Paragangliomas in Carney–Stratakis Syndrome

Arushi Khurana; Lin Mei; Anthony C. Faber; Steven C. Smith; Sosipatros A. Boikos

doi:10.1055/a-0918-8340

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2019; 51(07): 437-442
DOI: 10.1055/a-0918-8340

Review

Paragangliomas in Carney–Stratakis Syndrome

Arushi Khurana

¹VCU Massey Cancer Center - Hematology Oncology, Richmond, Virginia, USA

,

Lin Mei

¹VCU Massey Cancer Center - Hematology Oncology, Richmond, Virginia, USA

,

Anthony C. Faber

²Virginia Commonwealth University - Philips Institute for Oral Health Research, Richmond, Virginia, USA

,

Steven C. Smith

³Virginia Commonwealth University - Pathology, Richmond, Virginia, USA

,

Sosipatros A. Boikos

¹VCU Massey Cancer Center - Hematology Oncology, Richmond, Virginia, USA

› Author Affiliations

Abstract

Carney-Stratakis Syndrome (CSS) comprises of paragangliomas (PGLs) and gastrointestinal stromal tumors (GISTs). Several of its features overlap with Carney Triad (CT) - PGLs, GISTs, and pulmonary chondromas. CSS has autosomal dominant inheritance, incomplete penetrance, and greater relative frequency of PGL over GISTs. The PGLs in CSS are multicentric and GISTs are multifocal in all the patients, suggesting an inherited susceptibility and associating the two manifestations. In this review, we highlight the clinical, pathological, and molecular characteristics of CSS, along with its diagnostic and therapeutic implications.

