基于竞争最优原型的淋巴细胞协同分类

目的提出一种基于竞争最优原型的淋巴细胞协同分类方法。方法首先,采用改进的ISODATA算法聚类同型多态的淋巴细胞原型集;然后,依据待分类细胞样本,建立协同竞争机制求出各原型集中的最优原型;最后,将待分类样本分别与各型最优原型进行相似匹配,以最大相似结果作为分类结果。结果实现了淋巴滤泡套细胞、淋巴滤泡中心细胞、淋巴滤泡中心母细胞、中心母细胞性淋巴瘤细胞等4组类型的细胞分类。结论实验结果表明该方法分类效果理想,为下一步淋巴细胞定量分析打下基础。     

应用比较性基因组杂交对中心母细胞-中心细胞性非何杰金淋巴瘤的分子细胞遗传学分析

自从Brill等(1925年)首次将中心母细胞-中心细胞淋巴瘤的滤泡型描述为全身性淋巴结与脾脏的巨淋巴滤泡增生症以及Symmers(1927年)将其描述为滤泡性淋巴结病伴脾肿大以来,本病已成为非何杰金淋巴瘤(NHL)中最清楚明确的一个类型。这一B细胞肿瘤在所有重要的分类系统中被视为一个独立的类型,如在Kiel分类中,称之为中心母细胞-中心细胞淋巴瘤的滤泡型,在Lukes/Collins分     

单克隆抗体对T细胞性淋巴瘤免疫表型的诊断和预后判断

作者运用21组单克隆抗体检测了6例胸腺后T细胞性淋巴瘤(2例淋巴上皮样细胞性淋巴瘤,2例T区淋巴瘤,2例T免疫母细胞性淋巴瘤)和4例T淋巴母细胞性淋巴瘤。其结果显示:①淋巴上皮样细胞性淋巴瘤细胞增殖活性低,用通常的单抗检测不能区分出恶性克隆细胞。②T区淋巴瘤、T免疫母细胞性淋巴瘤要运用免疫标记和细胞学形态特征方可检出恶性克隆细胞。③4例T淋巴母细胞性淋巴瘤是常见的胸腺皮质表型(T4~+,T8~+,T6~+)并出现纵隔肿块。4例T淋巴母细胞性淋巴瘤     

弥漫大B细胞淋巴瘤分子亚型的细胞核形态参数的差异

目的通过图像分析观察中心母细胞型弥漫大B细胞淋巴瘤（CB—DLBCL）分子亚型之间的细胞核的形态是否存在差异。方法先采用免疫组化方法将CB,DLBCL分为生发中心B细胞样组（GCB）和非生发中心B细胞样组（non-GCB）两组,然后通过图像分析对两组细胞核的形态参数进行对比分析。结果GCB与non—GCB的11项细胞核形态参数之间均存在差异,差异有非常显著的统计学意义（P值〈0．01）。其中截面积以GCB高于non-GCB,截面周长、截面长径、截面短径和截面平均直径以non．GCB高于GCB。描述细胞核的形状不规则程度的异型指数allotype index、圆偏度circular skewness、圆球度sphericity、圆形因子spherical factor、规化形状因子normalized shapefactor和形状因子ARshape factor AR均显示,non—GCB细胞核的不规则程度显著大于GCB。结论本文证实non—GCB与GCB的细胞核形态参数存在显著差异,前者细胞核的不规则程度明显大于后者。这与non-GCB临床预后较差相符合。     

