Pathologic characterization of Felis catus papillomavirus type 5 (FcaPV-5)-associated viral plaques and Bowenoid in situ carcinoma in a Domestic Shorthair cat.

The present paper describes Felis catus papillomavirus (FcaPV) type 5-associated cutaneous mass in a Domestic Shorthair cat. Histological examination revealed multicentric epidermal acanthosis with papillomavirus-associated cytopathic changes, which progressed to a tumor lobule with intact basement membrane. An association between FcaPV-5 and the cutaneous lesions was confirmed by detection of virus antigen and genes using immunohistochemistry, polymerase chain reaction (PCR), sequencing analysis, and in situ hybridization. Based on these findings, the lesions were diagnosed as FcaPV-5-associated viral plaques and Bowenoid in situ carcinoma (BISC). To date, this is the first reported case of FcaPV-5 infection in a cat in Japan, and the second case reported worldwide. For the first time this papillomavirus type is associated with BISC development.

Identification of Felis catus papillomavirus 3 in skin neoplasms from four cats.

Bowenoid in situ carcinomas (BISCs) are papillomavirus (PV)-induced skin neoplasms that are thought to be caused by Felis catus papillomavirus (FcaPV) 2. As BISCs are typically multiple and can become extensive, they can be difficult to treat. Herein we describe 4 cats that developed skin neoplasms that contained FcaPV-3 DNA. One cat developed multiple basal cell carcinomas (BCCs), 1 a BISC with unusual extension into hair follicles, and 2 developed a single typical-appearing BISC. All neoplasms contained prominent PV-induced cell changes and intense p16CDKN2a protein immunostaining. Results from these 4 cats provide evidence that FcaPV-3 could cause a proportion of feline skin cancers, albeit less frequently than FcaPV-2. Excision of the typical BISCs and the BCCs appeared curative. Although the cat with the unusual BISC was euthanized because of the large size of the lesion, evidence from these 4 cats suggests that skin neoplasms that contain FcaPV-3 DNA may have a less aggressive clinical behavior than those associated with FcaPV-2. A consistent feature of the neoplasms in all 4 cats was the presence of prominent basophilic intracytoplasmic inclusion bodies; these inclusions have not been reported in lesions caused by FcaPV-2, to our knowledge, and their detection may allow differentiation between the different PV types and could therefore be a useful prognostic feature.

Papillomaviruses in dogs and cats.

Papillomaviruses (PVs) cause disease in both dogs and cats. In dogs, PVs are thought to cause oral papillomatosis, cutaneous papillomas and canine viral pigmented plaques, whereas PVs have been rarely associated with the development of oral and cutaneous squamous cell carcinomas in this species. In cats, PVs are currently thought to cause oral papillomas, feline viral plaques, Bowenoid in situ carcinomas and feline sarcoids. Furthermore, there is increasing evidence that PVs may also be a cause of cutaneous squamous cell carcinomas and basal cell carcinomas in cats. These diseases are discussed in this review. Additionally, there is a brief overview of PV biology, including how these viruses cause disease. Diagnostic techniques and possible methods to prevent PV infection are also discussed.

The detection of Felis catus papillomavirus 3 DNA in a feline bowenoid in situ carcinoma with novel histologic features and benign clinical behavior.

Bowenoid in situ carcinoma (BISC; papillomavirus-associated squamous cell carcinoma in situ) is an uncommon skin neoplasm of cats that can result in euthanasia because of the development of multiple lesions or because of progression to invasive squamous cell carcinoma. BISCs are currently thought to be caused by Felis catus papillomavirus 2 (FcaPV-2). The presently described cat developed a single 0.5 cm in diameter interscapular mass. Over the following 18 months, the mass doubled in size; no additional lesions developed. The mass was surgically excised and histologically diagnosed as a BISC. However, in contrast to previously reported BISCs, neither prominent thickening of the deep aspects of the follicular infundibula nor marked cell dysplasia were present. Furthermore, ~50% of the keratinocytes in the affected epidermis had prominent PV cytopathic changes that included shrunken angular nuclei and elongated basophilic cytoplasmic inclusions. As the histopathology was not typical for FcaPV-2 infection, polymerase chain reaction was performed and revealed only DNA sequences from Felis catus papillomavirus 3 (FcaPV-3). No further BISCs developed in this cat 6 months postremoval, hence surgical excision appeared to be curative. Results from this case suggest that, although FcaPV-2 appears to be the predominant cause of BISCs in cats, infection by FcaPV-3 can also cause these neoplasms. BISCs caused by FcaPV-3 appear to have unique histologic features that allow the causative PV type to be predicted. Results from this single case suggest that BISCs caused by FcaPV-3 may have a more benign clinical course than those caused by FcaPV-2.

