Initial Laboratory Workup for Multiple Myeloma
The initial diagnostic workup for a patient suspected of having multiple myeloma should include blood tests, urine tests, bone marrow evaluation, and imaging studies to assess for end-organ damage and establish the diagnosis. 1
Blood Tests
- Complete blood count (CBC) with differential and platelet counts 1
- Blood urea nitrogen (BUN), serum creatinine, and serum electrolytes 1
- Serum calcium 1
- Serum albumin 1
- Lactate dehydrogenase (LDH) 1
- Beta-2 microglobulin 1
- Serum protein electrophoresis (SPEP) 1
- Serum immunofixation electrophoresis (SIFE) 1
- Quantitative immunoglobulins (IgG, IgA, IgM) 1
- Serum free light chain (FLC) assay 1, 2
Urine Tests
- 24-hour urine collection for total protein 1
- Urine protein electrophoresis (UPEP) 1
- Urine immunofixation electrophoresis (UIFE) 1
Bone Marrow Evaluation
- Bone marrow aspirate and/or biopsy 1
- Cytogenetics (metaphase karyotype) 1
- Fluorescence in situ hybridization (FISH) to detect specific chromosomal abnormalities including del(17p), t(4;14), t(14;16), t(14;20), and gain 1q 1, 3
Imaging Studies
- Skeletal survey including spine, pelvis, skull, humeri, and femurs 1
- MRI, CT, and/or PET/CT as clinically indicated 1
Key Considerations for Laboratory Testing
Serum Protein Studies
Serum protein studies are essential for detecting and quantifying the monoclonal protein (M-protein) component. SPEP identifies the presence of an M-protein, while SIFE confirms the type of abnormal antibodies present 1. Quantitative immunoglobulin measurements help track disease progression and response to treatment 1.
Serum Free Light Chain Assay
The serum FLC assay is crucial for:
- Screening for MM with high sensitivity when combined with SPEP and SIFE 1
- Monitoring disease response in patients with light chain myeloma and nonsecretory myeloma 2
- Documenting stringent complete response according to International Myeloma Working Group criteria 1
It's important to use the same test for serial studies to ensure accurate relative quantification 2.
Urine Studies
A 24-hour urine collection is mandatory and cannot be replaced by a morning urine sample or random urine samples 1. Immunofixation should be performed even if there is no measurable protein or peak on urine electrophoresis 1.
Bone Marrow Evaluation
Bone marrow aspirate and/or biopsy is required to confirm the diagnosis when more than 10% clonal plasma cells are detected 1. CD138 stains should be used when possible to accurately determine the percentage of plasma cells 1. A trephine biopsy should be considered during the same procedure as it may provide a more reliable assessment of plasma cell infiltration 1.
Cytogenetic Studies
Cytogenetic abnormalities help identify high-risk multiple myeloma, which affects treatment decisions and prognosis 3. High-risk features include del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation 3.
Common Pitfalls and Caveats
- Serum FLC assay cannot replace 24-hour UPEP for monitoring patients with measurable urinary M-proteins 1, 2
- Urine-free light chain assay should not be performed 1, 2
- A 24-hour urine collection cannot be replaced by a morning urine sample 1, 2
- Approximately 3% of patients may have nonsecretory myeloma with neither serum nor urine proteins 1
- Renal impairment can cause decreased clearance of both kappa and lambda free light chains, potentially leading to false elevations 2
By following this comprehensive laboratory workup, clinicians can accurately diagnose multiple myeloma, assess disease burden, determine prognosis, and guide treatment decisions to improve patient outcomes.