Därr Roland, Nambuba Joan, Del Rivero Jaydira, Janssen Ingo, Merino Maria, Todorovic Milena, Balint Bela, Jochmanova Ivana, Prchal Josef T, Lechan Ronald M, Tischler Arthur S, Popovic Vera, Miljic Dragana, Adams Karen T, Prall F Ryan, Ling Alexander, Golomb Meredith R, Ferguson Michael, Nilubol Naris, Chen Clara C, Chew Emily, Taïeb David, Stratakis Constantine A, Fojo Tito, Yang Chunzhang, Kebebew Electron, Zhuang Zhengping, Pacak Karel
Section on Medical NeuroendocrinologyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Laboratory of PathologyNational Institutes of Health, Bethesda, Maryland, USA.
Endocr Relat Cancer. 2016 Dec;23(12):899-908. doi: 10.1530/ERC-16-0231. Epub 2016 Sep 27.
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 [F]-fluorodihydroxyphenylalanine ([F]-FDOPA). Therefore, [F]-FDOPA PET/CT, not [Ga]-(DOTA)-[Tyr3]-octreotate ([Ga]-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.
在全球范围内，只有少数患有缺氧诱导因子2α（HIF2A）体细胞突变的患者被描述患有副神经节瘤（PGL）、生长抑素瘤（SOM）和儿童早期红细胞增多症综合征。本研究提供了7例该综合征患者的临床情况和病程的详细信息，并将这些经验与相关文献进行了对比。6名女性和1名男性，中位年龄为28岁（范围11 - 46岁）。2例被发现存在HIF2A体细胞镶嵌现象。无亲属患病。所有患者在8岁前且在PGL/SOM出现之前被诊断为红细胞增多症。PGL在中位年龄17岁（范围8 - 38岁）时被发现，SOM在29岁（范围22 - 38岁）时被发现。PGL在所有病例中的多发性、复发性和转移性分别为100%（100%和29%），SOM的相应比例分别为40%、40%和60%。所有PGL主要分泌去甲肾上腺素。所有患者均有异常眼科检查结果，患有SOM的患者有胆囊疾病。计算机断层扫描（CT）和磁共振成像显示4例患者（57%）在多个部位有囊性病变和血管瘤，以前认为这是von Hippel - Lindau病的特征性表现。检测PGL最准确的放射性药物似乎是[F] - 氟二羟基苯丙氨酸（[F] - FDOPA）。因此，对于该综合征的肿瘤定位和随访，推荐使用[F] - FDOPA PET/CT，而非[Ga] - （DOTA） - [Tyr3] - 奥曲肽（[Ga] - DOTATATE）PET/CT。该综合征的长期预后尚不清楚。然而，迄今为止，6年随访后无死亡病例。医生应了解这种独特的综合征及其诊断和治疗挑战。
