Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorder. It is defined by the presence of a serum monoclonal protein (M-protein), at a concentration <3 g/dL, and a bone marrow with <10 percent monoclonal plasma cells, if done, and in the absence of end organ damage (lytic bone lesions, anemia, hypercalcemia, renal insufficiency, hyperviscosity) related to the proliferative process.
MGUS occurs in over 3 percent of the general Caucasian population over the age of 50 and is typically detected as an incidental finding when patients undergo a protein electrophoresis as part of an evaluation for a wide variety of clinical symptoms and disorders (eg, peripheral neuropathy, vasculitis, hemolytic anemia, skin rashes, hypercalcemia, or elevated erythrocyte sedimentation rate).
There are three distinct clinical types of MGUS, each with a risk of progressing through a unique intermediate (more advanced) premalignant stage and then to a malignant plasma cell dyscrasia or lymphoproliferative disorder :
●Non-IgM MGUS (IgG, IgA, or IgD MGUS) — Non-IgM MGUS is the most common subtype of MGUS and has the potential to progress to smoldering (asymptomatic) multiple myeloma and to symptomatic multiple myeloma. Less frequently, these patients progress to AL amyloidosis, light chain deposition disease, or another lymphoproliferative disorder.
●IgM MGUS — IgM MGUS accounts for approximately 15 percent of MGUS cases. It is considered separately from the non-IgM MGUS because it has the potential to progress to smoldering Waldenström macroglobulinemia and to symptomatic Waldenström macroglobulinemia and less often to lymphoma or AL amyloidosis. Infrequently, IgM MGUS can progress to IgM multiple myeloma.