Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
Mod Pathol. 2013 Mar;26(3):315-26. doi: 10.1038/modpathol.2012.173. Epub 2012 Oct 5.
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.
最近的研究表明，几乎所有弥漫性神经胶质瘤都显示出 bHLH 转录因子 OLIG2 的核免疫反应性，而 R132H 突变的异柠檬酸脱氢酶 1（IDH1）蛋白则表达于除原发性胶质母细胞瘤以外的大多数弥漫性神经胶质瘤中。然而，这些抗体尚未广泛应用于更罕见的胶质母细胞瘤变体，当星形细胞特征较细微时，这些变体在诊断上具有挑战性。因此，我们调查了 167 例非典型胶质母细胞瘤中 OLIG2 和 IDH1 的表达模式，包括 45 例小细胞胶质母细胞瘤、45 例胶质肉瘤、34 例具有原始神经外胚层肿瘤样灶（PNET 样灶）的胶质母细胞瘤、23 例具有少突胶质细胞成分的胶质母细胞瘤、11 例颗粒细胞胶质母细胞瘤和 9 例巨细胞胶质母细胞瘤。OLIG2 在所有具有少突胶质细胞成分的胶质母细胞瘤、98%的小细胞胶质母细胞瘤和所有颗粒细胞胶质母细胞瘤中均强烈表达，后者特别有助于排除富含巨噬细胞的病变。在 74%的具有 PNET 样灶的胶质母细胞瘤中，OLIG2 表达保留在 PNET 样灶中，与中枢神经系统 PNET 区分开来具有重要意义。在 93%的胶质肉瘤中，肉瘤成分 OLIG2 阳性，但只有 14%的肉瘤成分保留局灶性表达；因此，在大多数情况下，该标志物不能可靠地区分这些肿瘤与纯肉瘤。OLIG2 在 67%的巨细胞胶质母细胞瘤中表达。IDH1 在具有少突胶质细胞成分的胶质母细胞瘤中表达 55%、具有 PNET 样灶的胶质母细胞瘤中表达 15%、胶质肉瘤中表达 7%，而小细胞、颗粒细胞或巨细胞胶质母细胞瘤均不表达。这进一步支持了大多数具有少突胶质细胞成分的胶质母细胞瘤是继发性的，而小细胞胶质母细胞瘤、颗粒细胞胶质母细胞瘤和巨细胞胶质母细胞瘤是原发性变体的观点。因此，在最具挑战性的鉴别诊断之一中，IDH1 阳性可强烈支持具有少突胶质细胞成分的胶质母细胞瘤，而基本排除小细胞胶质母细胞瘤。
