title: Lessons from McCune-Albright syndrome-associated intraductal papillary mucinous neoplasms: : GNAS-activating mutations in pancreatic carcinogenesis.
abstract: GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in McCune-Albright syndrome, characterized by fibrous dysplasia, precocious puberty, and café au lait spots. Recently, IPMNs have been described as a McCune-Albright syndrome-associated tumor, present in about 15% of patients. The aim of the present work was to assess the prevalence of polyostotic fibrous dysplasia and McCune-Albright syndrome among patients operated on for presumptive sporadic IPMNs. All patients operated on for IPMNs between January 1, 2007, and December 31, 2012, with available imaging were retrospectively screened for polyostotic fibrous dysplasia based on their preoperative abdominal or thoracoabdominal spiral computed tomography images. Systematic screening of 272 patients operated on for IPMNs revealed 1 patient with axial and peripheral polyostotic fibrous dysplasia and café au lait spots on clinical examination suggestive of McCune-Albright syndrome. This patient had been operated on for an unusually large invasive colloid adenocarcinoma (pT3N0M0 R0) derived from an intestinal subtype GNAS-mutated IPMN. The patient underwent adjuvant chemotherapy with gemcitabine for 6 months and was alive without recurrence 6 years later. Besides providing additional evidence of a syndromic IPMN as a feature of McCune-Albright syndrome, this observation is further evidence of the functional oncogenic consequences of GNAS mutations in the pancreas.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Clichy, France2Institut National de la Santé et de la Recherche Médicale, Unité 773, Groupe Hospitalier Paris.
authors.forename: Alina
authors.initials: A
authors.lastname: Parvanescu
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 773, Groupe Hospitalier Paris-Nord Val de Seine, Paris, France3Assistance Publique-Hôpitaux de Paris, Department of Pathology, Hôpital Beaujon, Clichy, France4Université Paris Diderot, Paris.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cros
authors.affiliation: Université Paris Diderot, Paris, France5Assistance Publique-Hôpitaux de Paris, Department of Radiology, Hôpital Beaujon, Clichy, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Ronot
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Clichy, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Hentic
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 986, Groupe Hospitalier Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Grybek
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 773, Groupe Hospitalier Paris-Nord Val de Seine, Paris, France4Université Paris Diderot, Paris, France8Assistance Publique-Hôpitaux de Paris, Department of Pathology, Hôpital Bichat, Paris.
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.affiliation: Université Paris Diderot, Paris, France6Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Clichy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Levy
authors.affiliation: Université Paris-Sud 11, Unité Mixte de Recherche 693, Le Kremlin-Bicêtre, France10Assistance Publique-Hôpitaux de Paris, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Service d'Endocrinologie et des Maladies de la Reproduction.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 773, Groupe Hospitalier Paris-Nord Val de Seine, Paris, France4Université Paris Diderot, Paris, France6Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology, Hôpital Beaujon.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Clichy, France4Université Paris Diderot, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Sauvanet
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Clichy, France2Institut National de la Santé et de la Recherche Médicale, Unité 773, Groupe Hospitalier Paris.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gaujoux
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000150:complications / Q000235:genetics / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000150:complications / Q000235:genetics / Q000473:pathology; D002864:Chromogranins; D005359:Fibrous Dysplasia, Polyostotic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs