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At least 973 records · Page 54Linked to original sources

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) in primary effusion lymphoma: ultrastructural demonstration of herpesvirus in lymphoma cells.

Recent molecular evidence suggests an association with a new herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8), and primary effusion lymphomas (PELs). PELs have a characteristic morphology, phenotype, and clinical presentation, with malignant effusions in the absence of a contiguous solid tumor mass. We have established a cell line (KS-1) from a KSHV-positive human immunodeficiency virus (HIV)-negative patient with pleural cavity-based lymphoma that was passaged into triple-immunodeficient BNX mice. In contrast to cell lines from body cavity-based lymphomas derived from HIV-positive individuals that contain both KSHV and Epstein Barr viral genome, these cells contain only KSHV, allowing for uncontaminated virologic studies. Ultrastructural examination identified malignant cells with features of late differentiating B cells (immunoblasts). Cells with viral cytopathic effect contained typical 110-nm intranuclear herpesvirus nucleocapsids and complete cytoplasmic virions, confirming the association of PEL with KSHV.

Animals↗

[Splenic lymphoma with circulating hairy lymphocytes lymphoma. Clinical cytological study of 4 patients].

PURPOSE: The splenic lymphoma with circulating villous lymphocytes (SLCVL) is an infrequent disease included within the low grade non Hodgkin's lymphoma, B-cell type. The results of the study of four patients are reported. PATIENTS AND METHODS: Clinical, cytological, immunophenotypic, ultrastructural, evolutive and therapeutic data have been revised in all the cases. RESULTS: Two males and 2 females of 76, 66, 68 and 62 years, respectively were diagnosed as having SLCVL. The initial symptoms were scarce, basically asthenia, and a big spleen without significant lymphadenopaty was the most relevant physical finding in each of them. In peripheral blood leukocyte count was normal with a slight lymphocytosis and a variable percentage of villous circulating lymphocytes. The immunophenotype of peripheral blood obtained by flow cytometry was according with a mature B-cell lymphocyte population, CD 5 and CD 25 negative. The cells were positive to acid phosphatase with a diffuse pattern of variable intensity; the reaction was inhibited by tartaric acid. All the patients had BM infiltration, studied with aspiration and biopsy. One case (M,66) had an IgM monoclonal gammopathy. The ultrastructural study, performed in 3 cases, showed thin and short villous prolongations. After splenectomy, a low degree lymphoma therapy has been employed in all the cases. The follow-up ranges between, 4 years and 4 months, all the patients being alive. CONCLUSIONS: The SLCVL is a definitive entity regarding the clinical, morphologic and immunophenotype features. A long clinical evolution and a good prognosis after splenectomy are common.

Aged↗

Primary effusion lymphoma in women: report of two cases of Kaposi's sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women.

Recent molecular evidence suggests an association with a new herpes virus, Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8), and primary effusion lymphomas (PEL). PELs have a characteristic morphology, phenotype, and clinical presentation with malignant effusions in the absence of a contiguous solid tumor mass. Most cases of PEL have occurred in human immunodeficiency virus (HIV)-positive male patients who are coinfected with Epstein-Barr virus (EBV). This report describes two cases of PEL in HIV- and EBV-negative women. In one patient, a pleural cavity PEL was preceded by classic Kaposi's Sarcoma (KS) of the lower extremities. In the second patient, PEL developed in an artificial cavity related to the capsule of a breast implant. Both cases had the characteristic morphologic appearance of high-grade anaplastic/B-cell immunoblastic lymphomas, with loss of B-cell differentiation antigens, clonal immunoglobulin heavy chain gene rearrangements, and expression of activation antigen CD30. Both cases were negative for EBV, herpes virus simplex, and cytomegalovirus (CMV). DNA extracted from both lymphomas and skin KS specimen showed KSHV sequences by molecular analysis. This report expands the spectrum of KSHV-associated disease to include PEL in HIV-negative women.

Aged↗

An autopsy case of intravascular malignant lymphoma presenting with intracranial B-cell type malignant lymphoma.

