Monoclonal Gammopathy of Undetermined Significance: A Perspective from Laboratorians

Monoclonal Gammopathy of Undetermined Significance (MGUS) is defined as the presence of a monoclonal protein (M-protein) detected by electrophoresis in serum or urine or an abnormal free light chain ratio (FLCR). The concentration of M protein is <3.0 g/dl, with <10 percent plasma cells on bone marrow biopsy (if performed). Moreover, patients lack CRAB-related clinical features such as hyperCalcemia, Renal dysfunction, Anemia and lytic Bone lesions. MGUS is present in over 3% of persons > 50 years of age. Most MGUS are of the IgG subtype. For non-IgM –MGUS (IgG, IgA, IgD, IgE), the risk of progression to multiple myeloma, amyloidosis or a related disorder is 1.0 percent per year. For IgM-MGUS the risk of progression to Waldenstrom’s macroglobulinemia or IgM myeloma is 1.5 percent per year. For light chain MGUS the risk of progression to light chain myeloma or amyloidosis is 0.3% per year. The Mayo Clinic criteria for greatest progression over 20 years include a M-protein level ≥ 1.5 g/dl, non-IgG M-protein and an increase in the FLCR. In any patient with an M protein and unexplained end organ dysfunction, it is imperative to rule out Monoclonal Gammopathy of Clinical Significance manifesting as renal disease, neuropathy etc. since potential treatments could be offered. Most importantly, studies have suggested that MGUS screening should be actively discouraged. Finally, much further research is needed to identify biomarkers that will more accurately predict progression to malignancies in patients with MGUS.