Epithelioid hemangioma (EH) may be considered in the differential diagnosis because it contains endothelial cells with abundant eosinophilic and an epithelioid appearance. Differently from the case in exam, however, EH is a nodular proliferation of well-formed capillaries in relationship with a dense lymphoid infiltrate with occasional germinal centers, and abundant eosinophils. Many cases of EH are centered around a small artery.
Carcinoma should always be considered in the differential diagnosis when in the presence of cells with epithelioid morphology and vacuolated cytoplasm, even in the absence of clinical history of carcinoma; however, carcinomas are generally positive for different keratins and may contain mucin, and are negative for vascular markers, differently from our case.
Epithelioid angiosarcoma (EAS) is a high grade sarcoma that can be solid or composed of anastomosing vascular spaces. The tumor cells have abundant eosinophilic cytoplasm and large hyperchromatic nuclei with prominent nucleoli. Mitoses, including atypical forms are common, and necrosis and interstitial hemorrhage may be prominent. The majority of EAS are large neoplasms of the deep soft tissue.
EHE is a vascular neoplasm of unpredictable behavior, with the majority of cases characterized by a relatively benign course, and with the remaining 25% associated with metastasis to distant sites, mainly the lung, liver, bones, and lymph nodes, resulting in death of 15% of the patients. The majority of soft tissue EHE affects adults, with a peak incidence in the fifth decade of life; young children are generally spared. The deep soft tissue is more commonly affected, followed by subcutis and skin. The lower and upper extremities are the most frequently involved, followed by the trunk, head and neck, mediastinum, and abdominal cavity. EHE generally presents as a solitary, slightly painful soft tissue mass that on average measures 3 cm. The majority of the cases originate within vessels, usually a vein (50% to 75% of cases). EHE may have the gross appearance of an organizing thrombus with a variegated white-red cut surface, or it may be an ill-defined pale and firm lesion. Microscopically EHE is composed of cords and nests of round to slightly spindled endothelial cells embedded in myxohyaline matrix resembling cartilage. Individual tumor cells have round, regular nuclei and abundant eosinophilic cytoplasm that is often vacuolated, giving the cell the appearance of a “blister” cell. Mitotic activity is low (<3 mitoses per 20 HPF, on average) and tumor necrosis is seen in a minority of cases (<10%). Cases with increased cytologic atypia and mitotic activity are usually associated with a more aggressive behavior. The tumor cells characteristically stain for endothelial markers (CD31, CD34, FLI1, and Factor VIII). It is important to remember that keratins are commonly expressed in EHE. Recently, a recurrent t(1; 3) (p36.3; q25) translocation has been reported in EHE. Although the biological behavior is frequently unpredictable, a large clinical study has found that tumor larger than 3 cm and with a mitotic activity above 3 mitoses per 50 HPF have an increased risk for adverse outcome compared with smaller and less mitotically active cases, which are considered low-risk (59% 5-year-disease-specific survival in high-risk group versus 81% in low-risk group). Patients with high-risk soft tissue EHE may benefit from adjuvant chemotherapy, as patients with hepatic and pulmonary EHE.
Epithelioid sarcoma (ES) may resemble EHE both morphologically and immunohistochemically. ES, however, usually has a granulomalike architecture in which the tumor cells surround a necrotic center and does not produce the characteristic myxo-chondroid matrix seen in EHE. Immunohistochemically, ES shows strong reactivity for cytokeratin and may express in 40% of the cases positivity for CD34, with negativity for CD31, Factor VIII, and FLI-1. EHE, on the other hand, demonstrates only focal and weaker reactivity for cytokeratin and is generally positive for all endothelial markers.
