Pediatric ACT extensive experiency from 1979 to 2012: results from 77 patients from Hospital das Clinicas, Sao Paulo, Brazil

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 1-36-Adrenal Incidentaloma & Carcinoma
Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-20
Augusto Cezar Santomauro Junior Sr.*1, Talita Cardoso Goncalves2, Antonio Marcondes Lerario3, Madson Q Almeida3, Berenice Bilharinho Mendonca4 and Ana Claudia Latronico5
1Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 2Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, São Paulo, Brazil, 3Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, 4Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 5Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular/LIM42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil.
Introduction The most commonly encountered pediatric adrenocortical tumors (ACT) are carcinoma (ACC) and adenoma (ACA). Worldwide incidence is reported to be between 0.3-0.38 per million children<15 yrs, however in southern Brazil, the incidence is reported to be as high as 4.2 per million children, due to a founder effect by a unique germline mutation (TP53–R337H). Our aim is present the extensive experience over 33 yrs from a unique institution with ATC pediatric patients. Methods A retrospective analysis of clinical, laboratory, radiological, histopathological and molecular findings of the 77 pediatric patients treated in Hospital das Clinicas, Sao Paulo, Brazil between 1979-2012. Results: ACT incidence was 2.14 per year, with 83.7% from the Southern Brazil. Most were female (76.7%) and white (84.7%) and were less than 2 yrs (51,4%). The time interval between the onset and excision of tumor in 40.3% was <1yr. Most patients had clinical signs of virilization where in 90.1% was associated with clinical signs of Cushing's syndrome. Laboratory findings: 95.5% had elevated serum testosterone levels, 90.5% showed no suppression of cortisol after overnight dexamethasone suppression test. In most cases, US or MRI were used as the image diagnostic method. Tumor site: 53.3% in the right adrenal and only one had bilateral tumor. Tumor staging: 40% were in stage I and only 16% in stage IV. Surgical treatment: only 24.2% underwent laparoscopy. Complete surgical removal was achieved in 65.3%. In 14 patients was used mitotane and 4 underwent chemotherapy with systemic cytotoxic drugs. Tumor size and weight ranged from 1.5-15cm and 3-1230g. Mean points at Weiss system were 4.2±2.4 (diffuse architecture and nuclear atypia criteria were found more). A germline mutation in TP53 was found in 67.4%. The clinical follow-up period ranged from 0.16-26yrs. One year after surgery, 50% were considered in remission. In 20.8%, metastatic sites were identified (lung most common), between 2 and 68 months after surgery, and 55.5% died. Of 20 patients who have regular clinical follow and showed pubertal development, only 1 had early puberty that was treated with hormonal blockade. Nobody presented with features of classical or like Li-Fraumeni syndrome Conclusion: Childhood ACTs occur predominantly in females and most of them present virilization. Complete resection is required for cure or long term remission. Residual or metastatic disease carries a poor prognosis. Exposure to excess androgens in early childhood for a short period of time seems to not compromise pubertal development and also final stature. Although the majority of pediatric ACT is associated with p.R337H germline mutation, it’s not a predictor of poor outcome. IGF system has a central role in the malignant phenotype of ACT, in pediatric tumors it is mediated by IGF1R overexpression. The continued follow-up will provide more consistency to our findings.

Nothing to Disclose: ACS Sr., TCG, AML, MQA, BBM, ACL

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