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Aims  To determine clinicopathological criteria and molecular markers helpful in distinguishing adrenocortical carcinomas ( ACC s) from adrenocortical adenomas ( ACA s).    Methods and results  We analysed retrospectively the clinical and pathological features of 50 adrenal cortical tumours, and tested the expression of mi R 483‐3p by  in‐situ  hybridization as well as the expression of  IGF 2 and  S mad4 by immunohistochemistry. We found that tumour size, tumour weight, hormonal function and the  W eiss system are all high‐efficacy criteria for differentiating malignant from benign tumours ( P  <   0.001). Mi R 483‐3p was overexpressed in 68% (17 of 25) of  ACC s compared to 12% (three of 25) of  ACA s ( P  <   0.05). Using a combination of mi R 483‐3p and  S mad4 improved diagnostic accuracy. Molecular markers were then tested in an independent set of 15 borderline tumours. We confirmed that the combined use of mi R 483‐3p and Smad4 immunochemistry can complement the Weiss score in the diagnosis of  ACC  in cases that display borderline histology.    Conclusions  Tumour size, tumour weight, hormonal function and the Weiss system are useful clinicopathological criteria that can result in accurate diagnosis of most  ACC s and  ACA s. In challenging cases, mi R 483‐3p and  S mad4 expression may help in distinguishing these two entities.

Distinguishing adrenal cortical carcinomas and adenomas: a study of clinicopathological features and biomarkers