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Purpose <p>The T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign is a highly specific imaging biomarker of astrocytoma, IDH-mutant; however, its clinical utility is limited by its low sensitivity. This study aimed to investigate factors contributing to false-negative findings, focusing on the impact of tumor area and quantitative thresholds used for diagnosis.</p> Methods <p>This retrospective, single-institution study included 38 patients with pathologically confirmed, nonenhancing astrocytoma. The T2-FLAIR mismatch sign was evaluated using two quantitative area cutoffs (&gt; 50% and &gt; 33%). Associations with CNS WHO grade, <i>CDKN2A</i> homozygous deletion (HD) status (assessed by MTAP surrogate), and tumor area were analyzed. Subgroup analysis was performed for 33 patients excluding cases with <i>CDKN2A</i> HD.</p> Results <p>The positivity rate of the mismatch sign in nonenhancing astrocytoma increased from 55.3% at the &gt; 50% cutoff to 73.7% at the &gt; 33% cutoff. In the overall cohort, tumor area was significantly smaller in the mismatch-negative group compared to the mismatch-positive group; however, this difference was significant only at the &gt; 33% threshold (<i>p</i> = 0.0432, Mann–Whitney <i>U</i> test). The group difference in tumor area became more significant at the &gt; 33% threshold after excluding <i>CDKN2A</i> HD cases (<i>p</i> = 0.0078, Mann–Whitney <i>U</i> test). We observed mismatch-negative nonenhancing astrocytomas without <i>CDKN2A</i> HD became mismatch-positive during the tumor growth.</p> Conclusion <p>Absence of the T2-FLAIR mismatch sign is an ambiguous finding representing two distinct entities: biologically aggressive tumors with <i>CDKN2A</i> HD or early-stage, small astrocytoma. A negative mismatch sign should not exclude astrocytoma, IDH-mutant from the differential diagnosis—particularly in small nonenhancing glioma cases.</p>

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T2-FLAIR mismatch sign in nonenhancing astrocytoma, IDH-mutant: impact of tumor area on diagnostic sensitivity

  • 期刊论文

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  • 发表日期：

    2026年3月19日

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  • Iori Ozono,
  • Fumiyuki Yamasaki,
  • Shumpei Onishi,
  • Ushio Yonezawa,
  • Akira Taguchi,
  • Yusuke Takeishi,
  • Novita Ikbar Khairunnisa,
  • Vishwa Jeet Amatya,
  • Yukio Takeshima,
  • Nobutaka Horie

摘要

Purpose

The T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign is a highly specific imaging biomarker of astrocytoma, IDH-mutant; however, its clinical utility is limited by its low sensitivity. This study aimed to investigate factors contributing to false-negative findings, focusing on the impact of tumor area and quantitative thresholds used for diagnosis.

Methods

This retrospective, single-institution study included 38 patients with pathologically confirmed, nonenhancing astrocytoma. The T2-FLAIR mismatch sign was evaluated using two quantitative area cutoffs (> 50% and > 33%). Associations with CNS WHO grade, CDKN2A homozygous deletion (HD) status (assessed by MTAP surrogate), and tumor area were analyzed. Subgroup analysis was performed for 33 patients excluding cases with CDKN2A HD.

Results

The positivity rate of the mismatch sign in nonenhancing astrocytoma increased from 55.3% at the > 50% cutoff to 73.7% at the > 33% cutoff. In the overall cohort, tumor area was significantly smaller in the mismatch-negative group compared to the mismatch-positive group; however, this difference was significant only at the > 33% threshold (p = 0.0432, Mann–Whitney U test). The group difference in tumor area became more significant at the > 33% threshold after excluding CDKN2A HD cases (p = 0.0078, Mann–Whitney U test). We observed mismatch-negative nonenhancing astrocytomas without CDKN2A HD became mismatch-positive during the tumor growth.

Conclusion

Absence of the T2-FLAIR mismatch sign is an ambiguous finding representing two distinct entities: biologically aggressive tumors with CDKN2A HD or early-stage, small astrocytoma. A negative mismatch sign should not exclude astrocytoma, IDH-mutant from the differential diagnosis—particularly in small nonenhancing glioma cases.