Pleomorphic giant cell carcinoma of the urinary bladder.

In this report, we present the clinicopathologic features of 8 cases of the pleomorphic giant cell variant of urothelial carcinoma. This is a rare variant of bladder cancer recognized by the current World Health Organization classification of urologic tumors. The pleomorphic giant cell component varied from 20% to 100% of the tumor specimen; in 2 cases, the pleomorphic giant cell component composed greater than 50% of the tumor with 1 case showing pure pleomorphic giant cell carcinoma. The architectural pattern of the tumor varied from infiltrating pleomorphic tumor with bizarre giant cells to solid expansile nests with discohesive growth pattern; a hypocellular desmoplastic stromal response was present in 2 cases (25%) with single cells in sclerotic stroma. At histology, giant, bizarre, anaplastic cells with frequent typical or atypical mitotic figures were present in all cases. Seven mixed cases had concurrent conventional high-grade urothelial carcinoma; 2 cases presented features of micropapillary or lymphoepithelioma-like urothelial carcinoma. Variable size intracytoplasmic vacuoles were present in 2 cases. All patients had advanced-stage cancer (>/=pT3), and 6 (75%) had lymph node metastases. Immunohistochemical staining demonstrated that both pleomorphic giant cell and associated conventional urothelial carcinoma were positive for cytokeratins 7, CAM 5.2 and AE1/AE3, and epithelial membrane antigen; P63, thrombomodulin, and uroplakin III were positive in 6, 3, and 2 cases, respectively. Follow-up information was available in all cases (range, 6-74 months; mean, 20 months). Five of the patients died of disease from 6 to 17 months, and 2 patients were alive with metastases at 11 and 19 months. One patient had no evidence of disease at 74 months. In summary, pleomorphic giant cell is an aggressive variant of urothelial carcinoma associated with poor prognosis that presents at an advanced clinical stage. In limited samples, it may be misdiagnosed as secondary carcinoma or sarcoma, a pitfall of paramount importance for its clinical management.