35 Colorectal Polyps and Cancer Screening/Prevention
Douglas K. Rex
The two major classes of precancerous colorectal lesions are the conventional adenomas and the serrated lesions. Effective colonoscopy requires detailed understanding of the spectrum of appearances of these precancerous colorectal lesions. Precancerous lesions must be effectively recognized and completely resected during colonoscopy. This chapter reviews basic knowledge needed to perform effective colonoscopy, and also reviews the fundamentals of colorectal cancer screening and surveillance.
35.2 Polyp Classification and Polyp Cancer Sequences
Nearly all colorectal cancers are believed to arise from an endoscopically detectable benign precursor. The Paris classification (▶Fig. 35.1) divides the precursors into Paris type I lesions (polyps), which protrude into the colon lumen more than the diameter of a standard biopsy forceps, and the flat and depressed lesions (Paris type II), which project into the lumen less than the diameter of a standard 2.5-mm biopsy forceps. 1 Detailed knowledge of the Paris classification is useful to heighten awareness of the need to search for subtle precancerous and malignant lesions (▶Table 35.1).
The progression of polyps and flat lesions to cancer is generally referred to as the “polyp-cancer sequence.” The two main histologic classes of precursor lesions are the conventional adenomas and the serrated lesions. These two classes of lesions also account for more than 90% of all colorectal polyps and flat lesions (▶Table 35.2).
Conventional adenomas (all are dysplastic)
Serrated class lesions
Conventional adenomas are the precursor lesion of 70 to 85% of sporadically occurring colorectal cancers, as well as cancers arising in the major inherited syndromes with a defined genetic basis including Familial Adenomatous Polyposis and Lynch Syndrome (discussed in Chapter 37). Tumors arising from conventional adenomas are said to pass through the “adenoma–carcinoma sequence,” which is a subtype of the polyp cancer sequence. ▶Table 35.2 shows a classification of the two major groups of precancerous colorectal polyps and flat lesions.
Colorectal cancers arising through serrated class lesions account for 15 to 30% of all cancers. Serrated class lesions are distinct from conventional adenomas endoscopically, histologically, and in their molecular features. Serrated class lesions are missed more frequently during colonoscopy than conventional adenomas, 2 , 3 and account for a disproportionate percentage of cancers that occur after colonoscopy. 4 , 5 Because recognition and understanding of the serrated pathway is more recent than the adenoma–carcinoma sequence, the effective modern colonoscopist is characterized to a substantial degree by his or her ability to detect and effectively resect serrated class lesions.
Other types of colorectal polyps are infrequently encountered, including carcinoid tumors (largely submucosal and usually located in the rectum), inflammatory polyps, hamartomas, normal structures that mimic polyps such as “mucosal polyps” (an excrescence of normal mucosa) and lymphoid follicles, and rare growths such as leiomyoma, ganglioneuroma, cystic structures (e.g., pneumatosis cystoides intestinalis), and metastatic tumors to the colon. Although the expert colonoscopist should understand these uncommon and rare lesions, the expert is also often surprised by the pathology report of some of these lesions. These lesions are not discussed in detail here, because the greatest benefit to patients accrues when the endoscopist masters understanding of the conventional adenomas and serrated class lesions.
35.3 Conventional Adenomas
35.3.1 Low-Risk versus Advanced Conventional Adenomas
By definition all conventional adenomas are dysplastic and the degree of dysplasia should be characterized as low grade or high grade. The degree of dysplasia is subject to marked interobserver variation between pathologists. 6 Classification schemes such as mild, moderate, or severe dysplasia are unacceptable since these are subject to even greater interobserver variation than the two-category scheme of low versus high grade. The separation of low versus high grade is best made based on the low-power magnification morphologic characteristics. The use of cytologic criteria to designate high-grade dysplasia leads to a much higher percentage of adenomas having high-grade dysplasia compared to when only morphologic criteria are used. 6
Conventional adenomas can also be categorized as tubular versus tubulovillous (synonymous with villoglandular) versus villous. The great majority of conventional adenomas are tubular, which refers to an organized pattern of glands, and only a tiny fraction is villous (which refers to a frond-like growth pattern of glands). Polyps containing more than 25% villous elements should be designated tubulovillous, and more than 75% villous elements should be called villous. Villous histology is associated with a greater risk of high-grade dysplasia compared to tubular histology. As with dysplasia grade, there is marked interobserver variation between pathologists in designation of tubular versus tubulovillous, even when using identical definitions. 6
The magnitude of the problem with interobserver variation in pathologist interpretation of dysplasia grade and tubular versus villous is such that some postpolypectomy surveillance guidelines, particularly the British guideline, 7 do not acknowledge dysplasia grade and villous elements. Nevertheless, across a population of patients there is some association of both villous elements and high-grade dysplasia with the subsequent occurrence of advanced lesions at follow-up colonoscopy. 8
Tubular adenomas with low-grade dysplasia less than 1 cm in size are considered “low-risk” adenomas. Adenomas greater than or equal to 10 mm in size, or which have high-grade dysplasia, or have villous elements (either tubulovillous or villous histology) are considered “advanced adenomas.” In observational studies of colonoscopy findings after a baseline clearing examination, advanced adenomas are commonly used as a surrogate for cancer, because the incidence of colorectal cancer in observational postpolypectomy studies is typically low. 8 In postpolypectomy studies, three or more baseline adenomas, even if all were low-risk adenomas, are associated with the subsequent occurrence of advanced adenomas, 8 although a recent study found that at least five low-risk adenomas were needed before an increased risk of advanced adenomas at follow-up was present. 9 The occurrence of three or more adenomas is often referred to as “multiple” adenomas and is considered a “high-risk finding” even when constituted entirely from low-risk adenomas.
