Monoclonal gammopathy of undetermined significance classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2] Muhammad Saad, M.B.B.S.[3]

Overview

Monoclonal gammopathy of undetermined significance (MGUS) may be classified according to cytogenetic differences into subtypes/groups based on translocations. There is no established system for the staging of monoclonal gammopathy of undetermined significance (MGUS).

Classification

MGUS is typically divided into non-IgM MGUS, IgM MGUS, and light chain MGUS as described in the following flowchart:^[1]^[2]^[3]^[4]

Non IgM MGUS:

1. <10%BM plasma cells
2. Monoclonal protein <3.0g/dL
3. No symptoms

Smoldering MM:

1. No symptoms
2. >10%BM plasma cells

MM:

1. Symptoms
2. >10%BM plasma cells
AL Amyloidosis

IgM MGUS:

1. <10%BM lymphoplasmacytic cells
2. Monoclonal protein <3.0g/dL
3. No symptoms

Smoldering WM:

1. No symptoms
2. >10%BM lymphoplasmacytic cells

WM:

1. Symptoms
2. >10%BM lymphoplasmacytic cells
AL Amyloidosis
IgM MM

Clonal plasma cell or B lymphocyte

Light chain MGUS:

1. <10%BM plasma cells
2. Abnormal FLC ratio
3. No monoclonal protein
4. No symptoms

Light chain MM:

1. Symptoms
2. >10%BM plasma cells
AL Amyloidosis

Monoclonal gammopathy of clinical significance :

1. Presence of monoclonal protein or FLC
2. Symptoms attributable to presence of monoclonal protein
3. Diagnostic criteria of MM not met

Monoclonal gammopathy of undetermined significance (MGUS) may be classified according to cytogenetic differences into the following subtypes/groups:^[5]

Abnormalities in cytogenes	Affected genes
IgH translocation:
t(11;14), q(13;32)	cyclin D1
t(4;14)(p16;q32)	FGFR-3, and MMSET
t(14;16)(q32;q23)	C-MAF
t(6;14)(q32;q11)	MAFB
IgH non-translocated :
Hyper diploid	Numerous

References

↑ Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF (November 2014). “International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma”. Lancet Oncol. 15 (12): e538–48. doi:10.1016/S1470-2045(14)70442-5. PMID 25439696.
↑ Gertz MA (February 2023). “Waldenström macroglobulinemia: 2023 update on diagnosis, risk stratification, and management”. Am J Hematol. 98 (2): 348–358. doi:10.1002/ajh.26796. PMID 36588395 Check |pmid= value (help).
↑ Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, Kröger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet-Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M (June 2010). “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. 24 (6): 1121–7. doi:10.1038/leu.2010.60. PMC 7020664 Check |pmc= value (help). PMID 20410922.
↑ Gertz MA, Dispenzieri A (July 2020). “Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review”. JAMA. 324 (1): 79–89. doi:10.1001/jama.2020.5493. PMID 32633805 Check |pmid= value (help).
↑ Rajkumar SV, Kyle RA, Buadi FK (October 2010). “Advances in the diagnosis, classification, risk stratification, and management of monoclonal gammopathy of undetermined significance: implications for recategorizing disease entities in the presence of evolving scientific evidence”. Mayo Clin. Proc. 85 (10): 945–8. doi:10.4065/mcp.2010.0520. PMC 2947967. PMID 20884827.

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[pmid25439696-1] Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF (November 2014). “International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma”. Lancet Oncol. 15 (12): e538–48. doi:10.1016/S1470-2045(14)70442-5. PMID 25439696.

[pmid36588395-2] Gertz MA (February 2023). “Waldenström macroglobulinemia: 2023 update on diagnosis, risk stratification, and management”. Am J Hematol. 98 (2): 348–358. doi:10.1002/ajh.26796. PMID 36588395 Check |pmid= value (help).

[pmid20410922-3] Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, Kröger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet-Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M (June 2010). “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. 24 (6): 1121–7. doi:10.1038/leu.2010.60. PMC 7020664 Check |pmc= value (help). PMID 20410922.

[pmid32633805-4] Gertz MA, Dispenzieri A (July 2020). “Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review”. JAMA. 324 (1): 79–89. doi:10.1001/jama.2020.5493. PMID 32633805 Check |pmid= value (help).

[pmid20884827-5] Rajkumar SV, Kyle RA, Buadi FK (October 2010). “Advances in the diagnosis, classification, risk stratification, and management of monoclonal gammopathy of undetermined significance: implications for recategorizing disease entities in the presence of evolving scientific evidence”. Mayo Clin. Proc. 85 (10): 945–8. doi:10.4065/mcp.2010.0520. PMC 2947967. PMID 20884827.

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