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

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

Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors

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

Authors

Takahiro Hayashi^{1

2}, Kensuke Tateishi^{1

2

3}, Shinichiro Matsuyama^{1

2}, Hiromichi Iwashita⁴, Yohei Miyake^{1

2}, Akito Oshima^{1

2}, Hirokuni Honma^{1

2}, Jo Sasame^{1

2}, Katsuhiro Takabayashi^{1

2}, Kyoka Sugino^{1

2

3}, Emi Hirata^{1

2}, Naoko Udaka⁵, Yuko Matsushita⁶, Ikuma Kato⁷, Hiroaki Hayashi^{2

8}, Taishi Nakamura^{1

2

9}, Naoki Ikegaya¹, Yutaro Takayama^{1

2}, Masaki Sonoda^{1

2}, Chihiro Oka^{1

2}, Mitsuru Sato¹, Masataka Isoda^{1

2}, Miyui Kato^{2

3}, Kaho Uchiyama^{2

3}, Tamon Tanaka^{1

2}, Toshiki Muramatsu^{1

2}, Shigeta Miyake¹, Ryosuke Suzuki^{1

10}, Mutsumi Takadera^{11

12}, Junya Tatezuki¹¹, Junichi Ayabe¹², Jun Suenaga¹, Shigeo Matsunaga¹³, Kosuke Miyahara¹⁴, Hiroshi Manaka¹⁵, Hidetoshi Murata¹, Takaakira Yokoyama¹⁶, Yoshihide Tanaka¹², Takashi Shuto¹³, Koichi Ichimura⁶, Shingo Kato¹⁷, Shoji Yamanaka⁵, Daniel P Cahill¹⁸, Satoshi Fujii^{5

7}, Ganesh M Shankar¹⁸, Tetsuya Yamamoto¹

Affiliations

¹ Department of Neurosurgery, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
² Neurosurgical-Oncology Laboratory, Yokohama City University, Yokohama, Japan.
³ Laboratory of Biopharmaceutical and Regenerative Science, Graduate School of Medical Science, Yokohama City University, Yokohama, Japan.
⁴ Department of Pathology, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
⁵ Department of Diagnostic Pathology, Yokohama City University Hospital, Yokohama, Japan.
⁶ Department of Brain Disease Translational Research, Juntendo University Faculty of Medicine, Tokyo, Japan.
⁷ Department of Molecular Pathology, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
⁸ Department of Pediatrics, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
⁹ Department of Neurosurgery, Yokohama City University Medical Center, Yokohama, Japan.
¹⁰ Department of Neurosurgery, Odawara Municipal Hospital, Odawara, Japan.
¹¹ Department of Neurosurgery, Yokohama City Minato Red Cross Hospital, Yokohama, Japan.
¹² Department of Neurosurgery, Yokosuka Kyosai Hospital, Yokosuka, Japan.
¹³ Department of Neurosurgery, Yokohama Rosai Hospital, Yokohama, Japan.
¹⁴ Department of Neurosurgery, National Hospital Organization Yokohama Medical Center, Yokohama, Japan.
¹⁵ Department of Neurosurgery, Yokohama Minami Kyosai Hospital, Yokohama, Japan.
¹⁶ Department of Neurosurgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan.
¹⁷ Department of Clinical Cancer Genomics, Yokohama City University, Yokohama, Japan.
¹⁸ Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

PMID: 37851071
DOI: 10.1158/1078-0432.CCR-23-1660

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Brain Neoplasms* / diagnosis
Brain Neoplasms* / genetics
Brain Neoplasms* / pathology
Central Nervous System Neoplasms* / diagnosis
Central Nervous System Neoplasms* / genetics
Glioma* / diagnosis
Glioma* / genetics
Glioma* / surgery
Humans
Reproducibility of Results
Retrospective Studies

Abstract

Publication types

MeSH terms

Grants and funding