Endometrial Carcinoma In Women Research Articles

Hormone Replacement Therapy, Likely Neither Angel Nor Demon.

PurposeA decline in breast cancer incidence has been attributed to the reduction in hormone replacement therapy (HRT) prescriptions since the publication of the landmark WHIT paper in 2003. Concurrently, a relationship between HRT and cerebrovascular disease incidence has also been suggested. No generalized analysis of HRT prescription rates and breast cancer incidence rates that included more than seven years of data. We hypothesized that detailed analysis of SEER data would clarify the relationship between HRT use and breast cancer incidence. Given the large decline in HRT prescription rates uncovered, analyses of potential complications were also conducted, with the understanding that a small effect or one limited to a subpopulation, such as a single race, might not be detected.MethodsIncidence rates (per 100,000 women) and standard errors for ductal and lobular breast carcinomas, and endometrioid /endometrial carcinomas in women over 50 years were obtained from the Surveillance, Epidemiology, and End Results (SEER) database 1992–2012. From the Medical Expenditure Panel Survey 1996–2012 weighted counts and standard errors of hormone replacement therapy (HRT) prescriptions for women over 50 years were obtained. Using the National Hospital Discharge Survey (NHDS), 1996–2010 weighted counts and standard errors of femoral neck fractures, total hip replacements, acute myocardial infarctions, and cerebral infarctions were obtained for 50+ year men and women. Weighted counts and standard errors were divided by US census figures and multiplied by 100,000. Joinpoint regression was used to analyze rates.Main ResultsBeginning 2001, HRT prescription rates dropped dramatically, 2001–2012 AAPC -14.9 (95% CI -17.4, -12.4). Breast cancer rates, which began to decline in 1999, increased after 2003; 2012 rates were similar to those seen in 2001 for both ductal, AAPC 0.1 (-0.4, 0.6) and lobular, AAPC 0.5 (-0.4, 1.5), carcinoma. Endometrial carcinoma rates increased, 2001–2012 AAPC 3.5 (3.1, 3.8), arguing against a negative effect of HRT discontinuation of endometrial carcinoma. Tests for parallelism failed to detect APC differences among genders for femoral neck fractures (P = 0.24), for total hip replacements (P = 0.11), for myocardial infarctions (P = 0.10), or for cerebral infarctions (P = 0.19), precluding any assignment of general effect on these disorders by HRT.ConclusionsUsing SEER data, we demonstrated that changes in breast cancer rates cannot be explained by HRT prescription rate changes.

Uterine Carcinomas in Tetrabromobisphenol A-exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High-grade Type I Endometrial Carcinomas in Women.

Endometrial carcinoma is the most common gynecologic malignancy is the United States and accounts for 6% of all cancers in women. The disease is classified as type I or type II based on clinicopathologic and molecular features. It is a multifactorial disease with a number of risk factors, including environmental exposures. How environmental exposures, such as flame retardants, may affect the incidence of endometrial cancer is a topic of current and ongoing interest. Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant found in a variety of household products. A recent 2-year National Toxicology Program carcinogenicity study found that exposure to TBBPA was associated with a marked increase in the development of uterine tumors, specifically uterine carcinomas, in Wistar Han rats. Molecularly, TBBPA-induced uterine carcinomas in Wistar Han rats were characterized by a marked increase in tumor protein 53 mutation compared to spontaneous uterine carcinomas, as well as overexpression of human epidermal growth factor receptor 2. Similar to spontaneous carcinomas, tumors in TBBPA-exposed rats were estrogen receptor-alpha positive and progesterone receptor negative by immunohistochemistry. The morphologic and molecular features of uterine carcinomas in TBBPA-exposed rats resemble those of high-grade type I tumors in women, and these data suggest that exposure to TBBPA may pose an increased cancer risk.

Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia

ObjectiveAlthough a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia. MethodsA case–control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model. ResultsThe most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40–59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m2 (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors. ConclusionsOlder age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients.

Risk of high-grade cervical dysplasia and gynaecological malignancies following the cytologic diagnosis of atypical endocervical cells of undetermined significance: a retrospective study of a state-wide screening population in Western Australia.

