Molecular and therapeutic advances in the diagnosis and management of malignant pheochromocytomas and paragangliomas

Oncologist

Volumn 18, Issue 4, 2013, Pages 391-407

  Lowery, Aoife J ^a   Walsh, Siun ^a   McDermott, Enda W ^a   Prichard, Ruth S ^a  

^a ST VINCENT S UNIVERSITY HOSPITAL   (Ireland)

Author keywords

Genetic mutation; Malignant; Paraganglioma; Pheochromocytoma; Therapeutics

Indexed keywords

(3 IODOBENZYL) GUANIDINE I 123; (3 IODOBENZYL) GUANIDINE I 131; CIXUTUMUMAB; CYCLOPHOSPHAMIDE; DACARBAZINE; DOPAMINE BETA MONOOXYGENASE; ERLOTINIB; EVEROLIMUS; FLUORODEOXYGLUCOSE F 18; HYPOXIA INDUCIBLE FACTOR; LUTETIUM 177; MAX PROTEIN; MICRORNA; OCTREOTIDE; PENTETREOTIDE IN 111; SOMATOSTATIN RECEPTOR; SUCCINIC ACID; SUNITINIB; TANESPIMYCIN; THALIDOMIDE; TRASTUZUMAB; UNCLASSIFIED DRUG; VATALANIB; VINCRISTINE; YTTRIUM 90;

ADRENALECTOMY; CANCER PROGNOSIS; COMPARATIVE GENOMIC HYBRIDIZATION; DRUG EFFICACY; DRUG SAFETY; GENE EXPRESSION PROFILING; GENE MUTATION; GENOTYPE PHENOTYPE CORRELATION; HUMAN; IMMUNOHISTOCHEMISTRY; MICROARRAY ANALYSIS; MULTIPLE ENDOCRINE NEOPLASIA; MUTATIONAL ANALYSIS; NEUROFIBROMATOSIS; PARAGANGLIOMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHEOCHROMOCYTOMA; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SCINTIGRAPHY; SCORING SYSTEM; SENSITIVITY AND SPECIFICITY; SIGNAL TRANSDUCTION; VON HIPPEL LINDAU DISEASE;

ADRENAL GLAND NEOPLASMS; ADRENALECTOMY; DIAGNOSTIC IMAGING; HUMANS; MICRORNAS; MUTATION; NEOPLASM RECURRENCE, LOCAL; PARAGANGLIOMA; PHEOCHROMOCYTOMA; PROGNOSIS;

EID: 84877075989     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.2012-0410     Document Type: Review

References (225)

1. DeLellis RA, Lloyd RV, Heitz PU et al. Tumours of endocrine organs. Lyon, France: IARC Press, 2004.
2. Stenstrom G, Svardsudd K. Pheochromocytoma in Sweden, 1958-1981: An analysis ofthe National Cancer Registry Data. Acta Med Scand 1986;220: 225-232.
3. Andersen GS, Toftdahl DB, Lund JO et al. The incidence rate of phaeochromocytoma and Conn's syndrome in Denmark, 1977-1981. J Hum Hypertens 1988;2:187-189.
4. Beard CM, Sheps SG, Kurland LT et al. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc 1983;58: 802-804.
5. Hartley L, Perry-Keene D. Phaeochromocytoma in Queensland, 1970-83. Aust N Z J Surg 1985;55: 471-475.
6. Baysal BE. Hereditary paraganglioma targets diverse paraganglia. J Med Genet 2002;39:617-622.
7. Erickson D, Kudva YC, Ebersold MJ et al. Benign paragangliomas: Clinical presentation and treatment outcomes in 236 patients. J Clin Endocrinol Metab 2001;86:5210-5216.
8. Sinclair AM, Isles CG, Brown I et al. Secondary hypertension in a blood pressure clinic. Arch Intern Med 1987;147:1289-1293.
9. Omura M, Saito J, Yamaguchi K et al. Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan. Hypertens Res 2004;27:193-202.
10. Young WF Jr. Management approaches to adrenal incidentalomas. Aview from Rochester, Minnesota. Endocrinol Metab Clin North Am 2000;29: 159-185.
11. Neumann HP, Bausch B, McWhinney SR et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 2002;346:1459-1466.
12. Mannelli M, Ianni L, Cilotti A et al. Pheochromocytoma in Italy: A multicentric retrospective study. EurJ Endocrinol 1999;141:619-624.
13. Cohen DL, Fraker D, Townsend RR. Lack of symptoms in patients with histologic evidence of pheochromocytoma: A diagnostic challenge. Ann NY Acad Sci 2006;1073:47-51.
14. Zelinka T, Widimsky J, Weisserova J. Diminished circadian blood pressure rhythm in patients with asymptomatic normotensive pheochromocytoma. Physiol Res 2001;50:631-634.
15. Lai EW, Perera SM, Havekes B et al. Gender-related differences in the clinical presentation of malignant and benign pheochromocytoma. Endocrine 2008;34:96-100.
16. Zarnegar R, Kebebew E, Duh QY et al. Malignant pheochromocytoma. Surg Oncol Clin N Am 2006;15:555-571.
17. Offergeld C, Brase C, Yaremchuk S et al. Head and neck paragangliomas: Clinical and molecular genetic classification. Clinics (Sao Paulo) 2012; 67(suppl 1):19-28.
18. Proye C, Vix M, Goropoulos A et al. High incidence of malignant pheochromocytoma in a surgical unit. 26 cases out of 100 patients operated from 1971 to 1991. J Endocrinol Invest 1992;15:651-663.
19. Walz MK, Alesina PF, Wenger FA et al. Laparoscopic and retroperitoneoscopic treatment of pheochromocytomasand retroperitoneal paragangliomas: Results of 161 tumors in 126 patients. World J Surg 2006;30:899-908.
