Genetic analysis in the diagnosis of neoplasms of unknown primary tumor site.

The identification of nonrandom chromosomal abnormalities in hematologic and solid tumor malignancies, which can serve as specific diagnostic markers, has permitted the application of cytogenetic techniques to the diagnosis of poorly differentiated carcinomas of unknown primary tumor site. Cytogenetic markers specific for germ cell tumors, neuroepithelial tumors, and lymphoma have now been identified in these patients. In the case of germ cell tumor diagnosis, the finding of a cytogenetic marker specific for germ cell cancer was predictive of responsiveness to cisplatin-based chemotherapy and long-term disease-free survival. DNA hybridization techniques, including quantitative Southern blot analysis and FISH, were also used to establish the diagnosis of germ cell tumor, particularly in the setting in which conventional cytogenetic analysis was unsuccessful. In poorly differentiated tumors in which conventional light microscopic, immunohistochemical, and electron microscopic techniques fail to yield a specific diagnosis, the use of molecular and cytogenetic markers in human malignancy promises to increase diagnostic acuity. These techniques have the potential to give clearer insight into the biology of this heterogeneous group of tumors and assist in directing appropriate therapy to patients who indeed may have a highly treatable disease.