Uterine adenosarcoma with sarcomatous overgrowth versus uterine carcinosarcoma: comparison of treatment and survival.

OBJECTIVE: Uterine adenosarcoma with sarcomatous overgrowth (ASSO) is a rare variant of uterine sarcoma first described in 1989. This clinicopathologic study was undertaken to compare the treatment and survival of uterine adenosarcoma with sarcomatous overgrowth to that of uterine carcinosarcomas. METHODS: A review of uterine sarcomas diagnosed at Washington Hospital Center from January 1988 to December 1998 was performed. Records were reviewed for demographic data, surgical staging, primary and adjuvant therapy, metastatic site, disease recurrence, and survival. All pathology was reviewed and diagnosis confirmed. Statistical analysis included chi(2) test and Student's t test. Kaplan-Meier survival curves were plotted to estimate the median and 5-year survival times. The log-rank test was used to compare survival times. A P value <0.05 was considered significant. RESULTS: Sixty patients were diagnosed with uterine sarcoma at Washington Hospital Center. Of these, 33 (55%) were uterine carcinosarcomas, 11 (18%) ASSOs, 6 (10%) adenosarcomas, and 10 (17%) leiomyosarcomas. Of the patients diagnosed with uterine ASSO, 3 (27%) were stage I, 3 (27%) stage II, 1 (9%) stage III, and 4 (36%) stage IV. All 11 patients with uterine ASSO underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and tumor debulking. Postoperative adjuvant therapy included chemotherapy (n = 4), radiation (n = 4), combination radiation and chemotherapy (n = 1), and no adjuvant therapy (n = 2). The overall median survival time of patients with uterine ASSO was 13 months. Nine of eleven patients are dead of disease, and two patients (both with stage I) are alive without evidence of disease at 18 and 19 months. Thirty-three patients with carcinosarcoma were identified, with follow-up available on 29 patients. Of these, 10 (34%) were stage I, 6 (22%) stage II, 3 (10%) stage III, and 10 (34%) stage IV. Twenty-seven of the twenty-nine patients diagnosed with carcinosarcoma underwent surgical therapy to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, staging and tumor debulking. Two patients died prior to treatment. Postoperative adjuvant therapy included chemotherapy (n = 9), radiation (n = 13), combination (n = 1), and no further therapy (n = 4). Twenty of the twenty-nine patients are dead of disease; there were nine surviving patients at the time of this report (stage I-5, stage II-3, stage III-1). The median survival of these patients was 31 months, with an overall 5-year survival of 22%. Comparison of the Kaplan-Meier survival curves using the log-rank test suggests a worse prognosis for uterine ASSO. However, this did not reach statistical significance (P = 0.0522). CONCLUSIONS: Patients diagnosed with uterine ASSO have a poor prognosis similar to that of carcinosarcoma. Management should include complete surgical staging. Additional therapy in the form of radiation, chemotherapy, or both has been reported; however, the superiority of one modality could not be determined from our data.

Cluster of uterine mullerian adenosarcoma in the Washington, DC metropolitan area with high incidence of sarcomatous overgrowth.

Mullerian adenosarcoma is an uncommon variant of uterine sarcoma. Twelve uterine adenosarcomas were diagnosed during a 42-month period at the Washington Hospital Center in Washington, DC. Based on estimated incidence data derived from the US Department of Defense beneficiary population, an estimated relative risk of 15.4 (95% confidence interval, 7.7-31.0) was calculated, indicating a significantly increased incidence of adenosarcoma in the population studied (p<0.0000001). Among 10 patients who underwent hysterectomy, six (60%) of their tumors had sarcomatous overgrowth. In comparison with the previously reported proportion of adenosarcomas with sarcomatous overgrowth, approximately 16%, the proportion with sarcomatous overgrowth was significantly higher than expected (p<0.01). Mullerian adenosarcoma with sarcomatous overgrowth was first described in 1989 and suggests that the cluster of adenosarcomas reported herein may be due in part to the current classification of some uterine tumors as adenosarcoma with sarcomatous overgrowth that previously would have been classified as other types of uterine sarcoma. Nonetheless, even after reviewing and updating the classification of all sarcomas diagnosed at the Washington Hospital Center from 1985 to 1998, the ratio of adenosarcomas to uterine adenocarcinomas during the 1994-1998 period was 4.7 times (p<0.005) that of the 1985-1993 period, suggesting a more modest but real increase in the occurrence of this tumor. Correct classification of mullerian adenosarcomas with sarcomatous overgrowth is important because the limited available data suggest that the prognosis is notably worse than that for adenosarcomas without sarcomatous overgrowth.

Estrogen dose required to maintain parathyroid hormone mediated bone gain in osteopenic ovariectomized rats is probably higher than in preventive treatment with estrogen.

Successful prevention of bone loss in ovariectomized rats with 17 beta-estradiol (E2) at 10 micrograms/kg/d has been reported. Here we show that E2 dose twice that much is not enough to maintain PTH(1-34) mediated bone gain. Three-month-old female Wistar rats were ovariectomized and fed with regular rodent chow and water ad libitum. Three months later they were divided into 9 groups (5-8 per group) and treated cyclically with PTH(1-34) (20 micrograms/kg/d sc, 5d/w for 3w) and E2 (20 micrograms/kg/d sc, 5d/w for 4w). There were also a baseline group and five vehicle control groups. Cancellous bone volume (Cn.BV/TV) of distal femoral metaphyses was measured by computer-aided histomorphometry on trichrome stained thin sections, and 24-hour fasted urine was analyzed for pyridinoline/creatinine (PYR/CREA) by immunoassay. Histomorphometric results showed that PTH(1-34) progressively increased Cn.BV/TV but E2 failed to maintain them. Urinary PYR/CREA results showed that E2-treated groups had lower values. We conclude that E2 dose > 20 micrograms/kg/d is required to maintain the PTH mediated bone gain.