Abstract
Succinate dehydrogenase subunit B gene (SDHB) is associated with the development of hereditary paraganglioma (PGL) and pheochromocytoma (PCC). Here we describe a novel germline mutation in SDHB in a 69-year-old Japanese woman with a posterior mediastinal PGL. We summarize the clinical presentation, diagnostic work-up, and pathological features of a patient with a posterior mediastinal PGL and review the pertinent literature. Direct sequencing of SDHB and SDHD was performed. The patient presented with a posterior mediastinal tumor and was normotensive. She underwent abdominal tumor resection at the age of 38 years, but clinical and pathological diagnoses were unknown. She had no family history of hypertension, PGL, or PCC. Imaging studies suggested that the tumor was neurogenic. Endocrinological examinations showed normal plasma catecholamine levels. The tumor was completely removed without metastasis. Pathological findings confirmed PGL. Immunohistochemical staining showed that the tumor cells were positive for chromogranin A, synaptophysin, and CD56, and the Ki67 index was low (<1 %). The patient has not experienced recurrence or metastasis for the last 5 years. DNA sequencing revealed a novel P236S (c.843 C > T) mutation in SDHB. The P236S germline mutation in SDHB was associated with posterior mediastinal PGL. Strict follow-up of the patient is necessary because the SDHB mutation may be related to malignancy.
Similar content being viewed by others
References
DeLellis RA, Lloyd RV, Heitz PU, Eng C (2004) World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Endocrine Organs. IARC Press, Lyon, pp 147–166.
Eisenhofer G, Tischler AS, de Krijger RR. Diagnostic tests and biomarkers for pheochromocytoma and extra-adrenal paraganglioma: from routine laboratory methods to disease stratification. Endocr Pathol 23: 4–14, 2012.
Sun F, Huo X, Zhai Y, Wang A, Xu J, Su D, Bartlam M, Rao Z. Crystal structure of mitochondrial respiratory membrane protein complex II. Cell 121: 1043–1057, 2005.
Yankovskaya V, Horsefield R, Törnroth S, Luna-Chavez C, Miyoshi H, Léger C, Byrne B, Cecchini G, Iwata S. Architecture of succinate dehydrogenase and reactive oxygen species generation. Science 299: 700–704, 2003.
Astuti D, Latif F, Dallol A, Dahia PL, Douglas F, George E, Sköldberg F, Husebye ES, Eng C., Maher ER. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet 69: 49–54, 2001.
Schiavi F, Boedeker CC, Bausch B, Peçzkowska M, Gomez CF, Strassburg T, Pawlu C, Buchta M, Salzmann M, Hoffmann MM, Berlis A, Brink I, Cybulla M, Muresan M, Walter MA, Forrer F, Välimäki M, Kawecki A, Szutkowski Z, Schipper J, Walz MK, Pigny P, Bauters C, Willet-Brozick JE, Baysal BE, Januszewicz A, Eng C, Opocher G, Neumann HP; European-American Paraganglioma Study Group. Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. JAMA 294: 2057–2063, 2005.
Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PE, Rubinstein WS, Myers EN, Richard 3rd CW, Cornelisse CJ, Devilee P, Devlin B. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287: 848–851, 2000.
Benn DE, Gimenez-Roqueplo AP, Reilly JR, Bertheral J, Burgess J, Byth K, Croxson M, Dahia PL, Elston M, Gimm O, Henley D, Herman P, Murday V, Niccoli-Sire P, Pasieka JL, Rohmer V, Tucker K, Jeunemaitre X, Marsh DJ, Plouin PF, Robinson BG. Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab 91: 827–36, 2006.
Neumann HP, Pawlu C, Peczkowska M, Bausch B, McWhinney SR, Muresan M, Buchta M, Franke G, Klisch J, Bley TA, Hoegerle S, Boedeker CC, Opocher G, Schipper J, Januszewicz A, Eng C. Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 292: 943–951, 2004
Amar L, Bertherat J, Baudin E, Ajzenberg C, Bressac-de Paillerets B, Chabre O, Chamontin B, Delemer B, Giraud S, Murat A, Niccoli-Sire P, Richard S, Rohmer V, Sadoul JL, Strompf L, Schlumberger M, Bertagna X, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP. Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol 23: 8812–8818, 2005.
Brouwers FM, Eisenhofer G, Tao JJ, Kant JA, Adams KT, Linehan WN, Pacak K. High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing. J Clin Endocrinol Metab 91: 4505–4509, 2006.
Gimenez-Roqueplo AP, Tischler AS. Pheochromocytoma and paraganglioma: progress on all fronts. Endocr Pathol 23: 1–3, 2012
Timmers HJL, Kozupa A, Eisenhofer G, Raygada M, Adams KT, Solis D, Lenders JWM, Pacak K. Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas. J Clin Endocrinol Metab 92: 779–786, 2007.
Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith WM, Munk R, Manz T, Glaesker S, Apel T.W, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, Klein-Franke A, Klose P, Schmidt H, Maier-Woelfle M, Peczkowska M, Szmigielski C, Eng C. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 346: 1459–1466, 2002.
van Nederveen FH, Gaal J, Favier J, Korpershoek E, Oldenburg RA, de Bruyn EM, Sleddens HF, Derkx P, Rivière J, Dannenberg H, Petri BJ, Komminoth P, Pacak K, Hop WC, Pollard PJ, Mannelli M, Bayley JP, Perren A, Niemann S, Verhofstad AA, de Bruïne AP, Maher ER, Tissier F, Méatchi T, Badoual C, Bertherat J, Amar L, Alataki D, Van Marck E, Ferrau F, François J, de Herder WW, Peeters MP, van Linge A, Lenders JW, Gimenez-Roqueplo AP, de Krijger RR, Dinjens WN. An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis. Lancet Oncol 10: 764–71, 2009.
Gill AJ, Benn DE, Chou A, Clarkson A, Muljono A, Meyer-Rochow GY, Richardson AL, Sidhu SB, Robinson BG, Clifton-Bligh RJ. Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes. Hum Pathol 41: 805–14, 2010.
Vanharanta S, Buchta M, McWhinney SR, Virta SK, Peçzkowska M, Morrison CD, Lehtonen R, Januszewicz A, Järvinen H, Juhola M, Mecklin JP, Pukkala E, Herva R, Kiuru M, Nupponen NN, Aaltonen LA, Neumann HP, Eng C. Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma. Am J Hum Genet 74:153–159, 2004.
Pasini B, McWhinney SR, Bei T, Matyakhina L, Stergiopoulos S, Muchow M, Boikos SA, Ferrando B, Pacak K, Assie G, Baudin E, Chompret A, Ellison JW, Briere JJ, Rustin P, Gimenez-Roqueplo AP, Eng C, Carney JA, Stratakis CA. Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet 16: 79–88, 2008.
Pasini B, Stratakis CA. SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma-paraganglioma syndromes. J Intern Med. 266: 19–42, 2009.
Acknowledgments
The authors thank Mr. Hiroshi Kamiguchi and Ms. Michiyo Yoshino, Tokai University School of Medicine, Teaching and Research Support Center for their technical assistance.
The authors declare no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sato, H., Shoji, S., Kajiwara, H. et al. A Novel Mutation (P236S) in the Succinate Dehydrogenase Subunit B Gene in a Japanese Patient with a Posterior Mediastinal Paraganglioma. Endocr Pathol 24, 144–148 (2013). https://doi.org/10.1007/s12022-013-9252-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12022-013-9252-0