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Open Access 01-01-2012 | Review and Perspective

Adrenocortical neoplasia: evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants

Authors: Ronald R. de Krijger, Thomas G. Papathomas

Published in: Virchows Archiv | Issue 1/2012

Abstract

Adrenocortical carcinoma (ACC) is a rare, heterogeneous malignancy with a poor prognosis. According to WHO classification 2004, ACC variants include oncocytic ACCs, myxoid ACCs and ACCs with sarcomatous areas. Herein, we provide a comprehensive review of these rare subtypes of adrenocortical malignancy and emphasize their clinicopathological features with the aim of elucidating aspects of diagnostic categorization, differential diagnostics and biological behavior. The issue of current terminology, applied to biphasic tumors with pleomorphic, sarcomatous or sarcomatoid elements arising in adrenal cortex, is also discussed. We additionally present emerging evidence concerning the adrenal cortical tumorigenesis and the putative adenoma–carcinoma sequence as well.

Fassnacht M, Libe R, Kroiss M, Allolio B (2011) Adrenocortical carcinoma: a clinician's update. Nat Rev Endocrinol 7:323–335PubMedCrossRef

McNicol AM (2011) Update on tumours of the adrenal cortex, phaeochromocytoma and extra-adrenal paraganglioma. Histopathology 58:155–168PubMedCrossRef

Lau SK, Weiss LM (2009) The Weiss system for evaluating adrenocortical neoplasms: 25 years later. Hum Pathol 40:757–768PubMedCrossRef

Aubert S, Wacrenier A, Leroy X et al (2002) Weiss system revisited: a clinicopathologic and immunohistochemical study of 49 adrenocortical tumors. Am J Surg Pathol 26:1612–1619PubMedCrossRef

Blanes A, Diaz-Cano SJ (2007) Histologic criteria for adrenocortical proliferative lesions: value of mitotic figure variability. Am J Clin Pathol 127:398–408PubMedCrossRef

Volante M, Bollito E, Sperone P et al (2009) Clinicopathological study of a series of 92 adrenocortical carcinomas: from a proposal of simplified diagnostic algorithm to prognostic stratification. Histopathology 55:535–543PubMedCrossRef

Tissier F (2010) Classification of adrenal cortical tumors: what limits for the pathological approach? Best Pract Res Clin Endocrinol Metab 24:877–885PubMedCrossRef

Dehner LP, Hill DA (2009) Adrenal cortical neoplasms in children: why so many carcinomas and yet so many survivors? Pediatr Dev Pathol 12:284–291PubMedCrossRef

Bertherat J, Bertagna X (2009) Pathogenesis of adrenocortical cancer. Best Pract Res Clin Endocrinol Metab 23:261–271PubMedCrossRef

10.

Grumbach MM, Biller BM, Braunstein GD et al (2003) Management of the clinically inapparent adrenal mass (“incidentaloma”). Ann Intern Med 138:424–429PubMed

11.

Sidhu S, Marsh DJ, Theodosopoulos G et al (2002) Comparative genomic hybridization analysis of adrenocortical tumors. J Clin Endocrinol Metab 87:3467–3474PubMedCrossRef

12.

Gruschwitz T, Breza J, Wunderlich H, Junker K (2010) Improvement of histopathological classification of adrenal gland tumors by genetic differentiation. World J Urol 28:329–334PubMedCrossRef

13.

Kjellman M, Larsson C, Bäckdahl M (2001) Genetic background of adrenocortical tumor development. World J Surg 25:948–956PubMedCrossRef

14.

Gicquel C, Leblond-Francillard M, Bertagna X et al (1994) Clonal analysis of human adrenocortical carcinomas and secreting adenomas. Clin Endocrinol (Oxf) 40:465–477CrossRef

15.

Beuschlein F, Reincke M, Karl M et al (1994) Clonal composition of human adrenocortical neoplasms. Cancer Res 54:4927–4932PubMed

16.

Kjellman M, Roshani L, Teh BT et al (1999) Genotyping of adrenocortical tumors: very frequent deletions of the MEN1 locus in 11q13 and of a 1-centimorgan region in 2p16. J Clin Endocrinol Metab 84:730–735PubMedCrossRef

17.

