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Biomedical subjects

E Sabattini

Publications and source records attributed to E Sabattini.

At least 55 records · Page 3Linked to original sources
PubMed1995

Bone marrow findings further support the hypothesis that essential mixed cryoglobulinemia type II is characterized by a monoclonal B-cell proliferation.

One-hundred-sixteen consecutive bone-marrow biopsies were taken from 76 patients with essential mixed cryoglobulinemia type II (type II cryo), whose median follow-up was 97 months. Fifty-four out of fifty-six subjects who underwent ELISA and RIBA tests for HCV, were found to be positive. At conventional light microscopic examination, 64/76 patients showed discrete lymphoid infiltrates consisting of small elements with plasmacytoid differentiation and with frequent paratrabecular location. Thirty-nine biopsies were studied by immunohistochemistry that revealed the B-cell nature of the infiltrates (CD20+, CD45RA+, CD79 alpha+, CD3-, CD45RO-), with demonstrable monotypic Ig light-chain restriction in 22 cases. It is worthy of note that the lymphoid elements usually appeared protected against apoptosis, because of the strong expression of the bcl-2 oncogene product, and provided with a very low proliferative capacity, the Ki-67 index being lower that 3%. The latter findings are in keeping with the indolent behaviour of the clonal lymphoid population observed in type II cryo and allow some speculation as to the need for environmental stimuli for its maintenance as well as further mutagenic events for its eventual transformation into an overt lymphoma.

Adult↗
PubMed1995

Anaplastic large cell lymphoma: update of findings.

The problem of anaplastic large cell lymphoma (ALCL) is extensively reviewed by depicting the clinical, pathological and biological characteristics of the four main varieties of ALCL: common, Hodgkin's like/Hodgkin-related, lympho-histiocytic, and giant-cell rich. Special emphasis is given to the differential diagnosis between ALCL Hodgkin like and Hodgkin's disease in the light of possible therapeutical differences.

Genotype↗
PubMed1994

Anaplastic large cell lymphoma (CD30 +/Ki-1+): results of a prospective clinico-pathological study of 69 cases.

Sixty-nine anaplastic large cell lymphomas (ALCLs) were selected from an Italian comparative trial on MACOP-B and F-MACHOP. As no significant difference in effectiveness of the protocols emerged, they were considered homogeneously treated. The ALCLs were divided into two groups according to previously defined criteria: 41 were common type (ALCLs-CT) and 28 Hodgkin-related (ALCLs-HR). T-cell phenotype was most common (58%), while B-cell, null and hybrid forms accounted for 27%, 13% and 2%. Clinically, ALCLs CT and HR differed as to mean age (27 v 34.3 years) and presentation; all ALCLs-HR showed mediastinal involvement, with bulky disease in 57%, and more frequent occurrence in stage II. In contrast, ALCLs-CT showed mediastinal masses in 58.5%, infrequently revealed bulky disease (24%), and were not specifically associated to stage. Among the ALCLs-CT, 68.4% achieved complete remission (CR), 24.4% partial remission (PR), one (2.4%) was resistant to therapy, and two (4.8%) had fatal drug toxicity. Of the ALCLs-HR, 67.8% reached CR, 14.3% PR, and 17.9% did not respond. In CR, ALCLs-CT showed a greater tendency to relapse (32.1% v 14.2%). At present, 65.8% of ALCLs-CT and 67.8% of ALCLs-HR are alive with overall survival/disease-free survival averages of 31/27 and 29/24 months respectively. Our data emphasize that, independently of subtype, ALCLs benefit from the application of third-generation protocols for high-grade non-Hodgkin's lymphomas.

Adolescent↗
PubMed1994

[Anaplastic large-cell lymphoma. Conceptual and diagnostic assessment].

The authors critically review the concept of anaplastic large cell lymphoma (ALCL). In particular, they provide the guidelines to the morphologic identification of the four main varieties of the tumour: common, giant-cell-rich, lympho-histiocytic, and Hodgkin's-like. The phenotypic and molecular characteristics of the neoplasm are discussed with special emphasis to those which can assist in the differential diagnosis between ALCL and Hodgkin's disease. Finally, the clinical features are presented along with the results obtained in the course of long-term prospective therapeutical trials.

Diagnosis, Differential↗
PubMed1994

Retreatment with 2-CdA of progressed HCL patients.

Thirty seven hairy cell leukemia (HCL) patients, 35 males and 2 females with a median age of 53 years, were treated with a single course of 2-Chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily for 7 days by continuous infusion. Twenty nine (78%) achieved a complete remission (CR) and 8 (22%) a partial remission (PR); four of the latter progressed after 6, 12, 18 and 24 months. All have been retreated with 2-CdA and 2 achieved a CR, 1 a PR and the last one is not yet evaluable. The overall median duration of response was 18 months, ranging from 4 to 30 months from the end of therapy. Circulating hairy cells and spleen enlargement, when present, disappeared within 2 weeks after completing treatment. A significant neutropenia was observed in almost all patients mainly in those who had less than 1,000/microliters neutrophils when treatment was started, together with a significant lymphocytopenia which lasted for more than 12 months. The hemoglobin and platelet levels were marginally affected. Fever was observed in 14 patients; in 8 of them it was short-lived (< or = 48 hours) and apparently not infection-related, while in the remaining 6 it was attributed to infection. Clinical tolerance was very good and none of the patients complained of nausea, vomiting or hair loss. In conclusion, our study confirms the efficacy of 2-CdA in HCL, including patients who progressed after treatment with 2-CdA.

Adult↗
PubMed1994

Bone-marrow biopsy in hairy cell leukaemia (HCL) patients. Histological and immunohistological analysis of 46 cases treated with different therapies.

Serial bone-marrow biopsies were obtained from 46 hairy cell leukaemia (HCL) patients at different time intervals during the course of their disease. The patients were treated according to the following schemes: 14 received alpha-lymphoblastoid interferon (alpha-IFN), 11 2-Chlorodeoxyadenosine (2CdA), and 21 alpha-IFN first, followed by 2CdA. All the biopsies were studied by immunohistochemical means for the detection of minimal residual disease. The administration of 2CdA produced the highest reduction of both the tumor burden and HC index, with residual hairy cells (HCs) being undetectable at conventional light microscopy in most cases. In addition, 2CdA induced a higher degree of hypocellularity than alpha-IFN: the reduction in the amount of normal bone-marrow, however, was less pronounced in patients who had alpha-IFN before 2CdA. Of 9 patients who received both alpha-IFN and 2CdA and were followed for more than 2 years, 3 relapsed, while the remaining 6 continued to show rare HCs 2 years after 2CdA administration.

Adult↗
PubMed1993

Anaplastic large cell lymphoma (Ki-1+/CD30+) in childhood.

In 1985, Stein et al. (Blood 66:848-858) described a large cell lymphoma consisting of activated lymphoid elements, expressing the Reed-Sternberg cell-associated antigen Ki-1 (CD30); this tumor has recently been included in the updated Kiel classification and has been termed anaplastic large cell lymphoma (ALCL). This report concerns 13 patients with previously untreated ALCL who were admitted to the Pediatric Hematology and Oncology Department of Bologna University between January 1983 and December 1989. Ten cases were diagnosed as common type ALCL, 1 as Hodgkin's-related ALCL and the remaining 2 as histiocyte-rich ALCL/lymphohistiocytic T-cell lymphoma. T-cell markers were present in 85% of the cases, and B phenotype in the remaining 15%. About one-half of the patients presented systemic symptoms; all but one showed more than one involved site, mostly an association of nodal and extranodal sites. All patients (1 in stage I, 7 in stage II, and 5 in stage III) were treated with a modified version of the LSA2-L2 protocol. Survival and event-free survival at 4 years were 100% and 62.9%, respectively. Two out of 3 relapsed patients presented a recurrence of disease when they were off-therapy 24 and 36 months after first complete remission. Good response to salvage chemotherapy of all the relapsed patients and the long duration of the second complete remission were a distinctive characteristic of this neoplasm when compared to other histological subtypes. The clinical presentation, the tendency to develop late relapses and to achieve and maintain second remission easily suggest that ALCL is a high grade non-Hodgkin's lymphoma, from the histological point of view, but is similar to Hodgkin's disease from the clinical point of view. This would confirm the hypothesis that Hodgkin's disease and ALCL represent a continuous spectrum of the same disease.

