Skip to main content
Log in

Adrenal tumors: How to establish malignancy?

  • Review Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Discerning malignancy in adrenal tumors largely influences disease management and is, therefore, of utmost importance to both patient and physician. Clinical presentation (e.g. virilization) and baseline hormonal evaluation (e.g. high serum DHEAS) are occasionally of great value but usually provide only limited help in predicting malignancy. The probability of malignancy is clearly related to tumor size, as almost all lesions <3 cm are benign whereas a diameter of >6 cm indicates a high risk of malignancy. Computed tomography (CT) and magnetic resonance imaging (MRI) both contribute significantly to the characterization of adrenal masses. If the attenuation of a homogeneous mass with smooth border is 10 Hounsfield units or less in unenhanced CT the diagnosis of a lipid rich adenoma is established. Similarly, enhancement washout of more than 50% in CT at 10–15 min suggests a benign lesion. In MRI both rapid contrast enhancement after gadolinium followed by rapid washout and signal intensity loss using opposed-phase image in chemical shift analysis also indicate the presence of an adenoma. In contrast, adrenal carcinomas — but also pheochromocytomas — typically present as inhomogeneous lesion with intermediate-to-high intensity on T2 images in MRI. Margins and enhancement after contrast media in CT are irregular in adrenal carcinoma. Other imaging techniques either offer little additional information (NP-59 scintigraphy) or have not yet been fully established (positron emission tomography). Fine needle aspiration/cut biopsy is at present restricted to patients with a known extra-adrenal malignancy and suspected adrenal metastasis as the only evidence of disseminated disease. Adrenal tumors classified as benign undergo follow-up imaging to assess tumor growth. If an increase in diameter of >1 cm is seen, surgical removal is recommended. Even after tumor removal the diagnosis of dignity may remain difficult. Diagnostic scores together with new immunohistological markers are the methods of choice to assess malignancy. In conclusion, an interdisciplinary approach with a structured use of available diagnostic tools is needed to classify adrenal tumors correctly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Russi S, Blumenthal HT. Small adenomas of the adrenal cortex in hypertension and diabetes. Arch Int Med 1945: 284–91.

    Google Scholar 

  2. Commons RR, Callway CP. Adenomas of the adrenal cortex. Arch Int Med 1948: 37–41

    Google Scholar 

  3. Shamma AH, Goddard JW, Sommers SC. A study of the adrenal status in hypertension. J Chron Dis 1958: 587–95.

    Google Scholar 

  4. Kokko JP, Brown TC, Berman MM. Adrenal adenoma and hypertension. Lancet 1 1967: 468–70.

    CAS  PubMed  Google Scholar 

  5. Hedeland H, Ostberg G, Hokfelt B. On the prevalence of adrenocortical adenomas in an autopsy material in relation to hypertension and diabetes. Acta Med Scand 184 1968: 211–4.

    CAS  PubMed  Google Scholar 

  6. Russell R, Masi A, Richter E. Adrenal cortical adenomas and hypertension. A clinical pathologic analysis of 690 cases with matched controls and a review of the literature. Medicine (Baltimore) 1972, 51: 211–25.

    CAS  Google Scholar 

  7. NIH-State-of-science-art-statement 2002 Management of the Clinically Inapparent Adrenal Mass (Incidentaloma) February 4–6, 2002. http://consensus.nih.gov/ta/021/021_statement.htm.

  8. Nader S, Hickey R, Sellin R, Samaan N. Adrenal cortical carcinoma. A study of 77 cases. Cancer 1983, 52: 707–11.

    CAS  PubMed  Google Scholar 

  9. Crucitti F, Bellantone R, Ferrante A, Boscherini M, Crucitti P. The Italian Registry for Adrenal Cortical Carcinoma: analysis of a multiinstitutional series of 129 patients. The ACC Italian Registry Study Group. Surgery 1996, 119: 161–70.

