AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

October 2019

I-N31

 

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

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Digit: Extending from the nailbed epithelium and compressing the remodeled bone of P3 is an unencapsulated, well-demarcated, moderately cellular neoplasm composed of polygonal cells arranged in broad, up to 1mm diameter, anastomosing trabeculae with irregular scalloped borders that surround a 5x2mm central core of amorphous to lamellar, parakeratotic keratin with a central area of dropout (artifact). The neoplasm expands into the subungual space and replaces the palmar aspect of P3. Neoplastic cells have distinct cell borders and abundant amounts of eosinophilic cytoplasm. Nuclei are irregularly round to oval and vesiculate with 1-2 prominent nucleoli. The mitotic count averages <1/10 HPF. 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). Multifocally there is single cell necrosis characterized by cells with hypereosinophilic cytoplasm and pyknotic nuclei. The neoplasm compresses the adjacent P3 bone which is variably characterized by loss of mature, lamellar bone and osteoclasts within Howship’s lacunae (osteolysis), or formation of spicules of often immature woven bone lined by plump, reactive osteoblasts (new bone formation) (bone remodeling). Between the neoplasm and the remaining P3 bone is a rim of fibroblasts admixed with numerous small caliber blood vessels and fibrous connective tissue (granulation tissue and fibrosis). There are moderate numbers of lymphocytes and plasma cells diffusely surrounding the neoplasm, admixed within the fibrous connective tissue, and separating, surrounding and replacing adjacent apocrine glands (hydradenitis). Multifocally near the inner margin of the lamellar keratin within the central pore there are moderate numbers of neutrophils and numerous 1 to 2 um coccobacilli.

 

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

 

SYNONYMS: Nailbed keratoacanthoma

 

GENERAL DISCUSSION:

·      Subungual keratoacanthoma (subungual KA) is an uncommon, benign neoplasm of 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

·      There does not appear to be a breed or sex predilection

·      Affected animals are adults

·      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 may be present

·      Affected digits often have a broken or deformed nail

·      Most cases have radiographic evidence of lysis of the third phalanx (P3); lysis is due to compression from the expansile neoplasm and not due to neoplastic infiltration

·      Lysis of the second phalanx and periosteal bone proliferation are uncommon

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·      Symmetrical, circumscribed, but unencapsulated masses with a cup-shaped, tubular, or inverted funnel-shaped configuration

·      Central core of keratin that may open onto the skin surface directly ventral or adjacent to the nail

·      The epithelial wall of the neoplasm is contiguous with the nailbed epithelium

·      The wall of the neoplasm is composed of large squamous epithelial cells arranged in sheets, islands, and broad trabeculae

·      Orderly keratinization proceeds centripetally and usually without a granular cell layer, resulting in a central core of amorphous keratin

·      The central zone may contain large lakes of parakeratotic cells admixed with amorphous keratin

·      Neoplastic cells have a “ground glass cytoplasm” due to high glycogen content

·      Small to moderate numbers of apoptotic keratinocytes with hypereosinophilic cytoplasm and pyknotic nuclei

·      Small numbers of atypical epithelial cells with amphophilic cytoplasm, enlarged nuclei, and prominent nuclei are present at the periphery

·      Mitotic rate is low and confined to the peripheral proliferating zone

·      Secondary inflammation is common and includes plasma cells, lymphocytes, and neutrophils

·      Neoplasm DOES NOT invade bone

 

ADDITIONAL DIAGNOSTIC TESTS:

·      Periodic Acid-Schiff – to stain glycogen in the cytoplasm of neoplastic cells

·      Immunohistochemical Stains: In humans, Ki67 and p53 are diffusely positive in SCC and limited to the basal cell layer (Ki67) or rare (p53) in KAs

 

DIFFERENTIAL DIAGNOSIS:

Non-neoplastic nailbed lesions:

·      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

Nailbed epithelial tumors:

·      Squamous cell carcinoma (SCC): 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; secondary inflammation common

·      Melanoma: Gross and radiographic findings similar to subungual SCC; may be pigmented; junctional activity; invasion and destruction of phalangeal bones common

·      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:

·      Subungual KA has only been described in the dog and cat

·      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; in contrast to common cutaneous KA, the rare subungual variant 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.     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.

5.     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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