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

• Published in: Journal of cutaneous pathology 2019-08, Vol.46 (8), p.570-578
• Main Authors: Rodewald, Ann‐Katrin, Rushing, Elisabeth J., Kirschenbaum, Daniel, Mangana, Joanna, Mittmann, Christiane, Moch, Holger, Lugassy, Claire, Barnhill, Raymond L., Mihic‐Probst, Daniela
• Format: Article
• Language: English
• Subjects: Adult; Aged; angiotropism; Autopsy; Blood vessels; Blood-brain barrier; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - pathology; Brain; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain Neoplasms - secondary; Cell migration; Cell Movement; Central nervous system; extravascular migratory metastasis; Female; Humans; Immunohistochemistry; Localization; Male; Melanoma; Melanoma - metabolism; Melanoma - pathology; melanoma; metastasis; Metastases; Metastasis; Middle Aged; Mimicry; Neoplasm Metastasis; Pericytes - metabolism; Pericytes - pathology; pericytic mimicry; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; vascular co‐option
• ISSN: 0303-6987; 1600-0560
• DOI: 10.1111/cup.13465

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.