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Biomedical subjects

L Leoncini

Publications and source records attributed to L Leoncini.

At least 73 records · Page 4Linked to original sources
PubMed1995

Presence of the bcl-2 protein and apoptosis in non-Hodgkin lymphomas with diffuse growth pattern.

In an attempt to further clarify the role of the apoptosis-counteracting protein bcl-2, non-Hodgkin lymphomas (NHL, n = 170) were examined immunohistochemically, across the boundaries of histologic classification, for the presence of this oncoprotein, in comparison with apoptotic indices (AI) and percentages of Ki-67+ cells (growth fraction). The results of this retrospective study revealed a highly significant inverse relationship ("mirror image") between the proportion of bcl-2+ cells and the AI per case. Both these parameters, although variable, clearly distinguished low- from high-grade-malignancy lymphomas according to the Kiel classification. Cluster analysis detected 2 separate groups of high-grade NHL, one with rather high AI and low percentages of bcl-2+ cells, comprising most anaplastic large-cell lymphomas, the other group with reverse characteristics. We found no correlation between the percentage of bcl-2+ cells per case and overall survival.

Apoptosis↗
PubMed1995

Low versus high cell turnover in diffusely growing non-Hodgkin's lymphomas.

Cell loss, perhaps as important as cell production in determining the size of an expanding cell population, has not usually been registered in quantitative cellular kinetic analyses of neoplastic disorders. The present retrospective study on various types and subtypes of non-Hodgkin's lymphomas (NHLs; n = 170) was designed to test the usefulness of a novel additional parameter, the 'turnover index' (TI), which is the sum per case of the mitotic index and the apoptotic index. Results document that TIs clearly distinguished between categories and subtypes of NHLs according to the Kiel classification. Cluster analysis of TIs plotted against the percentage of Ki-67-positive cells per case revealed that about one-third of the high-grade malignancy lymphomas actually belonged to the low-turnover lymphomas. Overall survival was longer in the low- than in the high-turnover group of lymphomas. Assessment of TIs can, for practical diagnostic purposes, be replaced by counting mitotic figures and apoptotic cells in several high-power fields. The TI concept may help to interpret the kinetics of NHLs in terms of accumulation vs. proliferation of cells.

Adolescent↗
PubMed1995

Burkitt's lymphomas express VH genes with a moderate number of antigen-selected somatic mutations.

The normal counterpart of the neoplastic B cells occurring in Burkitt's lymphomas (BL) is an issue of controversial debate. To clarify this matter, a semi-nested primer polymerase chain reaction was performed to amplify the VDJ rearrangements of the immunoglobulin heavy chain (VH) gene of DNA extracts from 10 (8 sporadic and 2 endemic) BL cases. The resulting amplificates were sequenced for comparison with known germ line VH segments. The control cases comprised six cases of B cell chronic lymphocytic leukemia and six cases of mantle cell lymphoma known to display naive nonmutated, ie, pre-germinal center VH configurations; and eight cases of follicular center lymphoma known to display mutated VH genes with signs of a still-ongoing mutation reaction, characteristic for germinal center cells and lymphomas that derive therefrom. The results of this approach revealed that both sporadic and endemic BL express mutated VH genes with a mutation frequency considerably lower (4.9% and 5.4%, respectively) than that observed in follicular center lymphoma (11.8%). In addition, after subcloning the amplificates, sequence analysis revealed no signs of ongoing mutations. These results led us to conclude that the derivation of neoplastic B cells in BL is definitely not from naive, nonmutated pre-germinal center B cells. Instead, our findings support the view that BL cells stem either from early centroblasts that are arrested after an initial hypermutation reaction, or from germinal center B cells that have differentiated in terms of surface immunoglobulin profile and mutation pattern but not in terms of morphology and proliferation toward SIgM+ IgD- memory B cells because of the deregulated c-myc gene expression.

Burkitt Lymphoma↗
PubMed1995

Primary gastric lymphomas (MALTomas): a nuclear image analysis comparison with lymph node monocytoid B-cells and marginal zones of spleen and Peyer's patches.

