Karyometry in atypical endometrial hyperplasia: A Gynecologic Oncology Group study

Objectives: Treatment 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). Methods: 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. Results: 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 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. Conclusions: AEH 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.