Case Report: Synchronous Esophageal Squamous Cell Carcinoma and Gastric Cardia Adenocarcinoma with Hepatoid Differentiation After Neoadjuvant Chemoimmunotherapy

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.