Radiology Resident Case of the Week: August 4, 1995

Peripheral Neurofibromatosis

Kevin M. Baskin, M.D., John Chang, B.A.
Peer Review Status: Internally Peer Reviewed

Neurofibromatosis is a multisystemic neurocutaneous disorder involving both neuroectodermal and mesenchymal derivatives. Of the eight subtypes, at least 85 percent are represented by Type I (von Recklinghausen or classic peripheral neurofibromatosis, with a prevalence of 1:4000 live births) and an additional ten percent by Type II (acoustic or central neurofibromatosis, with a prevalence of 1:50000 live births). Our discussion centers on the former, classic, form.

Peripheral neurofibromatosis can be diagnosed in almost all affected patients within the first year of life. Systemic compromise typically develops before the age of twenty years. The expression of this disease is highly variable, even within an affected family, ranging from mild inconvenience with normal lifespan to serious and progressive manifestations leading to death as early as the perinatal period. Some of the life-threatening complications of this disorder are amenable to treatment. Therefore, alertness to the common clinical manifestations, a low index of suspicion, a thorough evaluation of potentially affected individuals and their families, close follow-up, and thoughtful genetic counseling are well warranted in this disease.

Clinical Signs and Symptoms:
Multisystemic involvement is common, and a variety of problems may present in childhood, including hyperpigmentation changes (classically, cafe-au-lait spots, as well as axillary freckling or diffuse duskiness), neurofibromas, melanocytic hamartomas of the iris (Lisch nodules), seizures and intellectual compromise, optic and acoustic involvement, intracranial and spinal tumors, an increased incidence of malignancies, osseous defects and congenital dislocations, oral pathology, endocrine disorders, autonomic involvement, gastrointestinal involvement, hypertension, and vascular anomalies.

Diagnostic criteria are published by the National Neurofibromatosis Foundation.

Etiology/Pathophysiology:
Cellular differentiation and expression of matrix genes in type I neurofibromatosis are abnormal, with changes in the amount of type III and type IV collagen and fibronectin. The affected gene product appears to be involved in regulation of growth, development, and differentiation, but the specific mechanisms and causal relationships have not been well characterized.

Pathology:
Neurofibromas are typically multicellular in origin, typically composed of Schwann cells, but also containing fibroblasts, mast cells, and macrophages. The common lesion of malignant degeneration (neurofibrosarcoma) is, however, monoclonal.

Vascular histologic changes in neurofibromatosis are commonly described in six types (intimal, advanced intimal, nodular-aneurysmal, periarterial, epithelioid-cell, and pericapillary).

Immunohistochemical and electron microscopic observations suggest a smooth-muscle-cell origin of proliferating spindle-shaped cells. The vasculopathic lesions produced may be separate from other lesions in neurofibromatosis, which have been associated with abnormal proliferation of cells of neural crest origin.

Imaging:
Radiologic and imaging abnormalities can be systematically approached by anatomic location (1):

• Skull and brain
• Facial bones, jaws, sinuses, and neck
• Spine
• Bones, joints, and soft tissues
• Chest
• Gastrointestinal and abdomen

DDx:
The differential diagnosis of neurofibromatosis is extensive, depending upon the specific manifestations of disease in the affected individual.

Keywords:
von Recklinhausen's disease, neurocutaneous disorders, hyperpigmentation, cafe-au-lait, neurofibroma, Lisch nodule, renovascular hypertension

References:
1 Reeder MM, Felson B. Gamuts in Radiology. Cincinnati: Audiovisual Radiology of Cinncinati, Inc., 1975.

Title Page

See related Provider Topics Brain and Nervous System, Cancers, Genetics/Birth Defects or Neurofibromatosis.

See related Patient Topics Brain and Nervous System, Cancers or Genetics/Birth Defects.

All contents copyright © 1992-2004 the Author(s) and The University of Iowa. All rights reserved.

http://www.vh.org/pediatric/provider/radiology/PedRadSecTF/080495/index.html