Bernard MH, Sidhu S, Berger N et al (2003) A case report in favor of a multistep adrenocortical tumorigenesis. J Clin Endocrinol Metab 88:998–1001PubMedCrossRef

18.

Trezzi R, Poli F, Fellegara G (2009) “Dedifferentiated” adrenal cortical neoplasm. Int J Surg Pathol 17:343–344PubMedCrossRef

19.

Gaujoux S, Tissier F, Groussin L et al (2008) Wnt/beta-catenin and 3',5'-cyclic adenosine 5'-monophosphate/protein kinase A signaling pathways alterations and somatic beta-catenin gene mutations in the progression of adrenocortical tumors. J Clin Endocrinol Metab 93:4135–4140PubMedCrossRef

20.

Schmitt A, Saremaslani P, Schmid S et al (2006) IGFII and MIB1 immunohistochemistry is helpful for the differentiation of benign from malignant adrenocortical tumours. Histopathology 49:298–307PubMedCrossRef

21.

van't Sant HP, Bouvy ND, Kazemier G et al (2007) The prognostic value of two different histopathological scoring systems for adrenocortical carcinomas. Histopathology 51:239–245CrossRef

22.

de Reyniès A, Assié G, Rickman DS et al (2009) Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival. J Clin Oncol 27:1108–1115PubMedCrossRef

23.

Giordano TJ, Kuick R, Else T et al (2009) Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res 15:668–676PubMedCrossRef

24.

Laurell C, Velázquez-Fernández D, Lindsten K et al (2009) Transcriptional profiling enables molecular classification of adrenocortical tumours. Eur J Endocrinol 161:141–152PubMedCrossRef

25.

Ragazzon B, Libé R, Gaujoux S et al (2010) Transcriptome analysis reveals that p53 and {beta}-catenin alterations occur in a group of aggressive adrenocortical cancers. Cancer Res 70:8276–8281PubMedCrossRef

26.

Ragazzon B, Assié G, Bertherat J (2011) Transcriptome analysis of adrenocortical cancers: from molecular classification to the identification of new treatments. Endocr Relat Cancer 18:R15–R27PubMedCrossRef

27.

Bussey KJ, Demeure MJ (2009) Genomic and expression profiling of adrenocortical carcinoma: application to diagnosis, prognosis and treatment. Future Oncol 5:641–655PubMedCrossRef

28.

Bussey KJ, Demeure MJ (2011) Toward a pathway-centered approach for the treatment of adrenocortical carcinoma. Curr Opin Oncol 23:34–44PubMedCrossRef

29.

Martinerie C, Gicquel C, Louvel A et al (2001) Altered expression of novH is associated with human adrenocortical tumorigenesis. J Clin Endocrinol Metab 86:3929–3940PubMedCrossRef

30.

Berthon A, Sahut-Barnola I, Lambert-Langlais S et al (2010) Constitutive beta-catenin activation induces adrenal hyperplasia and promotes adrenal cancer development. Hum Mol Genet 19:1561–1576PubMedCrossRef

31.

Tissier F, Cavard C, Groussin L et al (2005) Mutations of beta-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors. Cancer Res 65:7622–7627PubMed

32.

Tadjine M, Lampron A, Ouadi L, Bourdeau I (2008) Frequent mutations of beta-catenin gene in sporadic secreting adrenocortical adenomas. Clin Endocrinol (Oxf) 68:264–270

33.

Bonnet S, Gaujoux S, Launay P et al (2011) Wnt/{beta}-catenin pathway activation in adrenocortical adenomas is frequently due to somatic CTNNB1-activating mutations, which are associated with larger and nonsecreting tumors: a study in cortisol-secreting and -nonsecreting tumors. J Clin Endocrinol Metab 96:E419–E426PubMedCrossRef

34.

Tadjine M, Lampron A, Ouadi L et al (2008) Detection of somatic beta-catenin mutations in primary pigmented nodular adrenocortical disease (PPNAD). Clin Endocrinol (Oxf) 69:367–373CrossRef

35.

