JPC SYSTEMIC PATHOLOGY
Signalment (JPC # 4037525-00): Dog
HISTORY: Dermal mass over right temporalis
HISTOPATHOLOGIC DESCRIPTION: Haired skin (IN-33b): Expanding and compressing the dermis and adjacent adnexal structures and elevating the overlying epidermis is an unencapsulated, well demarcated, multilobulated neoplasm composed of polygonal cells arranged in islands, cords and trabeculae on a fine fibrovascular stroma. Neoplastic cells have distinct cell borders and a moderate amount of eosinophilic granular to fine lacy cytoplasm which often contains variably sized 12-25um clear vacuole that occasionally contains a small amount of pale, eosinophilic, fine lacy material, one to multiple round to oval to pleomorphic nuclei with coarse chromatin, and 1-4 distinct nucleoli. Anisocytosis and anisokaryosis are moderate to marked and mitoses average 4-6 per 10 hpf. Rare intranuclear cytoplasmic invaginations are present. Cords and trabeculae of neoplastic cells often form wide concentric bands around foci of lytic necrosis with necrotic debris, fibrin and hemorrhage (comedo necrosis), and the stroma is moderately edematous. Neoplastic lobules are separated by fine fibrous bands, islands of smudgy, pale sclerotic collagen, pools of eosinophilic edema fluid, which are multifocally populated by variable numbers of lympohcytes and plasma cells. There are aggregates of hemosiderin laden macrophages, small accumulations of hematoidin pigment, and rare foci of mineralization. There are few small intracorneal pustules.
MORPHOLOGIC DIAGNOSIS: Haired skin: Canine cutaneous clear cell adnexal carcinoma, mixed breed, canine.
SYNONYMS: Clear cell hidradenocarcinoma; follicular stem cell carcinoma; clear cell apocrine ductular carcinoma; clear cell epitrichial carcinoma
- Canine cutaneous clear cell adnexal carcinoma is rare primary cutaneous adnexal neoplasm without definitive apocrine, sebaceous or follicular differentiation
- Distinguished histologically by presence of a subset of “clear cells” with prominent clear or vacuolated cytoplasm
- Proposed origin includes both cutaneous epithelial stem cells as well as apocrine cell origin; has been suggested to have “multilineage potential”
- Surgical excision often curative, but lymph node metastasis and local recurrence has been reported in a low percentage of cases
TYPICAL GROSS FINDINGS:
- Cutaneous mass; may be sessile, ulcerated or pedunculated
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Large polygonal cells arranged in lobules and nests with areas of cystic degeneration
- Finely vacuolated or pale eosinophilic finely granular to reticulated cytoplasm
- Large nuclei that may be vesicular or have coarse chromatin and a single central, or multiple nucleoli
- Intranuclear cytoplasmic invaginations may be seen
- Multinucleated cells often seen as well as nuclear pleomorphism
- Presence of melanin pigment is variable
- Subtle tubules lined by 1-3 layers of cells may be present
- Mitotic rate is variable (often low)
- Sparse to moderate stroma
- Chondroid metaplasia has been reported
- May be located in subcutis or dermis
- Follicular dermal papilla-like structures (proposed as due to an “inductive effect”)
- Necrosis and mineralization may be seen
ADDITIONAL DIAGNOSTIC TESTS:
- 2 (CK7/8), CK13 positive: Allows differentiation from follicular, sebaceous and epidermal carcinomas
- 2 also stains follicular inner root sheath but presence of trichohyalin granules, indicating follicular origin, may help differentiate a purely follicular origin neoplasm from this tumor
- PAS staining is variably positive
- Majority is diastase sensitive, consistent with glycogen (i.e. the cells are glycogen rich)
- A small amount may be diastase resistant, consistent with mucin
- Melan-A: Cannot solely be used to rule out balloon cell melanoma as there may be Melan A positivity in sweat gland tumors (clear cell apocrine ductular carcinoma)
- Other reported positive IHC include: Cytokeratin, vimentin, S-100 (variable), and melan A
- Negative for calponin and alpha smooth muscle actin (reported positive in one study)
- Cytologic features reported include: High cellularity, marked cellular pleomorphism, light blue background, loose arrangement of cells, indistinct cell margins, oval to polygonal to spindle shaped cells with whispy cytoplasmic projections; may contain eosinophilic stippling, globular deposits or pink needle shaped inclusions as well as criteria of malignancy
For histologic findings:
- Balloon cell melanoma: Melanin pigment and spindle cells may be present in both; subtle tubular structures, focal epidermal or follicular infundibular contiguity, and the presence of follicular papillary mesenchymal bodies may help differentiate; balloon cell melanomas are not positive for CK and often have junctional activity
- Clear cell basal cell carcinoma: Differentiated by the presence of epidermal contiguity, horizontal orientation, infiltrative margins, stromal-epithelial retraction clefts and smaller size
- Sebaceous carcinoma: Does not have pure large cell variant and does not show immunoreactivity for Melan-A (or PNL-2)
- Not reported in other species
- Gross TH, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. 2nd ed. Ames, IA: Blackwell Publishing; 2005: 680-691.
- Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed.. Louis, MO: Saunders Elsevier; 2016: 719.
- Mikaelian I, Wong V. Follicular stem cell carcinoma: Histologic,immunohistochemical, ultrastructural, and clinical characterization in 30 dogs. Vet Pathol. 2003;40:433-444.
- Piviani M, Sanchez MD, Patel RT. Cytologic features of clear cell adnexal carcinoma in 30 dogs. Vet Clin Pathol. 2012;41(3):405-411.
- Sakuma A, Nishiyama S, Yasuno K, Ohmuro T, et al. A case of canine cutaneous clear cell adnexal carcinoma with prominent expression of smooth muscle actin. J Toxicol Pathol. 2010;23:265-269.
- Schulman FY, Lipscomb TP, Atkin TJ. Canine cutaneous clear cell adnexal carcinoma: histopathology, immunohistochemistry and biologic behavior of 26 cases. J Vet Diagn Invest. 2005;17:403-411.
- Walder EJ. Comment on: Follicular stem cell carcinoma: Histologic,immunohistochemical, ultrastructural, and clinical characterization in 30 dogs. Vet Pathol. 2005;42(1):107-108.