• Mineko Murakami, Akiko Mizutani, Shuichiro Asano, Hideki Katakami, Yoshinori Ozawa, Kazuto Yamazaki, Yasuo Ishida, Koji Takano, Hiroko Okinaga, and Akira Matsuno.
• Department of Neurosurgery, Teikyo University Chiba Medical Center, Ichihara City, Chiba, Japan.
• Neurosurgery. 2011 Jun 1; 68 (6): E1761-7; discussion E1767.

Background And ImportanceThe case presented here describes the clinical evolution of a pituitary carcinoma from an atypical prolactinoma after temozolomide (TMZ) treatment. The mechanism of acquisition of TMZ resistance was analyzed.Clinical PresentationA 60-year-old woman with atypical prolactinoma had been treated for 7 years with multiple therapies, including dopamine agonists, surgical intervention (5 times), conventional radiotherapy, and radiosurgery. The patient deteriorated as a result of tumor enlargement. Ten cycles of TMZ therapy, 200 mg/m for 5 days every 4 weeks, improved the patient's performance status and caused tumor shrinkage. Six months after discontinuation of TMZ, the tumor progressed into pituitary carcinoma with tumor regrowth and intraventricular dissemination. TMZ therapy was ineffective this time. A sixth surgery and salvage chemotherapy failed to improve the patient's condition, and she died 9 years after the first diagnosis. Throughout the treatment course, O6-methyl-guanine-DNA methyltransferase (MGMT) was immunonegative in the tumor specimens, including the TMZ-refractory pituitary carcinoma. Mutation of p53 was identified in both the atypical prolactinoma and pituitary carcinoma. In contrast, major differences were noted for mismatch repair protein MSH6 immunostaining: Although MSH6 was diffusely immunopositive in the atypical adenoma, it became immunonegative when the tumor evolved into TMZ-refractory pituitary carcinoma.ConclusionLoss of MSH6 occurred during the progression from an atypical prolactinoma to a pituitary carcinoma, which may have caused resistance to TMZ treatment. This case suggests that preserving MSH6 function is essential for responsiveness to TMZ treatment in MGMT-negative and p53-mutated atypical pituitary adenoma or pituitary carcinoma.Copyright © 2011 by the Congress of Neurological Surgeons

41 keywords...

hide…