JPC SYSTEMIC PATHOLOGY
MUSCULOSKELETAL SYSTEM
APRIL 2022
M-N06 (NP)

SIGNALMENT (JPC #3058415):  A mixed breed dog

 

HISTORY:  None

 

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, expansile, well demarcated, moderately cellular epithelial neoplasm composed of polygonal cells arranged in broad anastomosing trabeculae with irregular scalloped borders, undergoing keratinization, and surrounding a central core of amorphous parakeratotic keratin. Neoplastic cells have distinct cell borders, abundant brightly eosinophilic cytoplasm which is often vacuolated (intracellular edema), and an irregularly round to oval and vesiculate nucleus with finely stippled chromatin and 1-2 prominent nucleoli. Mitotic count is < 1 in 2.37mm^2. Neoplastic cells undergo orderly maturation and 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 adjacent to spicules of immature woven bone lined by osteoblasts. The neoplasm compresses the adjacent bone causing compression lysis and bony remodeling characterized by sclerosis of the underlying cancellous bone and deposition of immature woven bone. Within the adjacent distal interphalangeal joint, there are multiple small synovial fronds and papillary projections extending into the synovial space which are lined by cuboidal synoviocytes that occasionally pile up 3 to 4 cell layers thick with a euchromatic nucleus (reactive synoviocytes). 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) (see also I-N31)

 

GENERAL DISCUSSION:

• 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
• Uncommon neoplasm in adult (3 to 14 years old) dogs and cats (rare); no breed or sex predilection
• Amputation of the affected digit is curative

 

PATHOGENESIS:

• 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 be deformed with twisted 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
• Expansile mass causing partial lysis/loss of P3

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Symmetrical (but asymmetrical base), 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
• Orthokeratotic, parakeratotic keratinocytes and squamous eddies may be present
• Variable 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 or connective tissue; periosteal fibrosis and bone proliferation often present; secondary osteomyelitis may be observed
• Inflammation (lymphocytes, plasma cells, neutrophils) may infiltrate the connective tissue
• Large tumors: Interphalangeal joint tissue synovial tissue may display chronic proliferative and inflammatory changes

 

ADDITIONAL DIAGNOSTIC TESTS: 

• Periodic Acid-Schiff – To stain glycogen in the cytoplasm of neoplastic cells
• Fine needle aspirate/cytology – May reveal epithelial cells (clusters of basal and mature squamous) with abundant keratinized debris

 

DIFFERENTIAL DIAGNOSIS:

• 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

 

COMPARATIVE PATHOLOGY:

• This tumor has only been described in the dog and cat
• Avian keratoacanthoma (see I-N05) - Benign neoplasm primarily seen in young broilers; crater-shaped coalescing ulcers (may contain central core of keratin) with raised margins within feather tracts
• Human cutaneous KA is a common, rapidly evolving crateriform nodule with a central keratin plug that usually occurs in sun-exposed skin and spontaneously regresses in weeks to months; in contrast to common cutaneous KA, the rare subungual variant does not undergo spontaneous involution

 

REFERENCES:

1. Goldschmidt MH, Munday JS, Scruggs JL, Klopfleisch R, Kiupel M. Surgical Pathology of Tumors of Domestic Animals. Vol. 1, Epithelial tumors of the skin, Gurnee, IL: Davis-Thompson Foundation; 2018:121-123.
2. 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.; 2017:132-133.
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, 825-827.

 

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