原发性扁桃体滤泡性淋巴瘤的临床病理特征

目的:按照WHO 2008年淋巴造血组织肿瘤的最新分类,对原发性扁桃体滤泡性淋巴瘤(FL)的临床特征、形态学和免疫表型进行观察分析,探讨其与淋巴结原发性FL的异同,以利于诊断和鉴别诊断.方法:复习37例原发于扁桃体FL患者的临床资料及诊断切片,免疫组织化学染色后观察LCA、CD20、CD79a、CD45RO、CD3、CD10、Bcl-6和Bcl-2的表达情况.结果:37例原发性扁桃体FL患者中,活检前临床诊断扁桃体肿物28例,扁桃体癌6例,淋巴瘤3例.组织形态与淋巴结内FL类似,滤泡型4例,滤泡和弥漫型1例,少滤泡型32例,无弥漫型.低级别(1-2级)17例,高级别(3级)20例.免疫组织化学染色均表达LCA及B细胞标记物CD20和CD79a,不表达CK及T细胞的标记物CD45RO和CD3.CD10阳性率43.24%,Bcl-6阳性率86.48%,CD10和Bcl-6共表达率为37.83%;22例表达Bcl-2,阳性率59.46%;CD10、Bcl-6、Bcl-2在低级别FL和高级别FL中的表达率比较差异均无统计学意义(P>0.05).2例发生在儿童的扁桃体FL其形态及免疫表型均与WHO新分类的儿童FL相同.结论:扁桃体FL组织形态与淋巴结FL相似,本组活检标本中以少滤泡型为主,高级别占多数.B细胞和生发中心标记物的表达情况与淋巴结FL基本一致,而Bcl-2表达低.     

艾滋病病毒感染合并口腔浆母细胞型淋巴瘤一例临床病理分析

目的 分析艾滋病病毒(HIV)合并口腔浆母细胞型淋巴瘤的形态学特点、免疫表型及鉴别诊断.方法 对1例HIV合并口腔浆母细胞型淋巴瘤进行形态学、免疫组织化学分析及文献复习.结果 免疫组织化学显示CD-20、CD-3、CD-45、CD-30、ALK(-)、EBV(+)、CD138灶(+)、Ki-67 90%(+)、EMA灶(+)、CD68组织细胞(+)、CDRB灶(+)、CD45RO个别(+)、CD-79a、CD-56、IgM、IgG、IgA、HMB45、bcl-2、CD5、cyclinD1、CD43、CD10、Desmin、MPO、CD15、MYOD1、CK均为(-).病理诊断弥漫大B细胞淋巴瘤浆母细胞型分化.结论 弥漫性大B细胞淋巴瘤病理类型多样,HIV合并口腔浆母细胞型较少见,掌握其形态学特征,熟悉各类型的免疫表型的异同点对诊断与鉴别诊断有重要意义.     

组织细胞肉瘤六例临床病理学及免疫组织化学特点分析

目的 探讨组织细胞肉瘤(HS)的病理学特点、特异性标志物的意义及相关的鉴别诊断.方法 采用EnVision免疫组织化学方法检测6例发生于不同部位的HS.结果 6例HS中男性5例,年龄1～65岁,中位年龄18岁,女性1例,77岁.组织形态学:肿瘤细胞弥漫浸润,大小不一,部分区域细胞呈上皮样,胞质丰富嗜酸性,核圆形或不规则形,核仁大而嗜酸,核分裂象多见,个别区域可见双核、多核及瘤巨细胞,6例肿瘤细胞间质中均可见多少不等的炎性细胞.免疫表型:6例患者肿瘤细胞CD68、溶菌酶(1ysozyme)、LCA阳性,4例灶性细胞S-100阳性或弱阳性,2例个别细胞CD43阳性、1例个别细胞CD45RO阳性,Ki-67阳性率30%～90%,而CD21、CD35、CD4、CD1a、MPO、CD30、CD3、CD20、ALK、HMB45均阴性.结论 HS诊断相对比较困难,需结合肿瘤的镜下形态学改变及免疫表型.LCA、CD68、lysozyme是比较特异性的免疫表型,对HS的诊断及鉴别诊断有较大意义.     

