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Update in classification, diagnosis and prognosis of Canine malignant lymphomas
Lymphoid tumours are amongst the most common tumours to affect dogs. Many factors are known to influence the prognosis for the given patient. The prognostic importance of clinical, immunohistological, cytogenetic and cell proliferation characteristics has been investigated for canine malignant lymphomas.

Classification
Malignant lymphomas may be classified according to their anatomical location, cell morphology, growth pattern, or according to whether they are B cell, T cell or non-B-non-T cell lymphomas. Alimentary, thymic, skin, leukaemic and multicentric tumours, amongst others, are well known within this category. In a comprehensive classification system developed under the auspices of the National Cancer Institute [45], lymphomas are classified as low-, intermediate-, or high-grade, depending on their cell type (small lymphocytic, plasmacytoid, small cleaved, large cell, etc.) and growth pattern (follicular or diffuse). Another commonly used classification system, the Updated Kiel Classification, combines lymphocyte immunophenotype with cell morphology [61].


Diagnosis
For most lymphomas, the first indication of their presence is the rapid enlargement of the lymph nodes. Macroscopically, they exhibit different features depending on what part of the body is affected. The skin form, for instance, is usually generalised or multifocal and the tumours occur as nodules, plaques, ulcers, erythroderma and/or exfoliative dermatitis. The leukaemic form, which has no solid tumour growth, occurs in less than 10 per cent of dogs with lymphoma.

Cytology is a well-established diagnostic technique which alone may lead to a diagnosis. When the number of immature lymphocytes in a sample exceeds 50 per cent of the population it is considered diagnostic for lymphoma, although in cases of lymphocytic lymphoma the diagnosis is more difficult.

Histopathological examination allows tumour structure and cell morphology to be observed. Malignant lymphomas are known to consist of a wide variety of cells, ranging from small lymphocytic to immunoblastic cells. It is worth pointing out that follicular lymphomas are rarely seen in dogs.

Immunohistochemistry is used increasingly for the diagnosis and immunophenotypic description of canine malignant lymphomas and has been instrumental in demonstrating a lack of correlation between the morphology and immunophenotype of lymphoma cells [23, 63]. There are several antibodies available for the immunophenotyping of canine lymphocytes and malignant lymphomas. Anti-CD79 and anti-BLA36 are both widely used for the recognition of normal and tumorous B cells. Other antibodies that recognise B cells are against CD18, CD21 and different classes of immunoglobulins, while anti- CD3, CD4, CD5, CD8, CD49d and PanT antibodies react specifically with T cells. CD18, CD45 and CD45RA are common lymphocyte antigens expressed by both B and T cells. Non-B-non-T cell lymphomas are recognised by the expression of common lymphocyte antigens and a lack of B or T cell specific antigens.

Finally, molecular biological techniques used for the diagnosis of canine malignant lymphomas are limited. Recently, a PCR-based Vâ fingerprinting method was described for the diagnosis of canine T cell lymphomas and leukemias [18]. It allows the diversity and the proportion of clones in a population of T cells to be determined and is quite sensitive. So far, however, there are no reports of the routine use of this technique in veterinary practice.

Prognosis
The prognosis for dogs with malignant lymphomas is poor. Spontaneous regression is unusual, and dogs left untreated rarely survive more than a few months [60]. Animals diagnosed with the multicentric form of lymphoma have an average life expectancy of ten weeks, although many die sooner and a few may live substantially longer - between six months and one year. Dogs diagnosed with the alimentary form of lymphoma have an even shorter life expectancy, averaging eight weeks. Animals with the longest life expectancy after diagnosis of lymphoma are usually 12 years old or older. The estimated survival time after disease onset in untreated, middle-aged dogs is less than six months and is often les than two months in dogs younger than two years [59].

The prognostic importance of clinical, immunohistological, cytogenetic and cell proliferation characteristics has been investigated for canine malignant lymphomas. Neither age nor weight was found to be significant to the overall survival time or disease-free survival time of dogs undergoing chemotherapy [33, 64]. Although it has been reported in many studies that gender does not affect a dog`s prognosis [23, 37], in other studies male dogs were found to have shorter remission and survival times than female dogs [36]. It is well established that the prognosis for dogs with T cell lymphomas is worse than for those with B cell lymphomas [23, 33, 64]. The clinical stage of a lymphoma is significant in predicting both the length of the disease-free period and life expectancy [64]. Furthermore, the presence of chronic inflammatory diseases [6], the disease severity at initial presentation [64] and the use of corticosteroids prior to the start of chemotherapy [49] have all been shown to affect a patient`s relapse-free survival time, as well as the incidence of complete remission. Evaluation of the argyrophil nucleolar organiser regions (AgNORs) [32], the pre-treatment apoptotic index [46] and P-glycoprotein [7] can also be helpful in predicting remission and survival times. In a study of 61 dogs diagnosed with lymphoma, there was a treatment advantage in 25 per cent of dogs with trisomy of chromosome 13, confirmed by an increase in the time until patients` first remission as well as their overall survival time [24].

in: Taci Cangul: Improved classification, diagnosis and prognosis of canine round cell tumours, Veterinary Science Tomorrow.
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