{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:24:08Z","timestamp":1760300648322,"version":"3.40.5"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"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":[[2022,3]]},"abstract":"<jats:p>Although precursor lesions of pulmonary squamous carcinoma, adenocarcinoma and carcinoid tumour are well known and accepted entities, precursor lesions of pulmonary neuroendocrine carcinomas, i.e. small\u2010cell lung carcinoma and large\u2010cell neuroendocrine carcinoma, have never been identified. A small body of literature documenting intraepithelial involvement in cases of pulmonary neuroendocrine carcinoma begs the question of whether the intraepithelial lesion represents <jats:italic>de\u2010novo<\/jats:italic> intraepithelial neoplasia or invasion by underlying tumour. In this article, the literature on cases of invasive neuroendocrine carcinomas with an intraepithelial component showing a neuroendocrine immunophenotype is thoroughly and critically reviewed. The authors of the publications of cases of coexisting invasive and intraepithelial neuroendocrine carcinoma generally favour invasion as the explanation for the intraepithelial component. However, in practice, it is difficult or impossible to determine the direction of migration of tumour cells when there is both an invasive component and an intraepithelial component. Pulmonary neuroendocrine carcinomas <jats:italic>in\u2009situ<\/jats:italic> have been produced in genetically engineered mouse models. On the basis of the illustrations in the literature of human cases and the production of pulmonary neuroendocrine carcinomas <jats:italic>in\u2009situ<\/jats:italic> in genetically engineered mice, it seems likely that these tumours also exist in humans. However, their existence and acceptance require definitive proof. Studies should be undertaken to identify bronchial and other lung biopsies with <jats:italic>in\u2010situ<\/jats:italic> carcinoma showing a neuroendocrine immunophenotype and a subsequent negative resection specimen and no follow\u2010up evidence of invasive carcinoma. Documenting such cases would provide definitive proof for the existence of pulmonary neuroendocrine carcinomas <jats:italic>in\u2009situ<\/jats:italic> in humans.<\/jats:p>","DOI":"10.1111\/his.14596","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T20:52:55Z","timestamp":1636577575000},"page":"627-634","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pulmonary neuroendocrine carcinomas <i>in situ<\/i>: do they exist?"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-4134","authenticated-orcid":false,"given":"Yale","family":"Rosen","sequence":"first","affiliation":[{"name":"Department of Pathology SUNY Downstate Health Sciences University New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-20-269"},{"key":"e_1_2_9_3_1","unstructured":"MB Beasley E Brambilla H MacMahon Small cell lung carcinoma"},{"key":"e_1_2_9_4_1","unstructured":"N Rekhtman MB Beasley E Brambilla Large cell neuroendocrine carcinoma of the lung"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0096-5588(20)30545-6"},{"key":"e_1_2_9_6_1","first-page":"425","article-title":"Morphologic lesions in non\u2010neoplastic bronchial mucosa associated with bronchial carcinomas","volume":"137","author":"Kayser K","year":"1991","journal-title":"Zentralbl. 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