Angiotropic malignant melanoma and extravascular migratory metastasis: description of 36 cases with emphasis on a new mechanism of tumour spread

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Abstract
We have identified in malignant melanoma an angio-tumoural complex in which tumour cells occupy a pericytic location along the endothelium of microvessels without evidence of intravasation. This pericytic angiotropism of melanoma cells, without any sign of intravasation, suggests that melanoma cells may migrate along the external surface of vessels, a mechanism we have termed 'extravascular migratory metastasis' (EVMM), as distinct from intravascular dissemination. The present study describes, for the first time, a series of 36 invasive melanoma cases ascertained for the presence of the histopathological characteristic of angiotropism. All cutaneous melanomas (31/35) were level IV with the exception that two melanomas were level II and two level V. In all cases, angiotropism was easily observed at the advancing front of the tumour or in nearby tissue. The study demonstrates that angiotropism of melanoma cells can be easily detected microscopically in routine tissue sections, i.e., in close proximity to microvessels (in a pericytic location). This phenomenon may prove to be important both biologically and prognostically in the routine histopathological assessment of melanoma, since we have recently shown that angiotropism could be a prognostic factor predicting risk for metastasis of melanoma. Our continued investigations to elucidate the significance of angiotropism in melanoma may help in understanding the molecular basis of metastasis and EVMM.

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