Vascular endothelial growth factor receptor-3 (VEGFR-3): A marker of vascular tumors with presumed lymphatic differentiation, including Kaposi's sarcoma, kaposiform and Dabska-type hemangioendotheliomas, and a subset of angiosarcomas

Recently, a novel monoclonal antibody to vascular endothelial growth factor receptor 3 (VEGFR-3), a tyrosine kinase receptor expressed almost exclusiv ely by lymphatic endothelium in the adult, has been shown to react with a s mall number of cases of Kaposi's sarcoma (KS) and cutaneous lymphangiomas, We sought to extend these studies to a large number of well-characterized v ascular neoplasms to evaluate diagnostic uses of this antibody and to deter mine whether it defines them in a thematic fashion. Formalin-fixed, paraffi n-embedded sections from 70 vascular tumors were immunostained with antibod ies to VEGFR-3 von Willebrand factor (vWF), and CD31, Anti-VEGFR-3 was posi tive in 23 of 24 KS, 8 of 16 angiosarcomas (AS), 6 of 6 kaposiform hemangio endotheliomas, 4 of 4 Dabska tumors, and 2 of 13 hemangiomas. Positively st aining angiosarcomas were characterized either by a prominent lymphocytic c omponent, a hobnail endothelial cell similar to that encountered in the Dab ska tumor, or spindled areas resembling KS. No VEGFR-3 expression was noted in any cases of epithelioid hemangioendothelioma, pyogenic granuloma, litt oral angioma, or stasis dermatitis. vWF expression was seen in 10 of 13 KS; 13 of 14 AS; 4 of 5 kaposiform hemangioendotheliomas; and all Dabska tumor s, hemangiomas, lymphangiomas, epithelioid hemangioendotheliomas, vascular malformations, stasis dermatitis, and splenic littoral angiomas. CD31 expre ssion was present in 12 of 13 KS, 13 of 14 AS, and in all other cases. Expr ession of VEGFR-3 is a very sensitive marker of KS, kaposiform, and Dabska- type hemangioendotheliomas, suggesting that all show at least partial lymph atic endothelial differentiation, Expression of VEGFR-3 does not reliably d iscriminate KS from AS. However, the expression of VEGFR-3 by certain AS ha ving Kaposi-like areas, a prominent lymphocytic infiltrate, or hobnail endo thelium may define subset(s) having phenotypic, if not pathogenetic and bio logic, differences.