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Carcinosarcoma of urinary bladder: report of 5 cases with immunohistologic study.

We studied 5 cases of carcinosarcoma of the urinary bladder. Immunoperoxidase studies were performed to identify the nature of the tumor and to establish the diagnosis. We suggest that these tumors represent a transition of epithelial to mesenchymal malignancy. Three of our patients had a history of radiation therapy prior to development of carcinosarcoma; of which 2 had a long interval between exposure to radiation and tumor development. Radiation is a risk factor for endometrial carcinosarcoma, and in this report we strongly suggest such an association for the urinary bladder.

Aged↗

Complete response of carcinosarcoma of the ovary to therapy with doxorubicin, ifosfamide, and dacarbazine.

Although carcinosarcoma occurs in various locations throughout the body, it rarely originates in the ovary. Chemotherapy has been minimally beneficial. This case describes a patient with carcinosarcoma of the ovary who responded minimally to chemotherapy used for epithelial carcinomas but had a complete response after receiving chemotherapy used for sarcomas. The patient relapsed within 1 year after receiving cisplatin therapy. She was treated with mesna, ifosfamide, Adriamycin, and dacarbazine (MAID) chemotherapy and after one cycle of chemotherapy she had no evidence of tumor. She has received six cycles of chemotherapy without evidence of progression 13+ months since beginning MAID therapy. MAID chemotherapy may be useful in the treatment of carcinosarcoma of the ovary.

Antineoplastic Combined Chemotherapy Protocols↗

Carcinosarcoma of the lacrimal gland arising from a pleomorphic adenoma.

PURPOSE: To report a case of the lacrimal gland tumor diagnosed as carcinosarcoma (true mixed tumor) arising from a pleomorphic adenoma. DESIGN: Interventional case report. METHODS: An 80-year-old Japanese woman was referred with a well-circumscribed tumor in the lacrimal fossa. RESULTS: The tumor was excised, but the deepest portion remained because of heavy bleeding. Histopathologically, the tumor consisted of osteosarcomatous cells. No epithelial or myoepithelial component was identified by immunohistochemistry. Two months later, the tumor progressed further and was excised completely with lateral orbitotomy. The tumor consisted primarily of osteosarcomatous component but also had epithelial components including carcinoma and pleomorphic adenoma. Examinations did not detect local recurrence and metastasis at 10 post-operative months. CONCLUSION: The tumor was diagnosed as true carcinosarcoma of the lacrimal gland arising from a pleomorphic adenoma. When lacrimal gland tumors containing sarcomatous components are encountered, carcinosarcoma should be included in the differential diagnosis.

Adenoma, Pleomorphic↗

Radiology-Pathology Conference: carcinosarcoma of the colon.

Carcinosarcomas are very uncommon tumors, which are comprised of both malignant epithelial and mesenchymal elements. They occur most commonly in the head and neck, respiratory tract, and female reproductive organs. In the gastrointestinal tract, they are most often found in the oropharynx, esophagus, and, to a lesser extent, in the stomach. Carcinosarcomas rarely originate from the colon, but when they do, they are extremely aggressive malignancies. We report the radiologic and pathologic findings of a patient with a carcinosarcoma believed to have arisen from the colon and which involved the adjacent mesentery and omentum.

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Carcinosarcoma of the prostate with multiple metastases: case report and review of the literature.

A case of carcinosarcoma of the prostate in a previously healthy 65-year-old man is reported. The tumor was initially diagnosed as adenocarcinoma, but the prostatectomy specimen showed a 717-g prostate, with evidence of adenocarcinoma and carcinosarcoma without heterologous structures. By 3-month follow-up, local recurrence, and liver, lung, and bone metastases had developed in the patient. He died of disease 10 months postoperatively. Carcinosarcoma of the prostate is a very rare but highly aggressive cancer with limited therapeutic options that should be treated with surgery and managed symptomatically. We believe this article is the forty-second case reported in the literature.

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Retroperitoneal müllerian carcinosarcoma associated with endometriosis: a case report.

BACKGROUND: Mixed müllerian tumors are rare malignancies of the female genital tract and extremely uncommon in extragenital sites. CASE: A 71-year-old woman presented with a 3-month history of left-sided pelvic pain. Significant history included total abdominal hysterectomy and bilateral adnexectomy performed 19 years earlier for benign indications; she had no history of endometriosis. Bimanual exam and pelvic ultrasonography demonstrated a 6 x 5 x 6 cm complex mass in the left pelvis. Exploratory laparotomy revealed a retroperitoneal mass encasing the left ureter. The mass was debulked, necessitating resection of the distal ureter and ureteroneocystotomy. Histopathology demonstrated carcinosarcoma associated with endometriosis. CONCLUSION: Extragenital carcinosarcoma is a rare malignancy, with only one well-documented case associated with peritoneal endometriosis. We report a case of an extragenital retroperitoneal carcinosarcoma associated with endometriosis.