In 2006, Australia adopted a revised cervical cytology terminology system, known as the Australian Modified Bethesda System (AMBS). One substantial change in the AMBS was the introduction of the diagnostic category of atypical endocervical cells (AEC) of undetermined significance. The aim of this study was to investigate the incidence of histologically confirmed high-grade cervical dysplasia (cervical intra-epithelial neoplasia (CIN) grades 2 and 3 and adenocarcinoma in situ (ACIS)), cervical carcinoma and endometrial carcinoma in women presenting with AEC on cervical cytology. A seven-year retrospective study examining clinical outcomes of women with AEC on a screening cervical smear. Cytology and histology results were extracted from the Western Australia Cervical Screening Registry, and time-to-event analysis was used to predict the odds of having or developing in situ and invasive neoplasia. AEC was reported in index smears from 0.093% (584/622754) women during the study period. No follow-up was available in 35 AEC cases. Sixty-five of the remaining 549 women (11.8%) had, or developed, high-grade cervical dysplasia within five years of their index AEC diagnosis. Endometrial cancer was diagnosed in 21 women and cervical cancer in four women during the follow-up period. Cytologic demonstration of AEC requires careful gynaecologic evaluation, particularly in younger women who may be found to have either high-grade squamous (CIN) or glandular (ACIS) lesions, while in older women, the possibility of endometrial neoplasia needs to be considered.

Clinicopathologic factors predictive of concurrent endometrial carcinoma in women with a preoperative diagnosis of endometrial hyperplasia

Objectives: To evaluate the effect of a universal screening protocol for all newly diagnosed endometrial cancers for Lynch syndrome (LS) using immunohistochemistry staining (IHC) for mismatch repair (MMR) enzyme expression on subsequent genetic counseling and genetic testing referral and acceptance rates. Methods: We performed a retrospective cohort study of all womenwho underwent a hysterectomy for endometrial cancer at Barnes Jewish Hospital in St. Louis, MO, between January 1, 2011 and December 31, 2013, (n= 637). A universal screening protocol was initiated on December 17, 2012, and used IHC for MMR enzymes MLH1, MSH2, MSH6, and PMS2. Caseswith absentMLH1 stainingwere reflexed toMLH1 promoter methylation testing. The first cohort (Pre Em-USP) consisted of women who presented prior to initiation of the screening protocol and were selectively screened (n= 395). In the second cohort (Em-USP), women presented after initiation of this protocol and were all screened for LS (n= 242). Genetic counseling and genetic testing referrals in both cohortswere based on risk factors (family or personal history) and/or IHC results. Categorical variables were compared using the Fisher's exact tests and continuous variables were compared using the Kruskal–Wallis test. Results: Overall, a greater proportion of individuals in the Em-USP cohort underwent genetic testing than in Pre Em-USP (9.1% vs. 4.8%, P b 0.05). Of the individuals with an IHC screening result suggestive of LS, those in the Em-USP cohort were significantly more likely to accept genetic counseling compared to those in the Pre-Em-USP cohort (95% vs. 64%, P= 0.02). Within the Em-USP cohort specifically, patients referred for genetic counseling due to a concerning IHC screening result compared with those who had a normal MMR enzyme staining pattern and were referred based on other risk factors had a higher counseling acceptance rate (95% vs. 61%, P=0.03) and underwent genetic testing more readily (76% vs. 30%, P b 0.001). Conclusions: Implementation of a universal screening protocol utilizing IHC for LS in endometrial cancer leads to higher acceptance of genetic counseling and higher rates of genetic testing compared to referral based on family or personal history alone.

DNA methylation as a biomarker for the detection of hidden carcinoma in endometrial atypical hyperplasia

ObjectiveWomen with atypical hyperplasia (AH) are often found to have endometrial carcinoma (EC) at hysterectomy. The purpose of this study was to evaluate whether the hypermethylation of specific genes found by methylomic approaches to the study of gynecologic cancers is a biomarker for EC in women with AH. MethodsWe evaluated the methylation of AJAP1, HS3ST2, SOX1, and PTGDR from 61 AH patients undergoing hysterectomy. Endometrial biopsy samples were analyzed by bisulfite conversion and quantitative methylation-specific polymerase chain reaction. A methylation index was used to predict the presence of cancer. To confirm the silencing effects of DNA methylation, immunohistochemical analysis of AJAP1, HS3ST2, and SOX1 was performed using tissue microarray. ResultsFourteen (23%) patients had EC at hysterectomy. AJAP1, HS3ST2, and SOX1 were highly methylated in the EC patients' biopsy samples (p≤0.023). AJAP1, HS3ST2, and SOX1 protein expression was significantly higher in patients with AH only (p≤0.038). The predictive value of AJAP1, HS3ST2, and SOX1 methylation for EC was 0.81, 0.72, and 0.70, respectively. Combined testing of both AJAP1 and HS3ST2 methylation had a positive predictive value of 56%, methylation of any one of AJAP1, SOX1, or HS3ST2 had a 100% negative predictive value. ConclusionsHypermethylation of AJAP1, HS3ST2, and SOX1 is predictive of EC in AH patients. Testing for methylation of these genes in endometrial biopsy samples may be a hysterectomy-sparing diagnostic tool. Validation of these new genes as biomarkers for AH screening in a larger population-based study is warranted.

Endometrial Carcinoma in Women Aged 40 Years and Younger

Endometrial carcinoma is a disease of older postmenopausal women, and is relatively uncommon in patients younger than 40 years. Endometrial carcinomas in this age group may be familial, associated with Lynch syndrome, or sporadic. To present our current knowledge of endometrial carcinomas in women younger than 40 years. The review is based on previously published articles on this topic. Most endometrial carcinomas that occur in this age group are associated with estrogen excess. They are usually low-grade endometrioid carcinomas that present at low stages and are associated with favorable clinical outcomes. Tumors associated with mismatch repair abnormalities and Lynch syndrome appear to be distinct, with worse prognostic factors and, possibly, clinical behavior. Conservative hormonal therapy and ovarian conservation are reasonable considerations in the management of these young patients, but carry the risk of tumor progression, recurrence, and an occult synchronous or metachronous ovarian carcinoma.

Endometrial progesterone resistance and PCOS

Polycystic ovary syndrome (PCOS) is a state of altered steroid hormone production and activity. Chronic estrogen exposure or lack of progesterone due to ovarian dysfunction can result in endometrial hyperplasia and carcinoma. A key contributor to our understanding of progesterone as a critical regulator for normal uterine function has been the elucidation of progesterone receptor (PR) expression, regulation, and signaling pathways. Several human studies indicate that PR-mediated signaling pathways in the nucleus are associated with progesterone resistance in women with PCOS. The aim of this review is to provide an overview of endometrial progesterone resistance in women with PCOS; to present the PR structure, its different isoforms, and their expression in the endometrium; to illustrate the possible regulation of PR and PR-mediated signaling in progesterone resistance in women with PCOS; and to discuss current clinical treatments for atypical endometrial hyperplasia and endometrial carcinoma in women with PCOS and accompanying progesterone resistance.

Risk factor analysis of coexisting endometrial carcinoma in patients with endometrial hyperplasia: a retrospective observational study of Taiwanese Gynecologic Oncology Group

ObjectiveTo evaluate the clinical outcome and parameters related to coexisting endometrial carcinoma in women with tissue-diagnosed endometrial hyperplasia.MethodsBetween January 1991 and December 2009, three hundred and eighty-six patients with the presumptive diagnosis of endometrial hyperplasia were retrieved. Among these, one hundred and twenty-five patients were identified as having coexisting endometrial carcinoma in hysterectomy specimens. The three hundred and eighty-six patients were divided into two groups: the hyperplasia-benign group (261 cases) and the hyperplasia-malignant group (125 cases). Several clinical parameters including age, menopausal status, history of abnormal uterine bleeding, obstetrical history, medical history of diabetes and hypertension, BMI, and preoperative pathologic results were investigated.ResultsAge ≥53 (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.26 to 4.57), menopausal status (OR, 2.07; 95% CI, 1.14 to 3.76), diabetes history (OR, 7.33; 95% CI, 2.79 to 19.26), abnormal uterine bleeding (OR, 3.99; 95% CI, 1.22 to 13.02), atypical endometrial hyperplasia (OR, 7.38; 95% CI, 4.03 to 13.49), and body mass index ≥27 (OR, 3.24; 95% CI, 1.76 to 5.97) were independent risk factors for prediction of endometrial hyperplasia coexisting with endometrial carcinoma. The diagnostic efficacy of atypical endometrial hyperplasia to predict the endometrial hyperplasia coexisting with endometrial carcinoma was better than or similar to those of other independent factors and combinations of these factors.ConclusionCoexisting malignancy should be considered when examining endometrial hyperplasia patients with the related risk factors, especially atypical endometrial hyperplasia.

Endometrial Thickness Measurement for Detecting Endometrial Cancer in Women With Postmenopausal Bleeding

To estimate the accuracy of endometrial thickness measurement in the detection of endometrial cancer among women with postmenopausal bleeding with individual patient data using different meta-analytic strategies. Original data sets of studies detected after reviewing the included studies of three previous reviews on this subject. An additional literature search of published articles using MEDLINE databases was preformed from January 2000 to December 2006 to identify articles reporting on endometrial carcinoma and sonographic endometrial thickness measurement in women with postmenopausal bleeding. We identified 90 studies reporting on endometrial thickness measurements and endometrial carcinoma in women with postmenopausal bleeding. We contacted 79 primary investigators to obtain the individual patient data of their reported studies, of which 13 could provide data. Data on 2,896 patients, of which 259 had carcinoma, were included. Several approaches were used in the analyses of the acquired data. First, we performed receiver operator characteristics (ROC) analysis per study, resulting in a summary area under the ROC curve (AUC) calculated as a weighted mean of AUCs from original studies. Second, individual patient data were pooled and analyzed with ROC analyses irrespective of study with standardization of distributional differences across studies using multiples of the median and by random effects logistic regression. Finally, we also used a two-stage procedure, calculating sensitivities and specificities for each study and using the bivariate random effects model to estimate summary estimates for diagnostic accuracy. This resulted in rather comparable ROC curves with AUCs varying between 0.82 and 0.84 and summary estimates for sensitivity and specificity located along these curves. These curves indicated a lower AUC than previously reported meta-analyses using conventional techniques. Previous meta-analyses on endometrial thickness measurement probably have overestimated its diagnostic accuracy in the detection of endometrial carcinoma. We advise the use of cutoff level of 3 mm for exclusion of endometrial carcinoma in women with postmenopausal bleeding.

Concurrent endometrial carcinoma following hysterectomy for atypical endometrial hyperplasia

Objective To evaluate the prevalence of concurrent endometrial carcinoma in women diagnosed with atypical endometrial hyperplasia (AEH) by endometrial biopsy. Study design We retrospectively analyzed the medical records of 126 patients who underwent hysterectomies for AEH diagnosed by endometrial biopsy from 1999 to 2008. AEH was initially diagnosed by dilatation and curettage (98 cases) or endometrial biopsy with a Z-sampler (24 cases). The remaining four cases were diagnosed by hysteroscopic polypectomy. The results of the endometrial biopsies were graded on an ordinal scale and were compared with pathologic features obtained at the hysterectomy. Results In patients preoperatively diagnosed with AEH by biopsy, hysterectomy specimens revealed a rate of simple or complex endometrial hyperplasia without atypia of 27% with AEH and normal proliferative phases found in 54.7 and 7.9% of specimens, respectively. The incidence of endometrial carcinoma was considerably high (13/126, 10.3%). Eleven of 13 cases were confined to the endometrium and the remaining two were located at the adenomyosis without myometrial invasion. All patients with endometrial carcinoma displayed coexisting atypical complex hyperplasia following hysterectomy. Conclusions Biopsy specimens showing AEH, particularly atypical complex hyperplasia, are associated with a risk of coexisting endometrial carcinoma. When considering management strategies for women with a biopsy diagnosis of AEH, clinicians should take into account the considerable rate of concurrent endometrial cancer and the discrepancy with pathologic diagnosis. Treatment modalities may differ depending on population as the rates of concurrent endometrial cancer with AEH and myometrial invasion vary by geographical location.

Office Hysteroscopy After Ultrasonographic Diagnosis of Thickened Endometrium in Postmenopausal Patients

The most important sonographic sign of endometrial carcinoma in women with postmenopausal bleeding is a thickened endometrium. The likelihood of endometrial cancer in a patient with an endometrial thickness of 5 mm or less is only about 1%. Office hysteroscopy is widely used to investigate a pelvic ultrasound finding of endometrial thickness in postmenopausal women. The primary purpose of hysteroscopic examination of such women is to exclude endometrial cancer. This retrospective study investigated the results of office hysteroscopy in 245 postmenopausal women with a thickened endometrium detected in a previous ultrasound and assessed the presence or absence of abnormal bleeding on diagnostic outcomes. All office hysteroscopies were performed between 2005 and 2006 at a hospital in Portugal. Hysteroscopic and histopathologic findings were compared in 2 groups of patients: Group A (n = 172) contained patients with asymptomatic thickened endometrium; and group B (n = 73) consisted of symptomatic (bleeding) patients with increased endometrial thickness. The patients were evaluated for parameters of age, hormonal therapy, hysteroscopic findings, duration of the procedure, pain and associated complications, and histopathological diagnosis. The presence or absence of uterine bleeding was considered separately. The mean age of symptomatic patients was higher as compared to asymptomatic patients (67.9 vs. 64.9 years old) (P < 0.05). Symptomatic patients also had significantly longer mean procedure duration (36.1 vs. 31.5 minute) (P < 0.05). In both groups, the most frequent hysteroscopic and histopathological diagnosis was endometrial polyp. Pain was considered tolerable by the majority of patients (median 4 in a numeric 0–10 scale with 10 as the maximum). There were no procedure-related complications. The incidence of carcinoma was significantly higher in symptomatic than asymptomatic women (16.4% vs. 2.9%) (P < 0.05). These findings show that patients with endometrial thickening associated with postmenopausal bleeding are at higher risk for endometrial neoplasia than asymptomatic patients.

Endometrial Carcinomas in Women Aged 40Years and Younger: Tumors Associated With Loss of DNA Mismatch Repair Proteins Comprise a Distinct Clinicopathologic Subset

Endometrial Carcinomas in Women Aged 40Years and Younger: Tumors Associated With Loss of DNA Mismatch Repair Proteins Comprise a Distinct Clinicopathologic Subset

Endometrial Carcinomas in Women Aged 40 Years and Younger: Tumors Associated With Loss of DNA Mismatch Repair Proteins Comprise a Distinct Clinicopathologic Subset

Endometrial carcinomas (ECs) in young women (< or = 40 y) are usually managed conservatively in selected patients. Whether oophorectomy with total hysterectomy is mandated for patients failing hormonal therapy is controversial. Recognition of features that might discourage conservative management and ovarian preservation are currently poorly characterized. We evaluated these patients for DNA mismatch repair (MMR) protein defects to assess whether the MMR status had an impact on therapeutic decision making. Seventy ECs in women of 40 years of age or younger (n=70) were identified from review of institutional databases (1993-present). All available slides were reviewed and DNA MMR immunohistochemistry was performed using 4 markers (MLH1, PMS2, MSH2, and MSH6) in cases with available blocks (n=54). ECs were predominantly endometrioid (65/70), and most were low grade (1988 International Federation of Gynecology and Obstetrics grades 1 or 2, 83%). Five (7%) were undifferentiated carcinomas. Most patients presented at early stage (stages I to II, 90%). A significant number of patients also had synchronous ovarian carcinomas (9 of 70, 13%), predominantly endometrioid (7 of 9), whereas 2 were ovarian clear cell carcinomas. Sixty-six of the 70 patients are alive with no evidence of disease, whereas 4 patients (6%) died of disease. Immunohistochemistry for DNA MMR showed loss of at least 1 protein in 9 of 54 cases (16%) with slight predominance of MSH2/MSH6 abnormalities (5 of 9) compared with loss of MLH1/PMS2. Tumors with MMR loss frequently occurred in women with low body mass index; these tumors were of higher grade and associated with worse clinical outcomes. They frequently showed tumor characteristics associated with microsatellite instability, including tumor infiltrating lymphocytes, undifferentiated or dedifferentiated histology, and lower uterine segment origin. These tumors also showed lower estrogen receptor/progesterone receptor expression compared with tumors with retained staining for MMR proteins. None of the cases with synchronous ovarian and endometrial endometrioid carcinomas showed loss of MMR proteins, whereas 1 of 2 ECs with synchronous CCC of ovary showed loss of MSH2/MSH6.As young women with endometrioid carcinomas who show loss of mismatch proteins are at risk for high-grade tumors with worse clinical outcomes and lower estrogen receptor/progesterone receptor expression, they may not be appropriate candidates for conservative management. Although young EC patients are at increased risk for synchronous endometrioid ovarian carcinomas, this does not seem to be associated with MMR loss.

