Stewart-Treves syndrome angiosarcoma expresses phenotypes of both blood and lymphatic capillaries

BACKGROUND: The development of angiosarcoma in oedematous tissue is referred to as Stewart-Treves syndrome (STS). This rare and fatal complication is associated with chronic post mastectomy lymphoedema and radiotherapy for breast cancer. Angiosarcoma spread is facilitated by the formation of blood vessels (angiogenesis) and lymph vessels (lymphangiogenesis). In the future antiangiogenic therapy may improve the poor outcome of current treatments. There was evidence that blocking the angiogenenesis would inhibit progression of angiosarcoma. It seems reasonable to hypothesize that blocking the lymphangiogenesis may yield similar results. Although angiosarcomas commonly derive from blood vessels, in case of STS angiosarcomas chronic lymphoedema may suggest its lymphatic origin. The goal of this study was to visualize interstitial space and lymphatics in the central and peripheral regions of STS angiosarcoma. METHODS: On tissue samples obtained from STS angiosarcoma we have performed: first colour stereoscopic lymphography to visualise the morphology of lymphatic vessels and extracellular spaces, second immunohistochemical staining specific for lymphatic vessels endothelium (LYVE-1) and blood endothelial cells (CD31, factor VIII) and prolymphangiogenic vascular endothelial growth factor (VEGF-C) for precise identification of lymphatic endothelia. STS angiosarcoma morphology was assessed by comparison of pictures obtained on lymphography, microscopy and confocal microscopy. RESULTS: STS angiosarcomas present heterogenous morphology with areas dominated by hemangiosarcoma and lymphangiosarcoma structures. STS angiosarcoma expressed phenotypes of both blood and lymphatic endothelia. LYVE-1 and VEGF-C is expressed by STS angiosarcoma and may be used to discriminate tumour differentiation. Morphology of lymphatic vessels and spaces in the tumour suggest absence of their normal lymphatic function. CONCLUSIONS: Our results confirmed both hemangio- and lymphangiogenic origin of STS angiosarcoma. Expression of VEGF-C makes STS angiosarcoma a good candidate for targeted antilymphangiogenic therapy. However, morphology of intratumoral lymphatics on colour lymphography suggested their impaired function, which can hamper drug distribution.