What diagnostic test confirms multiple myeloma?

Bone Marrow Biopsy Confirms Multiple Myeloma

The diagnosis of multiple myeloma is confirmed by bone marrow aspirate and/or biopsy demonstrating ≥10% clonal plasma cells, combined with evidence of end-organ damage (CRAB criteria) or specific myeloma-defining events 1, 2.

Diagnostic Algorithm

The confirmation process requires a systematic approach integrating multiple tests:

Essential Confirmatory Tests

Bone marrow examination is the definitive confirmatory test - you need either:

• Unilateral bone marrow aspirate showing >10% clonal plasma cells, OR
• Bone marrow biopsy (trephine) with CD138 staining to accurately quantify plasma cells 1

The biopsy is often superior because it provides more reliable assessment of plasma cell infiltration and avoids inadequate sampling 1. Clonality must be established through immunoperoxidase staining or immunofluorescence demonstrating monoclonal immunoglobulin in plasma cell cytoplasm 1.

Supporting Laboratory Tests Required for Diagnosis

While bone marrow confirms the plasma cell burden, you need these additional tests to establish the complete diagnosis 1, 3:

• Serum protein electrophoresis with immunofixation - identifies and types the monoclonal protein
• 24-hour urine protein electrophoresis with immunofixation - detects urinary monoclonal protein (cannot be replaced by random urine samples) 1
• Serum free light chain assay - particularly important when involved/uninvolved ratio ≥100 (with involved FLC ≥100 mg/L), which itself can be a myeloma-defining event 2
• Complete blood count - documents anemia
• Serum calcium and creatinine - identifies hypercalcemia and renal failure (CRAB criteria)

Imaging to Complete Diagnosis

Skeletal survey (spine, pelvis, skull, humeri, femurs) or advanced imaging (CT, PET-CT, or MRI) identifies lytic bone lesions 1, 3. More than one focal lesion on MRI qualifies as a myeloma-defining event even without CRAB features 2.

Critical Diagnostic Criteria

The 2024 updated criteria require 2:

1. ≥10% clonal bone marrow plasma cells OR biopsy-proven plasmacytoma
2. PLUS one or more of:
   • CRAB features (hypercalcemia, renal failure, anemia, bone lesions)
   • Bone marrow clonal plasmacytosis ≥60%
   • Serum involved/uninvolved FLC ratio ≥100 (with involved FLC ≥100 mg/L)

   • 1 focal lesion on MRI

Common Pitfalls

• Don't rely on serum protein electrophoresis alone - immunofixation is mandatory to confirm monoclonality 1, 4
• Don't skip urine studies - approximately 20% of patients have Bence Jones proteinuria, and immunofixation should be performed even without visible protein on routine urinalysis 1
• Don't use bone marrow aspirate percentage from flow cytometry - this cannot reliably determine plasma cell percentage; use morphologic assessment with CD138 staining 1
• Nephelometric quantitation may overestimate monoclonal protein when concentrations are high 1

Risk Stratification After Confirmation

Once diagnosis is confirmed, cytogenetics (metaphase karyotype and FISH) from the bone marrow are essential 1 to identify high-risk features: del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, or p53 mutation 2. The Revised International Staging System combines β2-microglobulin, albumin, and lactate dehydrogenase with these genomic features to determine prognosis 3.