Monoclonal Gammopathy of Undetermined Significance (MGUS)

Key Features

Monoclonal immunoglobulin (ie, paraprotein) in the serum (< 3 g/dL {< 30 g/L}) or urine
Clonal plasma cells in the bone marrow < 10% (if performed)
No symptoms and no organ damage from the paraprotein
MGUS is present in 1% of all adults
- 3% of those over age 50 years
- > 5% of those over age 70 years
Among all patients with paraproteins, MGUS is far more common than plasma cell myeloma

Defined as bone marrow monoclonal plasma cells < 10% in the setting of a paraprotein (serum M-protein < 3 g/dL [30 g/L]) and the absence of plasma cell–related end-organ damage
If an excess of serum free light chains (kappa or lambda) is established, the kappa to lambda ratio is 100 or less or 0.01 or greater
In approximately one-quarter of cases, MGUS progresses to overt malignant disease in a median of one decade
The transformation of MGUS to plasma cell myeloma is ~ 1% per year
Twelve percent of patients with MGUS will convert to amyloidosis in a median of 9 years
Plasma cell myeloma, smoldering plasma cell myeloma, and MGUS must be distinguished from reactive (benign) polyclonal hypergammaglobulinemia (which is commonly seen in cirrhosis or chronic inflammation)

To establish the diagnosis,
- Serum or urine, or both, should be sent for protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) to search for a monoclonal protein
- Serum should be sent for free light chain analysis and quantitative immunoglobulins
Additional tests include a hemoglobin and serum albumin, calcium, and creatinine
If these additional tests are normal (or if abnormal but are otherwise explained), then a bone marrow biopsy is usually deferred provided the serum M-protein is < 3 g/dL (< 30 g/L)
Radiographs are obtained in asymptomatic individuals
MRI or PET-CT imaging is preferred there are some bone complaints or a question regarding bone disease
MGUS is diagnosed if patients do not meet the criteria for smoldering plasma cell myeloma or plasma cell myeloma