纵隔灰区淋巴瘤的研究进展

纵隔灰区淋巴瘤(mediastinal gray zone lymphoma)作为一个疾病实体,常不能依据现有的诊断标准进行分类.这类淋巴瘤同时具有纵隔弥漫大B细胞淋巴瘤(PMBL)和经典霍奇金淋巴瘤(cHL)的特征.在2008年WHO造血与淋巴组织肿瘤分类中将其命名为"B细胞淋巴瘤,不能分类,具有介于弥漫大B细胞淋巴瘤和经典霍奇金淋巴瘤之间的特征(BCLu)".BCLu具有独特的临床特点、免疫表型和分子遗传学特征,临床过程更具侵袭性,预后较差.目前尚无达成共识的治疗方案,可参照侵袭性B细胞淋巴瘤的方案化疗.     

原发肠道NK/T细胞淋巴瘤一例并文献复习

目的 提高对NK/T淋巴瘤的认识.方法 报道1例原发于肠道的NK/T淋巴瘤的诊断、治疗经过并结合文献复习讨论.结果 患者经3次肠镜及免疫组织化学确诊,肿瘤细胞免疫表型为CD+56、CD+45RO、CD+3,CD-20、CD-5、CD-79a,经EPOCH及Hyper-CVAD化疗无缓解,诊断3个月后死亡.结论 NK/T细胞淋巴瘤恶性程度高,进展快.易误诊,预后差.     

成年人伴CD2表达B系急性淋巴细胞白血病免疫表型特征分析

目的 了解成年人伴CD2表达B系急性淋巴细胞白血病(CD+2 B-ALL)的免疫表型特征,为临床诊断、治疗及预后判断提供依据.方法 应用流式细胞术及多种单克降抗体检测18例成年人CD+2B-ALL及68例CD-2 B-ALL患者的免疫表型,并对其结果进行分析比较.结果 CD+2 B-ALL的发病年龄明显小于CD-2 B-ALL,18例成年人CD+2 B-ALL的大部分表面标志物与CD-2 B-ALL相似,其中CD10表达水平[(73.78±26.67)%]高于CD-2 B-ALL[(52.84±35.25)%],差异有统计学意义(t=2.35,P<0.05),CD33表达水平[(15.46±27.41)%]则低于CD-2 B-ALL[(31.15±27.72)%],差异有统计学意义(t=2.16,P<0.05);所有B-ALL患者都高表达CD34,阳性表达率分别为72.2%(13/18)和80.9%(55/68),差异无统计学意义(χ2=0.64,P>0.05).CD+2 B-ALL的CD20阳性率明显低于CD-2 B-ALL,差异有统计学意义(χ2=11.38,P<0.05).CD+2 B-ALL伴髓系抗原(CD13或CD33)表达率为44.4%(8/18),明显低于CD-2 B-ALL的72.1%(49/68),差异有统计学意义(χ2=4.86,P<0.05).结论 成年人CD+2 B-ALL与CD-2 B-ALL具有相似的免疫表型,主要来源于造血干细胞的恶性转化,CD+2 B-ALL伴髓系抗原(CD13、CD33)及CD20表达明显低于CD2 B-ALL,提示成年人CD+2 B-ALL可能有较好的预后.     

中国人经典霍奇金淋巴瘤中人类白细胞共同抗原表达的研究

目的 既往的研究发现在高加索人中,经典霍奇金淋巴瘤肿瘤细胞人类白细胞共同抗原(HLA)的表达与EB病毒感染密切相关,研究在亚洲人中两者的相关性.方法 随机选取北京大学医学部病理学系常规外检及会诊病例中确诊为经典霍奇金淋巴瘤的145例,所有病例均有石蜡包埋组织蜡块.常规HE染色、形态学观察,根据WHO分类标准对所有病例进行重新分类.原位杂交方法检测EB病毒编码的小RNA(EBER)以提示肿瘤与EB病毒的相关性.HLA-Ⅰ类抗原的表达使用HC-10和β 2-微球蛋白抗体检测,而HLA-Ⅱ类抗原的表达使用CR3/43抗体检测.结果 145例中,40%(58例)的病例为EB病毒相关性.EB病毒阳性病例中,混合细胞型较结节硬化型更为常见(71%比16%,P＜0.001).HLA-Ⅰ类抗原在EB病毒阳性病例中的表达率明显高于EB病毒阴性的病例(79%比30%,P＜0.001).而HLA-Ⅱ类抗原的阳性率在EB病毒阳性和阴性病例中差异无统计学意义(52%比43%,P=0.277).结论 中国人经典霍奇金淋巴瘤HLA-Ⅰ类抗原的表达与EB病毒感染密切相关,与高加索人一样,但HLA-Ⅱ类抗原的表达与EB病毒感染无显著相关性.     

