Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
ARC-NET Research Centre, University and Hospital Trust of Verona, Verona, Italy.
Histopathology. 2022 Nov;81(5):661-669. doi: 10.1111/his.14768. Epub 2022 Aug 25.
Pleomorphic xanthoastrocytoma (PXA) is a rare circumscribed glioma, characterized by frequent BRAF p. V600E mutation, and classified as grade 2 or 3. Owing to overlapping clinical-pathological features, the histological distinction from glioblastoma (GBM) with giant cells (GCs) is challenging. Based on the high frequency of TP53 and RB1 alterations in the latter, this study aimed to assess the value of BRAF, p53, and pRB immunostainings in the differential diagnosis.
In 37 GBMs with ≥30% GCs and in eight PXAs, we assessed the alterations of 409 cancer-related genes and immunostainings for BRAF, p53, and pRB. GBMs with GCs were TP53-mutated in 30 cases, RB1-altered in 11, and BRAF-mutated in none. PXAs were BRAF-mutated in six cases, TP53-mutated in three, and RB1-altered in none. pRb immunostaining was lost in 25 GBMs (11 RB1-altered and 14 RB1-unaltered), retained in all PXAs and six GBMs, and inconclusive in six GBMs. pRb loss had 100% specificity and 80.6% sensitivity for GBM with GCs. P53 immunostaining was observed in 22 TP53-mutated GBMs and in one TP53-mutated PXA. It showed 87.5% specificity and 60% sensitivity to identify GBM with GCs. BRAF immunostaining corresponded to BRAF mutation status and it had 100% specificity and 75% sensitivity for detecting PXA.
This study shows for the first time that loss of pRB immunostaining is sensitive and specific for distinguishing GBM with GCs from PXA in routine practice. Thus, it could complement an immunohistochemical panel that includes BRAF and p53 immunostainings for the differential diagnosis.
多形性黄色星形细胞瘤（PXA）是一种罕见的局限性神经胶质瘤，其特征是频繁出现 BRAF p. V600E 突变，并被归类为 2 级或 3 级。由于具有重叠的临床病理特征，从具有巨细胞（GCs）的胶质母细胞瘤（GBM）中进行组织学区分具有挑战性。基于后者中 TP53 和 RB1 改变的高频，本研究旨在评估 BRAF、p53 和 pRB 免疫染色在鉴别诊断中的价值。
在 37 例具有≥30% GCs 的 GBM 病例和 8 例 PXA 病例中，我们评估了 409 种癌症相关基因的改变以及 BRAF、p53 和 pRB 的免疫染色。30 例 GBMs 存在 TP53 突变，11 例存在 RB1 改变，而无 BRAF 突变。6 例 PXA 存在 BRAF 突变，3 例存在 TP53 突变，而无 RB1 改变。25 例 GBM （11 例 RB1 改变和 14 例 RB1 未改变）存在 pRb 免疫染色缺失，所有 PXA 和 6 例 GBM 存在 pRb 免疫染色保留，6 例 GBM 存在 pRb 免疫染色不确定。pRb 缺失对具有 GCs 的 GBM 具有 100%的特异性和 80.6%的敏感性。p53 免疫染色在 22 例存在 TP53 突变的 GBM 中观察到，在 1 例存在 TP53 突变的 PXA 中观察到。它对具有 GCs 的 GBM 的特异性为 87.5%，敏感性为 60%。BRAF 免疫染色与 BRAF 突变状态相对应，对检测 PXA 的特异性为 100%，敏感性为 75%。
本研究首次表明，pRb 免疫染色缺失在常规实践中对区分具有 GCs 的 GBM 和 PXA 具有敏感性和特异性。因此，它可以补充包括 BRAF 和 p53 免疫染色在内的免疫组织化学组合，用于鉴别诊断。
