A 14-year-old girl from Delhi presents with a 2-month history of pain and swelling in the proximal tibia. MRI shows a lesion with marked soft tissue extension and bone marrow edema. Biopsy reveals small round blue cells with t(11;22) translocation. Which feature best distinguishes this Ewing sarcoma from Ewing-like tumors (primitive neuroectodermal tumor, PNET)?

## Ewing Sarcoma vs. PNET: Molecular Distinction ### Cytogenetic Gold Standard **Key Point:** The t(11;22)(q24;q12) translocation is the pathognomonic cytogenetic marker for Ewing sarcoma and is present in 85–95% of cases. This translocation is the single most reliable discriminator between Ewing sarcoma and morphologically similar small round blue cell tumors, including PNET. ### Molecular Basis **High-Yield:** The t(11;22) translocation results in the **EWS-FLI1 fusion gene**, which encodes an aberrant transcription factor. This fusion is: - Specific to Ewing sarcoma (and a subset of PNETs that are now reclassified as Ewing sarcoma family tumors) - Absent in other small round blue cell tumors (rhabdomyosarcoma, lymphoma, neuroblastoma) - Detectable by FISH, RT-PCR, or conventional cytogenetics ### Comparison of Ewing Sarcoma and PNET | Feature | Ewing Sarcoma | PNET | |---------|---------------|------| | **Translocation** | t(11;22); EWS-FLI1 | t(11;22) in ~90%; other translocations possible | | **Histology** | Small round blue cells | Small round blue cells + neural differentiation | | **Neural markers** | Absent or minimal | CD99+, synaptophysin+, neuron-specific enolase+ | | **Location** | Diaphysis of long bones | Soft tissues, thorax, pelvis | | **Prognosis** | Similar to modern PNET | Historically worse; now merged classification | **Clinical Pearl:** Modern WHO classification (2020) has merged Ewing sarcoma and PNET into a single entity called "Ewing sarcoma" because both harbor EWS-FLI1 fusion. The distinction is now based on degree of neural differentiation rather than separate diagnoses. ### Why Other Features Are Non-Discriminatory - **Small round blue cells:** Both Ewing sarcoma and PNET show this histology; it is not specific. - **Soft tissue extension:** Both tumors extend into soft tissues; this is not a discriminator. - **Age:** Both present in adolescence; overlap is complete. [cite:Robbins 10e Ch 26]