A Multicentric European Study Testing the Reproducibility of the WHO Classification of Endometrial Hyperplasia With a Proposal of a Simplified Working Classification for Biopsy and Curettage Specimens

Abstract

This study was designed to assess intraobserver and interobserver agreement in the diagnosis of 56 endometrial specimens by five European expert gynecologic pathologists using the WHO classification and to establish which histologic features are significantly associated with each classification category. The seven categories were simple hyperplasia, complex hyperplasia, atypical hyperplasia, well-differentiated adenocarcinoma, proliferative endometria, secretory endometria, and other. Slides were reviewed twice for diagnosis, with accompanying evaluation of a checklist of histologic features. These seven categories were eventually reduced to four and three for the purposes of data analysis. The four modified diagnostic categories consisted of hyperplasia (previously simple hyperplasia and complex hyperplasia), atypical hyperplasia, well-differentiated adenocarcinoma, and cyclical endometrium (previously proliferative, secretory, and other). The three diagnostic categories consisted of hyperplasia, endometrioid neoplasia (previously atypical hyperplasia and well-differentiated adenocarcinoma), and cyclical endometrium. Intraobserver and interobserver agreement was assessed using the percentage agreement and kappa statistics. The associations among the various histologic features and diagnoses was analyzed using multiple logistic regression to identify those features that were useful for distinguishing diagnostic categories. When using seven categories, kappa values ranged from 0.53 to 0.74 (percentage agreement, 61-79%) and from 0.33 to 0.59 (percentage agreement, 43-63%) for intraobserver and interobserver agreement, respectively. When using four categories, kappa values ranged from 0.68 to 0.73 (percentage agreement, 77-80%) and from 0.39 to 0.64 (percentage agreement, 54-73%) for intraobserver and interobserver agreement, respectively. When using three categories, kappa values ranged from 0.70 to 0.83 (percentage agreement, 80-89%) and from 0.55 to 0.73 (percentage agreement, 70-82%) for intraobserver and interobserver agreement, respectively. Data were analyzed in each diagnostic category. When using four or three diagnostic categories, the mean intraobserver and interobserver agreements varied less between categories and achieved higher values, with smaller 95% confidence intervals. The mean percentage agreement was lowest for complex hyperplasia and for atypical hyperplasia. For distinguishing cyclical endometrium versus hyperplasia, the useful histologic feature was glandular crowding. For hyperplasia versus atypical hyperplasia and for hyperplasia versus endometrioid neoplasia, the useful features were nuclear enlargement, nuclear pleomorphism, vesicular chromatin, and nucleoli, but of these, only nuclear pleomorphism achieved substantial mean intraobserver and interobserver agreements. For discriminating atypical hyperplasia from well-differentiated adenocarcinoma, the only useful feature was stromal alterations, which achieved only fair mean intraobserver and interobserver agreements. In summary, in endo...

Reproducibility of the diagnosis of atypical endometrial hyperplasia

“…By using multivariable logistic regression analysis, Kendall et al discovered that for most pathologists in their study, only gland crowding was significantly associated with diagnosis of complex hyperplasia, and only the presence of nucleoli was significantly associated with diagnosis of cytologic atypia. Interestingly, Bergeron et al 14 found that gland crowding was the most useful feature to distinguish hyperplasia from cycling endometrium, whereas nuclear pleomorphism was most significant in classifying a lesion as atypical hyperplasia. Three studies addressing the reproducibility of the ISGP/World Health Organization (WHO) classification of endometrial hyperplasia have been published during the past 7 years.…”

“…In contrast, interobserver agreement was highly variable, with almost perfect agreement for the diagnosis of proliferative endometrium or well differentiated adenocarcinoma, substantial for simple hyperplasia, moderate for complex nonatypical and atypical hyperplasia, but only slight for simple atypical hyperplasia. Bergeron et al 14 assessed reproducibility of the classification of 56 cases of endometrial hyperplasia by 5 expert European gynecologic pathologists. Intraobserver agreement was moderate, and interobserver agreement was fair to moderate.…”

Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis

“…This has been cited by a European group as one justification to contract biopsy diagnosis of premalignant and well-differentiated carcinoma into a single category. 19 The EIN schema continues to maintain adenocarcinoma as an entity separate from premalignant disease (EIN) because these may be treated differently in the United States, especially when EIN presents in women wishing to maintain fertility. Management of EIN is quite similar to that previously offered to women with an atypical hyperplasia diagnosis, and this may include an option in some cases for hormonal therapy with progestins and careful follow-up surveillance.…”

Significance of Concurrent Endometrial Cancer in Women With a Preoperative Diagnosis of Atypical Endometrial Hyperplasia

“…10 A high degree of intra-observer and interobserver variability is also found in other expert pathology review panels specifically examining the reproducibility of the AEH diagnosis. [20][21][22] Recent advances in molecular biology have led to the identification of biomarkers that can be used to allow accurate identification of high risk endometrial carcinomas preoperatively. 23,24 Biomarkers that can assist pathologists in distinguishing between endometrial cancer, atypical endometrial hyperplasia, and benign forms of hyperplasia (simple hyperplasia and complex hyperplasia without atypia) have also been found.…”