Super T2-FLAIR mismatch sign: a prognostic imaging biomarker for non-enhancing astrocytoma, IDH-mutant

Abstract

Purpose: The T2-FLAIR mismatch sign is a highly specific diagnostic imaging biomarker for astrocytoma, IDH-mutant. However, a definitive prognostic imaging biomarker has yet to be identified. This study investigated imaging prognostic markers, specifically analyzing T2-weighted and FLAIR images of this tumor.

Methods: We retrospectively analyzed 31 cases of non-enhancing astrocytoma, IDH-mutant treated at our institution, and 30 cases from The Cancer Genome Atlas (TCGA)/The Cancer Imaging Archive (TCIA). We defined "super T2-FLAIR mismatch sign" as having a significantly strong low signal comparable to cerebrospinal fluid at non-cystic lesions rather than just a pale FLAIR low-signal tumor lesion as in conventional T2-FLAIR mismatch sign. Cysts were defined as having a round or oval shape and were excluded from the criteria for the super T2-FLAIR mismatch sign. We evaluated the presence or absence of the T2-FLAIR mismatch sign and super T2-FLAIR mismatch sign using preoperative MRI and analyzed the progression-free survival (PFS) and overall survival (OS) by log-rank test.

Results: The T2-FLAIR mismatch sign was present in 17 cases (55%) in our institution and 9 cases (30%) within the TCGA-LGG dataset without any correlation with PFS or OS. However, the super T2-FLAIR mismatch sign was detected in 8 cases (26%) at our institution and 13 cases (43%) in the TCGA-LGG dataset. At our institution, patients displaying the super T2-FLAIR mismatch sign showed significantly extended PFS (122.7 vs. 35.9 months, p = 0.0491) and OS (not reached vs. 116.7 months, p = 0.0232). Similarly, in the TCGA-LGG dataset, those with the super T2-FLAIR mismatch sign exhibited notably longer OS (not reached vs. 44.0 months, p = 0.0177).

Conclusion: The super T2-FLAIR mismatch is a promising prognostic imaging biomarker for non-enhancing astrocytoma, IDH-mutant.

Keywords: Astrocytoma; Diffuse glioma; IDH-mutant; Imaging biomarker; Non-enhancing glioma; T2-FLAIR mismatch sign.

Fig. 1

Case 1 is a representative case with right frontal lobe astrocytoma, IDH-mutant featuring both the positive super T2-FLAIR mismatch sign and positive conventional T2-FLAIR mismatch sign. No evident contrast enhancement was observed (A, B). The T2-weighted image (C) illustrates a tumor exhibiting nearly uniform hyperintensity. Notably, the FLAIR image (D) reveals a distinctive area within the tumor displaying significantly strong low intensity, comparable to cerebrospinal fluid. Hematoxylin-eosin staining (E) showed enlarged intercellular space and a prominent microcystic background. Case 2 is a representative case with left insular astrocytoma, IDH-mutant displaying a positive super T2-FLAIR mismatch sign but a negative conventional T2-FLAIR mismatch sign. No evident contrast enhancement was observed (F, G). The T2-weighted image (H) illustrates a tumor exhibiting nearly uniform hyperintensity. In the FLAIR image (I), a distinct area within the tumor shows significantly strong low intensity, akin to cerebrospinal fluid. The size of the area with high-intensity T2WI but low-intensity FLAIR did not exceed 50% of the entire tumor. Hematoxylin-eosin staining (J) shows enlarged intercellular space and a prominent microcystic background.

Fig. 2

Case 3 is a representative case with left occipital lobe astrocytoma, IDH-mutant displaying the negative super T2-FLAIR mismatch sign and negative conventional T2-FLAIR mismatch sign. No evident contrast enhancement is observed (A, B). The T2-weighted (C) and FLAIR (D) images illustrate a tumor displaying a uniform hyperintensity. Hematoxylin-eosin staining showed (E) pleomorphic astrocyte tumor cells with a microcystic background. Case 4 is the representative case with left frontal lobe astrocytoma, IDH-mutant displaying a negative super T2-FLAIR mismatch sign but a positive conventional T2-FLAIR mismatch sign. No observable contrast enhancement was noted (F, G). The tumor manifests as a hyperintense area in the T2-weighted image (H) and exhibits a relatively low signal on the FLAIR image (I), except for a hyperintense peripheral rim. Hematoxylin-eosin staining (J) shows an astrocytic tumor amidst a fibrillary and microcystic background.

Fig. 3

Kaplan–Meier analyses of the median progression-free survival (PFS) and overall survival (OS). In our dataset, the cases with the super T2-FLAIR mismatch sign showed significantly longer PFS (122.7 months vs. 35.9 months, p = 0.0491) and longer OS (not reached vs. 116.7 months, p = 0.0232) (A, B). Among the patients with non-total resection, the super T2-FLAIR mismatch sign was also associated with significantly longer PFS (122.7 vs. 27.0 months, p = 0.0025) and OS (not reached vs. 60.7 months, p = 0.0085) (C, D). In the TCGA-LGG dataset, the cases with the super T2-FLAIR mismatch sign did not show a significant correlation with PFS (53.6 months vs. 39.4 months, p = 0.4321) but were significantly associated with a longer OS (not reached vs. 44.0 months, p = 0.0177) (E, F).