Objectives:Atypical teratoid/rhabdoid tumors (ATRTs) are rare, malignant central nervous system (CNS) neoplasms that predominantly affect infants and young children. While ATRT arises throughout the CNS, its extracranial counterpart, malignant rhabdoid tumor, occurs in other organs. A single-institutional cohort is reviewed to map anatomic distribution of pediatric ATRTs and to integrate a literature review to contextualize ATRT histogenesis from anatomical and embryological perspectives.Methods:A retrospective review was conducted on a cohort of 50 pediatric patients with ATRT treated over 20 years. Demographic, surgical, and neuroimaging data were correlated to define tumor location, extent, and compartmental involvement. A focused literature review synthesized molecular subclassifications and proposed cells of origin/cytogenesis.Results:Of the 50 ATRTs, 18 (36%) were infratentorial, 15 (30%) supratentorial, 11 (22%) in the pineal region, and 6 (12%) in the spinal compartment. Among infratentorial tumors, 10 were centered in the fourth ventricle, with or without extension into the cerebellopontine angle (CPA) cistern; the remainder arose in the CPA. Among ATRTs of the cerebral hemispheres, 3 showed bi-hemispheric involvement crossing the falx cerebri. ATRTs of the pineal region predominantly originated from the superior medullary velum. These topographic data were corelated with embryological and molecular information available in the literature.Conclusions:ATRTs arise across diverse neuroanatomical compartments—including intraparenchymal, intraventricular, extra-axial, and extradural sites—underscoring biological heterogeneity. Inactivation of SMARCB1 is the defining molecular event and principal oncogenic driver, although the upstream mechanisms precipitating these alterations remain incompletely resolved. Molecular subgroups—ATRT-TYR, ATRT-SHH, and ATRT-MYC—display distinct age distributions and anatomic predilections, implicating developmental context in tumor initiation. The characteristic cellular admixture of rhabdoid cells with mesenchymal and/or epithelial differentiation, together with intra- and extra-axial and occasional extradural presentations, supports a model in which at least a subset of ATRTs may originate from neural crest-derived lineages, despite little or no neural crest contribution to brain parenchyma development. Neural plate border progenitors with bipotent features represent a plausible intraparenchymal cell of origin. Definitive resolution of these origins and the mechanisms of SMARCB1 disruption will require integrated approaches. Further investigations are warranted to clarify these mechanisms.
目的：非典型畸胎样/横纹肌样瘤（ATRT）是一种罕见的恶性中枢神经系统肿瘤，主要累及婴幼儿。虽然ATRT可发生于整个中枢神经系统，但其颅外对应病变——恶性横纹肌样瘤——可出现在其他器官。本研究通过回顾单中心病例队列，描绘儿童ATRT的解剖分布特征，并结合文献综述从解剖学与胚胎学角度探讨ATRT的组织发生机制。 方法：回顾性分析20年间收治的50例儿童ATRT患者。通过整合人口统计学、手术及神经影像学数据，明确肿瘤位置、范围及解剖分区受累情况。聚焦文献综述，综合分子亚型分类及潜在起源细胞/细胞发生学说。 结果：50例ATRT中，幕下18例（36%），幕上15例（30%），松果体区11例（22%），脊髓区6例（12%）。幕下肿瘤中，10例以第四脑室为中心，伴或不伴桥小脑角池侵犯；其余起源于桥小脑角区。大脑半球ATRT中，3例表现为跨大脑镰的双侧半球受累。松果体区ATRT主要起源于上髓帆。这些解剖分布数据与文献中的胚胎发育及分子信息具有相关性。 结论：ATRT可发生于多种神经解剖区域（包括脑实质内、脑室内、轴外及硬膜外），凸显其生物学异质性。SMARCB1基因失活是其明确的分子事件和主要致癌驱动因素，但诱发该改变的上游机制尚未完全阐明。ATRT-TYR、ATRT-SHH和ATRT-MYC三种分子亚型具有不同的年龄分布和解剖偏好，提示发育背景参与肿瘤发生。横纹肌样细胞与间充质/上皮分化细胞的典型混合表现，结合轴内、轴外及偶发的硬膜外生长模式，支持至少部分ATRT可能起源于神经嵴谱系——尽管神经嵴对脑实质发育贡献甚微。具有双向分化潜能的神经板边界祖细胞可能是脑实质内ATRT的潜在起源细胞。明确这些起源机制及SMARCB1失活机制需要整合多学科研究手段，值得进一步深入探索。
Histogenesis of Atypical Teratoid Rhabdoid Tumors: Anatomical and Embryological Perspectives
肿瘤(癌症)患者之家