间变大细胞淋巴瘤的诊疗进展

正间变大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)是一种临床少见且异质性明显的恶性肿瘤,约占成人非霍奇金淋巴瘤的3%及儿童淋巴瘤的10%~15%~([1-2])。1985年Stein等~([3])首先将一组高表达CD30(Ki-1)、以大细胞增殖为主的淋巴瘤命名为ALCL。Morris等~([4])发现了ALCL中最常见的染色体异常t(2;5)(p23;q35),即2号染色体上的间变淋巴瘤激酶(ALK)基因和5号染色体上的核磷蛋白基因融合产生了融合基因NPM-ALK。根据ALK蛋白的表达状态,可将     

结缔组织病合并原发骨间变性大细胞淋巴瘤1例并文献复习

<正>间变性大细胞淋巴瘤(anaplastic large cell lymphomas,ALCL)属于非霍奇金淋巴瘤的一种特殊类型,约占非霍奇金淋巴瘤的2%~8%,属于侵袭性淋巴瘤。Stein等〔1〕最初于1985年对其命名,并描述了其组织学特征。ALCL分为原发系统型和皮肤型两种类型,原发系统型根据肿瘤细胞是否表达间变淋巴瘤激酶(ALK)分为ALK+ALCL和     

HIV/AIDS非相关霍奇金淋巴瘤的临床病理和免疫表型分析

目的 探讨HIV/AIDS非相关霍奇金淋巴瘤（HL）的病理组织学形态、免疫表型特点及鉴别诊断.方法 根据WHO（2008）造血和淋巴组织肿瘤分类,应用光镜、免疫组化EnVision法染色、FISH及原位杂交,并结合临床资料和文献复习对3例HIV/AIDS合并霍奇金淋巴瘤进行综合分析.结果 3例组织学形态均符合经典型HL,亚型为混合细胞型2例,1例为淋巴细胞消减型.免疫组化染色肿瘤细胞CD30、LMP1表达阳性,肝活检1例少数肿瘤细胞EMA、CD20及C D79α弱表达,Ki67增殖指数为60％～80％,LCA、CD15、CD68、PAX5、ALK、BOB.1、OCT2、CD3、p53均阴性;背景细胞可表达CD20、CD3、CD57、bcl-6.EBER原位杂交3例均阳性.FISH示IgH基因（14q32）重排1例.结论 在HIV感染者中,HL是最常见的AIDS非定义性肿瘤之一,预后较差.组织学是诊断非HIV/AIDS相关HL的基础,结合免疫组化进行分型和鉴别诊断可以减少误诊的发生,FISH和原位杂交是辅助检测HL分子遗传学改变的技术手段.     

肺原发性霍奇金淋巴瘤临床病理分析

目的 探讨肺原发性霍奇金淋巴瘤的诊断与鉴别诊断.方法 回顾性分析3例肺霍奇金淋巴瘤病例并复习相关文献.结果 3例患者均为男性,以咳嗽症状为主,肿瘤较大,平均直径为5 cm,可伴有肺门及纵隔淋巴结肿大,镜下均可见典型的RS细胞,背景细胞内有较明显嗜酸粒细胞浸润,并见干尸细胞,免疫组化CD15和CD30阳性.化疗、骨髓移植可使病情缓解,长期生存.结论 肺原发性霍奇金淋巴瘤病理学及免疫表型具有一定的特征,恰当的治疗预后良好.     

肝脾γδT细胞淋巴瘤合并Evans综合征一例报告并文献复习

目的探讨肝脾γδT细胞淋巴瘤的临床病理及免疫分型特征。方法应用常规病理、免疫组化及PCR方法观察1例肝脾γδT细胞淋巴瘤,并进行相关文献复习。结果患者以肝大、巨脾、发热为主要表现,肝脾活检病理结果显示淋巴瘤细胞侵犯脾红髓、肝窦及汇管区;免疫组化显示瘤细胞表达CD3、CD45RO、CD15,而CD20、CD79α表达阴性;PCR方法发现TCRγ链重排;且患者存在溶血及血小板减少,诊断符合肝脾γδT细胞淋巴瘤合并Evans综合征。结论肝脾γδT细胞淋巴瘤是罕见的淋巴瘤类型,具有独特的临床病理特征和免疫表型,应注意与其他造血系统疾病鉴别。Evans综合征是其少见的并发症之一,可能与自身免疫异常有关。     