35.3.2 Shape and Colonic Distribution of Conventional Adenomas
As noted above, precursor lesions, including conventional adenomas can be classified as polyps versus flat lesions versus depressed lesions. Polyps are also categorized as pedunculated or sessile. Pedunculated adenomas can occur in any section of the colon, but predominate in the sigmoid. Pedunculated lesions comprise 5 to 10% of all conventional adenomas. Sessile (Paris Is shape) comprises 40 to 50% of conventional adenomas, and approximately 40 to 50% have flat (Paris IIa) shape. Although flat shape has been associated with worse histology, the bulk of evidence suggests that the risk of high-grade dysplasia and invasive cancer is no higher or even less in flat (Paris IIa) lesions compared with sessile (Is) conventional adenomas. 10 Flat lesions are skewed in distribution toward the right colon compared to sessile lesions, which may contribute to the observation that proximal cancer location is more common in interval cancers compared to cancers diagnosed during a first colonoscopy. By far the most dangerous shape for conventional adenomas is the depressed lesion, which occurs in probably 1 in every 800 to 1,000 screening colonoscopies in persons age 50 and older. 11 Depressed lesions are at least 1 to 1.5 cm in diameter, and have a substantial surface area that is depressed compared to the rim or perimeter of the lesion. Further, the transition from the perimeter to the depressed portion is typically sharp rather than sloping. The risk of high-grade dysplasia or invasive cancer in depressed lesions is as great as 50%, which is at least 50 times higher than that of flat or sessile lesions of comparable size.
The modern expert colonoscopist is highly attuned to the shape classification of colorectal cancer precursors, and constantly attuned to subtle variations in mucosal color, surface texture, and disruption of normal mucosal vasculature that could signal the presence of a flat or depressed precursor.
35.3.3 Surface Features of Conventional Adenomas
Approximately 80 to 85% of conventional adenomas have a characteristic surface pattern that includes thick blood vessels that surround white structures that are variable in shape, but most characteristically are tubular (▶Fig. 35.2, Video 35.1). The Narrow-band imaging International Colorectal Endoscopic (NICE) classification scheme permits differentiation of conventional adenomas from serrated class lesions based on these features 12 (▶Table 35.3). A lesion that demonstrates a disrupted or amorphous vascular pattern, often in an area of relative depression, has a high risk of deeply invasive submucosal cancer, and should be biopsied and referred directly for surgical resection. This disrupted pattern is the NICE type III 13 (▶Table 35.3, Video 35.2).
35.3.4 Resection of Conventional Adenomas
Resection of large conventional adenomas that are flat or sessile can be technically challenging, and is the subject of Chapter 36. Approximately 80% of conventional adenomas are less than 1 cm in size, and many of these lesions are candidates for resection using cold techniques, which effectively remove lesions and nearly eliminate the risk of delayed hemorrhage and the rare perforation associated with thermal injury. Diminutive snares, or specialized snares made specifically for cold snaring can provide an advantage in resection. Cold snaring is the most efficient method for resection for most lesions in the 4- to 10-mm range, as the lesion can be resected in a single bite including a rim of normal tissue, which assures effective resection. 14 With larger lesions, mechanical resection without electrocautery is more difficult, and may leave a cord of submucosal tissue that has been trapped and elongated by the snare (Video 35.3). However, after mechanically pulling the snare through entrapped submucosa, the residual submucosa does not demonstrate polyp tissue on biopsy (▶Fig. 35.3). Polyps less than or equal to 3 mm are commonly identified with high-definition scopes, and if determined to be conventional adenomas, these are resected in most western countries. Cold snaring is still a very efficient method, but for very flat lesions, particularly if located in the upper left endoscopic field and rotation of the colonoscope to achieve 5 o’clock positioning is difficult, such tiny polyps can be engulfed and removed with cold forceps. Use of a jumbo or large-capacity forceps helps to ensure resection in a single bite. 15 Piecemeal resection of polyps using cold forceps is never advisable, since the risk of residual polyp is substantially greater compared to cold snaring. 14 For polyps that are pedunculated or bulky, the use of electrocautery is often preferred for polyps of 5- to 10-mm size, and electrocautery is used for most such polyps greater than 10 mm in size regardless of shape.