Serrated Epithelial Changes and Risk of Dysplasia in Inflammatory Bowel Disease

The global epidemiology of inflammatory bowel disease (IBD) is changing with a rising burden of disease in several developing countries, including India.[1] Patients with ulcerative or Crohn's colitis have an increased risk of developing dysplasia and neoplasia in the colon and need regular surveillance. Improvement in treatment and surveillance strategies has reduced the overall incidence of colorectal cancer (CRC), yet it is one of the leading causes of surgery and mortality.[2] Conventional adenoma, sessile serrated adenoma, and traditional serrated adenoma may all be precursors of CRC in IBD.[3] In addition, serrated epithelial change (SEC), a distinct pathologic entity, has also been implicated as a precursor to CRC in IBD. There is a lack of standard criteria for diagnosing SEC. One criterion defines SEC as a luminal serrated surface contour limited to the upper portion of the crypts, without any features of dysplasia on random mucosal biopsies (endoscopically not visible, definition 1).[4] Another definition does not consider endoscopic appearance (visible or invisible) and relies on histopathological features. This includes disorganized crypt architecture with crypts losing perpendicular orientation to the muscularis mucosae, diffuse irregular serrations, and goblet cell-rich epithelium (definition 2).[4] Information on the SEC in IBD is still emerging and, at times, conflicting.

This issue of the journal reports a retrospective study from Australia on SEC in IBD.[5] The authors identified 26 patients with SEC from the pathology database. A follow-up colonoscopy or sigmoidoscopy was essential for inclusion in this study. Crohn's disease was present in 16, while 10 had ulcerative colitis (UC). Overall, 30 SEC were noted among the 26 subjects (19.2% had multiple lesions). SECs were commonly located in the caecum and rectum, and 60% were visible endoscopically as polypoid or nodular lesions. The remaining were detected on random biopsies and were not visible despite high-definition endoscopy and/or chromoendoscopy being used in all the cases. SEC was defined as nondysplastic colonic mucosa with goblet cell-rich epithelium and distorted, serrated architecture involving the upper crypts, without distortion of the basal crypt architecture. The diagnosis was independent of endoscopic visibility of the lesion. The median follow-up was 24.5 months, and only one patient was noted to have dysplasia. This work provides useful insight into the characteristics, burden, and outcome associated with SEC in IBD. The clear inclusion/exclusion criteria, confirmation of SEC by two pathologists, and evaluation of follow-up data are the key strengths. Inclusion of patients with “IBD without SEC” as controls would have provided information on the added risk of dysplasia due to this entity. Lack of a comparison group is an important limitation of this study. Endoscopic inflammation was noted in 50% cases, and the association of SEC with background disease activity and its location in relation to the inflamed segment was not described. However, considering the infrequent nature of SEC, the authors must be commended for their efforts in presenting this data.

The literature on SEC in IBD is predominantly retrospective in nature and the majority has been published from the United States in the past decade. [Table 1] summarizes the key findings on SEC in IBD.[6] [7] [8] [9] [10] [11] As expected, due to the colonic location of SEC, most cases are reported in patients with UC.[6] [7] [9] [11] While the onset of IBD is commonly in the third or fourth decade, SECs have been reported in the fifth to sixth decade.[6] [7] [8] [9] [10] [11] The average time interval between the diagnosis of IBD and detection of SEC is about 15 to 20 years, and a male preponderance has been noted.[6] [7] [8] [9] [10] [11] This supports the notion that the SEC may be associated with longstanding inflammation in the colon. Interestingly, despite image-enhanced endoscopy being freely available and recommended for surveillance in IBD, this is infrequently used.[8] [9] [10] The vast majority of the SEC have been observed in the rectum or left colon.[6] [7] [10] [11] This is in contrast to the paper published in the current issue of this journal, which found caecum to be the most common site.[5] SEC may be multifocal in about 15 to 20% cases, although it was noted in 59% cases in one study.[6] [7] [10] [11] No association has been demonstrated between SEC and endoscopic or histological inflammation.[7] [11] A disproportionately higher number of cases with primary sclerosing cholangitis has also been observed among cases with SEC.[7] [10] [11] An important consideration is the endoscopic visibility of lesions. It is apparent from the available data that SEC occurs in both normal-appearing mucosa as well as in areas with nodularity, etc.[9] [10] [11] Hence, restricting this entity to endoscopically normal areas (definition 1) will result in missed lesions and underestimation of prevalence.

