眼结膜黏膜相关淋巴组织边缘带B细胞淋巴瘤临床病理分析

目的 探讨眼结膜黏膜相关淋巴组织边缘带B细胞淋巴瘤(marginal zone B cell lymphoma of mucosa-associated lymphoid tissue)(简称为MALT淋巴瘤)的临床病理特征、治疗及预后.方法 对15例眼结膜MALT淋巴瘤患者的临床病理资料进行回顾性分析及随访,复查和完善HE及免疫组化染色切片,4例进行Ig基因重排克隆性分析.结果 (1)15例患者中,男性5例,女性10例,中位年龄42岁,病史平均20个月.(2)病理形态:黏膜下大量密集淋巴样细胞弥漫浸润,并有模糊淋巴滤泡样结节.浸润细胞多为小～中等大小的淋巴样细胞及单核样B细胞.(3)免疫表型:浸润细胞CD20、CD79a、BCL-2均(+),CD3、CD5、CD10、Cyclin D1、TdT均(-).(4)Ig基因克隆性分析:4例均呈单克隆.(5)随访:随访时间2～35个月,截止随访日期,所有患者均生存,且病变无复发.结论 眼结膜MALT淋巴瘤好发于中年女性,结膜红肿突起为主要特征,镜下以小细胞样边缘带B细胞为主,具有典型MALT淋巴瘤的免疫表型和惰性临床经过,预后良好.     

眼部原发性黏膜相关淋巴组织结外边缘区B细胞淋巴瘤的临床病理分析

近年来眼部淋巴瘤日益多见,其中眼附属器淋巴瘤占老年人眼眶原发性恶性肿瘤的首位。根据2001年WHO恶性淋巴瘤分类诊断标准,眼附属器淋巴瘤大多属于黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT淋巴瘤）,其临床和组织病明学表现、治疗及预后均有其特殊性。我们对眼部MALT淋巴瘤的临床和病理资料进行了回顾性分析。     

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.     

肺原发性黏膜相关淋巴组织结外边缘区淋巴瘤5例临床病理分析

目的 探讨肺原发性黏膜相关淋巴组织结外边缘区(primary pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, MALT)淋巴瘤的临床病理学特征、诊断及鉴别诊断、治疗及预后。方法 回顾性分析5例肺原发性MALT淋巴瘤的临床病理学特征、免疫表型、治疗及预后等,并复习相关文献。结果 5例患者年龄42～59岁,中位年龄47岁,无相关肺部症状;CT示片状团块或斑片状高密度影。5例镜下形态相似,瘤细胞弥漫浸润肺组织,形如单核细胞样细胞和小淋巴细胞,其间散在分布少许免疫母细胞及中心母细胞样细胞,可见淋巴上皮病变,CD20、CD79a均呈阳性,CD3、CD5、Cyclin D1、CD10、BCL-6和CD30均阴性,Ki-67增殖指数为3%～20%。5例均行胸腔镜下肺叶或肺结节切除术,术后恢复良好,未见复发及淋巴结累及。结论 肺原发性MALT淋巴瘤于惰性淋巴瘤,临床易误诊,患者预后良好,诊断依赖于病理检查。     

膀胱原发结外黏膜相关淋巴组织边缘区淋巴瘤4例临床病理分析

目的探讨膀胱原发黏膜相关淋巴组织(mucosa-associated lymphoid tissue,MALT)边缘区淋巴瘤的临床病理学特征、诊断及鉴别诊断、治疗及预后。方法收集4例膀胱MALT淋巴瘤,行HE和免疫组化EnV ision两步法染色观察。应用原位杂交和基因重排技术检测4例膀胱MALT淋巴瘤,并复习相关文献。结果 4例膀胱MALT淋巴瘤中3例女性患者平均年龄60岁,1例男性患者44岁。所有病变均见肿瘤性淋巴样细胞弥漫或结节性浸润,以中心细胞样细胞和单核样B细胞构成为主,其中2例可见残存的增生淋巴滤泡伴滤泡殖入现象。淋巴上皮病变仅累及3例伴腺性膀胱炎患者中的腺样结构,而表面尿路上皮则缺乏。免疫表型:瘤细胞均表达CD20、Pax-5和BCL-2,未见轻链限制性反应。4例膀胱MALT淋巴瘤EBER原位杂交均阴性,其中3例免疫球蛋白基因检测提示单克隆性重排。结论膀胱MALT淋巴瘤属于罕见的膀胱原发低度恶性B细胞淋巴瘤,淋巴上皮病变的发生与腺性膀胱炎存在有关,但并非是病理诊断所必须。在膀胱镜小标本活检时,基因检测B细胞的单克隆性有助于诊断。     

原发性乳腺恶性淋巴瘤临床病理分析

目的：探讨原发性乳腺恶性淋巴瘤的临床病理、免疫组织化学及预后特征。方法：对8例原发性乳腺恶性淋巴瘤的临床资料、术前诊断、病理形态、免疫组织化学及预后进行分析。结果：8例原发性乳腺恶性淋巴瘤患者均为女性,发病年龄34－65岁,平均年龄46．4岁。左乳4例,右乳3例,双侧乳腺发病1例。7例患者为临床IE期,1例为ⅡE期。5例为弥漫大B细胞淋巴瘤,其中4例为中心母细胞形态,1例为免疫母细胞形态;3例为黏膜相关淋巴组织型边缘区淋巴瘤。8例均为白细胞共同抗原（LCA）、CD20、CD45RA阳性;CD43、CD45RO、CD5、CD10均阴性,3例雌、孕激素受体均阴性。治疗大多采用综合治疗,术后6例随访8－108个月未见复发。结论：原发性乳腺淋巴瘤少见,术前诊断较难。组织学类型主要为弥漫大B细胞淋巴瘤和黏膜相关淋巴组织淋巴瘤,经综合治疗后,原发性乳腺淋巴瘤的预后较好。     

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.     

胸腺黏膜相关淋巴组织结外边缘区淋巴瘤9例临床病理分析

目的探讨胸腺黏膜相关淋巴组织结外边缘区(extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, MALT)淋巴瘤的临床病理学特征、免疫表型、分子特征及鉴别诊断。方法回顾性分析9例胸腺MALT淋巴瘤的临床资料、病理学形态、免疫表型及分子遗传学特征,结合文献对其临床病理学特点进行探讨。结果 9例胸腺原发MALT淋巴瘤患者年龄35～72岁(平均50岁),男性2例,女性7例。5例患者体检发现纵隔占位,2例表现为胸痛、咳嗽及四肢面部浮肿等症状。4例患者既往伴有自身免疫性疾病。镜下肿瘤主要由小到中等的淋巴细胞样细胞构成,弥漫浸润生长,其内见大小不等的囊肿形成,囊腔内可见胆固醇结晶沉积,瘤细胞侵犯囊壁及胸腺小体而形成淋巴上皮病变。免疫表型:9例肿瘤细胞均表达B细胞标志物(CD20、CD79α、Pax-5),基因重排均显示单克隆性B细胞增生,FISH检测未见MALT1基因断裂。结论胸腺MALT淋巴瘤较少见,属于低度恶性肿瘤,多数伴有自身免疫性疾病。单一形态的瘤细胞结合免疫表型及基因重排可明确诊断,警惕漏诊或过诊。手术完整切除后密切随访即可。     

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。     

bcl-10蛋白异常表达对黏膜相关淋巴组织结外边缘区B细胞淋巴瘤的诊断价值

目的探讨bcl-10蛋白表达对黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT淋巴瘤）的诊断价值。方法收集140例不同部位的MALT淋巴瘤,包括胃38例、眼眶35例、肠16例、皮肤15例、涎腺15例、肺14例、甲状腺3例、其他部位4例。对照：10例扁桃体反应性滤泡增生（RFH）、5例眼眶的淋巴组织增生和143例非MALT淋巴瘤、不同类型的非霍奇金淋巴瘤（NHL）,包括20例NK／T细胞淋巴瘤、20例滤泡性淋巴瘤（FL）、20例间变性大细胞淋巴瘤（ALCL）、20例淋巴结内弥漫大B细胞淋巴瘤（DLBCL）、10例原发胃DLBCL、13例淋巴结边缘区淋巴瘤（NMZL）、12例套细胞淋巴瘤（MCL）、11例脾脏边缘区淋巴瘤（SMZL）、6例血管免疫母细胞性T细胞淋巴瘤（AITL）、6例外周T细胞淋巴瘤（PTCL）、3例B．小淋巴细胞淋巴瘤（B-SLL）、1例淋巴浆细胞性淋巴瘤（LPL）和1例浆细胞瘤。免疫组织化学EnVision法检测bcl-10蛋白;免疫组织化学双标记法检测CD20与bcl-10的共表达。结果在扁桃体RFH中,bel-10蛋白呈中等强度表达于生发中心B细胞质中,套细胞不表达,边缘区细胞和副皮质区T细胞呈弱表达。在眼眶淋巴组织增生中,2例bel-10阴性,3例主要呈淋巴滤泡生发中心B细胞质阳性,与扁桃体RFH的表达类似。在非MALT淋巴瘤的其他类型NHL中,除3例（3／10）原发胃DLBCL呈胞核阳性外,其余均未见胞核表达;在不同NHL中的胞质阳性分别为：结内（12／20）和胃（7／10）DLBCL、FL和ALCL（16／20）、PTCL（5／6）、AILT（6／6）、NMZL（13／13）、SMZL（11／11）、B-SLL（3／3）和浆细胞瘤（1／1）,11例MCL呈胞质可疑阳性,20例NK／T细胞淋巴瘤和1例LPL阴性;在部分淋巴瘤中可见肿瘤性细胞表达而反应性小淋巴细胞不表达：MALT淋巴瘤之bcl-10的总表达率为92．1％（129／140）,其中54．3％（76／140）胞质阳性,37．9％（53／140）胞核阳性;但不同部位之胞核阳性率有所不同。在MALT淋巴瘤中,bcl-10蛋白核强表达最常见于眼眶（25．7％,9／35）;除出现异常bcl-10胞核表达外,约20％有反应性滤泡的病例呈生发中心失表达。双标记显示bcl-10阳性细胞为CD20阳性细胞,但CD20阳性细胞多于bcl-10阳性细胞。结论（1）淋巴细胞增生性病变中bcl-10蛋白普遍表达,细胞质表达可出现在多数NHL和反应性增生中,但在淋巴瘤中呈肿瘤细胞表达而反应性细胞不表达,提示bcl-10异常可能与部分淋巴瘤的形成有关;（2）细胞核内bcl-10异常表达主要见于MALT淋巴瘤;眼眶、肺等部位的胞核强阳性和生发中心阴性的特殊模式,对MALT淋巴瘤的诊断及其与反应性病变的鉴别诊断有一定辅助意义。     

