{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:39:59Z","timestamp":1788781199141,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T00:00:00Z","timestamp":1693612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:italic>YAP1::MAML2<\/jats:italic>\n                    ,\n                    <jats:italic>PTBP1::MAML2<\/jats:italic>\n                    , and\n                    <jats:italic>EPC1::PHC2<\/jats:italic>\n                    have been detected in a small subset of cases with or without neuroendocrine expression. Herein, we present four additional cases with novel in\u2010frame fusions. The cohort comprises two females and two males with a wide age range at diagnosis (24\u201380\u2009years). 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\u2009cm 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\u201040 (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\u2009months, while two patients had no evidence of disease 4\u2009months post\u2010resection. Targeted RNA sequencing detected novel in\u2010frame fusions in each of the cases:\n                    <jats:italic>HSPG2::FGFR1, YAP1::FOXR1, ACTB::MAML2<\/jats:italic>\n                    , and\n                    <jats:italic>ARID1B::MAML2<\/jats:italic>\n                    . The two cases with neuroendocrine expression occurred as superficial lesions and harbored\n                    <jats:italic>YAP1::FOXR1<\/jats:italic>\n                    and\n                    <jats:italic>ARID1B::MAML2<\/jats:italic>\n                    fusions. Our study expands on the molecular spectrum of this enigmatic tumor, further enhancing our current understanding of the disease.\n                  <\/jats:p>","DOI":"10.1002\/gcc.23198","type":"journal-article","created":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T04:31:25Z","timestamp":1693629085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9462-652X","authenticated-orcid":false,"given":"Konstantinos","family":"Linos","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1139-2914","authenticated-orcid":false,"given":"Josephine K.","family":"Dermawan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"},{"name":"Department of Pathology Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Pulitzer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meera","family":"Hameed","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6991-2310","authenticated-orcid":false,"given":"Narasimhan P.","family":"Agaram","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-8161","authenticated-orcid":false,"given":"Abbas","family":"Agaimy","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Friedrich\u2010Alexander\u2010University Erlangen\u2010Nurnberg University Hospital  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-8205","authenticated-orcid":false,"given":"Cristina R.","family":"Antonescu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,2]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"WHO Classification of Tumours of Soft Tissue and Bone","author":"Rubin BPFA","year":"2020"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.2007.00781.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0000000000000079"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.83"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.23017"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-021-01393-7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001575"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0175-7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2020.151504"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-1720"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.078865"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.21.7688-7700.2002"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.613557"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1917969117"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22073"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00879-7"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22839"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-022-01096-6"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2021.02.009"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.23102"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cup.14265"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126185"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0382-x"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-022-03747-8"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-022-01423-7"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10014-022-00439-0"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001423"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001382"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001719"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2018-227475"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000002276"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20306"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3368-4"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000927"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.08.002"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26116"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90133-5"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2020.11.003"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14868"},{"issue":"6","key":"e_1_2_7_41_1","article-title":"Fibroblast growth factor receptor (FGFR) signaling in GIST and soft tissue sarcomas","volume":"10","author":"Napolitano A","year":"2021","journal-title":"Cell"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.16091"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4465"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20906"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2056"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001644"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.23030"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-12-758979"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1882-3"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.257246.119"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.23198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T08:23:33Z","timestamp":1705566213000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.23198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,2]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/gcc.23198"],"URL":"https:\/\/doi.org\/10.1002\/gcc.23198","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,2]]},"assertion":[{"value":"2023-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23198"}}