29例原发系统性间变大细胞淋巴瘤的病理特点及临床分析

目的:探讨原发系统性间变大细胞淋巴瘤(ALCL)的病理特点、临床特征与预后的关系.方法:对29例原发系统性ALCL患者的病理特点、临床特征、完全缓解率(CR)、长期生存率和预后因素进行了分析.结果:所有病例的瘤细胞均强表达CD30,58.62%间变性淋巴瘤激酶(ALK)阳性.接受了治疗的28例患者的CR率为50.0%,2年和5年生存率分别为51.3%与27.1%.ALK阳性患者CR为68.8%,2、5年无病生存率分别为60.2%、42.5%,明显高于ALK阴性组(P<0.05).国际预后指数(IPI)0～2分患者组CR率为57.1%,2年、5年无病生存率分别为80.2%、65.1%,明显高于IP13～5分患者组(P<0.05).Cox比例风险回归分析表明ALK的表达、IPI评分对预后的影响有统计学意义(P<0.05).结论:ALK表达、IPI评分有助于判断原发系统性ALCL的预后,并为个体化治疗提供了依据.     

胃肠道多发间变性大细胞淋巴瘤临床及病理观察

目的探讨胃肠道多发间变性大细胞淋巴瘤（ALCL）的临床病理特点、免疫组化特征及预后。方法应用组织病理学形态观察及免疫组化方法,研究1例发生在胃肠道的ALCL,并结合文献复习进行分析讨论。结果肿瘤位于肠壁黏膜固有层至肌层间,为多发性病变,病变的长径与肠管长径垂直,病变的中心呈脐样坏死。肿瘤形态学表现为多样性并伴有肉瘤样区域。高倍镜下,瘤细胞呈上皮样、组织细胞样和梭形细胞改变;可见显著的泡状核与明显嗜酸性的核仁,核分裂易见;局部可见灶性瘤细胞坏死。免疫组化显示CD45RO弥漫性表达,CK局灶性表达。结论 ALCL形态学和免疫表型有一定的特殊性,预后较差。     

免疫组化联合基因重排检测对发热待查伴骨髓分类不明细胞的诊断价值

目的:探讨发热待查伴有骨髓中发现分类不明细胞免疫组化联合基因重排检测的诊断价值。方法:对23例长期发热并骨髓或外周血中有分类不明细胞浸润的患者分离骨髓或外周血的单个核细胞进行免疫组化染色和基因重排检测。结果:23例患者中,诊断为非霍奇金淋巴瘤12例,其中滤泡性淋巴瘤(FL)3例、套细胞淋巴瘤(MCL)1例、弥漫性大B细胞淋巴瘤(DLBCL)2例、间变性大细胞淋巴瘤-T(ALCL)3例、血管免疫母细胞性T细胞淋巴瘤(AITCL)1例,侵袭性NK细胞白血病/淋巴瘤(ANKCL)1例,恶性组织细胞病1例;2例结合脾脏病理学诊断SLE;诊断为骨髓转移癌5例;4例未能确诊。结论:联合运用免疫组化和基因重排技术对长期发热并骨髓分类不明细胞浸润患者有一定的诊断价值。     

原发性肺大B细胞淋巴瘤的临床病理研究

目的探讨原发性肺弥漫性大B细胞淋巴瘤的组织学特点和免疫表形特征。方法运用组织形态学和免疫组织化学方法研究我院1例肺弥漫性大B细胞淋巴瘤患者的临床表现、病理特点和免疫组化标记特点。结果肉眼观察肿瘤为灰白色不规则分叶状团块,切面灰白色,鱼肉样,有大量坏死灶;显微镜观察被覆呼吸上皮下中心母细胞样细胞弥漫增生,浸润肺组织,瘤细胞坏死明显。免疫组化：CD20（＋）,CD79α（＋）,CD3（-）,CD45RO（-）,PCK（-）。结论弥漫性大B细胞淋巴瘤是一种少见的恶性肿瘤,而原发于肺的DLBCL更极为罕见。该病缺乏典型的临床表现,极易误诊。肺弥漫性大B细胞淋巴瘤的诊断和鉴别诊断,要以组织病理学形态为基础并与免疫组织化学相结合。     

