Adrenocortical tumors in children

Abstract

Childhood adrenocortical tumors (ACT) are rare. In the USA, only about 25 new cases occur each year. In Southern Brazil, however, approximately 10 times that many cases are diagnosed each year. Most cases occur in the contiguous states of São Paulo and Paraná. The cause of this higher rate has not been identified. Familial genetic predisposition to cancer (p53 mutations) and selected genetic syndromes (Beckwith-Wiedemann syndrome) have been associated with childhood ACT in general but not with the Brazilian counterpart. Most of the affected children are young girls with classic endocrine syndromes (virilizing and/or Cushing). Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA-S), which are abnormal in approximately 90% of the cases, provide the pivotal clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of a large, well-defined suprarenal tumor containing calcifications with a thin capsule and central necrosis or hemorrhage. The pathologic classification of pediatric ACT is troublesome. Even an experienced pathologist can find it difficult to differentiate carcinoma from adenoma. Surgery is the single most important procedure in the successful treatment of ACT. The role of chemotherapy in the management of childhood ACT has not been established although occasional tumors are responsive to mitotane or cisplatin-containing regimens. Because of the heterogeneity and rarity of the disease, prognostic factors have been difficult to establish in pediatric ACT. Patients with incomplete tumor resection or with metastatic disease at diagnosis have a dismal prognosis. In patients with localized and completely resected tumors, the size of the tumor has predictive value. Patients with large tumors have a much higher relapse rate than those with small tumors.

Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial

“…Noteworthy, both in univariate and multivariate analysis, tumors secreting androgens or precursors alone had a better prognosis than tumors secreting cortisol alone or with androgens. These data are in agreement with previous reports (Ribeiro et al 2000, Icard et al 2001 and are biologically plausible. In fact, while androgen excess may exert anti-catabolic effects and stimulate erythropoiesis, hypercortisolism has been advocated to be an adverse prognostic factor in advanced small cell lung cancer (Dimopoulos et al 1992).…”

Expression profile of apoptosis-related genes in childhood adrenocortical tumors: low level of expression of BCL2 and TNF genes suggests a poor prognosis

“…The characteristics of our sample regarding clinical data such as age, sex, stage, clinical symptoms, survival, and prognostic factors were similar to those described by the International Pediatric Adrenocortical Tumor Registry (IPACTR) (1) and the frequency of the TP53-p.R337H mutation was also similar to that observed in other Brazilian childhood ACT series (4,5,6).…”

“…However, in Southern Brazil, an inherited germline TP53 mutation (p.R337H) greatly increases the predisposition to the development of childhood ACT, estimated to be 10-15 times higher than the worldwide incidence, and this mutation has been found in over 80% of Brazilian patients with childhood ACT (4,5,6).…”

Adrenal Cortex Tumors and Hyperplasias

“…Its incidence is around 1 to 3 in 10.000.000 except in the southern regions of Brazil where it reaches 1 to 3 :1.000.000 (Agrons et al, 1999;Ribeiro et al, 2000, Wasserman et al, 2011.). In southern Brazil, these carcinomas are frequently associated with a particular mutation of TP53 (namely Arg337His) (Ribeiro et al, 1990).…”

“…These pediatric carcinomas are hormone secreting tumors more frequently than in adults (90% vs 50%) (Michalkiewicz et al, 2004;Patil et al, 2002;Bonfig et al, 2003). The classic endocrine syndromes (namely the virilising and the Cushing's syndromes) represent the most common presentations of adrenocortical carcinomas in this age group (Wilkins, 1948 andRibeiro et al, 2000). However in spite of being pathologically malignant these carcinomas have a much better prognosis, with many of them becoming cured by the first surgical intervention (Michalkiewicz et al, 2004;Sutter et al, 2006;Wieneke et al, 2003;27: Sabbaga et al, 1993) 10.…”