Type Of Endometrial Hyperplasia Research Articles

Ultrasonography evaluation of endometrial hyperplasia: A prospective case–control study

ABSTRACT Introduction: Endometrial hyperplasia is a condition characterized by the thickening of the endometrium, which is the lining of the uterus. This thickening is caused by an increased number of endometrial glands relative to the stroma. The condition is often due to prolonged exposure to estrogen without the counterbalancing effect of progesterone. Types of Endometrial Hyperplasia: Simple Hyperplasia (without atypia): Increased number of glands that are cystically dilated.Minimal risk of progression to endometrial carcinoma. Complex Hyperplasia (without atypia): Increased number of glands with crowding and branching.Slightly higher risk of progression to cancer compared to simple hyperplasia. Simple Hyperplasia (with atypia): Cellular abnormalities (atypia) in glandular cells.Higher risk of progressing to endometrial cancer. Complex Hyperplasia (with atypia): Significant glandular crowding and branching, with cellular atypia.Considered precancerous, with a substantial risk of progression to carcinoma. Objective: To identify the clinical factors and sonographic results related to EH in premenopausal and perimenopausal women. Materials and Methods: A prospective case–control study was done in the department of radiodiagnosis in diagnostic center in the field of Jung Ludhiana (Punjab). It was cross-sectional form of study control conducted over a span of 4.5 months (October 15, 2022–March 5, 2023). Results and Discussion: Twenty patients were premenopausal, and 18 were postmenopausal. TVS reported EH in 12 cases and pelvic USG shows 11 cases pathology results showed EH in 6 cases including simple cystic hyperplasia in 5 cases atypical, simple hyperplasia in 4 cases, and complex hyperplasia. Among these 38 cases, EH was confirmed by pathology in cases. Conclusion: EH is more common in women with postmenopausal bleeding and endometrial hypertrophy, especially when the endometrial image is nonhomogeneous and irregular.

Frequency and its Type of Endometrial Hyperplasia Among Perimenopausal Women Presenting with Polymenorrhagia

Objective: The goals of this study were (1) to assess the prevalence of endometrial hyperplasia in perimenopausal women presenting with polymenorrhagia, and (2) to identify the prevalence of different types of endometrial hyperplasia in this population. Methodology: In this Cross Sectional survey at the Sheikh Zyed Hospital, Lahore during May 2021 to December 2021, 100 cases with > 45 years of age with symptoms of perimenopause, presenting with polymenorrhagia were included in the study. Clinical evaluation began with comprehensive history taking. Patients were extensively examined after a detailed history was taken. A complete physical, internal, and pelvic examination were performed. All patients were examined by per rectum examination. TVS was performed to check for endometrial thickness and ovarian hypertrophy. Diagnostic curettage preferably in the second half of the cycle was done in patients positive for hyperplasia and histopathology of the specimens done to determine types of hyperplasia. Results: In our study, 61%(n=61) were between 45-50 years and 39%(n=39) were between 51-55 years, mean+sd was calculated as 47.34+6.84 years, frequency of endometrial hyperplasia among perimenopausal women presenting with polymenorrhagia revealed in 21%(n=21) and among them frequency of types of endometrial hyperplasia among perimenopasual women presenting with polymenorrhagia was recorded as 15(71.43%) with Cystic type of hyperplasia, 4(19.05%) had Adonomatous hyperplasia, and 2(9.52%) had atypical hyperplasia. Conclusion: Cystic hyperplasia was the most frequent kind of hyperplasia, and we determined that the prevalence of endometrial hyperplasia among perimenopausal women presenting with polymenorrhagia was not considerably prevalent in our population than in developed countries. Keywords: Perimenopausal women, polymenorrhagia, endometrial hyperplasia, Cystic, Adonomatous, Atypical type of hyperplasia.