CD38表达在侵袭性B细胞淋巴瘤诊断中的价值

目的:探讨CD38表达在侵袭性B细胞淋巴瘤诊断和鉴别诊断中的意义。方法:应用多参数流式细胞术检测102例初发侵袭性B细胞淋巴瘤[主要包括弥漫大B细胞淋巴瘤(DLBCL)73例、Burkitt淋巴瘤7例和高级别B细胞淋巴瘤22例]患者淋巴结或骨髓标本中流式免疫标记物的表达情况,比较CD38在各组患者肿瘤细胞上表达水平的差异,分析其在侵袭性B细胞淋巴瘤鉴别诊断中的特点。结果:3组患者肿瘤细胞膜表面CD5、CD19~(dim)、CD20~(dim)和CD45~(dim)表达水平差异无统计学意义(均P0.05),CD10表达水平以及缺乏免疫蛋白轻链表达差异有统计学意义(P=0.029,P=0.043);将DLBCL分为MYC-R~+和MYC-R~-患者,CD38~+、CD38~(++)和平均荧光强度在DLBCL MYC-R~+、DLBCL MYC-R~-、Burkitt淋巴瘤和双重/三重打击淋巴瘤4组患者肿瘤细胞表达水平差异有统计学意义(均P0.05),CD38~+在诊断这4组侵袭性B细胞淋巴瘤时除DLBCL MYC-R~+外特异性可达100%,但敏感性较低;CD38~(++)诊断DLBCL MYC-R~+时特异性可达100%,敏感性低至13%,而诊断Burkitt淋巴瘤和双重/三重打击淋巴瘤时敏感性则明显升高(分别为86%和79%)。结论:CD38不同表达水平在侵袭性B细胞淋巴瘤鉴别诊断中具有重要作用,尤其CD38高表达可以及时准确地早期诊断双重/三重打击淋巴瘤,对临床治疗具有指导意义。     

CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features

Anaplastic large cell lymphoma (ALCL) represents a generally recognized group of large cell lymphomas. Defining features consist of a proliferation of predominantly large lymphoid cells with strong expression of the cytokine receptor CD30 and a characteristic growth pattern. With the use of molecular and clinical criteria, 3 entities of ALCL have been identified: primary systemic anaplastic lymphoma kinase (ALK)(+) ALCL, primary systemic ALK(-) ALCL, and primary cutaneous ALCL. ALK expression is caused by chromosomal translocations, most commonly t(2;5). ALK(+) ALCL predominantly affects young male patients and, if treated with chemotherapy, has a favorable prognosis. It shows a broad morphologic spectrum, with the "common type," the small cell variant, and the lymphohistiocytic variant being most commonly observed. The knowledge of the existence of these variants is essential in establishing a correct diagnosis. ALK(-) ALCL occurs in older patients, affecting both genders equally and having an unfavorable prognosis. The morphology and the immunophenotype of primary cutaneous ALCL show an overlap with that of lymphomatoid papulosis. Both diseases have an excellent prognosis, and secondary systemic dissemination is only rarely observed. The described ALCL entities usually derive from cytotoxic T cells. In contrast, large B-cell lymphomas with anaplastic morphology are believed to represent not a separate entity but a morphologic variant of diffuse large B-cell lymphoma. Malignant lymphomas with morphologic features of both Hodgkin disease and ALCL have formerly been classified as Hodgkin-like ALCL. Recent immunohistologic studies, however, suggest that ALCLs Hodgkin-like represent either cases of tumor cell-rich classic Hodgkin disease or (less commonly) ALK(+) ALCL or ALK(-) ALCL. (Blood. 2000;96:3681-3695)     

Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype

Anaplastic large cell lymphoma (ALCL) is a distinct entity of non-Hodgkin lymphoma, characterized by a proliferation of pleomorphic large lymphoid cells that express CD30. Recent studies have found that a subset of ALCL aberrantly expresses a chimeric anaplastic lymphoma kinase (ALK) protein as a result of t(2;5)(p23;q35) or variant translocations. ALK-positive ALCLs feature good prognosis, but some of them lead to poor outcomes. Since CD56 is expressed in some ALCLs, its clinical significance was examined in a series of T/null cell type ALCLs. Of 143 patients, 83 (58%) showed ALK-positive staining, and of 140 patients, 25 (18%) expressed CD56. The ALK-positive subgroup was characterized by a younger age of onset (P <.0001), lower serum lactate dehydrogenase level (P =.01), better performance status (P =.03), less frequent extranodal involvement (P =.01), lower international prognostic index (IPI) categories (P =.002), and superior survival (P =.0009) in comparison with the ALK-negative group, suggesting that ALK is a specific marker defining a distinct subtype. CD56(+) cases showed a significantly poor prognosis overall (P =.002) as well as in both ALK-positive and ALK-negative subgroups (P =.02 and P =.04, respectively). Multivariate analysis confirmed that CD56 is independent of other prognostic factors, including IPI. Although CD56(+) cases showed a higher incidence of bone involvement, no other differences in clinicopathologic parameters were found between the CD56(+) and CD56(-) groups. These findings suggest that CD56 is not a marker to identify a distinct subtype of ALCL, but a strong clinical prognostic factor. Effective therapeutic approaches should be explored for high-risk ALCL patients, who can be identified by means of a prognostic model, including CD56.     

CD30 and the NPM-ALK fusion protein (p80) are differentially expressed between peripheral blood and bone marrow in primary small cell variant of anaplastic large cell lymphoma

The t(2;5)(p23;q35) translocation results in the formation of a unique chimeric NPM-ALK protein (p80). Expression of this protein is considered to be one of the clinical features of anaplastic large cell lymphoma (ALCL). Recently recognized as one clinical subtype of ALCL, the small cell variant is prone to have a leukemic presentation. Although the small cell variant has been recognized as a subtype of ALCL, the clinical properties of this subtype, especially the immunophenotype of lymphoma cells in peripheral blood, have not yet been fully described. This report shows that neither CD30 nor p80 is detected by immunostaining in the predominant small cell malignant clone and also in large lymphoma cells in peripheral blood, while large cells and occasionally observed small cells in bone marrow were found to be positive for CD30 and p80. Our findings suggest that differential expression of CD30 and p80 between peripheral blood and bone marrow lymphoma cells is a property of the small cell variant of ALCL.     

Clonal relation in a case of CLL,ALCL, and Hodgkin composite lymphoma

Large cell lymphomas and Hodgkin disease may develop during the course of chronic lymphocytic leukemia (CLL). In some cases the transformed cells are Epstein-Barr virus (EBV)-positive and not clonally related to the CLL cells. In other cases the transformed cells have the same clonal rearrangements as the CLL cells. Here we describe a composite lymphoma in a patient with CLL that exhibits a combination of CLL/small lymphocytic lymphoma, large cell lymphoma with anaplastic morphology, and Hodgkin lymphoma (HL). Although the large cell lymphoma cells are CD45R0 and TIA-1-positive, suggesting a T- or 0-cell anaplastic large cell lymphoma (ALCL), the genetic analysis demonstrates immunoglobulin heavy chain (IgH) gene rearrangements for both alleles, carrying the same somatic mutations as observed in the CLL component. The Reed-Sternberg (R-S) cells in the Hodgkin component also strongly express TIA-1 but differ from the anaplastic large cells by the expression of CD15 and TARC and the presence of a prominent lymphocytic infiltrate. The ALCL and HL components both are EBV negative. Analysis of the IgH gene rearrangements in micromanipulated R-S cells revealed identical Ig gene rearrangements carrying the same somatic mutations as the CLL and the large cell components. The findings indicate transformation of the CLL cells into a large cell lymphoma with anaplastic morphology and a Hodgkin component.     

