Journal of Crohn's and Colitis (2014) 8, 1735–1739

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SHORT REPORT

A rare case series of concomitant inflammatory bowel disease, sporadic adenomas, and serrated polyposis syndrome☆ J.D. Feuerstein a,b,⁎, S.N. Flier b , E.U. Yee c , D. Pleskow b , A.S. Cheifetz b a

330 Brookline Ave. E/Dana 501, Boston, MA 02215, United States Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, United States c Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, United States b

Received 23 May 2014; received in revised form 27 June 2014; accepted 2 July 2014 KEYWORDS IBD; Ulcerative colitis; Crohn's; Serrated polyposis syndrome; Hyperplastic polyposis syndrome; Adenoma

Abstract Background and aims: Inflammatory bowel disease (IBD) involving the colon is associated with an increased risk of colon cancer. Patients may develop sporadic adenomas further increasing their risk of colorectal cancer. Current knowledge of IBD with concomitant serrated polyposis syndrome (SPS) is limited. We describe four patients with both IBD and SPS. Methods: Four patients with inflammatory bowel disease and hyperplastic polyps referred to Beth Israel Deaconess Medical Center meeting the World Health Organization (WHO) criteria for SPS were identified. Results: Four patients with long standing IBD involving the colon were identified. All of these patients' IBD were in clinical remission. Additionally, 2 of the 4 patients were also noted to have sporadic adenomas. Each patient was also found to have multiple sessile serrated adenomas and hyperplastic polyps meeting the WHO criteria for SPS. Two of the patients had colonoscopy with chromoendoscopy which improved polyp detection. Discussions were held with each patient regarding the potentially increased risk of colorectal cancer with the combination of IBD and SPS. Patients were advised that colectomy would be the safest method to reduce the risk of cancer. None of the patients opted for colectomy and instead planned on a repeat colonoscopy with chromoendoscopy at 3–12 month intervals. Conclusion: Serrated polyposis syndrome develops in patients with IBD. It is unclear how high the risk of colon cancer is in patients who have both IBD and SPS and what the recommendations

☆ No funding was provided for this manuscript. ⁎ Corresponding author. E-mail addresses: [email protected] (J.D. Feuerstein), [email protected] (S.N. Flier), [email protected] (E.U. Yee), [email protected] (D. Pleskow), [email protected] (A.S. Cheifetz).

http://dx.doi.org/10.1016/j.crohns.2014.07.001 1873-9946/© 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

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J.D. Feuerstein et al. should be regarding the frequency of surveillance or surgery. Further studies are necessary to identify the optimal management of these patients. © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

1. Introduction

2. Case series

Inflammatory bowel disease (IBD) associated colitis is associated with an increased risk of colon cancer when the disease involves more than the rectum and sigmoid colon. Classically, in ulcerative colitis, the risk of cancer has been reported as 2% after 10 years, 8% after 20 years, and 18% after 30 years of disease. However, more recent studies have indicated that this risk may in fact be much lower.1,2 Current American Gastroenterological Association Guidelines recommend initiating colorectal cancer surveillance colonoscopies every 1–3 years starting 8 years after diagnosis in patients with left sided or extensive disease.3 The European Crohn's and Colitis Organisation guidelines have similar recommendations regarding colorectal cancer screening for patients with left sided or extensive disease beginning 8 years after the diagnosis, but the surveillance intervals range from 1 to 5 years depending on patient specific risk factors.4 The risk of colon cancer is increased further in patients with adenomas. Current recommendations suggest that close colonoscopic surveillance can be performed in patients with adenomas that are completely removed as long as there is no dysplasia elsewhere in the colon.3–5 Patients with IBD can also have a genetic colon cancer syndrome. Serrated polyposis syndrome (formerly referred to as hyperplastic polyposis syndrome) is a more recently described polyposis syndrome associated with an increased risk of colon cancer. Serrated polyposis syndrome is diagnosed based on criteria from the World Health Organization (WHO).6 A diagnosis can be made if a patient meets any of the three criteria: 1) at least five serrated polyps proximal to the sigmoid colon of which at least 2 are ≥ 10 mm, 2) any number of serrated polyps proximal to the sigmoid colon in an individual with a first degree relative with serrated polyposis syndrome, and 3) greater than 20 serrated polyps of any size throughout the colon.6 Patients with serrated polyposis syndrome are at increased risk of developing colon cancer. The exact increase in risk is unclear with studies reporting incidence of colon cancer in patients with serrated polyposis syndrome ranging from 25 to 70%.7–10 In contrast, one study of 15 patients with serrated polypsosis syndrome did not identify any cancers during a three year interval of surveillance colonoscopy.11 Importantly, prospective studies assessing the true cancer risk are lacking. Current guidelines advise for removal of all polyps and a US multi-task force guideline recommends yearly screening colonoscopy though it is based on expert opinion only.12,13 The European Society of Gastrointestinal Endoscopy (ESGE) endorses the use of high definition colonoscopy systems as well as chromoendoscopy or narrow band imaging (NBI) (strong recommendation, low quality evidence).14 In this case series, we report on 4 patients who have long standing IBD and serrated polyposis syndrome who may be at a significantly higher risk of developing colon cancer in the setting of both conditions.

