Diffuse Large Lymphoma Research Articles

Should Imaging Be Performed for Lymphoma in Remission

Periodic imaging to detect relapse is standard practice for patients with diffuse large B-cell lymphoma (DLBCL) in first remission. But the utility of

Re-Induction Therapy for Relapsed Aggressive Lymphoma

Standard of care for chemosensitive patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) is a “salvage” chemotherapy regimen followed by autologous stem-cell transplantation (ASCT). To evaluate a gemcitabine-based second-line regimen versus standard second-line therapy, Canadian investigators conducted a partially funded, randomized, multicenter, prospective, noninferiority, phase III trial involving 605 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or transformed B-cell lymphoma, peripheral T-cell lymphoma, or …

Comparison of pathological features and prognosis between orbital and systemic diffuse large B cell lymphoma

Background Orbital diffuse large B cell lymphoma(DLBCL) is a kind of malignant lymphoma with higher morbidity,but the systematic study is difficult for the fewer cases and the lack of orbital DLBCL cell line.Objective This study was to compare the differences or similarities of histopathological characteristics between orbital DLBCL and systemic DLBCL,and to discuss whether systemic DLBCL cell line is available to in vitro research of orbit DLBCL.Methods The histopathological specimens were collected from 3 orbital DLBCL patients and 15 systemic DLBCL patients in Tianjin Eye Hospital and Tianjin Tumor Hospital from 2004 to 2009.The prognosis of the patients was followed-up,and the survival curve was drew.The histopathological examination of the specimens was performed using hematoxylin and eosin staining,and the expressions of CD20,CD79α,CD45RO,CD10,BCL-6,mum-1,Ki-67 and surviving in the specimens were detected by immunochemistry.The results mentioned above were analyzed and compared between orbital DLBCL and systemic DLBCL.Results The histopathological examination showed that the centroblastic type was the primary form in both orbital DLBCL and systemic DLBCL,according with the diagnosis of DLBCL.The differences in the positive expression rate of CD20,CD79α,CD45RO,Ki-67,survivin were not statistically significant between the two types of DLBCL (P =0.167,0.442,1.000,1.000,0.442).Immunochemistry revealed that 3 orbital DLBCL patients were germinal center B-cell-like (GCB),and 2 of the patients showed the positive expression for BCL-6 and mum-1 as well as absent expression for CD10,but the other patient presented the absent expression for BCL-6,mum-1 and CD10.In 15 systemic DLBCL patients,7 were GCB type,with the positive expression for CD10 in all the 7 patients and absent expression for BCL-6 in 6 patients.In addition,in 8 of non-GCB type,3 appeared to be absent expressed for CD10 and BCL-6,and 5 were positive expressed for BCL-6 and mum-1 and absent expressed for CD10.No significant difference was found in the survival duration between the orbital DLBCL and systemic DLBCL (P =0.067).Conclusions There exists no clinically significant difference in the pathological features,the expression of tumor cell markers and prognosis in both orbital and systemic DLBCL.These two DLBCLs appear to be similar in epidemiology and clinical staging,inferring that systemic DLBCL cell line is available in the in vitro study of orbital DLBCL. Key words: Neoplasm; Orbit; Diffuse large B cell lymphoma; Pathology; Immunochemistry

Expression of Bcl-2 gene and its effect on prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma

To explore the expression of Bcl-2 mRNA and its effect on prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL). Real time quantitative PCR was used to determine the expression of Bcl-2 mRNA in 40 PGI-DLBCL patients and 17 healthy controls. The association of Bcl-2 expression with clinicopathological features and prognosis of the patients was analyzed. The expression level of Bcl-2 mRNA in PGI-DLBCL patients was 1.03 ± 0.93, significantly higher than that of the controls (0.41 ± 0.21) (P < 0.05). The expression of Bcl-2 mRNA in stage IIE-IV patients (1.28 ± 1.01) was significantly higher than that in the stage I-II2 patients (0.62 ± 0.61) (P < 0.05). The expression of Bcl-2 mRNA in patients with international prognostic index (IPI) score >2 (1.95 ± 1.27) was significantly higher than those with IPI score ≤ 2 (0.86 ± 0.75)(P < 0.05). The expression of Bcl-2 mRNA in patients with complete remission (CR) (0.71 ± 0.58) was significantly lower vs. 2.42 ± 0.91 in patients with no CR (P < 0.05). Univariate analysis indicated that β2-MG, IPI score>2, the Lugano staging, and Bcl-2 mRNA expression were associated with overall survival (OS) and progression-free survival (PFS) (P < 0.05). Multivariate analysis indicated that IPI score>2 was independently associated with OS (P < 0.05), and both IPI score >2 and Bcl-2 mRNA expression were independently associated with PFS (P < 0.05). The expression of Bcl-2 mRNA in the tumor tissue of PGI-DLBCL patients is significantly higher than that in controls. PGI-DLBCL patients with higher expression of Bcl-2 have a poor chemotherapy response and inferior prognosis. IPI score >2 and higher expression of Bcl-2 mRNA are independent poor prognostic factors for PFS in PGI-DLBCL patients.

Expression and significance of MYC/BCL2 protein coexpression in diffuse large B-cell lymphoma

Objective To explore the condition of MYC/BCL2 protein coexpression in 245 patients with diffuse large B-cell lymphoma （DLBCL）and to find the correlations among MYC/BCL2 protein coexpres-sion,the germinal center B-cell-like （GCB）subtype and non-GCB subtype.Methods Paraffin-embedded lymphoma samples from 245 patients with DLBCL were studied using immunohistochemistry for MYC,BCL2, CD10,BCL6,MUM1 and KI67.And the protein expressions of them were analyzed.Results In the speci-mens of 245 patients with DLBCL,the patients with non-GCB were 163 （66.5%）,and the patients with GCB were 82 （33.5%）.The group of MYC/BCL2 protein coexpression comprised 35.9% （88/246）of the all patients.Non-GCB subtype group had a significantly higher frequency of MYC/BCL2 protein coexpression than the GCB subtype group （41.7%∶24.4%;χ2 =7.116,P=0.008）.Conclusion The data shows that MYC/BCL2 protein coexpression occurs significantly more commonly in the non-GCB subtype.We can predict prog-nosis and choose therapeutic regimen base on the assessment for MYC and BCL2 protein expression. Key words: Lymphoma, large B-cell, diffuse ; Proto-oncogene proteins c-myc ; BCL2 protein

Relation between Caspase recruitment domain-containing membrane-associated guanylate kinase protein 1, clinicopathological features of gastrointestinal lymphoma also and Helicobacter pylori infection

