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Review
. 2023 Nov 18;85(11):1195-1209.
doi: 10.1292/jvms.23-0322. Epub 2023 Sep 22.

Feline papillomavirus-associated Merkel cell carcinoma: a comparative review with human Merkel cell carcinoma

James K Chambers  1 , Soma Ito  1 , Kazuyuki Uchida  1
Affiliations
Review

Feline papillomavirus-associated Merkel cell carcinoma: a comparative review with human Merkel cell carcinoma

James K Chambers et al. J Vet Med Sci. .

Abstract

Merkel cell carcinoma (MCC) is a rare skin tumor that shares a similar immunophenotype with Merkel cells, although its origin is debatable. More than 80% of human MCC cases are associated with Merkel cell polyomavirus infections and viral gene integration. Recent studies have shown that the clinical and pathological characteristics of feline MCC are comparable to those of human MCC, including its occurrence in aged individuals, aggressive behavior, histopathological findings, and the expression of Merkel cell markers. More than 90% of feline MCC are positive for the Felis catus papillomavirus type 2 (FcaPV2) gene. Molecular changes involved in papillomavirus-associated tumorigenesis, such as increased p16 and decreased retinoblastoma (Rb) and p53 protein levels, were observed in FcaPV2-positive MCC, but not in FcaPV2-negative MCC cases. These features were also confirmed in FcaPV2-positive and -negative MCC cell lines. The expression of papillomavirus E6 and E7 genes, responsible for p53 degradation and Rb inhibition, respectively, was detected in tumor cells by in situ hybridization. Whole genome sequencing revealed the integration of FcaPV2 DNA into the host feline genome. MCC cases often develop concurrent skin lesions, such as viral plaque and squamous cell carcinoma, which are also associated with papillomavirus infection. These findings suggest that FcaPV2 infection and integration of viral genes are involved in the development of MCC in cats. This review provides an overview of the comparative pathology of feline and human MCC caused by different viruses and discusses their cell of origin.

Keywords: Merkel cell; Merkel cell carcinoma; Review; cat; feline papillomavirus.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
Merkel cells in feline skin. Immunohistochemistry for cytokeratin 20. (a) Facial skin. Merkel cells in the outer root sheath of the sinus hair and basal layer of the infundibulum-epidermis junctional zone. (b) Glabrous skin of the paw pad. Merkel cells in the epidermal basal layer. (c) Hairy skin. A cluster of Merkel cells in the epidermal basal layer of a touch dome.
Fig. 2.
Fig. 2.
Histology of feline Merkel cell carcinoma. (a) Merkel cell carcinoma infiltrating dermis and subcutis. Neoplastic cells are associated with hair follicles (arrowhead) but not with the epidermis. Coincidental lesions of viral plaques are observed in the upper left. Inset: immunohistochemistry for papillomavirus L1 antigen. Immunolabelling of the upper layer of the hyperplastic epidermis of a viral plaque. (b) Magnified view of Merkel cell carcinoma. Neoplastic cells are arranged in a trabecular pattern.
Fig. 3.
Fig. 3.
(a) Gross image of feline Merkel cell carcinoma. Red dome-shaped skin tumor. (b) Cytology of feline Merkel cell carcinoma cells. Large round cells with one or two prominent nucleoli and scant cytoplasm resembling lymphoma cells.
Fig. 4.
Fig. 4.
Immunohistochemistry and RNA in situ hybridization of feline Merkel cell carcinomas. Immunolabeling for CK20 (a), CK18 (b), synaptophysin (c), and CD56 (d) are diagnostic hallmarks of Merkel cell carcinoma. Immunolabeling for p16 is associated with papillomavirus involvement: papillomavirus-positive Merkel cell carcinomas are strongly positive for p16 (e). Expression of the papillomavirus oncogene E6/E7 detected by RNA in situ hybridization (f).
Fig. 5.
Fig. 5.
Schematic image describing papillomavirus infection in the skin and development of Merkel cell carcinoma (MCC) and other proliferative lesions such as viral plaque, Bowenoid in situ carcinoma (BISC), and squamous cell carcinoma (SCC). Papillomavirus infects epidermal basal cells or Merkel cell progenitor cells in hair follicles through microwounds. Integration of the viral gene results in neoplastic cell proliferation, which is promoted by the viral oncoproteins E6 and E7.
Fig. 6.
Fig. 6.
Allogrooming cats. The older black cat licks and bites the younger tabby cat on its neck (a) and head (b).
See this image and copyright information in PMC

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