Recognizing hidden phenotypes in sarcomas through the electron microscope

Differentiation along a distinct cell lineage can be identified either morphologically or with the adjunct of different ancillary techniques. While immunohistochemistry has progressively supplanted electron microscopy as the method of choice to characterize the phenotype of neoplastic cells in soft tissue tumors and in solving most differential diagnoses, a number of lesions still lack reliable specific markers or show overlapping antigen expression, which can be categorized by ultrastructural analysis through the recognition of submicroscopic features indicative of a specific line of differentiation. This review discusses the role of electron microscopy in the identification of the phenotype of neoplastic cells in soft tissue sarcomas, with particular reference to the diagnostic aspects. Sarcomas in which the cellular phenotype that can be better recognized by electron microscopy include those belonging to the fibroblastic/myofibroblastic group, particularly those displaying a poorly differentiated/pleomorphic morphology. Occasionally, in tumors with smooth muscle, skeletal muscle, adipocytic, vascular endothelial, and Schwann cell differentiation electron microscopy may help in the differential diagnosis.