20. Gimenez-Roqueplo AP, Favier J, Rustin P et al. Mutations in the SDHBgeneare associated with extra-adrenal and/ormalignant phaeochromocytomas. Cancer Res 2003;63:5615-5621.
21. Thompson LD. Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) to separate benign from malignantneoplasms: Aclinicopathologicand immunophenotypic study of 100 cases. Am J Surg Pathol 2002;26:551-566.
22. Strong VE, Kennedy T, Al-Ahmadie H et al. Prognostic indicators of malignancy in adrenal pheochromocytomas: Clinical, histopathologic, and cell cycle/apoptosis gene expression analysis. Surgery2008;143:759-768.
23. Tischler AS. Pheochromocytoma: time to stamp out malignancy? Endocr Pathol 2008;19: 207-208.
24. Timmers HJ, Brouwers FM, Hermus AR et al. Metastases but not cardiovascular mortality reduces life expectancy following surgical resection of apparently benign pheochromocytoma. Endocr Relat Cancer 2008;15:1127-1133.
25. Chrisoulidou A, Kaltsas G, Ilias I etal. The diagnosis and management of malignant phaeochromocytoma and paraganglioma. Endocr Relat Cancer2007;14:569-585.
26. Nomura K, Kimura H, Shimizu S et al. Survivalof patients with metastatic malignant pheochromocytoma and efficacy ofcombined cyclophosphamide, vincristine, and dacarbazine chemotherapy. J Clin Endocrinol Metab 2009;94:2850-2856.
27. Sisson JC, Shulkin BL, Esfandiari NH. Courses of malignant pheochromocytoma: Implications for therapy. Ann NYAcad Sci 2006;1073:505-511.
28. Pacak K, Eisenhofer G, Ahlman H et al. Pheochromocytoma: Tecommendations for clinical practice from the First International Symposium. Nat Clin Pract Endocrinol Metab 2007;3:92-102.
29. Tischler AS. Pheochromocytomaandextra-adrenal paraganglioma: Updates. Arch Pathol Lab Med 2008;132:1272-1284.
30. Gimenez-Roqueplo AP, Dahia PL, Robledo M. An update on thegenetics of paraganglioma, pheochromocytoma, and associated hereditary syndromes. Horm Metab Res 2012;44:328-333.
31. Machens A, Brauckhoff M, Gimm O et al. Risk-oriented approach to hereditaryadrenal pheochromocytoma. Ann N Y Acad Sci 2006;1073:417-428.
32. Maher ER, Neumann HP, Richard S. von Hip-pel-Lindau disease: A clinical and scientific review. EurJHum Genet 2011;19:617-623.
33. 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.
34. Astuti D, Douglas F, Lennard TW et al. Germ-line SDHD mutation in familial phaeochromocytoma. Lancet 2001;357:1181-1182.
35. Peczkowska M, Cascon A, Prejbisz A et al. Extra-adrenal and adrenal pheochromocytom asassociated with a germline SDHC mutation. Nat Clin Pract Endocrinol Metab 2008;4:111-115.
36. Qin Y, Yao L, King EE et al. Germline mutations in TMEM127 confer susceptibility to pheochromocytoma. NatGenet 2010;42:229-233.
37. Schlisio S, Kenchappa RS, Vredeveld LC et al. The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor. Genes Dev 2008;22:884-893.
38. Ladroue C, Carcenac R, LeporrierMetal. PHD2 mutation and congenital erythrocytosis with paraganglioma. N Engl J Med 2008;359:2685-2692.
39. Comino-Mendez I, Gracia-Aznarez FJ, Schiavi F et al. Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nat Genet 2011;43:663-667.
40. Zhuang Z, Yang C, Lorenzo F et al. Somatic HIF2Again-of-function mutationsin paraganglioma with polycythemia. N Engl J Med 2012;367:922-930.
41. Bourgeron T, Rustin P, Chretien D et al. Mutation ofanuclearsuccinatedehydrogenasegene results in mitochondrial respiratorychain deficiency. Nat Genet 1995;11:144-149.
42. Burnichon N, Briere JJ, Libe R et al. SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet 2010;19:3011-3020.
43. Korpershoek E, Favier J, Gaal J et al. SDHAim- munohistochemistry detects germline SDHA gene mutations in apparently sporadic paragangliomas and pheochromocytomas. J Clin Endocrinol Metab 2011;96:E1472-E1476.
44. Hao HX, Khalimonchuk O, Schraders M et al. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science 2009;325:1139-1142.
45. Kunst HP, Rutten MH, de Monnink JP et al. SD- HAF2 (PGL2-SDH5) and hereditary head and neck paraganglioma. Clin CancerRes 2011;17:247-254.
46. Bayley JP, Kunst HP, Cascon A et al. SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma. Lancet Oncol 2010;11: 366-372.
47. Schiavi F, Milne RL, Anda E et al. Are we overestimating the penetrance of mutations in SDHB? Hum Mutat 2010;31:761-762.
48. Neumann HP, Pawlu C, Peczkowska M et al. Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA2004;292:943-951.
49. Ricketts CJ, Forman JR, Rattenberry E et al. Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHBand SDHD. Hum Mutat 2010;31:41-51.
50. Brouwers FM, Eisenhofer G, Tao JJ et al. High frequency ofSDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: Implications for genetic testing. J Clin Endocrinol Metab 2006;91:4505-4509.
51. Amar L, Baudin E, Burnichon N et al. Succinate dehydrogenaseBgenemutationspredictsurvival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocrinol Metab 2007;92: 3822-3828.
52. Gill AJ, Pachter NS, Clarkson A et al. Renal tumors and hereditarypheochromocytoma-paragan- glioma syndrome type 4. N Engl J Med 2011;364: 885-886.
53. Ricketts CJ, Shuch B, Vocke CD et al. Succinate dehydrogenase kidneycancer: An aggressive example ofthe warburg effect in cancer. J Urol 2012;188: 2063-2071.
54. Timmers HJ, Gimenez-Roqueplo AP, Mannelli M et al. Clinical aspects of SDHx-related pheochromocytoma and paraganglioma. Endocr Relat Cancer 2009;16:391-400.
55. Burnichon N, Rohmer V, Amar L et al. The succinate dehydrogenasegenetic testing in a large prospective series of patients with paragangliomas. J Clin Endocrinol Metab 2009;94:2817-2827.
56. Carney JA. The triad of gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma: A five-year review. Medicine(Baltimore) 1983;62:159-169.
57. 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.
58. Janeway KA, Kim SY, Lodish M et al. Defects in succinate dehydrogenase in gastrointestinalstro- maltumorslacking KIT and PDGFRAmutations. Proc Natl Acad Sci USA 2011;108:314-318.
59. Neumann HP, Sullivan M, Winter A et al. Germ- line mutations of the TMEM127 gene in patients with paraganglioma of head and neck and extraadrenal abdominal sites. J Clin Endocrinol Metab 2011;96:E1279-E1282.
60. Yao L, Schiavi F, Cascon A et al. Spectrum and prevalence of FP/TMEM127 gene mutations in pheochromocytomas and paragangliomas. JAMA 2010;304:2611-2619.
61. Yeh IT, Lenci RE, Qin Y et al. Agermline mutation of the KIF1B beta gene on 1p36 in a family with neural and nonneural tumors. Hum Genet 2008; 124:279-285.
62. Astuti D, Ricketts CJ, Chowdhury R et al. Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) inindividualswithfeaturesofphaeochromocytoma andrenalcellcarcinomasusceptibility. EndocrRelat Cancer 2011;18:73-83.
63. Lorenzo FR, Yang C, Ng Tang Fui M et al. Anovel EPAS1/HIF2A germline mutation in a congenital polycythemia with paraganglioma. J Mol Med (Berl). October23, 2012 [Epub ahead ofprint].
64. Burnichon N, Cascon A, Schiavi F et al. MAX mutations cause hereditary and sporadic pheo- chromocytomaand paraganglioma. Clin Cancer Res 2012;18:2828-2837.
65. Eisenhofer G, Goldstein DS, Kopin IJ et al. Pheochromocytoma: Rediscovery as a catechol- amine-metabolizingtumor. EndocrPathol 2003;14: 193-212.
66. Eisenhofer G, Lenders JW, Pacak K. Choice of biochemical test for diagnosis of pheochromocy- toma: Validation of plasma metanephrines. Curr Hypertens Rep 2002;4:250-255.
67. Lenders JW, Pacak K, Eisenhofer G. New advances in the biochemical diagnosis of pheochro- mocytoma: Moving beyond catecholamines. Ann NY Acad Sci 2002;970:29-40.
68. Hickman PE, Leong M, Chang J et al. Plasma free metanephrines are superior to urine and plasma catecholamines and urine catecholamine metabolites for the investigation of phaeochromo- cytoma. Pathology 2009;41:173-177.
69. Unger N, Pitt C, Schmidt IL et al. Diagnostic value of various biochemical parameters forthe diagnosis of pheochromocytoma in patients with adrenal mass. Eur J Endocrinol 2006;154:409-417.
70. Sawka AM, Prebtani AP, Thabane L et al. A systematicreviewoftheliteratureexaminingthe diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis ofpheochromocytoma. BMC Endocr Disord 2004;4:2.
71. Eisenhofer G, Pacak K, Huynh TT et al. Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma. EndocrRelatCancer 2011; 18:97-111.
72. Eisenhofer G, Lenders JW, Timmers H et al. Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochro- mocytoma. Clin Chem 2011;57:411-420.
73. Schlumberger M, Gicquel C, Lumbroso J et al. Malignant pheochromocytoma: Clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases. J Endocrinol Invest 1992;15:631-642.
74. Proye C, Fossati P, Fontaine P et al. Dopamine- secreting pheochromocytoma: An unrecognized entity? Classification of pheochromocytomas ac- cordingtotheirtype of secretion Surgery 1986;100: 1154-1162.
75. Foo SH, Chan SP, Ananda V et al. Dopamine- secreting phaeochromocytomas and paragangliomas: Clinical features and management. Singapore Med J 2010;51:e89-e93.
76. Zelinka T, Musil Z, Duskova J et al. Metastatic pheochromocytoma:Doesthesizeandagematter? Eur J Clin Invest 2011;41:1121-1128.
77. John H, Ziegler WH, Hauri D et al. Pheochro- mocytomas: Can malignant potential be predicted? Urology 1999;53:679-683.
78. Januszewicz W, Wocial B, Januszewicz A et al. Dopamine and dopa urinary excretion in patients with pheochromocytoma-diagnostic implications. Blood Press 2001;10:212-216.
79. Rao F, Keiser HR, O'Connor DT. Malignant pheochromocytoma Chromaffin granule transmitters and response to treatment. Hypertension 2000;36:1045-1052.
80. Guerin M, Guillemot J, Thouennon E et al. Granins and their derived peptides in normal and tumoral chromaffin tissue: Implications for the diagnosis and prognosis of pheochromocytoma. Regul Pept 2010;165:21-29.
81. Yon L, Guillemot J, Montero-Hadjadje M et al. Identification of the secretogranin II-derived peptide EM66 in pheochromocytomas as a potential marker for discriminating benign versus malignant tumors. J Clin Endocrinol Metab 2003;88:2579-2585.
82. Guillemot J, Thouennon E, Guerin M et al. Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: Implications forthe production of the tumoral markerEM66. J MolEndocrinol 2012;48:115-127.
