Surveillance Guidelines Should Be Updated to Recognize the Importance of Serrated Polyps

Abstract

See “Proximal and large hyperplastic and nondysplastic serrated polyps detected by colonoscopy are associated with neoplasia,” Schreiner MA, Weiss DG, Lieberman DA, et al, on page 1497; and “The presence of large serrated polyps increases risk for colorectal cancer,” by Hiroaka S, Kato J, Fujiki S, et al, on page 1503. See “Proximal and large hyperplastic and nondysplastic serrated polyps detected by colonoscopy are associated with neoplasia,” Schreiner MA, Weiss DG, Lieberman DA, et al, on page 1497; and “The presence of large serrated polyps increases risk for colorectal cancer,” by Hiroaka S, Kato J, Fujiki S, et al, on page 1503. Serrated polyps are common, but until recently have been regarded by some as inconsequential regardless of their size, number, or histologic features. Two important studies published in this month's Gastroenterology,1Hiroaka S. Kato J. Fujiki S. et al.The presence of large serrated polyps increases risk for colorectal cancer.Gastroenterology. 2010; 139: 1503-1510Google Scholar, 2Schreiner M.A. Weiss D.G. Lieberman D.A. et al.Proximal and large hyperplastic and nondyplastic serrated polyps detected by colonoscopy are associated with neoplasia.Gastroenterology. 2010; 139: 1497-1502Abstract Full Text Full Text PDF Scopus (207) Google Scholar however, add to a growing body of work that challenges this viewpoint. There is now unequivocal evidence that serrated polyps may progress via the serrated neoplasia pathway to colorectal adenocarcinoma, and there are reasons to suspect that this pathway may contribute disproportionately to interval or missed cancers.3Leggett B. Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.Gastroenterology. 2010; 138: 2088-2100Google Scholar It is increasingly recognized that screening colonoscopy provides imperfect protection from colorectal cancer (CRC), especially those occurring in the proximal colon.4Baxter N.N. Goldwasser M.A. Paszat L.F. et al.Association of colonoscopy and death from colorectal cancer.Ann Int Med. 2009; 150: 1-8Google Scholar, 5Singh H. Nugent Z. Demers A.A. et al.The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer.Gastroenterology. 2010; Google Scholar Missed or rapidly growing lesions likely are important contributors to this problem.6Lieberman D. Progress and challenges in colorectal cancer screening and surveillance.Gastroenterology. 2010; 138: 2115-2126Google Scholar Proximal serrated polyps may be more likely than conventional adenomas to be missed or incompletely removed, because many are nonpolypoid (flat) and have a subtle, poorly delineated appearance that may be misinterpreted as a thickened fold.7Oka S. Tanaka S. Hiyama T. et al.Clinicopathologic and endoscopic features of colorectal serrated adenoma: differences between polypoid and superficial types.Gastrointest Endosc. 2004; 59: 213-219Google Scholar, 8Lauwers G.Y. Chung D.C. The serrated polyp comes of age.Gastroenterology. 2006; 131: 1631-1634Google Scholar Recent data suggest also that the progression from polyp to cancer may be faster in the serrated neoplasia pathway.9Higuchi T. Sugihara K. Jass J.R. Demographic and pathological characteristics of serrated polyps of the colorectum.Histopathology. 2005; 47: 32-40Google Scholar Nevertheless, current clinical guidelines still do not recognize the clinical importance of serrated polyps.10Winawer S.J. Zauber A.G. Fletcher R.H. Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.Gastroenterology. 2006; 130: 1872-1885Google Scholar Although some uncertainty remains, we believe that the evidence available strongly supports a revision to our current polyp surveillance guidelines. Serrated polyps comprise a heterogeneous group of lesions, including hyperplastic polyps (HPs), sessile serrated adenomas (SSAs), traditional serrated adenomas (TSAs) and mixed lesions, all of which are characterized by the “saw-toothed” architecture of the crypt epithelium.3Leggett B. Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.Gastroenterology. 