What bloodwork and imaging studies are recommended for a workup of multiple myeloma?

Diagnostic Workup for Multiple Myeloma

The comprehensive diagnostic workup for multiple myeloma should include blood tests (CBC, chemistry panel, serum protein electrophoresis with immunofixation, serum-free light chains, immunoglobulin levels), 24-hour urine collection for protein electrophoresis and immunofixation, bone marrow aspirate/biopsy with cytogenetics, and whole-body low-dose CT as the preferred imaging modality. 1, 2

Blood Tests

Required Blood Tests:

• Complete blood count (CBC) with differential 1, 2
• Serum chemistry panel including:
  • Calcium
  • Creatinine and renal function tests
  • Liver function tests
  • Lactate dehydrogenase (LDH)
  • Albumin
  • Beta-2 microglobulin 1, 2

Protein Studies:

• Serum protein electrophoresis (SPEP) 1, 2
• Serum immunofixation (IFE) - essential even if SPEP is negative 1, 2
• Serum-free light chain (FLC) assay - critical for detecting light chain myeloma and monitoring disease 1, 2
• Quantification of serum immunoglobulin levels (IgG, IgA, IgM) 1, 2

Urine Tests

• 24-hour urine collection for:
  • Total protein quantification
  • Urine protein electrophoresis (UPEP)
  • Urine immunofixation (UIFE) 1, 2

Important note: Random urine samples are insufficient; a complete 24-hour collection is necessary. Immunofixation should be performed even if there is no measurable protein peak on electrophoresis. 1

Bone Marrow Assessment

• Bone marrow aspirate and/or biopsy - diagnosis confirmed when >10% clonal plasma cells are detected 1, 2
• CD138 staining - recommended to accurately determine plasma cell percentage 1, 2
• Plasma cell clonality assessment - by immunoperoxidase staining or immunofluorescence 1, 2
• Cytogenetic studies:
  • Conventional metaphase karyotyping
  • Fluorescence in situ hybridization (FISH) for high-risk abnormalities:
    • del(17p)
    • t(4;14)
    • t(14;16)
    • t(11;14)
    • amp1q/gain 1q 1, 2

Imaging Studies

• Whole-body low-dose CT (WBLD-CT) - recommended as first-line imaging 1, 2
• MRI of spine and pelvis - required in WBLD-CT-negative cases 1, 2
• PET-CT - optional but may be used instead of WBLD-CT if available 1

Clinical pearl: While traditional skeletal surveys (X-rays) have historically been used, modern guidelines now favor whole-body low-dose CT as the primary imaging modality due to superior sensitivity in detecting bone lesions. 1, 2

Risk Stratification

After diagnosis, risk stratification should be performed using:

• International Staging System (ISS) combining beta-2 microglobulin, albumin, and LDH levels
• Cytogenetic abnormalities from FISH analysis 2

Common Pitfalls to Avoid

1. Relying solely on SPEP without immunofixation - IFE is more sensitive and should always be performed 3
2. Using random urine samples instead of 24-hour collections - can lead to underestimation of light chain excretion 1
3. Omitting serum-free light chain assay - essential for detecting and monitoring light chain myeloma 2
4. Inadequate bone marrow sampling - both aspirate and biopsy are recommended to ensure accurate plasma cell percentage assessment 1
5. Using only conventional X-rays for imaging - less sensitive than CT, MRI, or PET-CT for detecting bone lesions 1, 2

By following this comprehensive diagnostic approach, clinicians can accurately diagnose multiple myeloma, determine disease stage, assess risk status, and establish baseline measurements for monitoring treatment response.