Table 1 Summary of findings from studies on serrated epithelial changes in inflammatory bowel disease

Reference Study design Country	No. of participants Demographic profile Disease duration Follow-up period		Definition and characteristics of SEC	Risk factors of SEC Dysplasia Comparison with controls Other details
I. UC and CD combined
Bahceci et al, American Journal of Surgical Pathology. 2024;48(10):1326–1334.   Retrospective case–control study   USA and New Zealand	Cases 46 IBD patients with SEC and dysplasia   UC-74% CD-26%   Mean age, years (range): 58 (26–76)   Males: 61%   Mean disease duration, years (range): 23 (< 1–52)   Mean follow-up period, years (range): 4.5 (< 1–22.8)	Controls 45 IBD patients with HP and dysplasia   UC-80% CD-20%   Mean age, years (range): 55 (22–80)   Males: 60%   Mean disease duration, years (range): 20 (< 1–59) Mean follow-up period, years (range): 3.4 (< 1–17.8)	Definition 1   Location: Left colon: 48%, rectum: 31%   Multifocal SEC: 59%   Concomitant PSC: 4%	No difference between SEC and the control groups regarding age, gender distribution, IBD phenotype, presence of PSC, and location   SEC vs. controls Dysplasias in left colon: 41% vs. 26%, p = 0.028 High-risk subtype of dysplasia: 18% vs. 0%, p < 0.001 Advanced neoplasia: 24% vs. 0%, p < 0.001   Location concordance between dysplasia and SEC or HP: 76% vs. 49%, p = 0.007
Batts et al, Postgraduate Medicine. 2021 Jan 2;133(1):66–70.   Retrospective case–control study   USA	Cases 94 IBD patients with SEC   UC- Major fraction   Mean age, years (SD): 52.8 (12.3)   Males: 58.5%   Mean disease duration, years (SD): 20.7 (10.9)   Follow-up period: 1–4 years	Controls 187 IBD patients without SEC   UC- Major fraction   Mean age, years (SD): 52.9 (13.8)   Males: 55.1%   Mean disease duration, years (SD): 18.2 (10.6)   Follow-up period: 1–4 years	Definition 1, but also included invisible SSL-like lesions   No data available regarding the characteristics of SEC	No difference between the SEC group and the control group with respect to age, gender distribution, disease duration, disease extent, activity and medications   SEC vs. controls Dysplasia: 12.8% vs. 4.3% Odds ratio: 2.53 (p = 0.081)
Parian et al, Gastrointestinal Endoscopy. 2016 Jul;84(1):87–95.e1.   Retrospective study   USA	187 patients with IBD and SEC   UC- 52.4% CD- 39% IBDU- 8.6%   Mean age, years (SD): 48.4 (15)   Males: 57.8%   Mean disease duration, years (SD): 16 (10.9)   Median follow-up period, years (range): 2.3 (0–14.3)		Definition 2   Prevalence: 3%   Location: Rectum: 37.8%, left colon: 37.1%   Multifocal SEC: 20.3%   Concomitant PSC: 6.4%   Extensive disease: 53.5%   Visible lesion and targeted biopsy: 17.6% Nontargeted biopsy: 71.7%	Synchronous dysplasia: 8% Metachronous dysplasia: 21% HGD and cancer: 6% (17/1000 patient-years)   Location concordance between dysplasia and SEC: 68%   Older age at IBD diagnosis, male gender, family history of CRC, and SEC at follow-up colonoscopy increased the risk of dysplasia
Johnson et al, Aliment Pharmacol Ther. 2014 Jun;39(12):1408–1417.   Retrospective case–control study   USA	Cases 79 IBD patients with SEC   UC-84% CD-16%   Median age, years (IQR): 57 (48–64.75)   Males: 62%   Median disease duration, years (IQR): 18 (10.5–29)	Controls 100 IBD patients without SEC (Baseline characters were not mentioned as a whole, rather stratified as per the presence or absence of prior or synchronous CRN)	Definition 1   Detection rate: 10/1000 colonoscopies (95% CI, 8-14)   Extensive disease: 77%   Concomitant PSC: 29%   Targeted biopsy: 38%	SEC patients were older, had longer disease duration and more frequent association with PSC   SEC vs. controls Cumulative incidence of subsequent CRN at 3 years: 30% vs. 9%, p = 0.047. Significance was lost following stratification for prior or synchronous SEC   Location concordance between SEC and dysplasia: 45%
II. UC
Bahceci et al, American Journal of Surgical Pathology. 2024 Jun;48(6):719–725.   Retrospective case–control study   USA	Cases 28 UC patients with SEC   Mean age, years (range): 47 (24–91)   Males: 43%   Mean disease duration, years (range): 13 (3–26)	Controls 51 UC patients without SEC   Mean age, years (range): 47 (19–75)   Males: 47%   Mean disease duration, years (range): 13 (1–35)	Definition 1   Location: Left colon: 86%   Multifocal SEC: 14%   Concomitant PSC: 4%   Pancolitis: 75%	No potential risk factor could be identified that predicted the development of SEC   No difference between the histological inflammatory scores between the SEC and non-SEC groups
Parian et al, Inflammatory Bowel Diseases. 2021 Aug 19;27(9):1475–1481.   Retrospective case–control study   USA	Cases 98 UC patients with SEC   Mean age, years (SD): 48.7 (14.4)   Males: 60.2%   Mean disease duration, years (SD): 16.8 (10.7)   Mean follow-up period, years (SD): 2.9 (2.9)	Controls 98 matched UC patients without SEC (matched for age, disease duration, and extent)   Mean age, years (SD): 48 (14.8)   Males: 44.9%   Mean disease duration, years (SD): 15.4 (9.3)   Mean follow-up period, years (SD): 3.1 (3.9)	Definition 2   Location: Rectum: 52% Sigmoid colon: 37.8%   Multifocal SEC: 22.4%   Concomitant PSC: 10.2%   Nontargeted biopsy: 66.3%	SEC vs. non-SEC Neoplasia: 26.5% vs. 3.1%, p < 0.001 HGD or CRC: 11.2% vs. 2%, p = 0.02   SEC was a strong predictor of neoplasia in UC patients (odds ratio, 11.4; 95% CI, 2.5–51.98; p < 0.01)

