JPC SYSTEMIC PATHOLOGY
SIGNALMENT (JPC #3058415): A mixed breed dog
HISTOPATHOLOGIC DESCRIPTION: Digit: Extending from the epidermis, contiguous with the nailbed epithelium, and expanding into the subungual space and replacing the palmar aspect of the third phalanx in an advancing front is an unencapsulated, moderately cellular epithelial neoplasm composed of polygonal cells arranged in broad anastomosing trabeculae with irregular scalloped borders that surround a central core of amorphous parakeratotic keratin. Neoplastic cells have distinct cell borders, abundant brightly eosinophilic cytoplasm which is often vacuolated (intracellular edema), and irregularly round to oval and vesiculate nuclei with 1-2 prominent nucleoli. Mitoses are fewer than 1 per 10 HPF. Neoplastic cells undergo orderly keratinization which is generally without a granular layer. The neoplasm is surrounded by numerous lymphocytes, plasma cells and macrophages with granulation tissue composed of loose connective tissue, fibroblasts and small caliber blood vessels which is adjacent to spicules of immature woven bone lined by osteoblasts. The neoplasm compresses the adjacent bone causing lysis and bony remodeling. Within a focally extensive area of the adjacent dermis, many lymphocytes, plasma cells, macrophages and fewer neutrophils separate, surround and replace adnexa, and apocrine glands often contain amphophilic homogenous secretory product or eosinophilic cellular and karyorrhectic necrotic debris.
MORPHOLOGIC DIAGNOSIS: Digit: Subungual keratoacanthoma, mixed breed, canine.
SYNONYMS: Nailbed keratoacanthoma (KA)
· Rare, benign neoplasm arising from the nailbed epithelium
· Not analogous to canine infundibular keratinizing acanthoma
· Prevalence is underestimated due to misdiagnosis as squamous cell carcinoma
· The frequency ratio of subungual KA to squamous cell carcinoma is approximately 1:4
· There does not appear to be a breed or sex predilection
· Affected animals are adults
· Amputation of the affected digit is curative
· Etiology unknown
· Currently highly controversial whether human cutaneous KA is a benign entity that may undergo malignant transformation or a biologically distinct variant of low-grade squamous cell carcinoma; no studies have dealt with subungual KA specifically
TYPICAL CLINICAL FINDINGS:
· Single, severely swollen digit
· Focal ulceration may be present
· Affected digits may have deformed or broken nails
· Most cases have radiographic evidence of lysis of the third phalanx
· Lysis of the second phalanx and periosteal bone proliferation are uncommon
TYPICAL GROSS FINDINGS:
· Circumscribed, unencapsulated, generally less than 1.5 cm mass with an irregular central zone of caseous keratin
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Symmetrical, circumscribed, unencapsulated mass with a cup-shaped, tubular, or inverted funnel-shaped configuration; irregular or scalloped borders
· Complex epithelial wall of neoplasm is contiguous with the nailbed epithelium and is composed of large squamous epithelial cells arranged in sheets, islands, and broad trabeculae that undergo orderly keratinization often without a granular cell layer, resulting in a central core of amorphous keratin
· Central core of keratin may open onto the skin surface ventral or adjacent to the nail
· May have large lakes of parakeratotic cells without nuclear atypia admixed with central amorphous keratin
· Neoplastic epithelial cells have abundant, pink cytoplasm with a ground glass appearance (high glycogen content) and moderately enlarged vesiculate nuclei with small nucleoli
· Moderate numbers of apoptotic keratinocytes
· Low numbers of atypical epithelial cells with amphophilic cytoplasm, enlarged nuclei, and prominent nucleoli are present at the periphery of most tumors
· Neoplastic cells do not breach the basal lamina
· Mitotic rate is low and confined to proliferating peripheral zone
· Pressure lysis/destruction of P3; tumor tissue does not invade bone; periosteal fibrosis and bone proliferation often present; secondary osteomyelitis may be observed
ADDITIONAL DIAGNOSTIC TESTS:
· Periodic Acid-Schiff – to stain glycogen in the cytoplasm of neoplastic cells
· Nailbed epithelial inclusion cyst: Similar histologic appearance to follicular cysts of infundibular origin; keratinize through a sparse granular cell layer; pressure induced lysis of P3
· Squamous cell carcinoma (SCC): Differentiation between nailbed KA and well-differentiated SCC can be difficult; asymmetrical; desmoplasia; nuclear/mitotic atypia; neoplastic cells may breach the basal lamina; bone invasion is a classic feature of SCC; multiple digits may be affected; secondary inflammation common
· Melanoma: Gross and radiographic findings similar to subungual SCC; may be pigmented; junctional activity; invasion and destruction of phalangeal bones common
· Nailbed inverted squamous papilloma: Well-circumscribed cup-shaped mass filled with compact keratin; smooth margins; squamous epithelial cells form delicate conical or papillary projections with narrow connective tissue cores and extend into a keratin core; orderly keratinization through a sparse granular layer; koilocytes may be present; no nuclear inclusions; pressure induced lysis of P3
· This tumor has only been described in the dog and cat
1. Goldschmidt MH, Dunstan RW, Stannard AA, von Tscharner C, Walder EJ, Yager JA. Histological Classification of Epithelial and Melanocytic Tumors of the Skin of Domestic Animals. Second Series, Vol 3, Washington, D.C.: Armed Forces Institute of Pathology; 1998:25-6, 62.
2. Goldschmidt MH, Hendrick MJ. Tumors of the skin and soft tissues. In: Meuten DJ, ed. Tumors in Domestic Animals. 4th ed. Ames, IA: Iowa State Press; 2002:63-4, 83.
3. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. 2nd ed. Ames, IA: Blackwell Science Ltd; 2005:695-703, 825-7.
4. Wobeser BK, et al. Diagnoses and clinical outcomes associated with surgically amputated canine digits submitted to multiple veterinary diagnostic laboratories. Vet Pathol. 2007; 44:355-61.