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Lymphoma Classification
Tissue Banking of Canine Lymph Nodes with Lymphomas Subtyped under the WHO Classification System
Sequencing of the canine genome in 2005 revealed the close phylogenetic relationship between humans and dogs. Domestic dogs share the same environment with humans and are subject to the same influences on tumor initiation and progression as their human counterparts. Lymphoma is the most common hematological malignancy in the dog and occurs with an incidence of approximately 24 cases per 100,000 dogs. Interestingly, there is a distinct breed predisposition for lymphoma in dogs, suggesting the presence of genetic risk factors, which has made this a popular model in which to study genetic risk factors for lymphomagenesis. The cytomorphological, cytogenetic, biological and behavioral similarities between canine and human lymphoma subtypes have led researchers studying genetic and epigenetic effects on lymphomagenesis, serological biomarkers, and novel therapeutics to utilize the dog model. For example, follicular lymphomas occur in both dogs and humans, and share cytomorphologic features and biological progression. Response to conventional chemotherapeutic agents is similar between dogs and humans with non-Hodgkin’s lymphoma (NHL), with well-documented responses of NHL patients to CHOP-based protocols (cyclophosphamide, doxorubicin, vincristine, and prednisone). Cytogenetic similarities have been identified in human and canine patients with chronic myelogenous leukemias. The Philadelphia chromosome and the Raleigh chromosome describe the chromosomal translocation that produces the BCR-ABL fusion product in humans and dogs respectively. Furthermore, as seen in human patients with Burkitt’s lymphoma, dogs with Burkitt-like lymphoma also have a translocation leading to constitutive expression of c-Myc. In addition, viral-induced lymphomagenesis in people with human T-lymphotropic virus-I may be due in part to inactivation of p16. High-grade T cell lymphomas in dogs have also been shown to have p16 deletion or inactivation.
In 2001, the World Health Organization publicized a classification system for human hematopoietic neoplasms which was developed over seven years and derived input from scientists, oncologists and pathologists. The system was extensively discussed at international meetings to ensure worldwide acceptance. Unlike its predecessors, this classification scheme is based on the diagnosis of disease rather than cell types, and thus requires complete patient data, anatomic localization of the neoplasm plus immunophenotyping. In considering treatment protocols for human lymphoid neoplasms, each lymphoid malignancy must be evaluated individually because approaches for one type of lymphoid malignancy may not be applicable to other diseases, even of the same cell lineage (Jaffe et al, 2008). For example, indolent lymphomas – most commonly follicular lymphoma – are often treated with radiotherapy, or single-agent therapy and has a generally good clinical outcome. More aggressive lymphomas, like diffuse large B cell lymphoma, are potentially curable with multi-agent chemotherapy which includes Rituximab. Furthermore, lymphomas and leukemias are no longer treated as separate disease entities. The WHO classification was updated in 2008 and incorporates the cytogenetic derangements of many neoplasms. In an international review by human medical pathologists, the inter- and intraobserver accuracy and reproducibility in employing this classification was greater than 85 percent. A similar study reviewing canine lymphomas was performed recently by a group of veterinary pathologists, and similar results were found. The WHO classification system is now used extensively in human oncology and researchers are in search of comparative animal models with similar lymphoma subtypes.
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