The African pygmy hedgehog (Atelerix albiventris) is becoming a popular pet in Japan. The aim of this study was to determine the incidence of various diseases in African pygmy hedgehogs. We histologically investigated 105 samples from 100 privately-owned pet African pygmy hedgehogs that were submitted to two laboratories (North Lab and Patho Labo) between 2012 and 2017. Tissues submitted for this study were taken from female reproductive organs (33 cases; 31.43%), skin (20 cases; 19.05%), and the oral mucosa (19 cases; 18.1%). The most common histological diagnoses included endometrial stromal nodules identified as benign uterine neoplasia (14 cases; 13.33%); endometrial polyps identified as non-neoplastic polyps (7 cases; 6.67%), gingival hyperplasia and chronic suppurative inflammation in the oral mucosa (11 cases; 10.48%), fibrosarcomas in the skin (8 cases; 7.62%), and mammary tumors (8 cases; 7.62%). In this study, lymphoma and oral squamous cell carcinoma were less common than in the previous reports. The present study revealed the disease prevalence in captive African pygmy hedghogs that were histopathologically examined.

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor. We recently demonstrated that cats with MCC often have other proliferative cutaneous lesions, such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Based on this finding, we hypothesize that Felis catus papillomavirus (FcaPV) is involved in the development of MCC in cats, similar to SCC and BCC. To investigate this hypothesis, the presence of FcaPV nucleic acid and immunoreactivity for tumor suppressor proteins were examined in 21 feline MCC cases. Polymerase chain reaction using FcaPV type-specific primers detected FcaPV2 DNA in 20/21 samples of MCC. The complete FcaPV2 sequence was characterized in one case. In situ hybridization for FcaPV2 E7 revealed punctate nuclear signals within tumor cells in 19/21 MCC. Increased immunoreactivity for p16CDKN2A protein and decreased immunoreactivity for retinoblastoma (pRb) and p53 proteins were observed in 20/21 MCC. These results suggest that feline MCC cases are infected with FcaPV2 and the subsequent inhibition of pRb and p53 induced by integrated viral oncogenes is associated with feline MCC tumorigenesis, similar to other PV-induced proliferative cutaneous lesions. On the other hand, the single case of FcaPV2-negative MCC showed strong p53 immunoreactivity, suggesting mutations in p53 caused by cancer inducers other than FcaPV2 infection in this case. The present study suggests FcaPV2 as a cause of feline MCC.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor, and most human MCC cases are infected by Merkel cell polyomavirus (MCPyV). However, the underlying pathogeneses of MCC in animals remain unclear. In the present study, newly established cell lines from feline and canine MCC, a MCPyV-positive human MCC cell line, and MCC tissues from 25 cats and 1 dog were examined and compared pathologically. Feline and canine MCCs were composed of tumor cells arranged in trabeculae and solid packets. Twenty out of 25 feline MCC cases (80%) had other proliferative cutaneous lesions, such as carcinoma in situ and squamous cell carcinoma. Among the 25 feline MCC cases, tumor cells were immunopositive for cytokeratins (CKs), including CK5/6 (4/25 cases, 16%), CK7 (5, 20%), CK18 (25, 100%), CK19 (20, 80%), and CK20 (20, 80%). The tumor cells of feline MCC were also immunopositive for synaptophysin (24/25, 96%) and CD56 (22/25, 88%). The tumor cells of canine MCC were immunopositive for CK18, CK19, CK20, and synaptophysin. Cultured feline and canine MCC cells grew in adherent monolayers and exhibited diffuse cytoplasmic immunoreactivity for CKs, whereas human MCC cells grew in suspension and exhibited dot-like cytoplasmic immunoreactivity for CKs. Differences in the distribution of CKs between human and animal MCC may be attributed to cell adhesion propensities. MCPyV genes and antigen were not detected in feline or canine MCC, suggesting a different etiology from human MCC.

The biological behaviour and prognostic factors of Merkel cell carcinoma (MCC) in 20 cats were studied. The tumours were surgically removed and histopathologically examined. The animals were 8 to 20 years old (median age: 14 years), and the tumours were predominantly located in the neck and head. Follow-up data were available in 17 cases, and 12 cats died within a year of surgery. The overall median survival time after resection was 243 days (range 16-360 days). Recurrence occurred in 11 cases, although 6 of them (55%) were found to be margin-negative. Possible metastasis occurred after the surgery in 10 cases, although 6 of them (60%) were found to be margin-negative. The histopathological features of MCC included tumour necrosis in 16 cases (80%), vascular invasion in 6 cases (38%) and high mitotic counts (median: 28.5 per high-power field). Irregular acanthosis was noted adjacent to the tumours in 9 cases (60%). Immunohistochemically, the tumour cells were positive for cytokeratin (CK) 20 and p63 in all cases, synaptophysin in 19 (95%) cases, and CK18 in 16 cases (80%). The study shows that feline MCC is associated with a poor prognosis and exhibited a strong tendency towards local recurrence, regional lymph node metastasis and distant spread.

The involvement of Felis catus papillomavirus type 2 (FcaPV2) in feline Merkel cell carcinoma (MCC) has been previously hypothesized. In this study, the expression and localization of FcaPV2 oncogene mRNA, the integration of FcaPV2 genes, and p53 mutations in feline MCC were examined by RNAscope in situ hybridization (ISH), whole genome sequencing (WGS), and Sanger DNA sequencing, respectively. Furthermore, the morphological and molecular characteristics of FcaPV2-positive (FMX-MCC01) and FcaPV2-negative (AS-MCC01) MCC cell lines were compared in vitro and in vivo using immunofluorescence, ISH, xenotransplantation into mice, and immunohistochemistry. ISH for FcaPV2 E6/E7 detected viral RNA in 18/21 FcaPV2-positive MCC and not in 1/1 FcaPV2-negative MCC. WGS of 2 FcaPV2-positive cases revealed the integration of FcaPV2 genes in both cases. In cultured cells and xenograft tissues of FMX-MCC01, most cells were positive for E6/E7 by ISH and p16CDKN2A, a few cells were positive for the retinoblastoma protein (pRb), and all cells were negative for p53. In cultured cells and xenograft tissues of AS-MCC01, all cells were negative for p16CDKN2A, most cells were positive for pRb, and some cells were positive for p53. Missense mutations in p53 were identified in 8/10 FcaPV2-positive and 1/1 FcaPV2-negative MCC. These results suggest that the expression of integrated FcaPV2 oncogenes might be associated with reduced expression of the tumor suppressor proteins pRb and p53 and might contribute to the development of feline MCC. On the other hand, p53 mutations may be involved in both FcaPV2-positive and FcaPV2-negative MCC tumorigenesis.