Abstract
The risk of developing colorectal cancer in patients with colitis-associated dysplasia is considerable. Surveillance programs in patients with ulcerative colitis and Crohn's disease aim to detect dysplastic lesions early and rely heavily on taking random biopsy samples along the length of the colon. Diagnosing dysplasia can be difficult because of the heterogenous endoscopic appearance of dysplasia and the poor interobserver agreement among pathologists when grading dysplasia. Colitis-associated dysplasia may present as a dysplasia-associated lesion or mass (DALM), which may be indistinguishable from a sporadic adenoma in non-colitic tissue, or may arise in flat mucosa of endoscopically normal appearance. Information about the endoscopic appearance, the colonic distribution and the histopathological grade of colitis-associated dysplasia is required to define the optimal treatment. This Review summarizes the endoscopic and histopathological features of colitis-associated dysplasia and the requirements for optimal interaction between endoscopists and pathologists, with the aim of reducing the uncertainties in the diagnosis of dysplastic lesions and improving the management of colitis-associated dysplasia.
Key Points
-
Identification and classification of colitis-associated dysplasia is still a challenge
-
It is important to distinguish sporadic adenomas that are not associated with inflammation from colitis-associated dysplasia, because the behavior of these lesions and the associated cancer risk differ greatly
-
To improve the accuracy of the histopathological diagnosis of colitis-associated dysplasia, pathologists may benefit from additional clinical and endoscopic information
-
Regular, scheduled meetings between pathologists and endoscopists to discuss difficult cases may be useful to help reach an unequivocal diagnosis of colitis-associated dysplasia
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Itzkowitz, S. H. & Yio, X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 287, G7–17 (2004).
Rutter, M. et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 126, 451–459 (2004).
Gupta, R. B. et al. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology 133, 1099–1105 (2007).
Levin, B. Ulcerative colitis and colon cancer: biology and surveillance. J. Cell Biochem. Suppl. 16G, 47–50 (1992).
Eaden, J. A., Abrams, K. R. & Mayberry, J. F. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48, 526–535 (2001).
Bernstein, C. N., Blanchard, J. F., Kliewer, E. & Wajda, A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 91, 854–862 (2001).
Gillen, C. D., Walmsley, R. S., Prior, P., Andrews, H. A. & Allan, R. N. Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. Gut 35, 1590–1592 (1994).
SEER Cancer Statistics Review 1975–2006 (updated May 29, 2009). http://seer.cancer.gov/csr/1975_2006/index.html
Eaden, J. A. & Mayberry, J. F. Guidelines for screening and surveillance of asymptomatic colorectal cancer in patients with inflammatory bowel disease. Gut 51 (Suppl. 5), V10–V12 (2002).
Winawer, S. et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology 124, 544–560 (2003).
Blackstone, M. O., Riddell, R. H., Rogers, B. H. & Levin, B. Dysplasia-associated lesion or mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: an indication for colectomy. Gastroenterology 80, 366–374 (1981).
Torres, C., Antonioli, D. & Odze, R. D. Polypoid dysplasia and adenomas in inflammatory bowel disease: a clinical, pathologic, and follow-up study of 89 polyps from 59 patients. Am. J. Surg. Pathol. 22, 275–284 (1998).
Bernstein, C. N., Shanahan, F. & Weinstein, W. M. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis? Lancet 343, 71–74 (1994).
Riddell, R. H. et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum. Pathol. 14, 931–968 (1983).
Eaden, J., Abrams, K., McKay, H., Denley, H. & Mayberry, J. Inter-observer variation between general and specialist gastrointestinal pathologists when grading dysplasia in ulcerative colitis. J. Pathol. 194, 152–157 (2001).
Melville, D. M. et al. Observer study of the grading of dysplasia in ulcerative colitis: comparison with clinical outcome. Hum. Pathol. 20, 1008–1014 (1989).
Karlen, P. et al. Is colonoscopic surveillance reducing colorectal cancer mortality in ulcerative colitis? A population based case control study. Gut 42, 711–714 (1998).
Connell, W. R. et al. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis. Gastroenterology 107, 934–944 (1994).
Friedman, S., Rubin, P. H., Bodian, C., Harpaz, N. & Present, D. H. Screening and surveillance colonoscopy in chronic Crohn's colitis: results of a surveillance program spanning 25 years. Clin. Gastroenterol. Hepatol. 6, 993–998 (2008).
Rutter, M. D. et al. Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis. Gastroenterology 130, 1030–1038 (2006).
Claessen, M. M., Vleggaar, F. P., Tytgat, K. M., Siersema, P. D. & van Buuren, H. R. High lifetime risk of cancer in primary sclerosing cholangitis. J. Hepatol. 50, 158–164 (2009).
Broome, U., Lofberg, R., Veress, B. & Eriksson, L. S. Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential. Hepatology 22, 1404–1408 (1995).
Rubin, C. E. et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology 103, 1611–1620 (1992).
Lutgens, M. W. et al. High frequency of early colorectal cancer in inflammatory bowel disease. Gut 57, 1246–1251 (2008).
Rutter, M. D. et al. Most dysplasia in ulcerative colitis is visible at colonoscopy. Gastrointest. Endosc. 60, 334–339 (2004).
Odze, R. D., Farraye, F. A., Hecht, J. L. & Hornick, J. L. Long-term follow-up after polypectomy treatment for adenoma-like dysplastic lesions in ulcerative colitis. Clin. Gastroenterol. Hepatol. 2, 534–541 (2004).
Odze, R. D., Brown, C. A., Hartmann, C. J., Noffsinger, A. E. & Fogt, F. Genetic alterations in chronic ulcerative colitis-associated adenoma-like DALMs are similar to non-colitic sporadic adenomas. Am. J. Surg. Pathol. 24, 1209–1216 (2000).
Fogt, F. et al. Distinction between dysplasia-associated lesion or mass (DALM) and adenoma in patients with ulcerative colitis. Hum. Pathol. 31, 288–291 (2000).
Matsumoto, T. et al. Endoscopic and chromoendoscopic atlas featuring dysplastic lesions in surveillance colonoscopy for patients with long-standing ulcerative colitis. Inflamm. Bowel. Dis. 14, 259–264 (2008).
Blonski, W. et al. Is dysplasia visible during surveillance colonoscopy in patients with ulcerative colitis? Scand. J. Gastroenterol. 43, 698–703 (2008).
Ullman, T., Croog, V., Harpaz, N., Sachar, D. & Itzkowitz, S. Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis. Gastroenterology 125, 1311–1319 (2003).
Befrits, R., Ljung, T., Jaramillo, E. & Rubio, C. Low-grade dysplasia in extensive, long-standing inflammatory bowel disease: a follow-up study. Dis. Colon Rectum 45, 615–620 (2002).
Jess, T. et al. Incidence and prognosis of colorectal dysplasia in inflammatory bowel disease: a population-based study from Olmsted County, Minnesota. Inflamm. Bowel Dis. 12, 669–676 (2006).
Dixon, M. F. et al. Observer variation in the assessment of dysplasia in ulcerative colitis. Histopathology 13, 385–397 (1988).
Odze, R. D. et al. Interobserver variability in the diagnosis of ulcerative colitis-associated dysplasia by telepathology. Mod. Pathol. 15, 379–386 (2002).
Pietsch, E. C., Sykes, S. M., McMahon, S. B. & Murphy, M. E. The p53 family and programmed cell death. Oncogene 27, 6507–6521 (2008).
Ajioka, Y., Watanabe, H. & Matsuda, K. Over-expression of p53 protein in neoplastic changes in ulcerative colitis: immunohistochemical study. J. Gastroenterol. 30 (Suppl. 8), 33–35 (1995).
Brentnall, T. A. et al. Mutations in the p53 gene: an early marker of neoplastic progression in ulcerative colitis. Gastroenterology 107, 369–378 (1994).
