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. 2020 May 20;20(1):450.
doi: 10.1186/s12885-020-06951-w.

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

Alba Corell  1   2 , Sandra Ferreyra Vega  3 , Nickoleta Hoefling  4   5 , Louise Carstam  6   3 , Anja Smits  3   7 , Thomas Olsson Bontell  8   9 , Isabella M Björkman-Burtscher  4   5 , Helena Carén  10 , Asgeir Store Jakola  6   3   11
Affiliations

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

Alba Corell et al. BMC Cancer. .

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.

Keywords: Astrocytoma; Biomarkers; Decision making, prognosis; Oligodendroglioma.

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Conflict of interest statement

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Figures

Fig. 1
Fig. 1
Flowchart of patient inclusion
Fig. 2
Fig. 2
a-b: a) FLAIR sequence demonstrating a relative hypointense signal with the exception of a hyperintense peripheral rim. b) T2W sequence demonstrating homogenous hyperintensive signal with a conspicuous border. This glioma was considered to have a mismatch sign and was diagnosed with an IDH-mutated and 1p19q codeleted glioma (i.e. oligodendroglioma)
Fig. 3
Fig. 3
a-b: a) FLAIR sequence demonstrating a relative hypointense signal with the exception of a hyperintense peripheral rim. b) T2W sequence demonstrating homogenous hyperintensive signal with a conspicuous border. This glioma was considered to have a mismatch sign and was diagnosed with an IDH-mutated and 1p19q codeleted glioma (i.e. oligodendroglioma)
Fig. 4
Fig. 4
a-b: a) FLAIR sequence demonstrating a relative hypointense signal with the exception of a hyperintense peripheral rim. b) T2W sequence demonstrating homogenous hyperintensive signal with a conspicuous border. This glioma was considered to have a mismatch sign and the histopathological diagnosis was glioblastoma (i.e. astrocytoma WHO grade IV, IDH-mut)
Fig. 5
Fig. 5
Overview over MRI mismatch sign assessment and agreement among raters
Fig. 6
Fig. 6
Unsupervised hierarchical clustering analysis on methylation levels for the 5000 most deviating CpG sites in the EPIC methylation array. A value of 0.2 indicated low percentage of methylation and 0,8 a high percentage of methylation. Clustering of the DNA-methylation profiles for the IDH-mut astrocytomas in the retrospective cohort (N = 29) did not identify a T2-FLAIR mismatch-methylation associated phenotype
See this image and copyright information in PMC

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