A 61-year old woman presented to the surgical OPD with severe low back pain, loss of weight & breathlessness. On examination he was anaemic and there was tenderness over mid thoracic vertebra. X-ray of chest & lumbar vertebra revealed punched out osteolytic y lesions in ribs & vertebral bodies. The following were the results of laboratory investigation Serum Albumin : 3.2 gm/dL Urine Bence Jones Protein : + ve Serum electrophoresis showed M band A. What is your Probable diagnosis B. Name the relevant tests to be performed in the above case
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International Myeloma Working Group diagnostic criteria multiple myeloma recommended diagnostic tests
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A. Probable diagnosis
Multiple myeloma (plasma-cell myeloma).
This is supported by:
- Bone pain and vertebral tenderness
- Anaemia and weight loss
- Multiple punched-out osteolytic lesions in ribs and vertebrae
- Serum M band indicating monoclonal immunoglobulin
- Urinary Bence-Jones protein indicating monoclonal free light chains
These findings are typical of symptomatic myeloma with the anaemia and bone-lesion components of CRAB end-organ damage. Multiple myeloma is a plasma-cell malignancy associated with marrow infiltration, anaemia, bone pain, fractures, and skeletal destruction. Goldman-Cecil Medicine, p. 2300.
B. Relevant tests
1. Tests to confirm and characterize the monoclonal protein
- Serum protein electrophoresis (SPEP) with quantification of M-protein
- Serum immunofixation electrophoresis (IFE) to identify immunoglobulin type, such as IgG-kappa or IgA-lambda
- 24-hour urine total protein, urine protein electrophoresis and urine immunofixation, with quantification of Bence-Jones protein
- Serum free light-chain assay with kappa/lambda ratio
- Quantitative serum immunoglobulins: IgG, IgA, IgM
Immunofixation is more sensitive than electrophoresis and should accompany electrophoresis when myeloma is suspected. Goldman-Cecil Medicine, pp. 1957-1958.
2. Bone marrow examination
- Bone marrow aspiration and trephine biopsy
- Percentage of plasma cells
- Morphology for atypical plasma cells
- Immunophenotyping by flow cytometry to demonstrate clonality, typically CD38/CD138 positive with light-chain restriction
- Cytogenetic/FISH testing for prognostic abnormalities, including del(17p), t(4;14), t(14;16), 1q gain/amplification, and t(11;14).
A diagnosis is supported by clonal marrow plasma cells of 10% or more, alongside a myeloma-defining event. Goldman-Cecil Medicine, p. 2300.
3. Assess CRAB complications and baseline organ function
- Complete blood count with peripheral smear, reticulocyte count
- Serum calcium, phosphate, alkaline phosphatase
- Renal function: serum urea, creatinine, eGFR, electrolytes
- Serum total protein, albumin, globulin and A/G ratio
- Serum uric acid and LDH
- Beta-2 microglobulin and serum albumin for International Staging System assessment
- LDH and cytogenetics for Revised ISS risk stratification
4. Skeletal and disease-extent imaging
- Conventional skeletal survey: skull, spine, ribs, pelvis, humeri and femora
- Preferably low-dose whole-body CT to define osteolytic lesions
- MRI of the spine urgently in this patient because of severe back pain and vertebral involvement, to exclude cord compression and detect marrow/focal lesions
- PET-CT where available for osseous and extramedullary disease assessment
The IMWG recommends whole-body low-dose CT, PET-CT, or MRI for appropriate assessment of suspected myeloma; CT-confirmed lytic lesions at least 5 mm qualify as myeloma bone disease under diagnostic criteria, according to IMWG diagnostic criteria.
Key diagnostic confirmation: bone marrow clonal plasma cells at least 10% plus this patient's lytic bone lesions and anaemia establishes active multiple myeloma.
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