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Adrenal Medulla and Paraganglia

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Endocrine Pathology:

Abstract

Paraganglia are of two types, associated with either the sympathetic or parasympathetic nervous systems. Tumors arising from these are paragangliomas. The term “pheochromocytoma” is reserved for intra-adrenal tumors and the others should be defined with respect to type and site. These are rare tumors, but it is now realized that more than 30% arise in the context of familial disease. In addition to the well-recognized associations with multiple endocrine neoplasia types 2A and 2B, von Hippel–Lindau syndrome, and neurofibromatosis type 1, the familial paraganglioma syndromes related to mutations in the genes encoding the B, C, and D subunits of succinate dehydrogenase have now been defined.

The diagnosis of malignancy is reserved for the presence of metastases in sites where paraganglial tissue would not be found. Local invasive growth may be lethal, but does not correlate with metastatic behavior. The identification of malignant potential in primary tumors can be difficult. Two recent multifactorial approaches show some promise in identifying tumors with a higher risk of metastasis, but benign behavior cannot be predicted with certainty. Emerging data from molecular genetic studies may be of help in future.

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References

  1. DeLellis RA, Lloyd RV, Heitz PU, Eng C (2004) Tumours of Endocrine Organs. In: Kleihues P, Sobin LH (eds) World Health Organization classification of tumours. IARC Press, Lyon

    Google Scholar 

  2. Kohn A (1903) Die Paraganglien. Arch Mikr Anat 52:262–365

    Google Scholar 

  3. Stilling H (1898) Die chromophilen Zellen und Korperchen des Sympathicus. Eine Berichtigung. Anat Anz 15:229–233

    Google Scholar 

  4. Watzka M (1934) Vom paraganglion caroticum. Anat Anz 78:108–120

    Google Scholar 

  5. Addison T (1937) On the constitutional and local effects of disease of the suprarenal capsules. 1855. In a collection of the published writings of the late Thomas Addison MD, physician to Guy's Hospital, London. New Sydenham Society, London, 1868. Med Classics 2:244–293

    Google Scholar 

  6. Oliver G, Schafer EA (1894) On the physiological action of extract of the suprarenal capsules. J Physiol 16:i–iv

    Google Scholar 

  7. Abel JJ, Crawford AC (1897) On the blood-pressure-raising constituent of the suprarenal capsule. Johns Hopkins Hosp Bull 8:151–157

    Google Scholar 

  8. Takamine J (1901/1902) The isolation of the active principle of the suprarenal gland. J Physiol London 27:xxix–xxx

    Google Scholar 

  9. von Euler US, Hamberg U (1949) 1-Noradrenaline in the suprarenal medulla. Nature 163:642–643

    Google Scholar 

  10. Hillarp NA, Lagerstedt S, Nilson B (1953) The isolation of granular fraction from the supra renal medulla containing the sympathomimetic amines. Acta Physiol Scand 29:251–263

    CAS  PubMed  Google Scholar 

  11. Blaschko H, Welch AD (1953) Localization of adrenaline in cytoplasmic particles of the bovine adrenal medulla. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol 219:17–22

    CAS  PubMed  Google Scholar 

  12. Lack E (1994) Major problems in pathology. In: LiVolsi VA (ed) Pathology of adrenal and extra-adrenal paraganglia. W.B. Saunders, Philadelphia, PA

    Google Scholar 

  13. Coupland RE (1954) Postnatal fate of the abdominal paraaortic bodies in man. J Anat 88:464

    Google Scholar 

  14. Hervonen A, Vaalasti A, Partanen M, Kanerva L, Vaalasti T (1976) The paraganglia, a persisting endocrine system in man. Am J Anat 146:207–210

    CAS  PubMed  Google Scholar 

  15. Jacobowitz D (1967) Histochemical studies of the relationship of chromaffin cells and adrenergic nerve fibers to the cardiac ganglia of several species. J Pharmacol Exp Ther 158:227–240

    CAS  PubMed  Google Scholar 

  16. Grillo MA, Jacobs L, Comroe JH (1974) A combined fluorescence histochemical and electron microscopic method for studying special monoamine containing cells (SIF cells). J Comp Neurol 153:1–14

    CAS  PubMed  Google Scholar 

  17. Kuo T, Anderson CB, Rosai J (1974) Normal paraganglia in the human gallbladder. Arch Pathol 97:46–47

    CAS  PubMed  Google Scholar 

  18. Kawabata K (1999) Paraganglia of the gallbladder: a report of two cases with an immunohistochemical study. Pathol Res Pract 195:781–786

    CAS  PubMed  Google Scholar 

  19. Wong DL (2006) Epinephrine biosynthesis: hormonal and neural control during stress. Cell Mol Neurobiol 26:891–900

    CAS  PubMed  Google Scholar 

  20. Park JJ, Koshimizu H, Loh YP (2008) Biogenesis and transport of secretory granules to release site in neuroendocrine cells. J Mol Neurosci 37(2):151–159

    PubMed  Google Scholar 

  21. Montero-Hadjadje M, Vaingankar S, Elias S et al (2008) Chromogranins A and B and secretogranin II: evolutionary and functional aspects. Acta Physiol (Oxf) 192:309–324

    CAS  Google Scholar 

  22. Feldman SA, Eiden LE (2003) The chromogranins: their roles in secretion from neuroendocrine cells and as markers for neuroendocrine neoplasia. Endocr Pathol 14:3–23

