Clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma

Objective： To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma （DLBCL）. Methods： A retrospective study of 37 patients with primary testicular DLBCL was carried out from November 2003 to May 2012. Their clinical features, survival and prognostic factors were analyzed. Results： During a median follow-up period of 39.8 months （5.4-93.0 months）, the median progression-free survival （PFS） was 26.2 months （95% CI：0-65 months） and the 3-year overall survival （OS） rate was 78.4%. Within the whole cohort, the factors significantly associated with a superior PFS were limited stage （stage Ⅰ/Ⅱ）, lactate dehydrogenase （LDH） ≤245 U/L, international prognostic index （IPI） ≤1, primary tumor diameter 〈7.5 cm, and patients who had complete response （CR） and received doxoruhicin-contained chemotherapy （P〈0.05）. There was a trend toward superior outcome for patients who received combined therapy （surgery/ chemotherapy/radiotherapy） （P=0.055）. Patients who had CR, primary tumor diameter 〈7.5 cm and IPI score ≤1 were significantly associated with longer PFS at multivariate analysis. Conclusions： Primary testicular DLBCL had poorer survival. CR, primary tumor diameter and IPI were independent prognostic factors. The combined therapy of orchectomy, doxorubicin-contained chemotherapy and contralateral testicular radiotherapy （RT） seemed to improve survival.

Dihydroartemisinin enhances cell apoptosis in diffuse large B cell lymphoma by inhibiting the STAT3 activity

Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess the antitumor effect of DHA on diffuse large B cell lymphoma cells and to determine the potential underlying mechanisms of DHA-induced cell apoptosis.Methods:Here,the Cell Counting Kit 8 assay was conducted to study cell proliferation.We performed Annexin V-FITC/propidium iodide staining,real-time polymerase chain reaction,and western blot analysis to analyze cell apoptosis and potential molecular mechanisms.Results:The results showed that DHA substantially suppressed cell proliferation and induced cell apoptosis in vitro in a time-and concentration-dependent fashion.Moreover,STAT3 activity could be inhibited after stimulation with DHA.Conclusion:These results imply that the underlying anti-tumoral effect of DHA may increase apoptosis in diffuse large B cell lymphoma cells via the STAT3 signaling pathway.In addition,DHA might be an effective drug for diffuse large B cell lymphoma therapy.

Clinical features and outcomes of diffuse large B-cell lymphoma based on nodal or extranodal primary sites of origin:Analysis of 1,085 WHO classified cases in a single institution in China

Objective: To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma(DLBCL)patients in China according to the primary site.Methods: A total of 1,085 patients diagnosed with DLBCL in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during a 6-year period were enrolled. Their clinical characteristics and outcomes were analyzed according to the primary site.Results: In the 1,085 patients, 679(62.6%) cases were nodal DLBCL(N-DLBCL) and 406 cases(37.4%) were extranodal DLBCL(EN-DLBCL). The most common sites of N-DLBCL were lymphonodus(64.8%), Waldeyer's ring(19.7%), mediastinum(12.8%) and spleen(2.7%), while in EN-DLBCL, stomach(22.4%), intestine(16.0%),nose and sinuses(8.9%), testis(8.4%), skin(7.9%), thyroid(6.9%), central nervous system(CNS)(6.4%), breast(5.7%), bone(3.4%), and salivary gland(2.7%) were most common. N-DLBCL patients tend to present B symptoms, bulky disease, and elevated LDH more often, while age >60 years, extranodal sites >1, Ann Arbor stage I or II, bone marrow involvement, and Ki-67 index >90% were usually seen in EN-DLBCL. The 5-year overall survival(OS) rate and progression-free survival(PFS) rate for all patients were 62.5% and 54.2%. The 5-year OS rate for patients with N-DLBCL and EN-DLBCL were 65.5% and 56.9%(P=0.008), and the 5-year PFS were57.0% and 49.0%(P=0.020). Waldeyer's ring originated DLBCL possessed the highest 5-year OS rate(83.6%) and PFS rate(76.9%) in N-DLBCL. The top five EN-DLBCL subtypes with favorable prognosis were stomach,breast, nose and sinuses, lung, salivary gland, with 5-year OS rate: 70.3%, 69.6%, 69.4%, 66.7% and 63.6%,respectively. While CNS, testis, oral cavity and kidney originated EN-DLBCL faced miserable prognosis, with 5-year OS rate of 26.9%, 38.2%, and 42.9%.Conclusions: In our study, primary sites were associated with clinical characteristics and outcomes. Compared with EN-DLBCL, N-DLBCL had better prognosis.

