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Abstract Background: Diffuse large B-cell lymphoma (DLBCL) makes up from 25% to 40% of all non-Hodgkin lymphomas (NHL) and is the most common histological subtype worldwide. In Ecuador, DLBCL makes up 49% of all NHL cases, but there have been no studies on the immunophenotypic classificationof DLBCL in germinal center (GC) and non-germinal center (NGC)subtypes.This study was conducted to ascertain the immunophenotypic profile of DLBCL in an Ecuadorian hospital. Methods: A total of 38 DLBCL cases from 2006 to 2015 were compiled from the Pathology Service at Metropolitan Hospital (HM) in Quito, Ecuador. Eleven of these cases failed to meet the inclusion criteria; thus, the final sample consisted of 27 cases. Manual tissue microarrays were constructed, and three immunohistochemical markers (CD10, BCL6, and MUM1) were applied according to the Hans algorithm; in addition, the expression of the c-myc protein expression was also investigated. Results: The results showed that 77.8% of cases were of the GC subtype, 11.1% were NGC, and 11.1% were unclassifiable according to the Hans algorithm. Conclusions: The most frequent DLBCL subtype was GC, with 21 cases; and 40.7% of these cases overexpressed c-myc.
Resumen Antecedentes: El linfoma difuso de células grandes B (LDCGB) constituye el 25 al 40% del total de los linfomas no Hodgkin (LNH) y es el subtipo histológico más frecuente en el mundo. En Ecuador el LDCGB corresponde al 49% del total de los casos de LNH, sin embargo no hay estudios de clasificación inmunofenotípica del LDCGB en centro germinal (CG) y no centro germinal (NCG). Este estudio se realizó para conocer el perfil inmunofenotípico del LDCGB en un hospital de Ecuador. Métodos: Se recopiló del Servicio de Patología del Hospital Metropolitano de Quito, Ecuador, un total de 38 casos de LDCGB desde el 2006 al 2015, de los cuales 11 no cumplieron con los criterios de inclusión. La muestra final fue de 27 casos. Se realizaron microarreglos tisulares manuales para la aplicación de tres marcadores de inmunohistoquímica según el algoritmo de Hans (CD10, BCL6 y MUM1) y luego se correlacionó con la sobreexpresión de la proteína c-MYC. Resultados: El 77,8% de casos fue tipo CG, 11,1% fue NCG y 11,1% fueron inclasificables según Hans. Conclusiones: El subtipo de LDCGB más frecuente fue CG con 21 casos y de estos 40,7% sobreexpresaron c-MYC.
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Humans , Lymphoma, B-Cell , Ecuador , Protein C , HospitalsABSTRACT
Objective To investigate the diagnosis and treatment of sequential diffuse large B-cell lymphoma (DLBCL) after peripheral T-cell lymphoma (PTCL).Methods A case with sequential DLBCL after PTCL was reported,and the characteristics and responses of this case were analyzed.The previous literature was reviewed in order to explain the mechanism and prognosis of such type of disease.Results This patient was diagnosed as PTCL not otherwise specified (PTCL-NOS) definitely,but after a period of treatment,DLBCL was developed as a second tumor.The characteristics and onset interval were just similar to those described in the literature,in which the mechanisms were mentioned as common effects of tumor cell,microenviroment and therapies.This patient got effects through the initial treatment,but considering the poor outcome by former researchers,the prognosis needed to be closely followed up.Conclusion Sequential development of EBV-unrelated DLBCL after PTCL-NOS is very rare,and the mechanism,therapy and prognosis need further investigation.
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Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of non-Hodgkin's lymphoma.An uncommon subset with myc and either bcl-2 or bcl-6 rearrangement,also known as ‘double-hit’ lymphomas,is considered very aggressive clinical course and poor prognosis despite high-intensity chemotherapy.Recently,these lymphomas have received increased attention.This review explores the existing literatures for the involved genes with their functions,clinical features,diagnosis and treatment.
