Anthropometric characteristics,physical activity and risk of hematological malignancies: A systematic review and meta-analysis of cohort studies

Overweight/obesity, adult attained height and physical activity are possible risk factors for hematological malignancies. This meta-analysis aims to evaluate the associations between these factors and hematological cancer risk in adults. Eligible cohort studies were sought in PubMed up to May 31, 2016; overall, 44 studies were included in the present analyses. Pooled relative risk estimates were calculated using random-effects models; separate analyses were conducted for non-Hodgkin lymphoma (NHL) and subtypes (diffuse large B-cell lymphoma, DLBCL; follicular cell lymphoma; small lymphocytic lymphoma/chronic lymphocytic leukemia, SLL/CLL), Hodgkin lymphoma (HL), multiple myeloma (MM), leukemia and subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, AML). Obesity was associated with increased risk of NHL, HL, MM, leukemia overall and AML in both sexes, as well as with higher DLBCL risk in women; the dose–response meta-regression analysis confirmed these associations. Less pronounced effects were observed regarding overweight, as it was associated with increased MM risk in both sexes, NHL risk in males, DLBCL and overall leukemia risk in females. Taller men presented with significantly higher risk of NHL and taller women were affected by higher risk of NHL, DLBCL, FL, CLL/SLL, MM, leukemia and AML. On the other hand, physical activity and abdominal fatness were not associated with the risk of hematological malignancies. In conclusion, this meta-analysis highlights the pivotal role of anthropometric measures in shaping the risk of hematological malignancies in adults. Additional, well-designed studies stemming from all the continents are needed for the further substantiation and generalization of the results.     

112例淋巴系统恶性肿瘤骨髓免疫表型分析

背景与目的:淋巴细胞白血病和淋巴瘤骨髓侵犯的诊断以细胞形态学为基础,而免疫分型可通过获得肿瘤细胞分化和发育阶段的信息使淋巴系统恶性肿瘤的诊断更为准确,为临床合理治疗和预后判断提供重要的科学依据.本研究应用多参数流式细胞术(flow cytometry,FCM)探讨淋巴细胞白血病和非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)骨髓侵犯的免疫表型特点.方法:收集112例病理确诊NHL并伴骨髓侵犯和淋巴细胞白血病患者的骨髓标本.应用FCM检测肿瘤细胞的免疫表型.结果:45例前驱B淋巴母细胞白血病/淋巴瘤(precursor B lymphoblastic lymphoma/leukemia,B-ALL/LBL)主要表达CD19、CD10、TdT、CD34、HLA-DR和CD20;32例前驱T淋巴母细胞白血病/淋巴瘤(precursor T lymphoblastic lymphoma/leukemia,T-ALL/LBL)主要表达胞内CD3(cytoplasmic CD3,CyCD3)、CD7、CD5、TdT、膜表面CD3(surface CD3,sCD3)和HLA-DR.77例前驱淋巴细胞肿瘤中,28例(36%)有髓系抗原CD13、CD33的表达;9例(20%)B-ALL/LBL病例有CD20与CD34共同表达,28例(87.5%)T-ALL/LBL病例有CyCD3与TdT共同表达.成熟淋巴细胞肿瘤35例,其中17例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤主要表达CD19、CD20、CD5和HLA-DR,并有CD19与CD5共同表达.4例弥漫大B细胞性淋巴瘤主要表达CD19、CD20、CD10和HLA-DR.3例伯基特淋巴瘤主要表达CD19、CD10、CD20、SIgM.1例套细胞淋巴瘤表达CD5、CD19、CD20、HLA-DR.5例外周T细胞淋巴瘤(PTCL)主要表达sCD3、CD5、CD7、CD4或CD8.1例间变性大细胞淋巴瘤主要表达sCD3、HLA-DR.4例NK/T细胞肿瘤表达CD56、HLA-DR,也表达CD7或CD4或CD8.成熟淋巴细胞肿瘤不表达早期抗原如CD34、TdT.成熟淋巴细胞肿瘤可伴有髓系抗原CD13、CD33的表达.结论:淋巴系统恶性肿瘤侵犯骨髓采用形态学结合FCM免疫学分型可获得T、B细胞来源、肿瘤细胞分化阶段和异常抗原表达等参数,有助于临床诊断和微小残留病灶的检测.     

Role of fluorine-18 fluoro-deoxyglucose positron emission tomography scan in the evaluation and follow-up of patients with low-grade lymphomas

BACKGROUND: Fluorine-18 fluoro-deoxyglucose positron emission tomography (FDG-PET) scanning has excellent sensitivity and specificity for staging non-Hodgkin lymphomas, but to the authors' knowledge few studies to date have evaluated FDG-PET in low-grade lymphomas only. METHODS: A retrospective study was performed on patients with biopsy-proven nontransformed and transformed follicular lymphoma (FL), B-cell small-cell lymphocytic lymphoma (SLL/CLL), or marginal zone lymphoma (MZL) who underwent PET and computed tomography (CT) scans within 3 weeks. Standard uptake values (SUV) of all abnormal foci were measured. RESULTS: In FL, PET demonstrated 94% sensitivity and 100% specificity for staging. PET was more specific than CT for detecting recurrence or assessing therapeutic responses (91% vs. 50%). FDG avidity among patients with WHO Grades 1, 2, and 3 disease was not significantly different (analysis of variance [ANOVA]). For MZL staging, PET had moderate sensitivity (71%) and outperformed CT alone in the depiction of extranodal sites (85% vs. 57% sensitivity). In SLL/CLL, PET sensitivity was 53% and underestimated disease extent in 5 of 19 patients (26%) compared with CT. PET did not affect initial management but confirmed suspected recurrences in 75% of patients. Nontransformed FL had a higher SUV (ANOVA, P < .05) compared with MZL and SLL/CLL. SUV was higher in transformed than in nontransformed tumors (P < .001, Student t test). CONCLUSIONS: PET usefulness in staging low-grade lymphomas varies depending on histology. PET sensitivity is excellent in FL and moderate in MZL. PET is more specific than CT for follow-up in all types. PET has limited usefulness for SLL/CLL staging. However, a suggestive pattern of hazy and mild uptake was often noted in positive scans. In all low-grade lymphomas, the emergence of foci of intense uptake should raise suspicion of conversion to high-grade disease.     

Insights into the multistep transformation process of lymphomas: IgH-associated translocations and tumor suppressor gene mutations in clonally related composite Hodgkin's and non-Hodgkin's lymphomas.

Clonally related composite lymphomas of Hodgkin's lymphoma (HL) and Non-Hodgkin's lymphoma (NHL) represent models to study the multistep transformation process in tumorigenesis and the development of two distinct tumors from a shared precursor. We analyzed six such lymphomas for transforming events. The HLs were combined in two cases with follicular lymphoma (FL), and in one case each with B-cell chronic lymphocytic leukemia, splenic marginal zone lymphoma, mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). In the HL/FL and HL/MCL combinations, BCL2/IGH and CCND1/IGH translocations, respectively, were detected in both the HL and NHL. No mutations were found in the tumor suppressor genes FAS, NFKBIA and ATM. The HL/DLBCL case harbored clonal replacement mutations of the TP53 gene on both alleles exclusively in the DLBCL. In conclusion, we present the first examples of molecularly verified IgH-associated translocations in HL, which also show that BCL2/IGH or CCND1/IGH translocations can represent early steps in the pathogenesis of composite HL/FL or HL/MCL. The restriction of the TP53 mutations to the DLBCL in the HL/DLBCL case exemplifies a late transforming event that presumably happened in the germinal center and affected the fate of a common lymphoma precursor cell towards development of a DLBCL.     