Експресія естрогенових і прогестеронових рецепторів у стромі ендометрія жінок з різними видами гіперплазії ендометрія та доброякісними новоутвореннями молочних залоз

The purpose of the study was to determine the level of expression of estrogen and progesterone receptors in endometrial tissue and to determine their relationship with the level of vitamin D in the blood of women of childbearing age with endometrial hyperplasia and benign breast tumors. Materials and methods. Examination of women of reproductive age who were diagnosed with hyperplastic processes in the endometrium was carried out. The examined patients were divided into two groups: Group I – the comparison group, which included patients with endometrial hyperplasia without concomitant pathology; Group II – women who, along with endometrial hyperplasia, were diagnosed with benign breast disease in the form of mastopathy. An immunohistochemical method using the En Vision imaging system with diaminobenzidine was used to detect estrogen and progesterone receptors in the endometrium. Determination of 25-hydroxyvitamin D (25OHD) content in blood plasma was performed by enzyme-linked immunosorbent assay using the 25-Hydroxy test kit. Results and discussion. It was found that the level of estrogen receptors expression increases in all types of endometrial hyperplasia and is exacerbated in concomitant mastopathy. Along with the increase in the level of estrogen receptors expression in endometrial cells, the expression of progesterone receptors decreases. It was found that the amount of progesterone receptors in the main group decreased by 38.3% – in endometrial hyperplasia without atypia, by 46.3% – in atypical endometrial hyperplasia and by 20.4% – in endometrial polyps compared with the control group of women. Analysis of the results shows an association between the form of hyperplasia and the receptor phenotype of the endometrium. It is established that the greatest changes are observed in atypical endometrial hyperplasia, which are exacerbated during the development of proliferative processes in the mammary glands. The relationship between vitamin D deficiency and estrogen and progesterone receptor expression in women with endometrial hyperplasia has been shown. Thus, when the level of estrogen and progesterone receptors changes in the endometrium of women with endometrial hyperplasia and mastopathy, the concentration of vitamin D in blood plasma decreases. Conclusion. The development of hyperplastic processes in the endometrium and mammary glands occurs against the background of increased expression of estrogen receptors and decreased expression of progesterone receptors. At the same time in the blood plasma of patients a decrease in vitamin D was revealed

Endometrial hyperplasia: without atypia and with atypia

The article analyzes and presents data for the last 70 years from the PubMed database on endometrial hyperplasia (EH), which is one of the leaders in the structure of gynecological diseases and the main predictor of endometrial cancer (EC). The chronicle of the EH classification is highlighted with a focus on changing the designation and relevance of adenomatous EH. It is shown how the current classification of EH, due to the fact that a large number of synonyms is limited by two options, allows to maximize the reproducibility of the diagnosis, improve the interaction of the obstetrician-gynecologist with the pathologist and reduce the treatment inefficiency. The results of modern studies on the prevalence and risk factors of EH and EC differ from previously accepted ones and destroy the Bohman triad. The risks of EH development with tamoxifen and menopausal hormone therapy are determined. The data of current research methods aimed at the diagnosis of EH and EC are indicated. The differences in etiopathogenesis, prevalence, diagnosis, risk factors for development and progression to the malignant process presented in the review represent two types of EH (without atypia and with atypia) as completely different endometrial diseases included in the same classification.

Simultaneous FTIR and Raman Spectroscopy in Endometrial Atypical Hyperplasia and Cancer.

Currently, endometrial carcinoma (EC) is the most common genital cancer in high-income countries. Some types of endometrial hyperplasia (EH) may be progressing to this malignancy. The diagnosis of EC and EH is based on time consuming histopathology evaluation, which is subjective and causes discrepancies in reassessment. Therefore, there is a need to create methods of objective evaluation allowing the diagnosis of early changes. The study aimed to simultaneously asses Fourier Transform Infrared (FTIR) and Raman spectroscopy combined with multidimensional analysis to identify the tissues of endometrial cancer, atypical hyperplasia and the normal control group, and differentiate them. The results of FTIR and Raman spectroscopy revealed quantitative and qualitative changes in the nucleic acid and protein in the groups of cancer and atypical hyperplasia, in comparison with the control group. Changes in the lipid region were also observed in Raman spectra. Pearson correlation coefficient demonstrated a statistically significant correlation between Raman spectra for the cancer and atypical hyperplasia groups (0.747, p < 0.05) and for atypical hyperplasia and the controls (0.507, p < 0.05), while FTIR spectra demonstrated a statistically significant positive correlation for the same group as in Raman data and for the control and cancer groups (0.966, p < 0.05). To summarize, the method of spectroscopy enables differentiation of atypical hyperplasia and endometrial cancer tissues from the physiological endometrial tissue.

