Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare malignancy with a generally poor prognosis. It is estimated that 10% of ACC cases (especially in children) can be a part of familial cancer predisposition syndrome (mainly Li-Fraumeni and Lynch syndromes), while the cause of the remaining of cases is unknown. The majority of ACC cases produce excessive amounts of steroids hormones, leading to distinct presentations such as Cushing syndrome and androgen excess manifestations. Comprehensive imaging studies are needed to evaluate the chest, abdomen, and pelvis in cases with suspected ACC to guide treatment and surveillance plans and to determine the staging. Key poor prognostic factors in ACC include advanced stage, cortisol overproduction, high tumor proliferation (measured as Ki67% >20%), and incomplete surgical resection/tumor rupture during surgery. Surgery is the mainstay therapy in localized ACC, but the majority of cases suffer tumor recurrences, and thus systemic options are often needed in ACC (advanced or recurrent). Adjuvant therapy (mitotane) has been used based on clinical guidelines to reduce the risk of ACC recurrence after radical surgical resection. Mitotane causes multiple adverse effects, including adrenal insufficiency that requires higher than the average glucocorticosteroid and sometimes mineralocorticosteroid replacement. Traditional chemotherapy in combination with mitotane has been associated with suboptimal responses, and thus there is a need to identify better options to improve long-term outcomes in ACC. The role of immunotherapy in ACC is evolving, and single-agent immune checkpoint inhibitors have shown low levels of responses, including infrequent complete response to therapy. A multidisciplinary team approach is needed in all cases of suspected ACC, considering the complex nature of ACC management.