Expression of DNA mismatch repair proteins in transformed non-Hodgkin's lymphoma: relationship to smoking

It has been hypothesized that defects in DNA-mismatch repair are associated with smoking in certain types of transformed non-Hodgkin lymphoma (NHL). We have analyzed biopsy samples from two indolent B-cell lymphomas, follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL), that have transformed to diffuse-large B-cell lymphoma (DLBCL). We correlated the presence or absence of DNA-mismatch repair enzymes by immunostaining as well as the p53 status to smoking history. Of all patients (n = 30), 37% showed negative immunostaining of MLH1, 16% showed negative immunostaining of MSH2 and 63% had p53 mutations and/or protein expression. Eighteen out of 20 transformed follicular lymphomas and seven out of 10 CLL/SLL that have transformed to DLBCL (Richter's syndrome) were informative for smoking histories. We found that the relative risk of negative immunostaining for either MLH1 or MSH2 was 2.2 times higher in smokers than non-smokers (relative risk = 2.2041, 95% confidence interval: 0.89714, 5.41491). No direct correlation was found between smoking and the mutations in the p53 gene. These results suggest that cigarette smoking may play a role in the development of transformed lymphomas through defective mismatch repair.     

Cardiovascular mortality among patients with non‐Hodgkin lymphoma: Differences according to lymphoma subtype

Survival rates of patients with non‐Hodgkin lymphoma (NHL) have improved over the last decade. However, cardiotoxicities remain important adverse consequences of treatment with chemotherapy and radiation, although the burden of cardiovascular mortality (CVM) in such patients remains unknown. We conducted a retrospective cohort study of patients greater than or equal to 20 years of age diagnosed with diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) between 2000 and 2013 using data extracted from the United States Surveillance, Epidemiology, and End Results (SEER) database. Our primary endpoint was CVM. The association between NHL and CVM was evaluated using multivariable Cox regression analysis after adjusting for other patient characteristics. We calculated standardized mortality ratios (SMRs) for CVM, comparing NHL patients with the general population. We identified 153 983 patients who met the inclusion criteria (69 329 with DLBCL, 48 650 with CLL/SLL, and 36 004 with FL). The median follow‐up was 37 months (interquartile range, 10‐78 months); the mean patient age was 66.24 (±14.69) years; 84 924 (55.2%) were men; 134 720 (87.5%) were White, and 131 912 (85.7%) did not receive radiation therapy. Overall, 9017 patients (5.8%) died from cardiovascular disease, and we found that NHL patients had a higher risk of CVM than the general population, after adjusting for age (SMR 15.2, 95% confidence interval: 14.89‐15.52). The rates of CVM were 5.1%, 8%, and 4.4% in patients with DLBCL, CLL/SLL, and FL, respectively. Furthermore, across all NHL subtypes, older age, higher stage at the time of diagnosis (particularly stage 4), male sex, and living in the south were associated with higher risks of CVM. Our data suggest that risk assessment and careful cardiac monitoring are recommended for NHL patients, particularly those with the CLL/SLL subtypes.     

Circulating immune markers and risks of non-Hodgkin lymphoma subtypes: A pooled analysis

Although prediagnostic circulating concentrations of the immune activation markers soluble CD27 (sCD27), sCD30 and chemokine ligand-13 (CXCL13) have been associated with non-Hodgkin lymphoma (NHL) risk, studies have been limited by sample size in associations with NHL subtypes. We pooled data from eight nested case-control studies to investigate subtype-specific relationships for these analytes. Using polytomous regression, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) relating study-specific analyte tertiles to selected subtypes vs controls (n = 3310): chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; n = 623), diffuse large B cell lymphoma (DLBCL; n = 621), follicular lymphoma (FL; n = 398), marginal zone lymphoma (MZL; n = 138), mantle cell lymphoma (MCL; n = 82) and T cell lymphoma (TCL; n = 92). We observed associations with DLBCL for elevated sCD27 [OR for third vs first tertile (OR_T3) = 2.2, 95% CI = 1.6-3.1], sCD30 (OR_T3 = 2.0, 95% CI = 1.6-2.5) and CXCL13 (OR_T3 = 2.3, 95% CI = 1.8-3.0). We also observed associations with sCD27 for CLL/SLL (OR_T3 = 3.3, 95% CI = 2.4-4.6), MZL (OR_T3 = 7.7, 95% CI = 3.0-20.1) and TCL (OR_T3 = 3.4, 95% CI = 1.5-7.7), and between sCD30 and FL (OR_T3 = 2.7, 95% CI = 2.0-3.5). In analyses stratified by time from phlebotomy to case diagnosis, the sCD27-TCL and all three DLBCL associations were equivalent across both follow-up periods (<7.5, ≥7.5 years). For other analyte-subtype comparisons, associations were stronger for the follow-up period closer to phlebotomy, particularly for indolent subtypes. In conclusion, we found robust evidence of an association between these immune markers and DLBCL, consistent with hypotheses that mechanisms related to immune activation are important in its pathogenesis. Our other findings, particularly for the rarer subtypes MZL and TCL, require further investigation.     

