It is most valuable in scenarios where morphology and immunohistochemistry are ambiguous or conflicting, where essential molecular biomarkers yield negative or indeterminate results, or where the differential diagnosis includes pediatric-type high-grade gliomas, posterior fossa ependymoma subgroups, or rare and emerging methylation-defined entities such as HGAP, HPAP, or BCOR-altered tumors (89). Here, ACP5 is linked to central nervous system cancer.