Hepatitis C virus infection in patients with overt B-cell non-Hodgkin's lymphoma in a French center.
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Adolescent↗
Biomedical subjects
P Gaulard
Publications and source records attributed to P Gaulard.
CD4+ CD56+ cutaneous neoplasms: a distinct hematological entity? Groupe Français d'Etude des Lymphomes Cutanés (GFELC).
We report seven cases of particular cutaneous tumors selected from the register of the French Study Group on Cutaneous Lymphomas. The patients (three men, four women) were aged 37-86 years. They initially presented with cutaneous nodules or papules. Three cases presented with regional lymph nodes. Stagings were negative, except for one patient with bone marrow involvement. Histological features were relevant with pleomorphic medium T-cell lymphoma, but these cells exhibited a distinguishing phenotype. They were positive for CD4, CD56, and also CD45, CD43, and HLA-DR. All other T-cell and B-cell markers were negative. The myelomonocytic markers (CD13, CD14, CD15, CD33, CD117, myeloperoxidase, and lysozyme) were negative excepted CD68, which was clearly positive in four cases and weakly in two cases. Others natural killer cell markers (CD16, CD57, TiA1, granzyme B), TdT, and CD34 were negative. Polymerase chain reaction studies did not detect any B or T clonal rearrangement. The cytogenetic studies, performed in five cases, showed a del(5q) in two cases. All patients were treated successfully by polychemotherapy, but relapsed quickly in the skin, between 4 and 28 months. Five patients developed bone marrow involvement, with leukemia in three cases, and they died in 5-27 months. One patient died at 17 months with skin progression. The seventh patient is alive at 33 months, with cutaneous progression. The origin of these cells is unclear. Despite expression of CD4 or CD56, we failed to demonstrate a T-cell, natural killer cell origin. However, CD4 and CD56 are not specific for T or natural killer lineages. Although these two markers are also known to be expressed by monocytic cells, classic myeloid antigens were negative. These seven cases, together with other rare similar cases already reported, seem to represent a distinct entity likely developed from hematological precursor cells.
Adult↗
Identification of a novel cDNA, encoding a cytoskeletal associated protein, differentially expressed in diffuse large B cell lymphomas.
Diffuse large B-cell lymphomas (DLBL) constitute an heterogeneous clinico-pathological entity. To characterize molecular events related to histological subtypes, clinical presentation or outcome, we compared the mRNAs expressed in a limited series of DLBL by Differential display-reverse transcription (DDRT) and cloned a differential cDNA, that we called LB1. LB1 open reading frame encodes a 683 amino-acid polypeptide that does not show significant homology upon comparison to protein databases, nor any structural domain relating LB1 to an already known protein family. Immunofluorescence analysis of transfected COS cells showed a cytoplasmic filamentous staining, indicating that LB1 protein is tightly associated with cytoskeletal fibers. Two LB1 transcripts, a major 3.6-3.9 Kb and a minor 2.2 Kb transcripts, were detected among human haematopoietic and non-haematopoietic lines and tissues. LB1 transcripts were abundant in testis, thymus and in tumour derived cell lines, while barely detectable in liver, prostate and kidney. Concerning DLBL, LB1 expression was high in two cases of DLBL, and low or undetectable in four others, confirming the differential expression previously observed in the DDRT experiment. Furthermore, LB1 gene mapped to chromosome 13q14, a region that has been involved as a chromosomal breakpoint in DLBL. The cellular function of LB1 and its relationship with B cell maturation and/or oncogenesis remain to be established.
Amino Acid Sequence↗
Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA).
