Endometrial vascularisation in hyperplasia without atypia

As endometrial hyperplasia has been characterized over the past 100 years, some investigators have questioned the hyperplastic nature of nonatrophic cystic glands associated with an increase in gland-to-stroma ratio, which is currently considered to represent simple endometrial hyperplasia. In the current study, the proliferative activity of simple endometrial hyperplasia was examined using an antibody to Ki-67 protein, a well-established marker of proliferative activity, and compared with the results of activity in inactive/atrophic endometrium, proliferative endometrium, and other forms of endometrial hyperplasia. In an evaluation of 68 endometrial biopsy specimens showing 110 histologic patterns, the mean Ki-67 index (percentage of Ki-67 positive nuclei) was 2.8% in inactive/atrophic endometrium, 23.2% in proliferative endometrium, 9.8% in simple hyperplasia, 12.7% in complex hyperplasia, and 10% in atypical complex hyperplasia. In simple hyperplasias, the mean Ki-67 index was 3.9% in dilated glands without infolding or outbranching, 14.6% in nondilated glands showing outbranching or slight crowding, and 6.9% in dilated glands with infolding or outbranching. Ki-67 indices for dilated glands were most similar, therefore, to atrophic/inactive endometrium with no statistical significant difference in the percentage of these cells staining between these two groups. In contrast, statistically significant differences were seen in staining between cystic patterns of simple hyperplasia and proliferative endometrium, simple hyperplasia showing outbranching and/or slight crowding but no dilation, complex hyperplasia, and atypical hyperplasia. The findings in the current study suggest that nonatrophic cystic glands with an increase in the gland-to-stroma ratio in the endometrium should not be considered a hyperplastic process and in the absence of other findings such as excessive bleeding or coexistent noncystic simple hyperplasia, treatment with progestin therapy, a widely used practice, is unnecessary. As discussed, the findings also suggest that these cystic forms of simple hyperplasia are precursors of cystic atrophies. Confirmation of these results on a larger population by a different research team appears desirable.

The aim of this study was to evaluate the effect of long-term use of progesterone treatment on proliferation and apoptosis in simple endometrial hyperplasia without atypia. In this prospective control study, endometrial tissue samples of 19 patients with simple endometrial hyperplasia without atypia (group 1), posttreatment biopsy materials of the patients after 3 months of cyclic progesterone treatment with noretisterone for 10 days (group 2), and 18 endometrial biopsy materials of the control group (group 3) were examined for proliferative and apoptotic activities. There was a statistically significant difference between the median values of the proliferative index of the three groups (P = 0.000). The proliferative index was significantly higher in the endometrial hyperplasia group than in posttreatment group (P = 0.000). But there was no significant difference between posttreatment group and control group. The median value of apoptotic activity was significantly different between three groups (P = 0.000). Apoptotic index was highest in hyperplasia group. A significant decrease in apoptosis was observed after the progesterone treatment (P = 0.002). The lowest apoptotic activity was detected in the control group. In conclusion, 3 months of cyclic progesterone treatment reduces both proliferative and apoptotic activities in endometrial tissue with simple hyperplasia.

Introduction: Endometrial hyperplastic processes (EHP) are characterized by recurrent course, high risk of malignancy, difficulties in diagnosing and predicting the course, which determines their great medical and social significance Objective: To evaluate the levels of proliferation markers Ki-67 and APRIL in serum of women with various forms of endometrial hyperplastic processes (EHP) and their correlation with clinical and anamnestic features. Materials and Methods: The study examined 95 women with endometrial hyperplasia and endometrial adenocarcinoma who underwent treatment in the gynecology department "City Clinical Hospital №7» in Zaporizhzhya and "Zaporozhye Regional Clinical Oncology Center". The first group consisted of 32 women with simple endometrial hyperplasia. The second group included 43 patients with complex endometrial hyperplasia. The third group consisted of 22 women with endometrial adenocarcinoma. Results: The analysis of Ki-67 level revealed an increasing in the patients with simple hyperplasia (p <0.05) and complex hyperplasia of endometrium (p <0.05) compare with control group. The level of the APRIL in serum is increased in group of complex hyperplasia compared with the control group (p <0,05) and simple hyperplasia (p <0,05). Conclusions: Level of APRIL in serum increased in patients with complex endometrial hyperplasia and endometrial adenocarcinoma. Level of Ki-67 in serum was highest in patients with complex endometrial hyperplasia. We found a significant positive association between Ki-67 levels in serum and thickness of M-echo in endometrium, duration of hyperplastic endometrial processes anamnesis, between APRIL in serum and age of patients, duration of hyperplastic endometrial processes anamnesis.

