Abstract
BACKGROUND: The incidence of malignant peripheral nerve sheath tumors (MPNSTs) is low in the general population, although individuals with Neurofibromatosis Type I (NF1) are particularly susceptible. These tumors generally have a high probability of metastasis. The rate and types of second malignancies (SMNs) after a primary diagnosis of MPNST are not well characterized. We aimed to quantify the rate of SMNs among individuals with a first primary MPNST using population-based data. METHODS: We estimated age-standardized incidence rates (SIRs) for SMNs among 1,579 primary MPNST cases between ages 0-85+ using SEER 18 (2000-2015). We estimated incidence rate ratios (IRRs) and 95% confidence intervals (95% CI) for SMNs in MPNST cases compared with general population rates. We conducted sex-stratified and age-restricted analyses (< 30 years at diagnosis). RESULTS: Seven percent (108/1579) of MPNST cases developed a SMN (SIR of 4635 cases/million). Compared to the general population, MPNST cases were more likely to develop SMNs (IRR: 29.3; 95% CI 23.8-34.8) and had a much higher rate of second MPNSTs (IRR: 15,992.9; 95% CI 9594.5-22,391.3). Aside from a second MPNST, second cancers were frequently diagnosed in the breast, lung, skin, and soft tissue in females and were myeloid and skin malignancies in males. When restricted to < 30 years of age, second MPNSTs were the most common cancers diagnosed. CONCLUSIONS: The rate of SMNs among MPNST cases is tremendously higher than that observed among individuals with other cancers, particularly for second MPNSTs. These findings suggest rates of SMNs may also be higher in NF1 individuals.