A 62-year-old man presents with bone pain, anemia, and hypercalcemia. Serum protein electrophoresis shows an M-spike. Which investigation is most specific for confirming the diagnosis of multiple myeloma?

Question

Accepted Answer

A. Bone marrow aspirate and trephine biopsy with immunophenotyping. ## Confirmatory Investigation for Multiple Myeloma

**Key Point:** Bone marrow aspirate and trephine biopsy with immunophenotyping is the gold standard confirmatory test for multiple myeloma, demonstrating ≥10% clonal plasma cells (or 5–9% if CRAB criteria or myeloma defining events are present).

### Why Bone Marrow Biopsy is Gold Standard

Multiple myeloma is defined by clonal proliferation of malignant plasma cells in the bone marrow. Morphologic identification of these cells, combined with immunophenotyping (CD38+, CD138+, CD19−, CD20−), establishes the diagnosis with certainty.

### Role of Other Investigations

| Investigation | Purpose | Diagnostic Value |
|---|---|---|
| Serum protein electrophoresis (SPEP) | Detects M-spike | Screening; not confirmatory |
| Serum free light chain ratio | Assesses clonality | Prognostic; supports diagnosis but not diagnostic alone |
| 24-hour urine protein (Bence Jones) | Detects light chain proteinuria | Supportive; present in ~50% of cases |
| Skeletal survey | Identifies lytic lesions | Staging; not diagnostic |

**High-Yield:** The CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions) and SLiM criteria (60% bone marrow plasma cells, involved/uninvolved free light chain ratio ≥100, >1 focal lesion on MRI) are used alongside bone marrow findings to diagnose myeloma.

**Clinical Pearl:** A bone marrow biopsy showing <10% plasma cells does NOT exclude myeloma if CRAB or SLiM criteria are met; these are myeloma-defining events per IMWG 2014 criteria.

**Mnemonic: IMWG Diagnostic Criteria** — Clonal bone marrow plasma cells (≥10%) OR (5–9% + CRAB or SLiM) = Myeloma.

Answer

B. 24-hour urinary protein electrophoresis

Answer

C. Serum free light chain ratio

Answer

D. Skeletal survey radiography

A 62-year-old man presents with bone pain, anemia, and hypercalcemia. Serum protein electrophoresis shows an M-spike. Which investigation is most specific for confirming the diagnosis of multiple myeloma?

Explanation

Confirmatory Investigation for Multiple Myeloma

Why Bone Marrow Biopsy is Gold Standard

Role of Other Investigations

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Investigation	Purpose	Diagnostic Value
Serum protein electrophoresis (SPEP)	Detects M-spike	Screening; not confirmatory
Serum free light chain ratio	Assesses clonality	Prognostic; supports diagnosis but not diagnostic alone
24-hour urine protein (Bence Jones)	Detects light chain proteinuria	Supportive; present in ~50% of cases
Skeletal survey	Identifies lytic lesions	Staging; not diagnostic