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SUMMARY The inter-and intra-observer reproducibility of three grading systems for breast cancer has been analysed: those of the World Health Organisation, of Black, and of Hartveit. In addition, the components forming the basis of these grading systems were analysed separately with regard to reproducibility and interrelationship. In this analysis, degree of differentiation was also included as a parameter.The grading systems of WHO and of Black gave a stratification of the material into three categories of tumours, but that of Hartveit did not. All three systems had a low inter-and intra-observer reproducibility.Truncated component analysis indicated that the grading systems of WHO and of Black are closely related to each other and to the 'nuclear lobulation' component of Hartveit's system. The components 'pleomorphism', 'mitotic frequency', and 'hyperchromasia' of the WHO system were closely interrelated. Descriptors such as 'differentiation' and 'tubule formation' were interrelated but acted in a different direction from the others.It is surprising that few of the many suggestions for the classification and grading of breast carcinoma have been analysed with regard to intra-and interobserver reproducibility. This paper analyses the subjective grading of breast cancer suggested by the World Health Organisation (WHO) (Bloom and Richardson, 1957;Scarff and Torloni, 1968), Speer (1957), andHartveit (1971) in order to determine: (a) intra-and inter-observer reproducibility; and (b) interrelationships between the different parameters forming the basis of these grading systems.Any valid grading of breast cancer must use uniform diagnostic criteria which can be applied consistently by individual observers. Moreover, the grading should correlate with survival.Some authors who have analysed the significance of nuclear atypia have not confirmed that it is important in regard to the prognosis (Kister et al., 1969). Others have expressed scepticism concerning the value of prognosis based on histological features Received for publication 21 February 1978 Revised version received 22 March 1979 in connection with breast cancer (Evans, 1933;Warren et al., 1933;Richards, 1948;Lewison et al., 1953;Ackerman, 1954; Sternberg, 1958). Most grading systems have considered the nuclear morphology of the tumour cell population as important, but in some, other factors have also been evaluated such as histological structure, manner of growth, and extent of lymphocytic infiltration.The concept that the nuclear morphology of tumour cells could have implications ior their biological behaviour is due to von Hansemann (1893), and his studies have been the starting point for many grading systems of carcinoma. He considered the mitotic rate in the tumour and the occurrence of abnormal mitoses as important characteristics (Hansemann, 1892) and concluded (Hansemann, 1902) that the higher the degree of anaplasia, the greater the tendency of the tumour to metastasise. Broders (1940) introduced a grading system for squamous carcinoma of the lip a...

The growth rate of Lewis lung carcinoma, either as primary subcutaneous tumors or as spontaneous lung metastases, decreases with increasing age or mass. The length of the median cell cycle of the primary tumors increased from 17.6 hr at Day 5 to 25.9 hr at Day 21 with a concomitant increase in experimental doubling time from 2.5 to 9.6 days. The length of the median cell cycle of the metastatic lung nodules was 15.2 hr in the mice bearing 21‐day primary tumors. Two mathematical models were used to analyse the per cent labeled mitoses data and the results are given for comparison. The labeling index of the primary tumors decreased in a nearly linear manner with time postimplant and the percentage of cells labeled in the metastatic nodules was higher than in the primary tumors when measured in the same hosts.

A prescreening instrument for cervical smears using computerized image processing and pattern recognition techniques requires that single cells in the specimen can be automatically isolated and analyzed. This paper describes a dual wavelength method for automatic isolation of the cytoplasm and nuclei of cells. Density-oriented, shape-oriented and texture-oriented parameters were calculated and evaluated for more than 600 cells. It is shown that the computer can be taught to distinguish between normal and atypical cells with an accuracy of ca. 97%, while human classification reproducibility is ca. 95%. In addition, an attempt to assign a measure of atypia to individual cells is described.

A major problem in the automation of cervical cytology screening is the segmentation of cell images. This paper presents the present status of the work on that problem at the University of Uppsala. A dual resolution system is used. Suspect malignant cells are located at 4 mu resolution. Each such cell is rescanned at 0.5 mu resolution at two different wavelengths, 530 and 570 nm. The nucleus and the cytoplasm are isolated each by two independent methods. For the nucleus adaptive thresholding in the histogram of the 570 nm image and a contouring in a radially transformed version of that image is used. For the cytoplasm a two dimensional thresholding in the 2D histogram and a contouring in a radially transformed version of the 530 nm image is used. If the two nuclear masks agree the surrounding area is checked for disturbing objects. If also the cytoplasm masks agree and are without disturbing objects the whole cell is accepted. The result of the cytoplasm masks agree and are without disturbing objects the whole cell is accepted. The result of the segmentation is thus three categories; free cells, free nuclei and rejected objects. The shape of the objects belonging to the former two categories is checked and irregularly shaped ones are rejected as probably consisting of several overlapping nuclei. Cells passing also this test are classified as normal or malignant. The experience from using this algorithm is discussed and areas for further research are pointed out.