Clinicopathological Characteristics of Endoscopically Detected and Undetected Lesions in Hereditary Diffuse Gastric Cancer.

INTRODUCTION: Hereditary diffuse gastric cancer (HDGC), caused by germline mutations in the CDH1 gene, carries a high risk of diffuse gastric cancer (DGC). In HDGC, gastric cancer lesions are often poorly visible during endoscopy, increasing the likelihood of being missed. We aimed to investigate the clinicopathological characteristics of lesions that were either detected or missed during endoscopic evaluation in patients with HDGC. METHODS: We conducted a retrospective review of patients diagnosed with HDGC between January 2017 and October 2024 at five institutions. Patients who underwent prophylactic or therapeutic total gastrectomy with detailed preoperative endoscopic evaluation were included. RESULTS: Among the seven patients diagnosed during the study period, five underwent gastrectomy and were analyzed. Histopathological examination identified 146 lesions, of which 39 (27%) were detected endoscopically. No clinicopathological differences were observed between detected and undetected lesions except for tumor size and anatomical location. Detection was significantly lower in the upper (U) region (1%) than in the middle (M) (81%) and lower (L) (68%) gastric regions (p <0.01). Lesions in the U region were significantly smaller, and even among those ≥4 mm, the detection rate remained substantially lower than that in the M/L regions (17% vs. 95%, p <0.01). CONCLUSION: Lesions in the U gastric region are particularly challenging to detect endoscopically, especially when they are small. Improved detection may require advancements in high-resolution and image-enhanced endoscopy, AI-assisted image analysis, and optimized observation techniques. These improvements may enable earlier diagnosis and intervention, ultimately leading to better outcomes for patients with HDGC.