Malignant Prolactinoma Discovered by D2 Receptor Imaging

Malignant prolactinomas are extremely rare (1, 2). The diagnosis of these carcinomas is mainly based on the patient’s medical history and the detection of metastases. Nuclear medicine offers new imaging modalities for the detection of metastases of pituitary carcinomas. These techniques may have serious consequences for subsequent investigations and therapy. The case presented here shows the clinical behavior of a malignant prolactinoma. The usefulness of dopamine D2 receptor scintigraphy for establishing the diagnosis and subsequently directing the therapeutic approach is illustrated. A 43-yr-old man presented with a macroprolactinoma in 1984. He was operated on by a transfrontal approach in 1984 and by two transsphenoidal approaches in 1985. Postoperatively, serum PRL levels did not normalize. The patient showed partial resistance to dopamine agonists; serum PRL levels decreased from 212 μg/L (normal, <20μ g/L) at baseline to 57 μg/L with bromocriptine therapy. From 1984–1991, a progressive rise in serum PRL levels was noted despite treatment with high doses of bromocriptine (55 mg/day) and thereafter quinagolide (0.8 mg/day). When he was referred to us in 1991, his serum PRL level was 757 μg/L on quinagolide and 1575 μg/L without treatment. Pituitary magnetic resonance imaging (MRI) showed a pituitary macroadenoma with bilateral extrasellar extension to the cavernous sinuses. Surgery was repeated using a transcranial approach. However, postoperative serum PRL values remained elevated (2181 μg/L). External pituitary irradiation was administered (total dose, 5000 rads), and treatment with cabergoline was started. From 1991–1993, a progressive decrease in PRL levels was observed (to 84 μg/L) while the patient was still being treated with cabergoline (2.0 mg every 2 days). After this period of relative efficacy of this drug, a progressive rise in serum PRL levels was observed again. The patient was then treated four times with γ-knife radiosurgery (in 1994, 1995, 1996, and 1997). The last γ-knife treatments were less effective than the first ones (Fig. 1). The patient underwent two additional pituitary explorations in 1997 and 1998 via the transcranial route in another center, which did not reveal further tumorous tissue. He was then referred back to us. At the last hospital admission (July 1998), 2 months after the last operation and discontinuation of cabergoline treatment, serum PRL levels were much higher than previously observed (7163 μg/L). Nevertheless, MRI study did not reveal important tumor residue. Because the clinical evolution of the patient strongly suggested a malignant prolactinoma, nuclear imaging studies were performed.