Anaplastic large cell lymphomas lack the expression of T-cell receptor molecules or molecules of proximal T-cell receptor signaling

Anaplastic large cell lymphoma (ALCL) designates a heterogeneous group of CD30(+) (systemic or primary cutaneous) peripheral T-cell lymphomas (PTCLs). A subgroup of systemic ALCL is transformed by anaplastic lymphoma kinase (ALK). We compared 24 ALK(+), 15 ALK(-) systemic, and 7 cutaneous ALCLs with 29 nonanaplastic PTCLs in terms of T-cell receptor (TCR) rearrangements, expression of TCRs and TCR-associated molecules (CD3, ZAP-70 [zeta-associated protein 70]). Despite their frequent clonal rearrangement for TCRbeta, only 2 (4%) of 47 ALCLs expressed TCRbeta protein, whereas TCRs were detected on 27 of 29 nonanaplastic PTCLs. Moreover, both TCRbeta(+) ALCLs lacked CD3 and ZAP-70 (ie, molecules indispensable for the transduction of cognate TCR signals). Defective expression of TCRs is a common characteristic of all types of ALCL, which may contribute to the dysregulation of intracellular signaling pathways controlling T-cell activation and survival. This molecular hallmark of ALCL is analogous to defective immunoglobulin expression distinguishing Hodgkin lymphoma from other B-cell lymphomas.     

Sialosylated lewis x expression in CD30-positive anaplastic large-cell lymphomas

Summary The expression of sialosylated Lewis ^x (SLEX), a ligand for endothelial leukocyte adhesion molecule 1 in malignant lymphomas, was immunohistochemically examined, using the monoclonal antibody, CSLEX1, which specifically reacts with SLEX. It was expressed in 6 out of 64 non-Hodgkin's lymphomas, which consisted of 1 nasal large-cell lymphoma and 5 of 8 (62%) Ki-1-positive anaplastic large-cell lymphomas (ALCL). One nasal lymphoma positive for SLEX co-expressed a T cell marker, cluster of differentiation (CD) 5, and natural killer (NK) cell markers such as CD56 and CD16, indicating that SLEX⁺ nasal lymphoma cells are possibly malignant counterparts of SLEX⁺ NK cells. SLEX did not react with 30 B cell lymphomas or most Hodgkin's disease lymphomas, though it did with one lymphocyte predominance type. Although SLEX⁺ ALCL exhibit T cell markers in some cases, some ALCL expressing SLEX may represent histiocytic differentiation of the neoplastic cells. The lymphoma cells of ALCL were preferentially positive for SLEX, in contrast to Hodgkin's disease cells, and thus CSLEX1 in conjunction, with CD30 and CD15 should be of use for analyzing and making differential diagnoses of routine paraffin-embedded sections of ALCL.Abbreviations SLEX sialosylated Lewis ^x - ALCL anaplastic large-cell lymphomas     

Detection of differentially expressed genes in lymphomas using cDNA arrays: identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas

This study reports the first use of gene array technology for the identification of a tumor-specific marker in lymphoid neoplasms. The differential gene expression of 31 hematopoietic cell lines, representing most major lymphoma subgroups of B- and T-cell origin, was assessed by hybridizing labeled complementary DNA to Atlas human expression arrays containing 588 genes. Genes known to be specific for B, T, or myelomonocytic lineages were appropriately identified in the arrays, validating the general utility of this approach. One gene, clusterin, not previously known to be expressed in lymphoid neoplasms, was specifically found in all 4 anaplastic large-cell lymphoma (ALCL) cell lines, but not in any of the 27 remaining tumor lines. Using a monoclonal antibody against clusterin, its differential expression was confirmed by Western blotting and immunohistochemistry. A total of 198 primary lymphomas (representing most major lymphoma subtypes), including 36 cases of systemic ALCL, were surveyed for clusterin expression by immunohistochemistry and Western blotting. All of the 36 ALCL cases marked for clusterin, with most cases showing moderate to strong staining in the majority of neoplastic cells. Clusterin expression was not related to expression of anaplastic lymphoma kinase-1. With 2 exceptions, none of the remaining 162 non-ALCL cases marked with the clusterin antibody, including Hodgkin disease and primary cutaneous ALCL. In reactive lymphoid tissues, only follicular dendritic cells and fibroblastic reticular cells exhibited staining. Clusterin is a highly conserved glycoprotein implicated in intercellular and cell matrix interactions, regulation of the complement system, lipid transport, stress responses, and apoptosis. Although its function in ALCL is unknown, the unique expression of clusterin within this category of lymphoma provides an additional marker for the diagnosis of ALCL. This study illustrates the enormous potential of gene array technologies for diagnostic marker discovery. (Blood. 2000;96:398-404)