{"title":"Rare dual‐genotype IDH mutant glioma: Review of previously reported cases and two new cases of true “oligoastrocytoma”","authors":"Isabella Sutherland, John DeWitt, Alissa Thomas","doi":"10.1111/neup.12975","DOIUrl":null,"url":null,"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 (<jats:italic>IDH</jats:italic>) with concurrent 1p19q codeletion, while astrocytomas are <jats:italic>IDH</jats:italic> mutant tumors, usually with <jats:italic>ATRX</jats:italic> 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, <jats:italic>IDH</jats:italic> mutant and 1p19q‐codeleted. Years later, at resection, pathology revealed an astrocytoma, with variable <jats:italic>ATRX</jats:italic> expression and mutations of <jats:italic>IDH</jats:italic>, <jats:italic>ATRX</jats:italic>, <jats:italic>TP53</jats:italic>, and <jats:italic>TERT</jats:italic> by DNA sequencing. Fluorescence in situ hybridization studies confirmed 1p19q codeletion in sections of the tumor shown to histologically retain <jats:italic>ATRX</jats:italic> expression. Separately, in 2017, a 36‐year‐old woman presented with a frontal brain tumor with pathology consistent with an oligodendroglioma, <jats:italic>IDH</jats:italic> mutant and 1p19q‐codeleted. Two years later, pathology revealed an astrocytoma, <jats:italic>IDH1</jats:italic> mutant, with <jats:italic>ATRX</jats:italic> loss. These two cases likely represent the rare occurrence of dual‐genotype <jats:italic>IDH</jats:italic> mutant infiltrating glioma. Nine cases of dual‐genotype <jats:italic>IDH</jats:italic> 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 <jats:italic>ATRX</jats:italic> 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 <jats:italic>IDH</jats:italic> mutant glioma.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/neup.12975","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.