Page 252 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 9-11 Integumentary System

CUTANEOUS AND SKELETAL MANIFESTATIONS OF NEUROFIBROMATOSIS

NEUROFIBROMATOSIS
(Continued)

and any two of the following tumors: neurofibroma,
glioma, schwannoma, meningioma, or juvenile poste-
rior subcapsular lenticular opacity.
Cutaneous findings in type II neurofibromatosis
include neurofibromas and café-au-lait macules.
Although both findings are less numerous than in type
I neurofibromatosis, most patients have only one or two
café-au-lait macules. Cutaneous schwannomas are
common in type II disease but are not seen in type I
disease. A unique form of cataracts can be seen in
neurofibromatosis type II; these are termed juvenile Neurofibromatosis. One
posterior subcapsular lenticular cataracts. of von Recklinghausen’s original
Histology: Skin biopsies of café-au-lait macules show patients, who had extensive sub-
epidermal hyperpigmentation. There is no increase cutaneous nodules but no neurological Girl with typical café-au-lait
spots but only a few skin nodules.
in the number of melanocytes, and no nevus cells symptoms. Such wide-spread skin Relatively mild neurofibromatous
are present. Macromelanosomes can be seen. Neuro- involvement is uncommon. scoliosis is present.
fibromas can be located within the dermis or sub-
cutaneous tissue. Histological evaluation shows a
well-circumscribed tumor composed of uniform-
appearing spindle cells of nerve origin. Special immune
histochemical stains can be performed to confirm the
nerve derivation of the tumors. Many mast cells are
seen intermingled within the spindle cell tumor.
Pathogenesis: Type I neurofibromatosis is caused by
a mutation in the NF1 gene. This gene is located on
the long arm of chromosome 17 and encodes the
protein neurofibromin. Defects in NF1 are responsible
for most cases of neurofibromatosis, making type I
neurofibromatosis the most common type of neuro-
fibromatosis. Because of the large size of the NF1 gene,
many spontaneous mutations occur and result in cases Spinal deformities in neuro-
of neurofibromatosis. The neurofibromin protein has fibromatosis. Boy with kypho-
been determined to be a tumor suppressor protein. scoliosis. Foreshortening of
It regulates the ras family of protooncogene. When Young woman with bilateral facial trunk secondary to kyphosis Severe scoliosis. Radiograph
neurofibromin is defective, the ras protooncogene palsy. Note drooping of cheeks due gives appearance of longer shows typical sharp angu-
loses its negative regulatory protein and is able to to compression of both facial (VII) upper limbs. lation unresponsive to
signal continuously. nerves by acoustic neuromas, which corrective measures, often
Type II neurofibromatosis is caused by a genetic also caused hearing loss. Proptosis
defect in the SCH (NF2) gene on the long arm of chro- resulted from bilateral optic (II) seen in neurofibromatosis.
mosome 22. The NF2 gene is approximately one third nerve tumors. Subcutaneous nodules
the size of NF1. It encodes the schwannomin (merlin) developed on her forehead, and
protein, a tumor suppressor protein that helps act as masses in her neck compressed
a go-between in the interactions between the cell the trachea. Disease was fatal in Dumbbell tumor
cytoskeleton/membrane and the extracellular matrix. this patient. Of spinal nerve root
Loss of function of the protein results in abnormal cell
signaling and unabated cell growth in various tissues.
Treatment: Once the diagnosis has been established,
patients need lifelong monitoring for the development
of various complications related to their disease. Spinal cord
Family members should be screened for the disease,
and genetic counseling should be offered to affected
patients. Adolescents and young adults may benefit
from annual physical examinations, and routine oph-
thalmological examinations should be recommended.
Screening in childhood for the development of scoliosis growth of a preexisting neurofibroma should make the disease, because of the presence of bilateral schwanno-
should be recommended. Patients should be screened clinician consider performing a biopsy to rule out mas, is a much more serious and life-altering disease
for hypertension at each visit because of the increased malignant degeneration. Optic gliomas are best surgi- than type I. The follow-up management of type II neu-
incidence of pheochromocytoma. Patients with neuro- cally excised if indicated, even though removal of the rofibromatosis requires a multidisciplinary approach.
fibromatosis are at increased risk for development optic glioma typically results in blindness. Ophthalmology, otolaryngology, neurosurgery, and
of malignant transformation of their neurofibromas Patients with type II disease should have screening internal medicine physicians need to coordinate care
into neurofibrosarcomas. These rare sarcomas can be MRI studies of the brain and the rest of the central for these patients. Neurosurgery and localized radio-
located anywhere, and any major change, pain, or nervous system to look for schwannomas. Type II therapy have been used to treat the brain tumors.

238 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS