Treatment of Aggressive Pituitary Adenomas and Carcinomas—An Overview

Most pituitary tumors are non-invasive, benign adenomas that remain confined to the sella turcica. Although there is, at present, no accepted definition of aggressive pituitary adenomas, one would suggest that these have a tendency to recur after initial surgery. They have a rapid growth rate and invade surrounding structures such as the sphenoid and cavernous sinus as well as the skull base bone. They are clinically difficult to manage and present major problems due to incomplete resection.¹

Most pituitary tumors are non-invasive, benign adenomas that remain confined to the sella turcica. Although there is, at present, no accepted definition of aggressive pituitary adenomas, one would suggest that these have a tendency to recur after initial surgery. They have a rapid growth rate and invade surrounding structures such as the sphenoid and cavernous sinus as well as the skull base bone. They are clinically difficult to manage and present major problems due to incomplete resection.¹

Pituitary carcinomas are rare—0.2 % of all pituitary tumors. They present major diagnostic and therapeutic challenges. They may initially appear as benign pituitary adenomas subsequently transforming into an aggressive neoplasm, or they may be aggressive tumors from the beginning.^2–4 A pituitary carcinoma is diagnosed when craniospinal and/or systemic metastases are documented.⁵ Predicting pituitary tumor behavior remains a real challenge. Studies suggest that increased mitotic activity, high Ki-67, nuclear labeling index, and P53 expression might be associated with tumor progression.^3,5

Multiple treatment approaches—including surgery, external beam radiotherapy, gamma knife, drugs, and various chemotherapeutic agents—have been used. Until recently, the treatment of pituitary carcinomas was mainly palliative and did not seem to increase overall survival. Progression of disease after a diagnosis of pituitary carcinoma was variable; approximately 75 % of patients with systemic metastasis died of the disease within one year.⁴ Recent publications report efficacy of temozolomide, an alkylating agent used to treat gliomas, in the management of aggressive pituitary adenomas and carcinomas.^6–36 As in gliomas, the outcome of treatment might depend on the expression of O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that counteracts the action of temozolomide.^6,13,37

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