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Review
. 2022 Jan 1;38(1):39-47.
doi: 10.1097/MOG.0000000000000796.

How many is too many? Polyposis syndromes and what to do next

Nina Gupta  1 , Christine Drogan, Sonia S Kupfer
Affiliations
Review

How many is too many? Polyposis syndromes and what to do next

Nina Gupta et al. Curr Opin Gastroenterol. .

Abstract

Purpose of review: The goal of this review is to help providers recognize, diagnose and manage gastrointestinal (GI) polyposis syndromes.

Recent findings: Intestinal polyps include a number of histological sub-types such as adenomas, serrated, hamartomas among others. Over a quarter of individuals undergoing screening colonoscopy are expected to have colonic adenomas. Although it is not uncommon for adults to have a few GI polyps in their lifetime, some individuals are found to have multiple polyps of varying histology throughout the GI tract. In these individuals, depending on polyp histology, number, location and size as well as extra-intestinal features and/or family history, a polyposis syndrome should be considered with appropriate testing and management.

Summary: Diagnosis and management of polyposis syndromes has evolved with advent of multigene panel testing and new data on optimal surveillance strategies. Evidence-based recommendations and current practice guidelines for polyposis syndromes are reviewed here. Areas of uncertainty and future research are also highlighted.

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Conflict of interest statement

3. Conflict of interest: SSK has performed collaborative research with Invitae in the last 12 months but did not receive financial compensation.

Figures

Figure 1:
Figure 1:. Gastrointestinal polyposis syndromes.
Gastrointestinal polyposis syndromes can be classified based on the predominant polyp histology: adenomas, serrated polyps and hamartomas. The most common and best characterized adenomatous polyposis syndromes include familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). A number of additional genes have been implicated in adenomatous polyposis including: POLE/POLD1, NTHL1, MSH3, MLH3, AXIN2 and GREM1 (associated with hereditary mixed polyposis syndrome). Other conditions that present with adenomatous polyposis include Lynch syndrome (especially MSH2 and MSH6), constitutional mismatch repair deficiency (CMMRD), therapy-associated polyposis (TAP) in childhood and young adult cancer survivors and colonic polyposis of unknown etiology (CPUE) which includes a heterogeneous group of patients with unexplained polyposis ranging from phenotypes similar to FAP to more attenuated phenotypes likely related to low-penetrance genetic and environmental factors (tobacco, alcohol, obesity and poor diet). Serrated polyposis syndrome is defined clinically by World Health Organization criteria based on number, size, and location of serrated lesions. Hamartomas are overgrowth of normal gastrointestinal tissue. Hamartomatous polyposis syndromes are rare and include Juvenile polyposis syndrome (JPS), Peutz-Jeghers syndrome (PJS) and PTEN Hamartoma Tumor Syndrome (PHTS) of which Cowden syndrome is the most commonly encountered.
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References

    1. National Comprehensive Cancer Network, Inc. 2021. Genetic/Familial High Risk Assessment: Colorectal v.1.2021 Available at https://www.nccn.org/guidelines/guidelines-detail?category=2&id=1436.

      ** NCCN summarizes their management recommendations for individuals with polyposis, which differs by mutated gene. NCCN guidelines are updated on a regular basis when new evidence becomes available.

    1. Heald B, Hampel H, Church J, Dudley B, Hall MJ, Mork ME, et al. Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position statement on multigene panel testing for patients with colorectal cancer and/or polyposis. Fam Cancer. 2020. July;19(3):223–39.

      ** Collaborative Group of the Americas on Inherited Gastrointestinal Cancers published their position statement on genetic testing in polyposis, who recommend multi-gene panel testing given the number of polyposis syndromes (which can have overlapping features), and improvements in sequencing technology. They recommend that individuals with 10+ adenomas or 3+ hamartomatous polyps should undergo multi-gene panel testing. This statement also includes review of the minimum gene set to be used when testing individuals for a polyposis syndrome.

    1. Serrated polyposis syndrome [Internet]. InSiGHT. [cited 2021 Aug 18]. Available from: https://www.insight-group.org/syndromes/serrated-polyposis-syndrome/
    1. Stoll J, Kupfer SS. Risk Assessment and Genetic Testing for Inherited Gastrointestinal Syndromes. Gastroenterol Hepatol. 2019. September;15(9):462–70. - PMC - PubMed

    1. Stanich PP, Pearlman R, Hinton A, Gutierrez S, LaDuca H, Hampel H, et al. Prevalence of Germline Mutations in Polyposis and Colorectal Cancer–Associated Genes in Patients With Multiple Colorectal Polyps. Clin Gastroenterol Hepatol. 2019. September 1;17(10):2008–2015.e3.

      ** Stanich et al summarizes genetic findings of 3789 patients and found that the chance to find a P/LP variant increases with age in adenomatous polyposis. With the exception of APC and MUTYH, pathogenic/likely pathogenic variants in adenomatous polyposis genes are rare. This study also showed that adenoma count is also associated with finding a pathogenic or likely pathogenic variant.

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