胃肠MALT淋巴瘤中bcl-10 mRNA和蛋白的表达

目的　探讨bcl- 10基因在胃肠黏膜相关淋巴组织(MALT)淋巴瘤中的表达情况及意义。方法　采用免疫组化S P 法及原位杂交技术检测40例胃肠MALT淋巴瘤和14例正常淋巴结中bcl- 10基因的表达。结果　40例MALT淋巴瘤中有36 例(90.0%)表达bcl- 10蛋白,其中21例仅在胞质表达,15例在胞质胞核同时表达;39例(97.5%)表达bcl 10mRNA。bcl -10 蛋白与mRNA表达之间差异无统计学意义(P>0.05)。MALT淋巴瘤临床分期与bcl- 10蛋白核表达明显相关(P<0.01)。14 例淋巴结中,8例(57.1%)表达bcl -10蛋白。淋巴滤泡内生发中心B细胞呈高度表达,边缘区B细胞中等强度表达,套区细胞 微弱表达。结论　bcl -10的高度表达在MALT淋巴瘤发生发展可能起着重要作用。bcl -10蛋白核表达与进展期MALT淋巴瘤 相关。bcl -10蛋白在淋巴滤泡各区域的表达差异提示它对B细胞分化成熟有着重要意义。     

MALT淋巴瘤中bcl-10与NF-κB的表达及其意义探讨

目的研究在黏膜相关淋巴组织结外边缘区淋巴瘤（extranodal marginal zone Bcell lymphoma of mucosa associated lymphoid tissue,MALT淋巴瘤）中bcl-10核表达和NF-KB／p65活化的关系,探讨bcl-10核表达对MALT淋巴瘤发生的价值。方法收集不同部位MALT淋巴瘤74例（包括29例胃、16例肠、15例眼眶、8例肺、2例唾液腺、1例甲状腺、1例唇、1例胸腺和1例附睾）,用免疫组化EnVision法检测bcl-10和NF—κB／p65的表达。结果在74例MALT淋巴瘤中,bcl-10的阳性率为94．6％（70／74）,其中胞质阳性率为52．7％（39／74）,胞核阳性率为41．9％（31／74）;NF—κB／p65的阳性率为100％（74／74）,其中细胞质阳性率47．3％（35／74）,细胞核和细胞质共同阳性率占52．7％（39／74）。统计结果显示bcl-10核阳性与NF—κB核表达间有显著相关性（P〈0．001）。结论在MALT淋巴瘤中,bcl-10核表达对NF—κB活化有显著影响,可能是促进细胞增生、导致肿瘤形成的重要因素。     

bcl—2癌基因蛋白在滤泡性淋巴瘤中的表达及意义

为了探讨滤泡性淋巴瘤与淋巴滤泡反应性增生的鉴别诊断方法，应用免疫组化ABC方法，对22例滤泡性淋巴瘤和14例淋巴滤泡反应性增生进行bcl－2肿瘤基因蛋白表达测定。结果显示22例滤泡性淋巴瘤中，19例bcl-2阳性，3例bcl-2阴性；14例淋巴滤泡反应性增生中，12例bcl-2阴性，2例bcl-2弱阳性。X2检验两者差异有显著性（P＜0．01）。结果提示bcl-2对滤泡性淋巴瘤与淋巴滤泡反应性增生具有重要的鉴别诊断意义。     

bcl-10蛋白在MALT淋巴瘤中的表达

目的 观察bcl-10蛋白在黏膜相关淋巴组织样结外边缘区B细胞淋巴瘤（MALT淋巴瘤）中的表达及其意义。方 法对62例MALT淋巴瘤进行回顾性研究,采用免疫组织化学SP法检测bcl-10及Ki-67的表达。结果 62例MALT淋巴瘤中,60例（96．8％）表达bcl-10,其中胞核和胞质同时表达33例（53．2％）,仅有胞质表达27例（43．6％）。10例桥本甲状腺炎bcl-10均表达于胞质。bcl-10核阳性组发病平均年龄（51．4岁）比bcl-10核阴性组（56．6岁）小5．2岁,bcl-10核阳性组以男性占优势,bcl-10核阴性组以女性发病较多。不同解剖部位核阳性表达率差异有统计学意义（P〈0．05）,肺和胃肠道检出率较高,而甲状腺较少;不同临床分期之间核阳性表达率差异P〉0．05;bcl-10核表达与不表达两组在肿瘤细胞形态上差异P〉0．05;在胃肠道40例病例中,不同浸润组别的核阳性率表达差异P〈0．05,浸出浆膜外的病例核阳性率高于局限在浆膜以内的病例;bcl-10核阳性组与核阴性组Ki-67增殖指数的差异无统计学意义。随访52例（83．9％）,bcl-10核阳性组（29例,96．3％）与核阴性组（23例,66．4％）的5年生存率差异无统计学意义。结论 bcl-10在MALT淋巴瘤中主要有胞质和胞核两种表达模式;胞核的表达在不同解剖部位之间检出率不同,并与肿瘤的浸润深度相关。bcl-10在MALT淋巴瘤的诊断、治疗和预后方面有一定的提示作用。     

肺黏膜相关淋巴组织边缘区B细胞淋巴瘤及良性淋巴组织增生性疾病的临床病理分析

目的 研究肺原发性黏膜相关淋巴组织边缘区B细胞(MALT)淋巴瘤及良性淋巴组织增生性疾病的临床病理形态、免疫组织化学表型和B细胞重链基因重排,比较肺MALT淋巴瘤和良性淋巴组织增生性疾病的差异.方法 回顾性的分析原发性肺MALT淋巴瘤13例,7例肺良性淋巴组织增生性疾病资料.对标本行常规HE染色,EnVision免疫组织化学染色(抗体包括AE1/AE3、CD20、CD79α、CD3、CD5、CD10、CD21、bel-2、bcl-6、cyclinD-1)及免疫球蛋白重链IgH基因重排检测.结果 13例肺MALT淋巴瘤,细胞成分多样,分别由不同比例的小淋巴细胞样细胞、中心细胞样细胞、单核样B细胞组成,常伴有浆细胞分化.肿瘤细胞以弥漫性和滤泡边缘区排列为主,常见反应性淋巴滤泡和滤泡中心的植入.肿瘤细胞呈串珠状直接侵犯肺泡间隔和沿支气管血管束向周边及肺膜扩散.MALT淋巴瘤中,均未见坏死.9例可见肿瘤细胞侵犯血管壁,6例可见胸膜累及,2例肺门淋巴结侵犯.9例肺MALT淋巴瘤可见淋巴上皮样病变,免疫组织化学显示上皮细胞内的淋巴细胞CD20阳性,CD3阴性.7例肺良性淋巴组织增生性疾病,2例可见淋巴上皮样病变,免疫组织化学显示,其淋巴上皮样病变内的淋巴细胞,部分CD20阳性,部分CD3阳性.9例肺MALT淋巴瘤进行了免疫球蛋白重链IgH基因重排,8例阳性;7例良性淋巴组织增生性疾病均为阴性.结论 肺MALT淋巴瘤在细胞组成和排列上与其他部位结外MALT淋巴瘤相同,肿瘤细胞呈串珠状直接侵犯肺泡间隔和沿支气管血管束向周边及肺膜扩散.在肺内淋巴上皮样病变常见于MALT淋巴瘤,并有助于诊断,但并非其特异性病变,一些肺的反应性淋巴组织增生也可出现,用免疫组织化学有助于区别两种病变.免疫球蛋白重链IgH基因重排可以帮助鉴别肺MALT淋巴瘤和良性淋巴组织增生性疾病.     

应用半套式聚合酶链反应检测非何杰金淋巴瘤bcl—2／JH融合基因

为研究我国非何杰金淋巴瘤（NHL）患者bcl－2基因重排的发生情况，以及其可能的临床应用价值，应用半套式聚合酶链反应（semi－nestedPCR）检测45例非何杰金淋巴瘤bcl-2／JH融合基因，发现12例阳性，其中15例滤泡性淋巴瘤中有9例阳性（60％）；30例弥漫性淋巴瘤中3例阳性（10％），5例反应性淋巴组织增生者阴性。并发现bcl-2基因断裂点绝大部分位于主要断裂区（11／1291．7％），少数位于次要断裂区（1／12，8．3％）。结果提示，形成bcl-2／JH融基因是B细胞非何杰金淋巴瘤发生的重要病因，检测bcl－2／JH融合基因对鉴别淋巴组织的良恶性增生、明确克隆来源，提示预后及检测微小残留病灶均有重要意义。     

弥漫性大B细胞淋巴瘤中bcl-6基因5′非编码区突变分析

目的 观察中国人弥漫性大B细胞淋巴瘤(DLBCL)中bcl-6基因5’非编码区的突变情况,并探讨其作用。方法选用bcl-6基因5‘非编码区的高频突变区2对引物,对38例DLBCL、2例淋巴结反应性增生、5例滤泡性淋巴瘤及5例T细胞淋巴瘤标本,于显微镜下提取淋巴瘤细胞,做聚合酶链反应(PCR)、直接测序分析。结果在2例淋巴结反应增生的边缘区、5例T细胞淋巴瘤及5例滤泡性淋巴瘤中均未发现有该范围内的突变,1例反应性增生的生发中心细胞中有突变,38例DLBCL中7例(18．4％)有突变。突变类型主要是碱基替代和点插入。结论在中国人DLBCL中bcl-6非编码区的突变阳性率较低（与国外资料比较）,它可能在一定程度上参与DLBCL的发生和发展。     

血管免疫母细胞性T细胞淋巴瘤的形态及免疫表型研究

目的 研究血管免疫母细胞性T细胞淋巴瘤(AITL)形态学特点、特异性标志物,并探讨AITL中滤泡树突状细胞网的增生状况及其起源.方法 对29例AITL行bcl-6、CD10、CXCL13、CD21染色(EliVision法)及bcl-6/CD3、CD10/CD21及CD10/CD20双重染色,并选取外周T细胞淋巴瘤,非特殊类型(PTL-U);结外NK/T细胞淋巴瘤,鼻型;间变性大细胞淋巴瘤(ALCL);肠病性T细胞淋巴瘤(ETTL);皮下脂膜炎性T细胞淋巴瘤及淋巴结反应性增生作为对照.结果 (1)22例(75.9%)AITL表达CD10,对照组除1例PTL-U外均阴性;24例(82.8%)AITL表达CXCL13,所有PTL-u均阴性;而AITL中bcl-6的表达情况和PTL-u及反应性增生病例有一定程度的交叉.(2)29例AITL显示特征性的CD21阳性滤泡树突状细胞网增生,4例具有明显生发中心的病例,2例显示增生的滤泡树突状细胞网覆盖并超过生发中心.结论 AITL具有典型的形态学变化,CD10和CXCL13是AITL特异性标志物,而bcl-6不具有特异性;AITL中增生的滤泡树突状细胞网可能部分起源于生发中心.     

