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The 2021 World Health Organization classification recognizes lung neuroendocrine neoplasms as an independent group, covering typical and atypical neuroendocrine tumors as well as small cell and large cell neuroendocrine carcinomas. Despite largely unchanged terminology, clinically relevant updates affect epidemiology, clinical behavior, diagnosis, therapy, and prognosis.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/neuroendocrine-neoplasms-of-the-lung-the-latest-updates-minireviews/371553/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/neuroendocrine-neoplasms-of-the-lung-the-latest-updates-minireviews/371553.png","ImageObject",300,407,{"name":92,"@type":93},"Quinn Holloway","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does the 2021 WHO classification define lung neuroendocrine neoplasms?","Question",{"text":113,"@type":114},"It classifies lung neuroendocrine neoplasms into typical and atypical neuroendocrine tumors, and into high-grade small cell and large cell neuroendocrine carcinomas as an independent tumor group.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What criteria distinguish typical carcinoid from atypical carcinoid and high-grade tumors?",{"text":118,"@type":114},"The distinction relies on histopathological features, Ki-67 index, mitotic rate, and necrosis. Typical carcinoid shows \u003C2 mitoses/2 mm² without necrosis, atypical carcinoid shows 2–10 mitoses/2 mm² or focal necrosis, while small cell and large cell neuroendocrine carcinomas have high mitotic rates with extended/diffuse necrosis.",{"name":120,"@type":111,"acceptedAnswer":121},"Which immunohistochemical markers are commonly used in lung neuroendocrine neoplasms?",{"text":122,"@type":114},"Lung neuroendocrine neoplasms are typically positive for chromogranin A, synaptophysin, and CD56 (NCAM1). INSM1 has been proposed as a useful neuroendocrine marker, and ASCL1 is another transcription factor expressed only in a subgroup.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},371553,1790217561,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":105,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},2336474466712,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","| W | J | C | O | World Journal of\u003Cbr>Clinical Oncology |\n| --- | --- | --- | --- | --- |\n\nSubmit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Clin Oncol 2025 May 24; 16(5): 106630  \nDOI: 10.5306/wjco.v16.i5.106630 ISSN 2218-4333 (online)  \nMINIREVIEWS  \nNeuroendocrine neoplasms of the lung: The latest updates  \nRiccardo Orlandi  \nSpecialty type: Oncology  \nProvenance and peer review:  \nInvited article; Externally peer reviewed.  \nPeer-review model: Single blind  \nPeer-review report’s classification Scientific Quality: Grade B  \nNovelty: Grade C  \nCreativity or Innovation: Grade C  \nScientific Significance: Grade B  \nP-Reviewer: Ren SQ  \nReceived: March 4, 2025  \nRevised: March 21, 2025  \nAccepted: April 1, 2025  \nPublished online: May 24, 2025  \nProcessing time: 77 Days and 8.4 Hours  \nRiccardo Orlandi, Department of Thoracic Surgery, University of Milan, Milan 20122, Italy  \nCorresponding author: Riccardo Orlandi, MD, Doctor, Department of Thoracic Surgery, University of Milan, Via Festa del Perdono, 7, Milan 20122, Italy. [riccardo.orlandi@unimi.it](riccardo.orlandi@unimi.it)  \nAbstract  \nNeuroendocrine neoplasms are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells, most frequently in the gastrointestinal tract and in the lung. The latest 2021 World Health Organization (WHO) classification of lung tumors defines neuroendocrine neoplasms of the lung as an independent group of tumors, including typical and atypical neuroendocrine tumors and small cell and large cell neuroendocrine carcinomas. Although the overall nomenclature is essentially unchanged from the fourth WHO classification, there are several clinically relevant updates. In this review article, we discuss the epidemiological, clinical, diagnostic, therapeutic and prognostic features of these fascinating neoplasms, including the latest insights, current challenges and future perspectives.  \nKey Words: Neuroendocrine lung cancer; Carcinoid; Small cell lung cancer; Large cell neuroendocrine lung cancer; Diagnosis; Management  \n©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.  \nCore Tip: Neuroendocrine neoplasms (NENs) arise from neuroendocrine cells and vary in malignancy, commonly affecting the gastrointestinal tract and lungs. The 2021 World Health Organization classification of lung tumors categorizes lung NENs into typical and atypical neuroendocrine tumors and high-grade small cell and large cell neuroendocrine carcinomas. While the classification remains largely unchanged, key clinical updates have been introduced. This review explores the epidemiology, diagnosis, treatment, and prognosis of lung NENs, highlighting emerging insights, and future directions.  \nCitation: Orlandi R. Neuroendocrine neoplasms of the lung: The latest updates. World J Clin Oncol 2025; 16(5): 106630  \nURL: [https://www.wjgnet.com/2218-4333/full/v16/i5/106630.htm](https://www.wjgnet.com/2218-4333/full/v16/i5/106630.htm)  \nDOI: [https://dx.doi.org/10.5306/wjco.v16.i5.106630](https://dx.doi.org/10.5306/wjco.v16.i5.106630)  \n WJCO  [https://www.wjgnet.com](https://www.wjgnet.com) 1 May 24, 2025  Volume 16  Issue 5   \nOrlandi R. Challenges and perspectives of neuroendocrine neoplasms  \nINTRODUCTION  \nLung neuroendocrine neoplasms (LNNs) represent a group of uncommon tumors with multiple grades of malignancy apparently deriving from Kulchitsky cells, which are argentaffin amine precursor uptake and decarboxylation cells of the bronchial epithelium [1] . In 2021, the latest World Health Organization (WHO) classification of lung tumors affirmed LNNs as an independent group of tumors with heterogeneous malignancy [2], as previously established in 2015 [3], including low-graded typical carcinoid (TC), intermediate-graded atypical carcinoids (AC), high-graded small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), as presented in Table 1. The distinction is based o","cbCainTphWuxUY3B","https://ap.wps.com/l/cbCainTphWuxUY3B","pdf",521054,"English","# Introduction\n## Classification of lung neuroendocrine neoplasms\n## Histopathological criteria and grading\n## Diagnostic biomarkers and evaluation","[{\"question\":\"How does the 2021 WHO classification define lung neuroendocrine neoplasms?\",\"answer\":\"It classifies lung neuroendocrine neoplasms into typical and atypical neuroendocrine tumors, and into high-grade small cell and large cell neuroendocrine carcinomas as an independent tumor group.\"},{\"question\":\"What criteria distinguish typical carcinoid from atypical carcinoid and high-grade tumors?\",\"answer\":\"The distinction relies on histopathological features, Ki-67 index, mitotic rate, and necrosis. Typical carcinoid shows \\u003c2 mitoses/2 mm² without necrosis, atypical carcinoid shows 2–10 mitoses/2 mm² or focal necrosis, while small cell and large cell neuroendocrine carcinomas have high mitotic rates with extended/diffuse necrosis.\"},{\"question\":\"Which immunohistochemical markers are commonly used in lung neuroendocrine neoplasms?\",\"answer\":\"Lung neuroendocrine neoplasms are typically positive for chromogranin A, synaptophysin, and CD56 (NCAM1). INSM1 has been proposed as a useful neuroendocrine marker, and ASCL1 is another transcription factor expressed only in a subgroup.\"}]","Neuroendocrine neoplasms of the lung - The latest updates - Minireviews | PDF",1790192317]