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PubMed2005

[The regulatory action of dipeptide "Deglutam" on the glutamine metabolized enzymes in the carcinosarcoma SM-1 cells].

The influence of modified antineoplaston AS2-1 (with altered ratio of L-phenylalanine and L-glutamine derivatives, "Deglutam") on the activity of glutamine synthetase, glutaminase isoforms in the carcinosarcoma SM-1, tumor weight, per cent of the inhibition of tumor growth and blood impact index was investigated in rats with carcinosarcoma SM-1. The preparation was administered in the dose of 125 mg/kg twice a day for 12 days (on the 7th day after tumor transplantation). Intensive growth of carcinosarcoma SM-1 was accompanied by activtion of the glutamine metabolizing enzymes. The dose-response effect of "Deglutam" on the studied enzymes depended on the mode of preparation administration. The intragastric administration of the preparation caused the same effect on the glutamine metabolizing of SM-1 cells; as it was earlier observed in rat liver. Administration of the modified preparation ANP AS2-1 (containing L-glutamine derivatives) influences regulation of glutamine metabolism in carcinosarcoma SM-1 cells, possibly, due to formation of substrates in the tissues of the tumor-bearing body similar to glutamine. It is also possible that in the tumor tissues these enzymes have different affinity to glutamine. This may explain greater effectiveness of the synthetic preparation on the basis of L-glutamine derivatives rather than the amino acid itself.

Animals↗

PubMed2005

Case report and literature review: primary cutaneous carcinosarcoma.

Carcinosarcomas are rare but aggressive neoplasms commonly described in organs such as the breast, urinary bladder, uterus, liver, and lungs. Histopathologically, they are characterized by the presence of malignant epithelial and mesenchymal components. The exact histogenesis of carcinosarcomas remains unknown and is debated in the literature. Primary carcinosarcomas of the skin are uncommon. To our knowledge, 20 cases of primary cutaneous carcinosarcoma have been described in the world literature. Most of these tumors were seen on the head and neck region of older individuals, both male and female. Microscopically, the more common carcinoma component is a squamous cell carcinoma followed by basal cell carcinoma, whereas the most common sarcoma component is an osteosarcoma. We report an example of this rare entity and speculate on its histogenesis in the skin.

Aged↗

PubMedDate not supplied

Pulmonary carcinosarcoma: report of a case with review of the literature.

Pulmonary carcinosarcoma is a very rare tumor, and its prognosis is usually worse than pulmonary carcinoma. We present a case with gigantic carcinosarcoma (10 x 7.7 x 7.2 cm) located in the right upper lobe, in which the discordance between the brief clinical course with limited symptoms and its large size are remarkable. No definite diagnosis was made preoperatively. He underwent right upper lobectomy and mediastinal lymph node dissection through thoracotomy. The postoperative course was smooth, and no tumor recurrence or metastasis was noted during the 9-month follow-up period. In the literature, carcinosarcoma have been divided into the endobronchial and peripheral types, which have different histological pictures. The controversy about pathology, diagnosis, and treatment of carcinosarcoma is also discussed.

Aged↗

PubMedDate not supplied

Association between carcinosarcoma and the transplanted kidney.

BACKGROUND: Renal carcinosarcoma is a rare tumor with 12 reported cases in the world literature. To our knowledge, carcinosarcoma of a renal allograft has not been reported to date. CASE REPORT: A multifocal urothelial carcinosarcoma of a transplanted kidney in a 49-year-old woman is described. Genomic analysis of the extracted nuclei of all the neoplastic cells showed uniformly XY genotype proving the transplant origin of the tumor. RESULTS: The carcinogenic role of immunosuppressive medications in kidney-transplanted patients is reported in the literature. In this case, immunosuppression may have promoted the carcinosarcoma. CONCLUSION: Renal transplant patients should be monitored for the development of malignancy in the allograft and elsewhere.

Carcinosarcoma↗

PubMedDate not supplied

A case of pulmonary carcinosarcoma (squamous cell carcinoma and osteosarcoma) treated with cisplatin and doxorubicin.

BACKGROUND: Pulmonary carcinosarcoma is a rare malignancy composed of epithelial and mesenchymal elements. Little information is available on systemic treatment options for this tumor entity. CASE REPORT: A 65-year-old man with severe chronic obstructive pulmonary disease (COPD) was diagnosed with primary pulmonary carcinosarcoma after percutaneous fine-needle biopsy of a right-sided calcified mass. The tumor was composed of squamous cell carcinoma and true osteosarcoma. A second, non-calcified mass was present in the left lung. The patient received six cycles of chemotherapy with cisplatin and doxorubicin, resulting in partial remission of both tumor manifestations. However, a few months thereafter, the patient died from spinal and cerebral metastases, the former of which was of adenocarcinomatous differentiation. CONCLUSION: Cisplatin and doxorubicin may be effective in pulmonary carcinosarcoma. Nevertheless, the aggressiveness of this rare tumor entity, its histological heterogeneity, and its potential coexistence with non-small cell lung cancer (NSCLC) make the management of patients with pulmonary carcinosarcoma a diagnostic and therapeutic challenge.

Aged↗

PubMed1985

Pulmonary carcinosarcoma and carcinoma: report of a case studied by electron microscopy, with critical review of the literature.

About 50 cases of pulmonary carcinosarcoma have been reported in the French and English literature. They have rarely coexisted with non-pulmonary neoplasms, never with other primary lung tumors. This report describes a 68 year old male smoker with a carcinosarcoma developing in the right upper lobe, one and a half years after a left upper lobectomy for a scar adenocarcinoma. By light microscopy, there was an admixture of adenocarcinomatous, chondrosarcomatous, and malignant spindle cell and giant cell areas. Electron microscopy showed well and poorly differentiated epithelial, smooth muscle and cartilaginous elements. This case is of interest because of its occurrence with another lung primary tumor; the specific diagnosis was made by transthoracic needle aspiration; and of the ultrastructural features. In the literature, carcinosarcomas have been divided into an endobronchial type, in which the carcinomatous component is squamous in 91% of cases, and a peripheral type, in which it is glandular in 50% of cases; the sarcomatous component shows no such correlation with type. The theories for the histogenesis of these tumors revolve around the concept that the carcinoma is the principal element, and the sarcomatous or stromal change secondary. Therefore, on the basis of this case, and of our literature review dealing with the pathology, clinical features and histogenesis of these tumors, we suggest that carcinosarcomas share important features with lung carcinomas.

Adenocarcinoma↗

PubMed1994

Carcinosarcoma of the lung: an analysis of 6 operated cases.

BACKGROUND: Carcinosarcoma of the lung is a rare malignant pulmonary neoplasm, and constitutes 0.1% to 0.3% of all lung tumors. Typically, these tumor have both carcinomatous and sarcomatous components with a poor prognosis due to late diagnosis and early metastases. METHODS: From July 1980 to December 1993, six patients with pulmonary carcinosarcoma who underwent surgical treatment were studied. None of them had accurate tissue diagnosis before operation except one case with peripheral variant carcinosarcoma who was diagnosed by percutaneous transthoracic fine needle biopsy under sonographic guidance. All of our patients had a huge peripheral lung tumor 3.8 to 10 cm in diameter. Pneumonectomy was done in two patients, and lobectomy in three. The other patient had unresectable tumor. RESULTS: The histopathological components in carcinoma were epidermoid carcinoma in and adenocarcinoma in 3. Differentiation of sarcomatous lesions included spindle cell sarcoma in 3, fibrosarcoma in 2 and undifferentiated mesenchymal sarcoma in one patient. In the resectable group, 1 was at stage II and 4 were at stage IIIa. None of the patients survived more than 2 years due to distant metastasis and cachexia. The mean survival was 140 days. CONCLUSIONS: The carcinomatous portion tends to metastasize to regional lymph nodes whereas the sarcomatous part gives rise to systemic dissemination. Due to early systemic dissemination and poor prognosis, combination of extensive surgical intervention resection with aggressive postoperative chemotherapy and radiotherapy might be a reasonable consideration to improve survival in primary pulmonary carcinosarcoma.

Adult↗

PubMed1993

[Carcinosarcoma of the urinary bladder].

A female patient is presented who had a large carcinosarcoma of the urinary bladder that became clinically manifest only 2 months before treatment. The initial treatment by transurethral resection was followed by radical cystectomy; 7 months postoperatively the patient died of local tumour recurrence with widespread metastases. Carcinosarcoma of the urinary bladder is a rare tumour with a poor prognosis. The majority of such tumours are not diagnosed until tumour growth is already far advanced. Owing to the small number of cases there is no clinically proven form of management. In contrast with superficial transitional cell carcinoma of the bladder, superficial carcinosarcoma of the bladder has always invaded the lamina propria, since in addition to the carcinomatous degeneration of the mucosa, sarcomatous degeneration of the underlying submucosal stroma is also present. Any local surgical treatment, such as TUR or partial cystectomy, involves the risk of incomplete tumor removal, because the sarcomatous elements typically invade the submucosa while the overlying mucosa remains intact. Therefore, radical cystectomy appears to be the treatment of choice for both superficial and invasive carcinosarcoma of the urinary bladder.

Carcinosarcoma↗

PubMed1977

[Malignant double tumor of the lung: endobronchial carcinosarcoma in the left and polypous squamous cell carcinoma in the right upper lobe].

According to MOORE, two types of carcinosarcoma in the lung may be distinguished: one with a peripheral and one with an endobronchial localization. The latter type is characterized by minimal local infiltration, absence of distant metastases and early symptomatology of bronchial obstruction. This report deals with the autopsy findings in a 67-year-old smoker in whom a typical endobronchial carcinosarcoma was found in the left upper lobe. In all the published cases, as well as in our patient, the epithelial part of the tumor was found to be a squamous cell carcinoma with varying grades of differentiation. On the other hand, the mesenchymal part has not been uniformly described. In the present case, it occurred as a spindle-cell shaped sarcoma. Morphologically, carcinosarcomas are to be distinguished from carcinomas associated with pseudosarcoma. Prognosis of successfully operated patients seems to be favourable. Survivals of up to 6 years without recurrence have been reported. In our patient the carcinosarcoma was associated with a polypoid squamous cell carcinoma in the right upper lobe. No other case with such a combination has been reported.

Aged↗

PubMed1997

Identical clonality of both components of mammary carcinosarcoma with differential loss of heterozygosity.

The histogenesis of carcinosarcomas is controversial, specifically with respect to clonality and cell of origin. To answer these questions, tumor cells from both epithelial and spindle-cell components were microdissected from three cases each of mammary carcinosarcoma and its postulated precursor, carcinoma with spindle-cell metaplasia. Clonality was assessed using the principle of X chromosome inactivation. Loss of heterozygosity (LOH) was evaluated at seven chromosomal loci to assess shared and distinctive genetic alterations for the two components in each tumor. All of the six cases demonstrated identical clonality of the carcinomatous and spindle-cell components, identical to a focus of ductal carcinoma in situ present in one case. LOH for NM23 was detected in both components in one carcinosarcoma, whereas LOH for INT-2 was detected in both components in one metaplastic carcinoma. Differential LOH for D11S904 was present in only the mesenchymal components of these two cases. We conclude that the two components of carcinosarcoma and its precursor are clonal and that the sarcomatous and spindle-cell components arise from mutation of the carcinoma. Presence of differential LOH at D11S904 in only the spindle-cell components suggests that this mutation might be critical to the development of this second phenotype.

