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

This study was designed to assess intraobserver and interobserver agreement in the diagnosis of 56 endometrial specimens by five European expert gynec ologic pathologists using the WHO classification and to establish which his tologic features are significantly associated with each classification cate gory. The seven categories were simple hyperplasia, complex hyperplasia, at ypical hyperplasia, well-differentiated adenocarcinoma, proliferative endom etria, secretory endometria, and other. Slides were reviewed twice for diag nosis, with accompanying evaluation of a checklist of histologic features. These seven categories were eventually reduced to four and three for the pu rposes of data analysis. The four modified diagnostic categories consisted of hyperplasia (previously simple hyperplasia and complex hyperplasia), aty pical hyperplasia, well-differentiated adenocarcinoma, and cyclical endomet rium (previously proliferative, secretory, and other). The three diagnostic categories consisted of hyperplasia, endometrioid neoplasia (previously at ypical hyperplasia and well-differentiated adenocarcinoma), and cyclical en dometrium. Intraobserver and interobserver agreement was assessed using the percentage agreement and kappa statistics. The associations among the vari ous histologic features and diagnoses was analyzed using multiple logistic regression to identify those features that were useful for distinguishing d iagnostic categories. When using seven categories, kappa values ranged from 0.53 to 0.73 (percentage agreement, 61-79%) and from 0.33 to 0.59 (percent age agreement, 43-63%) for intraobserver and intreobserver agreement, respe ctively. 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 a greement, 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 categorie s, the mean intraobserver and intraobserver agreements varied less between categories and achieved higher values, with smaller 95% confidence interval s. The mean percentage agreement was lowest for complex hyperplasia and for atypical hyperplasia. For distinguishing cyclical endometrium versus hyper plasia, the useful histologic feature was glandular crowding. For hyperplas ia versus atypical hyperplasia and for hyperplasia versus endometrioid neop lasia, 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 d iscriminating 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 endometrial biopsy or curettage specimens, the lack of agreement in the diagnoses of c omplex hyperplasia and atypical hyperplasia and the lack of reproducibility in the recognition of the histologic feature of stromal alterations to dif ferentiate atypical hyperplasia from well-differentiated adenocarcinoma sug gest that the histologic classification should be simplified by including a combined category for simple and complex hyperplasia, called hyperplasia, and a combined category for atypical hyperplasia and well-differentiated ad enocarcinoma, called endometrioid neoplasia. Diagnoses of hyperplasia and endometrioid neoplasia are highly reproducible between observers from different institutions. Glandular crowding is the b est histologic feature to differentiate cyclical endometrium from hyperplas ia, whereas nuclear pleomorphism is the reproducible cytologic feature to d ifferentiate hyperplasia from endometrioid neoplasia.