Diagnosis and therapy of primary lung diffuse large B cell lymphoma： a case report

我们学习了的目的主要的肺的诊断和治疗传播大 B 房间淋巴瘤(DLBCL ) 。方法分析临床的表明，病理学的特性和免疫一个肺的组织化学的特性弥漫的 B 房间淋巴瘤专利。在视觉观察的结果，它是一个灰色的不规则的 lobulated 团，节是灰色的，似鱼，并且坏死的 foci 的数字。在显微镜下面观察了，代替像卵母细胞的房间传播的上皮的呼吸中心 proliferative，在肺织物的渗入。Immunohistochemistry：CD20 (+) ， CD79α(+) ， CD3 (− ) ， CD45RO (− ) ， PCK (− ) 。结论弥漫的大 B 房间淋巴瘤是在 non-Hodgkin 淋巴瘤，而是主要的肺的最普通的子类型弥漫的大 B 房间淋巴瘤稀罕。这疾病是典型临床的表明的缺乏，因此容易误诊。弥漫的大 B 房间淋巴瘤的诊断应该基于病理和免疫组织化学。

Efficacy of rituximab in gastric diffuse large B cell lymphoma patients

AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[scheduled as cyclophosphamide,doxorubicin,vincristine and prednisone (CHOP)and CHOP-like],and chemotherapy combined with rituximab(group B,n=30).The primary end point of the study was complete response(CR)rate;the secondary end points were disease-free survival (DFS)at 5 years and overall survival(OS).RESULTS:Median follow-up was 62 mo(range:31102 mo).We observed a significant difference between the two groups(A vs B)in terms of CR[76.6%(23/30) vs 100%,P=0.04)and DFS at 5 years[73.3%(22/30) vs 100%,P=0.03).To date,19 group A(63.3%) patients are alive and 11 have died,while all group B patients are alive.No significant differences in toxicity were observed between the two groups.CONCLUSION:Rituximab in combination with chemotherapy improves CR rate,DFS and OS.Further prospective trials are needed to confirm our results.

New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma:a retrospective study

Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P < 0.05 was considered signiicant.Results: At a median follow?up of 46 months, 25(4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group(P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence interval(CI) 1.38–12.77], renal involvement(HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase(ALP) >110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement(HR = 4.44, 95% CI 1.08–18.35), bone marrow involvement(HR = 11.70, 95% CI 2.24–60.99), and renal involvement(HR = 10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R?CHOP set.Conclusions: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suicient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R?CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.

Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy:risk factors and survival

Introduction:Hepatitis B virus(HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B(hepatitis B surface antigen[HBsAg]-negative and hepatitis B core antibody[HBcAb]-positive).This study aimed to assess HBV reaaivation and hepatitis occurrence in diffuse large B-cell lymphoma(DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reaaivation and hepatitis occurrence and to analyze whether HBV reaaivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.Methods:We reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center,China.Prediaive faaors for HBV reaaivation,hepatitis development,and survival were examined by univariate analysis using the chi-square or Fisher's exact test and by multivariate analysis using the Cox regression model.Results:Among the 278 patients,165 were HBsAg-negative.Among these 165 patients,6(10.9%) of 55 HBcAb-positive(resolved HBV infeaion) patients experienced HBV reactivation compared with none(0%) of 110 HBcAb-negative patients(P=0.001).Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients(21.8%vs.8.2%,P = 0.013).HBcAb positivity and elevated baseline alanine aminotransferase(ALT) levels were independent risk factors for hepatitis.Among the 55 patients with resolved hepatitis B,patients with elevated baseline serum ALT or aspartate aminotransferase(AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels(P = 0.037,P = 0.005,respeaively).An elevated baseline AST level was an independent risk factor for hepatitis in these patients.Six patients with HBV reactivation recovered after immediate antiviral therapy,and chemotherapy was continued.HBcAb positivity,HBV reactivation,or hepatitis did not negatively affect the survival of DLBCL patients.Conclusions:DLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reaaivation and hepatitis than HBsAg-negative/HBcAb-negative patients.Close monitoring and prompt antiviral therapy are required in these patients.

