Phi Ji Hoon, Kim Seung-Ki
Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, Korea.
J Korean Neurosurg Soc. 2019 May;62(3):313-320. doi: 10.3340/jkns.2019.0033. Epub 2019 May 1.
Brain tumors are the second most common type of structural brain lesion that causes chronic epilepsy. Patients with low-grade brain tumors often experience chronic drug-resistant epilepsy starting in childhood, which led to the concept of long-term epilepsy-associated tumors (LEATs). Dysembryoplastic neuroepithelial tumor and ganglioglioma are representative LEATs and are characterized by young age of onset, frequent temporal lobe location, benign tumor biology, and chronic epilepsy. Although highly relevant in clinical epileptology, the concept of LEATs has been criticized in the neuro-oncology field. Recent genomic and molecular studies have challenged traditional views on LEATs and low-grade gliomas. Molecular studies have revealed that lowgrade gliomas can largely be divided into three groups : LEATs, pediatric-type diffuse low-grade glioma (DLGG; astrocytoma and oligodendroglioma), and adult-type DLGG. There is substantial overlap between conventional LEATs and pediatric-type DLGG in regard to clinical features, histology, and molecular characteristics. LEATs and pediatric-type DLGG are characterized by mutations in BRAF, FGFR1, and MYB/MYBL1, which converge on the RAS-RAF-MAPK pathway. Gene (mutation)-centered classification of epilepsyassociated tumors could provide new insight into these heterogeneous and diverse neoplasms and may lead to novel molecular targeted therapies for epilepsy in the near future.
脑肿瘤是导致慢性癫痫的第二常见的脑结构性病变类型。低级别脑肿瘤患者通常在儿童期就开始出现慢性耐药性癫痫,这催生了长期癫痫相关肿瘤(LEATs)的概念。胚胎发育不良性神经上皮肿瘤和神经节细胞胶质瘤是典型的LEATs,其特点是发病年龄小、常位于颞叶、肿瘤生物学行为良性以及慢性癫痫。尽管LEATs的概念在临床癫痫学中高度相关,但在神经肿瘤学领域却受到了批评。最近的基因组和分子研究对关于LEATs和低级别胶质瘤的传统观点提出了挑战。分子研究表明,低级别胶质瘤在很大程度上可分为三组:LEATs、儿童型弥漫性低级别胶质瘤(DLGG;星形细胞瘤和少突胶质细胞瘤)以及成人型DLGG。在临床特征、组织学和分子特征方面,传统的LEATs与儿童型DLGG之间存在大量重叠。LEATs和儿童型DLGG的特征是BRAF、FGFR1以及MYB/MYBL1发生突变,这些突变都集中在RAS-RAF-MAPK通路上。以基因(突变)为中心的癫痫相关肿瘤分类可能会为这些异质性和多样化的肿瘤提供新的见解,并可能在不久的将来带来针对癫痫的新型分子靶向治疗方法。