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R Montironi

Publications and source records attributed to R Montironi.

At least 19 recordsLinked to original sources

Serous borderline tumors of the ovary. A clinicopathologic, immunohistochemical, and quantitative study of 44 cases.

The clinicopathologic features of 44 serous borderline tumors (SBT) of the ovary were evaluated. Nineteen were Stages II and III, and 9 had invasive peritoneal implants. All 19 patients received chemotherapy and 4, who had invasive implants, died of disease after 3, 4.3, 8, and 9 years. The other 25 patients were free of tumor 1-14 years (mean, 5.3 years) after surgery. Coexpression of low molecular weight keratins (AE1, CAM 5.2) and vimentin was found in all tumors and their implants. No significant differences were found between SBT with different volume-corrected mitotic indices (M/Vi) with respect to gross features, presence or absence of implants, stage, and survival. Cytometric DNA analysis also was performed on the primary ovarian tumors and the implants. Twenty-one primary tumors had diploid or tetraploid histograms, and 23 had aneuploid histograms. DNA ploidy of the primary ovarian tumors did not correlate with gross features, the presence or absence of implants, M/Vi, stage, and survival. The data from this study confirm that most SBT are clinically benign, but SBT with invasive implants may behave aggressively. Expression of intermediate filaments, M/Vi, and DNA ploidy evaluation of the primary ovarian tumors seem to be of no value in predicting prognosis. However, four of seven patients with aneuploid DNA implants died of tumor.

Adolescent

Aneuploidy and nuclear features of prostatic intraepithelial neoplasia (PIN).

Quantitative analyses (QAs) of prostatic intraepithelial neoplasia (PIN) helped to objectively define some traditional features of the lesion because, first, changes in value are represented by numbers and not by subjective evaluation of morphologic clues. QAs have also helped to identify subtle abnormalities. For example, the degree of nucleolar margination is a new diagnostic feature which can be easily evaluated as the proportion of nucleoli touching the nuclear membrane. Thirdly, QAs have provided useful insights into understanding some morphologic changes. PIN, in fact, appears to be characterized by complex changes which involve the secretory cells as well as the basal layer and which affect the surrounding stroma. In the epithelial lining, two types of simultaneous changes take place, the first in the nucleus (expression of abnormal proliferative and/or renewal activity) and the second in the cytoplasm (expression of the disorder in cell differentiation), pointing out that only PIN samples of high grade can be considered as having acquired the characteristics of a neoplastic lesion.

Aneuploidy

Cytologic diagnosis of non-oxyphil follicular neoplasias of the thyroid. Multivariate classification procedure based on quantitative nucleolar features.

The study was done on cytologic material of 58 non-oxyphil follicular neoplasias of the thyroid, 32 of which were adenomas and 26 carcinomas. Three groups of nucleolar features were quantified using a routine microscope with an ocular micrometer: frequency-, size-, and margination-related features. Since value overlap was present between two categories for all the variables, stepwise discriminant analysis was applied. The following three features were selected by the computer for calculation of one canonical discriminant function: percentage of marginated nucleoli, percentage of nuclei with one nucleolus, mean major nucleolar diameter. The percentage of agreement between morphologic and computer classifications was 95%. Two follicular adenomas were allocated to the carcinoma category, whereas one follicular carcinoma was allocated to the adenoma category. Out of 58, 52 were diagnosed by the computer into one of the two diagnostic categories with a very high probability, i.e. P greater than 0.75, the remaining 6 being considered intermediate.

Adenoma

Quantitative analysis of quadriceps muscle biopsy in systemic sclerosis.

The lesser diameter of the fibers, separately of type 1 and type 2 fibers, and the capillary density evaluated as number of capillaries/area and number of capillaries/fiber were quantitatively estimated in muscle biopsies from 12 patients with systemic sclerosis. Nine patients with polymyositis or rheumatoid arthritis and six patients with muscle dystrophy and neurogenic atrophy served as controls. The results showed that patients with systemic sclerosis had low values of the lesser diameter of the fibers. This reduction was most obvious in type 2 fibers. The capillaries were also significantly reduced when compared with the control groups. When considering the capillaries/fiber ratio, seven out of eight patients with values lower than 0.7 belonged to the systemic sclerosis group. In systemic sclerosis the capillary density values were not significantly correlated with those of the lesser diameters of the fibers.

Adult

Well differentiated follicular neoplasms of the thyroid: reproducibility and validity of a 'decision tree' classification based on nucleolar and karyometric features.

This study was conducted on fine-needle aspirates of well differentiated follicular neoplasms of the thyroid. A 'decision tree' classification based on the percentage of nucleolated nuclei, percentage of nuclei with two or more nucleoli and mean major nuclear diameter was adopted. We observed that the reproducibility and the validity of the follicular adenoma vs follicular carcinoma discrimination are greater than in the subjective evaluation. Moreover, similar classification results were obtained when measurements were performed either with a fully automated image analysis system or with semiautomatic or manual instrumentation. As for reproducibility of the inter-instrument comparisons, the k statistic values ranged from 0.85 to 1.00 (mean value 0.90, that is, an 'almost perfect' degree of agreement); in the subjective evaluations, the inter-observer comparisons showed values ranging from 0.20 to 0.56 (mean value 0.37, that is, 'fair'). In the decision tree classification, feature value thresholds were selected in order to have specificity of 100% and the predictive value of a positive result (carcinoma) of 100%; accuracy was 87% (range 86-89%), sensitivity 74% (71-79%), the predictive value of a negative result (adenoma) 79% (78-82%). In the subjective evaluation the values were as follows: accuracy 67% (64-71%), sensitivity 57% (50-64%), specificity 77% (71-79%), predictive value of a negative result (adenoma) 64% (61-69%), predictive value of a positive result (carcinoma) 71% (67-75%). The conclusion is that, by using a routine microscope equipped with a micrometer, the preoperative diagnosis of follicular carcinoma from smears can be formulated with a high degree of certainty.

Adenocarcinoma

Computer-aided S-phase fraction determination in DNA static cytometry in breast cancer. A preliminary methodologic study on cytologic material.

This methodologic study was performed on a single-cell-cycle breast carcinoma to evaluate the feasibility of computer-aided S-phase fraction determination in DNA static cytometry. The investigation was performed on Feulgen-stained cytologic material in which the total optical density values of 1,000 consecutive, randomly selected nuclei were analyzed (MultiCycle software). A good correlation in the S-phase fraction value with flow cytometry was obtained when the G2/G1 ratio was fixed at 1.95, when the histogram data points were smoothed at least once and the coefficient of variation of the G2 peak was the same as that of G0-G1 or when a first-order S-phase polynomial model was used. The percentages of nuclei in G0-G1 and G2 were somewhat similar to those obtained with flow cytometry. The greatest discrepancy with flow cytometry was observed in the value of the coefficient of variation of the G0-G1 peak of the static cytometric data: it was at least twice as great. It always remained high despite the software options used. As for the influence of the sample size in the S-phase calculation, the software was also run on samples of 600 and 200 nuclei. When the G2/G1 ratio was fixed at 1.95, the data obtained from 600 nuclei did not differ from those obtained with 1,000 nuclei, whereas an analysis on 200 nuclei showed a substantial variation. The software also allowed calculation of the ratio of the G0-G1 peak of the neoplastic population against that of the diploid reference (DNA index), the value of which in flow cytometry was 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms

Cytometric evidence that cervical intraepithelial neoplasia I and II are dysplasias rather than true neoplasias. An image analysis study of factors involved in the progression of cervical lesions.

