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This narrative review integrates evidence on epidemiology, pathogenesis, diagnosis, and management, highlighting well- and poorly differentiated forms and common primary sites including gingiva and buccal mucosa. Definitive diagnosis relies on morphologic and immunohistochemical correlation (synaptophysin, chromogranin A, CD56). In the absence of oral-cavity-specific guidelines, treatment aligns with head and neck NEN management: surgical excision, often with adjuvant chemoradiotherapy for localized disease. For advanced or metastatic stages, platinum-based chemotherapy may yield transient control with limited survival benefit. Emerging options such as immune checkpoint inhibitors and peptide receptor radionuclide therapy show preliminary promise but need stronger validation. The rarity and heterogeneity support multidisciplinary care and multicenter registries to improve accuracy and standardize care.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/neuroendocrine-neoplasms-of-the-oral-cavity-a-narrative-review-of-clinicopathological-features-and-management/356070/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/neuroendocrine-neoplasms-of-the-oral-cavity-a-narrative-review-of-clinicopathological-features-and-management/356070.png","ImageObject",300,407,{"name":42,"@type":43},"PakDamar76","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why are oral cavity neuroendocrine neoplasms difficult to diagnose?","Question",{"text":63,"@type":64},"They are rare and show nonspecific clinical features, while histopathology overlaps with other intraoral tumors. Accurate diagnosis requires integrating morphology with immunohistochemical markers.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which immunohistochemical markers support definitive diagnosis?",{"text":68,"@type":64},"Definitive diagnosis typically demonstrates positivity for synaptophysin, chromogranin A, and CD56, combined with morphologic assessment.",{"name":70,"@type":61,"acceptedAnswer":71},"What is the recommended management for localized versus advanced disease?",{"text":72,"@type":64},"Localized disease is treated primarily with surgical excision, often followed by adjuvant chemoradiotherapy. In advanced or metastatic stages, platinum-based chemotherapy may provide transient disease control with limited survival benefit.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},356070,1790187313,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},962090893057,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Marino et al. Discover Oncology (2026) 17:1176 Discover Oncology  \n[https://doi.org/10.1007/s12672-026-05379-1](https://doi.org/10.1007/s12672-026-05379-1)  \nREVIEW Open Access  \nNeuroendocrine neoplasms of the oral cavity:  a narrative review of clinicopathological features and management  \nPaola Marino1, Desirèe Speranza2,3, Enrica Toscano1,4, Mariacarmela Santarpia5,6, Andrea Ballini7, Danila De Vito8, Nicola Fazio4, Massimiliano Berretta3,5 and Nicola Silvestris9*  \n*Correspondence:  \nNicola Silvestris [n.silvestris@oncologico.bari.it](n.silvestris@oncologico.bari.it)  \nFull list of author information is available at the end of the article  \nAbstract  \nNeuroendocrine neoplasms (NENs) of the oral cavity are extremely rare, accounting for less than 1% of all head and neck malignancies. Their diagnosis is challenging due to nonspecific clinical features and significant histopathologic overlap with other intraoral tumors. This narrative review summarizes current evidence on the epidemiology, pathogenesis, diagnosis, and management of head and neck NENsin general, with particular attention on the oral cavity side, encompassing bothwell-and poorly differentiated forms. Reported cases indicate the gingiva and buccal mucosa as the most frequent primary sites. Clinically, lesions usually present as painless nodules or ulcerated masses. Definitive diagnosis requires integration of morphologic and immunohistochemical findings, typically demonstrating positivity for synaptophysin, chromogranin A, and CD56 . In the absence of specific international guidelines for the oral cavity, given the limited availability of data in the literature, the most appropriate approach currently follows the guidelines for managing head and neck NENs, which consists of surgical excision, which remains the treatment of choice for localized disease and is often followed by adjuvant chemoradiotherapy. In advanced or metastatic stages, platinum-based chemotherapy may provide transient disease control but offers limited survival benefit. Novel therapeutic modalities, including immune checkpoint inhibitors and peptide receptor radionuclide therapy, show preliminary promise but lack robust clinical validation. Given the rarity and heterogeneity of these tumors, multidisciplinary management and the establishment of multicenter registries are crucial for improving diagnostic accuracy, standardizing treatment strategies, and enhancing clinical outcomes. Keywords Neuroendocrine neoplasm, Oral cavity, Target therapy, Immunotherapy  \n1 Introduction  \nNeuroendocrine neoplasms (NENs) of the oral cavity are sporadic tumors of the head and neck region, accounting for less than 1% of all malignancies [1].  \nAvailable reports suggest that oral cavity NENs predominantly affect middle-aged to older adults, with a mean age at diagnosis of approximately 56 years and a slight male  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by-nc-nd/4.0/.  \nMarino et al. Discover Oncology (2026) ","cbCaiudWSvV6zcHm","https://ap.wps.com/l/cbCaiudWSvV6zcHm","pdf",861256,15,"English","# Introduction\n# WHO classification and histological subtypes\n# Epidemiology and clinical presentation\n# Diagnostic approach (morphology and immunohistochemistry)\n# Treatment strategies (localized and advanced disease)\n# Emerging therapies and future directions","[{\"question\":\"Why are oral cavity neuroendocrine neoplasms difficult to diagnose?\",\"answer\":\"They are rare and show nonspecific clinical features, while histopathology overlaps with other intraoral tumors. Accurate diagnosis requires integrating morphology with immunohistochemical markers.\"},{\"question\":\"Which immunohistochemical markers support definitive diagnosis?\",\"answer\":\"Definitive diagnosis typically demonstrates positivity for synaptophysin, chromogranin A, and CD56, combined with morphologic assessment.\"},{\"question\":\"What is the recommended management for localized versus advanced disease?\",\"answer\":\"Localized disease is treated primarily with surgical excision, often followed by adjuvant chemoradiotherapy. In advanced or metastatic stages, platinum-based chemotherapy may provide transient disease control with limited survival benefit.\"}]","Neuroendocrine neoplasms of the oral cavity - a narrative review of clinicopathological features and management | PDF",1790123253,38]