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Hyperplastic polyps, once thought to have a benign course, are now part of a larger heterogeneous group known as serrated polyps, which include hyperplastic polyps (HPs), sessile serrated polyps (SSPs), and traditional serrated adenomas (TSAs). The latter group, once known as serrated adenomas, are relatively rare, accounting for less than 5% of all serrated polyps. Thus, it is not surprising that less is known about these lesions than about conventional adenomas or even SSPs. Because these lesions have dysplasia and can progress to colorectal cancer (CRC), more data regarding prevalence and risk factors TSAs are vital. In addition, with better attention to quality and bowel preparation, it is anticipated that more TSAs might be detected in the future.
examine the prevalence and risk factors associated with TSAs. In a sample population of 31,932 participants who had a screening colonoscopy, they observed that TSAs were present in 116 individuals (0.4%), of whom 69 had synchronous conventional adenomas. This low prevalence reinforces the current belief that TSAs are uncommon. Conversely, there were 736 (2.3%) individuals with SSPs.
The authors make some other important findings regarding TSAs, including the observation that these lesions are often synchronous with advanced conventional adenomas, including large adenomas, those with villous elements, and adenomas with high-grade dysplasia. Although advanced pathologic features have been shown to be strongly linked with SSPs,
these data regarding TSAs are novel and suggest that TSAs may be surrogate markers for advanced conventional lesions. Because the current U.S. Multi-Society Task Force on CRC recommendations for surveillance of large TSAs is 3 years, similar to that for advanced adenomas, the finding may not significantly change our surveillance of these lesions.
However, it should heighten the awareness of endoscopists that they should be looking for advanced adenomas elsewhere in the colon and that the affected individuals are at high risk for future lesions or CRC, even when under endoscopic surveillance, as suggested by recent long-term data.
The authors also examined risk factors for TSAs and observe that smoking is associated with TSAs and with SSPs and conventional adenomas. Although smoking is a well-known risk factor that is strongly linked with SSPs
Smoking and the association of advanced colorectal neoplasia in an asymptomatic average risk population: analysis of exposure and anatomical location in men and women.
the association with TSAs shown in the current article is a novel finding. However, this finding is not surprising, given the link between smoking and molecular mutations observed in TSAs, including BRAF
One interesting finding was that although older age was associated with TSAs and conventional adenomas, it was not associated with SSPs in comparison with individuals with no polyps. A lack of association between older age and SSPs has also been observed in previous studies.
The large sample size allowed the authors to further compare adults with SSPs with those with TSAs and to observe that older age was the only risk factor that distinguished SSPs from TSAs. These data suggest that although younger individuals may be equally at risk for SSPs in comparison with older adults, they are less likely to harbor TSAs. With regard to the lack of other differences between SSPs and TSAs, this may not be surprising, given the similar molecular mutations that they share and also the fact that TSAs and SSPs both originate from HPs.
There are many strengths in the design of the current study, including the large sample, which was vital in accruing the numbers of TSAs needed for this type of analysis. The inclusion of asymptomatic individuals in this study also allowed for a more accurate evaluation of risk factors by removing selection bias, which may occur with the inclusion of diagnostic or surveillance examinations. Another strength of the design was that the authors examined risk factors by analyzing individuals with only TSAs or SSPs, as opposed to previous studies that have analyzed TSAs regardless of whether there were synchronous conventional adenomas.
Having individuals with only TSAs in the analysis eliminated the possibility that the presence of the conventional adenomas was responsible for a significant association with the risk factor examined as opposed to the lesion of interest, TSA or SSP.
One concern is the homogeneous population from which the data were culled: a single center in Korea. Thus, the analysis needs to be repeated in another population. Another concern in studies examining risk factors and prevalence is the possibility that the TSA estimate in the study may not have been accurate because of missed lesions. Given the classic endoscopic appearance of the TSAs with protruding morphology, it seems unlikely that they were missed. Furthermore, the adenoma detection rate in the study was 34.1%, higher than the 25% benchmark. This supports the premise that the examinations were carefully performed.
To correctly identify those individuals who harbor TSAs or SSPs, careful pathologic interpretation of the polyps is also crucial. The authors state that the World Health Organization (WHO) classification was used to classify serrated polyps and to describe features that were diagnostic of SSPs or TSAs.
However, it is well recognized that there remains considerable confusion between SSPs and HPs. Given the possibility that some large or proximal HPs might actually be SSPs,
it would have been useful if the authors had included data on large HPs, especially in comparison with TSAs.
Moreover, how certain can we be regarding the histologic interpretation of TSAs? Histologically, TSAs have the serrated crypt architecture of a hyperplastic polyp but harbor cytologic dysplasia that typically manifests as nuclear elongation and stratification that involve the surface epithelium. TSAs also show a unique cytoplasmic eosinophilia and ectopic crypt foci that are helpful in diagnosis. The presence of such dysplastic changes in hyperplastic polyps, and the possibility that some HPs may be precursors of adenomas, was first proposed in 1970.
noted that it is possible that “the polyps containing admixed hyperplastic and adenomatous glands may represent adenomatous transformation of a hyperplastic polyp.” Can this overlap with HPs be associated with variations in pathologic interpretation? We now know that slightly over half of all TSAs show a background of nondysplastic serrated polyp that resembles either an HP or an SSP, depending on location within the colon
(Fig. 1A, B). When the background lesion is an HP, pathologists will almost always diagnose these lesions simply as a TSA because a category of HP with cytologic dysplasia does not exist. However, when the background lesion is consistent with an SSP, some pathologists will diagnose such polyps as a TSA, whereas others may use the “SSP with cytologic dysplasia” category for the same lesion.
