From the Guidelines
The diagnostic approach for Immunoglobulin M (IgM) monoclonal gammopathy should include serum protein electrophoresis, serum quantitative immunoglobulins, and serum immunofixation electrophoresis to identify and quantify the M-protein (IgM), as well as a bone marrow biopsy with immunohistochemistry and/or flow cytometry to document clonal lymphoplasmacytic cell population. When evaluating a patient for IgM monoclonal gammopathy, it is essential to consider the following key components:
- History and physical examination to assess for symptoms and signs of the disease
- Laboratory studies, including:
- CBC with differential
- Peripheral blood smear examination
- Comprehensive metabolic panel (CMP) to assess kidney and liver function
- Serum protein electrophoresis, serum quantitative immunoglobulins, and serum immunofixation electrophoresis to identify and quantify the M-protein (IgM) 1
- Bone marrow biopsy with immunohistochemistry and/or flow cytometry to document clonal lymphoplasmacytic cell population and detect MYD88 (L265P) mutation 1
- Imaging studies, such as CT scans of the chest, abdomen, and pelvis with intravenous contrast and/or PET-CT, to properly stage the patient and assess adenopathy, splenomegaly, and other extramedullary disease sites 1 It is crucial to distinguish between clinical Waldenström macroglobulinemia (WM), IgM monoclonal gammopathy of undetermined significance (IgM MGUS), and IgM multiple myeloma, as the diagnosis guides management decisions 1.
From the Research
Diagnostic Approach for Immunoglobulin M (IgM) Monoclonal Gammopathy
The diagnostic approach for IgM monoclonal gammopathy involves several steps and tests, including:
- Serum protein electrophoresis (SPEP) with high-resolution agarose gel as the first test for recognition of monoclonal gammopathies 2
- Immunofixation electrophoresis (IFE) for the differentiation of a monoclonal from a polyclonal increase in immunoglobulins 2, 3, 4
- Quantitation of immunoglobulins using a rate nephelometer 2
- Measurement of serum viscosity if the patient has signs or symptoms of hyperviscosity syndrome 2
- Collection of a 24-hour urine specimen for determination of the total amount of protein excreted each day 2
- Immunofixation of the urine if the patient has an M-protein level greater than 1.5 g/dL (15 g/L) in the serum or if multiple myeloma, Waldenström's macroglobulinemia, primary amyloidosis, or a related disorder is suspected 2
Test Characteristics
The characteristics of different tests used in the diagnostic approach for IgM monoclonal gammopathy are:
- High-resolution serum protein electrophoresis (HR SPEP) has a sensitivity of 95% and a specificity of 85% for the detection of paraproteins in patient serum 5
- Combined κ and λ light chain screening immunofixation (CLIF) has a sensitivity of 88% and a specificity of 97% for the detection of paraproteins in patient serum 5
- The combination of SPEP and free light chain (FLC) measurements has a sensitivity of 95% and a specificity of 99% for the diagnosis of monoclonal gammopathy 6
Test Selection
The selection of tests for the diagnostic approach for IgM monoclonal gammopathy depends on the clinical presentation and suspicion of the disease, and may involve: