{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T03:01:27Z","timestamp":1780628487655,"version":"3.54.1"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018935","name":"Universit\u00e4tsklinikum Erlangen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018935","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    ACTH-producing pancreatic neuroendocrine neoplasms (PanNENs) are a rare aggressive subset of panNETs associated with clinical symptoms of ectopic Cushing syndrome. Until recently, their molecular pathogenesis remained poorly understood. Following our prior study highlighting high frequency of gene fusions (mostly\n                    <jats:italic>EWSR1::BEND2<\/jats:italic>\n                    ) in them, we herein document our experience with 5 new tumors occurring in 4 women (one of unspecified sex) aged 36 to 79 (median, 45). All presented with clinical and biochemical signs of ectopic Cushing syndrome. Histologically, the tumors corresponded to NET grade 2 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093) and grade 3 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092). At last follow-up, three patients were alive with metastatic disease at 36, 48 and 72 months from initial diagnosis, one died of disease at 50 months and one was disease-free at 15 months. Targeted RNA sequencing revealed an\n                    <jats:italic>EWSR1::BEND2<\/jats:italic>\n                    fusion in two cases and a possible\n                    <jats:italic>CSE1L::TAF15<\/jats:italic>\n                    fusion in one. Two tumors were negative for fusions. This small series and review of the recent literature further confirm the significant association between the\n                    <jats:italic>EWSR1::BEND2<\/jats:italic>\n                    fusions and ectopic ACTH-production in PanNETs with an overall frequency of ectopic Cushing among\n                    <jats:italic>EWSR1::BEND2<\/jats:italic>\n                    fusion tumors of 70%. Given their highly aggressive course, recognition of this molecular subtype of panNETs is mandatory. Emerging BEND2 IHC represents a promising screening tool for recognizing these tumors.\n                  <\/jats:p>","DOI":"10.1007\/s00428-026-04599-8","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:02:22Z","timestamp":1780624942000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["EWSR1::BEND2 gene fusions characterize a majority of ACTH-producing neuroendocrine neoplasms of the pancreas: A follow-up study and brief review of the recent literature"],"prefix":"10.1007","author":[{"given":"Abbas","family":"Agaimy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volkan","family":"Adsay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Stoehr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne E.","family":"Pavel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Schiavo","family":"Lena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"4599_CR1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.tem.2023.12.003","volume":"35","author":"O Ragnarsson","year":"2024","unstructured":"Ragnarsson O, Juhlin CC, Torpy DJ, Falhammar H (2024) A clinical perspective on ectopic Cushing\u2019s syndrome. 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The authors have no financial or non-financial conflicts of interest to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure of potential conflicts of interest"}}]}}