Diagnosis: Neurofibroma

Benign tumors, neurofibromas can arise anywhere along a nerve fiber and usually involve nerves in or near the skin. The tumors are populated by Schwann cells, fibroblasts, mast cells, and vascular components. Neurofibromas can be soft or firm and brown, pink, purple, or skin-colored; they are almost never white or yellow. Pressure applied to the top of a neurofibroma yields the pathognomonic buttonhole invagination.

Most neurofibromas are painless and slow-growing; others can be occasionally painful. In some cases, palpation of the affected area can cause pain similar to an electric shock (Tinel sign). Most neurofibromas do not cause neurologic pathology unless they affect a major motor or sensory nerve or compress the involved nerve against a rigid structure.

Three neurofibroma subtypes have been defined: (1) plexiform (noncircumscribed), (2) cutaneous (circumscribed), and (3) subcutaneous (circumscribed). Plexiform neurofibromas are thick and irregular and feel like a bag of worms. They cause disfigurement and destruction by becoming entwined with important supportive structures. Our patient had a plexiform neurofibroma.

Plexiform neurofibromas are the most common benign tumor. They can occur in all forms of the genetic disorder neurofibromatosis, but they are the only subtype to occur in neurofibromatosis type 1 (NF-1).

Isolated neurofibromas of the skin are not uncommon and do not mean the patient has neurofibromatosis, a rare disease with an incidence of about 0.03% (or 90,666 people in the United States). A variety of solitary neurofibromas have been reported. One isolated giant plexiform neurofibroma affected all branches of the common peroneal nerve. Another solitary neurofibroma involved the spermatic cord. Solitary colonic neurofibromas have occurred in a patient with transient segmental colitis and manifested as massive lower GI bleeding and intussusception. Other authors have reported an isolated neurofibroma of the common bile duct.

The medical literature notes isolated plexiform neurofibromas in the mouth, larynx, and soft palate as well as hemimacroglossia due to one such tumor. A single neurofibroma of the orbit was associated with extensive myxoid changes, and isolated conjunctival neurofibromas at the puncta caused epiphora. In a Brazilian series of 66 neurofibromas of the head and neck, 51.2% of patients had isolated neurofibromas.1

Neurofibromatosis is an autosomal dominant disorder with eight different clinical phenotypes resulting from defects in two genes. NF-1 is linked to a defect in a tumor suppressor gene encoding neurofibromin, a protein essential for the negative regulation of the oncogene ras. A defect in a second tumor suppressor gene is responsible for neurofibromatosis type 2.

While genetic defects are seen with isolated neurofibromas, a diagnosis of neurofibromatosis requires two or more of the following: (1) six or more café-au-lait macules >5 mm in their largest diameter in prepubertal individuals and >15 mm in their largest diameter in postpubertal individuals, (2) two or more neurofibromas of any type or one plexiform neurofibroma, (3) freckling in the axillary or inguinal regions, (4) optic glioma, (5) two or more Lisch nodules (iris hamartomas), (6) distinctive osseous lesion, such as sphenoid dysplasia or thinning of the long bone cortex, with or without pseudoarthrosis, and (7) a first-degree relative with NF-1 that meets the diagnostic criteria.

Our patient chose not to have her tumor removed.

Dr. Scheinfeld is assistant clinical professor of dermatology at Columbia University in New York City, where he has a private practice.

Reference
1. Marocchio LS, Oliveira DT, Pereira MC, et al. Sporadic and multiple neurofibromas in the head and neck region: a retrospective study of 33 years. Clin Oral Investig. 2007;11:165-169.