Trametinib Combined with Pazopanib for Treating Malignant Peripheral Nerve Sheath Tumor in NF-1 Patients: A Case Report and A Review of the Literature

Neurofibromatosis type 1 is a pathological condition due to the mutation of the NF1 gene that occurs in one to 3000 newborns, in many ethnic groups, in both males and females equally. Almost all individuals with NF1 develop peripheral plexiform neurofibroma and about 10% of them will undergo malignant transformation to malignant peripheral nerve sheath tumors (MPNSTs). Rarely this kind of tumor localizes intracranial (not associated with any cranial nerve and more common in the supratentorial region) and may begin with unexplained spontaneous intracerebral bleeding without any other symptoms before. Since NF1 is also associated with intracerebral vascular malformations and Moya disease, often this highly malignant and aggressive tumor is underestimated, and the diagnosis is mistaken until the histological analysis is made. Current knowledge about clinical presentation and best therapeutic management is limited by the restricted number of patients reported over a long period and treated with various modalities. However, recent progression in genomic analysis allows highlighting the incidence of genomic alterations on intracellular signaling pathways leading to aberrant cell proliferation and targeting them with a targeted therapy. The current study presents the case of an 18-year-old man with MPNST without a family history of NF-1. The studies were retrospectively reviewed, and the patient’s clinicopathological data, including tumor site, treatment, follow-up, prognosis, and genomic profiling, were collected.