Comparative immunohistochemical analysis of pediatric Burkitt lymphoma and diffuse large B-cell lymphoma

Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) account for nearly all pediatric nonlymphoblastic B-cell lymphomas. Because clinical behavior, prognosis, and response to therapy might differ, diagnostic accuracy is important. Morphologic examination often is sufficient, but occasionally, diagnostic ancillary studies are required. In adults, immunophenotyping is useful; however, pediatric data are limited. We characterized the immunohistochemical expression of 6 proteins (c-myc, CD10, bcl-6, bcl-2, CD138, and MIB-1) in pediatric BL (33 cases) and DLBCL (20 cases) with classic morphologic features. Significant differences in c-myc (BL, 30/33 [91%] vs DLBCL, 5/20 [25%]; P < .0001), bcl-2 (BL, 1/25 [4%] vs DLBCL, 7/19 [37%]; P < .02), and mean MIB-1 (BL, 99% vs DLBCL, 56%; P < .0001) expression were observed. There were no significant differences for CD10 (100% expression in BL and DLBCL), bcl-6 (BL, 23/33 [70%] vs DLBCL, 15/20 [75%]), or CD138 (no expression). Thus, pediatric BL and DLBCL have distinctive immunohistochemical profiles, and staining for c-myc, MIB-1, and bcl-2 might be useful in morphologically difficult cases.     

儿童散发性伯基特淋巴瘤的分子遗传学特征分析

目的 研究儿童散发性伯基特淋巴瘤(BL)的分子遗传学特征及其诊断和鉴别诊断.方法 对64例儿童BL和6例儿童弥漫性大B细胞淋巴瘤(DLBCL)进行免疫组织化学染色(SP法)和荧光原位杂交(FISH)技术检测c-myc、bcl-2、bcl-6、IgH、myc/lgH及bcl-2/IgH基因重排的情况.根据细胞起源分类分为生发中心组(GC组)、生发中心晚期组(late-GC组)、生发中心后组(post-GC组).结果 BL表达CD20(64例)、CD10(63例)、bcl-6(62例)、MUM1(15例)、bcl-2(0例).GC组49例(76.6%)、late-GC组14例(21.9%)、post-GC组1例(1.6%).c-myc基因断裂54例(93.1%);IgH基因断裂48例(82.8%);c-myc与IgH基因同时断裂并myc/IgH基因易位46例(85.2%);c-myc基因断裂、IgH和myc/IgH基因正常4例(7.4%);c-myc、IgH和myc/IgH基因均正常4例(7.4%);bcl-2基因正常61例(100%);bcl-6基因正常59例,1例断裂并扩增具有BL的病理形态和免疫表型特征,同时具有c-myc基因断裂,将病理诊断修改为介于DLBCL和BL之间的未分类的B细胞淋巴瘤(DLBCL/BL).6例DLBCL中c-myc基因断裂2例;2例bcl-6基因扩增,其中1例伴c-myc基因断裂;无bcl-2/IgH基因重排.结论 儿童散发性BL大多数来源于生发中心B细胞,c-myc基因的断裂是其主要分子遗传学改变.应用FISH进行多基因的检测,有助于提高儿童BL的诊断和鉴别诊断水平.     

原发性中枢神经系统弥漫性大B细胞淋巴瘤主要为活化B细胞亚型

目的 对原发性中枢神经系统弥漫性大B细胞淋巴瘤分型,并探讨其组织起源和预后相关意义.方法 应用免疫组织化学EnVision二步法,检测CD10、bcl-6、MUM-1、CD138和FOXP1在47例原发性中枢神经系统弥漫性大B细胞淋巴瘤中的表达情况.结果 CD10、bcl-6、MUM-1、CD138和FOXPI表达率分别为6.4%、53.2%、91.5%、0和93.6%.47例中有43例(91.5%)为活化B细胞表型:21例(44.7%)为活化的生发中心亚型,22例(46.8%)为活化的非生发中心亚型.该分型及FOXP1的表达与预后无明显相关性(P=0.279和P=0.154).结论 原发性中枢神经系统弥漫性大B细胞淋巴瘤绝大多数为活化B细胞亚型,是系统性弥漫性大B细胞淋巴瘤中一种相对同质性的亚型,推测其组织起源是生发中心末期至后生发中心早期的B细胞.     

