Skip to content
Inciteful Med

The Road to Diagnosis: Symptoms and Testing

Last updated:

Multiple Myeloma is diagnosed using CRAB criteria (signs of organ damage like bone lesions or kidney failure) or SLiM biomarkers (early warning signs like high plasma cells). Meeting either set of criteria confirms the diagnosis and allows doctors to start treatment to prevent severe complications.

Key Takeaways

  • • The CRAB criteria (Calcium, Renal, Anemia, Bone) identify active myeloma that is causing organ damage.
  • • SLiM biomarkers allow doctors to diagnose and treat myeloma early, before severe symptoms occur.
  • • A bone marrow biopsy is the gold standard test to confirm the percentage of cancerous plasma cells.
  • • Whole-body MRI or low-dose CT scans are preferred over X-rays for detecting early bone lesions.
  • • Urine testing for Bence Jones proteins is essential for assessing and monitoring kidney health.

The process of diagnosing Multiple Myeloma has evolved. Doctors no longer wait for the disease to cause significant damage before starting treatment. Instead, they use a combination of physical symptoms and specific “biomarkers” to determine when to act [1][2].

The “Classic” Signs: CRAB

For decades, doctors used the CRAB criteria to identify active myeloma. These represent the “fire” of the disease—actual evidence of organ damage [3][4].

  • C - Calcium Elevation: Bone breakdown releases calcium into the blood [3]. This causes extreme thirst, nausea, and confusion [5].
  • R - Renal (Kidney) Insufficiency: Abnormal M-proteins clog the kidneys, leading to damage [3][6].
  • A - Anemia: Myeloma cells “crowd out” healthy red blood cells, causing fatigue [7][3].
  • B - Bone Lesions: “Punched-out” holes in the bone that are fragile and prone to fracture [3][8].

The “Early” Warning Signs: SLiM

In 2014, the criteria were updated to include SLiM biomarkers. Think of these as “heavy smoke”—proof that a fire is imminent. If any one of these is present, patients are treated for active myeloma [9]:

  • S - Sixty Percent Plasma Cells: Bone marrow biopsy shows ≥60%\ge 60\% cancerous plasma cells [9][10].
  • Li - Light Chain Ratio: A serum free light chain ratio of ≥100\ge 100 AND the “involved” light chain level is ≥100\ge 100 mg/L (10 mg/dL) [9][11].
  • M - MRI Lesions: MRI shows more than one focal lesion (≥5\ge 5mm) in the bone [9][12].

Key Diagnostic Tests

  • Bone Marrow Biopsy: The “gold standard.” A sample of marrow is taken from the hip to count plasma cells and check genetics [13][14].
  • Modern Imaging: Whole-Body Low-Dose CT or MRI are now preferred over X-rays because they can find bone damage much earlier [15][12].
  • Urine Testing: A 24-hour urine collection checks for Bence Jones proteins (light chains in urine), which is critical for monitoring kidney risk [16][17].

Diagnostic “Cousins”

  • MGUS and Smoldering Myeloma: Precursor stages where criteria are not yet met [18].
  • AL Amyloidosis: A related condition where proteins fold incorrectly and deposit in organs [19].

Frequently Asked Questions

What are the CRAB criteria for multiple myeloma?
CRAB stands for Calcium elevation, Renal (kidney) insufficiency, Anemia, and Bone lesions. These are the classic signs that multiple myeloma is active and has already caused damage to the body's organs or bones.
What do SLiM biomarkers mean for my diagnosis?
SLiM biomarkers are early warning signs that include 60% or more plasma cells in bone marrow, a high Light chain ratio, or MRI lesions. If you have even one of these markers, doctors treat it as active myeloma to prevent future organ damage.
How is a bone marrow biopsy used to diagnose myeloma?
A bone marrow biopsy is considered the gold standard for diagnosis. It involves taking a small sample of marrow from the hip to count the percentage of cancerous plasma cells and check for specific genetic changes.
Why did my doctor order a CT or MRI instead of an X-ray?
Modern imaging like whole-body low-dose CT or MRI is preferred because it can detect bone damage much earlier than standard X-rays. Finding lesions early allows for quicker treatment intervention.
What is a Bence Jones protein test?
Bence Jones proteins are light chains found in the urine of some myeloma patients. A 24-hour urine collection test detects these proteins, which is critical for monitoring the risk of kidney damage.

Questions for Your Doctor

  • • Based on my results, do I meet the CRAB criteria for organ damage or the SLiM biomarkers for early treatment?
  • • Why was a whole-body low-dose CT or MRI chosen over a traditional skeletal survey?
  • • What was the exact percentage of plasma cells in my bone marrow?
  • • Is my 'involved' free light chain level above 100 mg/L?
  • • Are my symptoms (like back pain) definitely from myeloma, or could they be something else?
  • • What steps should I take to protect my kidneys right now?

Questions for You

  • • Have I noticed any new or worsening bone pain, especially in my back or ribs?
  • • Have I felt unusually tired, weak, or short of breath (signs of anemia)?
  • • Have I experienced excessive thirst or confusion (signs of high calcium)?
  • • How did I feel during my bone marrow biopsy?

Want personalized information?

Type your question below to get evidence-based answers tailored to your situation.

References

  1. 1

    Updated Diagnostic Criteria and Staging System for Multiple Myeloma.

