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Multiple Myeloma

Laboratory Studies | Bone Marrow Evaluation | Imaging Studies | Diagnostic Criteria | References

Multiple Myeloma diagnostic overview

The diagnostic workup for multiple myeloma includes comprehensive laboratory testing, bone marrow evaluation, and advanced imaging to establish the diagnosis and assess disease burden.[1]

Laboratory Studies

The initial laboratory evaluation should include CBC with differential and platelet count, peripheral blood smear, comprehensive metabolic panel (BUN/creatinine, electrolytes, liver function tests, calcium), serum uric acid, albumin, lactate dehydrogenase (LDH), and beta-2 microglobulin.[1-2]

Creatinine clearance should be calculated or measured directly.[1]

Essential protein studies include serum quantitative immunoglobulins, serum protein electrophoresis (SPEP) with serum immunofixation electrophoresis (SIFE), 24-hour urine for total protein with urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE), and serum free light chain (FLC) assay.[1-2]

NT-proBNP or BNP should also be obtained.[1]

Bone Marrow Evaluation

A unilateral bone marrow aspirate and biopsy is required, including immunohistochemistry and/or multi-parameter flow cytometry to confirm clonality.[1-2]

Plasma cell fluorescence in situ hybridization (FISH) panel should be performed on a CD138-positive selected sample, testing for del(13), del(17p13), t(4;14), t(11;14), t(14;16), t(14;20), 1q21 gain/amplification, and 1p deletion.[1]

Next-generation sequencing (NGS) to assess for TP53 mutation is also recommended.[1]

Imaging Studies

Whole-body FDG-PET/CT is the preferred imaging modality, with whole-body low-dose CT as an alternative.[1]

If these are negative, whole-body MRI without contrast may be considered to distinguish smoldering myeloma from active multiple myeloma.[1]

In resource-limited settings, skeletal survey is acceptable.[1]

Additional Testing in Certain Circumstances

Consider tissue biopsy for suspected plasmacytoma, echocardiogram, evaluation for light chain amyloidosis, serum viscosity, hepatitis B/C and HIV screening, assessment for circulating plasma cells, and renal biopsy if albuminuria or abnormal renal function is present.[1]

Diagnostic Criteria

Multiple myeloma requires clonal bone marrow plasma cells ≥10% (or biopsy-proven plasmacytoma) plus at least one myeloma-defining event, which includes either CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions) or biomarkers of malignancy (≥60% bone marrow plasma cells, involved:uninvolved FLC ratio ≥100, or >1 focal lesion ≥5mm on MRI).[1-2]

References
  1. Multiple Myeloma. National Comprehensive Cancer Network. Updated 2026-01-09.
  2. Diagnosis and Management of Multiple Myeloma: A Review. The Journal of the American Medical Association. 2022. Cowan AJ, Green DJ, Kwok M, et al. JAMA. 2022.