Abstract
Pediatric adrenocortical tumors are rare and heterogeneous endocrine malignancies.
Objectives
To report clinical, biochemical, and histological features, staging, and therapeutic interventions in a cohort of 28 patients treated at a single tertiary center.
Methods
A retrospective review of medical records of children with PACT (diagnosed before <18 years of age) followed between 1987–2018 at Hospital de Pediatría Garrahan, Buenos Aires, Argentina.
Results
Mean age at diagnosis was 4.6 years (range, 0.3–17.3 years) and median follow-up was 4.17 years (range, 0–12 years). Female to male ratio was 2.5:1. Signs and symptoms that prompted medical intervention were hormonal overproduction (57%), abdominal complaints (36%), and hypertensive encephalopathy (7%). In patients with clinically virilizing tumors (n=16) mean height standard deviation score (SDS) and bone age advance were significantly higher while body mass index (BMI) SDS was significantly lower than in those with clinical Cushing’s (n=10) (p<0.05). Serum dehydroepiandrosterone sulfate (DHEAS) levels were significantly higher in stage IV than in stage I (p=0.03). Total adrenalectomy was performed in 26 patients. Eight patients (stage III-IV) received adjuvant chemotherapy. Five-year overall and disease-free survival were 100% for ST I-II, and 51% (95% CI 21–82) and 33% (95% CI 1.2–65) for ST III-IV, respectively (p=0.002). No statistical difference was found when comparing 2-year parameters with and without adjuvant chemotherapy.
Conclusions
Height SDS and BMI SDS seem to mirror hormonal secretion in pediatric adrenocortical tumors. Higher DHEAS levels were found in patients with more advanced disease. Further large-scale studies are needed to validate a possible role for DHEAS as a biochemical marker of tumor stage and to draw robust conclusions on the use of adjuvant chemotherapy.
Acknowledgments
We would like to thank the Departments of General Surgery and Oncology and all those involved in the care and follow-up of patients and families. We are grateful to Miss Janneke Deurloo for English editing.
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Research funding: None declared.
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Author contributions: María Celeste Mattone: contributed to data acquisition, analysis, and interpretation and wrote the manuscript with input from all authors. Silvia Gil: contributed to data acquisition, analysis, and interpretation. Mariana Costanzo: contributed to data acquisition, analysis, and interpretation, and contribute to manuscript writing. María Laura Galluzzo Mutti: reviewed, analyzed, and interpreted the histopathology data. Alejandra Casanovas: contributed to the acquisition and analysis of oncology data. Verónica Zaidman: contributed to the acquisition and analysis of laboratory data. Juan Manuel Lazzati: contributed to the acquisition and analysis of laboratory data. Marta Ciaccio: critically reviewed the manuscript and provided feedback. Alicia Belgorosky: critically reviewed the manuscript regarding important intellectual content and provided feedback. Gabriela Guercio: designed the study and critically reviewed the manuscript regarding important intellectual content. Final approval of the version to be published.
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Competing interests: The authors declare no conflict of interests.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The local Institutional Review Board deemed the study exempt from review.
References
1. McAteer, JP, Huaco, JA, Gow, KW. Predictors of survival in pediatric adrenocortical carcinoma: a surveillance, epidemiology, and end results (SEER) program study. J Pediatr Surg 2013;48:1025–31. https://doi.org/10.1016/j.jpedsurg.2013.02.017.Search in Google Scholar PubMed
2. Rodriguez-Galindo, C, Figueiredo, BC, Zambetti, GP, Ribeiro, RC. Biology, clinical characteristics, and management of adrenocortical tumors in children. Pediatr Blood Cancer 2005;45:265–73. https://doi.org/10.1002/pbc.20318.Search in Google Scholar PubMed
