Diagnosis and clinical management of aggressive pituitary tumors

Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial neoplasms, affecting 1/1000 of the worldwide population and they are largely benign tumors. Aggressive pituitary tumors (APT) are characterized by local aggressiveness, resistance to multimodal standard treatments and are associated with an elevated morbidity and mortality despite the absence of metastasis. Pituitary carcinomas (PC), defined by the presence of systemic metastasis, are rare and occur in the setting of an initially aggressive pituitary tumor. Pathological markers (Ki67 proliferation index ≥10%, elevated mitotic activity, and p53 expression) and genetic mutations (i.e., TP53, ATRX, SF3B1) have been increasingly linked to aggressiveness, metastatic potential, and poorer survival outcomes. Management of these tumors is based on optimizing conventional medical treatment, in combination with radiation therapy in some instances. Temozolomide is currently recommended as first-line chemotherapy in the treatment of APT/PC. Nevertheless, about 30% of patients do not respond to first line temozolomide and other drugs are emerging as potential alternative options with immune check-point inhibitors and bevacizumab being the most effective in selected cases. APT and PC management always requires a multidisciplinary and a multi-modal approach. More studies are needed to identify the best treatment strategies, especially in tumors resistant to first-line treatments.