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Biomedical subjects

G M Mariuzzi

Publications and source records attributed to G M Mariuzzi.

At least 37 records · Page 2Linked to original sources

Quantitative study of the precancerous and malignant lesions in colorectal adenomas.

150 endoscopically removed colorectal adenomas are quantitatively studied. In 90 cases dysplastic glands constituted the entire lesion (30 mild, 30 moderate, 30 severe); in 60 cases foci of adenocarcinoma were present (30 intramucosal, 30 submucosal). In each case the area, the perimeter and the integrated optical density of 100 nuclei were measured from Feulgen-stained paraffin sections. The results show a continuous neoplastic progression in the trends of the morphometric parameters as well as in the ploidy pattern. The stepwise discriminant analysis defined the morphometric features of the atypical nuclei, which were present in small numbers also in mild dysplasia; they progressively increased in number, reaching the maximum in submucosal carcinoma.

Adenocarcinoma↗

The value of necropsy in oncology.

The effectiveness of diagnostic procedures in cancer patients was evaluated by comparing clinical with necropsy findings. Necropsy and clinical records of 102 patients were reviewed for primary site and histology of tumour, metastatic sites, presence of second neoplasms, associated non-neoplastic diseases, terminal illness and cause of death. Major discordances between clinical and postmortem findings were found in 34 (33%) cases: in 10 of these a correct clinical definition of site and histology of the primary tumour would have resulted in a change of management and prognosis; in 4 cases in which a major non-neoplastic pathology had been responsible for death, correct diagnosis might have resulted in prolongation of survival. Spread of disease was generally underestimated, even for metastases in clinically accessible organs. Even more disappointing were the clinical data related to terminal illness and cause of death (43% overall concordance).

Autopsy↗

The number of nucleoli in benign and malignant thyroid lesions: a useful diagnostic sign in cytological preparations.

The slides of fine needle aspiration cytology specimens from 99 cases of cold thyroid nodules with known histology were reviewed and the number of nucleoli per nucleus counted and correlated with the different histopathological groups. Significant differences were observed between benign and malignant thyroid lesions in the number of nucleoli in the cytological material. Lower values were present in nodular goitres and follicular adenomas compared to carcinomas. In benign lesions the majority of nuclei contained one nucleolus and nuclei with two, three or more nucleoli were less frequent than in follicular, papillary, medullary and anaplastic carcinomas. Only one case of follicular adenoma had cells containing three or more nucleoli compared to more than half the cases of follicular carcinoma.

Cell Nucleolus↗

Quantitative analysis of prostatic intraepithelial neoplasia on tissue sections.

The changes in nuclear morphology (karyometry) and DNA content in prostatic intraepithelial neoplasia (PIN) were analyzed on tissue sections. The cases of PIN were subdivided into PIN 1 and PIN 2 based on the degree of proliferation and the anaplasia of the secretory cells lining the ducts and acini. Cases of nodular hyperplasia (NH) and adenocarcinoma were also studied for comparative purposes. Karyometric analysis showed a progression of most values from NH to PIN to carcinoma. The DNA analysis showed a decrease in the frequency of nuclei in the diploid range and an increase in the percentage of nuclei in the other ploidy regions (especially between 2c and 4c and in the tetraploid range) from NH to PIN to carcinoma. Forward stepwise discriminant analysis showed similarities between NH and PIN 1 and between PIN 2 and carcinoma. These findings suggest that the evolution towards adenocarcinoma is characterized by progressive morphologic derangements of the nuclei and by the transformation of the diploid DNA content into a nondiploid one, with the changes taking place at the level of PIN 2.

Adenocarcinoma↗

Morphological and quantitative analyses of intraductal dysplasia of the prostate.

The aim of our study was to characterize quantitatively the cellular and architectural features of intraductal dysplasia (ID) (subdivided into two grades), in comparison with benign prostatic hyperplasia (BPH) and adenocarcinoma (AC). The research was carried out on histological sections where the mean nuclear and cellular area, the mean nuclear cytoplasmic (N/C) ratio and parameters related to nuclear crowding and stratification were evaluated. The mean nuclear area and the mean N/C ratio steadily increased from BPH to ID and to AC. As for the mean cellular area, the values decreased from BPH to ID grade 1: in the two grades of ID the values remained about the same; in the AC, the mean cellular area was intermediate between ID and PBH. The mean crowding index showed increase in ID grade I, in comparison with BPH, and then a decline from ID grade 2 to AC. The stratification related features (mean epithelial height, mean nuclear stratification height, stratification index) showed ID values greater than in BPH, while in AC smaller than in BPH; in ID grades 1 and 2 the values were similar. The results clearly indicate that mean nuclear area helps to discriminate BPH and AC. A partial separation between the two grades of ID is possible by combining the mean nuclear area and the mean nuclear crowding index in a bivariate analysis.

Adenocarcinoma↗

Sources and nature of variation in DNA analysis of follicular thyroid adenoma.

We investigated the sources and nature of variation that may occur in the DNA analysis of thyroid adenomas from cytological and histological samples. Imprints and smears gave identical results. However, the nuclear area was higher in smears where the optical density of the nuclei was lower. In measuring imprints, the interactive selection of nuclei was preferred to the automatic, because the risk of measuring nuclear fragments or undesired objects was thus avoided. The reproducibility and the variation of the DNA measurements depended on the degree of observer training in quantitative pathology, the method of field selection, and the type of instrumentation. Biological variation in the spatial distribution of nuclei with different ploidy values in some adenomas seemed to hide the influence of section thickness on measurements. Our data seem to suggest that it is best to apply a constant section thickness and 5 micron sections seem acceptable.

Adenoma↗

Multiparametric quantitation of the progression of uterine cervix preneoplasia towards neoplasia.

The aim of the research was to quantify the malignancy progression of preneoplastic lesions towards carcinoma of the uterine cervix. The study has shown that the modifications to nuclear area, perimeter, DNA content, percentage of nuclei with nucleoli, nuclear/cytoplasmic ratio and percentage of SOYA BEAN AGGLUTININ stained cells are progressively greater moving from normal epithelium and mild dysplasia towards infiltrating carcinoma. In particular all the morphologic and histochemical parameters have shown an increasing derangement which appears to parallel the diploid reduction and the appearance of aneuploidy. In order to identify the changes in the stroma, the modifications to the capillaries were investigated: in mild dysplasia only the vessel density increases; the capillary area, perimeter and diameter increase in moderate and severe dysplasia, and in CIS; the values of these features are similar in the carcinoma groups. The capillary density increases mainly in the invasive carcinoma. The data obtained in the study have shown that: 1) the process of malignancy progression is characterised by a gradual and continuous derangement of cell characteristics and modifications to capillaries of the stroma; 2) the mild dysplastic changes have the characteristics of hyperplastic lesions; 3) CIS, qualitatively similar to severe dysplasia from which it differs quantitatively, has features of neoplastic proliferation; 4) the appearance of invasion is associated with DNA parameter changes which may indicate a ploidy reduction.

Capillaries↗

Quantitative evaluation of morphological parameters for infiltrating ductal breast cancer prognosis.

The aim of our study was to determine the parameters intrinsic to ductal infiltrating carcinoma. 42 cases of about the same diameter (greater than 1.5 and less than 2.5 cm) with a minimum follow-up of more than seven years were selected. The nuclear and nucleolar shape parameters of one hundred cells for each case and the DNA content of 100 nuclei were measured by static cytometry. By means of multivariate discriminant analysis, the nucleolus/nucleus ratio and the DNA content proved to be the two best prognostic indicators based only on the examination of the parameters of the primary neoplasia. We were able to correctly classify 90% of the cases, and in particular to assign 100% of living cases and 81% of deceased ones to their exact categories.

Adult↗

Quantitative evaluation of recurrent meningiomas.

Clinical, histological and karyometric parameters, nuclear DNA content and the number of nucleolar organizer regions were investigated in 9 recurrent meningiomas and 10 meningiomas which had not recurred within a 10-year period. There were no significant differences between the two groups as to age, sex, site of the tumours and most of the histological parameters scored. Recurrent tumours showed a higher number of mitotic figures and the nucleolus was visible in most of the cells. Cell density, nuclear area, perimeter and nuclear DNA content had values with no statistically significant differences between the two groups. However, significant differences were found in the distribution of the nuclei in the different ploidy regions. Most of the nuclei in the non recurrent cases were in the diploid range, whereas in recurrent tumours there was a reduction in the number of diploid cells associated with an increase in 2c--4c and 4c components. Recurrent tumours also showed a higher number of nucleolar organizer regions positively stained using an argyrophil method. The mitotic count and the nucleolar organizer regions appeared to be the best predictors for recurrence.