2010; 138: 2088-2100Google Scholar, 11Noffsinger A.E. Hart J. Serrated adenoma: a distinct form of non-polypoid colorectal neoplasia?.Gastrointest Endosc Clin North Am. 2010; 20: 543-563Google Scholar, 21Rustgi A.K. The genetics of hereditary colon cancer.Genes Dev. 2007; 21: 2525-2538Google Scholar HPs were the first serrated polyps to be defined and are the most common. These ubiquitous polyps are often diminutive (<5 mm), found disproportionately in the left colon and rectum, and traditionally considered harmless because they are devoid of cytological dysplasia and have little or no malignant potential. HPs can be further divided into microvesicular HPs, goblet cell-rich, or mucin-poor subtypes; however, this histologic distinction has no clinical importance at present.3Leggett B. Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.Gastroenterology. 2010; 138: 2088-2100Google Scholar Current clinical practice guidelines do not recommend surveillance colonoscopy for persons with a small number of diminutive HPs because the risk for CRC is not higher than individuals without polyps.10Winawer S.J. Zauber A.G. Fletcher R.H. Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.Gastroenterology. 2006; 130: 1872-1885Google Scholar, 12Imperiale T.F. Glowinski E.A. Lin-Cooper C. et al.Five-year risk of colorectal neoplasia after negative screening colonoscopy.N Engl J Med. 2008; 359: 1218-1224Google Scholar In 1990, Longacre and Fenoglio-Preiser13Longacre T.A. Fenoglio-Preiser C.M. Mixed hyperplastic adenomatous polyps/serrated adenomas A distinct form of colorectal neoplasia.Am J Surg Pathol. 1990; 14: 524-537Google Scholar first recognized that some serrated polyps can have cytological dysplasia and coined the term “serrated adenoma” for this subset. These lesions, now properly termed TSAs, were recognized rapidly as being premalignant. TSAs occur more commonly in the distal colon, may be pedunculated or sessile, and are described as having a villiform or ‘pineal’ appearance.3Leggett B. Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.Gastroenterology. 2010; 138: 2088-2100Google Scholar, 11Noffsinger A.E. Hart J. Serrated adenoma: a distinct form of non-polypoid colorectal neoplasia?.Gastrointest Endosc Clin North Am. 2010; 20: 543-563Google Scholar In 2003, Torlakovic et al14Torlakovic E. Skovland E. Snover D.C. et al.Morphologic reappraisal of serrated colorectal polyps.Am J Surg Pathol. 2003; 27: 65-81Google Scholar defined another subset of serrated polyps that they termed SSAs, now also referred to as sessile serrated polyps or sessile serrated lesions. SSAs more commonly are right sided, large, flat or sessile, poorly demarcated, waxy or pale, and may be covered with mucus.3Leggett B. Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.Gastroenterology. 2010; 138: 2088-2100Google Scholar, 7Oka S. Tanaka S. Hiyama T. et al.Clinicopathologic and endoscopic features of colorectal serrated adenoma: differences between polypoid and superficial types.Gastrointest Endosc. 2004; 59: 213-219Google Scholar, 8Lauwers G.Y. Chung D.C. The serrated polyp comes of age.Gastroenterology. 2006; 131: 1631-1634Google Scholar, 9Higuchi T. Sugihara K. Jass J.R. Demographic and pathological characteristics of serrated polyps of the colorectum.Histopathology. 2005; 47: 32-40Google Scholar, 11Noffsinger A.E. Hart J. Serrated adenoma: a distinct form of non-polypoid colorectal neoplasia?.Gastrointest Endosc Clin North Am. 2010; 20: 543-563Google Scholar Like HPs, SSAs typically do not have cytological dysplasia, but unlike HPs they demonstrate abnormal proliferation and/or abnormal architecture. Histologic features of SSAs include crypt branching, dilation, or horizontal orientation, and serration that extends into the lower third of the crypt.3Leggett B. Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.Gastroenterology. 2010; 138: 2088-2100Google Scholar, 11Noffsinger A.E. Hart J. Serrated adenoma: a distinct form of non-polypoid colorectal neoplasia?.Gastrointest Endosc Clin North Am. 2010; 20: 543-563Google Scholar Although some SSAs may harbor cytological dysplasia, they remain distinct from TSAs based on crypt architecture. Serrated cancers are common, likely accounting for 10%–20% of all CRC and >30% of interval cancers.3Leggett B. Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.Gastroenterology. 2010; 138: 2088-2100Google Scholar An understanding of the molecular pathogenesis of serrated pathway cancers helps explain the relationship among serrated polyp subtypes and their malignant potential. The molecular pathogenesis of serrated pathway cancers was reviewed recently by Leggett and Whitehall in Gastroenterology.3Leggett B. Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.Gastroenterology. 2010; 138: 2088-2100Google Scholar There seem to be 2 major pathways by which serrated lesions may evolve to adenocarcinomas. Many serrated pathway cancers derive from SSAs that are BRAF-mutation positive and have a high degree of CpG island methylation phenotype (CIMP-H). Two critical events in this neoplastic pathway are activation of the BRAF oncogene due to a V600E point mutation and inactivation of multiple tumor suppressor genes due to methylation of CpG-rich promoter regions. SSAs may derive from a subset of HPs, microvesicular HPs, which have a high frequency of BRAF mutations but usually are not CIMP-H. Thus, it seems that BRAF mutation occurs early and leads to constitutive activation of the mitogen-activated protein kinase pathway that results in increased cell proliferation and inhibition of apoptosis. Although subsequent up-regulation of tumor suppressor genes, such as p16INK4a, may halt the cell cycle and stop initial proliferation, inactivation of p16INK4a and other tumor suppressor genes via CpG island promoter methylation allows the cells to escape senescence and continue proliferation.22Bennecke M. Kriegl L. Bajbouj et al.Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis.Cancer Cell. 2010; 18: 135-146Google Scholar Later epigenomic or genomic events, such as CpG methylation of the MLH1 promoter or p53 mutation, may lead to “serrated” cancers that are either microsatellite unstable (MSI-H) or microsatellite stable, respectively. Serrated colon cancers arising through this pathway, especially those that are MSI-H, tend to occur in the proximal colon and to be poorly differentiated, mucinous tumors with infiltrating lymphocytes, yet have a better prognosis than adenocarcinomas that arise through the more common chromosomal instability pathway, reminiscent in this regard of colon cancers in the Lynch syndrome. Serrated adenocarcinomas may derive also from TSAs. Like SSAs, TSAs also have up-regulation of the mitogen-activated protein kinase pathway, but this is caused by activating point mutations of the K-ras oncogene rather than BRAF mutations. TSAs may arise from the goblet-cell subtype of HPs, which are often K-ras mutation positive. TSAs may give rise to a serrated cancer with a distinct pattern of CIMP that commonly includes promoter methylation and silencing of the DNA repair gene MGMT. Serrated cancers arising from TSAs are more common in the distal colon and have microsatellite stability or low-level instability. In summary, it seems that 1 subset of HPs may progress to SSAs and another subset to TSAs, each of which may undergo transformation to serrated cancers that have a distinct molecular profile.3Leggett B. Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.Gastroenterology. 2010; 138: 2088-2100Google Scholar, 11Noffsinger A.E. Hart J. Serrated adenoma: a distinct form of non-polypoid colorectal neoplasia?.Gastrointest Endosc Clin North Am. 2010; 20: 543-563Google Scholar If one includes diminutive HPs, serrated polyps (HPs, SSAs, TSAs) are commonly found in patients who undergo screening colonoscopy. Among the 3121 patients undergoing screening colonoscopy as part of VA Cooperative Study 380, 25.7% had ≥1 nondysplastic serrated polyps (ND-SP; ie, HPs and SSAs).2Schreiner M.A. Weiss D.G. Lieberman D.A. et al.Proximal and large hyperplastic and nondyplastic serrated polyps detected by colonoscopy are associated with neoplasia.Gastroenterology. 2010; 139: 1497-1502Abstract Full Text Full Text PDF Scopus (207) Google Scholar Most of these are diminutive HPs located in the distal colon that show no predilection based on patient age or gender; however, one third (7.9%) occur in the proximal colon.2Schreiner M.A. Weiss D.G. Lieberman D.A. et al.Proximal and large hyperplastic and nondyplastic serrated polyps detected by colonoscopy are associated with neoplasia.Gastroenterology. 2010; 139: 1497-1502Abstract Full Text Full Text PDF Scopus (207) Google Scholar SSAs and TSAs (regardless of size) are less prevalent, being found in 1%–2% of patients undergoing screening colonoscopy.9Higuchi T. Sugihara K. Jass J.R. Demographic and pathological characteristics of serrated polyps of the colorectum.Histopathology. 2005; 47: 32-40Google Scholar Large, serrated polyps (≥10 mm) also are much less common. In 3 recent, large cohorts of patients undergoing screening colonoscopy, 1.4%–2.3% had large serrated polyps.1Hiroaka S. Kato J. Fujiki S. et al.The presence of large serrated polyps increases risk for colorectal cancer.Gastroenterology. 2010; 139: 1503-1510Google Scholar, 2Schreiner M.A. Weiss D.G. Lieberman D.A. et al.Proximal and large hyperplastic and nondyplastic serrated polyps detected by colonoscopy are associated with neoplasia.Gastroenterology. 2010; 139: 1497-1502Abstract Full Text Full Text PDF Scopus (207) Google Scholar, 15Li D. Jin C. McCulloch C. et al.Association of large serrated polyps with synchronous advanced colorectal neoplasia.Am J Gastroenterol. 2009; 104: 695-702Google Scholar Unfortunately, these post hoc pathologic analyses do not allow determination of the relative proportion of HPs, SSAs, or TSAs among these large serrated lesions. Large serrated polyps have a slightly higher prevalence in the proximal colon,2Schreiner M.A. Weiss D.G. Lieberman D.A. et al.Proximal and large hyperplastic and nondyplastic serrated polyps detected by colonoscopy are associated with neoplasia.Gastroenterology. 2010; 139: 1497-1502Abstract Full Text Full Text PDF Scopus (207) Google Scholar, 15Li D. Jin C. McCulloch C. et al.Association of large serrated polyps with synchronous advanced colorectal neoplasia.Am J Gastroenterol. 2009; 104: 695-702Google Scholar and seem to be somewhat more common in Caucasians, the elderly, and women.3Leggett B. Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.Gastroenterology. 2010; 138: 2088-2100Google Scholar, 9Higuchi T. Sugihara K. Jass J.R. Demographic and pathological characteristics of serrated polyps of the colorectum.Histopathology. 2005; 47: 32-40Google Scholar The risk for CRC among patients with serrated polyps depends on the size, number, and histologic features of the polyps. On 1 end of the spectrum, individuals who meet the clinical criteria for the rare ‘hyperplastic polyposis’ syndrome (better termed ‘serrated polyposis’), have a markedly increased lifetime risk (20%–50%) for CRC, especially those with multiple (≥5) large serrated polyps.16Chow E. Lipton L. Lunch E. et al.Hyperplastic polyposis syndrome: phenotypic presentations and the role of MBD4 and MYH.Gastroenterology. 2006; 131: 30-39Abstract Full Text Full Text PDF Scopus (157) Google Scholar On the other end of the spectrum, individuals with a small number of diminutive HPs confined to the rectosigmoid colon are not at increased risk for CRC compared with individuals found to have no polyps at colonoscopy.12Imperiale T.F. Glowinski E.A. Lin-Cooper C. et al.Five-year risk of colorectal neoplasia after negative screening colonoscopy.N Engl J Med. 2008; 359: 1218-1224Google Scholar The risk for CRC in individuals with large (≥1 cm) serrated polyps is increased, but the magnitude of that risk remains unclear. Our group was the first to find that the presence of large serrated polyps was an independent predictor of synchronous advanced colorectal neoplasia.15Li D. Jin C. McCulloch C. et al.Association of large serrated polyps with synchronous advanced colorectal neoplasia.Am J Gastroenterol. 2009; 104: 695-702Google Scholar Among 4714 patients undergoing screening colonoscopy, the odds ratio (OR) of advanced colorectal neoplasia was >3 in patients with large serrated polyps.15Li D. Jin C. McCulloch C. et al.Association of large serrated polyps with synchronous advanced colorectal neoplasia.Am J Gastroenterol. 2009; 104: 695-702Google Scholar Importantly, we found that the risk for synchronous advanced neoplasia among patients with large serrated polyps was greater than that among patients with 1–3 small tubular adenomas. Our findings now are confirmed by the findings of Hiroaka et al,1Hiroaka S. Kato J. Fujiki S. et al.The presence of large serrated polyps increases risk for colorectal cancer.Gastroenterology. 2010; 139: 1503-1510Google Scholar who also found a strong and independent association between the presence of large serrated polyps with synchronous advanced neoplasia (OR, 4.01; 95% confidence interval [CI], 2.83–5.69) and synchronous CRC (OR, 3.34; 95% CI, 2.16–5.03), especially for proximal CRC, among a cohort of 10 199 patients undergoing their first colonoscopy.1Hiroaka S. Kato J. Fujiki S. et al.The presence of large serrated polyps increases risk for colorectal cancer.Gastroenterology. 2010; 139: 1503-1510Google Scholar Schreiner et al,2Schreiner M.A. Weiss D.G. Lieberman D.A. et al.Proximal and large hyperplastic and nondyplastic serrated polyps detected by colonoscopy are associated with neoplasia.Gastroenterology. 2010; 139: 1497-1502Abstract Full Text Full Text PDF Scopus (207) Google Scholar using data from a cohort of 3121 asymptomatic veterans undergoing screening colonoscopy, likewise found that patients with large ND-SPs (ie, mainly HPs or SSAs) were more likely to have synchronous advanced neoplasia (OR, 3.37; 95% CI, 1.71–6.62).2Schreiner M.A. Weiss D.G. Lieberman D.A. et al.Proximal and large hyperplastic and nondyplastic serrated polyps detected by colonoscopy are associated with neoplasia.Gastroenterology. 2010; 139: 1497-1502Abstract Full Text Full Text PDF Scopus (207) Google Scholar Schreiner et al also cast new light on the importance of proximal ND-SP, irrespective of size. Among 248 patients (7.9% of the screening cohort) with ≥1 proximal ND-SP, there was an increased likelihood of synchronous advanced adenoma (OR, 1.90; 95% CI, 1.33–2.70). Of greater clinical importance, they were also able to analyze findings at follow-up colonoscopy among patients with and without proximal ND-SD. Among 39 patients with proximal ND-SP but no adenomas at initial colonoscopy, advanced neoplasia was found in 2 (5.1%) and any neoplasia in 17 (43.6%) at follow-up colonoscopy performed within 5.5 years, representing an increased OR of 3.14 (95% CI, 1.59–6.20) for metachronous neoplasia compared with polyp-free controls.2Schreiner M.A. Weiss D.G. Lieberman D.A. et al.Proximal and large hyperplastic and nondyplastic serrated polyps detected by colonoscopy are associated with neoplasia.Gastroenterology. 2010; 139: 1497-1502Abstract Full Text Full Text PDF Scopus (207) Google Scholar Among patients with small tubular adenomas (<10 mm) at initial colonoscopy, the synchronous presence of proximal ND-SP did not increase likelihood of finding advanced neoplasia or any neoplasia during follow-up examination. By contrast, among patients with advanced neoplasia at baseline colonoscopy, a concomitant proximal ND-SP increased the likelihood at surveillance examination of finding advanced neoplasia (OR, 2.25) or any neoplasia (OR, 2.17) compared with patients without proximal ND-SP. The primary problem with our study,15Li D. Jin C. McCulloch C. et al.Association of large serrated polyps with synchronous advanced colorectal neoplasia.Am J Gastroenterol. 2009; 104: 695-702Google Scholar and those of Hiroaka et al1Hiroaka S. Kato J. Fujiki S. et al.The presence of large serrated polyps increases risk for colorectal cancer.Gastroenterology. 2010; 139: 1503-1510Google Scholar and Schreiner et al,2Schreiner M.A. Weiss D.G. Lieberman D.A. et al.Proximal and large hyperplastic and nondyplastic serrated polyps detected by colonoscopy are associated with neoplasia.Gastroenterology. 2010; 139: 1497-1502Abstract Full Text Full Text PDF Scopus (207) Google Scholar is that the serrated polyps are not well classified by histology. Hiroaka et al combined all serrated polyps (HPs, SSAs, and TSAs) in their definition and analysis of serrated polyps. Our study and that of Schreiner attempted to exclude serrated polyps with dysplasia (ie, most TSAs) from the analysis based on pathology reports generated at the time, but in neither study was the histology of the polyps re-reviewed in light of the new classifications of serrated polyps. Indeed, the initial screening colonoscopies in VA 380 were conducted between 1994 and 1997, 6 years before Torlakovic et al14Torlakovic E. Skovland E. Snover D.C. et al.Morphologic reappraisal of serrated colorectal polyps.Am J Surg Pathol. 2003; 27: 65-81Google Scholar first described SSAs as a distinct subtype of serrated polyps. Therefore, none of these 3 studies can discern the relative cancer risk among large or numerous or proximal HPs versus SSAs. This remains a critical shortcoming of the available data. Another critical clinical question regarding serrated polyps is whether they progress to invasive cancer faster than conventional adenomas. Again, we are hampered by a lack of prospective studies that carefully categorize serrated polyps based on histology and include a sufficient long-term follow-up. We do know that the proportion of SSAs relative to the number of serrated cancers is far greater than the proportion of tubular adenomas (even advanced adenomas) to conventional colorectal adenocarcinoma.9Higuchi T. Sugihara K. Jass J.R. Demographic and pathological characteristics of serrated polyps of the colorectum.Histopathology. 2005; 47: 32-40Google Scholar This observation provides indirect evidence that SSAs are more likely to progress to cancer and may do so faster than conventional tubular adenomas. By contrast, a recent large cross-sectional study reported that the median age of patients with SSAs is 61 years, whereas those with serrated cancers was 76 years, suggesting a late onset and slow progression.17Lash R.H. Genta R.M. Schuler C.M. Sessile serrated adenomas: prevalence of dysplasia and carcinoma in 2139 patients.J Clin Pathol. 2010; 63: 665-668Google Scholar Therefore, no conclusions can yet be drawn whether serrated polyps progress more quickly to invasive cancer. The short answer is yes. Large or proximal serrated polyps, viewed collectively, are a marker for increased risk of synchronous, and likely metachronous, advanced neoplasia and cancer at a level equal or greater to that observed in patients with ≥1 small tubular adenomas.1Hiroaka S. Kato J. Fujiki S. et al.The presence of large serrated polyps increases risk for colorectal cancer.Gastroenterology. 2010; 139: 1503-1510Google Scholar, 2Schreiner M.A. Weiss D.G. Lieberman D.A. et al.Proximal and large hyperplastic and nondyplastic serrated polyps detected by colonoscopy are associated with neoplasia.Gastroenterology. 2010; 139: 1497-1502Abstract Full Text Full Text PDF Scopus (207) Google Scholar, 15Li D. Jin C. McCulloch C. et al.Association of large serrated polyps with synchronous advanced colorectal neoplasia.Am J Gastroenterol. 2009; 104: 695-702Google Scholar In addition, missed or interval cancers remain a significant impediment to CRC prevention efforts, and these cancers are 4– times more likely to be CIMP-H and/or MSI, both features of serrated pathway cancers.18Sawhney M.S. Farrar W.D. Gudiseva S. et al.Microsatellite instability in interval colon cancers.Gastroenterology. 2006; 131: 1700-1705Google Scholar, 19Arain M.A. Sawhney M. Sheikh S. et al.CIMP status of interval colon cancers: another piece to the puzzle.Am J Gastroenterol. 