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 favourable behaviour, thus outlining the need to improve the histopathological 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 histological analysis of the tumour invasive front; we therefore systematically analysed the tumour 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 tumour 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 favourable small bowel carcinoma behaviour. In particular, association of tumour budding and poorly differentiated clusters in a combined invasive front score allowed identification of a minor subset of cancers [12/47, 25%] characterised 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.