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Pathological and molecular features of adrenocortical carcinoma: an update

¹ Division of Pathology, Department of Clinical & Biological Sciences, University of Turin at San Luigi Hospital, Orbassano, Torino, Italy
² Division of Oncology, Department of Clinical & Biological Sciences, University of Turin at San Luigi Hospital, Orbassano, Torino, Italy

Correspondence to:
Dr M Papotti, Department of Clinical and Biological Sciences, University of Turin at San Luigi Hospital, Regione Gonzole 10, I-10043 Orbassano, Torino, Italy; mauro.papotti{at}unito.it

The pathological diagnosis of adrenocortical carcinoma (ACC), which is based on gross and microscopic criteria, is subjective. None of the features are absolutely indicative of malignancy, although their combination in a scoring system may correctly identify ACC. The Weiss system, which is currently the most popular, combines nine morphological parameters, of which three are structural ("dark" cytoplasm, diffuse architecture, necrosis), three are cytological (atypia, mitotic count, atypical mitotic figures) and three are related to invasion (of sinusoids, veins and tumour capsule). Although there are strictly defined criteria for each feature, some are straightforward and objective, while others are potentially more problematic (diffuse architecture, necrosis, sinusoidal, venous and capsular invasions). The classification of oncocytic and paediatric adrenocortical tumours is even more challenging, as not all of the above morphological parameters are predictors of malignancy in these tumour types. As an alternative to the morphological approach, a wide array of chromosomal, genetic, molecular and immunohistochemical markers have been tested in ACC to identify reliable diagnostic and prognostic factors. Genetic and epigenetic alterations of p53, IGF-2 and molecules involved in cancer cell invasive properties seem the most promising. These molecular markers may not only play a role in the biology of these tumours and have prognostic implications, but may also be used as potential targets for treatment. However, these markers are not sufficiently sensitive and specific to replace conventional morphological criteria.