Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry

Management of endometrial precancers is compromised by longstanding debate over the natural history of endometrial hyperplasias, like cancers, are phe notypically monoclonal is useful in recognizing biological precancers, A cl onal analysis has been undertaken of a series of 93 endometrial tissues and their morphology has been evaluated by subjective diagnostic classificatio n and computerized morphometric analysis. A pathologist's diagnosis of atyp ical endometrial hyperplasia was highly associated with monoclonal growth. Both microsatellite-stable and microsatellite-unstable precancers were clas sified as atypical hyperplasias, indicating overlapping morphologies for th ese two groups, Diagnosis of non-atypical endometrial hyperplasias was not reproducible and identified a group of lesions equally likely to be monoclo nal as polyclonal, Computerized morphometry resolved these lesions into mon oclonal and polyclonal subgroups with a high degree of accuracy and reprodu cibility, The predictive value of morphometry was dominated by that fractio n of the sample which consisted of stroma (volume percentage stroma), This can be measured manually and used to predict monoclonality when below the t hreshold value of 55%, This study shows that morphometric analysis reproduc ibly and precisely identifies monoclonal endometrial precancers from histol ogical sections. It may serve, furthermore, to classify accurately lesions judged by pathologists as indeterminate (non-atypical hyperplasias), The ma terial from this study (available at www.endometrium.org from March 1, 2000 ) and precisely defined architectural diagnostic criteria provide new tools for diagnostic standardization of endometrial precancers, Copyright (C) 20 00 John Wiley & Sons, Ltd.