JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

October 2022

I-N31

 

Signalment (JPC# 3058415): Age and breed unspecified dog

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Digit: Extending from the nailbed epithelium, expanding the subungual space, and compressing and replacing the central trabecular bone and articular cartilage of P3 is an unencapsulated, well-demarcated, moderately cellular neoplasm composed of abruptly keratinizing columnar to polygonal epithelial cells arranged in broad anastomosing trabeculae with irregular scalloped borders and  surrounding a 5x2mm central core of amorphous to lamellar parakeratotic keratin and 2 mm superficial central pore. There is a large central area of drop out within the keratin core.Neoplastic cells have distinct cell borders, abundant amounts of intensely eosinophilic cytoplasm, irregularly round to oval nuclei with finely stippled chromatin with 1-2 prominent nucleoli. There is less than 1 mitotic figure per 2.37 mm². Neoplastic cells primarily undergo orderly keratinization without a granular layer (abrupt keratinization). Multifocally neoplastic cells contain abundant intracytoplasmic clear space and marginated nuclei (intracellular edema). The adjacent compressed P3 has variable loss of mature, lamellar bone with few osteoclasts within Howship’s lacunae (osteolysis), and elsewhere, has spicules of immature woven bone lined by plump, reactive osteoblasts (new bone formation/bone remodeling). Between the neoplasm and the remaining P3 is a band of loose fibrous connective tissue with plump fibroblasts and collagen bundles arranged perpendicularly to numerous small caliber blood vessels (granulation tissue) with abundant lymphocytes and plasma cells scattered throughout. Similar inflammatory cells separate, surrounding and replace adjacent eccrine glands (hydradenitis). 

 

MORPHOLOGIC DIAGNOSIS: Nailbed: Subungual keratoacanthoma, breed unspecified, canine.

 

SYNONYMS: Nailbed keratoacanthoma

 

GENERAL DISCUSSION: 

• Subungual keratoacanthoma (subungual KA) is an uncommon, benign neoplasm of adult dogs that arises from the nailbed epithelium 
• It is 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  
• No breed or sex predilection 
• Amputation of the affected digit is curative

 

PATHOGENESIS:

• Etiology unknown
• In humans, it is unknown whether 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
• Affected digits often have a broken or deformed nail which may progress to onychomadesis (sloughing of claw)
• Most cases have radiographic evidence of lysis of the third phalanx (P3) due to compression from the expansile neoplasm (not due to neoplastic infiltration)
• Lysis of the second phalanx and periosteal bone proliferation are uncommon

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Symmetrical, circumscribed, unencapsulated mass with a cup-shaped, tubular, or inverted funnel-shaped configuration;
• Neoplastic epithelial cells form the wall of the neoplasm: Large squamous epithelial cells arranged in sheets, islands, and broad trabeculae and undergoing abrupt keratinization (without a granular cell layer)
• Central core may open onto the skin surface adjacent or ventral to nail and contains amorphous keratin admixed with lakes of parakeratotic cells 
• Neoplastic cells have a “ground glass cytoplasm” due to high glycogen content
• Few atypical epithelial cells with amphophilic cytoplasm, enlarged nuclei, and prominent nuclei are present at the periphery and few apoptotic keratinocytes (shrunken, hypereosinophilic cytoplasm, pyknotic nucleus)
• Low mitotic rate
• Secondary inflammation common and includes plasma cells, lymphocytes, and neutrophils

 

ADDITIONAL DIAGNOSTIC TESTS: 

• Periodic Acid-Schiff: Stains glycogen in the cytoplasm of neoplastic cells
• IHCs: In humans, Ki67 and p53 are diffusely positive in SCC; in keratoacanthomas, they are limited to the basal cell layer (Ki67) or rare (p53) in KAs

 

DIFFERENTIAL DIAGNOSIS:

Non-neoplastic nailbed lesions:

Nailbed epithelial tumors:

• Squamous cell carcinoma (SCC, I-N04B): Differentiation between nailbed KA and well-differentiated SCC can be difficult; SCC are asymmetrical with desmoplasia, have nuclear/mitotic atypia; neoplastic cells may breach the basal lamina; bone invasion is a classic feature of SCC; multiple digits may be affected
• Melanoma: Gross and radiographic findings similar to subungual SCC; may be pigmented; has junctional activity; bone invasion common
• Inverted squamous papilloma (I-V01B): 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; gradual keratinization through a sparse granular layer; koilocytes may be present; no nuclear inclusions; pressure induced lysis of P3     

 

COMPARATIVE PATHOLOGY:

• Subungual KA has only been described in the dog, cat, human 
• Avian KA: see I-N05
• 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; subungual variant is rare and does not undergo spontaneous involution

 

References:

1. Goldschmidt MH, Goldschmidt KH. Epithelial and Melanocytic Tumors of the Skin. In: Meuten DJ. Tumors in Domestic Animals. 5th ed., Ames, IA: John Wiley & Sons, Inc.; 2017:132-133.
2. 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.
3. Kiupel, M, ed. Surgical Pathology of Tumors of Domestic Animals: Volume 1. Epithelial Tumors of the Skin. Gurnee, IL: Davis-Thompson Foundation, 2018: 121-123.
4. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1122.
5. Wobeser BK, Kidney BA, Powers BE, et. al. Agreement among surgical pathologists evaluating routine histologic sections of digits amputated from cats and dogs. J Vet Diagn Invest 2007;19:439-443.
6. Yoo CB, Kim DH, Lee AJ, Suh HJ, Yoo S, Sur JH, Eom KD. Canine nail bed keratoacanthoma diagnosed by immunohistochemical analysis. Can Vet J. 2015;56(11):1181-4.
   
   

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