Abstract Background Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. This study aims at evaluating the prognostic impact of molecular typing of pediatric spinal cord ependymomas. Methods Eighty-three patients with spinal ependymomas ≤22 years registered in the HIT-MED database between 1992 and 2022 were included. Forty-seven tumors were analyzed by DNA methylation array profiling. In six cases, HOXB13 and MYCN proteins were detected as surrogate markers for specific methylation classes. Ten patients had NF2-related schwannomatosis. Results With a median follow-up time of 4.9 years (y), 5y- and 10y-overall survival (OS) were 100% and 86%, while 5y- and 10y-progression-free survival (PFS) were 65% and 54%. Myxopapillary ependymoma (SP-MPE, n=32, 63%) was the most common molecular type followed by spinal ependymoma (SP-EPN, n=17, 33%) and MYCN-amplified ependymoma (n=2, 4%). One case could not be molecularly classified, and one was reclassified as anaplastic pilocytic astrocytoma. 5y-PFS did not significantly differ between SP-MPE and SP-EPN (65% versus 78%, p=0.64). MYCN-amplification was associated with early relapses (<2.3y) in both cases and death in one patient. Patients with SP-MPE subtype B (n=9) showed a non-significant trend for better 5y-PFS compared to subtype A (n=18; 86% versus 56%, p=0.15). The extent of resection and WHO tumor grades significantly influenced PFS in a uni- and multivariate analysis. Conclusions Molecular typing of pediatric spinal ependymomas aids to identify very-high-risk MYCN-amplified ependymomas. Further insights into the molecular heterogeneity of spinal ependymomas are needed for future clinical decision-making.
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