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Cytogenetic analysis shows that carcinosarcomas of the breast are of monoclonal origin.

Carcinosarcoma of the breast is a rare biphasic neoplasm composed of a carcinomatous component contiguous or admixed with a pleomorphic spindle cell component. The issues of the histogenesis and clonal composition of carcinosarcomas have long been debated. We present the first cytogenetic characterization of mammary carcinosarcomas by analysis of eight tumor samples from two patients with this disease. In the first case, the same karyotypically complex clone, as well as evidence of clonal evolution, was found in samples from three separate areas of the primary tumor. The analysis of one intramammary and one axillary lymph node metastasis from the same patient, both showing only the sarcomatous tumor component, also revealed the common complex stemline and one of the two sidelines found in the primary tumor. The carcinosarcoma of the second patient contained six complex but karyotypically related clones unevenly distributed among the three samples examined. From this case, cells belonging to the carcinomatous and sarcomatous tumor components were separated by differential sedimentation and culturing in specific growth media. Analysis of both fractions showed largely the same karyotype, although one of the subclones was restricted to the epithelial component. Our findings indicate that the epithelial and mesenchymal components of mammary carcinosarcomas are both part of the neoplastic parenchyma and that they have evolved from a single common stem cell, in agreement with the hypothesis that the tumors are of monoclonal origin.

Breast Neoplasms↗

Proliferative activity, p53 accumulation and neoangiogenesis in pulmonary carcinosarcomas and pulmonary blastomas.

Carcinosarcoma and pulmonary blastomas are rare biphasic tumors. Lung cancer pathogenesis is a multistep process. Proliferative activity, p53 accumulation and angiogenesis are of well-known relevance and ought to be evaluated in the epithelial and mesenchymal components of these tumors. Using antibodies against Ki-67 epitope MIB1 and proliferating cell nuclear antigen (PC 10) in 10 carcinosarcomas, tumors revealed a significantly higher proliferative activity in the epithelial component compared with the mesenchymal component in the MIB1 reaction (p = 0.013). In three pulmonary blastomas of the biphasic subtype, proliferative activity was similar in both parts. In five of 10 carcinosarcomas and in one of three pulmonary blastomas, accumulation of the p53 epitopes Pab 1801 and/or DO-1 was found. At the tumor front, a significantly higher vessel density was found compared with the central parts (p < or = 0.015) using a monoclonal antibody against human endothelium (CD 31). No differences were found between carcinosarcomas and pulmoblastomas. Higher proliferative activity in carcinosarcomas revealed a better prognosis regarding metastasis behavior (p = 0.05) and tumor-associated death in the follow-up (p < or = 0.017). p53 accumulation and microvessel density were of no prognostic value. This is in contrast to results in non-small cell lung cancer, pointing to a different biologic behavior.

Aged↗

Carcinosarcoma of the parotid gland: report of a case with cytohistologic and immunohistochemical findings.

True malignant mixed tumors (carcinosarcomas) of salivary gland origin are exceedingly rare and demonstrate malignant epithelial and stromal components. We report a case of parotid gland carcinosarcoma that showed squamous cell carcinoma and malignant fibrous hystiocytoma without clinical or histologic evidence of a preexisting pleomorphic adenoma. This tumor consisted of 2 histologically different populations of cells without evidence of a common origin from the myoepithelial cell, which is the putative precursor cell of pleomorphic adenoma and its derived carcinosarcoma. In addition to supplementing the literature, this case report includes cytohistologic and immunohistochemical analyses that provide further insights into the variable histogenesis of this neoplasm and the distinction between de novo carcinosarcoma and carcinosarcoma originating from pleomorphic adenoma.

Aged↗

The effect of chemotherapy on the different components of advanced carcinosarcomas (malignant mixed mesodermal tumors) of the female genital tract.

The effect of chemotherapy on the different components of uterine and ovarian carcinosarcoma is largely unknown. This report describes six patients with advanced carcinosarcoma, five of whom received 4 cycles of doxorubicin and ifosfamide (AI) directed at the sarcomatous component of the tumor. Responses in these five patients at second-look laparotomy were: one complete response, two partial responses (persistence of only the carcinomatous component), one stable disease, and one progressive disease (both components still present in both cases). Thereafter 4 cycles of a cisplatin-based regimen were scheduled. Response to the cisplatin-containing regimen was only evaluated clinically. The sixth patient (with no macroscopic disease left after initial surgery) received 6 cycles of a cisplatin-based chemotherapy from the onset and was found to be in complete response at relaparotomy. Median progression-free survival for all patients was 15 months and median survival 21 months. A literature survey showed that carcinosarcoma differs from adult soft tissue sarcomas with respect to responsiveness to chemotherapy. Cisplatin and ifosfamide are active as single agents, whereas the response to single-agent doxorubicin seems to be lower. The data suggest, however, that superior response rates and increased survival times are achieved with cisplatin/doxorubicin-based chemotherapy. The sensitivity of carcinosarcoma to cisplatin supports the recent view that carcinosarcoma of the female genital tract is possibly a high grade carcinoma with metaplastic sarcomatous elements.

Journal Article↗

Uterine carcinosarcomas (malignant mixed Mullerian tumors) are metaplastic carcinomas.

Uterine carcinosarcomas (malignant mixed mullerian tumors) are metaplastic carcinomas. Uterine carcinosarcomas (malignant mixed Mullerian tumors) have been traditionally regarded as a subtype of uterine sarcoma. Adjuvant oncological treatments have often been similar to those directed against high-grade uterine sarcomas such as leiomyosarcoma and undifferentiated uterine sarcoma. However, there is now convincing evidence that most uterine carcinosarcomas are monoclonal neoplasms and are in reality metaplastic carcinomas. Although aggressive, the behavior of uterine carcinosarcoma is more akin to that of high-grade endometrioid type endometrial adenocarcinoma and aggressive morphological subtypes of uterine carcinoma. The sarcomatous component is derived from the carcinomatous element which is the driving force. Although the designation carcinosarcoma is likely to remain, adjuvant treatments should probably be similar to those directed against aggressive high grade endometrial carcinomas. Prospective studies should be performed to ascertain whether such adjuvant therapies are more effective than traditional sarcoma based therapies in the treatment of these aggressive neoplasms.

Female↗

Non-gluten sensitivity-related small bowel villous flattening with increased intraepithelial lymphocytes: not all that flattens is celiac sprue.

Seven patients (mean age, 37.6 years; 5 women) had several weeks of gluten sensitivity (GS)-like symptoms; 2 had flu-like symptom prodromes. The 7 cases had morphologically similar biopsy specimens; all tissue fragments had uniform injury--increased lymphoplasmacytic lamina propria inflammation, moderate to complete villous flattening, numerous crypt mitoses, and markedly increased villous intraepithelial lymphocytes (IELs). All patients were diagnosed with GS and prescribed a gluten-free diet; all returned 9 to 38 weeks later questioning their diagnosis because symptoms had resolved substantially or completely. Clinical improvement was unrelated to gluten abstinence or ingestion. Repeated endoscopy and colonoscopy performed 4.1 to 16 months later showed normal mucosa in all 7 patients. Diseases other than GS can cause marked villous flattening and increased villous IELs in adults. The cause of small bowel mucosal injury is unknown. A similar non-GS-associated clinicopathologic complex, assumed to be due to a protracted viral enteritis or slow regression of a virus-induced immune reaction, occurs in children. The temporal aspects of symptom improvement and mucosal restitution in these 7 patients are similar to "acute self-limited colitis." An overly exuberant immune response to an infectious agent is possible.

Adult↗

Carcinosarcoma and carcinoma of the gallbladder.

Carcinosarcoma is a tumor-containing malignant epithelial and connective tissue elements. The 18th case of carcinosarcoma of the gallbladder is reported in the context of 17 prior cases from the world literature. The 18-year experience of St. Luke's Hospital with extrahepatic and primary gallbladder cancer is presented to provide perspective on this unusual tumor. The diagnosis of malignant disease of the gallbladder is reviewed with special emphasis on the roles of sonography, computerized tomography, and arteriography. The importance of staging as a guideline to prognosis and therapy of gallbladder cancer is discussed. Carcinosarcoma of the gallbladder behaves clinically like carcinoma and guidelines for surgical and palliative therapy of the more common malignancies of the gallbladder should be followed for carcinosarcoma as well.

Adenocarcinoma↗

Carcinosarcoma of the lung with spindle-cell epithelial component: report of a case.

A case of primary endobronchial carcinosarcoma with predominant spindle cell squamous carcinoma is described. The spindle cell component has not been previously reported as occurring in pulmonary carcinosarcomas. We suggest that this variety of carcinosarcoma closely resembles sarcoma of the lung histologically and emphasize that a distinction between the two neoplasms is important in view of the generally good prognosis of endobronchial carcinosarcomas.

Carcinosarcoma↗

Pulmonary blastoma, carcinosarcoma and spindle-cell carcinoma: an immunohistochemical study of keratin intermediate filaments.

We have examined 18 primary malignant lung tumours categorized as either carcinosarcoma, blastoma or spindle-cell carcinoma according to accepted criteria. Two monoclonal antibodies to keratins, CAM 5.2 and LP 34, were used to determine whether the non-epithelial or spindle-cell components of each tumour showed evidence of keratin expression. By this means the epithelial nature of the five tumours classified as spindle-cell carcinomas was confirmed. In all four pulmonary blastomas and in five of nine carcinosarcomas, the sarcomatous elements failed to stain for keratin but in the remaining four carcinosarcomas there was focal staining. The histogenesis of these tumours is discussed and it is suggested that the sarcomatous component of a carcinosarcoma may be derived from malignant epithelial cells by a process of mesenchymal metaplasia with a switch in intermediate filament type. It remains uncertain whether blastomas are derived from both endoderm and mesoderm, or from either one of these tissues, with one component representing complete metaplastic transformation.

Aged↗

MDM2 and CDK4 expression in carcinosarcoma of the esophagus: comparison with squamous cell carcinoma and review of the literature.

Certain tumors of the esophagus that display both sarcomatous and carcinomatous features have long been recognized. The nomenclature, classification, and histogenesis remain controversial and the microscopic differential diagnosis from other esophageal malignancies can be challenging, particularly in small biopsies. In this paper, we review the literature of carcinosarcoma and present two cases of esophageal carcinosarcoma, describing their salient histologic, immunohistochemical, and ultrastructural features. Also, we assess the expression of MDM2 and CDK4 in the carcinomatous and sarcomatous compartments of our cases and we compare them with the expression of these oncogenes in selected cases of esophageal squamous cell carcinoma with prominent stromal reaction. In both of our cases, identification of some epithelial ultrastructural and immunohistochemical features in cells of otherwise sarcomatous phenotype lends support to the common epithelial origin of these neoplasms. Moreover, positive staining for MDM2 and CDK4 in our cases with equally strong reactions in both carcinomatous and sarcomatous elements provides evidence of a role for these molecules in the pathogenesis of carcinosarcoma. In contrast, in cases of squamous cell carcinoma with prominent stromal reaction only the epithelial cells stained strongly for MDM2 and CDK4. These differences in the MDM2 and CDK4 immunohistochemical profile between carcinosarcomas and carcinomas of the esophagus may assist in their differential diagnosis.

Aged↗

Carcinosarcoma of the lung mis-diagnosed preoperatively as a mediastinal tumor.

Carcinosarcoma of the lung is an uncommon tumor and is rarely preoperatively correctly diagnosed. The prognosis of patients with carcinosarcoma is extremely poor, despite treatment. A 79-year-old man was mis-diagnosed preoperatively as having a malignant mediastinal tumor. Excision of the tumor with segmentectomy of the lung revealed it was composed of a variety of carcinomatous and sarcomatous elements, which is a clear manifestation of the histogenetic totipotentiality of carcinosarcoma. He was subsequently treated with adjuvant chemotherapy and irradiation. He remains well at sixteen months after the operation, to date. Here we report this rare true case of a carcinosarcoma, focusing on the difficulty of a correct preoperative diagnosis.

