From the Guidelines
The initial evaluation for a patient with monoclonal gammopathy should include serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (SIFE), serum free light chain assay, complete blood count, comprehensive metabolic panel, and 24-hour urine protein electrophoresis with immunofixation, as recommended by the European Myeloma Network 1.
Initial Evaluation
The following tests are essential for the initial evaluation of a patient with monoclonal gammopathy:
- Serum protein electrophoresis (SPEP)
- Serum immunofixation electrophoresis (SIFE)
- Serum free light chain assay
- Complete blood count
- Comprehensive metabolic panel
- 24-hour urine protein electrophoresis with immunofixation These tests help differentiate between monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma, and active multiple myeloma, as outlined in the guidelines by the International Myeloma Working Group 1 and the European Myeloma Network 1.
Additional Testing
Additional testing should include:
- A skeletal survey or low-dose whole-body CT scan to assess for bone lesions
- Bone marrow aspiration and biopsy with fluorescence in situ hybridization (FISH) to determine plasma cell percentage and cytogenetic abnormalities These tests are crucial in evaluating the extent of the disease and guiding treatment decisions, as recommended by the European Myeloma Network 1 and the International Myeloma Working Group 1.
Follow-up
For patients with MGUS, follow-up should occur at 6 months initially and then annually if stable, with repeat SPEP, complete blood count, serum creatinine, and calcium levels, as recommended by the European Myeloma Network 1. This approach helps monitor the patient's condition and detects any potential progression to symptomatic disease.
Importance of Comprehensive Evaluation
The comprehensive evaluation is necessary because monoclonal gammopathies exist on a spectrum of plasma cell disorders with varying clinical significance and treatment requirements, ranging from the benign MGUS (requiring monitoring only) to multiple myeloma (requiring immediate treatment), as outlined in the guidelines by the International Myeloma Working Group 1 and the European Myeloma Network 1.
From the Research
Study for Monoclonal Gammopathy
The study for a patient with monoclonal gammopathy involves several tests, including:
- Serum protein electrophoresis (SPE) with high-resolution agarose gel 2
- Immunofixation to differentiate between monoclonal and polyclonal increases in immunoglobulins 2
- Quantitation of immunoglobulins using a rate nephelometer 2
- Measurement of serum viscosity if the patient has signs or symptoms of hyperviscosity syndrome 2
- 24-hour urine specimen collection to determine the total amount of protein excreted each day 2
- Immunofixation of the urine to identify Bence-Jones proteinuria 3
Screening and Diagnosis
Screening and diagnosis of monoclonal gammopathies can be performed using various tests, including:
- Serum protein electrophoresis (SPE) with agarose gel or capillary zone electrophoresis 3
- Immunofixation electrophoresis (IFE) and immunosubtraction capillary electrophoresis 3
- Serum free light chains and quantitative immunoglobulins 3
- Heavy/light-chain combinations 3
- Urine protein electrophoresis and urine IFE to identify Bence-Jones proteinuria 3
Laboratory Practice
Laboratory practice for monoclonal gammopathy testing varies widely across laboratories 3. The most common test approaches used in screening include:
- SPE with reflex to IFE/immunosubtraction capillary electrophoresis 3
- SPE only 3
- SPE and IFE or immunosubtraction capillary electrophoresis 3
- SPE with IFE, serum free light chain, and quantitative immunoglobulins 3
Simplified Screening Panel
A simplified screening panel for detecting multiple myeloma and Waldenström's macroglobulinaemia can include SPEP and FLC alone, with little loss of diagnostic sensitivity 4. However, if primary amyloidosis is suspected, urine IFE should also be performed 4.
Differential Diagnosis
The differential diagnosis of monoclonal gammopathy includes various distinct malignant plasma cell disorders and lymphoproliferative diseases, as well as benign causes of secondary monoclonal gammopathy 5. A systematic plan of laboratory evaluation, including serum protein electrophoresis, immunofixation, and quantitation of immunoglobulins, can help arrive at a diagnosis and formulate a therapeutic plan 5.
Monitoring and Diagnosis
Monitoring and diagnosis of monoclonal gammopathies can be performed using various tests, including serum and urine protein electrophoresis, immunofixation electrophoresis, capillary zone electrophoresis, and immunosubtraction, serum-free light chain assay, and mass spectrometry 6. The various assays should be used in an algorithmic approach to avoid unnecessary testing, and reporting of test results should be tailored to the clinical context of each individual patient 6.