Cases Of Atypical Endometrial Hyperplasia Research Articles

Management of Atypical Endometrial Hyperplasia with a Focus on Conservative Treatment

Study Objective To compare local management of women diagnosed with atypical endometrial hyperplasia (AH) against RCOG Greentop Guideline No. 67 “Management of endometrial hyperplasia,” with specific emphasis on conservative treatment. Design An existing database of patients with endometrial pathology from 2012 to 2019 was used to identify 118 cases of AH. Patient demographics, management, and follow up were interrogated. Setting NHS Lanarkshire, Scotland (population 655,000). Patients or Participants Patient age ranged from 26-83 years with 50% over the age of fifty. 75% of patients were postmenopausal and 90% were overweight (BMI >25). Interventions Seventy-eight women (66%) had immediate hysterectomy. Thirty-five women (30%) underwent conservative management and five (4%) were lost to follow up. Conservative treatment comprised of levonorgestrel-releasing intrauterine system (LNG-IUS) (67%), oral progestogens (18%), GnRH analogues (9%), weight loss alone or no management (6%). Measurements and Main Results Follow up biopsy results in the conservative treatment group showed regression in fourteen patients (67%), persistence in five (23%) and progression to endometrial cancer in two (10%). Low rates of progression (12% overall) and persistence were observed overtime alongside continued regression rates. Eight women (23%) managed conservatively subsequently progressed to hysterectomy. Four of which required surgery due to the development of endometrial carcinoma. Conclusion Local management is consistent with current RCOG guidelines with more than half of women proceeding immediately to hysterectomy. The majority of patients managed conservatively had the LNG-IUS, consistent with guidelines. Follow up was appropriate in terms of monitoring and tissue sampling with four cases of endometrial cancer detected. This emphasises the importance of regular monitoring. Over 90% had an elevated BMI, a known risk factor for developing AH. Literature supports weight loss in improving regression rates in this demographic. In some cases, an initial conservative approach may allow peri-operative optimisation and risk factor modification which has a role in improving surgical outcomes. To compare local management of women diagnosed with atypical endometrial hyperplasia (AH) against RCOG Greentop Guideline No. 67 “Management of endometrial hyperplasia,” with specific emphasis on conservative treatment. An existing database of patients with endometrial pathology from 2012 to 2019 was used to identify 118 cases of AH. Patient demographics, management, and follow up were interrogated. NHS Lanarkshire, Scotland (population 655,000). Patient age ranged from 26-83 years with 50% over the age of fifty. 75% of patients were postmenopausal and 90% were overweight (BMI >25). Seventy-eight women (66%) had immediate hysterectomy. Thirty-five women (30%) underwent conservative management and five (4%) were lost to follow up. Conservative treatment comprised of levonorgestrel-releasing intrauterine system (LNG-IUS) (67%), oral progestogens (18%), GnRH analogues (9%), weight loss alone or no management (6%). Follow up biopsy results in the conservative treatment group showed regression in fourteen patients (67%), persistence in five (23%) and progression to endometrial cancer in two (10%). Low rates of progression (12% overall) and persistence were observed overtime alongside continued regression rates. Eight women (23%) managed conservatively subsequently progressed to hysterectomy. Four of which required surgery due to the development of endometrial carcinoma. Local management is consistent with current RCOG guidelines with more than half of women proceeding immediately to hysterectomy. The majority of patients managed conservatively had the LNG-IUS, consistent with guidelines. Follow up was appropriate in terms of monitoring and tissue sampling with four cases of endometrial cancer detected. This emphasises the importance of regular monitoring.