Diagnosis and prognostic value of markers of oncogenesis in patients with hyperplastic endometrial processes with uterine fibroids

Introduction: The relevance of the study of the problem of endometrial hyperplastic processes (EHP) is due primarily to the high risk of malignancy of this pathology and its recurrent course. Despite numerous studies on EHP, some issues of pathogenesis, diagnosis and treatment of this pathology remain debatable.Objective: To evaluate the levels of APRIL, survinin and phosphoPTEN in serum of women with various forms of EHP in combination with uterine fibroids and their prognostic value for recurrence.Materials and Methods: 105 women with endometrial hyperplastic processes and endometrial adenocarcinoma were examined during the study. The first group consisted of 34 women with simple endometrial hyperplasia without atypia (SEHWA), the second group included 47 patients with complex endometrial hyperplasia without atypia (CEHWA). The groups were divided into subgroups with or without uterine fibroids. The third group consisted of 26 women with endometrial adenocarcinoma.Results: Level of APRIL was increased in the CEHWA group compared to the control group (p&lt;0,05) and the SEHWA (p&lt;0,05). Women with endometrial adenocarcinoma had significantly higher APRIL levels compared to controls and patients with both types of endometrial hyperplasia (p&lt;0,05). Women with SEHWA had significantly higher level of survinin compared to controls (p&lt;0,05). Patients with CEHWA and adenocarcinoma had serum levels of survinin higher than those in the control and SEHWA groups (p&lt;0,05).Conclusions: Adequate prognostic significance for the occurrence of relapses of EHP had the increasing of APRIL level greater than 43 pg/ml and survinin level greater than 70 pg/ml. In patients with EHP in combination with uterine fibroids a significant risk factor for relapse was an increasing of APRIL level greater than 43 pg/ml.

Immunohistochemical features of cyclooxygenase-2 expression in endometrial hyperplasia without atypia

Hyperplastic processes of the endometrium without atypia have been an urgent problem for researchers around the world for a long time, given the current position of cancer alertness and violations of reproductive function.Objective. To study immunohistochemically the expression level of the new biomarker - cyclooxygenase-2 (COX-2) in various types of endometrial hyperplasia without atypia in samples of altered endometrial tissue from 30 patients of reproductive age (39.47 ± 1.1 years).Materials and methods. Endometrial hyperplasia manifested as glandular in 17 patients (56.7%), glandular-cystic - in 11 (36.7 %), stromal and cystic-atrophic forms – in one case for each form (3.3 %). The study was carried out according to the standardized protocol of primary monoclonal antibodies COX-2 manufacturer (Thermo Scientific, rabbit, working dilution 1:50-1:100) using the visualization system “UltraVision Quanto Detection System” of the Thermo Scientific company in paraffin sections. Samples were stained with methylene green and mounted using Canadian balsam. In this work we used the methods of optical light microscopy (Olympus BX 51,Japan) and immunohistochemistry. Localization of staining (gland/stroma) and intensity score were determined by the stain intensity (0 – no staining, 1 – weak, 2 – moderate, 3 – strong).Results. The presence of COX-2 expression in the stromal component of the endometrial tissue samples was found from the majority of the examined patients (in 24 cases, 80.0%), however, its levels were recorded only as weakly positive. In glandular endometrial structures, in the presence of endometrial hyperplasia without atypia, the levels of COX-2 expression were characterized by some variability and dependence on structural localization. Thus, in 16 patients (66.7 %) its weakly positive expression was revealed, in 7 examined persons (29.2 %) – moderately stained material. Intensive COX-2 expression was determined in one case (4.1%). COX-2 expression in the hyperplastic endometrium was not detected in 6 samples (20.0%). Morphological signs of chronic endometritis were revealed in 9 investigated samples (30.0 %) – lymphoplasmacytic infiltration, altered pseudostratification of glandular epithelium, lysis of individual epithelial gland structures which were confirmed immunohistochemically: positive expression of CD138 in plasma cells.Conclusions. The study data can serve as one of the criteria for the differential approach to a choice of treatment tactics in patients with a hyperproliferative endometrial pathology including prevention of possible malignant transformation.

