15-38: Nonfamilial Adenomatous & Serrated Polyps

Adenomas and serrated polyps may be non-polypoid (flat, slightly elevated, or depressed), sessile, or pedunculated (containing a stalk). Their significance is that over 95% of cases of adenocarcinoma of the colon are believed to arise from these lesions. Early detection and removal of these precancerous lesions through screening programs has resulted in a 34% reduction in deaths from colorectal cancer since 2000. It is proposed that there is a polyp → carcinoma sequence whereby nonfamilial colorectal cancer develops through a continuous process from normal mucosa to adenomatous or serrated polyp and later to carcinoma. An estimated 75% of cancers arise in adenomas after inactivation of the APC gene leads to chromosomal instability and inactivation or loss of other tumor suppressor genes. The remaining 25% of cancers arise through the serrated pathway in which hyperplastic polyps develop Kras (forming traditional serrated adenomas) mutations or BRAF oncogene activation (forming sessile serrated lesions) with widespread methylation of CpG-rich promoter regions that leads to inactivation of tumor suppressor genes or mismatch repair genes (MLH1) with microsatellite instability.

A. Adenomas

Adenomas (eFigures 15–32 and 15–33) are present in more than 30% of men and 20% of women over the age of 50. Most adenomas are smaller than 5 mm and have a low risk of becoming malignant. Adenomas and are classified as “advanced” if they are 1 cm or larger or contain villous features or high-grade dysplasia. In the general population, the prevalence of advanced adenomas is 6%. Advanced lesions are believed to have a higher risk of harboring or progressing to malignancy. It has been estimated from longitudinal studies that it takes an average of 5 years for a medium-sized polyp to develop from normal-appearing mucosa and 10 years for a gross cancer to arise.

B. Serrated Polyps

There are three types of serrated polyps: hyperplastic polyps, sessile serrated lesions (eFigure 15–34), and traditional serrated adenomas. It is believed that sessile serrated lesions (prevalence 5–15%) and traditional serrated adenomas (prevalence less than 1%) harbor an increased risk of colorectal cancer similar or greater to that of adenomas. Many pathologists cannot reliably distinguish between hyperplastic polyps and sessile serrated lesions. Diminutive hyperplastic polyps (less than 5 mm) are extremely common (prevalence 20–30%), especially in the rectum, and believed to be without significant risk.

A. Symptoms and Signs

Most patients with adenomatous and serrated polyps are completely asymptomatic. Chronic occult blood loss may lead to iron deficiency anemia. Large polyps may ulcerate, resulting in intermittent hematochezia.

B. Fecal Occult Blood or Multitarget DNA Tests

FOBT, FIT, and fecal DNA tests are available as part of colorectal cancer screening programs (see Chapter 39). FIT is a fecal immunochemical test for hemoglobin with a single specimen having a sensitivity of approximately 80% for colorectal cancer and 20–30% for advanced adenomas but a much lower sensitivity for serrated lesions. FIT is more sensitive than guaiac-based tests for the detection of colorectal cancer and advanced adenomas. In 2014, a test combining a fecal DNA test with a fecal immunochemical test for stool hemoglobin (under the proprietary name “Cologuard”) was approved by the FDA. In a prospective comparative trial conducted in persons at average risk for colorectal cancer undergoing colonoscopy, the sensitivity for colorectal cancer for Cologuard was 92.3% compared to 73.8% for FIT and the sensitivity for large (greater than 1 cm) adenomas or serrated polyps for Cologuard was 42.4% compared to 23.8% for FIT.

C. Radiologic Tests

CT colonography (“virtual colonoscopy”) uses data from helical CT imaging with computer-enabled luminal image reconstruction to generate two-dimensional and three-dimensional images of the colon. Using optimal imaging software with multidetector helical CT scanners, several studies report a sensitivity of 90% or more for the detection of polyps larger than 10 mm in size. However, the accuracy for detection of polyps 5–9 mm in size is significantly lower (sensitivity 50%). A small proportion of these diminutive polyps harbor advanced histology (up to 1.2%) or carcinoma (less than 1%). Abdominal CT imaging also results in a radiation exposure that may lead to a small risk of cancer. Barium enema is no longer recommended due to its poor diagnostic accuracy.

