Monoclonal Gammopathy of Unknown Significance
GENERAL PRINCIPLES
Definition
Monoclonal gammopathy of unknown significance (MGUS) is a commonly occurring premalignant condition characterized by the presence of a small (lt;10%) population of neoplastic, clonal plasma cells or lymphoplasmacytic cells in the BM that occurs in the absence of any end-organ damage.
DIAGNOSIS
• Patients with MGUS are asymptomatic and diagnosed when a monoclonal protein is detected on serum protein electrophoresis (SPEP) during workup of an elevated serum protein or other unrelated clinical finding.
• Serum free light chain assay is used in both the prognosis of MGUS and in the diagnosis of multiple myeloma.
• The Multiple Myeloma International Working Group diagnostic criteria for non-IgM MGUS requires all three of the following criteria28,29:
î Presence of a serum monoclonal protein (non-IgM type) lt;3 g/dL
î Presence of clonal BM plasma cells comprising lt;10% of the marrow
î Absence of end-organ damage attributed to the underlying plasma cell disorder, such as
hypercalcemia, renal insufficiency, anemia, or lytic bone lesions
• The Multiple Myeloma International Working Group diagnostic criteria for IgM MGUS requires the following diagnostic criteria28,29:
î Serum IgM monoclonal protein lt;3 g/dL
î BM lymphoplasmacytic infiltration lt;10%
î No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, hepatosplenomegaly, or other end-organ damage that can be attributed to the underlying lymphoproliferative disorder
TREATMENT
There is no treatment recommended for MGUS. The vast majority of patients will not progress to myeloma. Yearly surveillance with a CBC, serum creatinine and calcium, SPEP, urine protein electrophoresis (UPEP), and serum free light chains is recommended. If a patient develops an anemia, hypercalcemia, renal dysfunction, or bone pain, additional evaluation including a BM biopsy and imaging (i.e., skeletal survey, positron emission tomography, CT scan, or MRI) is recommended.
Prognosis
For non-IgM MGUS, progression to a more serious disorder including multiple myeloma, Waldenstrom macroglobulinemia (WM), or primary amyloidosis (AL) occurs at a rate of approximately 1% per year. For IgM MGUS, progression to WM or primary AL amyloidosis occurs at a rate of 1%-5% per year. Factors for higher risk of progression include an M protein gt;1.5 g/dL, non-IgG monoclonal gammopathy, and abnormal serum free light chain ratio (lt;0.26 or gt;1.65).