淋巴组织增生性病变中β Ⅲ-微管蛋白的表达及意义

目的 探讨βⅢ-微管蛋白(βⅢ-tubulin,TUBB3)在反应性增生淋巴结和淋巴瘤中的表达,分析TUBB3在淋巴瘤诊断与鉴别诊断中的价值。方法 采用免疫组化EnVision法检测20例反应性增生淋巴结和126例非霍奇金淋巴瘤(包括88例B细胞性淋巴瘤和38例T细胞性和NK细胞性淋巴瘤)中TUBB3的表达,并复习相关文献。结果 反应性增生淋巴结中,TUBB3高度局限于淋巴滤泡生发中心内。小淋巴细胞性淋巴瘤(small lymphocytic lymphoma,SLL)和结外黏膜相关性淋巴组织边缘区淋巴瘤(extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue,MALToma)中,除了残留的淋巴滤泡表达TUBB3外,肿瘤细胞均不表达TUBB3。5例套细胞淋巴瘤(mantle cell lymphoma,MCL)中,1例表达TUBB3。24例低级别滤泡性淋巴瘤(follicular lymphoma,FL)中,8例表达TUBB3。39例弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中,15例表达TUBB3,TUBB3在生发中心样(germinal center B-like,GCB)型中的表达高于非生发中心样(non-germinal central B-like,non-GCB)型,但差异无统计学意义(P0.05)。15例外周T细胞性淋巴瘤(非特指型)中,TUBB3阳性3例;15例NK/T细胞性淋巴瘤、3例间变性大细胞性淋巴瘤(anaplastic large cell lymphoma,ALCL)和5例血管免疫母细胞性T细胞性淋巴瘤(angioimmunoblastic T-cell lymphoma,AITL)均不表达TUBB3。TUBB3在DLBCL中的阳性率高于成熟性小B细胞性淋巴瘤(P0.05)。TUBB3在B细胞性淋巴瘤中的阳性率明显高于其在NK细胞/T细胞性淋巴瘤中的阳性率(P 0.05)。结论TUBB3高度局限于反应性增生淋巴结的淋巴滤泡生发中心内,有助于低级别FL、SLL和MALToma的鉴别诊断。     

肝脏原发黏膜相关淋巴组织结外边缘区淋巴瘤及肝脏假性淋巴瘤的临床病理特征北大核心CSCD

目的 探讨肝脏原发黏膜相关淋巴组织结外边缘区（MALT）淋巴瘤和肝脏假性淋巴瘤的临床病理特征、鉴别诊断.方法 收集2012年1月至2017年3月就诊于南京医科大学第一附属医院的3例肝脏原发MALT淋巴瘤和2例肝脏假性淋巴瘤患者资料,行HE和免疫组织化学EnVision法染色观察组织学形态,采用原位杂交法检测EB病毒编码小RNA,采用荧光原位杂交（FISH）技术检测MALT1基因,采用免疫球蛋白（Ig）基因重排检测技术分析克隆性基因重排情况,并复习相关文献.结果 3例MALT淋巴瘤,肿瘤结节状浸润汇管区,浸润及包绕周围肝组织并融合成结节或片状,多量小胆管陷入、散布其间伴淋巴上皮病变.瘤细胞围绕增生的淋巴滤泡,主要为中心细胞样和单核样B细胞,其中1例可见簇状上皮样组织细胞.瘤细胞CD20和PAX5阳性,不表达CD5、CD23、CD10、bcl-6及cyclin D1.2例肝脏假性淋巴瘤,病灶呈境界清楚的孤立性结节,其中1例可见部分纤维包膜.小胆管仅见于病灶周边,且缺乏淋巴上皮病变.淋巴组织增生以淋巴滤泡增生为主,缺乏明显异型性和单核样B细胞形态.免疫组织化学染色示增生的淋巴组织由B细胞和T细胞混合.Ig基因重排检测发现,3例肝脏原发MALT淋巴瘤呈单克隆性B细胞增生,而在2例假性淋巴瘤示多克隆性增生.FISH检测发现2例MALT淋巴瘤存在MALT1基因断裂.所有病例EBER原位杂交均为阴性.结论 肝脏原发MALT淋巴瘤和假性淋巴瘤均属肝脏罕见的淋巴组织增生性病变,两者具有重叠的组织学形态及免疫表型特征,互为首要鉴别诊断.综合分析组织形态、免疫表型和基因重排有助于区分两者.     

