Hereditary pheochromocytoma/paraganglioma and associated syndromes: a clinical and genetic study

Peng TANG; Weihua LAN; Yao ZHANG; Jun ZHANG; Zehua SHU; Ke LI; Zaoming HUANG; Yiqiang HUANG; Qiuli LIU; Jun JIANG

doi:10.16016/j.2097-0927.202302129

您当前的位置：

首页 >

文章列表页 >

Hereditary pheochromocytoma/paraganglioma and associated syndromes: a clinical and genetic study

Clinical Medicine | 更新时间：2026-01-09

- Hereditary pheochromocytoma/paraganglioma and associated syndromes: a clinical and genetic study
- Journal of Army Medical University Vol. 46, Issue 4, Pages: 377-383(2024)
- 作者机构：
  
  400042 重庆，陆军特色医学中心泌尿外科
- 作者简介：
- 基金信息：
  
  the Project of Clinical Medical Talent Training Plan of Army Medical University(2018XLC3073)
- DOI：10.16016/j.2097-0927.202302129
  CLC： R195.4;R394.1;R736.6
- Received：23 February 2023，
  
  Revised：2023-09-11，
  
  Published：28 February 2024
- 稿件说明：
移动端阅览
Peng TANG, Weihua LAN, Yao ZHANG, et al. Hereditary pheochromocytoma/paraganglioma and associated syndromes: a clinical and genetic study[J]. Journal of Army Medical University, 2024, 46(4): 377-383.
DOI：

Peng TANG, Weihua LAN, Yao ZHANG, et al. Hereditary pheochromocytoma/paraganglioma and associated syndromes: a clinical and genetic study[J]. Journal of Army Medical University, 2024, 46(4): 377-383. DOI： 10.16016/j.2097-0927.202302129.

摘要

目的

探讨不同遗传性嗜铬细胞瘤/副神经节瘤(pheochromocytoma/paraganglioma

PCC/PGL)及其相关综合征的临床表型、遗传特征及其治疗随访策略。

方法

共纳入陆军特色医学中心泌尿外科2000年1月至2022年8月临床确诊的44例PCC/PGL患者

收集患者及其家系成员的临床信息

采用二代测序对43例患者进行遗传学检测

以及采用Sanger测序对先证者和家系成员进行突变验证。

结果

共15例患者确诊为遗传性PCC/PGL

其中7例von Hippel-Lindau (VHL)综合征

3例多发性内分泌腺瘤病2型(multiple endocrine neoplasia type 2

MEN2)

5例家族性副神经节瘤综合征。7个VHL综合征家系按照临床表现分别诊断为VHL2A (c.500G>A)、VHL2B (c.239G>T和c.444_457del)和VHL2C (c.293A>G)3种亚型

先证者均接受了手术治疗

2例复发性PCC及多发性肾癌患者还接受了舒尼替尼靶向治疗。3个MEN2家系分别携c.1901G>C、c.1832G>A和c.1901G>A错义突变

临床诊断均符合MEN2A

所有患者接受肾上腺及甲状腺切除手术

其中1例为预防性甲状腺切除。5个家族性副神经节瘤综合征家系中

共检测到4例SDHB突变患者

1例SDHD突变患者(SDHB: c.343C>T

c.541-2A>G

c.575G>A

c.268C>T; SDHD: c.337_340del)

以散发性腹膜后PGL多见。

结论

超过1/3的PCC/PGL患者可携带胚系基因突变

并具有明显的基因型-表型相关性

基因诊断技术在临床精准治疗及随访、遗传咨询等方面具有重要的指导作用。

Abstract

Objective

To summarize and analyze the clinical phenotypes

hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas (PCC/PGL) and related syndromes.

Methods

Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled

and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection

and Sanger sequencing was applied to verify the mutation of the probands and family members.

Results

There were 15 patients diagnosed with hereditary PCC/PGL

including 7 cases of von Hippel-Lindau (VHL) syndrome

3 cases of multiple endocrine neoplasia type 2(MEN2)

and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A (c.500G>A)

VHL2B (c.239G>T and c.444_457del)

and VHL2C (c.293A>G) according to their clinical manifestations.All probands received surgical treatment

and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G>C

c.1832G>A

and c.1901G>A missense mutations

respectively

and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy

including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families

4 patients carried SDHB mutations (SDHB: c.343C>T

c.541-2A>G

c.575G>A

c.268C>T) and 1 patient carried an SDHD mutation (SDHD: c.337_340del).Sporadic retroperitoneal PGL were most common.