中枢神经系统血管内ALK阳性间变性大细胞淋巴瘤一例并文献复习

目的 报道1例血管内间变性大细胞淋巴瘤激酶阳性(ALK+)间变性大细胞淋巴瘤(ALCL),提高对血管内淋巴瘤(IVL)的认识.方法 分析1例中枢神经系统血管内ALK+ALCL的临床资料、组织病理学特点和免疫表型,并结合文献进行复习.结果 患者女性,41岁.CT示右侧顶枕叶不规则低密度灶,增强扫描壁结节及边缘明显强化;磁共振(MRI)示右顶枕叶斑片状不规则异常信号影,累及右侧胼胝体压部,增强扫描呈斑片状不规则强化.血常规示单核细胞比例增高,红细胞压积减少.光学显微镜下观察:脑实质小血管管腔内多量明显异型性大单核细胞,肿瘤细胞胞质丰富嗜伊红,核圆形或不规则,可见马蹄形或肾形核,核仁清楚.免疫组织化学:肿瘤细胞LCA(+)、CD,(+)、ALK-1(+)、EMA(+)、粒酶B(+)、CD20(-)、CD79a(-)、CD30(-)、CD56(-)、GFAP(-)、AE1/AE3(-)、HMB45(-),血管内皮细胞CD31(+)、CD34(+).患者手术后8个月死亡,未行放化疗.结论 血管内ALK+ ALCL是IVL的一种罕见亚型,细胞形态特点及免疫表型类似于淋巴结或结外ALCL,临床症状无特异性,预后差,确诊主要依靠组织病理学检查.     

MUM1/IRF4在滤泡性淋巴瘤中的表达及其临床病理意义

目的 探讨MUM1/IRF4在滤泡性淋巴瘤(FL)中的表达情况及临床病理意义.方法 对96例FL患者标本进行MUM1、CD10、bcl-2、bcl-6、Ki-67免疫组织化学染色,并与患者的临床资料和病理学特征比较.结果 MUM1在96例FL中总的阳性率为59.2%(58/96),其中1～2级组阳性率为36.2%(19/51),3级组阳性率为86.4%(39/45)(x2=24.406,P<0.001).68.9%伴有弥漫成分的FL患者MUM1阳性(x2=8.161,P=0.004).MUM1和CD10的表达呈负相关,83.3%的CD10阴性病例表达MUM1(x1=12.649,P<0.001).MUM1阳性者核分裂和Ki-67标记指数高于MUM1阴性者(t=-3.852、t=-4.610,P<0.001).结论 MUM1可作为FL分型的标志物.MUM1阳性的FL可能为类似非生发中心B细胞分化特征的高度恶性淋巴瘤.     

儿童侵袭性成熟B细胞淋巴瘤的临床病理学及分子遗传学特点

目的 分析总结中国儿童各类型侵袭性成熟B细胞淋巴瘤的临床病理学及分子遗传学特点,为其诊断的标准化提供依据.方法 收集97例儿童侵袭性成熟B细胞淋巴瘤石蜡包埋组织标本,包括伯基特淋巴瘤(BL)81例、弥漫大B细胞淋巴瘤(DLBCL)8例、介于BL和DLBCL间的不能分类的B细胞淋巴瘤(BL/DLBCL)8例,利用免疫组织化学技术和间期荧光原位杂交(FISH)技术检测其免疫表型和分子遗传学特征.结果 BL的bcl-2和MUM1的阳性率分别为3%(2/66)和17%(12/71),DLBCL分别为50%(4/8)和63%(5/8),BL/DLBCL分别为50%(4/8)和63%(5/8).BL、DLBCL和BL/DLBCL的Ki-67平均值分别为(93±4.4)%、(83±14.3)%和(80±11.5)%.BL、DLBCL和BL/DLBCL的c-myc基因易位的比例分别为98%(79/81)、38%(3/8)和50%(4/8).38%(3/8)的DLBCL和25%(2/8)的BL/DLBCL存在bcl-6基因的多拷贝,BL与DLBCL之间、BL与BL/DLBCL之间bcl-2、MUM1和Ki-67平均值的差异及c-myc基因易位和bcl-6基因多拷贝的差异均有统计学意义(均P＜0.05).结论 儿童侵袭性成熟B细胞淋巴瘤的诊断和分型需要综合分析形态学、免疫表型和分子遗传学特征.儿童BL/DLBCL可能是DLBCL的一个亚型.CD10+、bcl-6+、bcl-2-、Ki-67＞90%、伴有IGH/c-myc重排、不伴有bcl-2和bcl-6重排时,支持BL的诊断;bcl-2+、Ki-67为50%～90%,同时伴有bcl-6基因的多拷贝时,支持DLBCL或BL/DLBCL的诊断.     