Centrocyte-like cells of marginal zones of follicles of gastrointestinal lymphoid tissue, which have their analogous in marginal zone of splenic white pulp and in lymph node monocytoid B-lymphocytes, are thought to be the normal counterpart of lymphomas of MALT (MALTomas). However, the cell population of MALTomas is often polymorphic and also contains cells morphologically different from centrocytes. Since conventional morphologic analysis may not be accurate enough and the phenotype may change in different stages of B-cell lineage, the marginal zone of Peyer's patches (PMZ) and splenic white pulp (SMZ), the lymph node monocytoid B-lymphocytes (ML), 3 nodal monocytoid B-cell lymphomas (L) and 16 gastric MALTomas (M) were studied by means of automated nuclear image analysis for area, irregularity, and chromatin texture assessment. Immunophenotyping on paraffin sections and polymerase chain reaction (PCR) for detecting monoclonality and t(14-18) chromosome breakpoints at DNA levels, on paraffin section extractions, were also done. In 14 MALTomas, clonal Ig heavy chain rearrangement was detected and in none of these were found t(14-18) chromosome breakpoints. The nuclei of the control group (PMZ, SMZ and ML) showed the same morphologic characteristics, ie. size, irregularity, chromatin texture. MALTomas and nodal lymphomas were distributed into 3 clusters: (1) with larger nuclei, light chromatin (euchromatin-richer) (5 MALTomas, 2 nodal lymphomas together with the control group); (2) nuclei with the same area size, but darker (eterochromatin-richer) (6 MALTomas and 1 nodal lymphoma); (3) with smaller and darker nuclei (5 MALTomas). Chromatin textural differences were maintained in the same nuclear size class in the 3 clusters. Only a few MALTomas had nuclear features not significantly different from controls, inter-case and intra-case variability being evident.

B-Lymphocytes↗
PubMed1995

Revised European-American Lymphoma Classification.

The recently proposed Revised European-American Lymphoma Classification represents a serious attempt to overcome the controversies that have divided both pathologists and clinicians over the past three decades. It was formulated by 19 experienced hematopathologists, who agreed on a list of clinicopathologic entities, all well known from the literature and daily practice. Compared with previous schemes, the Revised European-American Lymphoma Classification offers the following advantages: 1) it incorporates all nodal and extranodal lymphoid tumors, including Hodgkin's disease; 2) it is histogenetically updated by recognizing new categories (such as the mantle cell category) and grouping tumors that need further validation to be considered as separate entities (eg, diffuse large B-cell lymphomas); 3) it avoids any morphologic grading, the clinical course of lymphomas being influenced by factors other than histology (tumor burden, cell kinetics, apoptotic rate, and so forth) and 4) it includes all molecular data (phenotype, genotype, cytogenetics, and so forth), which can assist in the diagnosis.

Hodgkin Disease↗
PubMed1995

Cervical intraepithelial neoplasia and human papillomavirus related lesions of the genital tract in HIV positive and negative women.

Two hundred and twenty one women at high risk for HIV (intravenous drug users and/or those with infected partners) were investigated, through a self-filled questionnaire and gynaecological examination, to define the relationship between genital Human Papilloma Virus (HPV) infections, preneoplastic cervical intraepithelial lesions (CIN) and behavioural risk factors. In the 121 HIV positive women, 58 (47%) had HPV lesions at colposcopic and/or cytologic examination and, out of these 58, 23 (40%) had CIN 1, CIN 2 or CIN 3. Six out of the 16 cases with CIN 1 and CIN 2 (37%) followed-up showed a rapid progression of the lesion to CIN 3; in 3 women the interval was 6 months, in the other 3 about 12 months. Only 5 (7%) of the remaining 66 women without HPV lesions had a CIN lesion, with an obviously significant difference on comparison with HPV positive subjects. Sixty two women out of the 121 (52%) had a previous diagnosis of condylomata. In the 100 HIV negative women, 23 (23%) had HPV lesions and, among these 23, 6 (26%) had CIN 1, CIN 2 or CIN 3; 1 of them had rapid progression from CIN 1 to CIN 3 within a year. Only 5 (3%) without HPV infection showed any kind of CIN. 33 women out of 100 (33%) had a previous clinical history of condylomata. Our findings strongly suggest that HIV infection is associated with HPV lesions and that cervical cytological abnormalities develop in this situation. There is a need for short interval cytological and colposcopic follow-up for women at high risk of HIV infection.

Adult↗
PubMed1994

Spatial distribution of mitosis, apoptosis and small blood vessels in malignant diffuse follicular-center-cell lymphomas: a nearest-neighbor analysis.

To better comprehend the relationships between cell birth and cell death in neoplastic disorders, the topography of these events needs to be considered. We applied a computerized nearest-neighbor analysis to malignant, diffuse follicular-center-cell lymphomas in order to examine the spatial distribution of pyknotic (apoptotic) cells/bodies (A) and mitotic figures (M) in relation to capillaries (C) and venules (V). The results revealed a complex dispersion pattern, with significant aggregations of A and M, in addition to an even greater random distribution component. The greatest clustering displayed by A was around capillaries (A-C, 42% reduction of object frequency between the first and second distance class), followed by A-A (33%), A-V (24%) and A-M (12%). Additional values for mitotic figures were: M-M (45%), M-V (33%) and M-C (22%). These findings may reflect the relative importance of inherent properties of the neoplastic and host factors, respectively, in the regulation of cell birth and cell death rates.

