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Hereditary nonpolyposis colorectal cancer, or Lynch syndrome, is responsible for 2-3% of all colorectal cancers. Lynch syndrome is also associated with a high risk of extracolonic cancers, including endometrial, stomach, small bowel, pancreas, biliary tract, ovary, urinary tract, brain, and skin cancer. In this Review, we discuss the risks, surveillance tests, and guidelines for the management of extracolonic tumours associated with Lynch syndrome. For all types of extracolonic cancer, evidence supporting surveillance is scarce. A benefit of surveillance is evident only for endometrial cancer, where transvaginal ultrasound and endometrial sampling detect tumours in early stages. Surveillance is generally recommended for urinary tract and gastric cancer, especially in families with more than one member with these types of cancer. For the other types of cancer, surveillance is typically not recommended. Prophylactic hysterectomy and bilateral salpingo-oophorectomy should be considered for women with Lynch syndrome who are past childbearing age, especially during surgery for colorectal cancer. No data show efficacy of chemopreventive drugs in reducing the risk of extracolonic cancers for patients with Lynch syndrome.

Small-bowel cancer is part of the tumour spectrum of Lynch syndrome. Lynch syndrome, or hereditary non-polyposis colorectal cancer, is caused by germline mutations in one of the mismatch repair genes. Mutation carriers have an estimated lifetime risk for the development of small-bowel cancer of around 4%, corresponding to a relative risk of more than 100 compared with the general population. Patients with Lynch syndrome generally present with small-bowel cancer 10-20 years earlier than the general population, and small-bowel cancer might be the first clinical manifestation of Lynch syndrome. Tumours in patients with Lynch syndrome are evenly distributed within the small bowel. No specific risk factors, such as type of gene mutation, have been identified thus far. Screening for small-bowel cancer in Lynch syndrome has, until now, not been included in guidelines for surveillance, which might partly be due to the fact that, until recently, the possibilities for visualisation of the small bowel were limited. In view of the improved accessibility of the small bowel with the introduction of capsule endoscopy and double balloon enteroscopy, the question of whether patients should be screened for small-bowel neoplasia has regained attention. In this paper, we discuss the rationale for surveillance of small-bowel cancer in Lynch syndrome and highlight issues that need to be addressed in future studies before recommendations can be made.

Small-bowel cancer is part of the tumour spectrum of Lynch syndrome. Lynch syndrome, or hereditary non-polyposis colorectal cancer, is caused by germline mutations in one of the mismatch repair genes. Mutation carriers have an estimated lifetime risk for the development of small-bowel cancer of around 4%, corresponding to a relative risk of more than 100 compared with the general population. Patients with Lynch syndrome generally present with small-bowel cancer 10-20 years earlier than the general population, and small-bowel cancer might be the first clinical manifestation of Lynch syndrome. Tumours in patients with Lynch syndrome are evenly distributed within the small bowel. No specific risk factors, such as type of gene mutation, have been identified thus far. Screening for small-bowel cancer in Lynch syndrome has, until now, not been included in guidelines for surveillance, which might partly be due to the fact that, until recently, the possibilities for visualisation of the small bowel were limited. In view of the improved accessibility of the small bowel with the introduction of capsule endoscopy and double balloon enteroscopy, the question of whether patients should be screened for small-bowel neoplasia has regained attention. In this paper, we discuss the rationale for surveillance of small-bowel cancer in Lynch syndrome and highlight issues that need to be addressed in future studies before recommendations can be made.