JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2022

I-N12

 

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 

• Adenoma:

• Common in aged intact males > females > rare in castrated males

• Carcinoma:

• Uncommon 
• Surveys on sex and reproductive status predispositions are conflicting

 

PATHOGENESIS: 

• Adenoma:  More likely androgen-dependent hyperplasia than true neoplasia 

• 95% regress after castration

• 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, neck, chin)
• Carcinoma:  Occur almost exclusively in perianal region; 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 +/- infection common
• Often multiple nodules; may present as annular perianal growth

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Adenoma:

• Difficult to distinguish from hyperplasia; compresses adjacent tissue
• Uniform lobular or trabecular proliferations of large polygonal cells with abundant eosinophilic cytoplasm (“hepatoid”) lined by a single layer of smaller basaloid reserve cells at the periphery 

• Occasionally form predominantly islands, often with abundant mature fibrous stroma (more common in females)

• Frequently small foci of squamous metaplasia with keratin pearl formation (abortive ductal differentiation); or may have sebaceous differentiation
• 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

• Carcinoma:

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

 

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:

 

REFERENCES:

1. 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; 2020: 94-95. 
2. Goldschmidt MH, Goldschmidt KH. Epithelial and Melanocytic Tumors of the Skin. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: John Wiley & Sons, Inc; 2017: 112-115.
3. Goldschmidt MH, Munday JS, Scruggs JL, Klopfleisch R, Kiupel M. In: Kiupel M, ed. Surgical Pathology of Tumors of Domestic Animals, Volume 1: Epithelial Tumors of the Skin. Washington DC, C.L Davis Foundation; 2019:132-139.
4. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. 2nd ed. Ames, IA: Blackwell Science; 2005: 655-662.
5. 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, 718.
6. 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. 
7. 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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