Neurofibroma
Neurofibromas are uncommon benign skin tumors that can be solitary but are
more commonly found in multiples in patients with neurofibromatosis. Neurofibromatosis
is one of the more common genodermatoses, afflicting 1 in every 3000 to 4000
individuals. It is caused by a defective tumor suppressor gene.
Clinical Findings: Neurofibromas are small (up to 1 cm on average)
papules or nodules that have a soft, rubbery feel. They are flesh colored to
slightly hyperpigmented. When pressed, they show a characteristic
“buttonholing” phenomenon, in which the neurofibroma invaginates into the
underlying dermis and subcutaneous fat. The neurofibroma returns to its natural
location once it is unconfined. Most solitary neurofibromas are asymptomatic.
The clinical differential diagnosis is between a neurofibroma and a common
acquired melanocytic nevus (compound or intradermal nevus). When multiple
neurofibromas are seen in an individual patient, the clinician should look for
other signs of neurofibromatosis.
Neurofibromatosis type 1 (previously
known as von Recklinghausen disease) is a common genetic systemic disease with
cutaneous findings. It is inherited in an autosomal dominant pattern but can
also result from a spontaneous mutation. The gene that has been impli- cated,
known as NF1, is located on the long arm of chromosome 17 and encodes
the tumor suppressor protein, neurofibromin. This guanosine triphosphatase
(GTPase) protein is critical in the regulation of the Ras cell signaling
pathway. Other forms of neurofibromatosis have been described and show
variations of the clinical phenotype. Neurofibromatosis type 2 is caused by a
defect in NF2, a gene on the long arm of chromosome 22.
Patients with neurofibromatosis type 1
begin developing neurofibromas at puberty, and the lesions increase in number
dramatically over their life span. They are often larger than solitary
neurofibromas and can range from a handful to thousands. The sheer number of
neurofibromas can cause significant disfigurement and can affect social and
psychological well-being. In this genetic disease, neurofibromas can occur not
only in the skin but along any nerve in the body. Neurofibromas that occur in
areas where there is minimal room for expansion (e.g., in the intervertebral
foramen) can cause significant morbidity and need for surgical intervention.
Patients with neurofibromatosis type 1
have many other skin findings, including multiple café-au-lait macules,
axillary freckling, and plexiform neurofibromas. Plexiform neurofibromas are a
unique variant of the neurofibroma and are considered pathognomonic for this
disease. They are composed of multiple indi- vidual neurofibromas grouped into
a large plaque. Systemic findings seen in neurofibromatosis include optic
gliomas, Lisch nodules on the iris, multiple bony findings, various impairments
of the central nervous system, and a number of endocrine disorders. The varying
phenotypes of this disease may result from different mutations in the involved
gene. These patients are also at much higher risk for malignancy than non-afflicted
controls.
Pathogenesis: Solitary neurofibromas have not been found to
contain defects in the neurofibromin protein. They arise as a result of unknown
factors that cause proliferation within the dermis of all the components of a
nerve filament. The neurofibromas found in neurofibromatosis are believed to be
caused by the genetic defect in the tumor suppressor gene. How this defect
ultimately regulates the formation of neurofibromas is not fully understood.
Histology: Individual neurofibromas have a well-
circumscribed, spindle-shaped proliferation within the dermis. No capsule is
present. Schwann cell proliferation and proliferation of the axonal components
of the nerve are seen. Many mast cells are present in these tumors. The
epidermis is uninvolved, and a small grenz zone is often appreciated.
Treatment: Definitive treatment of a solitary neurofibroma
is complete excision. This is curative and results in a very low recurrence
rate. No treatment is necessary, because the transformation into malignancy is
extremely low.
Any neurofibroma that starts growing
or becomes hard or tender should be removed to look for degeneration into
neurofibrosarcoma.
Patients with neurofibromatosis
require a multidisciplinary approach and need to see a good internist to
coordinate all the potential systemic complications. The neurofibromas may be
removed surgically. This approach is not ideal, because the number of lesions
typically precludes removal of only the bothersome ones. Plexiform
neurofibromas should be removed by a plastic surgeon, because they can have
large subcutaneous extensions that are not visible clinically. There is no cure
for this genetic disease; lifelong screening and follow-up are required, and
the patient should be referred for genetic counseling before reaching
child-bearing age.
