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Updated: Aug 4, 2025
A Murine Ommaya Xenograft Model to Study Direct-Targeted Therapy of Leptomeningeal Disease
Published on: January 29, 2021
Leptomeningeal dissemination in pediatric brain tumors
Carolina Cocito1, Brice Martin1, Alexandra M Giantini-Larsen1
1Weill Cornell Medical College, Department of Neurological Surgery, New York, NY, United States.
Abstract:
Leptomeningeal disease (LMD) in pediatric brain tumors (PBTs) is a poorly understood and categorized phenomenon. LMD incidence rates, as well as diagnosis, treatment, and screening practices, vary greatly depending on the primary tumor pathology. While LMD is encountered most frequently in medulloblastoma, reports of LMD have been described across a wide variety of PBT pathologies. LMD may be diagnosed simultaneously with the primary tumor, at time of recurrence, or as primary LMD without a primary intraparenchymal lesion. Dissemination and seeding of the cerebrospinal fluid (CSF) involves a modified invasion-metastasis cascade and is often the result of direct deposition of tumor cells into the CSF. Cells develop select environmental advantages to survive the harsh, nutrient poor and turbulent environment of the CSF and leptomeninges. Improved understanding of the molecular mechanisms that underlie LMD, along with improved diagnostic and treatment approaches, will help the prognosis of children affected by primary brain tumors.
Insights
Leptomeningeal disease (LMD) in pediatric brain tumors (PBTs) is complex and varies by tumor type. Further research into LMD's molecular mechanisms and improved diagnostics will enhance treatment and outcomes for affected children.
Area of Science:
- Neuro-oncology
- Pediatric oncology
- Cancer metastasis
Background:
- Leptomeningeal disease (LMD) in pediatric brain tumors (PBTs) presents a significant clinical challenge due to its poorly understood nature and varied presentation.
- Incidence, diagnosis, treatment, and screening for LMD differ substantially based on the primary PBT pathology.
- While common in medulloblastoma, LMD is observed across diverse PBT types and can manifest at diagnosis, recurrence, or as primary LMD.
Purpose of the Study:
- To elucidate the complexities of leptomeningeal disease in pediatric brain tumors.
- To highlight the variability in LMD diagnosis, treatment, and screening across different PBT pathologies.
- To emphasize the need for a deeper understanding of LMD's molecular underpinnings and improved clinical management strategies.
Main Methods:
- Review of existing literature on leptomeningeal disease in pediatric brain tumors.
- Analysis of dissemination and seeding mechanisms via cerebrospinal fluid (CSF) pathways.
- Exploration of cellular adaptation to the CSF and leptomeningeal microenvironment.
Main Results:
- Leptomeningeal disease in pediatric brain tumors is a heterogeneous condition with diverse clinical manifestations.
- Tumor cell dissemination into the CSF follows a modified invasion-metastasis cascade, requiring adaptation to survive the CSF environment.
- Variability in LMD presentation and management necessitates tailored approaches based on primary tumor type.
Conclusions:
- Improved understanding of the molecular mechanisms driving LMD is crucial for advancing pediatric neuro-oncology.
- Enhanced diagnostic tools and targeted therapeutic strategies are needed to improve the prognosis for children with PBTs and LMD.
- Further research into the unique challenges posed by LMD in pediatric brain tumors is warranted.
