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Carcinosarcoma of the nasal cavity and paranasal sinuses.

Malignant neoplasms consisting of an epithelial element and 1 or more nesenchymal components are variously termed teratocarcinosarcoma, carcinosarcoma, malignant teratoma, spindle cell carcinoma, and pseudosarcomatous squamous cell carcinoma. Carcinosarcoma, consisting of a malignant epithelial element and a single malignant mesenchymal component, is extremely rare in the sinonasal tract. We report a case of carcinosarcoma involving the nasal cavity, paranasal sinuses, and anterior cranial fossa. Rapid growth and extensive local destruction are prominent features of this tumor, emphasizing the need for early diagnosis and prompt institution of aggressive therapy. The clinical presentation, pathologic features, and clinical course are detailed.

Carcinosarcoma↗

Co-inoculation of tumorigenic rat prostate mesenchymal cells with non-tumorigenic epithelial cells results in the development of carcinosarcoma in syngeneic and athymic animals.

Co-inoculation of NbF-I and NbE-I s.c. into either adult male syngeneic rats or athymic nude mice induced the development of tumors that resembled carcinosarcoma on histopathologic evaluation. These tumors were composed of a mixture of adenocarcinoma and fibrosarcoma and were induced by the mixtures of NbF-I and NbE-I cells at a ratio ranging from 0.001 to 3.2; inoculation of NbF-I alone resulted in the development of fibrosarcoma. Flow-cytometric analysis showed that the epithelial cells subcloned from the carcinosarcoma had a DNA profile like that of their parental cell line and remained non-tumorigenic. When co-inoculated with the tumorigenic fibroblasts in syngeneic hosts, however, the subcloned epithelial cells again formed carcinosarcomas. Our results indicate that cell fusion between epithelial cells and fibroblasts is an unlikely explanation for tumorigenicity. We propose that prostatic fibroblasts exert a directive influence on their adjacent epithelial cells through a paracrine mechanism that determines epithelial growth and tumorigenicity in vivo.

Animals↗

Carcinosarcoma of the ovary in a patient with a germline BRCA2 mutation: evidence for monoclonal origin.

BACKGROUND: Themajority of hereditary breast and ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. While the occurrence of breast carcinoma and epithelial ovarian carcinoma in association with BRCA mutations is firmly established, the etiologic role of these genes in the development of other tumor types is less well documented. Carcinosarcoma of the ovary is an uncommon tumor consisting of both malignant epithelial and malignant mesenchymal components. OBJECTIVE: Here we report a patient with an ovarian carcinosarcoma who was found to harbor a germline mutation in BRCA2. We sought to link the BRCA2 mutation to the pathogenesis of this tumor as well as to determine whether both histologic components arose from the same progenitor cell. METHODS: Microdissection and molecular genetic analyses of the carcinomatous and sarcomatous components of this tumor were performed. RESULTS: Clonal loss of the wild-type BRCA2 allele as well as the same somatic mutation of the TP53 gene was evident in both histologic components. CONCLUSIONS: These data indicate that hereditary ovarian carcinosarcoma may result from a mutation in BRCA2 and that both histologic elements of this tumor arose from the same progenitor cell.

Aged↗

Paclitaxel in the treatment of carcinosarcoma of the uterus: a gynecologic oncology group study.

OBJECTIVE: The goal of this study was to estimate the clinical activity of paclitaxel in patients with persistent or recurrent carcinosarcoma of the uterus who have failed other treatments. METHODS: The Gynecologic Oncology Group (GOG) conducted a phase II study of paclitaxel 170 mg/m(2) (135 mg/m(2) in those with prior irradiation) intravenously every 3 weeks in patients with histologic confirmation of carcinoma and measurable disease who had failed appropriate local therapy. RESULTS: A total of 53 patients were entered into the study between September 1994 and January 1997; 44 patients were evaluable for response. The median age of the patients treated was 65 years (range: 38-79). Twenty-six patients had heterologous mixed mesodermal tumors (MMTs) and 18 patients had homologous tumors. A median of three courses were administered (range: 1-18). Fifteen patients had previous radiation therapy and 33 patients had failed prior chemotherapy. Eight patients (18.2%) had a response to paclitaxel: four patients had a complete response and four had a partial response. Neutropenia was the most common toxic effect. CONCLUSIONS: Paclitaxel had moderate activity in patients with carcinosarcoma of the uterus. The GOG is currently studying the combination of paclitaxel and ifosfamide versus ifosfamide alone for patients with advanced or recurrent carcinosarcoma of the uterus.

Adult↗

Carcinosarcoma of the uterus: immunohistochemical and genetic analysis of clonality of one case.

BACKGROUND: Carcinosarcomas of the uterus are characterized by admixtures of malignant epithelial and stromal cells, and their histogenesis remains controversial. CASE: An operated case of carcinosarcoma of the uterus in a 49-year-old woman is reported with clonal analysis. The tumor was composed of carcinomatous, sarcomatous, and transitional elements in the frontal wall of the uterine body and therefore was diagnosed as a carcinosarcoma. On immunohistochemical analysis, the sarcomatous component proved negative for epithelial membrane antigen and keratin while both components were positive for vimentin. Analysis of X-chromosome inactivation showed the same pattern throughout and additionally, the same K-ras and p53 mutations were homogeneously detected. Microsatellite instability analysis showed loss of heterozygosity at D5S346 in the sarcomatous but not the carcinomatous component. CONCLUSIONS: This tumor appears monoclonal in line with the combination tumor theory, with late divergence in genetic alteration in the sarcomatous elements.

Carcinosarcoma↗

Characterization of a human carcinosarcoma cell line of the ovary established after in vivo change of histologic differentiation.

OBJECTIVES: Cell lines are valuable in vitro models for clinical and basic research. Most ovarian cancer cell lines described are serous cystadenocarcinomas or poorly differentiated adenocarcinomas. The establishment of ovarian cancer cell lines with rare histologic differentiation is especially of interest. We describe the establishment of a carcinosarcoma cell line of the ovary after in vivo selection. METHODS: The cell line OV-MZ-22 was established from a solid tumor mass in the upper abdomen. At the time of establishment, the patient underwent secondary debulking and was pretreated with six cycles of cis-platinum/epirubicin/cyclophosphamide. Features of the cell line studied included morphology, ultrastructure, heterotransplantation, chromosome analysis, and analysis of intermediate filament proteins and actins by immunocytochemistry. RESULTS: The first histologic report of the patient described a papillary cystadenocarcinoma, which changed to a carcinosarcoma with predominantly sarcomatous differentiation at secondary debulking. This cell line is aneuploid and shows no expression of the tumor-associated antigens CA-125 and CEA, but an overexpression of MDR-1, lung resistance protein, p53, and topoisomerase I and II, but not of multidrug-resistance-associated protein. The cell line did not give rise to transplant tumors in nude mice. The histologic and immunocytochemical comparison of the primary and the relapsed tumor proved evidence of an in vivo change of differentiation from predominantly papillary cystadenocarcinoma to carcinosarcoma. Morphological characteristics and intermediate filament pattern underlined the sarcomatous differentiation and origin of this cell line. The differentiation phenotype of OV-MZ-22 cells is that of smooth-muscle cells. CONCLUSION: The change of histologic differentiation was apparently due to a selection process caused by platinum-containing chemotherapy. The origin of the cell line and its rarity make this new line an appropriate tool for further investigation.

Actins↗

Endobronchial carcinosarcoma. A case with osteosarcoma of pulmonary invasive part, and a review with respect to prognosis.