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Diffuse large B-cell lymphoma (DLBCL) has a high degree of heterogeneity in clinical manifestations,pathological morphology and genetic features.According to its classification by WHO in 2008 WHO,DLBCL is defined as large B-cell lymphoma with diffuse growth and having nuclei similar with or larger than those of normal macrophages.In recent years,the clinical features,morphology,immunohistochemistry,and even gene expression pattern are integrated for classification of DLBCL.It's a new era to stratify DLBLC by gene expression profile.This article summarized research progress in DLBCL classification based on gene expression profile and immunohistochemistry and its effects on prognosis of DLBCL.
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Objective To analyze the clinical characteristics and prognostic factors in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL),and to improve the diagnosis and treatment of PGI-DLBCL.Methods Retrospective analysis was conducted in 51 cases of PGI-DLBCL between January 2009 and August 2013.The data included clinical manifestations,pathological features,treatment regimens and prognosis.Results 51 patients included 31 males and 20 females,the range of ages was from 16 to 80 years old,median age was 48 years old.The major clinical presentation were abdominal pain,abdominal distension,abdominal mass,nausea and vomiting,abdominal mass.The occurrences in stomach,small intestine,colon,rectum and multiple involvement were 56.86 ％,29.41％,7.84 ％,1.90 ％ and 3.92 ％ respectively.The mass bigger than 10 cm was found in 13 cases (25.49 ％).47.06 ％ (24/51) of the cases belonged to the GCB subtype and 52.94 ％ (27/51) belonged to the non-GCB subtype.There was no significant impact of lymphoma cell origin,disease distribution (stomach or intestinal) and mass on prognosis of lymphoma treatment.The univariate analysis revealed that the patients with Lugano stage Ⅳ,increased level of serum lactate dehydrogenase (LDH),modified-international prognosis index (modified IPI) 3-5 and increased level of CA125 had poor prognosis (all P ＜ 0.05).There was no difference of survival rate between patients treated with rituximab plus chemotherapy and single CHOP like therapy.Surgery plus postoperative chemotherapy significantly improved survival of patients treated with simple chemotherapy (P ＞ 0.05).Conclusion The clinical Lugano stage,IPI score,increased LDH and CA125 are important prognostic factors of PGI-DLBCL.
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Objective To analyze the clinical pathological characteristics and prognosis of elderly patients with EB virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL).Methods 24 elderly patients with EBV + DLBCL were collected to evaluate their clinical pathological characteristics and prognosis by comparison with the EBV-DLBCL,NOS during the same period.Results 24 EBV + DLBCL cases demonstrated two morphologic subtypes:polymorphic and monomorphic.And polymorphic subtype showed geographic necrosis more frequently than that in monomorphic subtype.According to Hans and Choi models,the majority of EBV+ DLBCL of the elderly were classified as non-GCB subtype (91.3 ％ and 100.0 ％,respectively).55.0 ％ cases showed CD30 positive,which was significantly higher than that in EBV-DLBCL group (P ＜ 0.001).Under the treatment of R-CHOP regimen,the overall survival (OS) of the elderly EBV+ DLBCL patients showed no significant difference with the ＞50-year old EBV-DLBCL patients (the median OS were 44.2 months and 29.2 months,P =0.587).Conclusions The elderly EBV + DLBCL patients are normally presented with polymorphic and monomorphic patterns.And geographic necrosis are often seen in polymorphic cases.CD30 expression and non-GCB subtypes are high.With the R-CHOP regimen,the OS of the elderly EBV+ DLBCL patients is similar with that of ＞50-year old EBV-DLBCL patients.
