{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:51:41Z","timestamp":1783122701923,"version":"3.54.6"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Sinonasal respiratory epithelial adenomatoid hamartomas (REAH) are rare benign lesions with diverse clinical characteristics. Their pathogenesis remains unclear, with hypotheses suggesting either an inflammatory process or neoplastic origin. Despite their clinical heterogeneity, a formal subtype classification is lacking. This study analyzes the clinical features of surgically treated sinonasal REAH and investigates disease characteristics based on bilaterality, particularly in relation to type 2 chronic rhinosinusitis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This retrospective analysis included patients with REAH who underwent endoscopic surgery and received pathological confirmation between November 2008 and November 2023. Demographic data, including asthma history, prior sinus surgeries, serum eosinophil levels, and the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score, were analyzed in relation to REAH bilaterality.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Among 21 patients (17 males, 4 females; mean age 46.5 years), 11 cases (52.4%) exhibited bilateral origins (REAH_bi) in the superior nasal septum and olfactory cleft, while 10 cases (47.6%) presented as isolated unilateral lesions (REAH_uni). REAH_bi was significantly associated with asthma (p = 0.012), prior sinus surgery (p = 0.002), and inflammatory polyposis (p = 0.002) compared to REAH_uni. Elevated preoperative serum eosinophil levels and JESREC scores were also noted in REAH_bi cases (p = 0.021 and &lt;0.001, respectively). Neither group showed recurrence during a mean follow-up of 11.91 months.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Bilaterally originating REAH in the superior nasal septum and olfactory cleft demonstrates pronounced type 2 inflammatory characteristics, suggesting potential differences in pathogenesis compared to unilateral REAH. These findings underscore the need for further investigation into REAH pathophysiology and emphasize the importance of bilaterality in clinical assessment.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0318452","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T18:35:43Z","timestamp":1738607743000},"page":"e0318452","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Link between bilaterality and type 2 inflammation in respiratory epithelial adenomatoid hamartomas: A two-center retrospective cohort study"],"prefix":"10.1371","volume":"20","author":[{"given":"Yujin","family":"Heo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Duk","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Yeol","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwanghui","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Won","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-849X","authenticated-orcid":true,"given":"Yong Gi","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"pone.0318452.ref001","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1177\/000348949510400809","article-title":"Respiratory epithelial adenomatoid hamartomas of the sinonasal tract and nasopharynx: a clinicopathologic study of 31 cases","volume":"104","author":"BM Wenig","year":"1995","journal-title":"Ann Otol Rhinol 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Gauchotte","year":"2013","journal-title":"Am J Surg Pathol"},{"key":"pone.0318452.ref008","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1002\/lary.22399","article-title":"Respiratory epithelial adenomatoid hamartomas","volume":"121","author":"D Vira","year":"2011","journal-title":"Laryngoscope"},{"key":"pone.0318452.ref009","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.3174\/ajnr.A3345","article-title":"CT findings of sinonasal respiratory epithelial adenomatoid hamartoma: a closer look at the olfactory clefts","volume":"34","author":"KA Hawley","year":"2013","journal-title":"AJNR Am J Neuroradiol"},{"key":"pone.0318452.ref010","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1002\/lary.24778","article-title":"Predictors of respiratory epithelial adenomatoid hamartomas of the olfactory clefts in patients with nasal polyposis","volume":"124","author":"DT Nguyen","year":"2014","journal-title":"Laryngoscope"},{"key":"pone.0318452.ref011","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.amjoto.2006.09.013","article-title":"A case of respiratory epithelial adenomatoid hamartoma","volume":"28","author":"J Liang","year":"2007","journal-title":"Am J Otolaryngol"},{"key":"pone.0318452.ref012","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1097\/01.pas.0000213344.55605.77","article-title":"Tumor suppressor gene alterations in respiratory epithelial adenomatoid hamartoma (REAH): comparison to sinonasal adenocarcinoma and inflamed sinonasal mucosa","volume":"30","author":"JA Ozolek","year":"2006","journal-title":"Am J Surg Pathol"},{"key":"pone.0318452.ref013","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1097\/PAS.0b013e3181874ee8","article-title":"Low-grade sinonasal adenocarcinomas: the association with and distinction from respiratory epithelial adenomatoid hamartomas and other glandular 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Tokunaga","year":"2015","journal-title":"Allergy"},{"key":"pone.0318452.ref017","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3174\/ajnr.A1755","article-title":"Respiratory epithelial adenomatoid hamartoma of the bilateral olfactory recesses: a neoplastic mimic?","volume":"31","author":"JG Seol","year":"2010","journal-title":"AJNR Am J Neuroradiol"},{"key":"pone.0318452.ref018","article-title":"Beware the respiratory epithelial adenomatoid hamartoma-a malignant masquerador","author":"SA Kumar","year":"2021","journal-title":"J Surg Case Rep"},{"key":"pone.0318452.ref019","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1177\/014556130608500318","article-title":"Respiratory epithelial adenomatoid hamartoma: a case report","volume":"85","author":"WF Ingram","year":"2006","journal-title":"Ear Nose Throat J"},{"key":"pone.0318452.ref020","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1007\/s12070-018-1562-6","article-title":"Respiratory Epithelial 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