Multilobated B-cell lymphoma, a variant of centroblastic lymphoma. Report of four cases

Four cases of multilobated B-cell lymphoma, one follicular and three diffuse, are described. Many of the lymphoma cells show marked lobulation of the nuclei, and possess multiple prominent nucleoli. There are admixed classical centrocytes, classical centroblasts, and cells with morphology intermediate between classical centroblasts and multilobated cells. Multilobated cells are also observed in small numbers in germinal centres of lymph nodes showing reactive follicular hyperplasia. We believe that the multilobated B-cell may represent one form of centroblast during transition between the centroblastic and centrocytic stages. Multilobated B-cell lymphoma may be its neoplastic counterpart in which the nuclear lobulation is further exaggerated.     

High-grade non-Hodgkin''s lymphoma of B-cell type. I. Histopathology

One hundred and twenty-eight cases of high-grade malignant B-cell lymphoma were studied with a plastic re-embedding technique and classified according to the Kiel classification. The cytological details could be better recognized than in the original paraffin sections, thus permitting a more precise definition of the various lymphoma types. The entities centroblastic and immunoblastic lymphoma are more precisely defined and supplemented by the addition of several new variants. In contrast to the present Kiel classification we separate Burkitt's from lymphoblastic lymphoma. In all cases investigated, the B-cell nature of the tumour cells was proven by immunohistochemistry using monoclonal antibodies. The four entities of high-grade malignant B-cell lymphoma described in this paper are: (1) centroblastic lymphoma with four morphological variants (monomorphic, polymorphic, multilobated and centrocytoid); (2) immunoblastic lymphoma with three morphological variants (with or without plasmacytic differentiation, with many lymphocytes); (3) Burkitt's lymphoma and the closely related Burkitt's lymphoma-like lymphoma with plasmablastic differentiation; and (4) lymphoblastic lymphoma. Only the centroblastic lymphomas (in 17%) showed occasional follicular growth pattern, which further confirms the view that they are derived from germinal centre cells.     

Biclonality of Composite B- and T-cell Lymphomas A Case Report

Most composite lymphomas which are composed morphologically of two different tumor cell types are considered to represent different morphological expressions of a single clone. However, in recent years, composite B- and T cell lymphomas and biclonality of B cell lymphoma have been reported. We experienced a case of composite lymphoma which initially developed as cutaneous lymphoma composed of lymphoplasmacytes associated with large clear cells. It was confirmed that the tumor cells of these two systems were biclonal on the basis of surface markers and DNA rearrangements, i.e. B cells of the IgG kappa type, showing IgH and kappa chain DNA rearrangement, and Tcells with CD4 surface marker, showing rearrangement of the T cell receptor beta chain gene. This case showed a predominant B cell pattern at the initial stage, and terminated in T cell lymphoma, as revealed at autopsy. Therefore we considered this case to be a unique composite lymphoma showing biclonality of both B- and T-cell systems, providing a number of suggestions for future study of malignant lymphoma.     

Diagnostic features of gastric extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue

Gastric extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue may be difficult to distinguish from florid gastritis and other small B-cell lymphomas. The following review details a practical summary of the morphologic features, immunohistochemical markers, and molecular tests that currently provide for an accurate diagnosis in daily practice.     

