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Biomedical subjects

B Falini

Publications and source records attributed to B Falini.

At least 109 records · Page 6Linked to original sources
PubMed1995

Is Hodgkin's disease a unique entity?

The theoretical bases of Hodgkin's disease (HD) have recently been revised in the light of new findings obtained by means of immunohistochemistry and molecular analysis. These findings have questioned the concept that HD is a unique entity and have made the borders between HD and non-Hodgkin's lymphomas unclear. The clinical relevance of nodular lymphocyte predominance HD (LP-HD), the distinction between T-cell rich B-cell lymphoma and diffuse LP-HD, and the relationships between HD and anaplastic large cell lymphoma are reviewed and discussed.

Biomarkers, Tumor↗
PubMed1995

MACOP-B vs F-MACHOP regimen in the treatment of high-grade non-Hodgkin's lymphomas.

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities. Two hundred-eighty-six patients included between 15 and 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucositis among patients treated with MACHOP-B than among those given F-MACHOP (11% vs 3.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1995

Frequent expression of IL-7 gene transcripts in tumor cells of classical Hodgkin's disease.

Interleukin-7 (IL-7) is a pleiotropic cytokine acting mainly on cells of the hematolymphoid system. In vitro studies have shown enhanced proliferation of acute lymphoblastic leukemia cells in response to IL-7. On the other hand, tumor cell lines transfected with a functioning IL-7 gene and subsequently transplanted into mice resulted in a prominent inflammatory infiltrate and reduced tumorigeneicity. These data suggest an important role of this cytokine in the pathophysiology of lymphoid neoplasms. Because little is known about the in vivo expression of this cytokine in various neoplastic and nonneoplastic lesions of the lymphoid system, we examined frozen and paraffin-embedded tissue samples of normal, reactive, and malignant lymphoid lesions using in situ hybridization with a 35S-labeled RNA probe specific for IL-7. Tumor cells of nodular sclerosing and mixed cellularity type of Hodgkin's disease displayed IL-7-specific signals in 24 of 31 cases. Among reactive lesions, only thymic tissue showed labeling within both cortex and medulla (4 of 7 cases), whereas in tonsils clear-cut IL-7-specific signals could not be found. Tissues infiltrated by B-type chronic lymphocytic leukemia or T- or B-type lymphoblastic lymphoma showed cytokine-specific signals in only one case of lymphoblastic lymphoma in rare reactive cells. In conjunction with the finding of elevated levels of IL-7 in the serum of many patients with Hodgkin's disease, our data suggest an important role of this cytokine in the pathogenesis of Hodgkin's disease. The prominent reactive infiltrate observed in most cases of Hodgkin's disease could be a consequence of elevated local levels of this cytokine as similar infiltrates are also observed in tumors in mice resulting from injection of tumor cell lines transfected with a functioning IL-7 gene.

Child↗
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

Local expansion of allergen-specific CD30+Th2-type gamma delta T cells in bronchial asthma.

BACKGROUND: T lymphocytes infiltrating airways during the allergic immune response play a fundamental role in recruiting other specialized cells, such as eosinophils, by secreting interleukin 5 (IL-5), and promoting local and systemic IgE synthesis by producing IL-4. Whether these presumed allergen-specific T cells are of mucosal or systemic origin is still a matter of conjecture. MATERIALS AND METHODS: Immunophenotype, IL-4 production, and in vitro proliferative response to specific or unrelated allergens were analyzed in the bronchoalveolar lavage (BAL) fluid lymphocyte suspensions obtained from untreated patients with allergic asthma. Healthy subjects and patients affected by pulmonary sarcoidosis, a granulomatous lung disease characterized by infiltrating Th1 CD4+ lymphocytes, served as controls. RESULTS: The proportions of gamma delta T lymphocytes, mostly CD4+ or CD4- (-)CD8-, was higher in asthmatic subjects than in controls (p < 0.05). Most BAL gamma delta CD4+ lymphocytes of asthmatic patients displayed the T cell receptor (TCR)-gamma delta V delta 1 chain. While CD30 antigen coexpression on the surface of BAL alpha beta(+) T lymphocytes was low (ranging from 5 to 12%), about half of pulmonary gamma delta T cells coexpressed it. These cells produced IL-4 and negligible amounts of interferon-gamma (IFN gamma), and proliferated in vitro in response to purified specific but not unrelated allergens. In contrast, control or sarcoidosis gamma delta T cells never displayed the CD30 surface molecule or produced significant quantities of IL-4. CONCLUSIONS: These findings not only confirm our previous hypothesis that the allergen-specific Th2-type lymphocytes found in the lungs of asthmatic patients are gamma delta T cells belonging to airway mucosal immunocytes, but also strongly support the notion that asthma is a local rather than a systemic disease.

Adult↗
PubMed1994

Granular cell tumor: an immunohistochemical study.

