Epithelioid Angiosarcoma of the Bladder: A Series of 9 Cases.

Primary angiosarcoma of the bladder is very rare, with approximately 30 cases reported in the literature. Those with epithelioid morphology are even rarer, with only single-case reports published. We describe the histopathologic features and clinical follow-up of 9 patients with epithelioid angiosarcoma (EA) of the bladder retrieved from our Surgical Pathology files from 1998 to 2014. Eight cases were consults. The mean age at presentation was 65 years (range, 39 to 85 y). The M:F ratio was 8:1. The clinical presentation was hematuria and bladder mass in all cases. Six patients had a history of radiotherapy to the pelvis, 5 to treat prostate cancer and 1 to treat uterine cervical cancer. The time from radiotherapy to the diagnosis of EA ranged from 6 to 15 years. The average size of the tumor was 4 cm. (range, 1 to 8 cm.). The submitting diagnoses were poorly differentiated carcinoma (n=5), high-grade invasive urothelial carcinoma (n=3), and atypical vascular proliferation (n=1). Morphologically, the tumors were composed of nests and sheets of highly atypical cells with high nuclear to cytoplasmic ratio, occasional intracytoplasmic lumens, and a hemorrhagic background. None of the cases showed any urothelial carcinoma component. Three patients showed in addition usual angiosarcoma in the resection specimen. By immunohistochemistry, 5/9 cases were positive for cytokeratins, including CK7 (n=3), AE1/AE3 (n=3), and Cam5.2 (n=1). All cases were positive for at least 1 endothelial marker, including CD31 (n=7), CD34 (n=2), FVIII (n=3), and ERG (n=2). Urothelial markers (p63 and GATA3) were consistently negative. Surgical treatment included transurethral resection of the bladder (TURB) only (n=5), TURB followed by cystoprostatectomy (n=2), TURB followed by partial cystectomy (n=1), and cystoprostatectomy only (n=1). The tumor involved the muscularis propria in 5/9 patients, the periureteric adipose tissue in 1 patient, and the prostate and seminal vesicles in 1 patient. Five of 9 patients died of disease, with a median survival of 7 months (range, 6 to 14 mo). Two patients were alive with disease at 3 and 6 months of follow-up. One patient who underwent radical cystoprostatectomy was alive with no evidence of disease 12 months after surgery. EA of the bladder is a rare malignancy that is frequently misdiagnosed as high-grade carcinoma, especially due to positive immunostaining for cytokeratins. This tumor is more frequent in older men with a history of radiotherapy to the pelvis. Morphologic features that should suggest the vascular origin of the tumor include highly atypical nuclei with interspersed erythrocytes, hemorrhagic background, and occasional intracytoplasmic lumens. Patients usually present with muscle invasive disease, and the prognosis is dismal.