    CAS  PubMed  Google Scholar 

  10. Schulick RD, Brennan MF. Adrenocortical carcinoma. World J Urol 1999, 17: 26–34.

    CAS  PubMed  Google Scholar 

  11. Wajchenberg B, Albergaria PM, Medonca B, et al. Adrenocortical carcinoma: clinical and laboratory observations. Cancer 2000, 88: 711–36.

    CAS  PubMed  Google Scholar 

  12. Dackiw AP, Lee JE, Gagel RF, Evans DB. Adrenal cortical carcinoma. World J Surg 2001, 25: 914–26.

    CAS  PubMed  Google Scholar 

  13. Herrera M, Grant C, van HJ, Sheedy P, Ilstrup D. Incidentally discovered adrenal tumors: an institutional perspective. Surgery 1991, 110: 1014–21.

    CAS  PubMed  Google Scholar 

  14. Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. Incidentally discovered adrenal masses. Endocr Rev 1995, 16: 460–84.

    CAS  PubMed  Google Scholar 

  15. Favia G, Lumachi F, Basso S, D’Amico DF. Management of incidentally discovered adrenal masses and risk of malignancy. Surgery 2000, 128: 918–24.

    CAS  PubMed  Google Scholar 

  16. Proye C, Huart J, Cuvillier X, et al. Safety of the posterior approach in adrenal surgery: experience in 105 cases. Surgery 1993, 114: 1126–31.

    CAS  PubMed  Google Scholar 

  17. Brunt LM. The positive impact of laparoscopic adrenalectomy on complications of adrenal surgery. Surg Endosc 2002, 16: 252–7.

    CAS  PubMed  Google Scholar 

  18. Plouin PF, Duclos JM, Soppelsa F, Boublil G, Chatellier G. 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: 1480–6.

    CAS  PubMed  Google Scholar 

  19. Terachi T, Yoshida O, Matsuda T, et al. Complications of laparoscopic and retroperitoneoscopic adrenalectomies in 370 cases in Japan: a multi-institutional study. Biomed Pharmacother 2000, 54(Suppl 1): 211s–4s.

    PubMed  Google Scholar 

  20. Hallfeldt KK, Mussack T, Trupka A, Hohenbleicher F, Schmidbauer S. Laparoscopic lateral adrenalectomy versus open posterior adrenalectomy for the treatment of benign adrenal tumors. Surg Endosc 2002.

    Google Scholar 

  21. Schteingart DE. Management approaches to adrenal incidentalomas. A view from Ann Arbor, Michigan. Endocrinol Metab Clin North Am 2000, 29: 127–39, ix–x.

    CAS  PubMed  Google Scholar 

  22. Angeli A, Osella G, Ali A, Terzolo M. Adrenal incidentaloma: an overview of clinical and epidemiological data from the National Italian Study Group. Horm Res 1997, 47: 279–83.

    CAS  PubMed  Google Scholar 

  23. Kasperlik-Zeluska AA, Roslonowska E, Slowinska-Srzednicka J, et al. Incidentally discovered adrenal mass (incidentaloma): investigation and management of 208 patients. Clin Endocrinol (Oxf) 1997, 46: 29–37.

    CAS  Google Scholar 

  24. Proye C, Jafari MM, Combemale F, et al. Experience gained from operation of 103 adrenal incidentalomas. Langenbecks Arch Surg 1998, 383: 330–3.

    CAS  PubMed  Google Scholar 

  25. Grumbach MM, Biller BM, Braunstein GD, et al. Management of the clinically inapparent adrenal mass (“incidenta-loma”). Ann Intern Med 2003, 138: 424–9.

    PubMed  Google Scholar 

  26. Iino K, Oki Y, Sasano H. A case of adrenocortical carcinoma associated with recurrence after laparoscopic surgery. Clin Endocrinol (Oxf) 2000, 53: 243–8.

    CAS  Google Scholar 

  27. Kebebew E, Siperstein AE, Clark OH, Duh QY. Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms. Arch Surg 2002, 137: 948–51; discussion 952–3.

