Ependymomas are among the most enigmatic tumors of the central nervous system, posing enormous challenges for pathologists and clinicians. Despite the efforts made, the treatment options are still limited to surgical resection and radiation therapy, while none of conventional chemotherapies is beneficial. While being histologically similar, ependymomas show considerable clinical and molecular diversity. Their histopathological evaluation alone is not sufficient for reliable diagnostics, prognosis, and choice of treatment strategy. The importance of integrated diagnosis for ependymomas is underscored in the recommendations of Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy. These updated recommendations were adopted and implemented by WHO experts. This minireview highlights recent advances in comprehensive molecular-genetic characterization of ependymomas. Strong emphasis is made on the use of molecular approaches for verification and specification of histological diagnoses, as well as identification of prognostic markers for ependymomas in children.

Infant hemispheric high-grade gliomas (iHGGs) constitute a biologically and clinically distinct subgroup of pediatric HGGs. One defining hallmark of iHGG is rearrangement of receptor tyrosine kinase either ALK, ROS1, NTRK1,2,3, or MET. The ROS1-positive iHGGs are an exceptionally rare tumor subtype with a relatively poor prognosis.¹ The most typical ROS1 fusion partner for such tumors is GOPC.² Here we describe two extremely rare cases of iHGG with ROS1 fused with the Zinc Finger CCHC-Type Containing 8 (ZCCHC8) gene. Although these patients had major differences in clinical presentation, MRI characteristics, and histopathology, both children were successfully treated with the NTRK/ROS1/ALK inhibitor entrectinib. To date, only two ZCCHC8:ROS1-positive gliomas were described; one of the patients received targeted therapy.^3,4