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Objective To investigate the expression level and its significance of KLF13 in patients with diffuse large B-cell lymphoma (DLBCL).Methods Fifty-six DLBCL patients treated with CHOP chemotherapy regimen were followed up in 4-6 years.Tissue samples of the 56 DLBCL patients were collected.Then the expression level of KLF13 in tissue samples was detected by immunohistochemistry,the relationship between the expression level of KLF13 and the survival rate,clinical features of the patients were analyzed,respectively.Western blot was used to detect the expression level of KLF13 in DLBCL cell trains Pfeiffer and LY8.Subsequently,the expression of KLF13 in DLBCL cell strains was blocked by siRNA method.The proliferation rates of DLBCL cell strains were assayed by CCK-8.Results The expression of KLF13 was significantly over-increased in 32 patients with DLBCL (57.1％) and slightly increased in 24 patients with DLBCL (42.9 ％).The 5-year survival rate in the significant overexpression group (46.5 ％) was lower than that of slight overexpression group (75.0 ％) (P =0.01).Multivariate analysis demonstrated that KLF13 expression,serum LDH levels and clinical pathological stage were independent prognostic indicators for patients with DLBCL (all P ＜ 0.05).There was statistically significant association between the expression level of KLF13 and the clinical stage,the diameter of lymphoma,respectively.After the expression of KLF13 in DLBCL cells was blocked,the proliferation rate of cells decreased.Conclusion KLF13 might be regarded as a prognostic factor and used as a treatment target.
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ObjectiveTo investigate the expression of miR-21 in diffuse large B cell lymphoma (DLBCL)and normal lymph tissues and its potential relevance with clinicopathological characteristics.MethodsThe expression levels of miR-21 in 50 primary DLBCL and 12 normal lymph node tissue specimens were examined by TaqMan real-time polymerase chain reaction.The expression of bcl-2 and p53 was detected by immunohistochemistry staining. ResultsThe expression of miR-21 was significantly higher in tumor tissues than that in normal tissues, in GCB subtypes higher than in non-GCB subtypes. And it was negatively correlated with bcl-2(P=0.020),while positively correlated with p53(P=0.022). Up-regulated miR-21 expression was low in three years of survival rate. ConclusionMiR-21 may indicate a more aggressive phenotype and serve as a molecular prognostic marker in DLBCL. High-expression of miR-21 is a key feature that is correlated with cell proliferation in DLBCL.miR-21 may have some guiding significance in prognosis.bcl-2,p53 is possibly one of the targets of miR-21 in DLBCL.
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Objective To investigate peripheral blood T lymphocyte subsets and NK cells changes in the diffuse large B cell lymphoma (DLBCL) patients before and after chemotherapy,and analyse the relationship between the results and treatment.Methods Collect the 47 patients venous blood of the effective treatment DLBCL by pathology.T lymphocyte subsets and NK cells were determined by flow cytometric.Analyse the results statistically significant difference before treatment,the second chemotherapy cycle and the fourth chenmotherapy cycle compared with 50 healthy control persons.Results The levels of CD3+,CD4+,CD4+/CD8+ NK cells in DLBCL patients before chemotherapy [(70.04±8.87)％,(42.79±6.06)％,(1.68±0.59)％,(14.40±6.02)％]were lower than healthy controls [(63.89±6.67)％,(32.72±5.77)％,(0.85±0.25)％,(9.95±5.24)％](P ＜ 0.05),and the level of CD8+ cells is higher than the healthy controls [(27.21 ±6.54)％ vs.(39.92±7.11)％](P ＜ 0.05).The levels of CD3+,CD4+,CD4+/CD8+ cells had significant difference between the second and the fourth chemotherapy cycle in DLBCL patients (P ＜ 0.05).The levels of CD3+,CD4+,CD8+,CD4+/CD8+,NK cells had significant difference between the fourth chemotherapy cycle DLBCL patients and the DLBCL patients before chemotherapy (P ＜ 0.05).Conclusion The DLBCL patients exist immunosuppression before chemotherapy.Peripheral T lymphocyte subsets and NK cells can be used as good reflect of the cellular immune function in DLBCL patients.Clinical parameters can be used for the immune function monitoring and providing guidance for the treatment options.
