate the capsule into the adjacent dermis where they occasionally undergo squamous differentiation and form keratin pearls (abortive ductal differentiation). Separating and surrounding islands of neoplastic cells, pre-existing perianal glands, myocytes, and adnexa throughout the dermis are numerous viable and degenerate neutrophils, fewer hemosiderin-laden macrophages, mast cells, lymphocytes, and plasma cells admixed with fibrin, hemorrhage, and edema as well as small-caliber blood vessels and plump reactive fibroblasts (granulation tissue). The overlying epidermis is focally extensively ulcerated and replaced by a serocellular crust.

MORPHOLOGIC DIAGNOSIS: Haired skin, perianal region: Perianal gland (hepatoid gland) carcinoma, breed unspecified, canine.

GENERAL DISCUSSION:

• Perianal gland (synonyms: Hepatoid gland, circumanal gland):
  • Modified sebaceous glands found in dogs and wild canids.
  • Located primarily in perianal skin, but also circumferentially around the proximal third of the tail, in the dorsal lumbosacral area, lateral to the prepuce, and along the ventral midline
  • These glands are ductless due to regression during embryonal development; however these ducts may be evident in neoplasms.
  • Function is uncertain; may play a role in steroid metabolism, pheromone production, and aid in territorial marking
• Adenoma:
  • Common in aged intact males > females > rare in castrated males
• Epithelioma
  • Rare, can be benign or malignant
• Carcinoma:
  • Uncommon
  • Aggressiveness may depend on degree of differentiation
  • 15% have clinical evidence of metastasis at diagnosis

PATHOGENESIS:

• Adenoma: Local excision and castration is usually curative and prevents the development of new benign perianal gland tumors
• Carcinoma: No demonstrated response to castration
• Secondary ulceration/hemorrhage +/- infection is common

TYPICAL CLINICAL FINDINGS:

• See gross findings; +/- tenesmus, pruritus
• Carcinoma: may metastasize to regional lymph nodes (late event)

TYPICAL GROSS FINDINGS:

• Adenoma: Most in perineal area, but ~10% arise in ectopic perianal gland tissue (e.g. ventral skin of the tail, flank, back, prepuce, ventral neck, chin)
• Carcinoma: Occur almost exclusively in perianal region; at least 2 cm in diameter, may extend directly into the pelvic canal or metastasize to regional lymph nodes (late event)
• Raised, tan, rubbery, nodular growth from several mm to 10 cm diameter
• Secondary ulceration/hemorrhage especially in larger masses
• Often multiple nodules; may present as annular perianal growth

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Adenoma:

• May be difficult to distinguish from hyperplasia; compresses adjacent tissue, loses lobular architecture, and may be highly vascular
• Uniform lobular or broad anastomosing trabeculae or islands of well differentiated perianal gland cells [large polygonal cells with abundant eosinophilic cytoplasm (“hepatoid”)] surrounded by a single layer of smaller basaloid reserve cells at the periphery
• Often with abundant mature fibrous stroma (more common in females)
• Low mitotic rate with mitoses confined to the basal layer
• Infarction may occur and cause caseous necrosis, granulomatous inflammation and cholesterol clefts
• Angiomatoid variant: Highly vascular with markedly dilated and hyperemic sinusoidal blood vessels separating epithelial trabeculae

Epithelioma: Composed predominantly (>90%) of basal reserve cells; margin is irregular and mildly infiltrative; small ducts may be present, mitotic activity increased compared to adenoma but only in the basal reserve cells and no nuclear atypia

Carcinoma:

• Range from well-differentiated to undifferentiated
• Locally infiltrative +/- lymphatic invasion
• Lacks organized lobule formation; haphazard organization and maturation from basaloid cells
• Nuclei larger, slightly pleomorphic, and multiple or prominent nucleoli
• Mitoses present in both hepatoid and basaloid reserve cells; atypia common
• Number of reserve cells in well differentiated variant vary from mildly to moderately increased; usually peripheral, but can be centrally located
• Collagenous stroma ranges from sparse (well-differentiated tumor) to prominent/reactive (poorly-differentiated tumor)
• Squamous metaplasia with keratin pearl formation may be present
• Small foci of well-differentiated carcinoma may occur within adenomas (carcinoma in situ)

ADDITIONAL DIAGNOSTIC TESTING

• Cytology: Clusters of round to polygonal epithelial cells with abundant pink granular cytoplasm; round nuclei with prominent nucleoli; basophilic reserve cells are smaller, with dense nuclei and a high N:C; cannot distinguish between hyperplasia and neoplasia on cytology, histology is required
• Claudin-4 immunohistochemistry has been used to distinguish normal, hyperplastic, and neoplastic hepatoid cells
• C-kit immunolabeling may be beneficial (Ipek, 2023)
• Perianal gland tumors have negative immunolabeling with CAM5.2 (Ipek, 2022)

DIFFERENTIAL DIAGNOSIS:

• For adenoma:
  • Perianal gland hyperplasia: Uniform lobular architecture arranged around small ducts; usually not compressive; single layer of basaloid reserve cells
  • Perianal gland epithelioma: Benign or low grade malignancy; more than 90% basaloid reserve cells with uniform nuclei; no mitotic atypia; scattered clusters of cells exhibit hepatoid differentiation
  • Well-differentiated carcinoma
• For poorly differentiated carcinoma:
  • Poorly differentiated squamous cell carcinoma (I-N04)
  • Sebocytic sebaceous carcinoma
  • Apocrine sweat gland carcinoma (I-N06B)
  • Adenocarcinoma of the anal sac (I-N08)

COMPARATIVE PATHOLOGY:

• Reported only in dogs and wild canids; the supracaudal gland in cats and the cloacal gland in reptiles are both classified as hepatoid glands

REFERENCES:

1. Brannick EM, Newkirk KM, Schaefer MW. Neoplasia and Tumor Biology. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:388.
2. Fisher DJ. Cutaneous and subcutaneous lesions. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and hematology of the dog and cat. 5th ed. St. Louis, MO: Elsevier; 2019:87, 94-95.
3. Ipek E, Epikmen ET, Yildirim F, Ozsoy SY, Tunca R. Immunolabelling of SCF and c-KIT in canine perianal gland tumours. J Comp Pathol. 2023;200:51-58
4. İpek E, Epikmen ET, Tunca R. Immunolabelling of c-KIT and CAM5.2 in Canine Anal Sac Gland Adenocarcinoma. J Comp Pathol. 2022;198:56-61.
5. Lane LV, Yang PJ, Cowell RL. Selected Infectious Agents. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2019:42.
6. Mauldin EA, Peters-Kennedy J. Integumentary system In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:517, 717-718.
7. Raskin RE. Chapter 2: General Categories of Cytologic Interpretation. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:29.
8. Raskin RE, Conrado FO. Integumentary system. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:76-79.
9. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1209-1219.

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