Pathophysiology of Neurofibromatosis Type 1

Abstract

Neurofibromatosis type 1 (NF1) represents a major risk factor for development of malignancy, particularly malignant peripheral nerve sheath tumors (MPNST), optic gliomas, other gliomas, and leukemias. The oncologist will see NF1 patients referred for treatment of malignancy, and should be alert to the possibility of undiagnosed NF1 among patients with cancer. Brain tumors tend to have a more indolent course in NF1 than in the general population, and hence are best managed conservatively. MPNST, in contrast, do not respond to standard chemotherapy or radiation therapy. The most effective treatment of MPNST appears to be early diagnosis and surgery, but early diagnosis is hampered by frequent occurrence within preexisting large tumors, making new growth or change difficult to detect. New insights into pathogenesis now offer hope of development of specific methods of treatment with reduced toxicity and more precise molecular targeting. There is an urgent need, however, to develop methods to measure tumor growth and monitor outcomes, develop preclinical drug screening systems, and further explore the pathogenesis of the disorder to determine whether mechanisms other than Ras regulation may be important in pathogenesis.

Neurofibromin as a regulator of melanocyte development and differentiation

“…NF1 encodes a 260 kDa protein called neurofibromin which possesses Ras-GTPase-activating protein (Ras-GAP) activity (DeClue et al, 1992). Patients with NF1 are prone to developing a set of different conditions involving benign and malignant tumors, including neural tumors, such as dermal neurofibromas, plexiform neurofibromas, astrocytomas and optic gliomas (Korf, 2000;Theos and Korf, 2006). Juvenile myeloid leukemia and other hematologic malignancies have also been associated with NF1 (Bader and Miller, 1978;Stiller et al, 1994).…”

Analysis of Mitochondrial DNA in Discordant Monozygotic Twins With Neurofibromatosis Type 1

“…Further defining criteria include the presence of iris hamartomas (Lisch nodules), optic pathway gliomas, plexiform neurofibromas and bone dysplasias (NIH, 1988;Theos & Korf, 2006). The incidence of malignant tumors such as malignant peripheral nerve sheath tumors (MPNST) is increased.…”

A rare location for an infrequent tumor: Plexiform neurofibroma in hepatic hilum

“…Tumor won't turn malignant in time unless peripheral nerve sheath tumors develop over the lesion 3 . It consists of the same cell types as a cutaneous fibroma but has an expanded extracellular matrix, and its presence is one of the clinical criteria for the diagnosis of NF-1 3 . It may be present superficially or be located internally, and consists of proliferation of cells in the nerve sheath extending across the length of a nerve 4.…”