Actuarial Analysis↗
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

Antigen unmasking on formalin-fixed, paraffin-embedded tissue sections.

Enzymatic and non-enzymatic treatments for antigen unmasking on formalin-fixed, paraffin-embedded, dewaxed sections were optimized and compared by the use of a panel of antibodies of diagnostic relevance (anti-cytokeratins, vimentin, S-100, T- and B-cell receptors, Ki-67/MIB 1, muscle actin). Non-enzymatic unmasking was obtained by boiling the slides in a microwave oven in 0.01 M salt solution (pH 6) or in 6 M urea. Trypsin or pronase digestion was used for comparison and found to be necessary for some of the reagents. The investigation was then extended to 256 antibodies; the epitopic amino acid sequence was known for 48 of them. We found that enzymatic and non-enzymatic antigen unmasking are not dependent on the epitope sequence, but some antigens benefit selectively from one treatment but not from the other. Denaturation of proteins is the likely mechanism which leads to immunodetection on microwave oven-boiled slides; this suggestion is supported by the use of denaturating solutions and by the observation that endogenous enzymes were inactivated and a few antigens were no longer immunodetectable after boiling. Non-enzymatic methods for antigen unmasking are a powerful new tool for broadening the use of antibodies for immunostaining formalin-fixed, paraffin-embedded sections and should be used in parallel with the traditional enzymatic methods.

Antibodies↗
PubMed1993

Non-Hodgkin lymphomas of the central nervous system. Clinico-pathologic and immunohistochemical study of 147 cases.

We report on data gathered from five European centres regarding 147 primary non-Hodgkin Lymphomas (NHLs) of the Central Nervous System (CNS) in HIV-negative patients. The results lead us to make the following considerations: i) there has been a significant and progressive increase in the frequency of observation of this pathology during the course of the last two decades; ii) the pathology lacks specific characteristic symptoms; iii) the radiological profile, as observed by CAT and/or MNR, most frequently corresponds to an isodense or slightly hyperdense lesion which has clear margins and is capable of assuming the contrast medium homogeneously; iv) the tumour most often has a single supratentorial localisation; v) high grade B-cell lymphomas account for 66% of the observations, low grade B-cell varieties being relatively rare and cases of T-cell derivation exceptional (6/147); vi) immunohistochemistry allows the differential diagnoses with respect to primitive or secondary non-lymphoid tumours, and provides confirmation of the histogenetic assessment made on morphological grounds; vii) the course of the disease is not significantly influenced by the histotype, the phenotype, the number of lesions present or the chemotherapy regimen, but rather by the employment of combined surgery and radio- or radiochemotherapy. This study represents the largest series of CNS NHLs so far reported, and as such, provides precise clinico-pathological indications which were only partially obtainable from the relatively small previously published series. Some concluding remarks are made as to the genesis of CNS NHLs, along with some practical suggestions for reaching a better understanding of their complex biology.

Adolescent↗
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

Hairy cell leukemia. Diagnosis of bone marrow involvement in paraffin-embedded sections with monoclonal antibody DBA.44.