Expression and clinical value of programmed cell death-ligand 1(PD-L1)in diffuse large B cell lymphoma:a retrospective study

Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses.Diffuse large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.Results: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS(P < 0.01).Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.

R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal centerB-cell subtype diffuse large B-cell lymphoma

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-celllymphoma (DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen (R-CHOP regimen)significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001),Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and-negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.

Prognostic value of ^(18)F-fluorodeoxyglucose positron emission tomography using Deauville criteria in diffuse large B cell lymphoma treated with autologous hematopoietic stem cell transplantation

Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluorodeoxyglucose(18 F-FDG) positron emission tomography(PET)/computed tomography(CT) has been widely accepted in response assessment and prediction of prognosis in DLBCL. Here, we report the value of 18 FFDG PET/CT pre-and post-HSCT in predicting outcomes of patients with DLBCL.Methods: DLBCL patients who had PET/CT scan before and after HSCT were included. PET results were interpreted based upon Deauville criteria. The prognostic value of 18 F-FDG PET/CT in auto-HSCT was evaluated.Results: Eighty-four patients were enrolled. In univariate analysis, pre-and post-HSCT PET findings were correlated with 3-year progression-free survival(PFS) [hazard ratio(HR)=4.391, P=0.001; HR=7.607, P<0.001] and overall survival(OS)(HR=4.792, P=0.008; HR=26.138, P<0.001). Patients receiving upfront auto-HSCT after firstline treatment had better outcomes than relapsed/refractory DLBCL patients(3-year PFS, P<0.001; 3-year OS,P<0.001). In the relapsed/refractory patients, pre-and post-HSCT PET findings were also associated with 3-year PFS(P=0.003 vs. P<0.001) and OS(P=0.027 vs. P<0.001). A significant correlation was observed between clinical response to chemotherapy before auto-HSCT and outcomes of patients in the entire cohort(3-year PFS, P<0.001;3-year OS, P<0.001) and in the subgroup of 21 patients with positive pre-HSCT PET(3-year PFS, P=0.084; 3-year OS, P=0.240). A significant association between survival and post-HSCT PET findings was observed in multivariate analysis(HR=5.168, P<0.001).Conclusions: PET results before and after HSCT are useful prognostic factors for DLBCL patients receiving HSCT. Patients who responded to chemotherapy, even those with positive pre-HSCT PET, are appropriate candidates for auto-HSCT.

Composite diffuse large B-cell lymphoma and classical Hodgkin's lymphoma of the stomach:Case report and literature review

The combination of classical Hodgkin’s lymphoma(cHL)and non-Hodgkin lymphoma coexisting in the same patient is not common,especially in one extranodal location.Here we present a rare case of composite diffuse large B-cell lymphoma(DLBCL)and cHL occurring simultaneously in the stomach of a 53-year-old female who presented with upper abdominal discomfort and gas pain.Surgery was performed and the disease was diagnosed pathologically as composite lymphoma of DLBCL and cHL using hematoxylin-eosin and immunohistochemical staining.Epstein-Barr virus(EBV)infection was not detected by in situ hybridization for EBV-encoded RNA or immunohistochemistry for EBV latent membrane protein-1.Polymerase chain reaction analysis from the two distinct components of the tumor demonstrated clonal immunoglobulinκlight chain gene rearrangements.The patient died approximately 11 mo after diagnosis in spite of receiving eight courses of the CHOP and two courses of the rituximab-CHOP(RCHOP) chemotherapy regimen.This case report showed that the two distinct components,DLBCL and cHL,appeared to originate from the same clonal progenitor cell,and that EBV infection was not essential for transformation during the course of tumorigenesis.

