Okada Takuya, Natsumeda Manabu, Fujiwara Hidemoto, Higa Nayuta, Akahane Toshiaki, Watabe Yuki, Tomikawa Kaoru, Nishita Kyoka, Tsukamoto Yoshihiro, Ohshima Shinsuke, Horii Arata, Tanimoto Akihide, Hanaya Ryosuke, Shimizu Hiroshi, Kakita Akiyoshi, Oishi Makoto
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.
Advanced Treatment of Neurological Diseases Branch, Brain Research Institute, Niigata University, Niigata, Japan.
Front Oncol. 2025 Jul 8;15:1555986. doi: 10.3389/fonc.2025.1555986. eCollection 2025.
Brain stem gliomas harboring IDH mutations can be sensitive to temozolomide (TMZ) treatment, unlike their H3K27-altered counterparts, so distinguishing the two is essential.
Here, we report an adult brainstem glioma patient whose hearing loss normalized after treatment. He presented with gradual left hearing loss from two years before, and magnetic resonance (MR) images showed a diffuse mass lesion involving the pons to left middle cerebral peduncle, including the vestibular and cochlear nuclei. On MR spectroscopy (MRS), 2-hydroxyglutarate (2HG) was elevated to 3.602 mM, suggesting an IDH-mutant glioma. Subsequently, an open biopsy was performed via the lateral suboccipital approach, and the pathological diagnosis was astrocytoma, IDH-mutant, CNS WHO grade 3. Molecular analysis revealed a non-canonical R172S mutation. Left hearing improved from 87.5 dB to 8.3dB by 6-frequency pure tone audiogram (PTA) and 90% speech discrimination at 35 dB after concomitant TMZ and radiation treatment, followed by 12 cycles of adjuvant TMZ treatment. 2HG also decreased to 0.186 mM on MRS after treatment determining treatment strategy.
Studies have shown that as high as 31% of adult brainstem gliomas are IDH mutant, with most of these mutations being non-canonical mutations. Approximately 70% of IDH-mutant astrocytomas are known to harbor a methylated O6-methylguanine-DNA-methyltransferase () promoter and respond to TMZ treatment, whereas almost all H3K27M-mutant diffuse midline gliomas have unmethylated promoters and generally are not sensitive to TMZ treatment. Detection of 2HG by MRS and molecular analysis, including non-canonical mutations, were helpful in determining treatment response in this adult brainstem glioma case. Notably, hearing loss normalized after TMZ treatment.
The diagnosis of IDH-mutant brainstem gliomas by MRS and integrated analysis of surgically obtained specimens is essential to determine the proper treatment of these rare cases.
与H3K27改变的脑干胶质瘤不同，携带异柠檬酸脱氢酶（IDH）突变的脑干胶质瘤可能对替莫唑胺（TMZ）治疗敏感，因此区分这两者至关重要。
在此，我们报告一名成年脑干胶质瘤患者，其听力损失在治疗后恢复正常。他自两年前开始出现渐进性左耳听力损失，磁共振（MR）图像显示一个弥漫性肿块病变，累及脑桥至左侧大脑中脚，包括前庭和蜗神经核。在磁共振波谱（MRS）检查中，2-羟基戊二酸（2HG）升高至3.602 mM，提示为IDH突变型胶质瘤。随后，通过枕下外侧入路进行了开放活检，病理诊断为星形细胞瘤，IDH突变型，CNS WHO 3级。分子分析显示存在一种非典型的R172S突变。经TMZ与放疗联合治疗后，通过6频率纯音听力图（PTA）检测，左耳听力从87.5 dB改善至8.3 dB，在35 dB时言语辨别率达到90%，随后进行了12个周期的辅助TMZ治疗。治疗后MRS检查显示2HG也降至0.186 mM，据此确定了治疗策略。
研究表明，高达31%的成年脑干胶质瘤为IDH突变型，其中大多数突变为非典型突变。已知约70%的IDH突变型星形细胞瘤存在O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化，对TMZ治疗有反应，而几乎所有H3K27M突变型弥漫性中线胶质瘤的MGMT启动子未甲基化，通常对TMZ治疗不敏感。通过MRS检测2HG以及进行包括非典型突变在内的分子分析，有助于确定该成年脑干胶质瘤病例的治疗反应。值得注意的是，TMZ治疗后听力损失恢复正常。
通过MRS以及对手术获取标本的综合分析来诊断IDH突变型脑干胶质瘤，对于确定这些罕见病例的恰当治疗至关重要。