    CAS  PubMed  Google Scholar 

  23. Spinazzi R, Andreis PG, Nussdorfer GG (2005) Neuropeptide-Y and Y-receptors in the autocrine-paracrine regulation of adrenal gland under physiological and pathophysiological conditions. Int J Mol Med 15:3–13

    CAS  PubMed  Google Scholar 

  24. Tortorella C, Neri G, Nussdorfer GG (2007) Galanin in the regulation of the hypothalamic-pituitary-adrenal axis (Review). Int J Mol Med 19:639–647

    CAS  PubMed  Google Scholar 

  25. Kapas S, Hinson JP (2002) Adrenomedullin in the adrenal. Microsc Res Tech 57:91–97

    CAS  PubMed  Google Scholar 

  26. Mazzocchi G, Malendowicz LK, Rebuffat P, Gottardo L, Nussdorfer GG (2002) Expression and function of vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, and their receptors in the human adrenal gland. J Clin Endocrinol Metab 87:2575–2580

    CAS  PubMed  Google Scholar 

  27. Kontogeorgos G, Scheithauer BW, Kovacs K, Horvath E, Melmed S (2002) Growth factors and cytokines in paragangliomas and pheochromocytomas, with special reference to sustentacular cells. Endocr Pathol 13:197–206

    CAS  PubMed  Google Scholar 

  28. Grothe C, Meisinger C (1997) The multifunctionality of FGF-2 in the adrenal medulla. Anat Embryol (Berl) 195:103–111

    CAS  Google Scholar 

  29. Paciga M, Nurse CA (2001) Basic FGF localization in rat carotid body: paracrine role in O2 -chemoreceptor survival. Neuroreport 12:3287–3291

    CAS  PubMed  Google Scholar 

  30. Verna A (1979) Ulstrastructure of the carotid body in the mammals. Int Rev Cytol 60:271–330

    CAS  PubMed  Google Scholar 

  31. Lloyd RV, Blaivas M, Wilson BS (1985) Distribution of chromogranin and S-100 protein in normal and abnormal adrenal medullary tissues. Arch Pathol Lab Med 109:633–635

    CAS  PubMed  Google Scholar 

  32. Achilles EA, Padberg GC, Holl K, Klöppel G, Schröder S (1991) Immunocytochemistry of paragangliomas – value of staining for S-100 protein and glial fibrillary acidic protein in diagnosis and prognosis. Histopathology 18:453–458

    CAS  PubMed  Google Scholar 

  33. Parker TL, Kesse WK, Mohamed AA, Afework M (1993) The innervation of the mammalian adrenal gland. J Anat 183:265–276

    PubMed  Google Scholar 

  34. Portela-Gomes GM, Stridsberg M, Grimelius L, Falkmer UG, Falkmer S (2004) Expression of chromogranins A, B, and C (secretogranin II) in human adrenal medulla and in benign and malignant pheochromocytomas An immunohistochemical study with region-specific antibodies. APMIS 112:663–673

    CAS  PubMed  Google Scholar 

  35. Lloyd RV, Sisson JC, Shapiro B, Verhofstad AAJ (1986) Immunohistochemical localization of epinephrine, norepinephrine, catecholamine-synthesizing enzymes and chromogranin in neuroendocrine cells and tumours. Am J Pathol 125:45–54

    CAS  PubMed  Google Scholar 

  36. Portela-Gomes GM, Lukinius A, Grimelius L (2000) Synaptic vesicle protein 2, A new neuroendocrine cell marker. Am J Pathol 157:1299–1309

    CAS  PubMed  Google Scholar 

  37. Roth D, Burgoyne RD (1994) SNAP-25 is present in a SNARE complex in adrenal chromaffin cells. FEBS Lett 351:207–210

    CAS  PubMed  Google Scholar 

  38. Scopsi L, Gullo M, Rilke F, Martin S, Steiner DF (1995) Proprotein convertases (PC1/PC3 and PC2) in normal and neoplastic human tissues: their use as markers of neuroendocrine differentiation. J Clin Endocrinol Metab 80:294–301

    CAS  PubMed  Google Scholar 

  39. Braas KM, Harakall SA, Ouafik L, Eipper BA, May V (1992) Expression of peptidylglycine alpha-amidating monooxygenase: an in situ hybridization and immunocytochemical study. Endocrinology 130:2778–2788

    CAS  PubMed  Google Scholar 

  40. Colombo-Benkmann M, Klimaschewski L, Heym C (1996) Immunohistochemical heterogeneity of nerve cells in the human adrenal gland with special reference to substance P. J Histochem Cytochem 44:369–375

    CAS  PubMed  Google Scholar 

  41. Holgert H, Holmberg K, Hannibal J et al (1996) PACAP in the adrenal gland – relationship with choline acetyltransferase, enkephalin and chromaffin cells and effects of immunological sympathectomy. Neuroreport 8:297–301

    CAS  PubMed  Google Scholar 

  42. Ichikawa H (2002) Innervation of the carotid body: immunohistochemical, denervation, and retrograde tracing studies. Microsc Res Tech 59:188–195

    CAS  PubMed  Google Scholar 

  43. Barnes RD, Ward LE, Frank KP et al (2001) Nitric oxide modulates evoked catecholamine release from canine adrenal medulla. Neuroscience 104:1165–1173

