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Journal of Pediatric Biochemistry 2015; 05(04): 109-114
DOI: 10.1055/s-0036-1572321
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Pediatric Adrenocortical Tumors: Clinicopathological Features—An Update

Lucia Salvatorelli
1   Anatomic Pathology Section, Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia,” Hospital Policlinico, University of Catania, Catania, Italy
,
Giuseppe Angelico
1   Anatomic Pathology Section, Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia,” Hospital Policlinico, University of Catania, Catania, Italy
,
Fabio Motta
1   Anatomic Pathology Section, Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia,” Hospital Policlinico, University of Catania, Catania, Italy
,
Andrea Di Cataldo
2   Section of Pediatric Hematology and Oncology Unit, Department of Clinical and Experimental Medicine, Hospital Policlinico, University of Catania, Italy
,
Pietro Milone
3   Unit of Radiology, Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia,” Hospital Policlinico, University of Catania, Catania, Italy
,
Martino Ruggieri
4   Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, Hospital Policlinico, University of Catania, Catania, Italy
,
Gaetano Magro
1   Anatomic Pathology Section, Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia,” Hospital Policlinico, University of Catania, Catania, Italy
› Author Affiliations
Further Information

Publication History

23 December 2015

30 December 2015

Publication Date:
03 February 2016 (online)

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Abstract

Pediatric adrenocortical tumors (ACTs) are rare in children. Most tumors are hormonally active with overproduction of androgens and glucocorticoids, and less frequently mineralocorticoids and estrogens. Patients usually present with clinical signs of virilization or Cushing syndrome, while only a minority of ACTs are incidentally discovered. Unfortunately, the clinical behavior of pediatric ACTs is often unpredictable, and the distinction between benign and malignant tumors is still challenging. The present review deals with the main clinical and laboratory features which can help to diagnose pediatric ACTs, with special emphasis on the pathological criteria useful to stratify patients into three different prognostic categories: (1) patients with benign tumors; (2) patients with malignant tumors; and (3) patients with borderline tumors (tumors with indeterminate malignancy). In this regard, general guidelines and histological illustrations are provided to offer a practical approach for a correct identification of morphological predictors of clinical outcome.

Keywords

adrenocortical tumors - pediatric - virilization - Cushing syndrome
 

  • References

  • 1 Klein JD, Turner CG, Gray FL , et al. Adrenal cortical tumors in children: factors associated with poor outcome. J Pediatr Surg 2011; 46 (6) 1201-1207
    CrossrefPubMedSearch in Google Scholar
  • 2 Custódio G, Komechen H, Figueiredo FR, Fachin ND, Pianovski MA, Figueiredo BC. Molecular epidemiology of adrenocortical tumors in southern Brazil. Mol Cell Endocrinol 2012; 351 (1) 44-51
    CrossrefPubMedSearch in Google Scholar
  • 3 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 2001; 86 (10) 4970-4973
    CrossrefPubMedSearch in Google Scholar
  • 4 Cho MJ, Kim DY, Kim SC, Kim TH, Kim IK. Adrenocortical tumors in children 18 years old and younger. J Korean Surg Soc 2012; 82 (4) 246-250
    CrossrefPubMedSearch in Google Scholar
  • 5 Wieneke JA, Thompson LD, Heffess CS. Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients. Am J Surg Pathol 2003; 27 (7) 867-881
    CrossrefPubMedSearch in Google Scholar
  • 6 Gicquel C, Bertagna X, Le Bouc Y. Recent advances in the pathogenesis of adrenocortical tumours. Eur J Endocrinol 1995; 133 (2) 133-144
    CrossrefPubMedSearch in Google Scholar
  • 7 Cagle PT, Hough AJ, Pysher TJ , et al. Comparison of adrenal cortical tumors in children and adults. Cancer 1986; 57 (11) 2235-2237
    CrossrefPubMedSearch in Google Scholar
  • 8 Michalkiewicz E, Sandrini R, Figueiredo B , et al. Clinical and outcome characteristics of children with adrenocortical tumors: a report from the International Pediatric Adrenocortical Tumor Registry. J Clin Oncol 2004; 22 (5) 838-845
    CrossrefPubMedSearch in Google Scholar
  • 9 Ribeiro RC, Figueiredo B. Childhood adrenocortical tumours. Eur J Cancer 2004; 40 (8) 1117-1126
    CrossrefPubMedSearch in Google Scholar
  • 10 Gönç EN, Özön ZA, Cakır MD, Alikaşifoğlu A, Kandemir N. Need for comprehensive hormonal workup in the management of adrenocortical tumors in children. J Clin Res Pediatr Endocrinol 2014; 6 (2) 68-73
    PubMedSearch in Google Scholar
  • 11 Marques-Pereira R, Delacerda L, Lacerda HM, Michalkiewicz E, Sandrini F, Sandrini R. Childhood adrenocortical tumours: a review. Hered Cancer Clin Pract 2006; 4 (2) 81-89
    CrossrefPubMedSearch in Google Scholar
  • 12 Sutter JA, Grimberg A. Adrenocortical tumors and hyperplasias in childhood—etiology, genetics, clinical presentation and therapy. Pediatr Endocrinol Rev 2006; 4 (1) 32-39
    PubMedSearch in Google Scholar
  • 13 Duregon E, Volante M, Rapa I, Vatrano S, Papotti M. Dissecting morphological and molecular heterogeneity in adrenocortical carcinoma. Turk Patoloji Derg 2015; 31 (Suppl. 01) 98-104
    PubMedSearch in Google Scholar
  • 14 Keegan CE, Hammer GD. Recent insights into organogenesis of the adrenal cortex. Trends Endocrinol Metab 2002; 13 (5) 200-208
    CrossrefPubMedSearch in Google Scholar
  • 15 Bugg MF, Ribeiro RC, Roberson PK , et al; Brazilian Group for Treatment of Childhood Adrenocortical Tumors. Correlation of pathologic features with clinical outcome in pediatric adrenocortical neoplasia. A study of a Brazilian population. Am J Clin Pathol 1994; 101 (5) 625-629
    CrossrefPubMedSearch in Google Scholar
  • 16 Martínez León MI, Romero Chaparro S, Weil Lara B , et al. Adrenocortical tumors in children: imaging adenomas and carcinomas [in Spanish]. Radiologia 2012; 54 (4) 342-349
    CrossrefPubMedSearch in Google Scholar
  • 17 Ilias I, Sahdev A, Reznek RH, Grossman AB, Pacak K. The optimal imaging of adrenal tumours: a comparison of different methods. Endocr Relat Cancer 2007; 14 (3) 587-599
    CrossrefPubMedSearch in Google Scholar
  • 18 Magro G, Esposito G, Cecchetto G , et al. Pediatric adrenocortical tumors: morphological diagnostic criteria and immunohistochemical expression of matrix metalloproteinase type 2 and human leucocyte-associated antigen (HLA) class II antigens. Results from the Italian Pediatric Rare Tumor (TREP) Study project. Hum Pathol 2012; 43 (1) 31-39
    CrossrefPubMedSearch in Google Scholar
  • 19 Magro G, Vecchio GM, Alaggio R. Diagnosis and prognosis of pediatric patients with adrenocortical tumors. In: Hayat MA, ed. Pediatric Cancer, Volume 4: Diagnosis, Therapy, and Prognosis. Dordrecht: Springer Science+Business Media; 2013: 245-252
