A 14-year-old girl from Mumbai presents with a 6-week history of progressive left hip pain and a limp. She denies any history of trauma. On examination, she has restricted hip abduction and internal rotation. A plain radiograph of the pelvis shows a large lytic lesion in the left ilium with cortical destruction and a soft tissue mass. MRI reveals a heterogeneous mass with areas of necrosis and hemorrhage, and the tumor crosses the physeal line. Serum LDH is markedly elevated at 1200 U/L. A biopsy shows small round cells with immunohistochemical positivity for CD99 and FLI1. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Ewing Sarcoma of the Pelvis ### Clinical Presentation **Key Point:** Ewing sarcoma of the pelvis is a challenging diagnosis because it presents late with nonspecific symptoms (hip pain, limp) and can reach a large size before detection. Pelvic tumors account for ~20% of all Ewing sarcomas and have a worse prognosis due to delayed diagnosis. ### Distinguishing Features in This Case 1. **Age and demographics**: 14-year-old girl (peak incidence 10–20 years) 2. **Location**: Ilium (pelvis is the second most common site after femur) 3. **Imaging findings**: - Large lytic lesion with cortical destruction - Soft tissue mass (extraosseous component) - Tumor crosses physeal line (indicates aggressive behavior) - Heterogeneous signal with necrosis and hemorrhage on MRI 4. **Laboratory findings**: - **Markedly elevated LDH** (>1000 U/L indicates high tumor burden and poor prognosis) - LDH elevation is seen in ~80% of Ewing sarcomas and correlates with tumor aggressiveness 5. **Immunohistochemistry**: - **CD99 positivity** (membrane antigen, present in >95% of Ewing sarcomas) - **FLI1 positivity** (nuclear transcription factor, part of EWSR1-FLI1 fusion protein) ### Immunohistochemical Profile of Ewing Sarcoma | Marker | Ewing Sarcoma | Osteosarcoma | Lymphoma | |--------|---------------|--------------|----------| | **CD99** | Positive (>95%) | Negative | Negative | | **FLI1** | Positive (fusion protein) | Negative | Negative | | **CD45** | Negative | Negative | Positive | | **Desmin** | Negative | Negative | Negative | | **S100** | Negative/weak | Negative | Variable | **High-Yield:** **CD99 + FLI1 positivity is virtually diagnostic of Ewing sarcoma.** This immunophenotype, combined with small round cell morphology, is the gold standard for diagnosis. ### Genetic Confirmation **Mnemonic:** **EWSR1-FLI1** = **E**wing **S**arcoma **W**ith **R**eciprocal translocation **1** to **F**LI**1** - **t(11;22)(q24;q12)** is present in ~90% of cases - Results in fusion of EWSR1 gene (chromosome 22) with FLI1 gene (chromosome 11) - Fusion protein acts as an aberrant transcription factor driving oncogenic transformation - Detected by FISH, RT-PCR, or sequencing ### Prognostic Factors **Clinical Pearl:** This patient has several poor prognostic indicators: - Large tumor size (pelvic location allows larger size at presentation) - Elevated LDH (>1000 U/L) - Pelvic location (worse prognosis than femoral) - Soft tissue extension ### Diagnostic Flowchart ```mermaid flowchart TD A[Adolescent with hip/pelvic pain]:::outcome --> B{Imaging shows lytic lesion?}:::decision B -->|Yes| C[Small round cell tumor likely]:::action C --> D[Immunohistochemistry]:::action D --> E{CD99 + FLI1 positive?}:::decision E -->|Yes| F[Ewing sarcoma]:::outcome E -->|No| G[Consider lymphoma or other RMS]:::outcome B -->|No| H[Other diagnosis]:::outcome ``` ### Treatment and Prognosis **Key Point:** Ewing sarcoma is chemosensitive. Standard treatment is neoadjuvant chemotherapy (VAC/IE regimen) followed by surgery and/or radiation. 5-year survival for localized disease is 60–70%; for metastatic disease, it drops to 20–30%. [cite:Robbins 10e Ch 26]