Hyperplastic-Like Mucosal Change in Crohn's Disease: An Unusual Form of Dysplasia?

Abstract

Patients with Crohn's disease are at increased risk of developing intestinal adenocarcinoma. Dysplasia is both a marker and a precursor of adenocarcinoma in this setting. In a review of our cases of Crohn's-related adenocarcinoma, we noted a peculiar hyperplastic-like mucosal change (HPC) in mucosa both adjacent to and distant from the adenocarcinoma in some cases. However, the significance of this change is unknown.We evaluated 30 cases of Crohn's-related adenocarcinoma and 30 age-and site-matched resection specimens with Crohn's disease without adenocarcinoma to determine the prevalence of this mucosal alteration in these groups. HPC was recognized by a diffuse expanse of flat mucosa with an architecture resembling that seen in colorectal hyperplastic polyps and composed of cells with cytologically bland basal nuclei and apical cytoplasmic mucin distention. The relationship of the HPC to the adenocarcinoma was noted in the Crohn's-related adenocarcinoma cases. An immunohistochemical stain for p53 (antibody DO7) was performed on all cases with HPC in both groups.HPC was identified in 10 of 30 (33%) cases of Crohn's-related adenocarcinoma compared with 3 of 30 (10%) cases in the control group (P ‫؍‬ .03). In the 10 cases of Crohn's-related adenocarcinoma with HPC, this alteration was found adjacent to the adenocarcinoma in 3 cases, distant to the adenocarcinoma in 5 cases, and both adjacent to and distal from the adenocarcinoma in 2 cases. In two specimens, HPC was seen immediately adjacent to adenocarcinoma in the absence of adjacent dysplasia. p53 immunoreactivity was noted in HPC in 5 of 10 (50%) Crohn's-related adenocarcinomas. In contrast, p53 immunoreactivity was not seen in HPC in the three control cases with this mucosal alteration.In conclusion, HPC is found significantly more commonly in mucosa both adjacent to and distant from Crohn's-related adenocarcinoma when compared with age-and site-matched controls. In addition, p53 immunoreactivity is more commonly seen in HPC in cases of Crohn's-related adenocarcinoma compared with controls. These data suggest that this mucosal alteration may, in some cases, represent an unusual form of dysplasia in this setting.

Mutation Accumulation in the Intestine and Colon of Mice Deficient in Two Intracellular Glutathione Peroxidases

“…IBD includes Crohn's disease (CD) and ulcerative colitis (UC); each affects approximately one in a thousand people in Western countries. Although CD and UC may have different genetic origins and affect different areas of the gastrointestinal tract, both diseases result in an increased risk of cancer compared with the age-matched general population (10,11). Clearly, chronic inflammation contributes to carcinogenesis in the gastrointestinal tract; however, the mechanisms are not understood.…”

Clinical, pathologic, and outcome study of hyperplastic and sessile serrated polyps in inflammatory bowel disease

“…At this point in time, 3 morphologic subtypes of dysplasia in IBD have been described, all of which may exhibit flat or polypoid architecture: intestinal dysplasia, which cytologically resembles dysplasia seen in sporadic adenomas, hypermucinous/villous dysplasia, and serrated dysplasia [2,3,[6][7][8]. Polypoid serrated dysplasia resembling sporadic serrated polyps has also been observed in IBD patients [6,[8][9][10].…”

Serrated colorectal polyps in inflammatory bowel disease

“…Rubio et al 16 described higher rates of dysplastic serrated lesions near carcinomas in resection specimens from inflammatory bowel disease patients compared with non-inflammatory bowel disease patients. Kilgore et al 15 reported non-dysplastic serrated lesions in 33% of cancer-bearing resection specimens from patients with Crohn's disease compared with 10% of controls without cancer. Srivastava et al 17 described patients with longstanding inflammatory bowel disease and multiple hyperplastic polyps and sessile serrated adenoma/polyps (reminiscent of the serrated polyposis syndrome), nearly half of which contained KRAS but not BRAF mutations.…”

“…9,[11][12][13] Nonetheless, recognition of the full range of histologic lesions with malignant potential in the setting of inflammatory bowel disease is incomplete. Although several prior studies have described serrated colorectal lesions in patients with inflammatory bowel disease, [14][15][16][17] a systematic characterization of serrated polyps in this population has not been hitherto reported. We hypothesized that serrated polyps in patients with inflammatory bowel disease may have similar biologic characteristics to sporadic serrated polyps and therefore undertook a retrospective review of colorectal serrated polyps diagnosed over a 14-year period among inflammatory bowel disease patients undergoing routine colonoscopic surveillance at our institution.…”