{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:55:27Z","timestamp":1787673327384,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T00:00:00Z","timestamp":1703548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K15392"],"award-info":[{"award-number":["21K15392"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>The spread of lung adenocarcinoma cells into the bronchi and bronchioles is not well documented. We termed this histological finding \u201cendobronchial spreading of adenocarcinoma\u201d (EBSA) and investigated its prevalence and clinical significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>We reviewed 320 resected specimens from patients diagnosed with invasive adenocarcinoma, and EBSA was observed in 144 patients (45%). EBSA was significantly associated with advanced pathological stage, higher histological grade, larger tumour invasion, lymphovascular infiltration, and spread through air spaces. Patients with EBSA had significantly shorter relapse\u2010free survival (RFS) and cancer\u2010specific survival (CSS) in univariate analysis (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). In a subgroup analysis of patient with small\u2010sized (invasion size \u226430\u2009mm) adenocarcinoma in the localized stage, EBSA was an independent inferior prognostic indicator in multivariate analysis. In a subgroup analysis of patients with small\u2010sized Grade 1 nonmucinous adenocarcinoma (<jats:italic>n<\/jats:italic>\u2009=\u200961), EBSA was observed in 11 patients, and the presence of EBSA was associated with significantly shorter RFS and CSS (<jats:italic>P<\/jats:italic>\u2009=\u20090.026 and <jats:italic>P<\/jats:italic>\u2009=\u20090.001, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrated that EBSA is a significant risk factor for disease recurrence and cancer\u2010related deaths. EBSA can be regarded as a distinctive pattern of invasion and its recognition can be beneficial in the diagnosis of lung adenocarcinoma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15107","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T07:34:55Z","timestamp":1703662495000},"page":"646-660","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Endobronchial spread of adenocarcinoma is a distinct pattern of invasion and associated with inferior clinical outcomes in lung adenocarcinoma"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9219-8357","authenticated-orcid":false,"given":"Taishi","family":"Takahara","sequence":"first","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-6087","authenticated-orcid":false,"given":"Akira","family":"Satou","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuji","family":"Tsuyuki","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuki","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8284-567X","authenticated-orcid":false,"given":"Emiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyuichi","family":"Kadota","sequence":"additional","affiliation":[{"name":"Oncology Pathology, Department of Pathology and Host\u2010Defense, Faculty of Medicine Kagawa University  Miki\u2010cho, Kita\u2010gun Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4855-4366","authenticated-orcid":false,"given":"Toyonori","family":"Tsuzuki","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"key":"e_1_2_12_2_1","series-title":"Thoracic tumours","volume-title":"WHO classification of tumours","author":"WHO Classification of Tumours Editorial Board","year":"2021"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000134"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.2185"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3182769aa8"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e318206a221"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2010.232"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13922"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2012.106"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.338228.120"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1605"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198411000-00005"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005382-200201000-00014"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.5578\/tt.2322"},{"key":"e_1_2_12_15_1","article-title":"\"Real\" tumor\u2010spread through air spaces of lung adenocarcinoma presented intrapulmonary metastases through bronchiole air spaces: a case report","volume":"3","author":"Kaku S","year":"2022","journal-title":"JTO Clin. 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