title: Complex APC germline mutation associated metaplasia and intraepithelial neoplasia (CAM-IEN) of the gallbladder.
abstract: Preneoplasic and neoplastic changes of the gallbladder of patients with a familial adenomatous polyposis (FAP) are rare, and very little is known about their incidence in patients with an attenuated FAP. We herein report on a unique case of a woman with an attenuated FAP who shows eight distinct, partially preneoplastic differentiation patterns within the gallbladder mucosa, which are: (1) regular gallbladder epithelium, (2) low grade biliary intraepithelial neoplasia, (3) papillary adenoma, (4) Paneth cell metaplasia, (5) goblet cell metaplasia, (6) pancreatic metaplasia, (7) pseudopyloric metaplasia, and (8) neuroendocrine differentiation. Moreover, this is the first case of a KRAS mutation in a gallbladder adenoma of a patient with an APC germline mutation, which is highly suggestive of an early event of malignant transformation. As a consequence of our findings, clinicians should draw special attention to the gallbladder of FAP patients, and a simultaneous protective cholecystectomy of FAP patients, which undergo colectomy and show conspicuous changes of the gallbladder mucosa, should be performed in these patients in order to eliminate the risk of a synchronous or metachronous gallbladder neoplasia.
authors.affiliation: Department of Pathology, Christian-Albrechts-University, D-24105 Kiel, Germany. Electronic address: christine.boeger@uksh.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Böger
authors.affiliation: Department of Pathology, Christian-Albrechts-University, D-24105 Kiel, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Haag
authors.affiliation: Department of General Surgery, Visceral, Thoracic, Transplantation and Pediatric Surgery, Christian-Albrechts-University, D-24105 Kiel, Germany.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Egberts
authors.affiliation: Department of Pathology, Christian-Albrechts-University, D-24105 Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018256:Adenomatous Polyps / Q000235:genetics*; D005260:Female; D005704:Gallbladder / Q000473:pathology*; D005706:Gallbladder Neoplasms / Q000473:pathology*; D017491:Genes, APC / Q000502:physiology*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008679:Metaplasia; D008875:Middle Aged; D009154:Mutation / Q000235:genetics
keywords: Complex epithelial lesion; FAP; Gallbladder carcinogenesis