Monoclonal gammopathy of undetermined significance diagnostic study of choice
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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
There is no single gold standard test for the diagnosis of monoclonal gammopathy of undetermined significance. Bone marrow aspiration and biopsy is done in all patients having M-protein level ≥1.5 g/dL. Diagnostic criteria depends on the type of monoclonal gammopathy like non-IgM, IgM, or light chain gammopathy. The criteria includes serum monoclonal proteins, plasma cells in the marrow and absence of systemic signs.
Study of choice
There is no single gold standard test for the diagnosis of monoclonal gammopathy of undetermined significance. Bone marrow aspiration and biopsy is done in all patients having M-protein level ≥1.5 g/dL.
Diagnostic Criteria
Non-IgM MGUS (IgG, IgA, or IgD MGUS) is diagnosed on the basis of the following three criteria
- Serum monoclonal protein (M-protein, whether IgA, IgG, or IgD) level <3 g/dL.
- Less than 10 percent clonal plasma cells in marrow.
- Absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the plasma cell disorder.
IgM MGUS is diagnosed on the basis of the following three criteria[1][2][3]
- Serum monoclonal protein (M-protein, whether IgA, IgG, or IgD) levels <3 g/dL.[4]
- Fewer than 10 percent clonal lymphoplasmacytic/plasma cells in the marrow.
- Absence of end-organ damage such as anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly related to the plasma cell disorder
Light chain MGUS (LC-MGUS) is diagnosed on the basis of the following three criteria[2]
- Abnormal FLC ratio (ie, ratio of kappa to lambda FLCs <0.26 or >1.65)
- Increased level of light chain (eg, increased kappa FLC with a ratio >1.65 and increased lambda FLC with a ratio <0.26)
- No monoclonal immunoglobulin heavy chain (IgG, IgA, IgD, or IgM)
- Fewer than 10 percent clonal lymphoplasmacytic cells in the marrow
- Absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the plasma cell disorders
Testing in Monoclonal Gammopathy
Evaluation for MGUS involves a trio of complementary tests as described in the table below.[5][6][7][8] Combined, these tests identify more than 97% of patients with a monoclonal gammopathy. Mass spectrometry is more sensitive than existing methods and it can distinguish exogenous therapeutic antibodies from endogenous monoclonal gammopathies.[9][10]
| Test | Method | Purpose |
|---|---|---|
| Serum protein and electrophoresis | Agarose gel-based assay that separates proteins based on size, shape, and charge | Detects and quantifies monoclonal protein |
| Immunofixation | Gel-based assay that uses targeted anti-sera( anti-IgG, anti-IgM, anti-𝝹 light chain) | Identifies subtype of monoclonal protein and confirms monclonality |
| Serum free light chains | Nephelometric assay that quantifies unbound free light chains | Detects light chain-only MGUS, Ig light chain amyloidosis or MM |
References
- ↑ "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. June 2003. PMID 12780789.
- ↑ 2.0 2.1 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.
- ↑ Kyle RA (May 1978). "Monoclonal gammopathy of undetermined significance. Natural history in 241 cases". Am. J. Med. 64 (5): 814–26. PMID 645746.
- ↑ Kyle RA (November 1994). "The monoclonal gammopathies". Clin. Chem. 40 (11 Pt 2): 2154–61. PMID 7955402.
- ↑ Katzmann JA, Kyle RA, Benson J, Larson DR, Snyder MR, Lust JA, Rajkumar SV, Dispenzieri A (August 2009). "Screening panels for detection of monoclonal gammopathies". Clin Chem. 55 (8): 1517–22. doi:10.1373/clinchem.2009.126664. PMC 3773468. PMID 19520758.
- ↑ Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, Drew R (April 2001). "Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine". Clin Chem. 47 (4): 673–80. PMID 11274017.
- ↑ Murray DL, Seningen JL, Dispenzieri A, Snyder MR, Kyle RA, Rajkumar SV, Katzmann JA (October 2012). "Laboratory persistence and clinical progression of small monoclonal abnormalities". Am J Clin Pathol. 138 (4): 609–13. doi:10.1309/AJCPT6OWWMHITA1Y. PMC 3904358. PMID 23010717.
- ↑ Long TE, Indridason OS, Palsson R, Rognvaldsson S, Love TJ, Thorsteinsdottir S, Sverrisdottir IS, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Thorsteinsdottir I, Olafsson I, Thordardottir AR, Eythorsson E, Jonsson A, Gislason G, Olafsson A, Steingrimsdottir H, Hultcrantz M, Durie BG, Harding S, Landgren O, Kristinsson SY (September 2022). "Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study". Blood Cancer J. 12 (9): 133. doi:10.1038/s41408-022-00732-3. PMC 9470548 Check
|pmc=value (help). PMID 36100605 Check|pmid=value (help). - ↑ El-Khoury H, Lee DJ, Alberge JB, Redd R, Cea-Curry CJ, Perry J, Barr H, Murphy C, Sakrikar D, Barnidge D, Bustoros M, Leblebjian H, Cowan A, Davis MI, Amstutz J, Boehner CJ, Lightbody ED, Sklavenitis-Pistofidis R, Perkins MC, Harding S, Mo CC, Kapoor P, Mikhael J, Borrello IM, Fonseca R, Weiss ST, Karlson E, Trippa L, Rebbeck TR, Getz G, Marinac CR, Ghobrial IM (May 2022). "Prevalence of monoclonal gammopathies and clinical outcomes in a high-risk US population screened by mass spectrometry: a multicentre cohort study". Lancet Haematol. 9 (5): e340–e349. doi:10.1016/S2352-3026(22)00069-2. PMID 35344689 Check
|pmid=value (help). - ↑ Willrich MA, Ladwig PM, Andreguetto BD, Barnidge DR, Murray DL, Katzmann JA, Snyder MR (June 2016). "Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation". Clin Chem Lab Med. 54 (6): 1085–93. doi:10.1515/cclm-2015-1023. PMID 26812875.