1. Serrated Polyps of the Colon Aaron Sinclair, MD University of Kansas School of Medicine – Wichita Department of Family and Community Medicine Wesley Family Medicine Residency 8/7/14

2. Learning Objectives: Distinguish the malignant potential of serrated polyps and adenomas Identify when serrated polyps are considered serrated polyposis syndrome Describe the relationship between hyperplastic polyps and serrated polyps

3. Case Presentation 50 yo male presents for screening colonoscopy. Diverticula noted 40 cm and 80 cm there were 3-4 mm polyps completely excised with cold forceps biopsy. Operative Report Recommendation at 10 years. Pathology: Sessile Serrated Polyp – 2 days later. Treatment:?

4. Classification - Serrated Polyps World Health Organization (WHO) Hyperplastic Polyps (HP) Sessile Serrated Adenomas/polyps (SSA/P) Traditional Serrated Adenomas (TSA) Historical Context 1990 – First described in the literature 2005 - Pathological distinctions first appeared 2008 – First pathological diagnostic criteria and nomenclature introduced. 2010 – WHO adopted criteria

5. Importance of Serrated Polyps Prevalence of Proximal Serrated Polyps of 5-8% of all average risk screening colonoscopies 15-35% of all cancers are secondary to serrated polyps The progression of dysplasia to cancer for Sessile Serrated Adenomas and Polyps is 10-15 years. Only about 10% of all tubular adenomas progress to cancer Typically tubular adenomas are larger, progress in 8-12 years to cancer.

6. Importance of Serrated Polyps How many Repeat Normal 10 year follow-up Colonoscopies are you doing that quite possibly were serrated polyps not hyperplastic polyps?

7. Figure 3. A, Sessile serrated adenoma (SSA). Arrows mark edges of an SSA. B, An SSA with early carcinoma. The erythematous/ulcerated area represents the early carcinoma; the arrows indicate the edges of the residual SSA. Bars: 20 mm. The serrated pathway to colorectal carcinoma: current concepts and challenges. Bettington et al. Histopathology 2013, 62, 367–386.

8. Serrated Adenoma Pathway: Sessile serrated adenomas frequently (78%) have BRAF mutations or K-ras mutations (11%) Hyperplastic polyps which show frequent K-ras mutations (70%) with less common BRAF mutations (20%) MLH1 promoter methylation is frequent in serrated polyps, suggesting that they give rise to sporadic colorectal carcinoma with MSI Smoking and estrogen withdrawal may be associated with serrated pathway carcinoma

9. 80%

10. Classification - Serrated Polyps World Health Organization (WHO) Hyperplastic Polyps (HP) Sessile Serrated Adenomas/polyps (SSA/P) Traditional Serrated Adenomas (TSA)

11. Hyperplastic Polyps 80 - 90% of all Serrated Polyps Malignant potential - <1% Size: < 5mm Typical Location is Recto-Sigmoid Increases in number up to 50 years of age then stable thereafter.

12. Hyperplastic Polyps Mucosa is typically paler Size <5 mm

13. Sessile Serrated Adenomas/Polyps 8-15% of all Serrated Polyps Malignant Potential – uncertain but higher than adenomatous polyps which is at least 25% over 10 years if larger than 2 cm. Size is variable Equally distributed between right and left colon. Increases in number throughout life.

14. Sessile Serrated Polyp Typically covered with a “mucus cap” Grow horizontally, flat, sessile Size is variable 50% >5mm 12-20% > 10 mm Red and Puckered appearance

15. Sessile Serrated Adenoma Typically covered with a “mucus cap” Size is variable typically greater than 5 mm Red and Puckered appearance

16. Traditional Serrated Adenomas 2-5% of all Serrated Polyps Malignant Potential – 3 fold increased risk compared to Adenomatous Polyps Predominately Left Sided Increases in number throughout life

17. Traditional Serrated Adenoma Variable size up to 5 cm Often adenomatous appearing Red appearance

19. How accurate are pathologist in depicting a Serrated Polyp from a Hyperplastic Polyp? The Clinical Significance of Serrated Polyps - Christopher S Huang, Francis A Farraye, Shi Yang and Michael J O'Brien American Journal of Gastroenterology

20. How Reliable is the Diagnosis Virchows Archives, 2012 – 70 cases using World Health Organization Pathological Diagnostic Criteria/Worksheets – 16 European Pathologists 28 Hyperplastic Polyps 25 Sessile Serrated Adenomas/Polyps 11 Traditional Serrated Adenomas 15 Mixed HP with SSP features – How do you think the 16 pathologists do?