    CAS  PubMed  Google Scholar 

  44. Baysal BE (2002) Hereditary paraganglioma targets diverse paraganglia. J Med Genet 39:617–622

    CAS  PubMed  Google Scholar 

  45. De Graeff J, Horak BJV (1964) The incidence of pheochromocytoma in The Netherlands. Acta Med Scand 176:583–593

    Google Scholar 

  46. Beard CM, Sheps SG, Kurland LT, Carney JA, Lie JT (1983) Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc 58:802–804

    CAS  PubMed  Google Scholar 

  47. Oosterwijk JC, Jansen JC, van Schothorst EM et al (1996) First experiences with genetic counselling based on predictive DNA diagnosis in hereditary glomus tumours (paragangliomas). J Med Genet 33:379–383

    CAS  PubMed  Google Scholar 

  48. Erickson D, Kudva YC, Ebersold MJ et al (2001) Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients. J Clin Endocrinol Metab 86:5210–5216

    CAS  PubMed  Google Scholar 

  49. Young WF Jr (2006) Paragangliomas: clinical overview. Ann N Y Acad Sci 1073:21–29

    CAS  PubMed  Google Scholar 

  50. Tischler AS (2008) Pheochromocytoma and extra-adrenal paraganglioma: updates. Arch Pathol Lab Med 132:1272–1284

    PubMed  Google Scholar 

  51. Tischler AS (1998) The adrenal medulla and extra-adrenal paraganglia. In: Kovacs K, Asa SL (eds) Functional endocrine pathology. Blackwell, Malden

    Google Scholar 

  52. Walther MM, Herring J, Enquist E, Keiser HR, Linehan WM (1999) von Recklinghausen’s disease and pheochromocytomas. J Urol 162:1582–1586

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  54. Dahia PL, Hao K, Rogus J et al (2005) Novel pheochromocytoma susceptibility loci identified by integrative genomics. Cancer res 65:9651–9658

    CAS  PubMed  Google Scholar 

  55. Dahia PL, Ross KN, Wright ME et al (2005) A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet 1:72–80

    CAS  PubMed  Google Scholar 

  56. Tischler AS (2006) Molecular and cellular biology of pheochromocytomas and extra-adrenal paragangliomas. Endocr Pathol 17:321–328

    CAS  PubMed  Google Scholar 

  57. Dannenberg H, Komminoth P, Dinjens WN, Speel EJ, de Krijger RR (2003) Molecular genetic alterations in adrenal and extra-adrenal pheochromocytomas and paragangliomas. Endocr Pathol 14:329–350

    CAS  PubMed  Google Scholar 

  58. Petri BJ, Speel EJ, Korpershoek E et al (2008) Frequent loss of 17p, but no p53 mutations or protein overexpression in benign and malignant pheochromocytomas. Mod Pathol 21:407–413

    CAS  PubMed  Google Scholar 

  59. Bender BU, Gutsche M, Glasker S et al (2000) Differential genetic alterations in von Hippel-Lindau syndrome-associated and sporadic pheochromocytomas. J Clin Endocrinol Metab 85: 4568–4574

    CAS  PubMed  Google Scholar 

  60. Jarbo C, Buckley PG, Piotrowski A et al (2006) Detailed assessment of chromosome 22 aberrations in sporadic pheochromocytoma using array-CGH. Int J Cancer 118:1159–1164

    CAS  PubMed  Google Scholar 

  61. Edstrom E, Mahlamaki E, Nord B et al (2000) Comparative genomic hybridization reveals frequent losses of chromosomes 1p and 3q in pheochromocytomas and abdominal paragangliomas, suggesting a common genetic etiology. Am J Pathol 156:651–659

    CAS  PubMed  Google Scholar 

  62. Carney A (1983) The triad of gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma. Medicine 62:159–169

    CAS  PubMed  Google Scholar 

  63. Carney JA, Stratakis CA (2002) Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad. Am J Med Genet 108:132–139

    PubMed  Google Scholar 

  64. Kaufman BH, Telander RL, Van Heerden JA et al (1983) Pheochromocytoma in the pediatric age group. J Pediatr Surg 18:879–884

    CAS  PubMed  Google Scholar 

  65. Mehra S, Chung-Park M (2005) Gallbladder paraganglioma: a case report with review of the literature. Arch Pathol Lab Med 129:523–526

    PubMed  Google Scholar 

  66. Melicow MM (1977) One hundred cases of pheochromocytoma (107 tumors) at the Columbia-Presbyterian Medical Center, 1926–1976: a clinicopathological analysis. Cancer 40:1987–2004

    CAS  PubMed  Google Scholar 

  67. Gallivan MVE, Chun B, Rowden G, Lack EE (1980) Intrathoracic paravertebral malignant paraganglioma. Arch Pathol Lab Med 104:46–51

    CAS  PubMed  Google Scholar 

  68. Quinan C, Berger AA (1933) Observations on human adrenals with especial reference to the relative weight of the normal medulla. Ann Int Med 6:1180–1192

    Google Scholar 

  69. Studzinski GP, Hay DCF, Symington T (1963) Observations on the weight of the human adrenal gland and the effect of preparations of corticotropin of different purity on the weight and morphology of the human adrenal gland. J Clin Endocrinol Metab 23:248–254

    CAS  PubMed  Google Scholar 

  70. Kreiner E (1982) Weight and shape of the human adrenal medulla in various age groups. Virchows Arch A Pathol Anat Histol 397:7–15

