https://orcid.org/0000-0002-5442-4699
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Melissa R Snyder, Commentary on Hiding in Plain Sight: Protein Electrophoresis Profile Inconsistent with Patient’s Diagnosis, Clinical Chemistry, Volume 71, Issue 2, February 2025, Page 253, https://doi.org/10.1093/clinchem/hvae162
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In this article, Pandya and Delgado present a case of a patient with Waldenstrom macroglobulinemia (WM) in which the IgM monoclonal protein was not observed by capillary zone electrophoresis (CZE) but was detected by immunofixation electrophoresis (IFE). Assessment for monoclonal proteins is a critical part of the diagnostic evaluation of patients with suspected plasma cell proliferative disorders (PCPDs). A variety of methods are available for detection and characterization of monoclonal proteins, including CZE, serum protein electrophoresis, serum IFE, total immunoglobulin quantitation, and serum-free light chains (sFLCs). Because these assays are often used as screening tests, the goal is to achieve maximum sensitivity. As immunoglobulins are heterogeneous molecules, different methods may demonstrate different sensitivities depending on the specific characteristics of the monoclonal protein. To improve sensitivity, testing panels consisting of 2 or more methods could be considered. For example, the International Myeloma Working Group recommends a panel of serum protein electrophoresis, IFE, and sFLC for evaluation of patients with suspected multiple myeloma and related PCPDs (1). In the presented case, total IgM testing was performed; a significant increase above the reference range was observed, which was inconsistent with the negative finding by CZE. In addition, the authors noted an unusual pattern on the CZE, which could suggest altered migration due to the presence of a monoclonal protein. The authors mention the utility of sFLC as part of the investigation of this unusual electrophoresis pattern; in fact, guidelines from the British Society for Hematology include sFLC as a test useful for the diagnostic evaluation for WM (2). The sFLC test was not performed in this case, and it is interesting to consider whether this sample would have shown an abnormal ratio and whether a panel consisting of CZE and sFLC would improve overall sensitivity for WM and other PCPDs.
