Biomedical subjects
Publications and source records attributed to R Ricco.
A case of giant (32 Kg) malignant fibrous histiocytoma (MFH) arising from the uterus and occupying the entire abdomen and the pelvis is reported. The patient had debulking surgery, followed by combination chemotherapy, but died 7 months after diagnosis.
Malignant mesothelioma is difficult to distinguish from other pleural malignancies and also from benign mesothelial lesions. A morphometric study has been performed to distinguish between them using quantitative size and shape parameters. Seven cases of malignant mesothelioma, 5 cases of pleural metastatic adenocarcinoma and 4 cases of benign mesothelial lesions were selected and subjected to S.A.M. (Shape Analytical Morphometry). The results, statistically evaluated, showed that morphometric parameters can be proposed for diagnostic purposes being useful in the discrimination among the three populations. In fact, multivariate discriminant analysis (MDA) of the quantitative parameters obtained by morphometrical study distinguished the three groups of lesions with only 2% of error between BML/MM, 7% of error between BML/MA and 25% between MM/MA.
In the histological grading of oral squamous cell carcinoma (OSCC) nuclear features are very important. Nevertheless evaluation is usually performed in a subjective and not highly reproducible way. The aim of this work was to investigate the relationship between nuclear shape and survival in 30 cases of carcinoma of the tongue. All the patients were divided into two groups: short-term survival and long-term survival. Twenty nuclei for each tumour were submitted to a morphometrical study by the shape analytical morphometry (SAM) software system. It was thus possible to evaluate not only nuclear dimensions but also nuclear contour irregularities and nuclear shape asymmetries. Multivariate discriminant analysis (MDA) of the quantitative parameters obtained by the morphometrical study distinguished the patients of the two groups with only a 10% error; moreover successful cluster analysis was performed by using Fourier parameters. Both these sets of results were achieved mainly owing to the parameters for contour irregularities.
Sialadenoma papilliferum (SP) is a rare, benign, salivary gland tumor which most commonly arises in the palate. It has a typical biphasic gross and microscopic appearance which distinguishes this tumor from other papillary-like tumors of the oral cavity. This study reports the clinico-pathologic features of 5 new cases and analyzes the morphologic and immunophenotypic features of their cell components. Adluminal epithelial cells of duct-like structures appeared immunoreactive to cytokeratin 19 and to S-100 protein antibodies; two subsets of basally-located cells were identified by means of immunohistochemistry. One cell subset expressed cytokeratin 14, S-100 protein, GFAP, vimentin and smooth muscle actin immunoreactivity; this antigenic profile is consistent with myoepithelial differentiation. The second subset of basal cells expressed cytokeratins 13 and 14 reactivity but it was negative to all other antibodies. Anti-CD 1a and anti-S-100 protein antibodies revealed distinct cells with dendritic processes which resembled Langerhans cells. The extralobular location of SP, the continuity between neoplastic duct-like structures and the surface epithelium along with the presence, within the excretory ducts adjacent to the tumour, of lesions which possibly precede the development of SP give further strength to the hypothesis of an origin from the excretory ducts of this tumor. Langerhans cells seem to be present in sialadenoma papilliferum but their role in this tumor is still unclear.
OBJECTIVE: To determine whether nuclear morphometry can confirm or add useful information to classic clinicopathological prognosticators to identify the subpopulation of breast carcinoma patients with node-negative (N-) disease, at high risk of disease relapse. STUDY DESIGN: On the basis of results obtained by clinicopathologic evaluation of a group of patients with N- breast cancer, on a test group of 56 cases (32 patients disease free and 24 with relapse), we performed a morphometric analytical study of nuclei using the Shape Analytical Morphometry (SAM) software system; 20 nuclei for each case and 17 morphometric parameters for each nucleus were analyzed. RESULTS: The SAM system allowed us to quantify shape differences in nuclei in terms of contour irregularities and asymmetries along with evaluation of nuclear dimensions. Dimensional and analytic parameters were subjected to univariate (Student's t test) and multivariate (Hotelling's test) analysis. Multivariate discriminant analysis showed that an exact forecast of disease relapse could be made in 77% of patients with N- breast cancer by using a set of six both analytic and dimensional parameters. CONCLUSION: These results confirm that nuclear pleomorphism is the result of both contour irregularities and shape asymmetries and that even though they should be considered preliminary results, they stress the importance of quantitative shape evaluation.
Eighteen cases of astrocytomas diagnosed as grades 1-3 of malignancy were studied with analytical morphometry to determine if different grades can be discriminated by size and shape parameters related to the nuclei. The shape analytical morphometry system was used to calculate dimensional measurements and express shape irregularities through quantitative parameters. With the shape asymmetry evaluator procedure, nuclear symmetry was evaluated. All parameters subjected to univariate and multivariate strategies were the same in easily distinguishing grade 1 from the others. Grades 2 and 3 could not be discriminated completely by either dimensional or with analytical parameters revealing strong similarities of nuclear shape and dimensions.
In order to characterize medulloblastomas and to get over the difficulties sometimes encountered in differential diagnosis, a double morphometric procedure has been applied to its nuclei. The first consisted of size measurements (maximum diameter, area and perimeter), the latter is represented by S.A.M. (Shape Analytical Morphometry) software-system specifically implemented to describe shape of biological structure by analytical parameters. Analytical and dimensional parameters submitted to Hotelling's multivariate discriminant analysis gave the best results when used together in convenient discriminant subsets, thereby allowing a good distinction between medulloblastoma in comparison with neuroblastoma, Ewing's tumor, lymphoblastic and lymphocytic lymphoma. These results underline the usefulness of morphometric characterization also for practical diagnostic purposes.
The S.A.M. (Shape Analytical Morphometry) software system and its related work-station give a generalized and easy-to-handle tool to face a classic and intriguing problem in biomedical morphological diagnosis. What is the shape of an object in a microscopic image? How can we understand the relationship between size and shape? According to Holloway: "Measurements such as length, width, height, whether in chords or arcs only describe space, ... and further run into the abyss of allometric correction ... if additional information (shape?) to size is expected, some method of allometric correction must be used." The S.A.M. software system assumes a logic architecture able to separate and to parametrize independently shape characteristics in terms of allometry and local pertubation by analytical procedures (polynomials, parabolic fitting, Fourier analysis) in addition to the classic evaluations of size and density carried out by image analyzers for microscopical diagnosis.
An immunocytochemical investigation has been carried out on five cases of chordoma (2 of the sacrum, 2 in the spheno-occipital bone and 1 in the parapharyngeal area) to study the expression of the 5 classes of intermediate filaments (IF): cytokeratin (CK), desmin (DES), GFAP, neurofilaments (NF) and vimentin (VIM). Our results show that constant coexpression of CK, NF and VIM does occur in chordomas, whereas DES and GFAP are not demonstrable in tumor cells. The three detected IF are invariably present in all cell types but not in intracellular vacuoles or in the extracellular mucoid substance. The pattern of immunoreactivity of chordomas appears very unique as very few other neoplasms demonstrate the simultaneous occurrence of 3 distinct IF. Only choroid plexus tumors have been shown to manifest CK-NF-VIM immunoreactivity. The complex immunophenotype of chordomas may be related to their supposed origin from the notochord which normally undergoes conspicuous changes in location and morphology during embryonal development. Such changes might require the contemporary presence of multiple IF; IF expression, in fact, is known to be related to cell function and morphology. Notochordal cells and their neoplastic counterpart may consequently express an IF pattern which reflects unique architectural and morphological variations occurring during embryonal and tumor growth. Together with the speculative value of the detection of CK, NF and VIM in chordomas, the unusual immunocytochemical pattern of these tumors might provide useful diagnostic tool in differential diagnosis.