Key words

Carney–Stratakis syndrome - paragangliomas - GIST - pheochromocytomas

Full Text

References

References
1 Carney JA, Stratakis CA. Familial paraganglioma and gastric stromal sarcoma: A new syndrome distinct from the Carney triad. Am J Med Genet 2002; 108: 132-139
2 Martucci VL, Pacak K. Pheochromocytoma and paraganglioma: Diagnosis, genetics, management, and treatment. Curr Probl Cancer 2014; 38: 7-41
3 Drovdlic CM, Myers EN, Peters JA. et al. Proportion of heritable paraganglioma cases and associated clinical characteristics. Laryngoscope 2001; 111: 1822-1827
4 Sobol SM, Dailey JC. Familial multiple cervical paragangliomas: Report of a Kindred and Review of the Literature. Otolaryngol Neck Surg 1990; 102: 382-390
5 Pasini B, McWhinney SR, Bei T. et al. 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 2008; 16: 79-88
6 McWhinney SR, Pasini B, Stratakis CA. et al. Familial gastrointestinal stromal tumors and germ-line mutations. N Engl J Med 2007; 357: 1054-1056
7 Hirota S, Isozaki K, Moriyama Y. et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998; 279: 577-580
8 Huss S, Künstlinger H, Wardelmann E. et al. A subset of gastrointestinal stromal tumors previously regarded as wild-type tumors carries somatic activating mutations in KIT exon 8 (p.D419del). Mod Pathol 2013; 26: 1004-1012
9 Rossi S, Gasparotto D, Miceli R. et al. KIT, PDGFRA, and BRAF mutational spectrum impacts on the natural history of Imatinib-naive localized GIST. Am J Surg Pathol 2015; 39: 922-930
10 Janeway KA, Kim SY, Lodish M. et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci U S A 2011; 108: 314-318
11 Killian JK, Kim SY, Miettinen M. et al. Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor. Cancer Discov 2013; 3: 648-657
12 Boikos SA, Stratakis CA. The genetic landscape of gastrointestinal stromal tumor lacking KIT and PDGFRA mutations. Endocrine 2014; 47: 401-408
13 Dahia PLM. Pheochromocytoma and paraganglioma pathogenesis: Learning from genetic heterogeneity. Nat Rev Cancer 2014; 14: 108-119
14 Fishbein L, Leshchiner I, Walter V. et al. Comprehensive molecular characterization of pheochromocytoma and paraganglioma. Cancer Cell 2017; 31: 181-193
15 Crona J, Taïeb D, Pacak K. New perspectives on pheochromocytoma and paraganglioma: toward a molecular classification. Endocr Rev 2017; 38: 489-515
16 Astuti D, Latif F, Dallol A. et al. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet 2001; 69: 49-54
17 Astuti D, Douglas F, Lennard TW. et al. Germline SDHD mutation in familial phaeochromocytoma. Lancet 2001; 357: 1181-1182
18 Baysal BE, Ferrell RE, Willett-Brozick JE. et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 2000; 287: 848-851
19 Udager AM, Magers MJ, Goerke DM. et al. The utility of SDHB and FH immunohistochemistry in patients evaluated for hereditary paraganglioma-pheochromocytoma syndromes. Hum Pathol 2018; 71: 47-54
20 Clark GR, Sciacovelli M, Gaude E. et al. Germline FH mutations presenting with pheochromocytoma. J Clin Endocrinol Metab 2014; 99: E2046-E2050
21 Hoekstra AS, Bayley J-P. The role of complex II in disease. Biochim Biophys Acta Bioenerg 2013; 1827: 543-551
22 Bardella C, Pollard PJ, Tomlinson I. SDH mutations in cancer. Biochim Biophys Acta Bioenerg 2011; 1807: 1432-1443
23 Scheffler IE. Molecular genetics of succinate:quinone oxidoreductase in eukaryotes. Prog Nucleic Acid Res Mol Biol 1998; 60: 267-315
24 Gill AJ. Succinate dehydrogenase (SDH) and mitochondrial driven neoplasia. Pathology 2012; 44: 285-292
25 Favier J, Amar L, Gimenez-Roqueplo A-P. Paraganglioma and phaeochromocytoma: from genetics to personalized medicine. Nat Rev Endocrinol 2015; 11: 101-111
26 Mason EF, Hornick JL. Succinate dehydrogenase deficiency is associated with decreased 5-hydroxymethylcytosine production in gastrointestinal stromal tumors: implications for mechanisms of tumorigenesis. Mod Pathol 2013; 26: 1492-1497
27 Selak MA, Armour SM, MacKenzie ED. et al. Succinate links TCA cycle dysfunction to oncogenesis by Inhibiting HIF-α prolyl hydroxylase. Cancer Cell 2005; 7: 77-85. Available from http://www.ncbi.nlm.nih.gov/pubmed/15652751
