Eight autopsy cases of melanoma brain metastases showing angiotropism and pericytic mimicry. Implications for extravascular migratory metastasis.
angiotropism
extravascular migratory metastasis
melanoma; metastasis
pericytic mimicry
vascular co-option
Journal
Journal of cutaneous pathology
ISSN: 1600-0560
Titre abrégé: J Cutan Pathol
Pays: United States
ID NLM: 0425124
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
31
10
2018
revised:
08
03
2019
accepted:
26
03
2019
pubmed:
31
3
2019
medline:
14
2
2020
entrez:
31
3
2019
Statut:
ppublish
Résumé
Metastatic tumor spread is a complex multistep process. Due to the blood-brain barrier, metastasis to the central nervous system is restrictive with a distinct predilection for certain tumor types. In melanoma patients, brain metastasis is a common endpoint with the majority showing evidence of widespread disease at autopsy. In a previous murine melanoma model, we have shown that melanoma cells migrate along preexisting vessels into the brain, showing angiotropism/vascular co-option and pericytic mimicry. Using conventional morphology and immunohistochemistry, we analyze brain metastases from eight autopsy cases. In addition, tissue clearing, which enables three-dimensional visualization over a distance of 100 μm is used. We show the angiotropic localization of melanoma deposits in the brains in all eight autopsy cases. Tissue clearing techniques have allowed visualization of melanoma cells in one case exclusively along the abluminal surface of brain blood vessels over a distance of 100 μm, thus showing pericytic mimicry. Our analyses show clear-cut evidence of angiotropism and pericytic mimicry of melanoma cells within the brain over some distance. In addition, these results support the hypothesis of metastasis along pathways other than hematogenous spread, or extravascular migratory metastasis (EVMM). During EVMM, melanoma cells may metastasize to the brain through pericytic mimicry, circumventing the blood-brain barrier.
Sections du résumé
BACKGROUND
BACKGROUND
Metastatic tumor spread is a complex multistep process. Due to the blood-brain barrier, metastasis to the central nervous system is restrictive with a distinct predilection for certain tumor types. In melanoma patients, brain metastasis is a common endpoint with the majority showing evidence of widespread disease at autopsy. In a previous murine melanoma model, we have shown that melanoma cells migrate along preexisting vessels into the brain, showing angiotropism/vascular co-option and pericytic mimicry.
METHODS
METHODS
Using conventional morphology and immunohistochemistry, we analyze brain metastases from eight autopsy cases. In addition, tissue clearing, which enables three-dimensional visualization over a distance of 100 μm is used.
RESULTS
RESULTS
We show the angiotropic localization of melanoma deposits in the brains in all eight autopsy cases. Tissue clearing techniques have allowed visualization of melanoma cells in one case exclusively along the abluminal surface of brain blood vessels over a distance of 100 μm, thus showing pericytic mimicry.
CONCLUSIONS
CONCLUSIONS
Our analyses show clear-cut evidence of angiotropism and pericytic mimicry of melanoma cells within the brain over some distance. In addition, these results support the hypothesis of metastasis along pathways other than hematogenous spread, or extravascular migratory metastasis (EVMM). During EVMM, melanoma cells may metastasize to the brain through pericytic mimicry, circumventing the blood-brain barrier.
Types de publication
Case Reports
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
570-578Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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