Lower-grade gliomas (WHO grade II/III) have been classified into clinically relevant molecular subtypes based on and 1p/19q mutation status. The purpose was to investigate whether T2/FLAIR MRI features could distinguish between lower-grade glioma molecular subtypes. MRI scans from the TCGA/TCIA lower grade glioma database ( = 125) were evaluated by two independent neuroradiologists to assess (i) presence/absence of homogenous signal on T2WI; (ii) presence/absence of "T2-FLAIR mismatch" sign; (iii) sharp or indistinct lesion margins; and (iv) presence/absence of peritumoral edema. Metrics with moderate-substantial agreement underwent consensus review and were correlated with glioma molecular subtypes. Somatic mutation, DNA copy number, DNA methylation, gene expression, and protein array data from the TCGA lower-grade glioma database were analyzed for molecular-radiographic associations. A separate institutional cohort ( = 82) was analyzed to validate the T2-FLAIR mismatch sign. Among TCGA/TCIA cases, interreader agreement was calculated for lesion homogeneity [ = 0.234 (0.111-0.358)], T2-FLAIR mismatch sign [ = 0.728 (0.538-0.918)], lesion margins [ = 0.292 (0.135-0.449)], and peritumoral edema [ = 0.173 (0.096-0.250)]. All 15 cases that were positive for the T2-FLAIR mismatch sign were -mutant, 1p/19q non-codeleted tumors ( < 0.0001; PPV = 100%, NPV = 54%). Analysis of the validation cohort demonstrated substantial interreader agreement for the T2-FLAIR mismatch sign [ = 0.747 (0.536-0.958)]; all 10 cases positive for the T2-FLAIR mismatch sign were -mutant, 1p/19q non-codeleted tumors ( < 0.00001; PPV = 100%, NPV = 76%). Among lower-grade gliomas, T2-FLAIR mismatch sign represents a highly specific imaging biomarker for the -mutant, 1p/19q non-codeleted molecular subtype..

Epileptogenic tumors affecting children and young adults are a morphologically diverse collection of neuroepithelial neoplasms that, as a group, exhibit varying levels of glial and/or neuronal differentiation. Recent advances in molecular profiling technology, including comprehensive DNA sequencing and methylation analysis, have enabled the application of more precise and biologically relevant classification schemes to these tumors. In this report, we describe a morphologically and molecularly distinct epileptogenic neoplasm, the polymorphous low-grade neuroepithelial tumor of the young (PLNTY), which likely accounts for a sizable portion of oligodendroglioma-like tumors affecting the pediatric population. Characteristic microscopic findings most notably include infiltrative growth, the invariable presence of oligodendroglioma-like cellular components, and intense immunolabeling for cluster of differentiation 34 (CD34). Moreover, integrative molecular profiling reveals a distinct DNA methylation signature for PLNTYs, along with frequent genetic abnormalities involving either B-Raf proto-oncogene (BRAF) or fibroblast growth factor receptors 2 and 3 (FGFR2, FGFR3). These findings suggest that PLNTY represents a distinct biological entity within the larger spectrum of pediatric, low-grade neuroepithelial tumors.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-016-1639-9) contains supplementary material, which is available to authorized users.

The D2HG product of IDH1 may increase neuronal activity by mimicking the activity of glutamate on the NMDA receptor, and IDH1 gliomas are more likely to cause seizures in patients. This has rapid translational implications for the personalized management of tumor-associated epilepsy, as targeted IDH1 inhibitors may improve antiepileptic therapy in patients with IDH1 gliomas.

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