Diffuse midline glioma with extra central nervous system metastases in the pediatric, adolescent, and young adult population.

Diffuse midline gliomas (DMG) are malignant infiltrative gliomas enriched in the pediatric population and characterized by loss of the H3 K27me3 epigenetic marker, most frequently via mutation of the H3-3A gene. Few cases of extra-central nervous system (CNS) DMG metastasis with redemonstrated H3-3A p.K28M (H3K27M) mutation in metastatic tissue are reported in the literature. Here, we report two such patients, both females (ages 7 and 10), with DMG and extra-CNS metastasis who died 5 years after initial diagnosis. Both patients significantly exceeded the median life expectancy for DMG, raising the possibility that prolonged overall survival permitted progression to a rarely observed disseminated state of disease. There was absence of TP53/p53 modulating pathway mutation seen in classic DMG in the thalamic biopsy of the first patient, as well as the metastatic disease for the second patient, which may contribute to the prolonged survival observed. Molecular analysis of metastatic disease is important, as clinically and prognostically relevant alterations that vary from the primary site of disease may be detected, which shed light on clonal evolution patterns and further our understanding of disease biology.