Lessons from McCune-Albright syndrome-associated intraductal papillary mucinous neoplasms: : GNAS-activating mutations in pancreatic carcinogenesis

JAMA Surg. 2014 Aug;149(8):858-62. doi: 10.1001/jamasurg.2014.535.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / complications
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / pathology
  • Carcinoma, Pancreatic Ductal / complications
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Papillary / complications
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / pathology
  • Chromogranins
  • Fibrous Dysplasia, Polyostotic / complications
  • Fibrous Dysplasia, Polyostotic / genetics*
  • Fibrous Dysplasia, Polyostotic / pathology
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Pancreatic Neoplasms / complications
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Retrospective Studies

Substances

  • Chromogranins
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs