Epithelioid angiosarcoma is a highly aggressive vascular malignancy associated with a very poor prognosis and early metastasis. It is a rare histologic variant of angiosarcoma characterized by epithelioid morphology. The epithelioid appearance is especially problematic because it is commonly mistaken by pathologists as a nonsarcomatous neoplasm such as a carcinoma or melanoma. The tumor has a predilection for males in middle to late life. It most commonly arises in the deep soft tissues, but can also be found in the bone, skin, thyroid and adrenals. Although most angiosarcomas are de novo malignancies, some tumors are known to develop in the post-radiation setting, as in this case.

The cell block highlights many similar features including pleomorphic cells arranged singly and in clusters with ovoid-to-spindle shapes and abundant granular cytoplasm. Some of the dissociated cells also show “rhabdoid” morphology, including small peripheral nuclei and abundant, dense eosinophilic cytoplasm. This “rhabdoid” appearance has been described and may often be confused with other epithelioid sarcomatous tumors, carcinomas and melanomas.

Epithelioid angiosarcomas display a wide range of morphologies. Typically, the tumor has a diffuse growth pattern composed of sheets, nests or cords of epithelioid endothelial cells with abundant cytoplasm, large vesicular nuclei and prominent nucleoli. Angioformative areas are often present consisting of anastomosing vessels lined by cytologically atypical endothelial cells with numerous mitoses and often intraluminal papillary formations. Areas of necrosis and hemorrhage are common (Figures 4 and 5). A chondromyxoid matrix is commonly observed in epithelioid hemangioendothelioma, a low-grade malignant vascular tumor, which is also in the differential diagnosis.

Immunohistochemically, the epithelioid endothelial cells usually show strong reactivity for CD31 (Figure 6), and variable/focal positivity for CD34, Factor VIII, epithelial membrane antigen, vimentin and CD68.

Fli-1, a nuclear transcription factor, demonstrates strong and diffuse expression in 85% of epithelioid angiosarcomas. Although Fli-1 is highly sensitive and specific for both benign and malignant vascular neoplasms, positive expression can help to distinguish epithelioid angiosarcomas from important mimics such as epithelioid sarcomas and carcinomas. The lymphovascular marker, D2-40, has far less diagnostic value. D2-40 is weakly expressed in a majority of epithelioid angiosarcomas, but it lacks specificity and is commonly expressed in epithelioid sarcomas and in various carcinomas.

Cytokeratin is often diffusely and strongly positive in epithelioid angiosarcomas, with positivity ranging from 78 to 100 percent in various studies. This marker is not helpful in distinguishing epithelioid angiosarcomas from mimics which express cytokeratin, including epithelioid sarcomas and carcinomas.