Overview of Plexiform Neurofibromas in NF1

Kaleb H. Yohay, MD: What are plexiform neurofibromas? Plexiform neurofibromas are one of the most complex and difficult aspects of neurofibromatosis type 1. These are benign tumors that can develop anywhere in the peripheral nervous system from the spinal roots out to the periphery. They are basically hyperproliferative Schwann cells as well as infiltrating immune cells such as mast cells and fibroblasts. These tumors usually extend along long lengths of nerves or coalesce around groups of nerves, such as the brachial plexus or the lumbosacral plexus.

Where do plexiform neurofibromas develop? Plexiform neurofibromas can really develop anywhere in the peripheral nervous system, arising from paraspinal lesions on the spinal roots all the way out into the periphery. Their clinical manifestations are dependent on where the tumor develops. If they have a superficial component, there are often skin changes overlying the tumor such as thickened skin, hyperpigmentation, or increased hair growth. But tumors can also develop internally without any superficial manifestations and may be found only on the basis of feeling an underlying mass, based on clinical symptoms, or based on imaging findings.

Even though plexiform neurofibromas arise from nerves, they can impact other organ systems, often through direct impact physically on those organs and sometimes through invasion. For instance, sometimes a plexiform neurofibroma can develop intra-abdominally, and sometimes those tumors can involve the intestinal wall. They might also involve the wall of the bladder. When they grow in and around the face or the neck, they can impact blood vessels, the trachea, or the esophagus. But again, it’s primarily through a direct physical impact on those organs and vital structures as opposed to direct invasion.

Plexiform neurofibromas are very complex tumors, and as a result of their complexity, they’re often very difficult to remove surgically. They are highly vascular tumors, so surgery can often result in excessive bleeding. Also, the way these tumors grow within nerves essentially necessitates sacrifice of a nerve to remove the tumor. Any nerve that the tumor is growing on will often be injured at the time of surgery and the function of that nerve lost. The way these tumors grow, they often insinuate themselves around and into adjacent structures and organs, again making surgical resection very difficult. It’s almost impossible to resect these tumors completely.

How do we determine if these tumors are inoperable? It’s a difficult issue, and we’re often weighing the risk of resection with the potential benefit to the patient. The tumors that I would consider inoperable are the ones where there is going to be risk of significant neurologic impairment worse than the symptoms that the patient is already experiencing, or tumors that put the patient at too much risk of blood loss or injury to adjacent vital structures.

Our choices around surgery with the advent of new medical therapies is certainly changing. I do think that there is a role for debulking of these tumors in certain situations, particularly where a limited surgical procedure can provide a patient immediate and safe benefit, either cosmetic or functional. I think over time, we will better be able to ascertain how much medical therapy will replace some of the surgical procedures that we’ve done in the past, but I do think that at this point there’s still a role for both.