Serrated polyposis syndrome (SPS) is a condition characterized by the abundance of serrated lesions in the large intestine. These serrated lesions include hyperplastic polyps (HPs) and sessile serrated adenomas/polyps (SSA/Ps) with or without cytologic dysplasia as well as the less common traditional serrated adenomas and unclassified serrated polyps. Together, these serrated lesions are believed to be morphologic representations of a neoplastic continuum toward the progression to colorectal cancer (CRC).1–6 Although it appears that patients with SPS are at an increased risk for CRC,7–11 it is often difficult to identify patients with SPS before the development of a colorectal malignancy.
The World Health Organization (WHO) criteria for SPS, originally described by Burt and Jass,12 require patients to have 1) at least 5 serrated lesions proximal to the sigmoid colon with 2 or more of these being greater than 10 mm; 2) any number of serrated lesions proximal to the sigmoid colon in an individual who has a first-degree relative with SPS; or 3) greater than 20 serrated lesions of any size, but distributed throughout the colon13 (Table 1). Although useful for diagnosing SPS, serrated lesions may not be ideal as a screening tool for populations who appear to be at risk but do not initially meet diagnostic criteria. To increase the detection of SPS, this study examined the yield of using an initial screening tool of at least 2 pathologically confirmed HPs and/or SSA/Ps to identify patients who meet WHO criteria for SPS.
As previously demonstrated, screening cutoffs using 3 or more serrated lesions drastically decreases the sensitivity of the tool to detect SPS and can potentially lead to missed diagnoses.14 Therefore, the screening cutoff of at least 2 serrated lesions was chosen. Records of patients with at least 2 pathologically proven HPs and/or SSA/Ps in the colon and/or rectum diagnosed between 1999 and 2009 were retrospectively reviewed within a specialized cancer care center. Cumulative polyp data from available colonoscopy and pathology reports were included. Polyp categories included HPs and SSA/Ps, and adenomas (including tubular, tubulovillous, and villous). The total numbers of colonoscopies, total numbers of polyps, and polyp sizes and location were noted. In consultation with our study gastroenterologist, descriptive terms used in colonoscopy and pathology reports were quantified to address the study question. For example, the terms “several” and “multiple” were conservatively defined as 3 and 10 polyps, respectively, in cases where the total numbers of polyps were not clearly stated in the colonoscopy and pathology reports. Polyps described as “dimunitive” or “small” and those described as “large” were conservatively defined to be 1 mm and 10 mm. The frequency of colonoscopic screening and/or surveillance for each individual was in accordance with recommendations from the American Gastroenterological Association and the United States Multi-Society Task Force.15,16 Patients with known histories of IBD or other hereditary CRC syndromes were excluded.
Demographic and clinical data including age, sex, history of tobacco use, personal and family history of SPS and/or CRC, and personal history of other malignancies were extracted for those patients who met the first and/or the third WHO criteria for SPS. Because family histories are subjective and not always reliable, none of the patients were diagnosed with SPS based on the second criterion alone (any number of serrated lesions proximal to the sigmoid colon in an individual who has a first-degree relative with SPS). Age at SPS diagnosis was calculated from the date of the “index” colonoscopy, which was defined as the procedure when the first and/or the third WHO criteria for SPS was satisfied. For patients with a history of CRC, the age at the time of cancer diagnosis was collected.
Five hundred patients with at least 2 HPs and/or SSA/Ps were retrospectively identified from a total of 976 patients with at least 1 HP and/or SSA/P. Forty (8%) of these patients met WHO criteria for SPS. Table 2 lists the demographic information for these 40 individuals with SPS.
Overall, 229 colonoscopies were performed among the 40 patients with SPS, for a median of 4 colonoscopies per patient (range, 1–23). Only 1 of the 40 (3%) patients met WHO criteria for SPS during their initial colonoscopy. Five of the 16 (31%) patients with CRC met WHO criteria for SPS on subsequent postoperative colonoscopies. The other 11 (69%) SPS patients with a history of CRC met WHO criteria for SPS at the same time as CRC diagnosis. Specific colonoscopic findings for the SPS cohort are illustrated in Table 3.
Table 4 lists the frequency of individual WHO criteria satisfied by our SPS cohort. Thirty-two of the 40 (80%) patients had greater than 20 serrated lesions of any size distributed throughout the colon, making the third criterion the most commonly satisfied of the WHO criteria for SPS. Although we did not use the second WHO criterion of family history of SPS as a diagnostic criterion in our study, it should be noted that only 8% of SPS cases reported having a first-degree relative with SPS, and only 5 (13%) patients were enrolled in the institutional Hereditary Colorectal Cancer Family Registry before this study.
Our study from a single institution demonstrates that a cutoff of at least 2 pathologically confirmed HPs and/or SSA/Ps can be used as a screening tool for identifying individuals with SPS. Because pathology and colonoscopy reports are routinely available on all patients, we believe that this approach is feasible and may serve as a valuable complement to the WHO criteria for SPS. The need for such an adjunct to the WHO criteria for SPS is twofold. First, few patients with SPS are detected on the initial colonoscopy and/or at the time of CRC resection. Such patients therefore require careful documentation of the presence of pathologically proven serrated lesions on subsequent colonoscopies to assess whether the cumulative number of pathologically confirmed serrated lesions meets 1 of the WHO criteria for SPS diagnosis. Additionally, the use of family history for SPS diagnosis is unreliable because patients with SPS may not necessarily divulge their diagnoses to other family members, especially in cases where malignancy is not involved.
Although 40% of our cohort met the first WHO criterion (at least 5 serrated lesions proximal to the sigmoid colon with 2 or more of these being greater than 10 mm) for SPS diagnosis, only 1 of the 16 (6%) patients met this criterion on their first colonoscopy. All other patients meeting the first criterion required a median of 6 colonoscopies before enough lesions were detected to satisfy the number and size requirements. Thus, the majority of SPS patients meeting the first WHO criterion require multiple colonoscopies and a tracking mechanism to tabulate the cumulative number of serrated lesions over time.
Although we do not use the second WHO criterion (any number of serrated lesions proximal to the sigmoid colon in an individual who has a first-degree relative with SPS) in our study, it should be noted that using it as the lone diagnostic criterion would have yielded only 8% of our SPS cohort. Although first-degree relatives of patients with SPS have an associated risk of having SPS and developing CRC,17–19 the use of the second criterion for identifying new SPS cases will likely remain limited until SPS becomes a more readily recognized entity.
The use of the third WHO criterion (greater than 20 serrated lesions of any size distributed throughout the colon) as the stand-alone criterion for SPS diagnosis also has its limitations, because most endoscopists are unlikely to biopsy 20 polyps at one time. Meeting the third criterion likely requires the evaluation of multiple colonoscopies to accumulate the necessary number of lesions and to clinch a diagnosis of SPS. As demonstrated, patients in our cohort who met the third criterion needed a median of 5 colonoscopies to do so. Therefore, although the WHO criteria can be used to identify SPS patients in a retrospective manner, clinicians need a more accessible method to prospectively identify those individuals who harbor clinically suspicious phenotypes that may not yet meet WHO criteria for SPS but warrant careful follow-up that would include periodic reassessments for SPS.
Crowder et al14 demonstrated that setting the screening cutoff at only 1 serrated lesion resulted in a large cohort of 929 patients, of which only 17 (1.8%) met the WHO criteria for SPS. By using at least 2 pathologically proven HPs or SSA/Ps as a screening tool, we were able to reduce our cohort from 976 individuals with at least 1 HP or SSA/P to 500 and subsequently to identify 40 (8%) patients with colonoscopic phenotypes consistent with SPS. This suggests that using 2 as opposed to 1 pathologically proven HP or SSA/P as a screening tool is more efficient, because fewer patient records need to be reviewed to obtain a greater yield in patients meeting the WHO criteria for SPS.
There are a number of limitations to our study. The number of lesions observed in our study population may be skewed given that the study was performed at an institution specializing in cancer care and may not reflect the complete pathologic history and nature of SPS. An additional limitation is that we may not have been as accurate in capturing the number of polyps per patient, because we had to arbitrarily designate values to descriptive terms used in colonoscopy and pathology reports. Unfortunately, given the prevalent use of qualitative descriptors by endoscopists at most institutions, it would have been extremely difficult to omit colonoscopy reports containing these terms from our analysis without excluding a significant number of our SPS cases. Hence, we attempted to provide objective definitions for these subjective terms with the help of our study gastroenterologist, although this method of assessment has the previously discussed drawbacks. Because accurate reporting of colonoscopic findings remains a global issue, our study highlights the difficulties associated with interpreting these qualitative terms within the contexts of both research and clinical identification of potential patients with SPS. By discussing this important limitation of our study, we hope to encourage endoscopists to move away from using uninformative terms whose definitions are not universally agreed upon and, instead, move toward using a quantitative approach in data reporting, so that we can maximize the colonoscopic yield for identifying SPS cases.5
Furthermore, our initial screening included patients with serrated lesions of both the colon and rectum to be all-inclusive and to capture patients with polyps at the interface between the sigmoid and rectum. However, to increase specificity, the screening tool of at least 2 pathologically confirmed HPs and/or SSA/Ps can probably be limited solely to the colon. Therefore, until SPS becomes more clearly defined, a requirement of at least 2 serrated lesions throughout the colon as a cutoff point will serve to limit the number of screened patients while maximizing the yield of individuals potentially afflicted with SPS. The need for such a screening tool is demonstrated by the fact that 87% of our cohort with SPS was not enrolled in our Hereditary Colorectal Cancer Family Registry at the time of study, suggesting that, despite an institutional interest in SPS, a number of SPS cases had not been diagnosed.
