Skip to main content
SpringerLink
Log in

T2-fluid-attenuated inversion recovery mismatch sign in lower grade gliomas: correlation with pathological and molecular findings

  • Original Article
  • Published:
Brain Tumor Pathology Aims and scope Submit manuscript

Abstract

After the new molecular-based classification was reported to be useful for predicting prognosis, the T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign has gained interest as one of the promising methods for detecting lower grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutations and chromosome 1p/19q non-codeletion (IDH mut-Noncodel) with high specificity. Although all institutions could use T2-FLAIR mismatch sign without any obstacles, this sign was not completely helpful because of its low sensitivity. In this study, we attempted to uncover the mechanism of T2-FLAIR mismatch sign for clarifying the cause of this sign’s low sensitivity. Among 99 patients with LGGs, 22 were T2-FLAIR mismatch sign-positive (22%), and this sign as a marker of IDH mut-Noncodel showed a sensitivity of 55.6% and specificity of 96.8%. Via pathological analyses, we could provide evidence that not only microcystic changes but the enlarged intercellular space was associated with T2-FLAIR mismatch sign (p = 0.017). As per the molecular analyses, overexpression of mTOR-related genes (m-TOR, RICTOR) were detected as the molecular events correlated with T2-FLAIR mismatch sign (p = 0.020, 0.030. respectively). Taken together, we suggested that T2-FLAIR mismatch sign could pick up the IDH mut-Noncodel LGGs with enlarged intercellular space or that with overexpression of mTOR-related genes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Agarwal S, Sharma MC, Jha P et al (2013) Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing. Neuro Oncol 15(6):718–726. https://doi.org/10.1093/neuonc/not015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Claus EB, Walsh KM, Wiencke JK et al (2015) Survival and low-grade glioma: the emergence of genetic information. Neurosurg Focus 38(1):E6. https://doi.org/10.3171/2014.10.FOCUS12367

    Article  PubMed  PubMed Central  Google Scholar 

  3. Deguchi S, Oishi T, Mitsuya K et al (2020) Clinicopathological analysis of T2-FLAIR mismatch sign in lower-grade gliomas. Sci Rep 10(1):10113. https://doi.org/10.1038/s41598-020-67244-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Eckel-Passow JE, Lachance DH, Molinaro AM et al (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372(26):2499–2508. https://doi.org/10.1056/NEJMoa1407279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Eibl RH, Schneemann M (2021) Liquid biopsy and primary brain tumors. Cancers (Basel). https://doi.org/10.3390/cancers13215429

    Article  Google Scholar 

  6. Goyal A, Yolcu YU, Goyal A et al (2019) The T2-FLAIR-mismatch sign as an imaging biomarker for IDH and 1p/19q status in diffuse low-grade gliomas: a systematic review with a Bayesian approach to evaluation of diagnostic test performance. Neurosurg Focus 47(6):E13. https://doi.org/10.3171/2019.9.FOCUS19660

    Article  PubMed  Google Scholar 

  7. Jary H, Rylance J, Patel L, Gordon SB, Mortimer K (2015) Comparison of methods for the analysis of airway macrophage particulate load from induced sputum, a potential biomarker of air pollution exposure. BMC Pulm Med 15:137. https://doi.org/10.1186/s12890-015-0135-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jebali A, Dumaz N (2018) The role of RICTOR downstream of receptor tyrosine kinase in cancers. Mol Cancer 17(1):39. https://doi.org/10.1186/s12943-018-0794-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jian A, Jang K, Manuguerra M, Liu S, Magnussen J, Di Ieva A (2021) Machine learning for the prediction of molecular markers in glioma on magnetic resonance imaging: a systematic review and meta-analysis. Neurosurgery 89(1):31–44. https://doi.org/10.1093/neuros/nyab103

    Article  PubMed  Google Scholar 

  10. Kinoshita M, Uchikoshi M, Sakai M, Kanemura Y, Kishima H, Nakanishi K (2021) t(2)-FLAIR mismatch sign is caused by long t(1) and t(2) of IDH-mutant, 1p19q non-codeleted astrocytoma. Magn Reson Med Sci 20(1):119–123. https://doi.org/10.2463/mrms.bc.2019-0196

    Article  CAS  PubMed  Google Scholar 

  11. Lass U, Hartmann C, Capper D et al (2013) Chromogenic in situ hybridization is a reliable alternative to fluorescence in situ hybridization for diagnostic testing of 1p and 19q loss in paraffin-embedded gliomas. Brain Pathol 23(3):311–318. https://doi.org/10.1111/bpa.12003

    Article  CAS  PubMed  Google Scholar 

  12. Liu Y, Lu Y, Li A et al (2020) mTORC2/Rac1 pathway predisposes cancer aggressiveness in IDH1-mutated glioma. Cancers (Basel). https://doi.org/10.3390/cancers12040787

    Article  PubMed  PubMed Central  Google Scholar 

  13. Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of Tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1

    Article  PubMed  Google Scholar 

  14. Louis DN, Wesseling P, Aldape K et al (2020) cIMPACT-NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT-Utrecht meeting on future CNS tumor classification and grading. Brain Pathol 30(4):844–856. https://doi.org/10.1111/bpa.12832

    Article  PubMed  PubMed Central  Google Scholar 

  15. Makino Y, Arakawa Y, Yoshioka E, Miyamoto S et al (2021) Prognostic stratification for IDH-wild-type lower-grade astrocytoma by Sanger sequencing and copy-number alteration analysis with MLPA. Sci Rep 11(1):14408. https://doi.org/10.1038/s41598-021-93937-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nicholson C, Hrabětová S (2017) Brain extracellular space: the final frontier of neuroscience. Biophys J 113(10):2133–2142. https://doi.org/10.1016/j.bpj.2017.06.052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Onishi S, Amatya VJ, Kolakshyapati M et al (2020) T2-FLAIR mismatch sign in dysembryoplasticneuroepithelial tumor. Eur J Radiol 126:108924. https://doi.org/10.1016/j.ejrad.2020.108924

    Article  PubMed  Google Scholar 

  18. Park SI, Suh CH, Guenette JP, Huang RY, Kim HS (2021) The T2-FLAIR mismatch sign as a predictor of IDH-mutant, 1p/19q-noncodeleted lower-grade gliomas: a systematic review and diagnostic meta-analysis. Eur Radiol 31(7):5289–5299. https://doi.org/10.1007/s00330-020-07467-4

    Article  CAS  PubMed  Google Scholar 

  19. Patel SH, Poisson LM, Brat DJ et al (2017) T2-FLAIR Mismatch, an Imaging Biomarker for IDH and 1p/19q Status in Lower-grade Gliomas: a TCGA/TCIA Project. Clin Cancer Res 23(20):6078–6085. https://doi.org/10.1158/1078-0432.CCR-17-0560

    Article  CAS  PubMed  Google Scholar 

  20. Pinto C, Noronha C, Taipa R, Ramos C (2022) T2-FLAIR mismatch sign: a roadmap of pearls and pitfalls. Br J Radiol 95(1129):20210825. https://doi.org/10.1259/bjr.20210825

    Article  PubMed  Google Scholar 

  21. Pollo B (2011) Neuropathological diagnosis of brain tumours. Neurol Sci 32(suppl 2):S209–S211. https://doi.org/10.1007/s10072-011-0802-2

    Article  PubMed  Google Scholar 

  22. Sun H, Yin L, Li S et al (2013) Prognostic significance of IDH mutation in adult low-grade gliomas: a meta-analysis. J Neurooncol 113(2):277–284. https://doi.org/10.1007/s11060-013-1107-5

    Article  CAS  PubMed  Google Scholar 

  23. Tay KL, Tsui A, Phal PM, Drummond KJ, Tress BM (2011) MR imaging characteristics of protoplasmic astrocytomas. Neuroradiology 53(6):405–411. https://doi.org/10.1007/s00234-010-0741-2

    Article  PubMed  Google Scholar 

  24. van den Bent MJ, Smits M, Kros JM, Chang SM (2017) Diffuse infiltrating oligodendroglioma and astrocytoma. J Clin Oncol 35(21):2394–2401. https://doi.org/10.1200/JCO.2017.72.6737

    Article  PubMed  Google Scholar 

  25. Weller M, Weber RG, Willscher E et al (2015) Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups. Acta Neuropathol 129(5):679–693. https://doi.org/10.1007/s00401-015-1409-0

    Article  CAS  PubMed  Google Scholar 

  26. Yamashita S, Yokogami K, Matsumoto F et al (2018) MGMT promoter methylation in patients with glioblastoma: is methylation-sensitive high-resolution melting superior to methylation-sensitive polymerase chain reaction assay? J Neurosurg 130(3):780–788. https://doi.org/10.3171/2017.11.JNS171710

    Article  PubMed  Google Scholar 

  27. Yokogami K, Yamasaki K, Matsumoto F et al (2018) Impact of PCR-based molecular analysis in daily diagnosis for the patient with gliomas. Brain Tumor Pathol 35(3):141–147. https://doi.org/10.1007/s10014-018-0322-3

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank A. Nagatomo and Y. Miura for their excellent technical assistance.

Author information

Authors and Affiliations

  1. Division of Neurosurgery, Department of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, 5200 Kihara Kiyotake, Miyazaki, 889-1692, Japan

    Shinji Yamashita, Hideo Takeshima, Natsuki Ogasawara, Tomoki Kawano, Mitsuru Tamura, Jyunichiro Muta, Kiyotaka Saito, Go Takeishi, Asako Mizuguchi, Takashi Watanabe, Hajime Ohta & Kiyotaka Yokogami

  2. Department of Radiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Yoshihito Kadota & Minako Azuma

  3. Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Tsuyoshi Fukushima

Authors
  1. Shinji Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hideo Takeshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshihito Kadota
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Minako Azuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tsuyoshi Fukushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Natsuki Ogasawara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tomoki Kawano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mitsuru Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jyunichiro Muta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kiyotaka Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Go Takeishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Asako Mizuguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Takashi Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Hajime Ohta
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Kiyotaka Yokogami
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shinji Yamashita.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest related to this work.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamashita, S., Takeshima, H., Kadota, Y. et al. T2-fluid-attenuated inversion recovery mismatch sign in lower grade gliomas: correlation with pathological and molecular findings. Brain Tumor Pathol 39, 88–98 (2022). https://doi.org/10.1007/s10014-022-00433-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10014-022-00433-6

Keywords

Search

Navigation