Breast Neoplasms↗

PubMed1995

Is there an association between long-term tamoxifen treatment and the development of carcinosarcoma (malignant mixed Müllerian tumor) of the uterus?

A cluster of five patients with endometrial carcinosarcoma (malignant mixed Müllerian tumor) occurred at our center during 1993; four of these had been prescribed long-term tamoxifen for breast carcinoma. Searching the archives for the 9-year period 1983-1992 revealed two further cases of uterine carcinosarcoma occurring in patients prescribed tamoxifen, from a total of 16 cases of this tumor. Five of the six patients diagnosed with carcinosarcoma who had been taking tamoxifen had been maintained on the drug for at least 6 years, while the other had a 3-year history of tamoxifen therapy. From these data we raise the question of an association between long-term tamoxifen treatment and development of endometrial carcinosarcoma, following the dramatic increase in the prescribing of this drug after 1984.

Journal Article↗

PubMed2002

Contact guidance of Walker carcinosarcoma cells by the underlying normal fibroblasts is inhibited by RGD-containing synthetic peptides.

The metastatic spread of malignant neoplasms is associated with active migration of cancer cells. The migration of neoplastic cells during the metastatic process may be affected by various extracellular factors, including chemoattractants, haptotactic signals, electric fields, substrate anisotropy, and cell-to-cell contacts. We examined the effect of homotypic collisions and heterotypic interactions with normal human skin fibroblasts on the motile activity of Walker carcinosarcoma cells. It was found that Walker carcinosarcoma cells moving in a dense population neither show contact inhibition of movement when colliding with one another nor increase their motile activity as a result of contact stimulation of motility. On the other hand, when plated onto the surface of aligned fibroblasts, Walker carcinosarcoma cells migrated mainly along the long axes of underlying fibroblasts as a result of contact guidance. The directional character of movement (but not the speed of migration) of Walker carcinosarcoma cells on the surface of aligned fibroblasts was completely effaced by RGD-containing synthetic peptide at a concentration of 1 mg/ml but not by 5 microM verapamil (selective voltage-gated calcium channel inhibitor) or 10 microM gadolinium chloride (non-specific blocker of mechanosensitive ion channels). The suppression of directional character of migration of tumour cells by RGD-containing peptide was associated with the decrease in the amount of fibronectin macromolecules attached to fibroblasts. This suggests that alignment and anisotropic distribution of fibronectin macromolecules may be responsible for contact guidance of tumour cells moving on the surface of fibroblasts.

Amino Acid Sequence↗

PubMed1989

Toxicity of intrathecally administered cytotoxic drugs and their antitumor activity against an intrathecal Walker 256 carcinosarcoma model for meningeal carcinomatosis in the rat.

Meningeal carcinomatosis in humans is refractory to most attempts at therapy and has a grave prognosis. As part of a search for new agents to treat meningeal carcinomatosis, the toxicity of a series of antitumor agents administered through an implanted catheter directly into the cerebrospinal fluid (CSF) of the lumbar spinal cord of 200-g rats has been examined. The highest non-toxic dose (HNTD) of the agents producing no signs of histological damage, motor dysfunction, or neurobehavioral changes was bleomycin (80 micrograms), cytarabine (640 micrograms), dacarbazine (1 microgram), doxorubicin (20 micrograms), 5-fluorouracil (150 micrograms), methotrexate (1000 micrograms), mitomycin C (10 micrograms), and triethylene phosphoramide (800 micrograms). No toxicity was observed at the highest dose that could be administered because of limited solubility of 1,3-bis(2-chloroethyl)-1-nitrosourea (100 micrograms), or diaziquone (70 micrograms). The rat model gave reasonable prediction of the toxicity of antitumor agents that have been administered intra-CSF to humans but with a tendency to underpredict toxicity. The antitumor activity of the agents administered intra-CSF at the HNTD against a Walker 256 carcinosarcoma model for meningeal carcinomatosis in the rat was examined. Diaziquone, doxorubicin, methotrexate, and mitomycin C gave a 25% or greater increase in lifespan and diaziquone and mitomycin C gave some long-term survivors. BCNU, bleomycin and 5-fluorouracil gave less than a 25% increase in lifespan. When mitomycin C was administered intra-CSF at the HNTD and diaziquone at the limit of solubility daily for 4 days there was no toxicity and an increase in survival of Walker 256 carcinosarcoma tumored animals compared to animals administered a single daily dose. Intrathecal diaziquone was more active against meningeal Walker 256 carcinosarcoma than i.v. diaziquone. Intravenous methotrexate had no activity against meningeal Walker 256 carcinosarcoma. We conclude that intra-CSF administration of some anticancer agents such as diaziquone and mitomycin C at doses that do not produce toxicity can significantly increase the survival of rats with experimental meningeal carcinomatosis.

