Simple SummaryWaldenström’s macroglobulinemia is a lymphoproliferative disorder rarely described in veterinary medicine. According to the human classification of hematopoietic tumors, this disease is defined as a subtype of lymphoplasmacytic lymphoma with bone marrow involvement and monoclonal gammopathy of IgM type. Cytopathology is a convenient and accurate diagnostic procedure to diagnose lymphoma in dogs. However, ancillary techniques, such as PCR for antigen receptor rearrangement, flow cytometry, immunohistochemistry, and histology, are usually required to fully characterize the grade and phenotype, especially in ambiguous cases. Immunosecretory lymphoproliferative disorders result from malignant clonal expansion of B-cells and are usually characterized by hyperglobulinemia, although normoglobulinemia can also occur, hypoglobulinemia being rarer. Monoclonal gammopathy can be suspected on serum protein electrophoresis as it usually migrates as a narrow peak in the γ or β fractions, but immunofixation is required for confirmation and characterization. This case report describes clinicopathologic features, diagnosis, treatment, and the outcome of Waldenström’s macroglobulinemia in a 2-year-old neutered female Small Munsterlander dog with atypical bimorphic plasmacytoid differentiation and unusual M-protein migration on serum protein electrophoresis.AbstractA 2-year-old neutered female Small Munsterlander dog was presented for an insect bite. Physical examination revealed a poor body condition, a peripheral lymphadenomegaly, and suspected splenomegaly. A complete blood count (Sysmex XN-V) revealed marked leukocytosis with lymphocytosis and abnormal dot plots. An abnormal monomorphic lymphoid population and marked rouleaux formation were noted on the blood smear. Lymph node aspirates contained an atypical bimorphic population of lymphocytes, either with a plasmacytoid or a blastic appearance. This double population was also found in the spleen, liver, bone marrow, tonsils, and other tissues. Peripheral blood and lymph node clonality assays revealed clonal BCR gene rearrangement. Flow cytometry revealed a mixed population of small-sized B-cells (CD79a+ CD21+ MHCII+) and medium-sized B-cells (CD79a+ CD21− MHCII−) in lymph nodes and a dominant population of small-sized mature B-cells (CD21+ MHCII+) in peripheral blood. Though normoproteinemic, serum protein electrophoresis revealed an increased α2-globulin fraction with an atypical restricted peak, identified as monoclonal IgM by immunofixation. Urine protein immunofixation revealed a Bence-Jones proteinuria. A diagnosis of Waldenström’s macroglobulinemia was made. Chemotherapy was initiated, but the dog was euthanized 12 months after the initial presentation due to marked clinical degradation.