title: A Somatic HIF2α Mutation-Induced Multiple and Recurrent Pheochromocytoma/Paraganglioma with Polycythemia: Clinical Study with Literature Review.
abstract: A syndrome known as pheochromocytomas (PCC)/paragangliomas (PGL) and polycythemia resulted from gain-of-function mutation of hypoxia-inducible factor 2α (HIF2α) has been reported recently. However, clinical features of this syndrome vary from patient to patient. In our study, we described the clinical features of the patient within 15-year follow-up with a literature review. The patient presented with "red face" since childhood and was diagnosed with polycythemia and pheochromocytoma in 2000, and then, tumor was removed at his age of 27 (year 2000). However, 13 years later (2013), he was diagnosed with multiple paragangliomas. Moreover, 2 years later (2015), another two paragangaliomas were also confirmed. Genetic analysis of hereditary PCC/PGL-related genes was conducted. A somatic heterozygous missense mutation of HIF2α (c.1589C>T) was identified at exon 12, which is responsible for the elevated levels of HIF2α and erythropoietin (EPO) and subsequent development of paragangaliomas. However, this mutation was only found in the tumors from three different areas, not in the blood. So far, 13 cases of PCC/PGL with polycythemia have been reported. Among them, somatic mutations of HIF2α at exon 12 are responsible for 12 cases, and only 1 case was caused by germline mutation of HIF2α at exon 9. The HIF2α mutation-induced polycythemia with PCC/PGL is a rare syndrome with no treatment for cure. Comprehensive therapies for this disease include removal of the tumors and intermittent phlebotomies; administration of medications to control blood pressure and to prevent complications or death resulted from high concentration of red blood cell (RBC). Genetic test is strongly recommended for patients with early onset of polycythemia and multiple/recurrent PCC/PGL.
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Dali
authors.initials: D
authors.lastname: Tong
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Gaolei
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Qingxing
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine, 4170 City Ave., Philadelphia, PA, 19131, USA.
authors.forename: Dianzheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiangzhilu, Yuzhong District, Chongqing, 400042, People's Republic of China. jiangjun_64@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000473:pathology; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology; D011086:Polycythemia / Q000235:genetics* / Q000473:pathology; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1
keywords: HIF2α; Paraganglioma; Pheochromocytoma; Polycythemia