LE JOuRNAL CANADIEN DES SCIENCES NEuROLOGIquES

Endocrinologically active pituitary adenomas are treated either with surgery, radiotherapy or various drugs, including dopamine agonists, long-acting somatostatin analogs, growth hormone receptor antagonists, or corticosteroid secretion inhibitors. Fully 35% to 55% of pituitary adenomas invade adjacent structures. This figure is lower in gonadotroph adenomas, less than 5% compared to other adenoma types. Clinical management of invasive adenomas is challenging, and most of them tend to recur after surgery. Hormonally active pituitary adenomas may even be resistant to combined medical, surgical, and radiotherapy treatments. In comparison, pituitary carcinomas represent 0.2% of all adenohypophysial neoplasms1, and not only invade adjacent structures but give rise to cerebrospinal and/or systemic metastases with high mortality. The lack of response to aggressive pituitary adenomas, particularly carcinomas to conventional therapies, drives search for new approaches1. Temozolomide (TMZ) is a chemotherapeutic agent which can cross the blood-brain barrier and has proven utility in the treatment of glioblastoma. More recently, it has been used to treat aggressive pituitary adenomas and carcinomas2. To date, cases of such aggressive pituitary tumors have been reported in terms of clinical outcomes. The morphologic effects of therapy have been described in only three patients2. Of these, two tumors responded, both radiologically and morphologically. The first case, a prolactin cell adenoma, did not express MGMT (06methylguanine-DNA methyltransferase), a DNA repair protein that counteracts TMZ anti-neoplastic action. The second case, an aggressive silent subtype 2 corticotroph adenoma, showed no morphological change after therapy. This tumor showed highlevel immunoexpression of MGMT by immunohistochemistry. The third case, a corticotroph adenoma in a patient with Cushing’s disease, showed no MGMT immunoexpression, and 80% reduction in tumor volume was noted on magnetic resonance imaging (MRI) scan. The Ki-67 labeling index decreased after the therapy. Herein, we report a recurrent pituitary gonadotroph adenoma in which the partial response to TMZ appeared to result from non-uniform MGMT immunoexpression, portions of the tumor lacking immunoreactivity and the remainder showing high-level immunostaining.