Utility of PTEN, MLH1, ARID1A and β-catenin, biomarkers in endometrial hyperplasia and endometrioid endometrial carcinoma

Objective: Endometrial carcinomas are divided into two groups roughly:Endometrioid (Type I) and Non-endometrioid (Type II). The majority of the endometrial carcinomas are of endometrioid type and, this type of carcinoma is associated with hyperplasia which is formed due to unopposed estrogen.In this study, our purpose is to reveal the expression status of the PTEN, MLH1, ARID1A and β-catenin, biomarkers in all types of endometrial hyperplasia (EH) and endometrioid endometrial carcinoma (EC).Materials and metods: We conducted a retrospective study with 202 cases including 82 EC cases, 71 simple EH cases without atypia, 16 complex EH cases without atypia, 9 simple atypical EH cases, 24 complex atypical EH cases which were diagnosed at Istanbul Civilization University Göztepe Training and Research Hospital. 10 normal endometrial tissues were used for the purpose of control. Resuls: In our study, loss of PTEN ratio was 61%, loss of ARID1A ratio was 52,4%, loss of MLH1 ratio was 40,2% in patients with EC. These ratios were 87,5%, 41,7%, 20,8%, respectively in patients with atypical complex EH and 12,7%; 4,2%; 1,4% in patients with simple EH without atypia. Conclusions: In the light of these findings it has been demonstrated that PTEN, ARID1A and MLH1 have a role in the transition from simple EH to atypical complex EH, and also MLH1 has a role in the transition from aytpical complex EH to EC.

Аналіз клініко-епідеміологічних аспектів гіперпластичних процесів ендометрію жінок із застосуванням багато параметричної нейромережевої кластеризації

&lt;p&gt;Резюме . З метою підвищення ефективності діагностики гіперпластичних процесів ендометрія у жінок&lt;br /&gt;перименопаузального віку було проведено ретроспективний аналіз 52 карт стаціонарного хворого жінок, які&lt;br /&gt;перебували на лікуванні в гінекологічних відділеннях Тернополя і області. У відповідності з патогістологічним&lt;br /&gt;висновком 1 групу склали 28 жінок з простою гіперплазією ендометрія, 2 групу – 24 жінки з комплексною гіперплазією&lt;br /&gt;ендометрія. В групу порівняння увійшли 12 соматично здорових жінок. Середній вік хворих 1 групи – (47,0±1,0)&lt;br /&gt;років, 2 групи – (56,0±1,5) років. З метою поглибленого аналізу показників застосовано багатопараметричну&lt;br /&gt;нейромережеву кластеризацію. Встановлено, що до факторів ризику розвитку гіперпластичних процесів&lt;br /&gt;ендометрія у жінок перименопаузального періоду належать неблагополучні соціально-економічні фактори:&lt;br /&gt;проживання в сільській місцевості, тяжкі умови праці, шкідливі звички та обтяжений акушерсько-гінекологічний&lt;br /&gt;анамнез, 3 і більше вагітностей, велика кількість (4 і більше) акушерсько-гінекологічних втручань, використання&lt;br /&gt;внутрішньоматкової контрацепції. У жінок з різними видами гіперплазії ендометрія клімактеричний синдром&lt;br /&gt;перебігав середньотяжко чи тяжко з нейровегатативними, ендокринно-обмінними та психоемоційними проявами.&lt;br /&gt;Серед коморбідних станів найчастіше спостерігали дисгормональну патологію молочних залоз та порушення&lt;br /&gt;гепатобіліарного тракту.&lt;br /&gt;Ключові слова : гіперпластичні процеси ендометрія, клімактеричний синдром, перименопаузальний вік,&lt;br /&gt;дисфункційні маткові кровотечі, коморбідні стани, нейромережева кластеризація.&lt;/p&gt;

Bcl-2 may play a role in the progression of endometrial hyperplasia and early carcinogenesis, but not linked to further tumorigenesis

The role of Bcl-2 in initiation and progression of endometrial carcinoma is still with inconsistent results. The aim of this study is to determine the role of Bcl-2 in endometrial tumorigenesis. It is a retrospective cross sectional study. We used 100 endometrial paraffin embedded specimens for Bcl-2 oncoprotein immunohistochemical staining; 20 samples of normal endometrium, 40 specimens of endometrial hyperplasia (simple, complex and atypical) and 40 specimens of endometrioid adenocarcinoma. The results were statistically analyzed. There was a significant increase in Bcl-2 staining from normal through complex and atypical hyperplasia into well differentiated adenocarcinoma (P=0.002, P=0.0008 and P=0.0001, respectively). There was a significant difference between the staining of different types of endometrial hyperplasia; as it up streamed from the simple through the complex up to the atypical types (P<0.05). Bcl-2 staining showed no significant correlation with the moderately, poorly differentiated and the different stages of adenocarcinoma (P=0.6, P=0.29 and P=0.1 respectively).These results might indicate a substantial role for Bcl-2 as one of the initiating drives for endometrial tumorigenesis, but not in further tumor progression.

