CONTEXT.-: Malignant peripheral nerve sheath tumor (MPNST) is a rare, often high-grade sarcoma. A small subset of MPNST shows evidence of heterologous rhabdomyoblastic differentiation, also known as malignant triton tumor (MTT). Immunohistochemical loss of histone 3 lysine 27 trimethylation (H3K27me3) has previously been described as a reliable marker for both MPNST and MTT. OBJECTIVE.-: To assess the loss of H3K27me3 as a potential tool for discriminating MTT from embryonal rhabdomyosarcoma (ERMS). DESIGN.-: We studied the immunohistochemical expression of H3K27me3 in 23 pediatric cases of confirmed ERMS. Of the 23 patients, 21 were male and 2 were female, with an age range of 2 months to 18 years (median, 5 years). Most of the tumors arose in the paratesticular soft tissue (n = 14), with other locations including the pelvis (n = 3), thigh (n = 2), abdomen (n = 1), orbit (n = 1), prostate gland (n = 1), and parotid gland (n = 1). All cases had characteristic morphologic features of ERMS. RESULTS.-: By immunohistochemistry, all tested cases expressed desmin (18 of 18), myogenin (20 of 20), and MyoD1 (5 of 5). More than half of the cases (12 of 23
52%) showed loss (nuclear absence) of H3K27me3, defined as staining in less than 5% of the tumor cells. The remaining cases demonstrated some degree of partial staining with H3K27me3, ranging from 5 to 40% of the tumor cells. No significant correlation between H3K27me3 expression and clinicopathologic features was identified. CONCLUSIONS.-: Loss of H3K27me3 frequently occurs in ERMS (52%) and is not reliable in distinguishing ERMS from MTT.