Objective To investigate the relation between the expression of Caspase recruitment domain-containing membrane-associated guanylate kinase protein 1 (CARMA1),clinicopathological features of gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma,diffuse large B cell lymphoma (DLBCL),and Helicobacter pylori (H.pylori) infection.Methods From January 1999 to March 2011,34 patients with DLBCL and 20 patients with MALT lymphoma were selected,and at same period 21 cases with reactive hyperplasia of gastrointestinal lymphoid tissue were enrolled in as control.The expression of CARMA1,Ki-67 and cytotoxin-associated gene A (CagA) at protein level were examined by immunohistochemistry.The relative expression quantity of CARMA1 mRNA was detected by real-time polymerase chain reaction (PCR).The condition of H.pylori infection in 25 gastric lymphoma and 10 controls was detected by methylene boric acid and blue staining or semi-nested PCR.Chi-square test was used for counting data analysis,t test for measurement data.Multivariate COX regression analysis was implemented for survival analysis.Survival curve was drawn by Kaplan-Meier method and analyzed by Log-rank test.Results The relative expression quantity of CARMA1 mRNA of 28 patients with DLBLC (3.073±1.846) was higher than that of 14 patients with MALT lymphoma,and the difference was statistically significant (F 0.975,P＜ 0.05).The positive rate of CARMA1 expression at protein level of gastrointestinal lymphoma group (75.9 ％,41/54) was higher than that of control group (47.6％,10/21),and the difference was statistically significant (x2 =5.568,P＜0.05),and the positive rate of CARMA1 expression of MALT lymphoma group (11/20) was lower than that of DLBCL group (88.2％,30/34),and the difference was statistically significant (x2 =5.900,P＜0.05).Among 42 patients with gastrointestinal lymphoma who received surgery,the relative expression quantity of CARMA1 mRNA in cases with high proliferation (2.885±1.837) was higher than that in cases with low proliferation.The expression of CARMA1 mRNA in the cases at advanced stage of the disease (4.416± 1.010) was higher than that in cases at early stage,and the difference was statistically significant (F=3.317 and 2.972,both P＜0.05).Among 54 patients with gastrointestinal lymphoma,the positive rate of CARMA1 expression at protein level of patients with high proliferation (88.6％,31/35) was higher that that of patients with low proliferation (10/19),and the difference was statistically significant (x22 ＝ 6.847,P＜0.05).There were no significant differences in relative expression quantity of CARMA1 mRNA and the positive rate of CARMA1 expression at protein level between 11 gastric lymphoma patients without H.pylori infection and 14 gastric lymphoma patients with H.pylori infection (both P＞0.05).The positive rate of CARMA1 expression at protein level of CagA positive and CagA negative H.pylori infected gastric lymphoma patients was 11/11 and 2/3.The expression of CARMA1 at protein level was correlated with the prognosis of gastrointestinal lymphoma (RR＝4.160,P＜0.05).In the 29 cases of patients with gastrointestinal MALT lymphoma and 18 cases of patients with DLBCL who were followed up,the survival situation of gastrointestinal lymphoma patients with CARMA1 positive expression rate over 50％ was worse than that of patients with the rate less than 50％,and the difference was statistically significant (x2=5.383 and 4.028,both P＜0.05).Conclusions CARMA1 might be involved in the pathogenesis and progression of MALT and DLBCL; and it might be a related factor of poor prognosis.There was no correlation between the expression of CARMA1 and H.pylori infection in these two lymphomas. Key words: Lymphoma; CARMA1; Helicobacter pylori

Primary cauda equina lymphoma: case report and literature review.

The central nervous system, in particular the spinal cord, is a rare site for primary lymphoma occurrence, with very few published cases. We report an extremely rare primary lymphoma in the cauda equina in a single case with literature review. An immunocompetent 59-year-old male, who complained of progressive low back and bilateral leg pain for 7 months, was studied. Magnetic resonance imaging (MRI) revealed an intradural space-occupying lesion from T12 to S1, poorly demarcated to the normal cauda equina. The intradural lesion showed T1 low intensity, T2 low isointensity, and marked homogeneous enhancement with gadolinium-diethylenetriaminepentaacetic acid on MRI. We performed spinal tap to obtain additional information about the intradural lesion. Large-sized atypical lymphoid cells were found during pathological examination. Fluorodeoxyglucose accumulation was found only in the lumbar area, which corresponded with the MRI findings, and the primary lymphoma site was defined as the cauda equina area. For further detailed pathological diagnosis, we performed surgical biopsy of the cauda equina. Morphological and immunohistochemical assessment made a diagnosis of diffuse large B-cell lymphoma of the cauda equina. The patient received radiotherapy to the lumbosacral area (50 Gy) and methotrexate (MTX) therapy after surgery. The patient was able to walk without help after the therapies. Follow-up MRI performed 1 year after biopsy showed remission of the lesion. MRI and spinal tap were effective tools for the early definitive diagnosis of cauda equina lymphoma. Combined treatment with radiotherapy and MTX should be performed as early as possible.

MicroRNA and diffuse large B-cell lymphoma

MicroRNA (miRNA) is a kind of naturally occurring short non-coding small molecular RNA,which regulates gene expression at the posttranscriptional level through its sequence complementation with target mRNAs.Researches have shown that different malignant tumors,including diffuse large B cell lymphoma,have specific miRNA expression profiles.Therefore,miRNAs expression level of specimens of body fluids and tissues is expected to be the new indicator for assessing diffuse large B cell lymphoma. Key words: MicroRNAs; Lymphoma, large B-cell, diffuse

Predicting Long-Term Survival in Aggressive Non-Hodgkin Lymphoma

During the past decade, we have witnessed a gratifying improvement in overall response and survival in patients with diffuse large B-cell lymphoma

Grey zone lymphoma with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: clinicopathologic characterization of 16 cases showing different patterns

To profile the clinicopathologic features of a series of grey zone lymphoma (GZL) cases with hybrid features of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (CHL), with a purpose to gain an in-depth understanding of the borderline B-cell neoplasm. The clinical, morphologic and immunophenotyical characteristics of 16 cases were retrospectively analyzed. The patients were mostly male adults, with a male to female ratio of 1.7: 1.0 and a mean age of 40.2 years. Eight patients presented with peripheral nodal lesions and five cases with mediastinal involvement. Histologically and immunophenotypically, the 16 cases were classified into three sub-categories. In 4 cases, the morphologic features resembled CHL more closely, but the neoplastic cells showed uniform and intense positive staining of CD20 (pattern 1). Although the initial impression of the other 8 cases was that of DLBCL, the expression levels of CD20 and PAX5 were variable, and CD30 or CD15 was positive (pattern 2). A characteristic feature of pattern 3, observed in the remaining 4 cases, demonstrated a broad spectrum of morphology with hybrid features of both CHL and DLBCL. The neoplastic cells in pattern 3 were positive for CD20, CD30 and CD15. EBV-LMP1 was detected in 6 of the 11 tested cases. Clinically, most patients with GZL seemed insensitive to immuno-chemotherapy of the R-CHOP regimen. The diagnostic criteria for GZL with features intermediate between DLBCL and CHL is proposed by the three histologic patterns commonly seen in these lesions. Cases presented with peripheral lesions might differ from those with mediastinal presentation pathologically. At current time, there is no effective treatment for these borderline B-cell lymphomas and the prognosis is poor.

Hashimoto's thyroiditis with primary thyroid diffuse large B-cell lymphoma: Report of 4 cases and review of literature

原发性甲状腺恶性淋巴瘤在临床上较为少见,约占所有原发甲状腺肿瘤的1％ ～5％、所有淋巴瘤的1％ ～ 2.5％[1-3].其中弥漫性大B细胞淋巴瘤相对多见,但临床表现缺乏特异性,早期易漏诊误诊.近年来,由于诊断水平的不断提高,其报告例数略有上升,在临床上该疾病常合并桥本甲状腺炎,本研究收集了2007年至2011年4例桥本氏甲状腺炎合并弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma)患者,并复习了近15年来相关文献.这4例手术切除的肿瘤标本均经10％的中性福尔马林溶液固定,石蜡包埋,常规制片和HE染色.免疫组化标记采用Elivision plus二步法.所用抗体为CK、CD3、CD10、CD20、CD21、CD79a、Ki67、Kappa、Lambda等,均购自福州迈新生物技术有限公司。

Epstein-Barr Virus-Related Lymphoproliferative Disorder Caused by the Use of Antithymocyte Globulin and Cyclosporine for Aplastic Anemia

A 70-year-old woman with aplastic anemia treated by antithymocyte globulin (ATG), cyclosporine and prednisolone visited our hospital complaining of fever and general fatigue for a week. A chest computed tomography (CT) scan showed consolidation in both lungs, and histological analysis of the lung tissue showed Epstein-Barr virus-positive diffuse large B-cell lymphoma. We diagnosed immunodeficiency-associated lymphoproliferative disorder, and consolidation of the lung was reduced after the cessation of cyclosporine. We should consider the possibility of malignant lymphoma when CT scan showed multiple patchy consolidations with random pattern in both lungs as septic pulmonary emboli in patients with immunosuppressive treatment. J Med Cases. 2014;5(5):279-282 doi: http://dx.doi.org/10.14740/jmc1769w

