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Review
. 2023 Mar 21;15(6):1884.
doi: 10.3390/cancers15061884.

Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases

Mariam Lotfy Khaled  1   2 , Ahmad A Tarhini  3 , Peter A Forsyth  4 , Inna Smalley  1 , Yolanda Piña  4
Affiliations
Review

Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases

Mariam Lotfy Khaled et al. Cancers (Basel). .

Abstract

Leptomeningeal disease (LMD) is a devastating complication caused by seeding malignant cells to the cerebrospinal fluid (CSF) and the leptomeningeal membrane. LMD is diagnosed in 5-15% of patients with systemic malignancy. Management of LMD is challenging due to the biological and metabolic tumor microenvironment of LMD being largely unknown. Patients with LMD can present with a wide variety of signs and/or symptoms that could be multifocal and include headache, nausea, vomiting, diplopia, and weakness, among others. The median survival time for patients with LMD is measured in weeks and up to 3-6 months with aggressive management, and death usually occurs due to progressive neurologic dysfunction. In melanoma, LMD is associated with a suppressive immune microenvironment characterized by a high number of apoptotic and exhausted CD4+ T-cells, myeloid-derived suppressor cells, and a low number of CD8+ T-cells. Proteomics analysis revealed enrichment of complement cascade, which may disrupt the blood-CSF barrier. Clinical management of melanoma LMD consists primarily of radiation therapy, BRAF/MEK inhibitors as targeted therapy, and immunotherapy with anti-PD-1, anti-CTLA-4, and anti-LAG-3 immune checkpoint inhibitors. This review summarizes the biology and anatomic features of melanoma LMD, as well as the current therapeutic approaches.

Keywords: cerebrospinal fluid; leptomeningeal disease; melanoma; meninges; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The leptomeninges and CSF biology. The side view of the brain demonstrates the third and fourth ventricles where the cerebrospinal fluid (CSF) flows (red arrows). The upper square shows the three layers of the meninges covering the brain. The lower square represents the blood–CSF barrier and shows the choroid plexus layer, the specialized lining of the brain ventricles.
Figure 2
Figure 2
Tumor microenvironment of LMM. LMM CSF comprised a high number of apoptotic and exhausted CD4+ T-cells and a low number of CD8+ T-cells in addition to enrichment of MDSCs-like cells, indicating an immune-suppressed microenvironment ([33]).
Figure 3
Figure 3
Diagnosing LMD (upper panel) using CSF sampling and MRI. Signs/symptoms in LMD (lower panel) depending on the location(s) of CNS involvement.
See this image and copyright information in PMC

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