A 14-year-old boy presents to the orthopaedic clinic with a 3-month history of progressive pain and swelling over the left femur. He reports low-grade fever and night sweats. On examination, the left thigh is warm and tender with a palpable mass. Laboratory investigations show elevated ESR (78 mm/hr) and CRP (12 mg/dL). Plain radiographs reveal a mixed lytic and sclerotic lesion in the diaphysis of the femur with periosteal reaction. MRI shows a large soft tissue component. A biopsy reveals small round cells with scanty cytoplasm arranged in sheets, with positive immunohistochemistry for CD99 and FLI1. What is the most appropriate next step in management?

Explanation

## Diagnosis and Management of Ewing Sarcoma ### Clinical Presentation **Key Point:** Ewing sarcoma typically presents in adolescents (10–20 years) with pain, swelling, and systemic symptoms (fever, night sweats). The lesion is usually diaphyseal or metadiaphyseal, unlike osteosarcoma which is metaphyseal. ### Pathological Features **High-Yield:** Small round cell tumour with: - Scanty cytoplasm, round nuclei, minimal mitotic activity - Positive CD99 (membrane glycoprotein) and FLI1 (transcription factor) - t(11;22) translocation (EWSR1-FLI1 fusion gene) — diagnostic hallmark ### Treatment Algorithm ```mermaid flowchart TD A[Ewing Sarcoma Confirmed]:::outcome --> B[Staging: CT chest, bone scan/PET]:::action B --> C{Metastatic disease?}:::decision C -->|No| D[Neoadjuvant chemotherapy<br/>5-drug regimen]:::action C -->|Yes| E[Neoadjuvant chemotherapy<br/>+ palliative intent]:::action D --> F[Response assessment<br/>MRI/CT]:::action F --> G[Surgical resection<br/>with wide margins]:::action E --> G G --> H[Adjuvant chemotherapy<br/>to complete 12 months]:::action H --> I[Long-term surveillance<br/>2-year disease-free survival ~70%]:::outcome ``` ### Multimodal Treatment Protocol | Phase | Timing | Details | |-------|--------|----------| | **Neoadjuvant** | Weeks 0–12 | 5-drug regimen: Doxorubicin, Cisplatin, Ifosfamide, Etoposide, Actinomycin D | | **Surgical** | Week 12–14 | Wide local excision or amputation (limb salvage if feasible with adequate margins) | | **Adjuvant** | Weeks 14–52 | Continuation of chemotherapy to complete 12 months total | **Clinical Pearl:** Neoadjuvant chemotherapy improves survival from ~10% (surgery alone) to ~70% (multimodal therapy). It also allows time for limb salvage planning and assessment of chemotherapy response (good prognostic indicator). ### Why Surgery Alone Fails **Warning:** Ewing sarcoma is a systemic disease at presentation — micrometastases are present in ~90% of cases. Surgery without chemotherapy results in rapid local recurrence and distant metastases. **Key Point:** The 5-year survival with multimodal therapy is approximately 65–75%; with surgery alone, it drops to <10%. [cite:Robbins 10e Ch 26]