Plasma DNA methylation of shp1 in patients with diffuse large B cell lymphoma

To explore the methylation status of shp1 gene in plasma DNA from patients with diffuse large B cell lymphoma (DLBCL) and discuss its possible application in molecular diagnosis and targeted therapy of the disease. Methylation-specific polymerase chain reaction (MSP) was used to detect the methylation status of shp1 gene in plasma and peripheral blood leukocytes (PBLs) of 35 DLBCL patients. The formaldehyde-fixed, paraffin-embedded (FFPE) tumor tissue samples were collected from 28 DLBCL patients, 6 patients of benign lymphoid hyperplasia and 13 healthy volunteers were selected as nonmalignant controls from January 2012 to December 2013. Methylation frequencies of shp1 gene in different groups were compared and the associations of shp1 methylation status with clinicopathological characteristics were analyzed. No methylation of shp1 was detected in any of the 19 nonmalignant controls. The methylation rate of shp1 in plasma, PBLs and FFPE tumor tissues from patients with DLBCL was 51.4% (18/35), 28.6% (10/35) and 64.3% (18/28) respectively; there was a high methylation consistency of shp1 between plasma and FFPE tumor tissues (κ = 0.78, P = 0.00).However, methylation consistency was lower between PBLs and FFPE tumor tissues (κ = 0.36, P = 0.01). Methylation of shp1 was frequently detected in plasma and FFPE tumor tissues samples from patients with a high serum level of lactate dehydrogenase (13/16 vs 5/19, 11/12 vs 7/16, P = 0.02, 0.04) .However, no such association was detected in PBLs (P = 0.14). Methylation of shp1 in plasma DNA can represent shp1 methylation status in tumor tissue. And it may serve as a promising biomarker in aiding DLBCL diagnosis and guiding targeted therapy.

EPSTEIN -BARR VIRUS ASSOCIATION WITH MALIGNANT LYMPHOMA SUBGROUPS IN ZARIA, NIGERIA.

Epstein-Barr virus (EBV) is said to infect more than 90% of humans worldwide with latent infection for life. A recognized carcinogen, EBV is linked to malignant lymphoma (ML) subtypes of Burkitt's lymphoma (BL), plasmablastic lymphoma, diffuse large cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL). We report the association of EBV with ML in a segment of our patient population. Paraffin blocks from the archives of ABUTH, Zaria were used to construct tissue microarray sections stained using 30 monoclonal antibodies for common Non-Hodgkin's lymphoma/ Hodgkin's lymphoma antigen and chromogenic in situ hybridization (CISH) for EBV-encoded RNA were done. Fewer associations of ML with EBV were found than reported from elsewhere in Africa.

Efficacy and safety evaluation of gemcitabine combined with oxaliplatin in lymphoma patients after failure of multiple chemotherapy regimens

To evaluate the efficacy and safety of gemcitabine combined with oxaliplatin (GEMOX) in lymphoma patients after failure of multiple chemotherapy regimens. The clinical data of 27 lymphoma patients, who received GEMOX regimen after failure of two or more prior chemotherapy regimens, were retrospectively reviewed. The predictive factors related to the clinical efficacy of GEMOX regimen were explored. The efficacy could be evaluated in 24 patients. Complete response was obtained in 4 patients (16.7%), partial response in 7 patients (29.1%), stable disease in 6 patients (25.0%), and progressive disease in 7 patients (29.1%), with an overall response rate of 45.8%. Among the eleven CR and PR patients, four patients were with diffuse large B cell lymphoma, four patients with Hodgkin's lymphoma, one with peripheral T cell lymphoma, one with mantle cell lymphoma and one with gastric mucosa-associated lymphoid tissue lymphoma. The median PFS time of the whole group was 8 months (95%CI, 1.6-14.4 months). For 11 CR and PR patients who had response to the GEMOX regimen, the median PFS time was 19 months (95%CI, 11.1-26.8 months). Major adverse response was hematologic toxicity. Among them, grade III or IV neutropenia appeared in 16 patients (59.3%), and grade III or IV thrombocytopenia appeared in 11 patients (40.7%). The sensitivity to the last chemotherapy was related to the efficacy of GEMOX regimen. The response rate was 83.3% in patients who had response to the last chemotherapy, and only 31.2% in the patients who failed to the last chemotherapy (P = 0.001). GEMOX regimen can get a better response rate in lymphoma patients after failure of multiple chemotherapy regimens, and with a good tolerance and acceptable safety. Some patients can get long-term survival. Patients sensitive to the last chemotherapy are more likely to benefit from GEMOX regimen.