Gaujoux S, Grabar S, Fassnacht M et al (2011) β-catenin activation is associated with specific clinical and pathologic characteristics and a poor outcome in adrenocortical carcinoma. Clin Cancer Res 17:328–336PubMedCrossRef

36.

Durand J, Lampron A, Mazzuco TL, Chapman A, Bourdeau I (2011) Characterization of differential gene expression in adrenocortical tumors harboring {beta}-catenin (CTNNB1) mutations. J Clin Endocrinol Metab 96:E1206–E1211PubMedCrossRef

37.

Chapman A, Durand J, Ouadi L, Bourdeau I (2011) Identification of genetic alterations of AXIN2 gene in adrenocortical tumors. J Clin Endocrinol Metab (Epub ahead of print)

38.

Kakimoto S, Yushita Y, Sanefuji T et al (1986) Non-hormonal adrenocortical adenoma with oncocytoma-like appearances. Hinyokika Kiyo 32:757–763PubMed

39.

Wong DD, Spagnolo DV, Bisceglia M et al (2011) Oncocytic adrenocortical neoplasms—a clinicopathologic study of 13 new cases emphasizing the importance of their recognition. Hum Pathol 42:489–499PubMedCrossRef

40.

Saad R, Marsault S, Coloby P (2011) Adrenocortical oncocytic cells tumor: case report and review of literature. Prog Urol 21:288–290PubMed

41.

Mwandila M, Waller H, Stott V, Mercer P (2010) A case of a testosterone-secreting oncocytic adrenocortical carcinoma. N Z Med J 123:80–82PubMed

42.

Rosenkrantz AB, Do RK, Hajdu CH (2010) Imaging appearance of bulk fat within an oncocytic adrenocortical neoplasm, a rare and potentially malignant tumour. Br J Radiol 83:e204–e207PubMedCrossRef

43.

Cham E, Watkin W, Goldschmidt R, Liu L (2010) Fine needle aspiration cytology of adrenocortical oncocytic neoplasm: a case report. Acta Cytol 54:627–634PubMed

44.

Ohtake H, Kawamura H, Matsuzaki M et al (2010) Oncocytic adrenocortical carcinoma. Ann Diagn Pathol 14:204–208PubMedCrossRef

45.

Bisceglia M, Ben-Dor D, Pasquinelli G (2005) Oncocytic adrenocortical tumors. Pathol Case Rev 10:228–242CrossRef

46.

Bisceglia M, Ludovico O, Di Mattia A et al (2004) Adrenocortical oncocytic tumors: report of 10 cases and review of the literature. Int J Surg Pathol 12:231–243PubMedCrossRef

47.

Willems SM, Wiweger M, van Roggen JF, Hogendoorn PC (2010) Running GAGs: myxoid matrix in tumor pathology revisited: what's in it for the pathologist? Virchows Arch 456:181–192PubMedCrossRef

48.

Papotti M, Volante M, Duregon E et al (2010) Adrenocortical tumors with myxoid features: a distinct morphologic and phenotypical variant exhibiting malignant behavior. Am J Surg Pathol 34:973–983PubMedCrossRef

49.

Brown FM, Gaffey TA, Wold LE, Lloyd RV (2000) Myxoid neoplasms of the adrenal cortex: a rare histologic variant. Am J Surg Pathol 24:396–401PubMedCrossRef

50.

Raparia K, Ayala AG, Sienko A, Zhai QJ, Ro JY (2008) Myxoid adrenal cortical neoplasms. Ann Diagn Pathol 12:344–348PubMedCrossRef

51.

Dundr P, Novák K (2003) Pseudoglandular myxoid adenoma of the adrenal gland. Pathol Res Pract 199:493–496PubMedCrossRef

52.

Honda K, Kashima K, Daa T et al (2001) Myxoid adrenal cortical adenoma. Pathol Int 51:887–891PubMedCrossRef

53.

Jang KY, Chung MJ, Moon WS et al (2009) Adrenocortical adenoma with unusual myxoid histological pattern: a case report. Pathology 41:188–191PubMedCrossRef

54.

Ishida M, Yoshida K, Miyamoto K et al (2008) Cytological features of myxoid adrenocortical adenoma with a pseudoglandular component: a case report with differential diagnostic considerations. Diagn Cytopathol 36:576–580PubMedCrossRef

55.

Fine SW, Pindzola JA, Uhlman EJ, Epstein JI (2005) Pathologic quiz case: a 64-year-old man with an adrenal mass. Myxoid adrenal cortical neoplasm. Arch Pathol Lab Med 129:541–542PubMed

56.

De Padua M, Rajagopal V (2008) Myxoid adrenal adenoma with focal pseudoglandular pattern. Indian J Med Sci 62:199–203PubMedCrossRef

57.

Zhu Y, Wu YX, Zhang CY et al (2008) Myxoid adrenocortical adenoma: a case report. Chin Med J (Engl) 121:1598–1600

58.

Lu HS, Gan MF, Chen HS, Huang SQ (2008) Adrenal myelolipoma within myxoid cortical adenoma associated with Conn's syndrome. J Zhejiang Univ Sci B 9:500–505PubMed

59.

Bollito ER, Papotti M, Porpiglia F et al (2004) Myxoid adrenocortical adenoma with a pseudoglandular pattern. Virchows Arch 445:414–418PubMedCrossRef

60.

Tang CK, Harriman BB, Toker C (1979) Myxoid adrenal cortical carcinoma: a light and electron microscopic study. Arch Pathol Lab Med 103:635–638PubMed

61.

Forsthoefel KF (1994) Myxoid adrenal cortical carcinoma. A case report with differential diagnostic considerations. Arch Pathol Lab Med 118:1151–1153PubMed

62.

Hsieh MS, Chen JH, Lin LW (2010) Myxoid adrenal cortical carcinoma presenting as primary hyperaldosteronism: case report and review of the literature. Int J Surg Pathol (Epub ahead of print)

63.

Karim RZ, Wills EJ, McCarthy SW, Scolyer RA (2006) Myxoid variant of adrenocortical carcinoma: report of a unique case. Pathol Int 56:89–94PubMedCrossRef

64.

Suresh B, Kishore TA, Albert AS, Joy A (2005) Myxoid adrenal cortical carcinoma—a rare variant of adrenocortical carcinoma. Indian J Med Sci 59:505–507PubMedCrossRef

65.

Izumi M, Serizawa H, Iwaya K et al (2003) A case of myxoid adrenocortical carcinoma with extensive lipomatous metaplasia. Arch Pathol Lab Med 127:227–230PubMed

66.

DeLellis RA, Lloyd RV, Heitz PU, Eng C (2004) World Health Organization classification of tumours. Pathology and genetics of tumours of endocrine organs. IARC, Lyon

67.

Sturm N, Moulai N, Laverrière MH et al (2008) Primary adrenocortical sarcomatoid carcinoma: case report and review of literature. Virchows Arch 452:215–219PubMedCrossRef

68.

Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (2004) World Health Organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. IARC, Lyon

69.

Sasaki K, Desimone M, Rao HR, Huang GJ, Seethala RR (2010) Adrenocortical carcinosarcoma: a case report and review of the literature. Diagn Pathol 5:51PubMed

70.

Coli A, Di Giorgio A, Castri F (2010) Sarcomatoid carcinoma of the adrenal gland: a case report and review of literature. Pathol Res Pract 206:59–65PubMedCrossRef

71.

Lee MS, Park IA, Chi JG et al (1997) Adrenal carcinosarcoma—a case report. J Korean Med Sci 12:374–377PubMed

72.

Barksdale SK, Marincola FM, Jaffe G (1993) Carcinosarcoma of the adrenal cortex presenting with mineralocorticoid excess. Am J Surg Pathol 17:941–945PubMedCrossRef

73.

Fischler DF, Nunez C, Levin HS et al (1992) Adrenal carcinosarcoma presenting in a woman with clinical signs of virilization. A case report with immunohistochemical and ultrastructural findings. Am J Surg Pathol 16:626–631PubMedCrossRef

74.