28 Pantaleo MA, Nannini M, Astolfi A. et al. A Distinct Pediatric-type Gastrointestinal Stromal Tumor in Adults. Am J Surg Pathol 2011; 35: 1750-1752
29 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: 983-987
30 Wagner AJ, Remillard SP, Zhang Y-X. et al. Loss of expression of SDHA predicts SDHA mutations in gastrointestinal stromal tumors. Mod Pathol 2013; 26: 289-294
31 Gill AJ, Benn DE, Chou A. et al. Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes. Hum Pathol 2010; 41: 805-814
32 van Nederveen FH, Gaal J, Favier J. et al. 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 2009; 10: 764-771
33 Barletta JA, Hornick JL. Succinate Dehydrogenase-deficient Tumors. Adv Anat Pathol 2012; 19: 193-203
34 Dwight T, Benn DE, Clarkson A. et al. Loss of SDHA Expression Identifies SDHA Mutations in Succinate Dehydrogenase–deficient Gastrointestinal Stromal Tumors. Am J Surg Pathol 2013; 37: 226-233
35 Dwight T, Mann K, Benn DE. et al. Familial SDHA mutation associated with pituitary adenoma and pheochromocytoma/paraganglioma. J Clin Endocrinol Metab 2013; 98: E1103-E1108
36 Boikos SA, Pappo AS, Killian JK. et al. Molecular Subtypes of KIT/PDGFRA wild-type gastrointestinal stromal tumors. JAMA. Oncol 2016; 2: 922
37 Weldon CB, Madenci AL, Boikos SA. et al. Surgical management of wild-type gastrointestinal stromal tumors: A Report from the National Institutes of Health Pediatric and Wildtype GIST Clinic. J Clin Oncol 2017; 35: 523-528
38 Zhang L, Smyrk TC, Young WF. et al. Gastric stromal tumors in carney triad are different clinically, pathologically, and behaviorally from sporadic gastric gastrointestinal stromal tumors: Findings in 104 cases. Am J Surg Pathol 2010; 34: 53-64
39 Miettinen M, Wang Z-F, Sarlomo-Rikala M. et al. Succinate Dehydrogenase-Deficient GISTs. Am J Surg Pathol 2011; 35: 1712-1721
40 Wada R, Arai H, Kure S. et al. “Wild type” GIST: Clinicopathological features and clinical practice. Pathol Int 2016; 66: 431-437
41 Miettinen M, Killian JK, Wang Z-F. et al. Immunohistochemical Loss of Succinate Dehydrogenase Subunit A (SDHA) in Gastrointestinal Stromal Tumors (GISTs) Signals SDHA Germline Mutation. Am J Surg Pathol 2013; 37: 234-240
42 Gaal J, Stratakis CA, Carney JA. et al. SDHB immunohistochemistry: A useful tool in the diagnosis of Carney–Stratakis and Carney triad gastrointestinal stromal tumors. Mod Pathol 2011; 24: 147-1510271
43 Mason EF, Hornick JL. Conventional risk stratification fails to predict progression of succinate dehydrogenase–deficient gastrointestinal stromal tumors. Am J Surg Pathol 2016; 40: 1616-1621
44 Eisenhofer G, Lenders JWM, Timmers H. et al. Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma. Clin Chem 2011; 57: 411-420
45 Timmers HJLM, Kozupa A, Eisenhofer G. et al. Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B -associated pheochromocytomas and paragangliomas. J Clin Endocrinol Metab 2007; 92: 779-786
46 Schovanek J, Martucci V, Wesley R. et al. The size of the primary tumor and age at initial diagnosis are independent predictors of the metastatic behavior and survival of patients with SDHB-related pheochromocytoma and paraganglioma: a retrospective cohort study. BMC Cancer 2014; 14: 523
47 Turkova H, Prodanov T, Maly M. et al. Characteristics and outcomes of metastatic SDHB and Sporadic Pheochromocytoma/Paraganglioma: A National Institutes of Health study. Endocr Pract 2016; 22: 302-314
48 Janssen I, Chen CC, Taieb D. et al. 68Ga-DOTATATE PET/CT in the localization of head and neck paragangliomas compared with other functional imaging modalities and CT/MRI. J Nucl Med 2016; 57: 186-191
49 Naji M, Zhao C, Welsh SJ. et al. 68Ga-DOTA-TATE PET vs. 123I-MIBG in Identifying Malignant Neural Crest Tumours. Mol Imaging Biol 2011; 13: 769-775
50 Gimenez-Roqueplo A-P, Caumont-Prim A, Houzard C. et al. Imaging Work-Up for Screening of Paraganglioma and Pheochromocytoma in SDHx Mutation Carriers: A Multicenter Prospective Study from the PGL.EVA Investigators. J Clin Endocrinol Metab 2013; 98: E162-E173
