What are the initial steps for a myeloma (multiple myeloma) workup?

Initial Workup for Multiple Myeloma

The initial diagnostic workup for multiple myeloma should include blood tests, urine tests, bone marrow evaluation, and imaging studies to confirm the diagnosis and assess end-organ damage. 1

Blood Tests

• Complete blood count (CBC) with differential and peripheral blood smear to assess for anemia, evaluate for rouleaux formation, and detect circulating plasma cells 2, 1

• Chemistry screen including:

  • Calcium (to detect hypercalcemia) 2
  • Creatinine and BUN (to assess renal function) 2, 1
  • Albumin (for nutritional status and prognostic assessment) 2, 1
  • Liver function tests 2
  • Electrolytes 1

• Protein studies:

  • Serum protein electrophoresis (SPEP) and immunofixation (SIFE) to detect and characterize monoclonal proteins 2, 1
  • Quantitative immunoglobulins (IgG, IgA, IgM) 2
  • Serum free light chain (FLC) assay 2, 1

• Prognostic markers:

  • Beta-2 microglobulin 2, 1
  • Lactate dehydrogenase (LDH) 2, 1

Urine Tests

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

Bone Marrow Evaluation

• Bone marrow aspirate and/or biopsy to:
  • Confirm >10% clonal plasma cells 2
  • Establish clonality through immunohistochemistry (preferably with CD138 stains) 2, 1
  • Perform cytogenetic studies:
    • Standard metaphase karyotyping 2, 1
    • Fluorescence in situ hybridization (FISH) for high-risk features (chromosome 17p13, t(4;14), t(14;16)) 2, 1

Imaging Studies

• Skeletal survey (plain radiographs) including:

  • Posteroanterior view of chest 2
  • Anteroposterior and lateral views of cervical, thoracic, and lumbar spine 2
  • Anteroposterior and lateral views of skull 2
  • Anteroposterior view of pelvis 2
  • Views of humeri and femora 2, 1

• Advanced imaging as indicated:

  • MRI of spine and pelvis (mandatory for suspected solitary plasmacytoma) 2, 1
  • Consider MRI for smoldering myeloma to detect occult lesions 2
  • PET/CT for selected cases 1

Common Pitfalls and Important Considerations

• A 24-hour urine collection cannot be replaced by a morning urine sample 2, 1
• Urine-free light chain assay should not be performed 2, 1
• Serum FLC assay cannot replace 24-hour UPEP for monitoring patients with measurable urinary M-proteins 1
• When both bone marrow aspirate and biopsy are performed, the highest plasma cell percentage from either procedure should be recorded for diagnostic purposes 2
• CD138 stains should be used whenever possible to accurately determine plasma cell percentage in bone marrow biopsies 2
• Approximately 3% of patients may have nonsecretory myeloma with neither serum nor urine monoclonal proteins 1
• Renal impairment can cause decreased clearance of both kappa and lambda free light chains, potentially leading to false elevations 1

Diagnostic Criteria

The diagnosis of multiple myeloma requires:

• ≥10% clonal bone marrow plasma cells 2
• Presence of serum and/or urinary monoclonal protein (except in nonsecretory myeloma) 2
• Evidence of end-organ damage attributable to plasma cell proliferation (CRAB features):
  • Hypercalcemia: serum calcium ≥11.5 mg/dL 2
  • Renal insufficiency: serum creatinine ≥2 mg/dL 2
  • Anemia: hemoglobin <10 g/dL or >2 g/dL below lower limit of normal 2
  • Bone lesions: lytic lesions, severe osteopenia, or pathologic fractures 2