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Review
. 2024 Apr 1;221(4):e20212121.
doi: 10.1084/jem.20212121. Epub 2024 Mar 7.

The anatomic basis of leptomeningeal metastasis

Morgan E Freret  1 , Adrienne Boire  2
Affiliations
Review

The anatomic basis of leptomeningeal metastasis

Morgan E Freret et al. J Exp Med. .

Abstract

Leptomeningeal metastasis (LM), or spread of cancer to the cerebrospinal fluid (CSF)-filled space surrounding the central nervous system, is a fatal complication of cancer. Entry into this space poses an anatomical challenge for cancer cells; movement of cells between the blood and CSF is tightly regulated by the blood-CSF barriers. Anatomical understanding of the leptomeninges provides a roadmap of corridors for cancer entry. This Review describes the anatomy of the leptomeninges and routes of cancer spread to the CSF. Granular understanding of LM by route of entry may inform strategies for novel diagnostic and preventive strategies as well as therapies.

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Conflict of interest statement

Disclosures: M.E. Freret reported grants from the American Society for Radiation Oncology, grants from Gerstner Philanthropies, and grants from the National Institutes of Health–National Cancer Institute during the conduct of the study. A. Boire reported grants from the National Institutes of Health–National Cancer Institute and personal fees from Apellis Pharmaceuticals during the conduct of the study; in addition, A. Boire had a patent number 11305014 issued to MSKCC, a patent number 11058665 issued to MSKCC, and a patent number 10413522 issued to MSKCC.

Figures

Figure 1.
Figure 1.
CSF barrier systems. (A) The arachnoid–CSF barrier is formed by arachnoid fibroblast-like cells joined by tight junctions, which separate systemic blood within fenestrated dural capillaries from subarachnoid CSF. (B) The blood–CSF barrier is formed by choroid plexus (ChP) epithelial cells joined by tight junctions, which separate systemic blood within fenestrated choroidal capillaries from ventricular CSF. Created with https://BioRender.com.
Figure 2.
Figure 2.
Overview of the anatomical basis of LM. This chart represents the possible anatomical routes of cancer spread to the leptomeninges from the systemic circulation or brain. In this concentric circle representation, from inside to outside, circles represent (1) the extracranial site from which cancer originates (e.g., systemic circulation), (2) the cell types comprising each CSF barrier system, (3) anatomical mechanisms of spread, and (4) the CSF, with the upper half representing the subarachnoid space and the bottom half the ventricles. Tight junction–bound barriers are denoted with a thick solid black line (i.e., arachnoid–CSF barrier, blood–CSF barrier, and blood–brain barrier), while interfaces lacking tight junctions are denoted with thick black dashed lines. Asterisk (*) denotes proposed routes of CSF efflux. ChP, choroid plexus. Created with https://BioRender.com.
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