A. F. French

Papillomaviral DNA and increased p16CDKN2A protein are frequently present within feline cutaneous squamous cell carcinomas in ultraviolet-protected skin

Squamous cell carcinomas (SCCs) are common feline skin tumours. While exposure to ultraviolet (UV) light causes some SCCs, a subset develop in UV-protected skin. In cats, papillomaviruses (PVs) cause viral plaques and Bowenoid in situ carcinomas (BISCs). As both may progress to SCC, it was hypothesized that SCCs in UV-protected skin may represent neoplastic transformation of a PV-induced lesion. To investigate this hypothesis, PCR was used to amplify PV DNA from 25 UV-protected and 45 UV-exposed SCCs. Oncogenic human PVs cause neoplasia by mechanisms that also increase p16(CDKN2A) protein (p16). As increased p16 is present in feline viral plaques and BISCs, immunohistochemistry was used to detect p16 within the SCCs. Papillomaviral DNA was amplified from 76% of UV-protected SCCs, but only 42% of UV-exposed SCCs. Increased p16 was present in 84% of UV-protected SCCs, but only 40% of UV-exposed SCCs. The more frequent detection of PV DNA and increased p16 within UV-protected SCCs supports the hypothesis that some develop from a PV-induced plaque or BISC. Felis domesticus PV-2 is thought to cause viral plaques and BISCs. This PV was detected most frequently within the UV-protected SCCs, supporting development from a PV-induced lesion. Increased p16 and PV DNA were less frequent within UV-exposed SCCs, presumably because these developed from actinic keratosis rather than a PV-induced lesion. The results support the hypothesis that some feline cutaneous SCCs are caused by PV infection and suggest that PVs may cause neoplasia by mechanisms that also increase p16.

Detection of papillomaviral DNA sequences in a feline oral squamous cell carcinoma

Oral squamous cell carcinomas (OSCCs) are common and often fatal feline neoplasms. Factors that predispose to neoplasm development in cats are poorly defined. Around 25% of human OSCCs are caused by papillomaviruses (PVs). To determine if PVs are associated with OSCCs in cats, three sets of consensus primers were used to evaluate 20 feline OSCCs and 20 non-neoplastic feline oral lesions for the presence of PV DNA. Papillomaviral sequences were detected within one OSCC, but no non-neoplastic lesion. Sequencing of the amplified DNA revealed a previously unreported PV that was most similar to human PV type 76. This is the first time PV DNA has been amplified from the oral cavity of a cat. However, while these results suggest that feline gingival epithelial cells can be infected by PVs, they do not support a causal association between viral infection and the development of feline OSCCs.

Development of an Injection Site Sarcoma Shortly after Meloxicam Injection in an Unvaccinated Cat

Asingle dose of a rapidly-absorbed non-steroidal anti-inflammatory drug (NSAID) was injected into the subcutaneous tissue of the interscapular region of a 12.5-year-old cat. A mild swelling was noticed at the injection site 6 weeks later. This progressed into a 5 cm diameter mass which was removed 6 months after the injection had been given. An injection site sarcoma (ISS) was diagnosed histologically. As the cat had not been vaccinated for at least 12 years, the previous NSAID injection was considered to be a possible cause of the ISS. Inflammation is thought to be important in the development of ISS. If injection of a rapidly-absorbed NSAID can stimulate sufficient inflammation to promote the development of an ISS, other non-vaccine injections may also have the potential to influence ISS development. This suggests that injection of both vaccines and non-vaccine medications should be minimised to reduce the risk of ISS development.

Increased p16CDKN2A Protein Within Feline Cutaneous Viral Plaques, Bowenoid In Situ Carcinomas, and a Subset of Invasive Squamous Cell Carcinomas