Harpaz, N. et al. p53 protein expression in ulcerative colitis-associated colorectal dysplasia and carcinoma. Hum. Pathol. 25, 1069–1074 (1994).
Sato, A. & MacHinami, R. p53 immunohistochemistry of ulcerative colitis-associated with dysplasia and carcinoma. Pathol. Int. 49, 858–868 (1999).
Andersen, S. N., Rognum, T. O., Bakka, A. & Clausen, O. P. Ki-67: a useful marker for the evaluation of dysplasia in ulcerative colitis. Mol. Pathol. 51, 327–332 (1998).
Wong, N. A., Mayer, N. J., MacKell, S., Gilmour, H. M. & Harrison, D. J. Immunohistochemical assessment of Ki67 and p53 expression assists the diagnosis and grading of ulcerative colitis-related dysplasia. Histopathology 37, 108–114 (2000).
Shinozaki, M. et al. High proliferative activity is associated with dysplasia in ulcerative colitis. Dis. Colon Rectum 43, S34–S39 (2000).
Sjoqvist, U., Ost, A. & Lofberg, R. Increased expression of proliferative Ki-67 nuclear antigen is correlated with dysplastic colorectal epithelium in ulcerative colitis. Int. J. Colorectal Dis. 14, 107–113 (1999).
Aust, D. E. et al. Altered distribution of beta-catenin, and its binding proteins E-cadherin and APC, in ulcerative colitis-related colorectal cancers. Mod. Pathol. 14, 29–39 (2001).
van Dekken, H. et al. Wnt pathway-related gene expression during malignant progression in ulcerative colitis. Acta Histochem. 109, 266–272 (2007).
Dorer, R. & Odze, R. D. AMACR immunostaining is useful in detecting dysplastic epithelium in Barrett's esophagus, ulcerative colitis, and Crohn's disease. Am. J. Surg. Pathol. 30, 871–877 (2006).
Marx, A. et al. Combined alpha-methylacyl coenzyme A racemase/p53 analysis to identify dysplasia in inflammatory bowel disease. Hum. Pathol. 40, 166–173 (2009).
Strater, J., Wiesmuller, C., Perner, S., Kuefer, R. & Moller, P. Alpha-methylacyl-CoA racemase (AMACR) immunohistochemistry in Barrett's and colorectal mucosa: only significant overexpression favours a diagnosis of intraepithelial neoplasia. Histopathology 52, 399–402 (2008).
Floren, C. H., Benoni, C. & Willen, R. Histologic and colonoscopic assessment of disease extension in ulcerative colitis. Scand. J. Gastroenterol. 22, 459–462 (1987).
Niv, Y., Bat, L., Ron, E. & Theodor, E. Change in the extent of colonic involvement in ulcerative colitis: a colonoscopic study. Am. J. Gastroenterol. 82, 1046–1051 (1987).
Mathy, C. et al. Gross versus microscopic pancolitis and the occurrence of neoplasia in ulcerative colitis. Inflamm. Bowel Dis. 9, 351–355 (2003).
Yano, Y. et al. Risks and clinical features of colorectal cancer complicating Crohn's disease in Japanese patients. J. Gastroenterol. Hepatol. 23, 1683–1688 (2008).
Ekbom, A., Helmick, C., Zack, M. & Adami, H. O. Ulcerative colitis and colorectal cancer. A population-based study. N. Engl. J. Med. 323, 1228–1233 (1990).
Askling, J. et al. Family history as a risk factor for colorectal cancer in inflammatory bowel disease. Gastroenterology 120, 1356–1362 (2001).
Nuako, K. W. et al. Familial predisposition for colorectal cancer in chronic ulcerative colitis: a case-control study. Gastroenterology 115, 1079–1083 (1998).
Kornfeld, D., Ekbom, A. & Ihre, T. Is there an excess risk for colorectal cancer in patients with ulcerative colitis and concomitant primary sclerosing cholangitis? A population based study. Gut 41, 522–525 (1997).