Abstract. Objective: To study the frequency of endometrial hyperplasia in women with I-II degree obesity exposed to toxic-chemical factors, and to identify the most important immunohistochemical markers of the proliferative activity of endometrial cells. 60 women aged 45-65 years were examined, 30 of them worked in contact with a complex of toxic factors (the main group) and 30 – without them (the comparison group). The maximum single concentrations of toxicants exceeded the MPC by 2.1-5.4 times. The criterion of obesity was a BMI > 30.0. All underwent hysteroscopy and histological examination of scrapings. Immunohistochemical characteristics of the endometrial prescription apparatus were carried out by evaluating the proliferation marker Ki 67, estrogen (Eg) and progesterone receptors (Pr). Results. In all women, simple endometrial hyperplasia was most common, more often diagnosed in the main group in the presence of obesity and in the comparison group. The highest indicators of Ki 67 were found in workers of harmful production with complex and simple atypical endometrial hyperplasia in combination with obesity of I-II degree. Eg parameters were high in women of the main group with obesity, having complex atypical (71/48) and complex endometrial hyperplasia (66/30). Among the obese workers of the comparison group, high Eg values were found in simple and complex atypical hyperplasia (64/32 and 67/40, respectively). High values of Rg indicators in obese women who come into contact with chemical agents, who have complex (21/136) and simple atypical hyperplasia (26/124), as well as in obese workers of the comparison group and the presence of complex atypical hyperplasia (29/135). Conclusion. In women with endometrial hyperplasia, working

The Value of Curettage in Diagnosis of Endometrial Hyperplasia

O3-1-4 - Concentration of Blood Serum Melatonin in Patients with Simple and Complex Endometrial Hyperplasia

Background: based on numerous epidemiologic and experimental studies it has been speculated that unopposed estrogen has a central role in development of endometrial benign, premalignant and malignant lesions. Endometrial cancer is the most common malignancy of the female genital tract, and the fourth most common cancer in women in developed countries. EC is the seventh most common cancer in women worldwide. Objective: To examine the effect of metformin on disordered proliferative endometrium and simple endometrial hyperplasia in comparison with progesterone to assess metformin clinical usefulness in these situations. Patients and Methods: All patients who referred for abnormal uterine bleeding (perimenopausal) and underwent endometrial office biopsy or D&C in our hospital and their tissue diagnosis was disordered proliferative endometrium (DPE) or simple hyperplasia (SH) were included in this study. Past medical history gathered from patients’ interview records and patients with history of metformin sensitivity, renal failure, anorexia, anemia, skin rashes, diabetes mellitus, gynecologic neoplastic disorders and patients on estrogen or progesterone were excluded. Patients who fitted with including criteria were categorized in two groups in randomized fashion. Results: Our findings in this study revealed that metformin could be effective as well as progesterone in resolving of benign enodometrial proliferative lesions. Conclusion: The current study showed that treatment of the patients with abnormal endometrial proliferation (DPE and SH) with metformin induced endometrial atrophy and prevents abnormal cell growth and prevents perimenopausal bleeding subsequently.

