{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:23:17Z","timestamp":1791433397549,"version":"4.3.3"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,11,10]],"date-time":"2014-11-10T00:00:00Z","timestamp":1415577600000},"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":[[2015,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Neuroendocrine middle ear adenoma (<jats:styled-content style=\"fixed-case\">MEA<\/jats:styled-content>) is a rare epithelial neoplasm of uncertain histogenesis that frequently shows neuroendocrine features. To date, &lt;120 cases have been reported. The aims of the current study were to describe our experience with neuroendocrine <jats:styled-content style=\"fixed-case\">MEA<\/jats:styled-content>, to assess the frequency of specific neuroendocrine differentiation, and to test these lesions for transcription factors known to be expressed in a variety of other neuroendocrine tumours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We investigated six cases of neuroendocrine <jats:styled-content style=\"fixed-case\">MEA<\/jats:styled-content>, and stained them, for the first time, for the transcription factors <jats:styled-content style=\"fixed-case\">CDX<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">TTF<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>8, and <jats:styled-content style=\"fixed-case\">ISL<\/jats:styled-content>1 (islet\u20101). The patients were four men and two women (mean age, 39\u00a0years; range, 27\u201353\u00a0years). Two of four patients with extended follow\u2010up (4.5\u201322\u00a0years) experienced recurrence at 92\u00a0months, and at 9 and 22\u00a0years, respectively. One case extending into the external ear coexisted with cholesteatoma. Histological examination showed trabecular, solid, acinar, glandular, cribriform, organoid, nested, diffuse non\u2010cohesive plasmacytoid and pseudoalveolar patterns in varying combinations. Immunohistochemistry showed consistent expression of vimentin (4\/4), pancytokeratin (6\/6), synaptophysin (6\/6), <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56 (4\/4), and <jats:styled-content style=\"fixed-case\">ISL<\/jats:styled-content>1 (6\/6). A <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>7 antibody stained scattered cells in two of five cases. The myoepithelial markers and transcription factors <jats:styled-content style=\"fixed-case\">TTF<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">CDX<\/jats:styled-content>2 or <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>8 were not expressed in any of the cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Middle ear adenoma is an indolent, locally recurring, but generally non\u2010metastasizing neoplasm with uniform expression of synaptophysin and <jats:styled-content style=\"fixed-case\">ISL<\/jats:styled-content>1, indicating true neuroendocrine differentiation. Because of its highly varied cellular and architectural appearance, <jats:styled-content style=\"fixed-case\">MEA<\/jats:styled-content> should be distinguished from tympanic paraganglioma and a variety of rare benign and malignant lesions at this site.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.12447","type":"journal-article","created":{"date-parts":[[2014,4,26]],"date-time":"2014-04-26T06:48:40Z","timestamp":1398494920000},"page":"182-191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["\u2018Neuroendocrine\u2019 middle ear adenomas: consistent expression of the transcription factor <scp>ISL<\/scp>1 further supports their neuroendocrine derivation"],"prefix":"10.1111","volume":"66","author":[{"given":"Abbas","family":"Agaimy","sequence":"first","affiliation":[{"name":"Institute of Pathology University Hospital Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lell","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic and Interventional Radiology University Hospital Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Schaller","sequence":"additional","affiliation":[{"name":"Institute of Pathology Klinikum Augsburg Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"M\u00e4rkl","sequence":"additional","affiliation":[{"name":"Institute of Pathology Klinikum Augsburg Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Hornung","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery University Hospital Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2273.1976.tb00637.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1757-1626-0002-0000006508"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880561"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200403000-00003"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.40"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2012.34"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31826f042c"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31824aba59"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.111"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2007.09.008"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2009.02.014"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1102933"},{"key":"e_1_2_8_14_1","first-page":"199","article-title":"Middle ear adenoma\/carcinoid tumour: a case report and review of the literature","volume":"130","author":"Angouridakis N","year":"2009","journal-title":"Rev. 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