Dysplastic lesions in inflammatory bowel disease: molecular pathogenesis to morphology

* Context.--Inflammatory bowel disease (IBD) is a longstanding chronic active inflammatory process in the bowel with increased risk for the development of colorectal carcinoma. Several molecular events involved in chronic active inflammatory processes contribute to multistage progression of human cancer development, including reactive oxygen and nitrogen species, aberrant arachidonic acid metabolites and cytokines/growth factors, and immune dysfunction. These molecular events in IBD lead to genetic abnormality and promote aberrant cell proliferation, which further lead to epithelial changes encompassing a broad spectrum from inflammation-induced hyperplasia to dysplasia. Objective.--To review the (1) epidemiologic and molecular pathogenesis of the risk for colorectal cancer in IBD, (2) morphologic characterization, biomarker(s), and classification of dysplastic lesions, and (3) clinical management of dysplastic lesions arising in IBD. Data Sources.--The different IBD-related dysplastic lesions are illustrated by using morphology in conjunction with molecular pathways, and the 'field cancerization' theory and its potential significance are discussed with a review of the literature. Conclusions.--Patients with IBD are at increased risk of developing colorectal cancer. The risk of developing carcinoma is related to the extent/duration/activity of the patient's disease. There is no consensus regarding the extent of carcinoma risk associated with IBD; however, all would agree that patients with IBD represent a group at significant risk for developing carcinoma and as such, warrant adequate surveillance and prevention. With better screening modalities and detection/characterization of dysplastic lesions, IBD-associated serrated lesions, and 'field cancerization,' we will improve our understanding of and approach to risk stratification. (Arch Pathol Lab Med. 2013;137:338-350; doi: 10.5858/arpa.2012-0086-RA)
Chronic inflammation is a well-recognized risk factor for human cancer development, and at least one-third of all human cancers have been associated with inflammation, for example, long-standing chronic inflammatory bowel [...]