Monoclonal gammopathy of undetermined significance

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Monoclonal gammopathy of undetermined significance
Electrophoresis.png
Schematic representation of a normal protein electrophoresis gel. A small spike would be present in the gamma (γ) band in MGUS
Classification and external resources
ICD-10 D47.2
ICD-9-CM 273.1
ICD-O 9765/1
DiseasesDB 1341
eMedicine med/1495
MeSH D008998

Monoclonal gammopathy of undetermined significance (MGUS, unknown or uncertain may be substituted for undetermined), formerly benign monoclonal gammopathy, is a condition in which a paraprotein is found in the blood during standard laboratory blood tests. It resembles multiple myeloma and similar diseases, but the levels of antibody are lower,[1] the number of plasma cells (white blood cells that secrete antibodies) in the bone marrow is lower, it has no symptoms or major problems, although patients with MGUS have sometimes been reported to suffer from peripheral neuropathy,[2] and no treatment is indicated. However, multiple myeloma develops at the rate of about 1.5% a year, so doctors recommend monitoring it yearly. The progression from MGUS to multiple myeloma usually involves several steps. In rare cases, it may also be related with a slowly progressive symmetric distal sensorimotor neuropathy.[3]

Diagnosis[edit]

MGUS is a common, age-related medical condition characterized by an accumulation of bone marrow plasma cells derived from a single abnormal clone. Patients may be diagnosed with MGUS if they fulfill the following four criteria:[4]

  1. A monoclonal paraprotein band lesser than 30 g/L (< 3g/dL);
  2. Plasma cells less than 10% on bone marrow examination;
  3. No evidence of bone lesions, anemia, hypercalcemia, or renal insufficiency related to the paraprotein, and
  4. No evidence of another B-cell proliferative disorder.

Differential diagnosis[edit]

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

Pathology[edit]

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+);[9][10] in MGUS, on average 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.[11] What causes MGUS to transform into multiple myeloma is as yet unknown.

Prognosis[edit]

At the Mayo Clinic, MGUS transformed into multiple myeloma or similar lymphoproliferative disorder at the rate of about 1-2% a year, or 17%, 34%, and 39% at 10, 20, and 25 years, respectively, of follow-up—among surviving patients. However, because they were elderly, most patients with MGUS died of something else and did not go on to develop multiple myeloma. When this was taken into account, only 11.2% developed lymphoproliferative disorders.[12]

Kyle studied the prevalence of myeloma in the population as a whole (not clinic patients) 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.[13] A study of monoclonal protein levels conducted in Ghana showed a prevalence of MGUS of approximately 5.9% in African men over the age of 50.[14]

In 2009, prospective data demonstrated that all or almost all cases of multiple myeloma are preceded by MGUS.[15] In addition to multiple myeloma, MGUS may also progress to Waldenström's macroglobulinemia, primary amyloidosis, B-cell lymphoma, or chronic lymphocytic leukemia.

Management[edit]

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 hematologist is required. The hematologist, 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).

See also[edit]

References[edit]

  1. ^ Agarwal, A; Ghobrial, IM (1 March 2013). "Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: a review of the current understanding of epidemiology, biology, risk stratification, and management of myeloma precursor disease.". Clinical Cancer Research. 19 (5): 985–94. doi:10.1158/1078-0432.CCR-12-2922. PMC 3593941free to read. PMID 23224402. 
  2. ^ Nobile-Orazio E.; et al. (June 1992). "Peripheral neuropathy in monoclonal gammopathy of undetermined significance: prevalence and immunopathogenetic studies". Acta Neurologica Scandinavica. 85 (6): 383–390. doi:10.1111/j.1600-0404.1992.tb06033.x. 
  3. ^ Kahn S. N., Riches P. G., Kohn J. (1980). "Paraproteinaemia in neurological disease: incidence, associations, and classification of monoclonal immunoglobulins". Journal of clinical pathology. 33 (7): 617–621. doi:10.1136/jcp.33.7.617. PMC 1146171free to read. PMID 6253529. 
  4. ^ 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): 749–757. doi:10.1046/j.1365-2141.2003.04355.x. PMID 12780789. 
  5. ^ 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): 173–178. doi:10.1002/(SICI)1096-8652(199711)56:3<173::AID-AJH7>3.0.CO;2-V. PMID 9371530. 
  6. ^ 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): 269–276. doi:10.3109/08820139909060861. PMID 10454004. 
  7. ^ Czaplinski A, Steck A (2004). "Immune mediated neuropathies--an update on therapeutic strategies". J. Neurol. 251 (2): 127–137. doi:10.1007/s00415-004-0323-5. PMID 14991345. 
  8. ^ Sykes, David B.; Schroyens, Wilfried; O'Connell, Casey (2011). "TEMPI Syndrome – A Novel Multisystem Disease". N Engl J Med. 365 (5): 475–477. doi:10.1056/NEJMc1106670. PMID 21812700. 
  9. ^ 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): 1745–1757. doi:10.1182/blood.V99.5.1745. PMID 11861292. 
  10. ^ 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. doi:10.1182/blood-2002-11-3385. PMID 12623842. 
  11. ^ 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. PMC 1858455free to read. PMID 9626070. 
  12. ^ Bladé J (2006). "Clinical practice. Monoclonal gammopathy of undetermined significance". N Engl J Med. 355 (26): 2765–2770. doi:10.1056/NEJMcp052790. PMID 17192542. 
  13. ^ 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 (13): 1362–1369. doi:10.1056/NEJMoa054494. PMID 16571879. 
  14. ^ Landgren O, Katzmann JA, Hsing AW, Pfeiffer RM, Kyle RA, Yeboah ED, Biritwum RB, Tettey Y, Adjei AA, Larson DR, Dispenzieri A, Melton LJ 3rd, Goldin LR, McMaster ML, Caporaso NE, Rajkumar SV (Dec 2007). "Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana". Mayo Clin Proc. 82 (12): 1468–1473. doi:10.4065/82.12.1468. PMID 18053453. 
  15. ^ Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, Dispenzieri A, Kumar S, Clark RJ, Baris D, Hoover R, Rajkumar SV (28 May 2009). "Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study". Blood. 113 (22): 5412–7. doi:10.1182/blood-2008-12-194241. PMC 2689042free to read. PMID 19179464. 

Further reading[edit]