A Case of IDH-Mutant Astrocytoma Harboring an IDH2 R172_H173delinsSN Variant.

Abstract

IDH-mutant gliomas most commonly harbor the canonical IDH1 p.R132H mutation, followed by less common mutations involving IDH1 p.R132 or IDH2 p.R172 codons. We present a case of a 32-year-old male found to have a left temporal brain tumor with regional enhancement on brain MRI, for which he underwent resection. Histologic sections showed an infiltrating astrocytic tumor with increased mitotic activity and elevated Ki67 (MIB1) labeling. The tumor was negative for IDH1 p.R132H mutant protein expression with retained ATRX expression. 1p/19q was intact by FISH analysis, and next-generation sequencing identified a previously unreported IDH2 (p.R172_H173delinsSN) likely pathogenic variant. A diagnosis of astrocytoma, IDH-mutant, CNS WHO grade 3 was rendered. Subsequent tumor methylation profiling performed at the National Institutes of Health matched with high confidence to the class "IDH glioma, subclass astrocytoma" and confirmed lack of MGMT promoter hypermethylation. He received adjuvant concurrent radiation and temozolomide. Surveillance brain MRI at 32 months post resection demonstrated no evidence of interval tumor progression. We present a case of IDH-mutant astrocytoma with a somewhat atypical molecular presentation, including a previously uncharacterized IDH2 mutation, retained ATRX expression, and lack of MGMT promoter hypermethylation. Though it has not been biochemically or functionally validated, tumor methylation profiling is supportive of this previously uncharacterized IDH2 variant as tumorigenic.