边缘区淋巴瘤的研究进展

最新的世界卫生组织 (WHO)关于淋巴造血组织肿瘤分类中 ,把边缘区淋巴瘤分为三个不同的亚型 :结外黏膜相关组织的边缘区 B细胞淋巴瘤 (ex-tranodal marginal zone B- cell lymphoma of mu-cosa- associated lymphoid tissue)或 MALT型淋巴瘤、结内边缘区 B细胞淋巴瘤 (nodal marginal zoneB- cell lymphoma,NMZL)伴有或不伴有单核样 B细胞和脾脏的边缘区 B细胞淋巴瘤 (splenicmarginal zone lymphoma,SMZL)伴有或不伴有绒毛样的小淋巴细胞。并认为它们的瘤细胞都来自于淋巴结生发中心边缘区的记忆性 B细胞 ,在形态学、免疫表型及分…     

伴MYD88 L265P突变的脾边缘区淋巴瘤临床特征分析

目的 分析伴MYD88 L265P突变的脾边缘区淋巴瘤(splenic marginal zone lymphoma,SMZL)患者的临床特征.方法 回顾性分析本中心SMZL患者队列,将MYD88 L265P突变型患者的临床特征与野生型以及华氏巨球蛋白血症(Waldenstr?m macroglobulinemia,W...     

COX-2和P-gp在B细胞非霍奇金淋巴瘤组织中表达的相关性研究

背景与目的:P糖蛋白(P-glycoprotein,P-gp)高表达是复发淋巴瘤患者化疗失败的主要原因之一,有研究表明,P-gp呈环氧合酶-2(cyclooxygenase-2,COX-2)依赖性表达上调.本研究旨在通过检测COX-2与P-gp在B细胞非霍奇金淋巴瘤(B-cell non-Hodgkin's lymphoma,B-NHL)中的表达及其相关性,并初步观察两者表达与淋巴瘤临床特征之间的关系.方法:采用逆转录-聚合酶链反应及免疫组化SP法检测COX-2及P-gp在43例初治B-NHL、27例复发B-NHL中的表达.结果:COX-2和P-gp在初治B-NHL中的阳性率分别为23.3%(10/43)和11.6%(5/43),而在复发B-NHL中的阳性率分别为74.1%(20/27)和70.4%(19/27),差异有统计学意义(P＜0.01),且两者表达在复发B-NHL中呈显著正相关(r=0.998,P＜0.01).侵袭性B-NHL中的COX-2和P-gp表达均高于惰性B-NHL(P＜0.05).结论:COX-2和P-gp在复发B-NHL中高表达,可能与肿瘤转移有关.     

乙型肝炎病毒感染和弥漫大B细胞淋巴瘤相关性研究进展

弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）是临床上较常见的恶性肿瘤,近年来其发病率有明显上升的趋势。乙型肝炎病毒（hepatitis B virus,HBV）感染在世界范围内普遍存在。有研究发现 DLBCL 患者 HBV 感染率较一般人群高,二者存在一定的相关性。     

脾小B细胞淋巴瘤的临床病理特征、细胞遗传学和分子研究进展

脾边缘带淋巴瘤（splenic marginal zone lymphoma,SMZL）是由小淋巴细胞组成的脾B细胞新生物,小淋巴细胞环绕和取代脾白髓生发中心,正常的滤泡套区消失,并与包含分散的、转化原始细胞的周围（边缘）带融合。小和较大的细胞两者总是浸润红髓。脾门淋巴结和骨髓（BM）常受累。淋巴瘤细胞即绒毛状淋巴细胞可出现在外周血（PB）中。     

惰性淋巴瘤非化疗药物的治疗现状及进展

惰性B 细胞淋巴瘤是一类生长缓慢的淋巴系统肿瘤,主要包括滤泡性淋巴瘤（follicular lymphoma ,FL）、慢性淋巴细胞白血病（chronic lymphocytic leukemia ,CLL）/ 小淋巴细胞淋巴瘤（small lymphocytic lymphoma ,SLL）、华氏巨球蛋白血症（waldenstom macroglobulinemia ,WM）、边缘区淋巴瘤（marginal zone lymphoma ,MZL）以及低度恶性的套细胞淋巴瘤（low malignant mantle cell lym phoma ,MCL ）等,对化疗及免疫治疗敏感,但无法治愈。患者发病年龄、首次发病及再次复发时间、并发症等均可影响化疗疗效。当前,在惰性淋巴瘤信号转导通路及抗肿瘤免疫反应等方面,尤其是非细胞毒药物研究的突破,支持了“非化疗”理念的发展。本文将介绍抗CD20抗体与免疫调节剂、其他表面抗原单抗、PD- 1 受体抑制剂或B 细胞受体信号通路抑制剂等药物的应用。后继的Ⅲ期临床研究将进一步评估这些药物在无化疗背景下的疗效,明确其治疗价值。      

