Hereditary diffuse gastric cancer is a rare disorder and guidelines are based on expert opinion of the International Gastric Cancer Linkage Consortium. Updated clinical guidelines were published in 2015r based on information gathered since the original recommendations were published in 1999. The guidelines are based on observation, and the outcome of research protocols.
The published diffuse gastric and lobular breast cancer risks are derived from CDH1-families ascertained because of a history of diffuse gastric cancer. In the absence of a family history of diffuse gastric cancer, the risk of diffuse gastric or lobular breast cancer is unknown.
Gastrectomy in asymptomatic individuals is recommended in those with a germline CDH1 mutation. This is because of the high risk of death from gastric cancer, and elimination of risk of gastric cancer after gastrectomy.
In CDH1 mutation carriers, the foci of early diffuse gastric cancer are small, and cannot be reliably identified at endoscopy. Endoscopic surveillance, including multiple random biopsies in CDH1 mutation carriers, in most cases has a low sensitivity and is unable to detect the multiple foci of early diffuse gastric cancer present in the subsequent gastrectomy.
Endoscopy is recommended in CDH1 patients prior to total gastrectomy for staging.
For those declining gastrectomy, annual endoscopic surveillance should be offered and if undertaken, should be performed in centres with an experienced multi-disciplinary upper GI team. Where this is not practical, a local endoscopist in consultation with an expert centre on the endoscopy protocol and review of histology is recommended.
There is currently insufficient data on the role and outcome of breast cancer screening in carriers of a CDH1 mutation, so recommendations are based on the high lifetime risk of breast cancer, particularly the lobular subtype, and the precedents established in other hereditary breast cancer syndromes. MRI may be superior for detection of lobular cancer.