    CAS  PubMed  Google Scholar 

  71. DeLellis RA, Wolfe HJ, Gagel RF et al (1976) Adrenal medullary hyperplasia. A morphometric analysis in patients with familial medullary thyroid carcinoma. Am J Pathol 83:177–196

    CAS  PubMed  Google Scholar 

  72. Bornstein SR, Gonzalez-Hernandez JA, Ehrhart-Bornstein M, Adler G, Scherbaum WA (1994) Intimate contact of chromaffin and cortical cells within the human adrenal gland forms the cellular basis for important intraadrenal interactions. J Clin Endocrinol Metab 78:225–232

    CAS  PubMed  Google Scholar 

  73. Schinner S, Bornstein SR (2005) Cortical-chromaffin cell interactions in the adrenal gland. Endocr Pathol 16:91–98

    CAS  PubMed  Google Scholar 

  74. Khafagi FA, Shapiro B, Fischer M et al (1991) Phaeochromocytoma and functioning paraganglioma in childhood and adolescence: role of iodine 131 metaiodobenzylguanidine. Eur J Nucl Med 18:191–198

    CAS  PubMed  Google Scholar 

  75. Stenstrom G, Svardsudd K (1986) Pheochromocytoma in Sweden 1958–1981. An analysis of the National Cancer Registry Data. Acta Med Scand 220:225–232

    CAS  PubMed  Google Scholar 

  76. Hartley L, Perry-Keene D (1985) Phaeochromocytoma in Queensland–1970–83. Aust N Z J Surg 55:471–475

    CAS  PubMed  Google Scholar 

  77. McNeil AR, Blok BH, Koelmeyer TD, Burke MP, Hilton JM (2000) Phaeochromocytomas discovered during coronial autopsies in Sydney, Melbourne and Auckland. Aust N Z J Med 30:648–652

    CAS  PubMed  Google Scholar 

  78. Karagiannis A, Mikhailidis DP, Athyros VG, Harsoulis F (2007) Pheochromocytoma: an update on genetics and management. Endocr Relat cancer 14:935–956

    CAS  PubMed  Google Scholar 

  79. Vilar L, Freitas Mda C, Canadas V et al (2008) Adrenal incidentalomas: diagnostic evaluation and long-term follow-up. Endocr Pract 14:269–278

    PubMed  Google Scholar 

  80. Young WF Jr (2007) Clinical practice. The incidentally discovered adrenal mass. N Engl J Med 356:601–610

    CAS  PubMed  Google Scholar 

  81. Kasperlik-Zaluska AA, Roslonowska E, Slowinska-Srzednicka J et al (2006) 1, 111 patients with adrenal incidentalomas observed at a single endocrinological center: incidence of chromaffin tumors. Ann N Y Acad Sci 1073:38–46

    CAS  PubMed  Google Scholar 

  82. Bulow B, Ahren B (2002) Adrenal incidentaloma – experience of a standardized diagnostic programme in the Swedish prospective study. J Intern Med 252:239–246

    CAS  PubMed  Google Scholar 

  83. Page DL, DeLellis RA, Hough AJ (1985) Tumors of the adrenal. Fascicle 23: atlas of tumor pathology. Armed Forces Institute of Pathology, Washington, DC

    Google Scholar 

  84. Remine WH, Chong GC, Van Heerden JA, Sheps SG, Harrison E (1974) Current management of pheochromocytoma. Ann Surg 179:740–748

    CAS  PubMed  Google Scholar 

  85. Kimura N, Watanabe T, Noshiro T, Shizawa S, Miura Y (2005) Histological grading of adrenal and extra-adrenal pheochromocytomas and relationship to prognosis: a clinicopathological analysis of 116 adrenal pheochromocytomas and 30 extra-adrenal sympathetic paragangliomas including 38 malignant tumors. Endocr Pathol 16:23–32

    PubMed  Google Scholar 

  86. Thompson LD (2002) Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am J Surg Pathol 26:551–566

    PubMed  Google Scholar 

  87. DeLellis RA, Suchow E, Wolfe HJ (1980) Ultrastructure of nuclear ‘inclusions’ in pheochromocytoma and paraganglioma. Hum Pathol 11:205–207

    CAS  PubMed  Google Scholar 

  88. Medeiros LJ, Wolf BC, Balogh K, Federman M (1985) Adrenal pheochromocytoma: a clinicopathologic review of 60 cases. Hum Pathol 16:580–589

    CAS  PubMed  Google Scholar 

  89. Landas SK, Leigh C, Bonsib SM, Layne K (1993) Occurrence of melanin in pheochromocytoma. Mod Pathol 6:175–178

    CAS  PubMed  Google Scholar 

  90. Chetty R, Clark SP, Taylor DA (1993) Pigmented pheochromocytomas of the adrenal medulla. Hum Pathol 24:420–423

    CAS  PubMed  Google Scholar 

  91. Linnoila RI, Keiser HR, Steinberg SM, Lack EE (1990) Histopathology of benign versus malignant sympathoadrenal paragangliomas : clinicopathologic study of 120 cases, including unusual histologic features. Hum Pathol 21:1168–1180

    CAS  PubMed  Google Scholar 

  92. Unger PD, Cohen JM, Thung SN et al (1990) Lipid degeneration in a pheochromocytoma histologically mimicking an adrenal cortical tumor. Arch Pathol Lab Med 114:892–894

    CAS  PubMed  Google Scholar 

  93. Ramsay JA, Asa SL, van Nostrand AW, Hassaram ST, de Harven EP (1987) Lipid degeneration in pheochromocytomas mimicking adrenal cortical tumors. Am J Surg Pathol 11:480–486

