A 16-year-old boy presents with a 3-month history of progressive pain and swelling in the left femur. He reports fever and weight loss over the past 6 weeks. On examination, there is a firm, warm swelling over the mid-shaft of the femur with restricted hip and knee movements. Laboratory investigations show an elevated ESR (78 mm/hr) and CRP (12 mg/dL). Plain radiographs reveal a mixed lytic and sclerotic lesion in the diaphysis with an onion-skin periosteal reaction. MRI shows a large soft tissue mass with marrow involvement. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Ewing Sarcoma ### Key Clinical Features **Key Point:** Ewing sarcoma is the second most common primary malignant bone tumor in children and young adults (age 10–25 years), with a peak incidence in the second decade of life. ### Diagnostic Criteria Met in This Case | Feature | Finding in Case | Significance | |---------|-----------------|---------------| | **Age** | 16 years | Peak incidence for Ewing sarcoma | | **Location** | Femoral diaphysis (mid-shaft) | Diaphyseal origin is pathognomonic; osteosarcoma favors metaphysis | | **Radiographic pattern** | Mixed lytic/sclerotic with onion-skin periosteal reaction | "Onion-skin" (lamellated) periostitis is classic for Ewing | | **Systemic symptoms** | Fever, weight loss, elevated inflammatory markers | Aggressive tumor biology; B-symptoms common | | **Soft tissue mass** | Large extraosseous component on MRI | Ewing tends to produce large soft tissue masses | ### Pathological Hallmark **High-Yield:** Ewing sarcoma arises from the diaphysis or diaphyseal-metaphyseal region of long bones (femur > tibia > fibula > humerus). The tumor is a small round cell malignancy with t(11;22) translocation (EWSR1-FLI1 fusion gene) in 85–90% of cases. ### Radiological Features 1. **Lytic lesion** with ill-defined margins 2. **Onion-skin (lamellated) periosteal reaction** — concentric layers of new bone formation 3. **Sunburst pattern** — less common than in osteosarcoma 4. **Soft tissue mass** — often larger than the intraosseous component 5. **Marrow edema** on MRI — extensive intramedullary involvement ### Why This Is NOT the Other Options **Clinical Pearl:** Osteosarcoma typically occurs in the metaphysis (especially around the knee), produces a "sunburst" periosteal reaction, and occurs in slightly older adolescents (15–20 years). Giant cell tumor is an epiphyseal lesion in skeletally mature patients (20–40 years). Osteomyelitis would show sequestrum (dead bone) and involucrum, not a malignant soft tissue mass. ### Management Approach ```mermaid flowchart TD A[Suspected Ewing Sarcoma]:::outcome --> B[Confirm with biopsy]:::action B --> C[Histology + t11;22 translocation]:::action C --> D[Staging: CT chest, PET-CT]:::action D --> E[Neoadjuvant chemotherapy]:::action E --> F{Surgical resection feasible?}:::decision F -->|Yes| G[Wide excision + reconstruction]:::action F -->|No| H[Radiotherapy]:::action G --> I[Adjuvant chemotherapy]:::action H --> I ``` **Mnemonic:** **EWSR1** = Ewing Sarcoma Region 1 (the gene involved in the translocation). **Warning:** Do not confuse the "onion-skin" periosteal reaction of Ewing with the "sunburst" of osteosarcoma — they are radiologically distinct and have different prognostic implications.