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Monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance
Classification & external resources
ICD-10 D47.2
ICD-9 273.1
DiseasesDB 1341
eMedicine med/1495 
MeSH D008998

Monoclonal gammopathy of undetermined significance (MGUS, unknown or uncertain may be substituted for undetermined) or benign monoclonal gammopathy is a condition in which a low or non-quantifiable level of a monoclonal paraprotein is detected in the blood by means of protein electrophoresis. In addition, some patients develop a polyneuropathy (damage to peripheral nerves) or other problems related to the secreted antibody. MGUS is distinct from multiple myeloma, as described below.

Additional recommended knowledge



Patients may be diagnosed with MGUS if they fulfill the following three criteria:[1]

  1. A monoclonal paraprotein band less than 3 g/dl;
  2. Plasma cells less than 10% on bone marrow examination; and
  3. No evidence of bone lesions, anemia, hypercalcemia, or renal insufficiency related to the paraprotein.

Differential diagnosis

Several other illnesses can present with a monoclonal gammopathy, and the monoclonal protein may be the first discovery before a formal diagnosis is made:


Pathologically, the lesion in MGUS is in fact very similar to that in multiple myeloma. There is a predominance of clonal plasma cells in the bone marrow with an abnormal immunophenotype (CD38+ CD56+ CD19−) mixed in with cells of a normal phenotype (CD38+ CD56− CD19+);[5][6] in MGUS, more than 3% of the clonal plasma cells have the normal phenotype, whereas in multiple myeloma, less than 3% of the cells have the normal phenotype.[7] What causes MGUS to transform into multiple myeloma is as yet unknown.


MGUS may be considered a pre-malignant condition, given the possibility of transformation into multiple myeloma. However, because the condition tends to occur in the elderly, and because the rate of progression is slow, only a small proportion of people with MGUS go on to develop a haematological malignancy. In patients with MGUS, although the actuarial risk of myeloma at 25 years of follow-up is 30%, the actual risk (when competing causes of death are taken into account) is only 11%.[8]

The annual risk of progressing to multiple myeloma is around 1–2% a year. Kyle et al studied the prevalence of myeloma in a population-wide cohort in Olmsted County, Minnesota. They found that the prevalence of MGUS was 3.2% in people above 50, with a slight male predominance (4.0% vs. 2.7%). Prevalence increased with age: of people over 70 up to 5.3% had MGUS, while in the over-85 age group the prevalence was 7.5%. In the majority of cases (63.5%), the paraprotein level was <1 g/dl, while only a very small group had levels over 2 g/dl.[9]

In addition to multiple myeloma, MGUS may also progress to Waldenström's macroglobulinemia, primary amyloidosis, B-cell lymphoma, or chronic lymphocytic leukemia.

Annual review

The protein electrophoresis test should be repeated annually, and if there is any concern for a rise in the level of monoclonal protein, then prompt referral to a haematologist is required. The haematologist, when first evaluating a case of MGUS, will usually perform a skeletal survey (X-rays of the proximal skeleton), check the blood for hypercalcemia and deterioration in renal function, check the urine for Bence-Jones protein and perform a bone marrow biopsy. If none of these tests are abnormal, a patient with MGUS is followed up once every 6 months to a year with a blood test (serum protein electrophoresis).


  1. ^ International Myeloma Working Group (2003). "Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group.". Br J Haematol 121 (5): 749-57. PMID 12780789.
  2. ^ Murakami H, Irisawa H, Saitoh T, Matsushima T, Tamura J, Sawamura M, Karasawa M, Hosomura Y, Kojima M (1997). "Immunological abnormalities in splenic marginal zone cell lymphoma". Am. J. Hematol. 56 (3): 173-8. PMID 9371530.
  3. ^ Larking-Pettigrew M, Ranich T, Kelly R (1999). "Rapid onset monoclonal gammopathy in cutaneous lupus erythematosus: interference with complement C3 and C4 measurement". Immunol. Invest. 28 (4): 269-76. PMID 10454004.
  4. ^ Czaplinski A, Steck A (2004). "Immune mediated neuropathies--an update on therapeutic strategies". J. Neurol. 251 (2): 127-37. PMID 14991345.
  5. ^ Zhan F, Hardin J, Kordsmeier B, Bumm K, Zheng M, Tian E, Sanderson R, Yang Y, Wilson C, Zangari M, Anaissie E, Morris C, Muwalla F, van Rhee F, Fassas A, Crowley J, Tricot G, Barlogie B, Shaughnessy J (2002). "Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells.". Blood 99 (5): 1745-57. PMID 11861292.
  6. ^ Magrangeas F, Nasser V, Avet-Loiseau H, Loriod B, Decaux O, Granjeaud S, Bertucci F, Birnbaum D, Nguyen C, Harousseau J, Bataille R, Houlgatte R, Minvielle S (2003). "Gene expression profiling of multiple myeloma reveals molecular portraits in relation to the pathogenesis of the disease.". Blood 101 (12): 4998-5006. PMID 12623842.
  7. ^ Ocqueteau M, Orfao A, Almeida J, Bladé J, González M, García-Sanz R, López-Berges C, Moro M, Hernández J, Escribano L, Caballero D, Rozman M, San Miguel J (1998). "Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma.". Am J Pathol 152 (6): 1655-65. PMID 9626070.
  8. ^ Bladé J (2006). "Clinical practice. Monoclonal gammopathy of undetermined significance.". N Engl J Med 355 (26): 2765-70. PMID 17192542 Abstract.
  9. ^ Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, Dispenzieri A, Katzmann JA, Melton LJ 3rd. (28 December 2006). "Prevalence of monoclonal gammopathy of undetermined significance". N Engl J Med 354: 1362-9. PMID 16571879.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Monoclonal_gammopathy_of_undetermined_significance". A list of authors is available in Wikipedia.
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