Jane Dobson

Breed-Predispositions to Cancer in Pedigree Dogs

Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. This paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies.

Small Animal Oncology

Acknowledgements Disclaimer Introduction Pathogenesis & tumour biology Diagnosis and staging Treatment options Skin Mammary gland Soft tissues Skeletal system Head and neck Gastrointestinal tract Respiratory tract Urinary tract Genital tract Nervous system Endocrine system Haemopoietic system Miscellaneous Tumours Appendices Index.

Feline extranodal lymphoma: response to chemotherapy and survival in 110 cats

OBJECTIVE To determine response to treatment, survival and prognostic factors for feline extranodal lymphoma in the UK. METHODS Records of cats diagnosed with lymphoma of extranodal sites at seven referral centres were reviewed and information on signalment, tumour location, prior treatment and chemotherapy protocol recorded. Factors influencing response to treatment and survival were assessed. RESULTS One hundred and forty-nine cases met inclusion criteria. Sixty-nine cats had nasal lymphoma, 35 renal, 15 central nervous system, 11 laryngeal and 19 miscellaneous locations. Sixty-six cats received cyclophosphamide, vincristine, prednisolone, 25 Wisconsin-Madison doxorubicin-containing multi-agent protocol, 10 prednisolone alone and nine other combinations. The response rate for the 110 treated cats was 85.5 per cent. Of cyclophosphamide, vincristine, prednisolone treated cats 72.7 per cent achieved complete remission, median survival 239 days. Sixty-four per cent of Wisconsin-Madison treated cats achieved complete remission, median survival 563 days. Cats with nasal lymphoma achieving complete remission had the longest survival (749 days) and cats with central nervous system lymphoma the shortest (70 days). If complete remission was achieved, prior treatment with corticosteroids significantly reduced survival time. CLINICAL SIGNIFICANCE Cats with extranodal lymphoma respond to chemotherapy and achieve survival times comparable to other locations. Corticosteroid pretreatment reduced survival time in cats achieving complete remission.

Breed incidence of lymphoma in a UK population of insured dogs

Canine lymphoma is one of the commonest forms of spontaneous canine neoplasia. Improved understanding of the genetic and environmental risk factors for canine lymphoma, including breed differences, may have comparative benefits for the study of non-Hodgkins lymphoma in humans. In this study, data from a pet insurance company were used to estimate the incidences of canine lymphoma for pedigree breeds in the UK. Out of a total of 130,684 insured dogs, 103 had a diagnosis of lymphoma recorded. A significant breed effect was found with the boxer, bulldog and bull mastiff breeds, all having a high incidence of lymphoma. The small number of lymphoma cases recorded may have limited our ability to detect other breeds with an elevated risk. Incidence of lymphoma was found to increase with age, peaking at 10 years of age.

Immunohistochemical and histopathologic features of 14 malignant fibrous histiocytomas from Flat-Coated Retrievers.

Flat-Coated Retrievers seem to be at increased risk of developing soft-tissue sarcomas, and undifferentiated round cell or spindle cell sarcomas account for approximately 59% of sarcomas in the breed. In an attempt to classify these tumors further, formalin-fixed, paraffin-embedded sections from 14 undifferentiated sarcomas from Flat-Coated Retrievers were reviewed and examined with a panel of histologic and immunohistochemical stains. The panel included vimentin, desmin, Myo D1, smooth muscle actin, cytokeratin, S100, von Willebrand factor (factor VIII), Mac 387, CD3, major histocompatibility complex (MHC) class II, and CD79a. The majority of the sarcomas showed greater than 70% staining for MHC class II. We conclude that these undifferentiated sarcomas in Flat-Coated Retrievers belong to a spectrum of tumors with varying proportions of characteristic cell types and morphologic features, some of which fit the diagnostic criteria for malignant fibrous histiocytoma. Many of these sarcomas seem to have a significant myofibroblast component and a mild or moderate T cell infiltrate but the precise cell lineage is still uncertain.

Long-term outcome of 56 dogs with nasal tumours treated with four doses of radiation at intervals of seven days.

A retrospective study was undertaken on 56 dogs treated for nasal tumours by megavoltage radiotherapy with a hypofractionated schedule consisting of four doses of 9 Gy given at intervals of seven days. The dogs were followed until they died or were euthanased. The clinical signs had improved in 53 of the 56 dogs by the end of the treatment schedule. Mild acute radiation side effects were observed in the majority of the dogs but late radiation side effects were rare. Kaplan-Meier survival analysis revealed a median survival time after the final dose of radiation of 212 days. The oneand two-year survival rates were 45 per cent and 15 per cent. Fifty of the dogs were euthanased because the initial clinical signs recurred.

