SPS is associated with a high risk of colorectal cancer, not only in the affected patient but also family members. The carcinogenesis can be rapid, with several series describing interval cancers occurring quickly.
Serrated polyps of the colon and rectum can be found in approximately 20% of average risk patients coming to screening colonoscopy and comprise:
- Hyperplastic polyps – by far the most common. They are small and pale, usually left sided, and act more as a marker of significant proximal serrated lesions than being premalignant in themselves.
- Sessile serrated adenoma/polyps (SSA/P) – larger, right sided lesions that are difficult to see endoscopically and can progress to cancer relatively rapidly.
- Traditional serrated adenomas (TSA) – endoscopically more like adenomas, usually left sided and are premalignant in the same way as adenomas.
The ‘WHO Criteria’ for the Serrated Polyposis Syndrome (SPS) are:
- Five or more serrated lesions/polyps proximal to the rectum, all being at least 5 mm in size, with two or more being at least 10 mm in size.
- More than 20 serrated lesions/polyps of any size distributed throughout the large bowel, with at least five being proximal to the rectum.
With increased understanding of serrated polyps and the molecular pathways involved in serrated neoplasia, these criteria may change.
Small numbers of adenomas are a frequent occurrence in SPS and colorectal cancer in SPS is not confined to the serrated pathway. Data from a collaborative cohort reported molecular and clinical heterogeneity in both the polyps and the cancers arising in this syndrome.
Risk factors for the development of colorectal cancer in SPS include the presence of serrated polyps containing dysplasia, advanced adenomas and/or combined WHO 1 and 3 phenotype.
Serrated cancer pathway
Typically, the molecular basis of serrated lesions begins with an activating mutation in KRAS or BRAF oncogenes. On the left side of the colon this leads to hyperplastic polyps and sometimes TSA. On the right side of the colon DNA hypermethylation adds to the proliferative effect of a BRAF mutation to produce SSA/P. The hypermethylation shuts down expression of many genes, including the DNA mismatch repair gene MLH1. This event promotes microsatellite instability in SSA/P, leading to adenomatous dysplasia. Cancer may follow. Biologically these are usually CIMP high cancers.
SPS is commonly grouped with the hereditary polyposes even though it is not associated with a single gene mutation and it does not appear to be inherited in a simple Mendelian fashion.
Multi-gene panel testing of established colorectal cancer and polyposis susceptibility genes in people with SPS provides a low yield of actionable mutations. However, people fulfilling the phenotypic criteria for SPS who have co-existing germline mutations in MMR, PTEN, biallelic MUTYH and biallelic NTHL1 have been described. These people typically present with features indicative of the syndrome and underlying germline mutation (e.g. macrocephaly, multiple adenomas).
Early studies reported a cumulative risk of colorectal cancer in individuals with SPS under surveillance of 7% at 5 years, particularly if adequate polyp control has not been achieved in a timely manner. A number of studies are now reporting this to be lower , indicating that colonoscopic control of the neoplasia is possible. However, this needs to be performed in meticulous fashion because right sided serrated lesions are hard to see and may advance rapidly.
Patients with SPS are at high risk of developing colorectal cancer and need expert surveillance or surgery.
The US Multi-Society Task Force on colorectal cancer now recommends yearly surveillance in SPS, but 3-6 monthly procedures may be required to control the polyps initially. A possible algorithm of clinical and endoscopic management in SPS has recently been proposed.
Colonoscopy must be meticulous as SSA/P are hard to see and can grow rapidly. Enhanced imaging techniques such as chromendoscopy or narrow band imaging may be helpful. Hyperplastic polyps <5mm can be noted but left alone. All lesions >5mm diameter should be removed.
There will be some patients with SPS whose polyps are not adequately controlled by colonoscopy and polypectomy. In this situation surgery is the best management option and generally, because of the pancolonic location of the polyps, this involves colectomy and ileo-rectal anastomosis.
There is controversy as to whether first degree relatives of patients with SPS should be offered surveillance. Two studies have documented approximately a five- fold increase in risk of colorectal cancer in first degree relatives of individuals with SPS. A study reviewing the yield of a single surveillance colonoscopy in 77 first degree relatives of patients with SPS reported no colorectal cancer, but documented one or more significant polyps in 43% of the 77 relatives. Some consider it prudent to recommend surveillance colonoscopies for first- degree relatives of individuals with SPS while our understanding of SPS is emerging.
Content updated 16 July 2019