[New developments in grading of astrocytomas, IDH-mutant: Study of the impact of update 12 of cIMPACT-NOW].

Abstract

Introduction: The 2021 World Health Organisation (WHO) classification of the Central Nervous System tumors introduced, for the first time, a molecular biomarker (homozygous deletion of CDKN2A/B) into the grading of astrocytomas, IDH-mutant. Since then, the cIMPACT-NOW expert group has proposed a new prognostic algorithm (published in the update 12), incorporating epigenetic and genetic data. The aim of this study was to report on the experience of integrating this algorithm into the grading of astrocytomas, IDH-mutant diagnosed in routine practice.

Materials and methods: This study included astrocytomas, IDH-mutant diagnosed between 1st January 2024 and 1st June 2026, for which molecular analyses were recommended according to the cIMPACT-NOW update 12. Next-generation sequencing and DNA-methylation analyses (methylation class and copy number abnormalities) were carried out for each case.

Results: During this period, 81 astrocytomas, IDH-mutant were diagnosed, of which 50 required exploratory molecular testing (the remaining 31 cases being grade 4 tumors). In 24% of cases (12/50), the grade was revised following the incorporation of genetic and epigenetic data: seven grade 2 tumors were reclassified as grade 3, two grade 2 tumors as grade 4, and three grade 3 tumors as grade 4.

Discussion and conclusions: In our study, 24% of astrocytomas, IDH-mutant graded as grade 2 based on their mitotic index were reclassified as grade 3 or 4 tumors. The change in grading resulted from NGS analysis in three tumors (which led to the upgrading of three astrocytomas, IDH-mutant grade 2 to grade 3 on the basis of mutations in the CDKN2A, PIK3CA and PIK3R1 genes), from the copy number profile derived from the methylation array in eight tumors (which led to the reclassification of three astrocytomas, IDH-mutant grade 2 to grade 3, two astrocytomas, IDH-mutant grade 2 to grade 4 and three astrocytomas, IDH-mutant grade 3 to grade 4), and from methylation class analysis in one case. These changes highlight the value of carrying out molecular analyses or sending samples to a centre of expertise: NGS and DNA-methylation analysis (for astrocytomas, IDH-mutant grade 2) and a technique capable of detecting homozygous deletion of CDKN2A/B and amplification of PDGFRA in astrocytomas, IDH-mutant grade 3 (NGS, DNA-methylation analysis, SNP- or CGH-array). The cIMPACT-NOW Update 12 revolutionises the practice of pathologists in the grading of astrocytomas, IDH-mutant, who must now integrate genetic and epigenetic data with histopathological features.