Mittelbronn Michel
National Center of Pathology (NCP), Laboratoire national de santé (LNS), Dudelange, Luxembourg.
Luxembourg Centre of Neuropathology (LCNP), Luxembourg.
Free Neuropathol. 2024 Sep 27;5:21. doi: 10.17879/freeneuropathology-2024-5809. eCollection 2024 Jan.
As in previous years, including 2023, a major focus in the neurooncological area of neuropathology was put on more precise and constantly faster diagnostic procedures, even reaching the level of ultra-fast intraoperative diagnostics based on methylation profiling. Neuropathological diagnostic precision and clinical follow-up treatment has been further increased by combining DNA methylation profiling with targeted panel sequencing. A few new, molecularly defined tumor subtypes have been proposed, among others, a glioneuronal tumor with alteration, kinase fusion and anaplastic features (in its abbreviated form named GTAKA) and the de novo replication repair deficient glioblastoma, IDH-wildtype both having either distinct prognostic or therapeutic implications. Regarding the understanding of brain tumor development and progression, several novel mechanisms have been presented which might also be considered as treatment targets in the future, such as a) autonomous rhythmical Ca oscillations in interconnected glioma cell networks driving tumor growth; b) transfer of mitochondria from normal astrocytes to glioma cells enhancing proliferation and self-renewal; c) brain endothelial cell remodeling upon matrix-metalloprotease 9 secretion by tumor cells metastasizing into the CNS and d) anti-tumor activity of microglia in CNS metastasis of breast cancer. Finally, in contrast to previous years, several very promising neurooncological treatment studies have been conducted, focusing on specific targets such as H3K27M or IDH1/2 mutations for which a proper neuropathological assessment is key. The continuous translation of potential new treatment targets using faster and precise diagnostic procedures will further pave the way for better individualized clinical care of neurooncological patients.
与包括2023年在内的前几年一样,神经病理学的神经肿瘤学领域的一个主要重点是更精确且不断加快诊断程序,甚至达到基于甲基化谱分析的超快速术中诊断水平。通过将DNA甲基化谱分析与靶向基因panel测序相结合,神经病理学诊断的精确性和临床随访治疗得到了进一步提高。已经提出了一些新的、分子定义的肿瘤亚型,其中包括具有改变、激酶融合和间变性特征的神经胶质神经元肿瘤(简称为GTAKA)以及从头复制修复缺陷型胶质母细胞瘤,IDH野生型,这两种亚型都具有不同的预后或治疗意义。关于脑肿瘤的发生和进展的理解,已经提出了几种新机制,这些机制未来也可能被视为治疗靶点,例如:a)相互连接的胶质瘤细胞网络中自主节律性钙振荡驱动肿瘤生长;b)正常星形胶质细胞的线粒体转移到胶质瘤细胞中增强增殖和自我更新;c)肿瘤细胞分泌基质金属蛋白酶9转移至中枢神经系统时脑内皮细胞重塑;d)小胶质细胞在乳腺癌中枢神经系统转移中的抗肿瘤活性。最后,与前几年不同的是,已经开展了几项非常有前景的神经肿瘤治疗研究,重点关注H3K27M或IDH1/2突变等特定靶点,对此进行适当的神经病理学评估是关键。使用更快、更精确的诊断程序持续转化潜在的新治疗靶点,将进一步为神经肿瘤患者更好的个体化临床护理铺平道路。