CLINICAL, MORPHOLOGICAL, AND EPIDEMIOLOGICAL CHARACTERISTICS OF ENDOMETRIAL HYPERPLASTIC PROCESSES IN SUMY REGION

Endometrial hyperplastic processes take an important place among the gynecological diseases in women of various ages and are one of the most common reasons for admission at inpatient gynecology departments. The urgency of the pathology is due to the significant prevalence of endometrial hyperplastic processes, high incidence of malignancy, prolonged relapsing course, and decreased reproductive function, since these diseases are one of the most common causes of infertility in women of childbearing age. The statistics related to the incidence of endometrial hyperplastic processes in Ukraine is not available. An analysis of case histories and medical records showed that in 40% of cases, endometrial hyperplastic processes were asymptomatic. In 60% of cases, the clinical manifestations of endometrial hyperplastic processes were menstrual disorders, such as dysmenorrhea, oligomenorrhea, menorrhagia, and metrorrhagia. In 30% of cases, endometrial hyperplastic processes were recurrent. The most common concomitant pathologies of the pelvic organs were uterine leiomyoma and endometriosis; the most common concomitant extragenital diseases were hypertension and obesity. Our study and data analysis showed that there is an increasing trend in the incidence of endometrial hyperplastic processes in Sumy region in 2011–2020. The maximum incidence was in 2016. A correlation was found between hyperplasia incidence and age. Thus, the largest number of non-atypical and atypical endometrial hyperplasia cases was observed in women aged 45–55 years. The lowest number of non-atypical endometrial hyperplasia cases was registered in women aged 66+, while atypical hyperplasia cases – in women under 30 years of age. Glandular polyps of the endometrium were most often diagnosed at the age of 31–44; the lowest number of these was found in women over 66 years. Most glandular-fibrous endometrial polyps were observed in women aged 45–55 years, while women under 30 presented with the fewest cases. Fibrous endometrial polyps were most common in older age groups – 66+; the lowest number of such endometrial polyps was found in women under 30 years. We attributed the decreased incidence of endometrial hyperplastic processes in 2020 to the quarantine measures introduced, which, as a consequence, led to the decreased number of diagnosed cases, since they are often asymptomatic.

Risk factors for atypical hyperplasia and endometrial cancer in the infertility population: a case-control study

ObjectiveTo estimate the incidence and identify risk factors for atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in American women undergoing infertility evaluation.DesignCase-control study.SettingAcademic reproductive endocrinology and infertility practice.Patient(s)Female patients (18–50 years) seeking infertility evaluation from January 1, 2009 to December 1, 2018. Patients with known genetic predisposition to cancer or prior cancer diagnosis were excluded. Cases were defined as patients diagnosed with AH or EC during infertility workup (n = 22). Controls without AH or EC were randomly selected in a 10:1 ratio (n = 220) from all women undergoing infertility evaluation in the same year.Intervention(s)None.Main Outcome Measure(s)Incidence of AH or EC and odds of AH or EC accounting for age, race, body mass index (BMI), and ovulatory dysfunction.Result(s)Twenty-two cases of AH or EC were identified among 11,569 women undergoing infertility evaluation (incidence 2 per 1,000 women, 95% confidence interval [CI] 1.2–2.9 per 1,000). Of these women, 68% had a BMI ≥30 kg/m2 compared with 25% of controls. In multivariable analyses, women with a BMI ≥30 kg/m2 were 5.9 times more likely to be diagnosed with AH or EC (adjusted odds ratio 5.9, 95% CI 2.0–17.2). Women with ovulatory dysfunction were 3.4 times more likely to be diagnosed with AH or EC (adjusted odds ratio 3.4, 95% CI 1.1–10.1).Conclusion(s)The incidence of AH and EC in a population of women undergoing infertility evaluation is 10 times that in the general population of premenopausal women. Obesity is the strongest independent risk factor for AH and EC in women with infertility.

Value of endometrial thickness in diagnosis of endometrial hyperplasia during selective estrogen receptor modulator therapy in premenopausal breast cancer patients

ObjectiveThe weak estrogenic-like effect of selective estrogen receptor modulator (SERM) may lead to series of endometrial lesions, including proliferation, hyperplasia, polyp formation, and even endometrial cancer. This study aimed to explore the effectiveness of different endometrial thickness in diagnosis of endometrial hyperplasia during SERM therapy in premenopausal patients. MethodsThe clinical data of 115 patients receiving hysteroscopic endometrial biopsy during SERM therapy in Peking Union Medical College Hospital, China from January 2010 to December 2018 were retrospectively analyzed. ResultsAverage age at the beginning of SERM therapy was 43.4 ± 5.7 years old. Mean duration time of SERM therapy was 31.0 ± 22.1 months. The mean endometrial thickness was 14.3 ± 6.1 mm. 4 cases of atypical endometrial hyperplasia (3.5 %), and 4 cases of endometrial hyperplasia without atypia (3.5 %) were detected. Endometrial thickness was higher in endometrial hyperplasia patients than in no endometrial hyperplasia patients (18.8 vs 13.9 mm, p = 0.029). Endometrial thickness in 8 out of 8 endometrial hyperplasia patients and 38 out of 107 no endometrial hyperplasia patients were ≥ 15 mm (p = 0.002). The negative predictive value in the diagnosis of endometrial hyperplasia during SERM therapy in premenopausal patients was 100 % when endometrial thickness < 15 mm chosen as cutoff value. ConclusionEndometrial hyperplasia was less likely to occur in premenopausal patients during SERM therapy when endometrial thickness < 15 mm.