Although Crowder et al emphasize the pathologist’s role in identifying patients with SPS, our study suggests that endoscopists, along with their support teams, may be in a better position to implement a system in which the cumulative polyp burden over successive colonoscopies, histologies of biopsied lesions, and family histories of those individuals suspected to have SPS can be carefully and systematically documented. The goal is not only to increase the yield of SPS cases, but also to provide those identified as having SPS with annual colonoscopic surveillance to prevent the development of interval CRC.16 In our study, all 16 CRC patients developed CRC before or at the same time as meeting the WHO criteria for SPS. Thus, establishing a diagnosis not only requires time and thorough communication between the clinician and his support staff, but also underscores the value of a prospectively collected registry database to track clinically concerning patients.
Despite our current understanding of SPS, its definition remains vague, and, consequently, it is likely that the syndrome remains vastly underrecognized. Our study demonstrates that using a cutoff of 2 pathologically confirmed HPs and/or SSA/Ps either on initial colonoscopy results or based on a review of the cumulative polyps removed over time may allow physicians to more readily recognize patients who may have SPS. In conjunction with the WHO criteria, this simple tool may considerably enhance the identification of patients with SPS who warrant careful colonoscopic evaluation as well as improve our understanding of this disease by increasing the number of potential SPS cases for participation in future prospective studies.
1. Longacre TA, Fenoglio-Preiser CM. Mixed hyperplastic adenomatous polyps/serrated adenomas: a distinct form of colorectal neoplasia. Am J Surg Pathol. 1990;14:524–537
2. Leggett BA, Devereaux B, Biden K, Searle J, Young J, Jass J. Hyperplastic polyposis
: association with colorectal cancer. Am J Surg Pathol. 2001;25:177–184
3. Jass JR, Whitehall VL, Young J, Leggett BA. Emerging concepts in colorectal neoplasia. Gastroenterology. 2002;123:862–876
4. Torlakovic E, Skovlund E, Snover DC, Torlakovic G, Nesland JM. Morphologic reappraisal of serrated colorectal polyps. Am J Surg Pathol. 2003;27:65–81
5. Rex DK, Ahnen DJ, Baron JA, et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol. 2012;107:1315–1330
6. 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;37:25–46
7. Hyman NH, Anderson P, Blasyk H. Hyperplastic polyposis
and the risk of colorectal cancer. Dis Colon Rectum. 2004;47:2101–2104
8. Boparai KS, Mathus-Vliegen EM, Koornstra JJ, et al. Increased colorectal cancer
risk during follow-up in patients with hyperplastic polyposis
syndrome: a multicentre cohort study. Gut. 2010;59:1094–1100
9. Kalady MF, Jarrar A, Leach B, et al. Defining phenotypes and cancer risk in hyperplastic polyposis
syndrome. Dis Colon Rectum. 2011;54:164–170
10. Rosty C, Buchanan DD, Walsh MD, et al. Phenotype and polyp landscape in serrated polyposis
syndrome: a series of 100 patients from genetics clinics. Am J Surg Pathol. 2012;36:876–882
11. Edelstein DL, Axilbund JE, Hylind LM, et al. Serrated polyposis
: rapid and relentless development of colorectal neoplasia. Gut. 2013;62:404–408
12. Burt R, Jass JRHamilton SR, Aaltonen LA. Hyperplastic polyposis
. Pathology and Genetics of Tumours of the Digestive System. 2000;Vol 2 Lyon, France IARC:35–136
13. Snover DC, Ahnen D, Burt RW, Odze RDBosman FT, Carneiro F, Hruban RH. Serrated polyps of the colon and rectum and serrated polyposis
. Classification of Tumours of the Digestive System. 2010 Lyon IARC Press:160–165
14. Crowder CD, Sweet K, Lehman A, Frankel WL. Serrated polyposis
is an underdiagnosed and unclear syndrome: the surgical pathologist has a role in improving detection. Am J Surg Pathol. 2012;36:1178–1185
15. Levin B, Lieberman DA, McFarland B, et al.American Cancer Society Colorectal Cancer
Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee. Screening and surveillance for the early detection of colorectal cancer
and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology. 2008;134:1570–1595
16. Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TRUnited States Multi-Society Task Force on Colorectal Cancer. . Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143:844–857
17. Boparai KS, Reitsma JB, Lemmens V, et al. Increased colorectal cancer
risk in first-degree relatives of patients with hyperplastic polyposis
syndrome. Gut. 2010;59:1222–1225
18. Oquiñena S, Guerra A, Pueyo A, et al. Serrated polyposis
: prospective study of first-degree relatives. Eur J Gastroenterol Hepatol. 2013;25:28–32
19. Win AK, Walters RJ, Buchanan DD, et al. Cancer risks for relatives of patients with serrated polyposis
. Am J Gastroenterol. 2012;107:770–778