In recent years, borderline epithelial tumors of the ovary have been investigated by morphometric techniques to allow for a differential diagnosis from benign and malignant neoplasms. In order to enhance this discriminant power, we have applied a new analytical procedure to the evaluation of the nuclear shape in epithelial ovarian tumors. Sixty nuclei of benign ovarian serous neoplasms, 60 nuclei of serous borderline tumors and 60 nuclei of serous carcinomas (18 cases in all) were examined using the software system SAM (Shape Analytical Morphometry). The morphometric procedure consisted of three different phases: (i) extraction of nuclear fundamental curve: this is a function curve giving the smoothing of the original contour by two parametric equations (separately for x and y values as dependent variables); (ii) evaluation of nuclear contour irregularities by Fourier analysis; (iii) evaluation of nuclear shape asymmetry by SAE (Shape Asymmetry Evaluator): this is the ratio between the length of a segment of a parabola interpolating the original curve points and a straight line joining its extremities for a 180 degrees barycentric rotation according 10 degrees steps. All the obtained independent parameters were submitted to statistical analysis. Nuclei of borderline tumors showed dimensional parameters which were intermediate between those of benign and malignant tumors. Both the asymmetry and the irregularities of nuclear contour were greatest in carcinomas.
In order to enhance the discrimination power in the field of serous ovarian tumors, we applied the software system SAM (Shape Analytical Morphometry) to the analytic studies of biological forms. Besides the usual dimensional evaluations (perimeter, area, maximum diameter and shape index), this procedure permits the description of the nuclear form using analytical parameters: 1) extraction of nucleus fundamental curve; that is a functional curve giving the "smoothing" of the original contour by two parametric equations (separately for x and y values as independent variables); 2) evaluation of nuclei contour irregularities by Fourier analysis; 3) evaluation of shape asymmetry by SAE (Shape Asymmetry Evaluator); that is the ratio between the length of a segment of a parabola interpolating the original curve points, and a straight line joining its extremities for a 180 degrees barycentric rotation according 10 degrees steps. All parameters resulted to be independent and were submitted to multivariate discriminant analysis. We studied 180 nuclei from 18 cases of serous ovarian tumors, (6 benign, 6 borderline and 6 malignant tumors). With respect to the dimensional parameters, the application of analytical morphometry permitted us to reduce the minimum percentage error in the discrimination of the different classes. In fact, in the distinctions of benign and malignant nuclei, the minimum percentage error was 13.30%, against the 18.3% error when using dimensional morphometry. Furthermore, in the comparison of malignant and borderline nuclei there was a reduction of error from 23.3% to 22.5%, and in the comparison of benign and borderline nuclei, the error was reduced from 37.5% to 30%.(ABSTRACT TRUNCATED AT 250 WORDS)
In this study ten cases of breast infiltrating ductal carcinoma have been considered. In all of them the content of ER has been evaluated by using monoclonal antibodies. Five of them were ER positive and five were ER negative. For the morphometric study ten nuclei of each case have been considered. By using the S.A.M. (Shape Analytical Morphometry) work-station an analytical study of the nuclear shape was performed. The first step was the extraction of fundamental shape which describes the basic shape of original contour without its irregularities. It was obtained by using two parametric equations. The second step was the evaluation of shape asymmetry by S.A.E. (Shape Asymmetry Evaluator). Finally the contour irregularities were evaluated by Fourier analysis. Along with analytical parameters, dimensions (area, perimeter and maximum diameter) were considered too. All obtained data were submitted to univariate statistical analysis (Student's T test) to compare the two groups (ER positive and ER negative tumors). Area, perimeter and maximum diameter were significatively greater in ER negative cases while analytical parameters were not discriminant between the two groups.