    CAS  PubMed  Google Scholar 

  94. Li M, Wenig BM (2000) Adrenal oncocytic pheochromocytoma. Am J Surg Pathol 24:1552–1557

    CAS  PubMed  Google Scholar 

  95. Miranda RN, Wu CD, Nayak RN, Kragel PJ, Medeiros LJ (1995) Amyloid in adrenal gland pheochromocytomas. Arch Pathol Lab Med 119:827–830

    CAS  PubMed  Google Scholar 

  96. Steinhoff MM, Wells SA Jr, DeSchryver-Kecskemeti K (1992) Stromal amyloid in pheochromocytomas. Hum Pathol 23:33–36

    CAS  PubMed  Google Scholar 

  97. Koch CA, Mauro D, Walther MM et al (2002) Pheochromocytoma in von hippel-lindau disease: distinct histopathologic phenotype compared to pheochromocytoma in multiple endocrine neoplasia type 2. Endocr Pathol 13:17–27

    CAS  PubMed  Google Scholar 

  98. Kimura N, Nakazato Y, Nagura H, Sasano N (1990) Expression of intermediate filaments in neuroendocrine tumors. Arch Pathol Lab Med 114:506–510

    CAS  PubMed  Google Scholar 

  99. Fraga M, Garcia-Caballero T, Antunez J et al (1993) A comparative immunohistochemical study of phaeochromocytomas and paragangliomas. Histol Histopathol 8:429–436

    CAS  PubMed  Google Scholar 

  100. Schroder HD, Johannsen L (1986) Demonstration of S-100 protein in sustentacular cells of phaeochromocytomas and paragangliomas. Histopathology 10:1023–1033

    CAS  PubMed  Google Scholar 

  101. Raghay K, Garcia-Caballero T, Bravo S et al (2008) Ghrelin localization in the medulla of rat and human adrenal gland and in pheochromocytomas. Histol Histopathol 23:57–65

    CAS  PubMed  Google Scholar 

  102. Morimoto R, Satoh F, Murakami O et al (2008) Immunolocalization of urotensin II and its receptor in human adrenal tumors and attached non-neoplastic adrenal tissues. Peptides 29:873–880

    CAS  PubMed  Google Scholar 

  103. Mazzocchi G, Malendowicz LK, Aragona F et al (2001) Human pheochromocytomas express orexin receptor type 2 gene and display an in vitro secretory response to orexins A and B. J Clin Endocrinol Metab 86:4818–4821

    CAS  PubMed  Google Scholar 

  104. Ilias I, Torpy DJ, Pacak K et al (2005) Cushing’s syndrome due to ectopic corticotropin secretion: twenty years’ experience at the National Institutes of Health. J Clin Endocrinol Metab 90:4955–4962

    CAS  PubMed  Google Scholar 

  105. Aniszewski JP, Young WF Jr, Thompson GB, Grant CS, van Heerden JA (2001) Cushing syndrome due to ectopic adrenocorticotropic hormone secretion. World J Surg 25:934–940

    CAS  PubMed  Google Scholar 

  106. Meijer WG, Copray SC, Hollema H et al (2003) Catecholamine-synthesizing enzymes in carcinoid tumors and pheochromocytomas. Clin Chem 49:586–593

    CAS  PubMed  Google Scholar 

  107. Kimura N, Miura Y, Nagatsu I, Nagura H (1992) Catecholamine synthesizing enzymes in 70 cases of functioning and non-functioning phaeochromocytoma and extra-adrenal paraganglioma. Virchows Arch A Pathol Anat Histopathol 421:25–32

    CAS  PubMed  Google Scholar 

  108. Hayes WS, Davidson AJ, Grimley PM, Hartman DS (1990) Extraadrenal retroperitoneal paraganglioma: clinical, pathologic, and CT findings. AJR Am J Roentgenol 155:1247–1250

    CAS  PubMed  Google Scholar 

  109. Sclafani LM, Woodruff JM, Brennan MF (1990) Extraadrenal retroperitoneal paragangliomas: natural history and response to treatment. Surgery 108:1124–1129 discussion 9-30

    CAS  PubMed  Google Scholar 

  110. Shono T, Sakai H, Minami Y et al (1999) Paraganglioma of the urinary bladder: a case report and review of the Japanese literature. Urol Int 62:102–105

    CAS  PubMed  Google Scholar 

  111. Hirose T, Sano T, Mori K et al (1988) Paraganglioma of the cauda equina: an ultrastructural and immunohistochemical study of two cases. Ultrastruct Pathol 12:235–243

    CAS  PubMed  Google Scholar 

  112. Chetty R (1999) Cytokeratin expression in cauda equina paragangliomas. Am J Surg Pathol 23:491

    CAS  PubMed  Google Scholar 

  113. Cheng L, Leibovich BC, Cheville JC et al (2000) Paraganglioma of the urinary bladder: can biologic potential be predicted? Cancer 88:844–852

    CAS  PubMed  Google Scholar 

  114. Orrell JM, Hales SA (1992) Paragangliomas of the cauda equina have a distinctive cytokeratin immunophenotype. Histopathology 21:479–481

    CAS  PubMed  Google Scholar 

  115. Johnson TL, Zarbo RJ, Lloyd RV, Crissman JD (1988) Paragangliomas of the head and neck: immunohistochemical neuroendocrine and intermediate filament typing. Mod Pathol 1:216–223

