T2-FLAIR mismatch sign for diagnosis of 1p19q non-codeleted or ATRX mutant astrocytoma
Authors: Jen Jian Ping , Patel Markand , Bowen Michael , Pohl Ute , Nagaraju Santhosh , Wykes Victoria , Watts Colin , Sawlani Vijay 
Published: October 2021

Abstract

Aims
The World Health Organisation (WHO) classification of adult gliomas has undergone significant revision in recent years, with current emphasis on the role of the molecular biomarkers IDH, 1p19q, ATRX, and p53 for classification of glioblastoma, astrocytoma, and oligodendroglioma. When correctly applied the T2-FLAIR mismatch sign is reported to have 100% specificity for WHO grade II or III IDH mutant 1p19q non-codeleted astrocytoma. We sought to verify this classic imaging-molecular correlate in our cohort at a single tertiary level neurosurgical referral centre in the United Kingdom.

Method
Data were gathered by searching the histopathology database for cases between 2014 and 2019 containing the keywords ‘IDH Mutant’ AND ‘Astrocytoma’ or ‘Glioblastoma’ or ‘Oligodendroglioma’ in the report. Inclusion criteria: Biopsy/resection proven IDH mutant tumours in adults (age &gt;17). A strict application of the T2-FLAIR mismatch sign was used when evaluating MRI. Native T2 signal was required to be homogenous or near homogenous, with hypointense signal on T2 weighted FLAIR except for a hyperintense peripheral rim. In addition, the T2-FLAIR mismatch sign was not applied to tumours showing any unequivocal contrast enhancement or macrocystic change.

Results
66/185 cases were excluded for reasons of insufficient imaging, duplication, 1p19q partial deletion/unknown + ATRX wild type/unknown, IDH wild type/negative, Grade IV histology. 119 cases fit the inclusion criteria, all IDH positive. Group 1 comprised 49 (39%) 1p19q codeleted tumours, or oligodendrogliomas. ATRX was wild type (78%), unknown (18%), or mutated (&lt;1%). Group 2 comprised 37 (29%) 1p19q non-codeleted tumours, or astrocytomas. ATRX was mutated (70%), unknown (22%), wild type (5%), or equivocal (3%). Group 3 comprised 41 (32%) 1p19q unknown tumours, all ATRX mutated, p53 expressed (83%). When p53 status was unaltered/equivocal, microscopy was convincingly astrocytic. Groups 2 and 3 comprised the astrocytomas (61%). T2-FLAIR mismatch was positive in 5 1p19q non-codeleted astrocytomas, 5 1p19q unknown ATRX mutant astrocytomas, and no 1p19q co-deleted oligodendrogliomas. Test sensitivity and specificity was 14% and 100% for 1p19q non-codeletion, 13% and 100% for ATRX mutation.

Conclusion
Although relatively uncommon, when present and correctly applied we confirm 100% specificity of the T2-FLAIR mismatch sign for IDH mutant 1p19q non-codeleted astrocytoma. However, if 1p19q status is unknown, clear astrocytic histology and ATRX mutation and/or p53 overexpression is also considered sufficient to diagnose astrocytoma. When 1p19q status is unavailable we also report 100% specificity of T2-FLAIR mismatch for ATRX mutated astrocytomas. T2-FLAIR mismatch was not observed in any 1p19q codeleted oligodendrogliomas or ATRX wild type tumours. More accurate methods of non-invasive glioma diagnosis will help improve neurohistopathological correlation, prognostication, and guide the tempo of the pre-operative planning phase.