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Case Reports
Hyperplastic polyps and serrated adenomas: Colonoscopic surveillance?
M.L.C. Stellakis, K.M. Reddy, R.I. Swift
and A. Arnaout
Colorectal Unit, Mayday University Hospital, 530 London Road, Croydon,
London, CR7 7YE
Correspondence to: M.L.C. Stellakis, Mayday University Hospital, 530 London Road, Croydon, London, CR7 7YE Email: mr.stellakis@doctors.org.uk
Keywords: Hyperplastic polyp, adenomatous polyp, serrated adenoma, colonoscopic screening
Surg J R Coll Surg Edinb Irel., 2 April 2004, 112-114
INTRODUCTION
Currently very few hyperplastic polyps are under colonoscopic surveillance as it is
generally accepted that hyperplastic polyps present little malignant potential. However,
the existence of serrated adenomas (an adenomatous polyp with some hyperplastic
phenotypia) and their variants pose a challenge for this view. Serrated adenomas are rare and
make up less than 0.1 to 0.5% of all colonic polyps, however, our current state of knowledge
suggests that these histiologically distinct polyps may represent a stage in a sequence
from hyperplasia to malignancy.1-4 If this is
the case, then the management of a ‘serrated
adenoma’ may require more surveillance than
is currently practised.
We describe two cases, one where features of hyperplasia, mild, moderate and severe dysplasia and adenocarcinoma were present in a single specimen, and a second case where an adenocarcinoma was found within a tubulo-villous polyp synchronous with admixed adenomatous and hyperplastic polyps and serrated adenomata. We suggest that hyperplasia found at polypectomy or biopsy warrants detailed histological analysis to identify any evidence of mixed phenotypia, which may or may not be associated with dysplasia or neoplasia within the remaining tissue.
CASE REPORT ONE
An 80-year-old lady presented with a history of weight loss, anaemia and a change in
bowel habit. She underwent colonoscopic examination and an ulcerated polypoid tumour was found in the ascending colon. She
underwent a right hemicolectomy and made a good postoperative recovery.
Histological examination revealed an ulcerated moderately differentiated invasive mucinous adenocarcinoma of the ascending colon with associated hyperplastic polyps and a serrated adenoma exhibiting a mixture of hyperplastic and adenomatous / dysplastic features.
CASE REPORT TWO
A 37-year-old man presented with a one year history of bright red rectal bleeding.
He had no specific risk factors for colorectal disease. Clinical examination was normal.
He underwent colonoscopy which revealed a 1.2 cm tubulo-villous adenoma in the rectum,
with the changes of mild, moderate and severe dysplasia (Figure 1). In addition a focus of
stromal invasion was seen (Figure 2), indicative of a moderately differentiated
adenocarcinoma.Changes of mild dysplasia were seen in areas of mixed hyperplastic and adenomatous type
tissue (serrated adenoma), the latter exhibiting a villous architecture (Figure 3).
Figure 1: Tubulo-villous adenoma (x 40 magnification) with stromal invasive component (a) and hyperplastic (serrated) component (b). Higher magnification views of a and b are shown in figures 2 and 3, respectively.
Figure 2: Stromal invasive component (a). (x100 magnification)
Figure 3: Serrated/hyperplastic component (b). (x100 magnification)
DISCUSSION
Incorrectly, only three types of serrated polyps were previously described, the hyperplastic polyp, the admixed polyp and the
serrated adenoma. It was thought that these polyps were clearly distinguishable, but at the molecular (genetic) level these
polyps possess similarities and even the purely hyperplastic polyp may show characteristics of
neoplasia.5 Understanding of the family of polyps termed serrated adenomas has been
impeded by the lack of precise criteria for defining and diagnosing a serrated adenoma. Purely hyperplastic polyps
are characterised by abnormal retention of cells in the upper maturation zones giving rise to the appearance of
serratation. The classic serrated adenoma is defined as an adenomatous polyp histologically but with preservation of the serrations
of a hyperplastic polyp. Criteria for grading have not been established but these adenomas can possess the histological
characteristics of dysplasia seen in conventional adenomas.
