Abstract
The adrenal gland is not a common specimen in surgical pathology practice as, until recently, adrenal tumors were recognized in life only if associated with hypersecretion of hormones or evidence of malignancy. However, adrenal nodules are not uncommon at autopsy, and the number of these found in life is now increasing as they are identified when the abdomen is scanned for the investigation of other diseases using computed tomography or magnetic resonance imaging. It is therefore becoming increasingly important for the surgical pathologist to be aware of the range of pathology in the gland and to understand how to approach the specimens. This short review will deal with lesions of the adrenal cortex.
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McNicol AM, Johnson SJ. Dataset for histopathology reporting in adrenal cortical carcinoma and malignant phaeochromocytoma/paraganglioma. London: Royal College of Pathologists, 2006.
Association of Directors of Anatomic and Surgical Pathology. Recommendations for reporting of tumors of the adrenal cortex and medulla. Am J Clin Pathol 112:451–5, 1999.
Lack EE. Tumors of the adrenal gland and extra-adrenal paraganglia. Washington DC: Armed Forces Institute of Pathology, 1997.
Dobbie JW. Adrenocortical nodular hyperplasia. The ageing adrenal. J Pathol 99:1–18, 1969. doi:10.1002/path.1710990102.
Hedeland H, Östberg G, Hökfelt B. On the prevalence of adrenocortical adenomas in autopsy material in relation to hypertension and diabetes. Acta Med Scand 184:211–4, 1968.
Grumbach MM, Biller BM, Braunstein GD, et al. Management of the clinically inapparent adrenal mass (“incidentaloma”). Ann Intern Med 138:424–9, 2003.
Bovio S, Cataldi A, Reimondo G, et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest 29:298–302, 2006.
Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. Incidentally discovered adrenal masses. Endocr Rev 16:460–83, 1995. doi:10.1210/er.16.4.460.
Beuschlein F, Reincke M. Adrenocortical tumorigenesis. Ann NY Acad Sci 1088:319–34, 2006. doi:10.1196/annals.1366.001.
Nawar R, Aron D. Adrenal incidentalomas—a continuing management dilemma. Endocr-Relat Cancer 12:585–98, 2005. doi:10.1677/erc.1.00951.
Saeger W, Reinhard K, Reinhard C. Hyperplastic and tumorous lesions of the adrenals in an unselected autopsy series. Endocr Pathol 9:235–9, 1998. doi:10.1007/BF02739963.
Watanabe N, Tsunoda K, Sasano H, et al. Bilateral aldosterone-producing adenomas in two patients diagnosed by immunohistochemical analysis of steroidogenic enzymes. Tohoku J Exp Med 179:123–9, 1996. doi:10.1620/tjem.179.123.
Ueda Y, Tanaka H, Murakami H, et al. A functioning black adenoma of the adrenal gland. Intern Med 36:398–402, 1997. doi:10.2169/internalmedicine.36.398.
Brennan MF. Adrenocortical carcinoma. CA-A Canc J Clin 37:348–53, 1987. doi:10.3322/canjclin.37.6.348.
Correa P, Chen VW. Endocrine gland cancer. Cancer 75:338–52, 1995. doi:10.1002/1097-0142(19950101)75:1 + <338::AID-CNCR2820751316>3.0.CO;2-F.
Lubitz JA, Freeman L, Okun R. Mitotane use in inoperable adrenal cortical carcinoma. JAMA 223:1109–12, 1973. doi:10.1001/jama.223.10.1109.
Hutter AMJ, Kayhoe DE. Adrenal cortical carcinoma. Am J Med 41:572–80, 1966. doi:10.1016/0002-9343(66)90219-1.
Ibanez ML. The pathology of adrenal cortical carcinomas: study of 22 cases. In: Endocrine and nonendocrine hormone-producing tumors. Chicago, IL: Chicago Year Book Medical Publishers, 1971
MacFarlane DA. Cancer of the adrenal cortex. The natural history, prognosis and treatment in a study of fifty-five cases. Ann Royal Coll Surg Engl 23:155–86, 1958.
