Novel insights into the polycythemia-paraganglioma-somatostatinoma syndrome

被引：65

作者：

Darr, Roland ^{[1
]}

Nambuba, Joan ^{[1
]}

Del Rivero, Jaydira ^{[1
]}

Janssen, Ingo ^{[1
]}

Merino, Maria ^{[2
]}

Todorovic, Milena ^{[3
,4
]}

Balint, Bela ^{[5
,6
]}

Jochmanova, Ivana ^{[1
,7
]}

Prchal, Josef T. ^{[8
]}

Lechan, Ronald M. ^{[9
,10
]}

Tischler, Arthur S. ^{[11
]}

Popovic, Vera ^{[12
]}

Miljic, Dragana ^{[12
]}

Adams, Karen T. ^{[1
]}

Prall, F. Ryan ^{[13
,14
]}

Ling, Alexander ^{[15
]}

Golomb, Meredith R. ^{[16
]}

Ferguson, Michael ^{[17
]}

Nilubol, Naris ^{[18
]}

Chen, Clara C. ^{[19
]}

Chew, Emily ^{[20
]}

Taieb, David ^{[21
,22
,23
]}

Stratakis, Constantine A. ^{[24
]}

Fojo, Tito ^{[25
]}

Yang, Chunzhang ^{[26
]}

Kebebew, Electron ^{[18
]}

Zhuang, Zhengping ^{[26
]}

Pacak, Karel ^{[1
]}

机构：

[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, Bethesda, MD 20892 USA

[2] NIH, Pathol Lab, Bethesda, MD 20892 USA

[3] Univ Belgrade, Clin Ctr Serbia, Inst Hematol, Belgrade, Serbia

[4] Univ Belgrade, Fac Med, Belgrade, Serbia

[5] Univ Belgrade, Mil Med Acad, Inst Transfusiol & Hemobiol, Belgrade, Serbia

[6] Univ Belgrade, Inst Med Res, Belgrade, Serbia

[7] Pavol Jozef Safarik Univ Kosice, Fac Med, Dept Internal Med 1, Kosice, Slovakia

[8] Univ Utah, Div Hematol, Salt Lake City, UT USA

[9] Tufts Med Ctr, Tupper Res Inst, Boston, MA USA

[10] Tufts Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA USA

[11] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA USA

[12] Univ Belgrade, Fac Med, Clin Ctr Serbia, Inst Endocrinol, Belgrade, Serbia

[13] Indiana Univ Sch Med, Dept Ophthalmol, Indianapolis, IN 46202 USA

[14] Indiana Univ Sch Med, Marilyn Glick Eye Inst, Indianapolis, IN 46202 USA

[15] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA

[16] Indiana Univ Sch Med, Dept Neurol, Div Child Neurol, Indianapolis, IN 46202 USA

[17] Indiana Univ Hlth, Riley Hosp Children, Indianapolis, IN USA

[18] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA

[19] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA

[20] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA

[21] Aix Marseille Univ, La Timone Univ Hosp, Dept Nucl Med, Marseille, France

[22] Aix Marseille Univ, Inst Paoli Calmettes, Marseille Cancerol Res Ctr, CERIMED, Marseille, France

[23] Aix Marseille Univ, Inst Paoli Calmettes, Marseille Cancerol Res Ctr, Inserm UMR1068, Marseille, France

[24] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, NIH, Bethesda, MD USA

[25] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA

[26] NCI, Neurooncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

来源：

基金：

美国国家卫生研究院;

关键词：

pheochromocytoma; paraganglioma; somatostatinoma; polycythemia; HIF2A mutation; HIPPEL-LINDAU-DISEASE; OF-FUNCTION MUTATIONS; HIF2A MUTATIONS; FAMILIAL ERYTHROCYTOSIS; PHEOCHROMOCYTOMA; GENE; HYPOXIA; TUMORS; HYPERTENSION; SUPERIORITY;

D O I：

10.1530/ERC-16-0231

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 bringsinto 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 [F-18]- fluorodihydroxyphenylalanine ([F-18]-FDOPA). Therefore, [F-18]-FDOPA PET/CT, not [Ga-68]-(DOTA)-[Tyr3]-octreotate ([Ga-68]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The longterm 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.

引用

页码：899 / 908

页数：10

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