2.1. Patient 1 33 year old male with a history of extensive ulcerative colitis was diagnosed 15 years ago. He had multiple flares despite mesalamine and was transitioned to azathioprine while continuing mesalamine three years ago. Since that time he has remained in clinical remission. On a recent colonoscopy by a specialist in IBD, he had no evidence of active colitis but had a 3 mm sporadic adenoma at 50 cm. He presented for a repeat colonoscopy six months later by the same endoscopist with chromoendoscopy and was noted to have 15 hyperplastic polyps and 2 sessile serrated adenomas proximal to the rectosigmoid and an additional 10 hyperplastic polyps and 1 sessile serrated adenomas in the rectosigmoid area all ranging in size from 2 mm to 10 mm that were removed. The pathology was reviewed and confirmed by an expert gastrointestinal pathologist. This patient's findings met both the first and third WHO serrated polyposis syndrome criteria.

2.2. Patient 2 52 year old female with a history of Crohn's ileocolitis was diagnosed 27 years ago. Over the years, she was maintained in remission with sulfasalazine and eventually mesalamine. Two years prior to presenting to our medical center, she had a colonoscopy showing low grade dysplasia in a random biopsy from the left colon as well as two sporadic adenomas which were confirmed by an expert gastrointestinal pathologist. A repeat colonoscopy the following year did not demonstrate any dysplasia. After establishing care at our medical center she was scheduled for a colonoscopy with chromoendoscopy by a specialist in IBD. Thirty flat polyps, 10 of which were proximal to the rectosigmoid junction were found during chromoendoscopy ranging in size from 2 mm to 8 mm. All 30 specimens were consistent with hyperplastic polyps. The pathology was reviewed and confirmed by an expert gastroenterology pathologist. This patient met the 3rd WHO criteria for serrated polyposis syndrome.

2.3. Patient 3 51 year old male with a history of extensive ulcerative colitis was diagnosed 30 years ago. He was initially treated with sulfasalazine but discontinued therapy after 10 years and remained in remission off medications since that time. His two most recent colonoscopies showed multiple subtle flat polyps which were noted on pathology to be sessile serrated adenomas or hyperplastic polyps. The polyps ranged in size from 2 mm to 30 mm. At least 7 sessile serrated polyps over 10 mm in size were biopsied or removed, and 14 hyperplastic polyps were biopsied or removed. In total, 14 of the hyperplastic polyps and all 7 sessile serrated polyps were proximal to the rectosigmoid junction. He presented to our

A rare case series of concomitant IBD, sporadic adenomas, and SPS medical center for a second opinion and a repeat colonoscopy was performed. Numerous flat polyps ranging in size from 3 mm to 15 mm were noted throughout the colon. Given the countless number of polyps, the majority of the polyps were not removed. Of those removed, 3 were sessile serrated adenomas and 7 were hyperplastic polyps; all but two of the hyperplastic polyps were proximal to the rectosigmoid junction. The pathology was reviewed and confirmed by an expert gastroenterology pathologist. This patient qualified for both the first and third WHO criteria for serrated polyposis syndrome.

