Indefinite dysplasia in IBD

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Background

Dysplasia in colitis surveillance is classified as low-grade dysplasia (LGDLow grade dysplasia) or high-grade dysplasia (HGDHigh grade dysplasia). Rarely, following expert pathologist review, the histologic changes fall short of those required to make a diagnosis of LGDLow grade dysplasia, and are termed indefinite dysplasia (IDIndefinite dysplasia). Typically, the diagnosis of IDIndefinite dysplasia 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 IDIndefinite dysplasia changes have resolved, remain or progress towards LGDLow grade dysplasia or HGDHigh grade dysplasia. 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 IDIndefinite dysplasia to LGDLow grade dysplasia or beyond are unknown, with a paucity of literature referring to IDIndefinite dysplasia and outcomes.

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Evidence

What should be the protocol to manage indefinite dysplasia in IBDInflammatory bowel disease? (MNG4)

Systematic review evidence

No new publications were identified that compared management protocols for IDIndefinite dysplasia in those with inflammatory bowel disease (IBDInflammatory bowel disease).

Overview of additional evidence (non-systematic literature review)

Lai et al (2015) followed 125 subjects diagnosed with IDIndefinite dysplasia from a pathology database from 1989–2004.[1] Of 22 patients who underwent resection within 6 months of diagnosing IDIndefinite dysplasia, the prevalence of dysplasia was 27.3% (1 LGDLow grade dysplasia, 5 HGDHigh grade dysplasia). Of 59 subjects with IDIndefinite dysplasia that had follow up colonoscopy data, the progression rate to dysplasia or colorectal cancer (CRCColorectal cancer) was 3.2 cases per 100 person years. The progression rate to dysplasia was 1.5 cases per 100 person years at risk.[1] It must be noted that during the study period the diagnosis of IDIndefinite dysplasia relied on standard-definition colonoscopy, synchronous LGDLow grade dysplasia or HGDHigh grade dysplasia may have been missed, potentially accounting for the strong reported association of IDIndefinite dysplasia with dysplasia. van Schaik et al found 5 of 26 cases (19%) of IDIndefinite dysplasia developed advanced dysplasia after a median follow up of 24 months.[2]

If IDIndefinite dysplasia 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 IDIndefinite dysplasia (4%) eventually developed carcinoma and 5 (22%) developed LGDLow grade dysplasia after 9 years of follow-up.[3] In contrast, data from New York showed that the 5-year rate of progression from IDIndefinite dysplasia to HGDHigh grade dysplasia or CRCColorectal cancer was 9%.[4] 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.[5]Back to top

Evidence summary and recommendations

Evidence summary Level References
The predictive value of indefinite dysplasia in flat mucosa for imminent cancer is low. III-2,III-3 [3], [4]
Evidence-based recommendationA recommendation formulated after a systematic review of the evidence, indicating supporting references.Question mark transparent.png Grade
Indefinite dysplasia in flat mucosa does not require surgery, but follow-up colonoscopic surveillance is recommended, preferably with chromoendoscopy, at more frequent intervals.
D
Consensus-based recommendationA recommendation formulated in the absence of quality evidence, after a systematic review of the evidence was conducted and failed to identify admissible evidence on the clinical question.Question mark transparent.png

Indefinite dysplasia should be reviewed by a second gastro-intestinal pathologist.

Consensus-based recommendationA recommendation formulated in the absence of quality evidence, after a systematic review of the evidence was conducted and failed to identify admissible evidence on the clinical question.Question mark transparent.png

After detecting indefinite dysplasia, inflammation (if present) should be treated and colonoscopy should be repeated.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

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.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

If there are features of active inflammation, repeat colonoscopy following escalation of therapy may assist in further defining indefinite dysplasia.

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References

  1. 1.01.1 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25569733.
  2. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20824815.
  3. 3.03.1 Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MAMetachronous adenoma, et al. Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis. Gastroenterology 2006 Apr;130(4):1030-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16618396.
  4. 4.04.1 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18848502.
  5. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21122577.

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Appendices

Jutta's magnifying glass icon.pngPICO question MNG4 View Evidence statement form MNG4Evidence statement form MNG4 View Systematic review report MNG3Systematic review report MNG4
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