This report concerns a 79-year-old man with intravascular malignant lymphoma who was admitted to our hospital for slight right side hemiparesis. Radiological examinations showed a mass in the left parietal lobe, and a brain biopsy revealed a B-cell type malignant lymphoma. The tumor could not be detected on magnetic resonance images following focal radiotherapy, but the patient died of acute progressive pneumonia about 3 months after the onset of symptoms. An autopsy was performed. Microscopic examinations disclosed proliferation of neoplastic cells in the small and medium-sized blood vessels of the adrenal glands, liver, spleen, pancreas, kidneys and epididymis. A diagnosis of intravascular malignant lymphoma was established on the bases of these autopsy findings.

Aged↗

Long-term survival advantage of MACOP-B over CHOP in intermediate-grade non-Hodgkin's lymphoma. The Australian and New Zealand Lymphoma Group.

BACKGROUND: The initial publication of the results of the Australian and New Zealand Lymphoma Group (ANZLG) randomized controlled trial comparing MACOP-B and CHOP in patients with intermediate-grade non-Hodgkin's lymphoma (NHL) showed equivalent complete response rates, time to treatment failure, and survival. Here we report the long-term follow-up of the 236 patients entered on that study to determine if there were any long-term advantages or disadvantages associated with MACOP-B. PATIENTS AND METHODS: Two hundred thirty-six eligible patients were randomized between October 1986 and June 1991. The median duration of follow-up has been extended from 3.2 years in our previous publication to 6.5 years. RESULTS: As previously reported, the complete response (CR) rate for MACOP-B and CHOP chemotherapy was 51% and 59%, respectively. The estimated failure-free survival rate for MACOP-B and CHOP patients was 42% and 30%, respectively, at 5 years (P = 0.045) and 37% and 25%, respectively, at 8 year (P = 0.057). The estimated overall survival rate at 5 years was 54% for MACOP-B and 41% for CHOP patients (P = 0.035) and at 8 years was 45% and 36%, respectively (P = 0.16). CONCLUSION: With this extended follow-up, we have shown a long-term survival advantage for MACOP-B chemotherapy over standard CHOP in patients with intermediate-grade non-Hodgkin's lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

Reassessment of gastric lymphoma in light of the concept of mucosa-associated lymphoid tissue lymphoma: analysis of 53 patients.

BACKGROUND: The concept of mucosa-associated lymphoid tissue (MALT) lymphoma is now widely accepted. However, precise characterization of the features of MALT lesions in the stomach is needed. For this, extensive analysis of resected gastrectomy specimens from a large number of patients with MALT lymphoma is essential. METHODS: Fifty-three patients who underwent gastrectomy for the treatment of primary gastric lymphoma were studied. In the histologic examination, a mean of 46 specimens per case were analyzed; the distribution of lymphomatous lesions was plotted on maps of gastrectomy specimens, input into a computer, and used to measure the size of lesions. RESULTS: The median age of the patients was 56 years, and the male-to-female ratio was 27:26. Stage of disease was I(E) for 35 patients, II(E) for 15, and III for 3. Histologically, 25 patients had low grade lesions, 18 had combined high and low grade lesions, and had 10 high grade lesions. Macroscopically, low grade MALT usually had multiple instances of superficial spreading of lesions without ulceration, whereas high grade MALT exhibited a solitary tumor-forming lesion. All of the superficial spreading type without ulceration were low grade MALT. The higher the grade of tumor, the larger the tumor size. Twenty-four patients received chemotherapy. The 5-year survival rate was 67.2%. Multivariate analysis revealed that only the clinical stage was a significant factor in prognosis. CONCLUSIONS: Low grade MALT can be differentiated from other types of MALT by macroscopic findings. When the MALT concept is adopted, stage of disease is important in relation to survival.

Adult↗

High-dose chemotherapy with autologous bone marrow rescue in children with poor-risk Burkitt's lymphoma: a report from the European Lymphoma Bone Marrow Transplantation Registry.