Adult↗

Morphometric study of chromatin pattern in freeze-fractured rat liver nuclei during malignancy evolution.

Computerized image analysis was performed on freeze-fractured nuclei isolated from normal rat liver and rat liver with diethylnitrosamine induced hepatocarcinomas. Chromatin particles belonging to heterochromatin and interchromatin nuclear regions were measured, distributed into histograms and statistically processed. The ratio between nucleosome filaments (5-10 nm range diameter) and solenoid fibres (25-35 nm range) and Tukey's fitting line were calculated. The N/S ratio shows an inverse trend in treated nuclear samples with respect to the controls indicating that the malignancy progression is accompanied by characteristic derangement of the chromatin arrangement which can be evaluated by morphometric analysis.

Animals↗

Clinical significance of the histomorphometric evaluation of diabetic microangiopathy in the oral mucosa.

Several structural parameters of the capillary vessels were measured in the oral mucosa of patients with diabetes mellitus of type 1 (D.1) and of type 2 (D.2), and of control cases (C), by means of an image analyser in histological sections of routinely processed biopsies. The studied parameters included: a) capillary wall thickness; b) capillary diameter; c) the ratio of capillary wall thickness and diameter; d) capillary wall area; e) capillary area; f) the ratio of capillary wall area and capillary area; g) density of capillary vessels in the lamina propria; h) density of endothelial cells; i) endothelial nuclear area. Clinical and laboratory parameters were also evaluated (duration of the disease, systolic and diastolic blood pressure levels, glycemia, glycosylated haemoglobin, glycosylated albumin, fructosamines, apolipoproteins A1 and B), in order to assess whether a relationship exists with the morphometric parameters studied. Statistically significant differences, at the level of p less than 0.05, were found in the following morphometric parameters between controls and each group of diabetic patients: mean and standard deviation of capillary wall thickness, mean capillary wall area, mean ratio of the capillary wall area and capillary area. A reduction in the capillary density, i.e. the number of capillary vessels per mm2 of lamina propria, was also observed in diabetic patients with respect to the control group, although it was not statistically significant (C vs. D.1: p less than 0.21; C vs. D.2: p less than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Malignant glial tumours: prognostic value of quantitative microscopy.

Nuclear and cell density features have been measured in 22 cases of glioblastoma divided into two groups according to their survival periods, i.e. less than 12 months or more than 12. The results have demonstrated that the logarithmic transformation of the following features show up statistically significant differences (p less than 0.05): mean of the logarithm of nuclear area, standard deviation of the logarithm of perimeter and standard deviation of the logarithm of the roundness factor. The standard deviation of the roundness factor has been shown to be another parameter with statistically significant differences between the two groups. Forward stepwise discriminant analysis was adopted in order to identify the quantitative features which contributed most significantly to discriminating between the two groups. The results suggested a combination of two features, i.e. the standard deviation of the logarithm of the roundness factor and the mean of the logarithm of the roundness factor. The comparison between actual and predicted categories showed 68.18% agreement: 7 out of 22 cases were allocated incorrectly by the computer. However, when a classification probability threshold was adopted, the 7 incorrectly allocated cases assumed an "intermediate" position between the two groups, in agreement with their survival.

Aged↗

Discrimination between follicular adenoma and follicular carcinoma of the thyroid: preoperative validity of cytometry on aspiration smears.

The aim of our study was to evaluate the validity of the quantitative analysis of nuclear features on aspiration smears in the distinction between follicular adenoma and follicular carcinoma. Karyometric and DNA features, including the nucleolar count, were evaluated on the cytologic material of 28 cases; the values were in general slightly higher in the carcinomas than in the adenomas, with overlap between the two diagnostic groups. By plotting the two most discriminant and least correlated parameters against each other and by drawing two straight lines (one perpendicular to the axis representing the mean of the major nuclear diameter at the 9-microns point, the other perpendicular to the axis of the percentage of nucleolated cells at the 75% point), we obtained two regions: a rectangle delimited by the two axes and the two lines containing 86% of adenomas, and the remaining part of the plane containing 79% of carcinomas. The validity of this approach was tested in 32 new cases not included in the original bivariate classification: accuracy 87%; sensitivity 86%; specificity 88%; predictive value of adenoma 88%; predictive value of carcinoma 85%. In conclusion, a simple cytometric method, i.e., the combined evaluation of the mean of the major nuclear diameter with the percentage of nucleolated nuclei, allows a substantial distinction to be made between follicular adenoma and carcinoma.

Adenocarcinoma↗

Reproducibility of DNA measurements in imprints of thyroid adenoma. Variation sources.

DNA measurement represents a type of quantitative analysis which allows us to gain prognostic information on malignant tumors and to study the natural history of the epithelial neoplasia. However, there are sources of variation in evaluating the DNA content. These include variation due to field selection, variation between observers (interobserver variation), and variation between laboratories (interlaboratory variation). The influence of various variation sources was studied in 4 experiments. When DNA measurements were made from the same microscopic fields, the results did not differ remarkably. However, observer training proved to be important. Intra- and interobserver variation was lower among experienced morphometrists than among inexpert observers. Different laboratories and image analyzers may give different results when the same case is measured. To overcome at least part of the potential variation sources, undergraduates and postgraduates at the Departments of Pathology of Ancona and Kuopio Universities are specially trained in the use and application of morphometry. Special sampling rules should be applied and observers encouraged to follow the rules as uniformly as possible.

Adenoma↗

Reproducibility of mitotic counts and identification of mitotic figures in malignant glial tumors.

Quantitative pathology is a rapidly growing field of pathology. This field is developing methods allowing greater objectivity and better reproducibility in diagnostic decisions. The introduction of quantitative pathology as a teaching subject in medical education will help this field to become more widely and more correctly applied. Courses on quantitative pathology are organized yearly by the Department of Pathology at the University of Ancona. The 1986 course emphasized training of students in understanding basic problems such as variation caused by tissue processing, instrumentation, data handling and interpretation, and variation between observers. In this paper we describe experiments performed during the course on identification and quantitation of mitoses in malignant glial tumors. The participants, i.e. students of the postgraduate Pathology School, could identify mitoses with a 'substantial' reproducibility. However, when the observers were allowed freely to choose the fields to count, the reproducibility was 'slight'. The study suggests that sampling rules should be applied which secure reproducible application of morphometric method also on condition of free selection of fields. Because the application of such rules needs expertise in histopathology, it seems that morphometric method can best be applied by histopathologists themselves.

Glioma↗

Sampling in diagnostic morphometry: the influence of variation sources.

The variation sources relevant to a diagnostic morphometric study were analysed. The influence of each source was estimated in two experiments, performed in systems applying computer assisted interactive morphometry. In the first experiment one observer measured the areas of a large number of nuclei in a section from a grade II transitional cell carcinoma of the bladder. In the second experiment two groups of researchers, from Ancona and Kuopio, measured one field from five different samples of transitional cell tumours (including the case of grade II carcinoma). It turned out that pure interobserver variation was responsible for about a half of the total variation present in the diagnostic system. When the variation characteristics of the diagnostic system had been determined, the number of nuclei that had to be measured to reach a defined level of accuracy could be estimated. Such an estimate was also dependent on the predefined expectancy probability of reaching a correct estimate. The study showed that group morphometry (statistical, investigative morphometry) and diagnostic morphometry must be understood as two different approaches in histopathology. By applying group morphometry, good research results can be gathered with cruder measurements than in diagnostic morphometry. Because investigations in group morphometry are more standardized than in diagnostic morphometry, a larger number of structures has to be measured in diagnostic histopathology for the same level of accuracy.

Analysis of Variance↗

Multivariate classifications of transitional cell tumors of the bladder: nuclear abnormality index and pattern recognition analysis.

The authors report their experiences in applying two types of computer-aided multivariate classification systems in transitional cell tumors of the bladder. The systems are based on nuclear changes in urothelial papillary lesions. 19 out of 54 parameters, selected on the basis of the overlapping area between contiguous grades and the monotonic function, were combined mathematically to obtain the nuclear abnormality index. This index expresses the progressive nuclear abnormalities as a single number on a continuous scale from 0.5 to 2.6. The standard deviation (SD) of the 10 largest nuclear area values in the lower half of epithelial thickness (L), the mean perimeter (L), the SD of the roundness factor in the upper half of epithelial thickness (U), the SD of the logarithm of area (L) and the percentage of round nuclei (U) represent the smallest, the most discriminant and the least correlated set of features for the pattern recognition analysis. The latter shows an agreement of 92% between computer and histologic classifications-estimated by applying Bayes theorem. A good correlation exists between nuclear abnormality index and computer grading by pattern recognition analysis.

Carcinoma, Transitional Cell↗