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Adrenocortical Cancer in Children

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Abstract

Adrenocortical cancer (ACC) is a rare but aggressive childhood endocrine neoplasm. Its incidence in children is extremely low (only 0.2% of pediatric cancers) [1], and most pediatric oncologists see few cases or none. Little is known about this malignancy and most available information has been learned from its more frequent adult counterpart. In recent years, an international registry has provided insight into the clinical characteristics and relevant management issues regarding pediatric ACC and tumor tissue for biological studies. These studies have resulted in the discovery of a novel mechanism of tumorigenesis [2], the gift to science by one of the rarest childhood cancers.

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References

  1. Bernstein L, Gurney JG (1999) Carcinomas and other malignant epithelial neoplasms. In: Ries LAG et al (eds) Cancer and survival among children and adolescents: United States SEER program 1975–1995. National Cancer Institute, SEER program, Bethesda, MD, pp 139–147

    Google Scholar 

  2. Ribeiro RC et al (2001) An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma. Proc Natl Acad Sci USA 98:9330–9335

    Article  CAS  PubMed  Google Scholar 

  3. Wooten MD, King DK (1993) Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature. Cancer 72:3145–3155

    Article  CAS  PubMed  Google Scholar 

  4. Figueiredo BC et al (2006) Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation. J Med Genet 43:91–96

    Article  CAS  PubMed  Google Scholar 

  5. Pianovski MAD et al (2006) Mortality rate of adrenocortical tumors in children under 15 years of age in Curitiba, Brazil. Pediatr Blood Cancer 47:56–60

    Article  PubMed  Google Scholar 

  6. Ribeiro RC, Figueiredo B (2004) Childhood adrenocortical tumours. Eur J Cancer 40:1117–1126

    Article  CAS  PubMed  Google Scholar 

  7. Rodriguez-Galindo C et al (2005) Biology, clinical characteristics, and management of adrenocortical tumors in children. Pediatr Blood Cancer 45:265–273

    Article  PubMed  Google Scholar 

  8. Hoyme HE et al (1998) Isolated hemihyperplasia (Hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review. Am J Med Genet 79:274–278

    Article  CAS  PubMed  Google Scholar 

  9. Steenman M et al (2000) Genetics of Beckwith-Wiedeman syndrome-associated tumors: common genetic pathways. Genes Chromosomes Cancer 28:1–13

    Article  CAS  PubMed  Google Scholar 

  10. Varan A et al (2000) Adrenocortical carcinoma associated with adrenogenital syndrome in a child. Med Pediatr Oncol 35:88–90

    Article  CAS  PubMed  Google Scholar 

  11. Sutter JA, Grimberg A (2006) Adrenocortical tumors and hyperplasias in childhood – etiology, genetics, clinical presentation and therapy. Pediatr Endocrinol Rev 4:32–39

    PubMed  Google Scholar 

  12. Langer P et al (2002) Adrenal involvement in multiple endocrine neoplasia type 1. World J Surg 26:891–896

    Article  PubMed  Google Scholar 

  13. Kirschner LS (2002) Signaling pathways in adrenocortical cancer. Ann N Y Acad Sci 968:222–239

    Article  CAS  PubMed  Google Scholar 

  14. Barlaskar FM, Hammer GD (2007) The molecular genetics of adrenocortical carcinoma. Rev Endocr Metab Disord 8:343–348

    Article  PubMed  Google Scholar 

  15. Ilvesmaki V et al (1993) Insulin-like growth factors (IGFs) and their receptors in adrenal tumors: high IGF-II expression in functional adrenocortical carcinomas. J Clin Endocrinol Metab 77:852–858

    Article  CAS  PubMed  Google Scholar 

  16. Boulle N et al (1998) Increased levels of insulin-like growth factor II (IGF-II) and IGF binding protein-2 are associated with malignancy in sporadic adrenocortical tumors. J Clin Endocrinol Metab 83:1713–1720

    Article  CAS  PubMed  Google Scholar 

  17. Gicquel C et al (2001) Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors. Cancer Res 61:6762–6767

    CAS  PubMed  Google Scholar 

  18. Almeida MQ et al (2008) Expression of insulin-like growth factor-ii and its receptor in pediatric and adult adrenocortical tumors. J Clin Endocrinol Metab 93:3524–3531

