Abstract
Plexiform neurofibromas are congenital peripheral nerve sheath tumors characteristic
of neurofibromatosis type 1 (NF1)—a frequent neurocutaneous disorder caused by mutations
of the NF1 tumor suppressor gene. Since plexiform neurofibromas are a major cause
of the burden of disease and may also progress to malignancy, many efforts have been
undertaken to find a cure for these tumors. However, neither surgery nor medication
has so far produced a breakthrough therapeutic success. Recently, a clinical phase
I study reported significant shrinkage of plexiform neurofibromas following treatment
with the MEK inhibitor selumetinib. Here, we report an 11-year-old NF1 patient with
a large plexiform neurofibroma of the neck that had led to a sharp-angled kinking
of the cervical spine and subsequent myelopathy. Although surgical stabilization of
the cervical vertebral column was urgently recommended, the vertebral column was inaccessible
due to extensive tumor growth. In this situation, treatment with the MEK inhibitor
trametinib was initiated which resulted in a 22% reduction in tumor volume after 6
months of therapy and finally enabled surgery. These data show that MEK inhibitors
may not lead to complete disappearance of NF1-associated plexiform neurofibromas but
can be an essential step in a multimodal therapeutic approach for these tumors. The
course of our patient suggests that MEK inhibitors are likely to play a significant
role in providing a cure for one of the most devastating manifestations of NF1.
Keywords
plexiform neurofibroma - neurofibromatosis type 1 - MEK inhibitor - trametinib - tuberous
sclerosis - everolimus
