GERM CELL TUMORS

Abstract

Central nervous system (CNS) germ cell tumors (GCTs) are separated into germinomas and nongerminomatous germ cell tumors (NGGCTs). The latter group includes teratoma (mature and immature), teratoma with malignant transformation, yolk sac tumor, embryonal carcinoma, choriocarcinoma, and mixed GCTs. CNS GCTs can be classified based on their histologic appearance and immunohistochemical profiles with histologic subtype being the best predictor of outcome. Germinomas respond exceptionally well to chemotherapy and irradiation and have been shown to have survival rates in excess of 90 %. In contrast, NGGCTs are more resistant to therapy and require more intensive chemotherapy, as well as higher doses of irradiation. There is little information on the histogenesis and molecular genetics of CNS GCTs. Fluorescent in situ hybridization (FISH) studies have shown a gain of X chromosome in a majority of GCTs. Other studies have shown that 12p abnormalities (gains and isochromosome 12p) are common, especially in germinomas. Gene expression analysis studies show overexpression of self-renewing pluripotency genes and genes responsible for tumor growth and differentiation in various tumors with no significant differences in gene expression between CNS GCTs of similar histology arising at different sites and different ages within the pediatric age group. Differences in microRNA expression have been demonstrated between histologic subtypes of CNS GCTs, and their potential use as a biomarker in the serum and cerebrospinal fluid is being explored. KIT mutations are the most commonly found abnormality on whole genome sequencing, predominantly in germinomas, followed by genes involved in the MAPK signaling pathway, suggesting a role for KIT inhibitors in the management of these tumors.