Histogenesis of sarcomatoid urothelial carcinoma of the urinary bladder: evidence for a common clonal origin with divergent differentiation
ABSTRACT The histogenesis of sarcomatoid urothelial carcinoma, a rare neoplasm with bidirectional epithelial and mesenchymal differentiation, has been a matter of controversy. To clarify its origin, we analysed the status of X-chromosome inactivation in sarcomatoid urothelial carcinomas from 10 female patients and examined losses of heterozygosity (LOH) in these specimens and in additional 20 tumours from male patients. Six polymorphic microsatellite markers where genetic alterations occur frequently in early or advanced stages of urothelial carcinomas, including D3S3050, D8S261, IFNA, D9S177, D11S569 and TP53, were investigated in the current study. The identical pattern of non-random X-chromosome inactivation in both carcinomatous and sarcomatous components was identified in five of eight informative female patients, and the remaining three informative cases showed a random, but concordant, pattern of X-chromosome inactivation. The concordant X-chromosome inactivation results in all eight informative cases support the concept of a monoclonal origin of both components of this biphasic neoplasm. Among the tumours demonstrating loss of heterozygosity, high incidences of an identical pattern of allelic loss between carcinomatous and sarcomatous components were identified in genetic alterations associated with early carcinogenesis: 86% at D8S261, 78% at D11S569, 75% at D9S177 and 57% at IFNA. In contrast, concordant LOH patterns were less frequently observed for microsatellites related to advanced carcinogenesis: only 40% at D3S3050 and 40% at TP53. The significant overlap of loss of heterozygosity supports a monoclonal cell origin and suggests that clonal divergence may occur during tumour progression and differentiation. Divergent patterns of discordant allelic loss of microsatellite markers imply that heterogeneous pathogenetic pathways may exist in the evolution of this enigmatic neoplasm.
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ABSTRACT: Background and Objectives: This study aimed to present the clinicopathological characteristics and treatment of patients with bladder carcinoma with sarcomatoid differentiation at our institution. Methods: Between 1995- 2009, 950 patients were followed-up for bladder carcinoma. Among them, 14 patients with sarcomatoid carcinoma were retrospectively reviewed, and their clinical, pathological features and treatment were recorded. Results: Median age of the patients was 65 years (range: 41-86 years), 12 (86%) being male and 2 (14%) female. All the patients presented with hematuria and 11 (88%) had a history of smoking. The tumor growth pattern was solid in 10 patients, papillary in 2, and mixed in 2. In all, 5 of the patients had urothelial carcinoma with sarcomatoid differentiation and 9 were diagnosed with sarcomatoid carcinoma. Five patients underwent radical cystectomy with ileal conduit surgery, 2 patients refused cystectomy, and 8 patients underwent re-TUR. Following diagnosis ,12 of the patients died in mean 10.7 months (range: 1-48 months). Conclusion: Urothelial carcinomas with sarcomatoid features are aggressive and are usually at advanced stage at the time of diagnosis. The outcomes of multimodal treatment are not satisfactory. Significant findings of the present study are that early diagnosis positively affect survival and that gemcitabine and cisplatin in combination can positively affect survival.Asian Pacific journal of cancer prevention: APJCP 11/2012; 13(11):5729-33. DOI:10.7314/APJCP.2012.13.11.5729 · 1.50 Impact Factor
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ABSTRACT: Background To investigate the efficacy of initial biopsy or transurethral resection of bladder tumor for detecting histological variants on radical cystectomy and to assess the prognostic significance of variant histology on urothelial carcinoma outcomes after radical cystectomy. Methods Clinical and histopathological characteristics of 147 patients with variant histology who underwent radical cystectomy for urothelial carcinoma between 2006 and 2012 were assessed. Sensitivity was calculated as the proportion of radical cystectomy specimens with a particular variant that also presented the variant in the biopsy or transurethral resection specimen. The Kaplan-Meier method and multivariate Cox proportional hazard regression analysis were used to estimate cancer-specific survival. Results Of the 147 patients, 116 (79 %) were diagnosed with a single variant histology, and 31 (21 %) had multiple patterns. Squamous differentiation (31 %) was the most common single variant histology, followed by glandular differentiation (28 %). Except for small cell variant (100 %), the sensitivity of biopsy and transurethral resection was most effective for the diagnosis of squamous differentiation, 19 % vs. 40 % respectively, followed by glandular differentiation, 11 % vs. 21 % respectively. A total of 6 % and 49 % patients could be variant-free partially due to biopsy or complete resection(s) respectively. Presence of variant differentiation in urothelial carcinoma at cystectomy was significantly associated with inferior survival both in univariate analysis (P = 0.005) and multivariate analysis (HR4.48, 95 % CI:1.03-19.53). Conclusions Overall sensitivity of biopsy or transurethral resection to detect variant differentiation on cystectomy is relatively low. Patients with variant differentiation on cystectomy specimens have inferior survival.BMC Urology 05/2015; 15(1). DOI:10.1186/s12894-015-0037-2 · 1.94 Impact Factor
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ABSTRACT: The author reports a very rare and very unique urinary bladder carcinoma. This carcinoma occurred in a 68-year-old Japanese patient who underwent cystectomy for bladder tumor. The tumor was large polypoid and ulcerated one. Histologically, the tumor consisted of the following three elements: giant cell sarcomatoid carcinoma (70% in area), squamous cell carcinoma (20% in area), and papillary urothelial transitional cell carcinoma (10% in area). The former two elements were invasive into the peribladder fat tissue, while the latter one element invaded into the submucosa. There were gradual merges between the giant cell sarcomatoid element and squamous cell carcinoma element. Apparent transitions were not seen between the transitional cell carcinoma element and the giant cell sarcomatoid element or the squamous cell carcinoma element. Immunohistochemically, the giant cell sarcomatoid element was positive for various kinds of cytokeratins and vimentin while the squamous and transitional cell carcinoma elements were positive for various kinds of cytokeratins and negative for vimentin. The giant cell sarcomatoid element was free of other specific antigens. The author speculates that giant cell sarcomatoid carcinoma transdifferentiates into squamous cell carcinoma, and vice versa. The relationship between transitional cell carcinoma and the other two elements is unclear in the present case.Cases Journal 11/2009; 2:9111. DOI:10.1186/1757-1626-2-9111