Atypical mitotic figures and the mitotic index in cervical intraepithelial neoplasia

Abstract

We surveyed cervical intraepithelial neoplasia (CIN) to quantify the proliferation rate and the presence of normal and atypical mitotic figures. In the cervical tissue specimens of 127 women with CIN, the area with the highest cell proliferation was identified and, at that site, the proliferation rate was assessed by calculating the mitotic index (MI). Lesions with an MI < 2 were not considered further. In the area with the highest proliferation rate, 228 mitoses were classified into one of the following groups: normal mitotic figures (NMFs), lag-type mitoses (OLTMs) comprising three group metaphases (3GMs), two group metaphases (2GMs) and other lag-type mitoses (LTMs), multipolar mitoses (MPMs) comprising tripolar mitoses (3PMs) and quadripolar mitoses (4PMs), and other atypical mitotic figures (OAMFs). The median value of the MI increased significantly from 3 in CIN I through 4 in CIN II to 9 in CIN III (P < 0.001). The occurrence of the different LTMs was mutually correlated. The frequency of LTMs increased significantly with increasing CIN grade (P < 0.001), whereas the frequency of NMFs decreased significantly with increasing CIN grade (P < 0.001). The frequency of OAMFs was not related to CIN grade (P = 0.94). MPMs were present in low numbers in a minority of the lesions. Spearman's rank correlation coefficient (with 95% confidence limits) between the MI and the number of LTMs, OAMFs and NMFs was 0.66 (0.53; 0.75), -0.14 (-0.32; 0.05) and -0.51 (-0.63; -0.35), respectively. Increasing CIN grade is associated with increasing MI, increasing numbers of LTMs, and decreasing numbers of NMFs. MPMs are very rare events in CIN. The abundant presence of OAMFs seems to be independent of CIN grade and MI.

Mutagenicity of furan in female Big Blue B6C3F1 mice

“…The detection of DNA strand-breaks in splenocytes following oral exposure of mice to carcinogenic doses of furan required cell division [26]. We observed atypical mitotic figures with some degree of abnormal arrangement of chromosomes and spindle fibers, such as lag-type mitosis with non-attached condensed chromatin, multipolar mitoses with atypical configuration of the equatorial plate, and hollow metaphase mitoses, as described previously [53,54]. The presence of atypical mitotic figures in hepatocytes exposed to the 6-week treatment regimen (Fig.…”

Variations of mitotic index in normal and dysplastic squamous epithelium of the uterine cervix as a function of endometrial maturation

“…As previously noted, the intraepithelial distribution, density, nature (typical or atypical) of mitotic figures have emerged as important pathologic criteria for distinguishing low-grade cervical intraepithelial neoplasia from high-grade cervical intraepithelial neoplasia and for distinguishing high-grade cervical intraepithelial neoplasia from potential histologic mimics such as transitional metaplasia, atrophy or immature squamous metaplasia. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Mitotic figures in low-grade cervical intraepithelial neoplasia should be confined to basal third of the epithelium and should not be numerous and should only rarely be atypical. 37 High-grade cervical intraepithelial neoplasia, in contrast, may show numerous mitoses including numerous abnormal forms throughout the epithelium.…”

“…[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Compared to the endometrium and vaginal epithelium, where marked variations in the estrogen receptor (ER) content occur during the menstrual cycle, much less cyclic variation of ER expression occurs in the cervical lining. [20][21][22] Nonetheless, it has long been recognized that cervical squamous epithelial cells contain sex-steroid receptors and hence, their proliferation and differentiation are influenced, to some extent, by the menstrual cycle and/ or sex-steroid hormonal levels.…”

Poor agreement in recognition of abnormal mitoses: requirement for standardized and robust definitions

“…Some authors have made a very careful analysis of the mitotic figure with consequent detailed definitions of normality and abnormality 18–20 . However, the relevance of these studies for routine practice may be limited in that they were carried out under research conditions, were scored by one investigator in each case (so the issue of interobserver variability was not addressed).…”