The presence of p16 CDKN2A 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-p16(CDKN2A) 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.

Ménétrier disease and gastric adenocarcinoma in 3 Cairn terrier littermates.

Ménétrier disease is a rare hypertrophic gastropathy that is characterized by hyperplasia of the mucous cells with concurrent loss of chief and parietal cells within the gastric glands. There are few reports of this disease in dogs, and little is known about the clinical presentation and progression of canine Ménétrier disease. Three Cairn terrier littermates developed hypertrophic gastropathy with histological features of Ménétrier disease. One dog remained clinically asymptomatic for 2 years after diagnosis. The development of this disease in 3 siblings suggests a possible inherited predisposition. All 3 dogs also developed gastric neoplasia, which has been reported in human Ménétrier disease but has not been associated previously with hypertrophic gastropathy in domestic species.

Primary bone tumors in birds: a review and description of two new cases.

Primary bone tumors are only occasionally reported in avian species. This paper presents the cases of an osteosarcoma in a 6-yr-old free-range chicken and a chondrosarcoma in a 3-yr-old barred Plymouth Rock chicken. The well-differentiated, moderately productive osteoblastic osteosarcoma arose from the synsacral vertebrae and had metastasized to the liver. The chondrosarcoma was well differentiated and firmly attached to the left side of the keel. There was no evidence of metastasis.

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 p16(CDKN2A) 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.

Papillomaviral DNA sequences are not amplifiable from canine subungual squamous cell carcinomas.

AIM: To determine if papillomaviral DNA is more frequently present within canine subungual squamous cell carcinomas (SCCs) than in non-SCC digit lesions. METHODS: Total DNA was extracted from 23 canine subungual SCCs and 23 non-SCC digit lesions. The presence of amplifiable DNA within each sample was confirmed by amplifying a section of the glyceraldehyde-3-phosphate dehydrogenase (GADPH) gene. Two different consensus PCR primer sets were used to amplify papillomaviral DNA from the samples. RESULTS: The consensus primers only amplified papillomaviral DNA from the positive control samples. None of the 46 canine digit samples contained DNA that was amplifiable by the consensus PCR primers. CONCLUSION: Papillomaviruses are unlikely to be a significant cause of canine subungual SCCs. CLINICAL RELEVANCE: While circumstantial evidence suggests that canine subungual SCCs could develop due to papillomaviral infection, this study did not reveal any evidence to support papillomaviral aetiology of these neoplasms.

Extramedullary laryngeal plasmacytoma in a dog.

CASE HISTORY: An 8-year-old, female, spayed Border Collie presented with a 3-week history of coughing, choking and haemoptysis. CLINICAL FINDINGS: Inspiratory stridor was evident on clinical examination. Cervical radiographs revealed a round soft-tissue mass on the dorsal aspect of the epiglottis. A laryngeal mass was evident on examination under anaesthesia, and an incisional biopsy was obtained. Histopathology revealed a dense proliferation of neoplastic round cells morphologically consistent with plasma cell origin. Immunohistochemisty results were negative for CD3 (T cell marker) and positive for CD79a (B cell marker), resulting in a diagnosis of extramedullary plasmacytoma. The patient was treated with melphalan and prednisolone; clinical signs resolved within 1 week and the mass was no longer evident on laryngoscopy after 1 month of treatment. After 6 months of chemotherapy, the laryngeal mass recurred and euthanasia was requested. There was no evidence of systemic spread on post-mortem examination. DIAGNOSIS: Solitary extramedullary plasmacytoma of the canine larynx. CLINICAL RELEVANCE: Respiratory extramedullary plasmacytomas are extremely rare with only one laryngeal and two tracheal cases previously reported. This is the first published report of a laryngeal plasmacytoma that recurred despite combination chemotherapy with melphalan and prednisolone.

Widespread mismatch repair expression in feline small intestinal lymphomas.

Small intestinal lymphoma is a common feline tumour that most often develops in older cats, but also occurs in younger animals. In man, germline defects in the mismatch repair (MMR) genes most commonly cause hereditary non-polyposis colorectal cancer (HNPCC), or Lynch syndrome, while MMR defects have also been implicated in the development of lymphoid tumours in mice and in people. It was hypothesized that inherited MMR defects predispose a proportion of younger cats to the development of small intestinal lymphoma. MMR expression in 10 small intestinal lymphomas from younger cats (group 1, mean age 4.5 years) was compared with MMR expression in 30 small intestinal lymphomas from older cats (group 2, mean age 12.6 years). The cross-reactivity of the antibodies specific for the human MMR proteins MLH1, MSH2 and MSH6 with the corresponding proteins in feline tissues was first confirmed by western blotting. MMR expression was then investigated immunohistochemically in feline lymphomas. MLH1, MSH2 and MSH6 were detected immunohistochemically within neoplastic lymphocytes from all tumours examined. There were no significant differences between the two groups in either the intensity of immunolabelling or the percentage of neoplastic cells within which MMR proteins were detected. These results confirm the cross-reactivity of the human MMR antibodies with the corresponding proteins in feline tissues, but do not support the hypothesis that inherited germline MMR defects are a significant cause of feline small intestinal lymphomas.

