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L Leoncini

Publications and source records attributed to L Leoncini.

At least 55 records · Page 3Linked to original sources
PubMed1997

Growth patterns of diffuse non-Hodgkin's lymphomas estimated from mitotic and apoptotic indices.

Growth rates of neoplasms could be calculated only on the basis of mitotic and apoptotic indices (MI and AI, respectively), assessed on tissue sections, if the duration of mitosis and apoptosis (Tm and Ta, respectively) in vivo were known. For humans, this is practically never the case. What use then can be made of MI and AI to arrive at a relative, crude estimate of the state of growth? As a model system to study this problem, we chose diffusely growing stage I + II non-Hodgkin's lymphomas (dNHL, n = 94). Cluster analysis revealed the existence of 3 highly distinct groups of dNHL (clusters I, II and III) in the MI vs. AI per case plot, with a roughly linear relation between both parameters. Most nosologic entities defined by the REAL classification comprise cases that were represented in more than one cluster. We adopted the simple formula GI (growth index) = XMI - AI, where X (= Ta/Tm) remains to be evaluated. Based on the assumption that spontaneous regressions of dNHL are rare but do occur, we estimated that X = 2 or, possibly, 3 are best fits for the pooled dNHLs studied. With the assumption of X = 2, (i) 2MI - AI gave relatively lower values for dNHL than proliferative indices such as %Ki-67+ cells; (ii) values for 2MI/AI per cluster showed a pattern inverse to that for %bcl-2+ cells; and (iii) a plot of 2MI - AI vs. 2MI/AI per case allowed the recognition, especially among NHLs with a low cell turnover, of cases where accumulation of presumably longer-lived cells is an important factor in determining growth.

Adolescent↗
PubMed1997

Cellular kinetic and phenotypic heterogeneity in and among Burkitt's and Burkitt-like lymphomas.

This study asks whether the known genotypic heterogeneity within and between endemic or sporadic Burkitt's lymphomas (eBLs and sBLs, n = 10 each), and Burkitt-like lymphomas (BLLs, n-12), is reflected in divergent cytokinetics and related immunophenotypes. There was strong evidence that eBL and BLL grow markedly faster than sBL, as shown by differences in mitotic and apoptotic indices. Furthermore, in BLL, the median percentage of neoplastic cells immunoreactive for the bcl-2 protein was much higher than that observed in eBL and sBL. The reverse was true for the median fraction of cells containing c-myc protein. In eBL and sBL, the median fraction of bcl-6 protein-positive cells reached values above 50 per cent, while cells of 8/12 BLLs did not contain detectable amounts of this protein. This observation indicates that in this respect, eBL and sBL resemble normal germinal centres of lymphatic tissue much more than do BLL. Evidence for infection of neoplastic cells by the Epstein-Barr virus (EBV) was observed in 9/10 cases of eBL and in 3/10 of sBL, but not in BLL. EBV-positive lymphomas were associated with distinctly lower apoptotic indices and smaller median percentages of bcl-6-positive cells than EBV-negative tumours.

Adolescent↗
PubMed1997

Antigen retrieval techniques in immunohistochemistry: comparison of different methods.

Routine sections of normal and pathological samples fixed in 10 per cent buffered formalin or B5, including EDTA-decalcified bone-marrow biopsies, were tested with 61 antibodies following heating in three different fluids: 0.01 M citrate buffer (pH 6.0), 0.1 M Tris-HCl (pH 8.0), and 1 mM EDTA-NaOH solution (pH 8.0). The sections underwent either three cycles of microwave treatment (5 min each) or pressure cooking for 1-2 min. The alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique was used as the standard detection method; with 16 antibodies a slightly modified streptavidin-biotin complex (SABC)-immunoperoxidase technique was applied in parallel. The results obtained were compared with those observed without any antigen retrieval (AR), or following section digestion with 0.05 per cent protease XIV at 37 degrees C for 5 min. Chess-board titration tests showed that all antibodies but one profited by AR. Protease XIV digestion represented the gold standard for five antibodies, while 55 produced optimal results following the application of heat-based AR. By comparison with the other fluids, EDTA appeared to be superior in terms of both staining intensity and the number of marked cells. These results were independent of tissue processing, immunohistochemical approach, and heating device. Pressure cooking was found to be more convenient on practical grounds, as it allowed the simultaneous handling of a large number of slides and a time saving of 1 min 30 s, representing the proper time for the treatment.

