Relation of quantitative features of visually normal intermediate cells in cervical intraepithelial neoplasia I and II smears to progression or nonprogression of the lesion.

The relationship between the quantitative features extracted from digitized images of visually normal intermediate cells in cervical intraepithelial neoplasia (CIN) I and II smears and the subsequent follow-up diagnosis was studied. Using the ISPAHAN interactive system of pattern recognition, the average rate of correct classification of progressive or nonprogressive lesions was 80% at the specimen level. It is concluded that additional diagnostic information regarding the probability of progression of CIN I and II lesions may be obtained by studying the microphotometric features of visually normal intermediate cells in the cervical smears. Significant differences were found between intermediate cells close to obviously dysplastic cells and those at a distance. The implication of this finding and the problems involved in the selection of the cells are briefly discussed.

The accuracy of colposcopically directed biopsy in diagnosis of CIN.

During the last decade there has been an increasing interest in the use of the colposcope. A quality-control study for the evaluation and understanding of the limitations of cytology and colposcopy in our clinic is presented. The results in 132 patients are analysed and compared to previous reports from the literature. Cytologic results correlated with the histological diagnosis only in 47% of the patients. Colposcopically directed biopsies were accurate in 88.8% when the entire squamocolumnar junction was visualized. The accuracy of the directed biopsies in patients with unsatisfactory colposcopy was 58.3%. In the presence of a Gardnerella vaginalis cervicitis the colposcopic accuracy decreased to 70.9%.

Masking effect of hormonal contraceptives on discriminating quantitative features of visually normal intermediate cells in positive and negative cervical smears.

In quantitative studies of visually normal intermediate cells in smears from patients with cervical neoplasia, the contraceptive status of the patients has not previously been taken into account. In this study cervical smears from 151 patients with cervical intraepithelial neoplasia (CIN) III or invasive carcinoma and from 360 normal controls were grouped according to week of menstrual or pill cycle and mode of hormonal contraception. The nuclear-cytoplasmic (N/C) ratio of visually normal intermediate cells in smears from patients with neoplasia was significantly different from that of the normal controls (P less than .001). Based on nuclear area and N/C ratio, the percentages of intermediate cells correctly classified as having come from positive or negative smears were significantly better in women with ovulatory cycles (non-users) than in women using hormonal contraceptives (P less than .025). It is concluded that hormonal contraceptives can mask the salient quantitative features of visually normal intermediate cells from patients with CIN and the contraceptive status thus has to be taken into account in such studies.

PIP: The nuclear area and nucleus to cytoplasmic (N/C) ratio were measured in visually normal intermediate cells of cervical smears from 151 women with cervical intraepithelial neoplasia (CIN III) or invasive carcinoma, and from 360 normal controls, and the effect of timing of the menstrual cycle, or pill cycle or Depo-Provera contraception was determined. Morphometry was done on visually normal, polygonal intermediate cells without signs of human papilloma virus infection, with a graphic tablet and cursor under 40x oil immersion, and data were handled by microcomputer. The N/C ratio from abnormal smears taken together differed significantly from normals (p.001), but this difference was not apparent taking individual diagnoses separately. The percentages of cells correctly classified as positive or negative were significantly better in cycling women than in those using hormonal contraception (p.025), especially so in ovulatory cycle week II. The mean percentage of correct classification of intermediate cells as coming from positive or negative smears was low in women using any type of hormonal contraception. When hormonal contraception and neoplasia were both present, the increase in N/C ratio was less than expected in some cases. Thus hormonal contraceptives can mask the quantitative features of visually normal intermediate cells from patients with cervical intraepithelial neoplasia, and their contraceptive status needs to be taken into account.

Predictive value of a positive endocervical curettage in diagnosis and treatment of CIN.

Predictive values of endocervical curettage (ECC) in the investigation of patients with abnormal Pap-smears were calculated with regard to a second histological diagnosis and with regard to results of conservative treatment of CIN. By using the combined follow up data of all 290 patients with colposcopically directed biopsies and ECC, the predictive value of a positive ECC for invasive cancer in patients with satisfactory colposcopy was 2%, and for unsatisfactory colposcopy 15%. Predictive value of a negative ECC was 100% in patients with satisfactory colposcopy, and 98% for unsatisfactory colposcopy. It is concluded that ECC should be used routinely in the investigation of patients with abnormal Pap smears. However, a positive ECC is not considered an absolute contraindication to conservative treatment, provided that colposcopy is satisfactory, that there is no suspicion of invasive cancer, and that a strict follow-up scheme can be maintained during the first year.

Predictive value of the abnormal PAP smear: a retrospective analysis of error rates.