Peripheral T-cell lymphomas (PTCL) have been generally reported to have a worse prognosis than B-cell lymphomas (BCL). Because of their heterogeneity and scarcity, the outcomes of the different histological subtypes have not been compared. From October 1987 to March 1993, 1,883 patients with diffuse aggressive non-Hodgkin's lymphomas (NHL) included in the LNH87 protocol could be assessed for both morphology and immunophenotyping. Among them, 288 (15%) had PTCL and 1,595 (85%) had BCL. According to the Kiel classification, most PTCL were classified as angioimmunoblastic (AIL; 23%), pleomorphic medium and large T-cell (PML; 49%), or anaplastic large cell (ALCL; 20%) lymphomas. Comparing PTCL with BCL patients, the former had more disseminated disease (78% v 58%), B symptoms (57% v 40%), bone marrow involvement (31% v 17%), skin involvement (21% v 4%), and increased beta2-microglobulin (50% v 34%), whereas BCL patients had more bulky disease (41% v 26%). According to the International Prognostic Index (IPI), PTCL and BCL scores were, respectively: 0 factors, 13% and 15%; 1 factor, 17% and 22%; 2 factors, 24% and 25%; >/=3 factors, 45% and 37% (P = .09). For BCL and PTCL, respectively, complete remission rates were 63% and 54% (P = .004); the 5-year overall survival (OS) rates were 53% and 41% (P = .0004) and event-free survival (EFS) rates were 42% and 33% (P < . 0001). Comparison of the different histological subtypes of lymphoma showed that the 5-year OS rate for T-ALCL (64%) was superior to those of other PTCL (35%) as well as diffuse large B-cell (53%) NHL. When multivariate analysis was applied using the IPI score as one factor, nonanaplastic PTCL remained an independent parameter (P = . 0004). Although the poor prognosis of non-ALCL PTCL could be due in part to the presence of adverse prognostic factors at diagnosis, this study shows that the T-cell phenotype is an independent significant factor, which should be incorporated into the definition of prognostic groups.
Adolescent↗
[Physiopathology of Hodgkin's disease].
Reed-Sternberg cell, the neoplastic component of Hodgkin's disease, still remains "intriguante". Despite contreversies, there is more and more evidence for a lymphoid B cell origin of Hodgkin's disease. The role of Epstein-Barr virus, cytokines and (or) oncogenes expression in the pathogeny can be suggested, although the precise mechanisms leading to transformation and (or) accounting for tumour progression are still elusive. Advances in the biology of Hodgkin's disease have led to the distinction between two entities, "classical" Hodgkin's disease and Poppema's paragranuloma, with different clinical aspects. The definition of diagnostic criteria has been also helpful to separate Hodgkin's disease from other lymphomas mimicking Hodgkin's disease such as anaplastic large cell lymphomas?
Apoptosis↗
Nonhepatosplenic gammadelta T-cell lymphoma: a subset of cytotoxic lymphomas with mucosal or skin localization.
Human gammadelta T lymphocytes represent a minor subset of T cells in the peripheral blood, which exhibit a limited diversity and a tissue-restricted repertoire in contrast to their broad specificity. Most postthymic neoplasms that arise from this T-cell subpopulation belong to the hepatosplenic gammadelta lymphoma entity. Only a few cases of nonhepatosplenic gammadelta lymphomas have been described in detail previously. This study presents the clinicopathologic features of 11 consecutive cases of nonhepatosplenic gammadelta lymphoma. All were characterized by mucosal or skin initial involvement: nasal cavity (n = 3), gastrointestinal tract (n = 3), skin (n = 3), lung (n = 1), larynx (n = 1). Most patients presented with B symptoms (eight of 11), without peripheral lymphadenopathy and bone marrow involvement. A past history of chronic antigen exposure was noted in six cases, and four patients had features of immune deficiency. On histology, they were classified as pleomorphic tumors. Features of epitheliotropism and angiocentrism was observed in most cases. Tumor cells had a CD2+, CD3+, T-cell receptor (TCR)delta-1+), betaF1- phenotype. They were CD5- (9 of 10) and CD4-/CD8- (9 of 10) or CD8+ (1 of 10). A clonal gamma-chain gene rearrangement was detected in all tested cases (9/9). All cases had an activated cytotoxic T-cell intracellular antigen-1 (TIA-1)+, Granzyme B+ phenotype. Epstein-Barr virus (EBV) sequences were detected in six cases by in situ hybridization (ISH). Despite an aggressive clinical course, complete remission was obtained in three patients, and one of the latter required a peripheral blood stem-cell transplantation. Nonhepatosplenic gammadelta peripheral T-cell lymphoma can be regarded as a model of activated cytotoxic lymphoma, occurring in mucosae or skin. These appear to be derived from the subpopulation of tissue-restricted gammadelta lymphocytes, which are involved in the host epithelial surface surveillance. The role of chronic antigen exposure in the pathogenesis of these rare lymphomas can be suggested, in view of the past history observed in at least some patients.
Adult↗
Hodgkin's disease of donor origin after allogeneic bone marrow transplantation for myelogeneous chronic leukemia.
