## Distinguishing Ewing Sarcoma Histology from Mimics **Key Point:** Ewing sarcoma is composed of **small, uniform round cells with scant cytoplasm**, NOT large polygonal cells. This is a critical histological distinction that separates it from other small round cell tumors and from rhabdomyosarcoma (which has larger cells with abundant cytoplasm). ### Correct Features of Ewing Sarcoma | Feature | Detail | |---------|--------| | **Location** | Diaphysis or metadiaphyseal region of long bones (femur > tibia > humerus) | | **Histology** | Small, uniform round cells with scant cytoplasm, fine chromatin, inconspicuous nucleoli | | **Cytogenetics** | t(11;22)(q24;q12) → EWS-FLI1 fusion (>90% of cases) | | **Imaging** | Onion-skin (lamellated) periosteal reaction, wide zone of transition, sunburst pattern possible | | **Clinical** | Fever, elevated ESR/CRP, systemic symptoms ("toxic" presentation) | ### Why the Distractor is Wrong **Large polygonal cells with abundant cytoplasm and prominent nucleoli** describe: - **Rhabdomyosarcoma** (embryonal or alveolar) — a different small round cell malignancy - **Hepatocellular carcinoma** — not a bone tumor - **Renal cell carcinoma** — not a bone tumor Ewing sarcoma cells are notably **small and monotonous** with minimal cytoplasm — a key feature used to distinguish it from other round cell tumors on H&E microscopy. **High-Yield:** The morphological hallmark of Ewing sarcoma is the **small, uniform round cell with scant cytoplasm**. Large cells with abundant cytoplasm should immediately raise suspicion for a different diagnosis. **Clinical Pearl:** Immunohistochemistry helps confirm Ewing sarcoma: CD99 (membrane, "rosette" pattern) is positive in >95% of cases; desmin and myogenin are negative (ruling out rhabdomyosarcoma). [cite:Robbins 10e Ch 26]
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