A Rare Case of Pituitary Melanoma Metastasis: A Dramatic and Prolonged Response to Dabrafenib-Trametinib Therapy
Authors: Marilda Mormando, Giulia Puliani, Agnese Barnabei, Rosa Lauretta, Marta Bianchini, Alfonsina Chiefari, Michelangelo Russillo, Francesco Cognetti, Luisa Romano, Marialuisa Appetecchia
Journal: Front Endocrinol (Lausanne) (2020)
Keywords: dabrafenib, melanoma, pituitary, pituitary melanoma metastasis, therapy, trametinib
MeSH terms: Antineoplastic Combined Chemotherapy Protocols / therapeutic use, Melanoma / drug therapy, Pituitary Neoplasms / drug therapy, Skin Neoplasms / drug therapy, Case Reports, Adult, Humans, Imidazoles / administration & dosage, Male, Melanoma / genetics, Melanoma / secondary, Mutation, Oximes / administration & dosage, Pituitary Neoplasms / genetics, Pituitary Neoplasms / pathology, Prognosis, Proto-Oncogene Proteins B-raf / genetics, Pyridones / administration & dosage, Pyrimidinones / administration & dosage, Skin Neoplasms / genetics, Skin Neoplasms / secondary, Imidazoles, Oximes, Pyridones, Pyrimidinones, trametinib, BRAF protein, human, Proto-Oncogene Proteins B-raf, dabrafenib

Introduction: Pituitary metastases (PM) are rare events and to date only very few cases of melanoma PM have been described in literature up to now. Case Presentation: We describe the clinical history of a 33-year-old male patient who underwent surgical excision of an inter-scapular melanoma in 2008. The subsequent follow-up was negative for ~10 years. In September 2018, due to the onset of a severe headache, the patient underwent a brain magnetic resonance imaging, which showed an expansive mass in the saddle and suprasellar region with a maximum diameter of 17 mm. Pituitary function tests and visual field were normal. Worsening of the headache and the appearance of a left eye ptosis led the patient to surgical removal of the lesion in October 2018. The histological examination unexpectedly showed metastasis of the melanoma. Post-operative hormonal assessment showed secondary hypothyroidism and hypoadrenalism, which were both promptly treated, and a mild hypogonadism. Three months after surgery, a sellar MRI showed a persistent, increased pituitary mass (3 cm of diameter); fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) detected an increased radiopharmaceutical uptake in the sellar region. Due to the persistence of the disease and the evidence of a BRAF V600E mutation, in February 2019, the patient underwent a combined treatment with dabrafenib (a BRAF inhibitor) and trametinib (mitogen-activated extracellular signal-regulate kinase inhibitor). Sellar MRI performed 6 months later showed no evidence of mass in the sellar region. The patient was in a good clinical condition and did not complain of headaches or other symptoms; there were no significant side-effects from the anticancer therapy. After 13 months of treatment, the patient showed no recurrence of the disease on morphological imaging. Anticancer therapy was confirmed, replacement therapies with hydrocortisone and levothyroxine continued and the pituitary-gonadal axis was restored. Conclusion: This is a very interesting case, both for the rarity of the pituitary melanoma metastasis and for the singular therapeutic course carried out by the patient. This is the first case of a pituitary melanoma metastasis with BRAF mutation, successfully treated with the combination of dabrafenib and trametinib after incomplete surgical removal.