Pituitary carcinoma is a rare disorder accounting for 0.1–0.5% of pituitary neoplasia (1, 2), with a poor prognosis despite maximal multimodal standard therapies. Temozolomide has been suggested as effective in treating pituitary carcinomas (3–5). Here, we describe the case of a 58-year-old man with active Cushing's disease due to a huge pituitary tumor. Repeated adenomectomy failed to control the disease. Histology examination revealed a pituitary adenoma, with positive immunostaining for ACTH and a Ki-67 proliferation index of 10%, whereas Crooke's cells were absent. Ketoconazole and cabergoline treatment being ineffective, conventional radiotherapy (48.6 Gy) was administered. Five years later, magnetic resonance imaging showed a residual pituitary lesion of 28 × 16 mm with suprasellar extension. The hormonal evaluation indicated persistent severe hypercortisolism. Bilateral adrenalectomy was then performed. Twelve months later, plasma ACTH levels dramatically increased (up to 1250 pg/mL), and the pituitary neoplasm extended to the clivus and the C2 body (Figure 1A). Liver, vertebral, and meningeal lesions were detected (Figure 1B); biopsies of hepatic lesions confirmed ACTH-positive neuroendocrine metastases. Temozolomide (160 mg/m2 daily for 5 d) was started. Plasma ACTH levels were unaffected; 27 days later, the patient complained of severe headache, blindness, and rigor nucalis. He was admitted to the intensive care unit where severe thrombocytopenia (18 000/mm3), a previously reported adverse event of temozolomide (3), and multiple cerebral hemorrhagic foci from metastases were diagnosed (Figure 1, C and D). He died a few months after discharge. This case report emphasizes the risk of hemorrhages associated with temozolomide and the need for careful management in patients with aggressive pituitary tumors.
A and B, Pretreatment with temozolomide imaging. A, T1-weighted sagittal image: supra and parasellar right extended lesion involves clivus (arrowhead) and C2 body (arrow). B, Sagittal contrast-enhanced magnetic resonance imaging showed temporal and occipital subarachnoid small ring-enhanced lesions suspected for meningeal metastases (arrows). C and D, After first cycle of treatment with temozolomide imaging. C, CT scan performed in emergency showed multiple hemorrhagic foci. D, T1-weighted magnetic resonance axial image confirmed bilateral massive hemorrhagic lesions in occipital areas surrounded by vasogenic edema in correspondence to previously identified meningeal metastasis.
Acknowledgments
Written informed consent to clinical data publication was obtained from the relatives of the patient before the submission of this manuscript.
Disclosure Summary: All authors have nothing to disclose.
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