Tumor budding index and microvessel density assessment in patients with endometrial cancer: A pilot study.

The present study aimed to analyze the association between tumor budding index (TBI) and microvessel density (MVD) and selected clinicopathological features in female patients with endometrial cancer (EC). The present study included 137 patients, of whom 117 had endometrial endometrioid cancer and 3 had non-endometrioid EC (NEEC). Additionally, 8 cases of simple endometrial hyperplasia and 9 cases of atypical endometrial hyperplasia were included in the present study. Patient age, menopausal status, tumor histological type, grade and International Federation of Gynecologists and Obstetricians (FIGO) clinical stage were investigated. Immunohistochemistry was utilized to detect MVD using a CD34 antibody, and a laminin-5γ2 antibody was used for TBI assessment. In nonmalignant endometrial lesions, the TBI was significantly lower than that in patients with EC and NEEC (P=0.002). Significant differences in median TBI (MD-TBI) were also observed between patients with low-grade EC (MD-TBI, 4.5) and high-grade EC (MD-TBI, 16.2; P=0.01). Age, body mass index and tumor FIGO stage were not indicated to be associated with the MD-TBI. Premenopausal patients with EC had lower MD-TBI values than postmenopausal patients (0.3 vs. 11.1; P<0.005). The median MVD-CD34 in the study group was 19 (range, 13–29). Significant differences in MVD-CD34 were observed between malignant and nonmalignant endometrial lesions (P=0.01). Histological grade was markedly associated with tumor MVD-CD34 (P=0.001). The MVD was higher in high-grade cancer (G3; MVD-CD34, 24.9) than in grade G1 and G2 lesions (MVD-CD34, 14 and 18.6, respectively; P=0.01). FIGO clinical stage was not associated with MVD-CD34 in low and high stage lesions (MD, 18.4 for FIGO stage I/II; MD, 17.6 for FIGO stage III/IV; P=0.2). High MVD was markedly associated with high MD-TBI (P=0.0002). In conclusion, TBI could be a valuable indicator of tumor aggressiveness in patients with EC. The presence of the tumor budding phenomenon with increased MVD may have the potential to further refine clinical management decisions when endometrial malignancy is detected.

Risk factors for atypical hyperplasia and endometrial cancer in the infertility population: a case-control study

Objective To estimate the incidence and identify risk factors for atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in American women undergoing infertility evaluation. Design Case-control study. Setting Academic reproductive endocrinology and infertility practice. Patient(s) Female patients (18–50 years) seeking infertility evaluation from January 1, 2009 to December 1, 2018. Patients with known genetic predisposition to cancer or prior cancer diagnosis were excluded. Cases were defined as patients diagnosed with AH or EC during infertility workup (n = 22). Controls without AH or EC were randomly selected in a 10:1 ratio (n = 220) from all women undergoing infertility evaluation in the same year. Intervention(s) None. Main Outcome Measure(s) Incidence of AH or EC and odds of AH or EC accounting for age, race, body mass index (BMI), and ovulatory dysfunction. Result(s) Twenty-two cases of AH or EC were identified among 11,569 women undergoing infertility evaluation (incidence 2 per 1,000 women, 95% confidence interval [CI] 1.2–2.9 per 1,000). Of these women, 68% had a BMI ≥30 kg/m2 compared with 25% of controls. In multivariable analyses, women with a BMI ≥30 kg/m2 were 5.9 times more likely to be diagnosed with AH or EC (adjusted odds ratio 5.9, 95% CI 2.0–17.2). Women with ovulatory dysfunction were 3.4 times more likely to be diagnosed with AH or EC (adjusted odds ratio 3.4, 95% CI 1.1–10.1). Conclusion(s) The incidence of AH and EC in a population of women undergoing infertility evaluation is 10 times that in the general population of premenopausal women. Obesity is the strongest independent risk factor for AH and EC in women with infertility.

Could E-Cadherin and CD10 Expression be Used to Differentiate Between Atypical Endometrial Hyperplasia and Endometrial Carcinoma?