儿童腹腔非霍奇金B细胞淋巴瘤的临床病理及免疫表型分析

目的 探讨儿童腹腔原发性非霍奇金B细胞淋巴瘤的临床病理、免疫表型与EBER特征及其病理诊断和鉴别诊断.方法 按WHO(2008年)淋巴瘤分类标准分析74例儿童腹腔原发性非霍奇金B细胞淋巴瘤的临床病理资料,制备组织芯片,进行免疫组织化学SP法染色,EBER原位杂交和c-myc基因荧光原位杂交,观察CD20、CD79a、CD3、CD10、bcl-6、MUM1、bcl-2、CD43、CD38和Ki-67蛋白的表达和EBER表达特征,并区分伯基特淋巴瘤(BL)、弥漫性大B细胞淋巴瘤(DLBCL)和介于BL和DLBCL之间的不能分类的B细胞淋巴瘤(DLBCL/BL)病理类型,在DLBCL中再区分其生发中心B细胞型(GCB)和非生发中心B细胞型(non-GCB)的分化特征.结果 儿童腹腔非霍奇金B细胞淋巴瘤中BL为65例(87.8%),DLBCL为4例(5.4%),DLBCL/BL为5例(6.8%).临床以腹痛、腹部包块、肠梗阻及肠套叠为主要发病症状.BL免疫组织化学表达CD20(65例)、CD79a(65例)、CD10(63例)、bcl-6(62例)、MUM1(15例)、CD43(46例)和CD38(63例);不表达CD3、bcl-2;27例(41.6%)EBER阳性;54例(93.0%)c-myc基因位点断裂.DLBCL免疫组织化学表达CD20(4例)、CD79a(4例)、CD10(3例)、bcl-6(2例)、MUM1(2例)、bcl-2(3例)、CD43(2例)、CD38(2例);不表达CD3;其中2例GCB,2例non-GCB;EBER阴性;1例c-myc基因位点断裂.DLBCL/BL免疫组织化学表达CD20(5例)、CD79a(5例)、CD10(5例)、bcl-6(4例)、MUM1(3例)、CD43(5例)、CD38(3例),不表达CD3和bcl-2;4例EBER阴性;3例c-myc基因位点断裂.结论 儿童腹腔非霍奇金B细胞淋巴瘤具有侵袭性生长的特点,以BL为主要病理类型.临床以腹痛、腹部包块、肠梗阻及肠套叠为主要发病症状,主要累及回盲部肠组织及周围系膜淋巴结,病理形态、免疫表型、EBER、c-myc基因的检测对BL、DLBC及DLBCL/BL淋巴瘤的诊断和鉴别诊断有重要作用.     

Primary cutaneous large B-cell lymphoma of the leg: histogenetic analysis of a controversial clinicopathologic entity

This study analyzes the pathologic and molecular features of 5 cases of primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg), recently included in the European Organization for Research and Treatment of Cancer (EORTC) classification of primary cutaneous lymphoma. PCLBCL-leg accounts for 5% to 10% of all primary cutaneous B-cell lymphoma (PCBCL), usually affects elderly patients and carries a worse prognosis than other forms of PCBCL. It has been proposed that the malignant cells of PCLBCL-leg originate from germinal center (GC)-related cells, but their effective normal counterpart is unclear, and the rationale behind the inclusion of this lymphoma as a separate entity is based on its prognosis rather than on its proved histogenesis. All of our cases of PCLBCL-leg morphologically resembled diffuse large B-cell lymphoma (DLBCL), but to better define their histogenesis, we also analyzed various phenotypic and genotypic markers, including mutations of the Ig and of BCL-6 genes, as well as expression of the bcl-6, MUM1, and CD138/syndecan-1 proteins. Immunohistochemically, all of our cases stained for the L-26/CD20cy and CD79a antigens and expressed the bcl-2, bcl-6, and MUM-1 proteins but were negative for both the CD10/CALLA and CD138 antigens. With respect to molecular analysis, the lymphoma population of all PCLBCL-leg carried hypermutation of Ig genes, and all but 1 case also harbored mutations of the BCL-6 gene. Our results indicate that PCLBCL-leg are similar both under the morphofunctional and molecular profiles to most DLBCL of other sites. Thus, caution seems justified before definitely considering PCLBCL of the leg as a distinct entity.     

Coexpression of Bcl-6 and CD10 in diffuse large B-cell lymphomas: significance of Bcl-6 expression patterns in identifying germinal center B-cell lymphoma

Most follicular lymphomas (FLs) transform to diffuse lymphoma eventually, comprising a significant proportion of diffuse large B-cell lymphoma (DLBCL). Judging by bcl-2 rearrangement (bcl-2R), one third of DLBCLs are believed to be of FL derivation in the Western population. However, bcl-2R is not specific and is not detectable in every case of FL. In East Asia, FL is uncommon but DLBCL is not. The proportion of tumors of FL origin in DLBCL is not known in this region. The coexpression of Bcl-6 and CD10 proteins, a reliable marker to identify germinal center (GC) B-cell lymphoma including FL, was analyzed in primary nodal DLBCLs (n = 104) diagnosed at major hospitals in Seoul during a recent 2-year period, along with well-defined cases (n = 17) of nodal FL as controls. Bcl-2 protein expression (n = 77) was also studied along with bcl-2R (n = 64), by polymerase chain reaction. Formalin-fixed archival specimens were used in all these assays. The Bcl-6/CD10 coexpression was observed in 35 DLBCLs (34%) and 14 FLs (82%), and most of them showed a pattern of Bcl-6 expression similar to that of the GC. Bcl-2 expression or bcl-2R did not correlate with Bcl-6/CD10 coexpression. Histologically, compartmentalizing sclerosis was associated with a high rate of the coexpression (8 of 10). In conclusion, to detect GC B-cell lymphoma in routine biopsy specimens, a pattern of Bcl-6 staining similar to the GC must be identified. Bcl-6+/CD10+ GC B-cell lymphomas thus defined comprised one third of primary nodal DLBCLs in Korea. The incidence rate is similar to that in the West. The reasons for the discrepancy between the incidence of GC B-cell lymphoma and the paucity of the follicular pattern in East Asian subjects warrant further studies.     

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。     

Prognostic significance of CD44 expression in diffuse large B cell lymphoma of activated and germinal centre B cell-like types: a tissue microarray analysis of 90 cases

BACKGROUND: Gene expression profiling of diffuse large B cell lymphoma (DLBCL) revealed three disease types: germinal centre B cell-like (GC), activated B cell-like (ABC), and a "third" type. Expression of CD44 variant isoforms (CD44v) is associated with an unfavourable clinical outcome in DLBCL, but previous studies did not consider the clinicopathological heterogeneity of this disease. AIMS: To analyse the expression and prognostic significance of CD44 in DLBCL types. METHODS: A tissue microarray (TMA) comprising 90 DLBCLs was constructed. CD10, CD20, bcl-2, bcl-6, CD44 standard isoform (CD44s), and CD44v4, CD44v6, and CD44v9 were analysed immunohistochemically and correlated with clinical follow up. RESULTS: TMA expression of CD10, CD20, bcl-2, and bcl-6 showed 100% concordance with results from conventional sections in 60 cases. Samples were segregated into 22 GC (bcl-6+/CD10+/bcl-2-), 25 ABC (bcl-6-/CD10-/bcl-2+), and 35 unclassifiable DLBCLs. Overall survival (OS) at 30 months was 89%, 44%, and 58% in GC, ABC, and unclassified types, respectively. CD44v6 was coexpressed with bcl-2, appeared predominantly on bcl-6 negative cases, and correlated with disease stage. Cases negative for CD44s could be separated into CD44v6 negative (OS, 82% at 70 months) and CD44v6 positive (OS, 58%). CONCLUSIONS: TMA technology is useful for immunophenotyping and clinicopathological analysis of large lymphoma populations. The GC phenotype of DLBCL is of independent prognostic significance for OS. Expression of CD44v6 correlates with disease stage, and might contribute to lymphoma dissemination. CD44v6 is expressed predominantly in ABC DLBCL, and in CD44 negative cases is associated with worse OS.     

The t(14;18) in diffuse large B-cell lymphoma: correlation with germinal center-associated markers and clinical features.