    PubMed  Google Scholar 

  28. Osella G, Terzolo M, Borretta G, et al. Endocrine evaluation of incidentally discovered adrenal masses (incidentalomas) [see comments]. J Clin Endocrinol Metab 1994, 79: 1532–9.

    CAS  PubMed  Google Scholar 

  29. Terzolo M, Osella G, Ali A, et al. Different patterns of steroid secretion in patients with adrenal incidentaloma [see comments]. J Clin Endocrinol Metab 1996, 81: 740–4.

    CAS  PubMed  Google Scholar 

  30. Flecchia D, Mazza E, Carlini M, et al. Reduced serum levels of dehydroepiandrosterone sulphate in adrenal incidentalomas: a marker of adrenocortical tumour. Clin Endocrinol (Oxf) 1995, 42: 129–34.

    CAS  Google Scholar 

  31. Latronico AC, Chrousos G P. Extensive personal experience: adrenocortical tumors. J Clin Endocrinol Metab 1997, 82: 1317–24.

    CAS  PubMed  Google Scholar 

  32. Terzolo M, Ali A, Osella G, et al. The value of dehydroepiandrosterone sulfate measurement in the differentiation between benign and malignant adrenal masses. Eur J Endocrinol 2000, 142: 611–7.

    CAS  PubMed  Google Scholar 

  33. Dobbie JW. Adrenocortical nodular hyperplasia: the ageing adrenal. J Pathol 1969, 99: 1–18.

    CAS  PubMed  Google Scholar 

  34. Orentreich N, Brind JL, Rizer RL, Vogelman JH. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab 1984, 59: 551–5.

    CAS  PubMed  Google Scholar 

  35. Tippett PA, McEwan AJ, Ackery DM. A re-evaluation of dopamine excretion in phaeochromocytoma. Clin Endocrinol (Oxf) 1986, 25: 401–10.

    CAS  Google Scholar 

  36. 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: 631–42.

    CAS  PubMed  Google Scholar 

  37. John H, Ziegler WH, Hauri D, Jaeger P. Pheochromocytomas: can malignant potential be predicted? Urology 1999, 53: 679–83.

    CAS  PubMed  Google Scholar 

  38. Januszewicz W, Wocial B, Januszewicz A, Gryglas P, Prejbisz A. Dopamine and dopa urinary excretion in patients with pheochromocytoma—diagnostic implications. Blood Press 2001, 10: 212–6.

    CAS  PubMed  Google Scholar 

  39. van der Harst E, de Herder WW, de Krijger RR, et al. The value of plasma markers for the clinical behaviour of phaeochromocytomas. Eur J Endocrinol 2002, 147: 85–94.

    PubMed  Google Scholar 

  40. Hussain S, Belldegrun A, Seltzer SE, et al. Differentiation of malignant from benign adrenal masses: predictive indices on computed tomography. AJR Am J Roentgenol 1985, 144: 61–5.

    CAS  PubMed  Google Scholar 

  41. Khafagi FA, Gross MD, Shapiro B, et al. Clinical significance of the large adrenal mass. Br J Surg 1991, 78: 828–33.

    CAS  PubMed  Google Scholar 

  42. Siren J, Haapiainen R, Huikuri K, Sivula A. Incidentalomas of the adrenal gland: 36 operated patients and review of literature. World J Surg 1993, 17: 634–9.

    CAS  PubMed  Google Scholar 

  43. Mantero F, Terzolo M, Arnaldi G, et al. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab 2000, 85: 637–44.

    CAS  PubMed  Google Scholar 

  44. Singer AA, Obuchowski NA, Einstein DM, Paushter DM. Metastasis or adenoma? Computed tomographic evaluation of the adrenal mass. Cleve Clin J Med 1994, 61: 200–5.

