A 62-year-old man from Mumbai presents with progressive back pain and fatigue for 3 months. Examination reveals pallor and mild hepatomegaly. Laboratory investigations show: Hemoglobin 8.2 g/dL, serum calcium 11.8 mg/dL (corrected), serum creatinine 2.4 mg/dL, and serum albumin 2.8 g/dL. Serum protein electrophoresis reveals an M-spike in the gamma region. Bone marrow aspiration shows 35% plasma cells. X-ray spine shows multiple lytic lesions. Which of the following is the MOST likely diagnosis based on CRAB criteria?

Explanation

## Diagnosis: Multiple Myeloma with CRAB Criteria ### CRAB Criteria for Multiple Myeloma **Key Point:** The CRAB criteria are the hallmark diagnostic framework for symptomatic multiple myeloma. The patient meets ALL four criteria: | Criterion | Definition | Patient Status | |-----------|-----------|----------------| | **C** — Calcium | Serum calcium >11 mg/dL (corrected) | ✓ Present (11.8 mg/dL) | | **R** — Renal | Serum creatinine >2 mg/dL | ✓ Present (2.4 mg/dL) | | **A** — Anemia | Hemoglobin <10 g/dL | ✓ Present (8.2 g/dL) | | **B** — Bone lesions | Lytic lesions on imaging | ✓ Present (multiple lytic lesions on spine X-ray) | ### Pathophysiology of CRAB Manifestations 1. **Hypercalcemia (C):** Osteoclast activation by IL-6 and TNF-α secreted by myeloma cells → increased bone resorption → hypercalcemia 2. **Renal impairment (R):** Light chain nephropathy (cast nephropathy/myeloma kidney) from filtered immunoglobulin light chains → tubular obstruction and damage 3. **Anemia (A):** Bone marrow infiltration by plasma cells → reduced erythropoiesis; also IL-6 mediated suppression of erythropoietin 4. **Bone lesions (B):** Myeloma cells produce RANKL → osteoclast activation; suppression of osteoblasts by DKK-1 and sclerostin → net bone loss and lytic lesions **High-Yield:** A patient meeting ANY ONE CRAB criterion + clonal bone marrow plasma cells (≥10%) + clonal serum/urine M-protein = diagnostic of symptomatic multiple myeloma. This patient meets all four. **Clinical Pearl:** The M-spike on serum protein electrophoresis (gamma region) combined with 35% bone marrow plasma cells confirms clonal proliferation; lytic lesions distinguish myeloma from MGUS or smoldering disease. ### Why This Is NOT MGUS MGUS is defined as: - Serum M-protein <3 g/dL, AND - Bone marrow plasma cells <10%, AND - Absence of CRAB criteria and SLiM criteria (clonal bone marrow lymphocytes, light chain ratio, MRI bone lesions) This patient has 35% plasma cells and meets CRAB criteria → symptomatic myeloma, not MGUS. [cite:Robbins and Cotran 10e Ch 13]