A 14-year-old boy from Delhi presents with a 3-month history of progressive pain and swelling over the mid-shaft of the left femur. On examination, there is localized warmth, tenderness, and a firm mass over the anterolateral aspect of the thigh. His mother reports he had a low-grade fever intermittently over the past 6 weeks. Laboratory investigations show an elevated ESR (68 mm/hr) and CRP (12 mg/dL). Plain radiographs reveal a mixed lytic and sclerotic lesion in the diaphysis with a "onion-skin" periosteal reaction. MRI shows a large soft tissue component with marrow involvement. What is the most likely diagnosis?

Explanation

## Clinical Presentation & Diagnosis **Key Point:** Ewing sarcoma is a small round cell malignancy of bone that typically affects the diaphysis (shaft) of long bones in adolescents and young adults, with peak incidence 10–20 years. ### Distinguishing Features in This Case | Feature | Ewing Sarcoma | Osteosarcoma | Osteomyelitis | |---------|---------------|--------------|---------------| | **Age** | 10–20 years | 10–25 years (around growth plate) | Any age | | **Location** | Diaphysis (shaft) | Metaphysis (near joint) | Variable | | **Periosteal reaction** | Onion-skin (lamellated) | Sunburst or Codman triangle | Periosteal new bone | | **Soft tissue mass** | Large, prominent | Often present | Minimal | | **Systemic symptoms** | Fever, malaise common | Rare | Fever, chills typical | | **ESR/CRP** | Elevated | Normal/mild elevation | Markedly elevated | **High-Yield:** The **onion-skin (lamellated) periosteal reaction** is pathognomonic for Ewing sarcoma. The diaphyseal location (mid-shaft) is also classic — osteosarcoma favors the metaphysis near the knee. ### Pathology & Imaging **Clinical Pearl:** Ewing sarcoma arises from the medullary cavity and produces a large extraosseous soft tissue mass that often exceeds the bony lesion in size — this is a hallmark feature that helps differentiate it from osteosarcoma. **Mnemonic: EWING** — **E**xcentric location (diaphysis), **W**hite blood cell elevation (systemic inflammation), **I**ntramedullary origin, **N**ecrosis (extensive), **G**reat soft tissue mass. ### Diagnostic Workup 1. **Plain radiographs:** Mixed lytic-sclerotic lesion, onion-skin periosteal reaction, wide zone of transition. 2. **MRI:** Best for assessing marrow involvement and soft tissue extension (essential for surgical planning). 3. **Biopsy:** Small round blue cells, minimal cytoplasm, high mitotic rate; CD99 positive, FLI1 positive (EWS-FLI1 translocation t(11;22)). 4. **Staging:** Chest CT (pulmonary metastases in ~25% at diagnosis), bone scan or PET-CT. **Warning:** Do not confuse the fever and elevated inflammatory markers with infection — Ewing sarcoma can mimic osteomyelitis, but the imaging pattern (onion-skin, diaphyseal location, large soft tissue mass) and lack of response to antibiotics clarify the diagnosis. ### Treatment & Prognosis - **Multimodal therapy:** Neoadjuvant chemotherapy (doxorubicin, cisplatin, ifosfamide) → surgery (wide resection) → adjuvant chemotherapy. - **5-year survival:** ~70% with modern protocols (improved from ~10% with surgery alone). - **Poor prognostic factors:** Large tumor size, metastases, poor chemotherapy response. [cite:Robbins 10e Ch 26]