Extranodal diffuse large B cell lymphoma of cutaneous follicle centre lymphoma type: a study of 24 patients with non-cutaneous primary limited stage extranodal diffuse large B cell lymphoma in support of a new concept

Aigner F, Korol D, Schmitt A M & Kurrer M O
(2012) Histopathology  60, 774–784 Extranodal diffuse large B cell lymphoma of cutaneous follicle centre lymphoma type: a study of 24 patients with non‐cutaneous primary limited stage extranodal diffuse large B cell lymphoma in support of a new concept Aims: Follicle centre cell lymphoma of small cell type showing either a follicular or diffuse growth pattern similar to cutaneous follicle centre lymphoma (cFCL) has been recognized in extranodal non‐cutaneous sites. Our aim was (i) to investigate whether diffuse large B cell lymphoma (DLBCL) of cFCL type could be identified in extranodal non‐cutaneous sites and (ii) whether clinical characteristics similar to primary cFCL could be recognized. Methods and results: Of 24 extranodal non‐cutaneous DLBCLs, nine (38%) had large centrocytoid morphology and 15 (62%) were either ‘centrocytoid and centroblastic’ or ‘centroblastic and immunoblastic’. Six centrocytoid cases were Irf‐4 negative, Bcl‐6 positive and at most weakly CD10‐ or Bcl‐2‐positive by immunohistochemistry, consistent with DLBCL of cFCL type. All patients with cFCL type were stage IE and were significantly younger than other patients. Recurrences occurred in two patients and were exclusively extranodal. Conclusion: Our results suggest that DLBCL of cFCL type can be identified in extranodal non‐cutaneous sites and shows clinical characteristics similar to genuine cFCL. We propose to expand the concept of cFCL to encompass large cell lymphomas in extranodal sites.     

Composite marginal zone B-cell lymphoma and classical Hodgkin's lymphoma: a clinicopathological study of 12 cases

AIMS: Classical Hodgkin's lymphoma (cHL) rarely coexists as composite lymphoma with B-cell non-Hodgkin's lymphoma (B-NHL). We characterized 12 cases of composite marginal zone B-cell lymphoma (MZBL) and cHL by immunohistochemistry and molecular biology. METHODS AND RESULTS: Eight patients had gastric MZBL of mucosa-associated lymphoid tissue (MALT)-type, in five cases with a diffuse large B-cell lymphoma component. Concurrent cHL was observed either in the stomach wall, regional, or distant lymph nodes. One patient each had composite pulmonary/thyroid MZBL of MALT-type and cHL. In two cases, nodal composite MZBL and cHL was observed. cHL displayed features of mixed cellularity type in 10 cases, while in two cases only scattered Hodgkin- and Reed-Sternberg (H/RS) cells were noted. H/RS cells expressed CD30, multiple myeloma oncogene 1 protein (MUM1P), p53 (100%), CD15 (58%), CD20 (58%) and Epstein-Barr virus-associated LMP1 (50%). No t(11;18)(q21;q21) was detected in composite MZBL of MALT-type and cHL. CONCLUSIONS: MZBL and cHL may occur as composite lymphoma, possibly reflecting clonal lymphoma progression. Derivation from extranodal MZBL of MALT-type should be excluded in cases in which a diagnosis of primary extranodal cHL is considered.     

Mediastinal large-cell lymphoma of B-type, with sclerosis: Histopathological and immunohistochemical study of eight cases

Eight cases of mediastinal non-lymphoblastic large-cell lymphoma have been studied by histopathological and immunohistochemical methods. A common clinical, morphological and immunophenotypic pattern was identified. Six of eight cases proved to be of B-cell origin by the expression of B-associated antigens detected by specific monoclonal antibodies. Cells of large size with nuclei of varying morphology and a peculiar type of fine compartmentalizing fibrosis were observed in all specimens. Clinically the disease was characterized by the young age of the patients, primary mediastinal involvement, aggressive behaviour and spread to unusual sites (kidneys in four cases). This seems to be a hitherto unrecognized entity in the field of non-Hodgkin's lymphomas, often misdiagnosed because of location and a morphology uncommon for B-cell malignancies. Immunohistochemical analysis on frozen tissue sections appears to be mandatory for a correct diagnosis. Nevertheless, this type of lymphoma could be suspected also on the basis of its peculiar clinicopathological characteristics.     

Malignant lymphoma with myxoid stroma: a new pattern in need of recognition

We report a case of malignant lymphoma in the soft tissues exhibiting prominent myxoid stromal changes and cord-like cellular arrangement, mimicking the architectural as well as cytological features of myxoid chondrosarcoma, except for the absence of tumour lobulation. The only clue to the possible lymphomatous nature of the lesion was the past history of lymphoma. Immunohistochemical studies showed that this represented a B-cell lymphoma, staining positively for leucocyte common antigen and five B-lineage markers L26, MB2, B1 (CD20), B4 (CD19) and To15 (CD22). We conclude that malignant lymphoma should not be excluded from consideration when one encounters a myxoid tumour.