Morphologic and Immunophenotypic Spectrum of 11 Gastric Cancers with Elevated Serum Alpha-Fetoprotein: Emphasis on Hepatoid or Enteroblastic Differentiation.

AIM: A retrospective analysis of 11 gastric cancer patients with elevated serum alpha-fetoprotein levels was conducted to investigate the clinical-pathological characteristics, diagnostic approaches, and surgical experiences associated with this disease, thereby enhancing understanding of its biological behavior. METHODS: A retrospective analysis of clinical data from gastric cancer patients diagnosed at our hospital between 2020 and 2025 presented with elevated serum alpha-fetoprotein levels, combined with a discussion of disease classification based on relevant literature.The exclusion criteria were:such as hepatocellular carcinoma, cirrhosis/active liver disease, and germ cell tumors. RESULTS: Among the 11 patients, 9 were male, accounting for approximately 81.8%, and 2 were female, accounting for approximately 18.2%. The median age was 68 years.Clinical manifestations included upper abdominal pain, melena, and elevated serum alpha-fetoprotein levels. Eleven patients underwent radical gastrectomy for gastric cancer, including four cases of total gastrectomy. Tumors were located in the cardia in seven patients (63.6%), in the gastric body in three patients (27.3%), and in the gastric antrum in one patient (9.1%).Based on histological type, the cases can be classified as follows: 6 cases of hepatocellular adenocarcinoma and 5 cases of gastric adenocarcinoma with intestinal differentiation.Immunohistochemical staining revealed varying degrees of expression for alpha-fetoprotein, Glypican-3, and SALL-4. Five cases showed positivity for all three markers, eight cases showed positivity for two markers, and eleven cases showed positivity for only one marker. CONCLUSION: This type of gastric adenocarcinoma is rare, often detected at an advanced stage with a poor prognosis. In clinical diagnosis, it must be distinguished from conventional gastric adenocarcinoma.