Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium

Hirokazu Takami, Kohei Fukuoka, Shintaro Fukushima, Taishi Nakamura, Akitake Mukasa, Nobuhito Saito, Takaaki Yanagisawa, Hideo Nakamura, Kazuhiko Sugiyama, Masayuki Kanamori, Teiji Tominaga, Taketoshi Maehara, Mitsutoshi Nakada, Yonehiro Kanemura, Akio Asai, Hideo Takeshima, Yuichi Hirose, Toshihiko Iuchi, Motoo Nagane, Koji YoshimotoAkira Matsumura, Kazuhiko Kurozumi, Hiroyuki Nakase, Keiichi Sakai, Tsutomu Tokuyama, Soichiro Shibui, Yoichi Nakazato, Yoshitaka Narita, Ryo Nishikawa, Masao Matsutani, Koichi Ichimura

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)


Background: We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. Methods: Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews. Results: All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. Conclusions: The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

Original languageEnglish
Pages (from-to)1565-1577
Number of pages13
Issue number12
Publication statusPublished - Dec 1 2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research


Dive into the research topics of 'Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium'. Together they form a unique fingerprint.

Cite this