3. Antonini, SR, Leal, LF, Cavalcanti, MM. Pediatric adrenocortical tumors: diagnosis,management and advancements in the understanding of the genetic basis and therapeutic implications. Expet Rev Endocrinol Metabol 2014;9:445–64. https://doi.org/10.1586/17446651.2014.941813.Search in Google Scholar PubMed
4. Michalkiewicz, E, Sandrini, R, Figueiredo, B, Miranda, EC, Caran, E, Oliveira-Filho, AG, et al. Clinical and outcome characteristics of children with adrenocortical tumors: a report from the International Pediatric Adrenocortical Tumor Registry. J Clin Oncol 2004;22:838–45. https://doi.org/10.1200/jco.2004.08.085.Search in Google Scholar
5. Ribeiro, RC, Pinto, EM, Zambetti, GP. Familial predisposition to adrenocortical tumors: clinical and biological features and management strategies. Best Pract Res Clin Endocrinol Metabol 2010;24:477–90. https://doi.org/10.1016/j.beem.2010.03.002.Search in Google Scholar PubMed
6. Ribeiro, RC, Figueiredo, B. Childhood adrenocortical tumours. Eur J Cancer 2004;40:1117–26. https://doi.org/10.1016/j.ejca.2004.01.031.Search in Google Scholar PubMed
7. Almeida, MQ, Latronico, AC. The molecular pathogenesis of childhood adrenocortical tumors. Horm Metab Res 2007;39:461–6. https://doi.org/10.1055/s-2007-981476.Search in Google Scholar PubMed
8. Else, T. Association of adrenocortical carcinoma with familial cancer susceptibility syndromes. Mol Cell Endocrinol 2012;351:66–70. https://doi.org/10.1016/j.mce.2011.12.008.Search in Google Scholar PubMed PubMed Central
9. Speiser, PW, Azziz, R, Baskin, LS, Ghizzoni, L, Hensle, TW, Merke, DP, et al.. Endocrine Society. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2010;95:4133–60. https://doi.org/10.1210/jc.2009-2631.Search in Google Scholar PubMed PubMed Central
10. Gulack, BC, Rialon, KL, Englum, BR, Kim, J, Talbot, LJ, Adibe, OO, et al.. Factors associated with survival in pediatric adrenocortical carcinoma: an analysis of the National Cancer data base (NCDB). J Pediatr Surg 2016;51:172–7. https://doi.org/10.1016/j.jpedsurg.2015.10.039.Search in Google Scholar PubMed PubMed Central
11. Gupta, N, Rivera, M, Novotny, P, Rodriguez, V, Bancos, I, Lteif, A. Adrenocortical carcinoma in children: a clinicopathological analysis of 41 patients at the Mayo clinic from 1950 to 2017. Horm Res Paediatr 2018;90:8–18. https://doi.org/10.1159/000488855.Search in Google Scholar PubMed
12. Wieneke, JA, Thompson, LD, Heffess, CS. Adrenal cortical neoplasms in the pediatricpopulation: a clinicopathologic and immunophenotypic analysis of 83 patients. Am J Surg Pathol 2003;27:867–81. https://doi.org/10.1097/00000478-200307000-00001.Search in Google Scholar PubMed
13. Melo-Leite, AF, Elias, PC, Teixeira, SR, Tucci, S, Barros, GE, Antonini, SR, et al.. Adrenocortical neoplasms in adulthood and childhood: distinct presentation. Review of the clinical, pathological and imaging characteristics. J Pediatr Endocrinol Metab 2017;30:253–76. https://doi.org/10.1515/jpem-2016-0080.Search in Google Scholar PubMed
14. Das, S, Sengupta, M, Islam, N, Roy, P, Datta, C, Mishra, PK, et al.. Weineke criteria, Ki-67 index and p53 status to study pediatric adrenocortical tumors: is there a correlation? J Pediatr Surg 2016;51:1795–800. https://doi.org/10.1016/j.jpedsurg.2016.07.014.Search in Google Scholar PubMed
15. Ribeiro, RC, Pinto, EM, Zambetti, GP, Rodriguez-Galindo, C. The International pediatric adrenocortical tumor registry initiative: contributions to clinical, biological, and treatment advances in pediatric adrenocortical tumors. Mol Cell Endocrinol 2012;351:37–43. https://doi.org/10.1016/j.mce.2011.10.015.Search in Google Scholar PubMed
16. Pappo, AS, Krailo, M, Chen, Z, Rodriguez-Galindo, C, Reaman, G. Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 2010;28:5011–6. https://doi.org/10.1200/jco.2010.31.2603.Search in Google Scholar PubMed PubMed Central
17. Ferrari, A, Schneider, DT, Bisogno, G, EXPeRT Board. The founding of the European cooperative study group on pediatric rare tumors–EXPeRT. Expert Rev Anticancer Ther 2013;13:1–3. https://doi.org/10.1586/era.12.155.Search in Google Scholar PubMed
18. Cecchetto, G, Ganarin, A, Bien, E, Vorwerk, P, Bisogno, G, Godzinski, J, et al.. Outcome and prognostic factors in high-risk childhood adrenocortical carcinomas: a report from the European cooperative study group on pediatric rare tumors (EXPeRT). Pediatr Blood Cancer 2017;64. https://doi.org/10.1002/pbc.26368.Search in Google Scholar PubMed
