恶性中枢神经系统肿瘤术中综合诊断系统

Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

作者信息

Hayashi Takahiro, Tateishi Kensuke, Matsuyama Shinichiro, Iwashita Hiromichi, Miyake Yohei, Oshima Akito, Honma Hirokuni, Sasame Jo, Takabayashi Katsuhiro, Sugino Kyoka, Hirata Emi, Udaka Naoko, Matsushita Yuko, Kato Ikuma, Hayashi Hiroaki, Nakamura Taishi, Ikegaya Naoki, Takayama Yutaro, Sonoda Masaki, Oka Chihiro, Sato Mitsuru, Isoda Masataka, Kato Miyui, Uchiyama Kaho, Tanaka Tamon, Muramatsu Toshiki, Miyake Shigeta, Suzuki Ryosuke, Takadera Mutsumi, Tatezuki Junya, Ayabe Junichi, Suenaga Jun, Matsunaga Shigeo, Miyahara Kosuke, Manaka Hiroshi, Murata Hidetoshi, Yokoyama Takaakira, Tanaka Yoshihide, Shuto Takashi, Ichimura Koichi, Kato Shingo, Yamanaka Shoji, Cahill Daniel P, Fujii Satoshi, Shankar Ganesh M, Yamamoto Tetsuya

机构信息

Department of Neurosurgery, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.

Neurosurgical-Oncology Laboratory, Yokohama City University, Yokohama, Japan.

出版信息

Clin Cancer Res. 2024 Jan 5;30(1):116-126. doi: 10.1158/1078-0432.CCR-23-1660.

DOI:10.1158/1078-0432.CCR-23-1660

PMID:37851071

Abstract

PURPOSE

The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay.

EXPERIMENTAL DESIGN

FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability.

RESULTS

After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL.

CONCLUSIONS

The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

摘要

目的

2021年世界卫生组织（WHO）中枢神经系统（CNS）肿瘤分类采用了一种综合方法，涉及组织病理学和分子谱分析。由于大多数成人恶性脑肿瘤是胶质瘤和原发性中枢神经系统淋巴瘤（PCNSL），因此治疗决策需要快速区分这些疾病。此外，弥漫性胶质瘤需要有关单核苷酸变体（SNV）的分子信息，如IDH1/2。在此，我们报告了一种用于中枢神经系统恶性肿瘤分类的术中综合诊断（i-ID）系统，该系统通过纳入基于qPCR的基因分型检测来更新传统的冰冻切片（FS）诊断。

实验设计

对成人恶性中枢神经系统肿瘤进行FS评估，包括GFAP和CD20快速免疫组化。通过CD20阳性和GFAP阴性免疫染色诊断PCNSL。对于疑似胶质瘤，常规进行IDH1/2、TERT SNV和CDKN2A拷贝数改变的基因分型，而对选定病例评估H3F3A和BRAF SNV。i-ID根据2021年WHO分类确定，并与永久综合诊断（p-ID）进行比较以评估其可靠性。

结果

在回顾性分析153例病例后，使用i-ID系统对101例病例进行了前瞻性检查。i-ID与永久基因组分析对IDH1/2、TERT、H3F3AK27M、BRAFV600E和CDKN2A改变的评估一致性分别为100%、100%、100%、100%和96.4%。FS与术中基因分型检测相结合提高了胶质瘤的诊断准确性。总体而言，80/82（97.6%）例胶质瘤患者和18/19（94.7%）例PCNSL患者的i-ID与p-ID匹配。