弥漫性大B细胞淋巴瘤的临床病理和免疫组织化学特征

目的 探讨弥漫性大B细胞淋巴瘤临床和病理组织特征以及免疫组织化学特异性抗体在其诊断和鉴别诊断中的价值。方法 收集60例弥漫性大B细胞淋巴瘤,总结其临床资料和病理学特点,用免疫组织化学EnVision^TM两步法标记白细胞共同抗原（LCA）、L26、BLA36、CD30和bcl-6抗体。结果 76．7％（46／60）弥漫性大B细胞淋巴瘤的发病年龄集中在40－70岁,淋巴结内外均可累及,90．0％（54／60）患者临床分期为Ⅱ（24／54）、Ⅲ（21／54）、Ⅳ（9／54）期。组织病理形态：中心母细胞淋巴瘤占88．3％（53／60）,免疫母细胞淋巴瘤占3．3％（2／60）,间变性大细胞淋巴瘤占3．3％（2／60）,富于T细胞的B细胞淋巴瘤占5．0％（3／60）。免疫标记LCA、L26、BLA36表达率为100．0％（60／60）,CD30表达率为3．3％（2／60）,bcl-6表达率为95．0％（57／60）。结论 弥漫性大B细胞淋巴瘤是一组异质性肿瘤,侵袭性大,必需结合其组织病理形态和特异抗体的免疫组织化学检测进行诊断和鉴别诊断。     

小B细胞恶性淋巴瘤病理鉴别诊断

小Ｂ细胞恶性淋巴瘤主要包括 :( 1)Ｂ细胞慢性淋巴细胞性白血病 /小淋巴细胞性淋巴瘤 (Ｂ ＣＬＬ/ＳＬＬ) ;( 2 )淋巴浆细胞性淋巴瘤 (ＬＰＬ) ;( 3 )套细胞淋巴瘤 (ＭＣＬ) ;( 4 )滤泡性淋巴瘤 (ＦＬ) ;( 5 )边缘区Ｂ细胞淋巴瘤 (ＭＺＬ)。其中ＭＺＬ包括三种类型 :粘膜相关淋巴组织型 (ＭＡＬＴ) ;淋巴结边缘区Ｂ细胞淋巴瘤 ;脾边缘区Ｂ细胞淋巴瘤 (ＳＭＺＬ)。ＷＨＯ恶性淋巴瘤新分类将这几种淋巴瘤都归于各自具有临床表现、形态学、免疫表型、遗传学特点的独立疾病[1] 。各种不同类型小Ｂ细胞恶性淋巴瘤的病理诊断和鉴别诊断常会遇到困…     

胃肠道B细胞性淋巴瘤形态学及免疫组织化学分析

目的 探讨胃肠道B细胞淋巴瘤的分类特点及病理诊断.方法 对194例胃肠道B细胞淋巴瘤分别进行HE染色和免疫组织化学染色,临床病理学观察内容包括:患者性别、年龄、肿瘤发生部位、浸润深度、组织结构(淋巴上皮病变、反应性/残留淋巴滤泡、凝固性坏死/坏死碎片、结节状生长方式).免疫组织化学染色采用EnVision二步法,每例标记9种抗体,包括:Pan B、Pan T、bcl-6、CD10、bcl-10、cyclin D1,末端脱氧核苷酸转移酶(TdT)、MUM1、Ki-67.结果 194例胃肠道B细胞淋巴瘤的男女之比为1.4∶1;发病年龄最小为8岁,最大为85岁.诊断为弥漫性大B细胞淋巴瘤(DLBBCL)128例(66.0%),其中DLBCL伴黏膜相关淋巴组织边缘区B细胞淋巴瘤(MALT淋巴瘤)成分的有16例;MALT淋巴瘤40例(20.6%);滤泡性淋巴瘤(FL)8例(4.1%);淋巴浆细胞性淋巴瘤(LPL)5例(2.6%);套细胞淋巴瘤(MCL)3例(1.6%);B淋巴母细胞性淋巴瘤(B-LBL)1例(0.5%);不能分型9例(4.6%,其中5例为活检标本).发生于胃100例(51.5%)、小肠43例(22.2%)、回盲部26例(13.4%)、阑尾1例(0.5%)、结肠21例(10.8%)、直肠3例(1.6%).163例手术切除标本中侵犯黏膜层20例(12.3%)、浅肌层20例(12.3%)、深肌层19例(11.6%)、全层104例(63.8%).见有淋巴上皮病变、反应性/残留淋巴滤泡、凝固性坏死/坏死碎片、结节状生长改变者分别为52、29、66和30例.免疫组织化学标记,194例均表达CD20而不表达CD3,不同类型的淋巴瘤对bcl-6、CD10、bcl-10、cycin D1、TdT、MUM1、Ki-67有不同程度的表达.结论 胃肠道B细胞淋巴瘤主要分大B细胞性和小B细胞性两大类,小B细胞性淋巴瘤的分型是病理诊断的难点.对胃肠道B细胞淋巴瘤的诊断方法提出了建议路线.     

富于T细胞/组织细胞的B细胞淋巴瘤病理形态、免疫表型及鉴别诊断

目的 探讨富于T细胞／组织细胞的B细胞淋巴瘤（TCRBCL）的组织学特点、免疫表型及鉴别诊断。方法 根据WHO淋巴瘤新分类（2001）回顾性研究245例霍奇金淋巴瘤,发现8例TCRBCL;另有5例会诊病例及3例外检诊断病例,共16例;应用免疫组织化学SP方法检测瘤细胞及背景细胞的免疫表型,所用抗体包括CD20、CD79a、CD3、CD8、CD45RO、CDl0、bcl-6、CD21、CD35、CD57、T细胞限制性细胞内抗原（TIA）-1、CD15、CD30、上皮膜抗原（EMA）、细胞周期蛋白（cyclin）D1、CD68、潜伏膜抗原（LMP）-1;4例行原位杂交检测EBER;4例应用聚合酶链反应技术检测瘤细胞IgH基因重排。结果 16例TCRBCL,男8例,女8例,男女比为1：1。年龄10～68岁,平均年龄40．3岁,中位年龄46．5岁。主要表现为淋巴结肿大,伴发热及肝脾肿大。临床分期Ⅱ期3例,Ⅲ期10例,Ⅳ期3例。组织学上见少数非典型性大细胞散在分布于小淋巴细胞和组织细胞背景中。免疫组织化学显示大细胞呈CD20、CD79a、EMA阳性,CD15、CD30阴性;背景小淋巴细胞呈CD3、CD45RO阳性,其中CD8、TIA-1阳性细胞多于CD57阳性细胞;组织细胞呈CD68阳性。CD21、CD35均为阴性反应。所检测的4例均为EBER1／2阴性,4例行IgH基因重排检测均可见单克隆条带。结论 TCRBCL有着独特的组织学和免疫表型特征,诊断应结合形态学和免疫表型特征。鉴别诊断包括霍奇金淋巴瘤、反应性淋巴组织增生、淋巴瘤样肉芽肿病等。     

免疫组织化学在淋巴瘤诊断和鉴别诊断中的应用

免疫组织化学在淋巴瘤诊断和鉴别诊断中的应用李甘地近年来，免疫组化技术有了长足的进步，如抗原恢复技术（ａｎｔｉｔｇｅｎｒｅｔｒｉｅｖａｌ，包括微波，高压锅处理等），ＬＳＡＢ法，以及新的单克隆抗体等等。加上原位杂交技术，ＰＣＲ技术等分子生物学技术在病理学...     

