Clinical, imaging, and molecular features of radiation-induced glioblastomas developing more than 20 years after radiation therapy for intracranial germinomatous germ cell tumor: illustrative cases

Yoshihiro Tsukamoto; Manabu Natsumeda; Haruhiko Takahashi; Asuka Ueno; Kiichi Sakai; Kazuki Shida; Hiroki Seto; Taiki Saito; Satoshi Shibuma; Yoko Nakayama; Yuki Tanaka; Toshimichi Nakano; Atsushi Ohta; Katsuya Maruyama; Masayasu Okada; Takeyoshi Eda; Yasuhiro Seki; Yuichirou Yoneoka; Hiroshi Shimizu; Kouichirou Okamoto; Akiyoshi Kakita; Makoto Oishi

doi:10.3171/CASE23361

Clinical, imaging, and molecular features of radiation-induced glioblastomas developing more than 20 years after radiation therapy for intracranial germinomatous germ cell tumor: illustrative cases

J Neurosurg Case Lessons. 2023 Oct 16;6(16):CASE23361. doi: 10.3171/CASE23361. Print 2023 Oct 16.

Authors

Yoshihiro Tsukamoto¹, Manabu Natsumeda^{1

2}, Haruhiko Takahashi^{1

3}, Asuka Ueno¹, Kiichi Sakai¹, Kazuki Shida¹, Hiroki Seto¹, Taiki Saito¹, Satoshi Shibuma¹, Yoko Nakayama¹, Yuki Tanaka³, Toshimichi Nakano⁴, Atsushi Ohta⁴, Katsuya Maruyama⁵, Masayasu Okada¹, Takeyoshi Eda⁶, Yasuhiro Seki⁷, Yuichirou Yoneoka⁷, Hiroshi Shimizu³, Kouichirou Okamoto¹, Akiyoshi Kakita³, Makoto Oishi¹

Affiliations

¹ Departments of1Neurosurgery and.
² 2Advanced Treatment of Neurological Diseases Branch, Brain Research Institute, Niigata University, Niigata, Japan.
³ 3Pathology, Brain Research Institute, Niigata University, Niigata, Japan.
⁴ 4Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
⁵ 5Department of Radiology, Niigata Neurosurgery Hospital, Niigata, Japan.
⁶ 6Division of Pharmacy, Medical and Dental Hospital, Niigata University, Niigata, Japan; and.
⁷ 7Department of Neurosurgery, Uonuma Kikan Hospital, Uonuma Institute of Community Medicine, Medical and Dental Hospital, Niigata University, Niigata, Japan.

Abstract

Background: Germinomatous germ cell tumor is highly sensitive to chemoradiotherapy; patients are expected to survive for decades. Many radiation-induced malignant gliomas (RIMGs) occur >10 years after radiotherapy. Standard therapy for RIMGs has not been established because of the lesion's rarity, the patient's shorter survival period, and the risk of radiation necrosis by repeat radiation.

Observations: Two patients, a 32-year-old man and a 50-year-old man, developed glioblastomas more than 20 years after radiation monotherapy for germinoma with or without mature teratoma. The first patient showed a tumor in the left frontotemporal region with disseminated lesions and died 2 months after partial resection of the tumor without responding to the chemotherapy with temozolomide and bevacizumab. Methylation classifier analysis classified the pathology as closest to diffuse pediatric-type high-grade glioma, Rtk1 subtype. The second patient showed a tumor mass in the brainstem and left cerebellar peduncle, which worsened progressively during chemotherapy with temozolomide and bevacizumab. The tumor transiently responded to stereotactic radiotherapy with the CyberKnife. However, the patient died of RIMG recurrence-related aspiration pneumonia 11 months after the biopsy. Methylation classifier analysis classified the pathology as closest to infratentorial pilocytic astrocytoma.

Lessons: Chemoradiotherapy may improve the survival of patients with RIMGs. Furthermore, molecular features may influence the clinical, locoregional, and pathological features of RIMG.

Keywords: germ cell tumor; germinoma; glioblastoma; radiation-induced glioma; repeat radiation.