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PubMed2003

Cisplatin, doxorubicin and ifosfamide in carcinosarcoma of the female genital tract. A phase II study of the European Organization for Research and Treatment of Cancer Gynaecological Cancer Group (EORTC 55923).

Carcinosarcomas of the female genital tract are highly malignant tumours composed of carcinomatous and sarcomatous elements. In the past, these tumours were frequently treated as sarcomas. However, a number of arguments, including the sensitivity of these tumours to platinum-based chemotherapy, suggest that these tumours behave more like poorly differentiated carcinomas. The European Organization for Research and Treatment of Cancer (EORTC) Gynaecological Cancer Group therefore decided to perform a prospective phase II study in patients with advanced or metastatic carcinosarcoma with an approach such as that used in gynaecological carcinomas. Eligible patients could have primary or recurrent disease, but prior radiotherapy or chemotherapy was not allowed. The treatment plan recommended upfront debulking, followed by chemotherapy with cisplatin, ifosfamide and doxorubicin. Patients who could be debulked to non-measurable disease remained eligible for the study, but the response assessment was restricted to patients who had measurable disease before the start of chemotherapy. A total of 48 patients (39 primary disease, 9 recurrent disease) were registered, 41 of them being eligible. In 9 patients, all macroscopic lesions could be removed, 32 patients were left with residual disease and were assessable for response. The overall response rate was 56%: a complete response (CR) was observed in 11 (34%) patients and partial response (PR) in 7 (22%) patients. No change occurred in 5 patients and progression in 2 patients. In 7 patients, response could not be assessed. Median survival for all of the 41 eligible patients was 26 months. Severe leucopenia and thrombocytopenia were common and necessitated dose reductions or delays in 60% of patients. From a clinical point of view, the most severe non-haematological toxicity was renal dysfunction, and one patient died of this complication in the absence of disease progression. The results of this study are in-line with the hypothesis that carcinosarcomas are chemosensitive, in particular for the currently investigated regimen. The treatment also included upfront cytoreduction when feasible. Considering the observed toxicities, alternative platinum-based regimens with more favourable toxicity profiles should be explored.

Adult↗
PubMed1995

Carcinosarcoma of salivary glands with unusual stromal components. Report of two cases and review of the literature.

Carcinosarcomas are rare neoplasms that exhibit heterologous malignant epithelial and stromal components. We report two cases of salivary gland carcinosarcoma with immunohistochemical analysis and clinical follow-up that provide insights into the pathogenesis and behavior of these tumors. In one case, a 51-year-old black woman had a 15-year history of a hard, asymptomatic, infraauricular mass that recently had undergone rapid growth. The tumor showed adenocarcinoma and osteosarcoma. She died 9 months after diagnosis. In another case, a 78-year-old white woman had a large soft palate mass that had been present for several years and had recently caused dysphagia. The tumor showed adenocarcinoma and leiomyosarcoma. The patient is alive at 9 months follow-up. Although malignant epithelial and stromal components characterize carcinosarcomas, immunohistochemical studies suggest that both elements are derived from a common precursor cell, possibly of myoepithelial origin. These cases support this concept and perhaps suggest a spectrum of differentiation that this precursor cell may exhibit.

Aged↗
PubMedDate not supplied

Esophageal carcinosarcoma.

Carcinosarcoma is an uncommon malignancy of the esophagus that presents as a bulky intraluminal polypoid lesion of the esophagus. Histologically, both carcinomatous and sarcomatous components are seen. Because of accelerated intraluminal growth, esophageal carcinosarcoma often presents relatively early. This report describes a 64-year-old man with carcinosarcoma who was successfully treated with an esophagectomy. As in typical squamous cell carcinoma, early detection and treatment by surgical resection are needed to produce significant long-term survival.

Carcinosarcoma↗
PubMed2000

Salivary gland carcinosarcoma: immunohistochemical, molecular genetic and electron microscopic findings.