A case of endobronchial carcinosarcoma is reported in which a small area of epidermoid carcinoma at the base of the partly necrotic, polypoid part of the tumor was found, and where the pulmonary invasive part consisted of osteosarcoma. To our knowledge such a case has not been published before. In the literature 23 cases of endobronchial carcinosarcoma were found. All but one of those alive at the time of diagnosis were considered operable. The first year survival rate of the reviewed and the reported cases was 36% of all or 42% of the resected cases. The figures for bronchial carcinoma are 33% or 62% of the resected cases. The pre- and post-operative mortality for endobronchial carcinosarcoma was 23%. Because follow-up was too short, the 5 year survival rate cannot be estimated. Features common to pulmonary sarcoma and pseudosarcoma of the upper respiratory tract are also discussed.

Aged↗

Oxygen diffusivity in tumor tissue (DS-carcinosarcoma) under temperature conditions within the range of 20--40 degrees C.

The O2 diffusion constants D and K of tumor tissue (DS-Carcinosarcoma in the rat kidney) were determined at temperatures of 20, 30, 37, and 40 degrees C. The following mean values were obtained for the conditions of 37 degrees C: D = 1.75-10(-5) cm2/s and K = 1.9-10(-5) mlO2/cm-min-atm. Within the range of 20-40 degrees C, temperature variations in tumor tissue cause changes in the O2 diffusion coefficient D of 2.0-2.5%/C and in the Krogh O2 diffusion constant K of 0.5-1.5%/C. The measured O2 diffusion constants for tumor tissue correspond to values of normal tissue with similar water content. This indicates that the insufficient O2 supply in DS-Carcinosarcoma is due not to unfavorable O2 diffusivity of the tumor tissue but rather to a decreased convective O2 transport and to insufficient capillarization. An analysis of O2 diffusion in DS-Carcinosarcoma tissue using the determined O2 diffusion constants lead to the result that, under the conditions of arterial normoxia and normocapnia, critical O2 supply conditions are to be expected when the intercapillary distance exceeds approximately 120 micrometer.

Animals↗

A case of carcinosarcoma of the breast.

Carcinosarcoma is a rare malignant tumor of the breast. A 59-year-old woman was admitted to our hospital with a complaint of a right breast mass for one month. The mass grew rapidly, and modified radical mastectomy was performed. Based on the histological findings of carcinomatous and sarcomatous components entangled without a transition area, and the results of immunohistochemical staining, carcinosarcoma of the breast was diagnosed. Within 9 months of the surgery, a recurrent lesion appeared in her chest wall. As shown by local resection, this recurrent tumor had only a carcinomatous component. Such tumors are very rare, and there have been no detailed reports of recurrence patterns of carcinosarcoma. Here we report our pathological findings in detail.

Breast Neoplasms↗

Carcinosarcoma of the stomach.

In the gastrointestinal tract, carcinosarcomas are most frequently seen in the esophagus. Carcinosarcoma in the stomach is a rare tumor. We report a carcinosarcoma of the antrum of stomach. The tumor was polypoid and exophytic in appearance and located in the antrum. Immunohistochemical studies showed positivity for cytokeratin, epithelial membrane antigen and cytoplasmic carcinoembryonic antigen in the epithelial component. Positive staining with vimentin, desmin and focal smooth muscle actin and negative staining with chromogranin were observed in spindle cells. Nuclear positive staining was observed with p53 and Ki-67 in both glandular and spindle atypical cells.

Carcinosarcoma↗

Carcinosarcoma and pseudosarcoma of the esophagus: two names, one disease--comprehensive review of the literature.

