Pathogenesis and treatment of aggressive corticotroph pituitary tumors

Abstract

Although the majority of corticotroph pituitary tumors are microadenomas and amenable to complete surgical resection, a subset exhibits a higher frequency of local invasiveness, tendency to recur, and potential to progress to carcinoma. Specifically, Crooke’s cell adenomas, silent corticotroph adenomas, and corticotroph tumors in the setting of Nelson’s syndrome are often more aggressive. These tumors may exhibit higher Ki-67 and/or p53 immunostaining though this is not uniform. Emerging molecular markers show promise but have not yet been validated in routine clinical use. Therapy is generally multimodal with surgical debulking to alleviate compressive symptoms, radiation therapy to prevent or delay tumor growth, and medical therapies to manage the many adverse metabolic consequences of hypercortisolism. However, many of these agents do not inhibit tumor growth and recently temozolomide, an alkylating chemotherapy agent, has been demonstrated to offer stabilization and in some instances partial and/or complete regression of these aggressive corticotroph tumors.