AIMS AND BACKGROUND: Granular cell tumor, usually a benign neoplasm, has been the object of many studies because of its uncertain histogenesis and based on many immunohistochemical and ultrastructural studies it has been suggested that it originates from the Schwann cell. Our recent observation that granular cell tumor is positive with PG-M1, a new anti-macrophage monoclonal antibody, led us to further investigate the immunophenotypic profile of the tumor. STUDY DESIGN: We studied 11 granular cell tumors using a panel of 20 antibodies, 13 monoclonal and 7 polyclonal. RESULTS: The immunohistochemical study showed in all cases a constant diffuse positivity for S-100 protein, neuron-specific enolase, vimentin, KP1 and PG-M1, as well as occasional and focal positivity for alpha-1-antitrypsin, alpha-1-antichymotrypsin and lysozyme. CONCLUSIONS: The immunophenotypic profile constantly observed could be the expression, on one hand, of the neuroectodermic nature of the neoplasm, proven by positivity for S-100 protein, neuron specific enolase and vimentin, and on the other could be the expression of the phagocytic activity of the tumor cell, proven by positivity for KP1 and PG-M1 antibodies and also by the presence of numerous phagolysosomes.

Adult↗
PubMed1994

Nodular lymphocyte predominance Hodgkin's disease. A distinct clinicopathological entity.

This article reviews the evidence that the nodular form of lymphocyte predominance Hodgkin's disease ("nodular paragranuloma") should be recognised as a distinct clinico-pathological entity. The disease is characterised histologically by very large primary lymphoid follicles, containing polytypic small B lymphocytes and extensive meshworks of follicular dendritic cells. The "L and H" or "popcorn" cells scattered within the nodules show clear differences from classical Reed-Sternberg cells, both in their cytological appearance and in their marker profile, being frequently negative for CD15 and for the EBV genome, but often positive for B cell antigens, CD45 (leucocyte common antigen), CDw75 (LN1), epithelial membrane antigen (EMA) and J chain. These findings suggest that L and H cells may be Ig-synthesising monoclonal B cells. Nodular lymphocyte predominance Hodgkin's disease pursues a much more indolent courses that classical Hodgkin's disease, and long term survival is common. It has other distinctive clinical features, e.g. a unimodal age distribution, a predilection to involve single lymph nodes, and a very low incidence of thymic involvement. There is a tendency for diffuse large cell non-Hodgkin's lymphoma, usually of B cell type, to develop during the course of the disease. This type of Hodgkin's disease thus has many features that distinguish it from the nodular sclerosis and mixed cellularity varieties, and it is hoped that future studies will gather more information on its clinical behavior and on the nature of the putative neoplastic cells, as well as exploring different protocols for its treatment.

Hodgkin Disease↗
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

A proposal for classification of lymphoid neoplasms (by the International Lymphoma Study Group).

A new classification of lymphoid neoplasms, mostly based on existing terminology, is proposed by the International Lymphoma Study Group. The proposed classification was reached through a consensus of the members, despite their diverse backgrounds, and consists of a listing of currently recognized clinicopathological entities. These tumours are divided into three major categories: B-cell neoplasms, T-cell and postulated natural killer cell neoplasms, and Hodgkin's disease. The characterization of each entity is based on a synthesis of all available information. This concept departs from a purely morphological approach to lymphoma classification, which is considered to be inadequate, because many biologically distinctive lymphoma types can exhibit a broad and overlapping morphological spectrum. Some entities are provisional, pending further data to confirm that their recognition is reproducible. The salient clinicopathological features of each entity are summarized in this review.

Hodgkin Disease↗
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

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↗
PubMed1994

A novel internal antigen which distinguishes germinal centre cells from other B-cell types.

A new monoclonal antibody, 4KB51, is described which labels the majority of B cells in blood and in mantle and marginal zones but not germinal centre lymphocytes or plasma cells. Antibody 4KB51 also stains monocytes, neutrophils and the majority of T cells. It recognizes an intracellular antigen of 160,000 MW (unreduced) and 68,000 MW (reduced). Antibody 4KB51 labels the tumour cells in all cases of hairy cell leukaemia and in four of the 16 cases of centrocytic B-cell lymphoma studied. No labelling of the other lymphomas (114 cases) or lymphoid leukaemias (13 cases) tested was seen. Antibody 4KB51 may be of value in defining B-cell subsets and in the differential diagnosis of hairy cell leukaemia and centrocytic lymphomas. The pattern of reactivity of 4KB51 suggests that its target antigen may play a functional role, possibly involved in lymphocyte homing.

Antibodies, Monoclonal↗
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

Lymphotoxin, tumour necrosis factor and interleukin-6 gene transcripts are present in Hodgkin and Reed-Sternberg cells of most Hodgkin's disease cases.

Tissue specimens from 26 cases of Hodgkin's disease (HD) and six HD-derived cell lines were analysed for tumour necrosis factor (TNF), lymphotoxin (LT), and interleukin (IL)-6 RNA transcripts by in situ hybridization, in some cases subsequent to immunohistology for CD30 antigen. LT and TNF transcripts were found in tumour cells of all cases; IL-6 gene transcripts were detectable in 19/23 cases. Presence of RNA specific for these cytokines was not correlated with any of the following parameters: sex, symptoms and histotype, as well as immunophenotype and association of the tumour cells with Epstein-Barr virus. Rather, the presence of LT, TNF and IL-6 transcripts appeared to characterize Hodgkin and Reed-Sternberg cells in general, supporting concepts which suggest that HD represents a malignancy of cytokine secreting activated cells, and that many of the features distinguishing HD from other malignant lymphomas may ultimately be due to expression of cytokines. LT and TNF RNA transcripts were also found in five HD-derived cell lines, whereas supernatants of these cell lines contained high levels of LT, but low or undetectable levels of TNF activity. This suggests that, although not detectable at the level of RNA transcripts, differences between HD cases may exist on the level of cytokine gene transcript processing, translation and polypeptide secretion.

Adolescent↗