    CAS  PubMed  Google Scholar 

  45. Fontana D, Porpiglia F, Destefanis P, et al. What is the role of ultrasonography in the follow-up of adrenal incidentalomas? The Gruppo Piemontese Incidentalomi Surrenalici. Urology 1999, 54: 612–6.

    CAS  PubMed  Google Scholar 

  46. Hamper UM, Fishman EK, Hartman DS, Roberts JL, Sanders RC. Primary adrenocortical carcinoma: sonographic evaluation with clinical and pathologic correlation in 26 patients. AJR Am J Roentgenol 1987, 148: 915–9.

    CAS  PubMed  Google Scholar 

  47. Korobkin M, Giordano TJ, Brodeur FJ, et al. Adrenal adenomas: relationship between histologic lipid and CT and MR findings. Radiology 1996, 200: 743–7.

    CAS  PubMed  Google Scholar 

  48. Boland GW, Lee MJ, Gazelle GS, et al. Characterization of adrenal masses using unenhanced CT: an analysis of the CT literature. AJR Am J Roentgenol 1998, 171: 201–4.

    CAS  PubMed  Google Scholar 

  49. Lee M, Hahn P, Papanicolaou N, et al. Benign and malignant adrenal masses: CT distinction with attenuation coefficients, size, and observer analysis. Radiology 1991, 179: 415–8.

    CAS  PubMed  Google Scholar 

  50. Korobkin M, Brodeur FJ, Francis IR, et al. CT time-attenuation washout curves of adrenal adenomas and nonadenomas. AJR Am J Roentgenol 1998, 170: 747–52.

    CAS  PubMed  Google Scholar 

  51. Szolar DH, Kammerhuber FH. Adrenal adenomas and nonadenomas: assessment of washout at delayed contrast-enhanced CT. Radiology 1998, 207: 369–75.

    CAS  PubMed  Google Scholar 

  52. Caoili EM, Korobkin M, Francis IR, Cohan RH, Dunnick NR. Delayed enhanced CT of lipid-poor adrenal adenomas. AJR Am J Roentgenol 2000, 175: 1411–5.

    CAS  PubMed  Google Scholar 

  53. Pena CS, Boland GW, Hahn PF, Lee MJ, Mueller PR. Characterization of indeterminate (lipid-poor) adrenal masses: use of washout characteristics at contrast-enhanced CT. Radiology 2000, 217: 798–802.

    CAS  PubMed  Google Scholar 

  54. Caoili EM, Korobkin M, Francis IR, et al. Adrenal masses: characterization with combined unenhanced and delayed enhanced CT. Radiology 2002, 222: 629–33.

    PubMed  Google Scholar 

  55. Outwater EK, Siegelman ES, Huang AB, Birnbaum BA. Adrenal masses: correlation between CT attenuation value and chemical shift ratio at MR imaging with in-phase and opposed-phase sequences. Radiology 1996, 200: 749–52.

    CAS  PubMed  Google Scholar 

  56. Bilbey JH, McLoughlin RF, Kurkjian PS, et al. MR imaging of adrenal masses: value of chemical-shift imaging for distinguishing adenomas from other tumors. AJR Am J Roentgenol 1995, 164: 637–42.

    CAS  PubMed  Google Scholar 

  57. Korobkin M, Lombardi TJ, Aisen AM, et al. Characterization of adrenal masses with chemical shift and gadolinium-enhanced MR imaging. Radiology 1995, 197: 411–8.

    CAS  PubMed  Google Scholar 

  58. Heinz-Peer G, Honigschnabl S, Schneider B, et al. Characterization of adrenal masses using MR imaging with histopatho-logic correlation. AJR Am J Roentgenol 1999, 173: 15–22.

    CAS  PubMed  Google Scholar 

  59. Honigschnabl S, Gallo S, Niederle B, et al. How accurate is MR imaging in characterisation of adrenal masses: update of a long-term study. Eur J Radiol 2002, 41: 113–22.

