Large Retroperitoneal Paraganglioma Associated with Germline Mutation of the Succinate Dehydrogenase Gene
Main Article Content
Keywords
incidentaloma, paraganglioma, pheochromocytoma, retroperitoneal tumor, SDHB gene mutation
Abstract
Paragangliomas (PGLs) are rare neural tumors that can be benign or malignant and often associated with familial syndromes. We present a case of a 23-year-old male with a large retroperitoneal PGL found incidentally during the workup of elevated liver enzymes. After surgical excision, the patient was found to have an autosomal dominant mutation in the succinate dehydrogenase B (SDHB) gene, which when compared to sporadic PGLs or other familial syndromes is associated with a higher risk of tumor recurrence, occult metastasis, and development of other cancers. The patient’s first-degree relatives were recommended to undergo screening for the genetic mutation.
References
1. Benn DE, Gimenez-Roqueplo AP, Reilly JR, Bertherat J, Burgess J, Byth K, et al. Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab. 2006 Mar;91(3):827–36. doi: http://dx.doi. org/10.1210/jc.2005-1862
2. Tassone F. Pheochromocytoma and paraganglioma [Comment]. N Engl J Med. 2019 Nov 7;381(19):1882–3. http://dx.doi. org/10.1056/NEJMc1912022
3. Young WF. Paragangliomas. Ann NY Acad Sci. 2006 Sep;1073:21–9. doi: http://dx.doi.org/10.1196/annals.1353.002
4. Kantorovich V, King KS, Pacak K. SDH-related pheochromocytoma and paraganglioma. Best Pract Res Clin Endocrinol Metab. 2010 Jun;24(3):415–24. doi: http://dx.doi.org/10.1016/j. beem.2010.04.001
5. Benn DE, Robinson BG, Clifton-Bligh RJ. 15 Years of paraganglioma: Clinical manifestations of paraganglioma syndromes types 1-5. Endocr Relat Cancer. 2015 Aug;22(4):T91–103. doi: http://dx.doi.org/10.1530/ERC-15-0268
6. Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science. 2000 Feb;287(5454):848–51. doi: http://dx.doi.org/10.1126/ science.287.5454.848
7. Hao HX, Khalimonchuk O, Schraders M, Dephoure N, Bayley JP, Kunst H, et al. SDH5, a gene required for flavination of suc-cinate dehydrogenase, is mutated in paraganglioma. Science. 2009 Aug 28;325(5944):1139–42. doi: http://dx.doi.org/10.1126/ science.1175689
8. Niemann S, Müller U. Mutations in SDHC cause autoso-mal dominant paraganglioma, type 3. Nature Genet. 2000 Nov;26(3):268–70. doi: http://dx.doi.org/10.1038/81551
9. Astuti D, Latif F, Dallol A, Dahia PL, Douglas F, George E, et al. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma [published correction appears in Am J Hum Genet 2002 Feb;70(2):565]. Am J Hum Genet. 2001 Jul;69(1):49–54. doi: http://dx.doi.org/10.1086/321282
10. Rankin EB, Giaccia AJ. The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ. 2008 Apr;15(4):678–85. doi: http://dx.doi.org/10.1038/cdd.2008.21
11. Srirangalingam U, LeCain M, Tufton N, Akker SA, Drake WM, Metcalfe K. Four generations of SDHB-related disease: Complexities in management. Fam Cancer. 2017 Apr;16(2):279– 82. doi: http://dx.doi.org/10.1007/s10689-016-9946-9
12. Ricketts CJ, Forman JR, Rattenberry E, Bradshaw N, Lalloo F, Izatt L, et al. Tumor risks and genotype–phenotype–proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Human Mutat. 2010 Jan;31(1):41–51. doi: http://dx.doi. org/10.1002/humu.21136
13. Tufton N, Sahdev A, Akker SA. Radiological surveillance screening in asymptomatic succinate dehydrogenase mutation carriers. J Endocr Soc. 2017 Jun 6;1(7):897–907. doi: http://dx. doi.org/10.1210/js.2017-00230