Antigens↗
PubMed1997

Peripheral T-cell lymphomas. Clinico-pathologic study of 168 cases diagnosed according to the R.E.A.L. Classification.

BACKGROUND: One hundred sixty-eight peripheral T-cell lymphomas (PTCLs) were reviewed according to the Revised European-American Lymphoma (R.E.A.L.) Classification. PATIENTS AND METHODS: The cases, originally diagnosed on the basis of the Updated Kiel Classification (UKC), were all provided with histological preparations, immunophenotype, clinical information, and follow-up data. The slides were reclassified by five observers, who integrated the R.E.A.L. criteria with cell size measurements. The prognostic value of clinical and pathologic findings was assessed by univariate and multivariate analysis. RESULTS: The R.E.A.L. Classification was reproducibly applied by all of the observers. Clinically, anaplastic large cell lymphomas (ALCLs) differed from the remaining PTCLs by mean age (29.5 vs. 52.9 years), bulky disease (52.3% vs. 11.3%; P = 0.000), mediastinal mass (52.7% vs. 32%; P = 0.004), and disease-free survival (68.0% vs. 38.2%; P = 0.0001). Although each histological type displayed specific clinical aspects, PTCLs other than ALCL were basically characterised by a poor clinical outcome which was not influenced by the UKC malignancy grade. At multivariate analysis, the risk of a lower complete remission rate was related to bulky disease (P = 0.001), histologic group (non-ALCL) (P = 0.01), and advanced stage (III-IV) (P = 0.0002). CONCLUSIONS: The present study supports the classification of T-cell lymphomas proposed by the R.E.A.L. scheme.

Adolescent↗
PubMed1997

Pyothorax-associated lymphoma: description of the first two cases detected in Italy.

BACKGROUND: Pyothorax-associated lymphoma (PAL) is a rare, but distinct, clinico-pathologic entity which occurs most often in Japanese people; to the best of our knowledge, only six cases of it have been reported in Western countries. The tumour develops several decades following artificial pneumothorax or chronic pleuritis due to tuberculous infection, produces pleural effusion associated with extensive local lymphomatous infiltrates, and is sustained by a polymorphic large B-cell clonal proliferation showing EBV integration in the genoma of the neoplastic cells. PATIENTS AND METHODS: Herein we describe two cases of PAL observed in Italian patients, both extensively studied on the clinical, pathological, phenotypic, virological, and molecular levels. RESULTS: The two cases occurred, respectively, 45 and 50 years after therapeutic pneumothorax because of tuberculous pleuritis and were characterized by a pleural mass extending to the thoracic wall, which on histological examination were seen to consist of large elements with immunoblastic morphology. Immunohistochemistry show monotypic restriction of Ig light chains, as well as the expression of CD45, B-cell markers (CD20, CD79a, CD45RA), bcl-2 oncogene product, EBNA-2 and, partially, LMP-1. The ratio of cycling cells was extremely high as was the number of mitotic figures. In situ hybridization displayed the presence in the neoplastic cells of the EBV-related small RNAs EBER 1 and 2, which in turn, along with the positivity for EBNA-2 and LMP-1, further strengthened the close relationships between PAL and latent viral infection. Molecular studies revealed, on one hand, clonal rearrangement of the Ig heavy chain J region genes, and on the other, negativity for HHV8 in one case and positivity in the other. CONCLUSIONS: These cases of PAL are the first to be documented in Italy; they serve to direct attention to the fact that this condition is not confined to Japanese people, and that its occurrence in Western countries might be underestimated.

Aged↗
PubMed1997

Mitotic activity and nuclear DNA damage of large cells in Hodgkin's disease: comparison with the expression of p53 and bcl-2 proteins and the presence of Epstein-Barr virus.

The roles of the bcl-2 and p53 proteins in Hodgkin's disease (HD) are poorly understood. We therefore compared their detected presence in Hodgkin and Reed-Sternberg/large atypical (H-RS/LA) cells immunohistochemically with the percentages of these cells double-labeled for CD30 and DNA strand breaks (DNA fragmentation index, DFI); mitotic indices (MI); and the EBV infection status. We found a highly significant inverse correlation between the fractions per case of H-RS/LA cells expressing bcl-2/p53 proteins and the DFI of CD30+ elements. No marked effect of these two oncoproteins on MI was noticed, although these parameters and DFI of CD30+ cells were linearly related. EBV infection of H-RS/LA cells exerted only a limited effect on the parameters tested. The results of this study suggest that overexpressed bcl-2 and, to some extent, p53 proteins in H-RS/LA cells of HD primarily counteract deletion of these cells.

Adolescent↗
PubMed1997

Cell kinetics, morphology, and molecular IgVH gene rearrangements in Hodgkin's disease.

The present study dealt with the question of whether any cellular kinetic patterns correlate with clonal rearrangement of the IgVH gene as revealed by polymerase chain reaction on DNA extracted from lymph nodes with classical Hodgkin's disease (HD) and/or from single CD30+ cells (Hodgkin [H] and Reed-Sternberg [RS] cells). In 15/4 cases with H-RS cells of B or Null phenotype, signs of such monoclonality could be detected (group I) but not in the others (group II). CD30+/H-RS cells in group I differed slightly but significantly from those in group II in that they a) exhibited a larger fraction of cells attaining the anaphase/telophase stage of mitosis, and b) produced relatively more mononucleated cells (H) at the expense of multinucleated (RS) cells. In addition, reactive lymphoid cell (CD30-) infiltrates were considerably less dense in group I that in group II. These findings suggest that the cytokinesis of H-RS cells in group I was moderately more efficient than in group II. However, signs of monoclonality were not associated with the normalization of the mitotic process, which also proved to be disturbed in group I.

Adolescent↗
PubMed1997

Immunohistochemistry of bone-marrow biopsy.

In a percentage of cases, conventional morphologic evaluation of bone-marrow needle biopsy (BMNB) in insufficient to achieve a firm diagnosis. Under these circumstances, immunohistochemistry plays a basic role, providing an easy and objective key for the interpretation of the pattern observed in most instances. Herein, the authors focus on the technical procedures, which allow extensive application of immunohistochemistry to the study of BMNB, as well as on the panels of antibodies needed for the identification of the most relevant conditions.

Antigens, CD↗
PubMed1997

[Role of Doppler color in the differential diagnosis of benign and malignant adenopathies].

The diagnosis of enlarged lymph nodes is of the utmost importance especially in the treatment planning of cancer patients. US yields such morphological findings as node size, longitudinal/transverse diameter ratio, hilum visibility and cortical thickness, which however do not permit the differential diagnosis of benign from malignant forms. Some authors tried to distinguish inflammatory enlargement from metastatic forms on the basis of color Doppler findings, with conflicting and questionable results. We investigated the potentials of color Doppler US in the differential diagnosis of benign and malignant lymph node enlargement using morphological data and flow measurements in lymphatic hilum vessels. The palpable superficial lymph nodes of 70 patients were studied with color Doppler with a linear probe (7.5-10 MHz) equipped for Doppler flow measurements. The largest lymph node was studied in multiple enlargement. The final diagnosis was made with US-guided cytology and/or excisional biopsy. The venous hilar vessels were depicted with color Doppler US in 44/45 patients with lymphadenitis and only in 1/17 patients with metastatic enlargement. Spectral Doppler exams of the hilar arteries showed flows with a wide telediastolic component in lymphadenitis (relative RI:0.58), while flow was rapid and with poor telediastolic component (relative RI:0.84) in metastatic enlargement. Average RI was 0.62 in Hodgkin's lymphomas and 0.71 in all the other lesions. We conclude that the distortion and compression of the main hilar vessels in metastatic lymph node enlargement often prevents color Doppler depiction of venous vessels. Moreover, the compression and distortion of the intranodal capillary network (the "mass" effect) often results in increased RI, as detected with power Doppler in the lymphatic hilum. Even though color Doppler US studies of the hemodynamic changes in the hilar vessels need further validation in larger series of cases, our preliminary results suggest interesting potentials in distinguishing inflammatory from metastatic enlargement, which differentiation remains nevertheless difficult especially in Hodgkin's lymphoma.

