JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2025

I-N06A

SLIDE A

Signalment (JPC # 1945587): Age and breed unspecified dog

HISTORY: Tissue from a fluctuant mass

HISTOPATHOLOGIC DESCRIPTION: Haired skin: Expanding the subcutis and elevating the overlying dermis and epidermis is a 1 x 0.3 cm, well-circumscribed, unencapsulated, poorly cellular, multilocular neoplasm composed of a single layer of polygonal to flattened epithelial cells lining multiple cysts up to 2 mm in diameter, supported by a variably dense fibrous stroma. Neoplastic cells have indistinct cell borders with moderate amounts of eosinophilic granular cytoplasm, often exhibiting apical blebbing. Nuclei are round to oval with finely stippled chromatin and up to 2 variably distinct nucleoli. Mitotic figures are not observed. Multifocally within the adjacent dermis apocrine glands are ectatic and lined by attenuated epithelium. There is mild orthokeratotic hyperkeratosis of the overlying epidermis.

MORPHOLOGIC DIAGNOSIS: Haired skin: Apocrine gland adenoma, cystic (apocrine cystadenoma), breed unspecified, canine.

SLIDE B

Signalment (JPC# 2147438): Age and breed unspecified, dog

HISTORY: Ulcerated mass from the foot

HISTOPATHOLOGIC DESCRIPTION: Haired skin: Multifocally effacing the dermis, elevating the overlying extensively ulcerated epidermis, and infiltrating the subcutis is an unencapsulated, poorly circumscribed, moderately cellular, infiltrative neoplasm composed of polygonal cells arranged in variably sized, haphazardly arranged tubules lined by disorganized epithelial cells piling up to 3-4 layers thick and occasionally forming small papillary projections. Neoplastic tubules are surrounded by loosely arranged reactive fibroblasts on a dense collagenous stroma (desmoplasia). Neoplastic cells have indistinct cell borders and scant to moderate amounts of eosinophilic granular cytoplasm with occasional apical blebbing. Nuclei are irregularly round with finely stippled chromatin and generally one distinct nucleolus. Anisocytosis and anisokaryosis are moderate. Mitotic figures average one per 40x high power field. Frequently, tubules are filled with amorphous eosinophilic material (secretory product), sloughed epithelial cells, necrotic cellular debris, and degenerate neutrophils. Lymphatics throughout the deep dermis, subcutis, and underlying musculature contain islands and tubules of neoplastic cells and occasional aggregates of neutrophils. There are scattered perivascular nodular aggregates of lymphocytes, plasma cells, and fewer macrophages. The overlying epidermis is extensively ulcerated and overlain by a serocellular crust composed of many viable and necrotic neutrophils admixed with eosinophilic necrotic cellular debris. The adjacent epidermis is mildly hyperplastic with small rete ridges, mild acanthosis, spongiosis, intracellular edema, and multifocal orthokeratotic hyperkeratosis.

MORPHOLOGIC DIAGNOSIS: Haired skin, foot (per contributor): Apocrine gland adenocarcinoma, breed unspecified, canine.

GENERAL DISCUSSION:

• Sweat glands arise from the ectoderm. Sweat glands have traditionally been divided into apocrine or eccrine, though the terms epitrichial and atrichial (respectively) have recently been proposed due to questions regarding the mode of secretion
  • Most apocrine glands are epitrichial (ducts terminate in follicular infundibulum) while eccrine glands are atrichial (ducts terminate on the skin surface)
• Apocrine glands secrete by decapitation secretion (apical blebbing) which utilizes the cytoskeleton rather than the typical cell secretory mechanisms
  • Ceruminous, anal, and mammary glands are modified apocrine glands
• Apocrine gland neoplasms are found in older animals. Adenomas are most common
  • Adenomas are benign circumscribed lesions composed of well differentiated cells
  • Malignant are anaplastic and infiltrative
• Apocrine gland adenomas: May be cystic (AKA cystadenoma), simple and complex secretory, or ductular (I-N07, classical or solid-cystic variants). Frequently located on the head, neck and dorsal trunks in dogs, cats have similar location with the addition of the pinnae and tail
  • Most common lesions are apocrine cysts and apocrine ductular adenoma. Apocrine cystadenomas and secretory (simple and complex) adenomas are less frequent
  • Persian and Himalayan cats can get multiple cystadenomas on the eyelid (gland of Moll) or ear canals
• Apocrine gland adenocarcinomas:
  • Rare tumor, accounts for 2-3% of skin tumors in cats and dogs
  • May be subclassified in the same way as adenomas, but have more features of malignancy (poorly circumscribed and infiltrative)
  • Occur more commonly on the legs in dogs, and in cats they are on the head, legs, and abdomen
• Dogs with adenocarcinomas of apocrine glands of the anal sac (I-N08) may have humoral hypercalcemia of malignancy (HHM) related to increase concentrations of PTH-rp (parathyroid hormone related protein)

TYPICAL CLINICAL FINDINGS:

• Apocrine adenoma: Usually solitary, alopecic, +/- ulceration, contain clear to brown gelatinous liquid
• Apocrine adenocarcinoma: Usually solitary, firm, +/- areas of fluctuant consistency; may be poorly circumscribed

TYPICAL GROSS FINDINGS:

