IgM aggregation in a Waldenström macroglobulinemia patient caused pseudo-negative serum protein electrophoresis results, highlighting that false-negative electrophoresis can occur in WM and should not exclude the diagnosis.
Key Findings
Results
A 79-year-old male with Waldenström macroglobulinemia showed pseudo-negative (false-negative) serum protein electrophoresis results due to IgM aggregation.
The patient presented with anemia lasting 10 months accompanied by edema in both lower limbs and testicles.
Serum protein electrophoresis failed to detect the monoclonal IgM protein, producing a false-negative result.
The false-negative result was attributed to IgM aggregation, a known property of IgM molecules in WM patients.
The diagnosis of WM was ultimately confirmed through a series of tests including serological testing, serum protein electrophoresis, and genetic testing.
Background
The patient was diagnosed with Waldenström macroglobulinemia, a type of IgM-secreting lymphoplasmacytic lymphoma characterized by accumulation of clonal lymphocytes, lymphoplasmacytes, and plasma cells.
WM is primarily caused by the accumulation of clonal lymphocytes, lymphoplasmacytes, and plasma cells.
Monoclonal IgM proteins secreted by these cells result in high blood viscosity.
The patient presented with refractory anemia that progressively worsened over 10 months.
The case supports considering lymphomas such as WM in the differential diagnosis for elderly patients with refractory anemia.
Results
Treatment with red blood cell suspension transfusion and targeted therapy with zanubrutinib resulted in clinical improvement.
The patient received a red blood cell suspension transfusion and targeted therapy with zanubrutinib.
Following treatment, the patient's dizziness and fatigue symptoms improved.
No new blood blisters developed after treatment was initiated.
The anemia resolved following the treatment regimen.
Discussion
IgM aggregation in WM patients can cause false-negative electrophoresis results, potentially leading to diagnostic errors.
The case highlights that clinicians should be aware that IgM aggregates in WM patients can cause false-negative electrophoresis results.
Standard serum protein electrophoresis may fail to identify the monoclonal protein spike in WM due to this aggregation phenomenon.
Additional or alternative diagnostic testing should be considered when WM is clinically suspected despite negative electrophoresis.
The authors note this as a key diagnostic pitfall warranting attention in clinical practice.
What This Means
This case report describes a 79-year-old man who had worsening anemia for 10 months along with swelling in his legs and testicles. After extensive testing, he was diagnosed with Waldenström macroglobulinemia (WM), a rare type of blood cancer in which abnormal immune cells produce large amounts of a protein called IgM. A key finding was that one of the standard blood tests used to detect this disease — serum protein electrophoresis, which separates blood proteins to look for abnormal ones — gave a falsely negative result, meaning it appeared normal even though the disease was present. This happened because IgM proteins in WM tend to clump together (aggregate), which can prevent them from being detected by this test.
This research suggests that a negative serum protein electrophoresis result does not necessarily rule out Waldenström macroglobulinemia. Doctors evaluating elderly patients with persistent, worsening anemia that doesn't respond to typical treatments should consider WM as a possible diagnosis even when this standard test comes back normal. Additional testing methods may be needed to confirm or exclude the condition in such cases.
The patient was treated with blood transfusions and a targeted cancer drug called zanubrutinib, after which his symptoms — including dizziness, fatigue, and anemia — improved. The case serves as an important reminder that laboratory tests have limitations and that clinical judgment, combined with multiple types of testing, is essential for accurate diagnosis of complex blood cancers like WM.
Xie H, He E, Quan H, Zhang S. (2026). Pseudo-negative serum protein electrophoresis due to IgM aggregation in a patient with Waldenström macroglobulinemia: A case report.. Medicine. https://doi.org/10.1097/MD.0000000000050717