Comparison of lung dendritic cells and B cells in stimulating naive antigen-specific T cells

Dendritic cells (DCs) are specialized APCs that are important in priming naive T cells and can be manipulated in vitro and in vivo to enhance immunizations against microorganisms and tumors. A limitation in the development of suitable immunotherapeutic vaccines for the lung is incomplete information on the role of DCs and other potential APCs in the lung in priming naive T cells. In the current study, we analyzed the relative contributions of murine lung DCs and B cells to process and present OVA to naive CD4+ OVA323-339-specific (DO11.10) T cells in vitro. We also examined their expression of MHC class II and accessory molecules before and after maturation in culture. Similar to DCs from other sites, freshly isolated lung DCs can process OVA, spontaneously up-regulate MHC class II and accessory molecules during overnight culture, and stimulate naive T cells in an Ag-specific manner. In contrast, freshly isolated lung B cells were unable to both process and present native OVA. Furthermore, under conditions of limited OVA323-339 peptide exposure, B cells had a significantly diminished capacity to stimulate T cells, and this correlated with a decreased density of both MHC class II and important costimulatory molecules as compared with lung DCs.     

Ability of lymphokine-activated killer cells to lyse mycobacteria-infected cells

In cats and monkeys, we examined the parasympathetic component of the oculomotor complex, which directly innervates the ciliary muscle, using horseradish peroxidase (HRP). Labeled neurons of varying form and size were found in the Edinger-Westphal(EW) and the Perlia nuclei of the cat and in the anteromedian, EW, and Perlia nuclei of the monkey. Our study confirmed that a direct parasympathetic pathway exists from the midbrain to the ciliary muscles, and that accommodation is controlled in part by this direct link from the midsagittal region via a parasympathetic neuron of the oculomotor nuclear complex.     

Can cancer cells transform normal host cells into malignant cells?

A human prostate tumour cell line, LNCaP C4-2, when injected into athymic male nude mice, produced tumours containing: (1) only human cancer cells similar to those injected; (2) only murine stromal cells containing abnormal chromosome constitutions; or (3) both human prostate cancer cells similar to those injected and the transformed murine stromal cells with altered chromosome constitutions. Karyotypic analysis of murine metaphases from all the host-derived tumours showed mostly pseudodiploid chromosome constitutions, with multiple copies (amplification) of mouse chromosome 15 and the absence of a typical Y chromosome. Fluorescence in situ hybridization analysis of these murine cells, using a biotin-labelled total human DNA painting probe, further demonstrated the absence of human DNA and the presence of only mouse metaphase and interphase cells in these transformed stromal cells. These results suggest that cancer cells are capable of inducing neoplastic transformation in stromal cells of the host organ by some, as yet unknown, epigenetic mechanism(s).     

Differentiation of smooth muscle cells from undifferentiated cells of chicken gizzard occurs on the layer of fibroblast-like cells

Conflicting results have been reported in literature about the influence of beta-adrenergic stimulation on the fast cardiac sodium current (INa+). To elucidate these mechanisms in multicellular preparations we used the loose-patch-clamp technique to evaluate the effect of the beta-adrenergic agonist isoproterenol 1-1000 nmol/l. Isoproterenol enhanced INa+ at all membrane potentials by elevation of the maximal available INa+ . Only at the high concentration of 1 micromol/l was INa+ slightly depressed after depolarizing conditioning clamps. The most marked increase of the maximal available INa+ was 30+/-9% after application of 100 nmol/l isoproterenol. To learn about the mechanisms in view of sodium channel modulation we combined isoproterenol with the sodium channel blocker lidocaine (47 micromol/l). Under these circumstances the effects of both drugs were completely independent. This investigation shows clearly that low concentrations of isoproterenol increase INa+ in multicellular preparations by a gating-independent mechanism.     

Terminal differentiation of murine erythroleukemia cells: physical stabilization of end-stage cells

