Arch Pathol Lab Med—Vol 129, September 2005 Adrenocortical Tumors in Brazilian Children—Sbragia et al 1127 Adrenocortical Tumors in Brazilian Children Immunohistochemical Markers and Prognostic Factors Lourenco Sbragia, MD, PhD; Antonio Goncalves Oliveira-Filho, MD, MS; JoseVassallo, MD, PhD; Glauce Aparecida Pinto, BS; Gil Guerra-Junior, MD, PhD; Joaquim Bustorff-Silva, MD, PhD ● Context.—The behavior of adrenocortical tumors (ACTs) is usually difficult to establish in childhood, and the role of immunomarkers in predicting outcome has not yet been elucidated. Objective.—To investigate the relationship between clin- ical, pathologic, and immunohistochemical findings and prognosis in a series of children with ACTs. Patients and Methods.—Clinical data were evaluated ret- rospectively in 33 children with ACTs, including age at di- agnosis, sex, time between first symptoms and diagnosis, clinical signs and symptoms, tumor position, and follow- up. Histologic sections were reviewed, each tumor was classified, and staging was performed according to previ- ously published criteria. Immunohistochemical analysis of p53, Ki-67, c-Erb-B2, and Bcl-2 was performed according to previously published techniques. Results.—Sixty-four percent (n  21) of the patients were female, and the age at diagnosis in the cohort ranged from 2 to 96 months. Virilization alone affected 70% (n  23) of the patients, and 18 patients had stage 1 disease, 9 had stage 2 disease, and 3 each had stage 3 and stage 4 disease. Female sex and stage 1 and stage 2 disease were associated with good outcome. None of the histopatholog- ic criteria evaluated correctly predicted outcome. Only tu- mors with a volume exceeding 200 mL were associated with malignant behavior. Because only a small number of tumors expressed the antigens, results of these immuno- histochemical tests were considered inconclusive. Conclusion.—In this sample of pediatric ACTs, the clin- ical and surgical parameters are the most important prog- nostic factors, while the immunohistochemical markers evaluated were not predictive of outcome. (Arch Pathol Lab Med. 2005;129:1127–1131) T umors affecting the adrenal cortex in children are rare, corresponding to an incidence of 0.3 case per 1 000 000 persons per year and representing 0.2% of all childhood tumors. 1 There are 2 peaks of incidence, in those younger than 5 years and in those aged between 40 and 50 years. 1–3 Pathologically, adrenocortical tumors (ACTs) are gen- erally divided into adenomas (benign histologic results) and carcinomas (malignant histologic results). However, their behavior in childhood is usually unpredictable, and distinction based only on histologic classification is diffi- cult. 4–6 Because of the lack of an established relationship between histologic results and prognosis, some authors recommend that ACTs always be classified as carcinomas. 7 Immunomarkers have been extensively studied in these Accepted for publication May 6, 2005. From the Division of Pediatric Surgery, Department of Surgery (Drs Sbragia, Oliveira-Filho, and Bustorff-Silva), Department of Pathology (Dr Vassallo and Mr Pinto), and Pediatric Endocrinology, Department of Pediatrics (Dr Guerra-Junior), School of Medical Sciences, State Uni- versity of Campinas, UNICAMP, Campinas, Sao Paulo, Brazil; and De- partment of Surgery, Boldrini Children’s Cancer Center (Drs Sbragia and Oliveira-Filho), Campinas, Sao Paulo, Brazil. The authors have no relevant financial interest in the products or companies described in this article. Reprints: Lourenco Sbragia, MD, PhD, Division of Pediatric Surgery, Department of Surgery, School of Medical Sciences, State University of Campinas, UNICAMP, Rua Alexander Flemming, 110 Cidade Uni- versitaria, Campinas, Sao Paulo, Brazil 13083-970 (e-mail: sbragia@ fcm.unicamp.br). tumors. Although their role in predicting outcome has not yet been elucidated, the p53 protein has been, so far, the most investigated. 8–12 The Ki-67 nuclear antigen (as a pro- liferative index), the c-Erb-B2 antigen of the cell mem- brane (as a marker of growth factor receptor), and the Bcl- 2 antigen of cell cytoplasm (as an apoptosis marker) have been associated with several types of tumors, but the role of cell cycle regulatory proteins, such as p53 and Ki-67, in ACTs remains controversial, because the rarity of the dis- ease limits adequate study populations to correlate the ex- pression of these proteins with prognosis. 13–24 The objective of this study was to analyze if there were any associations of clinical features, histologic classifica- tion, and presence of immunomarkers with prognosis of these rare tumors in a consecutive series of children treat- ed by the same surgical team in 2 Brazilian medical ser- vices. PATIENTS AND METHODS A retrospective review of the medical charts of 33 consecutive children with ACTs was done. The patients had been treated and followed up on in the Pediatric Endocrinology Service and the Pediatric Surgery Service of the State University of Campinas and Boldrini Children’s Cancer Center since 1980. The principles out- lined in the Declaration of Helsinki were followed, and the Ethics Committee of the State University of Campinas School of Medical Sciences approved the publication of these data. Clinical data were reviewed, such as age at diagnosis, sex, time between first symptoms and diagnosis, clinical signs and symptoms, tumor position, type of surgery, staging, and follow-up.