Diagnostic Study for Suspected Multiple Myeloma
The most appropriate diagnostic study is serum and urine protein electrophoresis with immunofixation, serum free light chain assay, and bone marrow aspiration with biopsy. 1, 2
Clinical Presentation Analysis
This elderly man presents with the classic CRAB criteria indicating active multiple myeloma requiring immediate diagnosis:
- Hypercalcemia: Calcium 12.4 mg/dL (>11.5 mg/dL threshold) 3, 1
- Renal insufficiency: Creatinine 1.8 mg/dL (>2 mg/dL threshold approached) 3, 1
- Anemia: Hemoglobin 9.3 g/dL (<10 g/dL threshold) 3, 1
- Bone involvement: Three months of non-traumatic lower back pain, present at rest, unresponsive to NSAIDs 3, 4
The combination of these findings with worsening fatigue in an elderly patient makes multiple myeloma the primary diagnostic consideration. 2, 4
Essential Immediate Laboratory Tests
First-line diagnostic tests must include:
- Serum protein electrophoresis (SPEP) with immunofixation to detect and characterize monoclonal protein 1, 2
- 24-hour urine collection for protein electrophoresis and immunofixation (not random sample) to detect Bence Jones proteins 1, 2
- Serum free light chain (FLC) assay with kappa/lambda ratio to detect light chain myeloma and assess disease burden 1, 2
- Nephelometric quantification of IgG, IgA, and IgM to measure total immunoglobulin levels 1, 2
- Serum β2-microglobulin for prognostic staging 2, 4
These tests establish the presence of a monoclonal protein, which is required for diagnosis in secretory myeloma (>95% of cases). 1, 4
Bone Marrow Examination
Bone marrow aspiration and biopsy are mandatory to confirm the diagnosis and require:
- ≥10% clonal plasma cells on bone marrow examination for multiple myeloma diagnosis 3, 1
- CD138 staining to accurately quantify plasma cell percentage 3, 1
- Cytogenetic/FISH studies for risk stratification, specifically looking for del(17p), t(4;14), t(14;16), and del(13q) 1, 4
The bone marrow examination is essential because it differentiates multiple myeloma from MGUS (which has <10% plasma cells) and provides critical prognostic information. 3, 1
Skeletal Imaging
Complete skeletal survey or advanced imaging is required to document bone involvement:
- Complete skeletal survey (plain radiographs) as initial imaging 3, 4
- MRI of spine and pelvis if skeletal survey is negative but clinical suspicion remains high, as MRI is more sensitive for detecting bone marrow involvement 3
- PET/CT scan can detect active myeloma and is more sensitive than plain radiographs 3
Given this patient's persistent midline lumbar pain, imaging will likely reveal lytic lesions or vertebral involvement. 3, 4
Critical Diagnostic Pitfalls to Avoid
Do not assume CRAB criteria always indicate multiple myeloma. While highly suggestive, lymphoma (particularly diffuse large B-cell lymphoma) can present identically with hypercalcemia, renal dysfunction, anemia, and bone lesions. 5, 6 This is why protein electrophoresis and bone marrow biopsy are mandatory—if these are negative, alternative diagnoses including lymphoma must be pursued with tissue biopsy of any masses. 5, 6
Do not perform contrast studies without adequate hydration in this patient with renal insufficiency, as contrast can worsen renal function. 2
Do not delay bone marrow examination. The enlarged prostate is likely incidental; prostate cancer rarely causes this constellation of findings with hypercalcemia and the specific laboratory abnormalities seen here. 3
Immediate Management Considerations
While establishing the diagnosis, immediate supportive care is critical:
- Aggressive hydration (>3 L/24h) to protect renal function and treat hypercalcemia 3, 2
- Bisphosphonates or denosumab for hypercalcemia treatment 3
- Avoid nephrotoxins including NSAIDs (which the patient is already taking) 2
The hypercalcemia contributes to renal failure through volume depletion and direct nephrotoxicity, creating a medical emergency requiring prompt intervention. 2, 7