ObjectiveTo describe clinical and pathological characteristics and treatment outcomes in a large cohort of aggressive pituitary tumours (APT)/pituitary carcinomas (PC). DesignElectronic survey... Show moreObjectiveTo describe clinical and pathological characteristics and treatment outcomes in a large cohort of aggressive pituitary tumours (APT)/pituitary carcinomas (PC). DesignElectronic survey August 2020-May 2021. Results96% of 171 (121 APT, 50 PC), initially presented as macro/giant tumours, 6 were microadenomas (5 corticotroph). Ninety-seven tumours, initially considered clinically benign, demonstrated aggressive behaviour after 5.5 years (IQR: 2.8-12). Of the patients, 63% were men. Adrenocorticotrophic hormone (ACTH)-secreting tumours constituted 30% of the APT/PC, and the gonadotroph subtypes were under-represented. Five out of 13 silent corticotroph tumours and 2/6 silent somatotroph tumours became secreting. Metastases were observed after median 6.3 years (IQR 3.7-12.1) from diagnosis. At the first surgery, the Ki67 index was >= 3% in 74/93 (80%) and >= 10% in 38/93 (41%) tumours. An absolute increase of Ki67 >= 10% after median of 6 years from the first surgery occurred in 18/49 examined tumours. Tumours with an aggressive course from outset had higher Ki67, mitotic counts, and p53. Temozolomide treatment in 156/171 patients resulted in complete response in 9.6%, partial response in 30.1%, stable disease in 28.1%, and progressive disease in 32.2% of the patients. Treatment with bevacizumab, immune checkpoint inhibitors, and peptide receptor radionuclide therapy resulted in partial regression in 1/10, 1/6, and 3/11, respectively. Median survival in APT and PC was 17.2 and 11.3 years, respectively. Tumours with Ki67 >= 10% and ACTH-secretion were associated with worse prognosis. ConclusionAPT/PCs exhibit a wide and challenging spectrum of behaviour. Temozolomide is the first-line chemotherapy, and other oncological therapies are emerging. Treatment response continues to be difficult to predict with currently studied biomarkers. Show less
Pituitary adenohypophyseal tumors are considered as benign and termed "adenomas". However, many tumors are invasive and a proportion of these exhibit an "aggressive behavior" with premature death... Show morePituitary adenohypophyseal tumors are considered as benign and termed "adenomas". However, many tumors are invasive and a proportion of these exhibit an "aggressive behavior" with premature death due to progressive growth. Only very rare (0.2%) tumors with metastases are considered malignant and termed "carcinomas". Taking into account this variability in behavior and the oncological definition, pathologists have proposed changing the term adenoma to tumor. Here we explain why use the term tumor instead of adenoma and identify tumor characteristics, associated with a high risk for poor prognosis. In a cohort of 125 tumors with aggressive behavior (APT) and 40 carcinomas with metastases (PC), clinical and pathological features were very similar. The comparison of this cohort (APT+PC) with a reference surgical cohort of 374 unselected patients clearly shows that the two cohorts differ greatly, especially the percentage of tumors with Ki67 >= 10% (35%vs3%; p < 0.001). A five-tiered prognostic classification, associating invasion and proliferation, identified grade 2b tumors (invasive and proliferative), with a high risk of recurrence/progression. Because half of the APT+ PC tumors have a Ki67 index >= 10%, and 80% of them show 2 or 3 positive markers of proliferation, we suggest that tumors that are clinically aggressive, invasive and highly proliferative with a Ki67 >= 10%, represent tumors with malignant potential. The percentage of grade 2b tumors, suspected of malignancy, which will become aggressive tumors or carcinomas is unknown. It is probably very low, but higher than 0.2% in surgical series. Early identification and active treatment of these aggressive tumors is needed to decrease morbidity and prolong survival. Show less
