Metastatic adenocarcinoma of unknown primary origin

Adenocarcinomas account for up to 60% of all metastatic neoplasms of unknow n primary origin. In general, adenocarcinomas are the most difficult metast atic tumor to accurately identify the primary site. Some metastatic adenoca rcinomas have distinctive histological features that allow for their site d etermination (eg colonic adenocarcinoma, bronchioloalveolar cell carcinoma) , although the majority of metastatic adenocarcinomas have histological fea tures that are not distinctive enough to allow for a specific diagnosis of their origin. For this reason, electron microscopy and immunohistochemistry have been used to help identify the exact type (origin) of metastatic aden ocarcinomas. Relatively specific ultrastructural features used to diagnose metastatic adenocarcinomas of unknown primary origin include tubular myelin , intranuclear surfactant apoprotein tubular inclusions, Clara cell granule s, uniform short microvilli with filamentous cores and core rootlets, Lange rhans cells associated with neoplastic cells, cytoplasmic hyaline globules, lipid droplets, glycogen, and cytoplasmic crystals. Only a few of these ul trastructural features are absolutely specific. Relatively specific immunoh istochemical tests used to diagnose metastatic adenocarcinomas of unknown p rimary origin include prostate-specific antigen, thyroglobulin, estrogen an d progesterone receptor proteins, thyroid transcription factor-I, and surfa ctant apoproteins. Of these, prostate-specific antigen and thyroglobulin ar e the most specific. The purpose of this article is to discuss the use of e lectron microscopy and immunohistochemistry in the site-specific diagnosis of metastatic adenocarcinomas of unknown primary origin. HUM PATHOL 29:1393 -1402. Copyright (C) 1998 by W.B. Saunders Company.