ID #132 YAP1::MAML2 fusion-positive supratentorial ependymoma: a potential subtype of YAP1-fused ependymoma

Background Ependymoma (EPN) is a common pediatric central nervous system tumor. About 6% of supratentorial ependymoma (ST-EPN) have YAP1 fusions, classified as ST-EPN-YAP1, typically with MAMLD1 and occasionally with FAM118B, predominantly observed in infants. Here, we present the first pediatric case of ST-EPN with a rare YAP1::MAML2 fusion, in which detection of this fusion was critical for accurate diagnosis and treatment planning. Case The patient was a 13-year-old boy with a ST-EPN in the medial left parieto-occipital lobe, adjacent to the left lateral ventricle. The patient underwent a craniotomy, and gross total resection was achieved. Histopathology revealed features overlapping EPN and angiocentric glioma, making differentiation between the two entities challenging. Molecular analysis, including DNA methylation profiling and identification of a rare YAP1::MAML2 fusion with RNA sequencing, supported the diagnosis of ST-EPN-YAP1. The patient did not receive adjuvant radiotherapy and has remained recurrence-free for two years as of the last follow up. Conclusions Molecular analysis was essential for establishing an accurate diagnosis of ST-EPN-YAP1 when histopathological differentiation was challenging. Identifying YAP1::MAML2 fusion also played a critical role in treatment decision-making as ST-EPN-YAP1 is associated with a favorable prognostic. Integrated methylation analysis, including our case and a previously reported adult ST-EPN with the same fusion, demonstrated clustering within the ST-EPN-YAP1 subgroup, suggesting that YAP1::MAML2 may represent a possible distinct subtype. Given the small number of reported YAP1::MAML2-fused ST-EPNs, additional studies and the accumulation of further comparable cases are necessary to establish subgroup-specific management strategies.