Publications

Abstract

Aggressive pituitary tumors (APT) refer to pituitary adenomas exhibiting rapid growth, resistance to conventional treatments and/or early/multiple recurrences, with abandonment of the previous term 'atypical pituitary adenoma'. Pituitary carcinomas (PC) are defined by non-contiguous craniospinal or distant metastasis. Whilst PC is exceedingly rare, comprising only 0.1-0.2% of all pituitary neoplasms, APT may account for up to 15% of all pituitary neoplasms, depending on the definition used. Typically evolving from known pituitary macroadenomas, APT/PC is most commonly diagnosed in the fifth decade of life with corticotroph and lactotroph neoplasms predominating. Diagnosis relies on MRI, hormonal studies and histological assessment including proliferative markers and immunohistochemistry for pituitary hormones and, most recently, transcription factors. Structural and molecular mechanisms have been proposed in the pathogenesis of APT/PC, although there appears to be no contribution from known familial pituitary tumor syndrome genes such as MEN1. Treatment is multimodal, ideally delivered by an expert team with a high-volume caseload. Surgical resection may be performed with the aim of either gross total resection or tumor debulking. Radiotherapy may be administered either as fractionated external beam radiation or stereotactic radiosurgery. Standard pituitary medical therapies such as somatostatin analogues have limited efficacy in APT/PC, whereas temozolomide yields a clear survival benefit. Evidence is emerging for the use of peptide receptor radionuclide therapy, tyrosine kinase inhibitors, VEGF inhibitors, and immunotherapy. Avenues for further research in APT/PC include molecular biomarkers, nuclear imaging, establishment of an international register, and routine pituitary tumor biobanking.