Hyperplastic/Serrated Polyposis in Inflammatory Bowel Disease

Abstract

Herein, we describe the clinical, pathologic, immunohistochemical, and molecular features of 3 unique patients with long standing inflammatory bowel disease, all of whom developed numerous discrete hyperplastic/serrated colonic polyps similar to those described in the hyperplastic/serrated polyposis syndrome. The 3 patients (2 with ulcerative colitis and 1 with Crohn ileo-colitis) were evaluated for a variety of clinical, histologic (including the type, location and number of polyps in the colon), and immunohistochemical features [MLH-1, MSH-2, MGMT (O(6)-methylguanine-DNA methyltransferase), beta-catenin, and p53]. KRAS and BRAF mutation analysis was also performed on a subset of polyps from 2 patients. All patients had moderate-severe pancolitis of more than 10 years duration and had >20 colonic polyps. None had polyps in the upper gastrointestinal tract. Pathologically, a combination of conventional hyperplastic polyps and sessile serrated polyps (adenomas) were present in the 3 cases. In addition, serrated adenomas were present in 2 and conventional adenomas in 1. Two patients also had synchronous adenocarcinoma. All 3 cases showed retention of MLH-1 and MSH-2, and a membranous beta-catenin staining pattern. However, 2 cases showed loss of MGMT in several serrated polyps, and one also in adjacent colitic mucosa. KRAS mutations were detected in 5/11 serrated polyps. However, BRAF mutations were not present in any of the polyps tested. These findings suggest the possibility of a serrated pathway of carcinogenesis in inflammatory bowel disease characterized by silencing of MGMT, most likely by gene promoter methylation, KRAS mutations, and possibly other, as yet, uncharacterized molecular alterations, resulting eventually in progression to adenocarcinoma.

Serrated colorectal polyps in inflammatory bowel disease

“…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. They reported that cancers developed in two patients with conventional adenomatous dysplasia or traditional serrated adenomas but not in a third patient with non-dysplastic serrated lesions.…”

“…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.…”

Heterogeneity of colorectal adenomas, the serrated adenoma, and implications for screening and surveillance

“…Thus, current screening algorithms may not be adequate for detection. Moreover, hyperplastic/ serrated polyposis has also been observed in patients with chronic inflammatory bowel disease [14] . A prudent approach has been suggested to include complete resection and surveillance examinations as often as the intervals defined for the more traditional adenomatous polyps but this approach is not necessarily reflective of the natural biological history of these lesions.…”

Clinical Aspects of Idiopathic Inflammatory Bowel Disease: A Review for Pathologists

“…Serrated lesions may be associated with neoplastic progression in IBD; some have been reported to be associated with invasive adenocarcinoma. 110 However, data are limited and further investigation is needed for characterization. 95,[110][111][112] Patients with sessile serrated polyp-like lesions in the diseased colon should have repeat colonoscopy in 1 year following complete removal of the lesion (W. E. Jackson et al, unpublished data, 2015).…”

“…110 However, data are limited and further investigation is needed for characterization. 95,[110][111][112] Patients with sessile serrated polyp-like lesions in the diseased colon should have repeat colonoscopy in 1 year following complete removal of the lesion (W. E. Jackson et al, unpublished data, 2015). In addition, villous hypermucinous mucosa harboring K-RAS mutation and very well-differentiated adenocarcinoma with low-grade dysplastic precursor lesions have been described in IBD.…”