Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract

Lodewijk A. A. Brosens, Francis M. Giardiello, G. Johan Offerhaus, Elizabeth A. Montgomery

Marnix Jansen, Nicholas A. Wright

Gastric polyps occur in 1-4 % of patients undergoing gastroscopy. Although most are sporadic, some gastric polyps are part of an underlying hereditary syndrome. Gastric polyps can be seen in each of the well-known gastrointestinal polyposis syndromes, but also in Lynch syndrome and in several rare not primarily gastrointestinal syndromes. In addition, Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a recently described heritable syndrome characterized by isolated gastric polyposis and risk of gastric cancer.Some of these syndromes are associated with an increased risk of gastric cancer, whereas others are not. However, the neoplastic potential and the precursor status of these gastric polyps are not always clear, even in syndromes with a well-established risk of gastric cancer. For instance, the neoplastic potential of Peutz-Jeghers polyps is debatable, despite the well-established risk of gastric cancer in this syndrome. Also fundic gland polyps and gastric foveolar-type adenomas in FAP carry a low risk of malignant transformation. In contrast, gastric juvenile polyps are precursor lesions of gastric cancer in juvenile polyposis syndrome through neoplastic progression of juvenile polyps in these patients.Although these hereditary syndromes with gastric polyps are rare, recognition is important for individual patient management. Furthermore, the initiation and progression of these lesions can be influenced by environmental factors such as Helicobacter Pylori infection. This makes these rare lesions an appropriate model for understanding the clonal evolution of early gastric cancer in the wider population.