Serrated polyposis syndrome

History

The condition was originally called hyperplastic polyposis syndrome and was initially thought not to be associated with colorectal cancer. In 1996, a case series linked the syndrome to cancer and serrated adenomas, and later other serrated polyp types were recognized, prompting the name change to serrated polyposis syndrome. The World Health Organization released diagnostic criteria in 2010, which were updated in 2010 and again in 2019. The 2010 classification included three criteria; the 2019 revision modified the first criterion to include lesions in the sigmoid colon and exclude polyps smaller than 5 mm, and removed the criterion involving any serrated lesions proximal to the sigmoid colon in a person with a first-degree relative with SPS.

Pathophysiology

Serrated polyposis syndrome does not stem from a single gene mutation. While germline mutations in RNF43 are the only confirmed genetic cause, most people with SPS do not carry any germline mutation. Other genetic changes linked to the condition include BRAF mutations, abnormal CpG island methylator phenotype, and microsatellite instability.

Genes such as SMAD4, BMPR1A, PTEN, GREM1, and MUTYH are also implicated. Inheritance can be autosomal dominant, autosomal recessive, or sporadic. The polyps seen in SPS include hyperplastic polyps, traditional serrated adenomas, and sessile serrated polyps, and adenomas are also common.

Treatment

Colonoscopy with polypectomy is the mainstay of treatment for SPS, aiming to prevent colorectal cancer. If polyps are relatively few, removal can be achieved during colonoscopy, and repeat colonoscopy is recommended every one to three years. On average, about 2.8 colonoscopies are needed to achieve disease control. Narrow-band imaging may improve detection of serrated lesions, though one multicenter trial did not show improved detection.

Surgery is considered when polyps are very numerous, very large, or cannot be controlled endoscopically; a total abdominal colectomy with ileorectal anastomosis is then preferred to minimize cancer risk. If polyp involvement is focal, segmental resection may be performed, and segmental resection is also recommended for cancer. Any remaining colon or rectum requires annual surveillance. First-degree relatives of people with SPS have an increased risk of colorectal cancer and should undergo screening colonoscopy beginning at age 40, the age of the youngest SPS diagnosis in the family, or 10 years younger than the earliest SPS-related colorectal cancer, with repeat colonoscopy every five years.

Epidemiology

Serrated polyposis syndrome affects men and women at the same rate, with most people diagnosed between ages 40 and 60, averaging 55 years old. It is the most common polyposis syndrome of the colon, though its overall prevalence is estimated at about 1 in 100,000. Among those having a colonoscopy after an abnormal fecal occult blood test, prevalence ranges from 0.34 to 0.66 percent. Nearly half of those with the condition have a family member with colorectal cancer.

Tobacco use is linked to a higher risk, while aspirin and NSAIDs may lower it. Aside from colorectal cancer, no other cancer shows a clear association, though some evidence hints at a possible link to pancreatic cancer. People with a history of lymphoma face an increased risk of developing this syndrome.

Did You Know?

• Sessile serrated polyps are flat rather than raised and are easily overlooked during colonoscopy.
• Serrated lesions often have a mucous cap overlying the polyp and are frequently located on haustral folds.
• The cumulative number of serrated lesions is counted over time and includes multiple colonoscopies.