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.