Endometrial carcinoma contributes to morbidity and mortality among female individuals worldwide. The role of E-cadherin expression, as an adhesion molecule, in endometrial carcinoma is controversial. Moreover, the role of CD10-expressing stromal cells in endometrial carcinoma is still unclear. The aim of this work was to evaluate E-cadherin and CD10 expression in normal endometrium, atypical endometrial hyperplasia, and endometrial carcinoma, and assess their role to differentiate atypical endometrial hyperplasia from endometrial carcinoma. The association of E-cadherin and CD10 expression with clinicopathologic parameters of endometrial carcinoma was also determined. This retrospective study was carried out on 80 cases including 36 cases of endometrial adenocarcinoma (all were of endometrioid type), 34 cases of atypical endometrial hyperplasia, and another 10 cases of normal endometrial tissue. Immunohistochemistry for E-cadherin and CD10 was conducted. The studied patients were in their sixth and seventh decades of life with a mean age of 60.97 yr. Most of the carcinoma cases (18 cases) were grade 1, 10 cases were grade 2, and only 2 cases were grade 3. With regard to International Federation of Gynecology and Obstetrics (FIGO) staging, 28 cases were stage I, and only 2 cases were stage II. E-cadherin in normal endometrial tissue and atypical hyperplastic endometrial tissue showed predominantly membranous homogenous reactivity, and CD10 was detected as membranocyptoplasmic staining. However, we noticed the subcellular change of E-cadherin reactivity to be heterogenous and predominantly membranocytoplasmic in endometrial carcinoma, whereas CD10 remained membranocytoplasmic. Concerning E-cadherin expression, there was a statistically significant relationship between E-cadherin expression, tumor grade and FIGO staging, whereas there was an insignificant relationship between E-cadherin expression and patients' age, specimen type, tumor gross pattern, and histopathologic types. With regard to CD10 expression, there was a statistically significant relation between CD10 expression and tumor grade and FIGO staging with insignificant relation with patients' age, tumor gross pattern, specimen type, and tumor histologic types (villoglandular vs. usual endometrial adenocarcinoma). There was also a highly statistically significant positive relationship between E-cadherin expression and CD10 expression. This study puts the spot light on their role in differentiating between atypical endometrial hyperplasia and endometrial carcinoma, which is often difficult.

Occult uterine malignancy during laparoscopic supracervical hysterectomy.

To estimate the incidence of occult uterine malignancies during laparoscopic supracervical hysterectomy (LSH). Retrospective cohort study based on archival data (2010-2016) of the Department of Gynecology and Oncology, Jagiellonian University. Medical records of 696 women, who underwent LSH were analyzed. Two occult sarcomas (2/696; 0.29%, 0.003, 95% CI: 0.001 to 0.01), including one case of low-grade endometrial stromal sarcoma (ESS) with co-occurring atypical endometrial hyperplasia (AH) and one case of high-grade ESS were found postoperatively. One case of invasive primary fallopian tube cancer (1/696; 0.14%, 0.001, 95% CI: 0.00 to 0.008) and additional three cases of AH (3/696; 0.57%, 0.004, 95% CI: 0.001 to 0.013) were also identified. No case of EC was documented. One hundred sixty nine (24.3%) women of 696 had an endometrial sampling prior LSH including these with ESS. We did not observe worsening of the prognosis and all patients with confirmed malignancy are still alive and free from recurrence in 2-5 years of observations. Most commonly the occult malignancy would have not been recognized if the surgery had not been conducted. When appropriate diagnostics is conducted, rare incidents of malignant tissue morcellation should not be considered as a professional misconduct but as a possible adverse event. Patients should be informed about the risk of malignancy according to available estimations and that endometrial sampling cannot eliminate such a risk. A consensus regarding safe indications, required diagnostics, and justifiability of mandatory use of contained morcellation for LSH should be developed.