An important limitation in the use of the murine erythroleukenia (MEL) cell system as an in vitro system for the study of terminal erythroid differentiation has been the inability to produce significant numbers of cells which represent the end-point of the pathway in vitro. We show here that a major reason for the failure to observe end-stage cells in vitro is that such cells are physically unstable under the standard culture conditions used for MEL cell differentiation. Modification of these culture conditions by the addition of either bovine serum albumin or Ficoll leads to physical stabilization of end-stage cells. Under such culture conditions, uniform cultures of terminally differentiated MEL cells with morphological characteristics similar to those of normal mouse orthochromatophilic erythroblasts and reticulocytes are observed. Examination of physical and biochemical parameters of these cell populations give values which are similar to values characteristic of mouse reticulocytes. A physically stabilized MEL cell shows a narrow cell volume distribution with an average value of approximately 100 mum(3), similar to the cell volume distribution observed for mouse reticulocytes, while a typical MEL cell culture treated with DMSO but without a stabilizing agent exhibits a broader, more heterogeneous cell volume distribution with an average value of approximately 500 mum(3). Globin mRNA levels and levels of globin synthesis reach values almost equal to those in mouse reticulocytes in cultures of physically stabilized MEL cells while differentiating cultures not treated with a stabilizing agent reach substantially lower values for these parameters. We suggest that the ability to produce populations of MEL cells which undergo complete terminal erythroid differentiation in vitro will allow the analysis of the molecular mechanisms which control the terminal stages of the erythroid differentiation process.     

Artificial cells with emphasis on cell encapsulation of genetically engineered cells

Artificial cells are prepared in the laboratory for medical and biotechnological applications. Encapsulated cells are being studied for the treatment of diabetes, liver failure, and other conditions. More recently, there have been extensive studies into the use of encapsulated genetically engineered cells for gene therapy. We recently found that daily orally administered artificial cells, each containing a genetically engineered microorganism, can lower the elevated urea level in uremic rats to normal levels. This may solve the final obstacle of the lack of an effective oral urea removal system for the simple and inexpensive oral treatment of uremia. This is important because 85% of the world's uremic population cannot afford standard dialysis. Other areas of artificial cell application include use in hemoperfusion. Red blood cell substitutes based on modified hemoglobin are already in Phase 3 clinical trials in patients. Artificial cells containing enzymes are being developed for clinical trial in hereditary enzyme deficiency disease and other diseases. They are also being investigated for drug delivery and for use in other applications in biotechnology, chemical engineering, and medicine.     

Role of Langerhans cells and other dendritic cells in viral diseases

Langerhans cells are part of a vast system of potent antigen-presenting cells known under the name of dendritic cells. During the last decade, much has been learned on dendritic cell involvement in the immune response to infectious diseases. This review briefly summarizes our current understanding of the role played by Langerhans cells and other dendritic cells in the pathogenesis of DNA and RNA virus infections. These data may form the basis for the development of innovative approaches in the diagnosis, prevention, and treatment of viral diseases.     

Human bone cells stimulate the growth of human breast carcinoma cells

Human breast cancer cells were cultured together with their metastatic target, bone tissue, to analyze possible growth promotion effects. The coculture of human osteosarcoma cells (TE-85) with human mammary carcinoma cells (ZR-75.1) resulted in up to 8.4-fold stimulation of proliferation of the breast tumor cells. Cell contact of the two cultures was permitted through the channels of Nuclepore filters. However, physical contact turned out not to be necessary, since the proliferative stimulus was also mediated by a bone-derived diffusible factor. Conditioned medium (CM), collected from human primary bone cultures, enhanced the rate of proliferation of several breast tissue cell lines (ZR-75.1, BT-20, HBL-100), while some lines were not affected by osteoblast CM. Breast tissue lines responding to bone CM express low to intermediate levels of the c-erbB-2 gene, in contrast to nonstimulated lines, which overexpress the gene. Recent observations of metastatic spread in breast cancer patients suggest a distinctive pattern of secondary tumor distribution in association with c-erbB-2 protein expression. Bone tissue seems to be a preferential target for metastases of c-erbB-2-negative breast tumors.     

Internalization of Chlamydia by dendritic cells and stimulation of Chlamydia-specific T cells

Chlamydia species are the causative agents of trachoma, various forms of pneumonia, and the most common sexually transmitted diseases. Although the infection cycle has been extensively characterized in epithelial cells, where the Chlamydia entry-vacuoles avoid fusion with host-cell lysosomes, the cellular immune response has received less attention. Moreover, despite the abundant presence of dendritic cells (DC) in the sites of infection, the interaction between Chlamydia and DC has never been studied. We observe that DC kill Chlamydia trachomatis and Chlamydia psittaci. The chlamydiae are internalized by the DC in a nonspecific manner through macropinocytosis, and the macropinosomes fuse subsequently with DC lysosomes expressing MHC class II molecules. The interaction induces maturation of the DC, since presentation of an exogenous Ag is severely inhibited after a 1-day incubation, although chlamydial Ags are still presented and recognized by Chlamydia-specific CD4+ T cells. Thus, DC most likely play a role in initiating the T cell response in vivo and could potentially be used in adoptive transfer therapies to vaccinate against Chlamydia.