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.
Graphical abstract
Rosette-like tumour cell arrangements may be related with extracellular cues in interstitial fluid which is contained in their lumens. Tumour cell affinity to interstitial fluid and resulting tropism may result in tumour cells appearing in CSF and tumour spread along CSF pathways, including drop metastases and leptomeningeal spread. The glymphatic system provides a framework for a continuum between interstitial fluid and CSF spaces and tumour cell presence in glymphatic/CSF pathways could contribute to hydrocephalus.
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