Endometrial hyperplasia versus carcinoma

Context Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function and mutation in PTEN gene have been implicated in the pathogenesis of endometrial carcinoma (EC). Objective The aim was to evaluate the immunohistochemical expression of PTEN in endometrial hyperplasia and EC and to evaluate the relationship between its expression and tumor grade in EC. Materials and methods Specimens included 16 cases of endometrial hyperplasia without atypia, six cases of atypical endometrial hyperplasia, and 18 EC specimens. Immunohistochemical staining for PTEN was performed using diaminobenzidine detection kit on formalin-fixed and paraffin-embedded tissue samples. Tumor tissue blocks and clinical data were collected from the files of the Pathology Department of Al-Zahraa University Hospital during the period 2010–2014. Results Immunohistochemistry showed that PTEN was positive for nuclei and cytoplasm of glandular endometrial cells. The PTEN expression was decreased significantly in atypical hyperplasia or EC compared with simple or complex hyperplasia (P0.041). In EC, we proved that PTEN expression is downregulated in high-grade tumors. Conclusion A positive PTEN expression correlates significantly with hyperplasia without atypia and well-differentiated tumors. The downregulation of PTEN indicates a more malignant phenotype.

Management of atypical polypoid adenomyomas. A case series

ObjectiveAtypical polypoid adenomyomas (APAs) are endometrial, non-malignant, focal, and non-invasive lesions that are intriguing for their histological resemblence to invasive endometrioid adenocarcinoma or malignant mixed Müllerian tumor. The aim of this study was to present our clinical experience, regarding the reproductive outcome, the recurrence rate, and the association with hyperplasia and cancer, in a small series of patients with APA. Study designRetrospective case series of patients treated for APA in a single private hospital setting from 1998 to 2016. All patients underwent diagnostic hysteroscopy and hysteroscopic removal of the lesion. Follow-up was performed annually with endovaginal ultrasonography and hysteroscopy when necessary. ResultsNine patients (mean age: 37.9 years-old ±8.3years) were treated because of menorrhagia, infertility, and incidental asymptomatic endometrial lesions with operative hysteroscopy. Mean follow-up was 10.0 years (±5.8years). Three patients intended for pregnancy and 2 of them had achieved a full term delivery. There were 2 recurrences (22.2%), two cases of atypical endometrial hyperplasia (22.2%), and 2 patients with endometrioid adenocarcinoma (22.2%), all within the first 5 years. ConclusionsIt appears that APAs exhibit a significant recurrence rate and they may be related both to atypical endometrial hyperplasia and endometrial adenocarcinoma; therefore, clinicians should be aware of these lesions in order to individualize treatment according to the patent’s age and fertility history.

Value of H-TERT and CD10 in differentiating endometrial carcinoma from atypical endometrial hyperplasia: an immunohistochemical study

Context The histopathological differentiation between atypical endometrial hyperplasia and well-differentiated conventional endometrial carcinoma is sometimes tricky, particularly in endometrial dilatation and curettage specimens, to the extent that a differentiating marker is sought. Aim This study was devoted to evaluate the immunohistochemical expression of CD10 and human telomerase reverse transcriptase (H-TERT) in atypical endometrial hyperplasia and endometrial carcinoma to determine their role in differentiating both lesions. Patients and methods Thirty paraffin blocks of endometrial biopsy distributed as 15 cases of atypical endometrial hyperplasia and 15 cases of conventional endometrial carcinoma were studied immunohistochemically using antibodies against CD10 and H-TERT. Data were represented as mean, SD, and percentage. The Fisher exact test was used to compare immunoexpression between atypical endometrial hyperplasia and endometrial carcinoma. The Mann–Whitney U-test and the Kruskal–Wallis test were used to compare between the two marker expressions in both lesions. The one-way analysis of variance test was used to determine whether the difference was significant. A P-value of less than 0.05 was considered significant. Results A statistically significant difference was observed between CD10 and H-TERT expression in both lesions, but only H-TERT significantly correlated with international federation of gynecology and obstetrics (FIGO) tumor grades in endometrial carcinoma cases. Although H-TERT labeling index upregulates with CD10 weaker expression, the relation between the two markers was not significant. Conclusion Both CD10 and H-TERT may be involved in the progression from the atypical endometrial hyperplasia to endometrial carcinoma as well as to differentiate between the two lesions. However, only H-TERT may be associated with the prognosis of endometrial carcinoma.

The yield of endometrial aspiration in women with various risk factors and bleeding abnormalities.