In the present review we have collected 127 carcinosarcomas and 56 pseudosarcomas of the esophagus from the literature. There were no significant differences in age, sex, symptoms, location, or stalk involvement between the two groups. Infiltrative lesions were observed in 7.5% and 4.0%, respectively. The rate of lymph node metastasis was 52.5% for carcinosarcoma and 45.0% for pseudosarcoma. The resectability was similar in the two groups, and the recurrence rates were 38.0% and 45.5%, respectively. Although recent immunohistochemical and electron microscopic studies suggested that carcinosarcoma and pseudosarcoma are a single pathologic entity of epithelial origin, no one has ever compared the clinical behavior of the two entities. Our study showed that the two neoplasms have similar clinical and behavioral outcomes. These findings support, once more, the unifying theory; and we suggest that the definition of "polypoid spindle cell carcinoma of the esophagus" be adopted.

Age Factors↗

Carcinosarcoma of the prostate.

We present a rare case of carcinosarcoma of the prostate occurring in a 60-year-old white male. This diagnosis was initially missed after a transurethral resection of the prostate (TURP) had been performed to alleviate the patient's urinary obstructive symptoms. After recurrence of symptoms within a short period, another TURP was performed and the diagnosis of carcinosarcoma was then established. The patient then underwent a radical cystourethroprostatectomy with bilateral lymphadenectomy and ileal conduit diversion. Carcinosarcoma of the prostate is a very aggressive disease that often has a poor prognosis, especially when it has spread out of the prostate. Surgical removal of the prostate seems to be the best option for treatment in the select group of patients in which the disease remains confined to the prostate.

Carcinosarcoma↗

Electron microscopy and immunohistochemistry studies of pulmonary carcinosarcomas expressing the transcription factor MEF-2 and showing significant cell-to-cell, cell-to-matrix, and epithelial-mesenchymal interactions.

Pulmonary carcinosarcomas are typified by the rare histological combination of mixed epithelial and mesenchymal malignant tumor cells. The author has experienced three cases of pulmonary carcinosarcomas with large mass formation. Case 1 was the combination of adenocarcinoma with focal squamous cell differentiation and chondrosarcoma. In case 2, adenocarcinoma was combined with rhabdomyosarcoma. Case 3 demonstrated a large cell neuroendocrine carcinoma and rhabdomyosarcoma. The immunohistochemical findings showed that many of the carcinoma cells in case 3 and some carcinoma cells in case 2 demonstrated neuroendocrine cell differentiation. The nuclei in all sarcoma cells stained definitively positive for the transcription factor MEF-2. Many of the lineage-specific transcription factors for lung development were not distributed in the tumor tissue. Ultrastructurally, in all three cases, cell-to-cell (forming cellular junctions), cell-to-matrix, and epithelial-mesenchymal interactions were seen. In the interface or boundary between the carcinoma cell nests and the matrix-embedded sarcoma cells, well-developed basal lamina and fibroblastic spindle cells were frequently seen, with an appearance similar to primitive fibroblastic or mesenchymal cells, extending thin cytoplasmic process around the carcinoma cell nests. In summary, carcinosarcoma cells interacted with each other and with their extracellular matrix, revealed MEF-2 in the sarcoma cells, and showed unique histological findings associated with a variety of phenotypic differentiation patterns very different from normal lung development.

Aged↗

Carcinosarcoma of the extrahepatic bile duct.

A rare case of a carcinosarcoma of the extrahepatic bile duct demonstrating interesting features is described. A 75-year-old woman with a history of choledocholithotomy presented with acute obstructive suppurative cholangitis. Ultrasonography and computed tomography showed a thickened choledochal wall, with calcification. Percutaneous transhepatic and endoscopic retrograde cholangiography revealed a round filling defect accompanied by an irregular obstruction in the common bile duct. Carcinosarcoma was diagnosed from a protruding lesion in the common bile duct obtained by intraoperative frozen sectioning, and pylorus-preserving pancreatoduodenectomy was performed. Histological examination by light microscopy showed a transition between the carcinomatous and sarcomatous components and positive immunoreactivity for epithelial markers in the sarcomatous component. The patient died of a local recurrence 2 years after the surgery. Polypoid growth and ossification in the tumor could be representative features of carcinosarcoma of the extrahepatic bile duct.

