Primordial Germ Cells in the Human Fetal Brain: Origins of Intracranial Germ Cell Tumours

Germ cell tumours are heterogeneous tumours arising in the gonads, though they also affect extragonadal sites, including midline structures of the central nervous system (CNS). While intracranial germ cell tumours (iGCTs) are extensively characterised, their developmental origin remains speculative. The most frequently cited hypothesis posits that primordial germ cells (PGCs) from the embryonic yolk sac aberrantly migrate to the brain in-utero and form tumours after neoplastic transformation. However, there is currently no direct evidence for PGCs in the human brain. We report for the first time the presence of apparently non-tumour forming PGCs in 2 fetal brains, incidentally discovered on post-mortem examination for non-CNS indications. One case demonstrated PGCs in the ventrolateral thalamus, while the other demonstrated PGCs in the anterior germinal matrix, septal area, and anterior thalamus. These cases demonstrate for the first time the presence of PGC's in the human fetal brain, and that the foundation for iGCTs may be present in the CNS during early development. The distribution seems to favour the hypothesis that PGCs may be derived from germinal matrix neural stem cells rather than necessarily from extracranial midline migration to the brain.