Can lymphangiosarcoma be resurrected? A clinicopathological and immunohistochemical study of lymphatic differentiation in 49 angiosarcomas.

AIMS The term lymphangiosarcoma has largely been abandoned in the current classification of endothelial neoplasms. Recently, a number of lymphatic-associated antibodies have been developed for immunohistochemistry, which frequently stain angiosarcomas, implying lymphatic or mixed lymphatic and blood vascular differentiation is common. The aim was to investigate further lymphatic antigen expression, and to explore the relation of immunohistochemistry to morphological and clinical findings. METHODS AND RESULTS Forty-nine angiosarcomas in tissue microarrays were analysed with D2-40 and antibodies to Prox-1 and vascular endothelial growth factor receptor (VEGFR)-3. D2-40 was positive in 53%, Prox-1 in 76%, and VEGFR-3 in 57%. Tumours with features attributable to lymphatic differentiation such as hobnail and kaposiform morphologies were more often positive with these markers, including a statistical association between D2-40 and hobnailing. Ten tumours had features suggestive of lymphatic differentiation, namely well-differentiated histology, interanastomosing channels devoid of red cells, prominent hobnailing, lymphoid aggregates, and multi-antigen expression of D2-40 (100%), Prox-1 (100%) and VEGFR-3 (60%), which might be deserving of the appellation lymphangiosarcoma. Nine were cutaneous scalp/facial tumours in elderly patients and one arose within chronic lymphoedema. CONCLUSIONS Lymphatic differentiation is common in angiosarcoma, certain subsets show greater lymphatic differentiation than others, and lymphangiosarcoma may be defined pathologically, rather than clinically.