JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2022

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
• Old English sheepdog, golden retriever, and English springer spaniel may be predisposed
• 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: 

 

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 often thin and alopecic, but usually not 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
• Two distinct polygonal cell morphologies; both may become spindle-oid 

• Poroid cell type: Small, chromatic basaloid cuboidal cells; comprise majority of trabecular structure forming occasional ductules
• Cuticular cell type: Larger polygonal cells with rounded margins; in center of islands, occasionally contain intracytoplasmic vacuoles with smooth borders (intracellular ductal differentiation); positive for CAM5.2 (CK7/8) 

• 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 
• Solid-cystic apocrine ductular adenoma falls under cutaneous basilar epithelial tumor umbrella: cohesive cells in tight clumps, rows, or ribbons; uniform, small to cuboidal, with scant to moderate amounts of basophilic cytoplasm, high N:C ratio (Bohn)
• 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: 

 

References:  

1. Bohn AA, Wills T, Caplazi P. Basal cell tumor or cutaneous basilar epithelial neoplasm? Rethinking the cytologic diagnosis of basal cell tumors.Vet Clin Pathol. 2008; 25(4): 449-453.
2. Eguchi A, Inohana M, Nakamura M, et al. A case of rapid recurrence of apocrine ductal carcinoma originating from the oral scent gland of a Richardson’s ground squirrel (Urocitellus richardsonii). J Toxicol Pathol. 2018; 31(3):189-193.
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. 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: 115-120.
5. Goldschmidt MH, Munday JS, Scruggs JL, Klopfleisch R, Kiupel M. Volume 1: Epithelial Tumors of the Skin. In: Kiupel M, ed. Surgical Pathology of Tumors of Domestic Animals. Washington, DC, Davis-Thompson DVM Foundation; 2019: 157-164.
6. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat, 2nd ed. Ames, IA: Blackwell Science; 2005: 672-674, 681-689. 
7. Kok MK, Chambers JK, Ong SM, Nakayama H, Uchida K. Hierarchical Cluster Analysis of Cytokeratins and Stem Cell Expression Profiles of Canine Cutaneous Epithelial Tumors. Vet Pathol. 2018;55(6):821-837. 
8. 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.
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: 80-82.

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