The T2-FLAIR mismatch sign as an imaging marker for non-enhancing IDH-mutant, 1p/19q-intact lower-grade glioma: a validation study

Abstract
The purpose of this study was to assess the reproducibility of the previously described T2–fluid attenuated inversion recovery (FLAIR) mismatch sign as a specific imaging marker in non-enhancing isocitrate dehydrogenase (IDH) mutant, 1p/19q non-codeleted lower-grade glioma (LGG), encompassing both diffuse and anaplastic astrocytoma. MR scans (n = 154) from 3 separate databases with genotyped LGG were evaluated by 2 independent reviewers to assess (i) presence/absence of “T2-FLAIR mismatch” sign and (ii) presence/absence of homogeneous signal on T2-weighted images. Interrater agreement with Cohen’s kappa (κ) was calculated, as well as diagnostic test performance of the T2-FLAIR mismatch sign to identify IDH-mutant astrocytoma. There was substantial interrater agreement for the T2-FLAIR mismatch sign [κ = 0.75 (0.64–0.87)], but only fair agreement for T2 homogeneity [κ = 0.38 (0.25–0.52)]. The T2-FLAIR mismatch sign was present in 38 cases (25%) and had a positive predictive value of 100%, negative predictive value of 68%, a sensitivity of 51%, and a specificity of 100%. With a robust interrater agreement, our study confirms that among non-enhancing LGG the T2-FLAIR mismatch sign represents a highly specific imaging marker for IDH-mutant astrocytoma. This non-invasive marker may enable a more informed patient counsel and can aid in the treatment decision processes in a significant proportion of patients presenting with non-enhancing, LGG-like lesions.