复合性血管内皮瘤是一种罕见的局部侵袭性、极少有转移的血管肿瘤，影响儿童和成人。最近，我们在一小部分患者中检测到了一些基因融合情况，包括YAP1::MAML2，PTBP1::MAML2和EPC1::PHC2，其中有的患者表现为神经内分泌表达，有的患者没有。 在此，我们报道了四例新颖的框内融合情况。该队列包括两名女性和两名男性，诊断年龄范围广泛（24-80岁）。两个肿瘤位于深部，涉及右颈神经丛和纵隔，其余两个肿瘤位于浅表区域（右足底和腹壁）。最大尺寸范围从1.5到4.8厘米不等。形态学上，所有肿瘤都呈混合至少两种结构模式，包括网状血管内皮瘤、血管瘤、上皮样血管内皮瘤或血管肉瘤。肿瘤对内皮标志物CD31（3/3），ERG（4/4）和D2-40（1/4，局灶性）呈阳性，而SMA在2/3病例中表达，突触素在2/3病例中显示免疫反应。一名患者在手术后40个月出现了局部复发，而另外两名患者在手术后4个月没有发现疾病证据。目标RNA测序在每个病例中检测到了新颖的框内融合情况：HSPG2::FGFR1，YAP1::FOXR1，ACTB::MAML2和ARID1B::MAML2。神经内分泌表达的两例发生在浅表病变中，并且带有YAP1::FOXR1和ARID1B::MAML2融合。我们的研究拓展了这种神秘肿瘤的分子谱，进一步加深了我们对该疾病的当前认识。©2023 Wiley Periodicals LLC.

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.© 2023 Wiley Periodicals LLC.