Diagnostic Workup for Multiple Myeloma

Introduction to Diagnostic Criteria

The International Myeloma Society recommends a comprehensive diagnostic workup to rule out multiple myeloma, including laboratory tests for monoclonal protein detection, bone marrow evaluation, and imaging studies to assess for bone lesions 1, 2

Serum protein electrophoresis and immunofixation should be used to detect and characterize monoclonal (M-) protein, as recommended by the European Society for Medical Oncology 1, 2
A 24-hour urine collection for protein electrophoresis and immunofixation is necessary, as a random urine sample is insufficient, according to the American Society of Clinical Oncology 3
Nephelometric quantification of immunoglobulins (IgG, IgA, and IgM) is recommended by the International Myeloma Society 1, 2
Serum free light chain (FLC) assay with kappa/lambda ratio is especially important for detecting light chain myeloma, as suggested by the National Comprehensive Cancer Network 3, 4 is replaced with * Serum free light chain (FLC) assay with kappa/lambda ratio is especially important for detecting light chain myeloma, as suggested by the National Comprehensive Cancer Network 3

Bone marrow aspiration and biopsy should be performed to quantify plasma cell infiltration, with a diagnosis requiring ≥10% clonal plasma cells, as recommended by the European Society for Medical Oncology 1, 2
CD138 staining should be used to accurately determine plasma cell percentage in bone marrow biopsies, according to the American Society of Clinical Oncology 3
Immunohistochemistry or immunofluorescence should be used to establish clonality of plasma cells, as suggested by the International Myeloma Society 3

A full skeletal survey (X-rays) including spine, pelvis, skull, humeri, and femurs should be performed to detect lytic bone lesions, as recommended by the European Society for Medical Oncology 1, 2
MRI of the spine and pelvis is necessary if there are symptoms suggesting bone lesions even with negative X-rays, or if spinal cord compression is suspected, according to the American Society of Clinical Oncology 1, 2
CT scan may be needed to evaluate symptomatic bony sites, as suggested by the National Comprehensive Cancer Network 1, 2
PET scan may help distinguish between MGUS, smoldering myeloma, and overt myeloma, as recommended by the International Myeloma Society 5, 6

The diagnosis of multiple myeloma requires ≥10% clonal plasma cells in bone marrow or biopsy-proven plasmacytoma, as defined by the International Myeloma Society 1, 2
Evidence of end-organ damage (CRAB criteria) attributable to the plasma cell disorder is necessary for diagnosis, including hypercalcemia, renal insufficiency, anemia, and bone lesions, as defined by the European Society for Medical Oncology 1, 2

The workup allows differentiation between multiple myeloma, smoldering multiple myeloma, and monoclonal gammopathy of undetermined significance (MGUS), as recommended by the International Myeloma Society 1, 2