Multifocal synchronous or metachronous atypical teratoid rhabdoid tumors (ATRTs) and non-central nervous system malignant rhabdoid tumors (extra-CNS MRTs) are rare cancers. We reviewed the clinical and radiologic characteristics of affected patients seen at our institution. Genotyping and analysis of copy number abnormalities (CNAs) in SMARCB1 were performed in germline and tumor samples. Tumor samples underwent genome-wide DNA methylation and CNA analysis. The median age at diagnosis of 21 patients was 0.6 years. Two-thirds of ATRTs and extra-CNS MRTs were diagnosed synchronously. Although kidney tumors predominated, including two patients with bilateral involvement, at least 30% of cases lacked renal involvement. Histopathologic review confirmed MRTs in all cases and INI1 expression loss in all tumors tested. Fourteen (78%) of 18 patients tested had heterozygous germline SMARCB1 abnormalities. At least one allelic SMARCB1 abnormality was confirmed in 81 and 88% of ATRTs and extra-CNS MRTs, respectively. Unsupervised hierarchical clustering analysis of DNA methylation in 27 tumors and comparison with a reference group of 150 ATRTs classified the CNS tumors (n = 14) as sonic hedgehog (64%), tyrosinase (21%), and MYC (14%). The MYC subgroup accounted for 85% of 13 extra-CNS MRTs. Of 16 paired ATRTs and extra-CNS MRTs, the tumors in seven of eight patients showed a different pattern of genome-wide DNA methylation and/or CNAs suggestive of non-clonal origin. CNS and extra-CNS tumors had an identical SMARCB1 amplification (n = 1) or very similar DNA methylation pattern (n = 1) suggestive of clonal origin. All patients died of tumor progression. The clinical and molecular characteristics of multifocal ATRTs and extra-CNS MRTs are heterogeneous with most patients harboring a cancer predisposition. Although independent tumor origin was confirmed in most cases, metastatic spread was also documented. The recognition of their distinct molecular characteristics is critical in selecting new biologic therapies against these deadly cancers.

多灶同步或异时非典型类畸胎瘤样横纹肌瘤（ATRTs）和非中枢神经系统恶性瘤样横纹肌瘤（extra-CNS MRTs）是罕见的癌症。我们回顾了在我们机构看到的受影响患者的临床和放射学特征。SMARCB1中的基因分型和拷贝数异常（CNA）分析在种系和肿瘤样品中进行。肿瘤样品进行了全基因组DNA甲基化和CNA分析。诊断出的21名患者的中位年龄为0.6岁。三分之二的ATRT和CNS以外的MRT是同步诊断的。尽管肾脏肿瘤占主导，包括两名双边受累患者，但至少有30％的病例缺乏肾脏受累。组织病理学检查证实了所有病例中的MRT和所有测试的肿瘤中INI1表达的丧失。测试的18位患者中有14位（78％）具有杂合种系SMARCB1异常。至少一个等位基因SMARCB1分别在81％和88％的ATRT和CNS以外的MRT中确认了异常。在27个肿瘤中进行无监督的DNA甲基化分层聚类分析，并与150个ATRT的参考组进行比较，将CNS肿瘤（n  = 14）分类为声波刺猬（64％），酪氨酸酶（21％）和MYC（14％）。MYC子组占13种CNS捷运的85％。在16对配对的ATRT和CNS以外的MRT中，八位患者中有七位的肿瘤表现出不同的全基因组DNA甲基化和/或CNA模式，提示非克隆起源。CNS和CNS外肿瘤具有相同的SMARCB1扩增（n  = 1）或非常相似的DNA甲基化模式（n = 1）提示克隆来源。所有患者均死于肿瘤进展。多灶性ATRT和CNS以外的MRT的临床和分子特征是异质的，大多数患者具有癌症易感性。尽管在大多数情况下已确认独立的肿瘤起源，但也有转移扩散的报道。在选择针对这些致命癌症的新生物疗法中，识别其独特的分子特征至关重要。