不同类型淋巴瘤Survivin的表达及其意义

背景与目的:淋巴瘤的诊断与分型是临床病理诊断的难点。本研究检测抗凋亡基因survivin在不同类型淋巴瘤中的表达,并探讨其对淋巴瘤分型的意义。方法:用免疫组化法检测83例淋巴瘤、5例淋巴结反应性增生石蜡标本中survivin蛋白的表达;同时用RT-PCR检测K562、HL-60、Raji、Jurkat细胞系和以上病例中18例淋巴瘤及2例淋巴结反应性增生新鲜标本中survivinmRNA的表达;对不同类型的淋巴瘤survivin蛋白及mRNA表达进行半定量分析。结果:Survivin蛋白在非霍奇金淋巴瘤(non-Hodgkinslymphoma,NHL)的DLBL(diffuselargeBcelllymphoma)、BL(Burkittlymphoma)、LBL(lymphoblasticlymphoma)中有较高的表达,分别为87.2%(34/39)、100%(2/2)、85.7%(6/7),而在FL(follicularlymphoma)、MALT(extranodalmarginalzoneB-celllymphomaofmucosa-associatedlymphoidtissue)和MZL(marginalzonelymphoma)中表达较低,分别为22.2%、33.3%和40.0%,且多为弱阳性。高表达组(DLBL、BL、LBL)与低表达组(FL、MZL、MALT)之间差异有统计学意义(P<0.01)。并且DLBL中survivin阳性者中位年龄为57岁,明显高于阴性者41岁。霍奇金淋巴瘤(Hodgkinslymphoma,HL)中大部分R-S(Reed-Sternberg)细胞表达survivin蛋白。NHL中survivinmRNA的检测结果与其蛋白水     

A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non‐Hodgkin lymphoma

Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non‐Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre‐diagnosis red blood cell (RBC) specimens in the Nurses’ Health Study (NHS) and Health Professionals Follow‐Up Study (HPFS). RBC membrane fatty acid levels were measured using gas chromatography. Using multivariable logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL and major NHL subtypes including T cell NHL (T‐NHL), B cell NHL (B‐NHL) and three individual B‐NHLs: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma. RBC SFA and MUFA levels were not associated with NHL risk overall. However, RBC very long chain SFA levels (VLCSFA; 20:0, 22:0, 23:0) were inversely associated with B‐NHLs other than CLL/SLL; ORs (95% CIs) per standard deviation (SD) increase in level were 0.81 (0.70, 0.95) for 20:0, 0.82 (0.70, 0.95) for 22:0 and 0.82 (0.70, 0.96) for 23:0 VLCSFA. Also, both VLCSFA and MUFA levels were inversely associated with T‐NHL [ORs (95% CIs) per SD: VLCSFA, 0.63 (0.40, 0.99); MUFA, 0.63 (0.40, 0.99)]. The findings of inverse associations for VLCSFAs with B‐NHLs other than CLL/SLL and for VLCSFA and MUFA with T‐NHL suggest an influence of fatty acid metabolism on lymphomagenesis.     

