Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors

Teratoma with malignant transformation refers to a form of germ cell tumor in which a somatic teratomatous component becomes morphologically malignant and develops aggressive growth. We evaluated the spectrum of histologies, chromosomal abnormalities and clinical outcome in patients with teratoma with malignant transformation.

We identified 46 patients with germ cell tumor meeting morphologic criteria for malignant transformation. Histology, disease extent and treatment were correlated with survival. Tumors in 12 patients were studied by conventional cytogenetics or molecular genetic techniques for the isochromosome 12p [i(12p)], a marker for germ cell tumor, as well as other chromosomal abnormalities.

The site of first detection of malignant transformation occurred in the primary tumor of 21 cases (44%), at a metastatic site in 20 (43%) and in both sites in 5 (10%). Sarcoma was the most frequent histology, identified in 29 patients (63%) with rhabdomyosarcoma the most common subtype. Seventeen tumors (37%) contained a solid tumor histology other than sarcoma, with adenocarcinoma and primitive neuroectodermal tumor as the most common histologies. Four patients with mediastinal germ cell tumor containing sarcoma also had hematological malignancies, including a focus of nonHodgkin's lymphoma in the mediastinal primary tumor (1) and nonlymphocytic leukemia in spleen or bone marrow (3). Patients who had teratoma with malignant transformation components confined to the testis or retroperitoneum completely resected experienced a longer survival than those with distant metastases or incompletely resected tumors (p = 0.003). Chromosomal abnormalities associated with germ cell tumor (i[12p]) were identified in 11 of 12 tumors containing adenocarcinoma, primitive neuroectodermal tumor, sarcoma and leukemia. In addition to i (12p), chromosomal rearrangements characteristic of the transformed histology were detected in 4 tumors.

A variety of nongerm cell histologies, including sarcoma, adenocarcinoma, primitive neuroectodermal tumor and leukemia, may occur in association with germ cell tumor. Chromosomal abnormalities in these tumors include i (12p), reflecting germ cell tumor clonality, as well as chromosomal abnormalities associated with the transformed histology. These tumors do not respond like germ cell tumor to cisplatin-containing chemotherapy regimens. Treatment should be tailored according to that used in standard management of the transformed histology, and surgical resection is the mainstay of therapy.