BackgroundEven in the face of a substantial increase in the numbers of endometrial cancer cases and in the numbers of women who have risk factors, there is no clear agreement about the indications for assessing the endometria of women with abnormal bleeding or about the tools to use in that assessment. This study sought to determine in a group of high risk women with abnormal uterine bleeding, the probability that an outpatient endometrial aspiration would identify significant pathology.MethodsRetrospective cohort study of the histology from endometrial aspirations performed from 2001 to 2008 for abnormal uterine bleeding at Harbor-UCLA Medical Center and its satellite public health clinics. Medical records were reviewed in detail to assess risk factors, descriptions of bleeding abnormalities and histologic results.ResultsThe charts of 1601 women who underwent 1636 endometrial biopsies for a wide variety of abnormal uterine bleeding patterns yielded 73 (4.6 %) cases of endometrial carcinoma, 43 cases of atypical endometrial hyperplasia (2.7 %), for an overall yield of significant pathology of 7.2 %. Hyperplasia without atypia was found in another 83 cases (5.2 %). Obesity, diabetes and postmenopausal age are associated with an increased risk of significant pathology. Bleeding patterns were so poorly documented that analysis of yield by this factor should be viewed with caution.ConclusionsThe probability of detecting significant uterine pathology is greatest among obese, diabetic postmenopausal women with diabetes (26.3 %). Conversely, the probability of identifying significant pathology in younger women without risk factors is less than 2 %. For women who perceive their individualized risk estimate to be too small to justify an endometrial biopsy, it may be possible to offer oral higher dose progestin therapy on the condition that persistent abnormal bleeding will require more intensive evaluation. These estimates of absolute risk of being diagnosed with significant pathology on endometrial biopsy may be helpful to patients as they consider giving informed consent for the procedure.

Estrogenoterapia Prolongada en Postmenopausicas y Carcinoma de Endometrio: 20 Años de Seguimiento

Con el fin de mejorar los síntomas climatéricos, desde 1960 se comenzó a administrar de 6 -7.5 mg diarios de estrógenos, con la consecuente hemorragia. Algunos legrados mostraron hiperplasia endometrial quística. Luego, se realizaron estudios del endometrio, previos al tratamiento de las candidatas. Durante 20 años fueron seleccionadas 2814 mujeres. Fueron separadas del estudio aquellas con patología cervical, endometrial o mamaria; se les administró estradiol sintético y/o estrógenos conjugados: 0,265-1,25 mg en forma interdiaria. A pesar de los estudios clínicos y epidemiológicos retrospectivos publicados, en favor de que el estrógeno exógeno de reemplazo estaría asociado al cáncer endometrial, en este estudio prospectivo y prolongado se demuestra que no hay relación alguna. Este riesgo ha sido señalado de manera exagerada, porque dichos estudios incluían los casos de hiperplasia endometrial atípica, dentro de los casos de portadoras de cáncer endometrial. Muchas formas de estas han sido criticadas por la manera en que fueron analizadas ya que, confundieron y mal interpretaron la histopatología. Las dosis pequeñas, para satisfacer las necesidades climatéricas, pueden ser un indicador de patología endometrial subclínica, desde los primeros meses de su administración. Los que se apoyan en la evidencia epidemiológica de riesgo, debieran incluir esta información en sus estudios analíticos.

Use of Levonorgestrel-Releasing Intrauterine System in the Prevention and Treatment of Endometrial Hyperplasia

Endometrial hyperplasia is a commonly seen gynecological condition that affects women of all age groups. Whereas hysterectomy is the most preferred treatment option for complex endometrial hyperplasia with atypia, there is no consensus regarding the first-line management of women with hyperplasia without cytological atypia. Oral progestogen therapy was used with some success. Nonetheless, it may be plausible to argue that women with endometrial hyperplasia need continuous treatment and high level of compliance to ensure complete regression, which may not be guaranteed with oral therapy. Observational studies suggested that levonorgestrel-releasing intrauterine system (LNG-IUS) has been successfully used to treat endometrial hyperplasia without cytological atypia and selected cases of atypical endometrial hyperplasia. Furthermore, there is strong evidence from randomized controlled trials that LNG-IUS prevents the development of endometrial hyperplasia in exogenous estrogen users; however, its protective role and safety in tamoxifen-treated breast cancer survivors remain uncertain. This article evaluates the current evidence for the use of LNG-IUS, releasing 20 μg of LNG per day, in the prevention and treatment of endometrial hyperplasia.

