MUTYH-associated polyposis: Is it time to change upper gastrointestinal surveillance? A single-center case series and a literature overview

BACKGROUND The presence of Spigelman stage(SS)IV duodenal polyposis is considered the most significant risk factor for duodenal cancer in patients with MUTYH-associated polyposis(MAP).However,advanced SS disease is rarely reported in MAP patients,and no clear recommendations on small bowel(SB)surveillance have been proposed in this patient setting.AIM To research more because that case reports of duodenal cancers in MAP suggest that they may develop in the absence of advanced benign SS disease and often involve the distal portion of the duodenum.METHODS We describe a series of MAP patients followed up at the Regina Elena National Cancer Institute of Rome(Italy).A literature overview on previously reported SB cancers in MAP is also provided.RESULTS We identified two(6%)SB adenocarcinomas with no previous history of duodenal polyposis.Our observations,supported by literature evidence,suggest that the formula for staging duodenal polyposis and predicting risk factors for distal duodenum and jejunal cancer may need to be adjusted to take this into account rather than focusing solely on the presence or absence of SS IV disease.Core Tip:Case reports of duodenal cancers in MUTYH-associated polyposis suggest that they may develop in the absence of advanced Spigelman stage(SS)benign disease and often involve the distal portion of the duodenum.In our case series,we identified two(6%)small-bowel adenocarcinomas with no previous history of duodenal polyposis.Our observations,supported by literature evidence,suggest that the formula for staging duodenal polyposis and predicting risk factors for distal duodenum and jejunal cancer should be adjusted to take into consideration the presence of SS IV disease,rather than focusing only on this feature.suggestive of invasive adenocarcinoma.

Hereditary gastrointestinal polyposis: Diagnosis, genetic test and risk assessment

Colorectal cancer (CRC) is the second cause of cancer deaths, with over 1 million new cases estimated every year. Familial adenomatous polyposis, MUTYH-associated polyposis and hamartomatous polyposis are inherited syndromes that account for 2%-5% of all colon cancer. The mutated genes responsible for the vast majority of these disorders, are now known (MLH1, MSH2, MSH6, PMS2, APC, MYH, LKB1, SMAD4, BMPR1A, and PTEN) and specific mutations have been identified. Molecular caracterization of inherited CRCs allows pre-symptomatic diagnosis identifying at-risk individuals and improving cancer surveillance. Adenomatous polyposis includes familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and MUTYH-associated polyposis (MAP). Hamartomatous polyposis comprises Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS) and “PTEN hamartoma tumour syndrome” (PHTS). MAP is an autosomal recessive condition, while all other disorders are inherited in an autosomal dominant manner. Differential dyagnosis could be very difficult between syndromes because of their phenotypic variability. Attenuated FAP, MAP and Lynch syndrome could be all associated with fewer numbers of adenomas (3-10 polyps), nevertheless, each syndrome has distinct cancer risks, characteristic clinical features, and separate genetic etiologies. Thus, differential diagnosis is essential for correct management of the specific disease. In our laboratory we set up a methodology for genetic tests of the colorectal polyposis syndrome. In these reviews we summarize the literature data and our experience about diagnosis, genetic tests and cancer risk assesment associated with colorectal polyposis. According to literature data, in our experience, there is a portion of analyzing patients that remain without identified mutation, after molecular screening of the specific gene involved in the pathogenesis of the disease. Since the sensibility of used techniques, such as DHPLC, MLPA and sequencing, is now very high, we suggest that a different approach to molecular diagnosis of polyposis syndromes is necessary. In our laboratory, we are now planning to set up analysis of a larger pannel of genes that could be involved in colorectal poliposis syndromes, using a next generation sequencing techniques. In our opinion, a better characterization of molecular basis of the polyposis syndromes will allow a more efficient cancer prevention.