Hereditary Pheochromocytoma and Paraganglioma

Czech version

Authors: Z. Musil ^1,2; A. Vícha ²; T. Zelinka ³; H. Turková ³; T. Labudová ²; M. Kohoutová ¹; K. Pacák ⁴
Authors‘ workplace: Ústav biologie a lékařské genetiky, 1. LF UK a VFN v Praze ¹; Klinika dětské hematologie a onkologie, UK 2. LF a FN Motol (KDHO), Praha ²; III. interní klinika – klinika endokrinologie a metabolismu, 1. LF UK a VFN v Praze ³; Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA ⁴
Published in: Klin Onkol 2012; 25(Supplementum): 21-26

Overview

Pheochromocytomas and paragangliomas are tumors arising from chromaffin cells. These tumors produce catecholamines and are typically found with symptoms and signs that may include hypertension (persistent or episodic), palpitations, headache and sweating. So far, 10 different genes have been associated with both tumors and other genes are expected to be detected. Pheochromocytoma and paraganglioma can occur as a part of genetic syndromes – familial paragangliomas (SDH genes, SDHAF2 gene), von Hippel-Lindau syndrome (VHL gene), multiple endocrine neoplasia type 2 (RET gene), and neurofibromatosis type 1 (NF1 gene). These tumors may be the first and only manifestation of these genetic syndromes. Patients with SDHB mutations are at high risk to develop malignant disease and unfortunately current therapeutic options for malignant form of disease are poor. Genetic testing plays a key role in the management of these tumors and therefore not only index patients with pheochromocytoma but also relatives should be tested. Management of this disease requires multidisciplinary cooperation and should be performed in the specialized medical centres.

Key words:
pheochromocytoma – paraganglioma – genetic testing – follow up

This study was supported by PRVOUK-P27/LF1/1, sVV–2012–264514 grant, by a project of the research organisation 00064203 and by IGaMZ ČR NT12336-4/2011 grant.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
30. 5. 2012

Accepted:
27. 7. 2012

Sources

1. Boedeker CC. Paragangliomas and paraganglioma syndromes. Laryngorhinootologie 2011; 90 (Suppl 1): S56–S82.

2. Fishbein L, Nathanson KL. Pheochromocytoma and paraganglioma: understanding the complexities of the genetic background. Cancer Genet 2012; 205(1–2): 1–11.

3. Karasek D, Frysak Z, Pacak K. Genetic testing for pheochromocytoma. Curr Hypertens Rep 2010; 12(6): 456–464.

4. Opocher G, Schiavi F. Genetics of pheochromocytomas and paragangliomas. Best Pract Res Clin Endocrinol Metab 2010; 24(6): 943–956.

5. Bausch B, Malinoc A, Maruschke L et al. Genetics of pheochromocytoma. Chirurg 2012; 83(6): 511–518.

6. Neumann HP, Bausch B, McWhinney SR et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 2002; 346(19): 1459–1466.

7. Jafri M, Maher ER. The genetics of phaeochromocytoma: using clinical features to guide genetic testing. Eur J Endocrinol 2012; 166(2): 151–158.

8. Widimsky J Jr, Zelinka T, Petrak O et al. Pheochromocytoma: diagnosis and treatment. Cas Lek Cesk 2009; 148(8): 365–369.

9. Widimsky J Jr, Zelinka T, Petrak O et al. Diagnostic and therapeutic procedures in pheochromocytoma: current trends. Vnitr Lek 2007; 53(4): 428–433.

10. Zelinka T, Eisenhofer G, Pacak K. Pheochromocytoma as a catecholamine producing tumor: implications for clinical practice. Stress 2007; 10(2): 195–203.

11. Burnichon N, Cascon A, Schiavi F et al. MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res 2012; 18(10): 2828–2837.

12. Bardella C, Pollard PJ, Tomlinson I. SDH mutations in cancer. Biochim Biophys Acta 2011; 1807(11): 1432–1443.

13. Hensen EF, Bayley JP. Recent advances in the genetics of SDH-related paraganglioma and pheochromocytoma. Fam Cancer 2011; 10(2): 355–363.

14. Musil Z, Puchmajerova A, Krepelova A et al. Paraganglioma in a 13-year-old girl: a novel SDHB gene mutation in the family? Cancer Genet Cytogenet 2010; 197(2): 189–192.

15. Baysal BE, McKay SE, Kim YJ et al. Genomic imprinting at a boundary element flanking the SDHD locus. Hum Mol Genet 2011; 20(22): 4452–4461.

16. Opocher G, Schiavi F. Functional consequences of succinate dehydrogenase mutations. Endocr Pract 2011; 17 (Suppl 3): 64–71.

17. Kunst HP, Rutten MH, de Monnink JP et al. SDHAF2 (PGL2-SDH5) and hereditary head and neck paraganglioma. Clin Cancer Res 2011; 17(2): 247–254.

18. King KS, Prodanov T, Kantorovich V et al. Metastatic pheochromocytoma/paraganglioma related to primary tumor development in childhood or adolescence: significant link to SDHB mutations. J Clin Oncol 2011; 29(31): 4137–4142.

19. Celestino R, Lima J, Faustino A et al. A novel germline SDHB mutation in a gastrointestinal stromal tumor patient without bona fide features of the Carney-Stratakis dyad. Fam Cancer 2011; 11(2): 189–194.

20. Miettinen M, Wang ZF, Sarlomo-Rikala M et al. Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age. Am J Surg Pathol 2011; 35(11): 1712–1721.

21. Raygada M, Pasini B and Stratakis CA. Hereditary paragangliomas. Adv Otorhinolaryngol 2011; 70: 99–106.

22. Ricketts CJ, Forman JR, Rattenberry E et al. Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Hum Mutat 2010; 31(1): 41–51.

23. Pantaleo MA, Astolfi A, Indio V et al. SDHA loss-of-function mutations in KIT-PDGFRA wild-type gastrointestinal stromal tumors identified by massively parallel sequencing. J Natl Cancer Inst 2011; 103(12): 983–987.

24. Jiang S, Dahia PL. Minireview: the busy road to pheochromocytomas and paragangliomas has a new member, TMEM127. Endocrinology 2011; 152(6): 2133–2140.

25. Neumann HP, Sullivan M, Winter A et al. Germline mutations of the TMEM127 gene in patients with paraganglioma of head and neck and extraadrenal abdominal sites. J Clin Endocrinol Metab 2011; 96(8): E1279–E1282.

26. Eisenhofer G, Vocke CD, Elkahloun A et al. Genetic Screening for von Hippel-Lindau Gene Mutations in Non-syndromic Pheochromocytoma: Low Prevalence and False-positives or Misdiagnosis Indicate a Need for Caution. Horm Metab Res 2012; 44(5): 343–348.

27. Lenders JW, Pacak K, Walther MM et al. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA 2002; 287(11): 1427–1434.

28. Timmers HJ, Gimenez-Roqueplo AP, Mannelli M et al. Clinical aspects of SDHx-related pheochromocytoma and paraganglioma. Endocr Relat Cancer 2009; 16(2): 391–400.

29. Vicha A, Holzerova M, Krepelova A et al. Molecular cytogenetic characterization in four pediatric pheochromocytomas and paragangliomas. Pathol Oncol Res 2011; 17(4): 801–208.

30. Zelinka T, Musil Z, Duskova J et al. Metastatic pheochromocytoma: does the size and age matter? Eur J Clin Invest 2011; 41(10): 1121–1128.