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...
In eleven cases thirteen pancreatic islet cell adenomas were found in autopsy material from 1366 adult cases. Ten of the adenomas were solitary, while 3 small adenomas were observed in a single case. Another four possible solitary adenomas were observed, but their identity was uncertain owing to marked fibrosis. All the adenomas contained A-2 (A)-1 cells but no B (B)-1 cells. Nine of them also contained A-1 (D)-1 cells. The majority of cells in the adenomas were A-2 cells or cells which did not stain with any of the techniques used. The 4 possible adenomas contained islet cells (A-1, A-2, B) in different proportions. With one exception the patients with adenomas and possible adenomas were 65 years of age or older, and in some of these cases adenomas or hyperplasias were also found in other endocrine organs. The frequency of gastroduodenal ulcers or scars in the cases with adenoma or possible adenoma did not differ notably from that found in the cases without pancreatic adenomas. Among the cases with pancreatic adenoma and possible adenoma there were 3 patients with maturity onset diabetes mellitus, but otherwise no clinical symptoms of endocrine disturbances were noted.
Background. Amplification of erb‐B2 and myc shows prognostic value in patients with operable breast cancer. Amplification is usually detected in tumor samples remaining after pathologic work‐up, preventing the examination of small tumors. Methods. Tumor imprints that contained low numbers of contaminating normal cells were obtained from small tumors. The prognostic value of erb‐B2 and myc amplification in imprint breast preparations was examined, using the polymerase chain reaction (PCR) to determine gene copy number. Tumor material was obtained from 162 patients with breast cancer operated 1975‐1976. Results. Amplification of erb‐B2 existed in 21% and myc in 16% of the patients. Both erb‐B2 and myc amplification showed prognostic significance in univariate analysis for survival and relapse free survival. In multivariate analysis, erb‐B2 was a significant factor. In small tumors less than 13 mm in greatest dimension, erb‐B2 showed prognostic significance for survival but not for relapse free survival. Conclusions. The use of imprints/PCR allows the detection of gene amplification in breast cancer. The procedure is suitable for the analysis of small tumors and can be used to examine very small tumors, such as those detected mammographically. Cancer 1995;75:2681–7.
The prognostic value of 435 cytochemical, cytometrical, morphological, epidemiological, and clinical variables was analyzed in a prospective study of 179 breast cancer patients followed for five years after mastectomy. A variable reduction was obtained by first selecting variables correlated with recurrence rate in direct (Student's t test) or correlation analysis with consideration of the type of variable analyzed (nominal, interval, ordinal). The 20 variables most strongly correlated with recurrence were analyzed by logistic stepwise regression analysis in order to find out what combination of variables had most discriminatory power in predicting recurrence. It was found that axillary metastization as such was correlated with a combination of variables describing mitotic frequency, size of primary tumor and differentiation of the primary tumor (average cluster size in fine‐needle biopsies). It was also found that there was a strong time dependency in the predictive power of the variables, so that different variable combinations predicted the recurrence rate during the first 2.5 year period (size of axillary metastases and primary tumor, number of lymphocytes around the tumor, mitotic frequency, and degree of differentiation) compared with the second 2.5 year period (variance of DNA content among tumor cell nuclei, number of lymphocytes around the tumor, occurrence of multiple tumors in the operated breast and occurrence of breast cancer among relatives). While other factors previously shown to be correlated with risk of recurrence were also found to be positively correlated here, they were neither as highly predictive as, nor did they increase the predictive value of the above mentioned combined variables. The current study strongly emphasizes that, at the present time, studies of recurrence prediction in human breast cancer should be based on an optimal combination of a number of variables which, independently, influence the prognosis. Further, the current study indicates that prerequisite methods for predicting breast cancer recurrence exist today.
Ultrasonic examination of the parathyroid glands was performed in 55 consecutive patients with subsequent surgically verified hyperparathyroidism. Ultrasound located 26 of 37 parathyroid adenomas in the neck. Eleven of 48 hyperplastic glands in the neck were visualized by ultrasound in 16 patients with primary or uremic hyperplasia. A parathyroid adenoma was revealed in all 3 patients with hypercalcemic crisis and in all 5 patients with an adenoma and a previously unsuccessful exploration of the neck. Two of 3 glands were visualized by ultrasound prior to secondary explorations in 3 patients with primary hyperplasia associated with the multiple endocrine neoplasia syndrome type I. Undetected parathyroid glands were generally small and located in regions of the neck difficult to detect by ultrasound. It was often difficult to unequivocally establish that identified lesions represented a parathyroid gland. Nodules and cysts of the thyroid and lymph nodes were misinterpreted for parathyroid lesions. Ultrasonically guided fine-needle biopsies were obtained from 8 parathyroid lesions, 7 thyroid tumors, and 2 lymph nodes. By cytologic examination these tissues could be discriminated after a differential staining of the aspirates.
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