Cutaneous viral plaques and bowenoid in situ carcinomas (BISCs) in cats are thought to be caused by papillomavirus (PV) infection. There is evidence that PVs may also cause some feline invasive squamous cell carcinomas (ISCCs). Human oncogenic PVs degrade retinoblastoma (RB) protein, impairing cell cycle control. Loss of RB function also increases p16CDKN2A protein (p16), and increased p16 immunoreactivity within a human oral ISCC indicates that the neoplasm was caused by PV infection. In the present study, p16 immunoreactivity was evaluated in 14 feline viral plaques, 14 BISCs, 7 non–solar-induced ISCCs, 11 solar-induced ISCCs, and 14 trichoblastomas. Increased p16 was present within all viral plaques, BISCs, and non–solar-induced ISCCs. In contrast, little p16 immunoreactivity was visible in the solar-induced ISCCs or trichoblastomas. PV DNA was consistently amplified from viral plaques, BISCs, and non–solar-induced ISCCs. However, just 5 solar-induced ISCCs and 1 trichoblastoma contained PV DNA. Given that both increased p16 immunoreactivity and PV DNA were present within viral plaques, BISCs, and non–solar-induced ISCCs, all 3 may be caused by PV infection. This suggests that feline non–solar-induced ISCCs may develop as a result of neoplastic progression from viral plaques and BISCs. Whether PVs promote this progression is unknown; however, evidence from this study suggests the PV that is associated with viral plaques and BISCs is able to disrupt the p16–RB pathway and therefore could have oncogenic potential. Immunohistochemical detection of p16 appears to be a useful technique to investigate the role of PVs in feline skin disease.

Evaluation of feline oral squamous cell carcinomas for p16CDKN2A protein immunoreactivity and the presence of papillomaviral DNA

Oral squamous cell carcinomas (OSCCs) develop commonly in cats. While the cause of the feline neoplasms is unknown, a quarter of human OSCCs are caused by papillomavirus (PV) infection. As PV DNA has been previously detected in a feline OSCC, it was hypothesised that PV infection could be a significant cause of feline OSCCs. Human OSCCs that are caused by PVs contain increased p16(CDKN2A) protein (p16), which can be detected using immunohistochemistry. In cats, increased p16 immunoreactivity has been reported within PV-associated skin lesions. This study evaluated p16 immunoreactivity within 30 feline OSCCs. Additionally, PCR was used to amplify PV DNA from the OSCCs. Increased p16 immunoreactivity was present within 2 OSCCs. However, as PV DNA was not amplified from any OSCC in this study, it cannot be confirmed that the increased p16 was caused by PV infection. Therefore, these results do not support the hypothesis that PVs are a significant cause of OSCCs in cats. Loss of p16 expression is considered an important process in the development of human non-PV-induced OSCCs. In contrast, loss of p16 immunoreactivity was only present in 2 feline OSCCs. This suggests that human and feline OSCCs develop due to different molecular mechanisms.

Comparison of the histology and immunohistochemistry of vaccination-site and non-vaccination-site sarcomas from cats in New Zealand

Abstract AIMS: To compare the histology and immunohistochemistry of vaccination-site sarcomas (VSSs) with non-vaccination-site sarcomas (NVSSs) in cats in New Zealand. To determine whether VSSs in cats in New Zealand have similar histological and immunohistochemical features to those previously described in feline vaccine-associated sarcomas (VASs) in North American studies. METHODS: A retrospective survey of skin biopsies submitted between 2004 and 2006 was performed to identify cutaneous sarcomas from both vaccination and non-vaccination sites in cats. Vaccination sites included the interscapular, shoulder, or dorsal or lateral cervical and thoracic regions. All sarcomas were examined histologically, and smooth muscle actin and desmin were assessed immunohistochemically. Features previously described in VASs were assessed and compared. RESULTS: Sarcomas from 34 cats were identified, 10 of which occurred at vaccination sites. Compared with NVSSs, VSSs were more likely to be located in the hypodermis and have greater cellular pleomorphism, higher mitotic rates, more frequent peripheral lymphocytic aggregates and multinucleated giant cells. VSSs were also more likely than NVSSs to show partial myofibroblastic differentiation, demonstrable using immunohistochemistry. The histological and immunohistochemical features of VSSs in cats in New Zealand are consistent with those previously described in VASs in cats in North America. CONCLUSIONS: The results of this study suggest that VASs occur in cats in New Zealand. CLINICAL RELEVANCE: The occurrence of VASs in cats in New Zealand would provide further support for restriction of the vaccination of cats to the minimum necessary to protect health, and adoption of the New Zealand Veterinary Association guidelines on vaccination.