Adolescent↗
PubMed1996

Stage-related differences of mitotic and apoptotic indices, and bcl-2 protein expression in diffusely growing non-Hodgkin's lymphomas.

The present study examined whether growth characteristics of diffusely growing non-Hodgkin's lymphomas (NHL) may differ as a function of stage. Among 105 NHL of various types and sub-types (REAL [Revised European-American Lymphoma] classification), localized (Ann Arbor pathologic stages I + II) lymphomas exhibited clearly higher indices for mitotic activity, apoptosis and cell turnover, as well as a significantly lower percentage of cells containing immunohistochemically detectable bcl-2 protein, than disseminated (stages III + IV) NHL. A similar pattern emerged when high-grade (Kiel classification) lymphomas only were evaluated. Low-grade NHL showed analogous, but less marked, stage-dependent characteristics, with the exception of median percentages of bcl-2+ cells, which remained comparable in all stages. Our findings are consistent with the notion that dissemination of diffusely growing NHL is usually associated with reduced cell turnover and, in high-grade lymphomas, with the generation of longer-lived cells.

Adolescent↗
PubMed1996

Growth vs. DNA strand breaks in Hodgkin's disease: impaired proliferative ability of Hodgkin and Reed-Sternberg cells.

We re-appraised the cell renewal pattern in Hodgkin's disease (HD), considering that most, though not all, Hodgkin/Reed-Sternberg (H-RS) cells exhibit abortive mitoses and that a substantial fraction of these exhibits DNA damage suggestive of imminent or actual cell death. Using combined immunohistochemistry and in situ end-labeling to detect strand breaks, the percentage per case of CD30+ (mainly H-RS) cells with DNA fragmentation (DNA fragmentation index [DFI]) was estimated. For each case, we registered the mitotic index (MI) of CD30+ cells and the percentage of Ki-67+ atypical large cells. To quantify the sum of our parameters for mitosis, whether successful or not, and DNA damage, we introduced the kinetic event index (KEI = MI + DFI). Only DFI and KEI distinguished significantly between mixed cellularity and nodular sclerosis HD. The values for MI and DFI, and therefore for KEI, CD30+ and CD30- small lymphoid cells were proportional. The percentages of Ki-67+ large atypical cells (median 50%) did not correlate significantly with either MIs or DFIs of CD30+ cells. Cluster analysis revealed the existence, independent of histological subtype, of 2 large groups of HD with different KEIs. Our findings suggest that cell deletion plays an important role in HD. Further, it appears that proliferation-associated antigens in H-RS cells do not reflect successful cell production in this disorder.

Adolescent↗
PubMed1996

Neoplastic cells of Hodgkin's disease show differences in EBV expression between Kenya and Italy.

