{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T22:12:17Z","timestamp":1773439937610,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T00:00:00Z","timestamp":1604880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Papillary neoplasms of the middle and inner ear are rare and poorly characterised. The current World Health Organization classification divides them into two major subtypes: aggressive papillary tumours (APTs) and endolymphatic sac tumours (ELSTs). The aim of this article is to present two papillary neoplasms of the middle ear that do not fit into either the classic APT category or the classic ELST category, and compare them with three ELSTs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The patients were a 48\u2010year\u2010old female and a 59\u2010year\u2010old male without a history of other neoplasms. Histology showed papillary\u2010cystic growth of predominantly oncocytic (Case 1) or mucinous (Case 2) cells surrounded by a p63\u2010positive basal layer. The overall histology was reminiscent of oncocytic sinonasal papilloma (Case 1) and pancreatobiliary or salivary intraductal papillary mucinous neoplasms (Case 2). Ovarian\u2010type stroma, invasion and malignant features were absent. Immunohistochemistry revealed expression of cytokeratin (CK) 7, but not carbonic anhydrase IX (CAIX) or paired box gene 8 (PAX8) (except for very focal PAX8 expression in Case 1). The TST15 gene panel and <jats:italic>HRAS<\/jats:italic> sequencing revealed no pathogenic mutations in <jats:italic>BRAF<\/jats:italic>, <jats:italic>KRAS<\/jats:italic>, <jats:italic>EGFR<\/jats:italic>, <jats:italic>AKT1<\/jats:italic>, or <jats:italic>HRAS<\/jats:italic>. The TruSight RNA fusion panel revealed an <jats:italic>MKRN1<\/jats:italic>\u2013<jats:italic>BRAF<\/jats:italic> fusion in Case 1. No fusion was detected in Case 2. The three ELSTs showed classic features of the entity, expressed CK7, epithelial membrane antigen, PAX8, and CAIX, and lacked a basal cell layer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These novel cases suggest that papillary tumours of the ear represent a heterogeneous spectrum of distinct neoplasms unified by a prominent papillary\u2010cystic pattern rather than a single entity. Future studies should clarify whether the <jats:italic>MKRN1<\/jats:italic>\u2013<jats:italic>BRAF<\/jats:italic> fusion is a defining recurrent driver event, especially in those cases reported as sinonasal\u2010type middle ear papillomas.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14250","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T13:40:44Z","timestamp":1600350044000},"page":"306-314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Papillary\u2010cystic neoplasms of the middle ear are distinct from endolymphatic sac tumours"],"prefix":"10.1111","volume":"79","author":[{"given":"Cecilia","family":"Taverna","sequence":"first","affiliation":[{"name":"Institute of Pathology Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg University Hospital Erlangen Erlangen Germany"},{"name":"Division of Pathological Anatomy Department of Health Sciences University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Pollastri","sequence":"additional","affiliation":[{"name":"Audiology Unit Head and Neck Oncological and Robotic Surgery Department of Oncological and Robotic Surgery AOU Careggi Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudi","family":"Pecci","sequence":"additional","affiliation":[{"name":"Audiology Unit Head and Neck Oncological and Robotic Surgery Department of Oncological and Robotic Surgery AOU Careggi Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Giannoni","sequence":"additional","affiliation":[{"name":"Audiology Unit Head and Neck Oncological and Robotic Surgery Department of Oncological and Robotic Surgery AOU Careggi Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Fattorini","sequence":"additional","affiliation":[{"name":"Division of Pathological Anatomy Department of Health Sciences University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Santucci","sequence":"additional","affiliation":[{"name":"Division of Pathological Anatomy Department of Health Sciences University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarina K","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg University Hospital Erlangen Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Stoehr","sequence":"additional","affiliation":[{"name":"Institute of Pathology Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg University Hospital Erlangen Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1332-5838","authenticated-orcid":false,"given":"Alessandro","family":"Franchi","sequence":"additional","affiliation":[{"name":"Department of Translational Research University of Pisa School of Medicine Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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\u2010N\u00fcrnberg University Hospital Erlangen Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,9]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"266","volume-title":"World Health Organization classification of head and neck tumours","author":"Sandison A","year":"2017"},{"key":"e_1_2_8_3_1","first-page":"266","volume-title":"World Health Organization classification of head and neck tumours","author":"Sandison A","year":"2017"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-011-1729-1"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-018-0973-8"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2004.100.3.0480"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199412000-00009"},{"key":"e_1_2_8_8_1","first-page":"2641","article-title":"Sporadic endolymphatic sac tumor\u2014a diagnostic and therapeutic challenge","volume":"7","author":"K\u00fcnzel J","year":"2014","journal-title":"Int. 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