83. Eisenhofer G, Lenders JW, Siegert G et al. Plasma methoxytyramine: A novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status. Eur J Cancer 2012;48:1739-1749.
84. Lumachi F, Tregnaghi A, Zucchetta P etal. Sensitivity and positive predictive value of CT, MRI and 123I-MIBG scintigraphy in localizing pheochromo- cytomas: A prospective study. Nucl Med Commun 2006;27:583-587.
85. Maurea S, Cuocolo A, Reynolds JC et al. Io- dine-131-metaiodobenzylguanidine scintigraphy in preoperative and postoperative evaluation of paragangliomas: Comparison with CT and MRI. J Nucl Med 1993;34:173-179.
86. Timmers HJ, Chen CC, Carrasquillo JA et al. Comparison of 18F-fluoro-L-DOPA, 18F-fluoro- deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheo- chromocytoma and paraganglioma. J Clin Endocrinol Metab 2009;94:4757-4767.
87. Taieb D, Sebag F, Barlier A et al. 18F-FDG avidity of pheochromocytomas and paragangliomas: A newmolecularimagingsignature? J Nucl Med 2009; 50:711-717.
88. Vaidyanathan G. Meta-iodobenzylguanidine and analogues: Chemistry and biology. QJ Nucl Med Mol Imaging 2008;52:351-368.
89. Bombardieri E, Giammarile F, Aktolun C et al. 131I/123I-metaiodobenzylguanidine (mIBG) scin- tigraphy:Procedureguidelinesfortumourimaging. Eur J Nucl Med Mol Imaging 2010;37:2436-2446.
90. Jacobson AF, Deng H, Lombard J et al. 123I- meta-iodobenzylguanidine scintigraphy for the de- tectionofneuroblastomaandpheochromocytoma: Results of a meta-analysis. J Clin Endocrinol Metab 2010;95:2596-2606.
91. Van Der Horst-Schrivers AN, Jager PL, Boezen HM et al. Iodine-123 metaiodobenzylguanidine scintigraphy in localising phaeochromocytomas: Experience and meta-analysis. Anticancer Res 2006;26:1599-1604.
92. Kaji P, Carrasquillo JA, Linehan WM et al. The role of 6-[18F]fluorodopamine positron emission tomography in the localization of adrenal pheo- chromocytoma associated with von Hippel-Lindau syndrome. Eur J Endocrinol 2007;156:483-487.
93. Fonte JS, Robles JF, Chen CC et al. False-nega- tive(1)(2)(3)I-MIBGSPECTismostcommonlyfound inSDHB-related pheochromocytoma or paraganglioma with high frequency to develop metastatic disease. EndocrRelat Cancer 2012;19:83-93.
94. Fottner C, Helisch A, Anlauf M et al. 6-18F- fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to 123I-metai- odobenzyl-guanidine scintigraphy in the detection of extraadrenal and hereditary pheochromocyto- mas and paragangliomas: Correlation with vesicular monoamine transporter expression. J Clin Endocrinol Metab 2010;95:2800-2810.
95. Shulkin BL, Koeppe RA, Francis IR et al. Pheo- chromocytomas that do not accumulate metaiodo- benzylguanidine: Localization with PET and administration of FDG. Radiology 1993;186:711-715.
96. Timmers HJ, Kozupa A, Chen CC et al. Superior- ityoffluorodeoxyglucosepositron emission tomog- raphytootherfunctionalimagingtechniquesinthe evaluation of metastatic SDHB-associated pheo- chromocytoma and paraganglioma. J Clin Oncol 2007;25:2262-2269.
97. Blanchet EM, Martucci V, Pacak K. Pheochromocytoma and paraganglioma: Current functional and future molecular imaging. Front Oncol 2011; 1:58.
98. Ilias I, Yu J, Carrasquillo JA et al. Superiority of 6-[18F]-fluorodopamine positron emission tomography versus [131I]-metaiodobenzylguani- dine scintigraphy in the localization of metastatic pheochromocytoma. J Clin Endocrinol Metab 2003; 88:4083-4087.
99. Timmers HJ, Eisenhofer G, Carrasquillo JA et al. Use of 6-[18F]-fluorodopamine positron emission tomography (PET) as first-line investigation for the diagnosis and localization of non-metastatic and metastatic phaeochromocytoma (PHEO). Clin Endocrinol (Oxf) 2009;71:11-17
100. Zelinka T, Timmers HJ, Kozupa A et al. Role of positron emission tomographyand bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations. Endocr Relat Cancer 2008;15:311-323.
101. Timmers HJ, Hadi M, Carrasquillo JA et al. The effects of carbidopa on uptake of 6-18F-Fluoro-L- DOPA in PET ofpheochromocytoma and extraadrenal abdominal paraganglioma. J Nucl Med 2007;48: 1599-1606.
102. Krenning EP, Bakker WH, Breeman WA et al. Localisation of endocrine-related tumours with ra- dioiodinated analogue of somatostatin. Lancet 1989;1:242-244.
103. Limouris GS, Giannakopoulos V, Stavraka A et al. Comparison of In-111 pentetreotide, Tc-99m (V)DMSA and I-123 mlBG scintimaging in neural cresttumors. Anticancer Res 1997;17:1589-1592.
104. Duet M, Sauvaget E, Petelle B et al. Clinical impactofsomatostatin receptorscintigraphyin the management of paragangliomas of the head and neck. J Nucl Med 2003;44:1767-1774.
105. Khan MU, Khan S, El-Refaie S et al. Clinical indications for Gallium-68 positron emission tomography imaging. EurJSurgOncol 2009;35:561-567.
106. Krausz Y, Freedman N, Rubinstein R et al. 68Ga-DOTA-NOC PET/CT imaging of neuroendocrine tumors: Comparison with (1)(1)(1)In-DTPA- octreotide (OctreoScan(R)). Mol Imaging Biol 2011; 13:583-593.
