Colon polyps Peter Stanich, MD Assistant Professor; Division of Gastroenterology, Hepatology & Nutrition Director; Section of Intestinal Neoplasia and Hereditary Polyposis

Learning objectives: Identify the characteristics of neoplastic disease of the colon, rectum, and anus incorporating the causes, epidemiology, clinical features, diagnosis, and management concepts Define colon polyp. Describe the pathology and significance of: 1) tubular and tubulovillous adenoma; 2) villous adenoma; 3) hyperplastic polyp; 4) hamartomatous polyp. List the types of colon polyps. Describe the relationship between colon polyps and colon cancer. Identify current screening recommendations for colon cancer. Describe tests for screening and diagnosing colon polyps and colon cancer. List the most common signs and symptoms of colon cancer. Explain why colon carcinoma should be excluded when there is onset of altered bowel habit in patients of age at risk. Describe the epidemiology of adenocarcinoma of the colon. List the risk factors for the development of colon cancer. Explain staging of colon cancer and survival implications.

Neoplastic disease of the colon, rectum & anus Colon or rectal polyp – Protuberance from the flat colonic mucosa - or - raised lesion seen at endoscopy. Much more to come… Colorectal cancer (CRC) – Adenocarcinoma. Focus of second articulate module in series… Definitions: Dysplasia - Abnormality of growth and differentiation of cells Neoplasia – Atypical proliferation of cell growth

Colon polyps Asymptomatic, unusual but if large can cause microscopic blood loss or rarely small amount of rectal bleeding if distal location There are multiple different histologic types of polyps

Colon polyps Colon polyp Hyperplastic Neoplastic * Most common Non-neoplastic Hamartoma Inflammatory pseudopolyps - Not classic polyps Adenoma Serrated Submucosal - Not classic polyps

Adenomatous colon polyps 2/3 of all colon polyps are adenomas By definition, they are all dysplastic - Even the small tubular adenomas that don’t have it mentioned on path reports

Adenomatous colon polyps Classifications: Endoscopic appearance Sessile: Base is attached to the wall Pedunculated: Mucosal stalk from polyp to wall Pathology Tubular (80% of adenomas) Tubulovillous (mixed) Villous (finger-like glands, higher risk)

Adenomatous colon polyps Classifications: Advanced adenomas: High-grade dysplasia > 1 cm size Villous histology (ie. villous or tubulovillous) These are higher risk for progression to CRC and development of future CRC *3 or more adenomas at a single colonoscopy is also a risk factor

Adenomatous colon polyps Risk factors for development of adenomas: Age Male sex Obesity African Americans are at higher risk for large adenomas Family history Forsberg et al. Prevalence of colonic neoplasia and advanced lesions in the normal population. Scandinavian Journal of Gastro. 2012.

Adenomatous colon polyps Colonoscopy and adenoma removal (polypectomy) reduces mortality from colorectal cancer (CRC) Zauber et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. NEJM 2/23/12.

Adenoma to Carcinoma sequence Colon Carcinogenesis and the Effects of Chemopreventive Agents. Adenoma to Carcinoma sequence Jänne PA, Mayer RJ. N Engl J Med 2000;342:1960-1968. Figure 1. Colon Carcinogenesis. Colon cancers result from a series of pathologic changes that transform normal colonic epithelium into invasive carcinoma. Specific SOMATIC genetic events in tumor suppressor genes, shown by vertical arrows, accompany this multistep process. The APC gene mutation will be discussed later in the context of germline mutation giving rise to familial adenomatous polyposis. P53 germline mutations lead to Li Fraumeni which has a multitude of young onset cancers associated with it. These are both tumor suppressor genes and thus loss of function leads to unchecked cell growth. KRAS is an oncogene so mutation leads to gain of function. < 5% of polyps progress, takes 7-10 years

Colon cancer screening Terminology review: Screening: no personal history of cancer or precancerous lesions and no clinical signs Surveillance: History of CRC or polyps Diagnostic: Symptoms concerning for CRC

