Adrenocortical carcinoma is a rare heterogeneous
neoplasm with an incompletely understood pathogenesis and a poor prognosis. Previous studies have identified overexpression of
insulin-like growth factor 2 (IGF-2) and constitutive activation of β-
catenin as key factors involved in the development of
adrenocortical carcinoma. Most patients present with
steroid hormone excess, for example
Cushing syndrome or
virilization, or abdominal mass effects, but a growing proportion of patients with
adrenocortical carcinoma (currently >15%) is initially diagnosed incidentally. No general consensus on the diagnostic and therapeutic measures for
adrenocortical carcinoma exists, but collaborative efforts, such as international conferences and networks, including the European Network for the Study of Adrenal
Tumors (ENSAT), have substantially advanced the field. In patients with suspected
adrenocortical carcinoma, a thorough endocrine and imaging work-up is recommended to guide the surgical approach aimed at complete resection of the
tumor. To establish an adequate basis for treatment decisions, pathology reports include the Weiss score to assess
malignancy, the resection status and the Ki67 index. As recurrence is frequent, close follow-up initially every 3 months is mandatory. Most patients benefit from adjuvant
mitotane treatment. In metastatic disease,
mitotane is the cornerstone of initial treatment, and cytotoxic drugs should be added in case of progression. Results of a large phase III trial in advanced
adrenocortical carcinoma are anticipated for 2011 and will hopefully establish a benchmark
therapy. New targeted
therapies, for example,
IGF-1 receptor inhibitors, are under investigation and may soon improve current treatment options.