Conclusion

More than 1/3 of PCC/PGL patients carry germline gene mutations

showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up

and genetic counseling.

关键词

Keywords

references

NÖLTING S, BECHMANN N, TAIEB D, et al . Personalized management of pheochromocytoma and paraganglioma[J ] . Endocr Rev, 2022, 43(2): 199-239. DOI: 10.1210/endrev/bnab019.

LEUNG AA, PASIEKA J L, HYRCZA M D, et al . Epidemiology of pheochromocytoma and paraganglioma: population-based cohort study[J ] . Eur J Endocrinol, 2021, 184(1): 19-28. DOI: 10.1530/EJE-20-0628.

MUTH A, CRONA J, GIMM O, et al . Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma[J ] . J Intern Med, 2019, 285(2): 187-204. DOI: 10.1111/joim.12869.

HAMIDI O, YOUNG W F, GRUBER L, et al . Outcomes of patients with metastatic phaeochromocytoma and paraganglioma: a systematic review and meta-analysis[J ] . Clin Endocrinol (Oxf), 2017, 87(5): 440-450. DOI: 10.1111/cen.13434.

JIANG J J, ZHANG J, Pang Y X, et al . Sino-European differences in the genetic landscape and clinical presentation of pheochromocytoma and paraganglioma[J ] . J Clin Endocrinol Metab, 2020, 105(10): 3295-3307. DOI: 10.1210/clinem/dgaa502.

FISHBEIN L, LESHCHINER I, WALTER V, et al . Comprehensive molecular characterization of pheochromocytoma and paraganglioma[J ] . Cancer Cell, 2017, 31(2): 181-193. DOI: 10.1016/j.ccell.2017.01.001.

WANG Z, YAN X Z, TANG P, et al . Genetic profiling of hormone-sensitive and castration-resistant prostate cancers and identification of genetic mutations prone to castration-resistant prostate cancer[J ] . Prostate Cancer Prostatic Dis, 2023, 26(1): 180-187. DOI: 10.1038/s41391-022-00618-2.

HUANG Y H, ZHANG C Z, HUANG Q S, et al . Clinicopathologic features, tumor immune microenvironment and genomic landscape of Epstein-Barr virus-associated intrahepatic cholangiocarcinoma[J ] . J Hepatol, 2021, 74(4): 838-849. DOI: 10.1016/j.jhep.2020.10.037.

LIU Q L, YUAN G, TONG D L, et al . Novel genotype-phenotype correlations in five Chinese families with von Hippel-Lindau disease[J ] . Endocr Connect, 2018, 7(7): 870-878. DOI: 10.1530/EC-18-0167.

WACHTEL H, FISHBEIN L. Genetics of pheochromocytoma and paraganglioma[J]. Curr Opin Endocrinol Diabetes Obes, 2021, 28(3): 283-290. DOI: 10.1097/MED.0000000000000634.

JAIN A, BARACCO R, KAPUR G. Pheochromocytoma and paraganglioma—an update on diagnosis, evaluation, and management[J]. Pediatr Nephrol, 2020, 35(4): 581-594. DOI: 10.1007/s00467-018-4181-2.

EID M, FOUKAL J, SOCHOROVÁ D, et al . Management of pheochromocytomas and paragangliomas: review of current diagnosis and treatment options[J ] . Cancer Med, 2023, 12(13): 13942-13957. DOI: 10.1002/cam4.6010.

WANG K, CRONA J, BEUSCHLEIN F, et al . Targeted therapies in pheochromocytoma and paraganglioma[J ] . J Clin Endocrinol Metab, 2022, 107(11): 2963-2972. DOI: 10.1210/clinem/dgac471.

CHOU A, TOON C, PICKETT J, et al . von Hippel-Lindau syndrome[J ] . Front Horm Res, 2013, 41: 30-49. DOI: 10.1159/000345668.

GIMENEZ-ROQUEPLO A P, ROBLEDO M, DAHIA P L M. Update on the genetics of paragangliomas[J]. Endocr Relat Cancer, 2023, 30(4): e220373. DOI: 10.1530/erc-22-0373.

CIOTTI P, GARUTI A, GULLI R, et al . Germline mutations in the von Hippel-Lindau gene in Italian patients[J ] . Eur J Med Genet, 2009, 52(5): 311-314. DOI: 10.1016/j.ejmg.2009.05.007.

