The pathology of hereditary polyposis syndromes

Abstract

Our understanding of the genetics and pathology of familial colorectal cancer continues to evolve with both the discovery of underlying genetic defects and the description of entirely new entities. Genetic analysis has demonstrated phenotypic overlap between some of these syndromes, such that their nosology is rapidly becoming based on genetics with clinicopathological features playing a secondary, but important, role. Further clinical characterization of these syndromes has also demonstrated widely differing risks for the development of colorectal cancer and a range of other malignancies with implications for both the affected patient and members of their families. This review aims to outline the clinical, pathological and genetic features of this increasingly complex group of diseases.

Familial Adenomatous Polyposis Syndrome: An Update and Review of Extraintestinal Manifestations

“…13 While FAP is most widely recognized for the adenomatous polyps after which it is named, patients have a higher risk than the general population of developing other intestinal and extraintestinal manifestations such as gastric fundic gland polyps (FGPs), duodenal polyps, congenital hypertrophy of retinal pigment epithelium (CHRPE), fibromas, fibromatosis, nasal angiofibromas, thyroid carcinomas, hepatoblastomas (HBs), brain tumors, and pancreatobiliary tumors. 5,13 GASTROINTESTINAL MANIFESTATIONS…”

“…2,4 It is important to note that classifications made to distinguish different varieties of extraintestinal symptomatology, such as Gardner and Turcot syndromes, should no longer be used as both of these syndromes are now known to be a part of the FAP spectrum. 5 An average individual with classic FAP will develop colorectal carcinoma (CRC) around the age of 40 years if treatment is not provided. 5 Some people have a variant of the disorder, called attenuated FAP, in which polyp growth is delayed, with an average CRC onset at 55 years of age.…”

“…5 An average individual with classic FAP will develop colorectal carcinoma (CRC) around the age of 40 years if treatment is not provided. 5 Some people have a variant of the disorder, called attenuated FAP, in which polyp growth is delayed, with an average CRC onset at 55 years of age. 2 Extraintestinal manifestations of the disease may occur in attenuated FAP; however, this occurs far less commonly than in the classical form of FAP.…”

“…2 Extraintestinal manifestations of the disease may occur in attenuated FAP; however, this occurs far less commonly than in the classical form of FAP. 5 The incidence of FAP is approximately 1 in 7000 to 1 in 30,000 births. 6 It is a high penetrance autosomal dominant disease that affects men and women equally and exhibits variable expressivity.…”

“…[8][9][10][11][12] Gardner syndrome is now of historical interest rather than clinical significance, as these extraintestinal growths are known to be correlated more with mutation location in the APC gene, rather than occurring together in specific families. 5 We provide a review of gastrointestinal features and an in-depth update on clinicopathologic manifestations, immunohistochemical profiles, molecular features, screening and surveillance, and prognoses of extraintestinal entities of FAP. Furthermore, this review helps pathologists with practical information relevant to the recognition and workup of these cases.…”