Animals↗

PubMed2026

Association between pembrolizumab-based therapy exposure and survival outcomes in metastatic or recurrent uterine carcinosarcoma: a multi-center real-world study.

OBJECTIVE: To evaluate the association between exposure to pembrolizumab-based therapy in the post-platinum setting and survival outcomes in patients with metastatic or recurrent uterine carcinosarcoma. METHODS: In this retrospective study, patients with metastatic or recurrent uterine carcinosarcoma treated at three tertiary centers between January 2008 and April 2025 were included. Patients received various treatment modalities after recurrence or progression in the post-platinum setting. Survival outcomes were analyzed according to whether patients were exposed to pembrolizumab-based therapy after recurrence or progression. Survival after recurrence and overall survival were evaluated using Kaplan-Meier analyses and Cox proportional hazards models. Additional analyses using inverse probability of treatment weighting, doubly robust methods, and time-dependent Cox models were performed. RESULTS: A total of 147 patients were included, of whom 42 (28.6%) received pembrolizumab-based therapy in the post-platinum setting. In multi-variable analyses, pembrolizumab-based therapy exposure was independently associated with improved survival after recurrence (hazard ratio 0.44, 95% confidence interval 0.24 to 0.83, p = .01) and overall survival (hazard ratio 0.48; 95% confidence interval 0.26 to 0.89, p =.02). Positive peritoneal washing cytology was independently associated with poorer survival outcomes. In time-dependent Cox analyses using inverse probability of treatment weighting, pembrolizumab-based therapy exposure remained significantly associated with improved survival after recurrence (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p =.035), whereas the association with overall survival was no longer statistically significant. CONCLUSIONS: Exposure to pembrolizumab-based therapy in the post-platinum setting was associated with improved survival after recurrence in patients with metastatic or recurrent uterine carcinosarcoma. These findings support the potential clinical relevance of pembrolizumab-based therapy in the post-platinum setting and warrant further prospective validation.

Aged↗

PubMed1997

Uterine carcinosarcoma is derived from a single stem cell: an in vitro study.

Expression of intermediate filaments (IFs) has been suggested to be a reliable marker for differentiating epithelial and non-epithelial tumors. Moreover, the c-erbB-2 and p53 genes are considered to be involved relatively early in the process of human carcinogenesis. In order to elucidate the origin of uterine carcinosarcomas, we analyzed IF, c-erbB-2 and p53 expression in and the ultrastructural characteristics of clones derived from a human uterine-carcinosarcoma cell line, EMTOKA. The expression of IFs and other proteins in the EMTOKA clones was identical to that in the EMTOKA cell line. It and its 7 clones all expressed cytokeratins 8, 17, 18 and 19, vimentin, epithelial membrane antigen, S-100, myoglobin, type-II collagen, alpha-smooth-muscle actin, placental alkaline phosphatase and epidermal-growth-factor receptor. The c-erbB-2 and p53 expression levels of all the cell types of the EMTOKA cell line and its clones were the same. Interestingly, an ultrastructural study showed that the EMTOKA cell line and its clones at early and late passages possessed the characteristics of epithelial cell types without either transitional forms between the epithelial and stromal components or differentiation into sarcomatous components. The results of this study lend particular support to the combination tumor hypothesis that a precursor (stem) cell gives rise both to epithelial and to mesenchymal components during the histogenesis of uterine carcinosarcoma, the epithelial component of which appears to be dominant, suggesting that the established cell lines derived from a common stem cell.

Biomarkers, Tumor↗

PubMed1990

Carcinosarcoma of the prostate in combination with adenocarcinoma of the prostate and adenocarcinoma of the seminal vesicles. A case report with immunocytochemical analysis and review of the literature.

A unique triad of a carcinosarcoma and an adenocarcinoma of the prostate as well as an adenocarcinoma of the seminal vesicles in a 67-year-old man is reported. The carcinosarcoma was investigated by immunohistochemical methods. The mesenchymal parts of the sarcoma showed chondromatous differentiation expressed by S-100 protein and vimentin. The undifferentiated epithelial elements of the carcinosarcoma reacted positively to the panepithelial antibody lu-5 and to carcinoembryonic antigen (CEA). The adenocarcinoma of the prostate stained with antibodies to panepithelial antigen (lu-5), prostatic acid phosphatase, prostate specific antigen and CEA, whereas the adenocarcinoma of the seminal vesicles reacted only to lu-5 and CEA. The literature is reviewed.

Adenocarcinoma↗

PubMed1992

Carcinosarcoma of the submandibular salivary gland. Immunohistochemical findings.

Carcinosarcomas of the salivary glands are rare lesions that generally have been associated with benign mixed tumors. The authors report a case of a submandibular gland lesion, which occurred in a 64-year-old man, that was composed of intermingled ductal type adenocarcinoma and osteogenic sarcoma with a large component of osteoclast-like giant cells. The local recurrence of the tumor was entirely sarcomatous with no epithelial component observed. There was no histologic evidence of a preexisting or coexisting pleomorphic adenoma. Immunohistochemical studies confirmed two separate populations of tumor cells, corresponding to the histologic growth pattern. The authors review the literature and discuss histogenetic implications of distinction between de novo carcinosarcoma and carcinosarcoma in association with pleomorphic adenoma.

Carcinoma, Intraductal, Noninfiltrating↗

PubMed1993

Establishment and characterization of carcinosarcoma cell line of the human uterus.

BACKGROUND: The histogenesis of carcinosarcoma is still unknown. METHODS: A new human uterine cell line, EMTOKA, derived from a carcinosarcoma of the uterus, has been passed successfully in cell culture for more than 2 years. The cell line was established on April 11, 1989, in a uterine tumor of a 64-year-old Japanese woman who had a simple hysterectomy. The pathologic examination of the cultured material showed papillary and tubular adenocarcinoma (carcinomatous elements) and spindle-shaped fiber cells and chondrosarcoma (sarcomatous element). RESULTS: The cultured cells showed a cell-to-cell variability and at least five cell types, which included columnar cell, small epithelial cell, moderately sized or large epithelial-like cell, malignant tumor giant cell, and spindle cell types. The EMTOKA cells were transplantable to nude mice and produced tumors that consisted of the same carcinomatous and sarcomatous elements as those observed in the original tumor. The double labeling analysis of vimentin and cytokeratin showed that a large number of cultured cells had positive results for vimentin and a small number of cells had positive results for cytokeratin. Only a very small number of EMTOKA cells stained for vimentin and cytokeratin. The number of cells that expressed neither vimentin nor cytokeratin was very low. CONCLUSIONS: These findings may support the hypothesis that a uterine carcinosarcoma may be derived from a single stem cell that does not express both of the intermediate filaments.

Animals↗