title: Diagnostic implications of IDH1-R132H and OLIG2 expression patterns in rare and challenging glioblastoma variants.
abstract: Recent work has demonstrated that nearly all diffuse gliomas display nuclear immunoreactivity for the bHLH transcription factor OLIG2, and the R132H mutant isocitrate dehydrogenase 1 (IDH1) protein is expressed in the majority of diffuse gliomas other than primary glioblastoma. However, these antibodies have not been widely applied to rarer glioblastoma variants, which can be diagnostically challenging when the astrocytic features are subtle. We therefore surveyed the expression patterns of OLIG2 and IDH1 in 167 non-conventional glioblastomas, including 45 small cell glioblastomas, 45 gliosarcomas, 34 glioblastomas with primitive neuroectodermal tumor-like foci (PNET-like foci), 23 with an oligodendroglial component, 11 granular cell glioblastomas, and 9 giant cell glioblastomas. OLIG2 was strongly expressed in all glioblastomas with oligodendroglial component, 98% of small cell glioblastomas, and all granular cell glioblastomas, the latter being particularly helpful in ruling out macrophage-rich lesions. In 74% of glioblastomas with PNET-like foci, OLIG2 expression was retained in the PNET-like foci, providing a useful distinction from central nervous system PNETs. The glial component of gliosarcomas was OLIG2 positive in 93% of cases, but only 14% retained focal expression in the sarcomatous component; as such this marker would not reliably distinguish these from pure sarcoma in most cases. OLIG2 was expressed in 67% of giant cell glioblastomas. IDH1 was expressed in 55% of glioblastomas with oligodendroglial component, 15% of glioblastomas with PNET-like foci, 7% of gliosarcomas, and none of the small cell, granular cell, or giant cell glioblastomas. This provides further support for the notion that most glioblastomas with oligodendroglial component are secondary, while small cell glioblastomas, granular cell glioblastomas, and giant cell glioblastomas are primary variants. Therefore, in one of the most challenging differential diagnoses, IDH1 positivity could provide strong support for glioblastoma with oligodendroglial component, while essentially excluding small cell glioblastoma.
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Joseph
authors.forename: Joanna
authors.initials: J
authors.lastname: Phillips
authors.forename: Sonika
authors.initials: S
authors.lastname: Dahiya
authors.forename: Michelle
authors.initials: M
authors.lastname: M Felicella
authors.forename: Tarik
authors.initials: T
authors.lastname: Tihan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brat
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001932:Brain Neoplasms / Q000737:chemistry* / Q000145:classification / Q000473:pathology; D003937:Diagnosis, Differential; D005909:Glioblastoma / Q000737:chemistry* / Q000145:classification / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000032:analysis*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009457:Neuroglia / Q000737:chemistry* / Q000473:pathology; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000737:chemistry / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D007521:Isocitrate Dehydrogenase; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405708:OLIG2 protein, human; C543588:IDH1 protein, human