Auriemma, Renata Simona (2017) Pituitary aggressive tumors and carcinomas: epidemiological, molecular, clinical, radiological, pathological and therapeutic characterization. [Tesi di dottorato]

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Knowledge about epidemiological, clinical, molecular and pathological characteristics of pituitary aggressive tumors and carcinomas is still scant, and strong evidence about the best therapeutic approach is yet to be achieved. The current study has confirmed pituitary carcinomas to be exceptionally rare, but highlighted that atypical tumors might be more common than previously thought. Apart from the clear-cut definition of atypical and malignant pituitary tumors, based on WHO criteria and on the presence of distant metastases, respectively, nowadays tumors size, recurrence, laterosellar extension and responsiveness to conventional medical treatments appear to be the best clinical and radiological criteria to discriminate pituitary tumors with a true aggressive behavior. Conversely, tumor invasiveness is not a good predictor of tumor aggressiveness and cannot discriminate pituitary atypical and malignant tumors from typical and benign adenomas. Radiotherapy and medical treatments remain the most commonly used therapeutic approaches for pituitary aggressive tumors, but fail to induce the achievement of disease control in most patients. Experience with new target therapies, such as pasireotide and everolimus, is still scant, however in vitro data support the use of combined treatment with pasireotide and everolimus as potential valid alternative treatment in patients with aggressive pituitary tumors poorly responsive to conventional medical treatments. Drug responsiveness can be, however, influenced by specific tumor receptor eterogeneity, tachyphylaxis or other factors influencing drug effectiveness, such as somatostatin receptors and mTOR components expression profile, and in turn early identification of molecular markers able to predict responsiveness to treatment might drive endocrinologists through the choice of the best individualized adjuvant therapy in patients with pituitary aggressive tumors and carcinomas.

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