    Search in Google Scholar
  • 20 Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984; 8 (3) 163-169
    CrossrefPubMedSearch in Google Scholar
  • 21 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 2004; 12 (3) 231-243
    CrossrefPubMedSearch in Google Scholar
  • 22 Weiss LM, Medeiros LJ, Vickery Jr AL. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989; 13 (3) 202-206
    CrossrefPubMedSearch in Google Scholar
  • 23 Sandrini R, Ribeiro RC, DeLacerda L. Childhood adrenocortical tumors. J Clin Endocrinol Metab 1997; 82 (7) 2027-2031
    CrossrefPubMedSearch in Google Scholar
  • 24 Pereira BD, Rios ES, Cabrera RA, Portugal J, Raimundo L. Adrenocortical oncocytoma presenting as Cushing's syndrome: an additional report of a paediatric case. Endocr Pathol 2014; 25 (4) 397-403
    CrossrefPubMedSearch in Google Scholar
  • 25 Kawahara Y, Morimoto A, Onoue A, Kashii Y, Fukushima N, Gunji Y. Persistent fever and weight loss due to an interleukin-6-producing adrenocortical oncocytoma in a girl—review of the literature. Eur J Pediatr 2014; 173 (8) 1107-1110
    CrossrefPubMedSearch in Google Scholar
  • 26 Subbiah S, Nahar U, Samujh R, Bhansali A. Heterosexual precocity: rare manifestation of virilizing adrenocortical oncocytoma. Ann Saudi Med 2013; 33 (3) 294-297
    PubMedSearch in Google Scholar
  • 27 Lim YJ, Lee SM, Shin JH, Koh HC, Lee YH. Virilizing adrenocortical oncocytoma in a child: a case report. J Korean Med Sci 2010; 25 (7) 1077-1079
    CrossrefPubMedSearch in Google Scholar
  • 28 Tahar GT, Nejib KN, Sadok SS, Rachid LM. Adrenocortical oncocytoma: a case report and review of literature. J Pediatr Surg 2008; 43 (5) E1-E3
    PubMedSearch in Google Scholar
  • 29 Gumy-Pause F, Bongiovanni M, Wildhaber B, Jenkins JJ, Chardot C, Ozsahin H. Adrenocortical oncocytoma in a child. Pediatr Blood Cancer 2008; 50 (3) 718-721
    CrossrefPubMedSearch in Google Scholar
  • 30 Orhan D, Kale G, Cağlar M, Göğüş S, Karaağaoğlu E. Histone mRNA in situ hybridization and Ki 67 immunohistochemistry in pediatric adrenocortical tumors. Virchows Arch 2006; 448 (5) 591-596
    CrossrefPubMedSearch in Google Scholar
  • 31 West AN, Neale GA, Pounds S , et al. Gene expression profiling of childhood adrenocortical tumors. Cancer Res 2007; 67 (2) 600-608
    CrossrefPubMedSearch in Google Scholar
  • 32 Volante M, Sperone P, Bollito E , et al. Matrix metalloproteinase type 2 expression in malignant adrenocortical tumors: diagnostic and prognostic significance in a series of 50 adrenocortical carcinomas. Mod Pathol 2006; 19 (12) 1563-1569
    CrossrefPubMedSearch in Google Scholar
  • 33 Marx C, Wolkersdörfer GW, Brown JW, Scherbaum WA, Bornstein SR. MHC class II expression—a new tool to assess dignity in adrenocortical tumours. J Clin Endocrinol Metab 1996; 81 (12) 4488-4491
    CrossrefPubMedSearch in Google Scholar
  • 34 Dall'Igna P, Virgone C, De Salvo GL , et al. Adrenocortical tumors in Italian children: analysis of clinical characteristics and P53 status. Data from the national registries. J Pediatr Surg 2014; 49 (9) 1367-1371
    CrossrefPubMedSearch in Google Scholar
  • 35 Teinturier C, Pauchard MS, Brugières L, Landais P, Chaussain JL, Bougnères PF. Clinical and prognostic aspects of adrenocortical neoplasms in childhood. Med Pediatr Oncol 1999; 32 (2) 106-111
    CrossrefPubMedSearch in Google Scholar
  • 36 Yalçin S, Kirli E, Ciftci AO , et al. The association of adrenocortical carcinoma and thyroid cancer in a child with Peutz-Jeghers syndrome. J Pediatr Surg 2011; 46 (3) 570-573
    CrossrefPubMedSearch in Google Scholar
  • 37 Sakoda A, Mushtaq I, Levitt G, Sebire NJ. Clinical and histopathological features of adrenocortical neoplasms in children: retrospective review from a single specialist center. J Pediatr Surg 2014; 49 (3) 410-415
    CrossrefPubMedSearch in Google Scholar
  • 38 Bergadá I, Venara M, Maglio S , et al. Functional adrenal cortical tumors in pediatric patients: a clinicopathologic and immunohistochemical study of a long term follow-up series. Cancer 1996; 77 (4) 771-777
    CrossrefPubMedSearch in Google Scholar