    Article  CAS  PubMed  Google Scholar 

  19. West AN et al (2007) Gene expression profiling of childhood adrenocortical tumors. Cancer Res 67:600–608

    Article  CAS  PubMed  Google Scholar 

  20. Weber MM et al (2000) The role of the insulin-like growth factor system in adrenocortical tumorigenesis. Eur J Clin Invest 30(Suppl 3):69–75

    Article  CAS  PubMed  Google Scholar 

  21. Weber MM et al (1999) Postnatal overexpression of insulin-like growth factor II in transgenic mice is associated with adrenocortical hyperplasia and enhanced steroidogenesis. Endocrinology 140:1537–1543

    Article  CAS  PubMed  Google Scholar 

  22. Tissier F 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 65:7622–7627

    CAS  PubMed  Google Scholar 

  23. Birch J et al (2001) Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20:4621–4628

    Article  CAS  PubMed  Google Scholar 

  24. Kleihues P et al (1997) Tumors associated with p53 germline mutations. A synopsis of 91 families. Am J Pathol 150:1–13

    CAS  PubMed  Google Scholar 

  25. Gonzalez KD et al (2009) Beyond Li Fraumeni syndrome: clinical characteristics of families with p53 germline mutations. J Clin Oncol 27:1250–1256

    Article  CAS  PubMed  Google Scholar 

  26. Varley JM et al (1999) Are there low-penetrance TP53 alleles? Evidence from childhood adrenocortical tumors. Am J Hum Genet 65:995–1006

    Article  CAS  PubMed  Google Scholar 

  27. Wagner J et al (1994) High frequency of germline p53 mutations in childhood adrenocortical cancer. J Natl Cancer Inst 86:1707–1710

    Article  CAS  PubMed  Google Scholar 

  28. Ariffin H et al (2008) Li-Fraumeni syndrome in a Malaysian kindred. Cancer Genet Cytogenet 186:49–53

    Article  CAS  PubMed  Google Scholar 

  29. Khayat CM, Johnston DL (2004) Rhabdomyosarcoma, osteosarcoma, and adrenocortical carcinoma in a child with a germline p53 mutation. Pediatr Blood Cancer 43:683–686

    Article  PubMed  Google Scholar 

  30. Rossbach H-C et al (2008) Composite adrenal anaplastic neuroblastoma and virilizing adrenocortical tumor with germline TP53 R248W mutation. Pediatr Blood Cancer 50:681–683

    Article  PubMed  Google Scholar 

  31. Reincke M et al (1994) p53 mutations in human adrenocortical neoplasms: immunohistochemical and molecular studies. J Clin Endocrinol Metab 78:790–794

    Article  CAS  PubMed  Google Scholar 

  32. DiGiammarino EL et al (2001) A novel mechanism of tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer. Nat Struct Biol 9:12–16

    Article  CAS  Google Scholar 

  33. West AN et al (2006) Identification of a novel germ line variant hotspot mutant p53-R175L in pediatric adrenal cortical carcinoma. Cancer Res 66:5056–5062

    Article  CAS  PubMed  Google Scholar 

  34. Dohna M et al (2000) Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications. Genes Chromosomes Cancer 28:145–152

    Article  CAS  PubMed  Google Scholar 

  35. Figueiredo BC et al (1999) Comparative genomic hybridization analysis of adrenocortical tumors of childhood. J Clin Endocrinol Metab 84:1116–1121

    Article  CAS  PubMed  Google Scholar 

  36. Loncarevic IF et al (2008) Number of genomic imbalances correlates with the overall survival for adrenocortical cancer in childhood. Pediatr Blood Cancer 51:356–362

    Article  PubMed  Google Scholar 

  37. Doghman M et al (2007) Increased steroidogenic factor-1 dosage triggers adrenocortical cell proliferation and cancer. Mol Endocrinol 21:2968–2987