B细胞淋巴瘤73例临床病理分析

为了探讨B细胞淋巴瘤临床病理特征,应用组织形态学和免疫组织化学分析73例B细胞淋巴瘤患者的病理资料,同时行CD20、CD3、CD5、CD23、CD30、CD79α、TdT、Bcl-2、CyclinD1、Lysozyme和Ki-67的免疫表型测定,并根据WHO新分类重新分类。73例B细胞淋巴瘤患者中,弥漫性大B细胞淋巴瘤(DLBCL)38例(52.05%),包括中心母细胞型(CB)27例,免疫母细胞型(IB)5例,间变型(AV)4例,富于T细胞或组织细胞型2例;滤泡性淋巴瘤(FL)18例,黏膜相关淋巴组织型边缘区B细胞淋巴瘤9例,套细胞淋巴瘤(MCL)2例,B淋巴母细胞性淋巴瘤(B-LBL)4例,B小淋巴细胞淋巴瘤(B-SLL)2例。B细胞淋巴瘤低度恶性组Ki-67阳性率为20.69%(6/29),高度恶性组阳性率为75%(33/44),P<0.01。初步研究结果提示,WHO新分类对B细胞淋巴瘤的诊断便于掌握,实用性强,与临床治疗和预后判断有密切关系。通过标准的形态学和一套规范的免疫组化检测,结合WHO新分类可应用于B细胞淋巴瘤的诊断和预后。     

套细胞淋巴瘤

<正>套细胞淋巴瘤(mantle cell lymphoma,MCL)是2001年WHO淋巴造血组织肿瘤新分类中的一种独立的B细胞非霍奇金淋巴瘤[1],占非霍奇金淋巴瘤的5%~10%。它来源于初级淋巴滤泡未成熟生发中心前CD5+的B细胞或次级淋巴滤泡套区细胞。好发于中老年人。大多诊断时处于Ⅲ~Ⅳ期,有广     

bcl-6及p53在小B细胞淋巴瘤中的表达及意义

目的 :探讨小B细胞淋巴瘤中bcl 6、p5 3的表达及意义。方法 :对 34例小B细胞淋巴瘤进行bcl 6和p5 3的免疫组化S P法检测。结果 :bcl 6阳性率 35 3% (12 / 34) ,且全部表达于滤泡中心细胞性淋巴瘤 (12 / 12 ) ,与其他组类型小B细胞性淋巴瘤比较差异有极显著意义 ,P <0 0 0 1。p5 3蛋白阳性率 2 6 5 % (9/ 34) ,其中滤泡中心细胞性淋巴瘤为 4 1 7% (5 / 12 ) ,小淋巴细胞性淋巴瘤为 17 6 % (3/17) ,淋巴浆细胞性淋巴瘤为 33 3% (1/ 3) ,而套细胞淋巴瘤阴性为 0 (0 / 2 ) ,各组间比较差异无显著意义。结论 :bcl 6可作为滤泡中心细胞性淋巴瘤的特异标志而区别于其他类型小B细胞淋巴瘤 ;p5 3的异常表达在这一组恶性淋巴瘤中无类型倾向性 ;可能有多种基因异常参与了这一组疾病的发生发展     

胃黏膜相关淋巴组织型淋巴瘤临床病理分析

目的；研究胃黏膜相关淋巴组织（MALT）型淋巴瘤的形态特征。方法：应用HE染色及免疫组化Eivison二步法观察胃MALT型淋巴瘤。结果：17例胃MALT型淋巴瘤为B细胞表达。Kappa( )6例，Lambda( )8例。瘤细胞以CCL细胞型为主，淋巴上皮病变13例，滤泡克隆化8例，反应性滤泡增生11例。结论：淋巴上皮病变，滤泡克隆化，反应性滤泡增生及B细胞单克隆性是胃MALT型淋巴瘤的主要特征。有别于胃良性病变引起的淋巴组织反应性增生。     

套细胞淋巴瘤临床研究现况

非霍奇金淋巴瘤(NHL)在世界范围内逐年增多,自1950年以来每年发病率增加4%.在美国现已是第六位引起死亡的恶性肿瘤.近年来由于化疗、放疗的发展,NHL治疗效果明显提高.但是由于NHL的病理分类较为复杂,而且病理类型与治疗的方法及预后有密切的关系.套细胞淋巴瘤(Mantle Cell Lymphoma,MCL)近来受到临床医师的关注,有必要对其进一步的了解.套细胞淋巴瘤于1992年由Banks主持召开的国际会议上统一命名的.在不同的分类系统中,套细胞淋巴瘤有不同的名称:中心细胞性淋巴瘤(Kiel分类),中间淋巴细胞性淋巴瘤(Rappaport分类),弥漫性或结节性小裂细胞淋巴瘤(国际工作分类,成都会议)及外套层淋巴瘤(Weisenburger分类).近年来Real分类及WHO的肿瘤分类都包括了套细胞淋巴瘤.1 套细胞淋巴瘤的病理,免疫表型及分子遗传学套细胞淋巴瘤来源于滤泡淋巴细胞套区的B淋巴细胞,特点为以淋巴结发生中心周围套区的肿瘤性扩大.肿瘤细胞主要是小到中等的淋巴样细胞,一般比正常的淋巴细胞稍大,也有一些小而圆的淋巴样细胞与小淋巴细胞相似.套细胞淋巴瘤的瘤细胞呈弥漫性生长或不明显结节状,偶尔瘤细胞围绕反应性滤泡生长.套细胞淋巴瘤有多种分类.以套细胞淋巴瘤主要累及正常生发中心周围的套区并导致其扩大的,为套区型;当套细胞淋     

肝脏炎性假瘤样滤泡树突状细胞肿瘤的临 床病理分析

 目的探讨肝脏炎性假瘤样滤泡树突状细胞肿瘤的临床病理学特征,为临床提供诊断及鉴别诊断的依据。方法对1例肝脏炎性假瘤样滤泡树突状肿瘤、7列肝脏炎症性肌纤维母细胞性肿瘤、1例肝脏原发性霍奇金淋巴瘤及1例肝脏原发性恶性纤维组织细胞瘤进行临床病理分析、免疫组织化学染色及EBV encoded RNA(EBER)原位杂交检测。结果肝脏炎症性肌纤维母细胞性肿瘤、肝脏原发性霍奇金淋巴瘤和肝脏原发性恶性纤维组织细胞瘤与肝脏炎性假瘤样滤泡树突状细胞肿瘤临床症状、影像学表现及镜下表现比较相似,但肝脏炎性假瘤样滤泡树突状细胞肿瘤在临床上可以无症状或右上腹不适或疼痛、肝肿大、发热、体重减轻等。肿瘤呈实性,与周围组织间有明显界限。镜下肿瘤细胞为梭形、卵圆形,呈束状、席纹状排列,并散在分布于以淋巴细胞和浆细胞为主的炎症细胞背景中。梭形细胞核较小,常被扭转和不规则折叠,呈空泡状,但核仁明显。还可见到R S样细胞,且免疫表型CD21、CD35阳性,EBER原位杂交阳性。结论肝脏炎性假瘤样滤泡树突状细胞肿瘤是罕见的肿瘤,其形态的复杂性、相似性,使免疫组织化学标志物和EBER原位杂交成为诊断这类肿瘤不可或缺的辅助手段。 关键词：肝脏肿瘤;肝脏炎性假瘤样滤泡树突状细胞肿瘤;肝脏炎症性肌纤维母细胞性肿瘤;肝脏原发性霍奇金淋巴瘤;肝脏原发性恶性纤维组织细胞瘤     

B细胞淋巴瘤干细胞的研究进展

 淋巴瘤干细胞的发生机制十分复杂多样。对于滤泡淋巴瘤（FL）和套细胞淋巴瘤（MCL）来说,有观点认为在骨髓中经V-D-J重排过的淋巴祖细胞（CLP）是其肿瘤干细胞（TSC）的来源;而在弥漫性大B细胞淋巴瘤（DLBCL）和散发性Burkitt淋巴瘤（BL）中,生发中心B细胞是TSC的来源。另一种观点是,表观遗传学改变一次打击使正常造血细胞重新获得干细胞功能,然后经过进一步的染色体易位使这些“前-淋巴瘤干细胞”最终成为淋巴瘤干细胞。分离与鉴定非霍奇金淋巴瘤（NHL）的TSC能够为NHL的发病机制和治疗研究提供新的认识。     

Morphometric study of primary cutaneous germinal center cell lymphomas.