    PubMed  Google Scholar 

  60. Dunnick NR, Korobkin M. Imaging of adrenal incidentalomas: current status. AJR Am J Roentgenol 2002, 179: 559–68.

    PubMed  Google Scholar 

  61. Kostler H, Kenn W, Hummer C, Bohm D, Hahn D. [2D-SPLASH spectroscopy to determine the fat/water ratio in the muscle of the rotator cuff]. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2002, 174: 991–5.

    CAS  PubMed  Google Scholar 

  62. Rubello D, Bui C, Casara D, et al. Functional scintigraphy of the adrenal gland. Eur J Endocrinol 2002, 147: 13–28.

    CAS  PubMed  Google Scholar 

  63. Schteingart DE, Seabold JE, Gross MD, Swanson DP. Iodocholesterol adrenal tissue uptake and imaging adrenal neoplasms. J Clin Endocrinol Metab 1981, 52: 1156–61.

    CAS  PubMed  Google Scholar 

  64. Gross MD, Shapiro B, Bouffard JA, et al. Distinguishing benign from malignant euadrenal masses. Ann Intern Med 1988, 109: 613–8.

    CAS  PubMed  Google Scholar 

  65. Kloos RT, Korobkin M, Thompson NW, et al. Incidentally discovered adrenal masses. Cancer Treat Res 1997, 89: 263–92.

    CAS  PubMed  Google Scholar 

  66. Francis I, Smid A, Gross M, et al. Adrenal masses in oncologic patients: functional and morphologic evaluation. Radiology 1988, 166: 353–6.

    CAS  PubMed  Google Scholar 

  67. Young WF, Jr., Hogan MJ, Klee GG, Grant CS, van Heerden JA. Primary aldosteronism: diagnosis and treatment. Mayo Clin Proc 1990, 65: 96–110.

    PubMed  Google Scholar 

  68. Bravo EL. Evolving concepts in the pathophysiology, diagnosis, and treatment of pheochromocytoma. Endocr Rev 1994, 15: 356–68.

    CAS  PubMed  Google Scholar 

  69. Berglund AS, Hulthen UL, Manhem P, et al. Metaiodoben-zylguanidine (MIBG) scintigraphy and computed tomography (CT) in clinical practice. Primary and secondary evaluation for localization of phaeochromocytomas. J Intern Med 2001, 249: 247–51.

    CAS  PubMed  Google Scholar 

  70. Boland GW, Goldberg MA, Lee MJ, et al. Indeterminate adrenal mass in patients with cancer: evaluation at PET with 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1995, 194: 131–4.

    CAS  PubMed  Google Scholar 

  71. Maurea S, Mainolfi C, Bazzicalupo L, et al. Imaging of adrenal tumors using FDG PET: comparison of benign and malignant lesions. AJR Am J Roentgenol 1999, 173: 25–9.

    CAS  PubMed  Google Scholar 

  72. Yun M, Kim W, Alnafisi N, et al. 18F-FDG PET in characterizing adrenal lesions detected on CT or MRI. J Nucl Med 2001, 42: 1795–9.

    CAS  PubMed  Google Scholar 

  73. Becherer A, Vierhapper H, Potzi C, et al. FDG-PET in adrenocortical carcinoma. Cancer Biother Radiopharm 2001, 16: 289–95.

    CAS  PubMed  Google Scholar 

  74. Pacak K, Eisenhofer G, Carrasquillo JA, et al. 6-[18F]fluorodopamine positron emission tomographic (PET) scanning for diagnostic localization of pheochromocytoma. Hypertension 2001, 38: 6–8.

    CAS  PubMed  Google Scholar 

  75. Pacak K, Goldstein DS, Doppman JL, et al. A “pheo” lurks: novel approaches for locating occult pheochromocytoma. J Clin Endocrinol Metab 2001, 86: 3641–6.

    CAS  PubMed  Google Scholar 

  76. Hoegerle S, Nitzsche E, Altehoefer C, et al. Pheochromocytomas: detection with 18F DOPA whole body PET—initial results. Radiology 2002, 222: 507–12.

