Affiliation:
1. Larner College of Medicine University of Vermont Burlington Vermont USA
2. Department of Laboratory Services University of Vermont Medical Center Burlington Vermont USA
3. Department of Neuro‐Oncology University of Vermont Medical Center Burlington Vermont USA
Abstract
In 2016, the World Health Organization (WHO) eliminated “oligoastrocytoma” from the classification of central nervous system (CNS) tumors, in favor of an integrated histologic and molecular diagnosis. Consistent with the 2016 classification, in the 2021 classification, oligodendrogliomas are defined by mutations in isocitrate dehydrogenase (IDH) with concurrent 1p19q codeletion, while astrocytomas are IDH mutant tumors, usually with ATRX loss. In 2007, a 24‐year‐old man presented with a brain tumor histologically described as astrocytoma, but with molecular studies consistent with an oligodendroglioma, IDH mutant and 1p19q‐codeleted. Years later, at resection, pathology revealed an astrocytoma, with variable ATRX expression and mutations of IDH, ATRX, TP53, and TERT by DNA sequencing. Fluorescence in situ hybridization studies confirmed 1p19q codeletion in sections of the tumor shown to histologically retain ATRX expression. Separately, in 2017, a 36‐year‐old woman presented with a frontal brain tumor with pathology consistent with an oligodendroglioma, IDH mutant and 1p19q‐codeleted. Two years later, pathology revealed an astrocytoma, IDH1 mutant, with ATRX loss. These two cases likely represent the rare occurrence of dual‐genotype IDH mutant infiltrating glioma. Nine cases of dual‐genotype IDH mutant glioma were previously reported in the literature. We present two cases in which this distinct molecular phenotype is present in a tumor in the same location with surgeries at two points in time, both with 1p19q codeletion and ATRX loss at the time of resection. Whether this represents a true “collision tumor” or genetic switching over time is not known, but the co‐occurrence of these hybrid mutations supports a diagnosis of dual‐genotype IDH mutant glioma.