The clinical significance of the T2-FLAIR mismatch sign in grade II and III gliomas: a population-based study

Abstract

Background: The T2-FLAIR mismatch sign is an imaging finding highly suggestive of isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted (non-codel) gliomas (astrocytomas). In previous studies, it has shown excellent specificity but limited sensitivity for IDH-mut astrocytomas. Whether the mismatch sign is a marker of a clinically relevant subtype of IDH-mut astrocytomas is unknown. Methods: We included histopathologically verified supratentorial lower-grade gliomas (LGG) WHO grade II-III retrospectively during the period 2010-2016. In the period 2017-2018, patients with suspected LGG radiologically were prospectively included, and in this cohort other diagnoses than glioma could occur. Clinical, radiological and molecular data were collected. For clinical evaluation we included all patients with IDH-mut astrocytomas. In the 2010-2016 cohort DNA methylation analysis with Infinium MethylationEPIC BeadChip (Illumina) was performed for patients with an IDH-mut astrocytoma with available tissue. We aimed to examine the association of the T2-FLAIR mismatch sign with clinical factors and outcomes. Additionally, we evaluated the diagnostic reliability of the mismatch sign and its relation to methylation profiles. Results: Out of 215 patients with LGG, 135 had known IDH-mutation and 1p19q codeletion status. Fifty patients had an IDH-mut astrocytoma and 12 of these (24.0%) showed a mismatch sign. The sensitivity and specificity of the mismatch sign for IDH-mut detection were 26.4 and 97.6%, respectively. There were no differences between patients with an IDH-mut astrocytoma with or without mismatch sign when grouped according to T2-FLAIR mismatch sign with respect to baseline characteristics, clinical outcomes and methylation profiles. The overall interrater agreement between neuroradiologist and clinical neurosurgeons for the T2-FLAIR mismatch sign was significant when all 215 MRI examination assessed (κ = 0.77, p < 0.001, N = 215). Conclusion: The T2-FLAIR mismatch sign in patients with an IDH-mut astrocytoma is not associated with clinical presentation or outcome. It seems unlikely that the IDH-mut astrocytomas with mismatch sign represent a specific subentity. Finally, we have validated that the T2-FLAIR mismatch sign is a reliable and specific marker of IDH-mut astrocytomas.

Predictive accuracy of T2-FLAIR mismatch sign for the IDH-mutant, 1p/19q noncodeleted low-grade glioma: An updated systematic review and meta-analysis

“… 14–18 , 20 , 21 A study tried to amass the two independent patient groups (each retrospective and prospective manners). 19 The total included study population was 1342 with individual cohorts ranging from 59 to 408 patients. The patients had mean ages of 43–57 years.…”

The T2-FLAIR Mismatch Sign as an Imaging Indicator of IDH-Mutant, 1p/19q Non-Codeleted Lower Grade Gliomas: A Systematic Review and Diagnostic Accuracy Meta-Analysis

“…We used the QUADAS-2 tool to identify possible risk of bias within the included studies. The assessment revealed low risk of bias and applicability concerns in all studies, except three [ 9 , 10 , 13 ], where the risk was high in regard to the index test, due to the assessment of the MR images by a neurologist in one study and a neurosurgeon in two studies. A high applicability concern was found in one study regarding its index test, since there was no mentioning about the observers being blinded.…”

“…The relatively low diagnostic accuracy presented by the study, might be due to not relying on the strict imaging criteria for the mismatch sign identification that Patel et al first suggested [ 21 ]. In another study, apart from the diagnostic accuracy of the mismatch sign, Corell et al [ 13 ] investigated its relation to methylation profiles. They confirmed its high specificity and low sensitivity, while methylation analysis indicated that the sign does not compromise a separate subentity.…”

The Role of the T2–FLAIR Mismatch Sign as an Imaging Marker of IDH Status in a Mixed Population of Low- and High-Grade Gliomas

“…Throckmorton et al claimed that broadening the criteria to include T2-heterogeneous LGG lesions increased the sensitivity of the T2–FLAIR mismatch sign by 30% [ 26 ]. According to a population-based study focusing on LGGs by Correl et al, the sensitivity and specificity of the mismatch sign for IDH mutation detection were 26.4% and 97.6%, respectively [ 27 ]. Our study extended the spectrum of glioma to include patients with high-grade glioma (HGG).…”