El Naggar AK, Evans DB, Mackay B. Oncocytic adrenal cortical carcinoma. Ultrastruct Pathol 15:549–56, 1991. doi:10.3109/01913129109016262.
Hough AJ, Hollifield JW, Page DL, Hartmann WH. Prognostic factors in adrenal cortical tumours. Am J Clin Pathol 72:390–9, 1979.
Van Slooten H, Schaberg A, Smeenk D, Moolenaar AJ. Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer 55:766–73, 1985. doi:10.1002/1097-0142(19850215)55:4<766::AID-CNCR2820550414>3.0.CO;2-7.
Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 13:202–6, 1989.
Weiss LM. Comparable histologic study of 43 metastasizing and non metastasizing adrenocortical tumors. Am J Surg Pathol 8:163–9, 1984. doi:10.1097/00000478-198403000-00001.
Aubert S, Wacrenier A, Leroy X, et al. Weiss system revisited: a clinicopathologic and immunohistochemical study of 49 adrenocortical tumors. Am J Surg Pathol 26:1612–9, 2002. doi:10.1097/00000478-200212000-00009.
van’t Sant HP, Bouvy ND, Kazemier G, et al. The prognostic value of two different histopathological scoring systems for adrenocortical carcinomas. Histopathology 51:239–45, 2007. doi:10.1111/j.1365-2559.2007.02747.x.
Bisceglia M, Ludovico O, Di Mattia A, et al. Adrenocortical oncocytic tumors: report of 10 cases and review of the literature. Int J Surg Pathol 12:231–43, 2004. doi:10.1177/106689690401200304.
Lin BT, Bonsib SM, Mierau GW, Weiss LM, Medeiros LJ. Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature. The Am J Surg Pathol 22:603–14, 1998. doi:10.1097/00000478-199805000-00012.
Hoang MP, Ayala AG, Albores-Saavedra J. Oncocytic adrenocortical carcinoma: a morphologic, immunohistochemical and ultrastructural study of four cases. Mod Pathol 15:973–8, 2002. doi:10.1038/modpathol.3880638.
McNicol AM, Struthers AJ, Nolan CE, Hermans J, Haak HR. Proliferation in adrenocortical tumors: correlation with clinical outcome and p53 status. Endocr Pathol 8:29–36, 1997. doi:10.1007/BF02739705.
Sasano H, Suzuki T, Moriya T. Discerning malignancy in resected adrenocortical neoplasms. Endocr Pathol 12:397–406, 2001. doi:10.1385/EP:12:4:397.
Gicquel C, Le Bouc Y. Molecular markers for malignancy in adrenocortical tumors. Hormone Res 47:269–72, 1997.
Ilvesmaki V, Kahri AI, Miettinen PJ, Voutilainen R. Insulin-like growth factors (IGFs) and their receptors in adrenal tumors: high IGF-II expression in functional adrenocortical carcinomas. J Clin Endocrinol Metab 77:852–8, 1993. doi:10.1210/jc.77.3.852.
Barzon L, Chilosi M, Fallo F, et al. Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors. Eur J Endocrinol 145:207–12, 2001. doi:10.1530/eje.0.1450207.
McNicol AM, Nolan CE, Struthers AJ, et al. Expression of p53 in adrenocortical tumours: clinicopathological correlations. J Pathol 181:146–52, 1997. doi:10.1002/(SICI)1096-9896(199702)181:2<146::AID-PATH744>3.0.CO;2-7.
Ohgaki H, Kleihues P, Heitz PU. p53 mutations in sporadic adrenocortical tumors. Int J Cancer 54:408–10, 1993. doi:10.1002/ijc.2910540310.
Sullivan M, Boileau M, Hodges CV. Adrenal cortical carcinoma. J Urol 120:660–5, 1978.
Carr I. The human adrenal cortex at the time of death. J Pathol Bacteriol 78:533–41, 1959. doi:10.1002/path.1700780220.
Willenberg HS, Bornstein SR, Dumser T, et al. Morphological changes in adrenals from victims of suicide in relation to altered apoptosis. Endocr Res 24:963–7, 1998.
Rich AR. A peculiar type of adrenal cortical damage associated with acute infections and its possible relation to circulatory collapse. Bull Johns Hopkins Hosp 74:1–15, 1944.
Enberg U, Volpe C, Hamberger B. New aspects on primary aldosteronism. Neurochem Res 28:327–32, 2003. doi:10.1023/A:1022341619943.
Fiquet-Kempf B, Launay-Mignot P, Bobrie G, Plouin PF. Is primary aldosteronism underdiagnosed in clinical practice? Clin Exp Pharmacol Physiol 28:1083–6, 2001. doi:10.1046/j.1440-1681.2001.03585.x.
Melby JC. Diagnosis of hyperaldosteronism. Endocr Metab Clin North Am 20:247–55, 1991.
Omura M, Sasano H, Fujiwara T, Yamaguchi K, Nishikawa T. Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling. Metabolism 51:350–5, 2002. doi:10.1053/meta.2002.30498.
Sturrock ND, Morgan L, Jeffcoate WJ. Autonomous nodular hyperplasia of the adrenal cortex: tertiary hypercortisolism? Clin Endocrinol 43:753–8, 1995. doi:10.1111/j.1365-2265.1995.tb00546.x.
Irie J, Kawai K, Shigematsu K, et al. Adrenocorticotropic hormone-independent bilateral macronodular adrenocortical hyperplasia associated with Cushing’s syndrome. Pathol Int 45:240–6, 1995.
Aiba M, Hirayama A, Iri H, et al. Adrenocorticotropic hormone-independent bilateral adrenocortical macronodular hyperplasia as a distinct subtype of Cushing’s syndrome. Enzyme histochemical and ultrastructural study of four cases with a review of the literature. Am J Clin Pathol 96:334–40, 1991.
Christopoulos S, Bourdeau I, Lacroix A. Aberrant expression of hormone receptors in adrenal Cushing’s syndrome. Pituitary 7:225–35, 2004. doi:10.1007/s11102-005-1083-7.
Mazzuco TL, Chabre O, Feige JJ, Thomas M. Aberrant expression of human luteinizing hormone receptor by adrenocortical cells is sufficient to provoke both hyperplasia and Cushing’s syndrome features. J Clin Endocrinol Metab 91:196–203, 2006. doi:10.1210/jc.2005-1975.
Chabre O, Liakos P, Vivier J, et al. Gastric inhibitory polypeptide (GIP) stimulates cortisol secretion, cAMP production and DNA synthesis in an adrenal adenoma responsible for food-dependent Cushing’s syndrome. Endocr Res 24:851–6, 1998.
Chabre O, Liakos P, Vivier J, et al. Cushing’s syndrome due to a gastric inhibitory polypeptide-dependent adrenal adenoma: insights into hormonal control of adrenocortical tumorigenesis. J Clin Endocrinol Metab 83:3134–43, 1998. doi:10.1210/jc.83.9.3134.
Sandrini F, Stratakis C. Clinical and molecular genetics of Carney complex. Mol Gen Metab 78:83–92, 2003. doi:10.1016/S1096-7192(03)00006-4.
Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet 365:2125–36, 2005. doi:10.1016/S0140-6736(05)66736-0.
Stratakis CA, Rennert OM. Congenital adrenal hyperplasia: molecular genetics and alternative approaches to treatment. Crit Rev Clinical Lab Sci 36:329–63, 1999. doi:10.1080/10408369991239222.
Jaresch S, Kornely E, Kley HK, Schlaghecke R. Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia. J Clin Endocrinol Metab 74:685–9, 1992. doi:10.1210/jc.74.3.685.