BACKGROUND. Primary cutaneous germinal center cell lymphomas (PCGCCL) are B-cell neoplasias; most are mixed cell type, composed of small and large cleaved cells and large noncleaved cells (centrocytes and centroblasts). Because of the significant pleomorphism of the cells, which ranged in size from small elements with indented nuclei to larger ones with multilobulated vesiculous nuclei, histopathologic examination of PCGCCL of mixed cell type has the worst degree of histologic interobserver reproducibility. METHODS. In this study, the authors determined whether the light microscopic morphologic classification criteria applied in quantifying cleaved and noncleaved cells in these lymphomas are substantiated by morphometric analysis and have good reproducibility in differentiating the various cell subsets. They used an image analyzer (IBAS 2000, Zeiss Kontron, Munich, Germany) to study 17 centroblastic/centrocytic and centroblastic follicular and/or diffuse primary cutaneous lymphomas. RESULTS. The data obtained showed morphometric differences between the follicular and diffuse patterns of neoplastic cells. In follicular neoplasms, the cells tend to be smaller, more cleaved, and more monomorphic than those observed in the diffuse forms. In all the follicular and diffuse cases, the authors observed a unimodal population with a wide peak composed of cells with intermediate morphometric features that cannot be labeled properly. CONCLUSIONS. These data underline the considerable overlap of nuclear parameters of lymphocytes between the subtypes of cells in cutaneous mixed small and large cell lymphoma, making the Kiel classification and Working Formulation unsuitable for this kind of neoplasia and supporting revision of classification criteria in cutaneous germinal center cell lymphomas.     

Circulating buttock cells in non-Hodgkin's lymphoma

Leukemic B cells with a characteristically sharp nuclear cleft seemingly dividing the nucleus into two or more parts have been entitled "buttock cells" and are subject of this study. These cells were found in leukemic non-Hodgkin's lymphomas (NHL) and usually have been related to follicular center cell lymphomas. However, buttock cells also closely resemble cells present in intermediate lymphocytic lymphoma (ILL) and mantle zone cells of reactive lymphoid tissues. Ultrastructurally, it became apparent that the separate nuclear lobes of buttock cells were connected by chromatin bridges. Immunophenotypically, circulating buttock cells had a variable phenotype, which may indicate either a follicle center or mantle zone origin. The use of CD5 and FMC7 monoclonal antibodies might be of discriminative help. These leukemic NHL have to be differentiated from classical chronic lymphocytic leukemia (CLL) with help of cytomorphology and immunophenotyping, since the former usually have a worse prognosis and generally will require a different treatment.     

Mantle-zone lymphoma. An immunohistologic study

Mantle-zone lymphoma (MZL) is a histologically distinctive variant of follicular lymphocytic lymphoma which is characterized by a proliferation of atypical small lymphoid cells as wide mantles around benign-appearing germinal centers. Immunoperoxidase stains were performed on fixed and processed lymph nodes from four patients with MZL. Three cases were of the intermediate lymphocytic type, and one was of the small cleaved lymphocytic type. In all cases, the small lymphoid cells of the mantle zones did not stain. A monoclonal population (IgM, lambda) of plasma cells and large lymphoid cells was demonstrated predominantly in the paracortical areas in one case. In all cases, small numbers of plasma cells and large lymphoid cells in the follicle centers stained in a polyclonal pattern, confirming the benign nature of the centers. These findings suggest that follicular lymphomas of the mantle-zone type are exceptions to the theory that follicular B-cell lymphomas are derived from follicular center cells. Apparently, the lymphoid cells of MZL home to the mantle zones of secondary follicles, where they surround, proliferate, and eventually obliterate residual benign germinal centers.     

Surface phenotyping, histology and the nature of non-Hodgkin lymphoma in 157 patients.

