Advances in diagnosis and treatment of intracranial germ cell tumors and future directions.

Intracranial germ cell tumors (IGCTs) are a group of malignant central nervous system (CNS) tumors primarily affecting children and adolescents, whose pathogenesis remains incompletely understood. The embryonic cell theory suggests that IGCTs may originate from pluripotent embryonic cells that escape normal migration and differentiation during embryonic development. Research indicates that DNA hypomethylation, abnormalities in the MAPK and/or PI3K signaling pathways, and chromosomal abnormalities play significant roles in the development and progression of IGCTs. Diagnosis relies on a comprehensive evaluation of clinical presentation, tumor markers, and imaging studies, ultimately confirmed by histopathology. In recent years, novel biomarkers in serum and cerebrospinal fluid, such as microRNAs (miRNAs) and circulating tumor DNA (ctDNA), have gained increasing attention for their diagnostic and prognostic value. Current treatment predominantly relies on surgery, radiotherapy, and chemotherapy, though the optimal radiation field and dose remain controversial. With a deepening understanding of molecular drivers and the tumor microenvironment, targeted therapy and immunotherapy are gradually being applied clinically. As the survival rate of patients with IGCTs improves, we are also confronted with new clinical challenges: how to minimize treatment-related long-term sequelae while maintaining excellent therapeutic outcomes, and improve the prognosis for refractory non-germinomatous germ cell tumors (NGGCTs). This review summarizes recent advances in genetic variation, diagnosis, and treatment of IGCTs, serving as a reference for exploring personalized therapeutic strategies, reducing treatment-related toxicity, and improving long-term prognosis.