Aged↗

Carcinosarcoma of the gallbladder with chondroid differentiation.

Carcinosarcoma of the gallbladder is an uncommon neoplasm. We herein report the case of a patient with carcinosarcoma of the gallbladder with chondroid differentiation, treated by cholecystectomy with liver segmentectomy and lymph node dissection for a tumor which occupied the entire gallbladder and spread to the liver. Histologically, the tumor contained two distinct components: a mixture of both well and poorly differentiated tubular adenocarcinoma and sarcomatoid tissue with chondroid differentiation. From a review of the literature, it was seen that carcinosarcomas of the gallbladder could be divided into two groups: one group with apparent sarcomatous differentiation, such as chondroid, osteoid, and rhabdomyosarcomatous differentiation, and the other group, of carcinosarcomas with a sarcomatous portion composed of anaplastic spindle cells. Each group had a poor prognosis in spite of surgical resection of tumors. Our patient died of peritoneal dissemination 7 months after surgery.

Aged↗

Carcinosarcoma of the uterus: a 40-year experience from the state of Missouri.

Uterine carcinosarcoma is a rare and rapidly fatal malignancy. The records of 49 patients with carcinosarcoma were studied; from these studies emerged a symptom complex of vaginal bleeding and abdominal or pelvic pain. Eleven patients had been previously irradiated at an average of 16.4 years before they developed uterine carcinosarcoma. Celiotomies revealed more extensive tumor than could be determined by pelvic examination under anesthesia. The majority of the patients died from local recurrence in the pelvis rather than from distant metastases. The overall 5-year survival was 6%. Celiotomies are recommended to stage carcinosarcomas and guide treatment decisions.

Adult↗

Cisplatin as initial chemotherapy in ovarian carcinosarcomas: a Gynecologic Oncology Group study.

OBJECTIVES: Carcinosarcomas of the ovary are rare; hence, although most patients recur after surgical resection or have metastatic disease at the time of diagnosis, only anecdotal information is available concerning the activity of cytotoxic drugs against these lesions. The Gynecologic Oncology Group (GOG) initiated a concerted effort to study cytotoxic therapy for these cancers in 1976. This report presents data on cisplatin, the first of the agents to be studied in this disease. METHODS: One hundred thirty-six eligible patients with ovarian carcinosarcoma received cisplatin (50 mg/m(2)) every 3 weeks until disease progression or unacceptable toxicity. RESULTS: Among 44 patients evaluable for response, one complete (2%) and eight partial (18%) responses resulted. An additional 10 (23%) patients exhibited stable disease, while 25 (57%) had increasing disease. Median progression-free survival in 130 patients evaluable for this endpoint was 5.2 months. Median survival in the same 130 patients was 11.7 months. Adverse effects >/=grade 2 among the 132 patients evaluable for toxicity included leukopenia (14%), neutropenia (17%), thrombocytopenia (2%), anemia (10%), nausea and vomiting (40%), azotemia (3%), neurotoxicity (4%), fever (2%), and tinnitus (1%). CONCLUSIONS: These data provide the first objective evidence that cisplatin is active as an initial therapy for patients who have carcinosarcoma of the ovary. The overall response rate (20%) is similar to that seen in carcinosarcomas of the uterus.

Adult↗

EGFR expression and HER2/neu overexpression/amplification in endometrial carcinosarcoma.

