MGUS

Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which a monoclonal protein (M-protein) is present in the blood without evidence of a malignant plasma cell disorder or related organ damage. MGUS is typically asymptomatic and is often found incidentally during routine testing. It is considered premalignant because a proportion of cases progress to multiple myeloma or other hematologic cancers.

MGUS is more common in older adults. Prevalence increases with age, with about 3% of people over 50 affected and higher rates in the elderly. The condition carries a lifetime risk of progression to a malignant disorder of roughly 10–15%. The annual risk of progression is about 1%, though risk varies by subtype and other factors. IgM MGUS has a higher chance of progressing to Waldenström macroglobulinemia or related disorders, while non-IgG MGUS more often progresses to multiple myeloma or related diseases.

Diagnosis requires specific criteria: M-protein in serum less than 3 g/dL, bone marrow plasma cells less than 10%, and no CRAB features (hypercalcemia, renal failure, anemia, bone lesions) or myeloma-defining events. Tests such as serum protein electrophoresis, immunofixation, and free light-chain analysis help establish the presence and characteristics of the M-protein.

Risk stratification uses three factors: M-protein level greater than 1.5 g/dL, non-IgG isotype (IgA or IgM), and an abnormal free light-chain ratio. More adverse factors confer higher progression risk.

Management is watchful waiting. Patients undergo periodic monitoring with history, physical examination, and laboratory testing (CBC, calcium, creatinine, quantitative immunoglobulins, serum electrophoresis/immunofixation, and possibly free light chains). Bone marrow biopsy is not routinely required unless diagnostic doubt or progression occurs. Prognosis varies; many individuals live many years with MGUS without progression.