Image analysis was performed on 40 Feulgen-stained histologic samples and 48 Feulgen-stained cytologic preparations representing normal squamous epithelium and all grades of cervical lesions (from mild dysplasia to invasive carcinoma) in order to characterize the evolutionary progressive changes in cervical epithelial proliferative disease toward malignancy. Quantitative studies included the analysis of proliferative features, differentiation features, nuclear morphology and DNA content. The data obtained on the histologic sections showed that the various features, to a different extent, detected a gradual increase in phenotypic cellular disarrangements related to the progression of the cervical lesions toward malignancy--that is, the modifications to nuclear area, perimeter, DNA content, percentage of nuclei with nucleoli, nuclear/cytoplasmic ratio and percentage of cells with no membrane positivity for soybean agglutinin lectin were progressively greater, moving from normal epithelium and mild dysplasia toward infiltrating carcinoma. In particular, all the morphologic and histochemical features appeared to parallel a diploid reduction and the appearance of aneuploidy. The simultaneous evaluation of proliferation- and differentiation-related features, together with those of nuclear DNA content, showed two main successive preneoplastic lesions: one characterized by an increase in cell turnover without alterations in its organization and another by a true neoplastic disorder. The data obtained on sequential cytologic examinations showed that individual cell changes are detectable and seem basically to be characterized by the appearance of clusters of cells with somatic characteristics not observed in previous cytologic checks. From the results of our study, the cervical intraepithelial neoplasia (CIN) concept appears to be inaccurate. In fact, only CIN III (severe dysplasia/carcinoma in situ) lesions have the morphologic and proliferative alterations of true neoplasia. In contrast, CIN I and some cases of CIN II lesions lack these characteristics and seem to be properly classified as dysplasia, thus avoiding the term neoplasia, implicit in CIN. Moreover, the multivariate study of data sets of features related to the progressive somatic changes, both in histologically and cytologically studied cases, allows us to detect the steps of progression; they are marked by the appearance of cell clusters with qualitatively different phenotypic characters when compared to the cell populations from which they presumably arise. These results seem to provide a further argument against the CIN theory, which stresses the concept that progression is related only to a gradual numerical increase in an initially established phenotype with the characteristics of malignancy.

Biopsy

Quantitative analysis of nucleolar margination in diagnostic cytopathology.

The diagnostic value of nucleolar margination, defined as the percentage of nucleoli touching the nuclear membrane, was investigated in 359 cytological preparations of benign and malignant lesions of the thyroid, breast, prostate and central nervous system. Premalignant lesions of the uterine cervix and non-invasive papillary carcinomas of the bladder were also examined. It was observed that the percentages in benign lesions were, in general, lower than in the malignant and that the values increased progressively with increasing grade in the cervix and bladder. When the overlap index was calculated, this gave exact information on the usefulness of nucleolar margination in distinguishing benign from malignant lesions, particularly in the prostate and thyroid and, to a lesser extent, in the breast and central nervous system. As for lesions of different grades, the calculation of the index allowed the identification of two subgroups, one corresponding to low grades (mild cervical dysplasia or urothelial papillary carcinoma of grade 1), the other subgroup to high grades (severe cervical dysplasia and carcinoma in situ, or papillary carcinoma of grade 3). Moderate dysplasia cases and grade 2 papillary carcinomas do not appear as separate intermediate categories but rather show values falling into the range of either the higher or lower grades. The margination values obtained from the cytological preparations corresponded well to those in the histological slides obtained from the resected specimens. In conclusion, nucleolar margination appears to be a feature which is easy to evaluate in a reproducible way and useful in cytological diagnosis.

Biopsy, Needle

Quantitation of the prostatic intra-epithelial neoplasia. Analysis of the nucleolar size, number and location.

Correlation has previously been demonstrated between qualitative and quantitative architectural and cytological features of the prostatic intra-epithelial neoplasia. In the present study, a standard Zeiss microscope and a horizontal eyepiece micrometer were used in an attempt to quantitatively define the size, number and location of nucleoli in relation to the degree of prostatic intra-epithelial neoplasia and associated benign prostatic hyperplasia and adenocarcinoma. In total, 20 prostatectomies, where features of benign prostatic hyperplasia (20 cases), prostatic intra-epithelial neoplasia of grade 1 (10 cases) and grade 2 (10 cases), and adenocarcinoma (20 cases) were present, were studied. The quantitative analysis showed that, going from benign prostatic hyperplasia to prostatic intra-epithelial neoplasia of grade 1 and 2, and to adenocarcinoma, the values of the size-related nucleolar features, are progressively greater; when considering the frequency-related nucleolar features, the percentage of nucleolated nuclei increased sharply. This was associated with the decrease in the proportion of mononucleolated nuclei and increase in nuclei with two and three nucleoli. When considering the location-related nucleolar features, the degree of shift of the nucleoli to the periphery of the nucleus increased. Among all the quantitative features, the most evident changes in the nucleolar size were expressed by the nucleolar hypertrophy index after including in the calculation only those nucleoli with a diameter larger than 3 arbitrary units, whereas the percentage of nucleolated nuclei and the proportion of nuclei with two and three nucleoli best represented the modifications to the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

Value of quantitative nucleolar features in the preoperative cytological diagnosis of follicular neoplasias of the thyroid.

Nucleolar prevalence, size, and outline were investigated on cytological material from cold thyroid nodules obtained by fine needle aspiration. The percentage of nucleolated nuclei in follicular adenoma (32 cases) was less than in follicular carcinoma (26 cases). In adenoma most nuclei contained one nucleolus, and nuclei with two or more nucleoli were less common than in carcinoma where most cases showed the highest nucleolar diameter values. There was some overlap between adenomas and carcinomas, however, when the mean of the 10 largest values of the major nucleolar diameter was considered. In follicular carcinoma the percentage of marginated nucleoli--that is, those touching the nuclear membrane--was, in general, greater than 20%; in adenoma the values were equal to or lower than 16%. The overlap index showed that the percentages of marginated nucleoli and nucleolated nuclei are the two best discriminatory features between adenoma and carcinoma.

Adenocarcinoma

Consistency of quantitative methods in ovarian tumor histopathology.

Two mitotic activity indices, volume fraction of neoplastic epithelium, nuclear area, nuclear perimeter, and shortest nuclear axis were estimated in 46 ovarian tumors by three observers in two independent laboratories. The mitotic activity index, the volume corrected mitotic index (M/V index) and subjective volume fraction estimates showed a very good correlation from the same fields by two observers in the same laboratory (r = .999, .995, .950). Repeat estimates from different fields by the same observer showed coefficient values of .949, .939, and .813, and estimates by two different observers within one laboratory values of .949, .936, and .789, respectively. The correlation between two independent observers in different laboratories was also good (r = .894, .834, .834, respectively). Grading based on morphometric measurements was uniformly performed in 90-100% of cases in an interfield interobserver intralaboratory situation, and in 79-97% (M/V index) or 76-93% (mitotic activity index) in an interlaboratory situation. Because the cases near the grade limits were more often differently graded than other cases, the methods allowed the pathologist to locate the probably incorrectly graded cases. Morphometry of ovarian tumors was shown to be easy, which makes morphometric malignancy grading systems potentially able to support diagnostic and therapeutic decisions in practice.

Cell Nucleus

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

Verrucous carcinoma in situ of the bladder, not associated with urinary schistosomiasis.

Verrucous carcinoma is a variant of well differentiated squamous cell carcinoma that rarely affects the bladder. The bladder localization of this carcinoma is usually associated with urinary schistosomiasis. In this work we report on a rare case of verrucous carcinoma of the bladder not associated with urinary schistosomiasis. To complete this study, analysis of DNA was carried out on the histologic sections of the tumour.

Carcinoma in Situ

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