Lymphoma in dogs and cats (Proceedings)
Lymphoma is a very diverse group of neoplasms whose etiology remains largely unknown. Viral particles similar to those of retroviruses have been identified in short term culture. Exposure to phenoxyacetic acid herbicides has been implicated in both human and canine patients, but account for a very small percentage of cases. Its incidence is noted to be increased in immunosuppressed patients. Chromosome abnormalities are being described more frequently, and serve as markers, and in some cases prognostic factors, for subtypes of several lymphomas in human medicine. These chromosome abnormalities are now starting to be identified in our canine patients as well.
Classification in dogs has long been based on anatomic location and histologic criteria. Anatomic forms include multicentric (80%), anterior mediastinal (~5%), gastrointestinal (~5-7%), cutaneous (~5%) and extranodal (~5%). The clinical signs associated with each reflect the organ system involved. Hypercalcemia is a common paraneoplastic syndrome noted in the anterior mediastinal form. Anemia, neutrophilia, lymphocytosis, thrombocytopenia, monoclonal gammopathies and cachexia have all been reported.Histologically they are most often broken down into high, intermediate and low grades. The most striking difference between canine and human cases is the paucity of low-grade canine tumors (5.3-29%). The histologic classification does not predict survival times, but does predict the response to therapy. The high grade tumors are more likely to respond to chemotherapy, however the low grade tumors can live a long time without any treatment.
Lymphomas can also be B-cell or T-cell in origin. Approximately 85% of canine cases are B-cell in origin and historically they have been more responsive to treatment and associated with longer survival times. Chemotherapy protocols in the future will be based upon immunophenotype classification and this information should be requested routinely. The immunophenotype can be determined using cytologic or histologic samples, and is available through all of the commercial laboratories.
WHO clinical staging is broken down into five categories. I. Involvement limited to a single node or organ. II. Regional lymph node involvement on one side of the diaphragm. III. Generalized lymph node involvement on both sides of the diaphragm. IV. Liver and/or spleen involvement. V. Bone marrow and/or extranodal involvement. In addition each is further classified into a substage of a) without systemic signs and b) with systemic signs. Stage is not generally prognostic unless you are lucky enough to have a I or II. Substage however is highly prognostic with those animals without systemic signs generally living longer.
Baseline staging should always include a CBC, biochemical profile, urinalysis, and immunophenotyping. Thoracic and abdominal radiographs, bone marrow aspirates, and bronchoalveolar lavages can also be considered to thoroughly stage your patient. The more aggressively you stage them, the higher their classification will be. The treatment of these patients is going to be dictated by the stage and substage of the disease, the immunophenotype, the presence or absence of paraneoplastic signs, the overall physiologic status of the patient, the financial and time commitment of the owner, and the client's overall comfort with the potential side effects. Note that the last category is the only one you can impact.
Without treatment median survival times of 30-50 days are reported. Since with few exceptions, this is a systemic disease, systemic treatment is required, therefore chemotherapy is the treatment of choice. With the possible exception of doxorubicin, single agent therapy results in lower response rates and survival times. Approximately 90% of lymphoma patients can be placed into a complete clinical remission and a return to a normal quality of life. The median survival time is ~ 1 year in dogs treated aggressively and most dogs tolerate their chemotherapy with minimal side effects. The most effective chemotherapy agents include doxorubicin, cyclophosphamide, vincristine, l-asparaginase, CCNU and prednisone. Other drugs with activity include vinblastine, cytosine arabinoside, actinomycin-D, mitoxantrone, chlorambucil, mustargen, procarbazine and DTIC.