    Article  CAS  PubMed  Google Scholar 

  38. Wajchenberg BL et al (2000) Adrenocortical carcinoma: clinical and laboratory observations. Cancer 88:711–736

    Article  CAS  PubMed  Google Scholar 

  39. Ribeiro RC et al (1990) Adrenocortical carcinoma in children: a study of 40 cases. J Clin Oncol 8:67–74

    CAS  PubMed  Google Scholar 

  40. Ciftci AO et al (2001) Adrenocortical tumors in children. J Pediatr Surg 36:549–554

    Article  CAS  PubMed  Google Scholar 

  41. Driver CP et al (1998) Adrenal cortical tumors in childhood. Pediatr Hematol Oncol 15:527–532

    Article  CAS  PubMed  Google Scholar 

  42. Wieneke JA et al (2003) Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients. Am J Surg Pathol 27:867–881

    Article  PubMed  Google Scholar 

  43. Sandrini R et al (1997) Childhood adrenocortical tumors. J Clin Endocrinol Metab 7:2027–2031

    Article  Google Scholar 

  44. Bugg MF et al (1994) Correlation of pathologic features with clinical outcome in pediatric adrenocortical neoplasia. Am J Clin Pathol 101:625–629

    CAS  PubMed  Google Scholar 

  45. Teinturier C et al (1999) Clinical and prognostic aspects of adrenocortical neoplasms in childhood. Med Pediatr Oncol 32:106–111

    CAS  PubMed  Google Scholar 

  46. Michalkiewicz E et al (2004) Clinical and outcome characteristics of children with adrenocortical tumors. An analysis of 254 cases from the international pediatric adrenocortical tumor registry. J Clin Oncol 22:838–845

    Article  CAS  PubMed  Google Scholar 

  47. Narasimhan KL et al (2003) Adrenocortical tumors in childhood. Pediatr Surg Int 19:432–435

    Article  CAS  PubMed  Google Scholar 

  48. Hanna AM et al (2008) Outcome of adrenocortical tumors in children. J Pediatr Surg 43:843–849

    Article  PubMed  Google Scholar 

  49. Wang X et al (2007) Nine cases of childhood adrenal tumour presenting with hypertension and a review of the literature. Acta Paediatr 96:930–934

    Article  PubMed  Google Scholar 

  50. Tucci JR et al (2005) The impact of tumor stage on prognosis in children with adrenocortical carcinoma. J Urol 174:2338–2342

    Article  PubMed  Google Scholar 

  51. Ribeiro J et al (2000) Imaging findings in pediatric adrenocortical carcinoma. Pediatr Radiol 30:45–51

    Article  CAS  PubMed  Google Scholar 

  52. Mackie GC et al (2006) Use of [18F]fluorodeoxyglucose positron emission tomography in evaluating locally recurrent and metastatic adrenocortical carcinoma. J Clin Endocrinol Metab 91:2665–2671

    Article  CAS  PubMed  Google Scholar 

  53. Murphy JJ et al (2008) Early experience with PET/CT scan in the evaluation of pediatric abdominal neoplasms. J Pediatr Surg 43:2186–2192

    Article  PubMed  Google Scholar 

  54. Weiss LM (1984) Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 8:163–169

    Article  CAS  PubMed  Google Scholar 

  55. Slooten HV et al (1985) Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer 55:766–773

    Article  PubMed  Google Scholar 

  56. Weiss LM et al (1989) Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 13:202–206

    Article  CAS  PubMed  Google Scholar 

  57. Kendrick ML et al (2001) Adrenocortical carcinoma: surgical progress or status quo? Arch Surg 136:543–549

    Article  CAS  PubMed  Google Scholar 

  58. Stojadinovic A et al (2002) Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. J Clin Oncol 20:941–950

    Article  CAS  PubMed  Google Scholar 

  59. Harrison LE et al (1999) Pathologic features of prognostic significance for adrenocortical carcinoma after curative resection. Arch Surg 134:181–185

    Article  CAS  PubMed  Google Scholar 

  60. Rosati R et al (2008) High frequency of loss of heterozygosity at 11p15 and IGF2 overexpression are not related to clinical outcome in childhood adrenocortical tumors positive for the R337H TP53 mutation. Cancer Genet Cytogenet 186:19–24

