ANGI-21. THE VIRCHOW-ROBIN SPACE AS A CONDUIT FOR LEPTOMENINGEAL DISSEMINATION OF GLIOBLASTOMA

Abstract Leptomeningeal disease (LMD) is an uncommon but devastating mode of glioblastoma (GBM) progression. While animal models have suggested causes and routes of LMD, corroborating human evidence is incomplete. Among the proposed routes of tumor migration to the leptomeninges, Virchow–Robin (perivascular) spaces (VRS) are particularly anatomically compelling as their location would suggest the potential to serve as bidirectional conduits between the brain parenchyma and the meninges. To evaluate this hypothesis, we reviewed tissue sections from 32 patients with post-mortem brain histology specimens and confirmed GBM in the MCW Neuro-Oncology Brain Bank with SOX2 and Ki-67 immunohistochemistry-stained slides. VRS involvement was recorded categorically when confluent cuffs of neoplastic cells, identified by SOX2 and Ki-67 positive staining, were present in the VRS surrounding cortical blood vessels. LMD was assigned to patients with clinical autopsy report documentation of tumor extension into the subarachnoid space. 14 of 32 (44%) exhibited significant neoplastic proliferation within VRS and 10 of 32 brains (31%) met criteria for LMD. VRS involvement was significantly associated with LMD (Fisher exact, P = 0.0006); 9 of the 10 cases (90%) with LMD also had VRS invasion, compared to 1 of the 10 cases (10%) without it. In several of the overlapping cases, continuous cuffs of neoplastic cells were visualized extending from areas of LMD through VRS of penetrating blood vessels into deeper cortical parenchyma, illustrating a continuous anatomical path for tumor cells between these two compartments. These data provide initial insights that VRS invasion may be linked to leptomeningeal dissemination in GBM and act as a conduit for tumor trafficking and though the directionality and temporal precedence between VRS invasion and LMD is uncertain, the clinical identification of tumor cells in VRS on pathological review may point towards the likelihood of LMD, potentially warranting more intensive patient monitoring.