Serum Protein Electrophoresis And Multiple Myeloma With Link To And Excerpts From “Screening panels for detection of monoclonal gammopathies”

This infographic is from Dr. Ann Kumfer, @annkumfer on Twitter.

See also Screening panels for detection of monoclonal gammopathies [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Clin Chem. 2009 Aug;55(8):1517-22.

All that follows is from the above resource.



The repertoire of serologic tests for identifying a monoclonal gammopathy includes serum and urine protein electrophoresis (PEL), serum and urine immunofixation electrophoresis (IFE), and quantitative serum free light chain (FLC). Although there are several reports on the relative diagnostic contribution of these assays, none has looked at the tests singly and in combination for the various plasma cell proliferative disorders (PCPDs).


Patients with a PCPD and all 5 assays performed within 30 days of diagnosis were included (n = 1877). The diagnoses were multiple myeloma (MM) (n = 467), smoldering multiple myeloma (SMM) (n =191), monoclonal gammopathy of undetermined significance (MGUS) (n = 524), plasmacytoma (n = 29), extramedullary plasmacytoma (n = 10), Waldenström macroglobulinemia (WM) (n = 26), primary amyloidosis (AL) (n = 581), light chain deposition disease (LCDD) (n =18), and POEMS syndrome (n = 31).


Of the 1877 patients, 26 were negative in all assays. Omitting urine from the panel lost an additional 23 patients (15 MGUS, 6 AL, 1 plasmacytoma, 1 LCDD), whereas the omission of FLC lost 30 patients (6 MM, 23 AL, and 1 LCDD). The omission of serum IFE as well as urine lost an additional 58 patients (44 MGUS, 7 POEMS, 5 AL, 1 SMM, and 1 plasmacytoma).


The major impact of using a simplified screening panel of serum PEL plus FLC rather than PEL, IFE, and FLC is an 8% reduction in sensitivity for MGUS, 23% for POEMS (7 patients), 4% for plasmacytoma (1 patient), 1% for AL, and 0.5% for SMM. There is no diminution in sensitivity for detecting MM, macroglobulinemia, and LCDD.

Because of the secreted monoclonal immunoglobulin, plasma cell proliferative disorders (PCPDs)4 are generally classified among monoclonal gammopathies. These diseases include malignant disorders such as multiple myeloma (MM), plasmacytoma, plasma cell leukemia, and Waldenström macroglobulinemia (WM); premalignant diseases such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM); and protein or low tumor burden diseases such as primary amyloidosis (AL), light chain deposition disease (LCDD), and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes). Because of the wide range of biology and disease presentations, identification of the monoclonal immunoglobulin may often be the first clue to the diagnosis. The recognition of the monoclonal protein may be trivial or may require multiple approaches. The malignant disease of MM, for example, usually presents with a significant amount of monoclonal protein, but even within this malignant diagnosis, there is a subclassification of nonsecretory MM which secretes little or no monoclonal protein.

The diagnostic screening panels for patients suspected of MM, AL, and related monoclonal gammopathies have traditionally included protein electrophoresis (PEL) and immunofixation electrophoresis (IFE) of both serum and urine (). The recent introduction of quantitative serum assays for immunoglobulin free light chain (FLC), however, has increased the sensitivity of laboratory testing strategies for identifying monoclonal gammopathies (); this increased diagnostic sensitivity is readily apparent in the monoclonal light chain diseases (). Because of the increased sensitivity for free light chain diseases, the most recent diagnostic screening recommendations are that serum IFE plus FLC is a sufficient screening panel for PCPDs other than AL (). It is recommended, however, that screening for AL should also include urine IFE.



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