Urothelial Carcinoma of the Bladder, Lipid Cell Variant: Clinicopathologic Findings and LOH Analysis

Abstract

In this report, we present the clinicopathologic features of 27 cases of the lipid cell variant of urothelial bladder carcinoma. This is a rare variant of bladder cancer recognized by the current WHO classification of urologic tumors. The lipid cell component varied from 10% to 50% of the tumor specimen; in 11 cases the lipid cell component composed greater than 30% of the tumor. The architectural pattern of the tumor varied from solid expansile to infiltrative nests. The large epithelial tumor cells had an eccentrically placed nucleus and abundant vacuolated cytoplasm resembling signetring lipoblasts. Mucin stains were negative in all the cases. Typical features of high grade conventional urothelial carcinoma were present in all the cases with micropapillary or plasmacytoid carcinoma in 2 and 1 cases, respectively; extensive squamous or glandular differentiation was present in 2 additional cases. Most neoplastic cells had nuclei of intermediate nuclear grade with occasional nuclear pleomorphism. Immunohistochemical staining showed that the lipid cell component was positive for cytokeratins 7, 20, CAM 5.2, high molecular weight (34ssE12) and AE1/AE3, epithelial membrane antigen, and thrombomodulin; vimentin and S100 protein were negative. The loss of heterozygosity (LOH) analysis was done on 8 cases using 4 polymorphic microsatellite markers (D9S171, D9S177, IFNA, and TP 53); LOH at least in 1 marker was present in 6 cases. The LOH results were the same for lipid variant and conventional urothelial carcinoma. Pathologic stage was Ta (n=1), T1 (=2), T2, at least (n=7), T3a (n=4), T3b (n=8), and T4a (n=5). Electron microcopy analysis based on 2 cases supported lipid content in tumor cells. Follow-up information was available in all the cases, ranging from 6 to 58 months (mean, 28 mo). Sixteen of the patients died of disease at 16 to 58 months (mean, 33 mo) and 8 patients were alive with disease at 8 to 25 months (mean, 22 mo). Another 3 patients died of other causes at 6 to 15 months (mean, 10 mo). In summary, lipid cell urothelial bladder carcinoma is typically associated with advanced stage high-grade urothelial carcinoma, in which the prognosis is poor and clonally related to the concurrent conventional urothelial carcinoma. In limited samples, it may be misdiagnosed as liposarcoma, sarcomatoid carcinoma (carcinosarcoma), or signetring cell carcinoma. Morphologic distinction from other malignant neoplasms with lipid cell phenotype is critical for its clinical management.