DNA methylation profiling from cerebrospinal fluid as a diagnostic tool for pineoblastoma

Pineoblastoma is a rare and aggressive malignancy that often affects pediatric populations. Accurate diagnosis is challenging due to histological overlap with other central nervous system tumors and limited molecular data. DNA methylation profiling and analysis of circulating tumor DNA (derived from both cell dissemination as well as cell-free– cfDNA) in cerebrospinal fluid (CSF) are emerging tools for precise tumor classification, in the field of pediatric central nervous system tumors. Here, we report a challenging case of a 17-year-old refugee girl with a previous diagnosis of a primitive neuroectodermal tumor. Formalin-fixed, paraffin-embedded tissue was not available for histopathological re-evaluation. However, the methylation profiling of low amount of CSF-derived DNA classified the tumor as “pineoblastoma, subtype miRNA processing altered 1, subclass A,” enabling patient management. The diagnosis was later confirmed through tissue-based DNA methylation analysis of a secondary lesion, demonstrating that the epigenetic signature faithfully reflected tumor features. This case report highlights the potential of CSF-based DNA methylation profiling as a minimally invasive yet accurate diagnostic tool for pediatric CNS tumors. The concordance between CSF and tissue profiling supports the integration of liquid biopsy into diagnostic workflows, allowing for earlier diagnosis and personalized treatment strategies. However, more studies are needed to demonstrate the reliability of our approach in other CNS malignancies.