Adult↗
PubMed1994

Epstein-Barr virus infection in sinonasal non-Hodgkin's lymphomas.

Sinonasal non-Hodgkin's lymphomas (SNHLs) of B- or T-cell immunophenotype have been associated with Epstein-Barr virus (EBV) infection of neoplastic lymphoid tissue. Nine SNHLs were investigated using immunohistochemistry, the polymerase chain reaction (PCR) for EBV genome and in situ hybridization (ISH) for EBV encoded RNAs (EBER), immunoglobulin (CI-gHR) and clonal T-cell receptor (CTC beta R) gene rearrangements. Eight cases were diagnosed as peripheral pleomorphic T-cell lymphomas (pPTCL). PCR showed the presence of EBV genome in eight cases; ISH for EBER led to the detection of positive cells in five cases. Late membrane protein (LMP) immunostaining was observed in three cases. No EBV positivity has been detected in control cases. The frequent association with EBV infection in the cases illustrated confirms the previous suggestions that EBV may have a role in the genesis of lymphomas of the sinonasal region.

Adult↗
PubMed1993

Epstein-Barr virus and gastric cancer: data and unanswered questions.

Sixty-five unselected cases of gastric cancer have been analysed for EBV DNA by polymerase chain reaction, in situ hybridization and immunohistochemistry for CD21 antigen expression. Four cases were found EBV-positive by PCR, while ISH yielded positive results in 3 of these cases, demonstrating EBV in the nuclei of cancerous cells. CD21 antigen was expressed in cancerous cells in all 3 ISH-positive cases. All the EBV-positive cancers of the present series were poorly to moderately differentiated adenocarcinomas with prominent lymphoid infiltration. These results are discussed also on the basis of the literature.

Adenocarcinoma↗
PubMed1993

Comparison between the monoclonal antibodies Ki-67 and PC10 in 125 malignant lymphomas.

The monoclonal antibody (MAb) Ki-67 detects a nuclear proliferation-associated antigen which corresponds to a non-histone protein with a molecular weight of 395 and 345 kD. Its prognostic relevance has been assessed in both lymphoid and non-lymphoid tumours. The MAb PC10 picks up the proliferating cell nuclear antigen (PCNA), which is a 36 kD nuclear protein associated with the cell cycle. Whereas Ki-67 works only in fresh material, PC10 detects a fixation-resistant epitope of PCNA. Preliminary data have revealed a linear relationship between Ki-67 and PC10 reactivity in normal lymphoid tissue and in non-Hodgkin's lymphomas (NHLs). We applied Ki-67 and PC10 to frozen and routine sections, respectively, from 25 examples of Hodgkin's disease (HD) (14 nodular sclerosis, 6 lymphocyte predominance, 5 mixed cellularity) and 100 NHLs (corresponding to the main varieties of the updated Kiel classification). The results obtained can be summarized as follows: (1) both MAbs gave rise to extremely variable results within the same category of NHLs; (2) most Hodgkin and Reed-Sternberg cells (50-98 per cent) were labelled by the reagents; (3) Ki-67 and PC10 stained a similar ratio of neoplastic cells in 65 and 76 per cent of NHL and HD cases, respectively; in the remaining instances, no correspondence was observed, the PC10-positive elements usually outnumbering the Ki-67-positive ones significantly. These discrepancies, which might be due to low PCNA catabolism and/or PCNA expression by quiescent cells, underline the need for further kinetic and clinico-pathologic studies in order to define the specific relevance of PC10.

Antibodies, Monoclonal↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Correlations between apoptotic and proliferative indices in malignant non-Hodgkin's lymphomas.

Cell production versus cell loss rates were estimated, across the boundaries of histological classification, in 50 cases of malignant non-Hodgkin's lymphomas by use of mitotic indices, percentage of Ki-67+ cells and percentage of PC10+ cells as proliferative indices, and the relative number of apoptotic bodies (apoptotic indices, AIs) as parameters. Regression analysis revealed significant (P < 0.01) positive correlations between the AIs and the proliferative indices; among the immunohistochemically assessed proliferative indices; and between these, the mitotic indices and the AIs on the one hand and histological malignancy grades on the other hand. The cellular protein BCL-2, which counteracts apoptosis, was significantly (P < 0.01) more often expressed in lymphomas with low than in those with high AIs. Multivariate analysis of data showed that of all parameters tested in this series, only the AIs correlated significantly (P < 0.05) with overall lethality. The correlation between BCL-2 positivity of lymphoma cells and overall survival did not quite attain significance (P = 0.08). Results of the present study suggest that high AIs and lack of BCL-2 expression may be adverse prognostic factors, independent of histological grade.

