JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2022

I-N06  

 

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 0.3cm, well-circumscribed, unencapsulated, poorly cellular, multilocular neoplasm composed of a single layer of polygonal to flattened epithelial cells lining multiple cysts up to 2mm 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 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 proliferative lesions are the least common adnexal skin tumors of dogs and are relatively more common in cats; they range from hyperplastic to malignant
• Apocrine gland adenomas: May be cystic (AKA cystadenoma), secretory, or ductular (I-N07, classical or solid-cystic variants)

• Apocrine cystadenomas and secretory adenomas:

• Frequently located on the head, neck and dorsal trunks in dogs and head in the feline
• Persian and Himalayan cats can get multiple cystadenomas on the eyelid or ear canals
• Great Pyrenees, chow chows, malamutes, old English sheepdogs, and Persian cats are predisposed to secretory adenomas and cystadenomas

• Apocrine gland carcinomas: 
  • May be subclassified in the same way as adenomas, but have more features of malignancy
• Apocrine adenocarcinomas:
  • Uncommon in the dog and cat
  • Occur more commonly on the legs
  • 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, +/- fluctuant consistency; may be poorly circumscribed

 

TYPICAL GROSS FINDINGS: 

• Typically a single, raised, frequently alopecic, sometimes ulcerated nodule 0.5-10cm in diameter
• May have blue-purple hue when observed through the epidermis
• Most common on the neck, head, dorsal trunk and limbs

 

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 

• 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
• May have some tubules lined by an orderly bilayer of cuboidal epithelium
• Papillary projections into tubules can help differentiate adenoma from hyperplasia
• Low mitotic rate; no nuclear atypia; lacks infiltration

• Mixed/complex apocrine adenoma

• Zones of myoepithelial proliferation (complex) with myxoid and chondroid differentiation (mixed); osseous metaplasia is rare
• Similar to benign mixed mammary tumors (see R-N14 for discussion on mammary neoplasia)

• Apocrine adenocarcinomas (solid, cystic, or tubular/ductal)

• Locally aggressive and infiltrative within the dermis, subcutis, and muscle
• High mitotic rate, nuclear atypia, loss of cell polarity; apical blebbing is rare
• Fibrous desmoplasia and lymphatic invasion common

• Mixed/complex apocrine adenocarcinoma

• Well differentiated myoepithelial proliferation with myxoid and chondroid differentiation and stromal invasion by glandular epithelial component
• Osseous metaplasia is rare

 

ADDITIONAL DIAGNOSTICS:

• Cytologic findings in neoplasms of apocrine origin:  

• Clusters of basaloid 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; 
• Nuclei may be eccentric suggesting basal location

• Immunohistochemistry: 

• 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: 

• 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
• NHPs: Scent glands are modified apocrine glands and can have similar neoplasms
• Cats: Report of apocrine cystadenocarcinoma producing lipofuscin-like pigments (Fournier, J Comp Pathol 2020)
• Pigs: Cutaneous apocrine cystomatosis reported in pigs (Lopez-Figueroa, J Vet Diagn Invest 2020)
• Dogs: Ceruminous glands are modified apocrine glands 

 

References:

1. Brannik EM, Newkirk KM, Schaefer DMW. Neoplasia and Tumor Biology. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed., St. Louis, MO: Elsevier; 2022:388
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. 
3. Fournier Q, Höhn A, Deubel S, Milne E, Bavcar S, Morrison L. Characterization of Black Pigmenturia in a Cat with Apocrine Gland Cystadenocarcinoma. J Comp Pathol. 2020 Apr;176:145-150.
4. Goldschmidt MH, Goldschmidt KH. Epithelial and Melanocytic Tumors of the Skin. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Somerset, NJ: John Wiley & Sons, Inc.; 2017: 115-120. 
5. 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: 91-105, 151-152, 157-163.
6. Gross TL, Ihrke PJ, Walder WJ, Affolter VK. Sweat gland tumors. In: Skin Diseases of the Dog and Cat, 2nd ed. Ames, IA: Blackwell Publishing; 2005:665-691.
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. López-Figueroa C, Domingo M, Martí B, Vidal E, Segalés J. Cutaneous apocrine cystomatosis in three slaughter-aged pigs. J Vet Diagn Invest. 2020;32(1):159-161.
9. Mauldin EA and Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, Pennsylvania: Elsevier; 2015:718-720.
10. 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: 63.
11. Scott DW, Miller WH, Griffin CE. Muller & Kirk’s Small Animal Dermatology. 7th ed. Elsevier, St. Louis, Missouri, 2013 pp.730-731.
12. Suárez-Bonnet A, Priestnall SL, Ramírez GA, González-Sánchez C, Jaber JR. Scent (Apocrine) Gland Adenocarcinoma in a Wedge-Capped Capuchin Monkey (Cebus olivaceus): Histological and Immunohistochemical Features. J Comp Pathol. 2020 Aug;179:1-6. 
13. 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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