EPID-13. Are patients with LZTR1-related schwannomatosis at increased risk for gliomas?

Abstract BACKGROUND Somatic LZTR1 variants were initially identified in glioblastomas (GBM). Schwannomatosis (SWN) is a rare neurogenetic tumor suppressor syndrome in which affected individuals have a predisposition to multiple schwannomas and chronic pain. The condition arises from pathogenic variants in genes located on a small region on chromosome 22 including NF2, LZTR1, and SMARCB1. It is not clear if germline variants in LZTR1 predispose SWN patients to glioblastomas. Here, we present two patients with LZTR1-SWN and pathologically confirmed gliomas. Patient 1 presented in his 20s with a lump on his left thigh; pathology revealed schwannoma. Over the next 20 years, he underwent multiple resections of peripheral and spinal schwannomas. He did not undergo germline genetic testing due to cost. At age 60, he developed new headaches, visual changes, and cognitive dysfunction and was found to have a large heterogeneously enhancing right temporal lobe mass, which was subtotally resected. Pathology confirmed IDH-wildtype glioblastoma with an unmethylated MGMT promoter and a likely pathogenic variant in LZTR1 (c.1786-1G>A). Subsequent analysis confirmed the pathogenic variant in blood. He underwent concurrent radiation and temozolomide chemotherapy along with tumor-treating fields. Treatment is ongoing. Patient 2 presented with multiple peripheral schwannomas that were resected in his 40s. Germline genetic testing revealed a LZTR1 pathogenic variant (c.2083dupA). At age 46, he was diagnosed with thyroid cancer. At age 48, he was found to have a left temporal T2/FLAIR hyperintense lesion with punctate enhancement. Biopsy revealed low grade diffuse glioma, NOS. Surveillance is ongoing. DISCUSSION Additional studies are needed to determine if there is a heightened risk for gliomas in LZTR1-SWN. Future work to map genetic variants with clinical outcomes will guide surveillance and treatment choices for individuals with SWN.