Diffuse large B-cell lymphoma arising from follicular lymphoma with warthin’s tumor of the parotid gland-immunophenotypic and genetic features: A case report

BACKGROUND Warthin’s tumor(WT)is composed of several cysts that are lined with tall,bilayered oncocytic columnar cells and lymphoid stroma.Within WT,the two components rarely transform into carcinoma or lymphoma,and when it does,carcinoma is the most common type.Approximately 28 cases of lymphoma with WT have been reported,most of which were non-Hodgkin lymphomas,and only a few cases were Hodgkin lymphomas.In the present report,we studied a case of diffuse large B cell lymphoma(DLBCL)arising from follicular lymphoma(FL)with WT in the parotid gland and its immunophenotypic and genetic features.CASE SUMMARY A 67-year-old man presented with a slowly enlarging right cheek mass for 12 years,and the mass began to change in size over a 2-mo time period.Over time,the patient felt mild local pain and right cheek discomfort.His medical history included a hepatitis B virus infection for 20 years and 30 years of smoking.Gross examination of the excised specimen showed a gray-red and gray-white appearance and a soft texture lobulated external surface neoplasm that measured 9 cm×8 cm×7 cm and was well circumscribed by relative normal parotid gland tissue.In cross section,the cut surfaces of the neoplasm were multicystic and had a homogeneous scaly appearance.A small fluid was discovered in the cyst.Bilateral oxyphilic,cuboidal or polygonal epithelium cells and lymphoid intraparenchymal components were observed.Many medium-to large-sized lymphoid cells were observed diffusely in part of the neoplasm,and a few secondary lymphoid follicles were observed at the center or edge of the neoplasm.Immunohistochemical staining showed that the columnar oncocytic cells were positive for AE1/AE3;neoplastic cells located in coarctate follicular were positive for CD20,Pax-5,bcl-2 and bcl-6;and the adjacent diffusely medium-to large-sized lymphoid cells were positive for Pax-5,bcl-6,CD20,MUM-1,bcl-2 and CD79a.The bcl-6(3q27)break-apart rearrangement was observed,and an Epstein Barr virus test was negative in the tumor cells.The patient survived 6 months after being diagnosed without any treatment.CONCLUSION WT-associated lymphoma is a very rare neoplasm in the parotid gland.Most cases are B cell non-Hodgkin lymphomas and involve middle-age and older males.This case highlights the extremely rare association of DLBCL arising from FL with WT and the importance of deliberate evaluation of the WT intraparenchymal stroma.Molecular detection techniques have potential advantages in the diagnosis of lymphoma with WT.

Hepatitis C virus and diffuse large B-cell lymphoma: Pathogenesis, behavior and treatment

A significant association between hepatitis C virus(HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma(DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCVnegative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy(R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate.Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions(i.e., hepatitis B virus or immune immunodeficiency virus coinfected patients, presence of grade > 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.

Extranodal involvement in young patients with diffuse large B-cell lymphoma： distribution, prognostic value and treatment options

Objective： Extranodal involvement represents a peculiar presentation of diffuse large B-cell lymphoma（DLBCL）. Previous studies have suggested that older patients are more prone to extranodal involvement. This study retrospectively addressed the distribution, prognostic value and treatment options of extranodal involvement in young patients with DLBCL.Methods： A total of 329 patients were enrolled according to the inclusion requirements. The effects of gender,extranodal involvement, age-adjusted international prognostic index（aa IPI）, rituximab infusion and radiotherapy on patient outcomes were evaluated.Results： Among these patients, 59% presented extranodal involvement in 16 anatomic sites. More than one instance was linked to many poorer clinical characteristics and poorer survival compared with either nodal disease or one instance. In patients with one extranodal lesion, multivariate analysis revealed that the site of extranodal involvement, but not the aa IPI or rituximab infusion, was independently related to the outcome, and radiotherapy had a negative influence on survival.Conclusions： Extranodal involvement is common in younger patients and exhibits a ubiquitous distribution.The site of extranodal involvement is of strong prognostic significance. Radiotherapy for extranodal lesions does not improve patient outcomes.

