Gastroenteropancreatic Neuroendocrine Neoplasms and Celiac Disease: Rare or Neglected Association?

Background: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors originating from neuroendocrine cells in the gastroenteropancreatic system. They are increasingly recognized as being potentially associated with chronic intestinal inflammatory conditions, namely Crohn’s disease and ulcerative colitis. Celiac disease (CD) is an immune-mediated chronic gastrointestinal inflammation triggered by gluten in genetically predisposed individuals. This study aimed to explore the relationship between GEP-NENs and CD, providing a detailed review of the existing literature and addressing the (possible) gaps in current knowledge. Methods: We conducted an extensive search of international databases using relevant keywords, with the last update on 1 November 2024. A total of 19 studies, published between 1983 and 2024, were included: two prospective studies, five retrospective studies, and 12 case reports. Results: Overall, we included 107 GEP-NENs in our analysis. Among the 94 GEP-NENs identified in prospective and retrospective studies, the small intestine was the most common site (88.3%). The small intestine was also the most frequently reported site in the case report series (46.2%), accounting for 13 GEP-NENs in 12 patients with CD. Conclusions: Although most studies on the association between CD and GEP-NENs are heterogeneous, and while some lack crucial data, emerging evidence suggests that screening GEP-NEN patients for CD could offer valuable insights. Testing for the presence of CD might reveal whether the observed association is more than coincidental and possibly pave the way for exploring and understanding the role of chronic inflammation in the tumorigenesis of GEP-NENs in CD.