Brosens, Lodewijk A.A.

Abstract Pancreatic neuroendocrine tumors (PanNETs) have an age-adjusted incidence of 1.5 per 100,000 people, with a notable rise in the incidence of small (≤2 cm) non-functional PanNETs (NF-PanNETs) in recent decades. While surgery is traditionally the preferred treatment for localized NF-PanNETs, active surveillance is now an accepted management strategy for tumors smaller than 2 cm due to their relatively benign behavior. However, this approach has not yet been fully integrated into routine clinical practice. There is considerable histopathological heterogeneity observed in NF-PanNETs, which results in significant variability in clinical presentation, behavior and treatment outcomes. Hence, tumor size alone does not provide sufficient certainty regarding a benign clinical course for decision-making. Although studies advocate for incorporating WHO grade into clinical prognostic assessments, this marker also has limitations. Several established tissue-based markers, such as ATRX and DAXX alterations, alternative lengthening of telomeres, and copy number variations, can be used for PanNET subtyping and correlate with metastatic risk. Combining these markers with traditional histopathological parameters may yield a more comprehensive and accurate prognostic assessment. This review discusses the advantages and limitations of current prognostication methods for small NF-PanNETs and highlights recently established prognostic markers, along with the requirements for their implementation into routine clinical practice. It also proposes practical solutions to address the challenges associated with the immediate integration of these biomarkers into routine care.

Gastric polyps are found in 1% to 4% of patients undergoing gastroscopy. The vast majority are sporadic, but some gastric polyps indicate an underlying syndrome. Gastric polyps can manifest in each of the gastrointestinal polyposis syndromes, including the recently described gastric adenocarcinoma and proximal polyposis of the stomach syndrome. In addition, gastric polyps occur in Lynch syndrome and in a few rare conditions that are not primarily gastrointestinal. While some of these syndromes are clearly associated with an increased risk of gastric cancer, others are not. Interestingly, even in disorders with a well-established risk of gastric cancer, the neoplastic potential and the precursor status of these gastric polyps are not always clear. Although rare, recognition of syndromic gastric polyps is important for individual patient management. These conditions also serve as important models to study gastric homeostasis and gastric tumorigenesis.