Colonic polyps and tumors Dr Noha Noufal

Objectives: Upon completion of this lecture the students will :  Differentiate between the neoplastic and non-neoplastic polyps and to know common types of intestinal polyps.  Know the clinical presentation of left and right sided colon cancer, and the environmental factors that increase its risk. Understand the Pathology and pathogenesis of colon cancer.

Polyps  Definition: Polyp: refers to any overgrowth of tissue from the surface of mucous membranes. Polyps classified according to gross morphology into: Sessile- meaning growing directly from the bowel surface Pedunculated- the ones that have a stalk

Classification of Colonic Polyps Non Neoplastic Polyps 1- Hyperplastic Polyps 2- Hamartomatous Polyps (ex: Juvenile polyp) 3- Inflammatory Polyps Neoplastic Polyps 1- Adenomas. 2- Familial Adenomatous polyps

Non Neoplastic Polyps: Hyperplastic polyps It represents 75- 90 % of colonic polyps Commonly affect the left colon. May occur single or may be multiple. Small, sessile HPs occur because of proliferation in the basal portion of the crypts; the cells are produced faster than they are shed leading to a serrated appearance Composed of mature goblet cells and absorptive cells It has no malignant potential.

Increased number of colonic glands with serrated surface architecture. HPERPLASTIC POLYP Increased number of colonic glands with serrated surface architecture.

Non Neoplastic Polyps: Hamartomtous polyps Definition of Hamartomas: These are focal, benign over-growths of one or more mature cellular elements of a normal tissue, often arranged irregularly May occur sporadically or in association with many genetic syndromes. Hamartomatous Polyposis are rare but it needs familial screening.

Hamartomatous Polyp: Juvenile polyps Juvenile polyps are the most common type of hamartomatous polyp. May occurs sporadic or syndromic. Usually occur in children less than 5 years of age. Majority occurs in rectum and presented with rectal bleeding. Sporadic juvenile polyps are solitary and do not have an increased risk of malignancy Syndromic polyps may vary from 3-100 and is associated with autosomal dominant inheritance. Syndromic polyps increase the cancer risk for the development of colonic adenocarcinoma.

Neoplastic Polyps- Adenoma They are the most common and clinically important neoplastic polyp. They are benign but they give rise to the majority of colorectal adenocarcinoma. Occurs equally in males and females above the age of 50 years old. Usually there is positive family history which is important for screening of cancer. They are classified morphologically into tubular, villous and tubulovillous adenoma.

1- Tubular Adenoma Gross: Small pedunculated polyps Microscopic: it composed of small rounded or tubular glands.

2- Villous Adenoma These polyps constitute one tenth of colonic adenomas and are found predominantly in the rectosigmoid region. They are typically large, sessile and slender villi. 3- Tubulovillous Adenoma Mixture of tubular and villous elements.

Factors increased risk of cancer incidence of adenomas 1- Dysplasia: Presence of high grade dysplasia is increase the risk of cancer incidence in adenoma. 2- Histological type: Villous architecture increase the risk 3- Tumor size: cancer is extremely rare in adenomas less than 1 cm in diameter, nearly 40% of lesions larger than 4 cm in diameter contain foci of invasive cancer.

Neoplastic polyps: Familial Adenomatous Polyposis (FAP) FAP is an autosomal dominant disorder, marked by the appearance of numerous colorectal adenomas by the teenage years. It is caused by mutations of the adenomatous polyposis coli gene (APC). A count of at least 100 polyps is necessary for a diagnosis of classic FAP. Colorectal adenocarcinoma develops in 100% of patients with untreated FAP, often before 30 years of age. prophylactic colectomy is standard therapy for individuals carrying APC mutation.

Neoplastic polyps: Hereditary Non Polyposis Colorectal Cancer (HNPCC) HNPCC is caused by mutations in DNA mismatch repair genes. Patients develop cancer at an older age than that typical for patients with FAP but at a younger age than in patients with sporadic colon cancer.

Adenocarcinoma of the Colon Epidemiology: Adenocarcinoma of the colon is the most common malignancy of the gastrointestinal tract Adenocarcinoma incidence peaks at 60 to 70 years of age; less than 20% of cases occur before 50 years of age. Males are affected slightly more often than females.

Risk factors 1- Age: Above 50 years old 2- Diet: low fibers diet, rich in red meat, high intake of fat is increasing risk of incidence. 3- Obesity 3- low physical activity. 4- Processed meat 5- Alcohol consumption. 6- Male sex.

Major Risk Factors 1- Patients with IBD Ulcerative Colitis Chron’s Disease 2- Patients who have had adenomatous polyps 3- patient with positive family history of: Adenomatous Polyps CRC FAP HNCC

MOLECULAR PATHOGENESIS:- In 85% of cases of colorectal carcinoma, it is estimated that at least 8 to 10 mutational events must accumulate before an invasive cancer with metastatic potential develops. 1- APC/B- catenin pathway. Loss of APC gene Mutation of K-RAS Loss of SMADs (regulate transcription) Loss of p53 Activation of TELOMERASE 2-Microsatellite instability pathway (Deficiency of DNA mismatch repair gene)

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Morphology Gross: Tumors in the proximal colon often grow as polypoid, exophytic masses. Carcinomas in the distal colon tend to be annular lesions that produce “napkin ring” constrictions and luminal narrowing.

Morphology Microscopic: Adenocarcinoma formed of glands lined by epithelial cells with malignant features. Different degrees of differentiation (well, moderate, undifferentiated)/ About10% to 15% secrete abundant mucin and are called mucinous adenocarcinomas and associated with bad prognosis. Some tumors have signet ring differentiation

Fungating, Circumferential mass Moderately differentiated adenocarcinoma

Mucinous adenocarcinoma

Clinical Features Right-sided colon cancers most often are called to clinical attention by the appearance of fatigue and weakness due to iron-deficiency anemia. Left-sided colorectal adenocarcinomas may produce occult bleeding, changes in bowel habits, or cramping left lower- quadrant discomfort.

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