富于T细胞/组织细胞的B细胞淋巴瘤的诊断

目的：探讨富于T细胞／组织细胞B细胞淋巴瘤（TCRBCL）的诊断。方法：用S－P石蜡免疫组化法检测22例依据形态学诊断的霍奇金淋巴瘤细胞和背景细胞的免疫表型。结果：4／22例是TCRBCL,3例富于T小淋巴细胞,1例富含组织细胞;瘤细胞3例呈中心母细胞样和免疫母细胞样。1例呈腔隙型细胞样,弥漫散在分布。免疫组化瘤细胞呈CD20（＋）、CD15（－）、CD30（－）、CD21（－）、vimentin(-)。背景细胞CD45RO（＋）／CD68（＋）细胞占绝对优势,为浸润细胞的70％－90％;CD20（＋）细胞散在,CD57（＋）稀少。16例为经典型霍奇金淋巴瘤（CHL）,瘤细胞为CD15（＋）（75％）、CD30（＋）（100％）、vimentin( )(19%)、CD21（－）、CD20（－）及CD45（－）,背景细胞CD45RO（＋）和CD20（＋）数量基本相等,CD57（＋）较少。1例为结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）,瘤细胞呈CD20（＋）、CD45（＋）、CD30（－）、CD15（－）,而背景细胞中CD57（＋）较多。结论：石蜡免疫组化在TCRBCL诊断中起重要作用,而且也应用于CHL、NLPHL及TCRBCL间鉴别诊断。     

间变性大细胞淋巴瘤形态学及免疫表型观察

目的：探讨间变性大细胞淋巴瘤（ALCL）的形态学和免疫表型特征。方法：对6例ALCL和2例弥温性大B细胞淋巴瘤（DLBCL）进行形态学和免疫组织化学染色（ABC法）观察。结果：6例ALCL中，普通型2例、淋巴组织细胞型2例、ALK－变型2例，均可见单型性或多形性的标志性大细胞。普通型和ALK－变型大细胞沿淋巴窦内生长，而淋巴组织细胞型大细胞则呈散在分布；2例DLBCL形态上颇似ALCL；6例ALCL均为T细胞，CD30＋，儿童患者共同表达ALK＋和EMA＋，年长者则ALK－和EMA－。2例DLBCL均为B细胞，ALK＋、CD30－和EMA－。结论：不论何型ALCL，均可见CD30＋的标志性大细胞，淋巴窦内生长多见于普通型和ALK－变型。ALCK均为T细胞，儿童常有ALK和EMA共同表达，年长者则ALK和EMA－。DLBCL的免疫表型不同于ALCL。     

表达间变性淋巴瘤激酶蛋白的弥漫性大B细胞淋巴瘤的临床病理和免疫表型观察

目的探讨表达间变性淋巴瘤激酶（ALK）蛋白的弥漫性大B细胞淋巴瘤（DLBCL）的临床病理特点。方法根据2001年版WHO淋巴造血组织肿瘤分类收集945例DLBCL,以LSAB法作ALK-11染色。对阳性病例再用EnVision法作ALK-11染色,仅EnVision法阳性病例为最终纳入病例。对纳入病例标本用LSAB法加做CD20、CD3、CD30、上皮细胞膜抗原（EMA）、粒酶B、T细胞胞质内抗原（TIA）-1和浆细胞（PC）抗体等免疫表型检测,进行IgH基因重排检测并收集随访资料。结果945例弥漫性大B细胞淋巴瘤中仅5例表达ALK蛋白。4例男性,1例女性,年龄34—72岁,全部原发于淋巴结。临床分期Ⅰ期1例、Ⅱ期2例、Ⅲ期2例。5例随访最长32个月,最短4个月。随访截止时死亡4例,死亡病例最长存活时间32个月。表达ALK蛋白的DLBCL包括中心母细胞性2例、免疫母细胞性1例、间变性1例、浆母细胞性1例;2例中心母细胞性、1例免疫母细胞性和1例间变性均表达CD20。浆母细胞性表达K轻链而不表达CD20。5例均检测到IgH基因重排。ALK蛋白表达：在CD20阳性4例中,1例免疫母细胞性为胞膜和胞质阳性,2例中心母细胞性和1例间变性为胞质颗粒状阳性;1例浆母细胞性为胞核和胞质弥漫阳性。结论ALK蛋白阳性表达DLBLC是一种罕见的,临床过程具侵袭性且预后较差的淋巴瘤,可见于浆母细胞性、中心母细胞性、免疫母细胞性和间变性的大B细胞淋巴瘤。发现1例ALK蛋白表达于胞膜和胞质。     