    PubMed  Google Scholar 

  77. Pacak K, Eisenhofer G, Carrasquillo JA, et al. Diagnostic localization of pheochromocytoma: the coming of age of positron emission tomography. Ann NY Acad Sci 2002, 970: 170–6.

    CAS  PubMed  Google Scholar 

  78. Juhlin C, Tornblom S, Rastad J, et al. [Differential diagnosis in adrenal gland tumors using PET and 11C-metomidate]. Nord Med 1998, 113: 306–7.

    CAS  PubMed  Google Scholar 

  79. Bergstrom M, Juhlin C, Bonasera TA, et al. PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11C-metomidate. J Nucl Med 2000, 41: 275–82.

    CAS  PubMed  Google Scholar 

  80. Eriksson B, Bergstrom M, Sundin A, et al. The role of PET in localization of neuroendocrine and adrenocortical tumors. Ann N Y Acad Sci 2002, 970: 159–69.

    CAS  PubMed  Google Scholar 

  81. Khan TS, Sundin A, Juhlin C, et al. 11C-metomidate PET imaging of adrenocortical cancer. Eur J Nucl Med Mol Imaging 2003, 30: 403–10.

    PubMed  Google Scholar 

  82. McCorkell SJ, Niles NL. Fine-needle aspiration of catecholamine-producing adrenal masses: a possibly fatal mistake. AJR Am J Roentgenol 1985, 145: 113–4.

    CAS  PubMed  Google Scholar 

  83. Yankaskas B, Staab E, Craven M, et al. Delayed complications from fine-needle biopsies of solid masses of the abdomen. Invest Radiol 1986, 21: 325–8.

    CAS  PubMed  Google Scholar 

  84. Casola G, Nicolet V, vanSonnenberg E, et al. Unsuspected pheochromocytoma: risk of blood-pressure alterations during percutaneous adrenal biopsy. Radiology 1986, 159: 733–5.

    CAS  PubMed  Google Scholar 

  85. Habscheid W, Pfeiffer M, Demmrich J, Muller HA. [Puncture track metastasis after ultrasound-guided fine-needle puncture biopsy. A rare complication?]. Dtsch Med Wochenschr 1990, 115: 212–5.

    CAS  PubMed  Google Scholar 

  86. Lumachi F, Borsato S, Brandes AA, et al. Fine-needle aspiration cytology of adrenal masses in noncancer patients: clinicoradiologic and histologic correlations in functioning and nonfunctioning tumors. Cancer 2001, 93: 323–9.

    CAS  PubMed  Google Scholar 

  87. Fassina AS, Borsato S, Fedeli U. Fine needle aspiration cytology (FNAC) of adrenal masses. Cytopathology 2000, 11: 302–11.

    CAS  PubMed  Google Scholar 

  88. Mody MK, Kazerooni EA, Korobkin M. Percutaneous CT-guided biopsy of adrenal masses: immediate and delayed complications. J Comput Assist Tomogr 1995, 19: 434–9.

    CAS  PubMed  Google Scholar 

  89. Katz RL, Patel S, Mackay B, Zornoza J. Fine needle aspiration cytology of the adrenal gland. Acta Cytol 1984, 28: 269–82.

    CAS  PubMed  Google Scholar 

  90. Wadih G, Nance K, Silverman J. Fine-needle aspiration cytology of the adrenal gland. Fifty biopsies in 48 patients. Arch Pathol Lab Med 1992, 116: 841–6.

    CAS  PubMed  Google Scholar 

  91. Welch TJ, Sheedy PF, 2nd, Stephens DH, Johnson CM, Swensen SJ. Percutaneous adrenal biopsy: review of a 10-year experience. Radiology 1994, 193: 341–4.

    CAS  PubMed  Google Scholar 

  92. Silverman SG, Mueller PR, Pinkney LP, Koenker RM, Seltzer SE. Predictive value of image-guided adrenal biopsy: analysis of results of 101 biopsies. Radiology 1993, 187: 715–8.

