Diagnostic Criteria for Multiple Myeloma on Bone Marrow Biopsy
Multiple myeloma requires ≥10% clonal plasma cells on bone marrow examination (or biopsy-proven plasmacytoma) PLUS evidence of end-organ damage (CRAB criteria) or specific myeloma-defining biomarkers. 1, 2
Core Bone Marrow Requirements
The bone marrow component of the diagnosis requires:
- ≥10% clonal bone marrow plasma cells identified on aspiration and biopsy 1
- CD138 staining should be performed to accurately quantify the plasma cell percentage 1, 3
- Cytogenetic and FISH studies must be obtained for risk stratification 1, 3
Essential Additional Criteria Beyond Bone Marrow
The bone marrow finding alone is insufficient. You must also demonstrate ONE OR MORE of the following:
CRAB Criteria (End-Organ Damage)
- Hypercalcemia: Serum calcium >11.5 mg/dL 1
- Renal insufficiency: Serum creatinine >2 mg/dL or creatinine clearance <40 mL/min 1, 3
- Anemia: Hemoglobin <10 g/dL or ≥2 g/dL below lower limit of normal 1
- Bone lesions: Lytic lesions, severe osteopenia, or pathologic fractures on skeletal survey 1
Myeloma-Defining Biomarkers (Even Without CRAB)
- ≥60% clonal plasma cells in bone marrow 4, 5, 2, 6
- Serum involved/uninvolved free light chain ratio ≥100 (provided involved FLC ≥100 mg/L) 2, 6, 7
- >1 focal lesion on MRI (≥5 mm) 2, 6, 7
Required Confirmatory Laboratory Tests
Beyond the bone marrow biopsy, the complete diagnostic workup must include:
- Serum protein electrophoresis with immunofixation to identify monoclonal protein 1, 3
- 24-hour urine collection for protein electrophoresis and immunofixation (not random sample) 1, 3
- Serum free light chain assay with kappa/lambda ratio 3, 8
- Nephelometric quantification of IgG, IgA, and IgM 1, 3
- Presence of serum and/or urinary monoclonal protein (except in true non-secretory myeloma where >10% plasma cells are required) 1
Critical Distinctions to Avoid Misdiagnosis
MGUS (No Treatment Needed)
- Serum monoclonal protein <3 g/dL
- Clonal bone marrow plasma cells <10%
- No CRAB criteria or myeloma-defining biomarkers 1, 3
Smoldering Multiple Myeloma (Observation Only)
- Serum monoclonal protein ≥3 g/dL and/or clonal bone marrow plasma cells ≥10%
- No CRAB criteria or myeloma-defining biomarkers
- Higher progression risk (10% per year for first 5 years) but immediate treatment not recommended 1, 3
Common Pitfalls
The most critical error is diagnosing myeloma based on bone marrow plasma cell percentage alone. You must document either CRAB criteria or myeloma-defining biomarkers—otherwise the patient has smoldering myeloma or MGUS and should not receive treatment. 1, 9
For non-secretory myeloma (rare), you need >10% clonal plasma cells plus CRAB criteria, but monoclonal protein may be absent. 1
The 60% plasma cell threshold is particularly important because it defines myeloma even without CRAB criteria, representing a paradigm shift in diagnostic criteria. 4, 5, 2