14. Plouin PF, Amar L, Dekkers OM; Guideline Working Group. European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a pheo-chromocytoma or a paraganglioma. Eur J Endocrinol. 2016 May;174(5):G1–10. doi: http://dx.doi.org/10.1530/EJE-16-0033
15. Kayano D, Kinuya S. Current consensus on I-131 MIBG therapy. Nucl Med Mol Imaging. 2018;52(4):254–65. doi: http://dx. doi.org/10.1007/s13139-018-0523-z
16. Jimenez C, Erwin W, Chasen B. Targeted radionuclide therapy for patients with metastatic pheochromocytoma and paraganglioma: From low-specific-activity to high-specific-activity iodine-131 metaiodobenzylguanidine. Cancers (Basel). 2019 Jul;11(7):1018. doi: http://dx.doi.org/10.3390/cancers11071018
17. Niemeijer N, Alblas G, Hulsteijn LV, Dekkers O, Corssmit E. Chemotherapy with cyclophosphamide, vincristine and dacar-bazine for malignant paraganglioma and pheochromocytoma: Systematic review and meta-analysis. Clin Endocrinol. 2014;81(5):642–51. doi: http://dx.doi.org/10.1111/cen.12542
18. Nozières C, Walter T, Joly MO, Giraud S, Scoazec J-Y, Borson-Chazot F, et al. A SDHB malignant paraganglioma with dramatic response to temozolomide-capecitabine. Eur J Endocrinol. 2012;166(6):1107–11. doi: http://dx.doi.org/10.1530/ EJE-11-1098
19. Favier J, Igaz P, Burnichon N, Amar L, Libé R, Badoual C, et al. Rationale for antiangiogenic therapy in pheochromocytoma and paraganglioma. Endocr Pathol. 2012 Mar;23(1):34– 42. doi: http://dx.doi.org/10.1007/s12022-011-9189-0
20. Ayala-Ramirez M, Chougnet CN, Habra MA, Palmer JL, Leboulleux S, Cabanillas ME, et al. Treatment with sunitinib for patients with progressive metastatic pheochromocytomas and sympathetic paragangliomas. J Clin Endocrinol Metab. 2012 Nov;97(11):4040–50. doi: http://dx.doi.org/10.1210/jc.2012-2356
21. Neumann H, Bausch B, McWhinney S, Bender BU, Gimm O, Franke G, et al. Germline mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002 Sep;346(19):1459–66. doi: http://dx.doi.org/10.1056/NEJMoa020152
22. Lindberg, MR, editor Diagnostic pathology: Soft tissue tumors. 2nd ed. Philadelphia, PA: Elsevier; 2016. Paraganglioma; 794–6 pp.
2. Tassone F. Pheochromocytoma and paraganglioma [Comment]. N Engl J Med. 2019 Nov 7;381(19):1882–3. http://dx.doi. org/10.1056/NEJMc1912022
3. Young WF. Paragangliomas. Ann NY Acad Sci. 2006 Sep;1073:21–9. doi: http://dx.doi.org/10.1196/annals.1353.002
4. Kantorovich V, King KS, Pacak K. SDH-related pheochromocytoma and paraganglioma. Best Pract Res Clin Endocrinol Metab. 2010 Jun;24(3):415–24. doi: http://dx.doi.org/10.1016/j. beem.2010.04.001
5. Benn DE, Robinson BG, Clifton-Bligh RJ. 15 Years of paraganglioma: Clinical manifestations of paraganglioma syndromes types 1-5. Endocr Relat Cancer. 2015 Aug;22(4):T91–103. doi: http://dx.doi.org/10.1530/ERC-15-0268
6. Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science. 2000 Feb;287(5454):848–51. doi: http://dx.doi.org/10.1126/ science.287.5454.848
7. Hao HX, Khalimonchuk O, Schraders M, Dephoure N, Bayley JP, Kunst H, et al. SDH5, a gene required for flavination of suc-cinate dehydrogenase, is mutated in paraganglioma. Science. 2009 Aug 28;325(5944):1139–42. doi: http://dx.doi.org/10.1126/ science.1175689
8. Niemann S, Müller U. Mutations in SDHC cause autoso-mal dominant paraganglioma, type 3. Nature Genet. 2000 Nov;26(3):268–70. doi: http://dx.doi.org/10.1038/81551
9. Astuti D, Latif F, Dallol A, Dahia PL, Douglas F, George E, et al. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma [published correction appears in Am J Hum Genet 2002 Feb;70(2):565]. Am J Hum Genet. 2001 Jul;69(1):49–54. doi: http://dx.doi.org/10.1086/321282
