Primary Angiosarcoma of Urinary Bladder: 13th Reported Patient

Angiosarcoma of the urinary bladder is an extremely rare and poorly characterized tumor. We are presenting the 13th reported patient who was an 89-year-old man initially presented with massive hematuria. His past medical history included external-beam radiation for prostate cancer 12 years ago. His PSA was 0.26 ng/dL. His CT-Urography demonstrated a highly vascular mass originating from the bladder base. The mass was partially resected, transurethrally. The pathology was consistent with primary angiosarcoma of the urinary bladder. Bone scan and CT-U showed metastasis to spine. The patient was treated with palliative radiotherapy for back pain due to metastasis, and he refused chemotherapy. The patient died 3 months after his initial diagnosis.


Introduction
Nonurothelial tumors of the urinary bladder represent less than 5% of all bladder tumors, with sarcoma being the most common of which [1]. Angiosarcoma, one of the rarest types of sarcoma, arises from the endothelial layer of blood vessels. It is a highly aggressive cancer and carries very poor prognosis. Only 12 cases of primary angiosarcoma of the urinary bladder have been reported so far [2].

The
Patient. An 89-year-old male presented to ER with massive hematuria. Two large caliber intravenous cannulas were placed and blood tests for CBC, biochemistry, and blood type were taken. A 3-way 22Fr catheter was urethrally inserted and bladder irrigation with normal saline started. His past medical history included T1 prostatic adenocarcinoma for which he received external beam radiotherapy 12 years ago. His physical examination and digital rectal examination were unremarkable. His creatinine was 0.9 mg/dL, PSA was 0.26 ng/mL, and cytology was negative for malignant cells. CT-Urography demonstrated a large highly vascular mass with irregular margins originating from the left bladder wall (Figure 1(a)). Computed tomography also showed severe left-sided hydronephrosis and hydroureter ( Figure 1(b)) and lytic lesions in the vertebrae and pelvic bones suspected as metastases. Cystoscopy showed a large solid mass arising from the bladder base which was resected transurethrally.

Histopathology.
Macroscopically, the specimen was 6 × 5 × 4 cm 3 of grey tissue and blood clots. Microscopically, the tissue diagnosis was consistent with primary angiosarcoma of urinary bladder invading muscularis layer, with anastomosing vascular channels (Figure 2(a)). The tumor strongly stained for CD31 and CD34 and focally for f VIII (Figures 2(b) and 2(c)), three markers for endothelial cells, and was negative for Keratin P63, a marker of epithelial cells (Figure 2(d)). No prostatic tissue was found in the specimen.

Treatment.
The patient was referred to palliative radiotherapy because of symptomatic spinal metastasis. The patient was consulted about the option of chemotherapy but he denied. The patient died 3 months after the initial diagnosis.

Discussion
Nonurothelial neoplasms of the urinary bladder are extremely rare. Of these neoplasms, sarcoma represents the most common nonurothelial neoplasm of the urinary bladder [1]. The most common sarcoma of the bladder is leiomyosarcoma, which accounts for more than half of the sarcomas [1]. Angiosarcoma of the urinary bladder is a very rare subtype of sarcoma with only 12 reported cases [2]. All 12 cases reported presented with hematuria, 11 with gross hematuria, and one with microscopic hematuria. Almost all cases were muscle-invasive tumors. Twelve patients' characteristics are summarized in Table 1. Histological and immunohistochemical features are summarized in Table 2. Four cases of secondary angiosarcoma of the bladder were previously reported, originating from the penis [3], pelvis [4], Kaposi's sarcoma [5], and vagina [6].
Angiosarcoma is a very aggressive tumor carrying poor prognosis [7]. Most of the angiosarcomas are at least muscleinvasive when diagnosed [8]. Hematuria, the most common presenting symptom, may be life-threatening. Histolopathology mostly establishes the diagnosis, with typical microscopic features and immunohistochemical staining [8]. Cytology may be helpful in some cases [9].
Prior radiation is a well-documented risk factor [4] and should raise a suspicion of angiosarcoma in patients with hematuria and no evidence of urothelial carcinoma. Of the 13 angiosarcoma cases reported, including the one we are reporting, 38% were related to prior exposure to radiotherapy.
Because of the small number of patients reported, there is no accepted gold-standard treatment. Suggested treatment options include chemotherapy, radiotherapy, and radical surgery, with some sort of combinations [2,8].