    CAS  PubMed  Google Scholar 

  93. Wu HH, Cramer HM, Kho J, Elsheikh TM. Fine needle aspiration cytology of benign adrenal cortical nodules. A comparison of cytologic findings with those of primary and metastatic adrenal malignancies. Acta Cytol 1998, 42: 1352–8.

    CAS  PubMed  Google Scholar 

  94. de Agustin P, Lopez-Rios F, Alberti N, Perez-Barrios A. Fine-needle aspiration biopsy of the adrenal glands: A ten-year experience. Diagn Cytopathol 1999, 21: 92–7.

    PubMed  Google Scholar 

  95. Saeger W, Fassnacht M, Chita R, et al. High diagnostic accuracy of adrenal core biopsy: results of the German and Austrian adrenal network multicenter trial in 220 consecutive patients. Hum Pathol 2003, 34: 180–6.

    CAS  PubMed  Google Scholar 

  96. Saeger W. Histopathological classification of adrenal tumours. Eur J Clin Invest 2000, 30: 58–62.

    PubMed  Google Scholar 

  97. Hough AJ, Hollifield JW, Page DL, Hartmann WH. Prognostic factors in adrenal cortical tumors. A mathematical analysis of clinical and morphologic data. Am J Clin Pathol 1979, 72: 390–9.

    CAS  PubMed  Google Scholar 

  98. van Slooten H, Schaberg A, Smeenk D, Moolenaar AJ. Morphologic characteristics of benign and malignant adreno-cortical tumors. Cancer 1985, 55: 766–73.

    PubMed  Google Scholar 

  99. Weiss LM. Comparative histologic study of 43 metastasiz-ing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984, 8: 163–9.

    CAS  PubMed  Google Scholar 

  100. Weiss LM, Medeiros LJ, Vickery AL, Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989, 13: 202–6.

    CAS  PubMed  Google Scholar 

  101. Stojadinovic A, Ghossein RA, Hoos A, et al. Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. J Clin Oncol 2002, 20: 941–50.

    CAS  PubMed  Google Scholar 

  102. Clarke MR, Weyant RJ, Watson CG, Carty SE. Prognostic markers in pheochromocytoma. Hum Pathol 1998, 29: 522–6.

    CAS  PubMed  Google Scholar 

  103. Kubota Y, Nakada T, Sasagawa I, Yanai H, Itoh K. Elevated levels of telomerase activity in malignant pheochromocytoma. Cancer 1998, 82: 176–9.

    CAS  PubMed  Google Scholar 

  104. Brown HM, Komorowski RA, Wilson SD, Demeure MJ, Zhu YR. Predicting metastasis of pheochromocytomas using DNA flow cytometry and immunohistochemical markers of cell proliferation: A positive correlation between MIB-1 staining and malignant tumor behavior. Cancer 1999, 86: 1583–9.

    CAS  PubMed  Google Scholar 

  105. Thompson LD. 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 2002, 26: 551–66.

    PubMed  Google Scholar 

  106. Reincke M. Subclinical Cushing’s syndrome. Endocrinol Metab Clin North Am 2000, 29: 43–56.

    CAS  PubMed  Google Scholar 

  107. Reincke M, Seiler L, Rump LC. Normokaliaemischer primaerer Hyperaldosteronismus. Dtsch Ärzteblatt 2003, 100: A184–90.

    Google Scholar 

  108. Allolio B. Adrenal Incidentalomas. In: Margioris AN, Chrousos GP eds. Adrenal Disorders. Totawa: Humana Press. 2001, 249–61.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B. Allolio MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fassnacht, M., Kenn, W. & Allolio, B. Adrenal tumors: How to establish malignancy?. J Endocrinol Invest 27, 387–399 (2004). https://doi.org/10.1007/BF03351068

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03351068

Key-words

Navigation