Aged↗

Clinical experience with combination paclitaxel and carboplatin therapy for advanced or recurrent carcinosarcoma of the uterus.

OBJECTIVE: The purpose of the study was to evaluate the efficacy of combination chemotherapy with paclitaxel and carboplatin in patients with advanced or recurrent carcinosarcoma of the uterus. METHODS: A retrospective review was carried out at Miyagi Prefecture Cancer Research Center Hospital. Six patients pathologically diagnosed with uterine carcinosarcoma were treated with paclitaxel (175 mg/m(2) given intravenously over 3 h) and carboplatin (dosed at AUC 6) every 3 weeks at our center between 1997 and 2003. Responses and adverse effects were assessed according to Response Evaluation Criteria in Solid Tumors and National Cancer Institute-Common Toxic Criteria, respectively. RESULTS: All six patients were evaluable for toxicity, and no unacceptably severe toxicities were reported. Grades 3 and 4 hematologic toxicities occurred, but all of them were overcome by adequate treatment with granulocyte colony-stimulating factor and blood transfusions. Five of six patients had measurable disease and thus were evaluable for response: Four patients had a complete response (CR) and the remaining patient had progressive disease (PD). The median progression-free interval (PFI) for all six cases was 18 months, with a median overall survival of 25 months. CONCLUSIONS: Although the number of cases was small, the regimen evaluated in the current study demonstrated higher activity and lesser toxicity than those found in previous studies in patients with advanced or recurrent uterine carcinosarcoma. Additional phase II clinical studies are necessary to evaluate fully the benefits of this regimen.

Antineoplastic Combined Chemotherapy Protocols↗

Clinicopathological features of ovarian carcinosarcomas: a single institution experience.

OBJECTIVE: The aim of this study was to elucidate the clinicopathological and immunohistochemical prognostic factors of patients with ovarian carcinosarcoma treated with radical surgery and postoperative chemotherapy. METHODS: During a 6-year period, nine patients with ovarian carcinosarcoma were referred to our institution. Tissue blocks were reviewed and sections containing both carcinomatous and sarcomatous elements were stained for epithelial membrane antigen (EMA), vimentin, vascular endothelial growth factor (VEGF), CD45RO, c-erbB-2, p53, CD34, Ki67, S100, estrogen, and progesterone receptors. Histological and immunohistochemical findings as well as clinical characteristics were then correlated with progression-free interval and overall survival. RESULTS: There were four homologous and five heterologous carcinosarcomas. Five patients had early stage disease. Seven of the patients were optimally debulked. All patients were treated with anthracycline-based chemotherapy following surgery. With regard to immunohistochemistry, all specimens were negative for CD34, c-erbB-2, estrogen, and progesterone receptor expression. Five tumors overexpressed p53 and four specimens demonstrated a positive staining for Ki67. Reactivity for VEGF and CD45RO was observed in four and two tumor specimens, respectively. The median overall survival was 32.9 months with no statistical difference between early and advanced stages, while median time to progression was 13.5 months. p53 overexpression demonstrated a trend for better overall survival. CONCLUSIONS: Only p53 overexpression seems to influence overall survival although, due to the small number of patients studied, no safe conclusions can be drawn. Despite the predominance of early stage patients that favorably influenced overall survival, aggressive surgical cytoreduction followed by anthracycline-based treatment were the cornerstone in our multimodality approach.

Aged↗

Adjuvant ifosfamide and cisplatin in patients with completely resected stage I or II carcinosarcomas (mixed mesodermal tumors) of the uterus: a Gynecologic Oncology Group study.

