JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2025

I-N07

Signalment (JPC #2147437): Dog

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis: Expanding the deep dermis and subcutis, elevating the overlying dermis and epidermis is a multilobulated, unencapsulated, well circumscribed, densely cellular neoplasm composed of polygonal cells arranged in haphazard ductules and islands separated by variably thick bands of fibrous connective tissue. Ductules often have slit-like lumens lined by double layers of epithelial cells. The luminal layer is composed of cuboidal cells that have variably distinct cell borders, scant to moderate amounts of eosinophilic granular cytoplasm, and oval nuclei with finely stippled chromatin and generally one distinct nucleolus. The outer layer is composed of flattened cells often oriented parallel to the basal lamina. There is mild anisocytosis and anisokaryosis, and mitotic figures average 1 per 2.37 square millimeters. Ductules are often distended up to 1.5 mm diameter and contain brown to amphophilic, granular secretory product admixed with clear, acicular cholesterol clefts. Multifocally, there is squamous differentiation of neoplastic ductular epithelium with gradual keratinization characterized by keratohyaline granules and intraluminal lamellated keratin. Scattered within the fibrous connective tissue and within neoplastic ductules are moderate numbers of macrophages with light brown intracytoplasmic granular material (secretory product).

MORPHOLOGIC DIAGNOSIS: Haired skin and subcutis: Apocrine ductular adenoma, breed unspecified, canine.

CONDITION: Apocrine ductular adenoma

SYNONYMS: Epitrichial ductular adenoma, basaloid apocrine adenoma, ductular sweat gland adenoma, nodular hidradenoma

GENERAL DISCUSSION:

• An uncommon benign apocrine sweat gland neoplasm in older dogs and cats with differentiation to apocrine ductal epithelium
• Ductular adenomas are broken down into three variants:
  • Canine: Classical apocrine ductular adenoma; most commonly found on the head, thorax, abdomen, and back
  • Feline: Similar to canine apocrine ductular adenoma; primarily found on the head
  • Solid-cystic apocrine ductular adenoma: a subtype previously classified as basal cell tumor, more common in cats; may be locally aggressive but rarely metastasize; most common on the head, neck, and dorsal trunk of cats

PATHOGENESIS:

• Unknown

TYPICAL GROSS FINDINGS:

• Solitary, slow growing, well-demarcated, firm
• In dogs, often > 2 cm; solid-cystic variant usually smaller
• In cats, usually < 1 cm
• Overlying skin may be ulcerated
• Often has a blue or purplish tint when viewed through overlying skin
• Greyish or gelatinous material in cystic spaces

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Apocrine ductular adenoma (epitrichial ductular adenoma):
  • Double layer of cuboidal epithelial cells resembling basal cells lining a slit-like lumen or forming tubules (ducts) with possible secretory product, cholesterol clefts
  • There may be central cystic degeneration
  • Luminal, cuboidal cells have scant clear cytoplasm and a small hyperchromatic nucleus; outer layer cells are more fusiform with euchromatic nuclei
  • Little cellular or nuclear pleomorphism; moderate mitotic activity
  • No secretory activity
  • Not contiguous with the epidermis
  • Dogs: May have foci of squamous metaplasia, gradual (infundibular) keratinization with keratohyaline granules, and irregular keratin lakes
  • Cats: May have similar histologic appearance as canines, or may be irregularly cystic or form solid sheets of polygonal epithelial cells
• Solid-cystic apocrine ductular adenoma:
  • Oriented vertically within the dermis often with focal epidermal contiguity
  • Neoplastic lobules have central cystic degeneration and necrosis
  • Frequently pigmented
  • Cats may have apocrine ductular adenomas with dual morphologies
  • Previously included in the basal cell tumor category in cats; nodular hidradenoma is the human analog
• Apocrine ductular adenocarcinoma (ductal epitrichial carcinomas): Irregular, infiltrative borders; tubules lined by double layer of pleomorphic neoplastic cells with larger nuclei, prominent nucleoli, and atypical mitotic figures; larger areas of squamous metaplasia or necrosis; clear cell version exists
• Solid cystic apocrine ductular adenocarcinomas: Only reported in cats; oriented horizontally instead of vertically

ADDITIONAL DIAGNOSTIC TESTS:

• Apocrine ductal adenoma/carcinoma IHC staining patterns:
  • Luminal cells: positive for CK8, 18, 19; variably positive for CK16
  • Basal cells: positive for CK14, 5/6; positive for p63
• Cytology:
  • Epithelium may appear mildly anaplastic with occasional mitotic figures even in benign apocrine ductal adenomas
  • Apocrine ductal adenocarcinomas will have numerous cytologic criteria of malignancy +/- fibroblasts (fibroplasia)

DIFFERENTIAL DIAGNOSIS:

• Basaloid (ductular) mammary gland adenoma: Virtually identical except for identifiable mammary glands in adjacent tissue
• Trichoblastoma (I-N03): Lacks double layered tubules and gradual keratinization present in canine apocrine ductular adenomas; difficult to distinguish the two entities in cats but CAM5.2(CK7/8) may help
• Trichoepithelioma (I-N01B): Lack tubules or lobules; exhibits basaloid and squamous populations, true keratin cysts, and usually more superficial
• Apocrine cystadenoma (I-N06A): may have secretory activity (apical blebbing)

COMPARATIVE PATHOLOGY:

• Richardson’s ground squirrel: Apocrine adenocarcinomas were the most common finding in a retrospective study of RGS apocrine gland tumors (Okumura et al 2023)
• African wild dogs: Apocrine adenocarcinomas were overrepresented in older female animals between the shoulder blades and along the dorsum (Mitchell et al 2022)
• Recent case report of an apocrine carcinoma with malignant myoepithelial component in a dog (Matsumoto et al 2023)
• Recent case report of a vulvar apocrine adenocarcinoma in a cat associated with tissue eosinophilia (Conrado et al 2023)
• Sporadic case reports of apocrine adenomas and adenocarcinomas in wildlife species; more common tumor in ferrets (Terio)

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. Conrado FO, Kibler L, Cesar C, Piedra-Mora C, Taylor TG. Vulval apocrine adenocarcinoma with tumour-associated eosinophilia in a cat. J Comp Pathol. 2023;205:7-10.
3. 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.
4. Matsumoto K, Kishimoto TE, Yamamoto M, Michishita M, Takahashi K, Yoshimura H. Apocrine carcinoma-and-malignant myoepithelioma in a dog: a case of simultaneous malignant progression of both luminal epithelium and myoepithelium. J Vet Diagn Invest. 2023;35(6):789-794.
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. Philadelphia, PA: Elsevier Ltd. 2016: 718-719.
6. Mitchell EP, Henker MS, Lemberger K, Gohl C, Majzoub-Altweck M, Falkenau A, Caldwell P, Chenet B, Mosca M, Pin D, Denk D. Cutaneous apocrine gland neoplasia in 16 captive African wild dogs (Lycaon pictus). J Comp Pathol. 2023;207:59-65.
7. Okumura N, Takei R, Kondo H, Shibuya H. Morphological study of apocrine gland tumors in domestic Richardson's ground squirrels (Urocitellus richardsonii). Vet Pathol. 2023;60(2):276-281
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: 80-82.
9. Williams BH, Burek-Huntington KA, Miller M. Mustelids. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:287-304.

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