2.4. Patient 4 55 year old female was diagnosed with Crohn's colitis 17 years ago. She was treated with mesalamine and did quite well. She had a number of colonoscopies done outside our medical center. Notably, in 2009, 2011, and 2013 she had multiple polyps ranging in size from 1 mm to 20 mm and primarily occurring proximal to the sigmoid colon. On pathology from these procedures she had 18 hyperplastic polyps and 3 sessile serrated adenomas of which all but one hyperplastic polyp was proximal to the rectosigmoid junction. She was referred to our medical center for further discussion regarding colorectal cancer risk and future screening. Based on her records, she met the first and third WHO criteria for serrated polyposis syndrome. Despite recommendations for closer follow-up colonoscopy surveillance, none of the four patients have undergone repeat screening colonoscopies at 3–6 months of follow-up. See Figs. 1–3 for representative examples of endoscopic and pathologic images of an adenoma, a sessile serrated adenoma, and a hyperplastic polyp from these patients.

3. Discussion We describe 4 patients with longstanding, quiescent IBD and findings consistent with serrated polyposis syndrome. To date, there is only one case series describing serrated polyposis syndrome in association with IBD associated colitis.15 This report consisted of three patients, two of whom had the diagnosis made after colectomy for

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adenocarcinoma of the colon. All three patients had long-standing IBD for over ten years. Two patients had ulcerative colitis and one had Crohn's ileocolitis. The number of sessile polyps ranged from 20 to over 100 in these patients.15 The majority of sporadic colon cancers develop from adenomas. Adenomas form polypoid lesions via the chromosomal instability pathway with early mutations in the adenomatous polyposis coli gene and late mutations in the tumor suppressor gene p53.16,17 In IBD, loss of heterozygosity of tumor suppressor gene p53 and src activation occurs early, and dysplasia can be found in flat, non-polypoid appearing mucosa.17 Serrated polyposis syndrome appears to be associated with widespread DNA hypermethylation in the gene promoter regions (e.g. hmLH-1), and leads to microsatellite instability resulting in colon cancer.15,18 Importantly, these three pre-cancerous conditions all develop through different genetic pathways. It is as yet unclear if these three pathways have a synergistic effect to significantly increase the risk of colon cancer. In our case series, a number of the polyps were visible on standard white light endoscopy. However, in two cases, the use of chromoendoscopy appears to have markedly improved the polyp detection rate. In one patient, the colonoscopy was performed six months prior to using only white light endoscopy, and none of the hyperplastic lesions were identified. Similarly, in the second case in which chromoendoscopy was utilized, there were multiple polyps that were not identified on initial white light inspection and were only seen after spraying with indigo carmine. These findings are in line with the ESGE recommendation in patients with serrated polyposis syndrome to utilize pancolonic chromoendoscopy.14 In the two cases that chromoendoscopy was utilized, it enhanced the detection of subtle sessile polyps that were not initially seen with white light endoscopy. At this time there are no clear recommendations regarding the ideal management of patients with serrated polyposis syndrome and IBD. Current societal guidelines recommend screening colonoscopy every 1–3 years in patients with long-standing colitis.3 Based on expert opinions, guidelines recommend a yearly colonoscopy in patients with serrated polyposis syndrome given the potential high risk of developing colon cancer.12 Whether patients with both conditions are at an even higher risk of colon cancer

Figure 1 a. Sessile adenoma. b. Tubular adenoma. Colonic crypts contain columnar cells with enlarged, elongated hyperchromatic, and pseudostratified nuclei (200 × magnification).

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Figure 2 a. Sessile serrated adenoma with chromoendoscopy. b. Sessile serrated adenoma. The characteristic dilated crypt base is depicted here (200 × magnification).

and should be screened differently remains unknown at this time. In our series of patients, all were given the option to consider colectomy as the safest approach to prevent colon cancer given the limited understanding of how high the risk of colon cancer is when both diseases are present or continued close surveillance colonoscopy with the caveat that this may not be adequate. In patient 3 where removal of all the polyps did not seem feasible, he was advised that colectomy was the only acceptable option. The two patients with adenomas and the patient with the focal low grade dysplasia seen on one colonoscopy were advised that they had an additional potential risk factor for colon cancer separate from their IBD and serrated polyposis syndrome risks. The risks and benefits of colectomy versus ongoing colonoscopic surveillance were reviewed with the patients.

All the patients agreed to repeat screening intervals ranging from 3 months to 12 months. Given the importance of resecting all polyps and the ability of chromoendoscopy to highlight mucosal irregularities, all the patients were advised to undergo repeated colonoscopy with chromoendoscopy.

