The advent of the electron microscope opened up for exploration a realm of biological structure far beyond that visible with the light microscope. Results from the study of normal cells and tissues came rapidly and were often spectacular. Application of the technique in pathology was slower to develop, but ultimately it became clear that early hopes for its potential as a diagnostic tool would not be realized. In certain areas of surgical pathology, transmission electron microscopy provided significant contributions, and for some decades it was a valuable and widely used diagnostic method, but its practical value diminished as newer procedures, notably inununohistochemistry. were introduced and their use burgeoned. The most fertile field for the application of electron microscopy in service pathology has been the study of tumors, and my experience with its use in a large comprehensive cancer center over a thirty year period is the basis for the thesis. During this time, over 35,000 specimens were accessioned for electron microscopy, most of them neoplasms. Many of the specimens were examined when they were received in search of information to clarify a problem diagnosis, and the collection became a resource from which I drew material for elective studies on particular types of tumors. I have conducted projects alone and with the participation of staff colleagues, department fellows, or visiting scientists. Findings were frequently reported in the literature and presented at scientific meetings in the United States and other countries. The thesis begins with a brief account of the historical development of diagnostic electron microscopy. Practical considerations in the procurement and handling of specimens are then discussed. The major part of the thesis is an account and analysis of contributions that electron microscopy has provided in the study and diagnostic evaluation of human tumors, arranged under anatomic systems and structured around data from observations that I have made myself or with collaborators. Pertinent findings from a selection ofmy personal publications are briefly summarized and some are illustrated in order to demonstrate the breadth and variety of the information on tumor ultrastructure that electron microscopy has provided during the years that I have had the opportunity to apply the technique. The work of others in the field is frequently cited. The thesis concludes with a discussion of the role of diagnostic electron microscopy in surgical pathology. I review practical considerations and detail how the effective use of electron microscopy in a surgical pathology department is enhanced by efficient organization, optimal utilization of technical facilities, integration with other routine diagnostic activities of the department, and liaison with clinical services. I contend that transmission electron microscopy has revealed much valuable data on the structure of normal and neoplastic cells, clarified the classification of certain categories of tumors, yielded insight into histogenesis, elucidated appearances seen in routine light microscopic sections and smears, facilitated correlation ofmorphology with immunohistochemistry. provided an often invaluable aid in the solution of diagnostic dilemmas, served as an effective resource in the instruction of pathologists in training, and enhanced presentations and publications on surgical pathology topics. The application of electron microscopy in surgical pathology is limited by economic considerations and a dearth of pathologists experienced in ultrastructural studies, but it continues to be a valuable resource in the examination and diagnosis of human tumors, and in research and education in pathology.
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