Adrenocortical Carcinoma

Key-words Disease name and synonyms Definition Clinical Presentation Incidence Staging Prognosis Treatment Etiology Diagnostic methods Unresolved questions References Abstract ACC is a cancer that arises from the adrenal cortex, the outer layer of the adrenal gland. It comprises 0.2% of childhood malignancies with an international incidence of 0.5/1 million and occurs far more commonly in girls than boys (ratio 1.5:1). There is an increased incidence of ACC in patients with isolated hemihypertrophy, Wiedemann-Beckwith syndrom , congenital adrenal hyperplasia (CAH) and Li-Fraumeni syndrome (LFS). Most ACC in children and adolescents are hormone secreting and the clinical presentation reflects the pattern of adrenocortical hormones secreted by that tumor. Signs and symptoms of virilisation are present in over 90% of cases. Hirsutism, acne and deepening of the voice may be apparent in both sexes. Girls may also present with cliteromegaly and facial hair while boys present with phallomegaly and virilisation. Cushing's syndrome occurs in a third of cases with moon facies, centripetal fat distribution and plethora being the most common sign. Diagnosis is based on urine and blood tests, dexamethasone suppression test, abdominal ultrasound, CT and MRI scans. Complete, radical surgical resection is the treatment of choice and may be curative, especially in small tumors. In patients with incomplete resection or metastatic spread, treatment options include chemotherapy and/or Mitotane.ACC is a cancer that arises from the adrenal cortex, the outer layer of the adrenal gland. It comprises 0.2% of childhood malignancies with an international incidence of 0.5/1 million and occurs far more commonly in girls than boys (ratio 1.5:1). There is an increased incidence of ACC in patients with isolated hemihypertrophy, Wiedemann-Beckwith syndrom , congenital adrenal hyperplasia (CAH) and Li-Fraumeni syndrome (LFS). Most ACC in children and adolescents are hormone secreting and the clinical presentation reflects the pattern of adrenocortical hormones secreted by that tumor. Signs and symptoms of virilisation are present in over 90% of cases. Hirsutism, acne and deepening of the voice may be apparent in both sexes. Girls may also present with cliteromegaly and facial hair while boys present with phallomegaly and virilisation. Cushing's syndrome occurs in a third of cases with moon facies, centripetal fat distribution and plethora being the most common sign. Diagnosis is based on urine and blood tests, dexamethasone suppression test, abdominal ultrasound, CT and MRI scans. Complete, radical surgical resection is the treatment of choice and may be curative, especially in small tumors. In patients with incomplete resection or metastatic spread, treatment options include chemotherapy and/or Mitotane. Key-words Childhood malignancies, adrenal gland, adrenocortical hormones, chemotherapy, Mitotane Disease name and synonyms • Adrenocortical carcinoma (ACC) • Adrenocortical tumors (ACT) Definition ACC is a cancer, which originates in the adrenal cortex. The adrenal cortex arises from Brennan B. Adrenocortical carcinoma. Orphanet Encyclopedia. August 2004. http://www.orpha.net/data/patho/GB/uk-ACC.pdf 1 mesenchyme and at term the 'fetal' cortex represents about 80% of the adrenal gland. Within a few days there is rapid involution by apoptosis with little cortex remaining by 6 months of age. Clinical Presentation Most ACC in children and adolescents are hormone secreting and the clinical presentation reflects the pattern of adrenocortical hormones secreted by that tumor. Less than 10% of adrenocortical tumors are non-secreting [1]. Signs and symptoms of virilisation are present in over 90% of cases [Table 1]. Hirsutism, acne and deepening of the voice may be apparent in both sexes. The development of acne in a child under 6 years should make the exclusion of ACC a priority. Girls may also present with cliteromegaly and facial hair while boys present with phallomegaly and virilisation. Cushing's syndrome occurs in a third of cases with moon facies, centripetal fat distribution and plethora being the most common sign. Hypertension is often present and children may present in hypertensive crisis [Table 1]. Generally, ACT are inefficient in producing active hormones such as cortisol and about half will be large enough to palpate at diagnosis. In a recent retrospective study of 54 children with an ACT referred to a regional center, 60% had endocrine symptoms, virilisation, and 40% with an abdominal mass [1]. Careful examination of this cohort revealed endocrine signs and symptoms in 81% [1]. There is often a considerable delay between presentation with endocrine dysfunction and diagnosis [1, 2, 3]. In one large series only 11% of the patients were diagnosed within 6 months of their initial presentation [1]. Table 1: Clinical manifestations of ACT in children [1, 2, 4] Premature/ Secondary Sexual Hair 90% Cliteromegaly 92% Phallomegaly 81% Hirsutism 62.5% Palpable Abdominal Mass 61% Hypertension 54% Acne 47% Plethora 42% Deep Voice 42% Moon Face 35% Seizure (Hypertensive crisis ) 17%