山东地区520 例淋巴瘤临床病理特点分析

目的:分析山东省地区近3 年淋巴瘤患者的病理类型及临床特点。方法:回顾性分析山东省肿瘤医院及山东省医学科学院附属医院2011年9 月至2014年9 月收治的520 例淋巴瘤患者资料,从性别、发病年龄、病理类型、发病部位等方面进行总结分析。结果:520 例淋巴瘤患者中,男女比例为1. 2 :1,中位年龄51岁,霍奇金淋巴瘤（HL）67例占12.9% ,非霍奇金淋巴（NHL ）453 例占87.1% 。NHL 中75.9% 为B 细胞淋巴瘤,24.1% 为T/NK细胞淋巴瘤。HL以经典型霍奇金淋巴瘤结节硬化型为主,占52.2% ,年龄分布未见双峰性。NHL 最常见类型为弥漫大B 细胞淋巴瘤（DLBCL ）占54.1% ,其构成比高于其他国家和地区（18% ～42.7%）,男女比例为0. 9:1,发病年龄略早（中位年龄54岁）。 HL和NHL 发病部位均以颈部淋巴结多见,且NHL 结外起病多于结内起病。结论:520 例淋巴瘤以DLBCL 最常见,多数亚型以男性发病比例较高,但DLBCL 以女性发病率较高。结外淋巴瘤以鼻腔及胃肠道多见。      

Non-Hodgkin's lymphomas in childhood. A clinicopathologic and epidemiologic study in Finland

All cases diagnosed in Finland as non-Hodgkin's lymphoma (NHL), Hodgkin's disease or histiocytosis X in children younger than 15 years in 1953 to 1973, according to the Finnish Cancer Registry, were reexamined histologically. Only 55% of the cases originally diagnosed as NHL were regarded as such at reexamination. The others were mainly malignant nonlymphatic tumors such as neuroblastoma and different kinds of sarcomas. Seventy-two NHLs were diagnosed in 50 boys and 22 girls. The corrected age-specific incidence rate was 0.32/10(5). The most common histologic types were Burkitt's lymphoma (BL) (30 cases), lymphoblastic lymphoma (LBL) (26), large cell lymphomas (LCL) (six), and non-Burkitt's lymphoma (n-BL) (three). There were marked differences between BL and LBL in the course of the disease: BL was extranodal in 83%, LBL only in 4% (mediastinum was regarded as nodal); BL showed initial abdominal or pelvic involvement in 60% whereas LBL showed none; BL had initial mediastinal involvement in 7%, and LBL had it in 62%; all patients with LBL died whereas 23% of those with BL survived. Other types of NHL resembled BL in their course of disease. Patients with initial tonsillary involvement appeared to have the best prognosis and patients with mediastinal involvement the poorest. The importance of accurate histologic classification is emphasized. It appears to be most important to differentiate LBL from other types of NHL.     

Hodgkin transformation of chronic lymphocytic leukemia: the M. D. Anderson Cancer Center experience

BACKGROUND: Hodgkin transformation is a rare complication of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In this study, the authors assessed the incidence, presenting characteristics, and outcomes of patients with CLL/SLL who developed Hodgkin lymphoma (HL). METHODS: An electronic database search of patients with CLL/SLL who presented at The University of Texas M. D. Anderson Cancer Center Department of Leukemia between 1975 and 2005 was performed. RESULTS: Among 4121 patients with CLL/SLL, 18 patients (0.4%) developed HL. Presenting features included B-symptoms (67%), lymph node enlargement (79%), splenomegaly (43%), hepatomegaly (29%), hypercalcemia (6%), infection (6%), and mental status changes (6%). The median age was 72 years (range, 49-81 years), and there was a male preponderance (78%). The median time from CLL to HL diagnosis was 4.6 years (range, 0-12.9 years). Fourteen patients (78%) had been previously treated for CLL/SLL. Ten patients (56%) had received >1 prior therapy. The median beta2-microglobulin level was 4.5 mg/L, and the median lactate dehydrogenase level was 610 IU/L. Epstein-Barr virus (EBV) was positive by in situ hybridization for EBV-encoded RNA in 3 of 4 tested patients. Fourteen patients (78%) received chemotherapy. The overall response rate was 44% (complete response rate, 19%). The median overall survival duration was 0.8 years (range, 0.03 years-6.7+ years). The median failure-free survival (FFS) duration was 0.4 years. CONCLUSIONS: The rates of response, survival, and FFS in patients with Hodgkin transformation of CLL/SLL were inferior to those reported in patients with de novo HL and were similar to those in patients with Richter syndrome.     