Primary mediastinal large B-Cell lymphoma diagnosis at core biopsy

Primary mediastinal large B-cell lymphoma (PMBL) represents a distinct entity with unique clinicopathological features and a molecular gene expression signature reminiscent of nodular sclerosis subtype of classical Hodgkin's lymphoma. Recent studies suggest that it has a more favourable outcome than diffuse large B-cell lymphoma. It is a clinically aggressive B-cell lymphoma that arises from thymic medullary B cells and present as a locally invasive anterior mediastinal mass. Due to location of the tumour an excisional biopsy is not usually possible and small biopsies may be non-diagnostic due to inadequate sampling, crush artefacts or fibrosis obscuring the lesion. The tumour site, young age group, female predominance, immunohistochemistry, flow cytometry and gene rearrangement studies may help to establish the diagnosis. This is a case of primary mediastinal B-cell lymphoma (PMBL) diagnosed at core biopsy.

Expression and clinical significance of CD40 in diffuse large B-cell lymphoma

To study the expression of CD40 in diffuse large B-cell lymphoma (DLBCL) and its relationship with various clinical parameters, pathologic findings and prognostic data. The clinical information of 87 patients with DLBCL diagnosed in Jilin Province Cancer Hospital during the period from January, 2008 to october, 2012 was retrospectively reviewed. Immunohistochemical study using SP technique for CD40 was carried out. The correlation between clinicopathologic findings, CD40 expression and survival data was analyzed using statistical software. Cases of CD40-positive DLBCL were characterized by lower age group, early clinical stage, less extranodal involvement, lower IPI index and lower ECOG score. However, there was no significant correlation between gender of patients and site of involvement (P = 0.141 and 0.729). The overall survival of patients with CD40-positive DLBCL was significantly higher than that in patients with CD40-negative DLBCL. One-way analysis of variance showed that the prognosis of DLBCL was closely associated with CD40 expression, age of patients, ECOG score, IPI index, extranodal involvement and LDH level (P < 0.05, respectively). Stratified analysis showed that CD40-positive DLBCL carried a better prognosis, irrespective of other immunophenotyping results. COX model multivariate analysis showed that the expression of CD40 closely correlated with other immunophenotyping results, ECOG score, clinical staging, treatment regimen and prognosis (P < 0.05). The expression of CD40 is a favorable prognostic indicator in patients with DLCBL.

Chemotherapy With Infusion Related HLA-Mismatched Hematopoietic Stem Cells For Hematologic Malignancies: A Novel Therapeutic Strategy

Objective To investigate the therapeutic outcomes of chemotherapy with infusion related HLA-mismatched hematopoietic stem cells for hematologic malignancies. Method Therapy responses and hematopoietic recovery as well as complications of 9 patients were analyzed. Result In the 9 patients aged 29-67 years, four were acute myeloid leukemia, one was acute B lymphocytic leukemia, two were multiple myeloma, one was Hodgkin’s disease, one was diffuse large B cell lymphoma. The average MNC was (3.12±1.29)×108/kg, CD34+ cells was (1.71± 1.00)×106/kg, CD3+ cells was (2.13±0.99)×108/kg. There was complete remission in four patients, partial remission in one, disease progression in four. Following up 2 to 14 months, four patients was in survival. No donor chimerism was detected and no graft-versus-host disease was observed in any patient. Conclusion Chemotherapy with infusion related HLA-mismatched hematopoietic stem cells for hematologic malignancies may provide a promising treatment method as a novel therapeutic strategy. Disclosures: No relevant conflicts of interest to declare.

Stem-Cell Transplant Consolidation for Aggressive Non-Hodgkin Lymphoma

Patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and high-intermediate or high risk International Prognostic Index (IPI) scores have

Follicular Lymphoma Transformation in the Rituximab Era

The development of clinically and histologically transformed lymphoma (TL), usually diffuse large B-cell lymphoma, in patients with a prior diagnosis