Genomic characterization of Felis catus papillomavirus-3: a novel papillomavirus detected in a feline Bowenoid in situ carcinoma.

There is increasing evidence that papillomaviruses (PVs) may cause skin cancer in cats. Neoplasms most frequently contain Felis domesticus PV type 2 (FdPV-2) DNA, but other PV DNA sequences have also been detected suggesting multiple PVs could cause disease. One of these sequences, FdPV-MY2, was previously detected in 5 of a series of 70 feline skin cancers. The aim was to determine the genome sequence of this PV. Using the circular nature of PV DNA, 'outward facing' primers specific for FdPV-MY2 were designed and amplified a 7300 bp length of DNA from a feline Bowenoid in situ carcinoma (BISC) that showed microscopic evidence of a viral etiology and tested positive for FdPV-MY2 DNA. The PCR product was sequenced using next generation sequencing technology. The full genomic sequence of the virus, comprising 7583 bp, was assembled and analyzed. As this is the third PV from a domestic cat, the virus was designated Felis catus PV type 3 (FcaPV-3). Consistent with other PVs, the putative coding regions of FcaPV-3 were predicted to produce 6 early proteins and 2 late ones. Classification was difficult as the virus contained over 60% nucleotide similarity within the ORF L1 with PVs from 3 different genera. However, based on phylogenetic analysis of ORF L1, FcaPV-3 was most closely related to the tau-PVs CPV-2 and CPV-7. As FcaPV-3 has over 60% nucleotide similarity with the ORF L1 of both tau-PVs, it is proposed that FcaPV-3 is classified in the genus Taupapillomavirus and is the first non-canine PV in this genus.

Sequence and classification of FdPV2, a papillomavirus isolated from feline Bowenoid in situ carcinomas.

Bowenoid in situ squamous cell carcinoma (BISC) is a rare feline skin disorder, which has been described as often associated with papillomavirus infection. It is clinically characterized by solitary or multiple hyperkeratotic plaques affecting older cats. Papillomavirus (PV) sequences amplified from feline viral plaques, and BISC lesions seldom correspond to FdPV1. The goal of the present study was to investigate three cases of BISC and to carry out initial genomic analysis of the associated viral DNA. Samples of skin biopsies taken from three BISC cats were histologically characterized. DNA was extracted and rolling-circle amplification was performed on the skin samples. Restriction enzyme analysis of the amplified DNA revealed the presence of a putative unknown PV. The whole genome was subsequently sequenced and cloned. Alignments with previously described feline PV sequences were carried out and phylogenetic trees were generated. The circular 7,899 base pair sequence of Felis domesticus PV type 2 (FdPV2) contains a typical noncoding region and characteristic open reading frames (ORF) for six putative viral proteins. Phylogenetic analysis based on the nucleotide alignment of L1 genes or the amino acid alignment of E1 proteins of FdPV2 and 52 other PV types indicates that FdPV2 might represent a new genus.

Multicentric squamous cell carcinona in a paca (Agouti paca) resembling Bowen's disease.

An 8-yr-old female paca (Agouti paca) was admitted at the Veterinary Hospital of the Belo Horizonte Zoo (Brazil) with an ulcerated cutaneous nodule of approximately 1.5 cm in diameter in the left ear. One week later, other cutaneous nodules were detected in various body locations. The animal died during a surgical procedure to remove the tumors. All cutaneous nodules were histologically similar with features of squamous cell carcinoma. Considering the predominant in situ nature of the lesion as well as its multicentric localization, the disease reported here closely resembles Bowen's disease, which has been described in humans and which has been identified as a rare neoplastic disease of cats, with one single report in a dog. This is the first report of a neoplastic disease in Agouti

Use of imiquimod 5% cream (Aldara) in cats with multicentric squamous cell carcinoma in situ: 12 cases (2002-2005).

Multicentric squamous cell carcinoma in situ (MSCCIS) is a variant of squamous cell carcinoma in cats, commonly referred to as Bowen's-like disease. Imiquimod 5% cream (Aldara) is a novel immune response modifier (IRM) that has been reported as a successful treatment for Bowen's disease in humans. The purpose of this study was to describe clinical findings, treatment protocols and survival in cats with MSCCIS treated with imiquimod 5% cream and to examine the effects of imiquimod 5% cream in cats with MSCCIS. The expression of papillomavirus group-specific antigen in the study population was also determined. From review of medical records, 12 cats were identified with a histologic diagnosis of MSCCIS and treatment with imiquimod 5% cream. Initial lesions responded to imiquimod 5% cream in all cats. Most cats (75%) developed new lesions. New lesions also responded to imiquimod 5% cream in all cats treated. Five cats (41%) had side effects suspected to be associated with the use of imiquimod 5% cream, including local erythema (25%), increased liver enzymes and neutropenia (8%), and partial anorexia and vomiting (8%). Kaplan-Meier median treatment duration and median survival time probabilities for cats in this study were 1189 days, respectively. A time to failure model was generated as many cats were censored from analysis well before the aforementioned projected median. This model resulted in a shorter median survival time of 243 days. No patient-related, tumour-related or treatment-related prognostic variables were identified. No expression for papilloma group-specific antigen was found. Imiquimod 5% cream appears to be well tolerated in the majority of cats, and further studies are warranted to further examine its usefulness in cats with this disease.