The Epstein-Barr Virus (EBV) has been implicated in the pathogenesis of Hodgkin's disease (HD). However, the association of EBV with this disease varies greatly from series to series and from country to country. Epidemiological studies have shown differences in HD occurring in different parts of the world. In particular, it has been reported that HD in developing countries differs from HD in Western countries in terms of epidemiological, pathological and clinical characteristics. These discrepancies among populations suggest an interaction with environmental factors and a direct role of different etiological agents. At present, there are no data on the frequency of association of EBV with HD in equatorial Africa. In this study, a large series of HD cases have been collected at the University of Nairobi, Kenya, and at the Universities of Bologna and Siena, Italy. The cases have been reviewed and classified according to the REAL Classification and the presence of EBV has been assessed by in situ hybridization (ISH). A statistical difference in EBV expression was found between HD from Kenya and HD from Italy. EBV-positive neoplastic cells were detected in 92% of Kenyan cases, whereas only 48% of Italian cases showed EBER1/2 positivity in the neoplastic cells. Our results suggest that, in Kenya, EBV plays a more direct role in the pathogenesis of HD, as it does for endemic Burkitt lymphoma.

Adolescent↗
PubMed1996

Reliability and accuracy of reporting cervical intraepithelial neoplasia (CIN) in 15 laboratories throughout Italy: phase 1 of a national programme of external quality control in cervical screening. The National Working Group for External Quality Control in Cervical Screening.

This paper reports results of a first phase of a pilot study to assess and improve quality of diagnoses in cervical cytological laboratories located throughout Italy. It represents the first phase of an External Quality Assurance programme (EQA). In the first phase, two sets of cervical smears representing a range of diagnoses were circulated among participating laboratories. Responses were recorded on a standardized form. Participants were asked to assess the adequacy of the smear and formulate a diagnosis. They were also asked to recommend management of the patient on the basis of the smear report and judge the degree of diagnostic difficulty of each slide. Crude index of agreement, unweighted and weighted kappas, diagnostic specific kappas, sensitivity and specificity as well as clinical indices of variability were calculated. In the second phase, two additional sets of slides were circulated after discussion of the first phase. There was striking variability between laboratories, both in terms of diagnoses offered and recommendations for management on individual slides. Assessment of the degree of difficulty of each slide was also very variable. Discrimination between CINII and CINIII was poor, confirming the choice of merging these two categories in the Bethesda classification. However, discrimination between CINI and CINII was also unsatisfactory. The results were discussed in workshops and it was possible to reach a consensus diagnosis in 35 of 40 smears. This study confirms the need for external quality control programmes.

Clinical Laboratory Information Systems↗
PubMed1996

Molecular findings and classification of malignant lymphomas.

We review the problem of lymphoma classification in the light of the Revised European-American Lymphoma (REAL) scheme, recently proposed by the International Lymphoma Study Group (ILSG). The REAL classification is a list of clinicopathologic entities, all well known from the literature, upon which the ILSG members agreed. Although it contains nothing new, for the first time all the elements, including immunophenotype and molecular data, which characterise a given lymphoma entity are considered. This approach corresponds to the need for objective criteria integrating the often puzzling morphologic findings. Furthermore, better knowledge of the molecular events which contribute to tumour development and progression if of paramount importance for the development of more specific and successful therapies. Some relevant molecular findings included in the classification and additional data obtained by the ILSG members following its publication are discussed.

Chromosome Aberrations↗
PubMed1996

Abortive mitoses and nuclear DNA fragmentation in CD30+ large cells of Hodgkin's disease.

This study was undertaken to better comprehend the reasons for the scarcity of Hodgkin and Reed-Sternberg (H-RS) cells in Hodgkin's disease (HD) despite their expression of "proliferation-associated antigens". To this end, we assessed the relative frequency of mitotic phases and nuclear damage (detected by in situ end-labeling of DNA strand breaks) in CD30+ large cells of nodular sclerosis and mixed cellularity HD. Our results show that a) most CD30+ cells in HD exhibit abortive mitoses, with a highly significant arrest at the metaphase-ana/telophase transition, and b) many of these elements, i.e. mainly H-RS cells, show fragmentation of nuclear DNA, suggesting imminent or actual death. Percentages of CD30+ cells that entered mitosis and those with DNA strand breaks were of a similar order of magnitude and correlated significantly in a linear fashion. These findings are consistent with the concept that cell deletion is the major cause of the paucity of H-RS cells in HD.

