Abstract
Neurofibromatosis type 1 (NF1) is a common autosomal dominant condition caused by mutation in the NF1 tumor-suppressor gene which encodes neurofibrin, a regulator of cell proliferation through the RAS/MAPK pathway. NF1 patients frequently develop central nervous system low-grade gliomas (LGGs), but are also at increased risk for developing malignant tumors such as neuroblastoma which combined are associated with worse prognosis. The association between NF1 and neuroblastoma has been well established, though rarely reported, and its molecular basis still requires further investigation. Additionally, MEK inhibition via disruption of the RAS/MAPK pathway has been shown to be effective in neuroblastoma models in vitro, and is currently being tested in several LGG clinical trials. Co-occurrence of both tumors in a patient with NF1 is exceedingly rare and has been reported only once thus far. Here, we report on the first case in the literature for the use of a MEK inhibitor in a seven years old NF1 patient with high-risk metastatic neuroblastoma and optic pathway glioma without BRAF mutation or fusion. The patient is currently maintained on MEK inhibitor monotherapy for over a year with minimal dermatological side effects. Significant radiographic improvement in the optic pathway glioma as well as stability in the metastatic neuroblastoma has been demonstrated. Comprehensive clinical molecular testing of both tumors is currently pending.