脾边缘区淋巴瘤伴自身免疫性溶血性贫血1例并文献复习

目的：提高对脾边缘区淋巴瘤(splenic marginal zone lymphoma,SMZL)的认识。方法：详细报告1例典型患者临床及实验室特征,并复习相关文献。结果：SMZL是一少见的原发于脾脏的低度恶性B细胞淋巴瘤。临床以脾脏明显肿大、淋巴细胞增多为特征,易浸润骨髓,可合并自身免疫疾患。肿瘤细胞表达成熟B细胞免疫表型,CD5^-、CD10^-、CD23^-、CD103^-,不表达T细胞相关分化抗原。结论：SMZL起病潜隐,进展缓慢,生存期长,容易漏诊。糖皮质激素和环孢菌素A治疗SMZL合并自身免疫性溶血性贫血(AIHA)近期疗效好,对SMZL本身也有一定治疗作用。     

脾脏边缘区B细胞淋巴瘤二例临床病理分析

目的：提高对脾脏边缘区 B 细胞淋巴瘤（SMZL）的认识和诊治水平。方法对2例 SMZL患者外周血、骨髓及脾脏标本的病理形态及免疫组织化学进行观察及分析。结果2例 SMZL 患者肿瘤细胞 CD20、CD79a、Pax-5、 bcl-2、IgM 均表达阳性,CD5、CD10、bcl-6、CD23、CD43、CD138、Cyclin D1均表达阴性。结论 SMZL 是一类较罕见的肿瘤,对脾脏进行性增大不伴浅表淋巴结肿大患者应怀疑 SMZL,应与脾内其他滤泡性淋巴瘤和套区淋巴瘤进行鉴别,脾脏切除治疗效果好。     

艾滋病病毒感染合并口腔浆母细胞型淋巴瘤一例临床病理分析

 目的　分析艾滋病病毒（HIV）合并口腔浆母细胞型淋巴瘤的形态学特点、免疫表型及鉴别诊断。方法　对1例HIV合并口腔浆母细胞型淋巴瘤进行形态学、免疫组织化学分析及文献复习。结果　免疫组织化学显示CD-20、CD-3、CD-45、CD-30、ALK（-）、EBV（+）、CD138灶（+）、Ki-67 90 %（+）、EMA灶（+）、CD68组织细胞（+）、CDRB灶（+）、CD45RO个别（+）、CD-79a、CD-56、IgM、IgG、IgA、HMB45、bcl-2、CD5、cyclinD1、CD43、CD10、Desmin、MPO、CD15、MYOD1、CK均为（-）。病理诊断弥漫大B细胞淋巴瘤浆母细胞型分化。结论　弥漫性大B细胞淋巴瘤病理类型多样,HIV合并口腔浆母细胞型较少见,掌握其形态学特征,熟悉各类型的免疫表型的异同点对诊断与鉴别诊断有重要意义。     

原发性肝脾T细胞淋巴瘤三例报告并文献复习

 目的 探讨原发性肝脾T细胞淋巴瘤的临床表现、病理学特征和免疫表型特点。方法 对3例患者的临床资料进行回顾性分析并对相关文献进行复习。结果 患者肝脾明显肿大,伴有发热、全血细胞减少及肝功受损;病理示瘤细胞弥漫浸润肝/脾脏红髓血窦;免疫表型：瘤细胞表达CD+2、CD+3、CD-4、CD-8,TCR-γ／δ（+）。结论 肝脾T细胞淋巴瘤是较为罕见的外周T细胞淋巴瘤,预后较差,应注意与恶性组织细胞病鉴别。     

具有微绒毛特征的CD30阳性弥漫大B细胞淋巴瘤一例临床病理特征

目的 讨论具有微绒毛特征的CD30+弥漫大B细胞淋巴瘤的临床、病理特征,提高对该病的认识与诊断水平.方法 对1例76岁女性的颈部肿大的淋巴结进行组织学、免疫组织化学、EBER原位杂交和电子显微镜观察,并复习相关文献.结果 组织病理学示,淋巴结正常结构消失,形态单一的、胞质丰富的异型细胞呈片状增生,部分区域可见异型细胞淋巴窦内生长模式.免疫组织化学示,异型细胞CD20+、CD79a+、PAX-5+、CD10+、bcl-6+、MUM-1+,40％肿瘤细胞CD30+,80％肿瘤细胞Ki-67+,肿瘤细胞不表达CK、CD3、CD5、CD15、CD56、EMA、bcl-2.电子显微镜观察,瘤细胞体积大,胞质丰富,瘤细胞表面大量微绒毛,微绒毛长短不一,粗细较均匀,少数有分枝.结论 微绒毛淋巴瘤是一类具有独特形态学改变、免疫组织化学表型和超微结构的淋巴瘤.     

