PATH-42. DIAGNOSIS AND PROGNOSTICATION OF AN ATYPICAL ADULT PRESENTATION OF DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT) BY METHYLATION PROFILING

Abstract

Abstract BACKGROUND Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare central nervous system tumors first described in the 2016 WHO classification. A paucity of data exists on this tumor. This case describes an adult presentation of DLGNT, a classically pediatric tumor, and highlights the importance of genetic and epigenetic analyses in neuro-oncologic diagnoses. CASE: A 22-year-old male presented with shoulder paresthesias and back pain, progressing to bilateral leg weakness. Spine MRI demonstrated an enhancing intramedullary T8 lesion, prompting urgent laminectomy and resection. Frozen section suggested a glial neoplasm. Four-month follow-up MRI spine showed leptomeningeal dissemination at the C-spine and caudal thecal sac. CSF analysis revealed 110 mg/dL protein, 2 cells/mcl, and negative cytology. NCI methylation profiling demonstrated 1p deletion and KIAA1549:BRAF fusion, consistent with DLGNT, subtype 1, with MAPK pathway activation; Ki-67 index was 30%. Treatment with binimetinib was initiated. After 1 month of therapy, the patient is tolerating treatment and strength is improving. DISCUSSION This case describes a rare presentation of a rare tumor. DLGNT, subtype 1, has a median age of diagnosis of 5 years and an indolent course. We describe an adult patient with molecular features consistent with DLGNT subtype 1, but a high proliferative index suggesting a more aggressive growth potential. In this case, methylation profiling aided in diagnosing the tumor type and guided treatment. The KIAA1549:BRAF fusion is an activating mutation in the MAPK pathway, and binimetinib was selected as a MEK inhibitor with high CNS penetration. To our knowledge, this is the first case of an adult-onset DLGNT treated with binimetinib. Based on our single patient experience, we would advocate for methylation profiling for rare CNS tumor entities.