Novel insights into the polycythemia–paraganglioma–somatostatinoma syndrome
- Roland Därr1,
- Joan Nambuba1,
- Jaydira Del Rivero1,
- Ingo Janssen1,
- Maria Merino2,
- Milena Todorovic3,
- Bela Balint4,
- Ivana Jochmanova1,5,
- Josef T Prchal6,
- Ronald M Lechan7,
- Arthur S Tischler8,
- Vera Popovic9,
- Dragana Miljic9,
- Karen T Adams1,
- F Ryan Prall10,
- Alexander Ling11,
- Meredith R Golomb12,
- Michael Ferguson13,
- Naris Nilubol14,
- Clara C Chen15,
- Emily Chew16,
- David Taïeb17,
- Constantine A Stratakis18,
- Tito Fojo19,
- Chunzhang Yang20,
- Electron Kebebew14,
- Zhengping Zhuang20 and
- Karel Pacak1⇑
- 1Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
- 2Laboratory of Pathology, National Institutes of Health, Bethesda, Maryland, USA
- 3Institute of Hematology, Clinical Center of Serbia and Medical Faculty University of Belgrade, Belgrade, Serbia
- 4Institute of Transfusiology and Hemobiology of Military Medical Academy and Institute for Medical Research, University of Belgrade, Belgrade, Serbia
- 51st Department of Internal Medicine, Faculty of Medicine, Pavol Jozef Safarik University in Kosice, Kosice, Slovakia
- 6Division of Hematology, University of Utah, Salt Lake City, Utah, USA
- 7Tupper Research Institute and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, Massachusetts, USA
- 8Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, Massachusetts, USA
- 9Institute of Endocrinology, Clinical Center of Serbia, Medical Faculty, University Belgrade, Belgrade, Serbia
- 10Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA
- 11Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
- 12Division of Child Neurology, Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- 13Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, USA
- 14Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
- 15Division of Nuclear Medicine, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
- 16Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA
- 17Department of Nuclear Medicine, La Timone University Hospital & CERIMED & Inserm UMR1068 Marseille Cancerology Research Center, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France
- 18Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
- 19Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
- 20Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
- Correspondence should be addressed to K Pacak; Email: karel{at}mail.nih.gov
Abstract
Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A). This study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings into perspective these experiences with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11–46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8–38) and SOMs at 29 years (range 22–38). PGLs were multiple, recurrent and metastatic in 100, 100 and 29% of all cases, and SOMs in 40, 40 and 60%, respectively. All PGLs were primarily norepinephrine-producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel–Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA). Therefore, [18F]-FDOPA PET/CT, not [68Ga]-(DOTA)-[Tyr3]-octreotate ([68Ga]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The long-term prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges.
- Received 23 September 2016
- Accepted 27 September 2016
- Made available online as an Accepted Preprint 27 September 2016
- © 2016 Society for Endocrinology
