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Patterns of T2-FLAIR discordance across a cohort of adult-type diffuse gliomas and deviations from the classic T2-FLAIR mismatch sign

  • Diagnostic Neuroradiology
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Abstract

Purpose

T2-FLAIR mismatch serves as a highly specific but insensitive marker for IDH-mutant (IDHm) astrocytoma with potential limitations in real-world application. We aimed to assess the utility of a broader definition of T2-FLAIR discordance across a cohort of adult-type diffuse lower-grade gliomas (LrGG) to see if specific patterns emerge and additionally examine factors determining deviation from the classic T2-FLAIR mismatch sign.

Methods

Preoperative MRIs of non-enhancing adult-type diffuse LrGGs were reviewed. Relevant demographic, molecular, and MRI data were compared across tumor subgroups.

Results

Eighty cases satisfied the inclusion criteria. Highest discordance prevalence and > 50% T2-FLAIR discordance volume were noted with IDHm astrocytomas (P < 0.001), while < 25% discordance volume was associated with oligodendrogliomas (P = 0.03) and IDH-wildtype (IDHw) LrGG (P = 0.004). “T2-FLAIR matched pattern” was associated with IDHw LrGG (P < 0.001) and small or minimal areas of discordance with oligodendrogliomas (P = 0.03). Sensitivity and specificity of classic mismatch sign for IDHm astrocytoma were 25.7% and 100%, respectively (P = 0.06). Retained ATRX expression and/or non-canonical IDH mutation (n = 10) emerged as a significant factor associated with absence of classic T2-FLAIR mismatch sign in IDHm astrocytomas (100%, P = 0.02) and instead had minimal discordance or matched pattern (40%, P = 0.04).

Conclusion

T2-FLAIR discordance patterns in adult-type diffuse LrGGs exist on a diverging but distinct spectrum of classic mismatch to T2-FLAIR matched patterns. Specific molecular markers may play a role in deviations from classic mismatch sign.

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Data availability

The data that support the findings of this study are not openly available but are available from the corresponding author upon reasonable request.

Abbreviations

IDH:

Isocitrate dehydrogenase

LrGG:

Lower-grade glioma

IDHm:

IDH-mutant

IDHw:

IDH-wildtype

ATRX:

α-Thalassemia, mental retardation, X-linked

GBM:

Glioblastoma

References

  1. Broen MPG, Smits M, Wijnenga MMJ et al (2018) The T2-FLAIR mismatch sign as an imaging marker for non-enhancing IDH-mutant, 1p/19q-intact lower-grade glioma: a validation study. Neuro Oncol 20:1393–1399. https://doi.org/10.1093/neuonc/noy048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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 23:6078–6085. https://doi.org/10.1158/1078-0432.CCR-17-0560

    Article  CAS  PubMed  Google Scholar 

  3. Juratli TA, Tummala SS, Riedl A et al (2019) Radiographic assessment of contrast enhancement and T2/FLAIR mismatch sign in lower grade gliomas: correlation with molecular groups. J Neurooncol 141:327–335. https://doi.org/10.1007/s11060-018-03034-6

    Article  CAS  PubMed  Google Scholar 

  4. Jain R, Johnson DR, Patel SH et al (2020) “Real world” use of a highly reliable imaging sign: “T2-FLAIR mismatch” for identification of IDH mutant astrocytomas. Neuro Oncol 22:936–943. https://doi.org/10.1093/neuonc/noaa041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Johnson DR, Kaufmann TJ, Patel SH et al (2019) There is an exception to every rule—T2-FLAIR mismatch sign in gliomas. Neuroradiology 61:225–227. https://doi.org/10.1007/s00234-018-2148-4

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  7. Lasocki A, Gaillard F, Gorelik A, Gonzales M (2018) MRI features can predict 1p/19q Status in intracranial gliomas. Am J Neuroradiol 39:687–692. https://doi.org/10.3174/ajnr.A5572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lee MD, Patel SH, Mohan S et al (2023) Association of partial T2-FLAIR mismatch sign and isocitrate dehydrogenase mutation in WHO grade 4 gliomas: results from the ReSPOND consortium. Neuroradiology 65:1343–1352. https://doi.org/10.1007/s00234-023-03196-9

    Article  PubMed  Google Scholar 

  9. Nakasu S, Deguchi S, Nakasu Y (2023) IDH wild-type lower-grade gliomas with glioblastoma molecular features: a systematic review and meta-analysis. Brain Tumor Pathol. https://doi.org/10.1007/s10014-023-00463-8

    Article  PubMed  Google Scholar 

  10. Kibe Y, Motomura K, Ohka F et al (2023) Imaging features of localized IDH wild-type histologically diffuse astrocytomas: a single-institution case series. Sci Rep 13:23. https://doi.org/10.1038/s41598-022-25928-2

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rudà R, Bruno F, Ius T et al (2021) IDH wild-type grade 2 diffuse astrocytomas: prognostic factors and impact of treatments within molecular subgroups. Neuro Oncol 24:809–820. https://doi.org/10.1093/neuonc/noab239

    Article  PubMed Central  Google Scholar 

  12. Tay KL, Tsui A, Phal PM et al (2011) MR imaging characteristics of protoplasmic astrocytomas. Neuroradiology 53:405–411. https://doi.org/10.1007/s00234-010-0741-2

    Article  PubMed  Google Scholar 

  13. Franceschi E, De Biase D, Di Nunno V et al (2021) IDH1 non-canonical mutations and survival in patients with glioma. Diagnostics 11:342. https://doi.org/10.3390/diagnostics11020342

  14. Karsy M, Guan J, Cohen AL et al (2017) New molecular considerations for glioma: IDH, ATRX, BRAF, TERT, H3 K27M. Curr Neurol Neurosci Rep 17:19. https://doi.org/10.1007/s11910-017-0722-5

    Article  PubMed  Google Scholar 

  15. Lee S, Lee DK (2018) What is the proper way to apply the multiple comparison test? Korean J Anesthesiol 71:353–360. https://doi.org/10.4097/kja.d.18.00242

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mayson TA, Ward V, Davies KR et al (2013) Reliability of retrospective assignment of gross motor function classification system scores. Dev Neurorehabil 16:207–209. https://doi.org/10.3109/17518423.2012.755575

    Article  CAS  PubMed  Google Scholar 

  17. Poetsch L, Bronnimann C, Loiseau H et al (2021) Characteristics of IDH-mutant gliomas with non-canonical IDH mutation. J Neurooncol 151:279–286. https://doi.org/10.1007/s11060-020-03662-x

    Article  CAS  PubMed  Google Scholar 

  18. Park YW, Han K, Ahn SS et al (2018) Prediction of IDH1-mutation and 1p/19q-codeletion status using preoperative MR imaging phenotypes in lower grade gliomas. AJNR Am J Neuroradiol 39:37–42. https://doi.org/10.3174/ajnr.A5421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lotan E, Jain R, Razavian N et al (2019) State of the art: machine learning applications in glioma imaging. Am J Roentgenol 212:26–37. https://doi.org/10.2214/AJR.18.20218

    Article  Google Scholar 

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

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yamashita S, Takeshima H, Kadota Y et al (2023) P03.03.A T2-fluid-attenuated inversion recovery mismatch sign in lower-grade gliomas: correlation with pathological and molecular findings. Neuro-Oncology 25:ii36–ii37. https://doi.org/10.1093/neuonc/noad137.114

    Article  Google Scholar 

  22. Vasef MA, Auerbach A, Czuchlewski DR et al (2016) Low-grade astrocytoma. Diagnostic Pathology: molecular oncology. Elsevier, Philadelphia, pp 8–386

    Google Scholar 

  23. Lasocki A, Buckland ME, Molinaro T et al (2023) Correlating MRI features with additional genetic markers and patient survival in histological grade 2–3 IDH-mutant astrocytomas. Neuroradiology 65:1215–1223. https://doi.org/10.1007/s00234-023-03175-0

    Article  PubMed  PubMed Central  Google Scholar 

  24. Johnson DR, Giannini C, Vaubel RA et al (2022) A radiologist’s guide to the 2021 WHO Central nervous system tumor classification: part I—key concepts and the spectrum of diffuse gliomas. Radiology 304:494–508. https://doi.org/10.1148/radiol.213063

    Article  PubMed  Google Scholar 

  25. Liu X-Y, Gerges N, Korshunov A et al (2012) Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1/IDH2 and TP53 mutations. Acta Neuropathol 124:615–625. https://doi.org/10.1007/s00401-012-1031-3

    Article  CAS  PubMed  Google Scholar 

  26. Banan R, Stichel D, Bleck A et al (2020) Infratentorial IDH-mutant astrocytoma is a distinct subtype. Acta Neuropathol 140:569–581. https://doi.org/10.1007/s00401-020-02194-y

    Article  CAS  PubMed  Google Scholar 

  27. Nagase T, Ishida J, Sasada S et al (2023) IDH-mutant astrocytoma arising in the brainstem with symptom improvement by foramen magnum decompression: a case report. NMC Case Rep J 10:75–80. https://doi.org/10.2176/jns-nmc.2022-0159

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ye VC, Landry AP, Purzner T et al (2021) Adult isocitrate dehydrogenase-mutant brainstem glioma: illustrative case. J Neurosurg Case Lessons 1(12):CASE2078. https://doi.org/10.3171/CASE2078

  29. Babikir H, Wang L, Shamardani K et al (2021) ATRX regulates glial identity and the tumor microenvironment in IDH-mutant glioma. Genome Biol 22:311. https://doi.org/10.1186/s13059-021-02535-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Richard Q, Laurenge A, Mallat M et al (2022) New insights into the immune TME of adult-type diffuse gliomas. Curr Opin Neurol 35:794. https://doi.org/10.1097/WCO.0000000000001112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Qin T, Mullan B, Ravindran R et al (2022) ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization. Cell Rep 38:110216. https://doi.org/10.1016/j.celrep.2021.110216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Parmar HA, Hawkins C, Ozelame R et al (2007) Fluid-attenuated inversion recovery ring sign as a marker of dysembryoplastic neuroepithelial tumors. J Comput Assist Tomogr 31:348–353. https://doi.org/10.1097/01.rct.0000243453.33610.9d

    Article  PubMed  Google Scholar 

  33. Chen W, Jin S, Liu Q et al (2023) Spotlights on adult patients with pediatric-type diffuse gliomas in accordance with the 2021 WHO classification of CNS tumors. Front Neurosci 17:1144559. https://doi.org/10.3389/fnins.2023.1144559

  34. da Silva JFC, de Souza Machado GH, Pedro MKF et al (2019) Angiocentric glioma: literature review and first case in Brazil. Interdiscip Neurosurg 18:100508. https://doi.org/10.1016/j.inat.2019.100508

    Article  Google Scholar 

  35. Wefers AK, Stichel D, Schrimpf D et al (2020) Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course. Acta Neuropathol 139:193–209. https://doi.org/10.1007/s00401-019-02078-w

    Article  PubMed  Google Scholar 

  36. Kinoshita M, Arita H, Takahashi M et al (2020) Impact of inversion time for FLAIR acquisition on the T2-FLAIR mismatch detectability for IDH-mutant, non-CODEL astrocytomas. Front Oncol 10:596448. https://doi.org/10.3389/fonc.2020.596448

    Article  PubMed  Google Scholar 

  37. Kinoshita M, Uchikoshi M, Sakai M et al (2020) T2-FLAIR mismatch sign is caused by long T1 and T2 of IDH-mutant, 1p19q non-codeleted astrocytoma. Magn Reson Med Sci 20:119–123. https://doi.org/10.2463/mrms.bc.2019-0196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Contributions

Conceptualization: PM. Methodology: PM, SM. Formal analysis and investigation: PM, RS. Writing-original draft preparation: PM. Writing-review and editing: PM, YAC, SM, SD, AB, DGM. Resources: SD, DGM, RS, SM, YAC, AB. Supervision: SM, AB.

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Correspondence to Shobhit Mathur.

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This IRB-approved research study was conducted retrospectively from data obtained for clinical purposes. All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Malik, P., Soliman, R., Chen, Y.A. et al. Patterns of T2-FLAIR discordance across a cohort of adult-type diffuse gliomas and deviations from the classic T2-FLAIR mismatch sign. Neuroradiology 66, 521–530 (2024). https://doi.org/10.1007/s00234-024-03297-z

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