Cutaneous malignant melanoma in an 11-month-old Russian blue cat.

CASE HISTORY: A grey mass developed on the tail base of an 11-month-old Russian blue cat. The mass grew slowly for 2 months and then became ulcerated. CLINICAL FINDINGS: The mass was excised, and histology revealed it to be a malignant melanoma. Skin adjacent to the melanoma and underlying tissue contained large aggregates of melanin and numerous melanophages. Seven months later, an additional malignant melanoma was excised from the skin on the left thorax. Three months after the second melanoma was excised, the left axillary lymph nodes were enlarged; four were excised, and found to contain metastases. The cat became lethargic and anorexic, and was subject to euthanasia at 26 months of age. Post-mortem examination revealed numerous small well-circumscribed melanomas scattered within the S/C tissue overlying the left thorax and within the left axilla. These were interpreted to be in-transit metastases. Metastatic foci were also visible within the spleen, liver, lungs, lymph nodes and a rib; numerous small melanomas were also present throughout the mesentery. DIAGNOSIS: Cutaneous malignant melanoma with numerous distant and in-transit metastases. CLINICAL RELEVANCE: Although cutaneous malignant melanomas appear to be rare in young cats, they can display a similar clinical behaviour to malignant melanomas in humans, and a guarded prognosis should be suggested for neoplasms of this type. In humans, in-transit metastases are a well-recognised consequence of removing lymph nodes that drain areas containing neoplastic disease. This manifestation of metastatic disease has not previously been reported in the veterinary literature.

The development of multiple cutaneous inverted papilloma following ovariohysterectomy in a dog.

CASE HISTORY: Ovariohysterectomy was performed on an adult Cavalier King Charles Spaniel. The skin that had been clipped for surgery was noticed to be erythematous 8 days later. CLINICAL AND PATHOLOGICAL FINDINGS: Poorly defined patches containing multiple papules were visible bilaterally within the clipped skin. These became larger over the following 2 weeks, and samples were collected for histology. Seven days later, the lesions were multiple raised masses, up to 5 cm in diameter. Histology revealed numerous cup-shaped epidermal proliferations extending into the dermis. The presence of keratinocytes with increased quantities of blue-grey cytoplasm, and koilocytosis suggested papillomaviral infection; Canis familiaris papillomavirus (CfPV-2) DNA was amplified from two separate samples. Complete regression was observed 8 weeks after the lesions had been initially observed. DIAGNOSIS: Multiple inverted papilloma confined to skin that had been clipped for surgery. CLINICAL RELEVANCE: This is the first time that the development of canine cutaneous papillomas has been associated with surgery. The nature of the association between surgery and development of the papillomas is uncertain. However, it is possible that damage to superficial skin could promote the formation of papillomas. This is the first identification of CfPV-2 in New Zealand.

Possible parachordoma in a dog.

CASE HISTORY: A 15-mm diameter mass developed in the S/C tissue overlying the right lateral gluteal muscle of a 6(1/2)-year-old female Flat-coated Retriever. PATHOLOGICAL FINDINGS: Cytological preparations following aspiration of the mass were highly cellular and consisted of a population of large polygonal cells containing single to multiple nuclei, large prominent nucleoli, and intracytoplasmic vacuoles. Histologically, the neoplasm consisted of similar large cells surrounded by thick fibrous connective tissue trabeculae. The large polygonal cells reacted positively with antibodies against vimentin, low- and high-molecular-weight variants of cytokeratin (AE1/AE3), but not with antibodies to desmin or glial fibrillary acidic protein (GFAP). DIAGNOSIS: The clinical, gross, histological and immunohistochemical findings are similar to those reported for parachordomas in humans. Neither recurrence nor metastases were noted 18 months after surgical excision of the mass. CLINICAL RELEVANCE: This is the first reported case of a possible parachordoma in a dog, a benign tumour with cytological features of malignancy.

Widespread mismatch repair protein expression in canine cutaneous mast cell tumors.