    CAS  PubMed  Google Scholar 

  116. Tatekawa Y, Muraji T, Nishijima E, Yoshida M, Tsugawa C (2006) Composite pheochromocytoma associated with adrenal neuroblastoma in an infant: a case report. J Pediatr Surg 41:443–445

    PubMed  Google Scholar 

  117. Lam KY, Lo CY (1999) Composite pheochromocytoma-ganglioneuroma of the adrenal gland: an uncommon entity with distinctive clinicopathologic features. Endocr Pathol 10:343–352

    PubMed  Google Scholar 

  118. Sakaguchi N, Sano K, Ito M et al (1996) A case of von Recklinghausen's disease with bilateral pheochromocytoma-malignant peripheral nerve sheath tumors of the adrenal and gastrointestinal autonomic nerve tumors. Am J Surg Pathol 20:889–897

    CAS  PubMed  Google Scholar 

  119. Min KW, Clemens A, Bell J, Dick H (1988) Malignant peripheral nerve sheath tumor and pheochromocytoma. A composite tumor of the adrenal. Arch Pathol Lab Med 112:266–270

    CAS  PubMed  Google Scholar 

  120. Miettinen M, Saari A (1988) Pheochromocytoma combined with malignant schwannoma: unusual neoplasm of the adrenal medulla. Ultrastruct Pathol 12:513–527

    CAS  PubMed  Google Scholar 

  121. Candanedo-Gonzalez FA, Alvarado-Cabrero I, Gamboa-Dominguez A et al (2001) Sporadic type composite pheochromocytoma with neuroblastoma: clinicomorphologic, DNA content and ret gene analysis. Endocr Pathol 12:343–350

    CAS  PubMed  Google Scholar 

  122. Lee JH, Barich F, Karnell LH et al (2002) National Cancer Data Base report on malignant paragangliomas of the head and neck. Cancer 94:730–737

    PubMed  Google Scholar 

  123. Zak FG, Lawson W (1983) The paraganglionic chemoreceptor system. Physiology, pathology and clinical medicine. Springer, New York

    Google Scholar 

  124. Parry DM, Li FP, Strong LC et al (1982) Carotid body tumors in humans: genetics and epidemiology. J Natl Cancer Inst 68:573–578

    CAS  PubMed  Google Scholar 

  125. Shamblin WR, ReMine WH, Sheps SG, Harrison EG Jr (1971) Carotid body tumor (chemodectoma). Clinicopathologic analysis of ninety cases. Am J Surg 122:732–739

    CAS  PubMed  Google Scholar 

  126. Rodriguez-Cuevas S, Lopez-Garza J, Labastida-Almendaro S (1998) Carotid body tumors in inhabitants of altitudes higher than 2000 meters above sea level. Head Neck 20:374–378

    CAS  PubMed  Google Scholar 

  127. Saldana MJ, Salem LE, Travezan R (1973) High altitude hypoxia and chemodectomas. Hum Pathol 4:251–263

    CAS  PubMed  Google Scholar 

  128. Arias-Stella J, Valcarcel J (1973) The human carotid body at high altitudes. Pathol Microbiol 39:292–297

    CAS  Google Scholar 

  129. Kay JM, Laidler P (1977) Hypoxia and the carotid body. J Clin Pathol Suppl 11:30–44

    CAS  Google Scholar 

  130. Lack EE (1978) Hyperplasia of vagal and carotid body paraganglia in patients with chronic hypoxemia. Am J Pathol 91:497–516

    CAS  PubMed  Google Scholar 

  131. Heath D (1991) The carotid bodies in chronic respiratory disease. Histopathology 18:281–283

    CAS  PubMed  Google Scholar 

  132. Heath D, Edwards C (1971) The carotid body in cardiopulmonary disease. Geriatrics 26:110–111 passim

    CAS  PubMed  Google Scholar 

  133. Lack EE, Perez-Atayde AR, Young JB (1985) Carotid body hyperplasia in cystic fibrosis and cyanotic heart disease. Am J Pathol 119:301–314

    CAS  PubMed  Google Scholar 

  134. Bee D, Pallot DJ (1995) Acute hypoxic ventilation, carotid body cell division, and dopamine content during early hypoxia in rats. J Appl Physiol 79:1504–1511

    CAS  PubMed  Google Scholar 

  135. Brown JS (1985) Glomus jugulare tumors revisited: a ten-year statistical follow-up of 231 cases. Laryngoscope 95:284–288

    CAS  PubMed  Google Scholar 

  136. Imren Y, Tasoglu I, Benson AA, Sinci V (2007) A rare intracardiac mass: cardiac paraganglioma. Heart Lung Circ 16:116–117

    PubMed  Google Scholar 

  137. Fitzgerald PJ, Ports TA, Cheitlin MD, Magilligan DJ, Tyrrell JB (1995) Intracardiac pheochromocytoma with dual coronary blood supply: case report and literature review. Cardiovasc Surg 3:557–561

    CAS  PubMed  Google Scholar 

  138. Dresler C, Cremer J, Logemann F, Haverich A (1998) Intrapericardial pheochromocytoma. Thorac Cardiovasc Surg 46:100–102

    CAS  PubMed  Google Scholar 

  139. Lack EE (1997) Tumors of the adrenal gland and extra-adrenal paraganglia. Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Washington DC