Murakami C, Ishibashi M, Kondo M, et al. Adrenal myelolipoma associated with congenital adrenal 21-hydroxylase deficiency. Intern Med 31:803–6, 1992. doi:10.2169/internalmedicine.31.803.
Umpierrez MB, Fackler S, Umpierrez GE, Rubin J. Adrenal myelolipoma associated with endocrine dysfunction: review of the literature. Am J Med Sci 314:338–41, 1997. doi:10.1097/00000441-199711000-00012.
Bornstein SR, Stratakis CA, Chrousos GP. Adrenocortical tumors: recent advances in basic concepts and clinical management. Ann Int Med 130:759–71, 1999.
Komminoth P, Roth J, Schroder S, Saremaslani P, Heitz PU. Overlapping expression of immunohistochemical markers and synaptophysin mRNA in pheochromocytomas and adrenocortical carcinomas. Implications for the differential diagnosis of adrenal gland tumors. Lab Invest 72:424–31, 1995.
Arola J, Liu J, Heikkila P, Voutilainen R, Kahri A. Expression of inhibin alpha in the human adrenal gland and adrenocortical tumors. Endocr Res 24:865–7, 1998.
Munro LM, Kennedy A, McNicol AM. The expression of inhibin/activin subunits in the human adrenal cortex and its tumours. J Endocrinol 161:341–7, 1999. doi:10.1677/joe.0.1610341.
Ghorab Z, Jorda M, Ganjei P, Nadji M, Melan A. (A103) is expressed in adrenocortical neoplasms but not in renal cell and hepatocellular carcinomas. Appl Immunohistochem Mol Morphol 11:330–3, 2003. doi:10.1097/00129039-200312000-00009.
Shibata H, Ikeda Y, Mukai T, et al. Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors: possible implications in steroidogenesis. Mol Gen Metab 74:206–16, 2001. doi:10.1006/mgme.2001.3231.
Sasano H, Suzuki T, Moriya T. Recent advances in histopathology and immunohistochemistry of adrenocortical carcinoma. Endocr Pathol 17:345–54, 2006. doi:10.1007/s12022-006-0006-0.
Haak HR, Fleuren GJ. Neuroendocrine differentiation of adrenocortical tumors. Cancer 75:860–4, 1995. doi:10.1002/1097-0142(19950201)75:3<860::AID-CNCR2820750318>3.0.CO;2-G.
Kjellman M, Kallioniemi OP, Karhu R, et al. Genetic aberrations in adrenocortical tumors detected using comparative genomic hybridization correlate with tumor size and malignancy. Cancer Res 56:4219–23, 1996.
Sidhu S, Marsh DJ, Theodosopoulos G, et al. Comparative genomic hybridization analysis of adrenocortical tumors. J Clin Endocrinol Metab 87:3467–74, 2002. doi:10.1210/jc.87.7.3467.
Gicquel C, Bertagna X, Gaston V, et al. Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors. Cancer Res 61:6762–7, 2001.
Russell AJ, Sibbald J, Haak H, Keith WN, McNicol AM. Increasing genome instability in adrenocortical carcinoma progression with involvement of chromosomes 3, 9 and X at the adenoma stage. Br J Cancer 81:684–9, 1999. doi:10.1038/sj.bjc.6690748.
Srivastava S, Zou Z, Pirollo K, Blattner W, Chang EH. Germline transmission of a mutated p53 gene in a cancer-prone family with Li–Fraumeni syndrome. Nature 348:747–9, 1990. doi:10.1038/348747a0.
Reincke M, Karl M, Travis WH, et al. p53 mutations in human adrenocortical neoplasms: immunohistochemical and molecular studies. J Clin Endocrinol Metab 78:790–4, 1994. doi:10.1210/jc.78.3.790.
Latronico AC, Pinto EM, Domenice S, et al. An inherited mutation outside the highly conserved DNA-binding domain of the p53 tumor suppressor protein in children and adults with sporadic adrenocortical tumors. J Clin Endocrinol Metab 86:4970–3, 2001. doi:10.1210/jc.86.10.4970.
