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R Santopietro

Publications and source records attributed to R Santopietro.

At least 37 records · Page 2Linked to original sources

Proliferative activity, angiogenesis, and necrosis in peripheral nerve sheath tumors: a quantitative evaluation for prognosis.

Malignant peripheral nerve sheath tumors (MPNSTs) are distinguished from a control group of typical benign schwannomas and neurofibromas on the basis of a set of quantitatively evaluated parameters, i.e., the cell density; the number of mitoses and apoptotic bodies; the nuclear area and shape; the number and absolute and relative areas of silver-staining nucleolar organizer regions; necrosis; and angiogenesis. Only the extent of tumor necrosis, the mitotic rate, and the parameters related to silver-staining nucleolar organizer regions discriminate between less aggressive MPNSTs (disease-free patients after 4 years of follow-up) and more aggressive MPNSTs (with recurrences or metastases during the first 4 years of follow-up).

Adult↗

Gastric intestinal metaplasia type III cases are classified as low-grade dysplasia on the basis of morphometry.

The aim of this study was to try to place gastric intestinal metaplasia, type III (type III IM) in the stepwise chain of events from atrophic gastritis to cancer. A number of dysplastic, periulcer regenerative, and type III IM lesions were qualitatively diagnosed (and graded) blindly and independently by several pathologists. These lesions were further analysed by means of quantitative parameters, with the aim of differentiating dysplastic from regenerative changes. Inconsistencies between the qualitative and quantitative classification (about 7 per cent of cases) were eliminated and homogeneous groups (low-grade dysplasia, high-grade dysplasia, regenerative changes) were obtained. These cases were taken as the gold standard against which type III IM was compared. The results indicate that the great majority (91.4 per cent) of cases of type III IM fulfil the nuclear and architectural criteria for low-grade dysplasia.

Adult↗

Distinction between diffuse cutaneous malignant follicular center cell lymphoma and lymphoid hyperplasia by computerized nuclear image analysis.

The difficult differential diagnosis between the diffuse variants of cutaneous lymphoid hyperplasia (CLH; synonym; pseudolymphoma) and malignant follicular center cell lymphomas (FCCL) often requires a multidisciplinary approach. Eighteen CLH and 11 FCCL, diagnosed by conventional histology and immunophenotyping and subsequently examined with a polymerase chain reaction to show clonal immunoglobulin heavy-chain gene rearrangements, were subjected to a novel type of automated nuclear image analysis. Of all nuclear parameters tested in azure A-stained semithin sections, the mean nuclear profile area (TN) of lymphoid cells was the best criterion to distinguish between CLH and FCCL (p = 9 x 10(-6)). Additional distinctive features, in the order of decreasing significance, were the SD of TN; all chromatin textural parameters combined; and the light and the dark fractions of the central nuclear profile areas. Parameters related to the chromatin pattern were independent of nuclear profile size in FCCL, but not in CLH. Two lesions registered as CLH displayed the nuclear characteristics favoring this diagnosis, but showed B-cell monoclonality at the DNA level. In conclusion, computerized nuclear image analysis is a helpful additional diagnostic tool in the evaluation of diffuse CLH and cutaneous FCCL.

Adolescent↗

Apoptotic index: discriminant feature for the differentiation of cutaneous diffuse malignant follicular center cell lymphomas from lymphoid hyperplasia.

Diffuse subtypes of cutaneous lymphoid hyperplasia (CLH; n = 18) and primary malignant follicular center cell lymphoma of the skin (FCCL, n = 11) were diagnosed by conventional histology, immunophenotyping on paraffin sections, and gene rearrangement analysis. We then counted on semithin, Azur A-stained sections of resin-re-embedded biopsy specimens the relative numbers of apoptotic bodies among all lymphoid cells (apoptotic index [AI]). The diagnostic value of AI was compared to that of mitotic indices (MI) and percentages of various cell types in the cutaneous infiltrate. Features of cellular infiltrates distinguishing to two groups of lesions, in the order of decreasing significance, were percent large lymphoid cells, percent medium-sized lymphoid cells (both higher in FCCL); percent small lymphoid cells, percent epithelioid/giant cells, and percent histiocytes/macrophages (all three higher in CLH). However, of all parameters tested, AI had the greatest discriminant value (median in FCCL 1.11%, in CLH 0.14%; p = 8 x 10(-6)). Two cases, diagnosed as CLH with all morphologic and immunologic methods used, showed B-cell monoclonality at the DNA level. Linear discriminant analysis determined the following order of distinctive power of variables: 1) AI; 2) MI; 3) percent small lymphoid cells; 4) percent medium-sized lymphoid cells; 5) percent large lymphoid cells; 6) percent epithelioid/giant cells; and 7) percent histiocytes/macrophages. The present study thus establishes AI as an important parameter in the differentiation of diffuse CLH from diffuse cutaneous FCCL.

Adult↗

Bronchiolo-alveolar carcinoma: an analysis of survival predictors.

Macroscopic and microscopic features of tumours have been analysed in 37 bronchiolo-alveolar carcinomas. Lymphocytes, Langerhans cells, collagen (mature and/or myofibroblastic), were quantitatively or semiquantitatively evaluated. Histology, stage, type of fibrosis, nuclear profile features (area and shape factors), amount and type of mucin secreted, number of mitoses, Langerhans cells, myofibroblasts and LeuM1+ cells were not related to survival. Gross morphology of the tumour and, to a lesser extent, lymphoid infiltrates (in particular UCHL1+ and L26+ peritumoral lymphoid cells) were the only variables significantly related to survival. Estimated survival functions were computed according to Cox's model: well demarcated tumours behaved significantly better than poorly demarcated tumours and even more so than diffuse or multiple mass. Lymphoid infiltrates were significantly more represented in and around well demarcated tumours: however, their survival predicting value was less than that of the gross type.

Adenocarcinoma, Bronchiolo-Alveolar↗

Prognostic factors in invasive cervical carcinomas associated with human papillomavirus (HPV). Quantitative data and cytokeratin expression.

As a part of a larger programme to search for the prognostic factors in cervical cancer, quantitative morphometry, demonstration of AgNORs and expression of different cytokeratin polypeptides (SK2-27, SK1, A 53-B/A2) were used to study a series of 85 cervical squamous cell carcinomas, previously analysed for the presence of human papillomavirus (HPV) DNA by in situ hybridization and polymerase chain reaction (PCR). The following nuclear profile parameters were calculated: nuclear area, perimeter, maximum diameter, ellipsoidity (form Ell), regularity (form Ar) and roundness (form Pe). In each case, the number of small (< 3 microns), large (> 3 microns), the total number and the ratio large/small AgNORs were registered. The cancer cell density and the lymphoid cell density were assessed. In the survival analysis, neither the expression of different cytokeratin polypeptides or the pattern of cytokeratin staining proved to be an independent variable. Similarly, none of the nuclear profile parameters analysed possessed an independent prognostic value in the survival analysis. The ratio of large/small AgNORs proved to be a significant independent prognostic predictor (p = 0.0104), second only to the lymphoid cell density. Also the total number of AgNORs was a prognostic indicator. This suggests that AgNOR size and ratio reflect tumor proliferation also in cervical squamous cell carcinoma, as shown in other human malignancies. Similarly, the density of cancer cell nuclei proved to be an independent prognostic predictor (p = 0.0601) in that the tumours in patients with longer survival showed lower density of the nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Morphometry and the differential diagnosis between peripheral neuroepithelioma and neuroblastoma.

The differential diagnosis based on morphology between neuroblastoma (NB) and peripheral neuroepithelioma (PN) is difficult, since these tumors share many architectural and cytological features. In this study, a morphometrical approach to this diagnosis is made by using nuclear (shape factors) and tissue (volume density of nuclei and stroma) parameters. Quantitative morphological analysis adds important information, which when used with clinical and biochemical data facilitates the distinction. In the majority of cases, nuclei of PN are significantly less round than those of NB and their profile is much more irregular. The density of neoplastic nuclei is significantly higher in PN. However, in a certain number of cases, even the morphometrical study confirms how difficult it may be to differentiate these two neoplastic entities, since the values of parameters are largely overlapping. This suggests the existence of a "continuum" of changing features between NB and PN, which may substantiate the hypothesis of a common histogenesis.

Adolescent↗

Morphometric definition and grading of gastric intestinal metaplasia.

Type I and type III intestinal metaplasia in gastric mucosa have been examined using morphometric methods. Tissue (volume per cent gland, lumen, epithelium, goblet cell vacuoles) and nuclear parameters (area, with related standard deviation, and form factors) were used as indicators of gland crowding, nuclear-cytoplasmic ratio, nuclear atypia, and pleomorphism. In type III intestinal metaplasia, there is significantly (i) greater nuclear pleomorphism, (ii) a higher nuclear-cytoplasmic ratio, and (iii) smaller and less numerous goblet cell vacuoles in both the upper and the lower parts of the crypts. These two parameters have significantly higher values in the lower than in the upper part of individual crypts. No cell population with large pleomorphic nuclei characterized type III metaplasia, though there was more variation in nuclear size.

Adult↗

The nuclei in cutaneous malignant melanoma, stage I, are smaller in survivors than in non-survivors.

Cutaneous melanoma, stage I, from 35 survivors at 5 year follow-up and 16 non-survivors were studied. Mean nuclear area in the superficial layer was significantly larger than in the deep layer both in survivors and non-survivors, but the ratio between nuclear area in superficial and deep layers (so-called maturation index) did not differ between survivors and non-survivors. In comparison with the survivors, the mean nuclear area of non-survivors was significantly larger both in the superficial (51.1 microns2 vs 43.7 microns2, p less than 0.01) and deep (42.9 microns2 vs 36.4 microns2, p less than 0.05) layer. This points to a general increase in nuclear areas in metastasizing tumors. Furthermore, the coefficient of variation of nuclear area [(standard deviation/mean) x 100] was not different between survivors and non-survivors, either in the superficial or in the deep layer. Inspection of histograms of areas of 1000-2000 nuclei per case in 20 random cases (10 survivors and 10 non-survivors) showed a homogeneous increase in nuclear area in non-survivors. None of the histograms revealed a cell clone with especially large nuclei. These data show that the increased mean nuclear area in non-survivors is due to a homogeneous increase of all nuclei throughout the tumor and not to a special cell clone with large nuclei within nuclei of otherwise normal size. The difference in mean nuclear area in superficial and deep layers indicates that careful selection of nuclei in either of these layers is essential to obtain reproducible and comparable results with interactive morphometry.

Cell Nucleus↗

Estrogen receptor content, immunohistochemically determined by monoclonal antibodies, in endometrial stromal sarcoma.

The estrogen receptor content, determined immunohistochemically by staining with monoclonal antibodies, was studied in seven consecutive cases of endometrial stromal sarcoma. In addition, the mitotic rate and immunohistochemical patterns (vimentin, desmin, actin, cytokeratins) were determined. Five of seven cases contained estrogen receptors, three low-grade (fewer than 10 mitoses/10 high-power fields [hpf]) and two high-grade (10 or more mitoses/10 hpf), the latter having a relatively low mitotic rate. The two negative cases were high-grade with a very high number of mitoses. Tumor cells were positive only to vimentin. Based on these results, we postulate that estrogen receptors are undetectable only in highly proliferating neoplasms. Thus, immunohistochemically determined estrogen receptor levels may indicate the aggressiveness of endometrial stromal sarcoma, and might be a guideline in selecting patients for hormonal therapy. The presence of positive immunostaining to vimentin confirms the mesenchymal origin of endometrial stromal sarcoma.

Actins↗

Steriological analysis of peritumoral lymph nodes in patients operated for cervical and endometrial cancer after being treated with thymostimulin.