D. Endoscopic Tests

Colonoscopy allows evaluation of the entire colon and is the best means of detecting and removing adenomatous and serrated polyps (eFigures 15–35 and 15–36). It should be performed in all patients who have positive FOBT, FIT, or fecal DNA tests or iron deficiency anemia (see Occult Gastrointestinal Bleeding above), as the prevalence of colonic neoplasms is increased in these patients. Colonoscopy should also be performed in patients with polyps detected on radiologic imaging studies (CT colonography or barium enema) or adenomas detected on flexible sigmoidoscopy to remove these polyps and to fully evaluate the entire colon. The newest generation of capsule endoscopy of the colon has an 86% sensitivity and 88% specificity for detection of adenomas greater than 6 mm compared with colonoscopy, but only 29% sensitivity and 33% specificity for sessile serrated polyps. The bowel preparation required for the colon capsule study is more extensive than for colonoscopy and 10–30% of studies may be inadequate due to poor bowel preparation or failure to excrete the capsule. At this time, colonoscopy remains the best test in most patients to detect colorectal polyps. However, capsule endoscopy may be considered in patients who are unsuitable or unwilling to undergo colonoscopy or who have an incomplete colonoscopy.

A. Colonoscopic Polypectomy

Most adenomatous and serrated polyps are less than 2 cm in size, and are readily amenable to colonoscopic removal; this can be done with biopsy forceps (for those less than 3 mm), with cold snare excision (for those less than 8–10 mm), or with snare cautery (for those 10–20 mm). Sessile polyps larger than 2 cm may be removed by appropriately trained physicians using a variety of endoscopic techniques (eg, saline-lift mucosal resection or dissection) or infrequently may require surgical resection. Patients with large sessile polyps removed in piecemeal fashion should undergo repeated colonoscopy in 2–6 months to verify complete polyp removal. Complications after colonoscopic polypectomy include perforation in 0.2% and clinically significant bleeding in 0.3–1.0% of all patients, but 2–8% following mucosal resection of large lesions.

A malignant polyp is an adenoma that appears grossly benign at endoscopy but on histologic assessment is found to contain cancer that has penetrated through the muscularis mucosae into the submucosa. Malignant polyps may be considered to be adequately treated by polypectomy alone if: (1) the polyp is completely excised and submitted for pathologic examination, (2) it is well differentiated, (3) the margin is not involved, and (4) there is no vascular invasion. The risk of residual cancer or nodal metastasis with favorable histologic features is less than 1%. The excision site of these "favorable" malignant polyps should be checked in 3 months for residual tissue. In patients with malignant polyps that have unfavorable histologic features, cancer resection is advisable if the patient is a good operative candidate.

B. Postpolypectomy Surveillance

Adenomas and serrated polyps can be found in 30–40% of patients when another colonoscopy is performed within 3–5 years after the initial examination and polyp removal. Periodic colonoscopic surveillance is therefore recommended to detect these “metachronous” lesions, which either may be new or may have been overlooked during the initial examination. Most of these polyps are small, without high-risk features, and of little immediate clinical significance. The probability of detecting advanced neoplasms at surveillance colonoscopy depends on the number, size, and histologic features of the polyps removed on initial (index) colonoscopy. Current guidelines recommend that patients with 1–2 tubular adenomas smaller than 1 cm (without villous features or high-grade dysplasia) should have their next colonoscopy in 5–10 years. Patients with 3–10 adenomas, an adenoma larger than 1 cm, or an adenoma with villous features or high-grade dysplasia should have their next colonoscopy at 3 years. Patients with more than 10 adenomas should have a repeat colonoscopy at 1–2 years and may be considered for evaluation for a familial polyposis syndrome. Surveillance colonoscopy at 5 years is appropriate for patients with small (less than 1 cm) serrated polyps without cytologic dysplasia; surveillance colonoscopy at 3 years should be considered for serrated polyps larger than 1 cm and those with cytologic atypia. No surveillance is recommended for patients with small, typical hyperplastic polyps located in the distal colon and rectum.