Cold agglutination as a pivotal diagnostic clue for Waldenström macroglobulinemia: A rare case report with diagnostic and therapeutic insights.

Waldenström macroglobulinemia (WM) is a rare indolent B-cell lymphoproliferative disorder characterized by bone marrow infiltration and monoclonal immunoglobulin M (IgM) secretion, which poses diagnostic challenges in the early stage. The present study reported on a 63-year-old male with WM presenting with cough, hyperviscosity syndrome (dizziness, weakness, fatigue, blurred vision), severe anemia and cold agglutination in August 2023. After 37˚C incubation to eliminate cold agglutination interference, laboratory tests confirmed severe anemia (hemoglobin, 54 g/l), hyperglobulinemia (globulin, 92 g/l) and markedly elevated serum IgM (83.6 g/l). Peripheral blood smear showed erythrocyte rouleaux formation and plasmacytoid lymphocytes. Bone marrow biopsy revealed 80% infiltration of B-lymphomatous cells, 10% abnormal plasma cells and only 10% residual normal hematopoietic cells. Serum/urine immunoelectrophoresis identified IgM-λ paraprotein and free λ light chains. Bone marrow flow cytometry detected a prominent abnormally mature B-lymphocyte population (72.2% of lymphocytes) positive for CD19, CD20 and cytoplasmic λ (cλ); partially positive for CD23, CD25 and CD27; and negative for CD5, CD10 and CD103. Abnormal plasma cells (0.3% of nucleated cells) showed cλ restriction; strong expression of CD38, CD138 and CD19; partial expression of CD20 and CD27; and absence of CD5, CD10 and CD56. Genetic testing confirmed the MYD88 innate immune signal transduction adaptor (MYD88) L265P mutation positivity via allele-specific PCR and 14q32/11q13 translocation negativity using fluorescence in vitro hybridization, confirming the diagnosis of WM. The patient received therapeutic plasma exchange (TPE) followed by bortezomib-dexamethasone chemotherapy, resulting in resolved cold agglutination, alleviated hyperviscosity syndrome and improved laboratory indicators. Follow-up was performed immediately after discharge; however, it was terminated after 1 month (November 2023) due to re-admission for pulmonary infection. In conclusion, cold agglutination is a pivotal diagnostic clue for WM; combined immunophenotyping and MYD88 L265P detection enables definitive diagnosis, and early TPE plus chemotherapy effectively ameliorates clinical manifestations.