    Rajkumar SV

    American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting 2016; (35()):e418-23 doi:10.14694/EDBK_159009.

    PMID: 27249749
  2. 2

    Recent Advances in the Management of Smoldering Multiple Myeloma.

    Madhira BR, Konala VM, Adapa S, et al.

    World journal of oncology 2020; (11(2)):45-54 doi:10.14740/wjon1245.

    PMID: 32284772
  3. 3

    Cutaneous Multiple Myeloma.

    Miriyala LKV, Avasthi D

    Cureus 2021; (13(9)):e17779 doi:10.7759/cureus.17779.

    PMID: 34659990
  4. 4

    Hyperammonemic Encephalopathy in Multiple Myeloma: A Case Report.

    Vahora I, Panneerselvam E, Deoker A

    Cureus 2023; (15(1)):e33626 doi:10.7759/cureus.33626.

    PMID: 36788901
  5. 5

    Role of bone-modifying agents in advanced cancer.

    Desautels DN, Harlos CH, Jerzak KJ

    Annals of palliative medicine 2020; (9(3)):1314-1323 doi:10.21037/apm.2019.08.07.

    PMID: 31500423
  6. 6

    [Diagnosis and treatment of kidney involvement in plasma cell diseases : Renal involvement in multiple myeloma and monoclonal gammopathies].

    Gödecke V, Schmidt JJ, Bräsen JH, et al.

    Der Internist 2019; (60(1)):10-22 doi:10.1007/s00108-018-0538-7.

    PMID: 30635666
  7. 7

    Bone Marrow Disease Profile in Geriatric Patients: An Institutional Experience.

    Gulati A, Mandal T, Kaushal V, et al.

    Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 2018; (34(3)):540-543 doi:10.1007/s12288-017-0871-3.

    PMID: 30127568
  8. 8

    Bone Disease in Multiple Myeloma: Biologic and Clinical Implications.

    Bernstein ZS, Kim EB, Raje N

    Cells 2022; (11(15)) doi:10.3390/cells11152308.

    PMID: 35954151
  9. 9

    Diagnostics for multiple myeloma.

    Yamazaki E

    [Rinsho ketsueki] The Japanese journal of clinical hematology 2016; (57(10)):2096-2103 doi:10.11406/rinketsu.57.2096.

    PMID: 27795519
  10. 10

    Multiple myeloma: 2020 update on diagnosis, risk-stratification and management.

    Rajkumar SV

    American journal of hematology 2020; (95(5)):548-567 doi:10.1002/ajh.25791.

    PMID: 32212178
  11. 11

    Multiple myeloma: 2022 update on diagnosis, risk stratification, and management.

    Rajkumar SV

    American journal of hematology 2022; (97(8)):1086-1107 doi:10.1002/ajh.26590.

    PMID: 35560063
  12. 12

    Diagnostic Innovations: Advances in imaging techniques for diagnosis and follow-up of multiple myeloma.

    Talarico M, Barbato S, Cattabriga A, et al.

    Journal of bone oncology 2025; (51()):100669 doi:10.1016/j.jbo.2025.100669.

    PMID: 40124904
  13. 13

    Comparison of bone marrow aspiration cytology with bone marrow trephine biopsy histopathology: An observational study.

    Gilotra M, Gupta M, Singh S, Sen R

    Journal of laboratory physicians 2017; (9(3)):182-189 doi:10.4103/JLP.JLP_117_16.

    PMID: 28706388
  14. 14

    Bone marrow aspiration and biopsy: techniques and practice implications.

    Tomasian A, Jennings JW

    Skeletal radiology 2022; (51(1)):81-88 doi:10.1007/s00256-021-03882-w.

    PMID: 34398308
  15. 15

    A prospective study of Skeletal survey versus Low-dose whole-body CT for Osteolytic lesions in Multiple Myeloma.

    Gundesen MT, Asmussen JT, Haukås E, et al.

    European journal of haematology 2022; (108(5)):423-429 doi:10.1111/ejh.13749.

    PMID: 35113466
  16. 16

    Historical perspectives in clinical pathology: Bence Jones protein-early urine chemistry and the impact on modern day diagnostics.

    Sewpersad S, Pillay TS

    Journal of clinical pathology 2021; (74(4)):212-215 doi:10.1136/jclinpath-2020-206675.

    PMID: 32471887
  17. 17

    Multiple Myeloma Presenting as Acute Renal Failure in the Absence of Other Characteristic Features.

    Gastelum ZN, Biggs DM, Scott A

    Cureus 2017; (9(9)):e1703 doi:10.7759/cureus.1703.

    PMID: 29159010
  18. 18

    [Skeletal changes in plasma cell dyscrasias].

    Weber TF, Mokry T

    Der Radiologe 2021; (61(12)):1078-1089 doi:10.1007/s00117-021-00932-1.

    PMID: 34889973
  19. 19

    Multiple myeloma initially manifesting as a solitary deep ulcer on the tongue: a case study and literature review.

    Zhang Y, Wu Y, Yao L, et al.

    European journal of dermatology : EJD 2023; (33(6)):618-623 doi:10.1684/ejd.2023.4628.

    PMID: 38465542

This guide explains the diagnostic criteria for Multiple Myeloma for educational purposes. Always consult your hematologist or oncologist to interpret your specific test results and diagnosis.

Stay up to date

Get notified when new research about Multiple Myeloma is published.

No spam. Unsubscribe anytime.