Ependymoma-like tumor with mesenchymal differentiation harboring ZFTA::NCOA2 fusion: a case report

Ependymoma-like tumor with mesenchymal differentiation (ELTMD) is a recently proposed, but not yet formally defined, entity that is not recognized in the 2021 World Health Organization (WHO) classification of central nervous system tumors. Although it shares molecular features, such as ZFTA fusion, with ependymomas, it exhibits distinct histopathological and epigenetic profiles. Herein, we report the case of a 5-year-old girl with a supratentorial tumor harboring the ZFTA::NCOA2 fusion. Histopathology revealed atypical features including mesenchymal and undifferentiated components, which overlapped with those of ependymomas. DNA methylation profiling using two independent classifiers (DKFZ and NIH) yielded no matches, indicating that the tumor did not belong to any recognized CNS class. The failure of subclass assignment by both classifiers suggests that ELTMD represents a potentially epigenetically distinct subgroup. Despite being unclassifiable by the current WHO criteria, the tumor shared features with previously reported ELTMDs, supporting its recognition as an emerging tumor. This highlights the need for additional cases to refine the diagnosis, classification, and future therapeutic strategies.