Header

UZH-Logo

Maintenance Infos

Eight autopsy cases of melanoma brain metastases showing angiotropism and pericytic mimicry. Implications for extravascular migratory metastasis


Rodewald, Ann-Katrin; Rushing, Elisabeth J; Kirschenbaum, Daniel; Mangana, Joanna; Mittmann, Christiane; Moch, Holger; Lugassy, Claire; Barnhill, Raymond L; Mihic-Probst, Daniela (2019). Eight autopsy cases of melanoma brain metastases showing angiotropism and pericytic mimicry. Implications for extravascular migratory metastasis. Journal of Cutaneous Pathology, 46(8):570-578.

Abstract

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

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

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

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.

Abstract

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

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

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

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.

Statistics

Citations

Dimensions.ai Metrics
6 citations in Web of Science®
6 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 25 Jul 2019
0 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Pathology and Forensic Medicine
Health Sciences > Histology
Health Sciences > Dermatology
Language:English
Date:30 March 2019
Deposited On:25 Jul 2019 09:22
Last Modified:29 Jul 2020 10:58
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0303-6987
OA Status:Closed
Publisher DOI:https://doi.org/10.1111/cup.13465
PubMed ID:30927294

Download

Closed Access: Download allowed only for UZH members