Secondary malignancies (lymphomas, leukemias, and solid tumors) occurring after bone marrow transplantation are now more frequently reported, as the patients surviving the early phase of the graft and remaining free of their original disease are more numerous. Besides early Epstein-Barr virus-associated B-cell lymphoproliferative diseases, which are the most common type and most often of donor origin, few late-occurring lymphomas have been described that might represent a distinct entity. We report here a case of Hodgkin's disease developing 8 years after allogeneic bone marrow transplantation for chronic myelogeneous leukemia. Only two Hodgkin's diseases after allogeneic bone marrow transplantation have been reported in the literature so far. The case we report is of interest because of its donor origin and its association with Epstein-Barr virus infection.
Adult↗
Differences in Epstein-Barr virus expression between primary and secondary cutaneous angiocentric lymphomas. French Study Group of Cutaneous Lymphomas.
BACKGROUND: Epstein-Barr virus (EBV) has been demonstrated in angiocentric immunoproliferative lesions, suggesting that it could be a causative factor. We investigated for the presence of EBV in 12 primary and 2 secondary cutaneous angiocentric lymphomas (CALs). OBSERVATIONS: In the 2 secondary CALs, strong reactivity for EBV RNAs and latent membrane protein 1 were detected on paraffin-embedded sections. In contrast, 10 of 12 primary CALs were completely negative for EBV RNAs and latent membrane protein 1. In 2 primary CALs, EBV RNAs and latent membrane protein 1 were detected in few tumor cells. In the group of primary CALs, 8 of 12 were still alive at last follow-up, 3 died of systemic lymphoma, and 1 died of another cause, whereas both patients with secondary CALs died of disease within 1 year. CONCLUSION: Differences in the presence of EBV and clinical behavior between primary and secondary CALs suggest that different mechanisms are operative in the pathogenesis of these conditions, and indicate that the 2 groups should be considered separately.
Adult↗
Human interleukin-10 expression in T/natural killer-cell lymphomas: association with anaplastic large cell lymphomas and nasal natural killer-cell lymphomas.
Several cytokines have been implicated in the pathogenesis of human lymphomas. Among them, interleukin-10 (IL-10) is a pleiotropic cytokine with various biological effects on B and T lymphocytes. Its expression has been essentially studied in B-cell lymphomas, where it appears to act as an autocrine growth factor. BCRF1 (also called viral IL-10), an open reading frame of Epstein-Barr virus, exhibits extensive sequence and functional homologies with human IL-10. Some entities belonging to T- or natural killer (NK)-cell lymphomas are characterized by a frequent association with Epstein-Barr virus. We analyzed 39 cases of peripheral T-cell lymphoma, as well as 7 cases of nasal NK-cell lymphoma, for the presence of IL-10 transcripts by in situ hybridization, to see whether this cytokine was expressed in these tumors and whether its expression could be related to their histological subtype and to the presence of Epstein-Barr virus. Because the riboprobe used for in situ hybridization recognizes both human and viral IL-10, 12 cases were also analyzed by reverse transcription-polymerase chain reaction to verify the human or viral origin of IL-10. It was found that 8 of 11 (73%) anaplastic large cell lymphomas (ALCLs), 2 of 11 (18%) pleomorphic T-cell lymphomas, and 3 of 7 (43%) nasal NK-cell lymphomas exhibited a large number of IL-10-expressing cells, whereas only rare scattered cells were detected in angioimmunoblastic (11 of 11) and in gammadelta T-cell lymphomas (6 of 6). In ALCLs, the pattern of IL-10 mRNA-expressing cells showed an overlapping with the CD30 staining and preferential localization in sinusal and perifollicular areas, thereby suggesting that IL-10-expressing cells were tumor cells. Furthermore, IL-10 transcripts were detected in the SU-DHL-1 anaplastic lymphoma cell line. No correlation with Epstein-Barr virus profile was found, because all cases of ALCL were negative for EBER 1 and 2 genes by in situ hybridization. We confirmed the presence of human IL-10 mRNA by reverse transcription-polymerase chain reaction in ALCLs as well as in NK-cell lymphomas, whereas viral IL-10 was not detected. Thus, human and not viral IL-10 is frequently expressed by tumor cells in ALCLs and nasal NK-cell lymphomas. In view of its function in the proliferation and the differentiation of cytotoxic T and NK cells, and its immunosuppressive properties, IL-10 may have a role in the pathogenesis of these lymphomas.
Adolescent↗
[Non-Hodgkin's lymphoma. Aspects of clinical pathology].
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Humans↗
Report of the European Task Force on Lymphomas: workshop on peripheral T-cell lymphomas.
