The differential diagnosis and surveillance of hereditary gastrointestinal polyposis syndromes

Abstract

Background: Hereditary gastrointestinal polyposis syndromes account for about 1% of all cases of colorectal cancer and are associated with a broad spectrum of extracolonic tumors. The early detection and accurate classification of these syndromes are essential, since effective methods for surveillance and treatment are available.

Methods: This review article is based on a selective literature search, the author's own work, and evidence-based guidelines and recommendations.

Results and conclusions: The diagnosis is initially suspected on the basis of the endoscopic findings and polyp histology. Because different syndromes can resemble each other phenotypically, e.g., autosomal dominant familial adenomatous polyposis and autosomal recessive MUTYH-associated polyposis, molecular genetic studies are important for differential diagnosis and for assessing the risk of recurrence. Identification of the familial mutation in an affected patient is a prerequisite for predictive testing in asymptomatic persons at risk and sometimes enables prognostication. In recent years, the rate of detection of mutations has risen by 10% to 30%, and clinically relevant genotype-phenotype correlations have been described for juvenile polyposis syndrome. Except in cases of mild adenomatous polyposis, phenotypic overlap among the hamartomatous polyposes often causes difficulties in differential diagnosis. Thus, in unclear cases, a pathologist with special expertise in gastrointestinal disorders should be consulted for the evaluation of polyp tissue. Aside from the monogenic polyposes, there are many other types of polyposis that are non-hereditary or of unknown cause, including the hyperplastic and mixed polyposis syndromes. Risk-adapted surveillance programs have been established for the more frequently occurring polyposes.

Figure 1

Diagnostic workup of gastrointestinal polyposis in an index patient of a family; EGD, esophagogastroduodenoscopy; FAP, familial adenomatous polyposis; MAP, MUTYH-associated polyposis; PJS, Peutz–Jeghers syndrome; JPS, juvenile polyposis syndrome; HP, hyperplastic polyposis; CS, Cowden syndrome; MPLA, multiplex ligation-dependent probe amplification

Figure 2

Characteristic extraintestinal findings in polyposis syndromes

Figure 3

Predictive genetic testing of at-risk family members of an index patient with gastrointestinal polyposis; EGD, esophagogastroduodenoscopy

eFigure

Characteristic histological findings in polyposis syndromes b) Prof. M. Stolte, Bayreuth c) Prof. M. Stolte, Bayreuth d) From: Pathol Res Pract 2008; 204: 431–47, with permission: Elsevier Ltd e) From: Best Pract Res Clin Gastroenterol 2007; 21: 409–26, with permission: Elsevier Ltd. f) From: Pathol Res Pract 2008; 204: 431–47, with permission: Elsevier Ltd. g) From: Pathol Res Pract 2008; 204: 431–47, with permission: Elsevier Ltd. h) Prof. M. Stolte, Bayreuth i) Prof. M. Stolte, Bayreuth j) From: Pathol Res Pract 2008; 204: 449–58, with permission: Elsevier Ltd.