To evaluate the role of high-dose chemotherapy (HDC) followed by autologous bone marrow transplantation (ABMT) in children with poor-prognosis Burkitt's lymphoma, the European Lymphoma BMT registry was critically reviewed. Between February 1979 and July 1991, a selected group of 89 children (78 boys and 11 girls) were considered as ABMT candidates in 12 European cancer centers for the following reasons: poor initial response (PIR) to first-line chemotherapy in 28 patients, primary refractory disease (PRD) in nine patients, sensitive relapse (SR) in 38 patients, and resistant relapse (RR) in 14 patients. The median age at ABMT was 8.2 years (range, 2.8 to 16.2 years). Thus, this report reflects data for patients surviving the salvage attempt deemed appropriate for HDC/ABMT and who then actually underwent the transplant procedure. The median follow-up period after HDC/ABMT was 4.3 years (range, 2 to 12 years). The prognosis was dismal for PRD patients and those with RR, ie, all patients died within 1 year. The 5-year event-free survival (EFS) was 56.6% (P < .0001) for patients in partial remission (PR) and 48.7% (P = .002) for patients with SR. The toxic death rate was 11.1%. Continuous complete remissions (CRs) in 39.4% of these otherwise incurable children highlight the fact that HDC/ABMT was an effective complementary procedure after conventional-dose chemotherapy protocols used during the given period. In addition, these data show that patients with PRD or RR clearly had no advantage from this aggressive and cost-intensive procedure. It has to be considered that the need for HDC/ABMT has greatly diminished in parallel with the improvement in survival using the modern intensive pulsed CCT of current protocols. To further rescue patients failing to respond to modern protocols, new approaches appear necessary, ie, combinations of HDC with antibody-targeted therapy plus allogeneic BMT for the additional benefits of the potential graft-versus-lymphoma effect.

Antineoplastic Agents↗

[Cardiac lymphoma disclosed by tamponade and complete atrioventricular block: apropos of a surgically treated case. Heart and lymphoma].

Cardiac lymphoma is becoming increasingly frequent, especially in the context of acquired immune deficiency syndrome, and due to progress in imaging, particularly echocardiography. The authors report the case of a 49-year-old patient in whom the diagnosis of cardiac lymphoma was established in the presence of complete atrioventricular block, tamponade and right atrial tumour. The authors review the various electrocardiographic and echocardiographic features of cardiac lymphoma.

Cardiac Tamponade↗

Apoptosis during the development of radiogenic thymic lymphomas: effects of treatments inhibiting lymphoma development.

INTRODUCTION: Whole body fractionated irradiation induces thymic lymphomas in C57BL/Ka mice after a latent period during which preleukemic cells progressively transform into leukemic cells within an abnormal thymic microenvironment. A bone marrow graft or repeated cytokine injections prevent lymphoma development. We think that these treatments restore altered mechanisms controlling apoptosis. MATERIALS AND METHODS: Apoptosis was analyzed by flow cytometry in thymocytes from different groups of mice (control, preleukemic, prevented mice). RESULTS: The apoptotic rates did not change in freshly isolated thymocytes from different experimental groups. However, after culture, the level of apoptosis increased in preleukemic thymuses; and returned to normal value in cultured thymocytes from irradiated mice after lymphoma preventing treatments. Furthermore, thymic microenvironmental factors can control thymocyte apoptosis. CONCLUSION: We propose that after leukemogenic irradiation, there is an increase of cells with an activated suicide program, but that alterations of thymic environmental factors rescue them from apoptosis, allowing their further neoplastic transformation.

Animals↗

Germinal center and activated b-cell profiles separate Burkitt lymphoma and diffuse large B-cell lymphoma in AIDS and non-AIDS cases.

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.

Adolescent↗

[Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma].

