Endoscopic Surveillance and Pathology of Biopsies in CDH1, CTNNA1, and HDGC-Like Families

Abstract

In this chapter, the endoscopic surveillance indications, limitations, and histological findings in CDH1, CTNNA1, and HDGC-like families are discussed. Annual endoscopic surveillance following an extensive protocol in an expert center is accepted as an alternative for individuals with a pathogenic CDH1 variant who wish to postpone surgery. Since there are a limited number of CTNNA1 families described, the penetrance data is limited, and the indication for a prophylactic gastrectomy is unclear. Prophylactic gastrectomy can be discussed depending on the personal and family history, but annual endoscopic surveillance in an expert center is mostly preferred in carriers of a pathogenic CTNNA1 variant. Surveillance instead of prophylactic total gastrectomy is also advised in pathogenic CDH1 variant carriers with an unclear risk of diffuse gastric cancer, such as those families who present exclusively with breast cancer, or who do not meet HDGC genetic testing criteria. First-degree relatives and affected individuals from families with a variant of unknown significance and HDGC-like families may be considered for annual endoscopic surveillance for at least 2 years. Endoscopically, early signet ring cell lesions are subtle alterations such as pale areas and sessile lesions, and this may change regarding form, erosion, and vascular pattern, when lesions invade more deeply. Corresponding histological findings in biopsies from HDGC(-like) individuals can be subdivided into three categories: (1) small intramucosal signet-ring cell carcinoma, which can be considered as indolent, very early DGC lesions—T1a; (2) small to intermediate lesions with increased atypical cells, still restricted to the mucosa of the stomach—T1+ and; (3) advanced diffuse-type gastric cancer in which tumor cells are diffusely infiltrative—DGC ≥ T2.