How is rosette formation in brain tumours linked with cerebrospinal fluid spread?

Rosette formation, a characteristic histopathological feature of various paediatric brain tumours, appears to be linked with cerebrospinal fluid (CSF) dissemination. Tumours like medulloblastoma, ependymoma, retinoblastoma, pineal region, and embryonal tumours, known for their rosette formations, also exhibit a propensity for CSF spread, which can manifest as drop metastases and leptomeningeal involvement. CSF dissemination is detected early in the disease course and contributes to significant diagnostic and management challenges. The structure of rosettes, consisting of tumour cells arranged in a circular halo around a central lumen, may facilitate tumour spread along CSF pathways, potentially through interactions with interstitial fluid and CSF dynamics. Recent insights into the glymphatic system, which regulates fluid flow between brain parenchyma and CSF, suggest that tumours infiltrating perivascular spaces, particularly those expressing aquaporins such as aquaporin-4, may exploit these pathways for metastasis. Tumours with marked rosette formation also show a higher risk of associated hydrocephalus, which may persist post-tumour resection. Additionally, the mechanical and chemical affinities of rosette-forming tumour cells for interstitial and CSF spaces could drive this spread. Understanding the relationship between rosette formation and CSF dissemination offers potential therapeutic targets, including aquaporin modulation, to prevent metastasis and manage CSF-related complications in brain tumours.