Highlights & Basics
- Monoclonal gammopathy of undetermined significance is an asymptomatic premalignant disorder associated with relatively low risk (on average 0.5% to 1.0% per year) of progression to multiple myeloma or related plasma cell proliferative malignancies.
- No etiologic risk factors have been defined. Male sex, older age, family history of monoclonal gammopathy of undetermined significance, African ancestry, and exposure to radiation or pesticide are associated with a higher prevalence.
- There is no indication for specific treatment. Clinical- and laboratory-based follow up is recommended.
Quick Reference
History & Exam
Key Factors
Other Factors
Diagnostics Tests
Treatment Options
Definition
Epidemiology
Etiology
Pathophysiology
Images
Hematoxylin-eosin section of bone marrow biopsy showing mild increase in plasma cells
CD138 immunohistochemical staining highlighting small clusters of plasma cells
Using electrophoresis and immunofixation, figure A shows normal results while figure B shows evidence of an IgA kappa MGUS with polyclonal IgG background
Citations
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 Nov;15(12):e538-48.[Abstract][Full Text]
van de Donk NW, Palumbo A,R Johnsen HE, et al. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network. Haematologica. 2014 Jun;99(6):984-96.[Abstract][Full Text]
Bird J, Behrens J, Westin J, et al. UK Myeloma Forum (UKMF) and Nordic Myeloma Study Group (NMSG): guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol. 2009 Oct;147(1):22-42.[Abstract][Full Text]
Kyle RA, Durie BG, Rajkumar SV, et al; International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010 Jun;24(6):1121-7.[Abstract][Full Text]
1. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 Nov;15(12):e538-48.[Abstract][Full Text]
2. Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022 Jul;36(7):1720-48.[Abstract][Full Text]
3. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016 May 19;127(20):2375-90.[Abstract][Full Text]
4. Campo E, Jaffe ES, Cook JR, et al. The international consensus classification of mature lymphoid neoplasms: a report from the clinical advisory committee. Blood. 2022 Sep 15;140(11):1229-53.[Abstract][Full Text]
5. Kyle RA, Larson DR, Therneau TM, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018 Jan 18;378(3):241-9.[Abstract][Full Text]
6. Wadhera RK, Rajkumar SV. Prevalence of monoclonal gammopathy of undetermined significance: a systematic review. Mayo Clin Proc. 2010 Oct;85(10):933-42.[Abstract][Full Text]
7. Landgren O, Graubard BI, Katzmann JA, et al. Racial disparities in the prevalence of monoclonal gammopathies: a population-based study of 12,482 persons from the National Health and Nutritional Examination Survey. Leukemia. 2014 Jul;28(7):1537-42.[Abstract][Full Text]
8. Landgren O, Weiss BM. Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia. 2009 Oct;23(10):1691-7.[Abstract]
9. Landgren O, Katzmann JA, Hsing AW, et al. Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana. Mayo Clin Proc. 2007 Dec;82(12):1468-73.[Abstract]
10. Kyle RA, Therneau TM, Rajkumar SV, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Semin Oncol. 2003;30:169-171.[Abstract]
11. Landgren O, Gridley G, Turesson I, et al. Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood. 2006 Feb 1;107(3):904-6.[Abstract][Full Text]
12. Turesson I, Kovalchik SA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance and risk of lymphoid and myeloid malignancies: 728 cases followed up to 30 years in Sweden. Blood. 2014 Jan 16;123(3):338-45.[Abstract][Full Text]
13. Vachon CM, Kyle RA, Therneau TM, et al. Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance. Blood. 2009 Jul 23;114(4):785-90.[Abstract][Full Text]
14. Landgren O, Kristinsson SY, Goldin LR, et al. Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden. Blood. 2009 Jul 23;114(4):791-5.[Abstract][Full Text]
15. Brown LM, Gridley G, Check D, et al. Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders. Blood. 2008 Apr 1;111(7):3388-94.[Abstract][Full Text]
