Genomic profiling improves diagnostic accuracy. (A–C) Tectal glioma in a 9-year-old boy initially diagnosed as astrocytoma of uncertain grade found to have KIAA1549-BRAF fusion leading to amended diagnosis of pilocytic astrocytoma, WHO grade I. (A) Axial T2-weighted FLAIR MR image revealing a tectal mass with extension into bilateral thalami. (B) Sagittal T1-weighted post-gadolinium MR image revealing peripheral enhancement and exophytic growth into the third ventricle with obstructive hydrocephalus. (C) Hematoxylin and eosin (H&E) stained section of the tumor. (D–F) Primitive neuroectodermal tumor in the midline of the posterior fossa of an 18-month-old boy initially diagnosed as medulloblastoma found to have somatic DICER1 mutation leading to amended diagnosis of pineoblastoma. (D) Sagittal T2-weighted FLAIR MR image revealing a circumscribed solid mass centered in the midline within the region of the pineal gland causing compression of the subjacent cerebellar vermis. (E–F) H&E stained sections of the tumor. (G–I) Suprasellar mass with cerebrospinal dissemination in an 11-year-old boy initially diagnosed as ependymoma found to have FGFR1 mutation leading to amended diagnosis of high-grade glioma. (G) Coronal T1-weighted post-gadolinium MR image revealing a complex, solid, and cystic mass in the suprasellar space. (H) H&E stained section of the tumor. (I) Immunohistochemistry showing diffuse strong staining for OLIG2 in tumor cells. (J–L) High-grade neoplasm in the cerebellum of a 4-year-old girl initially diagnosed as medulloblastoma found to have internal tandem duplication within exon 15 of BCOR leading to amended diagnosis of CNS high-grade neuroepithelial tumor with BCOR alteration. (J) Coronal T2-weighted MR image. (K–L) H&E stained sections of the tumor. Sequencing reads containing the BCOR internal tandem duplication are shown in Supplementary Fig. 3. Scale bar, 20 µm.