Adrenocortical carcinoma: a literature review

Adrenocortical carcinoma (ACC) is reported to be present in 3–10% of the population with most tumors presenting as benign tumors. Most cases of ACC are a sporadic accumulation of mutations over time. However, studies show a predisposition to various genetic mutations may contribute. Research over the last couple of decades has elucidated causes of ACC to be driven by several molecular changes that include inactivation of tumor suppressor genes and activation of a myriad of different oncogenes, DNA mutations, and epigenetic changes. The widely adopted staging of ACC is by European Network of Study of Adrenal Tumors (ENSAT) due to its correlations with clinical outcomes. At the time of presentation, a detailed history taking with attention to the history of symptoms of hormonal excess and family history of possible hereditary influence is the first step of evaluation. It is followed by a thorough physical examination for evaluation of ACC. Management of ACC poses a unique challenge as it involves oncologic and endocrine issues. Except for one trial, treatment guidelines are based on retrospective studies and non-randomized trials, and therefore the level of evidence is grade II to grade IV. Personalized therapy including identifying the actionable target in each patient is the future of ACC management. The knowledge base of ACC is evolving based on the basic science and clinical trials conducted by worldwide groups such as COMITE of France, ENSAT of Europe, TCGA project and American Australian Asian Adrenal Alliance (A5). Future studies should aim at clear molecular and clinical standardization. Recommended therapeutic strategies should be prospectively recorded.