16. Amara S, Dezube BJ, Cooley TP, et al. HIV-associated monoclonal gammopathy: a retrospective analysis of 25 patients. Clin Infect Dis. 2006 Nov 1;43(9):1198-205.[Abstract][Full Text]
17. Iwanaga M, Tagawa M, Tsukasaki K, et al. Relationship between monoclonal gammopathy of undetermined significance and radiation exposure in Nagasaki atomic bomb survivors. Blood. 2009 Feb 19;113(8):1639-50.[Abstract][Full Text]
18. Landgren O, Kyle RA, Hoppin JA, et al. Pesticide exposure and risk of monoclonal gammopathy of undetermined significance in the Agricultural Health Study. Blood. 2009 Jun 18;113(25):6386-91.[Abstract][Full Text]
19. Rasillo A, Tabernero MD, Sanchez ML, et al. Fluorescence in situ hybridization analysis of aneuploidization patterns in monoclonal gammopathy of undetermined significance versus multiple myeloma and plasma cell leukemia. Cancer. 2003 Feb 1;97(3):601-9.[Abstract][Full Text]
20. Lakshman A, Paul S, Rajkumar SV, et al. Prognostic significance of interphase FISH in monoclonal gammopathy of undetermined significance. Leukemia. 2018 Jan 30;32(8):1811-15.[Abstract][Full Text]
21. Mailankody S, Mena E, Yuan CM, et al. Molecular and biologic markers of progression in monoclonal gammopathy of undetermined significance to multiple myeloma. Leuk Lymphoma. 2010 Dec;51(12):2159-70.[Abstract][Full Text]
22. Fonseca R, Bailey RJ, Ahmann GJ, et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood. 2002 Aug 15;100(4):1417-24.[Abstract][Full Text]
23. Kyle RA, Therneau TM, Rajkumar SV, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood. 2003 Nov 15;102(10):3759-64.[Abstract][Full Text]
24. McMaster ML, Caporaso N. Waldenström macroglobulinaemia and IgM monoclonal gammopathy of undetermined significance: emerging understanding of a potential precursor condition. Br J Haematol. 2007 Dec;139(5):663-71.[Abstract][Full Text]
25. Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002 Feb 21;346(8):564-9.[Abstract][Full Text]
26. Kristinsson SY, Björkholm M, Andersson TM, et al. Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance: a population-based study. Haematologica. 2009 Dec;94(12):1714-20.[Abstract][Full Text]
27. Kyle RA, Remstein ED, Therneau TM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med. 2007 Jun 21;356(25):2582-90.[Abstract][Full Text]
28. Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009 May 28;113(22):5412-7.[Abstract][Full Text]
29. Rajkumar SV, Kyle RA, Therneau TM, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005 Apr 26;106(3):812-7.[Abstract][Full Text]
30. Rosinol L, Cibeira MT, Montoto S, et al. Monoclonal gammopathy of undetermined significance: predictors of malignant transformation and recognition of an evolving type characterized by a progressive increase in M protein size. Mayo Clin Proc. 2007 Apr;82(4):428-34.[Abstract]
31. Dimopoulos M, Kyle R, Fermand JP, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011 May 5;117(18):4701-5.[Abstract][Full Text]
32. van de Donk NW, Palumbo A,R Johnsen HE, et al. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network. Haematologica. 2014 Jun;99(6):984-96.[Abstract][Full Text]
33. Bird J, Behrens J, Westin J, et al. UK Myeloma Forum (UKMF) and Nordic Myeloma Study Group (NMSG): guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol. 2009 Oct;147(1):22-42.[Abstract][Full Text]
34. Rawstron AC, Orfao A, Beksac M, et al. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica. 2008 Mar;93(3):431-8.[Abstract][Full Text]
35. Kyle RA, Durie BG, Rajkumar SV, et al; International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010 Jun;24(6):1121-7.[Abstract][Full Text]
36. Cesana C, Klersy C, Barbarano L, et al. Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. J Clin Oncol. 2002 Mar 15;20(6):1625-34.[Abstract]
37. Balakumaran A, Robey PG, Fedarko N, et al. Bone marrow microenvironment in myelomagenesis: its potential role in early diagnosis. Expert Rev Mol Diagn. 2010 May;10(4):465-80.[Abstract][Full Text]
38. Landgren O. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: biological insights and early treatment strategies. Hematology Am Soc Hematol Educ Program. 2013;2013:478-87.[Abstract][Full Text]
