Abstract

Abstract OBJECTIVE To assess the validity and pathophysiology of the T2/FLAIR mismatch sign for non-invasive identification of IDH-mutant 1p/19q non-codeleted glioma. METHODS MRI scans from 408 consecutive patients with newly diagnosed glioma (113 lower-grade glioma and 295 glioblastoma) were evaluated for the presence of a T2/FLAIR-mismatch sign (defined as complete/near-complete hyperintense signal on T2w, simultaneous hypointense signal on FLAIR except for a hyperintense peripheral rim) by two independent reviewers. Sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV) were calculated to assess the performance of the T2/FLAIR-mismatch sign for identifying IDH-mutant 1p/19q non-codeleted tumors. An exploratory analysis of spatial differences in ADC and rCBV values comparing the FLAIR-hypointense core vs. hyperintense rim in cases with presence of a T2/FLAIR-mismatch sign was performed. RESULTS There was substantial interrater agreement to identify the T2/FLAIR-mismatch sign (Cohen’s Kappa = 0.75 [95% CI 0.57–0.93]). The T2/FLAIR-mismatch sign was present in 12 cases with lower-grade glioma (10.6%), all of them were IDH-mutant, 1p/19q non-codeleted tumors (sensitivity=10.9%, specificity=100%, PPV=100%, NPV=3.0%, accuracy=13.3%). The T2/FLAIR-mismatch sign was not identified in any other molecular subgroup, especially not in any of the IDH-mutant glioblastoma cases (n=5). In tumors with T2/FLAIR-mismatch sign the ADC values were significantly lower in the rim as compared to the core (p=0.0005) whereas there was no difference in rCBV values (p=0.4258). CONCLUSION This study confirms the high specificity of the T2/FLAIR-mismatch sign for non-invasive identification of IDH-mutant 1p/19q non-codeleted gliomas, although sensitivity is low and applicability is limited to lower-grade gliomas. The identified spatial differences in ADC values between the core and rim of tumors with a T2/FLAIR-mismatch sign potentially reflects differences in tumor cellularity and microenvironment.

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