Corticotroph
pituitary carcinomas are
tumors, defined by the presence of distant
metastases that determine their poor prognosis. The diagnosis and
therapy of malignant
corticotroph adenomas remains a clinical challenge. The molecular mechanisms of malignant transformation of
pituitary adenomas are unclear, although they are believed to arise in an
adenoma-to-
carcinoma sequence. We describe two cases of malignant
Cushing's disease with
metastases in liver and bone, respectively. The primary
pituitary tumors were treated by a combination of
radiotherapy and transsphenoidal surgery, but recurred several times in both patients. The time interval between the diagnosis of
Cushing's disease and the discovery of
metastases was 32 and 17 years, respectively. In the first case the patient died within 6 months after diagnosis of
metastasis, whereas the second patient is alive at a follow-up of 2 years after the discovery of the
metastasis. Furthermore, we reviewed all available cases of corticotroph
pituitary carcinomas reported in the literature and analyzed their clinical features and therapeutical management. In conclusion, frequent relapses of
Cushing's disease, aggressive growth of macroadenoma, Nelson's syndrome after
adrenalectomy or persistently high
ACTH levels should prompt the clinician to consider the possibility of pituitary corticotroph
carcinomas.