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Biomedical subjects

M E Boon

Publications and source records attributed to M E Boon.

At least 145 records · Page 8Linked to original sources

Histologic distinction between malignant mesothelioma, benign pleural lesion and carcinoma metastasis. Evaluation of the application of morphometry combined with histochemistry and immunostaining.

Thirty men and 7 women with malignant mesothelioma seen at the Free University Hospital from 1st January 1960 until 1st July 1981 were reviewed. The histological, histochemical and morphometrical findings are reported. These findings are compared with 25 cases of pleural metastatic carcinoma and 25 cases of reactive pleural lesions. Fourty-nine percent of malignant mesotheliomas produced hyaluronic acid, however all cases of pleural metastatic carcinomas failed to produce this substance. All cases of malignant mesothelioma were D-PAS negative while 15 cases of pleural metastatic carcinoma showed reactivity to D-PAS. All cases of malignant mesothelioma and 9 cases of metastases were CEA negative. To distinguish malignant mesothelioma from metastases it is advisable to perform the D-PAS staining first. If it is negative mesothelioma can be confirmed by showing hyaluronic acid activity. A positive CEA staining rules out mesothelioma. In our study it was shown that with these methods 18 of 37 mesotheliomas could be identified with certainty, and 22 of the 25 carcinoma metastases. Morphometrically the malignant mesotheliomas could not be distinguished from the metastases, however the reactive pleural lesions had smaller nuclei than the malignant cells with mean values below 30 mu2. In the malignant cases these values had a range from 36 to 101 mu2. In distinguishing between reactive pleural lesions and malignant mesothelioma the production of hyaluronic acid points to the malignant character of the lesion. Thus histochemistry and immunostaining are important in the distinction of malignant mesothelioma from metastases, while the value of morphometry lies mainly in the seperation of reactive lesions from malignant mesothelioma.

Aged↗

Estrogen receptors in human breast cancer. II. Correlation between the histochemical method and biochemical assay.

The present study defines criteria for determining the presence of estrogen-receptors in human breast carcinomas demonstrated by a histochemical assay using 17 beta-estradiol-carboxy-methyl-oxim-bovine serum albumen-FITC. The criteria were: 1) the percentage of cells showing fluorescence; 2) the intensity of the fluorescence observed, and 3) the percentage of epithelial structures in tissue specimens. Using these predefined criteria in 132 human breast carcinomas as 91.6% agreement was found between the results of the histochemical assay and those of the biochemical Charcoal method. The main causes of disagreement (7 of the 11 cases) were sampling errors between the tissue specimens used for the histochemical and biochemical assay, and an insufficient percentage of epithelial structures (less than 15%) to allow biochemical identification of estrogen receptor activity. In the hands of pathologists with experience of the field of histochemistry this histochemical assay may be the method of choice for the assessment of estrogen receptors.

Adult↗

Prognostic indicators in breast cancer--morphometric methods.

Morphometric methods were applied to predict the clinical course of individual patients with breast cancer. Measurement of tumour diameter, assessment of mitotic and cellular indices, and quantitative microscopy of nuclear features were assessed together with nuclear features and histological grades. Of the tumours from 78 patients investigated, 42 had died from metastases within 6.5 years ('non-survivors'), while the other 36 were alive and well without evidence of metastases at the end of the follow-up period (minimum 6.5 years) ('survivors'). If the tumours of the 42 non-survivors are compared with those of 36 survivors, there are many reproducible significant differences, the most important being cellularity index and mitotic activity index, followed by quantitative microscopical nuclear parameters and nuclear and histological grade. Discriminant analysis, of the quantitative microscopical data alone showed 82% of all patients to be correctly classified as survivor or non-survivor. By contrast with the axillary lymph node invasion status alone, or the tumour diameter and axillary lymph node status together, 59% and 64% of the patients were predicted correctly as survivor or non-survivor. With a more realistic statistical approach of discriminant analysis, 78% of the patients were classified correctly with quantitative microscopy, in place of 54% with the axillary lymph node status, 56% with the TNM-system and 64% with a combination of TNM system and nuclear and histological grade. Morphometry thus seems possible to predict the outcome of individual patients more accurately than with the usual staging/grading methods. This technique might therefore prove to be useful in the selection of patients for adjuvant chemotherapy.

Axilla↗

Morphometrical analysis of urothelial cells in voided urine of patients with low grade and high grade bladder tumours.

The morphometric differences between the urothelial cells (wet-fixed Papanicolaoustained) in the voided urine of 2 patients with low grade and high grade bladder tumours were measured. The morphometrical data of this learning set resulted in a cytomorphometrical classification rule, which was applied to a test set of 21 cases with low grade and high grade bladder tumours. The results of the cytomorphometrical classification rule correspond very well with the histomorphometrical classification and the histological grade of the parent tumours. The results indicate that it is feasible to classify bladder tumours using the cytomorphometrical data of the exfoliated urothelial cells alone.

Epithelium↗

Investigation of possible changes in the detection of cervical carcinoma in patients of Dutch general practitioners.

In a series of 430,015 cervical smears made by general practitioners and coming from all regions of the Netherlands in the period 1972-1980, no significant changes were noted in the rates of positive smears (Papanicolaou IV and V). These data are especially relevant in deciding the age limits for the cytology health service programs. Women aged more than 55 years contribute only 5% of the smears made by house doctors: nevertheless, this group had just as many cases of invasive carcinoma as the younger group. Since 1974 there has been an increase in the diagnosis of adenocarcinoma in situ of the endocervix, probably due to better knowledge of the cytologic and histologic criteria of this lesion. The effects of underdiagnosis of this carcinoma precursor are stressed. It is concluded that it is more important at present to concentrate any additional cytological screening on the "forgotten group" of women aged over 55 years and not yet to extend health survey programs to women under 35 years. However, this policy may need to be reviewed if increased rates of preinvasive tumor in the future lead to an earlier average age for invasive tumor.

Adenocarcinoma↗

The implications of subjective recognition of malignant cells in aspirations for the grading of prostatic cancer using cell image analysis.

A pilot study of selective morphometry was performed in smear preparations from fine needle aspirates of six cytologically graded prostatic carcinomas. Given the instruction to select carcinoma cells with large nuclei for measurement, cytotechnologists and a cytopathologist differed in the selection of cells from grade III tumors. The cytotechnologists had discarded large bare atypical nuclei because they assumed that these were degenerated cells. Transmission electron microscopy, using an open-face embedding technique, demonstrated, however, that these cells were not degenerated but were poorly differentiated carcinoma cells that had lost their cytoplasm during smear preparation. It is obviously of great importance for the morphometric discrimination of grade I and grade III carcinomas that such bare atypical nuclei be included in the selections of cells to be measured. Our data indicate that the measurement of 20 selected cells per smear preparation is sufficient for accurate morphometric grading and that such measurements are reproducible.

Biopsy, Needle↗

Computation of preoperative diagnosis probability for follicular adenoma and carcinoma of the thyroid on aspiration smears.

Morphometric analysis of 23 follicular tumors (13 adenomas and 10 carcinomas) and 10 metastatic lesions from follicular thyroid carcinomas resulted in the identification of five significant parameters between the carcinoma and adenoma groups. With a classification rule using these features, the probability of a histologic diagnosis of adenoma versus carcinoma was computed for each case. Using threshold values of probabilities of 0.25 and 0.75, only 1 of the 33 cases was not correctly classified on the cytologic smear alone; the remaining 32 cases were correctly classified. These results indicate that morphometric analysis in follicular tumors of the thyroid may be of great help in individual patient care if used as a selective method by a well-trained cytopathologist.

Adenocarcinoma↗

Computer-aided application of quantitative microscopy in diagnostic pathology.

The quantitative analysis of microscopic images gives objective, consistently reproducible results. The number of applications of such analysis in diagnostic pathology is increasing rapidly. In this chapter, two examples have been given of the development and application of a quantitative microscopic classification rule. Both examples involve admittedly difficult areas of diagnostic pathology, in which considerable disagreement may not only exist among pathologists, but may affect the same pathologist judging the same specimen at different times. These areas are: (1) the discrimination of endometrial hyperplasia from carcinoma, and the grading of endometrial carcinomas; and (2) the preoperative distinction of follicular adenoma from carcinoma of the thyroid in cytologic specimens. With routine use of the classification rule in 148 cases of endometrial hyperplasia or carcinoma received in our laboratory in 1980, with each case judged by one of eight pathologists, there was mild or absolute disagreement in 7.4 percent and 4.7 percent of the cases, respectively (total: 12.1 percent). However, with blind review of one of us (J.B.), there were no absolute and only 3.3 percent mild disagreement. In this series, the quantitative microscopically assigned grades of carcinomas correlated significantly with the depth of invasion in the myometrial wall, whereas the grade routinely indicated by eight pathologists did not. These two facts strongly support the quality and utility of the developed quantitative microscopic rule for classifying endometrial lesions in a diagnostic setting. The rule can also be used to objectively define such endometrial lesions in order to evaluate more accurately their clinical outcome in a prospective study. In the thyroid adenoma cases discussed in the chapter, material from follicular tumors was subjected to quantitative analysis in 1980, again using a classification rule developed in our laboratory. All 10 cases of adenoma were correctly classified, whereas frozen-section diagnosis often gave erroneous or inconclusive results. The quantitative microscopic techniques that we have used are simple, inexpensive, and can be applied in most pathology laboratories. The classification rules can also be used in cases submitted for consultation. The pathologist must use his or her full diagnostic knowledge when applying these techniques. In doing so, he or she will learn that quantitative microscopy has an educative function, automatically results in an increase in the quality of histopathologic work, and supports and sometimes corrects the diagnosis in an objective, consistent way.

Adenocarcinoma↗

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.

Adenocarcinoma↗

Secreting peritoneal mesothelioma. Report of a case with cytological, ultrastructural, morphometric and histological studies.

A 29 year old woman, living in an area with a high level of asbestos exposure, developed the clinical features of peritoneal mesothelioma. The quantitative cytological features differed from those of other mesotheliomas described in the literature in that the tumor cells had a large amount of vacuolated cytoplasm and an extremely low N/C ratio, resulting in a "benign" appearance. The ultrastructural study provided evidence for the production and accumulation of secretory products (mucolipids) by the tumor cells. Treatment with chemotherapy and radiation resulted in temporary remission, lasting for 20 months. However the patient then developed pulmonary involvement of the carcinomatosa a form and pleural tumors. The cytological pattern and the morphometric features of the metastatic floating malignant mesothelial cells in the pleural fluid closely resembled those of the primary peritoneal tumor. This case appears to be an example of secretory peritoneal mesothelioma with a bad prognosis, not withstanding the well-differentiated appearance of the tumor cells.

Adult↗

Fluorescence-displacement from the median eminence towards the arcuate nucleus at puberty.

The transition from infancy to adulthood is characterized by a sequence of events which are not yet fully understood. Hormonal changes influencing neuronal circuits in various hypothalamic area are--at least in part--held responsible. Using catecholamine fluorescence techniques in rats it has been found that a displacement of dopaminergic cells can be seen; the fluorescence activity shifting from the median eminence at day 20 after birth to the dorsolateral part of the arcuate nucleus around day 45 after birth, as is the case for catalase positive cells in these areas. It is concluded that the displacement of at least two populations of cells from the median eminence to the arcuate nucleus runs parallel to the onset of puberty. The relation of this shift in respect to the suprachiasmatic-preoptic control will be discussed.

Aging↗

The prognostic significance of morphometry in T1 bladder tumours.

Only 3% of patients with T1 bladder tumours die of bladder carcinoma within 5 years (Williams, Hammonds & Saunders 1977), therefore these patients are initially treated conservatively. There would however be benefits from being able to predict which patients should be treated more aggressively. Morphometry was applied to quantitate characteristic microscopical features of the removed T1 tumours in 16 patients who had survived for five years and in seven patients dead from the tumour, in order to evaluate the prognostic value of this method. The measurements of nuclear and cytoplasmic areas were made on routine H & E sections with a graphic tablet (ASM, Leitz). Statistical analysis of the obtained data revealed that there were significant differences between the two groups. It indicated that morphometric parameters of T1 bladder tumours can have prognostic as well as therapeutic significance which will be further tested in a prospective study.

Aged↗

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.

Cell Nucleus↗

The morphogenesis of adenocarcinoma of the cervix-a complex pathological entity.

The cytological and histological features of 20 cases of adenocarcinoma of the cervix are presented of which 14 cases were in situ and two were microinvasive. The frequent association of atypia with malignancies of the cervical squamous epithelium is stressed. Abnormal reserve or stem cells were found in many of these cases. This study demonstrates the importance of the proper identification of these cells in cytological material and gives support to the theory that these cells play a role as a precursor cell to squamous and glandular neoplasms.

Adenocarcinoma↗

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.

Diagnosis, Computer-Assisted↗

Morphometric differences between urothelial cells in voided urine of patients with grade I and grade II bladder tumours.

The morphometric differences between the urothelial cells in the voided urine of 24 patients with grade I and grade II bladder tumours were measured. In both wet-fixed Papanicolaou-stained smears as in air-dried Giemsa-stained preparations, the cells in the grade I tumours are larger and have more pronounced anisocytosis and a smaller nucleus to cytoplasm area (N/C) ratio. Although absolute dimensions of cells and nuclei in the two preparatory technique differ significantly, the average N/C ratios are similar. In both methods almost all grade I tumours have average N/C cell size ratios of less than 0.6 and grade II tumours more than 0.6. Morphometrically urothelial cells could not be distinguished from cells exfoliated from grade I bladder tumours. The results indicate that it is feasible to classify bladder tumours using the morphometric values of the exfoliated urothelial cells alone.

Cell Nucleus↗