Performance of upper gastrointestinal endoscopy in CDH1 germline pathogenic variant carriers: A multicenter study

Hereditary diffuse gastric cancer (HDGC) is a syndrome primarily caused by pathogenic variants in the CDH1 gene, characterized histologically by the presence of signet ring cell carcinoma (SRCC). This observational multicenter study aimed to characterize CDH1 carriers undergoing endoscopic surveillance at 12 Spanish centers, evaluate the performance of upper gastrointestinal endoscopy (UGE) in detecting SRCC, and identify factors associated with its diagnosis. Fifty-three CDH1 carriers who underwent at least one surveillance UGE were included. SRCC was detected in nine individuals (17%) through biopsies, including seven cases by random biopsies and two by targeted biopsies, all confirmed in subsequent gastrectomy specimens. Among 44 patients with negative endoscopic findings, 22 underwent risk-reducing gastrectomy, and SRCC was identified in 11 of these cases (50%) during pathological examination. Overall, SRCC was diagnosed in 20 individuals (37.7%), with UGE initially detecting 45% of cases. Only one case identified through targeted biopsies was found at an advanced stage (T4). Chromoendoscopy was associated with a higher detection rate of SRCC compared to conventional white light endoscopy (p = .017, odds ratio = 20 [95%CI, 1.68-238.63]). Despite current endoscopic practices, SRCC remained undetected in half of the patients undergoing risk-reducing gastrectomy. Future efforts should focus on enhancing endoscopic techniques and improving our understanding of the progression of these lesions.