Plexiform Neurofibroma

An 11-year-old girl with type 1 neurofibromatosis presented for evaluation of a soft mass on the left shoulder. The mass first appeared when the child was 7 years old; it had slowly enlarged since then, and it eventually caused significant shoulder pain. The child also had neuropathic-type pain in the left hand that was relieved by gabapentin.

The patient was noted to have left deltoid swelling and multiple café au lait spots on the trunk (A and B). She also had decreased left forearm girth, increased perspiration, and discoloration of the left hand. An MRI scan of the brachial plexus showed a complex plexiform neurofibroma with almost complete replacement of the supraspinatus, infraspinatus, teres, and subscapularis muscles.


Ryan T. McCarthy, MD, of Morgantown, WVa, and Atiya Khan, MD, of Fort Wayne, Ind, write that type 1 neurofibromatosis, also known as von Recklinghausen disease, is a common autosomal dominant disorder that occurs in an estimated 1 in 2500 to 4300 live births worldwide.¹ Lisch nodules, café au lait spots, and cutaneous neurofibromas are characteristic manifestations.

Neurofibromin, the product of the NF1 gene, is thought to have a role as a tumor suppressor gene under normal circumstances. Defective neurofibromin synthesis leads to the proliferation of neural crest–derived tissues.^2,3 Multiple mutations of the NF1 gene on chromosome 17 produce defective neurofibromin and account for the malignant transformations. Of the known NF1 mutations, more than 80% have been identified as nonsense, or frameshift, mutations in the protein-coding region of the gene.^4,5

On pathologic examination, plexiform neurofibromas have intrafascicular growth along spinal or peripheral nerves. They can be discrete nodules along the nerve or root. Frequently, they are diffuse and cause connective tissue hypertrophy.⁶ Plexiform neurofibromas often develop in patients at a younger age than do dermal neurofibromas, and their growth is typically self-limited. Their presence in the neck can cause serious airway or spinal cord compromise.⁷ Even asymptomatic plexiform neurofibromas can cause significant cosmetic problems.

The diagnosis of type 1 neurofibromatosis requires 2 or more of the following criteria⁸:

•Six or more café au lait macules of more than 5 mm in prepubertal persons and more than 15 mm in postpubertal persons.⁹
•Two or more neurofibromas of any type or a single plexiform neurofibroma.
•Freckling in the axillary or inguinal region.
•Optic glioma.
•Two or more Lisch nodules (iris hamartomas).
•Sphenoid dysplasia or thinning of the long bone cortex with or without pseudoarthrosis.
•First-degree relative with type 1 neurofibromatosis.

Because plexiform neurofibromas are commonly seen in neurofibromatosis, a single occurrence is often diagnostic. Cutaneous neurofibromas are typically benign. However, there is a 5% lifetime risk that plexiform neurofibromas will become malignant peripheral nerve sheath tumors.¹⁰

Because of the risk of malignancy, surgery is often the treatment of choice for patients with plexiform neurofibromas. For this patient, a neurosurgeon determined that surgery was not an option, since tumor removal would probably require arm amputation.