眼附属器黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT）临床病理分析

目的:探讨6例眼附属器黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT)患者的临床病理特点及预后。方法:收集2010年01月至2019年01月病理学检查确诊的6例眼附属器MALT患者的临床资料及治疗方案、形态学特点及免疫组化表达,FISH检测MALT1基因断裂,电话随访,分析总结其临床病理特点及预后。结果:临床表现为眼部不适,眼睑肿胀及视物模糊等。镜下可见肿瘤由形态多样的小B细胞组成,包括边缘带细胞（中心细胞样细胞）、单核样细胞、小淋巴细胞,也可见散在的免疫母细胞和中心母细胞样细胞,部分细胞有浆细胞样分化。5例肿瘤细胞CD20（+）、CD3（-）、BCL2（+）、Ki67约10%~25%,3例BCL10及AEG1阳性,1例伴浆细胞分化,免疫组化表现为CD20（-）、CD79α（+）、CD38（+）、CD138（+）、MUM1（+）、Kappa、Lambda呈限制性表达,2例FISH检测结果阳性。结论:眼附属器MALT淋巴瘤常CD20、BCL2、BCL10、AEG1阳性,FISH可作为辅助诊断。     

胃原发性MALT淋巴瘤临床病理分析

目的:探讨我区胃原发性黏膜相关淋巴组织型结外边缘区B细胞淋巴瘤(下称MALT淋巴瘤)的临床病理特点.方法:对14例胃原发性MALT淋巴瘤临床病理资料进行回顾性分析,并用免疫组化S-P法作下列抗体染色:HP、LCA、CD3、CD5、CD10、CD20、cyclinD1、1gM、κ、λ及BCL-2等.结果:男性5例,女性9例,中位年龄56岁.7例位于胃窦部,7例位于胃体.临床分期为:Ⅰ期8例(57%),Ⅱ期6例.l4例均表现为溃疡型病灶,病灶周围黏膜呈息肉样增生.组织学特点为:肿瘤细胞以边缘区B细胞为主,混有少量母化的细胞及浆细胞,可见淋巴上皮病变及反应性淋巴滤泡,7例(50%)可见向弥漫性大B细胞淋巴瘤转化区.免疫组化染色:HP阳性7例(50%),肿瘤细胞表达LCA、CD20、IgM;表达单一的轻链κ阳性5例、λ阳性9例;CD3、CD5、CD10、cyclinD1均阴性,中小肿瘤细胞BCL-2阳性,大细胞BCL-2阴性.结论:胃MALT淋巴瘤好发于中老年女性,易向弥漫性大B细胞淋巴瘤转化.     

Laptm53′UTR对小鼠B细胞淋巴瘤38B9细胞增殖与凋亡的影响

目的:通过建立稳定过表达溶酶体相关穿膜蛋白5(lysosomal associated protein transmembrane 5,Laptm5)3'不翻译区(3'UTR)的B细胞淋巴瘤38B9细胞株,探讨Laptm5 3'UTR对小鼠B细胞淋巴瘤38B9细胞株增殖、凋亡的影响.方法:荧光定量PCR及Western blotting检测小鼠B细胞及38B9细胞中Laptm5 miRNA及其蛋白质的表达水平;将小鼠Laptm5 3'UTR及其含有的microRNA结合位点突变的突变型基因片段构建入逆转录病毒表达载体pMSCV-PIG,包装成逆转录病毒,感染小鼠B细胞淋巴瘤细胞38B9,流式细胞术检测逆转录病毒感染率,细胞计数法及流式细胞术观察Laptm53'UTR或其突变型过表达后389B9细胞的增殖、凋亡情况.结果:相比小鼠B细胞,B细胞淋巴瘤细胞中Laptm5的miRNA及蛋白均显著降低(P＜0.01).成功获得稳定过表达Laptm5 3'UTR(突变型)的38B9细胞株.Laptm5 3'UTR细胞株比Laptm5 3'UTR突变型过表达细胞株的增殖能力显著减慢,凋亡率显著增加[(7.87±1.08)％vs(0.45±0.07)％,P＜0.01].结论:小鼠Laptm5 3'UTR具有抑制B细胞淋巴瘤增殖、促进其凋亡的作用,该作用可能与其影响相关microRNA的调控有关.     

