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
ABSTRACT We created a registry for pediatric adrenocortical tumors (ACTs), which are rare and are not well characterized. We provide a descriptive analysis of 254 patients registered on the International Pediatric Adrenocortical Tumor Registry.
Between January 1990 and December 2001, 254 patients younger than 20 years of age with newly diagnosed or previously treated ACTs were registered. A histologic diagnosis of ACT was required, although central review was not mandatory. Follow-up information was periodically requested from the referring physician. Treatment was chosen by the primary physician.
The overall female-male ratio was 1.6:1, but it varied widely among age groups. The most common presenting sign (84.2%) was virilization. Cushing's syndrome without virilization was uncommon (5.5%). Tumors were completely resected in 83% of patients. Patients with disseminated or residual disease received mitotane, cisplatin, etoposide, and/or doxorubicin, and rarely, radiation therapy. At a median follow-up of 2 years and 5 months, 157 patients (61.8%) survived without evidence of disease and 97 patients (38.2%) had died. The 5-year event-free survival estimate was 54.2% (95% CI, 48.2% to 60.2%). In a multivariate analysis, disease stage, presenting signs of endocrine dysfunction, and age were independently associated with prognosis.
Childhood ACTs occur predominantly in females and almost always causes clinical signs. Complete resection is required for cure. Residual or metastatic disease carries a poor prognosis. Our results demonstrate the feasibility of a disease-specific database for obtaining meaningful clinical and outcome information.
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- "Dehner et al. suggested the importance of the vena cava invasion as the only independent predictor of unfavourable outcome, but proposed the tumor weight as the main prognostic indicator, defining as high risk tumors those weighing more than 400 g . In our experience, the scoring system suggested by Wienecke in 2001, which included tumor weight, vena cava invasion and other histological features (Table 1) , was a strong predictor of prognosis, and a volume less than 200 cm 3 positively correlated with OS and EFS  . It is true that in the group of patients who died the tumor was less than 200 cm 3 in 5, but two of them were infants, for whom it should be taken into account the different proportion between body weight and tumor size. "
ABSTRACT: Aim: Adrenocortical tumors are very rare in children. The distinction between adenoma and carcinoma is complex because of their clinical/histological characteristics. The analysis of the cases registered in two consecutive Italian Studies is described, in order to provide additional insight into their nature and possibly identify benign and malignant lesions. Materials and Methods: The analysis includes patients registered from?? 1.1982 to 6.2011 into two consecutive Italian protocols. Results: Fifty-eight children (age 2-210 months) were evaluated. Endocrine manifestations were the most frequent symptoms. Stage distribution at diagnosis was: ST I 35, ST II 17, ST III 1, ST IV 5. Treatment consisted in mitotane for ST II, mitotane + chemotherapy for ST III/IV. Forty-four patients are alive without evidence of disease, 1 is alive with disease, 12 died of disease and 1 because of cardiomyopathy. The Wienecke score system was applied in 24 patients with good significance. A p53 mutation was found in 7 cases, and it was diagnostic for Li-Fraumeni syndrome in 2 benign tumors. Conclusions: The results highlight the importance of a complete excision to obtain the cure of patients. The efficacy of chemotherapy is controversial, however it was able to control the disease in 4 patients in ST II. The value of the Wienecke score system in predicting patients' outcome was confirmed. p53 mutation was more frequent in malignant tumors and represented the sentinel of the Li-Fraumeni syndrome.Journal of Pediatric Surgery 09/2014; 49(9):1367-71. DOI:10.1016/j.jpedsurg.2014.03.006 · 1.31 Impact Factor
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- "In our case, the patient presented with precocious puberty which is in line with the observations made by Michalkiewicz et al.  who found in a registry of 254 pediatric patients with ACTs that 55% with virilization alone. Twenty-nine percent presented with mixed overproduction of adrenal hormones. "
ABSTRACT: Adrenocortical tumors (ACTs) causing Cushing's syndrome are extremely rare in children and adolescents. Bilateral macronodular adrenocortical disease which is a component of the McCune-Albright syndrome is the most common cause of endogenous Cushing's syndrome. We report the case of a boy with Cushing's syndrome who presented with obesity and growth retardation. The child was hypertensive. The biochemical evaluation revealed that his serum cortisol levels were 25.80 μg/dL, with a concomitant plasma ACTH level of 10.0 pg/mL and nonsuppressed serum cortisol on high-dose dexamethasone suppression test (HDDST) to be 20.38 μg/dL. Computed tomography of the abdomen demonstrated a 8 × 6 × 5 cm left adrenal mass with internal calcifications. Following preoperative stabilization, laparotomy was carried out which revealed a lobulated left adrenal mass with intact capsule weighing 120 grams. Histopathological examination revealed a benign cortical neoplastic lesion, suggestive of adrenal adenoma; composed of large polygonal cells with centrally placed nuclei and prominent nucleoli without capsular and vascular invasion. On the seventh postoperative day, cortisol levels were within normal range indicating biochemical remission of Cushing's syndrome. On followup after three months, the patient showed significant clinical improvement and had lost moderate amount of weight and adrenal imaging was found to be normal.03/2013; 2013:706989. DOI:10.1155/2013/706989
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- "In adult patients, the prognostic parameters associated with shorter survival were older age at diagnosis, cortisol hypersecretion and initial stage III or IV (Abiven et al., 2006). Data from the International Pediatric Adrenocortical Tumor Registry demonstrated that patients with localized disease, age between 0 and 3 years, virilization alone, disease stage I, absence of spillage during surgery, and tumor weight <200 g were associated with a greater probability of disease-free survival (Michalkiewicz et al., 2004). "
ABSTRACT: Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. The incidence of pediatric adrenocortical tumors (ACT) is remarkably high in Southern Brazil, where it is estimated to be 15 times greater than the world occurrence, due to a high frequency of a germline mutation (p.R337H) of the TP53 gene. Differently from adults, pediatric adrenocortical neoplasms with apparently poor prognosis based on histopathological features have often a good clinical outcome. A high Weiss score is definitely not a good predictor of survival in children, but it is much more discriminative of a poor outcome in adult tumors. Besides important differences in prognosis, adrenocortical tumorigenesis has distinct patterns between children and adults. In this review, we summarize recent data from ours and other Institutions, showing that the prognostic importance of molecular markers is striking different between pediatric and adult ACT. Although the majority of pediatric ACT are associated with p.R337H germline mutation, it is not a predictor of poor outcome in children and adolescents with ACT. On the other side, TP53 somatic mutations define a subgroup of adult ACC with different tumorigenesis and unfavorable prognosis. IGF system has a central role in the malignant phenotype of ACT, but in adult tumors it is mediated by IGF2 over-expression and in pediatric tumors by IGF1R over-expression. Finally, SF1 over-expression is associated with decreased overall survival and recurrence-free survival in adult ACC, but not in the pediatric group. In conclusion, discriminating benign and malignant behavior is more challenging in pediatric ACT than in adult tumors.Molecular and Cellular Endocrinology 03/2012; 351(1):52-7. DOI:10.1016/j.mce.2011.09.040 · 4.24 Impact Factor