    Google Scholar 

  140. Leestma JE, Price EB (1971) Paraganglioma of the urinary bladder. Cancer 18:1063–1073

    Google Scholar 

  141. Davaris P, Petraki K, Arvanitis D et al (1986) Urinary bladder paraganglioma (U.B.P.). Pathol Res Pract 181:101–106

    CAS  PubMed  Google Scholar 

  142. Timmers HJ, Kozupa A, Eisenhofer G et al (2007) 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

    CAS  PubMed  Google Scholar 

  143. Bezuglova TV (2003) Criteria for predicting the outcome of pheochromocytoma by the immunohistochemical and electron microscopic findings. Bull Exp Biol Med 136:408–410

    CAS  PubMed  Google Scholar 

  144. Unger P, Hoffman K, Pertsemlidis D et al (1991) S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas. Arch Pathol Lab Med 115:484–487

    CAS  PubMed  Google Scholar 

  145. Strong VE, Kennedy T, Al-Ahmadie H et al (2008) Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis. Surgery 143:759–768

    PubMed  Google Scholar 

  146. van der Harst E, Bruining HA, Jaap Bonjer H et al (2000) Proliferative index in phaeochromocytomas: does it predict the occurrence of metastases? J Pathol 191:175–180

    PubMed  Google Scholar 

  147. Clarke MR, Weyant RJ, Watson CG, Carty SE (1998) Prognostic markers in pheochromocytoma. Hum Pathol 29:522–526

    CAS  PubMed  Google Scholar 

  148. Garcia-Escudero A, de Miguel-Rodriguez M, Moreno-Fernandez A et al (2001) Prognostic value of DNA flow cytometry in sympathoadrenal paragangliomas. Anal Quant Cytol Histol 23:238–244

    CAS  PubMed  Google Scholar 

  149. Zhang XH, Wei SL, Wang FR et al (1992) Studies on pathological morphology, clinical features and nuclear DNA contents by flow cytometry in adrenal neoplasms. Chin Med J (Engl) 105:139–143

    CAS  Google Scholar 

  150. August C, August K, Schroeder S et al (2004) CGH and CD 44/MIB-1 immunohistochemistry are helpful to distinguish metastasized from nonmetastasized sporadic pheochromocytomas. Mod Pathol 17:1119–1128

    CAS  PubMed  Google Scholar 

  151. Eisenhofer G, Bornstein SR, Brouwers FM et al (2004) Malignant pheochromocytoma: current status and initiatives for future progress. Endocr Relat Cancer 11:423–436

    CAS  PubMed  Google Scholar 

  152. Isobe K, Yashiro T, Omura S et al (2004) Expression of the human telomerase reverse transcriptase in pheochromocytoma and neuroblastoma tissues. Endocr J 51:47–52

    CAS  PubMed  Google Scholar 

  153. Elder EE, Xu D, Hoog A et al (2003) KI-67 AND hTERT expression can aid in the distinction between malignant and benign pheochromocytoma and paraganglioma. Mod Pathol 16:246–255

    PubMed  Google Scholar 

  154. Boltze C, Mundschenk J, Unger N et al (2003) Expression profile of the telomeric complex discriminates between benign and malignant pheochromocytoma. J Clin Endocrinol Metab 88:4280–4286

    CAS  PubMed  Google Scholar 

  155. Thouennon E, Elkahloun AG, Guillemot J et al (2007) Identification of potential gene markers and insights into the pathophysiology of pheochromocytoma malignancy. J Clin Endocrinol Metab 92:4865–4872

    CAS  PubMed  Google Scholar 

  156. Brouwers FM, Elkahloun AG, Munson PJ et al (2006) Gene expression profiling of benign and malignant pheochromocytoma. Ann N Y Acad Sci 1073:541–556

    CAS  PubMed  Google Scholar 

  157. Linnoila RI, Lack EE, Steinberg SM, Keiser HR (1988) Decreased expression of neuropeptides in malignant paragangliomas: an immunohistochemical study. Hum Pathol 19:41–50

    CAS  PubMed  Google Scholar 

  158. Chetty R, Pillay P, Jaichand V (1998) Cytokeratin expression in adrenal phaeochromocytomas and extra-adrenal paragangliomas. J Clin Pathol 51:477–478

    CAS  PubMed  Google Scholar 

  159. Beltrami CA, Barbatelli G, Criante P, Paliaga A, Amadi CE (1987) An immunohistochemical study in thyroid cancer. Appl Pathol 5:229–245

    CAS  PubMed  Google Scholar 

  160. Rosai J (2003) Immunohistochemical markers of thyroid tumors: significance and diagnostic applications. Tumori 89:517–519

    PubMed  Google Scholar 

  161. Batistatou A, Zolota V, Scopa CD (2002) S-100 protein+ dendritic cells and CD34+ dendritic interstitial cells in thyroid lesions. Endocr Pathol 13:111–115

    CAS  PubMed  Google Scholar 

  162. Collina G, Maiorana A, Fano RA, Cesinaro AM, Trentini GP (1994) Medullary carcinoma of the thyroid gland with sustentacular cell-like cells in a patient with multiple endocrine neoplasia, type IIA. Report of a case with ultrastructural and immunohistochemical studies. Arch Pathol Lab Med 118:1041–1044

    CAS  PubMed  Google Scholar 

  163. Hirokawa M, Carney JA, Ohtsuki Y (2000) Hyalinizing trabecular adenoma and papillary carcinoma of the thyroid gland express different cytokeratin patterns. Am J Surg Pathol 24:877–881