21. How Reliable is the Diagnosis Virchows Archives, 2012 – 16 European Pathologists 28 Hyperplastic Polyps – 44% got all 28 25 Sessile Serrated Adenomas/Polyps – 40% got all 20 11 Traditional Serrated Adenomas – 10% got all 11 15 Mixed HP with SSP features – 6% got all 15 – How do you think the 16 pathologists did? After 2 rounds and a conference reviewing the WHO diagnostic criteria, they were able to come to near perfect alignment on diagnosis. The authors of this study stated that at best reproducibility of the histopathological diagnosis on a Serrated Polyp remains imperfect.

22. Identification in the presence of the prep. The Clinical Significance of Serrated Polyps - Christopher S Huang, Francis A Farraye, Shi Yang and Michael J O'Brien American Journal of Gastroenterology

23. Hyperplastic Polyps vs Serrated Adenomas – are we missing them. Polyp Miss Rates High for Colonoscopies Done After Poor Bowel Preparation ScienceDaily (June 13, 2011) In the context of suboptimal bowel preparation, of all adenomas identified, 42 percent were discovered only during a repeat colonoscopy.

24. Current Recommendation for Hyperplastic Polyps Remove all polyps when technically possible except for the small (<5mm) distal hyperplastic – appearing polyps that can be sample to confirm they are true HP’s

25. Serrated Polyposis Syndrome At least 5 hyperplastic polyps proximal to the sigmoid colon – At least two of them greater than 10 mm More than 30 hyperplastic polyps evenly distributed throughout the colon Any number of hyperplastic polyps proximal to the sigmoid colon with a family member with diagnosis of Serrated Polyposis Syndrome

26. Serrated Polyposis Syndrome Treatment is Colonoscopy every 1-3 years with complete removal of ALL polyps. Start at age of 45 for first degree relatives or 5 years younger than the age of initial diagnosis 40% risk of lifetime cancer Not all that different from Colorectal Cancer recommendations.

27. Surveillance Recommendations Every 5 years if the Sessile Serrated Polyp/Adenoma are less than two in number and/or greater than 1 cm in size. Every 3 years if the Sessile Serrated Polyp/Adenoma are three or more in number and/or greater than 1 cm in size If a Sessile Serrated Polyp/Adenoma is removed and any comments of cytological dysplasia are mentioned, perform a one year post removal to ensure complete removal.

28. Surveillance Recommendations Traditional Serrated Adenomas – follow the guidelines for typical adenomas.

29. Approach to the patient with colonic polyps. www.utdol.com

30. Measuring Quality Current quality markers suggest Screening Colonoscopy of Average Risk Patients – Men – 25% Adenoma Detection Rate – Women – 15% Adenoma Detection Rate Study of 15 Gastroenterologists between 2000-2009 – Showed a serrated adenoma detection risk of 4.5% (Expected Prevalence Rate of 5-8%) – Correlated with quality marker expectations of the Adenoma Detection Rate High colonoscopic prevalence of proximal colon serrated polyps in average-risk men and women. Kahi et al. Gastrointestinal Endoscopy 2012. 75.3

31. References High colonoscopic prevalence of proximal colon serrated polyps in average-risk men and women. Kahi et al. Gastrointestinal Endoscopy 2012. 75.3 The Clinical Significance of Serrated Polyps - Christopher S Huang, Francis A Farraye, Shi Yang and Michael J O'Brien. American Journal of Gastroenterology Serrated Polyps of the colon and rectum, and serrated polyposis. Snover DC, Ahnen DJ et al. (2010)In: Bosman Et al. WHO Classification of tumours of the digestive system, 4th edition. pp 160-165 The serrated pathway to colorectal carcinoma: current concepts and challenges. Bettington et al. 22 JAN 2013 Serrated plyps of the colon and rectum – proposal for diagnostic criteria. Daniela E. Aust and Gustavo B. Baretto. Virchows Arch (2010) 457:291-297. Cancer risks for relatives of patients with serrated polyposis. Win AK et al. Am j Gastroenterol. 2012 May; 107 (5): 770-778. Screening, management and surveillance for the sessile serrated adenomas/polyps. Xiangshen Fu, Ye Qiu, Yali Zhang. Int J Clin Exp Pathol 2014; 7 (4) 1275-1285. Serrated lesions of the colorectum, a new entity: What should a clinician/endoscopist know about it? A. Jouret-Mourin, K Geboes. Acta Gastro- Enterolgica Belgica, Vol. LXXV, April-June 2012 Serrated polyps of the colon: how reproducible is their classification? Ensari A et al. Virchows Arch (2012) 461:495-504.