不同类型淋巴瘤Survivin的表达及其意义

目的淋巴瘤的诊断与分型是临床病理诊断的难点。本研究检测抗凋亡基因survivin在不同类型淋巴瘤中的表达,并探讨其对淋巴瘤分型的意义。方法用免疫组化法检测中山大学附属一院及肿瘤医院2001年1月-2003年6月219例淋巴瘤、13例淋巴结反应性增生石蜡标本中survivin基因的表达;同时用RT-PCR检测K562、HL60、Raji、Jurkat细胞系和以上病例中18例淋巴瘤及2例淋巴结反应性增生新鲜标本中survivinmRNA的表达;对不同类型的淋巴瘤survivin蛋白及mRNA表达的结果进行半定量分析。结果Survivin蛋自在非霍奇金淋巴瘤(NHL)的弥漫性大B细胞性淋巴瘤(DLBL)(88.6%,70/79)、伯基特淋巴瘤(BL)(100%,2/2)、淋巴母细胞淋巴瘤(LBL)(92.3%,12/13)中有较高的表达,而在滤泡性淋巴瘤(FL)(18.2%),粘膜相关性结外边缘带B细胞淋巴瘤(MAL-oma)(40.9%)和MZL(marginalzonelymphoma)(33.3%)中表达较低,且多为弱阳性。高表达组(DLBL、BL、LBL)与低表达组(FL、MZL、MALT)之间差异有统计学意义,χ2检验,P<0.01。霍奇金淋巴瘤(HL)中大部分R-S(Reed-Sternberg)细胞表达survivin蛋白。NHL中survivinmRNA的检测结果与其蛋白水平的表达呈正相关(相关系数r=0.6270,P<0.01)。结论survivin蛋白及mRNA表达水平在不同类型淋巴瘤存在着明显的差异,survivin可能作为一个分子标记对淋巴瘤分型具有一定的价值。     

Promoter hypermethylation of multiple genes in gastric lymphoma

Aberrant hypermethylation of CpG islands in the promoter region of tumor suppressor and other important genes in neoplastic cells of lymphoma has been demonstrated to be one of the mechanisms for epigenetic loss of gene function. In this study, we analyzed promoter hypermethylation of the following genes in 49 cases of primary gastric lymphoma (PGL): ATM, p16^INK4a(CDKN2A), hMLH1, MGMT, DAPK, and CDH1(ECAD). The PGL cases studied included 26 (53%) cases of diffuse large B-cell lymphoma (DLBCL), 12 (25%) cases of extranodal marginal zone lymphoma (MZL), 7 (14%) cases of MZL with large cell transformation (MZL/DLBCL), 1 (2%) case of follicular lymphoma (FL), one (2%) case of Burkitt-like lymphoma (BL), one case (2%) of lymphoplasmacytic lymphoma (LPL) and one case (2%) of peripheral T-cell lymphoma. Available pathologic data regarding to extragastric involvement at the time of resection of the PGLs were reviewed and correlated. Promoter hypermethylation was detected in 6 of 49 (12.2%) cases for ATM; 13 of 49 (26.5%) for p16^INK4a, 19 of 49 (38.8%) for hMLH1; 22 of 49 (44.9%) for MGMT; 27 of 49 (55.1%) for DAPK and 16 of 49 (32.7%) for CDH1. A total of 85% of the PGLs had promoter hypermethylation in at least one of these genes. With different histologic subtypes, promoter hypermethylation of DAPK, hMLH1, and CDH1 genes occurred in 70%, 42%, and 42% respectively for DLBCL, which appeared to be higher than combined MZL and MZL/DLBCL subgroup. Approximately 81% PGLs demonstrated H. pylori infection by immunohistochemistry. H. pylori status did not appear to be statistically correlated with promoter hypermethylation of the genes. Of 37 PGL cases, 19 cases had extragastric involvement at the time of resection, indicating relatively higher stage disease. The frequencies of promoter methylation in those cases were 58% for DAPK, 42% for hMLH1, 37% for CDH1, 26% for p16^INK4a and 11% for ATM respectively. The promoter methylation at MGMT gene was significantly higher in the PGLs without extragastric involvement (61%) as compared to those with extragastric involvement (26%).     

CD45 expression in low-grade B-cell non-Hodgkin's lymphomas

CD45 is a glycoprotein expressed in all lymphohemopoietic cells. Its expression increases during B-lymphocyte ontogeny. Few data are available about CD45 expression in the various types of low-grade B-cell non-Hodgkin's lymphomas (NHL). Low levels of CD45 have been reported in pathologic lymphocytes from typical chronic lymphocytic leukemia (CLL) and higher levels of this antigen have been observed in some cases of atypical CLL and in some cases of other types of NHL. One hundred and seven bone marrow samples of NHL with bone marrow infiltration were investigated: 45 typical CLL, 15 atypical CLL, 9 mantle cell lymphomas (MCL), 1 MCL with CD23 expression, 18 marginal zone lymphomas (MZL), 6 lymphoplasmacytic lymphomas (LPL), 6 follicular lymphomas (FL), and 7 hairy cell leukemias (HCL). CD45 expression was evaluated by flow cytometry: pathologic lymphocytes were identified on the basis of specific immunophenotypic profile, CD19/K or CD19/lambda co-expression. Results were expressed as median fluorescence intensity (MFI) along a 1024 linear scale. CD45 expression was measured also on autologous T-lymphocytes and a "CD45 index" was calculated as the ratio MFI of pathologic B-lymphocytes/MFI of T-lymphocytes, to normalize the results obtained. We found four CD45 expression patterns: very low in typical CLL; relatively low in MCL; intermediate intensity in MZL, LPL, and FL; very high expression in HCL. Among the atypical cases, very high CD45 expression was found in one case of CD23-negative CLL, in CD23-positive MCL, and CLL with atypical morphology. The results indicate different levels of maturation in low-grade NHL and may help to characterize such neoplasias.     

Differential diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and other indolent lymphomas,including mantle cell lymphoma

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) accounts for approximately 1% of all lymphomas in our department. In this article, we describe the differential diagnosis of CLL/SLL from other indolent lymphomas, with special reference to follicular lymphoma, marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma, and mantle cell lymphoma, although the latter is considered to be aggressive. CLL/SLL often exhibits proliferation centers, similar to follicular lymphoma. Immunohistological examination can easily distinguish these two lymphomas. The most important characteristic of CLL/SLL is CD5 and CD23 positivity. Mantle cell lymphoma is also CD5-positive and there are some CD23-positive cases. Such cases should be carefully distinguished from CLL/SLL. Some marginal zone lymphomas are also positive for CD5 and such cases are often disseminated. Lymphoplasmacytic lymphoma should also be a differential diagnosis for CLL/SLL. It frequently demonstrates MYD88 L265P, which is a key differential finding. By immunohistological examination, the expression of lymphoid enhancer-binding factor 1 is specific for CLL/SLL and can be a good marker in the differential diagnosis.     

A Collaborative Nationwide Lymphoma Study in Lebanon: Incidence of Various Subtypes and Analysis of Associations with Viruses

Incidence of various Hodgkin (HL) and non-Hodgkin lymphoma (NHL) subtypes and association with viruses in Lebanon are not known. We undertook a nationwide study of 272 patients diagnosed with lymphoma in 2007. HL comprised 32.7 % (n?=?89) of cases while NHL represented 67.3 % (n?=?183). Consistent with the literature, nodular sclerosis was the most predominant HL subtype (n?=?57/89). Among NHL, B-cell NHL represented 88 % (n?=?161/183), T-cell NHL 9 % (n?=?17/183), whereas in 2.7 % it was not classifiable. The B-cell NHL comprised predominantly diffuse large B-cell lymphoma (46 %) and follicular lymphoma (23 %). 81 cases were reviewed by a panel of pathologists with 87.6 % concordance rate. Serology was negative for hepatitis C in 122 tested cases. HIV was positive in 2 cases. Two adult T-cell leukemia/lymphoma were HTLV-I positive. EBV IgG were positive in 88.5 % of cases. 38 EBV seropositive cases [27 NHL (24 B-cell, 3 T-cell) and 11 HL] were studied for EBV genome expression using EBV-encoded RNA (EBER)-in situ hybridization. EBER expression was positive in 8 (21 %) cases (6 HL, 2 T-cell NHL). The distribution of lymphoma subtypes in Lebanon appears similar to that of Western countries. The high rate of EBV positivity in HL and T-cell lymphoma by EBER deserves further investigation.     

CD5+ true SLL/CLL with plasmacytic differentiation and an unusual 1p36 translocation: case report and review of the literature

Lymphoplasmacytic lymphoma (LPL) and small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL)are distinct clinicopathologic entities. Although some cases of SLL/CLL may show plasmacytic differentiation and be associated with monoclonal immunoglobulin in serum, such cases appear to be very rare, and if plasma cell differentiation were marked, differentiation of SLL/CLL from LPL could be difficult. We report a rare case of true CD5-positive small lymphocytic lymphoma/chronic lymphocytic leukemia with unequivocal plasmacytic differentiation. This case also showed an abnormality of chromosome 1p36 not previously described in small lymphocytic lymphoma/chronic lymphocytic leukemia.     

Diabetes,metformin use and risk of non-Hodgkin's lymphoma in postmenopausal women: A prospective cohort analysis in the Women's Health Initiative

Epidemiologic evidence is limited about associations between T2DM, metformin, and the risk of non-Hodgkin's lymphoma (NHL). We aimed to examine associations between T2DM, metformin, and the risk of NHL in the Women's Health Initiative (WHI) Study. Information on T2DM status (diabetes status/types of antidiabetic drug use/diabetes duration) from study enrollment and during follow-up were assessed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate associations of T2DM status with risks of overall NHL and its three major subtypes [diffuse large B-cell lymphoma (DLBCL, n = 476), follicular lymphoma (FL, n = 301) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, n = 136)] based on multivariable-adjusted Cox proportional hazards models. During a median follow-up of 18.86 years (range, 0.01-25.13; SD ± 6.55), a total of 1637 women developed NHL among 147 885 postmenopausal women. Women with T2DM and with self-reported oral medication use had 38% and 55% higher risk of DLBCL, respectively [multivariable-adjusted model HR = 1.38, 95% CI (1.06-1.81) and HR = 1.55, 95% CI (1.16-2.06)] compared to the reference group (nondiabetics/untreated diabetes). Risks of NHL and DLBCL [multivariable-adjusted model: HR = 1.28, 95% CI (1.06-1.54) and HR = 1.56, 95% CI (1.13-2.14), respectively] were significantly higher in associations with relatively short duration (≤7 years) of diabetes, compared to reference group. Additionally, an increased risk of DLBCL [HR = 1.76, 95% CI (1.13-2.75)] was found in metformin users compared to the reference group. Postmenopausal women who had T2DM, who were oral antidiabetic drug users, especially metformin, and who had a shorter diabetes duration may have higher risks of DLBCL. Further well-designed research is needed to confirm our findings.