The aim of the present paper is to find analytical parameters to distinguish severe dysplasia from cancer. A population of 150 nuclei was selected randomly from: 5 cases of large bowel carcinoma, 5 cases of adenomatous polyps with severe dysplasia--according to Kozuka's criteria--(without any reference to the architecture: tubular, tubulo-villous and villous) and 5 cases of normal mucosa as control. The files of the coordinates of the nuclear contours were submitted to the S.A.M. (Shape Analytical Morphometry) work-station, which produces quantitative parameters (area, perimeter, maximum diameter and Roundness Factor) as well as analytical shape-descriptors. The latter were extracted by the S.A.E. (Shape Asymmetry Evaluator) procedure, which evaluates the symmetry of each contour studied, and by Fourier harmonic analysis which breaks up each curve into a defined set of harmonics which are then used to perform statistical tests. In the comparison between normal and severe dysplastic nuclei, normal and carcinomatous nuclei and severe dysplastic and carcinomatous nuclei univariate statistical evaluation (Student t test) proved to be highly significant for the most of the analytical parameters.
The aim of this study was to investigate the biological significance of tumor shape in breast cancer by considering the shape not as a casual event but as an expression of the behavior and natural history of the tumor. The shape was studied by an analytical morphometry procedure and was related to axillary metastases, which up to now are the most meaningful prognostic factors in this disease. Fifty cases of infiltrating breast carcinoma (25 N+ and 25 N-) were investigated. The shape, studied on subgross sections of the tumor, was considered as the result of two components: the subtle contour irregularities and the main distortions of the figure. The procedures used allowed us to distinguish and to parametrize these two components in order to submit them to univariate analysis (Student's t test), a principal components analysis and, finally, a multivariate discriminant analysis (Hotelling test). The utilized analytical procedures by work-station S.A.M. (S.A.M. work station is a product of "Metamorphosis") consisted of three steps: 1) Extraction of tumor function curve obtained by Kth order polynominals which gives a smoothing effect to the original curve; 2) Evaluation of contour irregularities by Fourier harmonic analysis; 3) Evaluation of shape asymmetry by SAE (shape asymmetry evaluator). We considered also the roundness factors of the original and function curves and finally the maximum tumor diameter. Three parameters relating to contour irregularities (sum and mean value of Fourier harmonic amplitude and percentage of superimposed points) and parameters relating to main distortions of the figure (mean value of SAE) were highly significant (p less than 0.001). The roundness factor of the original curve was more significant (p less than 0.001) than that of the function curve (p less than 0.01) whereas maximum tumor diameter was not significant when tested by Student's t test. Multivariate discriminant analysis allowed 20% of error to be reached by using 3 parameters relating to the shape analysis and the two roundness factors. By using 8 parameters, including maximum tumor diameter, the percentage error was 16%. The results obtained, while they stress the usefulness of the employed procedure, reveal that shape of the tumor, together with its dimensions, is an important expression of the biological behavior relating to metastatic spread.
A morphometric study of the nuclear and cytoplasmic shape of a blastic population in a case of HM-A.L.L. was performed by comparing the two differently shaped populations with and without HM configuration. The results obtained using analytical size-independent parameters created by the S.A.M. work-station enable us to characterize the shape of both blastic cell populations quantitatively, and strongly suggest the existence of shape modulation from one cellular type toward the other. Thus a possible sequence from blastic cells (having regular, rather round nuclei) to HM cells (characterized by high distortion of both nucleus and cytoplasm) was proposed.
In the attempt to discriminate between centroblasts and immunoblasts, an analytical morphometrical procedure was adopted, considering the nuclei of a randomly selected centroblastic and immunoblastic population from non-Hodgkin's lymphomas and the nucleoli of a more restricted number of the same neoplastic population. All the size-independent shape-descriptor parameters extracted for each step of the mathematical analyses used were submitted to Hotelling's multivariate discriminant analysis that enabled us to achieve a good distinction (3% error) between centroblasts and immunoblasts when nuclear and nucleolar parameters were used together.
In this study some nuclear dimensional and analytical parameters were evaluated in order to distinguish follicular atypical adenoma from follicular carcinoma of the thyroid. Eighty nuclei from carcinomas, 80 from adenomas and 80 from normal thyroid were studied. Analytical parameters obtained by the nuclear shape study (by S.A.M. system) as well as dimensional parameters were submitted to univariate statistical analysis. On the ground of our results atypical adenoma could be considered as an intermediate aspect of a progressive change from benign to malignant even if they are closer to normal thyroid than to carcinoma.
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