Malignant primary diffuse leptomeningeal gliomatosis (MPDLG) are rare central nervous system neoplasms associated with a poor outcome.

We report the case of a 40-year-old woman who presented with unusual worsening of bilateral sciatica, headaches, diplopia and a left proptosis. MRI of the head and spine showed multiple leptomeningeal lesions with no intra parenchymal involvement. The search for a primary tumor was negative. An open surgical biopsy of the prominent intradural lumbar tumor was performed within a week. Histopathology, immunochemistry and molecular analyses revealed a malignant glioma with histone H3.3 K27M mutation. The patient was referred to the neuro-oncologist for chemotherapy and craniospinal radiotherapy. Despite aggressive therapy, she died of disseminated tumoral progression, 18 weeks after the diagnosis.

MPLG is a rare tumor which should be considered whenever a patient presents with diffuse or multinodular meningeal contrast-enhancing lesions. Some cases of MLPG share histological and immunophenotypical features with diffuse midline gliomas H3-K27M-mutant, a rapidly fatal disease. The diagnosis remains histopathological and, therefore a biopsy is obligatory without delay. Immunohistochemistry and/or molecular analyses are now currently essential for a formal classification and, to provide a better prediction of clinical outcome, particularly in this heterogeneous group of tumors.