Germinal-center type B-cell classification and clinical characteristics of Chinese pediatric diffuse large B-cell lymphoma:a report of 76 cases

Pediatric diffuse large B-cell lymphoma(DLBCL)is a highly aggressive disease with unique clinical characteristics.This study analyzed the germinal-center type B-cell(GCB)classification and clinical characteristics of Chinese pediatric DLBCL.A total of 76 patients with DLBCL newly diagnosed in Sun Yatsen University Cancer Center between February 2000 and May 2011,with an age younger than 18 years,were included in the analysis.The male/female ratio was 3.47:1.The median age was 12 years(range,2 to 18 years),and 47(61.8%)patients were at least 10 years old.Of the 76 patients,48(63.2%)had stage III/IV disease,9(11.8%)had bone marrow involvement,1(1.3%)had central nervous system(CNS)involvement,and 5(6.6%)had bone involvement.The GCB classification was assessed in 45 patients:26(57.8%)were classified as GCB subtype,and 19(42.2%)were classified as non-GCB subtype.The modified B-NHL-BFM-90/95 regimen was administered to 50 patients,and the 4-year event-free survival(EFS)rate was 85.8%.Among these 50 patients,31 were assessed for the GCB classification:17(54.8%)were classified as GCB subtype,with a 4-year EFS rate of 88.2%;14(45.2%)were classified as non-GCB subtype,with a 4-year EFS rate of 92.9%.Our data indicate that bone marrow involvement and stage III/IV disease are common in Chinese pediatric DLBCL patients,whereas the percentage of patients with the GCB subtype is similar to that of patients with the non-GCB subtype.The modified B-NHL-BFM-90/95protocol is an active and effective treatment protocol for Chinese pediatric patients with DLBCL.

Clinical Impact of t(14;18) in Diffuse Large B-cell Lymphoma

Objective： Recent studies have suggested that t（14;18） is present in a significant proportion of diffuse large B-cell lymphomas （DLBCLs）. However, the prognostic significance of this translocation and its relationship with BCL-2 protein expression remains controversial. Our study aimed to investigate the predictive power of t（14;18） and BCL-2 protein expression in the prognosis of DLBCLs. Methods： Biopsy specimens from 106 DLBCLs were analyzed using interphase fluorescence in situ hybridization （FISH）. Immunophenotypic analysis of CD20, CD3, CD10, BCL-6, MUM1 and BCL-2 was performed by immunohistochemistry. SPSS 13.0 software was used for statistical analysis. Results： The t（14;18） was identified in 27 of 106 cases （25.5%）. The percentages of tumor cells expressing CD10, BCL-6, MUM1 and BCL-2 were 21.7%, 26.4%, 56.6% and 73.6%, respectively. The presence of this translocation was significantly correlated with the expression of CD10 and immunophenotypic subtype （p0.001）. No association was observed between BCL-2 protein expression and the presence of t（14;18）. Multivariate analysis confirmed that both t（14;18） and BCL-2 expression were significantly associated with survival. Moreover, patients with t（14;18） had worse prognosis, compared with those with BCL-2 expression （for overall survival： hazard ratio, 4.235; 95%CI, 2.153-8.329, p0.001 vs. hazard ration, 2.743; 95%CI, 1.262-5.962, p=0.011）. Conclusions： The t（14;18） is a useful prognostic tool for the evaluation of DLBCL immunophenotype and prognosis. The prognosis of GCB （germinal centre-like B cell） DLBCL patients should be made with the consideration of the presence of this translocation, and the detection of t（14;18） should be included as a routine diagnostic test in these cases.

Addition of rituximab is not associated with survival benefit compared with CHOP alone for patients with stage I diffuse large B-cell lymphoma

