MON-417 Is There a Cut-Off of Ki-67 Indicative of Pituitary Carcinoma?

Introduction: Carcinomas represent a small percentage (0.1-0.2%) of all pituitary tumours. Several histological, immunocytochemical and ultrastructural characteristics are currently used to classify these tumors. Proliferation and invasion were proposed as prognostic markers. A Ki‐67 proliferation index of ≥3%, as well as strong and diffuse immunopositivity to p53 and invasion of surrounding structures are associated with aggressive clinical behaviour, although no clear morphological difference or specific biomarkers can conclusively differentiate adenomas from pituitary carcinomas. Case: 68 years-old man presented to our department with diplopia, palpebral ptosis, decreased visual acuity, increased weight and easy bruising. On physical exam he presented anisocoria L>R, mild left ptosis and hyperpigmentation. MRI revealed a macroadenoma invading the left cavernous sinus and with posterior growth. The patient underwent transphenoidal surgery resection and the biopsy showed a Ki-67 index of 25%, marked p53 positivity and high mitotic activity. After radiosurgery he was treated with 17 cycles of temozolamide without significant clinical response, then treatment with ketoconazole was initiated and later, in association, pasireotide. The patient developed hepatic dysfunction, with midnight serum cortisol of 73.1 μg/dL (n 1.7-8.9 μg/dL), midnight salivary cortisol of 4910 μg/dL (n <0.320), morning cortisol 69.9 μg/dL (n 6.2-19,4 μg/dL) and ACTH 290.5 ng/L (n <63.3ng/L). Sodium and potassium levels remained within the normal range. An abdominal CT scan showed a hypodense hepatic lesion, with a hypercaptive ring measuring 25 mm and a nodule in the lower lobe of the right lung, suggestive of metastatic lesions. An octreoscan was performed but did not reveal any pathological uptake. The patient underwent liver biopsy which revealed hepatic involvement by a carcinoma with ACTH expression, compatible with pituitary metastasis. Meanwhile metyrapone was initiated with clinical and analytical improvement. Conclusion: The invasive behaviour, a Ki-67 ≥ 10%, strong p53 immunopositivity and high mitotic activity have been proposed as strong predictors of pituitary carcinoma. New data is needed and future research should focus on early identification of this type of tumours in order to improve treatment and prognosis of these patients.