Malignant peripheral nerve sheath tumors associated with neurofibromatosistype 1 - A clinicopathologic and molecular study of 17 patients

Objective To identify potential prognostic factors and criteria for early d etection of malignant peripheral nerve sheath tumors associated with neurof ibromatosis type 1 (NF1). Design: Retrospective study of malignant peripheral nerve sheath tumors in a cohort of 395 patients with NF1 followed up between October 1, 1988, and January 1, 1999; review of the clinical and histological characteristics of treatment and course: and analysis of p53 mutations and overexpression in tumors. Setting: Teaching hospital referral neurofibromatosis center for adults. Patients: Seventeen patients with NF1 (9 males and 8 females). Mean+/-SD pa tient age at diagnosis was 32+/-14 years. Main Outcome Measures (1) Clinical symptoms, (2) comparison of p53 mutation s and overexpression in benign vs malignant tumors: and (3) median survival . Results: Twelve patients had high-grade tumors. All tumors except 1 develop ed on preexisting nodular or plexiform neurofibromas. Pain and enlarging ma ss were the first and predominant signs. None of the benign tumors displaye d significant p53 staining or p53 mutations. Six of 12 malignant tumors sig nificantly overexpressed p53, and 4 of 6 harbored p53 missense mutations. M edian survival was 18 months overall, 53 months in peripheral locations, an d 21 months in axial locations. Conclusions: Malignant peripheral nerve sheath tumors are highly aggressive in NF1. They mostly arise from plexiform or nodular neurofibromas. Investi gations and deep biopsy of painful and enlarging nodular or plexiform neuro fibromas should be considered in patients with NF1. Late appearance of p53 mutations and overexpression precludes their use as predictive markers of m alignant transformation.