4. Conclusion In summary, we present four patients with a rare combination of IBD and serrated polyposis syndrome. It is unclear if the colorectal cancer risks of IBD, sporadic adenomas and serrated polyposis syndrome are additive or not but the overall risk of cancer is high. Further prospective studies are necessary to determine the appropriate recommendations to reduce the risk of colorectal cancer in this unique patient population.

Figure 3 a. Hyperplastic polyp on white light endoscopy. b. Hyperplastic polyps on chromoendoscopy. c. Hyperplastic polyp. This polyp shows the typical serrated glandular architecture with narrow crypt bases (100 × magnification).

A rare case series of concomitant IBD, sporadic adenomas, and SPS

Conflict of interest statement No author reports any relevant conflicts of interest pertaining to this manuscript.

Acknowledgments Each author participated in the acquisition of data in this case and in writing the manuscript. No authors report any relevant conflicts of interest. Study design: Feuerstein, Flier, Cheifetz, and Pleskow. Manuscript preparation: Feuerstein, Cheifetz, Flier, Pleskow, and Yee. Critical revisions: Feuerstein, Cheifetz, Flier, Pleskow, and Yee.

References 1. Farraye FA, Odze RD, Eaden J, Itzkowitz SH. AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010;138:746–774.e4. 2. Jess T, Simonsen J, Jørgensen KT, Pedersen BV, Nielsen NM, Frisch M. Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. Gastroenterology 2012;143:375–381. e1. 3. Farraye FA, Odze RD, Eaden J, et al. AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010;138:738–45. 4. Annese V, Daperno M, Rutter MD, et al. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis 2013;7:982. 5. Viani KL, Doyle LA, Farraye FA, et al. Polypoid lesions in inflammatory bowel disease. Tech Gastrointest Endosc 2013;15: 113–20. 6. Snover D, Ahnen D, Burt R, et al. Serrated polyps of the colon and rectum and serrated polyposis. WHO classification of tumours of the digestive system4th ed. Lyon: IARC; 2010;160–5.

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7. Hyman NH, Anderson P, Blasyk H. Hyperplastic polyposis and the risk of colorectal cancer. Dis Colon Rectum 2004;47:2101–4. 8. Rubio CA, Stemme S, Jaramillo E, et al. Hyperplastic polyposis coli syndrome and colorectal carcinoma. Endoscopy 2006;38: 266–70. 9. Boparai KS, Mathus-Vliegen EM, Koornstra JJ, Nagengast FM, van Leerdam M, van Noesel CJ, et al. Increased colorectal cancer risk during follow-up in patients with hyperplastic polyposis syndrome: a multicentre cohort study. Gut 2009;59(8):1094–100. 10. Kalady MF, Jarrar A, Leach B, et al. Defining phenotypes and cancer risk in hyperplastic polyposis syndrome. Dis Colon Rectum 2011;54:164–70. 11. Ferrandez A, Samowitz W, DiSario JA, et al. Phenotypic characteristics and risk of cancer development in hyperplastic polyposis: case series and literature review. Am J Gastroenterol 2004;99:2012–8. 12. Lieberman DA, Rex DK, Winawer SJ, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012;143:844–57. 13. Hassan C, Quintero E, Dumonceau J-M, et al. Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2013;45:842–64. 14. Kamiński MF, Hassan C, Bisschops R, et al. Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2014;46:435–57. 15. Srivastava A, Redston M, Farraye FA, et al. Hyperplastic/serrated polyposis in inflammatory bowel disease: a case series of a previously undescribed entity. Am J Surg Pathol 2008;32: 296–303. 16. Makkar R, Pai RK, Burke CA. Sessile serrated polyps: cancer risk and appropriate surveillance. Cleve Clin J Med 2012;79: 865–71. 17. Rubin DC, Shaker A, Levin MS. Chronic intestinal inflammation: inflammatory bowel disease and colitis-associated colon cancer. Front Immunol 2012:3. 18. Boparai K, Reitsma J, Lemmens V, et al. Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome. Gut 2010;59:1222–5.

A rare case series of concomitant inflammatory bowel disease, sporadic adenomas, and serrated polyposis syndrome.

Inflammatory bowel disease (IBD) involving the colon is associated with an increased risk of colon cancer. Patients may develop sporadic adenomas furt...
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