The validity and performance of the Papanicolaou (PAP) smear, as a diagnostic test, was retrospectively analysed in 806 patients who presented with at least one abnormal smear. Histological tissue examination was available in 620 of these patients. It is shown that the definition of errors, selection criteria of smears, time intervals between examinations, definition of 'disease' and the values separating 'positive' and negative' test results must be clearly defined before comparison with other published error rates is possible. Consequently, a standardized method of reporting is recommended. Exact agreement between the results of cytology and histology was poor. The use of sensitivity, specificity and predictive values is preferred, but it is shown that precise definitions are still necessary. The optimal choice of the value separating positive and negative test results, i.e., the choice between an expectant and an active management of patients, must be tailored to the anticipated prevalence of the disease.

The predictive value of immature dysplastic cells in CIN I and II smears.

This paper reports the predictive value of a subclassification of cervical intraepithelial neoplasm grade I and II smears. The follow-up period was a maximum of 1 yr. The subclassification was based on the presence of immature dysplastic cells ("IDC present") in the original smear. In 267 cases, these immature dysplastic cells were morphometrically defined. In an additional group of 14 cases, the immature dysplastic cells were exclusively in dense cell groupings which were unsuitable for morphometrical analysis; thus, only visual classification was possible. The predictive value negative (follow-up with negative findings or CIN I or II) of this method was 1.00. The predictive value positive (follow-up with CIN III) was 0.14. The sensitivity was 0.98 and the specificity 0.57. On the basis of this subclassification, cases that should be directly referred for further investigation can be selected. It is justifiable to follow-up the cases that are "IDC absent" with cytology alone. The described method is relatively simple, and can be performed in routine diagnostic laboratories. It is very valuable in settings where most of the initial smears and the follow-up are in the hands of general practitioners. Using the described method, patients who should be referred to the gynecologist for colposcopy and histology can be selected.

Laser or cryotherapy for cervical intraepithelial neoplasia: a randomized study to compare efficacy and side effects.

A randomized study was performed to compare efficacy and side effects of laser and cryotherapy: 51 patients were treated with laser vaporization and 50 patients with cryotherapy. Success rates for laser and cryotherapy were not significantly different. Success rates were significantly related to lesion size. Grade of CIN, positive endocervical curettage, parity, and age at treatment were not found to be related. Vaginal discharge, both in duration and amount, was significantly less in patients treated with laser vaporization, compared with cryotherapy, but pain and bleeding occurred more often in patients treated with laser vaporization. A brief review of possible sources of bias in comparative studies on laser and cryotherapy is given, indicating the preference for a randomized study. It is concluded that widespread introduction of laser facilities in smaller centers is not justified, because the success rates are not better than those of cryotherapy, and because the advantages of less discharge are outweighed by the high cost.

Fluctuations in quantitative features of intermediate cells in normal cervical smears during the menstrual cycle of ovulating women and contraceptive users.

In this study we report on the variation in nuclear and cytoplasmic size of intermediate cells in normal cervical smears, in relationship to the week of the menstrual cycle and in relationship to the mode of contraception. A total of 18000 cells from 360 different women was studied. A significant difference in nuclear size of intermediate cells in smears from ovulating women not using contraception was found in comparison with intermediate cells in smears from women using contraceptive pills (ANOVA: F(1.312) = 4.98, p less than 0.02). Also a significant difference in the nuclear size of intermediate cells in smears from women using norgestrel- (or levonorgestrel)-containing formulas compared with lynestrenol-containing formulas was found (ANOVA: F(1.232) = 5.82, p less than 0.01). The influence of exogenous and endogenous hormones on cell populations in cervical smears is discussed. It is concluded that in studies on intermediate cells in cervical smears the contraceptive status of the women has to be taken into account.

Clinical significance of 45XX, t(13q14Q) Robertsonian translocation: unexpected triploidy in third abortion of female carrier.

A case report is described of a female t(13q14q) Robertsonian translocation carrier. Her firstborn daughter appeared to be a carrier of the same translocation. Chromosomal investigation of the third of three subsequent spontaneous abortions revealed a triploidy (69XXX). Literature shows discrepancies in the reported abortion rate in the reproductive performance of t(13q14q) carriers. It is concluded that these could in part be explained by heterogenicity of the study groups due to variable presence of other factors known to influence the abortion risk. In our case report treatment for epilepsy, a luteal phase defect and high numbers of spermatozoa in the sperm count of the husband must be considered as contributory factors. It is recommended to perform systematic investigations in all cases of recurrent abortion even when a chromosomal anomaly is found in one of the partners.