The new monoclonal antibody DBA.44 recognizes an unknown fixation-resistant B-cell differentiation antigen expressed by mantle zone lymphocytes, reactive immunoblasts, monocytoid B cells, and a small proportion of high- and low-grade lymphomas. Among node-based lymphomas, the strongest membrane staining was observed in centroblastic, immunoblastic, and monocytoid B-cell lymphomas. In studying bone marrow biopsy specimens from 166 patients with hairy cell leukemia, strong positive staining of surface membrane 'hairy' features of leukemic cells was observed in routinely fixed and decalcified bone marrow biopsy specimens of nearly all cases. The antibody distinguished hairy cell leukemia from the more common B-cell chronic lymphocytic leukemia and bone marrow infiltrates of typical lymph node-based lymphomas by immunomorphologic criteria. DBA.44 was valuable to (1) confirm the diagnosis of hairy cell leukemia, (2) estimate the bone marrow density of hairy cell leukemia before and after treatment, and (3) make the diagnosis of hairy cell leukemia in ambiguous cases, which are all properties that indicate its usefulness in the practice of diagnostic hematopathology.

Adult↗
PubMed1992

Follicular mucinosis in alopecia areata.

The pathological features of alopecia areata were described in association with those of follicular mucinosis in the scalp pathology of an 18-year-old woman. The immunohistochemical picture of the inflammatory infiltrate showed a high CD4/CD8 ratio (25:1), which was significantly different from the CD4/CD8 ratio in patients with alopecia areata. The abundance of helper/inducer cells along with the involvement of the upper part of the hair follicles might explain the development of follicular mucinosis in this case. Different possibilities were discussed, but the clinical presentation and the follow-up favored the clinical and pathological interpretation of alopecia areata with incidental findings of follicular mucinosis.

Adolescent↗
PubMed1992

Results in hairy-cell leukemia patients treated with alpha-interferon: predictive prognostic factors.

Fourty-four evaluable patients with hairy cell leukemia (HCL) were treated with human lymphoblastoid alpha-interferon (alpha-IFN), at a dose of 3 x 10(6) Units a day for 12-18 months while 18 of them continued to receive a three times per week schedule at the same dose as maintenance treatment. Eighteen percent of patients achieved complete response, 64% partial response, and 18% minor response with a median duration of 37.5, 22.9 and 3.5 months respectively. Twenty patients (45%), all partial or minor responders, subsequently had progression of the disease. The progression occurred more frequently in patients who presented at diagnosis with a hairy-cell index value > 0.50 than in those who presented with a hairy-cell index < 0.50: 14/26 (54%) versus 2/11 (18%) respectively. In addition, the progression rate was more evident in "non-maintained" than in "maintained" patients: 16/26 (61.5%) versus 4/18 (22%). Restarting alpha-IFN treatment in 16 of the 20 progressed patients proved effective only in 9 of them. From these findings it appears that a low hairy-cell index at diagnosis correlates favorably with a good hematological response. Furthermore, continuous therapy with alpha-IFN seems very useful in reducing the progression of the disease, in particular in patients with a very high hairy-cell index at diagnosis.

Adult↗
PubMed1992

Serum soluble interleukin-2 receptor levels in hairy cell leukemia: correlation with clinical and hematological parameters and with alpha-interferon treatment.

The soluble Interleukin-2 Receptor (sIL-2R) serum levels were assessed in 42 patients with Hairy-Cell Leukemia (HCL) at diagnosis and after alpha-Interferon therapy and correlated with spleen size, peripheral hematological values, hairy cell index (HCI) and clinical response. Serum sIL-2R levels were significantly increased in all HCL patients, particularly in those with a higher HCI (> 0.50) and in non-splenectomized patients. Among the 26 HCL patients who were studied before and after 12 months of alpha-IFN treatment, 16 normalized the sIL-2R level and 10 did not. Our findings suggest that sIL-2R levels in HCL patients correlate with the splenic and bone marrow tumor burden as assessed by HCI. In addition patients with low levels of sIL-2R at diagnosis appear to have a better chance of achieving a good clinical response.

Biomarkers, Tumor↗