What is the initial workup for suspected multiple myeloma?

Initial Workup for Suspected Multiple Myeloma

The initial workup for suspected multiple myeloma must include complete blood count, comprehensive metabolic panel, serum and urine protein electrophoresis with immunofixation, serum free light chain assay, bone marrow biopsy with FISH analysis, and skeletal imaging. 1

Laboratory Studies

Blood Tests

• Complete blood count (CBC) with differential and platelet counts
  • Look for anemia (present in ~73% of patients at diagnosis) 2
  • Examine peripheral blood smear for rouleaux formation and circulating plasma cells 3
• Chemistry panel:
  • Serum calcium (to detect hypercalcemia)
  • Blood urea nitrogen (BUN) and serum creatinine (to assess renal function)
  • Serum electrolytes
  • Liver function tests
  • Albumin (important for staging)
  • Lactate dehydrogenase (LDH) (reflects tumor burden)
  • Beta-2 microglobulin (reflects tumor mass and standard measure of tumor burden) 3

Protein Studies

• Serum protein electrophoresis (SPEP) with immunofixation (SIFE)
• Quantitative immunoglobulin levels (IgG, IgA, IgM)
• Serum free light chain (FLC) assay with kappa/lambda ratio calculation
  • Essential for detecting light chain abnormalities missed by immunofixation 1
  • Required for documenting stringent complete response according to IMWG criteria 3
• 24-hour urine collection for:
  • Total protein
  • Urine protein electrophoresis (UPEP)
  • Urine immunofixation electrophoresis (UIFE) 3

Bone Marrow Evaluation

• Bone marrow aspirate and biopsy to:
  • Quantify plasma cell infiltration (diagnosis requires ≥10% clonal plasma cells) 4
  • Assess morphology of plasma cells
  • Perform immunohistochemistry and/or flow cytometry to confirm clonality 3
• Cytogenetic studies:
  • Fluorescence in situ hybridization (FISH) on plasma cells for high-risk features:
    • del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, p53 mutation 4
  • Conventional karyotyping (metaphase cytogenetics) may provide additional information 3

Imaging Studies

• Full skeletal survey including spine, pelvis, skull, humeri, and femurs 3
• Consider advanced imaging:
  • Low-dose whole-body CT (more sensitive than conventional radiography)
  • MRI (especially if spinal cord compression is suspected)
  • PET-CT (can detect extramedullary disease and assess disease activity) 1, 2

Diagnostic Criteria

Multiple myeloma diagnosis requires:

1. ≥10% clonal bone marrow plasma cells or biopsy-proven plasmacytoma, AND
2. One or more myeloma defining events:
   • CRAB features (hypercalcemia, renal failure, anemia, bone lesions)
   • Bone marrow clonal plasmacytosis ≥60%
   • Serum involved/uninvolved free light chain ratio ≥100 (provided involved FLC is ≥100 mg/L)

   • 1 focal lesion on MRI 4

Common Pitfalls to Avoid

1. Failing to perform immunofixation when protein electrophoresis is negative (approximately 3% of multiple myeloma patients have non-secretory disease) 3, 1
2. Using random urine samples instead of 24-hour urine collection for protein electrophoresis 3
3. Incomplete cytogenetic evaluation, which impacts prognosis and treatment decisions 1
4. Inadequate imaging assessment (conventional radiography may miss early bone lesions) 1
5. Not measuring serum free light chains, which are essential for detecting light chain abnormalities and monitoring non-secretory myeloma 3, 1

Risk Stratification

After diagnosis, risk stratification should be performed using:

• International Staging System (ISS), which combines:
  • Beta-2 microglobulin
  • Albumin
  • LDH
  • Cytogenetic abnormalities 1

This comprehensive workup allows for accurate diagnosis, risk stratification, and appropriate treatment planning for patients with suspected multiple myeloma.