Marginal zone B-Cell lymphoma among primary B-Cell lymphoma of Waldeyer's ring: histopathologic and immunohistochemical study of 16 tonsillectomy specimens

Two subtypes of marginal zone B-cell lymphoma (eg, mucosa-associated lymphoid tissue [MALT] type and splenic type) have been reported in the lymph node. To determine the presence or absence of marginal zone B-cell lymphoma of MALT type and the splenic type among Waldeyer's ring (WR) lymphomas, 16 tonsillectomy specimens were studied. Ten cases (63%) were marginal zone B-cell lymphoma. Among marginal zone B-cell lymphoma, 7 were the MALT type and the remaining 3 cases of marginal zone B-cell lymphoma were the splenic type. Moreover, 4 cases of 7 MALT-type lymphomas contained numerous large cells (diffuse large B-cell lymphoma arising from a low-grade marginal zone B-cell lymphoma of MALT type). The low incidence of primary mucosa-associated lymphoid tissue type lymphoma of WR in previous reports may be because it is difficult to correctly identify the characteristic histologic findings of MALT-type lymphoma because of the small biopsy size.     

Mutational analysis of the 5' noncoding region of the bcl-6 gene in primary gastric lymphomas.

Bcl-6 mRNA and protein are frequently expressed in the transformed counterparts of the germinal center B-cells, diffuse large B-cell lymphoma and follicular lymphoma, irrespective of the gene rearrangements. Most of the primary gastric lymphomas are thought to be of mucosa-associated lymphoid tissue (MALT) origin, and neither bcl-6 gene rearrangement nor protein expression is found in low-grade gastric lymphomas of the MALT type as in normal marginal zone cells. However, bcl-6 protein expression was identified in high-grade gastric lymphomas, suggesting its role in high-grade transformation. In this study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis for bcl-6 primer was performed in order to ascertain the molecular mechanisms of bcl-6 protein expression in primary gastric lymphomas. A total 31 cases of gastric lymphoma were classified into low-grade gastric lymphomas of MALT type (n = 13), high-grade gastric lymphomas of MALT type (n = 6) and gastric diffuse large B-cell lymphomas (n = 12). Bcl-6 mutations were observed in 11 of 13 (84.6%) low-grade gastric lymphomas of the MALT type and in 8 of 12 (66.7%) diffuse large B-cell gastric lymphomas. In 6 cases of the high-grade gastric lymphomas of the MALT type, both the low- and high-grade components demonstrated the same frequency (3/6, 50%) of mutations. The tissue obtained from the marginal zone of Peyer's patch by microdissection technique revealed no bcl-6 mutations by the PCR-SSCP analysis. These findings suggest that the acquisition process of bcl-6 mutations by the marginal zone cells may be involved in the lymphomagenesis of the stomach, but our data does not explain the reason why bcl-6 protein is expressed only in high-grade gastric lymphomas.     

Paediatric marginal zone lymphoma and hyperplasia

Marginal zone lymphomas (MZL) are low-grade B-cell lymphomas arising from post-germinal memory B-cells occurring in adults with a slight female predilection. They are sub-categorized into nodal (NMZL), extra-nodal/mucosa-associated lymphoid tissue (MALT) and splenic (SMZL). MALT lymphomas are the most common (70%) followed by SMZL (20%) and NMZL (10%). Histologic transformation into aggressive B-cell lymphoma can rarely occur. MZL is extremely uncommon in the paediatric population and unlike in adults, is predominantly nodal. Paediatric NMZL (pNMZL) is an indolent, low-grade lymphoma with unique clinical and morphologic features. In contrast paediatric MALT lymphoma and SMZL are extremely uncommon and resemble their adult counterparts. Paediatric marginal zone lymphomas must be differentiated from paediatric-type follicular lymphoma (PFL) and marginal zone hyperplasia (MZH) of lymph nodes and mucosa-associated lymphoid tissue. This review summarizes the pathogenesis, morphology, genetic features of paediatric MZL and marginal zone hyperplasia. Recognition of these entities is important to avoid unnecessary therapy.     

