JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2025

I-N10B

SLIDE A

Signalment (JPC #1956324): Aged poodle

HISTORY: One of several small dermal masses

HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis (2 sections): Expanding the dermis, elevating the epidermis, surrounding and separating adnexal structures is a 1 cm x 0.5 cm, unencapsulated, well circumscribed, multilobulated proliferation of epithelial cells arranged in lobules forming adenomeres on a scant to moderate fibrovascular stroma. Epithelial cells undergo orderly maturation from peripheral basaloid reserve cells (flattened to cuboidal epithelial cells with scant amounts of eosinophilic cytoplasm, round to oval nuclei with finely stippled chromatin and 1 to 2 distinct nucleoli) to central polygonal cells with abundant vacuolated cytoplasm and similar round nuclei (sebaceous differentiation). Lobules are centered on compressed, ectatic ducts (dilated up to 1.5 mm) that are lined by keratinized stratified squamous epithelium. There is 1 per 2.37 mm² and mitotic figures are confined to the basaloid reserve cells. Within the remaining dermis, apocrine glands are occasionally mildly dilated; lymphatics are mildly ectatic and collagen fibers are separated by clear space (edema).

MORPHOLOGIC DIAGNOSIS: Haired skin and subcutis: Nodular sebaceous hyperplasia, focal, poodle, canine.

SYNONYM: Senile sebaceous hyperplasia

SLIDE B

Signalment (JPC #2147441): Age and breed unspecified dog

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Haired skin: Expanding the dermis and subcutis, elevating the overlying epidermis, and compressing adjacent adnexa is a 1.0 cm x 0.75 cm, partially encapsulated, well circumscribed, multilobulated, densely cellular neoplasm composed of polygonal cells arranged in islands and trabeculae supported by a fine fibrovascular stroma. The majority of cells (approximately 80%) are basaloid reserve cells characterized by variably distinct borders, scant to moderate amounts of granular eosinophilic cytoplasm, and round to oval nuclei with finely stippled chromatin and 1 to 3 nucleoli. The remaining 20% of neoplastic cells are individual or small aggregates of polygonal cells with distinct cell borders, abundant vacuolated eosinophilic cytoplasm, and centrally located, round nuclei with finely stippled chromatin and 1 or 2 distinct nucleoli (sebaceous differentiation). There is 1 per 2.37 mm² and mitotic figures are confined to the basaloid reserve cells. There is multifocal single cell necrosis, large cystic spaces (up to 1 mm x 3 mm) filled with eosinophilic cellular and karyorrhectic debris (cystic degeneration), and few foci of ductular differentiation. Multifocal neoplastic cells and macrophages contain melanin. Multifocally within the mass and in the adjacent dermis are small aggregates of lymphocytes and plasma cells.

MORPHOLOGIC DIAGNOSIS: Haired skin and subcutis: Sebaceous epithelioma, breed unspecified, canine.

GENERAL DISCUSSION:

• Sebaceous gland proliferative lesions are derived from basal cells capable of multiple differentiation paths sometimes within the same tumor; classified according to the level of cellular maturation (but tumor classification based on basal differentiation correlates poorly with biological behavior):
• Nodular sebaceous hyperplasia: common (~50% of the sebaceous gland tumors in dogs)
• Neoplastic lesions:
  • Sebaceous adenoma
    • Uncommon in cats; Persians predisposed
  • Sebaceous epithelioma (low grade malignancy), common epithelial skin tumor in the dog; one case of intra-oral sebaceous epithelioma has been reported in a cocker spaniel
    • May recur if incompletely excised; rarely invade lymphatics and metastasize to regional lymph nodes and in one case to lung and CNS
  • Sebaceous carcinoma
    • Rare malignant neoplasms
    • Cocker spaniels may be predisposed
• Meibomian glands: Specialized sebaceous glands of the eyelid, develop analogous neoplasms to sebaceous glands

PATHOGENESIS:

• Unknown
  • Recent unvalidated publication investigating meibomian gland carcinomas on a limited sample size found the MYC oncogene was upregulated; there was also aberrant p53 expression, and diminished adipophilin expression, suggesting possible method of oncogenesis (Peterson, 2022)

TYPICAL CLINICAL FINDINGS:

• Nodular sebaceous hyperplasia:
  • Single or multiple raised, yellow-orange, single or multi-lobulated waxy to hyperkeratotic mass; most often on the head, eyelids, limbs, and trunks of aged animals
  • Predisposed breeds: Poodle, Cocker Spaniel
• Sebaceous epithelioma:
  • Solitary, firm, nodular or fungiform, or plaque-like mass frequently ulcerated
  • Low-grade malignancy, rarely may metastasize to local lymph nodes
  • Head, neck, ears, and dorsum are common sites
  • Common in dogs, particularly Lhasa Apsos and Shih Tzus

TYPICAL GROSS FINDINGS:

• Nodular sebaceous hyperplasia:
  • Exophytic firm papules; often multifocal in aged dogs
  • Multiple multilobulated, small (usually <1cm)
  • Epidermis is frequently hyperkeratotic and may be ulcerated
• Sebaceous epithelioma:
  • Solitary, raised, smooth, greasy to hyperkeratotic
  • Occasionally cauliflower-like, red to orange
  • Frequently pigmented and/or ulcerated
• Sebaceous carcinoma
  • Solitary, firm nodules, up to 7 cm in diameter; most common on head; ulceration and alopecia are common

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Nodular sebaceous hyperplasia:
  • Multiple, enlarged sebaceous lobules organized in clusters around one or more dilated sebaceous ducts and hair follicles
  • Secondary erosion and inflammation are common
  • Fully mature sebocytes; inconspicuous basal reserve cells
  • Occasional metaplastic transformation to perianal gland cells
  • Cytology: Identical to sebaceous adenoma; clusters of normal-appearing sebaceous epithelial cells
• Sebaceous adenomas differ from hyperplasia in that there are more basal (reserve) cells than in hyperplasia and the lobular proliferation is greater and less symmetrical
  • Simple: ducts are not a prominent feature; lesions composed of multiple large lobules of sebocytes that show normal maturation
  • Compound (ductal adenoma): contains glandular lobules and ducts in various proportions; grouped in radiating clusters around ductal structures; perianal metaplasia can be observed rarely
• Sebaceous epithelioma:
  • Basaloid reserve cells predominate
  • Multiple, large, irregular islands of epithelial basaloid reserve cells with variable margins; multiple small foci of distinct sebaceous differentiation; small ducts lined by squamous epithelial cells usually present
  • Basal reserve cells may have a high mitotic rate; mature sebocytes are not mitotically active
  • Foci of ductal differentiation as horn cysts
  • Lesions can be variably pigmented
  • Lymphatic invasion occasionally found at periphery
• Sebaceous carcinoma
  • Sebocytic carcinomas: neoplastic cells are polygonal and larger than basal reserve cells; absent or markedly distorted differentiation to sebocytes
  • Epitheliomatous sebaceous carcinomas: composed predominantly of slightly larger or more pleomorphic than normal basaloid reserve cells in islands, cords, and trabeculae
    • Distinction between epitheliomatous carcinoma and sebaceous epithelioma includes the following proposed criteria:
      • Carcinomas have increased nuclear size, higher mitotic rate, atypical mitotic figures, and mitotic figures in mature sebocytes; may be locally aggressive

DIAGNOSTICS:

• Cytology: Sebaceous epitheliomas resemble germinal cutaneous basilar neoplasm with small basophilic epithelial clusters; scattered groups of sebocytes; low numbers of individualized, well-differentiated squamous epithelial cells (ductal differentiation)

DIFFERENTIAL DIAGNOSIS:

• Sebaceous adenoma (if eyelid, Meibomian adenoma): Sebocytes predominate, lobules not arranged around a distended duct, degeneration and drop-out (cystic degeneration) of central zones of mature sebocytes common
• Sebaceous ductal adenoma (Meibomian ductal adenoma): Haphazard arrangement of predominantly ducts admixed with fewer basaloid reserve cells and sebocytes
• Sebaceous carcinoma (Meibomian carcinoma): Marked pleomorphism; high mitotic activity; variable cytoplasmic lipid content; sebaceous carcinomas co-express CK5/6 and adipophilin, whereas benign sebaceous neoplasms do not
• Meibomian epithelioma: Low grade malignancy; similar to sebaceous counterpart; frequently pigmented; differentiate from melanoma

COMPARATIVE PATHOLOGY:

• Diffuse sebaceous hyperplasia is rare in dogs and reported in one cat; results in a clinically greasy haircoat
• Guinea pigs: Sebaceous gland adenomas; rare
• Ferrets: Sebaceous epitheliomas and adenomas; common; head and neck; +/- concurrent mast cell tumors
• NHP: Tumors of the adnexa are uncommon; sebaceous gland adenoma reported in a rhesus macaque

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Guinea pig. In: Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016:250.
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; 2020:93-94.
3. Kramer JA and Bielitzki J. Integumentary System Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2^nd ed. San Diego, CA: Elsevier; 2012:585.
4. Mauldin EA, Peters-Kennedy J. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed, St. Louis, MO: Elsevier; 2016:523, 717-720.
5. Meinkoth JK, Cowell RK, Tyler RD. Cell Types and Criteria of Malignancy. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:49.
6. Peterson C, Hicks JL, De Marzo AM, et al. Upregulated MYC expression and p53 mutations may contribute to the oncogenesis of canine Meibomian gland carcinomas. Veterinary Pathology. 2022;60(2):185-189.
7. Raskin RE, Conrado FO. Integumentary System. In: Raskin RE, Meyer DJ, Boes KM ed. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:74.
8. Welle MM, Linder KE. The Integument. In: Zachary JF, 7th ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1146, 1209, 1219, 1363.

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