Introduction: Pituitary neuroendocrine tumors (PitNET) are frequent intracranial neoplasms, usually with indolent behaviour. However, a significant minority appear to be clinically aggressive, as suggested by early and frequent recurrences and resistance to standard treatments. Metastatic spread is rare. The term “aggressive PitNET” is still inconsistent and poses a diagnostic challenge. In 2013, a prognostic classification was proposed by Trouillas and colleagues and was validated by independent studies. Invasive and proliferative tumors (Trouillas 2b) showed a significantly increased risk of recurrence and progression, irrespective of tumor type. The WHO 2022 classification considers only specific tumor subtypes as more aggressive, but the evidence of a worse prognosis for these types is unclear.

Aims and methods: We aimed to collect and summarize retrospective clinical and pathological data of patients considered to have aggressive pituitary tumors according to our multidisciplinary pituitary tumor board (MPTB), based on the Trouillas classification system.

Result: Among patients discussed at our MPTB between 2017 and 2024, 16 patients (ten men, six women) were found to have aggressive pituitary tumors-all of them invasive and four of these 16 developed metastases. The mean age at diagnosis was 45.4±15.2 years, with a median follow-up of 54 months (range 11-216 months). All patients were diagnosed with a macroadenoma. 50% of patients showed progressive disease at the last follow-up. Three metastatic and two non-metastatic patients died as a result of disease progression. Immunohistochemically, seven tumors (44%) were corticotroph, four (25%) lactotroph, three (19%) gonadotroph, one hormone-negative and one plurihormonal tumor. The median Ki-67 index was 13% (range 3-70%). Ten patients (63%) received pituitary irradiation, and ten patients had more than one pituitary surgery. Two patients received temozolomide treatment.

Conclusion: No single morphological or histological marker has been shown to predict pituitary tumor behaviour. Our results with this limited number of patients’ data did not allow us to draw firm conclusions regarding the diagnosis and treatment of aggressive pituitary tumors. However, our experiences align with the growing evidence that more frequent use of pituitary irradiation and temozolomide treatment are needed for better outcomes.