Methotrexate-related Leukoencephalopathy Without Radiation Therapy: Distribution of Brain Lesions and Pathological Heterogeneity on Two Autopsy Cases

This report concerns two rare autopsy cases of methotrexate (MTX)-related leukoencephalopathy without radiation therapy. In the first case, there were widespread necrotic foci with prominent spheroids, that is, disseminated necrotizing leukoencephalopathy (DNL), mainly in the cerebral white matter. In contrast, in the second case, there were widespread demyelinated foci without significant axonal changes, which we would like to name disseminated demyelinating leukoencephalopathy (DDL), mainly in the cerebral white matter. We emphasize that the pathology of pure MTX-related leukoencephalopathy is not uniform, and may show at least two kinds of histologic change. Furthermore, both cases did not develop significant vascular changes, which are usually induced by radiation therapy. The distribution of the lesions in two cases was examined by large specimens, including hemisphere specimens. The distribution of the lesions in the brain of our cases was also different. In the first case, the DNL lesions were predominantly distributed in the frontal and temporal lobes. In the second case, the DDL lesions were prominently localized in the occipital lobe. To our knowledge, this is the first report describing not only the pathological findings of MTX-related leukoencephalopathy without irradiation but also the precise distributions of the lesions.