77例胃肠道间质肿瘤的病理形态学及免疫组化研究

目的：研究胃肠道间质瘤（GIST）的病理形态及免疫组化特点,方法：应用光镜观察77例GIST的形态特征,用免疫组化S－P法检测c-kit(CD117),CD34,vimentin,SMA及S－100蛋白在GIST中的表达情况。结果：GIST的瘤细胞较经典的平滑肌瘤更丰富,胞质嗜酸较弱,瘤细胞为酸形或上皮样,或酸形与上皮样细胞混合存在,胞质内常见空泡形成;排列成交织刺状、弥散片状、栅栏状或轮辐状、较为特征的是细胞团巢形成。常见间质或见管壁玻变。原发于肠系膜者恶性潜力较高。CD117和CD34的阳性率分别为90％和92％,结论：胃肠道间质肿瘤有较为特独的组织学形态,CD117和CD34联合使用可协助鉴别诊断。     

Primary gastric lymphomas: Morphologic, immunohistochemical and immunogenetic analyses

Morphologic, lmmunohistochemical and lmmunogenetic studies were performed on 28 cases of primary gastric lymphoma from fresh frozen tissue. Eight cases were diagnosed as diffuse large B-cell lymphoma, four as follicular center lymphoma (follicular), five as mucosa-associated lymphoid tissue (MALT) lymphoma, three as plasmacytoma, and three as T-cell lymphoma, two as mantle cell lymphoma, one as follicular center lymphoma (diffuse, predominantly small cell), and one as lymphoplasmacytoid lymphoma, and one as Hodgkin's disease.
From lmmunohistochemical studies, four types of morphologically similar low-grade lymphomas can be differentiated by a combination of various monoclonal antibodies. Cases of diffuse large B-cell lymphoma may have a germinal center origin. We observed lympho-epithelial lesions in cases of non-MALT lymphomas. We therefore consider that the current diagnostic criterion for MALT lymphoma may not always be valid.
Except for cases of T-cell lymphoma and Hodgkin's disease, 17 out of 22 cases revealed clonal rearrangement bands of the JH gene. In situ hybridization (ISH) and polymerase chain reaction (PCR) studies revealed the presence of Epstein-Barr (EB) virus genomes in two and three cases, respectively. Epstein-Barr virus may play a role in lympho-magenesis, although on relatively rare occasions.     

原发淋巴结边缘区淋巴瘤临床病理分析

目的：研究淋巴结MZL形态特征、诊断要点和鉴别诊断,为临床治疗和预后提供依据,方法：采用常规制片、免疫组化ABC法标记,光镜观察。结果：10例淋巴结MZL男性6例,女性4例,以淋巴结缓慢增大为特征,而无肝脾肿大,外周血未见异常。病理形态分为：边缘区增生型2例,结节型4例,弥漫型2例和母细胞样型2型。细胞类型：CCL细胞型5例,MBC型6例,淋巴浆细胞型2例,母细胞样型2例,10例均经免疫组化证实。结论：淋巴结MZL与MALT型淋巴瘤形态、免疫表型和起源相似。由于淋巴结组织结构特点,MZL有特殊性。     