The aims of this study were to identity the roles of tumor vessels and hormone receptor status in normal, hyperplastic, and neoplastic endometrium, and to explore their relationships with other prognostic factors of endometrial adenocarcinoma. Endometrial curettage specimens of proliferative phase and secretory phase endometrium, simple hyperplasia with or without atypia, complex hyperplasia with or without atypia, and grade 1 adenocarcinoma were examined for estrogen receptor alpha (ER alpha), progesterone receptor (PgR), Ki-67 labeling index (LI), cyclin D1, microvessel density (MVD), and area of venules (AV) using an immunoperoxidase method. The results showed high levels of ER alpha in complex hyperplasia, and high levels of PgR in simple hyperplasia without atypia. Expression of ER alpha in the endometrium decreased in a stepwise manner from complex hyperplasia without atypia to grade 1 adenocarcinoma. Expression of PgR in the endometrium decreased in a stepwise manner from simple hyperplasia without atypia to grade 1 adenocarcinoma. In contrast, the expressions of Ki-67 LI, cyclin D1, MVD and AV in the endometrium increased in a stepwise manner from normal, simple or complex hyperplasia with or without atypia to grade 1 adenocarcinoma. These changes may become irreversible on progression from simple or complex hyperplasia to neoplasia.

Background: Abnormal uterine bleeding (AUB) is a major clinical problem among women in the reproductive, perimenopausal and postmenopausal age groups. It may have a significant impact on woman physical, social, emotional and material quality of life. Along with the direct impact on the woman and her family, there are significant costs to both economy and health service. The AUB in women aged 40 and older, especially in peri and postmenopausal age group requires exclusive assessment, to exclude atypical endometrial hyperplasia and carcinoma. Objective: This study aimed to determine the efficacy of suction pipelle in diagnosis of endometrial lesions in cases of abnormal uterine bleeding. Patients and Methods: The current study was designed as cross-sectional study conducted in Zagazig University Maternity Hospitals, Al-Ahrar Teaching Hospital and the Department of Pathology, Zagazig University during the period from April 2018 to July 2019. The study was conducted on 92 patients presented with abnormal uterine bleeding. Results: The 2 methods were 100% matched in diagnosis of secretory endometrium, hormone-dependent endometrium, atypical hyperplasia and EEC grade 1. The pipelle succeeded to diagnose some cases of proliferative endometrial and simple hyperplasia, which were missed by D & C (18.5% and 17.4% by pipelle versus 16.3% and 13% by D & C respectively for proliferative endometrial hyperplasia and 8.7% and 17.4% by pipelle versus 16.3% and 19.6% by D&C for simple hyperplasia respectively). Conclusion: Pipelle had high sensitivity and specificity for diagnosis of proliferative endometrial, secretory endometrium, hormonedependent endometrium, simple endometrial hyperplasia, atypical hyperplasia and EEC grade 1.

Background: Abnormal uterine bleeding (AUB) is a major clinical problem among women in the reproductive, perimenopausal and postmenopausal age groups. It may have a significant impact on woman physical, social, emotional and material quality of life. Along with the direct impact on the woman and her family, there are significant costs to both economy and health service. The AUB in women aged 40 and older, especially in peri and postmenopausal age group requires exclusive assessment, to exclude atypical endometrial hyperplasia and carcinoma. Objective: This study aimed to determine the efficacy of suction pipelle in diagnosis of endometrial lesions in cases of abnormal uterine bleeding. Patients and Methods: The current study was designed as cross-sectional study conducted in Zagazig University Maternity Hospitals, Al-Ahrar Teaching Hospital and the Department of Pathology, Zagazig University during the period from April 2018 to July 2019. The study was conducted on 92 patients presented with abnormal uterine bleeding. Results: The 2 methods were 100% matched in diagnosis of secretory endometrium, hormone-dependent endometrium, atypical hyperplasia and EEC grade 1. The pipelle succeeded to diagnose some cases of proliferative endometrial and simple hyperplasia, which were missed by D & C (18.5% and 17.4% by pipelle versus 16.3% and 13% by D & C respectively for proliferative endometrial hyperplasia and 8.7% and 17.4% by pipelle versus 16.3% and 19.6% by D&C for simple hyperplasia respectively). Conclusion: Pipelle had high sensitivity and specificity for diagnosis of proliferative endometrial, secretory endometrium, hormonedependent endometrium, simple endometrial hyperplasia, atypical hyperplasia and EEC grade 1.

