Spinal cord astroblastoma with EWSR1-BEND2 fusion classified as HGNET-MN1 by methylation classification: a case report

The most recurrent fusion of central nervous system high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) is MN1 rearrangement. Here, we report the case of a 36-year-old man with spinal cord astroblastoma showing Ewing Sarcoma breakpoint region 1/EWS RNA-binding protein 1 (EWSR1)-BEN domain-containing 2 (BEND2) fusion. The patient presented with back pain, gait disturbance and dysesthesia in the lower extremities and trunk. Magnetic resonance imaging showed an intramedullary tumor at the T3–5 level, displaying homogeneous gadolinium enhancement. Partial tumor removal was performed with laminectomy. Histological examinations demonstrated solid growth of epithelioid tumor cells showing high cellularity, a pseudopapillary structure, intervening hyalinized fibrous stroma, and some mitoses. Astroblastoma was diagnosed, classified as HGNET-MN1 by the German Cancer Research Center methylation classifier. MN1 alteration was not detected by fluorescence in situ hybridization (FISH), but EWSR1-BEND2 fusion was detected by FISH and RNA sequencing. Previously, a child with EWSR1-BEND2 fusion-positive spinal astroblastoma classified as HGNET-MN1 was reported. In conjunction with that, the present case provides evidence that EWSR1-BEND2 fusion is identified in the entity of HGNET-MN1. Taken together, the BEND2 alteration rather than MN1 may determine the biology of a subset of the central nervous system HGNET-MN1 subclass.