Thomas, T., Nair, P., Dronfield, M. W. & Mayberry, J. F. Management of low and high-grade dysplasia in inflammatory bowel disease: the gastroenterologists' perspective and current practice in the United Kingdom. Eur. J. Gastroenterol. Hepatol. 17, 1317–1324 (2005).
Engelsgjerd, M., Farraye, F. A. & Odze, R. D. Polypectomy may be adequate treatment for adenoma-like dysplastic lesions in chronic ulcerative colitis. Gastroenterology 117, 1288–1294 (1999).
Rubin, P. H. et al. Colonoscopic polypectomy in chronic colitis: conservative management after endoscopic resection of dysplastic polyps. Gastroenterology 117, 1295–1300 (1999).
Ellis, K. K. & Fennerty, M. B. Marking and identifying colon lesions. Tattoos, clips, and radiology in imaging the colon. Gastrointest. Endosc. Clin. N. Am. 7, 401–411 (1997).
Shatz, B. A., Weinstock, L. B., Swanson, P. E. & Thyssen, E. P. Long-term safety of India ink tattoos in the colon. Gastrointest. Endosc. 45, 153–156 (1997).
Rutter, M. D. et al. Pancolonic indigo carmine dye spraying for the detection of dysplasia in ulcerative colitis. Gut 53, 256–260 (2004).
Kiesslich, R. et al. Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Gastroenterology 124, 880–888 (2003).
Marion, J. F. et al. Chromoendoscopy-targeted biopsies are superior to standard colonoscopic surveillance for detecting dysplasia in inflammatory bowel disease patients: a prospective endoscopic trial. Am. J. Gastroenterol. 103, 2342–2349 (2008).
Song, L. M. et al. Narrow band imaging and multiband imaging. Gastrointest. Endosc. 67, 581–589 (2008).
Matsumoto, T. et al. Magnifying colonoscopy with narrow band imaging system for the diagnosis of dysplasia in ulcerative colitis: a pilot study. Gastrointest. Endosc. 66, 957–965 (2007).
Kuznetsov, K., Lambert, R. & Rey, J. F. Narrow-band imaging: potential and limitations. Endoscopy 38, 76–81 (2006).
Dekker, E. et al. Narrow-band imaging compared with conventional colonoscopy for the detection of dysplasia in patients with longstanding ulcerative colitis. Endoscopy 39, 216–221 (2007).
van den Broek, F. J. et al. Endoscopic tri-modal imaging for surveillance in ulcerative colitis: randomised comparison of high-resolution endoscopy and autofluorescence imaging for neoplasia detection; and evaluation of narrow-band imaging for classification of lesions. Gut 57, 1083–1089 (2008).
Kiesslich, R., Goetz, M., Vieth, M., Galle, P. R. & Neurath, M. F. Confocal laser endomicroscopy. Gastrointest. Endosc. Clin. N. Am. 15, 715–731 (2005).
Kiesslich, R. et al. Chromoscopy-guided endomicroscopy increases the diagnostic yield of intraepithelial neoplasia in ulcerative colitis. Gastroenterology 132, 874–882 (2007).
Author information
Authors and Affiliations
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
van Schaik, F., Offerhaus, G., Schipper, M. et al. Endoscopic and pathological aspects of colitis-associated dysplasia. Nat Rev Gastroenterol Hepatol 6, 671–678 (2009). https://doi.org/10.1038/nrgastro.2009.162
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrgastro.2009.162
This article is cited by
-
Clonal evolution of colorectal cancer in IBD
Nature Reviews Gastroenterology & Hepatology (2017)
-
Forty-Year Analysis of Colonoscopic Surveillance Program for Neoplasia in Ulcerative Colitis: An Updated Overview
American Journal of Gastroenterology (2015)
-
WHO-Klassifikation 2010 für den unteren Gastrointestinaltrakt
Der Pathologe (2011)