Disagreement of histopathological diagnosis of different pathologists in ovarian tumors-with some theoretical considerations.

Microscopical sections of forty-nine ovarian tumors have been assessed as benign, borderline or malignant by four different pathologists, who were unaware of the FIGO stage and clinical follow-up of each patient and each others' diagnosis. There was absolute agreement in 37 cases (75.5%), and disagreement in 12 cases (24.5%). The majority of the disagreements involved borderline-malignant differences. If one of the pathologists did disagree with the other three (in 9 cases, or 18%), there is no correlation between disagreement and histopathological experience. In three cases (6.5%) two pathologists did disagree with the other two. It is concluded that in pathology, objective reproducible and if possible, quantitative techniques should be used instead of subjective grading methods. The probability of the diagnosis should be expressed in a numerical way.

Quantitative, microscopical, computer-aided diagnosis of endometrial hyperplasia or carcinoma in individual patients.

There are many significant differences, but also considerable overlap between the quantitative histopathological features of mild and marked atypical endometrial hyperplasias and well and moderately differentiated carcinomas, thus preventing its application to individual patient care. To try to overcome this problem, a classification rule for the diagnosis in individual patients, using discriminant analysis has been developed. Utilizing nine quantitative features, all the above four groups can be adequately separated. None of the carcinomas was misclassified as hyperplasia, and only one case of marked atypical hyperplasia was erroneously classified as well differentiated carcinoma, but with a probability of carcinoma 0.75, hyperplasia 0.25. By contrast, the classification probabilities of all the confirmed carcinomas exceeded 0.90. Therefore, using 0.90 as a classification level ('threshold'), a reliable rule is obtained. A slightly more simple classification rule distinguishes between all the hyperplasias and all the carcinomas. In this way, all the cases of the test set were correctly classified. The classification rules can be used to select patients with benign disease for hormone therapy (Kistner 1973) as an alternative to hysterectomy, and can be programmed in an inexpensive microcomputer, The quantitative techniques are relatively easy, and are capable of being performed in most histopathological laboratories.

Adenocarcinoma in situ of the cervix: an underdiagnosed lesion.

Although invasive adenocarcinoma of the cervix constitutes 5--15% of all cervical cancers, the in situ counterpart is underrepresented in the published series of percursor lesions of cervical cancer. Moreover, no cases are known to have been published in which in situ adenocarcinoma preceded invasive cancer. Partly, this can be explained by the fact that in situ adenocarcinoma is an underdiagnosed lesion. In a series of 52 cases of adenocarcinoma of the uterine cervix, 18 "negative" endocervical biopsies, taken 3--7 years prior to the clinical presentation of cancer, were available for study. In five of these cases, areas of adenocarcinoma in situ were found. The quantitative parameters of these "missed" adenocarcinomas in situ and adenocarcinomas in situ adjacent to invasive cancer were the same. The in situ lesions differed significantly from benign endocervical epithelium. This study strongly suggests that these lesions may progress to invasive cancer. With the acquired information on the quantitative features of adenocarcinoma in situ cells, the most significant criteria for routine diagnostic practice can be identified.

Quantitation of borderline and malignant mucinous ovarian tumours.

Discrimination between borderline and malignant mucinous ovarian tumours is a well-known diagnostic problem. In order to obtain objective reproducible and consistent features for differential diagnosis, 32 quantitative microscopical features were assessed in 10 benign, 10 borderline and 22 malignant mucinous ovarian tumours. There were many significant differences between the three groups, but using multivariate analysis there was 93% agreement between the histopathological assessment of these sections and the qualitative analyses. The following features were useful in the quantitative classification: the mean area, the mean perimeter and the mean of short axis of the nucleus; the volume percentage of the epithelium; the mitotic activity. In three cases, there was a difference between the original histopathological and computer classification. It was debatable whether the original diagnosis was correct, and therefore, all the cases were independently reassessed blind by three pathologists. Their diagnoses lend strong support to the computer classification in two of the three cases. The computer classification seems therefore to be even better than 93%. The present quantitative techniques are inexpensive, relatively easy to use, and, we believe, have a useful place in diagnostic histopathology.