Figure 1A, Rectal polyp with features of an early traditional serrated adenoma (TSA). The background lesion is a hyperplastic polyp with crypt separation and microvesicular mucin, but 2 crypts (top right) show nuclear enlargement, hyperchromasia, and stratification consistent with cytologic dysplasia (H&E, orig. mag. ×200). B, TSA-like dysplastic change in a sessile serrated polyp (SSP). The boot-shaped, basally dilatated crypts are indicative of the background lesion in which the dysplasia arose. Such lesions, particularly when present in the right colon segment, will be diagnosed simply as a TSA by some pathologists and as an SSP with cytologic dysplasia by others (H&E, orig. mag. ×200).
The consequences for clinical management and research outcome studies created by this discrepancy are obvious. A small serrated polyp that is diagnosed as a TSA, in the absence of large size or high-grade features, will be considered a low-risk adenoma by the expert panel, with a recommended 5-year follow-up.
even though both diagnoses are being used for the same lesion. We hope that this critical issue is addressed in the next revision of the WHO classification for serrated polyps. The overlap between these 2 lesions may explain the observation regarding older age in relation to TSAs and SSPs as described above. Dysplasia in SSPs, which advance with progressively increasing methylation across the genome, usually occurs at an older age.
Perhaps some of the TSAs in the older age group might have been called SSPs with dysplasia by some pathologists. Meanwhile, gastroenterologists must be aware of this terminology confusion when treating patients with a diagnosis of TSA.
Another concern is that TSAs could be confused with conventional adenomas. When TSAs increase in size or progress toward high-grade dysplasia, they begin to resemble conventional adenomas (Fig. 2A). Despite the low-grade appearance, such areas often show a mutant p53 pattern, confirming the advanced nature of these lesions (Fig. 2B). In routine practice, however, these TSAs with conventional adenoma-like areas are likely to be diagnosed simply as conventional adenomas (Fig. 2C). This may explain the strong association between TSAs and synchronous villous adenomas in the current study. It is possible that some of these villous adenomas might have been advanced TSAs. Perhaps a reinterpretation of all advanced adenomas might have helped to identify whether any TSAs, especially on the right side, were interpreted as conventional adenomas.
Figure 2Advanced traditional serrated adenomas (TSAs) may show conventional adenoma-like areas, as seen in the center of this large rectosigmoid polyp (A, H&E, orig. mag. ×100); this finding often correlates with an abnormal mutant staining pattern on a p53 immunostain, which may show diffuse strong expression (B, p53, orig. mag. ×100) or complete loss of staining. Polyps in which TSA (above, left) and conventional adenoma-like areas (below, right) are intimately admixed are often simply diagnosed as tubular or tubulovillous adenomas in routine practice (C, H&E, orig. mag. ×100) but may actually be advanced TSAs.
Finally, as observed in the current study, TSAs and SSPs often occur with synchronous advanced adenomas. Furthermore, recent data suggest that TSAs and SSPs that are synchronous with high-risk conventional adenomas may a have a metachronous risk for future high-risk adenomas that is significantly higher than that for patients with only high-risk adenomas at baseline.
Risk of metachronous high-risk adenomas and large serrated polyps in individuals with serrated polyps on index colonoscopy: data from the New Hampshire colonoscopy registry.
Specifically, those with both serrated polyps and conventional adenomas have an association with smoking that is stronger than those with either type of polyp only. Unfortunately, a risk profile analysis with the 69 individuals with both serrated and conventional adenomas was not performed in the current analysis. It would have been informative to examine the risk factors of those adults with synchronous serrated and conventional adenomas.
In summary, the data from this analysis have some implications for endoscopists. The observation that TSAs can be seen with conventional advanced adenomas should alert endoscopists who detect TSAs that their patients may be at higher risk for advanced lesions. We also believe that it is important for physicians to communicate with their pathologists regarding the diagnosis of TSAs in their practice. Although many endoscopists appreciate the difficulty in histologically differentiating HPs from SSPs, they should also recognize the variation in the interpretation of SSPs with dysplasia and TSAs. We may hope that new techniques, perhaps using molecular markers, will help to distinguish serrated subtypes.
Disclosure
All authors disclosed no financial relationships relevant to this publication.
References
Chetty R.
Traditional serrated adenoma (TSA): morphological questions, queries and quandaries.
Smoking and the association of advanced colorectal neoplasia in an asymptomatic average risk population: analysis of exposure and anatomical location in men and women.
Risk of metachronous high-risk adenomas and large serrated polyps in individuals with serrated polyps on index colonoscopy: data from the New Hampshire colonoscopy registry.
Traditional serrated adenoma (TSA) is rare and known to have a malignant potential. We aimed to investigate the prevalence and risk factors of TSA and compare the characteristics of synchronous conventional adenoma (AD) in patients with TSA with those of AD in patients with AD only.
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