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ObjectiveTo explore the relationship between the international prognosis indexes(IPT) and the cell-mediated immunity condition in DLBCL patients. Methods52 DLBCL patients were divided into 4 groups and the FCM was used to examine the T lymphocyte subsets,including CD3+、CD4+、CD8+、NK cells.T lymphocyte subsets absolute value and CD4+/CD8+ ratio were examined. Correlation with IPI were compared among groups.ResultsCD3+ cells in high risk group [(1570.9±370.5)/μl]were higher than other IPI groups;CD4+ cells in DLBCL groups were all lower than normal group(751.3±367.4)/μl]; CD8+ cells in high risk group [(1055.9±523.8)/μl] were higher than other groups; CD4+/CD8+ ratio in middle-high risk group and high risk group (1.0±0.2、0.7±1.0)were lower than other IPI groups and normal group;NK cells in middle-high risk group and high risk group were lower than the normal group[(199.5±68.4)/μl、(171.9±126.9)/μl];Age,clinical stage,body state had correlated with the CD3+ 、CD8+ cells and CD4+/CD8+ ratio of the DLBCL patients' peripheralblood T lymphosyte subsets. ConclusionsThe immunity condition in DLBCL patients has correlated with IPI; With increasing IPI value,the immunity depression and disorder become more serious,NK cells function become worse,and the prognosis is bad too.
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ObjectiveTo study the Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL)of the elderly and explore its clinical characteristics. MethodsThe clinical manifestation,laboratory examination and treatment of two cases of EBV positive DLBCL of elderly were lescribed.Results EBV positive DLBCL of elderly onset was often between 70-79 years,usually presented with lymphadenopathy and may be extranodal,may present with massive splenomegaly,secondary immune hemolytic anemia and often had B symptom.Pathologically,this disease was characterized by a proliferation of atypical large B cells with rich reactive cells,especially T cell.ConclusionImmunohistochemically,the tumor cells of EBV positive DLBCL of elderly present with CD20 or CD79a,EBV-encoded small RNA (EBER) positive.This disease has aggressive clinical course,a poor response to standard treatment.Rituximab may be effective in a short periods,but the long effect is limited.Overall survival is short.The cause of death is mainly respiratory failure due to factor infection.
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Objective To explore the prognostic significance of p53 mutation protein in patients with diffuse large B-cell lymphoma for the purpose of individualized therapy. Methods Newly diagnosed 62 cases were randomly chosen from our hospital, p53 mutation protein and CD10, bcl-6, MUM1 were tested by immunohistochemistry. Correlation of p53 mutation protein with patients ' characteristics, genotype and survival were analysed in the study. Results p53 mutation protein was found in 48.4 % (30/62) of patients.Its expression was only related to initial treatment response (x2 =20.365, P =0.040), including complete remission rate of 33.3 % (10/30) in positive group and 59.4 % (19/32) in negative group, and non-germinal center genotype (x2=31.023, P =0.021) with 83.3 % in positive group and 56.2 % in negative group. No other correlation was not verified with clinical features. Multivariate survival analysis showed that p53 mutation protein was an independent predictor for shorter progress-free and overall survival in positive group (x2 =30.784, P =0.005 and x2 =35.276, P =0.006). Conclusion p53 mutation protein should be an independent predictor with poor prognosis and to direct personalized therapy.
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The chemoresistance of diffuse large B-cell lymphoma (DLBCL) is mainly due to drug resistance. Studies have shown that DLBCL resistance is related to the resistance gene and its resistancerelated protein, cytokines, adhesion molecules, which led to drug resistance through signal transduction in the hematopoietic microenvironment.
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Objective To investigate the clinical significance of MTAP, CDKN2A and CDKN2B gene expression in diffuse large B-cell lymphoma (DLBCL). Methods MTAP, CDKN2A and CDKN2B gene expression were assessed by Real-time quantitative PCR in 40 cases of DLBCL and 19 cases of reactive hyperplasia. The clinical and follow-up data were also collected. Results Comparing with reactive hyperplasia, MTAP, CDKN2A and CDKN2B gene expression were decreased in DLBCL group (P = 0.024,0.044 and 0.047, respectively). Low-expression of all the three genes were associated with advanced Ann Arbor stage (P=0.004, 0.001 and 0.027, respectively). No obvious difference were observed according to gender, age, the number of the extra-nodal infiltration, ECOG score, bone marrow involvement and serum LDH level (P ＞0.05). MTAP and CDKN2A gene expression were associated with B symptoms (P =0.003 and 0.028, respectively) and IPI scores (P =0.001 and 0.011, respectively). With regard to survival rates,MTAP, CDKN2A and CDKN2B gene expression were significantly associated with OS (P =0.022, 0.019 and 0.042, respectively). Conclusion MTAP, CDKN2A and CDKN2B gene expression in DLBCL were decreased and related to disease progression and prognosis. They could be considered as biomarkers to evaluate biological behavior and clinical outcome of DLBCL patients.
