The Significance of Flat/Invisible Dysplasia and Nonconventional Dysplastic Subtypes in Inflammatory Bowel Disease: A Review of Their Morphologic, Clinicopathologic, and Molecular Characteristics

Abstract

Patients with inflammatory bowel disease are at significantly increased risk of dysplasia and colorectal cancer (CRC). The early detection, histologic grading, and removal of dysplasia plays a critical role in preventing the development of CRC. With advances in endoscopic visualization and resection techniques, colectomy is no longer recommended to manage dysplasia, unless surveillance colonoscopy detects flat/invisible dysplasia (either highgrade dysplasia or multifocal low-grade dysplasia) or an endoscopically unresectable lesion. Although there are numerous review articles and book chapters on the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, at least 7 distinct nonconventional morphologic patterns of epithelial dysplasia have been recently described in inflammatory bowel disease. Most practicing pathologists are not familiar with these nonconventional subtypes and thus, may even overlook some of these dysplastic lesions as benign or reactive. However, the recognition of these subtypes is important, as some of them appear to have a high risk of developing advanced neoplasia (high-grade dysplasia or CRC) and often show molecular alterations characteristic of advanced neoplasia. This review briefly describes the morphologic criteria of conventional dysplasia but predominantly focuses on all 7 nonconventional subtypes as well as our understanding of their clinicopathologic and molecular features that can assist in their risk stratification.

Increased histologic inflammation is an independent risk factor for nonconventional dysplasia in ulcerative colitis

“…We previously reported detailed diagnostic criteria for each nonconventional subtype (Figures 2 and 3). [11][12][13][14][15][18][19][20] As described in our previous study, 12 all dysplastic lesions were rereviewed by at least one gastrointestinal pathologist (W.T.C. and G.Y.L.)…”

“…6 More recently, our group and other investigators have reported that several different morphologic patterns of dysplasia, collectively known as nonconventional dysplasia, can occur in inflammatory bowel disease (IBD), which are characterized by unique clinicopathologic, molecular, and risk profiles compared with conventional dysplasia or sporadic adenomas. [11][12][13][14][15][16][17][18][19][20] There are seven subtypes: (i) hypermucinous dysplasia; (ii) goblet cell-deficient dysplasia; (iii) crypt cell dysplasia; (iv) dysplasia with increased Paneth cell differentiation (DPD); (v) sessile serrated lesion (SSL)like dysplasia; (vi) traditional serrated adenoma (TSA)-like dysplasia; and (vii) serrated dysplasia, not otherwise specified (NOS). Of these, hypermucinous, goblet cell-deficient, and crypt cell dysplasias appear to represent high-risk lesions, as they often present as flat/invisible lesions (~66%), show molecular features characteristic of advanced neoplasia (e.g.…”

Clinicopathologic features of undetected dysplasia found in total colectomy or proctocolectomy specimens of patients with inflammatory bowel disease

“…38 Detailed morphologic criteria for each nonconventional subtype have been previously published by our group (Figures 1 and 2). [29][30][31][32][33][34][35] Dysplasia found in the colectomy specimens was classified as undetected, only when there was no corresponding site of dysplasia detected and reported on previous colonoscopic biopsies. If dysplasia in the colectomy specimens was detected on prior colonoscopy, it was categorized as previously detected.…”

“…They appear to have distinct clinicopathologic and molecular features compared with conventional dysplasia or sporadic adenomas. [29][30][31][32][33][34][35][36][37] There are seven subtypes, including (i) hypermucinous dysplasia; (ii) goblet cell deficient dysplasia; (iii) crypt cell dysplasia; (iv) dysplasia with increased Paneth cell differentiation (DPD); (v) sessile serrated lesion (SSL)-like dysplasia; (vi) traditional serrated adenoma (TSA)-like dysplasia; and (vii) serrated dysplasia, not otherwise specified (NOS). Of these, hypermucinous, goblet cell deficient, and crypt cell variants have received the most attention, as they often present as flat/invisible dysplasia (~66%) and develop advanced neoplasia (40-93%) on follow-up.…”

“…This is further complicated by the fact that several underrecognized morphologic patterns of dysplasia, collectively known as “nonconventional” dysplasia, have been described in IBD. They appear to have distinct clinicopathologic and molecular features compared with conventional dysplasia or sporadic adenomas 29–37 . There are seven subtypes, including (i) hypermucinous dysplasia; (ii) goblet cell deficient dysplasia; (iii) crypt cell dysplasia; (iv) dysplasia with increased Paneth cell differentiation (DPD); (v) sessile serrated lesion (SSL)‐like dysplasia; (vi) traditional serrated adenoma (TSA)‐like dysplasia; and (vii) serrated dysplasia, not otherwise specified (NOS).…”