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Variant forms of hyperplastic polyps of the colorectum, the so-called sessile serrated polyp (SSP) or sessile serrated adenoma (SSA), have recently been described. These are characterised by crypts whose serrations extend all the way to the crypt base, with a widened base that may extend laterally in a ‘boot shape’. Cytological abnormalities of the sort usually required of traditional adenomas—nuclear enlargement and loss of basal orientation—are not essential to the newer SSA terminology.1–4 A tendency for pathologists to engage in descriptive and terminological splitting have the workaday endoscopist and pathologist struggling to keep up and to decide what is important. One might not care except for the presence of emerging details of associations between sessile serrated lesions and colorectal cancer (CRC).5 6 The complex categorisation of morphological subtypes and the specifics of cancer risk have been abetted by molecular pathology correlations.7 8
Complicating matters in the world of serrated neoplasia of the colorectum has been the relationship between multiple hyperplastic polyps (HPs), or ‘hyperplastic polyposis syndrome (HPS)’ and the serrated morphology/molecular signature/cancer risk story.9 Indeed, the very term hyperplastic polyposis is defined in terms of very arbitrary criteria that have never been validated and almost certainly involves a heterogeneous spectrum of conditions. However confusing the HPS story may be, most would agree that at least when the HPs of HPS are large, right sided and/or part of the SSA spectrum, they are important to endoscopists, pathologists and colorectal surgeons.
In this issue of Gut (see page 1094), members of a seven-institution Netherlands consortium conducted a retrospective review of their 1982–2008 experience with respect to demographic, endoscopic and pathological features in patients with hyperplastic polyposis.10 This followed the WHO classification11: at least five histologically diagnosed HPs proximal to the sigmoid colon, of which two >10 mm in diameter, or >20 HPs distributed throughout the colon. Of the 77 cases, 27 (35%) developed CRC, ∼80% of which were detected at baseline. Univariate analysis showed the number of HPs and of serrated adenomas to be predictors of CRC risk. Five cases (6.5% of the total series) were diagnosed at follow-up intervals as short as 1–2 years, and in several such cases the invasive malignancies were found in serrated polyps <1 cm in diameter, likely to have been missed on prior exam. This last point is probably the one of greatest interest to the endoscopist—that is, while more properly conducted, large, prospective series will need to be done to quantify cancer risk more accurately, it is evident that in patients with multiple HPs, especially if SSA, cancer risk in small, subtle lesions is real.12
Acknowledging the controversies noted at the beginning of this Commentary, this Dutch consortium has nevertheless undertaken to identify factors associated with cancer risk in hyperplastic polyposis, as distinguished from isolated serrated polyps, and has done so utilising a large number of cases drawn from a fairly integrated and well-curated database system in one country.
As with other similar efforts, significance was limited by the retrospective nature of the data set—one must be concerned about the consistency in descriptions and terminology over the long time period of the data collection. Such retrospective studies tend to overstate cancer risk and, in this series, 35% of subjects underwent resection for malignancy.
What is the endoscopist to do in response to such data?
The key question is how aggressively should right colon lesions be sought for and treated? Sessile serrated polyps can be very subtle and flat, commonly covered with a smooth cap of tenacious mucus. In a clean colon they can be characterised by means of high resolution colonoscopy, aided by narrow band imaging or by indigo carmine dye spray.13 The notion of a significant malignant potential in SSPs runs counter to a still prevalent dogma that HPs are inconsequential, a dogma that itself replaced even earlier dogmas.
Unlearning old dogmas, especially ones that we thought were evidence based, takes some doing. The current confusion over the significance of serrated colon polyps has led to inconsistent approaches to endoscopic management. There is variable aggressiveness in removing serrated lesions and no agreed-upon follow-up interval once they have been removed.
A sense of the need for polypectomy has changed considerably. HPs, if signed out as such by the pathologist, may at one time have simply been followed expectantly in the belief, now known to be erroneous, that cancer risk was minimal even if the lesion was large. Now, most would agree SSAs need to be removed, especially if large. Formal endoscopic mucosal resection may commonly be necessary. Boparai et al10 suggest that the large right-sided SSAs should be left to those with expertise in endoscopic mucosal resection (EMR). Probably all hyperplastic-appearing lesions of any size in the right colon should be treated as SSAs and completely removed.
The following perspective on hyperplastic polyposis/SSA is based on a synthesis of the literature and personal experience in the endoscopic management of patients with a range of serrated lesions:
Patients with only diminutive HPs of the left colon and rectum, even when numerous, can be managed very conservatively, with sampling of representative lesions to document that they are, in fact, only HPs of typical histology. They do not merit aggressive endoscopic treatment or follow-up and virtually never need come to surgical resection.
Isolated serrated polyps of the right colon, even if small, should be removed completely and followed in much the same fashion as adenomas, so long as the ‘newer’ features of SSP/SSA are present. Larger lesions warrant EMR in the same fashion as corresponding adenomas. The practising colonoscopist must establish a dialogue with his or her pathologist, making sure that they are communicating effectively regarding the status of patients with serrated polyps, while keeping mutually abreast of the evolving molecular and morphological literature.
Until more is known regarding the natural history of patients with SSA, follow-up colonoscopy should be conducted at an interval no less frequent than that employed for adenomas of corresponding number, size and degree of dysplasia. SSAs appear to be a part of the CpG island methylator phenotype (CIMP) pathway that can ultimately lead to malignancies that show microsatellite instability (MSI). In such cases the MSI is related to methylation of the promoter region of the hMLH1 and other genes, as well as mutations in the BRAF gene.
Although the basis for MSI differs from that seen in hereditary non-polyposis colorectal cancer (HNPCC), the discovery of cancers in small lesions at short intervals in the study of Boparai et al very much parallels the experience of rapid tumour evolution that is seen in HNPCC. As in HNPCC, this may support the case for follow-up at shorter intervals when SSAs are identified. Whether or not there is clinical utility in performing molecular studies in SSAs remains to be seen; however, prospective studies assessing molecular correlations in small lesions may help determine whether aggressive surveillance of otherwise histologically bland lesions can really be supported, and whether there is a role for molecular studies in clinical decision making when small lesions are removed. In this regard, a search of clinical practice guidelines, including those of the American Gastroenterology Association and American Society of Gastrointestinal Endoscopy failed to yield any guidelines for management of SSA, with or without associated HPS.14 15
Hyperplastic polyposis, according to the WHO criteria, remains heterogenous. Fortunately uncommon and always challenging to manage appropriately, each case must be handled individually. As noted by Boparai et al, cancer risk appears to increase with the number of HPs/SSAs, yet removal of numerous, flat lesions can be both tedious and risky. So, with the exception of the many cases that really fall into the category of common distal hyperplastic polyposis, most cases involving larger right-sided polyps can be approached in a fashion similar to that of corresponding multiple adenoma cases: when endoscopically manageable, manage endoscopically; when endoscopically unmanageable, refer for consideration of surgical resection. Invite the surgeon to join what should already be an ongoing conversation with the pathologist. Consider referring the case to a speciality centre, if only in the interest of obtaining a second opinion on the proper aggressiveness to be followed. Though the molecular pathways for serrated lesions are fascinating and rapidly being explored, patients that really have multiple hyperplastic polyposis are uncommon and should be considered for entry into family and molecular genetic studies to identify possible underlying genetic predisposition.