Initial Workup for Multiple Myeloma
The initial diagnostic workup for suspected multiple myeloma should include comprehensive laboratory testing, bone marrow evaluation, and imaging studies to confirm diagnosis and assess disease burden. 1
Laboratory Testing
Blood Tests
- Complete blood count (CBC) with differential and peripheral blood smear
- Blood chemistry including:
- Calcium
- Creatinine and BUN
- Serum electrolytes
- Albumin
- Lactate dehydrogenase (LDH)
- Beta-2 microglobulin (important for staging)
Protein Studies
- Serum protein electrophoresis (SPEP)
- Serum immunofixation electrophoresis (SIFE)
- Quantitative immunoglobulins (IgG, IgA, IgM)
- Serum free light chain (FLC) assay and ratio
- 24-hour urine collection for:
- Total protein
- Urine protein electrophoresis (UPEP)
- Urine immunofixation electrophoresis (UIFE)
Important note: Random urine samples cannot replace 24-hour urine collection. Immunofixation should be performed even if there is no measurable protein or visible peak on electrophoresis 1.
Bone Marrow Assessment
- Bone marrow aspirate and biopsy
- Diagnosis is confirmed when ≥10% clonal plasma cells are detected
- CD138 staining should be used when possible to accurately determine plasma cell percentage
- Establish clonality through immunoperoxidase staining or immunofluorescence
Cytogenetic Testing
- Standard metaphase cytogenetics
- Fluorescence in situ hybridization (FISH) on sorted plasma cells with probes for:
- Deletion 17p13
- t(4;14)
- t(14;16)
- t(11;14)
- Chromosome 1 abnormalities
Imaging Studies
- Skeletal survey including:
- Posteroanterior view of chest
- Anteroposterior and lateral views of cervical, thoracic, and lumbar spine
- Anteroposterior and lateral views of skull
- Anteroposterior view of pelvis, humeri, and femora
- Whole-body low-dose CT (may be used instead of skeletal survey)
- MRI of spine and pelvis (mandatory in suspected spinal cord compression)
- PET/CT scan (in selected cases)
Additional Tests Based on Clinical Presentation
- Serum viscosity (if hyperviscosity is suspected)
- Tissue biopsy (for solitary plasmacytoma)
- Bone densitometry
- Staining for amyloid (if amyloidosis is suspected)
Prognostic Assessment
- International Staging System (ISS) based on:
- Serum beta-2 microglobulin
- Serum albumin
- Revised ISS (R-ISS) incorporating:
- ISS stage
- Cytogenetic abnormalities
- LDH level
Common Pitfalls to Avoid
- Failing to perform immunofixation when protein electrophoresis is negative (can miss light chain myeloma)
- Substituting random urine samples for 24-hour collections
- Not performing FISH analysis on purified plasma cells
- Relying solely on conventional radiography when more sensitive imaging techniques are available
- Missing the diagnosis of non-secretory myeloma (3% of cases have neither serum nor urine M-protein)
Follow-up Recommendations
For patients diagnosed with multiple myeloma, monitoring should include:
- Quantitative immunoglobulins and M-protein quantitation every 3 months
- CBC, differential, platelets
- BUN, creatinine, calcium
- Bone survey annually or for symptoms
- Bone marrow biopsy as clinically indicated
- Serum free light chain assay as clinically indicated
For patients with smoldering myeloma, follow-up should be more frequent initially (every 3 months for the first year) to establish the pattern of evolution 1.