The existence of a precursor to typical invasive endometrial adenocarcinoma has been proposed for more than 100 years (50), but its histological characteristics and classification
have been disputed throughout its history. These debates reflect at least four features related to the endometrium. First, it is a highly dynamic tissue the histological appearance of which changes markedly throughout reproductive life and the menstrual cycle each month. Second, the precursor lesion cannot be examined without at least partial removal. Third, the lesions examined may represent either a physiological response to hyperestrinism (hyperplasia) or a selective clonal proliferation (neoplasia). Fourth, the endometrial glands exist as multiple units within a cellular stroma. Unlike the cervix, a basement membrane does not delineate in-situ from invasive lesions. Consequently, even today, the earliest features of invasion have yet to be defined.
In recent years, it has also become evident that there are probably two major categories of endometrial adenocarcinoma with differing etiology, pathogenesis, biological behavior, and response to therapy. Their precursor lesions also appear to be histologi-cally and biologically distinct, and they will be considered as separate entities— endometrial hyperplasia and endometrial intraepithelial carcinoma (51).
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