Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
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The diagnosis of malignant peripheral nerve sheath tumor is challenging, particularly in the sporadic setting. Inactivation of the polycomb repressive complex 2 (PRC2), resulting from inactivating mutations of its constituents SUZ12 or EED1, has recently been identified in 70-90% of malignant peripheral nerve sheath tumors. Homozygous PRC2 inactivation results in loss of histone H3K27 trimethylation (H3K27me3). ⋯ Among other tumor types, 4 (20%) unclassified postradiation sarcomas were negative for H3K27me3, whereas all other neoplasms were positive. Loss of H3K27me3 is highly specific for malignant peripheral nerve sheath tumor (although only modestly more sensitive than S-100 protein and SOX10) and may be a useful diagnostic marker. Our findings suggest that PRC2 inactivation in malignant peripheral nerve sheath tumor may occur during progression to higher grades.