Malignant Hematologic Disorders Arising from Mediastinal Germ Cell Tumors. A Review of Clinical and Biologic Features

Since 1985, the biological association of mediastinal germ cell tumors and certain hematologic malignancies has been recognized. Continued investigation of such patients and new cytogenetic information brings additional insights into the clinical aspects of this syndrome as well as hinting at the possible etiology. This syndrome only occurs in patients with non-seminomatous germ cell tumors arising within the mediastinum. The interval from the diagnosis of the germ cell tumor to the development of the hematologic malignancy is brief (usually less than 6 months). Careful characterization of the hematologic malignancies in this patient population suggests a predominance of abnormalities within the megakaryocytic lineage. Recent cytogenetic analysis in one patient identified the most common abnormality of germ cell cancers, isochromosome 12p, in the mediastinal germ cell tumor as well as in the subsequent leukemic blasts. i12p is not a cytogenetic abnormality associated with the development of leukemia. The clinical evidence as well as this new cytogenetic information suggest strongly that the two abnormalities are clonally related and that the hematologic malignancy may arise as a consequence of defferentiation of the multipotent malignant germ cell.