CSF hCG in the crossroads of neurotoxicity and disease: Lessons from germ cell tumor

Human chorionic gonadotropin (hCG) in cerebrospinal fluid (CSF) has emerged as a critical biomarker in the diagnosis, monitoring, and understanding of intracranial germ cell tumors (iGCTs). Beyond its canonical role in reproduction, CSF hCG dynamics may reflect intricate tumor biology, neuroimmune interactions, and paracrine signaling within the central nervous system.

This review critically examines the conceptual framework and clinical implications of CSF hCG as a defining biomarker axis in iGCTs, with a focus on its pathophysiological significance, dynamic regulation, and potential as a prognostic and therapeutic guide.

CSF hCG levels are influenced by tumor subtype, burden, blood-brain barrier permeability, and local neuroinflammatory milieu. Dysregulated CSF hCG correlates with tumor activity, microenvironmental alterations, and neural tissue vulnerability, providing insight into both disease progression and potential neurotoxic sequelae. Mechanistic studies suggest that hCG in the CSF may modulate microglial activation, oxidative stress, neurotransmitter signaling, and blood-brain barrier integrity. While the causal links between hCG dynamics and neurological dysfunction remain to be fully elucidated, these patterns offer a unique window into tumor-host interactions within the CNS and highlight hCG as a potential axis for targeted monitoring and intervention.

CSF hCG represents more than a diagnostic marker; it embodies a dynamic biomarker axis integrating tumor biology, neurophysiological signaling, and clinical prognosis in iGCTs. Understanding its regulation and mechanistic roles could inform precision monitoring, risk stratification, and therapeutic strategies, bridging biomarker discovery with translational neuro-oncology.