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

Abstract

Context.— Familial adenomatous polyposis (FAP) is a rare genetic disorder with autosomal dominant inheritance, defined by numerous adenomatous polyps, which inevitably progress to colorectal carcinoma unless detected and managed early. Greater than 70% of patients with this syndrome also develop extraintestinal manifestations, such as multiple osteomas, dental abnormalities, and a variety of other lesions located throughout the body. These manifestations have historically been subcategorized as Gardner syndrome, Turcot syndrome, or gastric adenocarcinoma and proximal polyposis of the stomach. Recent studies, however, correlate the severity of gastrointestinal disease and the prominence of extraintestinal findings to specific mutations within the adenomatous polyposis coli gene ( APC), supporting a spectrum of disease as opposed to subcategorization. Advances in immunohistochemical and molecular techniques shed new light on the origin, classification, and progression risk of different entities associated with FAP. Objective.— To provide a comprehensive clinicopathologic review of neoplastic and nonneoplastic entities associated with FAP syndrome, with emphasis on recent developments in immunohistochemical and molecular profiles of extraintestinal manifestations in the thyroid, skin, soft tissue, bone, central nervous system, liver, and pancreas, and the subsequent changes in classification schemes and risk stratification. Data Sources.— This review will be based on peer-reviewed literature and the authors' experiences. Conclusions.— In this review we will provide an update on the clinicopathologic manifestations, immunohistochemical profiles, molecular features, and prognosis of entities seen in FAP, with a focus on routine recognition and appropriate workup of extraintestinal manifestations.

An Unusual Giant Osteoma of the Maxillary Sinus: Case Report

“…Osteomas have an excellent prognosis. However, it should be kept in mind that multiple osteomas may be a usual extraintestinal manifestation of Gardner's syndrome [10].…”

Molecular findings in maxillofacial bone tumours and its diagnostic value

“…The genetic background of sporadic osteomass is unknown, and multiple osteomas can occur in a syndromal context, including Gardner syndrome (a syndrome known to be part of the extraintestinal manifestation of the familial adenomatous polyposis (FAP) spectrum, Fig. 2a) [3]. FAP is a rare genetic disorder with autosomal dominant inheritance caused by mutations in the tumour suppressor gene APC [3,4].…”

“…2a) [3]. FAP is a rare genetic disorder with autosomal dominant inheritance caused by mutations in the tumour suppressor gene APC [3,4]. Frameshift and nonsense mutations account for more than 90% of APC mutations, and different types of germ line mutations cause different phenotypes.…”

“…Frameshift and nonsense mutations account for more than 90% of APC mutations, and different types of germ line mutations cause different phenotypes. Overall, 65-80% of patients with FAP develop osteomas [3].…”

Familial adenomatous polyposis: a case study

“…Familial adenomatous polyposis (FAP) is an inherited syndrome characterized by several adenomatous polyps of the gastrointestinal (GI) mucosa [ 1 ]. The incidence of FAP is ~1 in 7000 to 1 in 30 000 births [ 2 ].…”