Mucins are the predominant glycoproteins found in gastrointestinal epithelia, and their structures differ according to the location in the GI tract and the state of cellular differentiation. Different forms of mucin are secreted in colonic polyps and cancers compared with those found in the normal colon.6 The principal biomarker for the serrated pathway consists of two mucin stains. In serrated adenomas, goblet cell mucin (MUC2) and gastric foveolar mucin (MUC5AC) are expressed by the columnar epithelium. By contrast, expression of MUC4 is down regulated, compared with normal or hyperplastic epithelium.5,7
Other polyps should be considered to be part of the serrated adenoma group. These include large hyperplastic polyps with or without eosinophilic change; hyperplastic polyps including foci of dyspalsia; admixed polyps (varying proportions of hyperplastic tissue, traditional or serrated adenomatous tissue within the same polyp); tubulovillous or villous adenomas with slight or focal serration and dysplastic epithelium with serration.5
The majority of hyperplastic polyps are probably innocuous, but there is a subset which may have malignant potential. It is unknown whether these hyperplastic polyps represent one end of a spectrum of disease with the potential for adenomatous change leading eventually to cancer via the adenoma carcinoma sequence. It is possible that hyperplastic polyps and neoplastic polyps represent two different biological variants and that there is a distinct pathway from hyperplastic polyp to adenocarcinoma.8,9
One study, comparing the loss of heterozygosity of specific onco- and tunour-suppressor genes in different polyp types, showed serrated adenomas to be genetically similar to conventional adenomas and dissimilar to pure hyperplastic polyps.10
What does appear likely is that serrated adenomas represent a stage from hyperplastic polyposis to colorectal cancer. In addition to the existence of the serrated adenoma family of polyps, there is both phenotypic and genotypic evidence of the malignant potential of some hyperplastic polyps. Hyperplastic polyps may contain foci of intraepithelial neoplasia resembling classic tubular, tubulo-villous and villous adenomas without the serrated architecture. These foci may exhibit varying degrees of dysplasia.11,12 Further evidence is the observation in some cases of the synchronicity of hyperplastic polyposis and colorectal cancer.3,4 Typical hyperplastic polyps may show clonal genetic changes, including chromosomal rearrangements at 1p and KRas mutations. Mutations of TP53 and increased immunoexpression of p53 are limited to areas of high grade dysplasia in serrated adenomas.13 DNA microsatellite instability (MSI) exists infrequently and at low levels (MSI-L) in typical hyperplastic polyps, but is relatively common in serrated adenomas and is now considered a useful second biomarker. Transition to high levels (MSI-H) coincides with dysplastic change and is associated with loss of the expression of the DNA mismatch repair gene hMLH1 in various types of serrated polyps.14 Indeed, more recent research showed decreased uptake of immunostains hMLH1 and hMSH2 in groups of serrated polyps with abnormal proliferation, compared with polyps with normal proliferation. Interestingly, this group also found major differences in hMLH1 and hMSH2 expression between left and right sided polyps.15
The association of colorectal cancer arising from hyperplastic polyps and serrated adenomas in areas of MSI has been hypothesised.16 It is likely that serrated polyps are the likely precursors of sporadic MSI-H cancers but may also evolve into MSI-L cancers. This is distinguished from the adenoma carcinoma sequence via the MSI pathway in hereditary non-polyposis colorectal cancer.14
CONCLUSION
Identifying which hyperplastic polyps are at risk of malignant change is paramount. Endoscopically those, which are
multiple, are large or occur predominantly in the right colon, are considered to have the greatest malignant potential.17,18
Any polyps, which possess the histological appearances of the serrated polyp family, with or without dysplasia, or those that
occur in areas of defined MSI should be placed under regular surveillance. This should be the policy until such time as we
are able to further delineate the natural history of these lesions. Serrated adenomas are rare but the histopathologist should
make the surgeon aware of their existence as distinct entities from typical hyperplastic polyps. More research is needed to
develop techniques of identifying which of these polyps is likely to progress to carcinoma.
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Copyright: 30 January 2004