We have evaluated, by means of stereological analysis, the dimensions of the lymph node functional areas (cortical, medullary, paracortical, histiocytosis of the sinuses, germinal centers) in regional lymph nodes of women with cervical cancer (15 women) and endometrial carcinoma (6 women) in Ist and IInd stage, treated 8 days before surgery with a dose of 1-1.5 mg/kg of body weight of thymostimulin directly into the uterine cervix. 4 women with cervical and endometrial cancer (stages I and II) and treated with the same doses of physiological saline solution were used as controls. The quantitative results show that in the lymph nodes of women treated with thymostimulin there is a statistically significant marked increase (P less than 0.001), of the paracortical areas.

Female↗

Morphometric assessment of the biological potential of human papillomavirus infections in the uterine cervix.

A series of 69 punch biopsies derived from 513 women prospectively followed up for cervical human papillomavirus (HPV) infections (including HPV lesions with and without cervical intraepithelial neoplasia; HPV-CIN, HPV-NCIN), and 42 control cases (consisting of normal epithelia, and classical CIN lesions) were analyzed morphometrically, using a semiautomatic image analyzer (IBS I-KONTRON), to assess the value of morphometric measurements in discriminating between HPV lesions and CIN, and to find out whether these methods are useful in predicting the outcome of cervical HPV infections. Nuclear area and the form factors Ell, Ar, and Pe were calculated on fifty nuclei in each of the three layers of epithelium; deep, intermediate and superficial. The reproducibility of the measurements was calculated for intra- and interobserver variation. HPV typing was completed using the in situ hybridization technique with DNA probes for HPV 6, 11, 16, 18 and 31. No significant differences were detected by using the form factors (Ell, Ar, Pe), when HPV lesions were compared with the normal epithelium, or with classical CIN lesions, in any of the epithelial layers. The nuclear area was significantly larger in all the epithelial layers in HPV-CIN I, and HPV-CIN II lesions as compared with CIN I and CIN II cases (p less than 0.001), p less than 0.001, p less than 0.005 and p less than 0.001, for deep, intermediate and superficial layers between HPV-CIN I/CIN I, and for all layers in HPV-CIN II/CIN II comparisons, respectively). This was also true when the values of nuclear area in HPV-NCIN I, HPV-CIN II and HPV-CIN III lesions were compared with the normal epithelium (p less than 0.001 for all layers). In the most severe lesions, no significant differences existed between HPV-CIN III and CIN III cases. Nuclear area measurement could not predict, however, the HPV type found in the lesion, or their natural history established by prospective follow-up.

Cervix Uteri↗

Non-Hodgkin's lymphoma primarily involving the bronchial tree.

Among extranodal localizations, the bronchial one is very unusual, especially as primary involvement. The authors present 2 cases of non-Hodgkin's lymphoma (NHL) admitted to the hospital because of thoracic abnormalities. Chest x-ray revealed lobar atelectasis. Fiberoptic bronchoscopic findings agreed with the diagnosis of unresectable bronchogenic tumor in both cases. Histologic examination of biopsy specimens was nonrevealing in the first patient, and suggested small cell lung cancer in the second one. Further histologic and immunohistochemical examinations excluded bronchial tumors (particularly small cell bronchogenic carcinoma) and led to the diagnosis of lymphocytic lymphoma in one case and centroblastic lymphoma in the other. In the differential diagnosis of bronchogenic tumors, it is necessary to keep in mind the hypothesis of lymphomatous involvement of the bronchial wall, although it rarely occurs.

Aged↗

Morphometry for the prognosis of acute lymphoblastic leukemia in childhood.

The morphology of acute lymphoblastic leukemia is of prognostic significance, but due to the qualitative subjective nature of the assessment, disagreement between pathologists may be considerable. In order to investigate the adjuvant potential of morphometry, the present study was undertaken. Morphometry was applied in 21 children between 2 and 10 years of age with acute lymphoblastic leukemia (ALL) with a follow-up of at least 5 years. Of these, 9 patients died, 12 (57.1%) survived for at least five years (maximally 12 years). Morphometry appeared to have an important prognostic value, independent of the FAB classification currently in use. Combination of the nuclear-cell area ratio and the cell area gave a rather good discrimination, although these quantitative data from a morphological continuum. The positive results of this pilot study point to the necessity of evaluating the data on a larger material.

