Aggressive pituitary adenomas: the dark side of the moon

Background: Although pituitary adenomas are considered benign lesions, a small group may exhibit a clinically aggressive behavior, sometimes independently from the classic markers of aggressiveness, including the Ki67 labeling index and/or p53 expression. Methods: We selected 7 subjects harboring a pituitary tumor with clinical features of aggressiveness. Patients underwent a full preoperative and postoperative endocrinological and neuroradiological work-up. Two were nonfunctioning, two PRL-secreting, two ACTH-secreting, and one a GH-secreting adenoma. Results: The 7 patients underwent a total of 17 surgical procedures. At the first surgical procedure in none of the patients a gross total removal was achieved, whereas a subtotal removal - > 90% of tumor removed - was achieved in 4/7 cases, and a partial removal - < 90% of tumor removed - was achieved in 3/7 cases. At first operation, 4/7 patients showed a Ki67 ≤ 3%, 2/7 > 3% ; it was not available in one patient. Postoperatively, all patients underwent radiation therapy. Three patients received chemotherapy with temozolomide. Three patients underwent peptide receptor radionuclide therapy (PRRT). To date, 1 patient died from tumor progression, two patients are in poor general conditions. The remaining 4 patients are in fair/good conditions, without any major complaints. The mean follow-up is 43.42 months. Conclusions: Aggressive pituitary adenomas represent a specific and still underestimated entity, often diagnosed late. Clinical and neuroradiological rapid progression is often the only marker of aggressiveness. Surgical debulking remains first therapeutic option. Multidisciplinary management is mandatory to offer to these patients targeted therapeutic options.