The Presence of p16CDKN2A Protein Immunostaining Within Feline Nasal Planum Squamous Cell Carcinomas Is Associated With an Increased Survival Time and the Presence of Papillomaviral DNA

In humans, oral SCCs are either caused by papillomavirus (PV) infection or by other carcinogens such as tobacco. As these 2 groups of SCCs have different causes they also have different clinical behaviors. Immunostaining using anti-p16CDKN2A protein (p16) antibodies is used to indicate a PV etiology in human oral SCCs and p16-positive SCCs have a more favorable prognosis. The present study investigated whether p16 immunostaining within feline nasal planum SCCs was similarly associated with the presence of PV DNA and with a longer survival time. Intense p16 immunostaining was visible in 32 of 51 (63%) SCCs. In 30 cats with nonexcised SCCs, cats with p16-positive neoplasms had a longer estimated mean survival time (643 days) than cats with p16-negative SCCs (217 days, P = .013). Papillomavirus DNA was amplified more frequently from p16-positive nasal planum SCCs (28 of 32) than p16-negative SCCs (5 of 19, P < .001). The different survival times in cats with p16-positive and p16-negative SCCs suggests that p16 could be a useful prognostic indicator in these common feline cancers. As the clinical behavior of the SCCs can be subdivided using p16 immunostaining, the 2 groups of SCCs may be caused by different factors, supporting a PV etiology in a proportion of feline nasal planum SCCs.

Infrequent detection of papillomaviral DNA within canine cutaneous squamous cell carcinomas, haemangiosarcomas and healthy skin on the ventrum of dogs

BACKGROUND Canine squamous cell carcinomas (SCCs) most frequently develop on the ventral abdomen and are thought to be caused by ultraviolet (UV) light. Papillomaviruses (PVs) have been associated with cutaneous SCCs in multiple species, including dogs. HYPOTHESIS That PVs act as cofactors in canine UV-induced SCCs. ANIMALS The study was performed on skin from the ventrum of 60 dogs. These samples included 20 SCCs, 20 haemangiosarcomas and 20 samples of clinically normal skin. Two canine viral plaques were included as positive controls for PV. METHODS PCR was used to amplify PV DNA from all samples. Primers used included two sets of consensus primers and two sets of primers that were designed specifically to amplify PV DNA sequences detected in the viral plaques. RESULTS The MY09/11 consensus primers amplified PV DNA from both viral plaques. One plaque contained a DNA sequence (CfPV-JM) that had been previously reported from a dog with multiple cutaneous SCCs. The other plaque contained a previously unreported PV DNA sequence. No PV DNA was amplified by either consensus primer from any of the ventrum skin samples. Primers designed specifically to amplify the CfPV-JM sequence amplified DNA from one SCC, but no other sample. No PV DNA was amplified using the other specific PCR primer set. CONCLUSIONS AND CLINICAL IMPORTANCE These results do not support a significant role for PVs in SCC development from the ventrum of dogs. However, they contribute another PV sequence to the list of PVs that have been associated with viral plaque development in dogs.

Felis catus papillomavirus types 1 and 4 are rarely present in neoplastic and inflammatory oral lesions of cats

Oral squamous cell carcinomas (OSCCs) are common feline cancers. Why OSCCs are so common in cats is unknown; however, 25% of human OSCCs are caused by papillomaviruses (PVs). Two feline oral PVs (FcaPV-1 and 4) are recognized. As PVs are highly host and location specific, if PVs do cause feline OSCCs, FcaPV-1 and 4 are the most likely etiological agents. PCR primers specific for FcaPV-1 amplified DNA from 1 of 36 feline OSCCs and 1 of 16 inflammatory oral lesions. No DNA was amplified by primers specific for FcaPV-4. PV DNA was not amplified from any additional sample using consensus primers. No PV cytopathology was visible in the OSCC that contained FcaPV-1 DNA, but viral cytopathology was present in a focus of epithelial hyperplasia in the non-neoplastic sample. This study does not support a PV etiology of feline OSCCs, but shows that FcaPV-1 can asymptomatically infect the mouth of cats.

Renal cystadenoma in a domestic shorthair

An 11-year-old domestic shorthair was examined after an enlarged left kidney was palpated by the referring veterinarian. No abnormalities were noted on complete blood count, serum biochemical profile and total thyroxine concentration, and the urine specific gravity was 1.039. An abdominal ultrasound identified the presence of a large cystic structure on the caudal pole of the left kidney. No abnormalities of the right kidney were seen. A left ureteronephrectomy was performed, and the cat recovered uneventfully from the procedure and was discharged from the hospital 5 days after surgery. The cat remains clinically normal 16 months postoperatively. Histopathology of the removed kidney demonstrated the presence of a renal cystadenoma. This report describes the successful surgical treatment of a renal cystadenoma. Renal cystadenoma should be considered as a differential diagnosis when renomegaly is noted. To the authors knowledge, a renal cystadenoma has not been previously reported in a cat.