Cell Nucleus↗

Correlation between immunohistochemically determined oestrogen receptor content, using monoclonal antibodies, and qualitative and quantitative tissue features in ductal breast cancer.

Previous studies have shown that oestrogen receptor content in breast cancer was correlated with qualitative and also, more strongly, with quantitative nuclear features in tissue sections. However, even with the better reproducible quantitative microscopical assessments, the variance in the correlation with oestrogen receptor was considerable. This might be due to the implicit problems of oestrogen receptor determination with the biochemical assay. Therefore, receptor content was studied using monoclonal antibodies in 50 consecutive invasive ductal breast cancers. Oestrogen receptor status was compared with qualitative features and with the mean and standard deviation of the nuclear area, morphometrically evaluated on immunostained and adjacent haematoxylin and eosin stained sections. In agreement with earlier observations, nearly all tumours with prominent elastosis were oestrogen receptor positive; but a minority of negative cases also showed elastosis. The correlation between the other qualitative features and receptor status was weak. A significant inverse correlation (P less than 0.001) existed between the receptor status and the mean and standard deviation of the nuclear area. Even with the highly reproducible morphometrical analysis, correlation between nuclear oestrogen receptor content and quantitative nuclear features was relatively weak. This might indicate that receptor status and nuclear morphometric features reflect different biological characteristics of breast cancers.

Adult↗

Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. III. Morphometric assessment of the dynamic changes in post-capillary venules as regulatory elements of lymphocyte recirculation in tumor-draining lymph nodes.

To evaluate the dynamics of lymphocyte recirculation in tumor-bearing mice, the post-capillary venules (PCV) were subjected to quantitative measurements in the regional (RLN) and nonregional (NRLN) lymph nodes during the progression of P815X2 mastocytoma in syngeneic DBA/2 mice. Mice were sacrificed at two-day intervals, and RLNs and NRLNs were analysed for their content of B- and T-lymphocytes and their subsets, demonstrated by immunoperoxidase technique using monoclonal antibodies; Anti-Thy 1.2 (T cells), Anti-Lyt 1 (T-helper cells), Anti-Lyt 2 (T-suppressor cells), and Anti-I-Ad (B cell) antigens, separately in the B- and T-cell compartments. In the PCVs, migration index (MI) and endothelial height (Hend) were measured. There was a biphasic elevation of MI in the RLNs, as compared with only a late rise in the NRLNs, reaching the peak (1.54) on day 14. In RLNs, there was a sharp reduction in Hend starting from the values (6.37 microns) on day 2, down to 4.79 microns on day 8. This is followed by rapid elevation close to the second-day values, e.g. 6.07 on day 10. The changes in MI paralleled the early influx of B cells, as evidenced by the decrease of Thy 1.2+/I-Ad+ cell ratio and a late recruitment of T cells as indicated by the elevation of that ratio as well as the Hend values in both the RLNs and NRLNs. The present experiment shows that morphology of PCVs in the RLNs and in NRLNs of P815X2-bearing mice is subjected to alterations reflecting the dynamics of lymphocyte recruitment into these organs. When combined with lymphocyte subset enumeration using monoclonal antibodies, the quantitative analysis of the PCVs permits predictions to be made on the recirculatory activity of these cell populations during the tumor progression.

Animals↗

Mycosis fungoides. Detection of OKT6+ cells by cytofluorographic analysis in one case.

An 86-year-old woman had a subjective history of pruritus and intermittent fever. The clinical diagnosis of mycosis fungoides was confirmed by cutaneous and lymph node biopsies. Immunohistochemical, cytofluorographic, and ultrastructural analysis was performed. According to immunohistochemical findings the lymphoid cells infiltrating the skin and lymph nodes were phenotypically T-helper cells. Cytofluorographic and ultrastructural analysis of the peripheral blood detected a small number of cerebriform lymphoid cells. By immunohistochemistry, these cells showed the same phenotype that was found in the skin and lymph nodes. OKT6+ cells, which are not usually present, were also found in the peripheral blood. These findings may suggest a functional relationship between the skin and the lymphoid system.

Aged↗