In a postmenopausal woman without vaginal bleeding, if the endometrium measures > 11 mm a biopsy should be considered as the risk of cancer is 6.7%, whereas if the endometrium measures < or = 11 mm a biopsy is not needed as the risk of cancer is extremely low.
Endometrial intraepithelial neoplasia (EIN) is a monoclonal premalignant endometrial glandular lesion that precedes the development of endometrioid-type endometrial adenocarcinoma. EIN arises through complex interactions involving the sequential accumulation of genetic damage in endometrial glands a …
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isks must be matched with an appropriate intervention to avoid undertreatment or overtreatment. Pathologic diagnosis of premalignant lesions should use criteria and terminology that clearly distinguish between clinicopathologic entities that are managed differently. At present, the endometrial intraepithelial neoplasia schema is tailored most closely to this objective, incorporating modified pathologic criteria based upon evidence that has become available since the creation of the more widely used 1994 four-class World Health Organization schema (in which atypical hyperplasia is equated with precancerous behavior). The accuracy of dilation and curettage compared with endometrial suction curette in diagnosing precancer and excluding concurrent carcinoma is unclear. Hysteroscopy with directed biopsy is more sensitive than dilation and curettage in the diagnosis of uterine lesions. When clinically appropriate, total hysterectomy for endometrial intraepithelial neoplasia provides definitive assessment of a possible concurrent carcinoma and effectively treats premalignant lesions. Systemic or local progestin therapy is an unproven but commonly used alternative to hysterectomy that may be appropriate for women who are poor surgical candidates or who desire to retain fertility....
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isks must be matched with an appropriate intervention to avoid undertreatment or overtreatment. Pathologic diagnosis of premalignant lesions should use criteria and terminology that clearly distinguish between clinicopathologic entities that are managed differently. At present, the endometrial intraepithelial neoplasia schema is tailored most closely to this objective, incorporating modified pathologic criteria based upon evidence that has become available since the creation of the more widely used 1994 four-class World Health Organization schema (in which atypical hyperplasia is equated with precancerous behavior). The accuracy of dilation and curettage compared with endometrial suction curette in diagnosing precancer and excluding concurrent carcinoma is unclear. Hysteroscopy with directed biopsy is more sensitive than dilation and curettage in the diagnosis of uterine lesions. When clinically appropriate, total hysterectomy for endometrial intraepithelial neoplasia provides definitive assessment of a possible concurrent carcinoma and effectively treats premalignant lesions. Systemic or local progestin therapy is an unproven but commonly used alternative to hysterectomy that may be appropriate for women who are poor surgical candidates or who desire to retain fertility....
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isks must be matched with an appropriate intervention to avoid undertreatment or overtreatment. Pathologic diagnosis of premalignant lesions should use criteria and terminology that clearly distinguish between clinicopathologic entities that are managed differently. At present, the endometrial intraepithelial neoplasia schema is tailored most closely to this objective, incorporating modified pathologic criteria based upon evidence that has become available since the creation of the more widely used 1994 four-class World Health Organization schema (in which atypical hyperplasia is equated with precancerous behavior). The accuracy of dilation and curettage compared with endometrial suction curette in diagnosing precancer and excluding concurrent carcinoma is unclear. Hysteroscopy with directed biopsy is more sensitive than dilation and curettage in the diagnosis of uterine lesions. When clinically appropriate, total hysterectomy for endometrial intraepithelial neoplasia provides definitive assessment of a possible concurrent carcinoma and effectively treats premalignant lesions. Systemic or local progestin therapy is an unproven but commonly used alternative to hysterectomy that may be appropriate for women who are poor surgical candidates or who desire to retain fertility....
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isks must be matched with an appropriate intervention to avoid undertreatment or overtreatment. Pathologic diagnosis of premalignant lesions should use criteria and terminology that clearly distinguish between clinicopathologic entities that are managed differently. At present, the endometrial intraepithelial neoplasia schema is tailored most closely to this objective, incorporating modified pathologic criteria based upon evidence that has become available since the creation of the more widely used 1994 four-class World Health Organization schema (in which atypical hyperplasia is equated with precancerous behavior). The accuracy of dilation and curettage compared with endometrial suction curette in diagnosing precancer and excluding concurrent carcinoma is unclear. Hysteroscopy with directed biopsy is more sensitive than dilation and curettage in the diagnosis of uterine lesions. When clinically appropriate, total hysterectomy for endometrial intraepithelial neoplasia provides definitive assessment of a possible concurrent carcinoma and effectively treats premalignant lesions. Systemic or local progestin therapy is an unproven but commonly used alternative to hysterectomy that may be appropriate for women who are poor surgical candidates or who desire to retain fertility....
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Context.—Developed in conjunction with molecular and progression data, the sequence classification schema for endometrial intraepithelial neoplasia (EIN)/benign hyperplasia (BH) provides an easy to adopt and reproducible method for classification of endometrial biopsies.Objective.—To review current data supporting the use of BH/EIN to classify endometrial biopsies, and to discuss the hormone-driven endometrial sequence from anovulation/disordered proliferative endometrium through BH and EIN and their diagnostic difficulty.Data Sources.—A comprehensive review of EIN literature based on literature indexed by PubMed (National Library of Medicine) and Google Scholar.Conclusions.—The BH/EIN schema is gaining wider acceptance among pathologist and clinicians. The research leading to the EIN criteria is based on molecular and progression data. The BH/EIN schema has better reproducibility among pathologists, is intuitively easy to use, and requires understanding of endometrial physiology and neoplasia.
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Context.—Developed in conjunction with molecular and progression data, the sequence classification schema for endometrial intraepithelial neoplasia (EIN)/benign hyperplasia (BH) provides an easy to adopt and reproducible method for classification of endometrial biopsies.Objective.—To review current data supporting the use of BH/EIN to classify endometrial biopsies, and to discuss the hormone-driven endometrial sequence from anovulation/disordered proliferative endometrium through BH and EIN and their diagnostic difficulty.Data Sources.—A comprehensive review of EIN literature based on literature indexed by PubMed (National Library of Medicine) and Google Scholar.Conclusions.—The BH/EIN schema is gaining wider acceptance among pathologist and clinicians. The research leading to the EIN criteria is based on molecular and progression data. The BH/EIN schema has better reproducibility among pathologists, is intuitively easy to use, and requires understanding of endometrial physiology and neoplasia.
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Context.—Developed in conjunction with molecular and progression data, the sequence classification schema for endometrial intraepithelial neoplasia (EIN)/benign hyperplasia (BH) provides an easy to adopt and reproducible method for classification of endometrial biopsies.Objective.—To review current data supporting the use of BH/EIN to classify endometrial biopsies, and to discuss the hormone-driven endometrial sequence from anovulation/disordered proliferative endometrium through BH and EIN and their diagnostic difficulty.Data Sources.—A comprehensive review of EIN literature based on literature indexed by PubMed (National Library of Medicine) and Google Scholar.Conclusions.—The BH/EIN schema is gaining wider acceptance among pathologist and clinicians. The research leading to the EIN criteria is based on molecular and progression data. The BH/EIN schema has better reproducibility among pathologists, is intuitively easy to use, and requires understanding of endometrial physiology and neoplasia.
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Context.—Developed in conjunction with molecular and progression data, the sequence classification schema for endometrial intraepithelial neoplasia (EIN)/benign hyperplasia (BH) provides an easy to adopt and reproducible method for classification of endometrial biopsies.Objective.—To review current data supporting the use of BH/EIN to classify endometrial biopsies, and to discuss the hormone-driven endometrial sequence from anovulation/disordered proliferative endometrium through BH and EIN and their diagnostic difficulty.Data Sources.—A comprehensive review of EIN literature based on literature indexed by PubMed (National Library of Medicine) and Google Scholar.Conclusions.—The BH/EIN schema is gaining wider acceptance among pathologist and clinicians. The research leading to the EIN criteria is based on molecular and progression data. The BH/EIN schema has better reproducibility among pathologists, is intuitively easy to use, and requires understanding of endometrial physiology and neoplasia.
