Management of Plexiform Neurofibromas in NF1

Herbert B. Newton, MD, FAAN: The prevalence of plexiform neurofibromas in patients with NF1 [neurofibromatosis type 1] is that they arise in around 30% to 50% of patients with this disease. They’re very variable in terms of their overall size, invasiveness, depth within tissues, and involvement with surrounding structures.

The prognosis is also variable because the phenotype in any 1 patient with NF1 can vary a lot from those who are mildly affected to those who have severe disease with large tumors that are very invasive and difficult to remove. So it depends on how severe and extensive their disease is as well as how many tumors they have and how severe those tumors are.

Malignant peripheral nerve sheath tumors are actually a type of neurofibrosarcoma. It’s a subtype of the sarcoma group of peripheral tumors. These derive from Schwann cells, and they comprise 3% to 10% of all soft tissue sarcomas. They can develop anywhere in the body, but there is an increased risk by 20-fold of them occurring in the area where there’s already an existing internal plexiform neurofibroma.

The cumulative lifetime risk of developing a malignant peripheral nerve sheath tumor in a patient who has NF [neurofibromatosis] is roughly 8% to 13%. It’s very hard for us to predict who’s going to get one and who isn’t. So we’ve got to watch for red flags in a given patient in terms of a tumor that’s growing very rapidly, has rapidly escalating pain, a change in consistency of a given tumor, going from very soft to very hard type of consistency, and then patients who are developing rapidly new neurological symptoms.

In the perfect world, we like to approach neurofibromatosis type 1 with a multidisciplinary team, and that will depend somewhat on whether you’re at an adult NF center versus a pediatric NF center. But in general, the team members we would like to see for the management of this type of disease would be a neurosurgeon, a neurooncologist or a general neurologist, an adult medical oncologist or a pediatric oncologist, an orthopedic surgeon for any spine-related issues or other bony related issues, an ophthalmologist to monitor the eyes and the vision, a physical therapist, an occupational therapist, a speech therapist, an audiologist to monitor hearing, and then a medical geneticist for advising on genetic issues.

Most patients with NF1 will be followed by either an oncologist, medical or pediatric, or a neurologist who could be a neurooncologist or a general neurologist. They will do most of the routine follow-up and visits with the patient and will do screening CTs and MRI scans. They will follow them for any increasing tumor growth or issues that need to be dealt with. Then they often bring in the other specialists when needed, whether that’s a neurosurgeon, an orthopedist, or an ophthalmologist, and they help coordinate the care.

NF1 is a genetic disease. It’s an autosomal dominant mutation in the NF1 gene located on chromosome 17. This is a tumor suppressor gene, and around 50% of this patient population will have a family history of NF1. The other 50% will develop the disease through de novo or spontaneous mutations. It’s very helpful to have a genetic counselor involved to talk to the patient’s family about their risk for transmitting this disease to their offspring. The genetic counselor will go through the family history and see if they really do have a familial form of NF1 or perhaps it was more of a spontaneous mutation. Then they’re going to give them advice on how likely it is to pass the disease on to their children.