Moul JW, Bishoff JT, Theune SM, Chang EH. Absent ras gene mutations in human adrenal cortical neoplasms and pheochromocytomas. J Urol 149:1389–94, 1993.
Yashiro T, Hara H, Fulton NC, Obara T, Kaplan EL. Point mutations of ras genes in human adrenal cortical tumors: absence in adrenocortical hyperplasia. World J Surg 18:455–60, 1994. doi:10.1007/BF00353735.
Lin SR, Tsai JH, Yang YC, Lee SC. Mutations of K-ras oncogene in human adrenal tumours in Taiwan. Br J Cancer 77:1060–5, 1998.
Heppner C, Reincke M, Agarwal SK, et al. MEN1 gene analysis in sporadic adrenocortical neoplasms. J Clin Endocrinol Metab 84:216–9, 1999. doi:10.1210/jc.84.1.216.
Li M, Squire JA, Weksberg R. Molecular genetics of Wiedemann–Beckwith syndrome. Am J Med Genet 79:253–9, 1998. doi:10.1002/(SICI)1096-8628(19981002)79:4<253::AID-AJMG5>3.0.CO;2-N.
Gicquel C, Raffin-Sanson ML, Gaston V, et al. Structural and functional abnormalities at 11p15 are associated with the malignant phenotype in sporadic adrenocortical tumors: study on a series of 82 tumors. J Clin Endocrinol Metab 82:2559–65, 1997. doi:10.1210/jc.82.8.2559.
Ilvesmaki V, Liu J, Heikkila P, Kahri AI, Voutilainen R. Expression of insulin-like growth factor binding protein 1–6 genes in adrenocortical tumors and pheochromocytomas. Horm Metab Res 30:619–23, 1998. doi:10.1055/s-2007-978945.
Weber MM, Auernhammer CJ, Kiess W, Engelhardt D. Insulin-like growth factor receptors in normal and tumorous adult human adrenocortical glands. Eur J Endocrinol 136:296–303, 1997.
McCluggage WG, Burton J, Maxwell P, Sloan JM. Immunohistochemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin. J Clin Pathol 51:114–6, 1998.
Latronico AC. Role of ACTH receptor in adrenocortical tumor formation. Braz J Med Biol Res 33:1249–52, 2000. doi:10.1590/S0100-879X2000001000016.
Giordano TJ, Thomas DG, Kuick R, et al. Distinct transcriptional profiles of adrenocortical tumors uncovered by DNA microarray analysis. Am J Pathol 162:521–31, 2003.
de Fraipont F, El Atifi M, Cherradi N, et al. Gene expression profiling of human adrenocortical tumors using complementary deoxyribonucleic acid microarrays identifies several candidate genes as markers of malignancy. J Clin Endocrinol Metab 90:1819–29, 2005. doi:10.1210/jc.2004-1075.
Bishop E, Eble JN, Cheng L, et al. Adrenal myelolipomas show nonrandom X-chromosome inactivation in hematopoietic elements and fat: support for a clonal origin of myelolipomas. Am J Surg Pathol 30:838–43, 2006. doi:10.1097/01.pas.0000202044.05333.17.
Torres C, Ro JY, Batt MA, et al. Vascular adrenal cysts: a clinicopathologic and immunohistochemical study of six cases and a review of the literature. Mod Pathol 10:530–6, 1997.
Bapat KC, Awad SM, Cooperman JS, et al. Adrenal pseudocyst: report of two cases. N J Med 92:33–6, 1995.
Ghandur-Mnaymneh L, Slim M, Muakassa K. Adrenal cysts: pathogenesis and histological identification with a report of 6 cases. J Urol 122:87–91, 1979.
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McNicol, A.M. A Diagnostic Approach to Adrenal Cortical Lesions. Endocr Pathol 19, 241–251 (2008). https://doi.org/10.1007/s12022-008-9055-x
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DOI: https://doi.org/10.1007/s12022-008-9055-x