The challenge of the microenvironment in B-cell lymphomas

B-cell non-Hodgkin lymphomas (B-NHL) represent the most common malignant lymphoid neoplasms, with the majority of these arising from germinal centre or post-germinal centre B cells, due to (at least) a disruption of the different phases of normal B-cell development. The most common B-cell lymphoma subtypes include follicular lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma and mantle cell lymphoma. As with other malignancies, it has been demonstrated that the development and progression of B-cell lymphomas involves complex interactions between the neoplastic B-cells and the surrounding microenvironment, including stromal cells, the intratumoral vasculature, the various types of macrophages, as well as T-cells, including regulatory T-cells (also termed T-regs). The complex communications between the cell populations involves interplay between chemokines, chemokine receptors and adhesion molecules, and the balance between these determines whether there is a tumour cell growth promotion or inhibition. The demonstration of the importance of the microenvironment in B-NHL has been shown recently using methodologies such as gene expression profiling, and has been validated in some B-NHL lymphoma subtypes using other techniques, such as immunohistochemistry. This is particularly in the case of follicular lymphomas, in which both T-regs and macrophages have been demonstrated to have prognostic value. As such, the microenvironment of B-cell lymphomas represents a challenge to the development of therapeutic agents, requiring re-direction and inclusion of these non-neoplastic supportive cells into future treatment strategies.     

An immunohistochemical study of non-Hodgkin''s lymphomas: correlation of morphological appearances and immunophenotype in 148 cases

An unselected series of 148 cases of non-Hodgkin's lymphoma has been studied by immunohistological methods. In each case, the morphological features displayed in paraffin sections were correlated with the immunophenotype, determined using a panel of monoclonal antibodies. Of the lymphomas 82% were B-cell type, 28% of follicle centre cell origin, 17% lymphocytic or immunocytic and 30% of large cell type. All the B-cell tumours expressed pan-B antigen, and nearly all HLA-DR. In most, light chain monoclonality was demonstrable. Nearly all had moderate to large numbers of T-cells of both subtypes interspersed amongst the B-lymphocytes. Follicle centre cell tumours expressed surface IgM and IgD and had numerous dendritic reticulum cells. Lymphocytic and immunocytic lymphoma expressed IgM but less IgD, and had fewer or no dendritic reticulum cells. Large cell lymphoma expressed either no immunoglobulin or only IgM, and contained ragged dendritic reticulum cells, giving the appearance of 'burnt-out' follicles. T-cell lymphomas usually showed a clear preponderance of either helper or suppressor subtype. Additionally, they contained residual B-cells and sometimes germinal centres. Only 3% of this series were 'non-B, non-T', and only one case HLA-DR negative, so the 'null' or 'unclassifiable' group is very small when information from antibody markers is available.     

Gastric and intestinal diffuse large B-cell lymphomas are clinically and immunophenotypically different. An immunohistochemical and clinical study

AIMS: To determine the immunophenotype of gastric and intestinal diffuse large B-cell lymphomas and investigate the clinical significance of patterns of antigen expression. METHODS AND RESULTS: Immunohistochemistry was performed for detection of CD10, Bcl-6, Bcl-2, MUM1 and p53 in paraffin-embedded tissue from 29 patients with primary diffuse large B-cell lymphoma of the stomach and intestine. Statistical analysis was performed using chi(2) and Fisher's exact tests. Survival data were analysed by the Kaplan-Meier method and compared using a log rank test. Thirteen of the 29 cases were of germinal centre phenotype (CD10+ or CD10-, Bcl-6+ and MUM1-). Sixteen were of activated B-cell phenotype (all CD10- and either Bcl-6-, or Bcl-6+ and MUM1+). Sixteen cases showed Bcl-2 expression. There was a statistically significant difference (P < 0.05) in immunophenotype of the neoplastic cells relating to tumour site. Of 15 gastric lymphomas, 11 were of activated B-cell phenotype and 9/14 intestinal tumours were of germinal centre phenotype. No significant survival difference was found between groups with regard to expression of any of the antigens investigated. CONCLUSIONS: Primary gastric and intestinal large cell lymphomas appear to show different patterns of antigen expression. This suggests that these tumours arise by different mechanisms and/or from different causes. Gastric diffuse large B-cell lymphomas are usually of activated B-cell phenotype that may reflect a relationship with low-grade gastric lymphomas of marginal zone type. Intestinal diffuse large B-cell lymphomas usually show a germinal centre phenotype, suggesting an origin from germinal centre B cells. In this study the tumour immunophenotype was not associated with any difference in survival.     