• Typically a single, raised, frequently alopecic, ulcerated nodule 0.5-10cm in diameter
• May have blue-purple hue when observed through the epidermis (cystic)
• Most common on the neck, head, dorsal trunk and limbs
• Adenoma will be circumscribed and may be cystic. Adenocarcinoma will be larger, firm and infiltrative; may resemble exudative dermatitis

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Apocrine hyperplasia/cyst
  • Groups of dilated apocrine glands near follicles
  • Thought to occur from blockage of ducts
  • Resembles normal epithelium with very orderly proliferation
  • Lined by cuboidal to columnar cells that contain granular secretory products
• Apocrine adenoma
  • May have acinar, tubular, or papillary patterns
  • One or more cystic cavities lined by well-differentiated cuboidal to columnar epithelium with basally located nuclei, often with apical blebbing
  • Cystic cavities may contain pale eosinophilic homogenous secretory material and clefts (cholesterol crystals)
  • Ductular variant may have some tubules lined by an orderly bilayer of cuboidal epithelium ( See I-N07)
  • Papillary projections into tubules can help differentiate adenoma from hyperplasia
  • Low mitotic rate; no nuclear atypia; lacks infiltration
• Mixed/complex apocrine adenoma
  • Similar to benign mixed mammary tumors, contains both epithelial and myoepithelial component (see R-N14 for discussion on mammary neoplasia)
  • Zones of myoepithelial proliferation (complex) with myxoid and chondroid differentiation (mixed); osseous metaplasia is rare
• Apocrine adenocarcinomas (solid, cystic, or tubular/ductal)
  • Locally aggressive and infiltrative within the dermis, subcutis, and muscle
  • Similar features as adenoma except these have high mitotic rate, nuclear atypia, loss of cell polarity; prominent nucleoli may be present, apical blebbing is rare
  • Poorly differentiated variants have fibrous desmoplasia, lymphatic invasion, and is ulcerated
• Mixed/complex apocrine adenocarcinoma
  • Myoepithelial component usually looks benign with myxoid and chondroid differentiation and stromal invasion by glandular epithelial component
  • In some cases myoepithelium may be the predominant cell population
  • Rarely do both the epithelial and myoepithelial component demonstrate features of malignancy. In these cases they are call epitrichial (apocrine) gland carcinosarcoma or mixed malignant epitrichial gland tumor

ADDITIONAL DIAGNOSTICS:

• Cytologic findings in neoplasms of apocrine origin:
  • Clusters of basaloid cuboidal to low columnar epithelial cells that may palisade and may have a slightly lower N:C than other basaloid epithelial cells;
  • Cytoplasmic blue-to-green-to-black globules are suggestive of apocrine origin, this material may also be in the background and within macrophages;
  • Round nuclei basally located
  • On a background of cholesterol crystals and granular basophilic material
  • Signs of malignancy include prominent nucleoli, intracytoplasmic punctate vacuoles
• Immunohistochemistry:
  • Can help distinguis glandular from ductular protions of apocrine glands
  • CK7, CK8, CK18, and CK19 are expressed in luminal cells in normal apocrine glands, and are present in apocrine tumors as well
  • CK5/6, CK14, p63, and SMA are expressed in myoepithelial cells
  • CK14 and vimentin are expressed in myoepithelial cells of apocrine glands; loss of CK14 and vimentin in apocrine carcinomas
  • Carcinoembryonic antigen (CEA) is expressed on inner surface of apocrine gland
  • SMA and p63 can distinguish glandular from ductular (positive in myoepithelial cells of glandular)

DIFFERENTIAL DIAGNOSIS:

• Apocrine cyst are common lesions in dogs and cats that is formed from occclusion of the apocrine (sweat gland)
• Adenomas/adenocarcinomas of the mammary gland may be identical to apocrine adenoma/carcinoma because mammary glands are modified apocrine glands; differentiation is usually based on location and presence of adjacent mammary gland
• It may be difficult to distinguish apocrine adenomas from carcinomas because the former can be mitotically active

COMPARATIVE PATHOLOGY:

• Horses: Rare; pinnae & vulva are relatively common sites
• Cattle: Rare
• Rabbits: Apocrine carcinomas are rare skin tumors
• Pigs: Rare.
• Dogs: Ceruminous glands are modified apocrine glands; apocrine gland adenocarcinoma of the anal sac is an epithelial tumor of the subcutis
  • 2023 retrospective study on African wild dogs, older females over represented, dorsal midline common location, cutaneous apocrine adenocarcinoma most common cutaneous neoplasm and having multiples
• Ferrets: common neoplasm in black footed ferret
• Elephants: Temporal glands is a modified apocrine gland unique to elephants
• Prosimians: Great bush baby reported with an apocrine gland papillary cystadenoma
• NHP: Gibbons and orangutans have sternal scent glands which are high coiled apocrine glands. Can have similar neoplasms
• Rodents: 2023 study on apocrine gland tumors in domestic Richardon’s ground squirrels found 84% were apocrine adenocarcinomas with subclassification of 33% as cystic papillary, 33% tubulopapillary, and 24% solid type

References:

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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; 2020:95, 99.
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7. Mitchell EP, Henker MS, Lemberger K, et al. Cutaneous apocrine gland neoplasia in 16 captive African wild dogs (Lycaon pictus). J Comp Pathol. 2023;207:59-65.
8. 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.
9. 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; 2023:62, 79-81
10. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013:599
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