Decorato JW, Gruber H, Petti M, Levowitz BS (1990) Adrenal carcinosarcoma. J Surg Oncol 45:134–136PubMedCrossRef

75.

Collina G, Maldarizzi F, Betts CM, Eusebi V (1989) Primary sarcomatoid carcinoma of the adrenal gland. First case report. Virchows Arch A Pathol Anat Histopathol 415:161–167PubMedCrossRef

76.

Okazumi S, Asano T, Ryu M et al (1987) Surgical resection of adrenal carcinoma extending into the vena cava, right atrium and ventricle: case report and review of the literature. Nippon Geka Gakkai Zasshi 88:231–238PubMed

77.

Weissferdt A, Moran CA (2011) Malignant biphasic tumors of the lungs. Adv Anat Pathol 18:179–189PubMedCrossRef

78.

Molberg K, Vuitch F, Stewart D, Albores-Saavedra J (1992) Adrenocortical blastoma. Hum Pathol 23:1187–1190PubMedCrossRef

79.

Lack EE (2007) Tumors of the adrenal glands and extraadrenal paraganglia—volume 8 (Afip Atlas of Tumor Pathology Series 4). American Registry of Pathology, Washington

80.

Liu J, Brown RE (2010) Immunohistochemical detection of epithelialmesenchymal transition associated with stemness phenotype in anaplastic thyroid carcinoma. Int J Clin Exp Pathol 3:755–762PubMed

81.

Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890PubMedCrossRef

82.

Guarino M, Tricomi P, Giordano F, Cristofori E (1996) Sarcomatoid carcinomas: pathological and histopathogenetic considerations. Pathology 28:298–305PubMedCrossRef

83.

Jin Z, Ogata S, Tamura G et al (2003) Carcinosarcomas (malignant mullerian mixed tumors) of the uterus and ovary: a genetic study with special reference to histogenesis. Int J Gynecol Pathol 22:368–373PubMedCrossRef

84.

Dacic S, Finkelstein SD, Sasatomi E, Swalsky PA, Yousem SA (2002) Molecular pathogenesis of pulmonary carcinosarcoma as determined by microdissection-based allelotyping. Am J Surg Pathol 26:510–516PubMedCrossRef

85.

Thompson L, Chang B, Barsky SH (1996) Monoclonal origins of malignant mixed tumors (carcinosarcomas). Evidence for a divergent histogenesis. Am J Surg Pathol 20:277–285PubMedCrossRef

86.

Roma AA, Malpica A, Deavers MT (2011) Malignant melanoma arising in an ovarian carcinosarcoma: case report and review of the literature. Int J Gynecol Pathol 30:158–162PubMedCrossRef

87.

Liu J, Wu H (2011) Carcinosarcoma of female urethra with melanocytic differentiation. Int J Clin Exp Pathol 4:206–209PubMed

88.

Amant F, Moerman P, Davel GH et al (2001) Uterine carcinosarcoma with melanocytic differentiation. Int J Gynecol Pathol 20:186–190PubMedCrossRef

89.

Kajo K, Zubor P, Spacek J, Ryska A (2007) Carcinosarcoma of the uterus with melanocytic differentiation. Pathol Res Pract 203:753–758PubMedCrossRef

90.

Zarineh A, Silverman JF (2011) Adrenal perivascular epithelioid cell tumor: a case report with discussion of differential diagnoses. Arch Pathol Lab Med 135:499–502PubMed

91.

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 20:889–897PubMedCrossRef

92.

Gupta R, Sharma A, Arora R, Vijayaraghavan M (2009) Composite phaeochromocytoma with malignant peripheral nerve sheath tumour and rhabdomyosarcomatous differentiation in a patient without von Recklinghausen disease. J Clin Pathol 62:659–661PubMedCrossRef

Title: Adrenocortical neoplasia: evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants
Authors: Ronald R. de Krijger
Thomas G. Papathomas
Publication date: 01-01-2012
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 1/2012
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-011-1166-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Adrenocortical neoplasia: evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants

Abstract

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Springer Medicine

Abstract

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