Apoptosis↗
PubMed1992

Phenotypic overlaps between pleomorphic malignant T-cell lymphomas and mixed-cellularity Hodgkin's disease.

Histologically diagnosed, or in part questionable, malignant pleomorphic peripheral T-cell lymphomas (pPTCLs, n = 16) and mixed-cellularity Hodgkin's disease (MCHD, n = 12) were objectively compared by the use of combined immunohistochemistry on paraffin sections, test-point analysis of tissue components, and semi-automated nuclear morphometry on semi-thin resin sections. Classical, qualitative histomorphological distinction of these sub-types of lymphomas proved to be valid and is probably still the best method. Quantitative discriminant features, in order of decreasing significance, were: (i) expression by large atypical cells (LACs) of CD45R0, CD43 and CD45 in pPTCLs, and of CD30 and CD15 in MCHD; (ii) means and standard deviations (SDs) of LAC nuclear-profile areas (greater in MCHD than in pPTCLs); (iii) expression of CD3 by LACs in pPTCLs; (iv) prominence of small lymphoid cells in MCHD; (v) higher percentage of medium-sized lymphoid cells in pPTCLs; and (vi) higher SDs of nuclear-profile circularity factor of small lymphoid cells in MCHD. The medians of the largest nucleolar profile areas in LACs per field did not differ in pPTCLs and MCHD, but dispersion of individual values towards higher levels was significantly greater in the latter. Stepwise discriminant analysis of test point and nucleometric variables that best distinguished pPTCLs from MCHD revealed considerable overlaps, and questionable cases tended to be intermediate between the two. In conclusion, our results confirm and expand the notion of intra-group heterogeneity, with indistinct borders and the existence of intermediate phenotypes between these two taxonomic categories of malignant lymphomas.

Adolescent↗
PubMed1992

[An autopsy study of patients who died at the Medical Clinic of the University of Siena from 1986 to 1989].

In the past twenty years autopsies are performed much less frequently in the elderly than in younger patients. The clinical diagnostic error rate documented by autopsy studies ranges from 6% to 68%. We analyzed the clinical and autopsy records of 214 patients who died from 1 January 1986 to 31 December 1989 at our Institute to determine the accuracy of clinical cause of death with respect to the pathologic cause of death. The most common cause of death were bronchopneumonia (25.2%) followed by gastroenteric and lung cancer (20%), cerebrovascular accident (15.8%), myocardial infarction (8%) and pulmonary embolism (7.4%). Pulmonary embolism was correctly classified only in 25% of patients. The most accurately diagnosed condition were neoplastic diseases (88%) and cerebrovascular accident (84.8%) while bronchopneumonia were correctly diagnosed antemortem in 72.2% of the patients studied. Our data suggest that advances in diagnostic technology have not reduced the value of the autopsy and that a goal-directed autopsy remains a vital component in the assurance of good medical care.

Age Factors↗
PubMed1991

Diffuse centrocytic and/or centroblastic malignant non-Hodgkin's lymphomas: comparison of mitotic and pyknotic (apoptotic) indices.

Mitotic indices (MIs) and pyknotic (apoptotic) indices (PIs) were assessed in diffuse centrocytic (CC, n = 10), centroblastic/centrocytic (CB/CC, n = 18) and centroblastic (CB, n = 20) malignant non-Hodgkin's lymphomas (NHL). Significant differences were observed. MIs were lowest in CC (median: 0.07%), intermediate in CB/CC (0.18%) and highest in CB (0.43%) NHLs. The PIs exhibited a similar pattern. The PIs of CC (0.11%) and CB/CC (0.17%) NHLs were significantly different from those of CB lymphoma (0.62%). The ratios MI/PI per case, as well as MIs and PIs per case, varied greatly and showed considerable overlapping, thus documenting a marked inter-case and inter-group heterogeneity. MIs tended to loosely correlate with PIs in a non-linear fashion, which raises the question of feedback mechanisms. More information is needed on mitotic time (TM) and apoptotic time (TA), in order to estimate cell doubling time from data on MIs and PIs.

Adult↗
PubMed1991

[Extraskeletal diffusion of multiple myeloma. A clinico-pathological description of 4 cases].

The authors describe 4 cases of multiple myeloma that developed one or more extraskeletal localizations. They have evaluated the relation between the onset of the extraskeletal localizations and the following myeloma characteristics: tumor burden, clinical phase, chemotherapy response, prognostic significance. All the patients showed these localizations in a plateau phase of myeloma. None of the patients had fever, pancytopenia and in no one the performance status worsened. All patients obtained at least a partial reduction of the localization and only the patient with the retro-orbital localization, got worse and died for myeloma. The other three patients are alive and do not show any sign of progression.

Aged↗