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'True' sarcomatoid carcinoma of the renal pelvis. First case report with immunocytochemical study.

A case of sarcomatoid carcinoma of the renal pelvis is reported. The neoplasm showed polypoid configuration and was composed exclusively of plump, spindle and pleomorphic cells. Light microscopy did not reveal any epithelial differentiation of the neoplastic cells. Immunoperoxidase staining for keratins and for epithelial membrane antigen was strongly positive in the spindle elements and showed the epithelial nature of the proliferation. The present case suggests that pleomorphic tumors, when occurring in visceral organs, should be carefully sampled and immunocytochemical markers for epithelial and sarcomatous differentiation studied, before diagnosis of carcinosarcoma or sarcoma may be accepted.

Carcinosarcoma↗

Adjuvant chemotherapy in early stage uterine sarcomas: an open question.

Uterine sarcomas are aggressive gynecological cancers even at early stage of disease. The most common histological types are represented by leiomyosarcoma, endometrial stromal sarcoma, and carcinosarcoma. The mainstay of treatment of stage I-II disease is total hysterectomy with bilateral salpingo-oophorectomy. Adjuvant radiotherapy may decrease local recurrence rates without any significant impact on survival. Adjuvant chemotherapy is a logical approach, since distant recurrences are more frequent than local failures. The chemotherapy regimens commonly used in advanced uterine sarcomas are similar to the ones for advanced soft tissue sarcomas, with anthracyclines and ifosfamide as the most active drugs. However, carcinosarcomas respond better to cisplatin-based regimens. It is advisable to design international cooperative randomized trials with the aim of defining the role of adjuvant chemotherapy in the treatment of early stage uterine sarcomas.

Antineoplastic Agents↗

A clinical and pathologic study of 34 sarcomas of the uterus.

The clinical and pathologic features of 34 uterine sarcomas were studied to determine the natural history of the disease. Sixteen patients had leiomyosarcoma, five mixed mesodermal sarcoma, ten endometrial stromal sarcoma, two carcinosarcoma and one endolymphatic stromal myosis. The patients were treated without an unique protocol. At 3 years the actuarial relapse-free survival was 53.6%: 68.4% in stage I-II patients and 22.2% in stage III-IV patients. As regards the histologic subtype mixed mesodermal sarcomas had the best prognosis; endometrial stromal sarcomas the worst. The necessity of a uniform clinical and histologic classification as well as the importance of controlled clinical trials are pointed out.

Adult↗

Endometrial stromal sarcoma: review of Mayo Clinic experience, 1945-1980.

Uterine sarcomas are uncommon malignancies. We retrospectively examined 24 cases of "high grade" endometrial stromal sarcomas (ESS). The histologic diagnosis was made if there was a high grade sarcoma with a high mitotic index and nuclear anaplasia. Heterologous elements could be present, if focal only. Leiomyosarcomas, mixed mesodermal sarcomas, and carcinosarcomas were excluded. Mitotic index was expressed as the number of mitoses per 10 high-power fields in active areas. Tumor grade was based on nuclear anaplasia. ESS were 5.7% of all uterine sarcomas. Median age was 58.2 years; median duration of symptoms was 67.5 days. Abnormal bleeding was the presenting complaint in 91.7%. Uterine enlargement was seen in 33%; protrusion through the cervical os was seen in 9 cases. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed in 95.8%. Twenty patients had myometrial involvement; 5 patients had serosal spread and extrauterine disease; residual disease was seen in 3 patients. Adjuvant radiation was not beneficial. Ten patients had recurrences: 60% in the pelvis, 50% each with subcomponent of abdominal or distant disease. Overall survival was 3.4 years and was significantly associated with extent of disease, size of the primary tumor, and grade.

Adult↗

[The antineoplastic activity of testiphenon].

The paper describes the antitumor activity of a newly-developed hormonocytostatic drug testiphenon--a complex ether of 5 alpha-dihydrotestosterone and chlorphenacyl (17 beta-[n-di/2-chloroethyl/aminophenylacetate]-5 alpha-androstan-17 beta-ol-3-on). Its antitumor properties were studied in 15 models of transplantable solid tumors and systemic neoplasms of mice and rats such as sarcoma 298, sarcoma 37, sarcoma-180, Lewis lung epidermoid carcinoma, carcinoma of the forestomach-5, large bowel adenocarcinoma, Harding-Passey's melanoma, cervical cancer-5, mammary adenocarcinoma Ca-755, hemoblastosis La, plasmacytoma MOPC-406, Rauscher's erythroblastosis, Walker's carcinosarcoma 256, sarcoma 45, alveolar carcinoma of the mammary gland and DMBA-induced mammary tumors of mice. The spectrum of antitumor activity of testiphenon proved wider than those of its components or other estrogeno-cytostatic drugs--phenestrol and estracyt. The drug is specifically intended for selective action upon target tissues for androgens and tumors developing from the said tissues.

Animals↗

Phase II trial of thalidomide for advanced and recurrent gynecologic sarcoma: a brief communication from the New York Phase II consortium.

OBJECTIVE: To define the efficacy of thalidomide on the overall survival of patients with metastatic recurrent gynecologic sarcomas. PATIENTS AND METHODS: All patients with sarcoma or carcinosarcoma of gynecologic origin and documented recurrence or persistence of disease after appropriate surgery, radiation therapy and/or chemotherapy were recruited to the study. All patients were ambulatory and had measurable disease that could be documented on CT scan. Patients were started on 200 mg/day of thalidomide orally every night and escalated by 100-200 mg every 7 to 14 days. The length of the treatment was separated into 2 cycles with the first 84 days defined as the first cycle and the next 56 days as the second cycle. Common Toxicity Criteria were used to record toxicities. Because thalidomide was postulated to induce cytostasis, the end-points were progression-free and overall survival in this mixed group of patients. RESULTS: Seventeen patients were enrolled. The drug was not well tolerated because of constipation, fatigue, worsening performance status, drowsiness and sleepiness. The total dosage of medication given to each patient ranged from 3200 mg to 40,500 mg. The maximum dosage reached in each patient ranged from 300 mg to 750 mg, with the total time of treatment ranging from 13 to 99 days. All patients had progression of disease with a median progression-free survival time of 1.84 months (CI 1.54-2.79 months) and a median overall survival of 6.64 months. DISCUSSION: Thalidomide has no activity in patients with advanced or recurrent gynecologic sarcomas and was not well-tolerated. The overall survival was <7 months. The progression-free survival was <3 months, and, since the therapy was not tolerated well, we unanimously decided to close the study at this point. Despite the poor result, we still believe in the strategy of anti-angiogenesis and will continue to pursue other potential treatment options using the same concept.

Administration, Oral↗

[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↗

SYT-SSX2 variant of primary pulmonary synovial sarcoma with focal expression of CD117 (c-Kit) protein and a poor clinical outcome.

Pulmonary synovial sarcoma is a rare neoplasm recently recognized as a distinct entity and characterized by t(X;18) translocation and production of at least 2 fusion genes, SYT-SSX1 and SYT-SSX2. We report a case of primary pulmonary synovial sarcoma with the SYT-SSX2 phenotype and a rapidly progressive downhill course. Previous reports have suggested that the soft tissue synovial sarcomas with SYT-SSX2 phenotype have a favorable clinical outcome. To the best of our knowledge, this is also the first report of CD117 (c-Kit) expression in a pulmonary synovial sarcoma. A 45-year-old woman presented with left chest pain and was found to have a left lower lobe tumor that was originally diagnosed as a sarcomatoid carcinoma. After the patient underwent chemotherapy and brachytherapy, the specimen from a left pneumonectomy showed a large spindle cell tumor, which was reclassified as a synovial sarcoma based on the results of immunophenotyping and molecular genetic studies. Differentiation between sarcoma and carcinosarcoma is crucial for implementing appropriate therapy. Furthermore, if the tumor expresses c-Kit, it may respond to target-based therapy.

Biomarkers, Tumor↗

[A case of true pulmonary carcinosarcoma].

The patient was a 47-year-old man who had visited a nearby physician with a chief complaint of bloody sputum. This patient underwent partial resection of the left upper lobe including a tumor adjacent to a huge bulla revealed by a plain chest radiograph. The resected tumor was composed of adenocarcinomatous and sarcomatous components, including partially-differentiated chondrosarcoma and rhabdomyosarcoma. The diagnosis was therefore true pulmonary carcinosarcoma. The sarcoma component recurred in the remaining part of the left lung. This recurrent lesion was surgically unresectable, but was regionally controlled with radiotherapy and bronchial arterial infusion of anticancer agents. However, distant metastases occurred to the brain, liver, and small intestine, and digestive tract bleeding also occurred. Nevertheless, chemotherapy, linac radiosurgery, percutaneous radiofrequency ablation, and partial small intestinal resection combined with rectal resection were performed. At autopsy, a metastatic lesion was also detected in the pancreas. Liver metastatic lesions were determined to be the adenocarcinomatous component, and the other recurrent or metastatic lesions, except for those in the brain, were all composed of poorly-differentiated sarcomatous tissue.

Adenocarcinoma↗

Uterine sarcomas: the Curie Institut experience. Prognosis factors and adjuvant treatments.

PURPOSE: With a retrospective study at a single institution, we propose to analyze the prognosis factors and adjuvant treatment for uterine sarcomas. MATERIALS AND METHODS: From 1975 to 1995, 73 uterine sarcomas were treated at the Institut Curie, corresponding to 61 T1, 5 T2, and 8 T4 tumors. Thirteen patients had metastatic disease at the time of diagnosis. The mean age was 58 years. In 71% of patients, the presenting sign was bleeding. This series consisted of 44% leiomyosarcomas (LMS), 19% endometrial stromal sarcomas (ESS), and 31% carcinosarcomas or mixed mesodermal sarcomas (MMS). For the grading classification, we used the classification of the Sarcoma Group of the French Federation of Cancer Centres for soft tissue sarcomas. Of the patients, 66% presented a high-grade tumor. RESULTS: The median overall survival was 42 months, with a 5-year survival of 45%. Histological grade, FIGO stage, histology types, and menopausal status were the four independent factors in multivariate analysis. Eighteen patients relapsed locally (25.7%), with 77% central pelvic sites. Patients with radiotherapy and ESS had better local control in multivariate analysis. Thirty-four patients developed metastases (48.6%), mainly pulmonary (58.8%). Eight patients presented with peritoneal disease. High grades and LMS had the worst survival without metastasis in multivariate analysis. CONCLUSION: This study validated our classification for sarcoma grading and confirmed the finding of worst prognosis for LMS and the importance of radiotherapy in local control.

Adult↗

Spindle cell carcinoma of the breast. A clinocopathologic and ultrastructural study.

The clinical and pathologic features in six cases of spindle cell carcinoma of the breast were reviewed. Histologically this tumor is characterized by sheets of spindle cells often containing squamous epithelial islands and numerous cystic spaces lined by epidermoid carcinoma or benign appearing squamous epithelium. Areas of transition from the squamous epithelium or epidermoid carcinoma to malignant spindle cells were seen in all cases. Features of squamous epithelial differentiation were found in the spindle areas of the one tumor examined by electron microscopy. The prognosis in this neoplasm is similar to that in the more common breast carcinomas. Spindle cell carcinoma therefore should be distinguished from fibrosarcoma, stromal sarcoma, and carcinosarcoma. Moreover, it should be separated from the broader category of "metaplastic carcinoma," since this term includes a heterogeneous group of tumors of uncertain histogenesis and prognosis.

Aged↗

New molecular complexes of heterocyclic bis-adducts with bacterial lectins: synthesis and structure-activity relationship studies.

A strongly antitumour effect has been discovered for lectins of Bacillus bacteria [Bacillus subtilis 668(1 + 2)IMV, Bacillus polymyxa 102(1 + 2) KGU] and for their molecular complexes with some heterocyclic bis-adducts of unsubstituted benzimidazole and 6-methyluracile for the first time. These were tested on the tumours: Lymphosarcoma Plissa, Sarcoma 45, Carcinosarcoma Yokera 256. A new convenient method for the preparation of the heterocyclic bisadducts of imidazole, benzimidazole, uraciles with 1,1,1-trifluoro-2-bromo-2-chloroethane is described. The reactions are catalysed by the 18-crown-6-complex.

Amino Acids↗

Nuclear beta-catenin in mesenchymal tumors.

Beta-catenin is a crucial part of the Wnt and E-cadherin signalling pathways, which are involved in tumorigenesis. Dysregulation of these pathways allow beta-catenin to accumulate and translocate to the nucleus, where it may activate oncogenes. Such nuclear accumulation can be detected by immunohistochemistry, which may be useful in diagnosis. Although the role of beta-catenin has been established in various types of carcinomas, relatively little is known about its status in mesenchymal tumors. A number of studies suggest that beta-catenin dysregulation is important in desmoid-type fibromatosis, as well as in synovial sarcoma. We wished to determine whether nuclear beta-catenin expression is specific to and sensitive for particular bone and soft-tissue tumors, including sporadic desmoid-type fibromatosis. We studied the nuclear expression of beta-catenin using tissue microarrays in a comprehensive range of bone and soft-tissue tumor types. A total of 549 cases were included in our panel. Nuclear immunohistochemical staining was determined to be either high level (>25% of cells), low level (0-25%) or none. High-level nuclear beta-catenin staining was seen in a very limited subset of tumor types, including desmoid-type fibromatosis (71% of cases), solitary fibrous tumor (40%), endometrial stromal sarcoma (40%) and synovial sarcoma (28%). Although occasional cases of fibrosarcoma, clear cell sarcoma and carcinosarcoma had high-level staining, no high-level nuclear beta-catenin expression was seen in any of 381 fibrohistocytic, muscular, adipocytic, chondroid or osseous tumor cases representing 42 diagnostic categories. All primary immunostain tissue microarray images are made publicly accessible in a searchable database. High-level nuclear beta-catenin staining serves as a useful diagnostic tool, as it is specific to a small subset of mesenchymal tumors.

Cell Nucleus↗