|
Final Diagnosis: Ewing Sarcoma Discussion: Primary Ewing sarcoma of the central nervous system (CNS) is a small round blue cell tumor defined by a fusion between a gene of the FET family (commonly EWSR1) to a gene of the ETS family (usually FLI1). A minority of Ewing sarcoma are extraosseous and only a fraction of these involve the craniospinal axis. These tumors most often occur in children and young adults and patients usually present clinically with signs/symptoms of intracranial pressure or other manifestations of mass effect. Most tumors arise sporadically. The histomorphology of Ewing sarcoma is that of a malignant small round blue cell tumor. Tumor cells are primitive-appearing and monomorphic with brisk mitotic activity and areas of necrosis. Occasionally one may encounter Homer-Wright rosettes or focal areas of ganglion cell differentiation. The differential diagnosis based on morphology alone is broad and includes other CNS embryonal malignancies, such as atypical teratoid/rhabdoid tumor (AT/RT), CNS tumor with BCOR internal tandem duplication, and CNS neuroblastoma with FOXR2 activation. One might also consider a high-grade meningioma or solitary fibrous tumor and other sarcomatous neoplasms. Immunohistochemistry is helpful to refine the differential diagnosis. Ewing sarcoma is negative for glial markers (such as GFAP and Olig2) and other lineage markers, though some tumors with neuronal differentiation may show focal immunoreactivity for synaptophysin. Tumors will show retained INI1 and BRG1 expression, helpful to rule out AT/RT. Ewing sarcoma shows diffuse membranous staining for CD99, but this is non-specific. Ewing sarcoma is also characteristically positive for Nkx2.2 and PAX7. Confirmation of the diagnosis relies on molecular demonstration of a FET:ETS family gene fusion due to translocation t(11;22), the most common of which is EWSR1::FLI1. While a sequencing based fusion platform is the preferred methodology, fluorescent in situ hybridization (FISH) can also be employed, keeping in mind that EWSR1 break apart by FISH can be seen in several other tumor types. Ewing sarcoma also has a distinct epigenetic signature which can be identified by DNA methylation methodologies. Clinically, patients who present with metastatic disease have the worst outcomes, with 5-year survival rate of only 30%. Optimal treatment involves induction chemotherapy followed by surgical resection and adjuvant radiation therapy. Favorable outcomes are observed in those patients with a complete response to induction chemotherapy. Tumors with co-occurring mutations in STAG2, CDKN2A, and/or TP53 are also associated with more aggressive disease. References
|
Our Sponsors