10. Rankin EB, Giaccia AJ. The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ. 2008 Apr;15(4):678–85. doi: http://dx.doi.org/10.1038/cdd.2008.21
11. Srirangalingam U, LeCain M, Tufton N, Akker SA, Drake WM, Metcalfe K. Four generations of SDHB-related disease: Complexities in management. Fam Cancer. 2017 Apr;16(2):279– 82. doi: http://dx.doi.org/10.1007/s10689-016-9946-9
12. Ricketts CJ, Forman JR, Rattenberry E, Bradshaw N, Lalloo F, Izatt L, et al. Tumor risks and genotype–phenotype–proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Human Mutat. 2010 Jan;31(1):41–51. doi: http://dx.doi. org/10.1002/humu.21136
13. Tufton N, Sahdev A, Akker SA. Radiological surveillance screening in asymptomatic succinate dehydrogenase mutation carriers. J Endocr Soc. 2017 Jun 6;1(7):897–907. doi: http://dx. doi.org/10.1210/js.2017-00230
14. Plouin PF, Amar L, Dekkers OM; Guideline Working Group. European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a pheo-chromocytoma or a paraganglioma. Eur J Endocrinol. 2016 May;174(5):G1–10. doi: http://dx.doi.org/10.1530/EJE-16-0033
15. Kayano D, Kinuya S. Current consensus on I-131 MIBG therapy. Nucl Med Mol Imaging. 2018;52(4):254–65. doi: http://dx. doi.org/10.1007/s13139-018-0523-z
16. Jimenez C, Erwin W, Chasen B. Targeted radionuclide therapy for patients with metastatic pheochromocytoma and paraganglioma: From low-specific-activity to high-specific-activity iodine-131 metaiodobenzylguanidine. Cancers (Basel). 2019 Jul;11(7):1018. doi: http://dx.doi.org/10.3390/cancers11071018
17. Niemeijer N, Alblas G, Hulsteijn LV, Dekkers O, Corssmit E. Chemotherapy with cyclophosphamide, vincristine and dacar-bazine for malignant paraganglioma and pheochromocytoma: Systematic review and meta-analysis. Clin Endocrinol. 2014;81(5):642–51. doi: http://dx.doi.org/10.1111/cen.12542
18. Nozières C, Walter T, Joly MO, Giraud S, Scoazec J-Y, Borson-Chazot F, et al. A SDHB malignant paraganglioma with dramatic response to temozolomide-capecitabine. Eur J Endocrinol. 2012;166(6):1107–11. doi: http://dx.doi.org/10.1530/ EJE-11-1098
19. Favier J, Igaz P, Burnichon N, Amar L, Libé R, Badoual C, et al. Rationale for antiangiogenic therapy in pheochromocytoma and paraganglioma. Endocr Pathol. 2012 Mar;23(1):34– 42. doi: http://dx.doi.org/10.1007/s12022-011-9189-0
20. Ayala-Ramirez M, Chougnet CN, Habra MA, Palmer JL, Leboulleux S, Cabanillas ME, et al. Treatment with sunitinib for patients with progressive metastatic pheochromocytomas and sympathetic paragangliomas. J Clin Endocrinol Metab. 2012 Nov;97(11):4040–50. doi: http://dx.doi.org/10.1210/jc.2012-2356
21. Neumann H, Bausch B, McWhinney S, Bender BU, Gimm O, Franke G, et al. Germline mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002 Sep;346(19):1459–66. doi: http://dx.doi.org/10.1056/NEJMoa020152
22. Lindberg, MR, editor Diagnostic pathology: Soft tissue tumors. 2nd ed. Philadelphia, PA: Elsevier; 2016. Paraganglioma; 794–6 pp.
Article Sidebar
Published
Jan 25, 2021
Article Details
How to Cite
Large Retroperitoneal Paraganglioma Associated with Germline Mutation of the Succinate Dehydrogenase Gene. (2021). Journal of Kidney Cancer, 8(1), 12-18. https://doi.org/10.15586/jkcvhl.v8i1.129
Section
Pheochromocytoma
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
Large Retroperitoneal Paraganglioma Associated with Germline Mutation of the Succinate Dehydrogenase Gene. (2021). Journal of Kidney Cancer, 8(1), 12-18. https://doi.org/10.15586/jkcvhl.v8i1.129