胃原发性MALT淋巴瘤临床病理分析

目的：探讨我区胃原发性黏膜相关淋巴组织型结外边缘区B细胞淋巴瘤(下称MALT淋巴瘤)的临床病理特点。方法：对14例胃原发性MALT淋巴瘤临床病理资料进行回顾性分析，并用免疫组化S-P法作下列抗体染色：HP、LCA、CD3、CD5、CDIO、CD20、cyclinD1、lgM、κ、λ及BCL-2等。结果：男性5例，女性9例，中位年龄56岁。7例位于胃窦部，7例位于胃体。临床分期为：Ⅰ期8例(57％)．Ⅱ期6例。14例均表现为溃疡型病灶，病灶周围黏膜呈息肉样增生。组织学特点为：肿瘤细胞以边缘区B细胞为主．混有少量母化的细胞及浆细胞，可见淋巴上皮病变及反应性淋巴滤泡，7例(50％)可见向弥漫性大B细胞淋巴瘤转化区。免疫组化染色：HP阳性7例(50％)，肿瘤细胞表达LCA、CD20、IgM；表达单一的轻链κ阳性5例、λ阳性9例；CD3、CD5、CD10、cyclinD1均阴性，中小肿瘤细胞BCL-2阳性，大细胞BCL-2阴性。结论：胃MALT淋巴瘤好发于中老年女性．易向弥漫性大B细胞淋巴瘤转化。     

葡萄球菌肠毒素A体内诱导小鼠T细胞增殖的实验研究

目的:观察葡萄球菌肠毒素A(staphylococcal enterotoxin A,SEA)体内对小鼠脾T淋巴细胞增殖的作用规律.方法:采用SEA不同的注射方式和注射剂量,对小鼠脾T淋巴细胞进行体内单次诱导,用流式细胞术检测CD3的表达和测定胞内、外IL-2水平.结果:四种注射方式均能刺激体内T细胞的增殖,但静脉和腹腔注射对T细胞的影响最显著.根据对T细胞刺激程度和效力维持时间,选择腹腔注射为最佳注射途径.SEA剂量在5-15μg范围内均能促进CD3表达显著上升,最佳剂量为10μg.SEA体内注射后能诱导IL-2的大量合成和释放,促进T细胞的增殖.结论:体内SEA刺激对T细胞具有强大的促增殖作用,并且受SEA注射途径和剂量的影响.     

肾脏黏膜相关淋巴瘤2例报道并文献回顾

背景与目的：原发肾脏的黏膜相关组织淋巴瘤十分罕见,目前世界报道不足50例。本文介绍2例肾脏黏膜相关淋巴瘤的形态学特点和免疫表型特征,旨在使临床和病理对这种低度恶性的B细胞肿瘤的特点有所了解。方法：收集病史资料,形态学评价根据HE切片,用免疫组化法检测肿瘤细胞的表型,使用的抗体包括CD20、CD79、CD5、CD10、CD43、CD23、BCL10和Cyc linD1。结果：2例患者均为女性,年龄分别为48岁和55岁,临床上均有慢性肾盂肾炎病史。B超和CT检查发现肾脏肿块,行全肾切除。大体检查可见肿块位于肾髓质,呈境界不清的暗红色;镜检见肾盂至肾实质弥漫淋巴样细胞浸润,以小淋巴细胞、中心细胞样细胞、淋巴浆细胞和浆细胞浸润为主,可见肿瘤细胞浸润肾小管和肾球囊形成淋巴上皮病变和反应性淋巴滤泡,但没有显著滤泡殖入;免疫组化显示增生细胞以B淋巴细胞为主,散在分布反应性T细胞,肿瘤细胞CD20、CD79 a阳性,CD43弱阳性,CD5、CD10、BCL10、CD23和Cyc linD1均为阴性。结论：原发肾脏黏膜相关淋巴瘤临床极为罕见,临床表现和辅助检查与肾细胞癌不易鉴别,但组织学特点符合经典黏膜相关淋巴瘤的所有特征,免疫表型有助于病理诊断。     