Prediction of coexistent carcinomas risks by subjective EIN diagnosis and comparison with WHO classification in endometrial hyperplasias

Endometrial intraepithelial neoplasia (EIN) classification is proposed as a new diagnostic system to resolve the limitations of the World Health Organization (WHO) classification in routine practice. Our aim was to find out whether EIN classification excels the WHO classification regarding the accurate prediction of coexisting endometrial carcinomas (EC) in biopsy specimens.We retrospectively re-classified 139 WHO-classified endometrial hyperplasia (EH) cases by subjective EIN diagnosis and compared the incidence of coexisting carcinomas using two classification systems by re-evaluating biopsy and corresponding hysterectomy specimens.Of 139 WHO-classified hyperplasia cases, 36 and 103 were classified as benign and EIN cases, respectively. Forty of 93 cases with atypical EH had EC at hysterectomy as compared with 2/46 cases without atypical EH, while EC was detected in 42/103 cases with EIN, and in 0 of 36 cases without EIN. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for atypical EH vs. non-atypical EH in biopsy specimen was 95.2%, 45.4%, 43.0% and 95.7%, respectively. For EIN vs. benign, the sensitivity was 100% and the specificity was 37.1%.The incidence of coexisting carcinomas in EIN cases was similar to that in atypical EH cases. However, regarding the exclusion of coexisting carcinomas, EIN criteria of benign lesions excelled the WHO criteria of non-atypical EH/CH.

Abstract 4614: Karyometry in atypical endometrial hyperplasia: A Gynecologic Oncology Group study

Abstract Treatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. The histopathologic classification of endometrial lesions is a difficult task requiring extensive experience. The Gynecologic Oncology Group (GOG) conducted a study (GOG 167A) that was designed to estimate the frequency of endometrial cancer in hysterectomy specimens in subjects who had a biopsy diagnosis of atypical endometrial hyperplasia. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC). Cases from GOG study 167A were classified by a central pathology committee as AEH (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis. Nuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is percentage of premalignant/neoplastic nuclei. When this percentage approaches 50-60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve. AEH comprises cases which may constitute a low risk group involving &amp;lt;40% of AEH cases. These cases hold a percentage of &amp;lt;20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have &amp;gt;40 % of nuclei of the preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. While karyometric assessment does not provide a distinctive diagnostic criterion for an individual patient, it does provide a measure of risk for the development of invasive disease. Studies to support the diagnostic assessment of endometrial lesions by computer aided morphometric analyses go back over 30 years. These efforts were aimed at two objectives, the diagnostic distinction between benign and cancer, and procedures that allow a stratification of patients into risk groups for the development of myometrial invasion. The percentage of nuclei of preneoplastic phenotype in AEH lesions might serve as criterion for assessment of risk for the development of invasive disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4614. doi:1538-7445.AM2012-4614

Progestin therapy for endometrial cancer: The potential of fourth-generation progestin (Review)

Progestin preparations are made of synthetic progesterone and have often been used for hormone therapy in gynecological patients with endometriosis or endometrial cancer. Hormone therapy using progestin is considered to be one of the effective means of treatment particularly when dealing with endometrial cancer (an estrogen-dependent tumor). Numerous reports have been published concerning its efficacy in advanced or recurrent cases of atypical endometrial hyperplasia or endometrial cancer. Dienogest has been developed as a fourth-generation progestin for hormone therapy for endometriosis that can be used with high safety for long periods of time. In Japan, dienogest has been recommended as a first-line drug for endometriosis-associated pain. However, its antitumor activity has also been attracting close attention following a report that this drug suppressed the proliferation in vitro of endometrial cancer-derived cell lines which failed to respond to other progestins such as medroxyprogesterine acetate (MPA). The mechanism for antitumor activity of dienogest is considered to differ from the mechanism for antitumor activity of conventional progestin preparations used for treatment of endometrial cancer. This drug is expected to be clinically applicable as a new drug for the treatment of endometrial cancer.

Karyometry in atypical endometrial hyperplasia: A Gynecologic Oncology Group study

ObjectivesTreatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC). MethodsCases from GOG study 167A were classified by a central pathology committee as AEH (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis. ResultsNuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is the percentage of premalignant/neoplastic nuclei. When this percentage approaches 50–60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve. ConclusionsAEH comprises cases which may constitute a low risk group involving <40% of AEH cases. These cases hold a percentage of <20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have >40% of nuclei of preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. The percentage of nuclei of the preneoplastic phenotype in AEH esions might serve as criterion for assessment of risk for the development of invasive disease.

