Satellitosis, a Crosstalk between Neurons, Vascular Structures and Neoplastic Cells in Brain Tumours; Early Manifestation of Invasive Behaviour

SIMPLE SUMMARY: This article reviews the concept of cellular satellitosis as originally described histologically by Santiago Ramón y Cajal in 1899 and Hans Joachim Scherer, more specifically in the context of glioblastoma invasiveness, during the early part of the 20th century. With the advent of new and emerging molecular technologies in the 21st century, the significance of both vascular and neuronal satellitosis by neoplastic cells offers intriguing possibilities into further clarifying the development, pathobiology and therapy of malignant glioma through closer investigation into the nature of these histological hallmarks. ABSTRACT: The secondary structures of Scherer commonly known as perineuronal and perivascular satellitosis have been identified as a histopathological hallmark of diffuse, invasive, high-grade gliomas. They are recognised as perineuronal satellitosis when clusters of neoplastic glial cells surround neurons cell bodies and perivascular satellitosis when such tumour cells surround blood vessels infiltrating Virchow–Robin spaces. In this review, we provide an overview of emerging knowledge regarding how interactions between neurons and glioma cells can modulate tumour evolution and how neurons play a key role in glioma growth and progression, as well as the role of perivascular satellitosis into mechanisms of glioma cells spread. At the same time, we review the current knowledge about the role of perineuronal satellitosis and perivascular satellitosis within the tumour microenvironment (TME), in order to highlight critical knowledge gaps in research space.