BCL11基因与淋巴细胞肿瘤

B细胞淋巴瘤／白血病（B—cell lymphoma／leukemia，BCL）家族蛋白在细胞的增殖和抗凋亡等方面起重要作用。BCL11基因是BCL家族的新成员，包括BCL11A和BCL11B基因，近年已初步认识其结构和功能特点。不仅与淋巴细胞的发育、增殖、分化和生存密切相关，其表达异常也与淋巴细胞恶性转化有一定的关系。本文主要介绍BCL11基因特点、功能及其与淋巴细胞肿瘤等关系的最新研究进展。     

结外B 细胞性非霍奇金淋巴瘤中MALT1 基因表达的检测及意义*

目的:探讨结外B 细胞淋巴瘤中MALT1 基因（mRNA）的表达与MALT和弥漫大B 细胞淋巴瘤发生发展的关系,及其对淋巴瘤临床病理特征和预后的影响。方法:用HE和免疫组化染色筛选出本院确诊的MALT和结外弥漫大B 细胞淋巴瘤106例,检查肿瘤组织Bcl- 2 和Ki-67的表达,用RT-PCR 检测肿瘤中的MALT1 基因mRNA 水平,收集临床病理资料并随访。结果:MALT1 mRNA 的表达:在DLBCL与MALT淋巴瘤组、淋巴结累及组和无累及组、临床分期Ⅲ～Ⅳ组和Ⅰ～Ⅱ组间均有统计学差异（P<0.05）,在Ki-67≥30% 与<30% 组间未见统计学差异（P>0.05）,而Bcl- 2 阳性组却高于阴性组（P<0.05）;MALT1mRNA 表达与不表达病例之间患者生存状况有明显差异（P<0.05）,表达组生存状况较差。结论:MALT1 基因在MALT淋巴瘤与DLBCL中有不同程度的表达,MALT1 基因活化NF-κ B 后可能通过调控Bcl- 2 使细胞凋亡抑制而导致淋巴瘤发生,MALT1mRNA 表达与B 细胞淋巴瘤的类型、淋巴结累及、临床分期有关,与患者的生存状况有关,MALT1 可能是一个MALT和弥漫大B 细胞淋巴瘤预后不良的相关因子。      

抗CD20单克隆抗体联合CHOP化疗方案治疗人B细胞淋巴瘤的实验观察

目的:以人B细胞淋巴瘤裸鼠皮下移植模型为基础,研究抗CD20单克隆抗体体内、体外活性,评价该抗体联合CHOP化疗方案治疗人B细胞淋巴瘤的有效性。方法:体内实验:建立人B细胞淋巴瘤裸鼠皮下移植模型。52只荷瘤鼠随机分为5组进行实验。用TUNEL法检测肿瘤凋亡,并绘制肿瘤体积曲线和裸鼠体质量曲线。体外实验:用CellTiter96 AQueous非同位素细胞增殖试验试剂盒检测抗CD20单克隆抗体、化疗和联合化疗对Raji细胞体外杀伤作用,并绘制剂量反应曲线。结果:体内实验:鼠抗人CD20单抗组及嵌合CD20抗体组均出现大量肿瘤细胞凋亡。联合治疗组疗效最佳,与其他组相比差异有统计学意义,P&lt;0.05。化疗组及联合治疗组体质量下降明显,与其他组相比差异有统计学意义,P&lt;0.05。体外实验:发现鼠抗人CD20单克隆抗体及嵌合型CD20抗体均可增加Raji细胞对化疗药物的细胞毒敏感性。结论:CD20单克隆抗体对B细胞淋巴瘤具有明显的抑制作用,可以诱发大面积肿瘤细胞凋亡,能提高肿瘤对化疗药物的细胞毒敏感性,且较常规化疗毒副反应小。     