107. Kroiss A, Putzer D, Uprimny C et al. Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzyl- guanidine. Eur J Nucl Med Mol Imaging 2011;38: 865-873.
108. 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.
109. Kimura N, Nakazato Y, Nagura H etal. Expression of intermediate filaments in neuroendocrine tumors. Arch Pathol Lab Med 1990;114:506-510.
110. Kimura N, Miura Y, Nagatsu I et al. Catechol- aminesynthesizingenzymesin70casesoffunction- ing and non-functioning phaeochromocytoma and extra-adrenal paraganglioma. Virchows Arch A Pathol Anat Histopathol 1992;421:25-32.
111. Meijer WG, Copray SC, Hollema H et al. Catecholamine-synthesizing enzymes in carcinoid tumors and pheochromocytomas. Clin Chem 2003; 49:586-593.
112. Wu D, Tischler AS, Lloyd RV et al. Observer variation in the application of the Pheochromocy- toma of the Adrenal Gland Scaled Score. Am J Surg Pathol 2009;33:599-608.
113. Kimura N, Watanabe T, Noshiro T et al. Histological grading of adrenal and extra-adrenal pheo- chromocytomas and relationship to prognosis: A clinicopathological analysis of 116 adrenal pheo- chromocytomas and 30 extra-adrenal sympathetic paragangliomas including 38 malignanttumors. En- docrPathol 2005;16:23-32.
114. Helman LJ, Cohen PS, Averbuch SD et al. Neuropeptide Y expression distinguishes malignant from benign pheochromocytoma. J Clin Oncol 1989;7:1720-1725.
115. Portela-Gomes GM, Stridsberg M, Grimelius L et al. Expression ofchromograninsA, B, and C (se- cretogranin II) in human adrenal medulla and in benign and malignant pheochromocytomas: An immunohistochemical study with region-specific antibodies. APMIS 2004;112:663-673.
116. August C, August K, Schroeder S et al. CGH and CD 44/MIB-1 immunohistochemistry are helpful to distinguish metastasized from nonmetastasized sporadic pheochromocytomas. Mod Pathol 2004;17:1119-1128.
117. Favier J, Plouin PF, Corvol P et al. Angiogene- sis and vascular architecture in pheochromocyto- mas: Distinctive traits in malignant tumors. Am J Pathol 2002;161:1235-1246.
118. Scholz T, Schulz C, Klose S et al. Diagnostic management of benign and malignant pheochro- mocytoma. Exp Clin Endocrinol Diabetes 2007;115: 155-159.
119. Boltze C, Mundschenk J, Unger N et al. Expression profile of the telomeric complex discriminates between benign and malignant pheochromocytoma. J Clin Endocrinol Metab 2003;88:4280-4286.
120. de Wailly P, Oragano L, Rade F et al. Malignant pheochromocytoma: New malignancy criteria. Langenbecks Arch Surg 2012;397:239-246.
121. Tavangar SM, Shojaee A, Moradi Tabriz H et al. Immunohistochemical expression of Ki67, c-erbB-2, and c-kitantigensin benign and malignant pheochromocytoma. Pathol Res Pract 2010;206: 305-309.
122. Feng C, Li HZ, Yan WG et al. Thesignificanceof Ki-67 antigen expression in thedistinction between benign and malignant pheochromocytomas. Zhon- ghua Wai Ke Za Zhi 2007;45:1697-1700.
123. van der Harst E, Bruining HA, Jaap Bonjer H et al. Proliferative index in phaeochromocytomas: Does it predict the occurrence of metastases? J Pathol 2000;191:175-180.
124. Brown HM, Komorowski RA, Wilson SD et al. Predicting metastasis of pheochromocytomas using DNAflowcytometryand immunohistochemical markers of cell proliferation: A positive correlation between MIB-1 staining and malignant tumor behavior. Cancer 1999;86:1583-1589.
125. Blank A, Schmitt AM, Korpershoek E et al. SDHB loss predicts malignancy in pheochromocy- tomas/sympathethic paragangliomas, but not through hypoxia signalling. Endocr Relat Cancer 2010;17:919-928.
126. Gill AJ, Benn DE, Chou A et al. Immunohisto- chemistry forSDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocy- toma syndromes. Hum Pathol 2010;41:805-814.
127. Ayala-Ramirez M, Feng L, Johnson MM et al. Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: Primarytumor size and primary tumor location as prognostic indicators. J Clin Endocrinol Metab 2011;96:717-725.
128. Feng F, Zhu Y, Wang X et al. Predictive factors for malignant pheochromocytoma: Analysis of 136 patients. J Urol 2011;185:1583-1590.
129. Agarwal A, Mehrotra PK, Jain M et al. Size of the tumor and pheochromocytoma of the adrenal gland scaled score (PASS): Can they predict malignancy? World J Surg 2010;34:3022-3028.
130. Amar L, Servais A, Gimenez-Roqueplo AP et al. Year of diagnosis, features at presentation, and risk of recurrence in patients with pheochromocy- toma or secreting paraganglioma. J Clin Endocrinol Metab 2005;90:2110-2116.
131. Park J, Song C, Park M et al. Predictivecharac- teristics of malignant pheochromocytoma. Korean J Urol 2011;52:241-246.
132. Amar L, Bertherat J, Baudin E et al. Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol 2005;23:8812-8818.
133. Paik S, Shak S, Tang G et al. A multigene assay to predict recurrence of tamoxifen-treated, nodenegative breast cancer. N Engl J Med 2004;351: 2817-2826.
134. Edstrom E, Mahlamaki E, Nord B et al. Comparative genomic hybridization reveals frequent losses of chromosomes 1p and 3q in pheochromo- cytomas and abdominal paragangliomas, suggesting a common genetic etiology. Am J Pathol 2000; 156:651-659.