Rescue therapies for relapsing/refractory primary central nervous system lymphoma (PCNSL) and intraocular lymphoma (IOL) remain a challenging problem for clinicians. In 2001, we published encouraging results for 22 patients treated at relapse with a CYVE regimen combining high doses of Ara-C (50 mg/m(2)/d in 12 hours infusion dl through d5; 2 g/m(2)/d d2 through d5) and VP16 (200 mg/m(2)/d d2 through d5), followed by intensive chemotherapy based on high doses of thiotepa (250 mg/m(2)/d d-9 through d-7), busulfan (10 mg/kg total dose d-6 through d-4) and cyclophosphamide (60 mg/kg/d, d-3 and d-2 with hematopoietic cell rescue at d0. Patients were enrolled onto the study for a relapse (n = 10; 2 IOL, 3 CSF, 5 brain lesion) or for a refractory disease (n = 12; 9 IOL, 3 brain lesion). CYVE rescue was not administered to patients with refractory IOL who had previously received high doses of methotrexate and Ara-C as part of their first-line treatment. Twenty patients received the intensive chemotherapy and hematopoietic cells rescue. We updated our results in March 2003. Seven patients had neurologic adverse events during the entire procedure. With a median follow up of 6.2 years, the median overall survival is 91 months, and the median survival after intensive chemotherapy has not been reached.

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↗

T-cell lymphomas of large cell type. A variety of malignant lymphomas: "histiocytic" and mixed lymphocytic-"histiocytic".

Clinical and morphologic features of seven T-cell lymphomas of the large cell type are described. The tumors were grouped into those with irregular (3 cases) and those with round and regular nuclei (4 cases). In both groups, variation in cell size, numerous histiocytes and vessels, and many mitoses were distinguishing features. In only 1 case in the round and regular nucleus group was there relatively little variation in cell size and a paucity of histiocytes. Abundant polyribosomes, long strands of rough endoplasmic reticulum, and lysosomal granules were prominent electron microscopic features in both groups of tumors. The clinical presentations and courses varied considerably, especially in patients with tumors of the round nucleus type. One patient presented initially with chronic lymphocytic leukemia, 1 with Lennert's lymphoma, another with bone marrow infiltration, and a fourth with subcutaneous tumors. Two patients with the round nucleus type are still alive one and a half and two years after the original diagnosis. Two patients died two years after the onset of symptoms. Each of the 3 patients with tumors of the irregular nucleus type had a rapid clinical course and died within ten months.

Aged↗

Clinical relevance of immunophenotype in a retrospective comparative study of 297 peripheral T-cell lymphomas, unspecified, and 496 diffuse large B-cell lymphomas: experience of the Intergruppo Italiano Linformi.

BACKGROUND: To assess the impact of T-cell/B-cell phenotype on clinical outcome, the authors retrospectively compared patients who had peripheral T-cell lymphoma, unspecified (PTCL-U), with patients who had diffuse large B-cell lymphoma (DLBCL). METHODS: Two hundred ninety-seven cases of PTCL-U and 496 cases of DLBCL that had been transferred from the files of the Intergruppo Italiano Linfomi or the Gruppo Italiano Linfomi were integrated into a unique working file and reviewed by the authors. RESULTS: The PTCL-U group and the DLBCL group had significantly different distribution patterns with respect to patient age, gender, disease stage, performance status (PS), the presence or absence of systemic "B" symptoms, the presence or absence of bulky disease, lactic acid dehydrogenase (LDH) levels, and number of extranodal sites (ENS). A significantly greater number of patients in the DLBCL group experienced complete remission (P < 0.0001). Multinomial logistic regression analysis confirmed that immunophenotype, PS, LDH concentration, and number of ENS were independent predictors of response. At a median follow-up duration of 43 months, there was no observable difference in disease-free survival (DFS) between patients with DLBCL and patients with PTCL-U; however, multivariate analysis did reveal that poorer PS and bone marrow involvement were significantly associated with shorter DFS. Furthermore, although the overall survival (OS) curves associated with the T-cell and B-cell immunophenotypes were significantly different from each other at a median follow-up duration of 37 months (P = 0.0012), Cox multivariate analysis excluded immunophenotype from the final OS model. CONCLUSIONS: The findings made in the current study indicate that the natural history of PTCL-U may differ from that of DLBCL. Patients with PTCL-U tended to have less favorable clinical outcomes, although the observed difference in outcome was only partially attributable to immunophenotype, which was independently associated with response, but not with survival. Differences in prognostic factor distributions between patients with PTCL-U and patients with DLBCL may account for some portion of the expected phenotype-associated risk.

