Indefinite dysplasia in IBD
Dysplasia in colitis surveillance is classified as low-grade dysplasia (LGD) or high-grade dysplasia (HGD). Rarely, following expert pathologist review, the histologic changes fall short of those required to make a diagnosis of LGD, and are termed indefinite dysplasia (ID). Typically, the diagnosis of ID is made when there is active colitis that might induce changes of atypia and interfere with a definitive diagnosis of dysplasia.
Frequently, repeat colonoscopy is performed following induction of mucosal healing, and repeat endoscopic biopsies are required to determine whether the ID changes have resolved, remain or progress towards LGD or HGD. It should be noted whether the dysplasia is within an endoscopically visible lesion, or in endoscopically normal mucosa, ideally with the assistance of enhanced endoscopic imaging. The rates of progression of ID to LGD or beyond are unknown, with a paucity of literature referring to ID and outcomes.
What should be the protocol to manage indefinite dysplasia in IBD? (MNG4)
Systematic review evidence
No new publications were identified that compared management protocols for ID in those with inflammatory bowel disease (IBD).
Overview of additional evidence (non-systematic literature review)
Lai et al (2015) followed 125 subjects diagnosed with ID from a pathology database from 1989–2004. Of 22 patients who underwent resection within 6 months of diagnosing ID, the prevalence of dysplasia was 27.3% (1 LGD, 5 HGD). Of 59 subjects with ID that had follow up colonoscopy data, the progression rate to dysplasia or colorectal cancer (CRC) was 3.2 cases per 100 person years. The progression rate to dysplasia was 1.5 cases per 100 person years at risk. It must be noted that during the study period the diagnosis of ID relied on standard-definition colonoscopy, synchronous LGD or HGD may have been missed, potentially accounting for the strong reported association of ID with dysplasia. van Schaik et al found 5 of 26 cases (19%) of ID developed advanced dysplasia after a median follow up of 24 months.
If ID is diagnosed, progression to a higher grade of dysplasia or carcinoma is unusual. In a large series, at a single tertiary referral centre, 1 of 23 patients with ID (4%) eventually developed carcinoma and 5 (22%) developed LGD after 9 years of follow-up. In contrast, data from New York showed that the 5-year rate of progression from ID to HGD or CRC was 9%. If a biopsy is diagnosed as indefinite for dysplasia by two sub-specialised gastrointestinal pathologists, follow-up surveillance colonoscopy (preferably with chromoendoscopy) at 6 months is reasonable, and thereafter at annual intervals. Treatment escalation to ensure that endoscopic and histological healing takes place can clarify or help exclude the diagnosis of dysplasia severity.
Evidence summary and recommendations
|The predictive value of indefinite dysplasia in flat mucosa for imminent cancer is low.||III-2,III-3||, |
|Indefinite dysplasia in flat mucosa does not require surgery, but follow-up colonoscopic surveillance is recommended, preferably with chromoendoscopy, at more frequent intervals.||D|
Indefinite dysplasia should be reviewed by a second gastro-intestinal pathologist.
After detecting indefinite dysplasia, inflammation (if present) should be treated and colonoscopy should be repeated.
If indefinite dysplasia is detected at random biopsy, repeat colonoscopy with enhanced imaging techniques may assist in defining an endoscopically resectable lesion, or a lesion amenable to further targeted biopsies.
If there are features of active inflammation, repeat colonoscopy following escalation of therapy may assist in further defining indefinite dysplasia.
- Lai KK, Horvath B, Xie H, Wu X, Lewis BL, Pai RK, et al. Risk for colorectal neoplasia in patients with inflammatory bowel disease and mucosa indefinite for dysplasia. Inflamm Bowel Dis 2015 Feb;21(2):378-84 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25569733.
- van Schaik FD, ten Kate FJ, Offerhaus GJ, Schipper ME, Vleggaar FP, van der Woude CJ, et al. Misclassification of dysplasia in patients with inflammatory bowel disease: consequences for progression rates to advanced neoplasia. Inflamm Bowel Dis 2011 May;17(5):1108-16 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20824815.
- Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MA, et al. Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis. Gastroenterology 2006 Apr;130(4):1030-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16618396.
- Ullman T, Croog V, Harpaz N, Hossain S, Kornbluth A, Bodian C, et al. Progression to colorectal neoplasia in ulcerative colitis: effect of mesalamine. Clin Gastroenterol Hepatol 2008 Nov;6(11):1225-30; quiz 1177 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18848502.
- Baars JE, Vogelaar L, Wolfhagen FH, Biermann K, Kuipers EJ, van der Woude CJ. A short course of corticosteroids prior to surveillance colonoscopy to decrease mucosal inflammation in inflammatory bowel disease patients: results from a randomized controlled trial. J Crohns Colitis 2010 Dec;4(6):661-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21122577.
|PICO question MNG4||Evidence statement form MNG4||Systematic review report MNG4|