Makise N, et al. - As, the majority of malignant peripheral nerve sheath tumors are characterized by mutations in SUZ12 or EED, which encode polycomb repressive complex 2 (PRC2) components, and resulting deficiency in H3K27me3, researchers investigated H3K27me3 and PRC2 status in dedifferentiated chondrosarcoma (a rare bone sarcoma). They evaluate 19 dedifferentiated chondrosarcoma cases, among these, six (32%) showed immunohistochemical loss of H3K27me3 only in the dedifferentiated component, whereas the well-differentiated component retained H3K27me3. H3K27me3-deficient dedifferentiated chondrosarcomas and H3K27me3-intact dedifferentiated chondrosarcomas were histologically different, as the former invariably demonstrated dedifferentiated histology with a striking similarity to classic malignant peripheral nerve sheath tumor, comprising sweeping to swirling fascicles of relatively uniform spindle cells. Outcomes thereby suggest that H3K27me3 deficiency defines a novel subset of dedifferentiated chondrosarcoma that requires recognition because of its diagnostic and potential clinical implications.