Colon cancer screening Multiple societies have proposed them, but most/all are similar Colonoscopy is preferred as diagnostic and PREVENTATIVE, other options discussed later only diagnostic

Colon cancer screening Credit: Colonversation Colonoscopy animation https://www.youtube.com/watch?v=hzxrBy6AnFA Colonoscopy movie plays in 24 seconds in a separate browser “Colonversation Colonoscopy animation” — Medical Illustration Copyright 2009 Nucleus Medical Art. All rights reserved. https://www.youtube.com/watch?v=hzxrBy6AnFA

Colon cancer screening Average risk: Colonoscopy at age 50 If no polyps, repeat in 10 years Increased risk due to family history Colonoscopy at age 40 or 10 years younger than earliest affected first degree relative If no polyps, repeat every 5 years Discuss what qualifies as family history: 1 FDR with CRC or advanced adenoma at < 60, 2 FDR with CRC or advanced adenoma at any age FDR = first degree relative ie parent, sibling, child

Colon cancer screening options Preferred (for all): Colonoscopy Other options (only in average risk): Every 5 years: Flexible sigmoidoscopy ± fecal occult blood test (FOBT), CT colonography or barium enema Annual: Fecal immunochemical test (FIT), FOBT (out of favor) Future of stool testing may be Fecal DNA (promising recent study)

Serrated colon polyps Referred to as sessile serrated adenomas or sessile serrated polyps Also includes the less common traditional serrated adenoma Despite names, they are distinct from adenomas Progress to CRC through a microsatellite instability pathway with BRAF mutation (likely similar risk to adenomas but still to be determined) They are more common in the proximal colon and are often flat and difficult to spot BRAF is an oncogene, thus similar to a somatic pathway of the germline Lynch syndrome

Serrated colon polyps They can be very hard to see!

Serrated colon polyps Malignant potential of these lesions is only recent realized Thought to account for majority of interval cancers (which occur more commonly in right colon and likely to show microsatellite instability)

Hyperplastic colon polyps Non-neoplastic, but have a serrated morphology Most common non-neoplastic polyp No known risk of progression to cancer Very common in rectosigmoid, usually a small sample are biopsied to confirm or “optical biopsied” but not all need to be removed

Hamartomatous colon polyps Hamartoma = Disorganized growths of native cells in native tissues Can be difficult to distinguish pathologically, but juvenile polyps and Peutz-Jegher polyps are in this category Can be sporadic if only a few, if multiple associated with specific hereditary syndromes (Peutz Jeghers, Juvenile polyposis, PTEN hamartoma tumor syndrome/Cowden syndrome) with high multi-organ cancer risks Have increased risk of CRC, due to rarity can be difficult to quantify

Inflammatory pseudopolyps Islands of intact colon mucosa that form secondary to bowel wall inflammation and regeneration Most often seen with ulcerative colitis Do not need to be resected and do not have malignant potential per se, but can complicate surveillance in IBD patients

Submucosal polyps/lesions They arise from beneath the epithelium to create protuberance into lumen but the epithelium is normal Although may technically fit the broadest definition of a polyp, most would consider a lesion or mass Examples include lipoma (pictured), leiomyoma, carcinoid tumors Surface biopsies unrevealing, often need deeper biopsy for diagnosis These often arise from the MM, submucosa or MP Copyright © 2011 John Wiley & Sons, Inc. All rights reserved. From http://onlinelibrary.wiley.com/higheredbcs/WileyCDA/

Key Points Adenomas are most common neoplastic polyp and removal of them reduces the incidence and mortality of colorectal cancer Sessile serrated adenomas/polyps are suspected as a cause of right-sided colon cancers Colonoscopy preferred screening method as both preventative and diagnostic, but other methods exist and can be utilized if needed Average risk CRC screening begins at age 50

Colon Polyps Quiz

Thank you Email with questions/comments: peter.stanich@osumc.edu

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