The clinical and biologic relevance of the t(14;18) and features of germinal center (GC) differentiation in diffuse large B-cell lymphoma (DLBCL) remain controversial. The authors examined the association of t(14;18) with GC-associated markers and clinical features in 44 de novo DLBCLs (22 nodal and 22 primary extranodal). CD10, bcl-2, and bcl-6 were expressed in 50%, 62%, and 54% of cases respectively. There were no significant differences in expression of these markers between nodal and extranodal cases. Coexpression of CD10 and bcl-6 was seen in 12 of 41 cases, and was more frequent in nodal than extranodal DLBCL (9 of 21 vs. 3 of 20; P = 0.05). A CD10+/bcl-6+ phenotype was not significantly associated with bcl-2 expression, stage, complete remission rate, or survival. The t(14;18) was found in 7 of 44 (16%) cases (6 nodal, 1 extranodal; P = 0.09). It was associated with a CD10+/bcl-6+ phenotype (5 of 7 vs. 7 of 27; P = 0.015) and a trend toward more frequent bcl-6 expression (6 of 7 vs. 15 of 34; P = 0.09), but no association with bcl-2 expression, CD10, clinical stage, complete remission, or survival. Among nodal or high-stage (III-IV) DLBCL, cases with the t(14;18) showed a trend toward decreased survival (P = 0.12).     

弥漫大B细胞淋巴瘤组织bcl-6蛋白表达及基因重排

目的探讨弥漫大B细胞淋巴瘤(DLBCL)中bcl-6和CD10蛋白表达以及基因重排的特点及其临床病理意义。方法应用免疫组织化学EnVision法分析51例DLBCL(22例为淋巴结内,29例为淋巴结外)和10例淋巴结反应性增生石蜡组织中bcl-6蛋白表达,并与CD10的表达作比较分析;应用断裂分离探针及间期核荧光原位杂交(FISH)技术检测32例淋巴结内DLBCL(22例为石蜡组织,10例为新鲜组织)和5例淋巴结反应性增生石蜡组织中bcl-6基因的重排。结果(1)淋巴结内、外DLBCL和淋巴结反应性增生中bcl-6蛋白均呈细胞核表达,阳性率分别为72.7%(16/22)、75.9%(22/29)、100.0%(10/10);CD10的阳性率分别为40.9%(9/22)、41.4%(12/29)、100.0%(10/10),所有CD10阳性肿瘤均共同表达bcl-6蛋白。(2)40.9%(9/22)的淋巴结内DLBCL和41.4%(12/29)的淋巴结外DLBCL为两蛋白共同阳性表达;将之与两蛋白均不表达的DLBCL(27.3%,6/22和24.1%,7/29)相比,前者(Ⅰ或Ⅱ期)的临床分期低于后者(Ⅲ或Ⅳ期,P<0.05)。(3)淋巴结内DLBCL样本中bcl6基因重排阳性率为28.1%(9/32),其中石蜡组织样本阳性率为27.3%(6/22),新鲜组织样本阳性率为30.0%(3/10),P>0.05。5例淋巴结反应性增生样本中均未检测到bcl-6基因重排,与DLBCL相比P<0.05。结论(1)在DLBCL中bcl6有较高的阳性表达率,bcl-6和CD10蛋白的联合检测可以协助DLBCL的诊断和鉴别诊断;bcl6和CD10共同阳性的DLBCL可能具有更好的预后。(2)bcl-6基因重排可能参与了部分DLBCL的发生,并可作为DLBCL诊断的参考指标。     

Expression of transmembrane adaptor protein PAG/Cbp in diffuse large B-cell lymphoma: immunohistochemical study of 73 cases

PAG/Cbp is a transmembrane adaptor protein involved in proximal immune signaling. It is expressed in reactive germinal centers (GC) of secondary lymphatic follicles and related malignant lymphomas. We studied PAG/Cbp expression in GC-like and non-GC-like diffuse large B-cell lymphoma (DLBCL) subtypes. Seventy-three cases of DLBCL identified among 155 malignant lymphomas were classified as GC-like DLBCL (CD10+ or CD10-, bcl-6+, and MUM1-) and non-GC-like DLBCL (CD10-, MUM1+ or CD10-, bcl-6+, MUM1+). PAG/Cbp was detected by monoclonal antibody MEM-255 following routine immunohistochemical procedures. Thirty-five of 40 GC-like DLBCLs (88%) and 20 of 33 non-GC-like DLBCL cases (61%) expressed PAG/Cbp. Four of 12 bcl-6-negative non-GC-like DLBCL cases (33%) were PAG/Cbp positive, and only 4 of 20 bcl-6-positive non-GC-like DLBCL cases (25%) were PAG/CBP negative. All 37 FL and all 5 Burkitt's lymphomas (BL) expressed PAG/Cbp, whereas all 6 mantle cell lymphomas (MCL) and 4 of 5 chronic lymphocytic leukemias (CLL/SLL) were PAG/Cbp negative. PAG/Cbp is a reliable GC marker. Its expression correlates with GC-like DLBC phenotype in a significant majority of cases. It is typically absent in MCL and SLL/CLL.     

Composite T lymphoblastic leukemia/lymphoma and diffuse large B-cell lymphoma: case report

This report concerns a unique case of a composite lymphoma composed of T-lymphoblastic leukemia/lymphoma (T-LBL) and diffuse large B-cell lymphoma (DLBCL) in a 72-year-old woman with generalized lymphadenopathy, splenomegaly and ascites. Laboratory findings showed increased lactate dehydrogenase and soluble interleukin-2 receptor. The biopsy specimen showed replacement of the normal architecture of the lymph nodes by a tumor containing a dual cell population composed of large lymphocytes and medium-sized lymphocytes. Sheets of large lymphocytes often were punctuated by clusters of medium-sized lymphocytes. Flow cytometry and immunohistochemical analysis showed a composite lymphoma with both T-LBL and DLBCL. The T-LBL expressed CD1a, CD3, CD4, CD8, and terminal deoxynucleotidyl transferase. The DLBCL expressed CD19 and CD20, CD23, bcl-2, bcl-6, MUM1 and immunoglobulin κ light chain. Polymerase chain reaction detected a monoclonal pattern of T-cell receptor γ and immunoglobulin heavy chain rearrangements in the same specimen. She received eight cycles of R-CHOP (rituximab+cyclophosphamide, doxorubicin, vincristine, prednisone) therapy and achieved complete remission. She has shown no signs of recurrence 20 months after the diagnosis. We describe here a very unusual and, to the best of our knowledge, an as yet never reported case of a primary composite lymphoma of T-LBL and DLBCL.     

Differentiating between Burkitt lymphoma and CD10+ diffuse large B-cell lymphoma: the role of commonly used flow cytometry cell markers and the application of a multiparameter scoring system

The goal of this study was to evaluate routine flow cytometric (FC) immunophenotypic markers in differentiating between Burkitt lymphoma (BL) and CD10+ diffuse large B-cell lymphoma (DLBCL). We performed retrospective analysis of FC data from 55 patients. We evaluated 9 FC parameters: forward and side scatter (FSC and SSC); mean fluorescent intensity (MFI) for CD20, CD10, CD38, CD79b, CD43, and CD71; and the percentage of neoplastic cells positive for CD71 (%CD71). The FSC; MFIs of CD10, CD43, CD79b, and CD71; and %CD71 cells were significantly different between BL and CD10+ DLBCL (P < .05; Student t test). A 5-point scoring system (FSC, %CD71, and MFIs of CD43, CD79b, and CD71) was devised, and 6 (60%) of 10 BLs scored 3 or greater and 1 (10%) of 10 CD10+ DLBCLs scored 3 (P = .04; χ(2)). Our findings indicate that routine FC parameters can aid in differentiating BL from CD10+ DLBCL.     

Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma presenting in nasal cavity: a case report and review of literature

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkin’s lymphoma (NHL) with distinct morphologic and immunohistochemical features. We reported a 57-year-old female with ALK-positive DLBCL in her left nasal cavity. Histologically, the tumor cells were characterized by plasmablastic morphology and tested positive for ALK in a cytoplasmic granular staining pattern. The neoplastic cells were positive for CD38, CD4, MUM1, CD138 and Vimentin. However, they failed to express CD56, CD30, as well as mature B cells markers, such as CD79a, CD20 and T cells markers such as CD2, CD3, CD5, CD7 and CD8. The patient achieved complete response after four cycles of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide) treatment. Then she received radiotherapy of the originally involved area. This case represented a rare ALK-positive DLBCL in the nasal region.     