OBJECTIVES: To determine progression-free survival (PFS) and overall survival (OS) in women with completely resected stage I or II carcinosarcoma of the uterus treated with adjuvant ifosfamide and cisplatin, and to assess the toxicity of this regimen. METHODS: Eligible patients had histologically confirmed carcinosarcoma (mixed mesodermal tumor) and no postoperative radiotherapy following complete resection for clinical stage I or II disease. They were to have adequate renal, hepatic, and hematologic functions and performance status of 2 or less. Study entry was to be within 8 weeks of hysterectomy. Patients with previous chemotherapy, or other noncutaneous malignancies, were ineligible. Ifosfamide was administered 1.5 g/m2 intravenously (IV) over 1 h and cisplatin was given 20 mg/m(2) over 15 min followed by mesna 120 mg/m2 IV bolus, then 1.5 g/m2/24 h as a continuous infusion. Initial doses (daily x 5 every 21 days x 3 cycles) were reduced by 20% (to 4 days) for myelotoxicity. RESULTS: Nine of seventy-six patients enrolled were deemed ineligible and another two who did not receive protocol treatment were inevaluable. Of the 65 evaluable patients, median age was 65 years; 50 patients (77%) were stage I and 15 (23%) were stage II. PFS and OS, respectively, were 69% and 82% at 24 months, and 54% and 52% at 84 months. Overall 5-year survival was 62%. Leukopenia was the most commonly reported, but manageable, toxicity. CONCLUSION: Adjuvant ifosfamide and cisplatin after primary surgery for stage I or II carcinosarcoma of the uterus is tolerable. In the absence of concurrent controls, the impact on PFS and OS is unclear. Pelvic relapse remains problematic.

Adult↗

Phase II evaluation of topotecan in carcinosarcoma of the uterus: a Gynecologic Oncology Group study.

OBJECTIVES: To estimate the antitumor activity of topotecan in patients with persistent or recurrent carcinosarcoma (malignant mixed mullerian tumors) of the uterus and to determine the nature and degree of toxicity of topotecan in this cohort of patients. MATERIALS AND METHODS: Eligible patients had measurable advanced or recurrent carcinosarcoma of the uterus. Topotecan at a target dose of 1.5 mg/m(2) was administered IV daily for 5 days, every 3 weeks, until progression of disease or adverse affects prohibited further therapy. RESULTS: Twenty-seven member institutions entered 51 patients. Of the patients entered, 48 were eligible. Patient characteristics included a median age of 65, with 33% having prior radiation and 92% having prior chemotherapy. Twenty-six patients (54%) had a performance status (PS) of 0, 18 (38%) had a PS of 1, and four (8%) had a PS of 2. Patients received from 1 to 21 (with a median of 2) courses of treatment. The most frequently observed grade 4 toxicities were neutropenia seen in 35 (73%) patients, leukopenia in 14 (29%), and thrombocytopenia in 10 (21%). Three (6%) patients developed neutropenic sepsis and died shortly after their first treatment cycle. There were five (10%) complete responses; 13 (27%) patients maintained stable disease, 26 (54%) experienced increasing disease, and reassessment did not occur in four (8%). CONCLUSION: Topotecan at this dose and schedule does not appear to have major activity in patients with advanced or recurrent uterine carcinosarcoma previously treated with chemotherapy.

Adult↗

Carcinosarcoma of the ovary-a case series.

OBJECTIVE: To evaluate our experience with ovarian carcinosarcoma and identify prognostic factors. METHODS: Thirty-one cases of ovarian carcinosarcoma were identified over a 6-year time period through tumor registry and pathology records. Fisher exact test and log rank using Kaplan-Meier method (P < 0.05) were used to compare variables with outcome. RESULTS: All 31 patients underwent initial surgical treatment with an appropriate staging procedure. Stage distribution: 1 stage I, 6 stage II, 23 stage III, and 1 stage IV. The median follow-up was 28 months. The median survival for the entire group was 21 months. Early vs. advanced stage significantly influenced progression-free interval, P = 0.05. Nineteen patients were found to have stage IIIC disease and required debulking procedures. In patients with stage IIIC disease, presence of residual disease was associated with decreased overall survival, P = 0.03. 29 patients received adjuvant chemotherapy with 11 patients receiving ifosfamide/cisplatin and 16 patients receiving carboplatin/taxol. Progression-free interval was improved with the use of ifosfamide/cisplatin vs. carboplatin/taxol. The median PFI was 12 months in the carbo/taxol group and has not been reached in the ifos/cisplatin group (P = 0.005). The overall survival was also significantly improved with the use of ifosfamide/cisplatin, P = 0.03. In advanced stage patients, overall survival was not significantly influenced by type of adjuvant chemotherapy administered, P = 0.13. CONCLUSIONS: Ovarian carcinosarcoma has a poor overall prognosis with median survival rates reported in the literature ranging from 7-10 months. Our series, although limited by a small number of patients, exhibits a more encouraging median survival of 21 months for the overall group. Aggressive debulking to eliminate residual disease and the use of ifosfamide/cisplatin chemotherapy seem to be factors in this improved outcome.

