{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:11:57Z","timestamp":1790683917275,"version":"4.1.0"},"reference-count":20,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Hepatoid adenocarcinoma is a rare adenocarcinoma subtype. Synchronous esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma with hepatoid differentiation is exceptionally uncommon. This report describes lesion-specific staging, pathological response assessment, and individualized management after neoadjuvant chemoimmunotherapy. Methods: De-identified clinical, imaging, laboratory, operative, and pathological data were retrospectively reviewed. Both lesions were staged according to the AJCC 8th edition and reassessed using the CAP modified Ryan four-tier tumor regression grading system. Results: A 61-year-old man presenting with dysphagia had separate ESCC and gastric cardia adenocarcinoma, both staged cT2N0M0. One cycle of pembrolizumab 200 mg, nab-paclitaxel 300 mg, and cisplatin 100 mg was administered. Agranulocytosis precluded further neoadjuvant therapy; after neutrophil recovery, R0 resection was performed. Pathological review showed ESCC ypT1aN0M0, score 1, and cardia adenocarcinoma ypT1aN0M0, score 3, with approximately 30% regional hepatoid differentiation. All 10 examined lymph nodes were negative. AFP was not measured before treatment; post-treatment\/preoperative values were 14.45 and 14.68 ng\/mL, and the postoperative value was 6.08 ng\/mL. Postoperative tislelizumab monotherapy was selected as an individualized, non-standard strategy, mainly because of affordability. At approximately 6 months after surgery, no recurrence, metastasis, or maintenance-related adverse event was identified. Conclusions: This case emphasizes biopsy under-sampling and lesion-specific staging and pathological assessment. The regression-score difference is descriptive and confounded by baseline burden, histology, and one-cycle exposure; the AFP findings do not validate a surveillance biomarker.<\/jats:p>","DOI":"10.3390\/jcm15155979","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:20:18Z","timestamp":1785486018000},"page":"5979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Synchronous Esophageal Squamous Cell Carcinoma and Gastric Cardia Adenocarcinoma with Hepatoid Differentiation After Neoadjuvant Chemoimmunotherapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8649-2527","authenticated-orcid":false,"given":"Chengang","family":"Weng","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Fourth Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"840","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: A case report","volume":"56","author":"Ishikura","year":"1985","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/1097-0142(19930915)72:6<1827::AID-CNCR2820720606>3.0.CO;2-8","article-title":"Hepatoid adenocarcinoma of the stomach: A clinicopathologic and immunohistochemical analysis","volume":"72","author":"Nagai","year":"1993","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"321","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. 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