Gastric adenocarcinoma with intestinal progenitor cell differentiation: a morphologically underdiagnosed and more invasive distinctive type of gastric adenocarcinoma

This study aims to explore the clinical and pathological characteristics, prognosis, diagnosis, and differential diagnosis of gastric adenocarcinoma with enteroblastic differentiation (GAED) in elderly patients. A total of 16 cases of GAED diagnosed from August 2019 to August 2022 at the First Affiliated Hospital of Nanchang University were retrospectively collected to analyze their clinical and pathological features. A control group of 360 cases of conventional gastric adenocarcinoma diagnosed during the same period was used for comparison. Among the 16 GAED patients, 11 were male and 5 were female, with ages ranging from 64 to 89 years (median age 75.5 years). Clinical manifestations of these patients included symptoms such as abdominal pain, bloating, hematemesis, and melena. The macroscopic classification revealed 11 cases of ulcerative lesions, 4 protruded lesions, and 1 diffusely infiltrative lesion. Tumor sizes varied from 3 to 9.5 cm in diameter, with a median diameter of 4.75 cm. Microscopically, the tumor cells exhibited tubular, papillary, and cribriform arrangements, with cuboidal or columnar morphology, relatively distinct cell boundaries, and cytoplasm that appeared clear or weakly acidophilic. Immunophenotyping analysis revealed the expression of SALL4 (15/16), Glypican-3 (12/16), CDX2 (12/16), CD10 (10/16), and p53 (12 cases exhibiting mutant expression, 4 cases exhibiting wild-type expression) within the tumor cells. There was no loss of mismatch repair proteins (MLH1, PMS2, MSH2, MSH6). The Ki-67 proliferation index ranged from 50% to 95%. In comparison to conventional gastric adenocarcinoma, GAED was frequently found in the gastric antrum (P<0.001) and exhibited a higher incidence of intravascular cancer emboli (P<0.001). Significant differences were noted in the Lauren classification, invasion depth, differentiation degree (P<0.01), and macroscopic type (P<0.05). However, no significant differences were found regarding age, gender, tumor diameter, neural invasion, or lymph node metastasis (P>0.05). The postoperative follow-up ranging from 5 to 29 months revealed one death and 15 cases of disease-free survival. GAED is a special subtype of gastric adenocarcinoma characterized by a combination of embryonal and intestinal differentiation immunophenotypes, as well as its increased propensity for biological invasion. Accurate identification of GAED is crucial in pathological practice, as it helps differentiate between GAED and conventional adenocarcinoma and aids in the evaluation of tumor malignancy. Furthermore, it is imperative to conduct a differential diagnosis that involves hepatoid adenocarcinoma, yolk sac tumor-like adenocarcinoma, and metastatic hepatocellular carcinoma.