Adult↗

Esophageal carcinosarcoma: a genetic analysis.

Carcinosarcoma of the esophagus is a rare malignant neoplasm that consists of both carcinomatous and sarcomatous elements. The histogenesis of the sarcomatous component is generally considered to result from metaplasia of carcinomatous cells toward mesenchymal differentiation. True carcinosarcoma, characterized as a collision between a carcinoma and a sarcoma, is extremely rare. We describe a patient with primary achalasia who developed a true carcinosarcoma of the esophagus in which clonal differences between carcinomatous and sarcomatous elements were genetically and immunohistochemically demonstrated. A polypoid tumor located in the middle third of the esophagus developed in a 51-year-old man with longstanding achalasia. The tumor was predominantly composed of spindle-shaped sarcomatous cells. Squamous cell carcinoma in situ and islands of well-differentiated squamous cell carcinoma in the sarcomatous element were histologically observed. The sarcomatous element was immunoreactive for both mesenchymal and myoid markers. The carcinomatous component expressed type I and type II cytokeratins as well as epithelial membrane antigen. Analysis for chromosomal loss of heterozygosity performed in multiple microdissected samples of each sarcomatous and carcinomatous element revealed distinct genetic clonalities. These differences in immunohistochemical and genetic clonalities suggest that the tumor composed of squamous cell carcinoma and leiomyosarcoma originated separately from epithelial and mesenchymal precursors.

Carcinosarcoma↗

Cyclin D1 gene amplification in esophageal carcinosarcoma shown by differential polymerase chain reaction.

We studied cyclin D1 gene amplification in four esophageal carcinosarcomas using the differential polymerase chain reaction. Three cases showed amplification in the sarcomatous components, and one of these also showed amplification in the carcinomatous component. No amplification was detected in the other case. We also examined p53 expression in these four tumors by immunostaining. Both components of all four cases showed diffuse overexpression of p53 protein in the nuclei. Our results showed that the cyclin D1 gene is frequently amplified in esophageal carcinosarcoma, especially in the sarcomatous component. Two cases showed amplification only in the sarcomatous component, suggesting that amplification may have a role in the pathogenesis of that component of this malignancy. The diffuse overexpression of p53 observed in both components suggests that such overexpression, which could be the result of somatic mutation, might be an early event in the pathogenesis of esophageal carcinosarcoma.

Blotting, Southern↗

Angiogenesis in carcinosarcomas of the uterus: differences in the microvessel density and expression of vascular endothelial growth factor between the epithelial and mesenchymal elements.

Carcinosarcoma of the uterus is a highly aggressive neoplasm. However, the angiogenesis of this neoplasm is still unknown. This is the first study to examine the differences in angiogenesis between the epithelial and mesenchymal elements of this biphasic neoplasm. Surgical specimens from 21 primary uterine carcinosarcomas were histopathologically evaluated, and then immunohistochemically analyzed for tumor angiogenesis, using an anti-vascular endothelial growth factor (VEGF) antibody. The microvessel density (MVD) was also measured in each element of these neoplasms, using anti-CD34 monoclonal antibody. The MVD in the epithelial element was found to be higher than that of the mesenchymal element in 20 of 21 (95.2%) primary tumors. The epithelial elements showed a higher MVD (mean, 81.6 +/- 41.1) than the mesenchymal elements (mean, 36.7 +/- 23.8) in these primary tumors (P < .0001). Moreover, the epithelial elements showed a higher VEGF expression (mean, 0.78 +/- 0.23) than the mesenchymal elements (mean, 0.37 +/- 0.20) (P < .0001). The tumors with lymph-vascular invasion showed a higher VEGF expression (n = 17; mean, 0.85 +/- 0.17) than the tumors without lymph-vascular invasion (n = 4, mean, 0.47 +/- 0.12) (P < .01). Microscopically, neither lymph-vascular space invasion nor metastatic tumors consisted of sarcoma alone in this series. In addition, a decrease in the VEGF expression was found in the transitional areas between carcinomatous and sarcomatous elements in all 10 homologous and 4 heterologous tumors evaluated. These results suggest that the tumor angiogenesis in the epithelial element may be more active than that of the mesenchymal element and also substantiated the high metastatic potential of the epithelial element in uterine carcinosarcoma. Based on these findings, carcinoma cells thus may play a key role in the angiogenesis of this biphasic neoplasm.