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Biomarkers, Tumor↗
High-dose therapy followed by stem cell transplantation in partial response after first-line induction therapy for aggressive non-Hodgkin's lymphoma.
Patients with aggressive non-Hodgkin's lymphoma who fail to achieve a complete remission (CR) with standard induction therapy have a poor prognosis with conventional-dose salvage therapy alone. Retrospective series have suggested that early introduction of high-dose salvage therapy with autologous stem cell transplantation (ASCT) may benefit partial-responder (PR) patients. However, two randomized studies (of 69 and 51 patients with partial clinical responses) failed to demonstrate any advantage of intensive therapy. By contrast, the GELA comparative study on 94 PR-patients (residual disease being histologically documented in 53 patients) suggested that high-dose therapy with ASCT improves survival. Interpretation of all these results is complicated by the heterogeneity of patient populations with respect to initial prognostic factors, induction regimens and, in particular, the criteria used to define partial response. Gallium CT scan and magnetic resonance imaging are now used to better explore residual masses. In the future, early restaging with these imaging techniques might be used to delineate patients who are likely to achieve CR from those who will fail to induction treatment and could be candidates for experimental treatments.
Antineoplastic Combined Chemotherapy Protocols↗
[Epstein-Barr virus: pathologic implications].
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Acquired Immunodeficiency Syndrome↗
[T-cell lymphomas and "natural killer". Histopathologic, immunologic and molecular aspects].
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Genome, Human↗
Primary anaplastic large-cell lymphoma in adults: clinical presentation, immunophenotype, and outcome.
Anaplastic, CD30+, large-cell lymphoma is now a well-recognized pathologic entity that accounts for 2% to 8% of all lymphomas. Recent progress has been made in the understanding of certain biologic features found in anaplastic large-cell lymphoma, but information about its clinical behavior, in comparison to other large-cell lymphomas, is limited. The pathologic review of a large multicenter study of the treatment of aggressive lymphoma identified 146 cases of anaplastic large-cell lymphoma (ALCL) on the basis of morphology and CD30 expression. We compared initial presentation, immunophenotype, and clinical outcome of these cases with those of the 1,695 nonanaplastic diffuse large-cell lymphomas (non-ALCL) included in the same trial. Patients with ALCL were more likely to be male (P = .018) and were younger (P < .0001) than those with non-ALCL. B symptoms were more frequent in ALCL (P = .006). Skin (P < .0001) and lung (P < .05) involvement was also more frequent in ALCL, but frequency of bone marrow involvement was identical (P = . 5). Tumor cell phenotype was B in 56 cases (38%), T in 49 cases (34%), and null in 33 cases (22%). Response to chemotherapy (P = . 001), event-free survival (P = .006), and overall survival (P = . 0004) were better for ALCL than for non-ALCL. Multivariate analyses identified anaplastic character as an independent factor that predicted a longer survival. Tumor cell phenotype did not influence event-free survival (P = .72) or overall survival (P = .83). ALCL in adults is a clinicopathologic entity which, independent of its phenotypic characteristics, has a better outcome than other diffuse large-cell lymphomas.
Adult↗
Cytotoxic protein expression in natural killer cell lymphomas and in alpha beta and gamma delta peripheral T-cell lymphomas.