OBJECTIVE: Endometrial carcinosarcomas are aggressive biphasic neoplasms traditionally treated as a high-grade uterine sarcoma. Epidermal growth factor receptor (EGFR) and HER2/neu (HER2) tyrosine kinases have been implicated in the development and progression of several human cancers and are targets for therapeutic intervention. The aim of this study was to evaluate for HER2 and EGFR expression in cases of endometrial carcinosarcoma. METHODS: Formalin-fixed, paraffin-embedded sections from 55 cases of confirmed endometrial carcinosarcoma were immunostained with commercially available antibodies to EGFR and HER2. Fluorescent in situ hybridization for HER2 gene amplification was performed on all cases showing 2+ or 3+ HER2 staining by immunohistochemistry. HER2 gene amplification and EGFR expression were correlated with several prognostic variables. RESULTS: EGFR expression was identified in the majority of tumors (45/55, 82%). HER2 overexpression (3+) was seen in 14/55 (25%) cases and HER2 gene amplification was seen in 11 (20%) cases. EGFR expression and HER2 gene amplification did not show significant correlation with disease progression, disease-free survival or overall survival. The carcinomatous component of tumors more frequently showed HER2 overexpression as compared to the sarcomatous component (25% vs. 4%, P = 0.008). The sarcomatous component of tumors more frequently showed EGFR overexpression as compared to the carcinomatous component (44% vs. 24%, P = 0.04). CONCLUSIONS: EGFR and HER2 appear to play a role in the carcinogenesis of endometrial carcinosarcomas. The carcinomatous and sarcomatous elements of these tumors showed consistent differences in HER2 and EGFR expression patterns supporting biologic differences between these components. Studies evaluating the clinical utility of HER2 or EGFR targeted therapy in these tumors appear warranted.

Aged↗

Primary yolk sac tumor concomitant with carcinosarcoma originating from the endometrium: case report.

BACKGROUND: A primary yolk sac tumor (YST) with carcinosarcoma originating from the endometrium is extremely rare, to our knowledge, this is the third documented instance. Several hypotheses exist is to its histogenesis. CASE: A 65-year-old Japanese woman was diagnosed with a uterine malignancy and underwent surgical treatment and chemotherapy. The postoperative diagnosis was primary carcinosarcoma concomitant with a YST of the uterus. Immunohistochemical staining revealed that the tumor area suspected to be a YST was positive for alpha-fetoprotein. CONCLUSION: We report a case of carcinosarcoma concomitant with a YST of uterus. This case is the third documented instance of a YST with concomitant with carcinosarcoma originating from the endometrium. The histogenesis in this case is suggests aberrantly differentiated somatic cells.

Aged↗

Clinical and pathological characteristics of carcinosarcoma of the esophagus: report of four cases.

Carcinosarcoma of the esophagus is a rare malignant neoplasm composed of both carcinomatous and sarcomatous elements. Four out of 850 patients with carcinoma of the esophagus or the cardiac portion of the stomach undergoing operation at Capital Hospital, Beijing, had carcinosarcoma of the esophagus. They ranged from 50 to 58 years old, but only 45% of all 850 patients with carcinoma were in the age group from 51 through 60 years old. All 4 patients with carcinosarcoma of the esophagus were men. On barium swallow esophagogram, the 4 patients had a characteristic intraluminal polypoid lesion in the middle third of the esophagus. Such lesions of the esophagus also can occur in patients with benign fibrovascular polyps, leiomyoma, and the polypoid form of esophageal carcinoma and esophageal melanoma. The last two can be differentiated from carcinosarcoma only by pathological examination after excision. After radical excision and esophagogastrostomy, the 4 patients were followed up for 19, 4, 4, and 3 years. They were in good condition without recurrence.

Carcinosarcoma↗

Bladder carcinosarcoma: histologic variation in metastatic lesions.

Carcinosarcoma is a tumor composed of malignant epithelial and mesenchymal elements, which occurs rarely in the bladder. Although the prognosis of bladder carcinosarcoma is known to be poor the histology of metastatic lesions is not well described. We report 2 cases of bladder carcinosarcoma with pelvic lymph node involvement. Pure sarcomatous metastasis was present in 1 patient and only carcinoma in the other. The histologic composition of metastatic lesions may be of significance in treatment planning in patients with bladder carcinosarcoma.

Aged↗