Discussion:

Genitourinary soft tissue sarcomas account for 2% of all soft tissue sarcomas and only 1% to 2% of all malignant genitourinary tumors. There are multiple sarcoma subtypes however all have connective tissue origin and extremely aggressive biologic behavior. Angiosarcomas are fatal and aggressive malignant vascular mesenchymal tumors that comprise only about 2% of all soft tissue sarcomas. They typically occur in skin or superficial soft tissue with the scalp of elderly men having the most frequent occurrence rates. These tumors with epithelioid morphology are even rarer. Epithelioid angiosarcomas typically arise in tumors of deep tissue and can be very difficult to distinguish from poorly differentiated carcinoma. Historically, the bladder is one of the rarest sites for primary angiosarcoma and has been minimally reported in literature. The majority of reported cases of primary bladder angiosarcomas presented with hematuria as the most common symptom.

The following criteria are used to help with diagnosis: (1) nests and sheets of highly atypical cells with high N:C ratio and cytoplasm is typically eosinophilic or amphophilic, (2) tumor cells display large nucleoli and nuclear pleomorphism (3) most cases have copious amounts of frank hemorrhage and fragments of erythrocytes between tumor cells are consistently found (4) positive endothelial marker including CD31, CD34, ERG and negative urothelial markers such as p63 and GATA3. Anastomosing vascular channels lined with hyper-chromatic cells can be found in angiosarcomas but maybe lacking in the epithelioid morphology. Sarcomatoid variant of poorly differentiated urothelial carcinoma is a common erroneous diagnosis since epithelioid angiosarcomas may express focal positivity for cytokeratin and if EA is not considered endothelial markers may not be ordered. Epithelioid Hemangioendothelioma is another potential differential pitfall due to epithelioid morphology and positive immunostaining for vascular markers. However, epithelioid hemangioendothelioma will lack the high-grade nuclear features of epithelioid angiosarcoma. Other differential diagnosis include metastatic angiosarcoma, Kaposi’s sarcoma and metastatic melanoma. When narrowing down one’s differential, keep in mind that melanomas will have a nesting pattern, melanin content and positivity for S-100 and negative for endothelial markers.

Epithelioid angiosarcomas of the bladder are a rare malignancy that is easily misdiagnosed due to the positive immunostaining for cytokeratins. This tumor is more common in older males especially with a previous history of radiotherapy to the pelvis. Morphologic features should suggest the vascular origin and include highly atypical nuclei with intermingled extravasated red blood cells and a hemorrhagic background. Occasional intracytoplasmic lumens can also be seen. Patients will typically present with muscle invasive disease and prognosis is poor.

Treatment of soft tissue sarcomas always involves radical surgery with wide circumferential margins whenever possible. Margin negativity is crucial for cure, and even then, 20%-25% recur locally despite adequate resections and margins. The tendency for local recurrence, distant metastases and poor prognosis of angiosarcomas is well documented in literature. Treatment should be as rapid and aggressive as possible and typically includes the radical surgery followed by high-dose adjuvant chemoradiation. Most patients with epithelioid angiosarcomas have an average survival of less than 2 years.