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

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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.

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Authors and Affiliations

  1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Laura D. Wood, Michaël Noë, Wenzel Hackeng, Lodewijk A. A. Brosens, Marija Debeljak, Jun Yu, Masaya Suenaga, James R. Eshleman, Michael G. Goggins, Ralph H. Hruban & Elizabeth A. Montgomery

  2. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Laura D. Wood & Ralph H. Hruban

  3. Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands

    Michaël Noë, Wenzel Hackeng & Lodewijk A. A. Brosens

  4. AmeriPath Indiana, Indianapolis, IN, USA

    Feriyl Bhaijee

  5. Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA

    Aatur D. Singhi

  6. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Atif Zaheer

  7. 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

    Alison Boyce, Cemre Robinson & Michael T. Collins

  8. Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Cemre Robinson

  9. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Michael G. Goggins & Anne Marie Lennon

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  1. Laura D. Wood
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  2. Michaël Noë
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  7. Jun Yu
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  8. Masaya Suenaga
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  11. Alison Boyce
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  13. James R. Eshleman
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  14. Michael G. Goggins
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  15. Ralph H. Hruban
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  16. Michael T. Collins
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  17. Anne Marie Lennon
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  18. Elizabeth A. Montgomery
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Corresponding author

Correspondence to Laura D. Wood.

Ethics declarations

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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Wood, L.D., Noë, M., Hackeng, W. et al. Patients with McCune-Albright syndrome have a broad spectrum of abnormalities in the gastrointestinal tract and pancreas. Virchows Arch 470, 391–400 (2017). https://doi.org/10.1007/s00428-017-2086-2

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  • DOI: https://doi.org/10.1007/s00428-017-2086-2

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