In a study of 157 patients with lymphoid malignancy, the phenotype of the tumour cells was correlated with the histological classification of the tumour using the Rappaport and the Kiel classifications. The markers used included E, Fc gamma, Fc micron (IgM) and C3d rosetting, estimation of SIg and CyIg, and tests for the expression of HTLA, Ia and ALL. Repeat biopsy specimens were studied in 23 of these patients. The phenotypic features of lymphoblastic malignancy indicated B-cell, T-cell and ALL-positive null-cell tumours in this group. Immunoblastic lymphomas were predominantly of non-capping B-cell type, but T-cell immunoblastic lymphoma occurred in 2 patients. Immunoblastic lymphomas of receptor-silent cells occur, and are ALL- and HTLA-negative. In the category of diffuse, poorly differentiated lymphocytic lymphomas, most cases are of centroblastic and centrocytic tumour of diffuse type, but pure centrocytic tumours and centroblastic tumours occur. The dominant phenotype in this group is of B cells expressing C3d receptors. Nodular poorly differentiated lymphocytic lymphomas (Rappaport) are classified as centroblastic and centrocytic follicular (Kiel) and most express SIg+ C3d+ phenotype. The frequency of this phenotype appeared the same in both diffuse and nodular poorly differentiated lymphocytic neoplasms. The Rappaport group of diffuse well-differentiated lymphocytic lymphoma includes 2 Kiel categories, malignant lymphoma lymphocytic, and malignant lymphoma lymphoplasmacytoid. Cells of the former tumour were considered to be immature B cells resembling those seen in CLL, and characteristically expressing SIg weakly, with a high frequency of single kappa light chain. Cells of the latter tumour are by contrast mature, and are related to the centroblastic and centrocytic follicular tumour by their histogenesis and phenotypic features. Repeat biopsy examinations indicate that T-cell predominance occurs in the prodromal phase of B-cell-predominant tumours of SIg+ C3d+ phenotype. It is concluded that non-Hodgkin lymphoma can be divided into 2 categories: (1) tumours of immature immunologically incompetent cells of lymphoblastic histology and with phenotypic features akin to T, B and Null-cell ALL, and (2) tumours of differentiated lymphocytes expressing the phenotypic features of B lymphocytes, with maturation arrested at one of several stages of an antigen-dependent immune response.     

B-cell lymphoma of 708 cases in Japan: incidence rates and clinical prognosis according to the REAL classification

New insights into the pathogenesis of lymphoid malignancies have been gained through novel techniques such as genetic, molecular and immunologic methods. Recently, based on those findings, a new classification system for lymphoid malignancies, known as the REAL classification, has been proposed. To clarify the relation between the histological classification and prognosis of B-cell lymphoid malignancies, we re-classified 708 cases. In all cases, the B-cell phenotype and/or genotype was confirmed by immunohistochemical staining and/or receptor gene analysis. The most common B-cell lymphoma types were diffuse large B-cell lymphoma (58.8%), follicular lymphoma (12.1%), marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) (9.0%) and mantle cell lymphoma (5.9%). Minor types were lymphoblastic lymphoma (3.4%), Burkitt's lymphoma (2.4%), nodal marginal zone lymphoma (2.1%), lymphoplasmacytic lymphoma (2.0%) and plasmacytoma (1.4%). Rare types were prolymphocytic lymphoma and splenic marginal zone lymphoma. Using overall survival rates, the various B-cell lymphoma types could be divided into three broad groups for prognostic purposes: (1) the low risk group consisted of follicular lymphoma, marginal zone lymphoma of MALT, nodal marginal zone lymphoma, plasmacytoma and lymphoplasmacytic lymphoma; (2) the intermediate risk group consisted of diffuse large B-cell lymphoma, Burkitt's lymphoma and mantle cell lymphoma; and (3) the high risk group consisted of lymphoblastic lymphoma. In MALT, the low grade type had a better prognosis than the high grade type. In diffuse large B-cell lymphoma, the common type had a better prognosis than the variant type, which mainly consisted of the immunoblastic lymphoma. The histological classification will have a benefit for the clinical approach.     

