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PubMed2004

Diagnostic hysteroscopy in endometrial hyperplasia.

OBJECTIVES: To assess the reproducibility of hysteroscopic diagnosis in the various types of endometrial hyperplasias and to compare different classifications of endometrial hyperplasia from this point of view. STUDY DESIGN: 109 endometrial hyperplasias, diagnosed in the last 5 years with hysteroscopy, were all biopsied and had a pathological examination. We tried to estimate the accuracy of hysteroscopy comparing the various classifications of endometrial hyperplasia to the final pathologic diagnosis. RESULTS: Using older endometrial hyperplasia classification, the overall diagnostic accuracy of hysteroscopy was 76% as for the correct type of hyperplasia. Classifying them at hysteroscopy into two categories only, i.e. hyperplasias and neoplasias, gave a more accurate result (90.26%). CONCLUSIONS: The newer classification is better from the hysteroscopist's point of view.

Diagnosis, Differential↗
PubMed2005

Prevalence of underlying adenocarcinoma in women with atypical endometrial hyperplasia.

There is controversy regarding the prevalence of underlying endometrial adenocarcinoma among women with a diagnosis of atypical endometrial hyperplasia. This study further defines that risk. At our institution atypical endometrial proliferations non-diagnostic for invasive adenocarcinoma are diagnosed as either atypical endometrial hyperplasia (ATHY) or as an "atypical proliferative lesion of the endometrium, suggestive but not diagnostic of atypical endometrial hyperplasia" (APL). Between 1996 and 2003, these diagnoses were made on either endometrial biopsy or endometrial curettings in 60 women who subsequently received a hysterectomy. Endometrial adenocarcinoma was identified in 48% (29/60) of the hysterectomy specimens. Age and sampling method had no significant impact on the prevalence of adenocarcinoma. Adenocarcinoma was no more likely to be subsequently identified when a woman had a preoperative diagnosis of ATHY (24 of 52, 46%) compared to APL (5 of 8, 63%). In some women with a diagnosis of ATHY a comment was made in the report that "carcinoma cannot be ruled out". These cases had a significantly higher prevalence of underlying adenocarcinoma (16 of 25, 64%) compared to cases of ATHY in which such a comment was not made (8 of 27, 30%) (p = 0.025). In conclusion, there is a high prevalence of underlying endometrial adenocarcinoma among women undergoing hysterectomy for any of atypical endometrial proliferation.

Adenocarcinoma↗
PubMed2006

Deregulation of tissue homeostasis in endometria from patients with polycystic ovarian syndrome with and without endometrial hyperplasia.

OBJECTIVE: To study the proteins involved in endometrial homeostasis in PCOS women. METHODS: Protein expression of Ki67, Bcl-2, Bax, Pro-Caspase-3 and Caspase-3 by immunohistochemistry and/or Western blot, and DNA fragmentation using in situ 3'-end labeling of apoptotic cells, was measured in 9 samples of normal endometrium (NE), 12 PCOS endometria without treatment (PCOSE), 7 endometria from PCOS women with endometrial hyperplasia (HPCOSE) and 9 endometria from patients with endometrial hyperplasia (HE). RESULTS: Cell proliferation was higher in epithelium from PCOSE (P<0.05), HPCOSE and HE vs NE. A higher Bcl-2/Bax relative ratio in PCOSE and HPCOSE was observed, in absence of active Caspase-3 and scarce DNA fragmentation in the four groups of endometria studied. CONCLUSION: As the apoptosis was scarce in all of the groups studied, endometrial homeostasis deregulation in PCOS could be a result of increased proliferation. Therefore, the onset of endometrial hyperplasia in PCOS endometrium could be linked to inadequate cell proliferation, and concomitantly to inadequate cell survival.

Adult↗
PubMed2005

The management of endometrial hyperplasia: an evaluation of current practice.

OBJECTIVE: To identify current management practices and evaluate subsequent outcomes of treatment for women diagnosed with endometrial hyperplasia. STUDY DESIGN: All women with a histological diagnosis of endometrial hyperplasia at the Birmingham Women's Hospital were identified between October 1998 and September 2000. A retrospective case note review was performed for each woman using a standardised data abstraction sheet. Baseline characteristics including clinical presentation and treatment strategy were obtained. Results of subsequent endometrial tissue examinations were used to assess histological response to treatment and the need and indication for hysterectomy was used to assess clinical response. RESULTS: There were 351 women diagnosed with endometrial hyperplasia during the study period of which 84% presented with symptoms of abnormal uterine bleeding and 54% were postmenopausal. Complex endometrial hyperplasia was the most common diagnosis accounting for 60% of all cases. Eighty percent of women with atypical endometrial hyperplasia were treated by hysterectomy compared with 30% without evidence of cytological atypia (relative hysterectomy rate of 2.6, 95% CI 2.0-3.3). Hysterectomy was avoided in 138/172 (80%, 95% CI 74-86%) women managed conservatively during the study period. Overall 35/108 (36%, 95% CI 27-46%) of women managed conservatively had persistent or progressive disease identified (mean follow up 36 months). 20/143 (14%) women initially diagnosed with endometrial hyperplasia who subsequently underwent hysterectomy were found to have endometrial cancer, the majority of whom had been diagnosed with atypical disease (14/20, 70%). CONCLUSION(S): The majority of women with atypical endometrial hyperplasia were managed by hysterectomy and the substantial risk of diagnostic under-call supports this approach to treatment. In contrast, there is no consensus regarding the initial management of women with endometrial hyperplasia without cytological atypia.

Aged↗
PubMed2003

Preoperative and postoperative correlation of histopathological findings in cases of endometrial hyperplasia.

OBJECTIVES: To determine the preoperative and postoperative correlation of histopathological findings in cases of endometrial hyperplasia. MATERIAL AND METHODS: One hundred and three patients with endometrial hyperplasia detected by surgical curettage performed due to various gynecologic pathologies were treated by hysterectomy. We compared retrospectively the histopathological diagnoses found on curettage with those found on hysterectomy specimens. The classification scheme endorsed by the International Society of Gynecological Pathologists was used to classify the endometrial hyperplasia. The histologic findings found on the endometrial tissue of curettage specimens were correlated with those from hysterectomy specimens. Histopathologic evaluation was performed by a single skilled gynecologic pathologist. RESULTS: A total number of 103 women--76 (73.8%) premenopausal and 27 (26.2%) postmenopausal--were determined to have endometrial hyperplasia on histopathological evaluation of endometrial tissues obtained by endometrial curettage performed for evaluation of various bleeding abnormalities. These included 94 patients with simple hyperplasia without atypia (91.3%), two patients with simple hyperplasia with atypia (1.9%), five patients with complex hyperplasia without atypia (4.9%), and two patients with complex hyperplasia with atypia (1.9%). Histopathological evaluation of endometrial tissue obtained from hysterectomy specimens (of patients diagnosed with hyperplasia on curettage) revealed a total number of 65 cases (63.1%) with endometrial hyperplasia, and 38 cases (36.9%) with various histopathological findings. The correlation between preoperative and postoperative endometrial histologic findings was found to be statistically insignificant (r = 0.105, p = 0.29). Among 94 patients who were found to have simple hyperplasia without atypia on curettage specimens, 55.3%, were found to have simple hyperplasia without atypia, 1.1% simple hyperplasia with atypia, 5.3% complex hyperplasia without atypia, 9.6% secretory endometrium, 4.3% proliferative endometrium, 21.3% disorganized proliferative endometrium, 1.1% corpus luteum persistency, 1.1% basal endometrium, and 1.1% endometrium cancer on final hysterectomy specimens. CONCLUSION: Postoperative diagnosis of endometrial pathology might be different from that of preoperative especially in cases with simple endometrial hyperplasia without atypia.

Adult↗
PubMed2003

Atypical endometrial hyperplasia: grounds for possible misdiagnosis of endometrial adenocarcinoma.

OBJECTIVE: The diagnoses of atypical hyperplasia and well-differentiated adenocarcinoma imply totally different approaches because of clinical and patient-oriented ramifications, especially when morphological differences are not entirely conclusive. The purpose of this study was to examine the relationship between the diagnosis of atypical hyperplasia during curettage or endometrial biopsy and the definitive histological findings from hysterectomy material. STUDY DESIGN: 23 patients were found fit for the current study and subsequently their clinical histories were reviewed for relevant clinical data, histopathological profiling and type of therapeutic interventions. RESULTS: Adenocarcinoma was observed in 12 (52.17%) of 23 hysterectomy cases. The hyperplasia was found in 10 (43.47%) cases, although 4 of them lacked atypia and 1 case proved to be hyperplasia-free. CONCLUSION: Hysterectomy was prescribed as the next step in the diagnosis of atypical endometrial hyperplasia. Other wait-and-see approaches could have easily forfeited the chances of providing an adequate treatment for an operable and curable cancer in approximately half of the studied cases.

Adenocarcinoma↗
PubMedDate not supplied

Diagnosis of endometrial hyperplasia in women with abnormal uterine bleeding.

BACKGROUND: Reliability of hysteroscopy in diagnosing endometrial hyperplasia in women with abnormal uterine bleeding. METHODS: Out of 105 patients with abnormal uterine bleeding 47 showed structural abnormalities. Comparative analysis between hysteroscopic and histological results in 58 women without gross abnormalities has been performed in order to verify sensitivity and specificity of hysteroscopy in the diagnosis of endometrial hyperplasia. RESULTS: Specificity of hysteroscopy in diagnosing endometrial hyperplasia was 84.7% while sensitivity resulted to be 80%. CONCLUSIONS: Women with abnormal uterine bleeding and normal uterine cavity has a low rate (3.4%) of false negative endometrial hyperplasia. On the contrary findings of endometrial hyperplasia at hysteroscopy has a high incidence of false positive (25.8%). In conclusion, abnormal uterine bleeding could cause an increased thickness in endometrium, appearing as hyperplasia on hysteroscopic examination.

Adult↗
PubMed2000

Descriptive epidemiology of endometrial hyperplasia in patients with abnormal uterine bleeding.

PURPOSE OF INVESTIGATION: To evaluate the prevalence and epidemiologic characteristics of endometrial hyperplasias in women with abnormal uterine bleeding. METHODS: We performed a retrospective analysis on data gained from 294 patients with histologically documented endometrial hyperplasia (with or without atypia), detected among 1,469 women who underwent fractional dilatation and curettage in our department due to abnormal uterine bleeding from 1986 to 1998. Epidemiologic characteristics were abstracted from the patients' medical charts. RESULTS: 294/1469 women were found with endometrial hyperplasia (258 without atypia and 36 atypical hyperplasias). Thirty-six of them were under 40 years of age. Four of the detected endometrial hyperplasias progressed to endometrial carcinoma (one with simple hyperplasia, two with complex and one with atypical hyperplasia). Obesity and hypertension were justified as risk factors in our study population. CONCLUSIONS: The prevalence of endometrial hyperplasia according to our data was 20%. There were statistically significant differences in most epidemiologic parameters between the two types of hyperplasia. The progression of four endometrial hyperplasias to endometrial adenocarcinoma indicates the need for intense follow-up even in cases where patients undergo conservative therapy.

Adult↗
PubMed2006

Cellular features of endometrial hyperplasia and well differentiated adenocarcinoma using the Endocyte sampler: Diagnostic criteria based on the cytoarchitecture of tissue fragments.