Malignant histiocytosis in three Bernese mountain dogs

Malignant histiocytosis is a rare disease which is characterised by the neoplastic proliferation of tissue macrophages (histiocytes) leading to excessive phagocytosis of erythrocytes. The clinical signs and pathological findings in three Bernese mountain dogs are described. Two of the dogs had the same sire. The disease has been established as a familial problem in Bernese mountain dogs in other countries, although it has not been previously recorded in the United Kingdom.

The Clinical Presentation and Histopathologic–Immunohistochemical Classification of Histiocytic Sarcomas in the Flat Coated Retriever

The Flat Coated Retriever is a breed at risk of development of histiocytic sarcoma (HS), but in contrast to the disseminated form of disease recognized in the Bernese Mountain Dog, most reports of HS in Flat Coated Retrievers describe a localized lesion affecting the musculature or fascia of limbs. The purpose of this study was to review data and material received though an ongoing Flat Coated Retriever tumor survey to better define the presentation of HS in the breed and to determine the utility of subclassification of tumors arising at different sites by histology and immunohistologic phenotyping. Data on 180 dogs bearing HS-like tumors were available for review, which showed that although the majority (101 lesions, 57%) were primary limb lesions, 47 dogs (26%) had visceral, mainly splenic lesions with no peripheral primary tumor. A detailed histologic and immunohistologic review of 20 limb tumors and 20 splenic tumors showed that 2 distinct phenotypic subtypes could be identified: a histiocytic subtype, most prevalent in the splenic tumors, and a histiocytic–spindle–pleomorphic subtype, mainly seen in the limb tumors. Despite their variable morphology, all tumors expressed major histocompatibility complex class II and the leukocyte antigen CD18, but only those tumors in the spleen consistently expressed CD11d. The majority of tumors also contained a mild to moderate infiltrate of T lymphocytes.

Chlorambucil and prednisolone chemotherapy for dogs with inoperable mast cell tumours: 21 cases

OBJECTIVES To evaluate the response of measurable canine mast cell tumours unsuitable for other treatment modalities to a chemotherapy protocol comprising chlorambucil and prednisolone. METHODS Dogs bearing measurable mast cell tumours, unsuitable for treatment by surgery or radiotherapy, were treated with orally administered prednisolone and chlorambucil, and their responses assessed. RESULTS Twenty-one dogs were enrolled in the study; 13 had intermediate-grade mast cell tumour, six were high grade and two were diagnosed by cytology alone. Eight dogs had multiple tumours and 13 dogs had single tumours, and six dogs had lymph node metastases and no dogs had visceral metastases detected. Three dogs achieved complete remission, five achieved partial remission (overall response rate 38 per cent), nine had static disease and four dogs had progressive disease. Median progression-free interval for the eight responders was 533 days, and median survival time for all dogs in the study was 140 days. Progression-free interval and median survival time were not influenced by the age, sex, weight or neutering status of the patient, by the grade or stage of the tumour or whether the patient had single or multiple tumours. No toxicity was detected. CLINICAL SIGNIFICANCE Response and survival rates of inoperable canine MCT to chlorambucil and prednisolone are comparable to previously described protocols, with no apparent toxicity.

Photodynamic Therapy of Superficial Nasal Planum Squamous Cell Carcinomas in Cats: 55 Cases

BACKGROUND Squamous cell carcinomas (SCCs) are common skin tumors in cats. We investigated photodynamic therapy (PDT) using the photosensitizing agent 5-aminolaevulinic acid (5-ALA) topically and a high-intensity red light source. HYPOTHESIS PDT is a safe and effective treatment for feline SCCs. ANIMALS Fifty-five client-owned cats with superficial nasal planum SCCs. METHODS Prospective, uncontrolled clinical trial. PDT was performed using topical 5-ALA and light of peak wavelength 635 nm. Adverse effects, response, and tumor control were evaluated. RESULTS 53/55 (96%) cats responded to therapy, and there was a complete response in 47/55 (85%). Six cats (11%) had a partial response. Of the 47 cats with complete response to a single treatment, 24 recurred (51%), with a median time to recurrence of 157 days (95% confidence interval, 109-205 days). Repeat PDT was performed in 22 cats, and at a median follow-up of 1,146 days, 23 (45%) cats were alive and disease free, 17 (33%) had to be euthanized due to tumor recurrence, and 11 (22%) were euthanized for other reasons. Only transient mild local adverse effects were observed after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE PDT using 5-ALA and a red light source was safe, well tolerated, and effective in the treatment of superficial nasal planum SCCs of cats and offers an alternative to conventional therapy. Although initial response rates were high, this treatment did not lead to a durable remission or cure in all cases.