脾边缘区淋巴瘤伴自身免疫性溶血性贫血1例并文献复习

目的：提高对脾边缘区淋巴瘤(splenic marginal zone lymphoma,SMZL)的认识。方法：详细报告1例典型患者临床及实验室特征,并复习相关文献。结果：SMZL是一少见的原发于脾脏的低度恶性B细胞淋巴瘤。临床以脾脏明显肿大、淋巴细胞增多为特征,易浸润骨髓,可合并自身免疫疾患。肿瘤细胞表达成熟B细胞免疫表型,CD5^-、CD10^-、CD23^-、CD103^-,不表达T细胞相关分化抗原。结论：SMZL起病潜隐,进展缓慢,生存期长,容易漏诊。糖皮质激素和环孢菌素A治疗SMZL合并自身免疫性溶血性贫血(AIHA)近期疗效好,对SMZL本身也有一定治疗作用。     

非霍奇金淋巴瘤患者乙型肝炎病毒感染情况分析

目的 分析非霍奇金淋巴瘤(NHL)患者乙型肝炎病毒(HBV)感染发生情况.方法 采用全自动微粒子化学发光免疫分析法检测2014年1月至2016年12月西南医科大学附属医院确诊的305例NHL患者血清中HBV标志物,并与同期住院的312例大肠癌患者及81775名全国普通人群HBV检出率进行比较.结果 305例NHL患者的乙型肝炎病毒表面抗原(HBsAg)阳性率、乙型肝炎病毒表面抗体(HBsAb)阳性率、乙型肝炎病毒核心抗体(HBcAb)阳性率与全国普通人群比较,差异均有统计学意义[19.0％(58/305)比7.2％(5888/81775),44.3％(135/305)比50.1％(40969/81775),45.9％(140/305)比34.1％(27885/81775),χ2值分别为63.1、4.1、18.8,均P<0.05],且NHL患者的HBsAg阳性率与大肠癌患者及全国普通人群比较,差异有统计学意义(χ2=65.7,P<0.01).B细胞NHL(B-NHL)和T细胞NHL(T-NHL)患者的HBsAg阳性率比较,差异有统计学意义[21.3％(51/239)比10.6％(7/66),χ2=3.869,P<0.05],而两组患者的HBsAb、HBcAb阳性率比较,差异无统计学意义(均P>0.05).133例NHL患者进行HBV DNA检测,其中44例(33.1％)阳性,58例HBsAg阳性患者中43例(74.1％)HBV DNA阳性,HBsAg阴性但HBcAb阳性的24例患者中1例(4.2％)HBV DNA阳性.结论NHL患者的HBV感染率高于大肠癌患者及全国普通人群,其中HBV的隐匿性感染是值得重视的问题.T-NHL患者的HBsAg阳性率低于B-NHL患者.如果NHL患者合并HBV感染,为预防HBV激活应在抗肿瘤治疗前给予抗病毒治疗.     

HBV感染与非霍奇金淋巴瘤的关系

背景与目的:文献报道乙型肝炎病毒(hepatitis B virus,HBV)感染率在非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)患者中较同一地区的非原发性肝癌实体瘤患者和普通人群高,但HBV和NHL之间的关系尚无定论.本研究旨在对比同一地区NHL患者与结直肠癌患者HBV的感染率.方法:比较109例NHL患者和128例结直肠癌患者乙型肝炎病毒表面抗原(HBsAg)的阳性率,并与普通人群对照,通过卡方检验判断有无统计学意义.结果:NHL患者HBsAg阳性率(40.4%)明显高于结直肠癌患者(14.1%)及当地普通人群(约17.3%),有统计学意义(P＜0.01);以结直肠癌患者作参照组,HBsAg阳性者患NHL的优势比为2.87,95%可信区间为1.830～4.502.结论:NHL患者的HBsAg阳性率高于结直肠癌患者和普通对照人群.     

黏膜相关淋巴样组织型结外边缘区B细胞淋巴瘤的分子细胞遗传学研究进展

黏膜相关淋巴样组织型结外边缘区B细胞淋巴瘤（extranodal marginal zone B—cell lymphoma of mucosa-associated lymphoid tissue，MZL—MALT）是结外最常见的淋巴瘤，近年研究表明慢性感染或自身免疫性疾病所致的直接或间接感染及分子遗传学异常是MZL—MALT发生、发展的基础。     

Splenic marginal zone lymphoma: current knowledge and future directions

Splenic marginal zone lymphoma (SMZL), along with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and nodal marginal zone lymphoma (NMZL), share a common origin from the "marginal zone." However, these three entities display different clinical characteristics, reflecting probable biological variations according to the organ and cellular origin. Within the past decade, new data have been reported regarding pathogenic mechanisms as well as therapeutic advances. Clinically, SMZL presents as an indolent and disseminated disease at diagnosis, with a specific clinical presentation that includes predominantly splenomegaly, and in half of patients, autoimmune manifestations. Establishing the diagnosis may be difficult, especially distinguishing SMZL from other low-grade lymphomas, such as small B-cell lymphomas; however, recent findings have contributed to a better characterization of the disease, and the criteria for diagnosis have been improved. Therapeutic approaches consist of splenectomy or immunochemotherapy, but there is no consensus regarding the best treatment, except when SMZL is associated with hepatitis C virus infection. In this article, we review the current knowledge on the biological findings, clinical features, and therapeutic approaches for SMZL.     

Hepatitis C virus infection and locally advanced splenic marginal zone lymphoma

Splenic marginal zone lymphoma (SMZL) is a rare malignant B-cell neoplasm, usually with an indolent clinical course and favorable prognosis. Treatment options include chemotherapy, surgery, radiation and immunotherapy. In some recent studies an increased incidence of hepatitis C virus (HCV) infection in patients with SMZL was reported and its possible role in lymphomagenesis was emphasized. A 66-year-old woman with twelve-year history of HCV infection was admitted due to locally advanced abdominal tumor involving the spleen and the left part of the diaphragm. Transaminase serum levels were not elevated. Neither peripheral lymphadenopathy nor bone marrow pathology was found. Absolute blood lymphocyte, erythrocyte and platelet counts were normal. A splenectomy with partial diaphragm resection in one block was performed. Recovery was uneventful. Pathologic examination with immunohistochemistry revealed SMZL and confirmed a neoplastic infiltration of the resected diaphragm. Following surgery, chemotherapy (CHOP regimen) and immunotherapy (anti-CD20 antibody) were given. At the last follow-up 15 months after surgery, the patient was free of any symptoms of lymphoma. Surgical resection of even locally advanced SMZL with involvement of adjacent tissues can be performed as a diagnostic and therapeutic procedure. Splenectomy is especially indicated in symptomatic patients without other sites of the disease. HCV infection may result in increased risk of SMZL due to the induction of B-cell lymphoproliferation. Because of possible lymphoma regression following anti-viral therapy, a systematic screening for HCV in patients with SMZL seems to be valuable and helpful for treatment planning.     

Hepatitis B infection increases the risk of non-Hodgkin lymphoma: A meta-analysis of observational studies

Hepatitis B virus (HBV) infection is a major public health problem and the association between HBV infection and non-Hodgkin lymphoma (NHL) is unclear. The primary aim of our study was to evaluate the association between HBV infection assessed by a positive hepatitis B surface antigen (HBsAg) and the incidence of NHL and subtypes using a meta-analysis of epidemiological studies. The random effects model was used to calculate the outcome. Our search yielded 17 case–control and 5 cohort studies, including over 40,000 NHL cases. HBV infected individuals had an OR of 2.24 (95% CI 1.80–2.78; p ≤ 0.001) of developing NHL. In high HBV prevalent countries, there were increased odds of diffuse large B-cell lymphoma and a trend toward increased odds of developing follicular and T-cell lymphoma. Future research is needed to better understand the biological mechanisms responsible for lymphomagenesis in patients with HBV infection.     

乙型肝炎病毒感染与B细胞型非霍奇金淋巴瘤的关系．

目的探讨B细胞型非霍奇金淋巴瘤（NHL）与乙型肝炎病毒（HBV）之间的关系。方法统计2003年1月至2009年12月住院的284例B细胞型NHL患者的乙肝5项标志物阳性率,并与同期住院的大肠癌患者作比较。结果B细胞型NHL以18—39岁和Ⅲ一Ⅳ期患者乙型肝炎表面抗原（HBsAg）阳性率较高,分别为42．6％（26／61）和37．0％（50／135）,分别与其他年龄段及I一Ⅱ期患者比较,差异均有统计学意义（x。值分别为7．573和6．874,P值分别为0．023和0．009）;B细胞型NHL患者HBsAg、乙型肝炎e抗原（HBeAg）的阳性率较大肠癌患者高[29．6％（84／284）比14．5％（155／1070）,6．7％（19／284）比0．8％（9／1070）,Wald值分别为25．174和20．496,P值均为0．0011;乙型肝炎表面抗体（抗HBsAb）阳性率较大肠癌患者低『45．4％（129／284）比58．0％（621／1070）,waid=11．062,P=0．0011;HBsAg、HBeAg及乙型肝炎核心抗体（抗HBcAb）同时阳性和HBsAg、乙型肝炎e抗体（抗HBeAb）及抗HBcAb同时阳性的发生率较大肠癌患者高『6．0％（17／284）比0．8％（9／1070）,16-2％（46／284）比11．5％（123／1070）,x0值分别为31．619和4．542,P值分别为0．000和0．033];抗HBcAb阳性且抗HBsAb阴性的发生率也较大肠癌患者高[37．0％（105／284）比24．5％（262／1070）,Wald=17．708,P〈0．001];抗HBcAb和抗HBsAb同时阳性的发生率较大肠癌患者低『20．8％（59／284）比27．8％（297／1070）,Wald=5．646,P=0．017]。结论HBV感染和B细胞型NHL存在一定相关性,HBV感染可能在B细胞型NHL的病原学中起作用。     

New Insights into the Biology and Diagnosis of Splenic Marginal Zone Lymphomas

Splenic marginal zone lymphoma (SMZL) is a small B-cell lymphoma, which has been recognized as a distinct pathological entity since the WHO 2008 classification. It classically presents an indolent evolution, but a third of patients progress rapidly and require aggressive treatments, such as immuno-chemotherapy or splenectomy, with all associated side effects. In recent years, advances in the comprehension of SMZL physiopathology have multiplied, thanks to the arrival of new devices in the panel of available molecular biology techniques, allowing the discovery of new molecular findings. In the era of targeted therapies, an update of current knowledge is needed to guide future researches, such as those on epigenetic modifications or the microenvironment of these lymphomas.     

The usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and a comparison of (18)F-FDG-pet with (67)gallium scintigraphy in the evaluation of lymphoma: relation to histologic subtypes based on the World Health Organization classification

BACKGROUND: Although studies comparing conventional imaging modalities with (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) for the detection of lymphoma and although the relations between (18)F-FDG-PET and histologic types were reported previously, most studies were not systematic and involved relatively small numbers of patients. METHODS: Two hundred fifty-five patients with lymphoma had their disease staged using (18)F-FDG-PET, and 191 of those patients also were assessed using gallium-67 scintigraphy ((67)Ga). Disease sites were identified on a site-by-site basis using computed tomography scans and/or magnetic resonance imaging. The results of these conventional imaging modalities were compared with the results from (8)F-FDG-PET and (67)Ga, and correlations between the imaging results and pathologic diagnoses were evaluated by using the World Health Organization classification system. RESULTS: Of 913 disease sites in 255 patients, (18)F-FDG-PET identified >97% of disease sites of Hodgkin lymphoma (HL) and aggressive and highly aggressive non-Hodgkin lymphoma. For indolent lymphoma, the detection rate of (18)F-FDG-PET was 91% for follicular lymphoma (FL); 82% for extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, irrespective of plasmacytic differentiation; and approximately 50% for small lymphocytic lymphoma (SLL) and splenic marginal zone lymphoma (SMZL). The results from (67)Ga were similar to those from (18)F-FDG-PET for most histologic subtypes. However, the sensitivity of (67)Ga was unexpectedly poor for FL, for mantle cell lymphoma (MCL), and for the nasal type of natural killer/T-cell lymphoma (NK/T-nasal), ranging from 30% to 38%. CONCLUSIONS: (18)F-FDG-PET was useful for all histologic subtypes of lymphoma other than SLL and SMZL. Compared with (67)Ga, the authors strongly recommend the use of (18)F-FDG-PET in patients with FL, MCL, and NK-nasal.     

Nodal and splenic marginal zone B cell lymphomas

Splenic marginal zone lymphoma (SMZL) and nodal marginal zone lymphoma (NMZL) are newly defined, separate clinicopathological entities. Both are rare lymphoma types, with low reproducibility in the diagnosis, although a conjunction of molecular and clinical studies seems to be now facilitating a more accurate diagnosis and understanding of the neoplastic process. SMZL is a disease involving the spleen, bone marrow and peripheral blood since the initial manifestations of the disease. The diagnosis has been until very recently based on the pathological study of the spleen with the conjunction of the clinical features, although the integration of the morphology in bone marrow and peripheral blood with the immunophenotype and molecular characteristics of the tumour makes a more accurate diagnosis now possible. The most frequent molecular alteration found in SMZL is allelic loss at the 7q chromosomal region. SMZL is an indolent lymphoma, although there is small subset of patients in which it follows an aggressive course. Molecular studies of SMZL are starting to reveal new diagnostic and prognostic markers, and to identify new potentially useful therapeutic targets. Nodal marginal zone lymphoma is a B-cell neoplasm originated in the lymph node, whose histology resembles the nodal infiltration by MALT- or Splenic-type marginal zone lymphoma, in the absence of clinical evidence of extranodal or spleen disease. The lack of characteristic phenotypic or molecular diagnostic findings is still hampering the reproducibility of this diagnosis. Here we review the main morphological and immunophenotypical markers, discussing the differential with other overlapping entities, singularly follicular lymphoma. Specific therapeutic protocols and prognostic factors are required to more precisely define this tumour.