Adolescent↗
PubMed1996

Low incidence of Epstein-Barr virus presence in primary cutaneous T-cell lymphoproliferations.

Multiple biopsies taken from 76 European human immunodeficiency virus (HIV)-negative patients with primary cutaneous T-cell lymphoproliferations, including mycosis fungoides (MF), pleomorphic T-cell lymphoma (PMTCL), anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis (LyP) were investigated for the presence of Epstein-Barr virus (EBV) through a combined approach. Polymerase chain reaction (PCR) was employed for EBV-DNA detection, in situ hybridization (ISH) for cellular localization of EBV-encoded nuclear RNAs (EBER1 and EBER2) and immediate early Bam H-fragment; lower frame (BHLF) RNA, and immunohistology (IH) for the identification of EBV-encoded latent membrane protein 1 (LMP1) and of nuclear antigen (EBNA) 2 expression. EBV-DNA was detectable by PCR in 15 of 76 cases (19.7%). EBER-ISH combined with IH identified a variable, usually very low, number of infected neoplastic cells in only seven of the 15 EBV-DNA-harbouring cases. This discrepancy between the results obtained with PCR and ISH is apparently caused by the low number of the infected cells per tissue section. The PMTCL entity produced the greatest number of positive cases, whilst ALCL and LyP cases were almost constantly devoid of the virus. BHLF transcripts were not detectable in any case, nor did any of the EBER-positive cells show an LMP1 or EBNA2 expression. These data show that primary cutaneous T-cell lymphoproliferations display an infrequent association with a latent EBV infection and that the pathogenic role of the virus in the positive cases remains obscure as the virus frequently infects only a minority of the atypical cells.

DNA, Viral↗
PubMed1996

Heterogeneous nuclear expression of the promyelocytic leukemia (PML) protein in normal and neoplastic human tissues.

The RING-finger promyelocytic leukemia (PML) protein is the product of the PML gene that fuses with the retinoic acid receptor-alpha gene in the t(15; 17) translocation of acute promyelocytic leukemia. Wild-type PML localizes in the nucleus with a typical speckled pattern that is a consequence of the concentration of the protein within discrete subnuclear domains known as nuclear bodies. Delocalization of PML from nuclear bodies has been documented in acute promyelocytic leukemia cells and suggested to contribute to leukemogenesis. In an attempt to get new insights into the function of the wild-type PML protein and to investigate whether it displays an altered expression pattern in neoplasms other than acute promyelocytic leukemia, we stained a large number of normal and neoplastic human tissues with a new murine monoclonal antibody (PG-M3) directed against the amino-terminal region of PML. As the PG-M3 epitope is partially resistant to fixatives, only cells that overexpress PML are detected by the antibody in microwave-heated paraffin sections. Among normal tissues, PML was characteristically up-regulated in activated epithelioid histiocytes and fibroblasts in a variety of pathological conditions, columnar epithelium in small active thyroid follicles, well differentiated foamy cells in the center of sebaceous glands, and hypersecretory endometria (Arias-Stella). Interferons, the PML of which is a primary target gene, and estrogens are likely to represent some of the cytokines and/or hormones that may be involved in the up-regulation of PML under these circumstances. In keeping with this concept, we found that PML is frequently overexpressed in Hodgkin and Reed-Sternberg cells of Hodgkin's disease, a tumor of cytokine-producing cells. Among solid tumors, overexpression of PML was frequently found in carcinomas of larynx and thyroid (papillary), epithelial thymomas, and Kaposi's sarcoma, whereas carcinomas of the lung, thyroid (follicular), breast, and colon were frequently negative or weakly PML+. We did not observe any changes in the levels of PML expression as the lesion progressed from benign dysplasia to carcinoma. Our immunohistological data are consistent with the hypothesized growth suppressor function of PML and strongly suggest that PML expression levels are likely to be modulated by a variety of stimuli, including cytokines and hormones.

Amino Acid Sequence↗