Defects and countermeasures in laboratory diagnosis of rare IgE multiple myeloma

Abstract

Background: IgE multiple myeloma (MM) is a rare subtype of MM that is easily misdiagnosed. We report a rare case of IgE-MM and investigate the application of the SLiM-CRAB criteria to screen for high-risk smoldering MM (SMM) patients, so as to summarize the causes and methods used to prevent missed diagnosis or misdiagnosis in IgE-MM.

Methods: The serum monoclonal protein (M-protein) classification and IgE quantification was performed and sent to several individual institutions. The results were collected and the causes of IgE detection defects were analyzed.

Results: Upon admission to our hospital, the patient's serum free kappa light chain was 1069.9 mg/L, free lambda light chain was 9.2 mg/L, and free kappa/lambda ratio was 115.9, which met the SLiM criteria, but without CRAB features. Immunofixation electrophoresis (IF) showed "M-like protein aggregation bands" in all lanes. After pretreatment with 1% β-mercaptoethanol to depolymerize the aggregation of monoclonal protein, the "M-like protein aggregation bands disappeared. The other five institutions did not provide the correct typing results. The quantification of serum IgE was as high as 2.06 × 10⁷ IU/mL, whereas 7 other testing institutions reported IgE levels ranging from 1.0 to 1100 IU/mL.

Conclusion: High-risk biomarkers in SLiM criteria can achieve good therapeutic effects in rare IgE-MM patients. Serum immunofixation performed without antisera against IgE, insufficient identification of the lytic bands produced by high macromolecule aggregation in IF, and the absence of a prozone effect avoidance procedure during IgE quantitative detection are the primary causes of missed diagnosis or misdiagnosis in patients with IgE-MM.

Keywords: Free light chain; Monoclonal protein; Multiple myeloma; Prozone effect; immunoglobulin E.