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