Aged↗

Carcinosarcoma of the colon: report of a case and review of the literature.

We report a case of carcinosarcoma in the transverse colon in a 60-year-old woman. She was admitted to our hospital for further examination of occult blood in October, 1995. Colonoscopy disclosed an elevated lesion with ulceration in the transverse colon, and she underwent right hemicolectomy. Histopathological examination revealed the tumor to consist of both carcinomatous and sarcomatous elements, the latter being more predominant. Immunohistochemistry revealed vimentin immunoreactivity in most of the sarcomatous cells, and S-100 and myoglobin in a few carcinomatous cells. Distinct carcinomatous features were noted in one superficial portion of the tumor, and these carcinomatous cells showed immunoreactivity for epithelial membrane antigen. The patient is alive 14 months after surgery without evidence of recurrence. To our knowledge, this is the fourth reported case of carcinosarcoma of the colon. Our review of the literature disclosed poor prognosis in colonic carcinosarcoma.

Carcinosarcoma↗

So-called carcinosarcoma of the gallbladder; spindle cell carcinoma of the gallbladder: report of a case.

We report a so-called carcinosarcoma of the gallbladder in a 53-year-old man. The findings of ultrasonography, computed tomography, endoscopic retrograde cholangiopancreatography, and angiography revealed a large mass of the gallbladder with a cholesterol stone. He underwent three operations, and died from liver failure with multiple liver metastasis immediately after the third operation. A pathological examination revealed neoplastic tissue composed of sarcomatous and glandular components. Hematoxylin-eosin stain proved the presence of carcinosarcoma in the gallbladder, but an immunohistochemical study proved that the sarcomatous component was stained by antivimentin and also anticytokeratin antibodies, which thus proved it to be so-called carcinosarcoma of the gallbladder. As a result, an immunohistochemical study is considered to provide valuable information regarding the identification of sarcomatous elements in such cases.

Carcinoma↗

Squamous cell carcinoma with sarcomatous feature (so-called carcinosarcoma) of stomach probably metastasized from esophageal tumor: a case report with quick-freezing and deep-etching method.

A squamous cell carcinoma (SCC) with sarcomatous features (so-called carcinosarcoma) of stomach is reported in a 72-year-old man. The gastric submucosal tumor (12 x 11 x 6 cm) consisted of carcinoma cells and sarcomatous spindle cells, which were immunohistochemically recognized to contain high molecular weight cytokeratin. These histological and immunohistochemical results indicated that carcinoma cells and spindle tumor cells had cytokeratin similar to that of stratified squamous epithelium. These features were consistent with so-called carcinosarcoma of esophagus. A combined type of tumor consisting of polypoid and shallow ulcerative lesions (5.5 cm in diameter) was demonstrated by the biopsy to have SCC on the polypoid surface area. Therefore, the gastric tumor was thought to have metastasized from the esophageal tumor. The quick-freezing and deep-etching (QF-DE) method demonstrated that many spindle tumor cells in the gastric tumor had abundant intermediate filaments, which were evenly distributed in more peripheral cytoplasm along the cell membrane. This feature was similar to that of the control SCC. Intramembranous protein particles in the cell membrane of the tumor cells were markedly decreased as compared with those of control SCC. These ultrastructures by QF-DE method could be used for the pathological diagnosis of so-called carcinosarcomas of esophagus.

Aged↗

Carcinosarcoma of prostate. Immunohistochemical and ultrastructural observations.

Carcinosarcoma of the prostate is a most uncommon disease, and only a few cases have been reported previously. We report the clinical and histopathologic findings in a seventy-three-year-old man with a prostatic carcinosarcoma. The mesenchymal component of the tumor was classified as malignant fibrous histiocytoma (MFH) by electron microscopy and immunohistochemical staining methods. This is to our knowledge the first case in which the stromal component of a prostatic carcinosarcoma has been classified as MFH.

Adenocarcinoma↗