Pseudo-negative serum protein electrophoresis due to IgM aggregation in a patient with Waldenström macroglobulinemia

Rationale: Waldenström macroglobulinemia (WM) is a type of immunoglobulin M (IgM)-secreting lymphoplasmacytic lymphoma primarily caused by the accumulation of clonal lymphocytes, lymphoplasmacytes, and plasma cells. The monoclonal IgM proteins secreted by these cells result in high blood viscosity. Patient concerns: A 79-year-old male presented with anemia lasting 10 months accompanied by edema in both lower limbs and testicles. Diagnoses: After a series of tests, including serological testing, serum protein electrophoresis, and genetic testing, the patient was ultimately diagnosed with WM. Interventions: The patient received a red blood cell suspension transfusion and targeted therapy with zanubrutinib. Outcomes: The patient’s dizziness and fatigue symptoms improved, no new blood blisters developed, and the anemia resolved. Lessons: This case highlights that clinicians should consider lymphomas such as WM in the differential diagnosis for elderly patients with refractory anemia that progressively worsens. Also, note that IgM aggregates in WM patients can cause false-negative electrophoresis results.