Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis

The two main peripheral nerve sheath tumors found in patients with neurofibromatosis, type 1 (NF1), are neurofibroma, a benign tumor, and malignant peripheral nerve sheath tumor (MPNST). The tumors are related in that most MPNSTs are thought to arise by malignant transformation of neurofibromas. Such an event occurs in about 2% of NF1 patients. There are five forms of neurofibroma; three of them-localized cutaneous neurofibroma when multiple, plexiform neurofibroma, and massive soft-tissue neurofibroma-are highly specific for NF1. Only two forms of neurofibroma, plexiform and localized intraneural neurofibroma, are significant precursors of MPNST. Massive soft-tissue neurofibromas are worrisome in that they may mask MPNST arising from one of the mentioned neurofibromas. The vast majority of MPNSTs are high-grade malignant tumors with a high rate of distant metastasis. The overall 5-year survival rate for patients with MPNSTs ranges from 34% to 52%. MPNSTs generally are solitary, deep-seated globoid or fusiform tumors. They are firm, fleshy, tan, and often focally to extensively necrotic, and they invade surrounding soft tissue. On histological examination, MPNSTs are most often hypercellular, hyperchromatic, fasciculated, and mitotically active tumors. Low-grade tumors account for only about 10-15% of cases. Twenty percent of MPNSTs have unusual and potentially misleading histological features, such as epithelioid cells and divergent mesenchymal or glandular differentiation. Am. J. Med. Genet. (Semin. Med. Genet.) 89:23-30, 1999.