Malignant corticotrophinoma a clinical report
Márcia Alves1, Isabel Paiva1, Jacinta Santos1, Mariana Martinho2, Alexandra Vieira1, Sofia Gouveia1, Francisco Belo3, Margarida Bastos1 & Manuela Carvalheiro1
Pituitary carcinoma is rare (0.10.2% of pituitary tumors), with a poor prognosis. It usually presents as invasive and secretory (ACTH or prolactin) macroadenoma. The diagnosis is confirmed by the presence of metastases. The latency period between the diagnosis of adenoma and carcinoma is variable (9.5 years for corticotrophinoma). The treatment includes surgery, radiotherapy and chemotherapy.
We report a 58-year-old male, complaining of visual disturbances and headache, without endocrine stigmata. Cranial MRI, performed after an ischemic stroke, detected a sellar mass lesion (24×19×17 mm) with optic chiasm compression and sphenoid sinus invasion. Perimetry was normal. Hormonal study showed: failure of the gonadal, thyroid and GH axis; normal PRL; high levels of cortisol and ACTH with increased response of ACTH to CRH: basal 408 pg/ml (NR:952 pg/ml), at 60 min 4646 pg/ml; free urinary cortisol 585 ug/24 h (NR:1080 ug/24 h); overnight 1mg dexametasone test: cortisol 31 ug/dl (NR:<1.8 ug/dl). Transphenoidal surgery was performed with macroscopically total tumorectomy (histology - corticotrophinoma). Postoperative evaluation showed: normal levels of ACTH and cortisol; gonadal, thyroid and GH insufficiency and diabetes insipidus. He began replacement therapy. Recurrences were detected, with re-interventions: transphenoidal at 3rd, 6th, 7th, 9th and 10th year after initial surgery and subfrontal at 10th year. At the 6th year the histology changed: cellular atypia and progressive increase of proliferative index (PI-27%, p53 positive, Ki-67-11%). Radiotherapy (54Gy/30 sessions) was performed 7 years after diagnosis. After 10 years, lesions suspicious of metastases were found in the right lung, mediastium and bilateral bronchial lymph nodes. Biopsy by mediastinoscopy was performed, but inconclusive. He died with intracranial hypertension one month later.
This case illustrates the slow and progressive evolution of pituitary carcinomas, supporting the hypothesis of progressive loss of differentiation of an adenoma. Therapy available to date is ineffective. There is need to identify markers of malignant potential, to allow early treatment.