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In this case-control study, the authors analyzed associations of uterine leiomyoma with atherogenic risk factors and potential sources of uterine irritation. The study included 318 case women with uterine leiomyoma that was first confirmed between 1990 and 1993 in the Baltimore, Maryland, area and 394 controls selected from women visiting the same gynecologists' offices for routine reasons. Telephone interviews were conducted with 77.8% of eligible cases and 78.0% of eligible controls. Compared with participants with no hypertension history, increased risks were observed among participants with any history of hypertension (odds ratio (OR) = 1.7; 95% confidence interval (CI): 1.0, 2.8), hypertension requiring medication (OR = 2.1; 95% CI: 1.1, 4.1), hypertension diagnosed at ages less than 35 years (for hypertension requiring medication, OR = 2.7; 95% CI: 1.0, 7.6), and hypertension of 5 or more years' duration (for hypertension requiring medication, OR = 3.1; 95% CI: 1.2, 8.2). Estimates of associations with diabetes history were very imprecise but followed similar patterns. Adjusted associations were observed with pelvic inflammatory disease (three or more episodes vs. none: OR = 3.7; 95% CI: 0.9, 15.9), chlamydial infection (history vs. no history: OR = 3.2; 95% CI: 0.8, 13.7), and use of an intrauterine device when it caused infectious complications (use vs. no use: OR = 5.3; 95% CI: 1.8, 16.3). Risk of uterine leiomyoma was also associated in a graded fashion with frequency of perineal talc use (daily use vs. no use: OR = 2.2; 95% CI: 1.4, 3.1). The authors conclude that nonhormonal factors may influence risk of uterine leiomyoma.

Objective: The purpose of this study was to assess the blood flow characteristics of adnexal masses before surgical excision and to determine whether color flow Doppler sonography is useful for distinguishing benign from malignant masses., Subjects and Methods: Thirty-one adnexal masses were evaluated with color flow Doppler transvaginal sonography. The pulsatility index and resistive index were calculated from the waveforms generated from blood flow within the ovary. Twenty-five lesions were benign and six were malignant on pathologic examination. Benign lesions included six endometriomas, six mesothelial cysts, three serous and one mucinous cystadenoma, three mature cystic teratomas, two hemorrhagic corpus luteum cysts, one cystadenofibroma, one sclerosing stromal cell tumor, one paratubal cyst, and one ovary that had undergone torsion with infarction. The malignant lesions consisted of three papillary serous cystadenocarcinomas, one granulosatheca cell tumor, one immature teratoma, and one metastasis of colon cancer to the ovaries., Results: Benign tumors and cysts had a significantly higher pulsatility index (mean, 1.93 +/- 1.02; range, 0.23-3.99) and resistive index (mean, 0.77 +/- 0.22; range, 0.2-1.0) than did malignant tumors (pulsatility index: mean, 0.77 +/- 0.33; range, 0.31-1.09; resistive index: mean, 0.5 +/- 0.17; range, 0.27-0.67). However, some overlap in individual values for benign and malignant lesions was found., Conclusion: Our preliminary data suggest that high pulsatility and resistive indexes indicate benign adnexal processes; however, considerable overlap in pulsatility and resistive indexes between benign and malignant lesions was noted, and further work is needed before the validity of these factors is proved.