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Objective To detect the correlation of immunophenotyping of DLBCL with Choi's and Han' s classification to the prognos is. Methods Ninty-nine cases of DLBCL were studied using immunohistochemistry EnVision method for bcl-6, CD10, FOXP1, GCET1, MUM1 in Shanxi cancer hospital. The follow-up was included. All cases they were classified according to Hans' s and Choi' s algorithm. Fluorescence in situ hybridization (FISH) for bcl-6 gene expression (located on chromosome 3q27) was performed on paraffin-embedded tissues of 35 cases. Results In Hans classification, 21 cases were GCB and 78 were nonGCB subtype. In Choi's classification, 23 cases were GCB and 76 cases were nonGCB subtype. According to the both classification, the prognosis in GCB group was much better than that in nonGCB's (P = 0.000). The expression of FOXP1 was inverse proportion to the prognosis (P =0.011), on the contrary GCET1 expression was in proportion to the prognosis (P =0.027). Among all of 35 DLBCL cases, bcl-6 rearrangement was more frequently encountered in the nonGCB type, bcl-6 gene rearrangement was no correlated to bcl-6 protein expression. Conclusion On the basis of classification, GCB group had a better clinical outcome than that of nonGCB group. FOXP1, GCET1, bcl-6 protein expression is associated with different outcome in DLBCL. Both of Choi's and Hans's algorithm play an important role in the immunophenotyping and prognosis.
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Objective To improve the clinical diagnosis and treatment outcome of primary renal lymphoma.Methods The clinical data of one primary renal lymphoma case were reviewed with its clinical manifestation,imaging,pathological study results and treatment outcome in our institute.This was a 61 yrs female patient presented with progressive left flank pain.The abdominal CT scan revealed enlarged left kidney lost ocortico-medullary differentiation and with a lower kidney pole 9.8 cm × 8.9 cm × 8.8 cm hypodensity mass.Results The patient was diagnosed with B-cell non-Hodgkinˊs lymphoma after radical nephrectomy.Extrarenal origin was ruled out by bone marrow biopsy.The pathological results showed that the tumor was limited to the lower kidney pole.Microscopically,there were large sheets of lymphoma cell infiltration in kidney parenchyma.The lymphoma cells were oval or polygonal.The nuclei of the lymphoma cells were anachromasised and irregular in size.The final pathological diagnosis was diffused large B cell lymphoma.The patient was subsequently given six cycles of CHOP (cyclophosphamide,adriamycin,vincristine and prednisone) in conjunction with rituximab.Twenty months post chemotherapy the patient was diseas-free at follow-up.Conclusions Primary renal lymphoma is rare and the mechanism of its development is unclear.Most of the cases reported showed rapid systemic progression and poor prognosis.The clinical manifestation is similar to renal cell carcinoma.Ultrasound and CT have no distinct characteristic.Diagnosis is established on renal biopsy or radical nephrectomy.Effective post-operative treatment is chemotherapy (CHOP) in conjunction with rituximab.
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Diffuse large B-cell lymphoma (DLBCL) represents the most common type of malignant lymphoma. DLBCL is heterogeneous with respect to morphology, immunophenotype, biology, clinical presentation and outcome. Constitutive activity of the NF-κB pathway may contribute to the poor prognosis of patients with activated B cell-like (ABC) subgroup of DLBCL, caspase recruitment domain 11 (CARD11) is the important signal protein in the signaling pathway of NF-κB. Furthermore, various pre-clinical data have proved the importance of CARD11 in DLBCL. This review summarizes the biological characteristics of CARD11, and its relationship with NF-κB signaling transduction pathway and the outcome of DLBCL, so that we can better understanding the pathogenesis and new therapeutic target of DLBCL.