Large cell lymphomas. I. Differential diagnosis of centroblastic and B-immunoblastic subtypes by morphometry on histologic preparations

Thirty-three large cell lymphomas, 18 centroblastic or large noncleaved follicle center cell lymphomas and 15 B-immunoblastic lymphomas, diagnosed by morphology and marker studies, were studied with morphometry. The following parameters were studied: nuclear and nucleolar area, nuclear shape, cytoplasm-to-nucleus ratio, number of nucleoli per nuclear cross section, location of the nucleolus within the nucleus as expressed by the relative nucleolar eccentricity (rNE), and the percentage of morphometrically defined immunoblasts. Mean values and standard deviations (SDs) were calculated and statistically analyzed. The two groups differed significantly in their nucleolar area (mean and SD), cytoplasm-to-nucleus ratio (mean), number of nucleoli per nuclear cross section (mean and SD), rNE (mean), and percentage of immunoblasts. Using nonlinear discriminant analysis, the possibility of classifying individual cases with the studied parameters was investigated. Twenty-nine cases were reliably classified (88%); three were classified correctly, but with less than a 95% certainty, and 1 case was misclassified. The results indicate a spectrum ranging from centroblastic to B-immunoblastic lymphoma. Transition forms occur and can be accurately defined with morphometry.     

Reduced phagocytosis of apoptotic cells in malignant lymphoma

Efficient removal of lymphocytes undergoing programmed cell death (apoptosis) by macrophages plays an important role for the proper function of normal immune system. Furthermore, in malignant lymphoma, elimination of apoptotic tumor cells by phagocytes contributes to the anti-tumor immune response. It is unknown, however, whether macrophages in normal and malignant lymphoid tissues differ in their ability to recognize and remove apoptotic cells. Our present results demonstrate that normal and malignant lymphoid tissues differ according to the extent of the infiltration by macrophages. The highest densities of macrophages (p < 0.0001) were detected in diffuse large B-cell lymphoma, centroblastic (DLBCL-CB) and immunoblastic variants and Burkitt's lymphoma. The grade of the macrophage infiltration correlated with the proliferation rates of the tumors (p < 0.0001). Compared with normal lymphoid organs, malignant lymphoma contained lower percentages of apoptotic cells phagocytosed by tissue macrophages (p < 0.001). Of all lymphomas tested, mantle cell lymphoma and DLBCL-CB expressed the lowest percentages of phagocytosed apoptotic cells (p < 0.0001). Int. J. Cancer 75:675–679, 1998.© 1998 Wiley-Liss, Inc.     

Overexpression of heterogeneous nuclear ribonucleoprotein B1 in lymphoproliferative disorders: high expression in cells of follicular center origin

It is reported that overexpression of hnRNP A2 and B1 proteins is useful for detecting early cancers, and that B1, a splicing minor isoform of A2, is more specific than A2. The B1 expression is still undetermined in human lymphoid tissues. We quantitatively studied the B1 expression in 85 lymph node specimens, comprising reactive lymphoid hyperplasia (RLH; n=8), B-cell lymphoma (n=23), T-cell lymphoma (n=22), and metastatic carcinoma (n=32). Immunostaining and immunoblotting analyses with an anti-B1 monoclonal antibody, 2B2 were performed, and the two sets of results correlated with each other (p<0.05). In RLH specimens, B1 expression rate was significantly higher in follicular centers (FC; 44%) than in mantle zone (MZ; 15%) and paracortex (16%) (p<0.01). B1 expression was statistically higher in B-cell lymphoma than in T-cell lymphoma (p<0.01). In B-cell lymphomas, B1 expression rates were 51% in diffuse large B-cell lymphoma (DLBL; n=5) and 45% in follicular lymphoma (FL; n=16), and they were almost the same as that of the FC. Especially in DLBLs, CD10+ FC-origin lymphomas expressed greater amount of B1 than CD10- non-FC-origin lymphomas. B1 expression rate was low in mantle cell lymphoma (MCL; n=2) and similar to that of MZ in RLH. These results suggest that B1 expression is associated with differentiation in lymphoid tissue rather than transformation. B1 expression increases during the process of B-cell differentiation in the FC, and that high B1 expression is maintained in B-cell lymphomagenesis, especially in cells of FC-origin DLBL.