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Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists’ diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.
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Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists’ diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.
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Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists’ diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.
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Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists’ diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.
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Endometrial intraepithelial neoplasia (EIN) with secretory differentiation and ordinary EIN occurring in a secretory context are rare but recognized findings. We determined how often secretory differentiation in EIN was associated with evidence of circulating progestins in the background endometrium, and studied clinical characteristics and clinical outcomes of affected patients. We selected 41 patients with secretory differentiation in either the EIN itself (n=31) and/or background endometrium (n=38). Most (90%, 28/31) secretory EINs were associated with circulating progestins. Rare exceptions were observed, suggesting that secretory EIN may occur as a hormone-independent phenomenon. Circulating progestins are not sufficient, however, to induce EIN secretory differentiation, as 26% (10/38) of EIN within a secretory background were of the ordinary (non-secretory) type. EIN patients with secretory endometrium in the background are younger (averaging 45 years) than the aggregate group of all patients with EIN (53 years in previously published studies) and are often premenopausal with a cyclical source of endogenous progestins. Involution of EIN during follow-up was more frequent (81%, 17/21) for those with a secretory background at the time of initial EIN diagnosis compared with historical averages (25%, 36/142). These results suggest a potential role for endogenous progesterone, as well as therapeutic progestins, in modulating EIN outcomes.
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Exemestane in Treating Patients With Complex Atypical Hyperplasia of the Endometrium/Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer - Full Text View.
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Uterus - Endometrial hyperplasia / endometrioid intraepithelial neoplasia (EIN)
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Our study is to determine the presence of endometrial intraepithelial neoplasia (EIN) in endometrial biopsy specimens classified by the 1994 World Health Organization (WHO) criteria for endometrial hyperplasia. Endometrial biopsy specimens that were stained with hematoxylin and eosin (HE) were examined and categorized by the WHO 1994 criteria and for the presence of EIN as defined by the International Endometrial Collaborative Group.
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Endometrial cancer is the most common gynecologic malignancy in developed countries. Estrogen-dependent tumors (type I, endometrioid) account for 80% of cases and non-estrogen-dependent (type II, nonendometrioid) account for the rest. Endometrial cancer type 1 is generally thought to develop via precursor lesions along with the increasing accumulation of molecular genetic changes. Indeed, Endometrial hyperplasia with atypia or Endometrial Intraepithelial Neoplasia (AH/EIN) is the least common type of hyperplasia, but is the type most likely to progress to type 1 cancer, whereas endometrial hyperplasia without atypia (BH) rarely progresses to carcinoma. MicroRNAs are a class of small, non-coding, single-stranded RNAs that negatively regulate gene expression mainly binding to 3’-untranslated region (UTR) of target mRNAs. In the current study we identified a microRNAs signature (miR-205, miR-146a, miR-1260b) able to discriminate between atypical and typical endometrial hyperplasia. The identification of molecular markers that can differentiate between these two distinct pathological conditions is highly considered to be useful for the clinical management of the patients, owing to the fact that hyperplasia with atypical change is associated with a higher risk of develop cancer. A ROC curve analysis showed that each microRNA has a high predictive power in discriminating the two conditions (>90%). With the aim to find a biological role for these three microRNAs we focused our attention on a common putative target involved in endometrial carcinogenesis: the oncosuppressor gene SMAD4. We demonstrated that miR-146a, miR-205 and miR-1260b directly target SMAD4 and induced proliferation and migration of Hec1a cells. These data suggest that impairment microRNAs-mediated of TGF-β pathway, due to inhibition of its effector molecule SMAD4, is a relevant molecular alteration in endometrial carcinoma development. Our findings showed a potential diagnostic role of microRNAs for accurate detection of complex atypical hypeprlasia and improved the understanding of its pivotal role in SMAD4 regulation.
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