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Summary:

  • Screening symptomatic patients using serum protein electrophoresis and serum free light chains is a clinically sensitive strategy for identifying patients with monoclonal gammopathies.
  • The inclusion of serum free light chain analysis in routine screening can identify additional patients with plasma cell malignancies and B cell leukaemia/lymphoma.
  • Adding urine tests to the initial screen is only necessary if AL amyloidosis is suspected.

Whether or not serum free light chains (sFLCs) should be measured as part of an initial diagnostic request for “possible myeloma - please investigate” is an important issue. Traditionally, serum protein electrophoresis (SPE) and/or serum immunofixation electrophoresis (sIFE) tests have been performed first, sometimes alongside total immunoglobulin (IgG, IgA and IgM) measurements. SPE can detect monoclonal proteins with sensitivities down to 500 - 2000 mg/L (Chapter 4), which is adequate to identify most intact immunoglobulin multiple myeloma (IIMM) patients. However, many patients with light chain multiple myeloma (LCMM) will not be identified. Some centres screen using sIFE: although this technique is 10 times more sensitive than SPE, it is time-consuming, non-quantitative and occasionally monoclonal FLCs are not detected. Furthermore, additional low-level monoclonal gammopathy of undetermined significance (MGUS) patients are detected that are unlikely to progress to malignancy, provided sFLC levels are also normal (Chapter 13) [257]. A few laboratories measure total serum κ and λ in the initial screen, but this is clinically inadequate as the assay is insensitive for the detection of monoclonal FLCs (Chapter 4) [139].

As a consequence of the inadequacy of serum electrophoretic procedures for identifying monoclonal FLC production, urine protein electrophoresis (UPE) and urine IFE (uIFE) have, historically, been performed alongside serum tests, but many patients with nonsecretory multiple myeloma (NSMM), AL amyloidosis and other FLC-associated disorders are still missed. Furthermore, only a minority of patients have accompanying urine samples (14% in a recent UK pathology review) (Table 23.5) [188]. It is therefore logical to test for sFLCs on receipt of the first blood sample. The results will also provide baseline values for subsequent disease monitoring.

A strategy of using SPE/sIFE combined with sFLC analysis in an initial screen increases the identification of clinically significant monoclonal gammopathies, facilitates risk assessment for disease progression in MM (Chapter 20), MGUS (Chapter 13), smouldering multiple myeloma (SMM, Chapter 14) and plasmacytomas (Chapter 21), as well as aiding appropriate clinical decisions for monitoring patients.

This chapter discusses the current and potential screening options for identifying monoclonal proteins. As a general rule, intact monoclonal immunoglobulins can be identified using serum electrophoretic tests while monoclonal light chain diseases should be identified using sFLC assays. The combination of the two procedures produces good diagnostic accuracy and this has been recognised in the current International Myeloma Working Group (IMWG) guidelines. These state that, with the exception of light chain amyloidosis (AL amyloidosis), serum electrophoretic and sFLC assays are sufficient to screen for all pathological plasmaproliferative disorders (Chapters 25 and 28) [167].