Mesodermal adenosarcoma of the testis.

Biphasic neoplasms with a benign to atypical epithelial component and a usually low-grade malignant stromal component have been reported in various sites, probably being best known for their occurrence in the uterine corpus (mullerian adenosarcoma). We report a tumor of this type that occurred in the testis of a 76-year-old man and, to our knowledge, is the first mesodermal adenosarcoma reported at this site. The patient had scrotal swelling for many years with a pronounced increase in the swelling over the past 2 years. A large complex solid-cystic testicular tumor was evident on ultrasound, and examination of a radical orchiectomy specimen showed a 6.5-cm mass. On microscopic examination, the neoplasm had a phyllodes-like appearance with bland cuboidal to flattened epithelium covering polypoid fronds, and lining glands and cysts. The stroma varied from cellular, particularly where it condensed around the glands and cysts, to hypocellular and hyalinized. It was immunoreactive for muscle specific actin, CD10, and to a lesser degree, desmin. This case expands the known sites where mesodermal adenosarcoma may occur. The histogenesis is speculative, but possible options are discussed.

Simultaneous bilateral occurrence of a mixed mesodermal tumor and cystadenocarcinoma in the ovary.

The mixed mesodermal tumor is a very uncommon malignancy. The aggressiveness of this lesion is illustrated by extremely poor prospects for afflicted patients: postoperative survival is usually shorter than 24 months. According to the literature, malignant mixed tumor of the ovary is rather rare and its occurrence with other malignancy is exceptional. We report here a case of a 62-years old woman with serous cystadenocarcinoma in the right ovary and a heterologous malignant mixed mesodermal tumor in the left one. Both tumors expressed cytokeratins, while only the mesodermal tumor expressed S-100 and focal NSE.

[Estimation of DNA methylation level in nonendometrial uterus malignancies]. / Ocena poziomu metylacji DNA w tkankach zlosliwych nowotworów nienablonkowych trzonu macicy.

OBJECTIVES: Rebuilding of genome structure leads to many pathological states including neoplastic malignancies. Rebuilding often occurs as a process caused by disturbances in gene silencing mechanism. DNA methylation pattern is one of the most important mechanisms connected to gene's silencing. Estimation of DNA methylation level in nonendometrial uterine neoplastic tissues compared to normal endometrial samples was the aim of this study. DESIGN: It was to be shown, that changes in methylation rate in promotory regions could lead to carcinogenesis in particular cell. Authors describe an analysis of DNA methylation level in nonendometrial neoplastic uterine tissues compared to DNA methylation level in normal endometrium. MATERIALS AND METHODS: Tissue samples from 9 women with tumor mixtus mesodermalis were collected. 12 samples were normal endometrium-control group. DNA was isolated from tissues and than we performed an estimation of DNA methylation levels. Than we performed a statistical analysis of results. RESULTS: The median DNA methylation level was significantly higher in neoplastic tissues than in normal endometrium. CONCLUSIONS: Authors conclude, that DNA methylation level is higher in neoplastic tissues, but does not correlate with clinical stage of the disease.

Primary heterologous carcinosarcoma (metaplastic carcinoma) of the urinary bladder: a clinicopathologic, immunohistochemical, and ultrastructural analysis of eight cases and a review of the literature.

BACKGROUND: Heterologous carcinosarcomas of the urinary bladder are rare neoplasms, the histogenesis of which is still disputed. METHODS: The clinicopathologic, immunohistochemical, and ultrastructural features of eight cases were analyzed. RESULTS: The patients, 5 males and 3 females, had a median age of 70 years. Gross hematuria, dysuria, and urinary tract infections were the main presenting symptoms. Tumors were solitary in all cases and located in the right wall in six cases. Tumor size ranged from 2 to 12 cm (median, 5 cm). Four patients died of disease 2, 6, 17, and 42 months postoperatively, respectively. Microscopically, the tumors consisted mostly of a varied mixture of high grade transitional cell carcinoma with chondrosarcoma, osteosarcoma, rhabdomyosarcoma, and undifferentiated spindle cell (leiomyosarcoma-like) components with occasional transitional features between one component and another. All tumors but one invaded the muscularis propria or the perivesical fatty tissue. Immunohistochemically, keratin expression was observed focally in the sarcoma component as well as the carcinoma component. Reactivity for vimentin, desmin, muscle specific actin, and S-100 protein was observed in poorly differentiated areas in addition to the expected positivity of each histologic subtype of sarcoma. Ultrastructurally, one tumor showed evidence of both epithelial and chondrosarcomatous differentiation, whereas three contained rhabdomyosarcomatous elements. CONCLUSIONS: On the basis of the current series and a review of 55 reports from the literature, primary heterologous carcinosarcoma of the urinary bladder proved to be a highly malignant type of neoplasm occurring predominantly in elderly males that was most often in an advanced stage at presentation and rapidly became lethal. Histogenetically, some heterologous carcinosarcomas should be regarded as a variant of sarcomatoid carcinoma (metaplastic carcinoma) that shows prominent heterologous differentiation.

Pharmacokinetic and phase I trial of intraperitoneal carboplatin and cyclosporine in refractory ovarian cancer patients.

PURPOSE: The feasibility and pharmacokinetics of cyclosporine (CsA) delivered intraperitoneally (IP) have not been previously explored. We performed a pharmacokinetic study of IP CsA followed by a phase I dose-escalation trial of the combination of IP CsA and carboplatin in refractory ovarian cancer patients. PATIENTS AND METHODS: A pilot study was performed of three patients who received 1, 10, and 20 mg/kg IP CsA alone. Subsequently, a phase I trial of 35 patients was performed between April 1990 and April 1993. Whole-blood and IP fluid CsA concentrations were measured at serial time points. The highest dose delivered IP was 34.6 mg CsA/kg in combination with carboplatin (250 mg/m2 or 300 mg/m2, depending on creatinine clearance), which was not dose-escalated. The area under the concentration-time curve (AUC) for CsA and half-life (T1/2) were calculated. Objective and serologic responses were noted, and toxicity was graded using the National Cancer Institute common toxicity criteria. RESULTS: The feasibility of delivering IP CsA alone was established. We observed a 1,000:1 ratio between IP fluid and blood concentrations at 20 mg CsA/kg. Pharmacokinetic analysis confirmed that at 20 mg CsA/kg, there was an IP fluid-to-blood AUC ratio of 600:1 in favor of peritoneal exposure. At the highest dose delivered, 34.6 mg CsA/kg, the mean IP CsA levels of 1,110 micrograms/ mL were tolerated moderately well and the IP fluid-to-blood ratio of 1,000:1 was maintained. Blood and IP CsA concentrations were analyzed in the presence and absence of IP carboplatin. At 20 mg CsA/kg, there was no difference in either mean blood CsA levels (0.9 microgram/ mL) or mean IP CsA concentrations (1,000 micrograms/mL) obtained in the absence or presence of carboplatin. The most common toxicity in the phase I study was anemia, seen in 66% of patients. Common toxicities at the maximum CsA dose delivered (34.6 mg/kg) were anemia, leukopenia, thrombocytopenia, and hypertension. In this trial, three objective responses (two complete and one partial) were observed for a duration of 3 to 11 months. Control of platinum-resistant ascites was an important feature, noted in five of eight patients. CONCLUSION: We have established the feasibility of delivering IP CsA up to doses of 34.6 mg/kg in conjunction with carboplatin, and the sustaining of IP fluid to blood ratios of 1,000:1. The IP administration of CsA resulted in a favorable ratio of exposure for the peritoneal cavity compared with systemic exposure, indicating a therapeutic advantage of this approach with a significant decrease in systemic toxicity. We recommend that 34.6 mg/ kg of IP CsA be tested as a phase II dose in combination with carboplatin in refractory ovarian cancer patients. This report provides the groundwork for future studies using IP CsA, both as a chemomodulator of platinum and of multidrug resistance.

A mixed mesodermal tumor of the cecum: report of a case.

We herein report the case of a 69-year old woman presenting with an abdominal mass, who was found to have a mixed mesodermal tumor (MMT) of the cecum. Imaging studies and endoscopic investigations were consistent with the diagnosis of a nonepithelial malignant tumor of the cecum. On laparotomy, a knuckle-sized firm mass involving the cecum was noticed. As a result, a right hemicolectomy was performed. Pathological examinations, including immunohistochemical staining, resulted in the diagnosis of mesodermal mixed tumor, homologous type. The patient was advised to undergo postoperative chemotherapy but she did not comply. She has been followed up as an outpatient and is still alive 1.5 years after the operation.

Specific receptors and growth effects of insulin and insulin-like growth factors in a human cell line derived from mixed mesodermal tumor of the uterus.

OBJECTIVE: Mixed mesodermal tumors of the uterus are highly malignant. The purpose of our present study was to investigate possible roles of insulin and insulin-like growth factors I and II (IGF-I and IGF-II) in the growth and development of these tumors. METHODS: Specific binding and growth effects of insulin, IGF-I, and IGF-II were studied in SK-UT-1 cells, derived from a human mixed mesodermal tumor of the uterus. The receptors were further characterized by competitive binding and chemical cross-linking studies. RESULTS: Binding studies with 125I-insulin, 125I-IGF-I, and 125I-IGF-II revealed the presence of specific binding sites for these three growth factors. Specificity studies revealed that the binding sites for IGF-I and IGF-II are distinct. Binding of IGF-II was much higher than insulin and IGF-I binding. Scatchard analysis of the binding data revealed that the cell line has a higher number of IGF-II receptor (100,000 sites per cell) than insulin (1400 sites per cell) and IGF-1 (1200 sites per cell) receptors. The effect of these growth factors on cell growth was studied by monitoring the cell number and incorporation of [3H] thymidine into the DNA of the cells. Insulin-like growth factor-II was potent in stimulating the growth of these cells, but IGF-I did not have any effect. Insulin stimulated DNA synthesis only at pharmacologic concentrations. CONCLUSION: These results indicate that IGF-II is mitogenic to mixed mesodermal tumors of the uterus. Insulin-like growth factor II may be involved in the growth regulation of mixed mesodermal tumors of the uterus.