Serrated Polyps of the Colon Aaron Sinclair MD

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

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

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: ?

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

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.

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?

• 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.

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%) MLH 1 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

80%

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

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

Hyperplastic Polyps Mucosa is typically paler Size <5 mm

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.

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

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

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

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

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

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?

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.

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

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

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

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

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.

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 any comments of cytological dysplasia are mentioned, perform a one year post removal to ensure complete removal.

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

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

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

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, 4 th 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.