135. Dannenberg H, Speel EJ, Zhao J et al. Losses of chromosomes 1p and 3q areearlygeneticevents in thedevelopmentofsporadicpheochromocytomas. Am J Pathol 2000;157:353-359.
136. Liu TH, Chen YJ, Wu SF et al. Distinction between benign and malignantpheochromocytomas. Zhonghua Bing Li Xue Za Zhi 2004;33:198-202.
137. Dannenberg H, de Krijger RR, Zhao J et al. Differential loss of chromosome 11q in familial and sporadic parasympathetic paragangliomas detected bycomparativegenomichybridization. Am J Pathol 2001;158:1937-1942.
138. Sandgren J, Diazde Stahl T, Andersson R et al. Recurrentgenomicalterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis. Endocr Relat Cancer 2010;17:561-579.
139. Eisenhofer G, Huynh TT, Pacak K et al. Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: Activation of hypoxia-driven angiogenic pathways in von Hippel- Lindau syndrome. Endocr Relat Cancer 2004;11: 897-911.
140. Dahia PL, Hao K, Rogus J et al. Novel pheo- chromocytoma susceptibility loci identified byin- tegrative genomics. Cancer Res 2005;65:9651-9658.
141. Dahia PL, Ross KN, Wright ME et al. A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet 2005;1:72-80.
142. Huynh TT, Pacak K, Wong DL et al. Transcrip- tional regulation ofphenylethanolamine N-methyl- transferase in pheochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2. Ann N Y Acad Sci 2006; 1073:241-252.
143. Brouwers FM, Elkahloun AG, Munson PJ et al. Gene expression profiling of benign and malignant pheochromocytoma. Ann NY Acad Sci 2006;1073: 541-556.
144. Waldmann J, Fendrich V, Holler J et al. Microarray analysis reveals differential expression of benign and malignant pheochromocytoma. Endocr RelatCancer2010;17:743-756.
145. Thouennon E, Elkahloun AG, Guillemot J et al. Identification of potential gene markers and insights into the pathophysiology of pheochromocy- toma malignancy. J Clin Endocrinol Metab 2007;92: 4865-4872.
146. Suh I, Shibru D, Eisenhofer G et al. Candidate genes associated with malignant pheochromocytomas by genome-wide expression profiling. Ann Surg 2009;250:983-990.
147. Meyer-Rochow GY, Jackson NE, Conaglen JV et al. MicroRNA profiling of benign and malignant pheochromocytomas identifies novel diagnostic and therapeutic targets. Endocr Relat Cancer 2010; 17:835-846.
148. Calin GA, Dumitru CD, Shimizu M et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad SciUSA 2002;99: 15524-15529.
149. Patterson EE, Holloway AK, Weng J et al. Mi-croRNA profiling of adrenocortical tumors reveals miR-483 as a marker of malignancy. Cancer 2011; 117:1630-1639.
150. Tombol Z, Eder K, Kovacs A et al. MicroRNA expression profiling in benign (sporadic and hereditary) and recurring adrenal pheochromocytomas. Mod Pathol 2010;23:1583-1595.
151. Patterson E, Webb R, Weisbrod A et al. The microRNA expression changes associated with malignancy and SDHB mutation in pheochromocy- toma. Endocr Relat Cancer 2012;19:157-166.
152. Benhammou JN, Boris RS, Pacak K et al. Functional and oncologic outcomes of partial adrenalectomy for pheochromocytoma in patients with von Hippel-Lindausyndromeafteratleast5yearsoffol- lowup. J Urol 2010;184:1855-1859.
153. Adler JT, Meyer-Rochow GY, Chen H et al. Pheochromocytoma: Current approaches and future directions. The Oncologist 2008;13:779-793.
154. Gagner M, Lacroix A, Bolte E. Laparoscopic adrenalectomy in Cushing's syndrome and pheochromocytoma. N Engl J Med 1992;327:1033.
155. Gumbs AA, Gagner M. Laparoscopic adrenalectomy. Best Pract Res Clin Endocrinol Metab 2006; 20:483-499.
156. Germain A, Klein M, Brunaud L. Surgicalman-agement of adrenal tumors. J Visc Surg 2011;148: e250-e261.
157. Ippolito G, Palazzo FF, Sebag F et al. Safety of laparoscopic adrenalectomy in patients with large pheochromocytomas: A single institution review. World J Surg 2008;32:840-844.
158. Li ML, Fitzgerald PA, Price DC et al. Iatrogenic pheochromocytomatosis: A previously unreported result of laparoscopic adrenalectomy. Surgery 2001;130:1072-1077.
159. Brunt LM, Molmenti EP, Kerbl K et al. Retroperitoneal endoscopic adrenalectomy: An experimental study. Surg Laparosc Endosc 1993;3:300-306.
160. Walz MK, Peitgen K, Hoermann R et al. Posterior retroperitoneoscopy as a new minimally invasive approach for adrenalectomy: Results of 30 adrenalectomies in 27 patients. World J Surg 1996; 20:769-774.
161. Rubinstein M, Gill IS, Aron M et al. Prospective, randomized comparison of transperitoneal versus retroperitoneal laparoscopic adrenalectomy. J Urol 2005;174:442-445.
162. Suzuki K, Kageyama S, Hirano Y et al. Comparison of3 surgicalapproaches to laparoscopic adrenalectomy: A nonrandomized, background matched analysis. J Urol 2001;166:437-443.
163. Li QY, Li F. Laparoscopic adrenalectomy in pheochromocytoma: Retroperitoneal approach versus transperitoneal approach. J Endourol 2010; 24:1441-1445.
