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Carcinosarcoma of the esophagus: a twenty-case study.

The present report reviews results from 20 carcinosarcoma patients, and compares them with 773 cases of squamous cell carcinoma of the esophagus treated surgically at the National Cancer Center Hospital from 1971 to 1988. Although there were no significant differences in age, sex, symptoms or location between the two groups, the carcinosarcoma group had morphological characteristics as follows. (1) Seventy-five percent of the carcinosarcomas were of the elevated type. (2) The tumor was large. (3) The depth of invasion was limited to the esophageal wall in 80% of the carcinosarcomas. The rate of lymph node metastasis was almost the same, at greater than 65%, in both groups. Moreover, lymph node metastasis occurred at various stages, of the depth of invasion in the carcinosarcoma group. The curative resection rate was higher for carcinosarcoma (80%) than for squamous cell carcinoma (46.5%). There was no significant difference in recurrence rate between them. Compared with the high frequency of lymph node recurrence in the squamous cell carcinoma group, the recurrence due to hematogenous metastasis was more frequent in the carcinosarcoma group. Although the three-year survival rate was higher for carcinosarcoma (62.8%) than for squamous cell carcinoma (28.1%), there was no significant difference in the five-year survival rate between them (26.7 vs. 22.4%). In conclusion, radical esophagectomy with lymph node dissection is a necessary therapy for carcinosarcoma, and careful follow-up, paying special attention to hematogenous metastasis, is required.

Adult

Utility of immunohistochemistry in distinguishing ovarian sertoli-stromal cell tumors from carcinosarcomas.

Poorly differentiated Sertoli-stromal cell tumors and carcinosarcomas of the ovary both show biphasic epithelial and stromal patterns and may both show heterologous stromal elements, presenting a difficult diagnosis. We studied the immunohistochemical profile of Sertoli cell differentiation in human testes and applied these findings to the ovarian tumors. Eleven Sertoli-stromal cell tumors, six carcinosarcomas of the ovary, and 11 testes (six fetal, one infant, and four adult) were studied using antibodies to cytokeratin AE1:AE3 (AE1:3), cytokeratin CAM 5.2 (CAM), epithelial membrane antigen (EMA), vimentin, desmin, muscle-specific actin (MSA), S-100 protein (S-100), CA 19-9, CA 125, carcinoembryonic antigen monoclonal (CEA-M), carcinoembryonic antigen polyclonal (CEA-P), and placental alkaline phosphatase (PLAP). In the fetal testes, immature gonadal stroma and sex cord areas stained with vimentin (six of six cases), AE1:3 (five of six cases), and CAM (six of six cases). Sertoli cells in immature gonadal stroma areas, sex cords, and seminiferous tubules of normal fetal, infant, or adult testes never showed immunoreactivity for EMA, S-100, CA 19-9, CA 125, CEA-M, CEA-P, or PLAP. All Sertoli-stromal cell tumors stained with AE1:3 and CAM in areas of Sertoli cell differentiation (11 of 11 cases) but did not stain with EMA, PLAP, CEA-P, CEA-M, CA 19-9, CA 125, or S-100 (none of 11 cases). Carcinosarcomas expressed AE1:3 and CAM in all epithelial areas (six of six cases) and most stromal areas (five of six cases). Carcinomatous areas of carcinosarcoma also showed immunoreactivity for EMA (six of six cases), CA 125 (two of six cases), PLAP (two of six cases), CEA-P (two of six cases), and CEA-M (one of six cases), while stromal areas of carcinosarcoma expressed EMA (four of six cases) and S-100 (four of six cases). Heterologous stromal elements were present in three of 11 Sertoli-stromal cell tumors (two showed skeletal muscle and one showed both skeletal muscle and cartilage differentiation) and in four of six carcinosarcomas (one skeletal muscle, one cartilage, and two cartilage and skeletal muscle). All skeletal muscle heterologous elements expressed desmin, vimentin, and MSA. The heterologous cartilage in carcinosarcoma stained with S-100 (three of three), while the one case of heterologous cartilage in Sertoli-stromal cell tumor did not. These results suggest that ovarian Sertoli-stromal cell tumor can be distinguished from carcinosarcoma by the absence of staining for EMA, PLAP, CEA, CA 125, or CA 19-9 in epithelial areas of Sertoli-stromal cell tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

An immunohistological comparison of primary lung carcinosarcoma and sarcoma.

We wished to assess the antigenic expression of primary lung tumors diagnosed as either carcinosarcoma or sarcoma in order to determine whether this information would be useful in distinguishing the two. We therefore immunohistochemically analyzed six pulmonary carcinosarcomas and five primary lung sarcomas for the presence of carcinoembryonic antigen (CEA), S100 protein, cytokeratin and vimentin using commercially available monoclonal and polyclonal antibodies on formalin fixed tissues. Six of six carcinosarcomas stained positively for cytokeratin while none of the sarcomas stained. In three carcinosarcomas both the carcinomatous and sarcomatous areas were positive while in three only the carcinomatous areas were positive. CEA staining was present in five carcinosarcomas and absent in all the sarcomas. CEA positivity was strong and not confined to those tumors with obvious gland formation. Staining for S100 protein was positive in two carcinosarcomas but only in those areas showing chondroid differentiation. Immunohistochemical staining for vimentin using two different monoclonal antibodies gave inconsistent results. We conclude that in differentiating between a carcinosarcoma and a sarcoma of the lung, immunohistochemical staining for both cytokeratin and CEA are useful with cytokeratin marginally preferable. The data indicate that carcinosarcoma of the lung, like that of the upper aerodigestive tract, expresses antigens suggesting both epithelial and mesenchymal differentiation.

Antigens, Neoplasm

Polypoid carcinoma of the esophagus. A unifying term for "carcinosarcoma" and "pseudosarcoma".

Polypoid carcinomas with spindle-cell sarcomatous features have been designated either as carcinosarcoma or pseudosarcoma. The distinction between these two tumors has depended on the presence of "intermingling" of the carcinomatous and sarcomatous components in so-called carcinosarcoma. But unlike the carcinosarcoma, the sarcomatous component in pseudosarcoma has been considered benign. A polypoid tumor of the esophagus in a 57-year-old male was predominantly composed of spindle cell, sarcomatous cells. The presence of adjacent intraepithelial epidermoid carcinoma with transitional and ultrastructural features confirmed the epithelial origin of this tumor. Because of the absence of "intermingling," the primary tumor was considered to be a pseudosarcoma. However, our postmortem examination showed metastases composed of both carcinomatous and sarcomatous features. A review of the literature on carcinosarcomas and pseudosarcomas shows that only one case of pseudosarcoma reported by Hughes and Cruickshank showed a similar situation and indicates that the sarcomatous component in pseudosarcomas has the same metastatic potentiality as has been reported in carcinosarcomas. We conclude from these studies a basic similarity of the carcinosarcoma and pseudosarcoma. The term polypoid carcinoma is proposed for both these lesions.

Bronchial Fistula

'Pleural' and pulmonary carcinosarcomas.

The histological distinction between carcinosarcoma and mesothelioma has received little attention. The object of this study was to describe the histology and immunohistochemistry of two carcinosarcomas presenting as pleural tumours. These were compared with 12 carcinosarcomas from sites within the lung, and with the established features of mesothelioma. Histologically and immunohistochemically, these 'pleural' carcinosarcomas are similar to conventional pulmonary carcinosarcomas but accurate recognition is hindered by their gross appearance and biphasic histology which closely mimic mesothelioma. They may exhibit features such as neutral mucin, expression of carcinoembryonic antigen, squamous differentiation, and neuroendocrine differentiation which, when present, are evidence against mesothelioma. These tumours are rare and have passed unnoticed until now.

Aged

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

Malignant mixed müllerian tumor of the ovary with prominent neuroectodermal differentiation (teratoid carcinosarcoma).

We report a unique carcinosarcoma of the ovary having an organoid growth pattern that resembled immature teratoma. The tumor contained both adenocarcinoma and squamous carcinoma (focally sebaceous) admixed with chondrosarcoma, rhabdomyosarcoma, and malignant neuroectodermal components. The neuroectodermal components were prominent, resembling ependymoblastoma, medulloepithelioma, ganglioneuroblastoma, glioblastoma multiforme, and pigmented neuroectodermal tumor. Immunohistochemical studies dramatically revealed carcinoma and rhabdomyosarcoma admixed with malignant neuroectodermal tumor. Implants of papillary serous carcinoma (with psammoma bodies) were present in the opposite ovary, uterine serosa, omentum, and appendiceal serosa. Although a variant not previously described in the ovary, this ovarian carcinosarcoma closely resembled nasopharyngeal tumors described as teratoid carcinosarcoma or terato-carcinosarcoma.

Carcinosarcoma

Intermediate-sized filament proteins (keratin, vimentin, desmin) in metaplastic carcinomas, carcinosarcomas and stromal sarcomas of the breast.

The distribution of intermediate-filament (IF) proteins of the keratin, vimentin and desmin type in breast stromal sarcomas, carcinosarcomas, metaplastic carcinomas and phyllodes tumors has been compared using the avidin-biotin complex immunoperoxidase technique. Keratin reactivity was found in carcinomatous and pseudosarcomatous areas of all metaplastic carcinomas, in the cuboidal epithelial cells of carcinosarcomas and in the epithelial component of phyllodes tumors. Vimentin and desmin were detected in the sarcomatous portion of carcinosarcoma, focally in the stromal component of phyllodes tumors and not always in the stromal sarcomas. These data confirm that combined analysis of IF expression is a reliable and convincing way to differentiate stromal sarcomas, metaplastic carcinomas and carcinosarcomas in breast pathology.

Breast Neoplasms

[A case of pulmonary metastasis from carcinosarcoma of uterus with subcutaneous implantation of tumor cells along the needle tract after percutaneous needle biopsy of lung].

A 68-year-old female who had undergone total hysterectomy for carcinosarcoma five months previously was noted to have a solitary nodular shadow in the right lung on chest X-ray. Percutaneous needle biopsy of the lung was performed via the right anterior chest wall, and the histologic findings showed metastasis from carcinosarcoma of uterus. Two months after needle biopsy, a chest wall mass appeared of the site of puncture of the lung needle biopsy. The mass was resected to relieve the chest wall pain and the specimen showed carcinosarcoma of uterus histologically. We consider that tumor cells were implanted to the chest wall along the needle tract after percutaneous needle biopsy of the lung. The postoperative chest computed tomogram showed the route of tumor implantation from the metastasis of right lung into the right chest wall. Dissemination and chest wall implantation of malignant cells after percutaneous lung needle biopsy have been rarely reported. However there are no reports of tumor implantation of sarcoma. The possibility of implantation of tumor cells along the needle tract after percutaneous lung needle biopsy should be carefully considered in cases of carcinosarcoma.

Aged

[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

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

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

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

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

Carcinosarcoma of the nasal cavity and paranasal sinuses.

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

Carcinosarcoma

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

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

Animals

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

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

Aged