Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management

Hereditary diffuse gastric cancer ( HDGC ) is an autosomal dominant syndrome characterised by multigenerational diffuse gastric cancer, and is mainly caused by germline alterations in the CDH 1 gene. Currently, endoscopy has limited diagnostic accuracy, and total gastrectomy ( TG ) is the treatment of choice for asymptomatic CDH 1 carriers. In this study, we aimed to obtain a better understanding of HDGC syndrome by exploring the histopathological findings of TG specimens from asymptomatic HDGC patients. A comprehensive literature review was carried out, searching for TG s performed in asymptomatic HDGC patients. Fourteen unpublished cases, analysed in our institution, were also included. The series encompassed 174 CDH 1 carriers. Preoperative endoscopic biopsies were positive in 28.3%. A macroscopic lesion was apparent in 11.7% of TG s. Histopathological analysis revealed intraepithelial lesions and/or intramucosal signet ring cell carcinoma in 87.9% of TG s. When we explored the type of protocol used for handling the specimens, we found that microscopic cancer foci were detected in 95.3% of TG s when a total‐embedding protocol (assessment of the totality of gastric mucosa) was applied, and only in 62.5% when no specific protocol was used ( P  < 0.001). Helicobacter pylori infection was found in 23.4% cases. In conclusion, a thorough histopathological examination of gastric mucosa remains the gold standard for detection of cancer foci in HDGC gastrectomy specimens, requiring experienced pathologists for an accurate diagnosis. A better understanding of the natural history of HDGC will enable better clinical management of HDGC patients, particularly regarding the optimal timing for the performance of TG .