胃MALT淋巴瘤发病机制研究进展

胃粘膜相关淋巴组织(MALT)型结外边缘区B细胞淋巴瘤通常是在幽门螺杆菌(Hp)感染基础上发展起来的.Hp感染可引起淋巴细胞浸润,使胃粘膜获得MALT.在Hp刺激、自身抗原刺激和T细胞辅助下,浸润的B细胞活化增殖,偶尔发生遗传学异常进而向恶性转化.研究发现Hp感染是胃MALT淋巴瘤发生的重要病因.现综述根治Hp的临床研究及抗原选择、自身免疫在淋巴瘤发病中的作用.     

肾脏黏膜相关淋巴瘤,是慢性肾孟肾炎的后果吗?

Objective:To report 2 cases of primary renal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma), and observe the relations between this rare tumor of kidney and chronic pyelonephritis. Methods: 2renal MALT lymphomas were collected from referral consultation. Detailed clinical information were reviewed, morphological analysis based on the HE section, and immunohistochemistry were performed by CD20, CD79a, CDS, CD10, CD43, CD23,BCL10 and Cyclin D1 antibodies. Results: 2 female patients with age of 48 and 55, respectively, all had a history of chronic pyelonephritis. Under the B ultrasonic and CT scanning a bump in the kidney was found. Renal carcinoma suspected and hereby the whole nephrectomy performed. In the macroscopic, tumors were laid in the renal medulla, with dark red color and ill-defined boundary. In the microscopic, there were mixed lymphoid cells infiltrate which mainly consisted of small lymphocytes, centrocyte-like cells, lymphoplasmacytoid and plasma cells, reactive follicles and lymphoepithelial lesions also could be seen in the lesion, but follicles colonization was rare. In fact, except changes of lymphoma, basic renal disease also could be seen. Most glomeruli were atrophic, some glomeruli were hyperplastic and hypertrophic. Tubules were dilated or contacted, many dilated tubules contained pink-color glassy-appearing casts that suggest the appearance of thyroid tissue.As a result, those 2 cases showed juxtaposed changes of lymphoma and pyelonephritis. Immunohistochemistry showed that tumor cells were CD20 and CD79a positive, CD43 was weak positive, but CD5, CD10, CD23, BCL10 and Cyclin D1 were all negative. Conclusion: Primary renal MALT lymphoma was very rare disease. According to the clinical manifestation, it's hard to differentiate from renal cell carcinoma. But the morphological features were consistent with the classic MALT lymphomas in other sites. Immunophenotypic profiles were helpful for diagnosis. Based on the truth that many MALT lymphomas in other sites were connected with chronic inflammations, we suppose that the renal MALT lymphoma may originate from chronic pyelonephritis.     

Primary renal mucosa-associated lymphoid tissue ymphoma, the result of chronic pyelonephritis？

Objective： To report 2 cases of primary renal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue （MALT lymphoma）, and observe the relations between this rare tumor of kidney and chronic pyelonephritis. Methods： 2 renal MALT lymphomas were collected from referral consultation. Detailed clinical information were reviewed, morphological analysis based on the HE section, and immunohistochemistry were performed by CD20, CD79a, CD5, CD10, CD43, CD23, BCL10 and Cyclin D1 antibodies. Results： 2 female patients with age of 48 and 55, respectively, all had a history of chronic pyelonephritis. Under the B ultrasonic and CT scanning a bump in the kidney was found. Renal carcinoma suspected and hereby the whole nephrectomy performed. In the macroscopic, tumors were laid in the renal medulla, with dark red color and ill-defined boundary. In the microscopic, there were mixed lymphoid cells infiltrate which mainly consisted of small lympho- cytes, centrocyte-like cells, lymphoplasmacytoid and plasma cells, reactive follicles and lymphoepithelial lesions also could be seen in the lesion, but follicles colonization was rare. In fact, except changes of lymphoma, basic renal disease also could be seen. Most glomeruli were atrophic, some glomeruli were hyperplastic and hypertrophic. Tubules were dilated or contacted, many dilated tubules contained pink-color glassy-appearing casts that suggest the appearance of thyroid tissue. As a result, those 2 cases showed juxtaposed changes of lymphoma and pyelonephritis. Immunohistochemistry showed that tumor cells were CD20 and CD79a positive, CD43 was weak positive, but CD5, CD10, CD23, BCL10 and Cyclin D1 were all negative. Conclusion： Primary renal MALT lymphoma was very rare disease. According to the clinical manifestation, it＇s hard to differentiate from renal cell carcinoma. But the morphological features were consistent with the classic MALT lymphomas in other sites. Immunophenotypic profiles were helpful for diagnosis. Based on the truth that many MALT lymphomas in other sites were connected with chronic inflammations, we suppose that the renal MALT lymphoma may originate from chronic pyelonephritis.     

综合影像学、组织学和免疫组织化学特点诊断肺MALT淋巴瘤

背景与目的:肺的黏膜相关淋巴组织淋巴瘤(MALT淋巴瘤)是原发性肺恶性肿瘤中的少见类型,但在全身各部位所有的MALT淋巴瘤中,肺MALT淋巴瘤并不罕见。由于肺MALT淋巴瘤的临床表现和影像学特点不典型,常与炎症或肺上皮性恶性肿瘤不易鉴别。本研究综合肺MALT淋巴瘤的影像学、大体形态、组织学和免疫组织化学特点,帮助对肺MALT淋巴瘤的认识和诊断。方法:收集15例肺MALT淋巴瘤,根据大体形态和HE图像其组织学特点;并回顾各病例的胸片或(和)CT资料,收集特异性表现;免疫组织化学EnVision法评价BCL10蛋白的表达。结果:在组织学图像上,肺MALT淋巴瘤具有与胃MALT淋巴瘤类似的细胞学特点,但也有肺组织特异性的诊断图像;BCL10免疫组化显示61.5%(8/13)的病例具有核染色;影像学分析显示肺MALT的图像可分为两型:炎症型和肿块型。炎症型表现为单发或多发或弥漫性斑片状模糊影、毛玻璃样影和实变影,内可有支气管充气征;肿块型表现为单发或多发结节或肿块,周围型多见,呈类圆形,边界清楚或模糊,可有分叶及毛刺。结论:肺MALT淋巴瘤有相对特异性的病理形态学特点,BCL10免疫组化能辅助MALT淋巴瘤的诊断,影像特点可能对手术、治疗反应和复发等有作用,但临床病理的关键是与肺"炎性假瘤"及其他非特异性炎症的鉴别诊断。     

BCL6 gene rearrangement and protein expression are associated with large cell presentation of extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue

Extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) is an indolent B‐cell lymphoma, which is often localized in the stomach. It is characterized by typical morphology, immunology, cytogenetics and expression profile. The coexistence of a large B‐cell lymphoma and a MALT lymphoma in the gastrointestinal tract is defined as a composite lymphoma (ComL) and, as we have previously shown, is almost always the consequence of secondary transformation of MALT lymphoma. Here, we have analyzed a panel of seven MALT lymphomas, seven ComL and thirteen large cell variants of marginal zone B‐cell lymphomas (MZBL) using FISH for the detection of rearrangements of IGH, MALT1, BCL6, BCL10 and FOXP1 and immunohistochemistry for Bcl6, Bcl10 and FoxP1. Translocations involving IGH were found in 10/27 lymphomas including two cases with IGH‐BCL6 fusion and one with IGH‐BCL10 fusion; in 7/10 cases, the translocation partner was not identified. Bcl10 and FoxP1 protein expression was heterogeneous throughout the series. Genetic rearrangements of BCL6 and Bcl6 protein expression were found almost exclusively in the large cell components of the ComL and the large cell extranodal MZBL (p = 0.2093 and p = 0.0261, respectively). These findings suggest Bcl6 as a marker for transformation of MALT lymphoma.     

Translocations involving the immunoglobulin heavy chain gene locus predict better survival in gastric diffuse large B-cell lymphoma.

PURPOSE: The pathogenesis and clinical heterogeneity of gastric diffuse large B-cell lymphoma (DLBCL) are poorly understood. We have comprehensively investigated the incidence and clinical significance of lymphoma-associated chromosomal translocations, particularly those involving the immunoglobulin heavy chain (IGH) gene locus, in a large series of gastric DLBCL. EXPERIMENTAL DESIGN: One hundred forty-one cases of primary gastric DLBCL [58 with mucosa-associated lymphoid tissue (MALT) lymphoma and 83 without MALT lymphoma] were enrolled. Translocations involving BCL6, c-MYC, FOXP1, MALT1, and IGH were investigated using interphase fluorescence in situ hybridization. In positive cases, additional fluorescence in situ hybridization was done with appropriate probes for potential partner genes. Cases were classified into germinal center B-cell-like (GCB) or non-GCB subgroups by immunophenotyping with CD10, BCL6, and MUM1. RESULTS: Translocations involving IGH were detected in 36 (32%) of 111 cases; their partner genes included BCL6 (n = 10), c-MYC (n = 5), and FOXP1 (n = 3) but remained unknown in the remaining 18 cases. t(14;18)/IGH-BCL2, t(14;18)/IGH-MALT1, and t(1;14)/BCL10-IGH were not detected in any case. t(11;18)/API2-MALT1 was detected in none of the cases, except for one case of DLBCL with MALT lymphoma, which showed positive signals only in MALT lymphoma cells. IGH-involved translocation was associated with younger age but not with any other clinicopathologic factors including GCB or non-GCB immunophenotypes. Cox multivariate analysis revealed that IGH-involved translocation, in addition to younger age and early stage, was an independent prognostic factor for better overall and EFSs. CONCLUSION: IGH-involved translocations are frequent in gastric DLBCL and seem to identify cases with favorable prognosis.     

Distinctive cell properties of B cells carrying the BCL2 translocation and their potential roles in the development of lymphoma of germinal center type

The BCL2/IGH translocation is a hallmark of follicular lymphoma and germinal center B-cell type diffuse large B-cell lymphoma. Although a strong determinant of these histological subtypes, this translocation is insufficient by itself for lymphomagenesis, so that other genetic alterations are required. To clarify how the BCL2 translocation contributes to the development of specific lymphoma subtypes, we used chimeric mouse models and a bone marrow transplantation system to examine the biological features of BCL2 -overexpressing B cells. These cells showed a cell-autonomous differentiation preference for follicular B cells. Their cell cycle progression was enhanced in wild-type but not in Eμ-BCL2 transgenic mice, indicating that the low proliferative activity of B cells in Eμ-BCL2 transgenic mice is partly due to their specific microenvironment, which is caused by the abnormal B cells themselves. Moreover, in vitro experiments demonstrated that Eμ-BCL2 ⁺ B cells have reduced responsiveness to terminal differentiation stimulation. According to these results, we hypothesize that B cells that have undergone BCL2/IGH translocation might possibly be forced to localize in follicles, and accumulate genetic abnormalities by being subjected to recurrent stimulation. Our findings lead us to propose that B cells carrying the BCL2/IGH translocation comprise a distinctive cell population that leads to the development of germinal center B-cell type lymphoma. ( Cancer Sci 2009; 100: 2361–2367)