BACKGROUND: Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare subtype of gastric cancer (GC), but its imaging features and diagnostic challenges remain underexplored. Currently, there is no unified approach for distinguishing between AFPGC and convectional gastric cancer (CGC). This study aimed to fill this gap by analyzing the unique imaging characteristics of AFPGC to improve its diagnostic accuracy and aid in its early detection. METHODS: This retrospective study included patients diagnosed with AFPGC who were treated at Lanzhou University Second Hospital between 2019 and 2021. The participants were selected using a consecutive sampling method to ensure that all eligible patients during the recruitment period were included in the study. The clinical, pathological, and imaging features of AFPGC were analyzed. The independent samples RESULTS: AFPGC differed significantly from CGC in terms of the clinical, pathological, and computed tomography (CT) features. Clinically, the age range of the patients was 45-70 years, and the male-to-female ratio was 2:1. The AFPGC patients had significantly higher serum carcinoembryonic antigen levels (P=0.047) and a higher rate of liver metastasis (P<
0.002). Pathologically, significant differences were observed in terms of tumor gross classification (P=0.002), vascular/lymphatic invasion (P=0.002), and N stage (P=0.002). On CT imaging, AFPGC differed significantly from CGC in terms of the liver metastasis rate (P<
0.002), tumor ulceration rate (P<
0.002), necrosis rate (P=0.004), enhancement patterns (P<
0.002), and arterial phase CT values (P<
0.002). There were significant differences between the high AFP group (≥100 ng/mL) and the low AFP group (<
100 ng/mL) in terms of the liver metastasis rate (P=0.006), tumor length (P=0.003), and lymph node diameter (P=0.010). No significant correlation was found between AFP staining and the CT parameters, but hepatocyte paraffin-1 (HepPar-1) staining was correlated with the tumor diameter (P=0.009), lymph node diameter (P=0.011), and necrosis rate (P=0.002). The amalgamated assessment of necrosis, ulceration, enhancement pattern, and arterial phase CT value showed superior diagnostic performance (area under the curve: 0.829
95% confidence interval: 0.760-0.885
sensitivity: 90.38%, and specificity: 65.00%). CONCLUSIONS: AFPGC is a clinical, radiological, and pathological enigma in the spectrum of GCs. The integration of morphological features observed on CT scans and CT values during the arterial phase could be used to predict AFPGC before surgery, and demonstrated commendable diagnostic efficiency. AFP levels and HepPar-1 expression may be associated with the aggressiveness of GC.