Primary Central Nervous System Germ Cell Tumors: A Review and Update

Abstract

Importance: Primary central nervous system (CNS) germ cell tumors (GCT) are a heterogeneous group of tumors that are still poorly understood. In North America, GCTs comprise approximately 1% of primary brain tumors in pediatric and young adult patients. GCTs can occur as pure or mixed subtypes; they are divided into germinomas, which are the most common subtype, and non-germinomatous germ cell tumors (NGGCTs), which consist of approximately one-third of GCTs and include teratomas, embryonal carcinomas, choriocarcinomas, and yolk sac tumors. Observations: While the etiology of primary CNS GCT is not entirely clear, the various subtypes are lineage-related and may involve progenitor germ cells that fail to migrate and become trapped in midline locations. Primary CNS GCT most commonly arises in the pineal region but also occur in other areas. Presenting symptoms can include headache, Parinaud syndrome, diabetes insipidus, precosious puberty, ataxia, or hemiparesis. Diagnosis of primary CNS GCTs can be difficult and is often delayed. Various imaging studies and tumor markers can assist in specific diagnosis. Treatment plans differ depending on the subtype of GCT and may vary among physicians and institutions. Germinomas have a favorable prognosis with a greater than 90% overall survival, while NGGCTs only have survival rates ranging from 40-70%. Conclusions and Relevance: Germinomas seem to be most effectively treated with chemotherapy and radiation, while NGGCT usually require surgical resection, chemotherapy, and radiation with the exception of mature teratomas frequently curable with surgery alone. Gamma knife radiosurgery is a promising treatment that may be an effective additional treatment option. Cytogenic and molecular analyses are attempting to further specify the different GCT subtypes and are helping to direct the development of distinct therapeutic targets to improve treatment and prognosis.