BCL10 expression in normal and neoplastic lymphoid tissue. Nuclear localization in MALT lymphoma

BCL10 is an apoptotic regulatory molecule identified through its direct involvement in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma. We examined BCL10 protein expression in various normal tissues and B-cell lymphomas by immunohistochemistry of formalin-fixed and paraffin-embedded tissues using mouse BCL10 monoclonal antibodies. BCL10 protein was expressed in lymphoid tissue but not in 21 various other tissues with the exception of breast. In normal B-cell follicles, the protein was expressed abundantly in the germinal center B cells, moderately in the marginal zone, but only weakly in the mantle zone B cells. Irrespective of their stage of B-cell maturation, BCL10 was predominantly expressed in the cytoplasm. In contrast, each of the four MALT lymphomas with t(1;14)(p22;q32) showed strong BCL10 expression in both the nucleus and cytoplasm. Twenty of 36 (55%) MALT lymphomas lacking the translocation exhibited BCL10 expression in both the nucleus and cytoplasm although at a much lower level, whereas the remaining 16 cases displayed only cytoplasmic BCL10. Unlike MALT lymphoma, both follicular and mantle cell lymphomas generally displayed BCL10 expression compatible to their normal cell counterparts. Our results show differential expression of BCL10 protein among various B-cell populations of the B-cell follicle, indicating its importance in B-cell maturation. The subcellular localization of BCL10 was frequently altered in MALT lymphoma in comparison with its normal cell counterparts, suggesting that ectopic BCL10 expression may be important in the development of this type of tumor.     

Significance of C4d deposition in the follicular lymphoma and MALT lymphoma and their relationship with follicular dendritic cells

We evaluated the deposition of C4d in follicular lymphomas (FL) and extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). Deposition of C4d was detected in 118 lymphoma tissues from patients with lymphoma and in 20 reactive hyperplasia lymphadens (RHL) using immunohistochemistical methods. FL, MALT lymphoma, and RHL were studied using double staining for CD35/C4d and Bcl-2/C4d. We studied 26 FL tissues, 19 of which showed C4d deposition. C4d deposition was detected around the follicular dendritic cells (FDCs) in the neoplastic follicles. There was no significant difference between the positive ratio of C4d and the grades of FL. We studied 12 MALT lymphoma tissues, six of which displayed C4d deposition. In these tissues, C4d deposition was detected in the peripheral region of partially colonized follicles in the form of an irregular ring, but was not found in the central region. C4d deposition was negative in completely colonized follicles. There was no C4d deposition in diffuse large B-cell lymphomas, mantle cell lymphomas, B-small lymphocytic lymphomas, T-lymphoblastic lymphomas, peripheral T-cell lymphomas, and anaplastic large cell lymphomas. C4d around the FDCs in the neoplastic follicles was a specific indicator for FL. C4d deposition in partially colonized follicles of MALT lymphoma was completely different from that in neoplastic follicles of FL, forming a key point for differential diagnosis.     

胸腺原发黏膜相关淋巴组织淋巴瘤及淋巴上皮性涎腺炎样胸腺增生的临床病理分析

目的探讨胸腺原发黏膜相关淋巴组织(mucosa associated lymphoid tissue,MALT)淋巴瘤和淋巴上皮性涎腺炎(lymphoepithelial sialadenitis,LESA)样胸腺增生的临床病理学特征、两者相关性及鉴别诊断。方法分析3例胸腺MALT淋巴瘤和1例LESA样胸腺增生的临床病理学和免疫表型特征,并复习相关文献。结果 3例胸腺MALT淋巴瘤,其中2例伴Sj9gren综合征;镜下胸腺正常结构损毁,增生的淋巴滤泡间可见肿瘤性淋巴样细胞浸润伴明显的淋巴上皮病变,以中心细胞样和单核样B细胞形态为主。瘤细胞表达CD20、PAX-5和BCL-2,其中1例伴显著浆细胞分化者Lambda轻链限制性表达。3例胸腺MALT淋巴瘤免疫球蛋白(immunoglobulin,Ig)基因检测均示单克隆性重排。LESA样胸腺增生镜下胸腺分叶状结构大体尚存,可见包含增生滤泡的丰富淋巴细胞浸润,胸腺上皮增生伴显著淋巴上皮病变,未见有单核样B细胞形态。免疫组化染色示增生淋巴组织由B和T细胞混合;Ig基因重排检测示多克隆性增生。结论 LESA样胸腺增生和胸腺MALT淋巴瘤均是胸腺少见的淋巴增生性病变,两者具有相似的组织学和免疫表型特征;结合基因重排技术详细分析两者的鉴别要点,有助于鉴别。     

