Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland.
University of Zurich, Zurich, Switzerland.
J Neuropathol Exp Neurol. 2018 Aug 1;77(8):727-735. doi: 10.1093/jnen/nly050.
Primary intracranial neoplasms with features of extraskeletal myxoid chondrosarcomas (EMC) are extremely rare and poorly characterized tumors with only ∼12 cases described, the majority lacking molecular confirmation. There is an urgent need for the integration of molecular studies for correct subclassification of these tumors in order to predict clinical behavior, guide therapeutic decision-making, and provide novel targets for therapy. Clinical and pathologic data of 3 intracranial EMC-like myxoid neoplasms were retrospectively reviewed. In 2/3 cases, immunohistochemistry showed loss of nuclear SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1; integrase interactor 1 [INI1]) staining accompanied by monosomy of chromosome 22q (fluorescence in situ hybridization [FISH]). These 2 cases had no evidence of any fusion products by next generation sequencing (NGS). The third case had intact SMARCB1 expression and showed instead a rearrangement of the EWSR1 gene detected by FISH, with an EWSR1-CREB1 gene fusion on NGS. None of the cases showed rearrangement of the NR4A3 gene, neither by FISH nor by NGS. This small case series highlights the molecular heterogeneity of intracranial neoplasms in the morphologic spectrum of EMC. Distinct molecular alterations found in tumors with morphologic features of EMC encompass SMARCB1(INI1) loss and EWSR1-CREB gene fusions. None of the cases showed rearrangements of NR4A3 genes, suggesting they are distinct from conventional EMC.
原发性颅内肿瘤具有 extraskeletal myxoid chondrosarcomas（EMC）的特征，是极其罕见且特征描述不完善的肿瘤，仅有约 12 例被描述，其中大多数缺乏分子确认。为了正确对这些肿瘤进行分类，需要整合分子研究，以便预测临床行为、指导治疗决策，并为治疗提供新的靶点。回顾性分析了 3 例颅内 EMC 样黏液性肿瘤的临床和病理数据。在 2/3 的病例中，免疫组织化学显示核 SWI/SNF 相关基质相关肌动蛋白依赖性染色质调节剂亚家族 B 成员 1（SMARCB1；整合酶相互作用蛋白 1 [INI1]）染色缺失，同时伴有 22q 染色体单体缺失（荧光原位杂交 [FISH]）。这 2 例均未通过下一代测序（NGS）检测到任何融合产物。第 3 例具有完整的 SMARCB1 表达，而是通过 FISH 检测到 EWSR1 基因的重排，在 NGS 上显示 EWSR1-CREB1 基因融合。FISH 和 NGS 均未显示 NR4A3 基因的重排。这个小的病例系列突出了 EMC 形态学谱中颅内肿瘤的分子异质性。在具有 EMC 形态特征的肿瘤中发现的不同分子改变包括 SMARCB1（INI1）缺失和 EWSR1-CREB 基因融合。没有病例显示 NR4A3 基因的重排，表明它们与传统的 EMC 不同。