51 Elston MS, Meyer-Rochow GY, Conaglen HM. et al. Increased SSTR2A and SSTR3 expression in succinate dehydrogenase–deficient pheochromocytomas and paragangliomas. Hum Pathol 2015; 46: 390-396
52 Amar L, Servais A, Gimenez-Roqueplo A-P. et al. Year of diagnosis, features at presentation, and risk of recurrence in patients with pheochromocytoma or secreting paraganglioma. J Clin Endocrinol Metab 2005; 90: 2110-2116
53 Amar L, Lussey-Lepoutre C, Lenders JWM. et al. Management of endocrine disease: Recurrence or new tumors after complete resection of pheochromocytomas and paragangliomas: a systematic review and meta-analysis. Eur J Endocrinol 2016; 175: R135-R145
54 Pacak K. Preoperative Management of the Pheochromocytoma Patient. J Clin Endocrinol Metab 2007; 92: 4069-4079
55 Plouin P-F, Duclos J-M, Soppelsa F. et al. Factors Associated with Perioperative Morbidity and Mortality in Patients with Pheochromocytoma: Analysis of 165 Operations at a Single Center. J Clin Endocrinol Metab 2001; 86: 1480-1486
56 Goldstein RE, O’Neill JA, Holcomb GW. et al. Clinical experience over 48 years with pheochromocytoma. Ann Surg 1999; 229: 755-764 discussion 764–766
57 Krempf M, Lumbroso J, Mornex R. et al. Treatment of malignant pheochromocytoma with [131I]metaiodobenzylguanidine: A French multicenter study. J Nucl Biol Med 1991; 35: 284-287
58 Loh KC, Fitzgerald PA, Matthay KK. et al. The treatment of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine (131I-MIBG): A comprehensive review of 116 reported patients. J Endocrinol Invest 1997; 20: 648-658
59 Huang H, Abraham J, Hung E. et al. Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine. Cancer 2008; 113: 2020-2028
60 Niemeijer ND, Alblas G, van Hulsteijn LT. et al. Chemotherapy with cyclophosphamide, vincristine and dacarbazine for malignant paraganglioma and pheochromocytoma: Systematic review and meta-analysis. Clin Endocrinol (Oxf) 2014; 81: 642-651
61 Asai S, Katabami T, Tsuiki M. et al. Controlling tumor progression with cyclophosphamide, vincristine, and dacarbazine treatment improves survival in patients with metastatic and unresectable malignant pheochromocytomas/paragangliomas. Horm Cancer 2017; 8: 108-118
62 Tanabe A, Naruse M, Nomura K. et al. Combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine in patients with malignant pheochromocytoma and paraganglioma. Horm Cancer 2013; 4: 103-110
63 Hadoux J, Favier J. Scoazec J-Yet al. SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma. Int J Cancer 2014; 135: 2711-2720
64 Ayala-Ramirez M, Chougnet CN, Habra MA. et al. Treatment with sunitinib for patients with progressive metastatic pheochromocytomas and sympathetic paragangliomas. J Clin Endocrinol Metab 2012; 97: 4040-4050
65 Jasim S, Suman VJ, Jimenez C. et al. Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma. Endocrine 2017; 57: 220-225
66 Jasperson KW, Kohlmann W, Gammon A. et al. Role of rapid sequence whole-body MRI screening in SDH-associated hereditary paraganglioma families. Fam Cancer 2014; 13: 257-265
67 Aufforth RD, Ramakant P, Sadowski SM. et al. Pheochromocytoma Screening Initiation and Frequency in von Hippel-Lindau Syndrome. J Clin Endocrinol Metab 2015; 100: 4498-4504
68 Williamson SR, Eble JN, Amin MB. et al. Succinate dehydrogenase-deficient renal cell carcinoma: Detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma. Mod Pathol 2015; 28: 80-94
69 Gupta S, Zhang J, Milosevic D. et al. Primary Renal Paragangliomas and Renal Neoplasia Associated with Pheochromocytoma/Paraganglioma: Analysis of von Hippel–Lindau (VHL), Succinate Dehydrogenase (SDHX) and Transmembrane Protein 127 (TMEM127). Endocr Pathol 2017; 28: 253-268
70 Mei L, Smith SC, Faber AC. et al. Gastrointestinal stromal tumors: The GIST of precision medicine. trends. Cancer 2018; 4: 74-91
71 Zhuang Z, Yang C, Lorenzo F. et al. Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia. N Engl J Med 2012; 367: 922-930