A 16-year-old boy from Delhi presents with a 3-month history of progressive pain and swelling over the mid-shaft of the right femur. He reports low-grade fever and unintentional weight loss of 3 kg over the past 2 months. On examination, there is localized warmth and tenderness over the anterior thigh with a palpable mass. Plain radiographs show a mixed lytic and sclerotic lesion in the diaphysis with periosteal reaction and an onion-skin appearance. Laboratory investigations reveal an elevated ESR (78 mm/h) and CRP of 45 mg/L. A core needle biopsy shows sheets of small round cells with high mitotic activity. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Ewing Sarcoma ### Key Diagnostic Features **Key Point:** Ewing sarcoma is the second most common primary malignant bone tumor in children and adolescents, typically presenting in the second decade of life with diaphyseal involvement of long bones. ### Clinical Presentation This case demonstrates the classic triad of Ewing sarcoma: 1. **Age and location**: 16-year-old with femoral diaphyseal involvement (femur is the most common site, followed by pelvis and tibia) 2. **Systemic symptoms**: Low-grade fever, weight loss, and elevated inflammatory markers (ESR, CRP) reflecting the aggressive nature 3. **Local findings**: Progressive pain, swelling, warmth, and a palpable mass ### Radiological Features | Feature | Ewing Sarcoma | Osteosarcoma | |---------|---------------|---------------| | **Location** | Diaphysis (shaft) | Metaphysis (end of shaft) | | **Lesion type** | Mixed lytic/sclerotic | Predominantly sclerotic | | **Periosteal reaction** | Onion-skin (lamellated) | Sunburst pattern | | **Age of onset** | 10–20 years | 10–25 years | **High-Yield:** The **onion-skin periosteal reaction** is pathognomonic for Ewing sarcoma, caused by alternating layers of new bone and tumor. ### Histopathology **Key Point:** Sheets of small, round, uniform cells with high nuclear-to-cytoplasmic ratio and abundant mitotic figures. Cells are PAS-positive and contain glycogen. The hallmark genetic finding is **t(11;22)(q24;q12)** translocation resulting in EWSR1-FLI1 fusion gene, which is present in ~90% of cases. ### Diagnostic Algorithm ```mermaid flowchart TD A[Adolescent with diaphyseal bone pain]:::outcome --> B{Radiological pattern?}:::decision B -->|Onion-skin periosteal reaction| C[Ewing sarcoma likely]:::action B -->|Sunburst pattern| D[Osteosarcoma likely]:::action C --> E[Core needle biopsy]:::action E --> F{Small round cells + t 11;22?}:::decision F -->|Yes| G[Confirm Ewing sarcoma]:::outcome F -->|No| H[Consider alternative diagnosis]:::outcome ``` ### Management Implications **Clinical Pearl:** Ewing sarcoma is chemosensitive (unlike osteosarcoma which is osteoid-producing). Neoadjuvant chemotherapy followed by surgery ± radiation is the standard of care, with 5-year survival rates of 60–70% in localized disease. **High-Yield:** Always perform **FISH or RT-PCR for EWSR1-FLI1 fusion** to confirm diagnosis, as this is the gold standard and has prognostic significance. [cite:Robbins 10e Ch 26]