    Article  CAS  PubMed  Google Scholar 

  61. Erickson LA et al (2001) Pathologic features and expression of insulin-like growth factor-2 in adrenocortical neoplasms. Endocr Pathol 12:429–435

    Article  CAS  PubMed  Google Scholar 

  62. de Reynies A et al (2009) Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival. J Clin Oncol 27:1108–1115

    Article  PubMed  Google Scholar 

  63. Michalkiewicz EL et al (1997) Clinical characteristics of small functioning adrenocortical tumors in children. Med Pediatr Oncol 28:175–178

    Article  CAS  PubMed  Google Scholar 

  64. Zancanella P et al (2006) Mitotane associated with cisplatin, etoposide, and doxorubicin in advanced childhood adrenocortical carcinoma. Mitotane monitoring and tumor regression. J Pediatr Hematol Oncol 28:513–524

    Article  CAS  PubMed  Google Scholar 

  65. Hovi L et al (2003) Adrenocortical carcinoma in children: a role for etoposide and cisplatin adjuvant therapy? Preliminary report. Med Pediatr Oncol 40:324–326

    Article  CAS  PubMed  Google Scholar 

  66. Stewart JN et al (2004) A surgical approach to adrenocortical tumors in children: the mainstay of treatment. J Pediatr Surg 39:759–763

    Article  PubMed  Google Scholar 

  67. Leung LYJ et al (2002) Ruptured adrenocortical carcinoma as a cause of paediatric acute abdomen. Pediatr Surg Int 18:730–732

    CAS  PubMed  Google Scholar 

  68. Kardar AH (2001) Rupture of adrenal carcinoma after biopsy. J Urol 166:984

    Article  CAS  PubMed  Google Scholar 

  69. Gonzalez RJ et al (2005) Laparoscopic resection of adrenal cortical carcinoma: a cautionary note. Surgery 138:1078–1086

    Article  PubMed  Google Scholar 

  70. Crucitti F et al (1996) the Italian registry for adrenal cortical carcinoma: analysis of a multiinstitutional series of 129 patients. The ACC Italian registry study group. Surgery 119:161–170

    Article  CAS  PubMed  Google Scholar 

  71. Lee JE et al (1995) Surgical management, DNA content, and patient survival in adrenal cortical carcinoma. Surgery 118:1090–1098

    Article  CAS  PubMed  Google Scholar 

  72. Ayass M et al (1991) High-dose carboplatinum and VP-16 in treatment of metastatic adrenal carcinoma. Am J Pediatr Hematol Oncol 13:470–472

    Article  CAS  PubMed  Google Scholar 

  73. Coelho Netto AS et al (1963) Treatment of adrenocortical cancer with o,p' -DDD. Ann Intern Med 59:74–78

    Google Scholar 

  74. Ostuni JA, Roginsky MS (1975) Metastatic adrenal cortical carcinoma: documented cure with combined chemotherapy. Arch Intern Med 135:1257–1258

    Article  CAS  PubMed  Google Scholar 

  75. De Leon DD et al (2002) Long-Term (15 Years) outcome in an infant with metastatic adrenocortical carcinoma. J Clin Endocrinol Metab 87:4452–4456

    Article  PubMed  CAS  Google Scholar 

  76. Wood BJ et al (2003) Radiofrequency ablation of adrenal tumors and adrenocortical carcinoma metastases. Cancer 97:554–560

    Article  PubMed  Google Scholar 

  77. Hoffer FA et al (2009) A phase 1/pilot study of radiofrequency ablation for the treatment of recurrent pediatric solid tumors. Cancer 115:1328–1337

    Article  PubMed  Google Scholar 

  78. Kirschner LS (2006) Emerging treatment strategies for adrenocortical carcinoma: a new hope. J Clin Endocrinol Metab 91:14–21

    Article  CAS  PubMed  Google Scholar 

  79. Barlaskar FM et al (2009) Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma. J Clin Endocrinol Metab 94:204–212

    Article  CAS  PubMed  Google Scholar 

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Rodriguez-Galindo, C., Zambetti, G.P., Ribeiro, R.C. (2009). Adrenocortical Cancer in Children. In: Hammer, G., Else, T. (eds) Adrenocortical Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77236-3_28

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