What diagnostic tests are used to rule out multiple myeloma?

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Last updated: June 4, 2025View editorial policy

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From the Guidelines

To rule out multiple myeloma, a combination of diagnostic tests including serum and urine protein electrophoresis, bone marrow biopsy, and imaging studies like X-rays, MRI, or CT scans should be used, as recommended by the most recent guidelines 1.

Diagnostic Tests for Multiple Myeloma

The diagnosis of multiple myeloma involves several key tests, including:

  • Blood tests: complete blood count, blood chemistry, serum protein electrophoresis (SPEP), immunofixation electrophoresis, and free light chain assay to detect abnormal proteins produced by myeloma cells.
  • Urine tests: 24-hour urine collection for protein electrophoresis to identify Bence Jones proteins.
  • Bone marrow biopsy: to examine the percentage of plasma cells and their characteristics.
  • Imaging studies: X-rays, MRI, CT scans, or PET scans to detect bone damage.

When to Rule Out Multiple Myeloma

Multiple myeloma should be ruled out in patients with suspected symptoms, such as anemia, bone pain, or kidney damage. The diagnosis typically requires meeting specific criteria, including:

  • Presence of myeloma cells in the bone marrow
  • Monoclonal protein in blood or urine
  • Evidence of end-organ damage or biomarkers of malignancy The most recent guidelines from the National Comprehensive Cancer Network (NCCN) provide updated criteria for the diagnosis of multiple myeloma, including the use of serum-free light chain measurement and imaging studies like MRI or PET/CT scans 1.

Key Recommendations

  • Bone marrow biopsy is crucial to examine the percentage of plasma cells and their characteristics 1.
  • Imaging studies like X-rays, MRI, or CT scans are used to detect bone damage 1.
  • Serum and urine protein electrophoresis are essential to detect abnormal proteins produced by myeloma cells 1. By following these recommendations and using the most recent guidelines, clinicians can effectively rule out multiple myeloma and provide accurate diagnoses for patients with suspected symptoms.

From the Research

Diagnostic Tests for Multiple Myeloma

To rule out multiple myeloma, several diagnostic tests are used, including:

  • Serum protein electrophoresis with immunofixation 2
  • 24-hour urine protein electrophoresis 2
  • Measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels 2
  • Full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging 2
  • Bone marrow biopsy 3, 4, 5, 2, 6
  • Fluorescence in situ hybridization to assess malignant plasma cell genomic features 2

When to Rule Out Multiple Myeloma

Multiple myeloma should be considered in patients with:

  • Hypercalcemia, renal failure, anemia, or lytic bone lesions 3, 4
  • Monoclonal paraprotein in the serum or urine 5, 6
  • Unexplained bone pain, malaise, or renal insufficiency 6
  • Incidental discovery of a monoclonal paraprotein on comprehensive laboratory panels 6

Staging and Risk Stratification

The Revised International Staging System is used to assess estimated progression-free survival and overall survival in patients with multiple myeloma 2. This system combines data from serum biomarkers and malignant plasma cell genomic features. High-risk multiple myeloma is defined by the presence of certain genetic abnormalities, such as del(17p), t(4;14), or p53 mutation 3, 4.

Additional Evaluations

Additional evaluations, such as skeletal radiographs, magnetic resonance imaging, and positron emission tomography or computed tomography, are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Multiple myeloma: from diagnosis to treatment.

Australian family physician, 2013

Research

Multiple myeloma: diagnosis and treatment.

American family physician, 2008

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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