BACKGROUND: Because cellular atypia is often limited in endometrial hyperplasia and well-differentiated endometrial adenocarcinoma (WHO Grade 1 adenocarcinoma), diagnostic criteria for endometrial cytology have not been fully established. New diagnostic criteria based on the composition and architecture of tissue fragments (cytoarchitecture) in the smears were used in the present study. Cytologic features are of less importance because the distinction between endometrial hyperplasia and Grade 1 adenocarcinoma relies more on architectural features than cellular changes. Cell clumps of various size are usually collected abundantly with cytologic material using a disposable scraping device and it was noticed that those cell clumps reflected the histologic architecture. The purpose of the current study was to determine the form of the cytoarchitecture that reflects the histologic structure and to examine the cellular features in endometrial hyperplasia and Grade 1 adenocarcinoma. METHODS: The frequency of each type of cell clump (tube or sheet-shaped pattern, dilated or branched pattern, irregular protrusion, and papillotubular pattern) were obtained from 49 cases of normal proliferative endometrium (NPE) (patient age range, 28-51 yrs; average age, 39.9 yrs), 63 cases of endometrial hyperplasia without atypia (EH) (patient age range, 35-65 yrs; average age, 47.7 yrs), 13 cases of endometrial hyperplasia with atypia (AEH) (patient age range 47-65 yrs; average age, 53.8 yrs), and 49 cases of Grade 1 adenocarcinoma (patient age range, 42-73 yrs; average age, 58.9 yrs). RESULTS: Certain characteristics of the cytoarchitecture were observed. In the NPE, cell clumps with a tube or sheet-shaped pattern were found in 97.5% of cases. In the EH, cell clumps with a dilated or branched pattern were found in 34.9% of cases. In the Grade 1 adenocarcinoma, cell clumps with irregular protrusions were found in 61.8% cases, whereas a papillotubular pattern was present in 29.7% of cases. CONCLUSIONS: The results of the current study revealed that cytoarchitectural criteria appear to be more useful for the cytologic assessment of endometrial lesions, especially for the diagnosis of endometrial hyperplasia and Grade 1 adenocarcinoma.

Adenocarcinoma↗
PubMed1990

Flow cytometry (FCM) analysis of endometrial hyperplasia and carcinoma.

In a series of 52 biopsy specimens (31 endometrial carcinomas, 10 atypical endometrial hyperplasias, and 11 cases of normal endometrium), DNA ploidy and S-phase cell fraction were estimated in paraffin-embedded material. DNA aneuploidy was detected in 2 of the 10 atypical endometrial hyperplasias and 7 of the 31 endometrial carcinomas. The majority of aneuploidy was found to be connected with the loss of tumor differentiation. No ploidy disturbances were found in normal endometrium. The S-phase cell fraction value of normal endometrium was significantly lower when compared with that of endometrial carcinoma. The broad variation in S-phase cell fraction values of the endometrial carcinomas and atypical endometrial hyperplasias was in contrast with the low variability of S-phase cell values of normal endometrium. Very low incidence of aneuploidy in the group of well differentiated endometrial carcinomas (Grade I) enables the suggestion that the presence of aneuploidy predicts a more aggressive disease and that the detection of an aneuploid stemline in atypical endometrial hyperplasia may already indicate the neoplastic transformation.

Cell Transformation, Neoplastic↗
PubMed1993

Mutation of the p53 tumor-suppressor gene is not a feature of endometrial hyperplasias.

OBJECTIVE: Mutation and overexpression of the p53 gene occur in approximately 20% of endometrial carcinomas. To determine whether alteration of the p53 gene is an early event in endometrial carcinogenesis, we examined the p53 gene in endometrial hyperplasias. STUDY DESIGN: Genomic deoxyribonucleic acid was extracted from 117 endometrial hyperplasias (36 simple, 40 complex, 41 atypical) and 30 endometrial cancers. Exons 5 through 8 of the p53 gene were amplified by means of the polymerase chain reaction. Mutations in the p53 gene were sought with single-stranded conformation polymorphism analysis and confirmed by direct deoxyribonucleic acid sequencing. RESULTS: None of 117 endometrial hyperplasias were found to have mutations in the p53 gene, whereas mutations were seen in three of 30 (10%) endometrial cancers (p < 0.02). The p53 mutations seen in three cancers were confirmed by direct sequencing (codons 157, 180, 272). CONCLUSION: Because it does not appear to be a feature of endometrial hyperplasias, mutation of the p53 gene may represent a relatively late event in endometrial carcinogenesis.

Base Sequence↗
PubMed1999

Management of endometrial hyperplasia: a retrospective analysis.

