Kao Yu-Chien, Sung Yun-Shao, Zhang Lei, Chen Chun-Liang, Vaiyapuri Sumathi, Rosenblum Marc K, Antonescu Cristina R
*Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan †Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY ‡Department of Musculoskeletal Pathology, The Royal Orthopaedic Hospital NHS Foundation Trust, Birmingham, UK.
Am J Surg Pathol. 2017 Apr;41(4):482-490. doi: 10.1097/PAS.0000000000000788.
Recurrent gene fusions involving EWSR1 with members of the cAMP response element binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and hyalinizing clear cell carcinoma of salivary gland. We have recently encountered a group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the CREB family member (ATF1, CREB1, and CREM), with histologic features distinct from any of the previously described pathologic entities. Tumors occurred in children or young adults (12 to 23 y; mean, 18 y), with equal sex distribution. All except 1 were intracranial (intra-axial, 2; meningeal, 2), whereas 1 was perirectal. Histologically, the tumors were well circumscribed, often lobulated, composed of uniform ovoid to round cells, and arranged in cord-like or reticular structures in a myxoid background. All except 1 displayed unique sunburst amianthoid fibers. Immunohistochemically, tumors were positive for epithelial membrane antigen (5/5; 4 focal, 1 diffuse) and desmin (3/5). A novel EWSR1-CREM fusion was identified by RNA sequencing in the perirectal tumor, which was further confirmed by fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). A second case with similar EWSR1-CREM fusion was identified by RT-PCR and FISH in a meningeal tumor. The remaining cases studied by FISH showed the presence of EWSR1-CREB1 fusion in 2 cases and EWSR1-ATF1 in 1. In conclusion, we report a distinct group of myxoid mesenchymal neoplasms occurring in children or young adults with a predilection for intracranial locations. Although the immunoprofile [epithelial membrane antigen (EMA), desmin] and the fusion type raise the possibility of a myxoid AFH, none of the typical histologic findings of AFH were present, suggesting a novel entity.
在包括血管样纤维组织细胞瘤（AFH）、软组织和胃肠道透明细胞肉瘤、原发性肺黏液样肉瘤以及涎腺透明变性透明细胞癌在内的多种肿瘤中，均有涉及EWSR1与环磷酸腺苷反应元件结合蛋白（CREB）家族成员（ATF1和CREB1）的复发性基因融合的报道。我们最近遇到了一组5例黏液样间叶性肿瘤，其EWSR1与CREB家族成员之一（ATF1、CREB1和CREM）融合呈阳性，组织学特征与任何先前描述的病理实体均不同。肿瘤发生于儿童或年轻人（12至23岁；平均18岁），男女分布均等。除1例位于直肠周围外，其余均位于颅内（脑内，2例；脑膜，2例）。组织学上，肿瘤边界清楚，常呈分叶状，由均匀的卵圆形至圆形细胞组成，在黏液样背景中呈条索状或网状结构排列。除1例以外，所有肿瘤均显示独特的放射状石棉样纤维。免疫组化显示，肿瘤上皮膜抗原阳性（5/5；4例局灶阳性，1例弥漫阳性），结蛋白阳性（3/5）。通过RNA测序在直肠周围肿瘤中鉴定出一种新的EWSR1-CREM融合，荧光原位杂交（FISH）和逆转录-聚合酶链反应（RT-PCR）进一步证实了这一结果。通过RT-PCR和FISH在1例脑膜肿瘤中鉴定出第二例具有相似EWSR1-CREM融合的病例。通过FISH研究的其余病例中，2例显示存在EWSR1-CREB1融合，1例显示存在EWSR1-ATF1融合。总之，我们报告了一组发生于儿童或年轻人的、倾向于颅内部位的独特的黏液样间叶性肿瘤。尽管免疫表型[上皮膜抗原（EMA）、结蛋白]和融合类型增加了黏液样AFH的可能性，但AFH的典型组织学表现均未出现，提示这是一种新的实体。