We sought to determine the predictors of treatment response in simple endometrial hyperplasia without atypia. We prospectively treated 67 women with simple endometrial hyperplasia without atypia who were administered cyclic oral medroxyprogesterone acetate 10 mg/day for 12 days of luteal phase for 3 months and underwent control endometrial sampling after treatment. All subjects were evaluated in terms of age, gravidity, parity, body mass index (BMI), menstrual cycle, endometrial thickness, uterine fibroids, ovarian cysts, serum CA 125 levels, systemic disorders and cigarette smoking. All parameters were used to predict treatment success. Persistent hyperplasia was observed in 11 subjects. Endometrial thickness was significantly correlated with treatment failure (r=0.293, p=0.015). In ROC analysis, endometrial thickness was found to be predictive for persistent hyperplasia (area under curve: 0.724, P=0.019). Optimal cut off value was calculated to be 16.5 mm with 64% sensitivity, 72% specificity and 91% negative predictive value. The number of persistent hyperplasia in women with and without endometrial thickness greater than 16.5 mm was significantly different (7/23 vs. 4/45, p=0.029). Odds ratio of endometrial thickness higher than 16.5 mm for treatment failure was 4.4 (95% CI, 1.2-17.4, p=0.03). Results of this study suggest treatment modification according to the baseline endometrial thickness in patients with simple endometrial hyperplasia without atypia.

In this study, women with nonatypic endometrial hyperplasia were treated with thermal balloon ablation therapy to investigate the effects of this technique. The heat from thermal balloon ablation causes coagulation and necrosis of the endometrium and superficial myometrium. Thirty-four perimenopausal women (mean age, 48 years; range, 37-64 years) with simple or complex endometrial hyperplasia were enrolled in a randomized trial to compare thermal balloon ablation therapy (n = 17) with traditional progestin therapy (n = 17). Study patients were randomized according to menopausal status. The oral progestin administration regimen for premenopausal women consisted of 3 consecutive months of sequential medroxyprogesterone acetate given at 10 mg per day for 10 days starting on day 15 of their menstrual cycle. Postmenopausal women received 10 mg per day continuous medroxyprogesterone acetate for 3 months. Thermal ablation balloon therapy was performed from day 3 to day 8, in premenopausal women, and on the day of randomization in postmenopausal patients. At 6 months and 12 months after treatment, all study patients returned for clinical evaluation, which included physical examination, transvaginal ultrasonography, and endometrial biopsy. Women with abnormal ultrasound but negative endometrial biopsy underwent dilation and curettage or hysterectomy. Eighteen months after the end of the study period, patient records were reviewed and any further medical interventions were recorded. At the 6-month follow-up examinations, 3 women in the thermal balloon ablation group were found to have simple hyperplasia and were treated by hysterectomy. None had hyperplasia on final histopathologic review of the uterine specimen. In the progestin-treated group, a single postmenopausal woman was diagnosed with complex, atypical hyperplasia. She was diagnosed with stage IIIA, grade 1 endometrial adenocarcinoma and was treated with surgery followed by chemotherapy. At the 12-month follow up, one additional woman in the thermal ablation and 5 women in the progestin arm of the study were found to have simple hyperplasia by endometrial biopsy. These women all had hysterectomy with no abnormal endometrial findings on final pathology review. In addition to the 10 women who underwent hysterectomy for hyperplasia, by 18 months after the initial treatment, one patient in the ablation therapy group and 2 in the progestin group had undergone hysterectomy for irregular bleeding and pain. All had normal endometrial histology.

