Histone-mutant glioma presenting as diffuse leptomeningeal disease.

Lay abstract Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Histones are molecules around which DNA winds. GBM and other gliomas sometimes have genetic alterations called mutations in histone genes. Of these, a specific alteration in histone 3 called H3K27M has been described in a variety of primary brain tumors. In adult gliomas, the H3K27M mutation is typically associated with tumors located within the brainstem or other structures in the midline of the central nervous system and a poor prognosis. Although previously reported, involvement of the leptomeninges (the thin membranes covering the brain and spinal cord) is uncommon at the time of initial diagnosis of gliomas harboring H3K27M mutations. We describe a case of GBM that initially presented with vision loss due to diffuse leptomeningeal involvement. Imaging and laboratory studies, including two cerebrospinal fluid analyses by lumbar puncture, did not establish a diagnosis. Brain biopsy confirmed the presence of a tumor, and genetic testing performed on the tumor tissue identified the histone mutation. This case highlights the importance of including primary central nervous system malignancies as a possible diagnosis when there is diffuse radiographic leptomeningeal enhancement.