{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:49:41Z","timestamp":1790347781424,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Ameloblastic fibrosarcoma (<jats:roman>AFS<\/jats:roman>) is an aggressive odontogenic neoplasm featuring malignant mesenchymal stroma in addition to an ameloblastic epithelial component, and is hence considered to be the malignant counterpart of ameloblastic fibroma (<jats:roman>AF<\/jats:roman>). <jats:roman>AFS<\/jats:roman> is exceedingly rare, with &lt;110 cases having been reported so far. Although <jats:italic>BRAF<\/jats:italic> mutations are recognised driver mutations in ameloblastoma, the molecular pathogenesis of <jats:roman>AFS<\/jats:roman> remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We herein describe seven <jats:roman>AFS<\/jats:roman>s that were analysed, for the first time, for mutations in the <jats:italic>BRAF<\/jats:italic>\u2013<jats:italic>NRAS<\/jats:italic> pathway. The patients were four females and three males aged 23\u201357\u00a0years (median, 26\u00a0years). Three tumours developed after one or multiple recurrences of <jats:roman>AF<\/jats:roman> (4\u201320\u00a0years after initial diagnosis), two showed transition from <jats:roman>AF<\/jats:roman>\u2010like bland areas, and two developed <jats:italic>de novo<\/jats:italic>. All patients were treated with surgery; adjuvant chemotherapy was given to one patient. At the last follow\u2010up, five patients were alive and well (19\u2013344\u00a0months). The remainder were lost to follow\u2010up. Histological examination showed variable sarcomatous overgrowth with varying degrees of atypia and increased mitotic activity. The epithelial component varied greatly according to the degree of sarcomatous overgrowth. Molecular testing revealed <jats:italic>BRAF<\/jats:italic> V600E mutations in five cases and <jats:italic>NRAS<\/jats:italic> p.Gln61Lys mutation in one case. One tumour was wild\u2010type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>To our knowledge, this is the first study on <jats:italic>BRAF<\/jats:italic>\/<jats:italic>NRAS<\/jats:italic> mutations in <jats:roman>AFS<\/jats:roman>. Given the activity of <jats:roman>RAF<\/jats:roman> and <jats:roman>MEK<\/jats:roman> inhibitors across different cancers harbouring V600E mutations, our data strongly suggest that all <jats:roman>AFS<\/jats:roman> cases should be genetically tested, and that targeted treatment approaches for this extremely rare sarcoma subtype should be clinically investigated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14053","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T17:15:26Z","timestamp":1578071726000},"page":"814-821","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Ameloblastic fibrosarcoma: clinicopathological and molecular analysis of seven cases highlighting frequent <i>BRAF<\/i> and occasional <i>NRAS<\/i> mutations"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-8161","authenticated-orcid":false,"given":"Abbas","family":"Agaimy","sequence":"first","affiliation":[{"name":"Institute of Pathology University Hospital Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Skalova","sequence":"additional","affiliation":[{"name":"Department of Pathology Charles University, Faculty of Medicine in Plzen Plzen Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1332-5838","authenticated-orcid":false,"given":"Alessandro","family":"Franchi","sequence":"additional","affiliation":[{"name":"Department of Translational Research School of Medicine University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Alshagroud","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Diagnostic Science King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Gill","sequence":"additional","affiliation":[{"name":"Sydney Medical School University of Sydney St Leonards NSW Australia"},{"name":"Cancer Diagnosis and Pathology Group Kolling Institute St Leonards NSW Australia"},{"name":"NSW Health Pathology Department of Anatomical Pathology Royal North Shore Hospital St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Stoehr","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Hospital Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Baumhoer","sequence":"additional","affiliation":[{"name":"Department of Pathology University Hospital Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Bauer","sequence":"additional","affiliation":[{"name":"Sarcoma Centre Western German Cancer Centre University of Duisburg\u2010Essen Medical School Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"214","volume-title":"World Health Organization classification of head and neck tumours","author":"Wright JM","year":"2017"},{"key":"e_1_2_8_3_1","first-page":"213","volume-title":"World Health Organization classification of head and neck tumours","author":"El\u2010Mofty SK","year":"2017"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12622"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12130"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4317"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-018-2305-5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-018-2323-3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31828f233d"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.12659\/AJCR.892284"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1079-2104(05)80130-1"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2015.07.010"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1069"},{"key":"e_1_2_8_14_1","first-page":"4","article-title":"BRAF gene mutations in ameloblastic fibromas","volume":"51","author":"You Z","year":"2019","journal-title":"Beijing Da Xue Xue Bao Yi Xue 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