Monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell disorder and refers to the presence of an abnormal monoclonal antibody in the blood but the absence of the overt bone marrow and clinical signs of multiple myeloma.

MGUS is the most common plasma cell disorder. In one American study it was found to be present in 3.2% of patients over the age of 50 years 6. MGUS prevalence increases with advancing age 6.

The condition is asymptomatic.

The criteria for MGUS diagnosis according to the International Myeloma Working Group include 1:

  • serum M-protein <3 g/dL
  • clonal plasma cell population present in the bone marrow (<10% cellularity)
  • absence of end-organ damage (e.g. hypercalcemia, renal insufficiency, lytic lesions, anemia)

Genetic changes including hyperdiploidy, IgH translocations and cyclin D gene dysregulation seem to be important in the transition from a normal plasma cell to a pre-malignant plasma cell such as that found in MGUS or smouldering myeloma 2. Clonal expansion of a single pre-malignant plasma occurs which produces excess paraprotein of one of the immunoglobulin types (e.g. IgG, IgM). However, further changes are needed to transition into a myeloma cell 2.

Ninety-percent of multiple myeloma patients are seen to have been in an MGUS phase before transitioning into multiple myeloma 5. Factors that predict an increased risk of multiple myeloma progression from MGUS include non-IgM MGUS and paraprotein levels over 1.5 g/dL 2.

Osteoporosis and vertebral fractures are more common in MGUS patients than in healthy controls 3.

MRI is not indicated in the initial work-up of MGUS patients unless there is an increased suspicion of multiple myeloma progression 4.

MGUS patients usually will have a normal appearing bone marrow:

  • T1: hyperintense
  • T2: hypointense

However, focal lesions that may represent infiltration by monoclonal plasma cells may be present and these patients have an increased risk to transforming into multiple myeloma 4

MGUS patients are generally under surveillance with regular repeat blood tests and imaging. Up to 1% of patients with MGUS transition into multiple myeloma per year 7.

The condition now known as MGUS was first described by the Swedish physician Jan Walderström (1906-1996) in 1961 and termed "essential benign hypergammaglobulinemia" 2. The term MGUS first appeared in 1978 2.

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Article information

rID: 60248
System: Haematology
Tag: cases
Synonyms or Alternate Spellings:
  • Monoclonal gammopathy of uncertain significance
  • Monoclonal gammopathy of unknown significance
  • MGUS

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