Light microscopy has limited value in predicting where the primary site of a metastatic adenocarcinoma might be located. In our series, electron microscopy was useful in determining the primary site in approximately 85% of patients with a metastatic adenocarcinoma of unknown origin. This study is based on the ultrastructural examination of more than 100 such cases. In the remaining 15% of the cases, electron microscopy usually provided assistance in reducing the differential diagnosis to a minimum, usually to two possible primary sites. The majority of the metastatic adenocarcinomas showed rather specific ultrastructural features to suggest the site of origin. This application of electron microscopy has never been fully explored and has considerable clinical importance and economic impact in health care systems. An extensive work-up to determine the primary site, with its inconvenience to patient and family, as well as delay in adequate treatment, can be avoided with early diagnosis of the primary site.
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