Small Bowel Adenocarcinomas Complicating Crohnʼs Disease Are Associated With Dysplasia

Abstract

These results suggest that there is an inflammation-dysplasia-adenocarcinoma sequence in at least half of CD-related SBA, similar to what is observed in chronic colitis-related colorectal cancer and may have implications for the prevention and treatment of this cancer.

Genetic risks and familial associations of small bowel carcinoma

“…In addition, excessive formation of reactive oxygen and nitrogen free radicals are potentially damaging to DNA and the integrity of cell surface membranes [15] . Adenocarcinoma in CD is seen in the effected segments of the bowel which suggests inflammationdysplasia-carcinoma sequence [45,48,54,55] . Genetic alterations occur, which transform dysplastic mucosa to carcinoma.…”

Dysplasia Involves Enteritis Cystica Profunda in the Setting of Crohn’s Disease

“…This is further supported by positive immunohistochemistry staining for gastric markers, MUC5AC and MUC6 [7]. Dysplasia has been reported to be present in at least 50% of Crohn's disease-associated small bowel adenocarcinoma [4,5] and overexpression of p53 has been noted in 60% of Crohn's disease-associated dysplasia [5].…”

“…The presence of dysplasia and intramucosal adenocarcinoma of gastric type in the overlying mucosa and the adjacent mucosa further supported the interpretation of neoplastic involvement of enteritis cystic profunda in this case. The neoplastic/dysplastic nature of this lesion was further supported by the diffuse nuclear immunoreactivity for p53, which had been reported previously in Crohn's enteritis-associated dysplasia/adenocarcinoma [5,13]. The major differential diagnosis for this case included a deeply invasive, well-differentiated, adenocarcinoma (the socalled "intestinal low-grade tubuloglandular adenocarcinoma" in inflammatory bowel disease [14] and an endometriosis-like adenocarcinoma) [6].…”

“…First, this highgrade dysplasia and intramucosal adenocarcinoma occurred in a patient of an older rather than young age. The mean age at onset of Crohn's disease-associated small bowel adenocarcinoma in one report is 48 years [5]. Second, this neoplastic process extensively involves the enteritis cystica profunda.…”

“…Chronic inflammation, mucosa injury, mucosa regeneration, and mural fibrosis may lead to enteritis cystic profunda, a rare non-neoplastic condition characterized by misplaced glands deep to the muscularis mucosae of the small bowel which may cause stricture radiographically or obstruction clinically [1,2]. Chronic inflammation of mucosa (chronic enteritis) in Crohn's disease also increases the risk of small bowel adenocarcinoma via an inflammation-dysplasiaadenocarcinoma sequence [3][4][5]. Crohn's disease-associated small bowel adenocarcinomas have been reported to have an endometriosis-like invasion pattern and manifest gastric differentiation in the majority of cases [6,7].…”