Journal List > Lab Med Online > v.2(2) > 1057187

Hwang, Chung, and Hong: Evaluation of the Screening Tests for the Diagnosis of Plasma Cell Neoplasm

Abstract

Background

Plasma cell neoplasm is diagnosed by performing bone marrow examination, serum- and urine-protein electrophoresis, and quantification of free light chains of immunoglobulins. We characterized and quantified monoclonal proteins typical of different diagnosed conditions to determine the best screening test(s).

Methods

We retrospectively reviewed diagnosis of and the characteristics of monoclonal proteins from 113 patients with monoclonal gammopathy. Monoclonal proteins were detected by agarose-gel electrophoresis and capillary electrophoresis, and if the results were ambiguous, they were confirmed by immunofixation electrophoresis. Free light chains were measured using nephelometry.

Results

The concentrations of monoclonal proteins in 113 patients with different conditions were as follows: multiple myeloma (MM) (67%), 2.66 (0.87-9.48) g/dL; monoclonal gammopathy of undetermined significance (MGUS) (26%), 0.62 (0.08-2.95) g/dL; lymphoma (3%), 3.65 (1.59-6.54) g/dL; Waldenstrom's macroglobulinemia (2%), 1.99 (1.08-2.90) g/dL; amyloidosis (2%), 0.61 g/dL; and POEMS syndrome (1%), 0.99 g/dL. There was a significant difference in the concentration and κ/λ ratio (which was based on the immunetype of the monoclonal proteins) of the monoclonal proteins in patients with MM and MGUS (P<0.001 and P=0.004, respectively). The diagnostic sensitivity of serum-protein electrophoresis, free-light-chain assay, and bone marrow analysis was 87.6%, 84.1%, and 84.5%, respectively. The sensitivity of a combination of 2 or 3 of these tests was higher at 100%.

Conclusions

A combination of protein electrophoresis with immunotyping and serum free-light-chain assay may be the best screening method for detecting monoclonal proteins since its non-invasiveness.

Figures and Tables

Table 1
Characterization of monoclonal proteins and ratio of free light chains according to the diagnosis
lmo-2-80-i001

*Individual sample results with an unquantifiable M-protein concentration were excluded; Normal reference interval: 0.26-1.65; Serum-protein electrophoresis and immunoelectrophoresis showed only IgA-M protein, and the corresponding light chain was not confirmed using immunofixation electrophoresis; §M proteins of other six patients were too small to quantify.

Abbreviations: MM, multiple myeloma; MGUS, monoclonal gammopathy of undetermined significance; WM, Waldenstrom's macroglobulinemia; POEMS, POEMS syndrome; n, the number of cases; NT, not tested; NA, not applicable.

Table 2
Comparison of the diagnostic sensitivity of each test for different diagnosed conditions
lmo-2-80-i002

Abbreviations: SEP, electrophoresis and immunoelectrophoresis (IEP) and/or immunofixation electrophoresis (IFE) performed on serum samples; UEP, electrophoresis and immunoelectrophoresis (IEP) and/or immunofixation electrophoresis (IFE) performed on urine samples; rFLC, ratio of free light chain; BM, bone marrow biopsy; MM, multiple myeloma; MGUS, monoclonal gammopathy of undetermined significance; WM, Waldenstrom's macroglobulinemia; POEMS, POEMS syndrome; NT, not tested; n, positive cases over the total cases in each screening tests.

References

1. Kyle RA. The monoclonal gammopathies. Clin Chem. 1994. 40:2154–2161.
crossref
2. Jenkins MA. Serum and urine electrophoresis for detection and identification of monoclonal proteins. Clin Biochem Rev. 2009. 30:119–122.
3. Kyle RA, Greipp PR. 3. The laboratory investigation of monoclonal gammopathies. Mayo Clin Proc. 1978. 53:719–739.
4. Bossuyt X. Advances in serum protein electrophoresis. Adv Clin Chem. 2006. 42:43–80.
crossref
5. Katzmann JA, Clark R, Wiegert E, Sanders E, Oda RP, Kyle RA, et al. Identification of monoclonal proteins in serum: a quantitative comparison of acetate, agarose gel, and capillary electrophoresis. Electrophoresis. 1997. 18:1775–1780.
crossref
6. Bossuyt X, Lissoir B, Mariën G, Maisin D, Vunckx J, Blanckaert N, et al. Automated serum protein electrophoresis by Capillarys. Clin Chem Lab Med. 2003. 41:704–710.
crossref
7. Abraham RS, Katzmann JA, Clark RJ, Bradwell AR, Kyle RA, Gertz MA. Quantitative analysis of serum free light chains. A new marker for the diagnostic evaluation of primary systemic amyloidosis. Am J Clin Pathol. 2003. 119:274–278.
crossref
8. Bakshi NA, Gulbranson R, Garstka D, Bradwell AR, Keren DF. Serum free light chain (FLC) measurement can aid capillary zone electrophoresis in detecting subtle FLC-producing M proteins. Am J Clin Pathol. 2005. 124:214–218.
crossref
9. Mayo MM, Johns GS. Serum free light chains in the diagnosis and monitoring of patients with plasma cell dyscrasias. Contrib Nephrol. 2007. 153:44–65.
crossref
10. Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, Chanan-Khan A, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011. 117:4701–4705.
crossref
11. Rajkumar SV. Multiple myeloma: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol. 2012. 87:78–88.
crossref
12. Swerdlow SH, Campo E, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 2008. 4th ed. Lyon: IARC;200–213.
13. Katzmann JA, Dispenzieri A, Kyle RA, Snyder MR, Plevak MF, Larson DR, et al. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc. 2006. 81:1575–1578.
crossref
14. Katzmann JA, Abraham RS, Dispenzieri A, Lust JA, Kyle RA. Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice. Clin Chem. 2005. 51:878–881.
crossref
15. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011. 364:1046–1060.
crossref
16. Tate JR, Gill D, Cobcroft R, Hickman PE. Practical considerations for the measurement of free light chains in serum. Clin Chem. 2003. 49:1252–1257.
crossref
17. Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem. 2001. 47:673–680.
crossref
18. Kang SY, Suh JT, Lee HJ, Yoon HJ, Lee WI. Establishment of serum reference range for free light chains and its clinical usefulness in multiple myeloma. Korean J Lab Med. 2004. 24:273–278.
19. Jaskowski TD, Litwin CM, Hill HR. Detection of kappa and lambda light chain monoclonal proteins in human serum: automated immunoassay versus immunofixation electrophoresis. Clin Vaccine Immunol. 2006. 13:277–280.
crossref
20. Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002. 48:1437–1444.
crossref
21. Katzmann JA. Screening panels for monoclonal gammopathies: time to change. Clin Biochem Rev. 2009. 30:105–111.
TOOLS
Similar articles