    CAS  PubMed  Google Scholar 

  164. Fornes P, Lesourd A, Dupuis G et al (1990) Hyalinizing trabecular adenoma of the thyroid gland. Histologic and immunohistochemical study. Report of 2 cases. Arch Anat Cytol Pathol 38:203–207

    CAS  PubMed  Google Scholar 

  165. Ferlito A, Friedmann I (1991) Contribution of immunohistochemistry in the diagnosis of neuroendocrine neoplasms of the larynx. ORL J Otorhinolaryngol Relat Spec 53:235–244

    CAS  PubMed  Google Scholar 

  166. Komminoth P, Roth J, Schroder S, Saremaslani P, Heitz PU (1995) Overlapping expression of immunohistochemical markers and synaptophysin mRNA in pheochromocytomas and adrenocortical carcinomas. Implications for the differential diagnosis of adrenal gland tumors. Lab Invest 72:424–431

    CAS  PubMed  Google Scholar 

  167. Haak HR, Fleuren GJ (1995) Neuroendocrine differentiation of adrenocortical tumors. Cancer 75:860–864

    CAS  PubMed  Google Scholar 

  168. Zhang H, Bu H, Chen H et al (2008) Comparison of immunohistochemical markers in the differential diagnosis of adrenocortical tumors: immunohistochemical analysis of adrenocortical tumors. Appl Immunohistochem Mol Morphol 16:32–39

    CAS  PubMed  Google Scholar 

  169. Zhang PJ, Genega EM, Tomaszewski JE, Pasha TL, LiVolsi VA (2003) The role of calretinin, inhibin, melan-A, BCL-2, and C-kit in differentiating adrenal cortical and medullary tumors: an immunohistochemical study. Mod Pathol 16:591–597

    PubMed  Google Scholar 

  170. Munro LM, Kennedy A, McNicol AM (1999) The expression of inhibin/activin subunits in the human adrenal cortex and its tumours. J Endocrinol 161:341–347

    CAS  PubMed  Google Scholar 

  171. McCluggage WG, Burton J, Maxwell P, Sloan JM (1998) Immunohistochemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin. J Clin Pathol 51:114–116

    CAS  PubMed  Google Scholar 

  172. Jungbluth AA, Busam KJ, Gerald WL et al (1998) A103: An anti-melan-a monoclonal antibody for the detection of malignant melanoma in paraffin-embedded tissues. Am J Surg Pathol 22:595–602

    CAS  PubMed  Google Scholar 

  173. Laforga JB, Aranda FI (1994) HMB-45 reactivity in sustentacular cells of paragangliomas. Histopathology 24:199

    CAS  PubMed  Google Scholar 

  174. Caya JG (1994) HMB-45 reactivity in adrenal pheochromocytomas. Arch Pathol Lab Med 118:1169

    CAS  PubMed  Google Scholar 

  175. Bastide C, Arroua F, Carcenac A et al (2006) Primary malignant melanoma of the adrenal gland. Int J Urol 13:608–610

    PubMed  Google Scholar 

  176. Amerigo J, Roig J, Pulido F et al (2000) Primary malignant melanoma of the adrenal gland. Surgery 127:107–111

    CAS  PubMed  Google Scholar 

  177. Visser JW, Axt R (1975) Bilateral adrenal medullary hyperplasia: a clinicopathological entity. J Clin Pathol 28:298–304

    CAS  PubMed  Google Scholar 

  178. Dobbie JW, Symington T (1966) The human adrenal gland with special reference to the vasculature. J Endocrinol 34:479–489

    CAS  PubMed  Google Scholar 

  179. Carney JA, Sizemore GW, Sheps SG (1976) Adrenal medullary disease in multiple endocrine neoplasia, type 2: pheochromocytoma and its precursors. Am J Clin Pathol 66:279–290

    CAS  PubMed  Google Scholar 

  180. Diaz-Cano SJ, de Miguel M, Blanes A et al (2000) Clonal patterns in phaeochromocytomas and MEN-2A adrenal medullary hyperplasias: histological and kinetic correlates. J Pathol 192:221–228

    CAS  PubMed  Google Scholar 

  181. Montalbano FP, Baronofsky ID, Ball H (1962) Hyperplasia of the adrenal medulla. JAMA 182:264–267

    Google Scholar 

  182. Bisceglia M, Nirchio V, Attino V et al (1998) ‘Black adenoma’; associated with medullary nodular hyperplasia in the ipsilateral adrenal gland. Case report and review of the literature regarding 'mixed' cortico-medullary pathology. Pathologica 90:306–312

    CAS  PubMed  Google Scholar 

  183. Borrero E, Katz P, Lipper S, Chang JB (1987) Adrenal cortical adenoma and adrenal medullary hyperplasia of the right adrenal gland – a case report. Angiology 38:271–274

    CAS  PubMed  Google Scholar 

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  1. Molecular and Cellular Pathology, UQ Centre for Clinical Research, University of Queensland, The Royal Brisbane and Women’s Hospital, Level 6 Building 71/918, 4029, Herston, Brisbane, QLD, Australia

    Anne Marie McNicol

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  1. Dept. Laboratory Medicine & Pathology, Mayo Clinic, First Street SW 200, Rochester, 55905, U.S.A.

    Ricardo V. Lloyd

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McNicol, A.M. (2010). Adrenal Medulla and Paraganglia. In: Lloyd, R. (eds) Endocrine Pathology:. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1069-1_12

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