YUAN G, LIU Q L, TONG D L, et al . A retrospective case study of sunitinib treatment in three patients with Von Hippel-Lindau disease[J ] . Cancer Biol Ther, 2018, 19(9): 766-772. DOI: 10.1080/15384047.2018.1470732.

DEEKS E D. Belzutifan: first approval[J]. Drugs, 2021, 81(16): 1921-1927. DOI: 10.1007/s40265-021-01606-x.

TAKAYA K, YOSHIMASA T, ARAI H, et al . Expression of the RET proto-oncogene in normal human tissues, pheochromocytomas, and other tumors of neural crest origin[J ] . J Mol Med (Berl), 1996, 74(10): 617-621. DOI: 10.1007/s001090050065.

MATHIESEN J S, EFFRAIMIDIS G, ROSSING M, et al . Multiple endocrine neoplasia type 2: A review[J ] . Semin Cancer Biol, 2022, 79: 163-179. DOI: 10.1016/j.semcancer.2021.03.035.

AMODRU V, TAIEB D, GUERIN C, et al . MEN2-related pheochromocytoma: current state of knowledge, specific characteristics in MEN2B, and perspectives[J ] . Endocrine, 2020, 69(3): 496-503. DOI: 10.1007/s12020-020-02332-2.

WELLS S A Jr, PACINI F, ROBINSON B G, et al . Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update[J ] . J Clin Endocrinol Metab, 2013, 98(8): 3149-3164. DOI: 10.1210/jc.2013-1204.

HEDAYATI M, ZARIF YEGANEH M, SHEIKHOLESLAMI S, et al . Diversity of mutations in the RET proto-oncogene and its oncogenic mechanism in medullary thyroid cancer[J ] . Crit Rev Clin Lab Sci, 2016, 53(4): 217-227. DOI: 10.3109/10408363.2015.1129529.

王宇, 田文, 嵇庆海, 等. 甲状腺髓样癌诊断与治疗中国专家共识(2020版)[J]. 中国实用外科杂志, 2020, 40(9): 1012-1020. DOI: 10.19538/j.cjps.issn1005-2208.2020.09.03.

WANG Y, TIAN W, JI Q H, et al. Expert consensus on the diagnosis and treatment of medullary thyroid carcinoma (2020 edition)[J ] . Chin J Pract Surg, 2020, 40(9): 1012-1020. DOI: 10.19538/j.cjps.issn1005-2208.2020.09.03.

BEN AIM L, PIGNY P, CASTRO-VEGA L J, et al . Targeted next-generation sequencing detects rare genetic events in pheochromocytoma and paraganglioma[J ] . J Med Genet, 2019, 56(8): 513-520. DOI: 10.113 6/jmedgenet-2018-105714.

BUFFET A, BURNICHON N, FAVIER J, et al . An overview of 20 years of genetic studies in pheochromocytoma and paraganglioma[J ] . Best Pract Res Clin Endocrinol Metab, 2020, 34(2): 101416. DOI: 10.1016/j.beem.2020.101416.

BURNICHON N, ROHMER V, AMAR L, et al . The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas[J ] . J Clin Endocrinol Metab, 2009, 94(8): 2817-2827. DOI: 10.1210/jc.2008-2504.

BAYSAL B E, RUBINSTEIN W S, TASCHNER P E. Phenotypic dichotomy in mitochondrial complex Ⅱ genetic disorders[J]. J Mol Med, 2001, 79(9): 495-503. DOI: 10.1007/s001090100267.

BITEMAN B R, RANDALL J A, BRODY F. Laparoscopic bilateral cortical-sparing adrenalectomy for pheochromocytoma[J]. Surg Endosc, 2016, 30(12): 5622-5623. DOI: 10.1007/s00464-016-4919-5.

ROSSITTI H M, SÖDERKVIST P, GIMM O. Extent of surgery for phaeochromocytomas in the genomic era[J]. Br J Surg, 2018, 105(2): e84-e98.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Clinical characteristics and antimicrobial therapy of only intracranial infection in patients after posterior fossa tumor craniotomy: report of 26 cases

Clinical characteristics and pathogenic drug resistance analysis of deep sternal wound infection after cardiac surgery

Clinical features and operative method of complicated spinal tuberculosis

Related Author

Xiaochuan Sun

Wenyuan Tang

Haijian XIA

Haoyang Huang

Dong Lyu

Jiong LI

Shuang Shi

Dong Zhong

Related Institution

No data

⁰