Simple hyperplasia of the endometrium: an evaluation of proliferative activity by Ki-67 immunostaining

As endometrial hyperplasia has been characterized over the past 100 years, some investigators have questioned the hyperplastic nature of nonatrophic cystic glands associated with an increase in gland-to-stroma ratio, which is currently considered to represent simple endometrial hyperplasia. In the current study, the proliferative activity of simple endometrial hyperplasia was examined using an antibody to Ki-67 protein, a well-established marker of proliferative activity, and compared with the results of activity in inactive/atrophic endometrium, proliferative endometrium, and other forms of endometrial hyperplasia. In an evaluation of 68 endometrial biopsy specimens showing 110 histologic patterns, the mean Ki-67 index (percentage of Ki-67 positive nuclei) was 2.8% in inactive/atrophic endometrium, 23.2% in proliferative endometrium, 9.8% in simple hyperplasia, 12.7% in complex hyperplasia, and 10% in atypical complex hyperplasia. In simple hyperplasias, the mean Ki-67 index was 3.9% in dilated glands without infolding or outbranching, 14.6% in nondilated glands showing outbranching or slight crowding, and 6.9% in dilated glands with infolding or outbranching. Ki-67 indices for dilated glands were most similar, therefore, to atrophic/inactive endometrium with no statistical significant difference in the percentage of these cells staining between these two groups. In contrast, statistically significant differences were seen in staining between cystic patterns of simple hyperplasia and proliferative endometrium, simple hyperplasia showing outbranching and/or slight crowding but no dilation, complex hyperplasia, and atypical hyperplasia. The findings in the current study suggest that nonatrophic cystic glands with an increase in the gland-to-stroma ratio in the endometrium should not be considered a hyperplastic process and in the absence of other findings such as excessive bleeding or coexistent noncystic simple hyperplasia, treatment with progestin therapy, a widely used practice, is unnecessary. As discussed, the findings also suggest that these cystic forms of simple hyperplasia are precursors of cystic atrophies. Confirmation of these results on a larger population by a different research team appears desirable.