Aggressive pituitary tumors

Abstract

Pituitary adenomas are common intracranial tumors that are mainly considered as benign. Rarely, these tumors can exhibit an aggressive behavior, characterized by gross invasion of the surrounding tissues, resistance to conventional treatment leading to early and frequent recurrences. Even more rarely, pituitary tumors can give rise to cerebrospinal or systemic metastases qualifying as pituitary carcinomas according to the latest WHO definition. In the same classification, a subset of tumors with relatively distinct histopathological features was identified and defined as atypical adenomas designated to follow a more aggressive clinical course. This classification, although clinically useful, does not provide an accurate correlation between histopathological findings and the clinical behavior of these tumors, neither is it adequate to convey the precise features of 'aggressive' tumors. Thus, 'aggressive' pituitary adenomas need to be properly defined with clinical, radiological, histological and molecular markers in order to identify patients at increased risk of early recurrence or subsequent tumor progression. At present, no single marker or classification system of pituitary tumor aggressiveness exists, and clinically useful information in the literature is insufficient to guide diagnostic and therapeutic decisions. Treatment of patients with aggressive pituitary tumors is challenging since conventional treatments often fail, necessitating multiple surgical procedures with additional radiotherapy. Although traditional chemotherapy applied in other neuroendocrine tumors has not been shown to be efficacious, newer agents, particularly temozolomide, have shown promising results and are currently used despite the lack of data from a randomized prospective trial. Molecular targeted therapies such as mTOR and epidermal growth factor inhibitors have also been applied and might prove to be useful in the management of these patients. In the present review, we provide information regarding the epidemiology and clinical, histopathological and molecular features of aggressive pituitary tumors using recent employed definitions. In addition, we review currently employed therapeutic means providing a therapeutic algorithm and highlight the need to identify more specific disease-related and prognostic markers and the necessity for central registration of these tumors.