Squamous cell carcinoma (Bowens disease) in situ in three cats

Três casos de carcinoma multicêntrico in situ de células escamosas (doença de Bowen) são descritos na espécie felina. As neoplasias ocorreram em gatos idosos e acometeram a região pré-auricular, cervical, abdominal e flancos. Um gato apresentou lesão única e os demais apresentaram lesões multifocais, que se caracterizaram por placas que variavam de hiperceratóticas a verruco-crostosas e eram hiperpigmentadas. Algumas eram ulceradas, com fissuras que sangravam facilmente. Histologicamente, as células neoplásicas encontravam-se confinadas à epiderme e aos folículos pilosos, sem o envolvimento da membrana basal. Em um dos casos houve melhora significativa das lesões após terapia oral com acitretina.

Clinical, histological and immunohistochemical study of feline viral plaques and bowenoid in situ carcinomas.

Feline viral plaques (FVP) induced by papillomavirus (PV) are often hyperpigmented and flat warts. The fact that up to 47% of bowenoid in situ carcinomas (BISC), which also usually occur in the form of hyperpigmented plaques, are positive for PV antigen in immunochemistry suggests that BISC could evolve from FVP. The relationship between the presence of PV antigens and the clinical and histological features of 26 cases of feline dermatoses (clinically described as pigmented plaques and with histological diagnosis of FVP and/or BISC) was therefore determined. The cases were classified into one of the three following groups: FVP, FVP + BISC or BISC. Immunohistological detection of papillomavirus group-specific antigen was performed using a polyclonal rabbit antibovine papillomavirus antiserum. Of the seven cases in the FVP group, six were deemed positive by immunohistology as were all 10 cats in the FVP + BISC group. On the other hand, only one of the nine BISC cats was positive. The presence of both FVP and BISC lesions in some cats and the high detection rate of PV antigens in the FVP and FVP + BISC groups suggest that both conditions might have the same viral cause and that some BISC may evolve from FVP. The low rate of viral antigen detection in the BISC group indicates another cause or a loss of viral replication during the cancerogenesis.

Cutaneous horn and squamous cell carcinoma in situ (Bowen's disease) in a cat.

Cutaneous horn and squamous cell carcinoma (SCC) in situ (i.e., Bowen's disease) were documented concurrently in a cat. The cat had multiple, crusted lesions and a cutaneous horn on the right dorsal lumbar area. All the crusted cutaneous lesions were diagnosed as SCC in situ. Other findings included the presence of a thymoma and hepatoma. This cat was tested, and results were negative for feline leukemia and feline immunodeficiency viruses. At necropsy (eight months after the initial diagnosis was made) the hepatoma had ruptured, resulting in exsanguination and death.

Multicentric squamous cell carcinoma in situ resembling Bowen's disease in cats.

Multicentric squamous cell carcinoma in situ was studied in 12 cats (eight castrated males and four spayed females). The neoplasms occurred in middle-aged to old (mean age = 12 years) mixed-breed cats with a variety of hair-coat colors. The lesions were found in haired pigmented regions of the skin, including the trunk, limbs, feet, head, and neck, and were unrelated to exposure to sunlight. Lesions occurred at multiple sites in nine cats and at solitary sites in three cats and were from 0.5 cm to 3.0 cm in diameter, irregular, slightly elevated, plaque-like or papillated, and partially alopecic. Histologically, the lesions consisted of sharply demarcated regions of neoplastic, keratinocytic infiltration of the epidermal and follicular infundibular epithelium. Neoplastic cells were confined to the epithelium without frank invasion of the dermis. Two histologic subclasses of multicentric squamous cell carcinoma in situ were identified, the irregular nonhyperkeratotic type and the verrucous hyperkeratotic type. Three cats also had invasive squamous cell carcinoma adjacent to lesions characteristic of multicentric squamous cell carcinoma in situ. Grossly, these were solitary 2.0-4.0 cm-diameter firm, crusted, crateriform cutaneous masses. During follow-up periods of 4 to 20 months (mean follow-up period = 11 months), neoplasms did not recur locally after surgical excision; however, similar lesions developed at new sites in four cats.(ABSTRACT TRUNCATED AT 250 WORDS)