Immunoglobulin M Multiple Myeloma: Case Report of a Rare Variant of Multiple Myeloma with Diagnostic and Treatment Challenges

Immunoglobulin M (IgM) multiple myeloma (MM) is an exceptionally rare plasma cell malignancy, representing <0.5% of all MM cases. The diagnosis presents significant challenges due to overlapping clinical features with Waldenström macroglobulinemia and other IgM-producing lymphoproliferative disorders. We report a 64-year-old female who presented with a 3-week history of persistent lower back pain. Initial laboratory evaluation revealed mild anemia (hemoglobin 9.2 g/dL), markedly elevated serum IgM levels (5,070 mg/dL), and a prominent M-spike (3.09 g/dL) on serum protein electrophoresis. Immunofixation electrophoresis confirmed monoclonal IgM lambda gammopathy with an abnormal free light chain ratio (0.12). Beta-2 microglobulin was elevated at 2,413 ng/mL, suggesting a high tumor burden. Bone marrow trephine biopsy demonstrated 25% plasma cell infiltration with lambda light chain restriction on in situ hybridization. Positron emission tomography computed tomography imaging revealed multiple hypermetabolic lytic skeletal lesions throughout the axial and appendicular skeleton. The absence of lymphoplasmacytic infiltration, hepatosplenomegaly, or hyperviscosity symptoms and negative MY88 and negative Cxcr4 mutation effectively differentiated this presentation from Waldenström macroglobulinemia. The patient was treated with a bortezomib-based regimen including bortezomib, lenalidomide, and dexamethasone, along with supportive therapy including bisphosphonates and thromboprophylaxis. This case highlights the diagnostic complexity of IgM MM and emphasizes the importance of comprehensive evaluation, including bone marrow examination, advanced imaging, and detailed protein studies for accurate differentiation from other IgM-producing disorders. Early recognition and appropriate treatment with novel agents may improve outcomes in this rare myeloma variant.