Comprehensive characterization and prognostic analysis of multifocal intracranial germ cell tumors

Given the limited evidence on multifocal intracranial germ cell tumors (iGCTs)-a rare but clinically distinct entity-this study comprehensively characterizes their clinical features and identifies key prognostic factors.

A retrospective analysis was conducted on 48 patients diagnosed with multifocal iGCTs from 2006 to 2025 in our center. Demographics, clinical presentation, MRI characteristics, pathology, treatment modalities, and survival outcomes were analyzed. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methods. Prognostic factors were identified through univariate and multivariate analyses.

Median age at diagnosis was 13 years (range: 6-31), with male predominance (87.5%). The most common symptoms were diabetes insipidus (81.2%) and hemiparesis (56.2%). Significant imaging features included hemiatrophy (47.9%) and heterogeneous enhancement (68.8%). Germinoma was diagnosed in 66.7% of patients and combined chemoradiotherapy (CHT + RT) was administered to 58.3% of patients. The 10-year OS and PFS rates were 84.6% and 70.6%, respectively. In this exploratory analysis, factors associated with favorable outcomes included germinoma histology (HR = 0.06, 95% CI 0.01-0.53, P = 0.011), combined CHT + RT (HR = 0.09, 95% CI 0.01-0.76, P = 0.027), and absence of tumor-infiltrating lymphocytes (HR = 0.14, 95% CI 0.02-1.06, P = 0.050 for PFS).

Multifocal iGCTs represent a distinct clinical entity with outcomes that are poorer compared to solitary iGCTs. Germinoma, combined chemoradiotherapy, and lymphocyte infiltration may be associated with survival, warranting further investigation. These findings emphasize the importance of histology-driven, multimodal treatment strategies for optimizing outcomes in this rare disease.