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Collaborative Care, New Therapies Improve Neurofibromatosis Outcomes

February 2018

Patients who have neurofibromatosis (NF), a disorder characterized by tumors of the nervous system and skin, have an increased risk of additional tumors and cancers. With NF, benign and malignant tumors develop over time, and a multidisciplinary, proactive care approach best aids these patients. Emerging drug therapies, collaborative care and research networks, as well as novel diagnostic and treatment techniques for brain tumors are also improving outcomes.

NF appears in 3 types, each of which manifests varying signs and symptoms. Neurofibromatosis 1 (NF1) is more common than neurofibromatosis 2 (NF2) (96% versus 3%) and occurs in about 1 in 3,000 births.1 A third form, schwannomatosis, is rarer and unlike NF1 and NF2, generally emerges in early adulthood. NF1 arises from mutations in neurofibromin 1, a gene coding for a tumor-suppressor protein, while NF2 is caused by a mutation in merlin, a gene coding for a cell membrane protein that also is a tumor suppressor.1,2,3 More severe cases of NF2 arise from nonsense or frameshift mutations.1,2 NF1 and 2 are autosomal dominant disorders and can have variable expression (complete, segmented, mosaic). About half of NF1 cases arise from spontaneous mutations.

— University of Minnesota Health neurosurgeon Clark C. Chen, MD, PhD, confers with a patient.

Signs of NF1 include multiple café au lait spots on the skin, axillary or groin area freckling, Lisch nodules, neurofibromas, bone deformities, optic gliomas, large head size, and short stature.1,2,3 Hearing loss, the most typical symptom of NF2, arises from benign, slow-growing, bilateral acoustic neuromas. In NF1 patients, tumors develop over time with the most common being dermal or plexiform neurofibromas, malignant peripheral nerve sheath tumors, and gliomas. NF2 patients develop schwannomas, meningiomas, and ependymomas. Most common nerve-associated tumors in NF1 are neurofibromas whereas schwannomas are more common in NF2.3

NF is progressive, and tumor type and growth can evolve over time. Café au lait spots and dermal neurofibromas in NF1 are usually benign but can increase during hormonal changes, such as during puberty, pregnancy, or menopause. Symptomatic lesions can be surgically excised; however, plexiform neurofibromas can grow progressively and become malignant, and 8% to 13% of these develop into malignant peripheral nerve sheath tumors.1,3 Acoustic neuromas are common in NF2, and these patients should be evaluated periodically for hearing loss. Bilateral vestibular schwannomas are pathognomonic, but not all NF2 patients have bilateral tumors.1,3

Monitoring for NF1 includes neurologic, ophthalmologic, radiologic examinations. Patients with NF should also be observed for learning and behavioral changes, since these can signal the disorder in young patients.4 Most NF patients have elevated risks for other types of cancer, including breast cancer, leukemias, and brain tumors.5,6

Because NF patients often harbor multiple benign tumors, including neurofibromas and schwannomas, removal of these tumors is not necessary unless they cause pain, neurologic deficit, or show evidence of malignant degeneration/growth. Most often, these benign tumors are carefully observed. For symptomatic tumors, surgery is the first-line therapy. New drug therapies have shown promise, and NF patients with brain tumors can benefit from the use of magnetic resonance imaging combined with stereotactic laser ablation. (See case study.)

Clinical and research collaborations also hold promise in the care of patients with NF. University of Minnesota Health specialists in NF lead Minnesota Neurofibromatosis Clinic without Walls, a multidisciplinary, cross-health system effort to provide care to NF patients from diagnosis through adulthood. They also participant in Children’s Tumor Foundation-supported research, including work on new treatments for nerve tumors and the development of swine models of neurofibromatosis.7 The study of genetically engineered pigs is expected to aid testing of new therapies for their possible inclusion in clinical trials. Investigations into the transformation of Schwann cells into malignant peripheral nerve sheath tumors may lend insight into the progress of the disease.


  1. Kehrer-Sawatzki M, Mautner VF, Cooper DN. Emerging genotype-phenotype relationships in patients with large NF1 deletions. Hum Genet 2017 Apr; 136(4):349-376.
  2. Le C, Bedocs PM. Neurofibromatosis. StatPearls [Internet]. Treasure Island (FL) StatPearls Publishing; 2017 Oct 6.
  3. Campian J, Gutmann DH. CNS tumors in neurofibromatosis. J Clin Oncol. 2017;35(21):2378-85.
  4. Torres Nupan MM, Velez Van Meerbeke A, Lopez Cabra CA, Herrera Gomez PM. Cognitive and behavioral disorders in children with neurofibromatosis type 1. Front Pediatr. 2017;5:227.
  5. Uusitalo E, Rantanen M, Kallionpää RA, Pöyhönen M, Leppävirta J, Ylä-Outinen H, et al. Distinctive cancer associations in patients with neurofibromatosis. J Clin Oncol. 2016;34(17):1978-1986.
  6. Uusitalo E, Kallionpää RA, Kurki S, Rantanen M, Pitkäniemi J, Kronqvist P, et al. Breast cancer in neurofibromatosis type 1: overrepresentation of unfavourable prognostic factors. Br J Cancer. 2017;116:211-217.
  7. Watson Al, Carlson DF, Largaespada DA, Hackett PB, Fahrenkrug SC. Engineered swine models of cancer. Front Genet. 2016;7:1-16.

When to refer

University of Minnesota Health specialists provide innovative care for patients who have neurofibromatosis (NF). Because NF is progressive, poses a risk of tumor development, and affects many body systems, patients require monitoring and multidisciplinary care. Our highly skilled NF specialists include pediatric and adult neurooncologists, neurosurgeons, endocrinologists, radiologists, nurse practitioners, social workers and child-family life specialists. Our physicians conduct regular patient care conferences to help patients address their condition. The team provides a proactive plan to fight tumors and help patients heal.

The Minnesota Neurofibromatosis Clinic without Walls, led by University of Minnesota Health physicians, provides collaborative care to NF patients from infancy through adulthood and is open to any patient with NF, regardless of age or previous treatment. We are also a member of the Children’s Tumor Foundation Neurofibromatosis Network, an organization that funds innovative research into the causes of the disease and avenues for treatment. The Pediatric Cancer Survivor Program at University of Minnesota Masonic Children’s Hospital is the only regional program able to offer care specific to survivors of pediatric cancer without regard to age.

To find current clinical trials available through M Health providers:

Physician Outreach Program

The Cancer Care Outreach Program is designed to provide education and facilitate knowledge sharing between our team and the medical community.

To schedule a physician meeting or to visit our facility, contact Melinda Tuma Arvold, System Manager, Outreach Services. Phone: 612-273-9947; email

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