Clinical Forum Highlights Shifting Paradigm in NF1 Plexiform Neurofibroma Care

On September 17, 2026, NeurologyLive convened a clinical forum in Philadelphia titled "Recognizing and Treating Plexiform Neurofibromas in NF1: A New Era of Systemic Management," bringing together community oncologists, hematologists, and neurologists over dinner to discuss the recognition, referral, and treatment of neurofibromatosis type 1 (NF1) and its associated plexiform neurofibromas (PN). The program was moderated by Jessica D. Schulte, MD, PhD, director of adolescent and young adult neuro-oncology and associate professor of neurology at NYU Grossman School of Medicine.

NF1 is one of the most common single-gene disorders in humans, with a birth incidence of about 1 in 2,662. It is an autosomal dominant condition caused by mutations in the NF1 gene, which encodes neurofibromin, a RAS GTPase-activating protein. Loss of function in that gene drives unregulated RAS and MAPK signaling, fueling tumor growth along central and peripheral nerves. About half of all cases arise from de novo mutations, and nearly all carriers show some sign of disease by age 20, though diagnosis is frequently delayed well into adulthood.

Schulte walked attendees through the disease's tumor spectrum, from low-risk cutaneous neurofibromas, largely a cosmetic concern, to the deeper, multifascicular PN that can infiltrate muscle and connective tissue and, rarely, transform into malignant peripheral nerve sheath tumor. Roughly 47% of patients with NF1 develop PN, and about a quarter to half of those become symptomatic with pain, disfigurement, or functional impairment. PN is present from birth in most patients but grows unpredictably, and craniofacial and trunk locations carry the highest morbidity given their proximity to the airway, cranial nerves, and major vasculature.

Despite how common the disease is, Schulte described just how often NF1, and PN specifically, goes unrecognized even among specialists who should be positioned to catch it. "I'm a neurologist by training. I thought I saw zero NF1 patients during my whole residency, and that was probably not the case, and then came to learn about it later," she told attendees. PN is frequently discovered incidentally, through imaging for unrelated conditions or a chance observation from a family member or primary care provider, and attendees described patients who had lived with visible, painful tumors for years, sometimes decades, before anyone connected the dots to NF1.

Schulte illustrated the diagnostic and treatment journey using the case of a 44-year-old man with a genetically confirmed NF1 diagnosis and a facial PN that had progressed for more than two decades before he sought care. Imaging showed a roughly 270 cm³ mass infiltrating the masticator space with the facial nerve directly involved, and the multidisciplinary tumor board unanimously deemed the tumor inoperable because no safe surgical plane existed. The case became a recurring touchpoint for why surgery, long the default approach for PN, so rarely offers a lasting solution. Because these tumors infiltrate nerves and surrounding tissue, complete resection is almost never possible. "It's not a forever solution, and it will continue to grow back over and over again," Schulte said, noting that incomplete resections can leave patients facing repeat surgeries and persistent pain without addressing the underlying tumor.

That reality has helped push MEK inhibitors, selumetinib and mirdametinib, to the center of the conversation since their respective FDA approvals for symptomatic, inoperable PN. In the case patient, a MEK inhibitor produced a confirmed partial response, a 24% reduction in tumor volume at 12 months, along with a meaningful improvement in quality of life. Attendees discussed how to counsel patients that a partial response, rather than tumor disappearance, represents success. Schulte emphasized that pain and quality of life, not tumor volume alone, are the more telling markers of benefit, since pain can improve within weeks while volumetric response can take close to eight months to appear. "I have patients with these huge tumors, and I actually say probably nothing will change with the size of your tumor even if it does. That's a win, but your pain will probably get better, and that's meaningful for them," she said.

Despite the expanded treatment options, barriers to care remain significant. Live polling found that most attendees relied on partial, ad hoc referrals rather than a formal NF1 multidisciplinary pathway, routing patients to tertiary centers as needed rather than a dedicated team. A separate poll found that 66% of attendees cited a lack of familiarity or uncertainty about patient selection as their primary barrier to prescribing or referring for systemic therapy, ahead of access and insurance hurdles. Discussion returned repeatedly to an underlying awareness gap: many clinicians in the room had treated patients with NF1 for years, often through dermatology or incidental oncology referrals, without recognizing PN as a distinct, treatable entity requiring its own referral pathway.

Schulte closed the evening with a direct charge to the room, encouraging clinicians to carry the forum's lessons back to their own networks. “I hope you guys feel empowered to prescribe MEK inhibitors and spread the word to your neurology friends,” she said. For a disease that so often hides in plain sight, that kind of peer-to-peer education, organizers said, may prove as important as any single therapy in closing the gap between diagnosis and treatment.