JPC SYSTEMIC PATHOLOGY

MUSCULOSKELETAL SYSTEM

April 2025

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, compressing and replacing the palmar aspect of the third phalanx is an unencapsulated, expansile, well demarcated, moderately cellular epithelial neoplasm composed of polygonal cells arranged in broad anastomosing trabeculae, 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 per 2.37mm². 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 proliferative woven bone with multifocal central areas of cartilaginous differentiation. 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, seen in adult dogs and rarely cats without breed or sex predilection
  • This tumor is NOT analogous to canine infundibular keratinizing acanthoma (I-N01)
• Prevalence is underestimated due to misdiagnosis as squamous cell carcinoma
  • The frequency ratio of subungual KA to squamous cell carcinoma is approximately 1:4
• 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 or deformed, twisted, or broken nails or onychomadesis (sloughing of the claw)
• There is usually radiographic evidence of lysis of the third phalanx (P3)
  • Lysis of the second phalanx (P2) and periosteal bone proliferation uncommon

TYPICAL GROSS FINDINGS:

• Circumscribed, unencapsulated, generally <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, circumscribed, cup or funnel-shaped mass with a complex epithelial wall contiguous with the nailbed epithelium
  • Irregular or scalloped borders, may be partially encapsulated
  • Wall composed of sheets, islands, and broad trabeculae of large squamous epithelial cells with abundant pink cytoplasm with a ground glass appearance (high glycogen content) and moderately enlarged vesiculate nuclei that that undergoes orderly keratinization, without a granular cell layer; there may be prominent apoptosis of keratinocytes present
  • There is often a central core of amorphous keratin which may open onto the skin surface ventral or adjacent to the nail; orthokeratotic, parakeratotic keratinocytes and squamous eddies may be present
  • Mitotic rate is low and confined to proliferating peripheral zone; neoplastic cells do not breach the basal lamina
• Bone:
  • There may be pressure lysis/destruction of P3, however tumor tissue does not invade bone or connective tissue; periosteal fibrosis and bone proliferation often present; secondary osteomyelitis may be observed
  • Large tumors: Interphalangeal joint tissue synovial tissue may display chronic proliferative and inflammatory changes

ADDITIONAL DIAGNOSTIC TESTS:

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

DIFFERENTIAL DIAGNOSIS:

• 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; prominent keratinocytes apoptosis is not usually present; no nuclear inclusions; 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
• 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
• Melanoma: Gross and radiographic findings similar to subungual SCC; may be pigmented; junctional activity; invasion and destruction of phalangeal bones common

COMPARATIVE PATHOLOGY:

• This tumor has only been described in the dog and cat
• Avian keratoacanthoma (see I-N05): Benign neoplasm primarily seen in young broiler chickens; crater-shaped coalescing ulcers (may contain central core of keratin) with raised margins within feather tracts; a similar process has been occasionally reported on the beak or nail/talon bed of psitticines
• 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. Epithelial neoplasms and other tumors. In: Gross TL, et al. Skin Diseases of the Dog and Cat.2nd ed. Ames, IA: Blackwell Science; 2005:698-700.
4. Shivaprasad HL, Barnes HJ. Integumentary system. In: Abdul-Aziz T, Fletcher OJ, Barnes HJ, eds. Avian Histopathology. 4th ed. Jacksonville, FL: American Association of Avian Pathologists; 2016: 615,622,639.
5. Raidal S. Integument. In Schmidt R, Struthers JD, Phalen DN. Pathology of Pet and Aviary Birds. 3rd ed. Ames, IA: John Wiley & Sons, Inc.; 2024: 405-438.
6. Raskin RE, Conrado FO. Chapter 3: Integumentary System. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:72-73.
7. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1122.

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