A multivariate statistical study to obtain effective criteria to detect well‐differentiated adenocarcinoma in endometrial cytology

Consistency in endometrial cytology is relatively poor. This can be partly attributed to generally accepted criteria based on cellular features. The cytological distinction between grade-1 adenocarcinoma and endometrial hyperplasia is more reliant on architectural features than cellular features. We examined statistical criteria based on cytoarchitecture for detecting grade-1 adenocarcinoma in endometrial cytology. Histologically, the study population consisted of 11 cases of grade-1 adenocarcinoma, 6 of atypical endometrial hyperplasia, 16 of endometrial hyperplasia without atypia, and 74 of a normal proliferative endometrium. In each case, all cellclumps were divided into five patterns (tubular; sheet; dilated and/or branched tubular; regular overlapping; atypical). The frequencies of each pattern were submitted to five-variate cluster analysis. The validity and reproducibility of cluster analysis were tested by canonical discriminant analysis and multigroup linear discriminant analysis, respectively. All 107 cases were classified into three groups, A (11), B (36), and C (60), by five-variate cluster analysis. In comparison with this classification and histopathologic diagnosis, group A corresponded to adenocarcinoma, and groups B and C correlated with non-carcinoma. Most cases of atypical endometrial hyperplasia were included in group B. These data suggest that statistical groupings based on cytoarchitecture are useful in the discrimination of grade-1 adenocarcinoma from endometrial hyperplasia and normal tissue.

Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort

The increase in the worldwide incidence of endometrial cancer relates to rising obesity, falling fertility, and the ageing of the population. Transvaginal ultrasound (TVS) is a possible screening test, but there have been no large-scale studies. We report the performance of TVS screening in a large cohort. We did a nested case-control study of postmenopausal women who underwent TVS in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) following recruitment between April 17, 2001, and Sept 29, 2005. Endometrial thickness and endometrial abnormalities were recorded, and follow-up, through national registries and a postal questionnaire, documented the diagnosis of endometrial cancer. Our primary outcome measure was endometrial cancer and atypical endometrial hyperplasia (AEH). Performance characteristics of endometrial thickness and abnormalities for detection of endometrial cancer within 1 year of TVS were calculated. Epidemiological variables were used to develop a logistic regression model and assess a screening strategy for women at higher risk. Our study is registered with ClinicalTrials.gov, number NCT00058032, and with the International Standard Randomised Controlled Trial register, number ISRCTN22488978. 48,230 women underwent TVS in the UKCTOCS prevalence screen. 9078 women were ineligible because they had undergone a hysterectomy and 2271 because their endometrial thickness had not been recorded; however, 157 of these women had an endometrial abnormality on TVS and were included in the analysis. Median follow-up was 5·11 years (IQR 4·05-5·95). 136 women with endometrial cancer or AEH within 1 year of TVS were included in our primary analysis. The optimum endometrial thickness cutoff for endometrial cancer or AEH was 5·15 mm, with sensitivity of 80·5% (95% CI 72·7-86·8) and specificity of 86·2% (85·8-86·6). Sensitivity and specificity at a 5 mm or greater cutoff were 80·5% (72·7-86·8) and 85·7% (85·4-86·2); for women with a 5 mm or greater cutoff plus endometrial abnormalities, the sensitivity and specificity were 85·3% (78·2-90·8) and 80·4% (80·0-80·8), respectively. For a cutoff of 10 mm or greater, sensitivity and specificity were 54·1% (45·3-62·8) and 97·2% (97·0-97·4). When our analysis was restricted to the 96 women with endometrial cancer or AEH who reported no symptoms of postmenopausal bleeding at the UKCTOCS scan before diagnosis and had an endometrial thickness measurement available, a cutoff of 5 mm achieved a sensitivity of 77·1% (67·8-84·3) and specificity of 85·8% (85·7-85·9). The logistic regression model identified 25% of the population as at high risk and 39·5% of endometrial cancer or AEH cases were identified within this high risk group. In this high-risk population, a cutoff at 6·75 mm achieved sensitivity of 84·3% (71·4-93·0) and specificity of 89·9% (89·3-90·5). Our findings show that TVS screening for endometrial cancer has good sensitivity in postmenopausal women. The burden of diagnostic procedures and false-positive results can be reduced by limiting screening to a higher-risk group. The role of population screening for endometrial cancer remains uncertain, but our findings are of immediate value in the management of increased endometrial thickness in postmenopausal women undergoing pelvic scans for reasons other than vaginal bleeding.