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[Carcinosarcoma of the skin].

BACKGROUND: Carcinosarcoma of skin is a biphasic tumor composed of intimately admixed malignant epithelial and mesenchymal components. Various terms have been used to designate these tumors (metaplastic carcinoma, pseudosarcoma, spindle cell carcinoma, etc.). However, the histogenetic conception has changed and carcinosarcoma is currently regarded as authentic sarcomatoid carcinoma. CASE REPORT: The authors report the case of a 32-year-old women initially presenting with a budding and ulcerating tumor at the site of an old cutaneous scar on the right leg. Histopathological and immunohistochemical evaluation led to a diagnosis of cutaneous carcinosarcoma. One month after treatment, the patient developed inguinal lymph node metastasis. DISCUSSION: Our case and a review of other cases in the literature confirm the dual epithelial and sarcomatous phenotype of sarcomatoid carcinoma. Progressive transition between the cells of the two components on microscopic analysis and their positive immunostaining for anti-p53 antibody suggest a clonal origin of the tumor. The carcinomatous component seems to influence the course of the disease with the development of metastases, particularly at the lymph nodes. It thus seems advisable to combine lymphadenectomy with surgical tumor excision.

Adult↗

[Synchronous prostatic carcinosarcoma: report of 2 cases and review of the literature].

OBJECTIVE: Carcinosarcoma of the prostate is a biphasic tumor containing adenocarcinoma and recognisable sarcomatous components. It is a rare neoplasm with less than 40 reported cases. We describe two additional examples showing carcinosarcoma in the initial pathologic material (synchronous presentation). METHODS AND RESULTS: The patients were 71 and 78 year-old, respectively. The primary prostatic tumour in case one was composed of adenocarcinoma admixed with a neoplastic mesenchymal component that displayed foci of chondrosarcoma, rhabdomyosarcoma and angiosarcoma. The adenocarcinoma in the second case was admixed with spindle cell sarcoma and chondrosarcoma. Both patients died of disease after surgery, 3 and 9 months respectively. CONCLUSION: Synchronous carcinosarcoma of the prostate is a highly malignant neoplasm that may need an aggressive therapy.

Aged↗

Loss of IGF-II imprinting in endometrial tumors: overexpression in carcinosarcoma.

The genomic imprinting of the maternal allele defines the monoallelic expression of the IGF-II gene in most human tissues. The loss of imprinting (LOI) leading to biallelic overexpression of IGF-II has been reported in several human malignancies, including uterine leiomyosarcoma. To ascertain if LOI occurs in endometrial malignancies, the allelic expression of the IGF-II gene was examined in samples of normal human endometrium (n=22) and endometrial tumors (n=12) by assessing the ApaI polymorphism in cDNA segments amplified by RT-PCR. The biallelic overexpression of IGF-II mRNA, involving activation of all four (P1-P4) promoters, was detected in one normal endometrium and in one endometrial carcinosarcoma. Low level biallelic expression of IGF-II was also detected in two samples of hormone-unresponsive/Type II endometrial carcinomas. The level of IGF-I mRNA in these four samples was low. The IGF-IR mRNA was overexpressed in all endometrial cancers including the carcinosarcoma sample, but not in normal endometrium. These data suggest that LOI associated with overexpression of IGF-II and concomitant overexpression of IGF-IR may play a role in the rare carcinosarcoma of the endometrium.

Carcinosarcoma↗

Carcinosarcoma of the parotid gland: cytological, clinicopathological and immunohistochemical study of a case.

Manifesting a putative origin from a pleomorphic adenoma, carcinosarcoma of the salivary gland is a heterologous neoplasm in which a sarcomatous and a carcinomatous component coexist. We present a parotid gland carcinosarcoma in a 77-year-old man with peculiar morphological findings. Fine-needle aspiration cytology allowed a preoperative diagnosis of poorly differentiated carcinoma. At histologic examination, the tumor showed biphasic differentiation with an epithelial component made up of well-differentiated keratinizing squamous carcinoma and ductal-type adenocarcinoma, and a mesenchymal component, revealing focal areas of osteosarcoma and myoepithelial malignant proliferation. Carcinosarcoma is a very rare malignant neoplasm, accounting for 0.16% of malignant salivary gland tumors: only 60 cases have been reported, some of which arose "de novo", i.e., without clinico-pathologic evidence of a pre- or co-existing pleomorphic adenoma.

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