Unmasking complex polymerization interferences in multiple myeloma diagnostics: A case study

Monoclonal gammopathies, defined by the clonal overexpression of immunoglobulins, are typically diagnosed using serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and serum free light chain (FLC) assays. However, atypical immunoglobulin structures can introduce diagnostic challenges. We describe a case of IgG-lambda multiple myeloma presenting with a double M-spike on SPEP: one in the anodal gamma region and another in the cathodal gamma region, mimicking biclonal gammopathy. IFE showed biclonal-like lambda bands, and serum lambda FLC levels were markedly elevated by turbidimetric analysis. These discrepancies were resolved following treatment with dithiothreitol (DTT), which disrupted disulfide-linked lambda FLC polymers, confirming that polymerization was the source of the assay interferences. This case study highlights the critical role of DTT treatment in FLC lambda multiple myeloma that by breaking FLC lambda polymers into monomers, the overestimation by turbidimetric method of FLC lambda level can be dramatically improved.