Disease-Free Survival↗

Identification of chromosomal copy number changes associated with transformation of follicular lymphoma to diffuse large B-cell lymphoma.

The histological transformation from a follicular lymphoma (FL) to a diffuse large B-cell lymphoma (DLBL) occurs in 22% to 30% of all cases of FL. The aim of this study was to identify specific chromosomal gains/losses associated with transformation of FL to DLBL, in addition to the well-known mechanisms like p53 mutation and protein expression and c-myc translocation and up-regulation. This is the first study to meet 2 important conditions for such a comparison. First, we demonstrate that the FL and the DLBL were clonally related, based on identical immunoglobulin gene rearrangements in 5 of the 6 cases. Second, we used laser microdissection microscopy to isolate only the neoplastic cells from the initial FL samples. The results indicate that no single chromosomal abnormality seems to be responsible for the transformation of FL to DLBL. P53 protein overexpression was found in 4 and c-myc translocation in 3 of the 6 transformed DLBLs, but not in the initial FL samples. Additional chromosomal abnormalities were detected by comparative genomic hybridization in all 6 cases when the DLBL was compared with the FL. In the 5 cases with transformation of grade 1 or 2 FL to DLBL, gains at chromosomes 7 (5 of 5 cases), 10p1 (3 of 5 cases), 12 (3 of 5 cases), and 20p13 (2 of 5 cases) and loss at 9q (4 of 5 cases) were the most frequently found abnormalities. A gain on chromosome 7p, in combination with a loss on 9q, was found in 4 of the 5 DLBL that transformed from FL grade 1 or 2.

Cell Transformation, Neoplastic↗

A randomised comparison of a third-generation regimen (PACEBOM) with a standard regimen (CHOP) in patients with histologically aggressive non-Hodgkin's lymphoma: a British National Lymphoma Investigation report.

A combination of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) has been a standard therapy for histologically aggressive non-Hodgkin's lymphomas for over 20 years, but several newer regimens, referred to as second or third generation, have been reported to give improved results in single-centre studies. Positive evidence from randomised trials has been lacking, and the British National Lymphoma Investigation therefore commenced a randomised comparison of CHOP vs a third-generation regimen, PACEBOM, in November 1987. A total of 459 eligible patients were entered into the trial: 226 in the CHOP arm and 233 in the PACEBOM arm. Overall, there was no significant difference in outcome between the two arms of the trial. In patients with stage IV disease there was an apparent improvement in survival for those treated with PACEBOM, but considerable caution must be exercised with such subgroup analysis.

Aged↗

A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma.

The role of TP53 mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire TP53 coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated TP53 arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the TP53 locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with wtTP53. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68-76%) than FL (mean 58% positive; 95% CI 54-62%) (P<0.001) but did not correlate with TP53 status. TP53 mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target..

Cell Transformation, Neoplastic↗

Copy number gain at 12q12-14 may be important in the transformation from follicular lymphoma to diffuse large B cell lymphoma.

The purpose of this study was to identify novel areas of genomic copy number change associated with transformation from follicular lymphoma (FL) to diffuse large B cell lymphoma (DLBL). DNA was extracted from tumour cells micro-dissected from paraffin- embedded tissue sections in 24 patients with FL and subsequent transformation to DLBL and 18 patients with de novo DLBL. Tumour DNA was compared to reference DNA using comparative genomic hybridization. Abnormalities common to all 3 groups were gains on chromosomes 4q, 5q, 7q, 11q and X and losses on 3p, 8p and 10q. Copy number changes seen in both transformed and de novo DLBL and not seen in FL were gains on 2p and losses on 1q, 15q and Xq. Gains on 2q, 6p, 7p and 17q and losses on 5p and 8q were specific to transformed DLBL cases. Gain on 12q12-14 was found in 52% of the transformed DLBL cases and was never seen in its follicular counterpart. Patterns of genomic copy number change associated with specific clinical events in NHL have been demonstrated and suggest that gains on 2q, 6p, 7p, 12q and 17q and losses on 5p and 8q may be important in the transformation from low to high-grade disease.

Cell Transformation, Neoplastic↗