Endometrial hyperplasia – the dilemma of management remains: a retrospective observational study of 280 women

ObjectiveTo quantify the rate of inconsistency in histopathological reporting between endometrial biopsy specimens (obtained by Pipelle® endometrial sampler or curettage) and hysterectomy specimens using the World Health Organization classification criteria. Study designA retrospective review of the records of 280 women with a histopathological diagnosis of endometrial hyperplasia treated in Ipswich Hospital NHS Trust, UK from 1 January 1998 to 31 May 2009. ResultsDiscrepancy was found between the histopathological results of endometrial samples and hysterectomy specimens. The discrepancy was doubled for specimens obtained using a Pipelle® endometrial sampler, with false-positive (i.e. overdiagnosis when the hysterectomy specimen showed a better diagnosis) and false-negative (i.e. underdiagnosis when the hysterectomy specimen showed a worse diagnosis) rates of 5.3% and 22.6%, respectively. For curettage specimens, the false-positive and false-negative rates were 1.8% and 13.2%, respectively. All cases of curettage were performed under general or regional anaesthesia, and were preceded by hysteroscopy. Apart from age, no risk factors were associated with a worse diagnosis. The association of age differed between types of endometrial hyperplasia and cancer; the strongest association was seen for cancer and the weakest association was seen for simple hyperplasia. ConclusionHysteroscopy and curettage may be considered when simple or complex hyperplasia is diagnosed from a specimen obtained with a Pipelle® endometrial sampler. When a diagnosis of atypical hyperplasia is made, irrespective of the method of endometrial sampling, the gynaecologist must be concerned that endometrial carcinoma exists concomitantly within the uterus.

Endometrial stromal sarcoma: a case diagnosed during infertility treatment

The patient with irregular menstruation went to our Department (Gynecological Department, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China) with the complaint of no pregnancy at the age of 26 in 2007, and oral contraceptive pills were given when simple type of endometrial hyperplasia was pathologically diagnosed, and then ovulation induction was performed. But after nearly two years from the beginning of infertility treatment, endometrial stromal sarcoma was diagnosed and radical treatment was performed for the young patient. And the relative relationship between endometrial stromal sarcoma and infertility is worth discussing.

Invited Commentary: Endometrial Hyperplasia--Getting Back to Normal

Cancer precursors can help to reveal clues about how and when risk factors influence the development of carcinoma. Endometrial carcinoma is well-suited to studies of precursors: Strong risk and protective factors exist, as does a good candidate precursor lesion, called atypical endometrial hyperplasia. Atypical hyperplasia is the most severe type of endometrial hyperplasia, which ranges from mild, reversible proliferation to incipient carcinoma. In this issue of the Journal, Epplein et al. (Am J Epidemiol 2008;168:563-70) report that three established risk factors for endometrial carcinoma—obesity, parity, and smoking—are similarly associated with two types of endometrial hyperplasia: complex hyperplasia and atypical hyperplasia. How much these findings reveal about mechanistic pathways for endometrial carcinoma depends, in part, on three issues that specifically affect endometrial hyperplasia but also affect other precursors. They are: 1) potential misclassification of intermediate endpoints, 2) unsettled thresholds between low-risk and high-risk lesions, and 3) uncertain boundaries between normal tissue and early-stage precursors. In this commentary, the author explores how these issues might influence interpretation of the new data from Epplein et al. and shape future research on endometrial carcinoma precursors.

Oxidative stress in endometrial hyperplasia

Reactive oxygen species seem to be involved in the onset and promotion of carcinogenesis. In 80% of cases of endometrial adenocarcinoma type I, a clear association exists with endometrial hyperplasia, which is considered a key factor in the endometrial oncological spectrum. The presence or absence of atypical cells determines oncological potential. This study explored the behavior of oxidative stress (catalase and malondialdehyde) in endometrial hyperplasia (with or without atypical cells) by comparing it with the oxidative stress existing in both the proliferative and secretory phases. Endometrial specimens from 55 women were used, 32 of which were histologically diagnosed as physiological (17 proliferative and 15 secretory endometria) and 23 as endometrial hyperplasia (18 nonatypical and 5 atypical endometrial hyperplasia). Significant differences were found in the malondialdehyde variable between the proliferative endometrium and the endometrium with atypical hyperplasia (P = 0.0208) and between both types of endometrial hyperplasia (P = 0.0441). The other comparisons were not statistically significant. No changes in catalase activity were observed. Our findings seem to suggest that the presence of atypical cells in endometrial hyperplasia induces a reduction in lipid peroxidation, which could permit survival and growth of these cells. This possible decrease in lipid peroxidation does not seem to be mediated by an increase in endometrial catalase activity.

