S100-negative epithelioid malignant peripheral nerve sheath tumor with possible perineurial differentiation

Epithelioid malignant peripheral nerve sheath tumor (MPNST) is a rare subtype of MPNST composed of epithelioid cells with abundant cytoplasm. Currently, strong and diffuse immunostaining for S100 protein and SOX10 is generally regarded as a characteristic feature of epithelioid MPNST. However, malignant tumors with epithelioid morphology that arise from a peripheral nerve or a pre-existing benign nerve sheath tumor should be regarded as epithelioid MPNSTs when they do not show characteristic features that definitively lead to other specific diagnoses. Here, we describe 3 cases of epithelioid MPNST in the peripheral nerve or schwannoma that was negative for S100 protein and SOX10 expression. Instead, these tumors were positive for EMA, GLUT1, claudin 1, and cytokeratin to varying degrees, while all of them retained SMARCB1 and H3K27me3 by immunohistochemistry. EMA, GLUT1, and claudin 1 are known markers of perineurial cell differentiation; thus, they could possibly represent epithelioid MPNST with perineurial cell differentiation.