Aggressive and malignant prolactinomas

Prolactin-secreting tumours (prolactinomas) represent the most common pituitary tumour type, accounting for 47-66% of functional pituitary tumours. Prolactinomas are usually benign and controllable tumours as they express abundant levels of dopamine type 2 receptor (D2), and can be treated with dopaminergic drugs, effectively reducing prolactin levels and tumour volume. However, a proportion of prolactinomas exhibits aggressive features (including invasiveness, relevant growth despite adequate dopamine agonist treatment and recurrent potential) and few may exhibit metastasizing potential (carcinomas). In this context, the clinical, pathological and molecular definitions of malignant and aggressive prolactinomas is still to be clearly defined, as primary prolactin-secreting carcinomas are similar to aggressive adenomas until the presence of metastases is detected. Indeed, standard molecular and histological analyses do not reflect differences between carcinomas and adenomas at a first glance and have limitations to predict the aggressive progression of prolactinomas, wherein the causes underlying the aggressive behaviour remain unknown. Herein we present a comprehensive, multidisciplinary review of the most relevant epidemiological, clinical, pathological, genetic, biochemical and molecular aspects of aggressive and malignant prolactinomas..