What is the diagnostic workup for suspected multiple myeloma?

Diagnostic Workup for Suspected Multiple Myeloma

The diagnostic workup for suspected multiple myeloma requires serum and urine protein studies, complete blood count, comprehensive metabolic panel, bone marrow examination, and skeletal imaging to effectively rule out or confirm multiple myeloma. 1

Laboratory Tests

Serum Studies

• Serum protein electrophoresis (SPEP): Detects and quantifies monoclonal protein (M-protein) 1
• Serum immunofixation electrophoresis (SIFE): Characterizes heavy and light chains of the M-protein 1
• Serum free light chain (FLC) assay: Measures kappa and lambda free light chains and their ratio (essential for detecting light chain abnormalities and monitoring non-secretory myeloma) 1
• Quantitative immunoglobulins: Measures IgG, IgA, and IgM levels by nephelometry 2
• Complete blood count with differential: Evaluates for anemia and examines peripheral blood smear for rouleaux formation 1
• Comprehensive metabolic panel: Includes:
  • Serum calcium (to detect hypercalcemia)
  • Blood urea nitrogen and serum creatinine (to assess renal function)
  • Serum electrolytes
  • Liver function tests
  • Albumin
  • Lactate dehydrogenase (LDH)
  • Beta-2 microglobulin (for prognostication) 2, 1

Urine Tests

• 24-hour urine collection: Necessary for total protein quantification 1
• Urine protein electrophoresis (UPEP): Detects and quantifies urinary M-protein 2
• Urine immunofixation electrophoresis (UIFE): Confirms presence and type of urinary M-protein 1

Bone Marrow Examination

• Bone marrow aspirate and biopsy: Evaluates plasma cell percentage and morphology (≥10% clonal plasma cells is diagnostic for myeloma when combined with other criteria) 2
• Immunohistochemistry: Confirms clonality of plasma cells 1
• Cytogenetics: Standard metaphase karyotyping for prognosis and treatment decisions 1
• Fluorescence in situ hybridization (FISH): Detects specific genetic abnormalities, especially chromosome 17p13, t(4;14), t(14;16), and others that determine risk stratification 1, 3

Imaging Studies

• Skeletal survey: X-rays of spine, pelvis, skull, humeri, and femurs to detect lytic bone lesions 2
• Advanced imaging: When skeletal survey is negative but bone lesions are suspected:
  • MRI: Provides greater detail and is recommended for suspected spinal cord compression 2
  • CT scan: May be needed to evaluate symptomatic bony sites 2
  • PET/CT: Can help distinguish between MGUS, smoldering and overt myeloma 4

Diagnostic Criteria

The diagnosis of symptomatic multiple myeloma requires:

1. ≥10% clonal plasma cells on bone marrow examination or a biopsy-proven plasmacytoma, AND
2. Evidence of end-organ damage (CRAB criteria) attributable to the plasma cell disorder:
   • C: Hypercalcemia (serum calcium >11.5 mg/dl)
   • R: Renal insufficiency (serum creatinine >1.73 μmol/l or >2 mg/dl or creatinine clearance <40 ml/min)
   • A: Anemia (hemoglobin <10 g/dl or ≥2 g/dl below the lower limit of normal)
   • B: Bone lesions (lytic lesions, severe osteopenia, or pathologic fractures) 2

OR one or more of the following myeloma-defining events:

• 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 3

Common Pitfalls to Avoid

1. Relying solely on serum studies without urine assessment: Can miss light chain myeloma, as approximately 3% of multiple myeloma patients have non-secretory disease 1

2. Inadequate bone marrow sampling: Can lead to inaccurate diagnosis 1

3. Limited skeletal imaging: Can miss bone lesions, leading to misdiagnosis of smoldering myeloma instead of symptomatic disease 1

4. Failing to perform immunofixation when protein electrophoresis is negative: Can lead to missed diagnoses 1

5. Using random urine samples instead of 24-hour urine collection: Can lead to inaccurate results 1

6. Incomplete cytogenetic evaluation: Can impact prognosis and treatment decisions 1

7. Not measuring serum free light chains: Can lead to missed diagnoses and inadequate monitoring of non-secretory myeloma 1

By following this comprehensive diagnostic approach, clinicians can accurately diagnose multiple myeloma and distinguish it from related plasma cell disorders such as MGUS and smoldering multiple myeloma, allowing for appropriate treatment decisions that will impact patient morbidity, mortality, and quality of life.