Background： The role of rituximab in combination with CHOP regimen in patients with stage I diffuse large B-cell lymphoma （DLBCL） remains to be defined. We aimed to compare CHOP plus rituximab （R-CHOP） with CHOP alone and determine the value of radiotherapy in these patients. Methods： Between 2003 and 2009, 140 untreated patients with stage I DLBCL were retrospectively analyzed in this study. Results： Seventy-eight patients were treated in R-CHOP group and 62 in CHOP group. Ninety-one patients received additional radiotherapy at the end of chemotherapy. The different treatment groups were well-balanced with respect to baseline characteristics. Complete response （CR） rate was 77% both in R-CHOP and CHOP groups （P=0.945）. After a median follow-up period of 56 months, patients received R-CHOP regimen had similar 5-year progression-free survival （PFS） （76% vs. 85%; log-rank P=0.215） and 5-year overall survival （OS） （90% vs. 96%; log-rank P=0.175） compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone （86% vs. 71%; log-rank P=0.005）. At multivariate analysis, patients who had CR （P=0.008） and received radiotherapy （P=0.003） were significantly associated with superior PFS. Conclusions： CHOP alone could be as effective as R-CHOP regimen and additional radiotherapy would be necessary for stage I or stage I non-bulky DLBCL patients.

Case report of acute-on-chronic liver failure secondary to diffuse large B-cell lymphoma

Acute liver failure is a rare presentation of hematologic malignancy. Acute on chronic liver failure(ACLF) is a newly recognized clinical entity that describes acute hepatic decompensation in persons with preexisting liver disease. Diffuse large B-cell lymphoma(DLBCL) is an aggressive non-Hodgkin's lymphoma(NHL) with increasing incidence in older males, females and blacks. However, it has not yet been reported, to present with acute liver failure in patients with preexisting chronic liver disease due to human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infection. We describe a case of ACLF as the presenting manifestation of DLBCL in an elderly black man with HIV/HCV coinfection and prior Hodgkin's disease in remission for three years. The rapidly fatal outcome of this disease is highlighted as is the distinction of ACLF from decompensated cirrhosis. Due to the increased prevalence of HIV/HCV co-infection in the African American 1945 to 1965 birth cohort and the fact that both are risk factors for chronic liver disease and NHL we postulate that the incidence of NHL presenting as ACLF may increase.

Gastric infiltration of diffuse large B-cell lymphoma: Endoscopic diagnosis and improvement of lesions after chemotherapy

Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of the non-Hodgkin’s lymphoma (NHL) accounting for about 40% of all NHLs. This is a case report about the endoscopic appearance of a DLBCL with infiltration to the stomach in a 39-year-old female. She had a 6-mo history of lumbar and left upper quadrant pain with intermittent episodes of melena. A computer tomograghy (CT) scan showed mural thickening of the gastric antrum. Endoscopic examination revealed multiple gastric ulcers. Definite diagnosis could be made by endoscopic biopsies and the patient had a good response to chemotherapy. This response correlated well with a further endoscopic follow-up. A follow-up endoscopic examination could be considered to evaluate a good response to chemotherapy in DLBCL patients with secondary gastric dissemination.

Blimp-1 protein and Hans classification on prognosis of diffuse large B-cell lymphoma and their interrelation

Background and Objective:Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma (NHL), is heterogeneous on molecular and clinical levels, therefore, its prognosis is difficult to predict.This study aimed to evaluate the value of Blimp-1 protein and Hans classification in predicting the prognosis of DLBCL and their interrelation.Methods:The clinical records of 136 patients with DLBCL were reviewed.The patients were followed up for 5-80 months (median, 39 months).Immunohistochemical staining for CD10, MUM1, Bcl-6, and Blimp-1 were performed on paraffin-embedded tumor tissues from the 136 patients.The correlations of Blimp-1 protein and Hans classification in prognosis of DLBCL and their interrelation were analyzed.Results:Blimp-1 was detected in 38 (30.0%) patients, and was associated with a significantly shorter overall survival (OS) (P=0.030).Using the Hans classification based upon the expression of CD10, Bcl-6, and MUM1, 54 patients had germinal center B-cell (GCB) phenotype and 82 had non-GCB phenotype.The 5-year OS rate was 75% in the GCB group and 52% in the non-GCB group (P=0.020).The positive rate of Blimp-1 was 22.2% in the GCB group and 31.7% in the non-GCB group (P=0.329).The Cox regression multivariate analysis showed that international prognosis index (IPI) and Hans classification had independent prognostic significance, whereas Blimp-1 was not an independent prognostic factor.Conclusions:The patients with GCB subtype of DLBCL had better prognosis than the non-GCB subtype.High level of Blimp-1 expression in the patients with DLBCL implies a shorter survival, but it is not associated with Hans classification.