Metastatic Pituitary Neuroendocrine Tumors

Abstract Metastatic pituitary neuroendocrine tumors (PitNETs), formerly known as pituitary carcinomas, represent a rare subset of pituitary neoplasms, accounting for approximately 0.1% to 0.2% of cases. These tumors typically arise from pre-existing functional macroadenomas and most commonly metastasize to the liver, bone, lungs, and throughout the central nervous system. Given that there are no specific clinical, histopathological, or imaging features that can reliably distinguish metastatic PitNETs from benign or aggressive pituitary adenomas at early stages, timely diagnosis remains challenging. Multidisciplinary management is essential, with therapeutic strategies including repeat surgical resection, radiotherapy, and systemic therapy with temozolomide, either as monotherapy or as part of the Stupp protocol. Emerging therapeutic options, such as peptide receptor radionuclide therapy and immune checkpoint inhibitors, have also shown encouraging results in selected refractory cases. Despite multimodal treatment approaches, sustained responses are uncommon, and the prognosis remains poor, with a mean survival of approximately 2 years following the detection of metastases. Given their rapid progression and unfavorable outcomes, early recognition of metastatic PitNETs is critical. Neurosurgeons should be particularly vigilant in patients with rapidly recurring, hormonally active, and treatment-refractory macroadenomas, as these features may indicate an increased risk of metastatic transformation and warrant closer surveillance. This article reviews the initial clinical presentations, imaging and histopathological characteristics, prognosis, and current management strategies for metastatic PitNETs.