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

Abstract

Cervical intraepithelial neoplasia is a premalignant (dysplastic) lesion that is characterized by abnormal cellular proliferation, maturation and nuclear atypia. The intraepithelial distribution, density, and nature (typical or atypical) of mitotic figures are routinely utilized diagnostic criteria to grade dysplasia and to distinguish highgrade dysplasia from potential histologic mimics such as transitional metaplasia, atrophy or immature squamous metaplasia. In this study, we evaluated the total mitotic indices of the cervical epithelia in hysterectomy specimens from patients with and without dysplastic lesions and investigated a possible relationship between mitotic index and hormonal status, using the endometrial maturation phase as a surrogate indicator of the latter. Two hundred seventy-four cervices from hysterectomy specimens (135 cases without dysplasia, 33, 35 and 71 cases with grades 1, 2 and 3 cervical intraepithelial neoplasia, respectively) were analyzed. A cervical mitotic index (total mitotic figures/10 high-power fields in the most proliferative area) was determined for each case. The endometrium in each case was classified into atrophic, early proliferative, late proliferative and secretory. For all three dysplasia grades, cases in the proliferative endometrium group always had a higher average mitotic index than those in the secretory and atrophic endometrium groups; this observation also held true for the benign cases. Furthermore, in all three dysplasia grades, the average mitotic index was always lowest in the atrophic endometrium group. Although the mitotic index showed expected patterns of increases with increasing dysplasia grades for most of the endometrial phases, this was not a universal finding. Notably, the average mitotic index for our cervical intraepithelial neoplasia 1 cases with late proliferative endometrium was higher than our cervical intraepithelial neoplasia 2 cases with secretory and atrophic endometrium. It is concluded that hormonal status, as reflected in endometrial maturation, can significantly affect the mitotic index of dysplastic squamous epithelium of the uterine cervix. Our findings confirm that the pathologic grading of dysplasia, especially in equivocal cases such as in metaplastic squamous epithelium, should not be solely dependent on the finding mitoses in the cervical squamous epithelium. The full composite of histopathologic features should form the basis for this determination. The ectocervical epithelium, as does squamous epithelium at other anatomic locations, continuously undergoes an organized program of maturation and differentiation from the basal to the superficial layers, with morphologic correlates of a progressive decrease in nuclear size, nuclear/cytoplasmic ratio and a progressive increase in nuclear chromatin density, cytoplasmic size and cytoplasmic glycogen of constituent cells.

Clinicopathological correlation of uterine cervical lesions with focus on premalignant and malignant lesions

“…Thus, the goal of cervical cancer prevention program is to detect and treat all committed cancer precursors before invasion develops. 9,10 Mean age of patient in present study of CIN 1 was 43.5 years, CIN 2 was 48 years, CIN 3 was 43.4 years, Invasive squamous cell carcinoma was 53.97 years and adenocarcinoma was 72 years which correlates with the mean ages observed by Gupta M et al and Fadare O et al 1,11 A total 11 cases of CIN were graded CIN 1 (2 cases: 18.18%), CIN2 (1 case; 9.09%) and CIN3; 72.7%). However the study of Gupta M et al showed out of 36 cases, CIN 1 was36.1%, CIN 2 was 33.3%, and CIN 3was 30.6%.…”

The Early Histological Effects of Intravesical Instillation of Platelet-Rich Plasma in Cystitis Models

“…The average mitotic index was calculated as the average number of mitotic figures per 10 fields of urothelium with ×400 magnification [8]. …”

“…The quantification of PCNA-positive cells was accomplished by counting the number of PCNA-positive nuclei observed in the microscopic fields while counting 100 cells to determine the labeling index. The proliferation index was calculated as the number of PCNA-labeled mitotic cells divided by the total number of cells counted (labeled cells/100 cells) [8]. …”