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Objective To investigate the expression and significance of survivin and p63 in diffuse large B-cell lymphoma (DLBCL). Methods Immunohistochemical staining was used to detect the expression of survivin and p63 in the lymphnode tissues from DLBCL patients and lymph node reactive proliferation.Results The positive expression rate of p63 and survivin proteins in DLBCL patients was 63.5 %(33/52) and 76.9 %(40/52), respectively. p63 was not expressed in lymph node reative proliferation. The positive expression rate of survivin in lymph node reactive proliferation was 20.0 %. The expression rates of survivin and p63 between two groups was significant different. The replase rate of groups with positive expression of survivin and p63 were higher than that of the negative groups. The mean survival in groups with positive expression of survivin and p63 were shorter than that of the negative groups. Conclusion Survivin and p63 are useful in therapeutic and prognostic assessment. Patients with poor prognostic can be screened out in the early period of treatment using expression of survivin and p63, which may help to improve the outcome of diffuse large B-cell lymphoma.
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Objective To investigate the correlation between expression levels of serum cytokines IL-2,IL-6, IL-8, IL-10, TNF-α and IFN-γ in patients with diffuse large B-cell lymphoma(DLBCL) and chemotherapy resistance. Methods 30 cases of DLBCL patients with chemotherapy resistant, 30 cases of DLBCL patients with chemotherapy sensitive and 20 cases of healthy individuals as normal control group were enrolled. The levels of serum cytokines IL-2, IL-6, IL-8, IL-10, TNF-α and IFN-γbefore, during and after treatment in both DLBCL groups and normal control group were detected by ELISA assay. Results The expression level of serum IL-6 and IL-10 before treatment in DLBCL patients with chemotherapy resistance was significantly higher than that in DLBCL patients with chemotherapy sensitive and normal control group (P ＜ 0.05), however,that after treatment in DLBCL patients with chemotherapy resistance was significantly lower than that before treatment (P = 0.02, P = 0.015). The level of serum IL-6 and IL-10 in patients with DLBCL recurrence into drug resistance was higher than that during of remission (P = 0.004, P ＜0.001). Before treatment, the expression level of serum IL-6 in patients with Ⅲ-Ⅳ stage in chemotherapy resistant group was significantly higher than that in ones with Ⅰ - Ⅱ stage(P ＜0.05). Levels of IL-2, IL-8, TNF-α and IFN-γin chemotherapy resistant group, chemotherapy sensitive group and the normal control group were no differences (P ＞0.05).Conclusion The expression levels of the serum IL-6 and IL-10 were closely correlated with the chemotherapy efficacy of DLBCL, they may be involved in drug resistance of DLBCL.
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Objective To investigate the expressions and clinicopathological significance of 3q27-3q29-related p63 protein in diffuse large B-cell lymphoma (DLBCL). Methods An immunohistochemical Envision~(TM) method was used to detect the expressions of p53 and 3q27-3q29-related p63 protein in 102 cases of DLBCL and 15 cases of reactive hyperplasia of lymph node (RHL). Results The tumor cell expressions of p53(62 %) and p63(56 %) in DLBCL were significantly higher than that in RHL (0 and 13 % P < 0.05). The expressions of p53 and p63 were significantly different (1) between stage Ⅰ + Ⅱ (the positive rate 48.3 % and 41.4 %, respectively) and stage Ⅲ+Ⅳ(the positive rate 79.5 % and 75 %, respectively; P <0.05), (2) between GCB type (the positive rate 28 % and 28 %, respectively) and non-GCB type(the positive rate 72.7 % and 64.9 %, respectively; P <0.05). The expressions of p53 and p63 had no relationship to gender, age, B symptoms and locations. The expression of p53 was positively correlated with that of p63 in DLBCL (P <0.05, Cp=0.629). p53 and p63 protein expression in negative group the 5-year overall survival rate is higher than that in positive group (38 % and 6 %, 51% and 4 %, respectively), the difference was statistically significant (P <0.05). Conclusion It was likely that p63, as the oncogene, participated in the occurrence and development of DLBCL together with p53. Also, p63 and p53 might play a synergistic role in the occurrence DLBCL. Combined detection of 3q27-3q29-related 1963 protein and p53 protein in DLBCL, might be one of the indicators to the prognosis of DLBCL.