The T2-FLAIR mismatch sign in oncologic neuroradiology: History, current use, emerging data, and future directions

The T2-Fluid-Attenuated Inversion Recovery (T2-FLAIR) mismatch sign is a radiogenomic marker that is easily discernible on preoperative conventional MR imaging. Application of strict criteria (adult population, cerebral hemisphere location, and classic imaging morphology) permits the noninvasive preoperative diagnosis of isocitrate dehydrogenase (IDH)-mutant 1p/19q-non-codeleted diffuse astrocytoma with near-perfect specificity, albeit with variably low sensitivity. This leads to improved preoperative planning and patient counseling. More recent research has shown that the application of less strict criteria compromises the near-perfect specificity of the sign but remains adequate for ruling out IDH-wildtype (glioblastoma) phenotype, which bears a far grimmer prognosis compared to IDH-mutant diffuse astrocytic disease. In this review, we elaborate on the various definitions of the T2-FLAIR mismatch sign present in the literature, illustrate these with images obtained at a comprehensive cancer center, discuss the potential of the mismatch sign for application to certain pediatric-type brain tumors, namely dysembryoplastic neuroepithelial tumor and diffuse midline glioma, and elaborate upon the clinical, histologic, and molecular associations of the T2-FLAIR mismatch sign as recognized to date. Finally, the sign's correlates in diffusion- and perfusion-weighted imaging are presented, and opportunities to further maximize the diagnostic and prognostic applications of the sign in the context of the 2021 revision of the WHO Classification of Central Nervous System Tumors are discussed.