{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:54:48Z","timestamp":1790747688733,"version":"4.1.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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, malignant, extrahepatic tumor with hepatocellular differentiation. HAC is often associated with elevated serum alpha-fetoprotein (AFP) concentrations, which makes it difficult to distinguish from primary hepatocellular carcinoma (HCC). It is a difficult diagnosis based on histopathology, as the immunohistochemistry (IHC) profile often overlaps with hepatocellular carcinoma. HAC can arise from multiple organs, including the stomach, esophagus, colon, pancreas, duodenum, and peritoneum, with the stomach being the most common site. The treatment of HAC is not well defined, as randomized trial data is not available. The overall prognosis of metastatic HAC with standard combination chemotherapy is extremely poor. Here, we present a case of metastatic duodenal HAC that achieved a sustained complete response to chemotherapy-free dual immune checkpoint blockade, which, to our knowledge, represents the first published report of a sustained complete response to chemotherapy-free dual immune checkpoint blockade in metastatic duodenal HAC and suggests a potential approach that warrants further clinical investigation. We acknowledge that a degree of diagnostic uncertainty remains, as HAC and HCC can exhibit essentially identical morphologic and immunophenotypic features, making the distinction largely clinical.<\/jats:p>","DOI":"10.3389\/fonc.2026.1896620","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:56:15Z","timestamp":1790744175000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Metastatic duodenal hepatoid adenocarcinoma: a rare pathology with exceptional response to dual immune checkpoint blockade"],"prefix":"10.3389","volume":"16","author":[{"given":"Ranju","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Hematology Oncology, Lehigh Valley Health Network","place":["Allentown, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darshan","family":"Lal","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, WellSpan Health","place":["Reading, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Walia","sequence":"additional","affiliation":[{"name":"Department of Radiology, Lehigh Valley Health Network","place":["Allentown, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanth","family":"Goonewardene","sequence":"additional","affiliation":[{"name":"Department of Pathology, Lehigh Valley Health Network","place":["Allentown, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Dellers","sequence":"additional","affiliation":[{"name":"Department of Pathology, Lehigh Valley Health Network","place":["Allentown, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanchan","family":"Gupta","sequence":"additional","affiliation":[{"name":"Tufts University","place":["Medford, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216104","article-title":"Hepatoid adenocarcinoma\u2014clinicopathological features and molecular characteristics","volume":"559","author":"Li","year":"2023","journal-title":"Cancer Lett"},{"key":"B2","article-title":"Existence of alpha-fetoprotein during gastric-origin secondary cancer of the liver","volume":"78","author":"Bourreille","year":"1970","journal-title":"Presse M\u00e9d"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19850815)56:4<840::aid-cncr2820560423>3.0.co;2-e","article-title":"An AFP-producing gastric carcinoma with features of hepatic differentiation. 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