PDF(Pubmed)
Abstract：
Composite hemangioendothelioma is a rare, locally aggressive, and rarely metastasizing vascular neoplasm which affects both children and adults. Recently, a number of gene fusions including YAP1::MAML2, PTBP1::MAML2, and EPC1::PHC2 have been detected in a small subset of cases with or without neuroendocrine expression. Herein, we present four additional cases with novel in-frame fusions. The cohort comprises two females and two males with a wide age range at diagnosis (24-80 years). Two tumors were deep involving the right brachial plexus and mediastinum, while the remaining were superficial (right plantar foot and abdominal wall). The size ranged from 1.5 to 4.8 cm in greatest dimension. Morphologically, all tumors had an admixture of at least two architectural patterns including retiform hemangioendothelioma, hemangioma, epithelioid hemangioendothelioma, or angiosarcoma. The tumors were positive for endothelial markers CD31 (3/3), ERG (4/4), and D2-40 (1/4, focal), while SMA was expressed in 2/3 highlighting the surrounding pericytes. Synaptophysin showed immunoreactivity in 2/3 cases. One patient had a local recurrence after 40 months, while two patients had no evidence of disease 4 months post-resection. Targeted RNA sequencing detected novel in-frame fusions in each of the cases: HSPG2::FGFR1, YAP1::FOXR1, ACTB::MAML2, and ARID1B::MAML2. The two cases with neuroendocrine expression occurred as superficial lesions and harbored YAP1::FOXR1 and ARID1B::MAML2 fusions. Our study expands on the molecular spectrum of this enigmatic tumor, further enhancing our current understanding of the disease.
摘要：
复合血管内皮瘤是一种罕见的，当地的侵略性，很少发生影响儿童和成人的转移性血管肿瘤。最近,在一小部分有或没有神经内分泌表达的病例中检测到了许多基因融合,包括YAP1::MAML2,PTBP1::MAML2和EPC1::PHC2.在这里，我们提出了另外四例新的帧内融合。该队列包括两名女性和两名男性，在诊断时年龄范围很广（24-80岁）。两例肿瘤累及右臂丛神经和纵隔，其余为浅表（右足底和腹壁）。最大尺寸为1.5至4.8cm。形态学上,所有肿瘤都有至少两种结构模式的混合，包括网状血管内皮瘤，血管瘤,上皮样血管内皮瘤，或者血管肉瘤.肿瘤内皮标志物CD31阳性（3/3），ERG(4/4),和D2-40（1/4，焦点），而SMA在突出周围周细胞的2/3中表达。2/3例突触素呈免疫反应性。一名患者在40个月后局部复发，而两名患者在切除后4个月没有疾病的证据。靶向RNA测序在每种情况下检测到新的框内融合：HSPG2::FGFR1，YAP1::FOXR1，ACTB::MAML2和ARID1B::MAML2。2例神经内分泌表达为浅表病变，并带有YAP1：：FOXR1和ARID1B：：MAML2融合。我们的研究扩展了这种神秘肿瘤的分子光谱，进一步加强我们目前对这种疾病的认识。
