title: Patients with McCune-Albright syndrome have a broad spectrum of abnormalities in the gastrointestinal tract and pancreas.
abstract: McCune-Albright Syndrome (MAS) is a rare sporadic syndrome caused by post-zygotic mutations in the GNAS oncogene, leading to constitutional mosaicism for these alterations. Somatic activating GNAS mutations also commonly occur in several gastrointestinal and pancreatic neoplasms, but the spectrum of abnormalities in these organs in patients with MAS has yet to be systematically described. We report comprehensive characterization of the upper gastrointestinal tract in seven patients with MAS and identify several different types of polyps, including gastric heterotopia/metaplasia (7/7), gastric hyperplastic polyps (5/7), fundic gland polyps (2/7), and a hamartomatous polyp (1/7). In addition, one patient had an unusual adenomatous lesion at the gastroesophageal junction with high-grade dysplasia. In the pancreas, all patients had endoscopic ultrasound findings suggestive of intraductal papillary mucinous neoplasm (IPMN), but only two patients met the criteria for surgical intervention. Both of these patients had IPMNs at resection, one with low-grade dysplasia and one with high-grade dysplasia. GNAS mutations were identified in the majority of lesions analyzed, including both IPMNs and the adenomatous lesion from the gastroesophageal junction. These studies suggest that there is a broad spectrum of abnormalities in the gastrointestinal tract and pancreas in patients with MAS and that patients with MAS should be evaluated for gastrointestinal pathology, some of which may warrant clinical intervention due to advanced dysplasia.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ldwood@jhmi.edu.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ldwood@jhmi.edu.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Michaël
authors.initials: M
authors.lastname: Noë
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Wenzel
authors.initials: W
authors.lastname: Hackeng
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Lodewijk A A
authors.initials: LA
authors.lastname: Brosens
authors.affiliation: AmeriPath Indiana, Indianapolis, IN, USA.
authors.forename: Feriyl
authors.initials: F
authors.lastname: Bhaijee
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Marija
authors.initials: M
authors.lastname: Debeljak
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Masaya
authors.initials: M
authors.lastname: Suenaga
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Aatur D
authors.initials: AD
authors.lastname: Singhi
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Atif
authors.initials: A
authors.lastname: Zaheer
authors.affiliation: Section on Skeletal Disorders and Mineral Homeostasis, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Boyce
authors.affiliation: Section on Skeletal Disorders and Mineral Homeostasis, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.|Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Cemre
authors.initials: C
authors.lastname: Robinson
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Eshleman
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Goggins
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.affiliation: Section on Skeletal Disorders and Mineral Homeostasis, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Collins
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Lennon
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Montgomery
mesh_terms: D000328:Adult; D002864:Chromogranins / Q000235:genetics; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000235:genetics / Q000473:pathology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D005767:Gastrointestinal Diseases / Q000235:genetics / Q000473:pathology*; D041981:Gastrointestinal Tract / Q000473:pathology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs
keywords: GNAS; Gastric heterotopia; Intraductal papillary mucinous neoplasm; McCune-Albright syndrome