2010; 105: 1189-1195Google Scholar Although firm conclusions regarding the absolute and differential risk and rate of progression of CRC among the different types of serrated polyps remains uncertain, it seems prudent to err on the side of caution to treat all serrated lesions, other than diminutive HPs of the rectosigmoid colon, as premalignant and worthy of complete resection and appropriate surveillance colonoscopy. The inability of most clinical pathologists to distinguish reliably between the subtypes of serrated polyps at this time further argues that we should regard these lesions as important and worthy of increased vigilance.20Glatz K. Pritt B. Glatz D. et al.A multinational, internet-based assessment of observer variability in the diagnosis of serrated colorectal polyps.Am J Clin Pathol. 2007; 128: 348Google Scholar Based on the best available data, we propose a modification to the current surveillance guidelines that explicitly recognizes the importance of large or proximal serrated polyps (Table 1). Key to our recommendations is a recognition that serrated polyps once removed require endoscopic surveillance similar to that recommended in patients with traditional colonic adenomas.Table 1Proposed New Guidelines for Serrated PolypsaSerrated polyps include HPs, sessile serrated adenomas and TSAs.Lesion foundSurveillance interval (y)Serrated polyposisbWorld Health Organization defines hyperplastic (serrated) polyposis as (1) ≥5 histologically diagnosed HPs proximal to the sigmoid colon, of which 2 are >10 mm in diameter; or (2) any number of HPs that occur proximal to the sigmoid colon in an individual who has a first-degree relative with HPS; or (3) >30 HPs of any size that are distributed throughout the colon.1Serrated polyp with any cytological dysplasia3Serrated polyp proximal to the splenic flexure3Serrated polyp ≥10 mm3Serrated polyps <10 mm and distal to the splenic flexure10a Serrated polyps include HPs, sessile serrated adenomas and TSAs.b World Health Organization defines hyperplastic (serrated) polyposis as (1) ≥5 histologically diagnosed HPs proximal to the sigmoid colon, of which 2 are >10 mm in diameter; or (2) any number of HPs that occur proximal to the sigmoid colon in an individual who has a first-degree relative with HPS; or (3) >30 HPs of any size that are distributed throughout the colon. Open table in a new tab Our recommendation to repeat colonoscopy in 3 years for patients with serrated polyps with any dysplasia, or those ≥1 cm in size, or those proximal to the splenic flexure regardless of size, remains empirical. Future research may allow us to modify these recommendations recognizing the unique cancer risks and growth rates of large HPs versus SSAs versus TSAs factoring in their size and number and location. It may prove to be that SSAs, for example, require a surveillance interval of <3 years. Given the uncertainty, it is important for the precise interval for a specific patient be customized in close coordination with the pathologist. Also, it remains crucial that these lesions be completely removed when initially encountered, and there should be a low threshold to repeating colonoscopy if there is any uncertainty in this regard, understanding that serrated polyps may be more likely than conventional adenomas to be missed or incompletely removed because many are nonpolypoid and can have a subtle, poorly delineated appearance. Proximal and Large Hyperplastic and Nondysplastic Serrated Polyps Detected by Colonoscopy Are Associated With NeoplasiaGastroenterologyVol. 139Issue 5PreviewThe family of serrated lesions includes hyperplastic polyps and sessile serrated adenomas without dysplasia, as well as traditional serrated adenoma with dysplasia. We investigated whether detection of proximal nondysplastic serrated polyps (ND-SP) at screening and surveillance colonoscopies is associated with advanced neoplasia. Full-Text PDF The Presence of Large Serrated Polyps Increases Risk for Colorectal CancerGastroenterologyVol. 139Issue 5PreviewThere is evidence that serrated polyps (serrated adenomas and hyperplastic polyps) have different malignant potential than traditional adenomas. We used a colonoscopy database to determine the association between the presence of serrated colorectal polyps and colorectal neoplasia. Full-Text PDF