164. Fernandez-Cruz L, Saenz A, Taura Petal. Retroperitoneal approach in laparoscopic adrenalectomy: Is itadvantageous? Surg Endosc 1999;13:86-90.
165. Alesina PF, Hinrichs J, Meier B et al. Minimally invasive cortical-sparing surgery for bilateral pheochromocytomas. Langenbecks Arch Surg 2012;397: 233-238.
166. Brauckhoff M, Thanh PN, Gimm O et al. Functional results after endoscopic subtotal cortical- sparing adrenalectomy. Surg Today 2003;33:342-348.
167. Parnaby CN, Galbraith N, O'Dwyer PJ. Impor- tanceoftheadrenalglandbloodsupplyduringlapa- roscopic subtotal adrenalectomy. J Laparoendosc AdvSurgTechA 2010;20:311-315.
168. Walz MK, Peitgen K, SallerBetal. Subtotal adrenalectomy by the posterior retroperitoneoscopic approach. World J Surg 1998;22:621-626.
169. Lee JE, Curley SA, Gagel RF et al. Cortical-spar- ing adrenalectomy for patients with bilateral pheo- chromocytoma. Surgery 1996;120:1064-1070.
170. Inabnet WB, Caragliano P, Pertsemlidis D. Pheochromocytoma: Inherited associations, bilaterality, and cortex preservation. Surgery 2000;128: 1007-1011.
171. Yip L, Lee JE, Shapiro SE et al. Surgical management of hereditary pheochromocytoma. J Am Coll Surg 2004;198:525-534.
172. Brauckhoff M, Dralle H. Function-preserving adrenalectomy for adrenal tumors. Chirurg 2012; 83:519-527.
173. Miyajima A, Hattori S, Maeda T et al. Tran- sumbilical approach for laparo-endoscopic singlesite adrenalectomy: Initial experience and shortterm outcome. Int J Urol 2012;19:331-335.
174. Walz MK, Groeben H, Alesina PF. Single-access retroperitoneoscopic adrenalectomy (SARA) versus conventional retroperitoneoscopic adrenalectomy (CORA): Acase-control study. World J Surg 2010;34:1386-1390.
175. Zou X, Zhang G, Xiao R et al. Transvaginal natural orifice transluminal endoscopic surgery (NOTES)-assisted laparoscopic adrenalectomy: first clinical experience. Surg Endosc 2011;25:3767-3772.
176. Morris LF, Perrier ND. Advances in robotic adrenalectomy. CurrOpin Oncol 2012;24:1-6.
177. Henry JF, Sebag F, Iacobone M et al. Resultsof laparoscopic adrenalectomy for large and potentially malignant tumors. World J Surg 2002;26: 1043-1047.
178. Sarmiento JM, Heywood G, Rubin J et al. Surgical treatment of neuroendocrine metastases to the liver: A plea for resection to increase survival. J Am Coll Surg 2003;197:29-37.
179. Basuroy R, Srirajaskanthan R, Ramage JK. A multimodal approach to the management of neuroendocrine tumour liver metastases. Int J Hepatol 2012;2012:819193.
180. Steinmuller T, Kianmanesh R, Falconi M et al. Consensus guidelines for the management of patients with liver metastases from digestive (neu- ro)endocrine tumors: Foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 2008; 87:47-62.
181. Touzios JG, Kiely JM, Pitt SC et al. Neuroendo- crine hepatic metastases: Does aggressive management improve survival? Ann Surg 2005;241:776-783.
182. Osborne DA, Zervos EE, Strosberg J et al. Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid and neuroendocrine tumors. Ann Surg Oncol 2006;13:572-581.
183. Saxena A, Chua TC, Perera M et al. Surgical resection of hepatic metastases from neuroendocrine neoplasms: A systematic review. Surg Oncol 2012;21:e131-e141.
184. Simmonds PC, Primrose JN, Colquitt JL et al. Surgical resection of hepatic metastases from colorectal cancer: A systematic review of published studies. BrJ Cancer 2006;94:982-999.
185. Nazario J, Gupta S. Transarterial liver-directed therapies of neuroendocrine hepatic metas- tases. Semin Oncol 2010;37:118-126.
186. Vogl TJ, Naguib NN, Zangos S et al. Liver metastases of neuroendocrine carcinomas: Interventional treatment via transarterial embolization, chemoembolization and thermal ablation. Eur J Ra- diol 2009;72:517-528.
187. Cao CQ, Yan TD, Bester L et al. Radioembolization with yttrium microspheres for neuroendocrine tumour liver metastases. Br J Surg 2010;97: 537-543.
188. Gamblin TC, Christians K, Pappas SG. Radiofrequency ablation of neuroendocrine hepatic metastasis. Surg Oncol Clin N Am 2011;20:273-279.
189. Shapiro B, Gross MD, Shulkin B. Radioisotope diagnosisandtherapyofmalignantpheochromocy- toma. Trends Endocrinol Metab 2001;12:469-475.
190. Sisson JC, Shapiro B, Beierwaltes WH et al. Radiopharmaceutical treatment of malignant pheo- chromocytoma. J NuclMed 1984;25:197-206.
191. Vetter H, Fischer M, Muller-Rensing R et al. 131-I-meta-iodobenzylguanidine in treatment of malignant phaeochromocytomas. Lancet 1983;2:107.
192. Fitzgerald PA, Goldsby RE, Huberty JP et al. Malignant pheochromocytomas and paragangliomas: A phase II study of therapy with high-dose 131I-metaiodobenzylguanidine (131I-MIBG). Ann N Y Acad Sci 2006;1073:465-490.
193. Gonias S, Goldsby R, Matthay KK et al. Phase II studyofhigh-dose[131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromo- cytoma and paraganglioma. J Clin Oncol 2009;27: 4162-4168.
