Distinct IDH1/IDH2 mutation profiles in purely insular versus paralimbic WHO Grade II gliomas.

The molecular profile of diffuse WHO Grade II gliomas involving the insular lobe, with a possible impact on outcome, is controversial. The authors undertook this study to investigate a possible difference of molecular patterns between purely insular Grade II gliomas and paralimbic Grade II gliomas that involve both the insular lobe and the frontal and/or temporal structures. From a consecutive series of 47 patients who underwent resection of a Grade II glioma invading the insula, 2 subgroups were identified. The first subgroup included 11 patients with a purely insular tumor. The second subgroup included 36 patients with a paralimbic Grade II glioma also involving the frontal and/or temporal lobe. The authors searched systematically for TP53 mutations, 1p19q codeletion, and IDH1/IDH2 mutations. There was no significant difference between the 2 subgroups with respect to 1p19q codeletion or TP53 mutations rates. Conversely, IDH1/IDH2 mutations were found in all 11 (100%) of the insular Grade II gliomas but only 20 (55%) of 36 paralimbic Grade II gliomas (p = 0.008). Ten (28%) of the 36 patients in the paralimbic tumor group experienced a malignant transformation, and 6 of them died; whereas neither transformation nor death occurred in the insular tumor group (trend toward significance, p = 0.088). These findings demonstrate for the first time distinct IDH1/IDH2 and consequently distinct "triplenegative" patterns in purely insular versus paralimbic Grade II gliomas. Such findings could explain discrepancies reported in the literature, because insular and paralimbic gliomas have not been separated in previous reports. These results may enable physicians to refine the management of Grade II gliomas involving the insula according to the presence or lack of invasion of the frontal and/or temporal areas.