Composite diffuse large B-cell lymphoma and CD20-positive peripheral T-cell lymphoma

Composite lymphoma is defined as two or more distinct types of lymphoma in a single anatomical site. Among various combinations, composite B-cell and T-cell non-Hodgkin's lymphomas (CBTL) are very infrequent. Herein we describe a 66-year-old female with CBTL presenting with lymphadenopathy, multiple bone lesions and an epidural tumor. Light microscopic examination of a biopsied cervical node revealed a dual population of lymphoid cells: sheets of large cells admixed with medium-sized cells. The large cells expressed B-cell markers and showed immunoglobulin light chain restriction, consistent with diffuse large B-cell lymphoma (DLBCL). The medium-sized cells were positive for CD20 as well as T-cell markers. Because polymerase chain reaction amplification showed monoclonal rearrangement of the T-cell receptor β chain gene, this population was compatible with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). We therefore made a diagnosis of composite DLBCL and CD20-positive PTCL-NOS. Complete remission was achieved after six cycles of R-CHOP regimen (rituximab, doxorubicin, vincristine, cyclophosphamide and prednisolone). This is the first report of CD20-positive PTCL-NOS associated with composite lymphoma. Moreover, a literature review of composite DLBCL and PTCL-NOS indicates that this rare clinical entity may be featured by efficacy of systemic chemotherapy in spite of prevalent extranodal lesions.     

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.     

Primary cutaneous diffuse large B-cell lymphoma: a clinicopathologic study of 15 cases

Primary cutaneous diffuse large B-cell lymphoma (DLBCL) is an uncommon lymphoma. Some authors have suggested that large B-cell lymphoma can be segregated based on anatomic site, with tumors of the lower extremity being unique. We report 15 cases of primary cutaneous DLBCL. Each case was analyzed immunohistochemically using antibodies specific for CD3, CD5, CD10, CD20, bcl-2, bcl-6, and p53. Polymerase chain reaction analysis for t(14;18)(q32;q21) also was performed. There were 13 men and 2 women (median age, 64 years). Thirteen tumors were composed predominantly of centroblasts, and 2 were immunoblastic. There was a median follow-up of 72 months. Of the 4 patients with primary cutaneous DLBCL of the lower extremity (thigh, knee, leg), 2 (50%) experienced a recurrence and 1 patient died of disease. In the non-lower extremity cases, 18% (2/11) recurred and no patients died of disease. We conclude that primary cutaneous DLBCL usually occurs in elderly patients with a male predominance. Recurrences are common, but death of disease is rare.     

Telomerase activity and proliferation index in aggressive mature B-cell lymphoma: comparison to germinal center phenotypic markers

Cell proliferation may be evaluated by various methods, including Ki-67 immunohistochemistry and measures of telomerase activity. Both methods would theoretically show comparable increases in a given case. To evaluate the relationship between these 2 markers of proliferation in aggressive mature B-cell lymphomas, 48 cases were studied. The study group included 5 cases of mantle cell lymphoma (MCL); 6 cases of Burkitt's/Burkitt's-like lymphoma (BL); 9 cases of follicular lymphoma, grade 3 (FLC); and 28 cases of diffuse large B-cell lymphoma (DLC). Telomerase activity was measured as total product generated (TPG) units, and TPG results for the aforementioned cases were compared to the TPG results for 10 cases of reactive follicular hyperplasia. An overlap in TPG scores between reactive cases and lymphoma cases was found. Significant differences in both log TPG (P = 0.0443) and Ki-67 (P = 0.0006) were seen in the different lymphoma types. A positive correlation between Ki-67 percentage and TPG score was identified in FLC (r = 0.9281; P = 0.0003), but a poor correlation between these 2 indicators was seen in the other lymphoma types. Cluster analysis identified distinct patterns for MCL, FLC, and BL, but heterogeneous patterns for DLC. Because increases in both Ki-67 proliferation and telomerase activity are reported in normal germinal centers (GCs), these tests were also evaluated for usefulness as markers of a GC cell phenotype. Among the FLC and DLC cases, features of a GC phenotype significantly correlated with increased Ki-67 percentage (P = 0.0152), but not with increased log TPG. An elevated log TPG correlated with CD10 expression, and elevated Ki-67 percentage correlated with both CD10 and BCL-6 expression. TPG level and Ki-67 percentage did not correlate with the presence of t(14;18) or BCL-2 protein expression. Although the proliferation patterns were fairly distinctive for MCL, FLC, and BL, these studies show that markers of cell proliferation do not by themselves,identify distinct subtypes of large cell lymphomas. With the exception of FLC, the tumors exhibited poor correlation between telomerase activity and Ki-67 proliferation index. These tests did show some correlation with expression of GC cell phenotypic markers, however.     

Composite B-cell and T-cell non-Hodgkin lymphoma of the tibia

We report a unique case of de novo composite lymphoma in the tibia of a 35-year-old man who presented with increasingly frequent and intense pain in the right upper leg. He was otherwise healthy without significant medical history. A plain radiograph of the right leg showed a permeative lesion with alternating areas of radiolucency and radiodensity in the upper third of the tibia. Magnetic resonance imaging showed a large, heterogeneous enhancing lesion involving the medullary and cortical bone of the proximal tibia with cortical disruption and extension into the adjacent soft tissue. A biopsy showed sheets and clusters of large cells, punctuated by clusters of small, irregular lymphocytes. Flow cytometry and immunohistochemical analysis showed composite lymphoma: diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell non-Hodgkin lymphoma with predominantly small cell morphologic features. The DLBCL expressed CD19, CD20, CD79a, CD5, CD10, CD23, CD38, CD117, bcl-2, and bcl-6, with monotypic expression of immunoglobulin kappa light chain. The T cells expressed CD2, CD3, CD5, CD7, and CD8, with partial loss of CD4. Clonal rearrangement of T-cell receptor gamma chain gene was found. Neither the large B cells nor the small T cells expressed Epstein-Barr virus-encoded RNA. Physical examination and radiologic studies showed no evidence of lymphadenopathy, organomegaly, or other mass lesions in the body. No peripheral lymphocytosis or bone marrow involvement was present.     

弥漫性大B细胞淋巴瘤各分子亚型中的bcl-6基因重排与蛋白表达的临床意义

目的 探讨弥漫性大B细胞淋巴瘤(DLBCL)各分子亚型中的bel-6基因重排、蛋白表达情况及其临床病理意义.方法 运用组织芯片技术,通过荧光原位杂交(FISH)技术对149例DLBCL组织中bcl-6基因重排进行检测,应用免疫组织化学技术(EnVision法)检测bcl-6以及细胞增殖指标Ki-67、细胞周期蛋白(cyclin)D3、p27Kill及Geminin等蛋白表达水平;结合临床病理资料,分析它们之间的相关性.结果 149例DLBCL可被分成3个分子亚型,其中4J0例为生发中心B细胞样(GCB样)亚型,75例为活化的非生发中心B细胞样(ABC样)亚型,34例为Type 3亚型.有118例成功进行了FISH检测,33例可检测到bcl-6基因重排,阳性率为28.0%.其中35.5%(22/62)的ABC样亚型DLBCL呈现bcl-6基因重排;较GCB样亚型(6/31,19.4%)和Type 3亚型(5/25,20.0%)的bcl-6基因重排高(P=0.160).在绝大部分(26/33,78.8%)有bcl-6基因重排的DLBCL中,伴随有bcl-6蛋白的过度表达,明显高于无bcl-6基因重排的病例(53/84,62.4%,P=0.088).有bcl-6基因重排的DLBCL中,24例(24/33,72.7%)cyclin D3呈现高水平表达,明显高于bcl-6基因无易位DLBCL组中的cyclin D3表达(37/81,45.7%,P=0.009).在33例bcl-6基因易位的DLBCL中,29例(87.9%)为Ann Arbor Ⅲ-Ⅳ期,较bcl-6基因无易位高者(65/85,76.5%,P=0.167).单变量Cox风险比模型分析发现,bcl-6基因重排与患者的生存率呈负相关,是一个危险因子,相对危险度(RR)为1.842.结论 bcl-6基因重排导致的bcl-6蛋白表达上调参与了部分DLBCL的发病过程,并可能成为DLBCL的ABC样亚型的一个分子标志.