{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:56:32Z","timestamp":1790571392322,"version":"4.1.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    As gallbladder large cell neuroendocrine carcinoma (GB-LCNEC) is extremely rare and highly aggressive, with limited reports in both domestic and international literature, we herein report two cases of GB-LCNEC accompanied by contiguous high-grade intraepithelial neoplasia of the overlying mucosa. One of the patients had pancreaticobiliary maljunction. Microscopically, the tumor cells were large and arranged in organoid, nested, palisading or trabecular patterns. They exhibited abundant cytoplasm, vesicular nuclei with coarse granular chromatin, prominent nucleoli, and mitotic figures exceeding 20 per 2\u2005mm\n                    <jats:sup>2<\/jats:sup>\n                    . Immunohistochemically, both tumors showed diffuse positivity for the neuroendocrine markers chromogranin A (CgA) and synaptophysin (Syn), and both exhibited a Ki-67 proliferative index exceeding 20%. They demonstrated wild-type and aberrant (mutant) p53 expression patterns, respectively. Although the 2 cases reported in this study were confirmed to have space-occupying lesions in the gallbladder via CT\/MRI, preoperative diagnosis was not achieved due to insufficient understanding of the disease. Through a systematic literature review, this study delineates the clinicopathologic and molecular features, diagnostic criteria, differential diagnoses, treatment, and prognosis of GB-LCNEC, as well as its potential pathogenesis\/origin that may involve a multistep carcinogenic process of chronic inflammation\u2013metaplasia\u2013dysplasia\u2013carcinogenesis. It aims to enhance clinical understanding of this rare disease and lay the foundation for future related research.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1885339","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:29:39Z","timestamp":1790569779000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Two cases of large cell neuroendocrine carcinoma of the gallbladder: case reports and systemic literature review"],"prefix":"10.3389","volume":"13","author":[{"given":"Yan","family":"Yang","sequence":"first","affiliation":[{"name":"Clinical Medical College, Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Medical College, Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Lin","sequence":"additional","affiliation":[{"name":"Clinical Medical College, Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1111\/his.13975","article-title":"The 2019 WHO classification of tumours of the digestive system","volume":"76","author":"Nagtegaal","year":"2020","journal-title":"Histopathology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"664","DOI":"10.5858\/arpa.2019-0665-RA","article-title":"What is new in the 2019 World Health Organization (WHO) classification of tumors of the digestive system: review of selected updates on neuroendocrine neoplasms, appendiceal tumors, and molecular 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