{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:01:10Z","timestamp":1791414070510,"version":"4.3.3"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"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":["Histopathology"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Simple bone cysts are benign intramedullary tumours primarily involving the long bones in skeletally immature individuals. Several mechanisms have been proposed for their pathogenesis. Although the diagnosis is typically straightforward, the interpretation can be problematic, because of superimposed fracture causing them to resemble aneurysmal bone cysts and other tumours. <jats:italic>EWSR1<\/jats:italic>\u2013<jats:italic>NFATC2<\/jats:italic> or <jats:italic>FUS<\/jats:italic>\u2013<jats:italic>NFATC2<\/jats:italic> fusions, which are characteristic of a subset of aggressive round cell sarcomas, have been recently detected in simple bone cysts. The aim of this study was to examine the clinicopathological and molecular features in a series of simple bone cysts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Using RNA\u2010based next\u2010generation sequencing and\/or fluorescence <jats:italic>in\u2010situ<\/jats:italic> hybridisation, we investigated the presence of <jats:italic>EWSR1<\/jats:italic> or <jats:italic>FUS<\/jats:italic> rearrangements in nine simple bone cysts. The patients were five females and four males, aged 3\u201323\u00a0years (median, 14\u00a0years); the tumours ranged from 19\u00a0mm to 160\u00a0mm (median, 46\u00a0mm) in size, and involved the femur (<jats:italic>n<\/jats:italic>\u00a0=\u00a03), humerus (<jats:italic>n<\/jats:italic>\u00a0=\u00a02), fibula (<jats:italic>n<\/jats:italic>\u00a0=\u00a02), tibia (<jats:italic>n<\/jats:italic>\u00a0=\u00a01), and iliac wing (<jats:italic>n<\/jats:italic>\u00a0=1). We identified three cases with <jats:italic>EWSR1<\/jats:italic>\u2013<jats:italic>NFATC2<\/jats:italic> fusion (showing identical breakpoints to those in <jats:italic>EWSR1<\/jats:italic>\u2013<jats:italic>NFATC2<\/jats:italic> sarcomas) and one additional case with <jats:italic>FUS<\/jats:italic> rearrangement. Unlike in <jats:italic>EWSR1<\/jats:italic>\u2013<jats:italic>NFATC2<\/jats:italic> sarcomas, immunohistochemical expression of NKX3.1 and NKX2.2 was absent in two simple bone cysts tested.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>More than 40% of simple bone cysts harbour genetic alterations confirming that they are neoplastic, investigation of <jats:italic>EWSR1<\/jats:italic> and\/or <jats:italic>FUS<\/jats:italic> rearrangement may help to distinguish simple bone cysts from mimics, and <jats:italic>NFATC2<\/jats:italic> rearrangement is not pathognomonic of malignancy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14314","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T04:07:07Z","timestamp":1608005227000},"page":"849-856","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Identification of <i>EWSR1\u2013NFATC2<\/i> fusion in simple bone cysts"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-1591","authenticated-orcid":false,"given":"Yin P","family":"Hung","sequence":"first","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S","family":"Fisch","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8166-7314","authenticated-orcid":false,"given":"Julio A","family":"Diaz\u2010Perez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Miami Miller School of Medicine Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A John","family":"Iafrate","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen K","family":"Lennerz","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Nardi","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam A","family":"Bredella","sequence":"additional","affiliation":[{"name":"Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A","family":"Raskin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago A","family":"Lozano\u2010Calderon","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew E","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Miami Miller School of Medicine Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G Petur","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"467","volume-title":"World Health Organization classification of tumours: soft tissue and bone tumours","author":"Reith JD","year":"2020"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1942.01210240043003"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-197052070-00030"},{"key":"e_1_2_8_5_1","first-page":"295","article-title":"Cementum\u2010like bone production in solitary bone cysts (so\u2010called \u2018cementoma\u2019 of long bones). Report of three cases. Electron microscopic observations supporting a synovial origin to the simple bone cyst","volume":"135","author":"Mirra JM","year":"1978","journal-title":"Clin. Orthop. Relat. Res."},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(02)00563-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1148\/92.5.949"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00256-009-0685-y"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.5435\/JAAOS-22-05-295"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/00003086-198603000-00004","article-title":"Unicameral and aneurysmal bone cysts","volume":"204","author":"Campanacci M","year":"1986","journal-title":"Clin. Orthop. Relat. Res."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.03962.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2013.07.001"},{"key":"e_1_2_8_13_1","first-page":"326","volume-title":"World Health Organization classification of tumours: soft tissue and bone tumours","author":"Loarer F","year":"2020"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-2184"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9386390"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2019.05.001"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001260"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0542-z"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001441"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001584"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2019.08.006"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3729"},{"key":"e_1_2_8_23_1","first-page":"369","article-title":"Uber die Bildung von Knochenzysten","volume":"2","author":"Virchow R","year":"1876","journal-title":"Monatsber. Konigl. Preuss. Akad. Wiss."},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2011-0557-RA"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.15.255"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2827"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199112123252403"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.1.120"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.4"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22857"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0095-6"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5053"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2014.09.015"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31827ae13b"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31824ee43c"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2016.31"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14314","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.14314","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14314","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T04:47:02Z","timestamp":1693543622000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.14314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,16]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1111\/his.14314"],"URL":"https:\/\/doi.org\/10.1111\/his.14314","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,16]]},"assertion":[{"value":"2020-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}