{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:51:43Z","timestamp":1787014303506,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009629","name":"Fondazione Cassa di Risparmio di Trento e Rovereto","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009629","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2017,11]]},"abstract":"\n Aims<\/jats:title>\n \n The association between lung cancer and idiopathic pulmonary fibrosis (\n IPF<\/jats:styled-content>\n ) is well known, but the significance of this association is poorly understood. Bronchiolar honeycomb cysts have been proposed as possible precursors for the development of carcinoma, but limited evidence in support of this hypothesis is available. The aim of this study was to investigate this hypothesis analysing a series of carcinomas arising in\n IPF<\/jats:styled-content>\n by immunohistochemistry.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and results<\/jats:title>\n \n Thirty\u2010three lung carcinomas arising in patients with\n IPF<\/jats:styled-content>\n were analysed with a panel of immunohistochemical markers. The antibodies included those against pneumocyte markers [thyroid transcription factor 1 (\n TTF<\/jats:styled-content>\n 1), napsin\u2010A, and surfactant protein A], the goblet cell marker mucin 5\n AC<\/jats:styled-content>\n , markers of basal\/squamous cell differentiation [cytokeratin (\n CK<\/jats:styled-content>\n ) 5\/6 and \u0394N\u2010p63], and markers related to enteric differentiation (\n CDX<\/jats:styled-content>\n 2, mucin 2,\n CK<\/jats:styled-content>\n 20, and villin). A series of 100 consecutive lung adenocarcinomas arising in smokers without\n IPF<\/jats:styled-content>\n were investigated as controls. All carcinomas arising in\n IPF<\/jats:styled-content>\n patients were peripherally located on imaging analysis. The diagnoses were: eight squamous cell carcinomas, 20 adenocarcinomas, three small\u2010cell carcinomas (including one composite small\u2010cell carcinoma and adenocarcinoma), and two large\u2010cell carcinomas. Among adenocarcinomas, a \u2018pneumocyte\u2019 profile (\n TTF<\/jats:styled-content>\n 1\/napsin\u2010A\/\n SPA<\/jats:styled-content>\n 1\u2010triple\u2010positive) was observed in seven of 20 (35% versus 84% in non\u2010\n IPF<\/jats:styled-content>\n controls,\n P<\/jats:italic>\n = 0.0001). The remaining 13 adenocarcinomas (65%) showed rare histotypes: four invasive mucinous adenocarcinomas (20% in\n IPF<\/jats:styled-content>\n patients versus 1% in non\u2010\n IPF<\/jats:styled-content>\n controls,\n P<\/jats:italic>\n = 0.002), seven tumours (35%) that were characterized by variable expression of markers of enteric differentiation, and two tumours (10%) that showed a peculiar basaloid component.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The immunohistochemical characterization of carcinomas arising in\n IPF<\/jats:styled-content>\n patients shows striking divergence from that in non\u2010\n IPF<\/jats:styled-content>\n smokers. The prevalence of rare entities showing bronchiole\u2010related markers is in line with the hypothesis that these tumours arise from transformed small airways in honeycomb lung areas where abnormal bronchiolar proliferation takes place.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/his.13269","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T09:51:19Z","timestamp":1496137879000},"page":"725-735","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Increased frequency of bronchiolar histotypes in lung carcinomas associated with idiopathic pulmonary fibrosis"],"prefix":"10.1111","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7352-6327","authenticated-orcid":false,"given":"Anna","family":"Cali\u00f2","sequence":"first","affiliation":[{"name":"Department of Pathology AOUI University of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Lever","sequence":"additional","affiliation":[{"name":"Department of Pathology AOUI University of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Pneumology AOUI University of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Gilioli","sequence":"additional","affiliation":[{"name":"Department of Pathology AOUI University of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Brunelli","sequence":"additional","affiliation":[{"name":"Department of Pathology AOUI University of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Dubini","sequence":"additional","affiliation":[{"name":"Department of Pathology Forl\u00ec Hospital Forl\u00ec Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Tomassetti","sequence":"additional","affiliation":[{"name":"Department of Pneumology Forl\u00ec Hospital Forl\u00ec Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Piciucchi","sequence":"additional","affiliation":[{"name":"Department of Radiology Forl\u00ec Hospital Forl\u00ec Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Nottegar","sequence":"additional","affiliation":[{"name":"Department of Pathology AOUI University of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Rossi","sequence":"additional","affiliation":[{"name":"Operative Unit of Pathology Azienda USL Valle d'Aosta Aosta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Kambouchner","sequence":"additional","affiliation":[{"name":"Department of Pathology Avicenne Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Cancellieri","sequence":"additional","affiliation":[{"name":"Department of Pathology Maggiore Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Barbareschi","sequence":"additional","affiliation":[{"name":"Department of Pathology Santa Chiara Hospital Trento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pelosi","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Doglioni","sequence":"additional","affiliation":[{"name":"Department of Pathology San Raffaele Hospital Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Cavazza","sequence":"additional","affiliation":[{"name":"Department of Pathology Arcispedale S. 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