2044 Next Generation Genetic Sequencing of Malignant Peripheral Nerve Sheath Tumors: A 5-Year Institutional Experience

INTRODUCTION: Malignant peripheral nerve sheath tumors (MPNSTs) are a rare and aggressive form of soft-tissue sarcomas. We describe our single-center case series of surgical resection of MPNSTs. METHODS: Adults who underwent surgical resection of MPNSTs at a tertiary center within the last 5 years were reviewed. All patients had genetic evaluation with UCSF 500 next-generation sequencing (NGS). Clinical, surgical, molecular, and postoperative variables were summarized. RESULTS: Ten patients (4 female) with mean age 38 years (range 15.5 to 58.4) underwent resection of MPNSTs. Seven had a diagnosis of NF1. Tumors were located in the cervical spine (4), lower extremities (3), as well as the scapular, submandibular, and suboccipital regions (1 each). All patients with spinal tumors (4) presented with neuropathy while those with extraspinal tumors (6) presented with a mass that exhibited notable growth or tenderness. Tumors showed positive staining for S100 (6/10), Sox100 (3/10), and H3K27Me3 (3/9). UCSF 500 NGS showed the most frequent mutations were in NF1 (10/10), CDKN2A/B (6/10), Suz12 (3/10), and TP53 (3/10). Five patients also had alterations in tumor suppressor and telomere-related genes that are not well-described. Recurrence occurred in 7 patients. Seven patients underwent adjuvant chemotherapy, and 6 underwent radiation therapy. A total of 3 patients died with a mean survival of 1.1 years. For the surviving 7 patients, the median follow-up time was 1.7 years (IQR: 2.8). Median cohort Karnofsky Performance Scale did not change from 80 preoperatively (IQR: 25). CONCLUSIONS: This is one of the largest case series on MPNSTs incorporating surgical, clinical, and molecular characteristics. Although we saw classical and novel genetic alterations, the tumors were too heterogeneous to correlate specific genes with survival.