OBJECTIVE: To determine the incidence of endometrial hyperplasia and to analyse the management of patients with this disorder. METHOD: Retrospective descriptive study at the Department of Obstetrics and Gynecology, Ramathibodi Hospital. The medical records of patients with endometrial hyperplasia from 1990 to 1995 were analysed. Descriptive statistic was used. RESULT: Medical records could be obtained in 87 per cent of cases. Incidence of endometrial hyperplasia was 1 per cent of gynecological out-patients and 11 per cent of uterine curettage. Half of the patients had cystic hyperplasia. Main treatment options of patients with cystic hyperplasia were expectant and progestogen therapy. The major treatments of adenomatous hyperplasia were progestogen and hysterectomy. Most patients with atypical hyperplasia underwent hysterectomy. Most of the patients with expectant or hormonal therapy have recurrence of abnormal uterine bleeding. CONCLUSION: Endometrial hyperplasia is not uncommon in gynecological practice. All gynecologists should be familiar with the pathophysiology and the natural history of this disorder. The unopposed estrogen stimulation should be investigated and corrected. Treatment options should be tailored to individuals according to disease grading, age of the patient and desire of pregnancy. Long-term follow-up until menopause is mandatory to prevent the excessive uterine blood loss and the progression to carcinoma.

Adolescent↗
PubMed1999

The effect of medroxyprogesterone acetate on angiogenesis in complex endometrial hyperplasia.

OBJECTIVE: To evaluate the effect of orally administered medroxyprogesterone acetate upon angiogenesis in the myometrium of patients with complex endometrial hyperplasia. METHODS: Microvessel counts in the myometrium of consecutive patients with complex endometrial hyperplasia, treated with oral medroxyprogesterone acetate prior to hysterectomy (n = 12), were compared with microvessel counts of consecutive control patients with complex endometrial hyperplasia without prehysterectomy medroxyprogesterone acetate treatment (n = 15). All specimens were stained immunohistochemically for factor VIII-related antigen as a sensitive and specific marker for vascular endothelium. Areas with the highest angiogenic intensity, within the myometrium immediately underlying complex endometrial hyperplasia, were selected. Three fields (x400) were selected for each slide, and the mean microvessel count per high-power field was calculated. Statistical analysis included factorial analysis of variance/covariance, and multiple regression analysis with P < 0.05 considered significant throughout. RESULTS: Microvessel counts of uterine specimens of patients with complex endometrial hyperplasia treated with oral medroxyprogesterone acetate were significantly lower than microvessel counts of control patients with complex endometrial hyperplasia without medroxyprogesterone acetate therapy (median 20, range 11-37 versus median 38, range 20-130, respectively, P < 0.001). CONCLUSION: Orally administered medroxyprogesterone acetate has a significant antiangiogenic effect upon myometrium immediately underlying complex endometrial hyperplasia.

Administration, Oral↗
PubMed1996

Diagnostic accuracy of hysteroscopy in endometrial hyperplasia.

OBJECTIVES: To determine the diagnostic accuracy of hysteroscopy in the diagnosis of endometrial hyperplasia in women with abnormal uterine bleeding. METHODS: From 1993 through 1995, 980 women referred to our institution for abnormal uterine bleeding underwent diagnostic hysteroscopy with eye direct biopsy of the endometrium in case of macroscopic abnormalities. Hysteroscopic features were compared with pathologic findings in order to detect the reliability of the endoscopic procedure. Statistical analysis was performed with the McNemar test. RESULTS: Positive predictive value of hysteroscopy in the diagnosis of endometrial hyperplasia accounted for 63%. In fact hysteroscopic diagnosis of endometrial hyperplasia was confirmed at pathologic examination in 81 out of 128 patients. Sensitivity and specificity of the endoscopic procedure accounted for 98% and 95%, respectively. Negative predictive value accounted for 99%, as only two cases of atypical hyperplasia were missed at hysteroscopy. Positive predictive value was higher in postmenopausal patients compared to women in the fertile age (72 vs. 58%). CONCLUSIONS: Overall, results appear encouraging, since no case of endometrial hyperplasia was missed by hysteroscopy. The high diagnostic accuracy, associated with a minimal trauma, renders hysteroscopy the ideal procedure for both diagnosis and follow-up of conservative management of endometrial hyperplasia.

Adult↗
PubMed1999

An evaluation of risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding.

OBJECTIVE: We sought to determine the clinical risk factors for endometrial hyperplasia in premenopausal women with abnormal bleeding. STUDY DESIGN: A laboratory database was searched to identify all endometrial samples taken in 1033 premenopausal women over a 30-month period from January 1995 to July 1997. Clinical data were extracted from the patients' clinical records retrospectively, and univariate and multivariate analyses were performed. The setting was the gynecologic service of a large teaching hospital. RESULTS: There were 46 cases of endometrial hyperplasia and 5 cases of endometrial cancer diagnosed. The following factors were independently associated with increased risk of endometrial hyperplasia or the presence of carcinoma: age >/=45 years (odds ratio, 3.1; 95% confidence interval, 1.5-6.1), weight >/=90 kg (odds ratio, 5.5; 95% confidence interval, 2.9-10.6), history of infertility (odds ratio, 3.6; 95% confidence interval, 1.3-9.9), family history of colonic carcinoma (odds ratio, 5.0; 95% confidence interval, 1.3-19.1), and nulliparity (odds ratio, 2.8; 95% confidence interval, 1.1-7.2). There was no increased association of endometrial hyperplasia on the basis of irregularity of menstrual cycle or duration of menstrual bleeding. CONCLUSIONS: The following are risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding: body weight >/=90 kg, age >/=45 years, infertility, family history of colonic carcinoma, and nulliparity. Current guidelines may need to be reconsidered.

Adolescent↗
PubMed2000

Direct effect of danazol on endometrial hyperplasia in adenomyotic women: treatment with danazol containing intrauterine device.

It is well known that danazol has a direct effect on endometriosis tissue and cell. We have been treating adenomyotic women with danazol containing intrauterine device (D-IUD) from June 1993 to August 2000 and significant decrease of dysmenorrhea and serum CA-125 levels were observed. Of fifty-nine adenomyotic women, eight women were also diagnosed by endometrial biopsy as endometrial hyperplasia and one woman was diagnosed as atypical endometrial hyperplasia. In these endometrial hyperplastic patients, endometrial tissues were obtained before insertion and at the time of removal or exchange of D-IUD and examined pathologically. In all of the 9 women, histopathological findings of endometrial hyperplasia disappeared after D-IUD treatment. In particular, in one patient, findings of atypical endometrial hyperplasia also disappeared after D-IUD treatment. She is now closely observed at our clinic using D-IUD. By these evidences, we postulate that D-IUD is one of the treatment choices of endometrial hyperplasia given exposure of the endometrium to such an extraordinary high concentration of danazol released by D-IUD and avoidance of adverse effects of oral danazol or general administration of GnRH and progesterone. In particular, in atypical endometrial hyperplasia case, its mechanisms might give great benefit to patient. However, mechanisms of direct effect of danazol on endometrial hyperplasia remain to be elucidated in the future study.

Adult↗
PubMed1994

The prognostic and therapeutic implications of cytologic atypia in patients with endometrial hyperplasia.

From 1970 to 1992, 136 patients with a histologic diagnosis of endometrial hyperplasia underwent total abdominal hysterectomy at the University of Kentucky Medical Center. Slides of the curettage or biopsy specimens were reviewed and classified according to the International Society of Gynecologic Pathologists System as simple or complex endometrial hyperplasia with or without cytologic atypia. Slides of the hysterectomy specimens were likewise reviewed independently and classified according to the same system. Eighty-two patients had a preoperative diagnosis of simple or complex endometrial hyperplasia without atypia. There were no cases of occult endometrial carcinoma in the hysterectomy specimens of these patients. Simple or complex hyperplasia with atypia was present in 54 patients and endometrial adenocarcinoma was observed in 19 of these cases (35%). The International Federation of Gynecology and Obstetrics stage and histologic grade of these patients was as follows: Stage IA grade 1--5; Stage IB grade 1--10; Stage IB grade 2--1; Stage IC grade 1--1; Stage IC grade 2--1; and Stage IIIA grade 2--1. The risk of associated endometrial cancer in patients with atypical hyperplasia was independent of age, diabetes mellitus, hypertension, or the use of exogenous estrogens. All patients with endometrial cancer have been followed for 1-12 years (mean 3.0 years) after therapy and no patient has experienced tumor recurrence. These data suggest that there is a significant risk of endometrial cancer in patients with histologic evidence of atypical endometrial hyperplasia on curettage or biopsy. At the time of surgery, patients with atypical endometrial hyperplasia should have careful inspection of the uterine specimen. Any endometrial tissue suspicious for malignancy should be examined histologically, and if cancer is confirmed, complete surgical staging should be performed.

Adenocarcinoma↗