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Waldenström Macroglobulinemia:  What Testing Should Be Performed?



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September 2014

Immunoglobulin M (IgM) usually circulates as a pentameric molecule with a molecular mass of almost 1 million. An IgM monoclonal gammopathy is therefore termed a “macroglobulinemia.” The IgM gammopathies are clonal lymphoplasmacytic cell proliferations that include monoclonal gammopathy of undetermined significance of the IgM type (IgM MGUS), smoldering Waldenström macroglobulinemia (SWM), and Waldenström macroglobulinemia (WM). The laboratory distinctions among IgM MGUS, SWM, and WM are similar to those for the triad of MGUS, smoldering multiple myeloma, and multiple myeloma. However, because the clonal cells in WM are at an earlier developmental stage than mature plasma cells, WM is a distinct clinical entity and presents with different clinical symptoms.

The detection of a monoclonal IgM in WM is usually a straightforward laboratory finding on serum protein electrophoresis. Immunofixation electrophoresis is used to identify the protein as an IgM. Monitoring WM can be done by serum protein electrophoresis M-spike or IgM quantitation by immunonephelometry. Nephelometry values are almost twice as high as electrophoretic M-spike values, and clinicians should not compare results from the 2 methods. Persons with IgM monoclonal proteins without neuropathy, axonal neuropathy, demyelinating neuropathy, or amyloid neuropathy may have anti-myelin-associated glycoprotein (MAG) immunoglobulins. Therefore, the presence of these antibodies may be misleading in consideration of the underlying hematologic cause.  Since specificity and sensitivity of this testing is poor, it is  not performed at Mayo Clinic.

Waldenström Macroglobulinemia

Cryoglobulinemia occurs in 10% of WM patients. The presence of a cryoprecipitate should indicate cryoglobulin testing to quantitate and characterize the cryoprecipitate. Because individual cryoglobulins may precipitate significantly below body temperature, they rarely cause  cold hypersensitivity. Laboratories, however, should be aware to look for cryoprecipitates and their effects on laboratory tests.

There is not a perfect correlation among IgM concentration, hyperviscosity, and clinical symptoms of hyperviscosity syndrome, but IgM M spikes >4 g/dL should suggest testing serum viscosity.

Primary Testing for WM:

  • Detection and quantitation of the monoclonal protein
  • Characterization of the protein as IgM
  • Bone marrow aspirate and biopsy including immunophenotyping analysis by flow cytometry or immunohistochemistry and molecular genetic analysis for MYD88 mutation

Tests Available at Mayo Medical Laboratories

Secondary Testing for WM:

  • If serum protein electrophoresis IgM M spike >4 g/dL, perform serum viscosity assay.
  • If serum cold precipitate, perform cryoglobulin assay.

Tests Available at Mayo Medical Laboratories

 

Authored by Dr. Jerry Katzmann

 


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