Endometrial hyperplasia (EH) is one of the most common gynecologic diseases in the world. Different statistical categories implicate an imbalance of estrogens and progestogens in the etiology of this disease. We propose that inflammation also plays a key role in the progression of endometrial hyperplasia. The aim of this study is to evaluate the role of inflammation in the transformation and progression of endometrial hyperplasia, using local inflammatory cytokines and nonspecific protease levels, CD 45(+) expression, and histological examination. The study included 107 patients (ages 29-49years) with different forms of endometrial hyperplasia. The enrolled patients were randomized into one of the four groups: normal endometrium (n=18) as the control group, simple hyperplasia (n=41), complex hyperplasia without atypia (n=36), complex atypical hyperplasia or endometrioid adenocarcinoma (n=12). The following were evaluated for patients with different forms of EH: steroid hormone levels in blood serum and uterine flushings, immunohistochemical estrogen and progesterone receptor expression patterns in the endometrial tissue, CD 45(+) (common leukocyte antigen) expression, the levels of the cytokines IL-1β, IL-6, and TNF-α, and nonspecific proteases and their inhibitors. The level of estradiol in blood serum and especially in uterine flushings was elevated dramatically in simple EH as compared to that of controls, but there was no significant difference between estradiol levels among the different forms of EH. The estimation of CD 45(+), the levels of the cytokines IL-1β, IL-6, and TNF-α, and the activity of proteases (elastase-like and trypsin-like activities) and their inhibitors showed that levels of nonspecific inflammatory markers increase with EH progression. We suggest that the initial responsibility for the development of simple endometrial hyperplasia belongs to systemic hyperestrogenemia and, in particular, local hyperestrogenia, but that the role of inflammatory processes increases in complex and atypical EH. Development of inflammatory changes in endometrial hyperplasia may be considered as a factor in the promotion and progression of pathology, as well as an attributed risk factor for malignancy in endometrial hyperplasia. In this study, we have established a role for CD 45(+) expression cells, non-specific proteases, and the inflammatory cytokines IL-1β, IL-6, and TNF-α in endometrial hyperplasia-related inflammation.

To study the possible role of hTERT and c-myc in endometrial carcinogenesis. The expression of hTERT and c-myc mRNA was examined by in situ hybridization of endometrial samples from 14 cases with simple hyperplasia, 10 with complex hyperplasia, 8 with atypical hyperplasia and 42 with endometrioid carcinoma. Expression of hTERT was demonstrated in samples with simple hyperplasia, complex hyperplasia, atypical hyperplasia and carcinoma at frequencies of 2/14, 4/8, 8/10 and 39/42 (92.9%), respectively. The prevalence and intensity of the hTERT signal was greater in the carcinomas and lesions with atypical hyperplasia than those with simple or complex hyperplasia (P < 0.05). The expression of c-myc was demonstrated in samples with simple hyperplasia, complex hyperplasia, atypical hyperplasia and carcinoma at frequencies of 3/14, 1/8, 5/10 and 23/42 (54.8%), respectively. The frequency of c-myc expression was higher in carcinomas and hyperplastic lesions with atypia than those in lesions with simple or complex hyperplasia without atypia (P < 0.05). The expression of hTERT was shown to be correlated with the level of differentiation (P < 0.05), while the c-myc expression appeared to be associated with the depth of myometrial invasion (P < 0.05). The expression levels of hTERT and c-myc were not found to be correlated with each other in the tissues examined (P > 0.05). The expression of hTERT and c-myc may be involved in the progression from the endometrial aypical hyperplasia to invasive carcinoma. The correlation between hTERT and c-myc in endometrial hyperplasia and carcinoma are not found.

To evaluate the clinical as well as histomorphologic features in different cases of endometrial hyperplasia along with its relative occurrence. A one-and-a-half-year prospective study was conducted on histopathologically diagnosed cases of endometrial hyperplasia in a tertiary care hospital. Apart from relevant clinical findings, histomorphologic details were noted and statistically analyzed. Maximum number (46.5%) of endometrial hyperplasia occurred in patients of 41-50years age group. Majority (55.2%) of the patients were found to be premenopausal. Menorrhagia was the most common (49.6%) clinical presentation followed by postmenopausal bleeding (30.8%). Simple hyperplasia without atypia was the most common type (95.6%) followed by complex hyperplasia without atypia (3.6%) and complex hyperplasia with atypia (0.8%), respectively. The study of gland-stroma ratio revealed 65:35 to be the most frequent (34%) ratio; variable-sized glands with cystic dilatation (60.4%) was the commonest gland architecture and most of the cases (99.2%) showed the absence of atypia. Associated histopathological findings included a case each of endometrial adenocarcinoma and undifferentiated endometrial stromal sarcoma along with the common leiomyoma and progesterone effects. Menorrhagia was the most common presenting complaint in cases of endometrial hyperplasia. The cases were mostly in the premenopausal age group. Simple endometrial hyperplasia without atypia was the commonest type diagnosed histopathologically. Histopathological examination along with clinical details is essential to give the final opinion regarding the diagnosis.