19. Greulich, W, Pyle, S. Radiographic atlas of skeletal development of the hand and wrist. Stanford, CA: Stanford University Press; 1959.10.1097/00000441-195909000-00030Search in Google Scholar
20. Vaiani, E, Lazzati, JM, Ramirez, P, Costanzo, M, Gil, S, Dratler, G, et al.. The low-dose ACTH test: usefulness of combined analysis of serum and salivary maximum cortisol response in pediatrics. J Clin Endocrinol Metab 2019;104:4323–30. https://doi.org/10.1210/jc.2019-00304.Search in Google Scholar PubMed
21. Weiss, LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984;8:163–9. https://doi.org/10.1097/00000478-198403000-00001.Search in Google Scholar PubMed
22. Aubert, S, Wacrenier, A, Leroy, X, Devos, P, Carnaille, B, Proye, C, et al.. Weiss system revisited: a clinicopathologic and immunohistochemical study of 49 adrenocortical tumors. Am J Surg Pathol 2002;26:1612–9. https://doi.org/10.1097/00000478-200212000-00009.Search in Google Scholar PubMed
23. Di Rienzo, JA, Casanoves, F, Balzarini, MG, Gonzalez, L, Tablada, M, Robledo, CW. InfoStat versión 2018. Universidad Nacional de Córdoba, Argentina: Software Estadístico; 2018.Search in Google Scholar
24. IBM Corp. IBM SPSS statistics for windows, Version 24.0. Armonk, NY: IBM Corp; 2016.Search in Google Scholar
25. Izbizky, G, Elias, D, Gallo, A, Farias, P, Sod, R. Prenatal diagnosis of fetal bilateral adrenal carcinoma. Ultrasound Obstet Gynecol 2005;26:669–71. https://doi.org/10.1002/uog.2623.Search in Google Scholar PubMed
26. Sherer, DM, Dalloul, M, Wagreich, A, Sokolovski, M, Duan, H, Zinn, H, et al.. Prenatal sonographic findings of congenital adrenal cortical adenoma. J Ultrasound Med 2008;27:1091–3. https://doi.org/10.7863/jum.2008.27.7.1091.Search in Google Scholar PubMed
27. Chatterjee, G, DasGupta, S, Mukherjee, G, Sengupta, M, Roy, P, Arun, I, et al.. Usefulness of Wieneke criteria in assessing morphologic characteristics of adrenocortical tumors in children. Pediatr Surg Int 2015;31:563–71. https://doi.org/10.1007/s00383-015-3708-x.Search in Google Scholar PubMed
28. Kerkhofs, TM, Ettaieb, MH, Verhoeven, RH, Kaspers, GJ, Tissing, WJ, Loeffen, J, et al.. Adrenocortical carcinoma in children: first population-based clinicopathological study with long-term follow-up. Oncol Rep 2014;32:2836–44. https://doi.org/10.3892/or.2014.3506.Search in Google Scholar PubMed
29. Dall’Igna, P, Virgone, C, De Salvo, GL, Bertorelle, R, Indolfi, P, De Paoli, A, et al.. Adrenocortical tumors in Italian children: analysis of clinical characteristics and P53 status. Data from the national registries. J Pediatr Surg 2014;49:1367–71. https://doi.org/10.1016/j.jpedsurg.2014.03.006.Search in Google Scholar PubMed
30. Bulzico, D, de Faria, PA, de Paula, MP, Bordallo, MA, Pessoa, CH, Corbo, R, et al.. Recurrence and mortality prognostic factors in childhood adrenocortical tumors: analysis from the Brazilian national institute of cancer experience. Pediatr Hematol Oncol 2016;33:248–58. https://doi.org/10.3109/08880018.2016.1173148.Search in Google Scholar PubMed
31. Wang, Z, Liu, G, Sun, H, Li, K, Dong, K, Ma, Y, et al.. Clinical characteristics and prognosis of adrenocortical tumors in children. Pediatr Surg Int 2019;35:365–71. https://doi.org/10.1007/s00383-018-4409-z.Search in Google Scholar PubMed
32. Berruti, A, Grisanti, S, Pulzer, A, Claps, M, Daffara, F, Loli, P, et al.. Long-term outcomes of adjuvant mitotane therapy in patients with radically resected adrenocortical carcinoma. J Clin Endocrinol Metab 2017;102:1358–65. https://doi.org/10.1210/jc.2016-2894.Search in Google Scholar PubMed
33. Zancanella, P, Pianovski, MA, Oliveira, BH, Ferman, S, Piovezan, GC, Lichtvan, LL, et al.. Mitotane associated with cisplatin, etoposide, and doxorubicin in advanced childhood adrenocortical carcinoma: mitotane monitoring and tumor regression. J Pediatr Hematol Oncol 2006;28:513–24. https://doi.org/10.1097/01.mph.0000212965.52759.1c.Search in Google Scholar PubMed
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2021-0392).
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