Malignant tumors that display a biphasic pattern are relatively unusual. They are more commonly observed in the female genital tract but may also be encountered in other locations, including the male genital system, lower and upper respiratory tract, and urinary tract [3
]. Although their existence was recognised as early as the mid 19th century, the exact histogenesis of these neoplasms remains a controversial issue in tumor pathology. According to the most widely accepted theories, these tumors may develop from a pluripotent neoplastic cell or may be true collision tumors, in which both malignant epithelial and mesenchymal components arise independently of each other [4
]. Histologically, the first theory is supported by the presence of ultrastructural features (desmosomes or tonofilaments) of epithelial differentiation in sarcomatoid elements. Genetic and molecular studies argue for a monoclonal origin of both the epithelial and mesenchymal components in SC of the urinary bladder [6
]. Interestingly, Sung et al found that a subset of tumors displayed discordant allelic losses associated with advanced urothelial carcinoma, which may reflect genetic divergence during the clonal evolution of SC [6
SCs of the bladder are true biphasic malignant neoplasms exhibiting morphologic and immunohistochemical evidence of epithelial and mesenchymal differentiation with the presence or absence of heterologous elements [1
]. Microscopically, the sarcomatoid component is composed of a urothelial glandular or small cell component showing a variable degree of differentiation. The most common is urothelial carcinoma (80%), followed by squamous cell carcinoma (32%), adenocarcinoma (26%), and small cell carcinoma (5%). The mesenchymal component most frequently observed is osteosarcoma (97%), followed by chondrosarcoma (30%), rhabdomyosarcoma (20%), undifferentiated high-grade spindle cell neoplasm (17%), leiomyosarcoma (7%), liposarcoma, angiosarcoma, and other mixed types of mesenchymal differentiation [1
]. By immunohistochemistry, the epithelial component reacts with cytokeratins. Mesenchymal cells react with vimentin or specific markers corresponding to mesenchymal differentiation. SC does not pose diagnostic difficulties to pathologists. In most cases, the diagnosis can be established by conventional H&E examination. Differential diagnosis should include pure sarcoma, particularly in cases composed exclusively of spindle cells; leiomyosarcoma; carcinoma with pseudosarcomatous stroma; and sarcomas with pseudoepitheliomatous hyperplasia [7
]. Pseudosarcomatous stroma and other morphologic forms of pseudosarcomatous proliferations (such as inflammatory pseudotumors and postoperative spindle cell nodules) are usually highly vascularized with numerous small slit-like vessels. The cells show minimal reactive-type atypia and atypical mitotic Figures are absent. Pseudoepitheliomatous hyperplasia associated with sarcoma of the urinary bladder can resemble the architecture of malignant epithelial proliferation on low-power examination. More detailed examination shows a less intimate association between the two components with a more abrupt interface between true malignant sarcomatous elements and epithelial elements of purely hyperplastic nature. According to the literature, these tumors occur predominantly in male smokers, with a mean age of 72 years. Usual signs and symptoms include hematuria, dysuria, and urinary tract infection [2
]. Less often, SC arises in patients with a history of radiotherapy, chemotherapy, or conditions that cause cell replication abnormalities [1
]. In our cases, the patients had no such history; however, a progression of the preexisting grade 3 urothelial carcinoma to a sarcomatoid tumor at the time of diagnosis cannot be excluded (Case 2, 3).
The appropriate treatment for such rare tumors has not yet been defined; however, the aggressive behavior suggests radical therapy whenever possible [9
]. Total cystectomy often followed by radiation therapy and/or chemotherapy seems to be the preferred treatment [10
]. The effectiveness of these treatments is not known because of the varying results of each case. The only factors predictive of long-term survival are negative surgical margins and the absence of metastatic disease at the time of presentation [1
]. Unfortunately, cases with metastasis, such as our case 3, have a very poor prognosis. Further study with more cases and experience would be of great value both pathologically and clinically.