Clinico-pathologic, histophenotypic, molecular and prognostic characterization of small bowel carcinomas associated with celiac disease or Chron’s disease.

Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Celiac disease and Crohn’s disease are predisposing conditions for small bowel carcinoma development. In this study, small bowel carcinomas associated with celiac disease (n=26), small bowel carcinomas associated with Crohn’s disease (n=25) and sporadic small bowel carcinomas (n=25) were systematically compared. We found that in patients undergoing surgery for small bowel carcinomas the underlying immune-mediated disorder represents a stage-independent prognostic factor. Despite their common origin in a chronically inflamed mucosa, celiac disease-associated and Crohn’s disease-associated small bowel carcinomas differ substantially in tumor cell phenotype, tumor-infiltrating lymphocyte density, microsatellite instability status, Wnt pathway activation, as well as mucosal precursor lesions. Moreover, Epstein-Barr virus-positive carcinomas may occur in the ileum of Crohn’s disease patients and are characterised by increased tumor-infiltrating lymphocytes, either with lymphoepithelioma-like or with a more conventional glandular histology.