Epithelial phenotype in Ewing's sarcoma/primitive neuroectodermal tumor

Neural differentiation is an integral component of Ewing's sarcoma/primitive neuroectodermal tumor (PNET), which exhibits a continuous spectrum from minimal to prominent neural phenotype. Differentiation of Ewing's sarcomas/PNETs along other lineages or the expression of an epithelial phenotype is less common and-if present-may cause diagnostic difficulties. In this study we evaluated the frequency of epithelial differentiation in formalin-fixed and paraffin-embedded tissues of 33 (22 primary and 11 metastatic) Ewing's sarcomas/PNETs by using an immunohistochemical assay with several antikeratin antibodies. Focal positivity for low- or high-molecular-weight keratins was documented in 18% of the cases, and diffuse coexpression of low- and high-molecular-weight keratins was observed in two cases. Expression of the MIC-2 gene product was documented in 94% of the tumors. The primitive neural phenotype as revealed by expression of either neuron-specific enolase or synaptophysin was observed in 30% of the cases, but coexpression of both neural markers was present in only 15% of the tumors. This study documents that, in addition to primitive neural differentiation, Ewing's sarcomas/PNETs frequently exhibit focal positivity for keratins, with rare strong diffuse coexpression of both low- and high-molecular-weight keratins. The findings indicate that the expression of an epithelial phenotype, at least in a focal fashion, is a relatively frequent finding in otherwise typical Ewing's sarcomas/PNETs.