Diagnostic Workup to Rule Out Multiple Myeloma
The comprehensive diagnostic workup to rule out multiple myeloma should include laboratory tests for monoclonal protein detection, bone marrow evaluation, and imaging studies to assess for bone lesions. 1
Laboratory Tests
Protein Studies
- Serum protein electrophoresis and immunofixation to detect and characterize monoclonal (M-) protein 1
- 24-hour urine collection for protein electrophoresis and immunofixation (a random urine sample is insufficient) 1
- Nephelometric quantification of immunoglobulins (IgG, IgA, and IgM) 1
- Serum free light chain (FLC) assay with kappa/lambda ratio (especially important for detecting light chain myeloma) 1, 2
Complete Blood Count and Chemistry
- Complete blood count with differential to assess for anemia 1, 2
- Serum calcium to evaluate for hypercalcemia 1
- Serum creatinine to assess renal function 1
- Serum β2-microglobulin and lactate dehydrogenase (LDH) for prognostic assessment 1, 2
Bone Marrow Evaluation
- Bone marrow aspiration and biopsy to quantify plasma cell infiltration (diagnosis requires ≥10% clonal plasma cells) 1
- CD138 staining should be used to accurately determine plasma cell percentage in bone marrow biopsies 1
- Immunohistochemistry or immunofluorescence to establish clonality of plasma cells 1
- Cytogenetic studies including standard metaphase karyotyping and FISH analysis for high-risk features (del(17p), t(4;14), t(14;16), etc.) 1, 3
Imaging Studies
- Full skeletal survey (X-rays) including spine, pelvis, skull, humeri, and femurs to detect lytic bone lesions 1
- MRI of the spine and pelvis if there are symptoms suggesting bone lesions even with negative X-rays, or if spinal cord compression is suspected 1
- CT scan may be needed to evaluate symptomatic bony sites 1
- PET scan may help distinguish between MGUS, smoldering myeloma, and overt myeloma 1
Diagnostic Criteria
The diagnosis of multiple myeloma requires:
- ≥10% clonal plasma cells in bone marrow or biopsy-proven plasmacytoma 1
- Evidence of end-organ damage (CRAB criteria) attributable to the plasma cell disorder 1:
- Hypercalcemia: serum calcium >11.5 mg/dl
- Renal insufficiency: serum creatinine >2 mg/dl or creatinine clearance <40 ml/min
- Anemia: hemoglobin <10 g/dl or 2 g/dl below lower limit of normal
- Bone lesions: lytic lesions, severe osteopenia, or pathologic fractures
Differential Diagnosis
The workup allows differentiation between 1:
- Multiple myeloma (symptomatic disease requiring treatment)
- Smoldering multiple myeloma (asymptomatic but with ≥3 g/dl monoclonal protein and/or ≥10% clonal plasma cells)
- Monoclonal gammopathy of undetermined significance (MGUS) (<3 g/dl monoclonal protein, <10% clonal plasma cells, no end-organ damage)
Important Considerations
- A complete workup is essential as early diagnosis impacts mortality and morbidity outcomes 3, 4
- Bone marrow biopsy and aspirate should be performed simultaneously to avoid repeat procedures 1
- The highest percentage of plasma cells from either procedure should be recorded for diagnostic purposes 1
- FISH analysis should be performed preferably after sorting of plasma cells 1
- MRI provides more detailed information about bone marrow involvement and is mandatory when spinal cord compression is suspected 1, 5
By following this comprehensive diagnostic approach, clinicians can accurately diagnose or rule out multiple myeloma, allowing for appropriate management decisions that directly impact patient outcomes.