Salivary gland carcinosarcoma, or true malignant mixed tumor, is a very rare and extremely aggressive neoplasm. The clonality and clonal origin of this tumor are discussed controversially. We report a carcinosarcoma of the left parotid gland in a patient who subsequently died of cutaneous, lymphatic and pulmonary metastases. Immunohistochemical staining, electron micrograph analysis, loss of heterozygosity (LOH) analysis and sequence analysis were performed on this tumor with an adenocarcinomatous and a predominant spindle cell-like component. While smooth muscle actin was undetectable by immunohistochemistry, cytoplasmatic myoepithelial structures could be detected by electron microscopy. LOH analysis at 12 genomic locations detected complete deletion of one allele at 17p13.1, 17q21. 3, and 18q21.3 indicating allelic loss in both components of the tumor. Double strand sequencing of the remaining allele of the p53 tumor suppressor gene revealed a wild-type allele. Based on our results, we favor the hypothesis of monoclonal origin of this salivary gland carcinosarcoma with a common stem cell that could be the myoepithelial cell and an inactivated tumor suppressor gene on chromosome 17 other than p53.

Aged↗
PubMed2003

Carcinosarcoma of the ureter: a rare, pleomorphic, aggressive malignancy.

AIM: To examine histological nature and clinical process of ureteral carcinosarcomas. METHODS: We report on a new case of carcinosarcoma of the ureter. The literature was reviewed and histological and clinical features were elucidated. RESULTS: Fourteen cases of ureteral carcinosarcomas have been reported. The nomenclature used for these tumors either in the pathology reports or in literature is confusing. In contrary to obscure tumor biology, prognosis was clearly bad as the majority of the patients died within 2 years after diagnosis. CONCLUSIONS: Terminology confusion is due to the rarity of this entity and lack of its biology knowledge. Patients present after the age of 60 with hematuria and obstruction. Nephroureterectomy is the only hope of cure but, due to tumor aggressiveness, recurrences occur almost always and prognosis is poor.

Aged↗
PubMed1996

Carcinosarcoma of the uterus with extensive neuroectodermal differentiation.

A case of uterine carcinosarcoma with extensive neuroectodermal differentiation occurring in a 54-year-old woman is described. Microscopically, the endometrial tumour was predominantly composed of a sheet-like proliferation of small- and medium-sized cells. These cells were characterized by fibrillary cytoplasmic processes, rosette-like formations, perivascular palisading patterns, and immunoreactivity for glial fibrillary acidic protein, synaptophysin, leu 7 and neuron-specific enolase. In limited areas, features of conventional carcinosarcoma, including squamous cell carcinoma, leiomyosarcoma and islands of the above mentioned small- to medium-sized cells that were intermingled, were observed. The tumour was aneuploid by flow cytometry. The patient is alive with tumour for three months. It is suggested that at least some cases of uterine primitive neuroectodermal tumour may be explained by one-sided neuroectodermal development within a carcinosarcoma.

Biomarkers↗
PubMed2001

Ovarian carcinoma recurring as carcinosarcoma.

Malignant mixed mesodermal tumor is a rare tumor of the ovary and its histogenesis is controversial. We report the case of an ovarian tumor that seemed to be a pure carcinoma and recurred as a carcinosarcoma, and suggest a possible histogenesis for this kind of tumor. The patient was a 62-year-old Japanese woman. The primary tumor was confined to the right ovary and was a histologically poorly differentiated endometrioid adenocarcinoma with focal squamous differentiation. The tumor recurred as peritoneal dissemination 9 months later showing a histological appearance of carcinosarcoma of heterologous type. The recurrent tumor also contained intermingled foci of similar histology as the primary tumor. The carcinomatous component of the recurrent tumor showed more obvious differentiation to adenocarcinoma with increased expression of epithelial markers compared to the primary tumor. Epithelial membrane antigen was positive also in a few cells of the sarcomatous component, which implies that this tumor had features of metaplastic carcinoma. The DNA ploidy pattern of the primary ovarian tumor was diploid, while an additional aneuploid subpopulation appeared in the recurrent tumor. These findings suggest the possible histogenesis of carcinosarcoma of the ovary as progression and clonal evolution of endometrioid adenocarcinoma.

Carcinoma, Endometrioid↗
PubMedDate not supplied

Carcinosarcoma of ovary associated with previous radiotherapy.

Carcinosarcoma is a rare neoplasm which, in the female genital tract, arises mainly in the endometrium. Although the pathogenesis remains obscure, there is an apparent association between pelvic irradiation and uterine sarcomas. There have been sporadic case reports of the development of carcinosarcomas of the cervix, vagina, and extragenital areas, but not of the ovary, after previous pelvic irradiation. We describe a case of ovarian carcinosarcoma arising in a 74-year-old female who had pelvic irradiation 33 years previously. Exploratory laparotomy showed a 25 x 18 x 9 cm left ovarian tumor with adjacent organ invasion including peri-uterine serosa and rectum. The patient was treated by optimal cytoreduction, followed by chemotherapy with adriamycin and cisplatin. However, acute hepatitis caused by reactivation of hepatitis B virus infection developed just before the fifth course of chemotherapy. She died of hepatic failure two weeks later.

Aged↗
PubMedDate not supplied

Tamoxifen-related uterine carcinosarcomas occur under/after prolonged treatment: report of five cases and review of the literature.

The risk of tamoxifen-related endometrial adenocarcinoma is well established with daily dose and treatment duration of adjuvant tamoxifen as risk factors. There have also been in the past years, a few descriptions of uterine nonepithelial malignancies occurring after tamoxifen. We describe five recent cases of uterine carcinosarcomas occurring under/after tamoxifen administered in an adjuvant setting. None of these patients had received prior pelvic radiation therapy. Their median age at the diagnosis of breast cancer was 58 years (41-68), and 69 years (50-84) at the diagnosis of uterine carcinosarcoma. The median length of exposure to tamoxifen was 9 years (5-20), and the median time from the initiation of tamoxifen to the diagnosis of the uterine malignancy (latency period) 9 years (7-20). All patients presented with an advanced stage (IIA-IVA). Our data, together with those of the literature, plead for a causal role of a prolonged exposure to tamoxifen on the subsequent development of uterine carcinosarcoma. The long latency period observed even in patients receiving only 5 years of treatment leads us also to consider a prolonged gynecologic follow-up of the patients.

Adult↗
PubMed2001

Adjuvant pelvic radiotherapy for uterine carcinosarcoma in a high risk population.

OBJECTIVES: The purpose of this study was to examine the clinical outcomes of patients with uterine carcinosarcoma and to review the role of adjuvant pelvic radiotherapy in the management of patients with high pathologic risk factors for recurrences. METHODS: A retrospective review was carried out at the Saskatoon Cancer Agency. All patients with a diagnosis of uterine carcinosarcoma from 1990-1995 were identified. Clinical and pathologic data were analysed in a computerized database. Kaplan-Meier survival estimates were computed. Log-rank test was used to compare survival curves and disease-free survival estimates. RESULTS: Thirty-two patients are reported. The median age at presentation was 71. Most patients presented with abnormal postmenopausal bleeding. Eighty-four percent of patients had disease confined to the uterus at the time of evaluation. Patients with high-grade (2, 3) adenocarcinoma, deep myometrial invasion, or gross pelvic metastatic disease were offered adjuvant pelvic irradiation. The overall 5-year survival for the whole group is 38%. There is no statistically significant difference in the progression-free or overall survival in the radiated group compared to the expectantly treated group. CONCLUSION: Uterine carcinosarcoma is a rare and aggressive form of uterine malignancy even in early stages. Adjuvant pelvic radiotherapy seems to improve the progression-free survival and overall survival in patients with poor histologic prognostic factors. The role of chemotherapy deserves further investigation as all recurrences were in the upper abdominal and distant locations outside of the radiation field. PRECIS: Uterine sarcoma has a poor prognosis even in early stage. Adjuvant pelvic radiotherapy seems to improve the outcomes of patients with adverse histologic risk factors.

Adult↗
PubMed2001

Thymic carcinosarcoma consisting of squamous cell carcinomatous and embryonal rhabdomyosarcomatous components. Report of a case and review of the literature.

A case of thymic carcinosarcoma in an 83-year-old Japanese man is presented. He died of superior vena cava syndrome caused by a rapidly enlarged anterior mediastinum tumor eight months after initial symptoms. Autopsy revealed a 16 x 12 x 25 cm-sized, tan yellow, whitish tumor with a multinodular and microcystic appearance located in the left anterior mediastinum, which involved the residual thymus. The tumor had directly invaded the left pleura, and had metastasized to the right lung and spleen. Histologic examinations of the primary tumor showed a sarcomatous component consisting of racquet- or spindle-shaped cells with cross striations, and small nests of atypical squamous cells scattered throughout the tumor; neither transition between the two components nor intermediate cells with both epithelial and mesenchymal features was seen. Electron microscopic and immunohistochemical examinations confirmed the rhabdomyomatous differentiation of the sarcomatoid component. To our knowledge, there have been only two reported cases showing histologic features similar to the present tumor. For the histogenesis of thymic carcinosarcoma, we propose two hypotheses. The first is that sarcomatous cells are derived from carcinomatous cells by tumoral metaplasia. Secondly, that this type of tumor originates from thymic primitive cells with multidirectional differentiation potential. In accordance with the latter, we consider that the present tumor originated from thymic primitive cells. Thymic carcinosarcoma is a highly malignant tumor, and most patients die within a year. Appropriate therapies must be developed.

Aged↗
PubMed2005

Primary peritoneal carcinosarcoma (malignant mixed mullerian tumor): Report of a case with five-year disease free survival after surgery and chemoradiation and a review of literature.

Malignant mixed mullerian tumors (MMMTs), also known as carcinosarcoma because they contain both carcinomatous and sarcomatous elements are aggressive tumors, which usually arise in the uterus and ovary. Extragenital carcinosarcomas are extremely rare and most cases develop from the peritoneum. To our knowledge, only 29 cases have been described in English literature. Here we report a case of a primary carcinosarcoma of the pelvic peritoneum with five-year disease-free survival after managing the patient with surgery, chemotherapy and radiotherapy.

Antineoplastic Agents↗
PubMed1989

Prostatic carcinosarcomas. Clinical, histologic, and immunohistochemical data on two cases, with a review of the literature.

Carcinosarcomas of the prostate gland are exceedingly rare, and previous reports exist on only seven of these neoplasms. The authors studied two such tumors, which occurred in 63- and 69-year-old patients. One of them had osseous metastases develop, which were treated unsuccessfully by irradiation and diethylstilbestrol therapy. The other patient is free of disease 15 months after radical prostatectomy. Both tumors contained an intimate mixture of carcinoma and sarcoma; patient 1 displayed foci of chondrosarcoma, osteosarcoma, and leiomyosarcoma, whereas patient 2 exhibited areas of chondrosarcoma, osteosarcoma, rhabdomyosarcoma, and angiosarcoma. The phenotypic nature of these tissues was confirmed by immunohistochemical studies, showing reactivity for vimentin, S-100 protein, desmin, actin, myoglobin, or Ulex europaeus I agglutinin. Conversely, the sarcomatous components lacked prostate-specific antigen, epithelial membrane antigen, and cytokeratin, whereas carcinomatous elements expressed these three markers. The authors' data support the existence of true carcinosarcomas of the prostate, that is, malignant neoplasms with conjoint epithelial and mesenchymal differentiation. The question of whether prostatic carcinosarcoma is an entity that is totally distinct from sarcomatoid or metaplastic carcinoma remains problematic.

Actins↗
PubMed1998

Carcinosarcoma of the esophagus with metastases showing osteosarcoma: a case report and review of the literature.

Carcinosarcoma of the esophagus includes both carcinomatous and sarcomatous elements. The classification and histogenesis of carcinosarcoma is controversial. In a polypoid carcinosarcoma diagnosed in a resected esophagus the sarcomatous component was composed of dense interlacing bundles of spindle-shaped cells in the submucosa. Areas with transitional features between the two components were observed. Immuno-histochemical examination showed vimentin-positive cells in the sarcomatous areas. Subsequently, obtained autopsy specimens from the lung, kidney and iliac bone showed metastatic osteosarcoma composed of an interlacing pattern of bone or osteoid components. We suspected that the sarcomatous elements in the esophagus resulted from sarcomatous transformation of carcinoma cells, and that the metastatic lesions showed differentiation of neoplastic cells to the osteosarcoma.

Carcinosarcoma↗
PubMed1995

Carcinosarcoma of the ovary: incidence, prognosis, treatment and survival of patients.