Cutaneous mast cell tumors (MCTs) are common canine neoplasms. Some dog breeds more frequently develop MCTs, suggesting a genetically mediated predisposition. In humans, the most common inherited cancer predisposition is caused by germline defects in the mismatch repair (MMR) genes. To investigate whether inherited defects in the MMR genes predispose some dogs to MCT development, MMR expression in 22 MCTs from young and predisposed breed dogs was compared with MMR expression in 22 MCTs from old dogs of non-MCT-predisposed breeds. MMR expression was investigated immunohistochemically using antibodies against MLH1, MSH2, and MSH6. Mast cells within all MCTs expressed MLH1, MSH2, and MSH6. There were no significant differences in the intensity of immunoreactivity or the percentage of cells expressing MMR proteins between MCTs from the 2 groups of dogs. There were no significant differences in MMR protein expression between grade II and grade III MCTs. These results do not support the hypothesis that inherited MMR defects predispose some dogs to MCT development.

Black-hair follicular dysplasia in a New Zealand Huntaway Dog.

CASE HISTORY: A 6-year-old intact male New Zealand Huntaway dog had slowly progressive alopecia that was first observed at 12 weeks of age. CLINICAL FINDINGS: Patchy alopecia was confined to the black-haired areas of the body, and was most evident on the head and dorsum of the body; tan-haired areas of skin appeared normal. Histological examination of black-haired skin revealed distended melanocytes and large aggregates of melanin within, and surrounding, the hair follicles and the epidermis. Macrophages distended with melanin were also visible within the peri-follicular and superficial dermis, and follicular lumina were often plugged by keratin that contained aggregates of melanin. The follicles were dysplastic and few hair shafts were visible emerging from follicular infundibula within the sections. DIAGNOSIS: The clinical and histological findings were consistent with black-hair follicular dysplasia (BHFD). CLINICAL RELEVANCE: This is the first report of BHFD in a dog in New Zealand, and is the first report in a Huntaway. The most significant effect of BHFD is a predisposition to follicular plugging and secondary bacterial skin infections. Due to the hereditary nature of the follicular dysplasias, breeding from affected dogs should be discouraged. Histological examination of the skin is required to differentiate between the different follicular dysplasias as well as differentiating between follicular dysplasia and follicular atrophy due to endocrinopathy.

Probable malignant catarrhal fever presented as transient generalised crusting dermatitis in a cow.

CASE HISTORY: A 2-year-old crossbred cow developed crusting ulcerative lesions that covered approximately 40% of the body. They were first observed 2 weeks after the cow calved, and were most severe over the caudal aspect of the proximal hindlegs and perineum. CLINICAL FINDINGS AND DIAGNOSIS: Generalised variably confluent 1-2-cm diameter foci of ulceration and crusting were visible. No ocular or oral lesions were visible, and the cow did not have diarrhoea. Skin biopsies revealed lesions consistent with those previously described for malignant catarrhal fever (MCF). Additionally, prominent multinucleate cells were visible. The DNA for ovine herpesvirus type 2 (OHV-2) was amplified from the skin biopsies, using PCR. The cow spontaneously made a complete clinical recovery. CLINICAL RELEVANCE: Malignant catarrhal fever should be considered in cases of ulcerative skin disease in cattle. The disease is difficult to diagnose, and a combination of skin histology as well as PCR is required. Although probably rare, it appears complete recovery from MCF is possible when the disease is confined to the skin.

Feline cutaneous viral papilloma associated with human papillomavirus type 9.

A 12-year-old domestic Shorthaired cat developed a multinodular exophytic mass on the dorsal surface of the nose. The skin surrounding the mass was nonpigmented, and actinic keratosis had been diagnosed in this area 3 years previously. Histologic examination revealed hyperkeratosis, epidermal hyperplasia, papillomatosis, koilocytosis, and possible intranuclear viral inclusions. Polymerase chain reaction amplified papillomaviral deoxyribonucleic acid from formalin-fixed samples of the lesion. Sequencing of the amplicon revealed 98% similarity to human papillomavirus (HPV) type 9. To the authors' knowledge, this is only the second reported feline cutaneous viral papilloma. In addition, this is the first report of a feline papilloma being associated with an HPV.

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

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.

Lameness in a dog caused by thoracic wall invasion by a pulmonary neoplasm.

A 12-year-old fox-terrier dog presented with forelimb lameness of 3-weeks duration. Ultrasonography revealed a mass within the thoracic wall and osteolysis of the left third rib. A squamous cell carcinoma was diagnosed by cytological examination of an ultrasound-guided fine needle aspirate of this mass. As a result of the diagnosis of neoplasia, the dog was euthanatized. Necropsy revealed a solitary expansile mass within the left cranial lung lobe, and a mass within the adjacent thoracic wall. Thickening of the pleura between the two masses was visible, although adhesions were not present. Histology of both masses revealed a well-differentiated squamous cell carcinoma. To the authors' knowledge, this is the first detailed description of direct invasion of the thoracic wall by a canine lung tumour.