This study compares the clinicopathologic features of 13 pure uterine papillary serous carcinomas (UPSC) with 19 tumors consisting of UPSC admixed with other types of endometrial carcinoma and nine UPSC associated with endometrial polyps. The mean patient age, frequency of preoperative clinical understaging, postoperative pathologic stage, and survival of patients was similar for the three groups. Surprisingly, widespread metastasis, recurrence, and death occurred even in those cases where myometrial invasion amounted to less than 1 mm or where tumor was confined to an endometrial polyp. Poor prognosis appeared to be related to a propensity for vascular invasion and multifocal carcinogenesis. The latter was manifested by the presence of cytologically malignant cells closely resembling the invasive serous carcinoma in the surface endometrium adjacent to the tumor in 89% of cases and in multiple sites in the genital tract and abdomen. This lesion, designated "intraepithelial carcinoma," was present in the endocervix in nine (22%) of the 41 cases, in the fallopian tube in two cases (5%), on the surface of the ovary in four cases (10%), and on peritoneal surfaces or omentum in 10 cases (25%). In addition, we found that UPSC display considerable morphologic heterogeneity. Foci of clear-cell carcinoma were identified in 13 (32%) of the 41 tumors. In five (12%) neoplasms, the invasive component was composed primarily of glands; and in 22 (54%) tumors, thin as opposed to thick papillae predominated. Accordingly, UPSC may be broadly defined as a carcinoma that displays foci of well-differentiated papillae lined by cells that are markedly atypical cytologically. UPSC frequently contain areas of clear cells. Glands with papillary infoldings sometimes predominate in the invasive component. Because the behavior of endometrial neoplasms, in which at least 25% of the carcinoma exhibits a glandular or papillary architecture with serous differentiation, is similar, the term "uterine serous carcinoma" is an appropriate designation for these tumors, regardless of whether other patterns of differentiation are present or whether the tumor is associated with a polyp.

It has long been known that the risks of some cancers, including endometrial, are associated with obesity. Recent evidence suggests that body fat distribution patterns also affect the risk of developing some diseases. A question that remains is whether cancers are associated with specific distributions of body fat. In this study, women with endometrial cancer were compared to community controls of similar age and race. Participants were interviewed and then measured to determine fat distribution patterns defined by the waist-to-hip circumference ratio. Women with upper body fat distribution had a 3.2-fold (95% confidence limits 1.2, 8.9) higher risk of endometrial cancer than women with lower body fat distribution even with correction for age, parity, and smoking. Obese women with an upper body fat pattern had a 5.8-fold (confidence limits 1.7, 19.9) higher risk of endometrial cancer than nonobese/lower body fat patterned women. Obese women who never smoked had a 3.3-fold statistically significant higher risk of endometrial cancer than nonobese women who never smoked. Current smokers had lower risks than their nonsmoking counterparts. The 3-fold increased risk of endometrial cancer associated with upper body fat did not disappear with adjustment for obesity and smoking.

Use of exogenous estrogens has been associated with endometrial cancer in a number of case-control studies. This observed association could be biased as a result of frequent misclassification of estrogen-induced hyperplasia as endometrial cancer. To evaluate this possibility, pathology slides from 233 patients with a hospital diagnosis of endometrial cancer were reviewed independently by two pathologists. The hospital diagnosis was confirmed by both pathologists in 86% of the cases, indicating that the misclassification of hyperplasia as carcinoma is uncommon.

Five cases of endometrial carcinoma with cutaneous metastases are reported. Cutaneous metastases of endometrial carcinoma are uncommon. There are no other cases reported in the literature. In 91 autopsy cases only one example (1%) could be found. The appearance of subcutaneous nodules is evidence of widespread dissemination and a harbinger of early demise.

Our case-control study of the relation between estrogen use and endometrial cancer involved 451 cases and 888 controls. The overall risk of endometrial carcinoma was sixfold for estrogen users as compared with nonusers; long-term users (greater than five years) had a 15-fold risk. Excess risk was present for both diethylstilberstrol and conjugated estrogens. The risk associated with cyclic use was as great as that for continuous use. Increased risk was associated with estrogen use for all histologic grades of the tumor. The risk of advanced-stage carcinoma was fourfold for estrogen users, but rhe confidence interval was wide, and this question requires further study. Finally, this investigation contradicts the speculation that the association between this cancer and estrogen use can be explained by swifter diagnosis for estrogen users, misclassification of estrogen-related hyperplasia or treatment of early symptoms of the tumor with estrogen.

Peritoneal lavage fluid for cytologic study was obtained in 73 patients undergoing primary surgery for stage I endometrial adenocarcinoma. Preoperative irradiation was not used. Malignant cells consistent with endometrial adenocarcinoma were present in eight (11 percent) cases. There was no significant difference in the proportion of patients with "positive peritoneal cytology" when patients with grade 1 and 2 tumors, five of 45 (11 percent), were compared with those with grade 3 and adenosquamous tumors, three of 28 (10.7 percent), between deeply invasive tumors, two of 20 (10 percent), and those with superficial or no invasion, six of 52 (11.5 percent), between stage IA, six of 42 (14.5 percent) and stage IB disease, two of 31 (6.5 percent). The prevalence of positive peritoneal cytology in this series of 73 patients who received no preoperative irradiation is similar to that reported in other series where preoperative irradiation was used. No correlation between positive peritoneal cytology and other reported poor prognostic indicators in stage I endometrial adenocarcinoma was found.

The 10-year experience at The Johns Hopkins Hospital with 61 cases of mixed Mullerian tumors were reviewed. The patients had a mean age of 63.7 years and the similar constitutional factors of diabetes mellitus, hypertension and nulliparity of endometrial adenocarcinoma. Only one patient had estrogen exposure. Eighteen percent had had prior exposure to pelvic radiation. The life table survival of the 61 patients was 41.1% at 5 years. The 2-year life table survival was 76% for disease confined to the uterus and 16.5% for extrauterine disease. There was no difference in survival between homologous and heterologous tumors. The surgical staging and the autopsies reviewed documented widely disseminated disease even when the tumor appeared to be confined to the uterus. It thus appears essential in order to improve survival these patients require aggressive staging and consideration of systemic adjuvant chemotherapy.

Trophoblastic pseudotumor, a type of gestational trophoblastic neoplasia, is discussed in the context of a case report. The criteria for diagnosis, lack of placental villi, cytotrophoblast, extensive hemorrhage, and necrosis, can only be fulfilled on histopathologic study of a hysterectomy specimen. Clinical management should be based on the titer of the beta subunit of human chorionic gonadotropin, not on the type of gestational trophoblastic neoplasia.

Complete or 'true' hydatidiform mole, an abnormality of human gestation, is characterized by hydropic degeneraton of all placental villi, marked hypertrophy of the trophoblast, absence of a fetus and a propensity to become malignant. The chromosome constitution of complete moles is usually 46,XX, and Kajii et al. reported that the entire genome in seven out of seven cases was paternal in origin, with all centromere markers homozygous for paternal heteromorphisms. These observations, since confirmed, can be explained by the fertilization of an 'empty' egg--no effective genome--by either a haploid sperm that then duplicates without cytokinesis, to restore the diploid number, or by a diploid sperm resulting from failure of the second meiotic division. We report here a study of a series of complete moles that shows the first alternative to be correct in the majority of cases.

All 190 cases of gestational trophoblastic neoplasia diagnosed in the Baltimore metropolitan area from 1975-1982 were identified. Histologic slides were requested and reviewed independently by two pathologists who agreed upon uniform criteria for the diagnosis of hydatidiform (complete) mole, invasive mole, and choriocarcinoma. A representative sample of the slides was selected and resubmitted to one of the study pathologists for a second review. The inter- and intra-pathologist variability in the diagnosis of gestational trophoblastic neoplasia was calculated using the kappa statistic (K). Our findings indicated that the variability in the diagnosis of gestational trophoblastic neoplasia was low whereas that for the related tumor of incomplete mole was high.

A case-control study to determine the gynecologic and reproductive risk factors for gestational trophoblastic neoplasia was conducted in the Baltimore Metropolitan Area. All cases (N = 190) that were pathologically diagnosed from 1975 to 1982 as hydatidiform mole, invasive mole, or choriocarcinoma were ascertained. Slides were independently reviewed by two pathologists. Cases were matched by age, race, and last menstrual period to controls who were delivered of normal pregnancies at term. In the analysis of medical record and interview data, factors found to be positively associated with gestational trophoblastic neoplasia included professional occupations (odds ratio = 2.56, p less than 0.0001), prior spontaneous abortions (odds ratio = 2.32, p = 0.02), and the mean number of months from the last pregnancy to the index pregnancy (cases = 35.9, controls = 28.2; p = 0.03). Factors found not to be associated with disease included contraceptive history, irradiation, ABO blood group, and smoking factors of the male partner. The findings suggest that gestational trophoblastic neoplasia may be part of a continuum of early (first-trimester) reproductive abnormalities.

The rate of regression of the beta subunit of human chorionic gonadotropin in patients successfully treated by single-agent chemotherapy with methotrexate (MTX) for postmolar nonmetastatic gestational trophoblastic neoplasia (NMGTN) has not previously been described. In 21 patients with NMGTN treated with MTX, the rate of regression was determined. Nineteen patients had a log-exponential disappearance of serum beta-hCG titers within 100 days. There was a 50% probability of a negative titer at 50 days. Two patients had plateauing titers within 63 days after therapy. There was no difference in beta-hCG disappearance whether MTX with citrovorum factor or MTX alone was administered. Also, the regression rate of beta-hCG titer in the treated patients was compared to 63 patients with spontaneous decline of titers postevacuation of trophoblastic disease. In the postevacuation group there was a 50% probability at 49 days of negative serum titers. All 63 patients had negative titers within 105 days after evacuation.

Gestational trophoblastic disease, most commonly hydatidiform mole, is an unusual condition within the United States. The incidence of hydatidiform mole has been reported to vary from 1 in 1,200 to 1 in 2,000 pregnancies. This report described eight cases of hydatidiform mole among 4,829 patients presenting for elective first-trimester abortion. Factors which might account for the frequency of hydatidiform mole of 1 in 600 are discussed. Although the clinical course of patients with hydatidiform mole appears benign- gross examination of tissue obtained at suction curettage and the liberal use of histologic evaluation in questionable cases is required to make the diagnosis.

Uterine epithelioid leiomyosarcoma is an unusual smooth muscle neoplasm. It is distinguished on cytoarchitectural grounds from the majority of leiomyosarcomas that arise in the uterus. Three cases of this atypical lesion are presented and the pathologic features are discussed. One patient is alive with no evidence of disease at 3.5 years, one patient has persistent disease at 4 years, and the third patient died of disease at 8 months. Fundamental differences in biologic behavior of this subset of uterine smooth muscle tumors cannot be discerned.

Because of evidence of reduced estrogen excretion in the urine of women who smoke cigarettes and evidence linking estrogen levels to the risk of cancer of the female reproductive system, we evaluated the risk of endometrial cancer in relation to cigarette use in a hospital-based case-control study of 510 women with endometrial cancer (cases) and 727 women with other cancers (controls). The rate-ratio estimate (relative risk) for current smokers as compared with women who had never smoked was 0.7 (95 per cent confidence interval, 0.5 to 1.0), and for former smokers the estimate was 0.9 (0.6 to 1.2). For women currently smoking 25 or more cigarettes per day, the rate-ratio estimate was 0.5 (0.3 to 0.8). The effect of current smoking of at least 25 cigarettes per day appeared to be confined to postmenopausal women, among whom the estimate was 0.5 (0.2 to 0.9). Among premenopausal women the estimate was 0.9 (0.4 to 2.2), but the difference between these two estimates could have been due to chance. The data suggest that women who smoke heavily may have a lower risk of endometrial cancer than nonsmokers. The present findings do not have direct public health importance since cigarettes, overall, have serious deleterious effects. However, if these results are confirmed, elucidation of the underlying mechanisms whereby smoking reduces the risk would be of interest and might be useful in the development of strategies for preventing endometrial cancer.

Utilization of literature review to evaluate peritoneal cytology as a test for the detection of malignant cells in the peritoneal cavity is limited by the size of the study populations, varied use of preoperative radiation, the lack of consistent methodology for specimen retrieval and processing, and the inherent subjectivity of cytologic interpretation. A standardized methodology for retrieval and processing of peritoneal cytologic specimens should be developed to allow meaningful comparisons of future studies. However, certain conclusions are permitted from published data: 1. The incidence of positive peritoneal cytology is 11.4 per cent among 3091 patients with FIGO stage I endometrial cancer. 2. The depth of the uterus does not influence the incidence of positive peritoneal cytology. 3. Positive peritoneal cytology is predictive of other known prognostic factors including advanced histologic grade, depth of myometrial invasion, and pelvic/periaortic lymph node metastases. 4. The presence of malignant cells in the peritoneal washings from some patients with no myometrial invasion and the high incidence of lymph node metastases in other patients with positive peritoneal cytology suggest that malignant cells gain access to the peritoneal cavity in a variety of ways. It is unclear whether each of these modes of access result in viable tumor cells with the potential for viable metastasis. The high incidence of lymph node metastasis in such patients suggests that lymphatic dissemination of malignant cells plays a significant role in the development of positive peritoneal cytology. In this setting positive peritoneal cytology clearly identifies that individual at high risk for recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

To summarize the review, the medical literature indicates that certain constitutional factors as well as the use of exogenous estrogen are associated with an increased risk of endometrial cancer. In addition, the absolute increase in the risk of this neoplasm with use of estrogen does not appear to be constant but depends upon the specific constitutional factors present. Therefore, particular caution should be exercised in prescribing replacement estrogens for women who already have an increased risk of endometrial cancer, such as those who are overweight or those who give a history of late onset of menopause. It should be noted, however, that the greatest absolute increase in risk with estrogen use appears to occur in women with no other known risk factors for the disease.

In a case-control study of the risk of adenocarcinoma of the endometrium in relation to conjugated-estrogen use, we found that 31 per cent of 425 women with endometrial cancer and 15 per cent of 792 controls reported having used conjugated estrogens; the rate-ratio estimate was 3.5 with a 95 per cent confidence interval of 2.6 to 4.7. For use that lasted at least one year, the rate-ratio estimate for Stage I or II cancer was 5.2 (95 per cent confidence interval, 3.7 to 7.2), and for Stages III and IV combined it was 3.1 (1.5 to 6.4). Among women who had used estrogen for at least one year and then discontinued it, the risk of endometrial cancer remained significantly elevated even after estrogen-free intervals of over 10 years. The findings suggest that long-term use of conjugated estrogen increases the risk of both localized and widespread endometrial cancer. The data also suggest that women who have taken conjugated estrogen for one or more years remain at increased risk for at least 10 years after they discontinue use. Such women should be considered for long-term gynecologic surveillance.

It has been suggested that the reported association between estrogen use and endometrial cancer may have been biased because estrogens provoke uterine bleeding in women with otherwise asymptomatic disease. To evaluate this hypothesis we compared 149 patients with endometrial cancer and 402 control subjects with other conditions with reference to the time when they had last used conjugated estrogens. In women who had last used conjugated estrogens two or more years previously and who had taken them for at least five years, the rate-ratio estimate was 3.3 (95 per cent confidence interval, 1.4 to 8.0) relative to women who had never used them. Uterine bleeding, and hence the diagnosis of otherwise asymptomatic cancer, cannot be attributed to estrogen use that ceased in the distant past. Our results suggest that such use has a residual effect on the risk of endometrial cancer; this effect is not accounted for by biased selection of cases according to estrogen use.

Rhabdoid tumors are highly malignant neoplasms resembling rhabdomyosarcomas, which most commonly occur in the kidney in young children. Several cases of extrarenal malignant rhabdoid tumors have been described, many in adolescents and young adults. We describe a 46-year-old woman with a primary uterine tumor that has the histologic, immunohistochemical, and ultrastructural characteristics of a malignant rhabdoid tumor. To our knowledge, this is the first report of a rhabdoid tumor in this site. Furthermore, this woman's age expands the range for which pathologists and clinicians should consider this diagnosis, even in extrarenal sites.