Embryonic ultrastructure as a guide in the diagnosis of tumors

The purpose of this article has been to illustrate the applications and limitations of comparing the ultrastructural morphology of certain poorly differentiated neoplasms with normal human embryonic tissues. The examples used--embryonal rhabdomyosarcoma, Wilms' tumor, and fibrous mesothelioma, in comparison with embryonic mesoderm and its early derivatives--are but a few of the entities that can be investigated in this manner. Ewing's sarcoma was included in the report because of the long-standing and unsolved mystery concerning its histogenesis and because we believe it probably fits into the same category of poorly differentiated mesodermal neoplasms as the other lesions described. However, unlike the other more definite examples of primitive neoplasms manifesting focal markers of secondary mesenchymal differentiation, Ewing's sarcomas exhibit no ultrastructural evidence for myogeneous, nephrogenic, or mesothelial lines of maturation. Nor are there any morphologic indications of ectodermal or endodermal differentiation. The questions arise as to whether the category of Ewing's sarcoma has been perpetuated by so classifying all small-cell neoplasms having no recognizable line of differentiation, and whether this category may include cells of more than one type, that is, cells that are biologically determined to develop along several different pathways. This concept would be one explanation for the occurrence of Ewing's tumors in soft tissue as well as in bone, and we know that the cells contained in somites are ultrastructurally very similar to the least-differentiated cells making up the myotomes and sclerotomes. Apparently, questions such as these cannot be answered by morphologic studies alone. However, a number of other useful diagnostic and academic points of information can be gleaned.