194. Safford SD, Coleman RE, Gockerman JP et al. Iodine -131 metaiodobenzylguanidine is an effective treatment for malignant pheochromocy- toma and paraganglioma. Surgery 2003;134: 956-962.
195. Kaltsas GA, Papadogias D, Makras P et al. Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues. Endocr RelatCancer 2005;12:683-699.
196. Kwekkeboom DJ, de Herder WW, Kam BL et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26:2124-2130.
197. Kam BL, Teunissen JJ, Krenning EP et al. Lute- tium-labelled peptides for therapy of neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2012; 39:S103-S112.
198. Fishbein L, Bonner L, Torigian DA et al. External beam radiation therapy (EBRT) for patients with malignant pheochromocytoma and non-head and -neck paraganglioma: Combination with 131I- MIBG. Horm Metab Res 2012;44:405-410.
199. Kasliwal MK, Sharma MS, Vaishya S et al. Metachronous pheochromocytoma metastasis to the upper dorsal spine-6-year survival. Spine J 2008; 8:845-848.
200. Richter A, Halm HF, Lerner T et al. Long-term follow-up after en bloc resection and reconstruction of a solitary paraganglioma metastasis in the first lumbar vertebral body: A case report. J Med Case Rep 2011;5:45.
201. Lazaro B, Klemz M, Flores MS et al. Malignant paraganglioma with vertebral metastasis: Case report. Arq Neuropsiquiatr 2003;61(2B):463-467.
202. Yoshida S, Hatori M, Noshiro T et al. Twentysix- years' survival with multiple bone metastasis of malignant pheochromocytoma. Arch Orthop Trauma Surg 2001;121:598-600.
203. Huang H, Abraham J, Hung E et al. Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: Recommendationfroma 22-year follow-up of 18 patients. Cancer 2008;113:2020-2028.
204. Averbuch SD, Steakley CS, Young RC et al. Malignant pheochromocytoma: Effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. Ann Intern Med 1988;109: 267-273.
205. Keiser HR, Goldstein DS, Wade JL et al. Treatment of malignant pheochromocytoma with combination chemotherapy. Hypertension 1985;7:I18-I24.
206. Banerji U. Heat shock protein90as a drug target: Some like it hot. Clin Cancer Res 2009;15:9-14.
207. Maloney A, Workman P. HSP90asanewtherapeutic target for cancer therapy: The story unfolds. Expert Opin Biol Ther 2002;2:3-24.
208. Powers MV, Workman P. Targeting of multiple signalling pathways by heat shock protein 90 molecular chaperone inhibitors. Endocr Relat Cancer 2006;13:S125-S135.
209. Modi S, Stopeck AT, Gordon MS et al. Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study J Clin Oncol 2007;25:5410-5417.
210. Modi S, Stopeck A, Linden H et al. HSP90 inhibition is effective in breast cancer: A phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin Cancer Res 2011; 17:5132-5139.
211. Sausville EA, Tomaszewski JE, Ivy P. Clinical development of 17-allylamino, 17-demethoxygeldanamycin. Curr Cancer Drug Targets 2003;3:377-383.
212. Druce MR, Kaltsas GA, Fraenkel M et al. Novel and evolving therapies in the treatment of malignant phaeochromocytoma: Experience with the mTOR inhibitor everolimus (RAD001). Horm Metab Res 2009;41:697-702.
213. Yuan R, Kay A, Berg WJ et al. Targeting tumorigenesis: Development and use of mTOR inhibitors in cancer therapy. J Hematol Oncol 2009; 2:45.
214. Zitzmann K, Ruden J, Brand S et al. Compensatory activation of Akt in response to mTOR and Raf inhibitors: Arationale for dual-targeted therapy approaches in neuroendocrine tumor disease. Cancer Lett 2010;295:100-109.
215. Joshua AM, Ezzat S, Asa SL et al. Rationale and evidence for sunitinib in the treatment of malignant paraganglioma/pheochromocytoma. J Clin Endocrinol Metab 2009;94:5-9.
216. Park KS, Lee JL, Ahn H et al. Sunitinib, a novel therapy for anthracycline- and cisplatin-refractory malignant pheochromocytoma. Jpn J Clin Oncol 2009;39:327-331.
217. Jimenez C, Cabanillas ME, Santarpia L et al. Use of the tyrosine kinase inhibitor sunitinib in a patient with von Hippel-Lindau disease: Targeting angiogenic factors in pheochromocytoma and other vonHippel-Lindau disease-related tumors. J Clin Endocrinol Metab 2009;94:386-391.
218. Gross DJ, Munter G, Bitan M et al. The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R. Endocr Relat Cancer 2006;13: 535-540.
219. Nolting S, Grossman AB. Signaling pathways in pheochromocytomas and paragangliomas: Prospects for future therapies. Endocr Pathol 2012;23: 21-33.
220. Rooijens PP, de Krijger RR, Bonjer HJ et al. The significance of angiogenesis in malignant pheochromocytomas. Endocr Pathol 2004;15:39-45.
221. Favier J, Igaz P, Burnichon N et al. Rationale for anti-angiogenic therapy in pheochromocytoma and paraganglioma. Endocr Pathol 2012;23: 34-42.
222. Zhang C, Tan C, Ding H et al. Selective VEGFR inhibitors for anticancer therapeutics in clinical use and clinical trials. Curr Pharm Des 2012;18:2921-2935.
223. Kulke MH, Stuart K, Enzinger PC et al. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol 2006;24:401-406.
224. Korpershoek E, Pacak K, Martiniova L. Murine models and cell lines for the investigation of pheochromocytoma: Applications for future therapies? Endocr Pathol 2012;23:43-54.
225. Andersen KF, Altaf R, Krarup-Hansen A et al. Malignant pheochromocytomas and paragangliomas: The importance of a multidisciplinary approach. Cancer Treat Rev 2011;37:111-119.