Smoldering Waldenström macroglobulinemia coexisting with myelodysplastic syndrome: a rare case report and literature review.

Waldenström macroglobulinemia (WM) is a low-grade non-Hodgkin lymphoplasmacytic lymphoma of the bone marrow, characterized by production of monoclonal immunoglobulin M (IgM) protein. Smoldering Waldenström macroglobulinemia (SWM) is asymptomatic and exhibits an increased risk of progression to WM. Myelodysplastic syndrome (MDS) arises from blood cancer in the hematopoietic stem cell compartment, featuring dysplastic changes in bone marrow and blood cells, along with cytopenias, including anemia, neutropenia, or thrombocytopenia. Their coexistence is extremely rare. We report a 74-year-old woman with IgM monoclonal gammopathy, anemia, and bone marrow dysplasia. Initially treated as WM, persistent cytopenias prompted reevaluation, leading to a revised diagnosis of SWM with MDS-IB-1 MDS with increased blasts-1. After six cycles of azacitidine, she achieved remission of MDS but rapidly progressed to AML and ultimately died. This case provides a key clinical lesson: persistent cytopenias during ibrutinib therapy were attributable to MDS progression rather than SWM, underscoring the importance of re-evaluation. Furthermore, it completely documents clonal evolution from 2.5% blasts (MDS with low blasts) to 6% blasts (MDS with increased blasts-1) and ultimately to AML (66% blasts), and it introduces the emergence of an FLT3-ITD mutation that rapidly drove the disease into AML even after the patient had achieved MDS remission. We also review the rare coexistence of WM and MDS/AML, and MGUS with MDS.