Increased natural killer cells and decreased regulatory T cells are seen in complex atypical endometrial hyperplasia and well-differentiated carcinoma treated with progestins

Progestins are used to treat complex atypical hyperplasia and well-differentiated endometrial carcinoma in women who desire fertility preservation and those who are poor surgical candidates. Although sensitivity to progestins is thought to be associated with the presence of estrogen and progesterone receptors, it is known that receptor-negative tumors can also respond to the agent, suggesting that there is another direct antitumor action of progestin. Because tumor immune response is an additional predictor of survival in well-differentiated endometrial carcinoma, it is surprising that the role of progestins in tumor immunity has not been investigated. Regulatory T cells modulate the immune response, whereas cytotoxic T cells directly target tumor cells. In this study, we investigated the effect of progestins on regulatory T cells and cytotoxic T cells. The pre- and posttreatment endometrial samples of 15 progestin-treated patients with complex atypical hyperplasia or well-differentiated endometrial carcinoma were evaluated for therapeutic response and the presence of cytotoxic T cells and regulatory T cells. Immunohistochemical analysis was performed for FOXP3 to identify regulatory T cells and for granzyme B to identify activated cytotoxic T cells. To further characterize the cytotoxic T cell's subpopulations, we performed CD8 (cytotoxic T-cell marker) and CD56 (natural killer cells marker). Ten of 15 patients had normal morphology on follow-up endometrial samplings, and 4 patients had persistence or progression of the disease. Regulatory T-cell counts pretreatment were significantly higher in complex atypical hyperplasia and well-differentiated endometrial carcinoma than in posttreatment normal endometrium. Residual complex atypical hyperplasia and well-differentiated endometrial carcinoma present in posttreatment samples maintained high regulatory T cells and low number of cytotoxic T cells. Progestin treatment was associated with striking increase in cytotoxic T cells in areas with decidual reaction. Before treatment, most of the granzyme B+ cytotoxic T cells in complex atypical hyperplasia and well-differentiated endometrial carcinoma were CD8(+) T cells, whereas after treatment, up to 80% of cytotoxic T cells were natural killer cells. These results suggest that progestin treatment affects subpopulations of lymphocytes in the endometrium and may induce immune suppression of complex atypical hyperplasia and well-differentiated endometrial carcinoma.

Endometrial carcinoma in a patient having 45,X Turner syndrome with gonadal mosaicism

Only three cases of endometrial carcinoma in women with possibly pure 45,X Turner syndrome without previous unopposed estrogen therapy have been reported. A 46-year-old single nulligravid woman with Turner syndrome phenotype, spontaneous menstruation, and well-differentiated adenocarcinoma of the endometrium was diagnosed as having the 45,X karyotype from peripheral blood, skin, buccal cells, and endometrium, which was confirmed using fluorescence in situ hybridization (FISH). Analysis of the ovarian tissue using FISH confirmed 45,X/46,XX mosaicism. Gonadal mosaicism may help to interpret spontaneous menstruation and endometrial carcinoma in possibly pure 45,X Turner syndrome. We conclude that a molecular analysis of lymphocytes and various tissues is necessary for detecting low-level mosaicism in apparently homogeneous 45,X women.

Concurrent Endometrial Carcinoma in Women with a Biopsy Diagnosis of Atypical Endometrial Hyperplasia: A Gynecologic Oncology Group Study

Concurrent Endometrial Carcinoma in Women with a Biopsy Diagnosis of Atypical Endometrial Hyperplasia: A Gynecologic Oncology Group Study

Transvaginal ultrasound and lactate dehydrogenase isoenzyme activity profile in uterine aspirate for diagnosis of endometrial carcinoma in women with postmenopausal bleeding

Postmenopausal patients with vaginal bleeding (n = 72) were evaluated with the combination of transvaginal ultrasonography (TVS) and analysis of the lactate dehydrogenase (LD) isoenzyme activity profile in uterine fluid aspirates. TVS evaluation of the endometrium was classified as <5 mm, > or =5 mm, or poorly defined. The LD isoenzyme activity profile was characterized as abnormal or normal. Pathologic findings were further evaluated with diagnostic curettage. TVS found the endometrium to be > or =5 mm or poorly defined in 44 patients (61%). Endometrial carcinoma was found in 6 of 72 patients (8%). They appeared in the TVS groups endometrium >5 mm (n = 2) and endometrium poorly defined (n = 4) but not in the endometrium <5 mm. The LD isoenzyme activity profile was abnormal in the six malignant cases and in ten benign cases. Thus, the need for further evaluation with hysteroscopy and curettage was reduced to 16 cases. Since TVS had 100% sensitivity but only 42% specificity, it is suitable for first-level examination in patients with postmenopausal bleeding. The second-level method should have similarly high sensitivity but much higher specificity. The LD isoenzyme activity profile in uterine fluid aspirates had 100% sensitivity and 85% specificity. Another important feature is that the method is not sensitive to endometrial thickness, amount of sample, sampling device, or dilution. Thus, it is more reliable than aspiration histology. For every hysteroscopy or curettage that can be replaced by LD analysis, the cost is reduced by approximately EUR 720 or 540, respectively.

Concurrent Endometrial Carcinoma in Women with a Biopsy Diagnosis of Atypical Endometrial Hyperplasia: A Gynecologic Oncology Group Study

Concurrent Endometrial Carcinoma in Women with a Biopsy Diagnosis of Atypical Endometrial Hyperplasia: A Gynecologic Oncology Group Study

Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia

Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for approximately 36,000 diagnoses of invasive carcinoma annually. The most common histologic type, endometrioid adenocarcinoma (EC), accounts for 75-80% of patients. The objective of this work was to estimate the prevalence of concurrent carcinoma in women with a biopsy diagnosis of the precursor lesion, atypical endometrial hyperplasia (AEH). This prospective cohort study included women who had a community diagnosis of AEH. Diagnostic biopsy specimens were reviewed independently by three gynecologic pathologists who used International Society of Gynecologic Pathologists/World Health Organization criteria. Study participants underwent hysterectomy within 12 weeks of entry onto protocol without interval treatment. The hysterectomy slides also were reviewed by the study pathologists, and their findings were used in the subsequent analyses. Between November 1998 and June 2003, 306 women were enrolled on the study. Of these, 17 women were not included in the analysis: Two patients had unreadable slides because of poor processing or insufficient tissue, 2 patients had only slides that were not endometrial, the slides for 5 patients were not available for review, and 8 of the hysterectomy specimens were excluded because they showed evidence of interval intervention, either progestin effect or ablation. In total, 289 patients were included in the current analysis. The study panel review of the AEH biopsy specimens was interpreted as follows: 74 of 289 specimens (25.6%) were diagnosed as less than AEH, 115 of 289 specimens (39.8%) were diagnosed as AEH, and 84 of 289 specimens (29.1%) were diagnosed as endometrial carcinoma. In 5.5% (16 of 289 specimens), there was no consensus on the biopsy diagnosis. The rate of concurrent endometrial carcinoma for analyzed specimens was 42.6% (123 of 289 specimens). Of these, 30.9% (38 of 123 specimens) were myoinvasive, and 10.6% (13 of 123 specimens) involved the outer 50% of the myometrium. Among the women who had hysterectomy specimens with carcinoma, 14 of 74 women (18.9%) had a study panel biopsy consensus diagnosis of less than AEH, 45 of 115 women (39.1%) had a study panel biopsy consensus diagnosis of AEH, and 54 of 84 women (64.3%) had a study panel diagnosis of carcinoma. Among women who had no consensus in their biopsy diagnosis, 10 of 16 women (62.5%) had carcinoma in their hysterectomy specimens. The prevalence of endometrial carcinoma in patients who had a community hospital biopsy diagnosis of AEH was high (42.6%). When considering management strategies for women who have a biopsy diagnosis of AEH, clinicians and patients should take into account the considerable rate of concurrent carcinoma.