MPTH-12ISOCITRATE DEHYDROGENASE MUTANT DIFFUSE GLIOMAS GRADES II AND III ARE RADIOLOGICAL INDISTINGUISHABLE AND UNDERLIE ONLY MOLECULAR ALTERATIONS

OBJECTIVES: There has recently been increasing evidence that IDH-mutant diffuse gliomas WHO grades II and III – which are still graded based upon light microscopical criteria – share many clinical similarities. Here, we sought to determine whether IDH-mutant diffuse gliomas grades II/III have similar radiological presentations in magnetic resonance imaging (MRI). METHODS: Clinical and radiological data of 79 patients; 40 patients with an glioma WHO grade II and 39 patients with glioma WHO grade III were collected. Sequencing of IDH1 codon 132, IDH2 codon 172 as well as of the TERT-promoter (C146 and C160) was performed. Moreover, The 1p/19q-co deletion status was determined in gliomas harboring oligodendroglial components (n = 32). Using immunohistochemistry, the MIB-1 index and the p53 over-expression status were detected. All molecular data were correlated to the tumor features on MRI before treatment. RESULTS: IDH mutations were present in 63 patients (79.7%; in 34 patients with grade II and 29 patients with grade III gliomas, respectively). TERT mutations were detected in 36% and a co-deleted 1p/19q status in 31% of the entire group. Both groups of glioma grades with an IDH mutation depicted similar radiological features – in regard to tumor size, tumor localization, insular involvement, contrast enhancement, local and/or bilateral infiltration pattern, midline shifting and diffusion restriction – without any significant differences. IDH-mutant gliomas with TERT mutations and/or 1p/19q co-deletion were predominantly located in the frontal lobe and did not cross the midline nor involve insular structures, making a gross total resection more amenable. A high MIB-1-index and a p53 over-expression were associated with a bigger tumor size and bilateral infiltration of the hemispheres. CONCLUSIONS: Our analysis implicates that IDH-mutant gliomas WHO grades II and III are MR-radiologically indistinguishable. We further elucidate that the clinical behavior of diffuse gliomas more likely underlines molecular alterations than the pathological subclasses.