Separation of low versus high grade Crohn's disease-associated small bowel carcinomas is improved by invasive front prognostic marker analysis

Background and aims: Crohn's disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a minority of cases displaying a relatively favorable behavior, thus outlining the need to improve the histopathologic prediction of Crohn's disease-associated small bowel carcinoma prognosis. Methods: As in recent studies on colorectal cancer a substantial improvement in prognostic evaluations has been provided by the histologic analysis of the tumor invasive front, we therefore systematically analyzed the tumor budding and poorly differentiated clusters in the invasive front of 47 Crohn's disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium. Results: Both tumor budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn's disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favorable small bowel carcinoma behavior. In particular, association of tumor budding and poorly differentiated clusters in a combined invasive front score allowed to identify a minor subset of cancers (12/47, 25%), characterized by combined invasive front-low grade coupled with a glandular histology and a low stage (I or II) and showing no cancer-related death during a median follow-up of 73.5 months. Conclusions: The improved distinction of lower from higher grade Crohn's disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms.