Histogenesis of sarcomatoid urothelial carcinoma of the urinary bladder: Evidence for a common clonal origin with divergent differentiation

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA, and Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan.
The Journal of Pathology (Impact Factor: 7.43). 03/2007; 211(4):420-30. DOI: 10.1002/path.2129
Source: PubMed


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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    • "It has been stated that although sarcomatoid variant of urothelial carcinoma is rare, sarcomatoid carcinoma including carcinosarcoma is more common than primary sarcoma of the urinary bladder [2, 4, 6, 11, 15–21]. In 2009, Amin [15] stated that more than 100 cases of sarcomatoid variant of urothelial carcinoma had been reported in the literature at that time and that a recent SEER data analysis revealed that 301 cases were sarcomatoid carcinomas and carcinosarcomas among 46,515 patients (0.6%) of carcinoma of the urinary bladder. "
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    ABSTRACT: Background. Sarcomatoid variant of urothelial carcinoma (SVUC) was added to the WHO classification in 2004. Aims. To review the literature. Materials and Method. Various internet databases were used. Result. SVUCs are rare biphasic malignant neoplasms exhibiting morphologic/immunohistochemical evidence of epithelial and mesenchymal differentiation with the presence or absence of heterologous elements. Some cases of SVUC have been associated with radiation therapy and cyclophosphamide treatment. Patients' ages range from 50 to 77 years (mean age 66). Patients tend to be younger and they more commonly presented with high-grade histology and advanced stage disease, in comparison with patients who had conventional urothelial carcinoma (CUC). Results of molecular/genetic studies strongly argue for a common monoclonal cell origin of both the epithelial and mesenchymal components in SUVC. The cancer specific survival of SVUC is poor in comparison with CUC. Radical surgical excision and chemoradiation may be associated with improved prognosis; chemoradiation as an organ preserving alternative to radical excision may be associated with improved outcome. There is no consensus opinion on the best treatment modalities for SUVC. Conclusions. SVUC is rare and is associated with inferior outcome compared with CUC. A multicentre trial of various treatment options is required. Cases of SVUC should be reported.
    01/2014; 2014:794563. DOI:10.1155/2014/794563
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    • "The monoclonal theory (divergent hypothesis) proposes that carcinomatous and sarcomatous elements are derived from a single pluripotential stem cell that subsequently develops divergent differentiation along separate epithelial and mesenchymal pathways (5). Through the detection of associated gene fragments using molecular biology methods, specific studies have demonstrated that carcinosarcomas originating from the uterus, breast, lung and gastrointestinal tract are all monoclonal (6). Dacic et al(7) performed an extensive comparative genotypic analysis using microdissection to secure representative mesenchymal and epithelial components. "
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    ABSTRACT: Gallbladder carcinosarcoma is one of the rarest subsets of gallbladder malignancies. The first case of carcinosarcoma of the gallbladder was reported in 1907. To date, <100 cases have been reported in the English literature. The present study reports a case of gallbladder carcinosarcoma accompanied with tumor thrombi, presenting as a soft tissue mass in the common bile duct and resulting in the obstruction and inflammation of the biliary tract. Initially, the patient was diagnosed with a gallbladder tumor and choledocholithiasis. No cases of carcinosarcoma of the gallbladder accompanied with bile duct tumor thrombus formation have been reported to date. A cholecystectomy with liver segmentectomy (S4a+S5) and a lymph node dissection were performed. The presence of a tumor thrombus in the common bile duct was confirmed by analysis of a frozen section during surgery. Resection of the extrahepatic bile duct and Roux-en-Y type hepatic cholangiojejunostomy were also performed. In addition, the gallbladder carcinosarcoma was observed to produce α-fetoprotein. The patient underwent an uneventful post-operative recovery and, to date, no clinical or radiological evidence of disease recurrence or metastasis has been identified. Carcinosarcoma of the gallbladder accompanied with tumor thrombi is extremely rare. Tumor thrombi in the common bile duct may easily be misdiagnosed as choledocholithiasis. The treatment and prognosis of gallbladder carcinosarcoma is similar to that of gallbladder carcinoma.
    Oncology letters 06/2013; 5(6):1809-1812. DOI:10.3892/ol.2013.1289 · 1.55 Impact Factor
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    • "It is thought that both diagnostic categories are variations of the same neoplastic transformation. Recently performed molecular investigations suggest that epithelial and mesenchymal components seen in these tumors are of monoclonal origin (Sung et al., 2007). According to the latest classification of the World Health Organization (WHO), sarcomatoid carcinomas and carcinosarcomas are regarded as the same entity, and these heterogenous biphasic tumors are classified as sarcomatoid carcinomas (Table 2) (Eble et al., 2004). "
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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 · 2.51 Impact Factor
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