Lymphomas with T-cell phenotype represent a heterogeneous group of diseases differing in histopathology, tumour site, and cell origin. They include peripheral T-cell lymphomas (PTCLs) derived from alpha beta cells, but also some recently recognized entities such as gamma delta, hepatosplenic lymphomas and natural killer (NK) cell lymphomas. Only a few studies have investigated the possibility that at least some PTCLs could be derived from lymphocytes with cytotoxic potential. In order to investigate this possibility, 60 cases of PTCL, including 27 cases expressing the alpha beta T-cell receptor (TCR alpha beta), 15 TCR gamma delta cases and 18 cases expressing neither TCR (TCR silent), as well as 14 cases of NK-cell lymphomas, were studied by immunohistochemistry for the expression of TIA-1, perforin, and granzyme B proteins. Expression of TIA-1 is characteristic of cytotoxic cells regardless of their activation status, whereas expression of perforin and granzymes is highly increased in activated cytotoxic cells and correlates with the induction of cytolytic activity. All NK-cell lymphomas (11 sinonasal, three systemic cases) expressed TIA-1, perforin, and granzyme B in most tumour cells. All gamma delta PTCLs (15 cases) expressed TIA-1 protein in most tumour cells, with a different cytotoxic antigen profile in hepatosplenic gamma delta PTCL (TIA-1+, perforin-, granzyme B-) and in non-hepatosplenic gamma delta PTCLs (three nasal, one skin, one lung), the latter expressing the three cytotoxic proteins. Of the 45 cases of alpha beta and TCR silent PTCL, 15 (33 per cent) were considered to be derived from cytotoxic lymphocytes with expression of at least one cytotoxic protein (TIA-1, 15/45; perforin, 10/41; granzyme B, 14/38) in tumour cells. This cytotoxic protein expression appeared to be related to the site of localization, since 7/13 (54 per cent) extranodal and only 8/32 (25 per cent) nodal alpha beta and TCR silent PTCLs expressed TIA-1, and to histology, since this pattern was observed in a proportion of anaplastic (6/8, 75 per cent) and pleomorphic (8/17, 47 per cent) lymphomas, but not in AILD-type NHL (0/16). Taken together, our data suggest that NK-cell lymphomas and non-hepatosplenic gamma delta PTCLs represent tumours of activated cytotoxic NK cells and gamma delta T cells, respectively; that hepatosplenic gamma delta PTCLs represent tumours of non-activated cytotoxic gamma delta T cells; and that a small proportion of alpha beta and TCR silent PTCLs, mostly extranodal cases, or nodal anaplastic lymphomas, represent tumours of cytotoxic T cells.
Granzymes↗
Distinctive clinicopathologic features associated with regressive primary CD30 positive cutaneous lymphomas: analysis of 6 cases.
A distinct group of cutaneous lymphomas has been described on the basis of CD30 antigen expression by at least 75% of the tumoral cells. When confined to the skin, these CD30 positive cutaneous lymphomas seem to be associated with a better prognosis than CD30 negative counterparts and spontaneous regression may even occur. We observed a spontaneously regressive evolution in 6 out of 9 CD30 positive primary cutaneous large cell-lymphomas diagnosed during a 5-year period. Clinicopathological data of regressive cases were analysed. The mean age of patients was 56.5 years. They were 3 males and 3 females. Skin lesions were solitary nodule or plaque measuring from 1.5 cm to 11 cm in diameter. Histologically, the lesions were classified as pleomorphic, medium and large cell (5 cases) or large cell anaplastic lymphoma (1 case) according to the updated Kiel classification. Delay for spontaneous regression varied from 1 to 6 months. Three of the 6 patients had cutaneous relapses, followed by a spontaneous regression. All patients remained disease-free with an overall median follow-up of 30 months. Histologically, some distinctive signs such as epidermal pseudo-epitheliomatous hyperplasia, epidermotropism, edema, dermal vascular hyperplasia, seemed to be more frequently associated with spontaneously regressive evolution.
Adult↗
Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2. Groupe d'Etude des Lymphomes de l'Adulte.
PURPOSE: To update the randomized study that compared consolidative sequential treatment (ifosfamide, etoposide, asporaginase, and cytarabine) versus the high-dose regimen of cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission and to focus on high-intermediate and high-risk patients identified by the international prognostic index. PATIENTS AND METHODS: Nine hundred sixteen patients received induction treatment on the LNH84 protocol with open randomization for the anthracycline. In a subsequent randomization, 541 patients in complete remission were assigned to receive consolidation by either sequential chemotherapy (n = 273) or autotransplant (n = 268). Among the higher risk population (two or three risk factors), 236 patients in complete remission were assessable for the consolidation phase, with 111 in the sequential chemotherapy arm and 125 in the autotransplant arm. RESULTS: Among 541 randomized patients, disease-free survival and survival did not differ significantly between the two consolidative treatment arms. In the higher risk population, CBV was superior to sequential chemotherapy, with 5-year disease-free survival rates of 59% (95% confidence interval, 49% to 69%) and 39% (95% confidence interval, 28% to 50%), respectively (P = .01, relative risk = 1.19). The 5-year survival rate was superior in the CBV group at 65% (95% confidence interval, 56% to 74%) compared with 52% in the sequential chemotherapy group (95% confidence interval, 42% to 62%) (P = .06, relative risk = 1.49). CONCLUSION: This study shows a superior disease-free survival for higher risk patients in complete remission. Dose-intensive consolidation therapy should be considered for patients at higher risk who achieve complete remission after induction treatment.
Adolescent↗