{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T04:59:00Z","timestamp":1780894740070,"version":"3.54.1"},"reference-count":6,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010883","name":"Traditional Chinese Medicine Bureau of Guangdong Province","doi-asserted-by":"publisher","award":["20251430"],"award-info":[{"award-number":["20251430"]}],"id":[{"id":"10.13039\/501100010883","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gallbladder cancer is a highly lethal biliary tract malignancy. Among them, mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN), particularly those containing large cell neuroendocrine carcinoma (LCNEC) components, are extremely rare and highly aggressive. Due to its low incidence and insidious symptoms, reports on the clinicopathological characteristics and optimal treatment strategies for such tumors are very limited, with diagnosis primarily relying on pathology and immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 78-year-old female was incidentally found to have a gallbladder mass during a routine physical examination, accompanied by a significantly elevated carcinoembryonic antigen (CEA) level (84.09 ng\/ml). MRI imaging indicated gallbladder malignancy with multiple liver and hilar lymph node metastases. The patient underwent extended radical surgery, including partial hepatectomy, pancreaticoduodenectomy, and partial portal vein resection with anastomosis. Postoperative pathology and immunohistochemistry confirmed a mixed adenoma-large cell neuroendocrine carcinoma of the gallbladder with multiple metastases. Immunohistochemistry showed Syn (+), CK19 (+), Ki-67 (+) approximately 80%, INSM1 (+), and CgA (+) approximately 10%. All surgical margins were negative. The patient recovered well postoperatively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case report describes a rare case of locally advanced mixed adenoma-large cell neuroendocrine carcinoma of the gallbladder in primary hospital. Achieving negative margins through aggressive extended radical surgery may be a feasible treatment option in carefully selected patients; however, the oncological benefit remains to be validated. It emphasizes the critical role of multidisciplinary collaboration in diagnosis and treatment and adds new data to the limited literature on this rare disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1834076","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T04:23:40Z","timestamp":1780892620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case report: A challenging case of stage IVB mixed neuroendocrine-non-neuroendocrine neoplasm of the gallbladder treated with extended radical resection including portal vein reconstruction"],"prefix":"10.3389","volume":"16","author":[{"given":"Quanlei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Surgery, Dongguan Nancheng Hospital","place":["Dongguan, China"]},{"name":"Dongguan Institute of Gallbladder Disease Research, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Dongguan Nancheng Hospital","place":["Dongguan, China"]},{"name":"Dongguan Institute of Gallbladder Disease Research, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Surgery, Dongguan Nancheng Hospital","place":["Dongguan, China"]},{"name":"Dongguan Institute of Gallbladder Disease Research, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quli","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Surgery, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Administration, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhui","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Laboratory, Dongguan Nancheng Hospital","place":["Dongguan, 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Surgery, Dongguan Nancheng Hospital","place":["Dongguan, China"]},{"name":"Dongguan Institute of Gallbladder Disease Research, Dongguan Nancheng Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00261-025-05204-3","article-title":"Gallbladder neuroendocrine neoplasms: a review","author":"Bhosale","year":"2025","journal-title":"Abdom Radiol (NY)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.37398","article-title":"An unusual case of large cell neuroendocrine cancer of the gallbladder with mixed adenocarcinoma component in a patient with pancreatobiliary maljunction","volume":"15","author":"Fick","year":"2023","journal-title":"Cureus"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1664914","article-title":"Gallbladder large cell neuroendocrine carcinoma in a patient with 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