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Serrated Polyps, Part 2: Their Mechanisms and Management

Posted February 7, 2014

Ryan C. Romano, DO

In the prelude to this article (Serrated Polyps Part I: Their Confusing History) we discussed the evolution of colorectal serrated polyp classification, a group that comprises hyperplastic polyps (HP), sessile serrated polyps/sessile serrated adenomas (SSP/SSA), and traditional serrated adenomas (TSA). Classification of these lesions is complicated by overlap of morphologic features and significant diagnostic interobserver variability.1 These features include prominent serration of the crypt epithelium and varying degrees of nuclear atypia and dysplasia (rare in HP, variable in SSA/SSP, and common in TSA).2-6

When serrated polyps progress to malignancy, they do so via a novel molecular pathway, and this pathway may be attributed to up to 30% of sporadic colorectal cancers and up to 15% to 20% of all colorectal cancers.3,5,7 The CpG-island-methylation-phenotype (CIMP), as this pathway is known, refers to hypermethylation of dense clusters of cytosine-guanine dinucleotides, CpG islands, which are present in promoter regions of approximately half of all genes.3,8 Aberrant hypermethylation leads to silencing of genes that encode tumor suppressor genes and mismatch repair genes, leading to microsatellite instability.3-5 This pathway may promote earlier progression from SSA to carcinoma when compared to the traditional adenomacarcinoma timeline, making surveillance intervals a critical metric to reevaluate.5 In addition, the oncogene BRAF is mutated in approximately 80% of serrated adenomas. This is often a single, activating point mutation (V600E) leading to constitutive signaling of the mitogen-activated protein kinase (MAPK) pathway, resulting in cell proliferation and survival. To contrast, BRAF mutations are rare in conventional adenomas.3

Risk factors for the development of serrated polyps appear to be the same as those for development of other colonic polyps and include advancing age, smoking, increased body mass index, and inflammatory bowel disease, among others.9-12 Clinical diagnosis and detection of serrated polyps may be difficult using CT colonography or traditional endoscopy, as the lesions are often flat, pale with minimal vascular changes of the mucosa, and may be masked by prominent mucous3 Chromoendoscopy may significantly improve detection.3,13 Fecal occult blood testing is of little value given that serrated polyps are less likely to bleed than adenomatous polyps.14 Novel biomarkers such as SDC2, which detect DNA hypermethylation, show promise for noninvasive detection of colorectal cancer, though further investigation is needed to validate its use in screening, to clarify expression profiles of SDC2 in various polyps, and to determine if its expression is indeed exclusive to colorectal cancer.15

All but the most diminutive distal hyperplastic polyps should be completely removed whenever possible.3 Patients found to have a nondysplastic sessile serrated polyp = 10 mm should undergo repeat screening colonoscopy in five years. A three-year surveillance interval is assigned to SSAs = 10 mm, an SSA of any size with dysplasia, and TSAs. Patients with serrated polyposis syndrome should be screened annually.16

Inconsistent or confusing terminology, along with the lack of clear histologic criteria for diagnosis, has led to frequent misclassification of serrated polyps, severely impacting our ability to accurately study the epidemiological, clinical, and pathological characteristics of these lesions. As a result, little is known about the true risk of progression to carcinoma, creating a challenge for clinicians and pathologists in formulating proper management strategies. Detailed molecular profiling and the establishment of standardized diagnostic criteria will go a long way in helping to better understand the behavior of this group of polyps.3,5 Serrated polyps are but one example highlighting the importance of clinicopathologic correlation and communication between pathologists and clinicians.

See Table 1

References

  1. Glatz K, Pritt B, Glatz D, Hartmann M, O’Brien MJ, Blaszyk H. A multinational, internet-based assessment of observer variability in the diagnosis of serrated colorectal polyps. Am J Clin Pathol. 2007;127(6):938-945.
  2. Snover DC, Jass JR, Fenoglio-Preiser C, Batts KP. Serrated polyps of the large intestine: a morphologic and molecular review of an evolving concept. Am J Clin Pathol. 2005;124(3):380–391.
  3. Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138(6):2088-2100. doi:10.1053/j.gastro.2009.12.066.
  4. Odze RD, Goldblum JR. Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. 2nd ed. Philadelphia, PA: Saunders Elsevier: 2009: 498-507.
  5. Aust DE, Baretton GB, Members of the Working Group GI-Pathology of the German Society of Pathology. Serrated polyps of the colon and rectum (hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed polyps) – proposal for diagnostic criteria. Virchows Arch. 2010;457(3):291-297.
  6. Longacre TA, Fenoglio-Preiser CM. Mixed hyperplastic adenomatous polyps/serrated adenomas. A distinct form of colorectal neoplasia. Am J Surg Pathol. 1990;14(6):524-537.
  7. Sugumar A, Sinicrope FA. Serrated polyps of the colon. F1000 Medicine Reports. 2010;2:89. doi:10.3410/M2-89.
  8. Bird AP. CpG-rich islands and the function of DNA methylation. Nature. 1986;321(6067):209-213.
  9. Heitman SJ, Ronksley PE, Hilsden RJ, Manns BJ, Rostom A, Hemmelgarn BR. Prevalence of adenomas and colorectal cancer in average risk individuals: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2009;7(12):1272–1278. doi:10.1016/j.cgh.2009.05.032.
  10. Ben Q, An W, Jiang Y, et al. Body mass index increases risk for colorectal adenomas based on meta-analysis. Gastroenterology. 2012;142(4):762–772. doi:10.1053/j.gastro.2011.12.050.
  11. Ji BT, Weissfeld JL, Chow WH, Huang WY, Schoen RE, Hayes RB. Tobacco smoking and colorectal hyperplastic and adenomatous polyps. Cancer Epidemiol Biomarkers Prev. 2006;15(5):897-901.
  12. Srivastava A, Redston M, Farraye FA, Yantiss RK, Odze RD. Hyperplastic/serrated polyposis in inflammatory bowel disease: a case series of a previously undescribed entity. Am J Surg Pathol. 2008;32(2):296-303.
  13. Ward RL, Cheong K, Ku SL, Meagher A, O’Connor T, Hawkins NJ. Adverse prognostic effect of methylation in colorectal cancer is reversed by microsatellite instability. J Clin Oncol. 2003;21(20):3729-3736.
  14. East JE, Saunders BP, Jass JR. Sporadic and syndromic hyperplastic polyps and serrated adenomas of the colon: classification, molecular genetics, natural history, and clinical management. Gastroenterol Clin North Am. 2008;37(1):25-46,v. doi:10.1016/j.gtc.2007.12.014.
  15. Oh TJ, Kim N, Moon Y, et al. Genome-wide identification and validation of a novel methylation biomarker, SDC2, for blood-based detection of colorectal cancer. J Mol Diagn. 2013;15(4):498-507. doi:10.1016/j.jmoldx.2013.03.004.
  16. Lieberman DA, Rex DK, Winawer SJ, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143(3):844–857. doi:10.1053/j.gastro.2012.06.001.

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NewsPath® Editor: Kyle L. Eskue, MD, FCAP
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