Silent corticotroph carcinoma of the adenohypophysis - A report of five cases

We report five silent corticotroph carcinomas of the pituitary gland. They represent 0.05% of adenohypophyseal tumors surgically treated at Mayo Clinic during a 20-year period and about 5% of all reported pituitary carcinomas. The patients (three females and two males), ranging in age from 26 to 58 years (mean 39 years, median 35 years) presented with symptoms of mass effect; none had Cushing's disease. All tumors were initially invasive macroadenomas, recurred locally, and metastasized, three outside the central nervous system. The follow-up period ranged from 2 to 23 years (mean 10.6 years). All patients died, four of disseminated tumor and one of myocardial infarction. Histologically, three of the primary lesions were indistinguishable from an ordinary benign adenoma. Two were initially diagnosed as atypical adenomas as they featured nuclear pleomorphism, prominent nucleoli, mitotic activity, high MIB-1 labeling indices, and p53 overexpression. For the purpose of comparison, 17 silent corticotroph adenomas were also investigated. In addition, the clinicopathologic features of the silent carcinomas were compared with those of a meta-analysis of published Cushing's disease-associated pituitary carcinomas. The silent adrenocorticotropin carcinomas showed a propensity for extraneural dissemination and an outcome similar to those of the Cushing's disease-associated carcinomas. The two patients with initial atypical tumors died with metastases outside the central nervous system at 2 and 4 years, whereas the three patients with tumors lacking atypia died 16, 18, and 23 years after initial sellar surgery.