Summary: Pretreatment characteristics of 138 dogs with malignant lymphoma were analyzed to determine prognostic factors associated with outcome (ie, complete response rate, time to relapse after complete response, survival time). Dogs were all treated for 10 weeks, using a standard induction chemotherapy protocol, and were then given asparaginase weekly. Once the disease became progressive, second-line chemotherapy was instituted. Age, sex, weight, clinical stage, performance grade, immunophenotype, and malignancy grade assigned according to the National Cancer Institute's Working Formulation were not associated with complete response rate. However, malignancy grade assigned according to the Kiel classification was found to be associated with complete response rate; dogs with high-grade malignancies had a significantly higher complete response rate than did dogs with low-grade malignancies. By means of multivariate analysis, clinical stage and immunophenotype were found to be prognostic factors for time to relapse (among dogs that had had a complete response) and survival time. In addition, malignancy grade assigned according to the Kiel classification was found to be a prognostic factor for time to relapse; whereas, malignancy grade assigned according to the Working Formulation was determined to be a prognostic factor for survival time.

Histologic grade is an important determinant in clinical outcome of human osteosarcoma (OS). In this study, the histologic characteristics of primary and metastatic canine OS were evaluated using a new classification system. Histologic characteristics were classified in 166 primary and 34 metastatic canine OS. Prognostic variables for clinical outcome were determined using multivariate analysis. Most OS were histologically characterized by severe to extreme cellular pleomorphism, a variable number of mitoses, small to moderate amounts of matrix, a high percentage of tumor cells, and minimal to moderate amounts of necrosis. Tumor invasion into vessels was present in 117/152 (71%) tumors, and 12/50 (24%) of the regional lymph nodes had evidence of metastasis. Classification of the 166 tumors resulted in seven (4%) grade I, 34 (21%) grade II, and 125 (75%) grade III OS. In the multivariate analysis, histologic grade III OS and elevated pretreatment plasma alkaline phosphatase (AP) levels were independent predictors of clinical outcome. Dogs with high-grade tumors and elevated AP should be carefully evaluated for the presence of metastatic disease before starting adjunctive therapy protocols.

The aim of this study was to investigate the prognostic importance of different clinical, immunohistologic and tumorproliferation characteristics in dogs with malignant lymphoma treated with chemotherapy. From 74 dogs with malignant lymphoma at least one enlarged peripheral lymph node was taken for biopsy before chemotherapy following a standardized protocol (vincristine, cyclophosphamide, prednisolone, doxorubicin, and L-asparaginase). The variables evaluated as prognostic factors were age, sex, and tumor stage, as well as histomorphologic grade (Kiel classification, Working Formulation), immunophenotype (using markers for CD3 and CD79a), and cell proliferation (Ki-67, proliferation cell nuclear antigen, mitotic index, and argyrophil nucleolar organizer regions [AgNORs]) in extirpated lymph nodes. All markers were used on routinely formalin-fixed, paraffin-embedded tissues. The AgNORs were assessed qualitatively, based on the AgNOR pattern distribution, and quantitatively using image analysis and routine counting. In both univariate and multivariate survival analyses, AgNORs were a valuable prognostic marker for the treatment of canine malignant lymphomas. Based on the results of the multivariate analysis longer survival time correlated with a B-cell type, a larger mean AgNOR area, a larger total AgNOR area, a shorter distance between two AgNORs, and a smaller AgNOR area to nucleus ratio. Longer disease-free survival time correlated with a smaller number of AgNORs per nucleus, a larger mean AgNOR area, a larger maximal AgNOR area, and a larger total AgNOR area. This study clearly demonstrates the additional benefit of the use of AgNORs in predicting treatment outcome in dogs with malignant lymphoma.

(1994). Canine malignant lymphoma: A review and comparison with human non‐hodgkin's lymphoma. Veterinary Quarterly: Vol. 16, No. 4, pp. 209-219.