title: Hepatobiliary and Pancreatic neoplasms in patients with McCune-Albright syndrome.
abstract: BACKGROUND
  McCune-Albright syndrome (MAS), which includes polycystic fibrous dysplasia, precocious puberty, and café au lait spots, is a rare disorder caused by somatic activating mutations of the GNAS gene. GNAS mutations have also been implicated in various sporadic tumors, including hepatobiliary and pancreatic neoplasms.
  
  
  OBJECTIVE
  The aim of this study was to assess the prevalence of hepatobiliary and pancreatic neoplasms in patients with McCune-Albright syndrome.
  
  
  METHODS
  Nineteen patients diagnosed between 1995 and 2012 with MAS in a tertiary referral center for rare growth disorders were screened with dedicated gadolinium-enhanced magnetic resonance imaging for hepatobiliary and pancreatic neoplasms between June 2011 and December 2012.
  
  
  RESULTS
  Six (32%) of the 19 screened patients were found to have hepatic, pancreatic, or biliary lesions, excluding liver hemangiomas, liver cysts, and focal nodular hyperplasia. This includes pancreatic ductal lesions observed in 4 patients, including numerous branch-duct intraductal papillary mucinous neoplasms in 3 patients. Biliary lesions were observed in 1 patient, with a large choledochal cyst also involving the left biliary branch. Finally, multiple inflammatory/telangiectatic hepatic adenomas were observed in 2 patients, including 1 with proven somatic GNAS mutation.
  
  
  CONCLUSIONS
  We describe the first observation of syndromic intraductal papillary mucinous neoplasms and the new association between MAS and pancreatic neoplasms, namely intraductal papillary mucinous neoplasms of the pancreas but also rare hepatobiliary neoplasms including liver adenomas and choledochal cysts. These findings strongly suggest that somatic activating GNAS mutations, possibly through cAMP pathway disorders, are involved in the tumorigenesis of hepatobiliary and pancreatic tissues originating from the foregut endoderm and have led us to use a routine screening by dedicated magnetic resonance imaging including both pancreatobiliary and liver sequences in patients with MAS.
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Beaujon, Departments of Hepato-Pancreato-Biliary Surgery-Pôle des Maladies de l'Appareil Digestif (PMAD) (S.G., J.B., A.S.), Radiology (M.R.), Pathology (J.C.), and Gastroenterology-PMAD (P.R.), and Inserm Centre de Recherche Biomédicale Bichat Beaujon (CRB3) Unité 773 (S.G., M.R., J.C., J.B., A.S., P.R.), Clichy F-92110, France; Faculté de Médecine, Université Paris Diderot (S.G., M.R., J.C., J.B., A.S., P.R.), F-75010 Paris, France; AP-HP, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Service d'Endocrinologie et des Maladies de la Reproduction (S.S., P.C.) and Service de Radiologie (A.-S.R.), and Université Paris-Sud 11 (P.C.), Le Kremlin Bicêtre F-94275, France; and Inserm Unité 693 (P.C.), Faculté de Médecine Paris-Sud, F-94276 Le Kremlin-Bicêtre, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gaujoux
authors.forename: Sylvie
authors.initials: S
authors.lastname: Salenave
authors.forename: Maxime
authors.initials: M
authors.lastname: Ronot
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Rangheard
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cros
authors.forename: Jacques
authors.initials: J
authors.lastname: Belghiti
authors.forename: Alain
authors.initials: A
authors.lastname: Sauvanet
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
mesh_terms: D000328:Adult; D000368:Aged; D001661:Biliary Tract Neoplasms / Q000453:epidemiology* / Q000235:genetics; D002864:Chromogranins; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000453:epidemiology* / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D009154:Mutation / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000235:genetics; D015995:Prevalence; D055815:Young Adult
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs