Enrico Martin

12 Chapter 1 Epidemiology of MPNST Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of soft tissue sarcoma (STS). STS comprise approximately 80 different subtypes of which at least half are aggressive and carry the potential of metastasizing. MPNSTs are aggressive sarcomas originating from peripheral nerve supporting tissues and can therefore occur in any part of the body making up 2-3% of all STS. 1,2 Based on data from the Dutch cancer registry (IKNL) the incidence of MPNST is approximately 1.7 per million inhabitants ( Figure 1 ). This means that 25-30 new patients present annually in the Netherlands. Although most patients present with sporadic disease, 25-50% of MPNSTs are associated with neurofibromatosis type 1 (NF1). 3–6 NF1 is an autosomal dominant condition with an incidence of 1:3000. 7 NF1 patients carry a loss-of-function germline mutation in the NF1 gene which encodes the Ras inhibiting protein neurofibromin. 8 Activated Ras signaling consequently results in cell survival and proliferation. Due to their germline mutation, NF1 patients commonly have multiple benign dermal neurofibromas or plexiform neurofibromas, but are also at an increased risk of developing malignant tumors over the course of their life. MPNSTs are the main cause of death in the NF1 population and patients carry an estimated 8-16% lifetime risk of developing an MPNST. 7,9 Besides sporadic and NF1-associated MPNSTs, a smaller subset (5-10%) of MPNSTs are radiation-induced. 3,4,6 MPNSTs have a dismal prognosis with 5-year survival rates varying between 40-60% for localized disease. 3–6,10–12 Additionally, 10-20% of patients will present with metastatic or unresectable disease and up to 50% will develop metastases over time. 3–6,13–15 0 1 2 3 1990 2000 2010 Year Incidence per million Figure 1 Incidence of MPNST in the Netherlands