Use of monoclonal antibodies MSN-1 and B72.3 in the prediction of the natural history of endometrial hyperplasia.

Forty patients, originally diagnosed as endometrial hyperplasia, were reviewed histopathologically and evaluated for immunohistochemical staining with antibodies directed against TAG-72 and MSN-1 antigens. All patients had follow-up endometrial biospies or hysterectomies from 1 to 13 years later. The extent of regression to normal of nonhyperplastic endometrium, persistence as any type of endometrial hyperplasia, or progression to endometrial adenocarcinoma was correlated with the histologic hyperplastic subtype and immunohistochemical staining. As expected, cases of complex or atypical hyperplasia more often progressed to carcinoma than cases of simple or no hyperplasia. Interestingly, MSN-1 positivity was more prevalent in cases of higher grades than lower grades of hyperplasia and was associated with the tendency to show persistent hyperplasia or progression to carcinoma. B72.3 positivity was uncommon in the hyperplastic endometrium and was not correlated with clinical regression or progression. Although the tendency for progression of endometrial hyperplasia to endometrial carcinoma is best judged histologically, MSN-1 may add prognostic information in subgroups of hyperplasia.

PRECURSORS OF CORPUS CARCINOMA ESTROGENS AND ADENOMATOUS HYPERPLASIA

34 histological sections and 9 case histories comprise the case for a causal relationship between estrogen administration (e.g. diethylstilbestrol) and endometrial hyperplastic changes. A pattern of adenomatous hyperplasia of the endometrium emerges which bears constant relation in these cases to estrogen stimulation in both benign and malignant tissues. The data to support this endocrine-tumor relationship was presented in 4 groups exemplified in the accompanying figures and case histories: 1) Endometrial hyperplasia produced by granulosa cell tumors. 2) Endometrial hyperplasia produced by prolonged estrogen administration. 3) Endometrial adenocarcinoma arising in patients receiving prolonged estrogen administration. And 4) endometrial patterns in patients with recurrent episodes of functional bleeding sometimes called stilbestrol bleeding. The typical cystic glandular hyperplasia atypical (metaplastic) hyperplasia and adenocarcinoma occurred side-by-side in some sections. The multifocal processes often separated by areas of typical hyperplasia present the picture of some generally stimulated tissue which has responded more intensely in some areas. There is a characteristic pattern which constantly recurs through these tissues; it is almost papillary in form; and it shares morphological properties with other tissues known to have been stimulated by estrogens. The above pattern is identified as a type of endometrial hyperplasia which is a cancer precursor and the histological pattern suggested that endogenous or exogenous estrogens had a role in the development.

Precursors of Corpus Carcinoma Estrogens and Adenomatous Hyperplasia

34 histological sections and 9 case histories comprise the case for a causal relationship between estrogen administration (e.g. diethylstilbestrol) and endometrial hyperplastic changes. A pattern of adenomatous hyperplasia of the endometrium emerges which bears constant relation in these cases to estrogen stimulation in both benign and malignant tissues. The data to support this endocrine-tumor relationship was presented in 4 groups exemplified in the accompanying figures and case histories: 1) Endometrial hyperplasia produced by granulosa cell tumors. 2) Endometrial hyperplasia produced by prolonged estrogen administration. 3) Endometrial adenocarcinoma arising in patients receiving prolonged estrogen administration. And 4) endometrial patterns in patients with recurrent episodes of functional bleeding sometimes called stilbestrol bleeding. The typical cystic glandular hyperplasia atypical (metaplastic) hyperplasia and adenocarcinoma occurred side-by-side in some sections. The multifocal processes often separated by areas of typical hyperplasia present the picture of some generally stimulated tissue which has responded more intensely in some areas. There is a characteristic pattern which constantly recurs through these tissues; it is almost papillary in form; and it shares morphological properties with other tissues known to have been stimulated by estrogens. The above pattern is identified as a type of endometrial hyperplasia which is a cancer precursor and the histological pattern suggested that endogenous or exogenous estrogens had a role in the development.