Abstract
Laboratory detection of monoclonal immunoglobulins is essential for the diagnosis and monitoring of monoclonal gammopathies (MGs). In alignment with the recent effort from the College of American Pathologists (CAP) to develop evidence-based clinical practice guideline for laboratory detection and initial diagnosis of MGs, we retrospectively collected 1-year laboratory results from three tests, including serum protein electrophoresis (SPEP) with reflex to immunofixation (IFE), urine protein electrophoresis (UPEP) with reflex to immunofixation (IFE), and serum free light chain analysis (FLC), to identify the current ordering patterns from clinical care providers and analyze the diagnostic performances of these tests. From February 2018 to February 2019, there were a total of 5,614 SEPEs ordered with 19% reflexed for IFE. Among these, 70% were reported negative for SPEP without reflexing to IFE and 5% were reported negative after confirmation by IFE, with the rest being positive for monoclonal immunoglobulin(s) confirmed by either current or previous IFE results. Together with SPEP, FLC was ordered more often than UPEP (36% vs 19% of the total SPEP orders), with 12% of these having all three tests ordered. Using serum immunofixation results as a reference, we compared the diagnostic performance of UPEP and FLC as initial screening tools, with FLC considered abnormal if abnormal kappa/lambda ratio was accompanied with at least one elevated free light chain concentration. FLC had slightly higher sensitivity compared to UPEP (63% vs 56%) but with lower positive predictive value (69% vs 82%). When combining FLC with UPEP, the sensitivity increased to 79% with a positive predictive value of 71%. Interestingly, FLC and UPEP also showed various sensitivity in detecting specific type of free light chains, with FLC being positive in 81% of UPEP with detectable free kappa light chain, but only positive in 62% of UPEP with detectable free lambda light chain. Due to the reflex algorithm nature, those specimens with negative SPEP were not reflexed for IFE and therefore could not be used to assess the performance of FLC and UPEP. In summary, FLC was more frequently ordered than UPEP in addition to SPEP by our clinicians, although the majority of SPEPs were still ordered alone. In our practice, FLC and UPEP had comparable performance, with FLC showing slightly higher sensitivity but lower specificity. The current data did not support the replacement of one with the other, given that there was only 50% overlapping on positive identifications between FLC and UPEP. Further studies to include serum IFE for all specimens and clinical correlations would be beneficial to fully assess the diagnostic performance of FLC and UPEP, as well as their utilizations for various patient populations and clinical purpose.
Serum Free Light Chain Analysis for Diagnosis, Monitoring, and Prognosis of Monoclonal Gammopathies