Systemic CD5 MALT lymphoma: presentation with Waldenstrom syndrome

We report a case of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in a 75-year-old woman with a neuropathy related to high levels of serum immunoglobulin M and a history of rheumatoid arthritis and polymyositis. The patient developed a mass in the right submandibular salivary gland, and this mass demonstrated histopathologic features that are typical of MALT lymphoma, including infiltrates of small monocytoid B cells in the epithelium (forming “lymphoepithelial lesions”), a reactive background of florid germinal center hyperplasia, and follicular colonization by the monocytoid B cells. Many plasma cells in the background expressed cytoplasmic immunoglobulin M lambda, matching the serum spike. Flow cytometric analysis confirmed the presence of clonal mature B cells; however, unlike most MALT lymphomas, these cells coexpressed dim CD5. Clinical staging revealed evidence of systemic distribution with documented disease involving the bone marrow, the lung, and a paratracheal lymph node. Analysis of this unusual systemic MALT lymphoma, and a comparison with similar examples from the literature, illuminates relationships among MALT lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and Waldenstrom macroglobulinemia.     

眼附属器淋巴组织增生性病变的临床病理和分子遗传学特征及其意义

目的 分析眼附属器淋巴组织增生性病变的临床病理特点,探讨其分子遗传学特征及其意义.方法 收集1995-2007年37例眼附属器淋巴组织增生性病变石蜡组织标本(其中5例为反应性增生性病变,32例为淋巴瘤),依据2001年WHO肿瘤分类标准对32例淋巴瘤标本重新诊断分类.采用IgH、MALT1、bcl-6、c-Mye、bcl-2、CCND1、bcl-10、FOXP1双色分离重排探针、IgH/bcl-2双色融合易位探针和18号染色体着丝粒探针,利用间期荧光原位杂交(FISH)的方法 检测眼附属器淋巴组织增生性病变的分子遗传学特点.结果 32例淋巴瘤均为非霍奇金B细胞淋巴瘤.其中,黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT)淋巴瘤28例(87.5%),滤泡性淋巴瘤2例,弥漫性大B细胞淋巴瘤2例.60.7%(17/28)的眼附属器MALT淋巴瘤携带分子遗传学异常.其中,IgH基因断裂1例,但未找到与其发生相互易位的伙伴基因;基因3拷贝者16例,其中MALT1基因、bcl-6基因和c-Myc基因3拷贝的发生率分别为25%(7/28)、43%(12/28)和7%(2/28).16例基因3拷贝病例中,两种基因3拷贝合并存在者5例,其中bcl-6基因合并MALT1基因3拷贝者4例,bcl-6基因合并c-Myc基因3拷贝者1例.进一步研究显示,MALT1基因3拷贝者均存在18号染色体三体.2例滤泡性淋巴瘤都携带t(14;18)(q32;q21)/IgH-bcl-2.2例弥漫性大B细胞淋巴瘤均存在遗传学异常,1例表现为bcl-6基因3拷贝合并18号染色体三体,另1例表现为bcl-6基因3拷贝合并IgH和c-Myc基因双断裂.5例反应性淋巴组织增牛性标本均未见分子遗传学异常.结论 MALT淋巴瘤是眼附属器最常见的淋巴瘤类型;间期FISH有助于淋巴组织增生性病变的良恶性鉴别及淋巴瘤的分类;MALTI基因3拷贝者由18号染色体三体所致;18号染色体三体和bcl-6基因3拷贝(可能为3号染色体三体所致)是眼附属器MALT淋巴瘤常见的分子遗传学异常.