Abbreviations: CD, Crohn's disease; CI, confidence interval; CRC, colorectal cancer; CRN, colorectal neoplasia; HGD, high-grade dysplasia; HP, hyperplastic polyps; IBD, inflammatory bowel disease; IBDU, inflammatory bowel disease unclassified; IQR, interquartile range; PSC, primary sclerosing cholangitis; SD, standard deviation; SEC, serrated epithelial change; SSL, sessile serrated lesion; UC, ulcerative colitis.

The clinical significance of SEC lies in its reported association with dysplasia and the future risk of CRC. The risk of dysplasia, including high-risk dysplasia, more than doubles in the presence of SEC.[6] [8] [11] A systematic review and meta-analysis including three studies with 195 IBD patients with SEC found a significantly higher risk of neoplasia compared with the non-SEC group (relative risk 4.11, 95% confidence interval 2.23–7.58, p < 0.001).[11] Older age, male gender, and family history of CRC increase the risk of dysplasia.[10] A higher risk of both synchronous and metachronous dysplasia has been observed.[10] The concordance between the location of SEC and dysplasia ranges from 45 to 75%.[6] [9] [10] This further supports the link between SEC and dysplasia. The future risk of CRC also appears to be increased, but this outcome is infrequently reported.[9] [10] The risk of dysplasia in the paper by Vaitiekunas et al cannot be estimated due to the lack of a control group, and there were no cases of CRC.[5] Only one patient was found to have dysplasia, and the frequency appears to be lower than the studies included in [Table 1].

While the awareness of SEC is increasing, there are several issues that need to be addressed. These include identification of risk factors for SEC, the strategy to improve their endoscopic detection, formulation of standard histopathological criteria for diagnosis, appropriate follow-up protocol in those with visible and invisible lesions, etc.[4] Studies are also needed from different parts of the world, as the current data are generally from the West. The epidemiology of CRC varies globally, and how this impacts SEC requires confirmation by data from different regions of the world. Prospective, multicentric, registry-based data may help to understand the characteristics and natural history of SEC more clearly and guide surveillance strategy.

Conflict of Interest

None declared.

• References

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• 2 Shah SC, Itzkowitz SH. Colorectal cancer in inflammatory bowel disease: mechanisms and management. Gastroenterology 2022; 162 (03) 715-730.e3
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• 11 Parian AM, Limketkai BN, Chowdhury R. et al. Serrated epithelial change is associated with high rates of neoplasia in ulcerative colitis patients: a case-controlled study and systematic review with meta-analysis. Inflamm Bowel Dis 2021; 27 (09) 1475-1481

Publication History

Article published online:
17 November 2025