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.
J Clin Endocrinol Metab. 2014 Jan;99(1):E97-101. doi: 10.1210/jc.2013-1823. Epub 2013 Dec 20.
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.
The aim of this study was to assess the prevalence of hepatobiliary and pancreatic neoplasms in patients with McCune-Albright syndrome.
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.
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.
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.
McCune-Albright 综合征（MAS）包括多囊性纤维性骨发育不良、性早熟和咖啡牛奶斑，是一种由 GNAS 基因的体细胞激活突变引起的罕见疾病。GNAS 突变也与各种散发性肿瘤有关，包括肝胆胰肿瘤。
本研究旨在评估 MAS 患者中肝胆胰肿瘤的患病率。
在一家罕见生长障碍的三级转诊中心，1995 年至 2012 年间诊断出 19 例 MAS 患者，于 2011 年 6 月至 2012 年 12 月期间，对这些患者进行了专用钆增强磁共振成像筛查，以发现肝胆胰肿瘤。
在 19 例筛查患者中，有 6 例（32%）发现存在肝、胰或胆道病变，不包括肝血管瘤、肝囊肿和局灶性结节性增生。这包括 4 例患者的胰腺导管病变，其中 3 例存在多个分支导管内乳头状黏液性肿瘤。1 例患者存在胆道病变，胆总管大囊肿也累及左胆管分支。最后，2 例患者存在多个炎症/静脉扩张性肝腺瘤，其中 1 例存在证实的体细胞 GNAS 突变。
我们首次观察到了综合征性胰管内乳头状黏液性肿瘤，并发现 MAS 与胰腺肿瘤（即胰腺内乳头状黏液性肿瘤）之间存在新的关联，还发现了罕见的肝胆肿瘤，包括肝腺瘤和胆总管囊肿。这些发现强烈提示，体细胞激活的 GNAS 突变可能通过 cAMP 通路障碍，参与了源自前肠内胚层的肝胆胰组织的肿瘤发生，这促使我们对 MAS 患者进行了常规筛查，采用了包括胰胆管序列的专用磁共振成像。
