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

Hereditary diffuse gastric cancer (HDGC), caused by germline mutations in CDH1, is associated with a high risk of diffuse gastric cancer. In HDGC, gastric cancer lesions are often poorly visualized during endoscopy, increasing the likelihood of missed lesions. We aimed to investigate the clinicopathological characteristics of endoscopically detected and undetected lesions in patients with HDGC.

We conducted a retrospective review of patients diagnosed with HDGC between January 2017 and October 2024 at 4 institutions. Patients who underwent prophylactic or therapeutic total gastrectomy with detailed preoperative endoscopic evaluation were included.

Among 7 patients diagnosed during the study period, 5 underwent gastrectomy and were included in the analysis. Histopathological examination identified 146 lesions, of which 39 (27%) were detected endoscopically. No significant clinicopathological differences were observed between detected and undetected lesions, except for tumor size and anatomical location. Detection rates were 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 in a subgroup analysis of lesions measuring ≥4 mm, the detection rate was lower in the U region than in the M/L regions (17% vs. 95%, p < 0.01), although lesion size still differed between regions.

Endoscopic detection of HDGC-associated gastric cancer lesions remains challenging, particularly for small lesions and those located in the U gastric region. These findings should be interpreted in light of lesion size and may help refine surveillance strategies by clarifying the characteristics of lesions that may be overlooked during HDGC surveillance.