A Case of Pituitary Carcinoma Initially Diagnosed as an Ectopic Growth Hormone Producing Pituitary Adenoma with a High Ki-67 Labeling Index

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We report a case of a 66-year-old woman with a malignant transformation of a growth hormone (GH)-producing pituitary adenoma that was mainly located in the clivus. The patient originally presented with left oculomotor and abducens nerve palsies. Magnetic resonance imaging revealed a clival tumor separated from the normal pituitary gland, and the patient subsequently underwent transsphenoidal surgery. Analysis of the resected clival tissue revealed proliferation of tumor cells with slightly irregular nuclei but no mitosis. Although the Ki-67 labeling index was as high as 8.7%, p53 was negative. Histologic analysis confirmed the diagnosis of a GH-producing pituitary adenoma. Two months after the first operation, the tumor acutely enlarged and caused a subarachnoid hemorrhage. Pathologic findings of the second surgical specimen showed significant nuclear atypia. The Ki-67 labeling index increased to 27.7% and the p53 was positive; there was no GH immunoreactivity. Following the second surgical intervention, the patient was diagnosed with an atypical pituitary adenoma and underwent postoperative local radiotherapy (50 Gy in 25 fractions). Twenty months after the first surgery, multiple bone metastases were detected that led to the diagnosis of pituitary carcinoma. This is the first report of a clival pituitary adenoma undergoing malignant transformation. Because neuroimaging may underestimate local invasiveness in ectopic pituitary tumors, it is essential to conduct a histologic examination to evaluate it. Further analysis of similar cases is necessary to improve clinical management for this confused diagnostic criterion.

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