What is the workup for a patient with suspected multiple myeloma?

Workup for Suspected Multiple Myeloma

The standard diagnostic workup for suspected multiple myeloma should include blood tests (CBC, chemistry panel, protein studies), 24-hour urine collection, bone marrow examination, cytogenetic analysis, and skeletal imaging. 1

Initial Laboratory Assessment

Blood Tests

• Complete blood count (CBC) with differential and peripheral blood smear examination to assess for anemia, rouleaux formation, and circulating plasma cells 1
• Chemistry panel including:
  • Blood urea nitrogen (BUN) and serum creatinine to evaluate renal function 1
  • Serum calcium to detect hypercalcemia 1
  • Albumin and lactate dehydrogenase (LDH) for prognostic assessment 1
  • Beta-2 microglobulin to determine tumor burden and for staging 1

Protein Studies

• Serum protein electrophoresis (SPEP) and immunofixation electrophoresis (SIFE) to identify and characterize monoclonal proteins 1
• Quantitative immunoglobulin levels (IgG, IgA, and IgM) by nephelometry 1
• Serum free light chain (FLC) assay to detect and quantify kappa and lambda free light chains 1

Urine Studies

• 24-hour urine collection for:
  • Total protein quantification 1
  • Urine protein electrophoresis (UPEP) to detect and quantify Bence Jones proteinuria 1
  • Urine immunofixation electrophoresis (UIFE) to confirm and type monoclonal proteins 1

Bone Marrow Examination

• Bone marrow aspirate and biopsy to:
  • Quantify plasma cell infiltration (diagnosis requires ≥10% clonal plasma cells) 1
  • Assess plasma cell morphology and distribution 1
  • Establish clonality through immunohistochemistry (preferably using CD138 stains) 1

Cytogenetic Analysis

• Standard metaphase cytogenetics to identify chromosomal abnormalities 1
• Fluorescence in situ hybridization (FISH), preferably on sorted plasma cells, to detect:
  • Deletion 17p13 1
  • Translocation t(4;14) 1
  • Translocation t(14;16) 1
  • Other high-risk abnormalities (t(14;20), gain 1q, deletion 1p) 2

Imaging Studies

• Full skeletal survey with plain radiographs including:
  • Posteroanterior view of chest 1
  • Anteroposterior and lateral views of cervical, thoracic, and lumbar spine 1
  • Anteroposterior and lateral views of skull 1
  • Anteroposterior view of pelvis 1
  • Views of humeri and femora 1
• Advanced imaging options:
  • Whole-body low-dose CT as an alternative to conventional radiography 1, 3
  • MRI of spine and pelvis when symptomatic myeloma is suspected but conventional imaging is negative 1
  • PET/CT in selected cases to assess disease extent and activity 3, 2

Diagnostic Criteria

The diagnosis of multiple myeloma requires:

• ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma 1, 4
• Plus at least one of the following multiple myeloma defining events:
  • CRAB features (hypercalcemia, renal failure, anemia, bone lesions) attributable to the plasma cell disorder 1, 4
  • Bone marrow clonal plasmacytosis ≥60% 4, 2
  • Serum involved/uninvolved free light chain ratio ≥100 (provided involved FLC is ≥100 mg/L) 4, 2
  • More than one focal lesion on MRI 4, 2

Risk Stratification

After diagnosis, risk stratification should be performed based on:

• Revised International Staging System (R-ISS) using:
  • Serum beta-2 microglobulin 3, 2
  • Serum albumin 3, 2
  • Serum LDH 3, 2
  • High-risk cytogenetic abnormalities 3, 2
• Presence of high-risk features:
  • del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, or p53 mutation 4, 2
  • Two high-risk factors constitute "double-hit" myeloma 4, 2
  • Three or more high-risk factors constitute "triple-hit" myeloma 4, 2

Common Pitfalls to Avoid

• Failing to perform 24-hour urine collection - random urine samples are inadequate for proper assessment 1
• Relying solely on serum protein studies without urine studies - some patients have light chain myeloma with minimal or no serum monoclonal protein 1
• Not performing immunofixation when electrophoresis is negative - immunofixation is more sensitive and should be done even with negative electrophoresis 1
• Neglecting to perform bone marrow biopsy when aspirate is inadequate - biopsy provides more reliable assessment of plasma cell infiltration 1
• Using only conventional radiography without considering advanced imaging when clinically indicated 1, 3
• Failing to perform cytogenetic analysis which is crucial for risk stratification and treatment planning 1, 3