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BACKGROUND: The histogenesis of extragonadal germ cell tumors remains an enigma. The majority of patients with retroperitoneal tumors are male, and careful histologic evaluation reveals preinvasive intratubular germ cell neoplasia (ITGCN) or scars in the testis suggesting a so-called "burnt out" germ cell tumor. However, in the testes of patients with primary mediastinal germ cell tumors, no ITGCN has been described in the literature to date. The authors report the first case of simultaneous germ cell neoplasia in the mediastinum and the testis, providing further insights into the biology and origin of these lesions. METHODS: The authors report the pathologic features and cytogenetic findings in an adult male with a mediastinal germ cell tumor and asymmetric testis. This patient died shortly after diagnosis. RESULTS: A locally invasive mediastinal nonseminomatous germ cell tumor was associated with ITGCN in one testis. Metastases were not present clinically or on autopsy during a detailed and systematic examination of retroperitoneal lymph nodes and other viscera. Neither an invasive germ cell tumor nor a scar was found in either testis (both testes were serially sectioned and entirely examined histologically). CONCLUSIONS: The findings of this study suggest that the mediastinal tumor is a primary neoplasm with concomitant in situ lesion in one testis, suggesting a more generalized defect of germ cell and thus providing new information about the unresolved issue of the histogenesis of extragonadal germ cell tumors. This article presents a review of the literature concerning the issues highlighted by this case and discusses the hypotheses regarding the development of extragonadal germ cell tumors.