{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T04:44:55Z","timestamp":1776660295014,"version":"3.51.2"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"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. Oncol."],"abstract":"<jats:p>Hepatoid adenocarcinoma (HAC) is a rare extrahepatic malignant tumor that exhibits histological features resembling those of hepatocellular carcinoma. It is typically accompanied by an abnormal elevation in serum alpha - fetoprotein (AFP) levels. HAC can occur in multiple organs, with the stomach being the most common site. It has also been reported in organs such as the esophagus, colon, pancreas, lung, ovary, and uterus. After reviewing the relevant literature, to date, there have been no reports of primary HAC in the vagina. This article presents the first case of primary vaginal hepatoid adenocarcinoma. The patient was a post - menopausal elderly woman. By presenting the characteristics of the disease onset, clinical manifestations, clinicopathological features, molecular characteristics, and the treatment process, and through a literature review, the objective is to improve the understanding of this rare disease and offer a reference for clinical diagnosis and treatment.<\/jats:p>","DOI":"10.3389\/fonc.2026.1799019","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T04:13:50Z","timestamp":1776658430000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A case report of primary hepatoid adenocarcinoma of the vagina and literature review"],"prefix":"10.3389","volume":"16","author":[{"given":"Mingyuan","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Gynecology, Jiaozhou Central Hospital of Qingdao","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qige","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Jiaozhou Central Hospital of Qingdao","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyuan","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Gynecology, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengxiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Jiaozhou Central Hospital of Qingdao","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.21037\/tcr-20-1126","article-title":"Incidence and prognostic factors of hepatoid adenocarcinoma:a population-based analysis","volume":"9","author":"Wang","year":"2020","journal-title":"Transl Cancer Res"},{"key":"B2","volume-title":"Existenceofalphafetoproteinduringgastric-originsecondarycanceroftheliver","author":"Bourreille","year":"1970"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142","article-title":"An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report","volume":"56","author":"Ishikura","year":"1985","journal-title":"Cancer"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e7706","DOI":"10.1002\/ccr3.7706","article-title":"SALL4 as an indicator for the diagnosis of hepatoid carcinoma of the ovary: A case report and literature review","volume":"11","author":"Li","year":"2023","journal-title":"Clin Case Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.19723\/j.issn.1671-167X.2024.06.030","article-title":"Beijing da xue xue bao yi xue ban","volume":"56","author":"Luo","year":"2024"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e14534","DOI":"10.1097\/MD.0000000000014534","article-title":"Hepatoid adenocarcinoma of fallopian tube: A case report and review of the literature","volume":"98","author":"Li","year":"2019","journal-title":"Med (Balt)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.asjsur.2023.05.162","article-title":"Hepatoid adenocarcinoma in the urethrovaginal septum","volume":"46","author":"Fan","year":"2023","journal-title":"Asian J Surg"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2023-004695","article-title":"ESTRO\/ESGO\/SIOPe Guidelines for the management of patients with vaginal cancer","volume":"33","author":"Nout","year":"2023","journal-title":"Int J Gynecol Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142","article-title":"Hepatoid adenocarcinoma in the urinary bladder.Unusual localization of a newly recognized tumor type","volume":"73","author":"Sinard","year":"1994","journal-title":"Cancer"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.012","article-title":"Wnt\/\u03b2-catenin signaling and disease","volume":"149","author":"Clevers","year":"2012","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11246","article-title":"Histogenesis of hepatoid adenocarcinoma of the stomach: molecular evidence of identical origin with coexistent tubular adenocarcinoma","volume":"106","author":"Akiyama","year":"2003","journal-title":"Int J Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/0031302021000062389","article-title":"Further evidence of hepatic transdifferentiation in hepatoid adenocarcinomas of the stomach: quantitative analysis of mRNA for albumin and hepatocyte nuclear factor-4alpha","volume":"35","author":"Yano","year":"2003","journal-title":"Pathology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.56.12.942","article-title":"Genetic evolution of alpha fetoprotein producing gastric cancer","volume":"56","author":"Fujii","year":"2003","journal-title":"J Clin Pathol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-019-00965-5","article-title":"Hepatoid adenocarcinoma of the stomach:a unique subgroup with distinct clinicopathological and molecular