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Virchows Archiv

, Volume 470, Issue 4, pp 391–400 | Cite as

Patients with McCune-Albright syndrome have a broad spectrum of abnormalities in the gastrointestinal tract and pancreas

  • Laura D. Wood
  • Michaël Noë
  • Wenzel Hackeng
  • Lodewijk A. A. Brosens
  • Feriyl Bhaijee
  • Marija Debeljak
  • Jun Yu
  • Masaya Suenaga
  • Aatur D. Singhi
  • Atif Zaheer
  • Alison Boyce
  • Cemre Robinson
  • James R. Eshleman
  • Michael G. Goggins
  • Ralph H. Hruban
  • Michael T. Collins
  • Anne Marie Lennon
  • Elizabeth A. Montgomery
Original Article

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.

Keywords

McCune-Albright syndrome GNAS Intraductal papillary mucinous neoplasm Gastric heterotopia 

Notes

Compliance with ethical standards

The authors acknowledge the following sources of support: Intramural Research Program of the National Institute of Dental and Craniofacial Research; NIH/NCI P50 CA62924; NIH/NIDDK K08 DK107781; Sol Goldman Pancreatic Cancer Research Center; Buffone Family Gastrointestinal Cancer Research Fund; Kaya Tuncer Career Development Award in Gastrointestinal Cancer Prevention; AGA-Bernard Lee Schwartz Foundation Research Scholar Award in Pancreatic Cancer; Sidney Kimmel Foundation for Cancer Research Kimmel Scholar Award; AACR-Incyte Corporation Career Development Award for Pancreatic Cancer Research; Rolfe Pancreatic Cancer Foundation; Joseph C Monastra Foundation for Pancreatic Cancer Research; The Gerald O Mann Charitable Foundation (Harriet and Allan Wulfstat, Trustees); Sigma Beta Sorority; Tampa Bay Fisheries Inc.; Dutch Digestive Foundation (MLDS CDG 14-02).

Conflict of interest

Dr. Wood is a paid consultant for Personal Genome Diagnostics.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Laura D. Wood
    • 1
    • 2
  • Michaël Noë
    • 1
    • 3
  • Wenzel Hackeng
    • 1
    • 3
  • Lodewijk A. A. Brosens
    • 1
    • 3
  • Feriyl Bhaijee
    • 4
  • Marija Debeljak
    • 1
  • Jun Yu
    • 1
  • Masaya Suenaga
    • 1
  • Aatur D. Singhi
    • 5
  • Atif Zaheer
    • 6
  • Alison Boyce
    • 7
  • Cemre Robinson
    • 7
    • 8
  • James R. Eshleman
    • 1
  • Michael G. Goggins
    • 1
    • 9
  • Ralph H. Hruban
    • 1
    • 2
  • Michael T. Collins
    • 7
  • Anne Marie Lennon
    • 9
  • Elizabeth A. Montgomery
    • 1
  1. 1.Department of PathologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of OncologyJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of PathologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  4. 4.AmeriPath IndianaIndianapolisUSA
  5. 5.Department of PathologyUniversity of PittsburghPittsburghUSA
  6. 6.Department of RadiologyJohns Hopkins University School of MedicineBaltimoreUSA
  7. 7.Section on Skeletal Disorders and Mineral Homeostasis, Craniofacial and Skeletal Diseases BranchNational Institute of Dental and Craniofacial Research, National Institutes of HealthBethesdaUSA
  8. 8.Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA
  9. 9.Department of MedicineJohns Hopkins University School of MedicineBaltimoreUSA

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