Marginal zone and mantle cell lymphomas: assessment of cytomorphology in subtyping small B-cell lymphomas

The diagnosis of malignant lymphomas by fine-needle aspiration biopsy (FNAB) is increasing in utilization. The cytomorphologic distinction among the small B-cell lymphomas may be quite difficult. We are unaware of anyone who has compared directly mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL) in FNAB. Our major goal was to examine the cytomorphologic attributes of MCL and MZL and to look for features distinctive of or suggestive of either neoplasm. Seven immunophenotypic MCL and seven immunophenotypic MZL aspirates were evaluated for a number of cytomorphologic features in direct smears. Features favoring MCL include a relatively monomorphic cellular population, prominent nuclear membrane contour irregularities, and mitotic figures. Conversely, a polymorphic cellular population suggested MZL. However, due to extensive overlap of specific cytologic features, the two lymphomas cannot be definitively distinguished based solely on cytomorphology. Although there are cytomorphologic attributes suggestive of either MCL or MZL, considerable overlap exists. Based on an individual case basis, the distinction cannot be made reliably by morphology alone; ancillary studies, e.g., immunophenotyping, are essential.     

脾边缘区B细胞淋巴瘤临床病理和免疫组化研究

目的：研究脾边缘区B细胞淋巴瘤（SMZL）临床病理和免疫组化特征,为临床治疗和预后提供依据。方法：组织常规制片,应用ABC免疫组化法标记,光镜观察。结果：6例SMZL以脾肿大为主要临床特征,无全身淋巴结肿大,仅1例外围血和骨髓内查出异形淋巴细胞。病理形态显示结节型4例,弥漫型2例,细胞呈现CCL细胞型3例,MBC型2例,淋巴浆细胞型1例,6例均经免疫组化证实。结论：SMZL与MALT型淋巴瘤／淋巴结边缘区B细胞淋巴瘤组织形态和免疫表型相似,但并不完全相同,SMZL与其它B细胞起源的淋巴瘤临床治疗和预后亦不相同。     

Primary lymphomas of the lung: morphological, immunohistochemical and clinical features

Sixty-two cases of primary malignant lymphoma of the were investigated. Fifty-eight lymphomas were of B- and two of T-cell type. Two cases of high-grade homa could not be further classified. The largest group (43 cases) consisted of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue. These showed features similar to low-grade B-cell lymphomas of the mucosa-associated lymphoid tissue of the stomach. The low-grade lymphomas showed a peak occurrence in the sixth decade, the high-grade lymphomas in venth decade. Males predominated slightly. Three-quarters of the patients with low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue showed solitary or multiple sharply defined nodules of the lung. The prognosis of the B-cell-derived lung lymphomas without constitutional symptoms was relatively favourable, regardless of whether they were of low- or high-grade malignancy, whereas patients with constitutional symptoms and the two patients with T-cell lymphomas showed a bad prognosis. However, recurrences and metastases in the lung, stomach, lymph nodes and salivary glands were seen in about 46% of the cases of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue.     

扁桃体B细胞淋巴瘤的病理特征观察

一、材料和方法 收集我院2001年1月-2005年12月病理活检诊断的扁桃体淋巴瘤23例,筛选19例B细胞淋巴瘤,总结其临床表现。病理特征,治疗方式和临床生存情况。标本均经4%的甲醛固定,石蜡包埋,HE染色,由两位资深病理医师行形态学观察,淋巴瘤分类参照2001年WHO关于淋巴造血组织肿瘤分类。