BACKGROUND: Carcinosarcomas (also known as malignant mixed mullerian tumours) are rare malignant neoplasms that histologically contain both epithelial and stromal components. METHODS AND MATERIALS: All cases of carcinosarcoma of the ovary presenting to the Royal Marsden Hospital from January 1975 to August 1993 were retrospectively analysed and the histological sections reviewed. RESULTS: There were 37 cases of carcinosarcoma of the ovary representing 1.12% of the ovarian neoplasms seen at this institution. The median age of presentation was 65 years (range 26-85 years) and 70% of patients had advanced disease (FIGO stage III and IV). Clinical features at presentation were similar to those encountered in patients with epithelial ovarian cancer. The overall median survival was 247 days with 40% 1-year survival and 6% 5-year survival for all stages. Early FIGO stage was the only independent prognostic factor for survival. Histology (homologous/heterologous subtypes; grade, type or percentage of the epithelial component) had no significant impact on survival. Adjuvant radiotherapy may have a role and single agent platinum compounds are active, giving a response rate of 35%. CONCLUSIONS: The management of this tumour is difficult and randomised trials are needed to accrue sufficient patient numbers to demonstrate optimal therapy.

Adult↗
PubMed1978

Pulmonary blastoma evolving into carcinosarcoma. A case study.

A rare lung tumor composed of contiguous foci of classical blastoma and carcinosarcoma with transitional features is described. Based on these observations and a review of the literature, we propose that pulmonary carcinosarcomas are composed of a heterogeneous population of tumors. This case supports the concept that blastomas are a distinctive subtype of carcinosarcomas. An unusual feature in the clinical presentation was the expectoration of an endobronchial portion of tumor.

Adolescent↗
PubMed1997

p53 and K-ras mutational genotyping in pulmonary carcinosarcoma, spindle cell carcinoma, and pulmonary blastoma: implications for histogenesis.

In an attempt to understand the molecular pathogenesis of biphasic pulmonary neoplasms, the authors studied 25 cases of carcinosarcoma, spindle cell carcinoma, and pulmonary blastoma using a combined immunohistochemical and topographic genotyping approach for the presence of p53 abnormalities within the different epithelial and mesenchymal components of these tumors. Genotyping involved a search for point mutational damage in p53 exons 5-8, which was correlated with p53 immunoreactivity. This analytical approach demonstrated p53 missense point mutations in four of nine cases of spindle cell carcinoma with a 100% concordance rate between p53 immunopositivity and the presence of DNA mutational damage. One of six carcinosarcomas, heterologous in type, exhibited a p53 mutation. The concordance rate among carcinosarcomas was also 100%. However, the concordance rate among classic biphasic pulmonary blastomas was only 43%, with one of seven cases demonstrating a p53 mutation by DNA genotyping. The lack of concordance in pulmonary blastomas was possibly due to the existence of genotypically distinct subsets of tumor cells likely bearing mutations among largely nonmutated cells. In a similar fashion, among three well-differentiated fetal type adenocarcinomas, no p53 mutations were detected despite the presence of focal p53 immunopositivity in one of the cases. No K-ras mutations were detected in any of the 25 tumors examined. Monoclonal histogenesis from a single totipotential cell in a subset of these neoplasms (six of 22 cases) was supported by the finding of p53 overexpression and identical p53 mutational genotype in both the epithelial and spindle elements of the tumors. Furthermore, the finding of a small percentage of p53-positive tumor cells within one or both components suggests late acquisition of p53 mutational change in a subset of pulmonary blastomas.

Aged↗
PubMed2002

Co-existent carcinosarcoma and adenoid basal carcinoma of the uterine cervix and correlation with human papillomavirus infection.

A case of carcinosarcoma associated with an adenoid basal carcinoma of the uterine cervix in an 84-year-old woman is described. The tumor formed a pelvic mass, and total hysterectomy with bilateral salpingo-oophorectomy was performed. The tumor was 17 cm in maximal dimension, arose in the posterior wall of the uterine cervix, and had a solid and cystic, focally myxoid sectioned surface. The tumor was composed of keratinizing squamous cell carcinoma and a mostly nonspecific sarcomatous component with focal chondrosarcomatous differentiation. Multiple foci of adenoid basal carcinoma were observed in the adjacent cervical wall. The HPV L1 gene was detected by PCR in each of the carcinomatous and sarcomatous components of the carcinosarcoma and the adenoid basal carcinoma. To our knowledge, this is the fifth case of coexisting carcinosarcoma and adenoid basal carcinoma of the uterine cervix in the English language literature.

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