The emerging role of intraoperative nanopore sequencing on the neurosurgical strategy in paediatric embryonal brain tumours.

Paediatric neurosurgeons have traditionally relied on preoperative imaging and intraoperative frozen section pathology to guide surgical decision-making in paediatric embryonal brain tumours. However, substantial radiological overlap between medulloblastoma, atypical teratoid/rhabdoid tumour (AT/RT) and embryonal tumour with multilayered rosettes (ETMR) often creates diagnostic uncertainty to support the optimal strategy concerning the balance between the oncological need of radical resection and a maximal safe resection in order to avoid neurological morbidity. For this Child's Nervous System special collection on paediatric embryonal tumours, we present our experience with the potential role of intraoperative real-time molecular diagnostics ('nanopore sequencing') to address this innovation with the potential to inform surgical decision-making. Specifically, we describe the aspects of workflow implementation, integration with neuropathology and surgical decision dynamics, and we illustrate how intraoperative molecular classification can influence surgical decision-making. Particular attention is given to discrimination of subgroup-specific identification in medulloblastoma, AT/RT and ETMR, tumour entities in which real-time confirmation of aggressive biology may support better informed decisions regarding extent of resection. Finally, we discuss key unresolved questions and outline priorities for future clinical and translational studies aimed at defining the impact of intraoperative nanopore sequencing on surgical morbidity, extent of resection and long-term outcomes.