features","volume":"22","author":"Wang","year":"2019","journal-title":"Gastric Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.7081","article-title":"Long-term results of gastrectomy for alpha-fetoprotein-producing gastric cancer","volume":"97","author":"Inoue","year":"2010","journal-title":"Br J Surg"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.02.002","article-title":"Overcoming immunotherapy resistance in hepatocellular carcinoma by targeting myeloid IL-8\/CXCR2 signaling","volume":"33","author":"Kwong","year":"2025","journal-title":"Mol Ther"},{"key":"B17","doi-asserted-by":"publisher","first-page":"108339","DOI":"10.1016\/j.jbc.2025.108339","article-title":"Immune checkpoint protein PD-L1 promotes transcription of angiogenic and oncogenic proteins IL-8, Bcl3, and STAT1 in ovarian cancer cells","volume":"301","author":"Reddy","year":"2025","journal-title":"J Biol Chem"},{"key":"B18","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12964-023-01068-6","article-title":"Paracrine secretion of IL8 by breast cancer stem cells promotes therapeutic resistance and metastasis of the bulk tumor cells","volume":"21","author":"Wu","year":"2023","journal-title":"Cell Commun Signal"},{"key":"B19","doi-asserted-by":"publisher","first-page":"294","DOI":"10.2174\/0115680096337237240909101904","article-title":"Tumor-activated neutrophils promote lung cancer progression through the IL-8\/PD-L1 pathway","volume":"25","author":"Zheng","year":"2025","journal-title":"Curr Cancer Drug Targets"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2012.677440","article-title":"Targeting IL-8 in colorectal cancer","volume":"16","author":"Ning","year":"2012","journal-title":"Expert Opin Ther Targ"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/life15020135","article-title":"Genetic variants of interleukin-8 and interleukin-16 and their association with cervical cancer risk","volume":"15","author":"Watrowski","year":"2025","journal-title":"Life (Basel)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e2101","DOI":"10.1002\/cnr2.2101","article-title":"Clinicopathological features of hepatoid adenocarcinoma of the stomach: A multicenter retrospective study","volume":"7","author":"Yanagawa","year":"2024","journal-title":"Cancer Rep (Hoboken)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i3.321","article-title":"Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma: a literature review","volume":"19","author":"Su","year":"2013","journal-title":"World J Gastroenterol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-012-1353-5","article-title":"SALL4 is a useful marker in the diagnostic work-up of germ cell tumors in extra-testicular locations","volume":"462","author":"Camparo","year":"2013","journal-title":"Virchows Arch"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.92","article-title":"Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area","volume":"112","author":"Sideras","year":"2015","journal-title":"Br J Cancer"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2017-0485-RS","article-title":"Hepatoid carcinoma of the ovary: clinical,Histopathologic,and immunophenotypic features","volume":"143","author":"Acosta","year":"2019","journal-title":"Arch Pathol Lab Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/01.PGP.0000055173.04957.66","article-title":"Hepatoid carcinoma of the ovary: a report of three cases admixed with a common surface epithelial carcinoma","volume":"22","author":"Tochigi","year":"2003","journal-title":"Int J Gynecol Pathol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01976-2","article-title":"Genomic and transcriptomic profiling of hepatoid adenocarcinoma of the stomach","volume":"40","author":"Liu","year":"2021","journal-title":"Oncogene"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14163849","article-title":"Comprehensive analysis of genomic alterations in hepatoid adenocarcinoma of the stomach and identification of clinically actionable alterations","volume":"14","author":"Zhao","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12336","article-title":"Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach","volume":"42","author":"Zhu","year":"2022","journal-title":"Cancer Commun(Lond)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.633916","article-title":"Hepatoid adenocarcinoma of the stomach: current perspectives and new developments","volume":"11","author":"Xia","year":"2021","journal-title":"Front Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1392430","article-title":"Endoscopic ultrasound diagnosis of a primary hepatoid carcinoma of the pancreas","volume":"47","author":"Antonini","year":"2015","journal-title":"Endoscopy"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1177\/15330338211057983","article-title":"Hepatoid adenocarcinoma of the lung","volume":"20","author":"Li","year":"2021","journal-title":"Technol Cancer Res Treat"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1799019\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T04:13:52Z","timestamp":1776658432000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1799019\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":33,"alternative-id":["10.3389\/fonc.2026.1799019"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1799019","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]},"article-number":"1799019"}}