利妥昔单抗治疗老年人脾边缘区淋巴瘤二例并文献复习

 目的　探讨老年人脾边缘区淋巴瘤（SMZL）的诊断、治疗方法。方法　报道2例年龄＞70岁伴有巨脾的SMZL,并对其临床表现、诊断及治疗进行文献复习。结果　SMZL多见于老年患者,常表现为脾大,具有与脾功能亢进相似的症状和体征。骨髓流式细胞术结合细胞形态学检查有助于诊断。可行利妥昔单抗单药治疗,疗效较好。结论　流式细胞术对SMZL的诊断及治疗均有重要的指导作用。     

脾边缘区淋巴瘤的诊断

目的:探讨脾边缘区淋巴瘤的临床特征、诊断及鉴别诊断。方法:回顾性分析华中科技大学同济医学院附属同济医院2019年收治的3例表现为脾大、血细胞减少的CD5 - CD10 - B细胞非霍奇金淋巴瘤患者的临床诊断及鉴别诊断过程,并复习相关文献。 结果:3例均为老年患者,均出现不同程度的脾大和血细胞减少,均在骨髓或淋巴结中发现CD5 - CD10 -单克隆B淋巴细胞。综合患者的临床特征、外周血及骨髓形态、免疫表型和遗传学特征,2例患者诊断为脾边缘区淋巴瘤,1例患者诊断为弥漫大B细胞淋巴瘤。 结论:脾边缘区淋巴瘤的诊断需综合临床特征、外周血及骨髓形态、免疫表型和遗传学特征,与其他CD5 - CD10 -小B细胞淋巴瘤进行仔细鉴别。新一代基因突变高通量检测和表达谱分析有助于不典型疑难病例的精准诊断。     

肾脏黏膜相关淋巴瘤2例报道并文献回顾

背景与目的：原发肾脏的黏膜相关组织淋巴瘤十分罕见,目前世界报道不足50例。本文介绍2例肾脏黏膜相关淋巴瘤的形态学特点和免疫表型特征,旨在使临床和病理对这种低度恶性的B细胞肿瘤的特点有所了解。方法：收集病史资料,形态学评价根据HE切片,用免疫组化法检测肿瘤细胞的表型,使用的抗体包括CD20、CD79、CD5、CD10、CD43、CD23、BCL10和Cyc linD1。结果：2例患者均为女性,年龄分别为48岁和55岁,临床上均有慢性肾盂肾炎病史。B超和CT检查发现肾脏肿块,行全肾切除。大体检查可见肿块位于肾髓质,呈境界不清的暗红色;镜检见肾盂至肾实质弥漫淋巴样细胞浸润,以小淋巴细胞、中心细胞样细胞、淋巴浆细胞和浆细胞浸润为主,可见肿瘤细胞浸润肾小管和肾球囊形成淋巴上皮病变和反应性淋巴滤泡,但没有显著滤泡殖入;免疫组化显示增生细胞以B淋巴细胞为主,散在分布反应性T细胞,肿瘤细胞CD20、CD79 a阳性,CD43弱阳性,CD5、CD10、BCL10、CD23和Cyc linD1均为阴性。结论：原发肾脏黏膜相关淋巴瘤临床极为罕见,临床表现和辅助检查与肾细胞癌不易鉴别,但组织学特点符合经典黏膜相关淋巴瘤的所有特征,免疫表型有助于病理诊断。     

眼附属器黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT）临床病理分析

目的:探讨6例眼附属器黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT)患者的临床病理特点及预后。方法:收集2010年01月至2019年01月病理学检查确诊的6例眼附属器MALT患者的临床资料及治疗方案、形态学特点及免疫组化表达,FISH检测MALT1基因断裂,电话随访,分析总结其临床病理特点及预后。结果:临床表现为眼部不适,眼睑肿胀及视物模糊等。镜下可见肿瘤由形态多样的小B细胞组成,包括边缘带细胞（中心细胞样细胞）、单核样细胞、小淋巴细胞,也可见散在的免疫母细胞和中心母细胞样细胞,部分细胞有浆细胞样分化。5例肿瘤细胞CD20（+）、CD3（-）、BCL2（+）、Ki67约10%~25%,3例BCL10及AEG1阳性,1例伴浆细胞分化,免疫组化表现为CD20（-）、CD79α（+）、CD38（+）、CD138（+）、MUM1（+）、Kappa、Lambda呈限制性表达,2例FISH检测结果阳性。结论:眼附属器MALT淋巴瘤常CD20、BCL2、BCL10、AEG1阳性,FISH可作为辅助诊断。     

脾边缘区淋巴瘤诊治和预后研究进展

脾边缘区淋巴瘤（SMZL）发病率低,占非霍奇金淋巴瘤1%,临床表现呈惰性过程。本文就脾边缘区淋巴瘤临床病理特征、治疗策略和预后因素方面的研究进展作一综述。     

Clinicopathologic features of Waldenstrom's macroglobulinemia and marginal zone lymphoma: are they distinct or the same entity?

Waldenstrom's macroglobulinemia (WM) is considered in the World Health Organization classification as a clinical syndrome associated with monoclonal immunoglobulin (Ig) M secretion, mainly observed in patients with lymphoplasmacytic lymphoma (LPL) and occasionally with other small B-cell lymphomas. Some authors consider it a rare distinct lymphoproliferative disorder with primary bone marrow infiltration and IgM monoclonal gammopathy. As LPL shares important morphologic and immunophenotypic overlaps with marginal zone B-cell lymphomas (MZLs) in cases showing plasmacytic maturation, it remains unclear if they constitute unique or distinct entities. Both diseases are composed of lymphocytes, lymphoplasmacytoid cells, and tumoral plasma cells with a surface (s) IgM-positive sIgD+/ cytoplasmic IgMpositive CD19+ CD20+ CD27+/ CD5 CD10 CD23 phenotype, without a specific marker. Extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, nodal MZL (NMZL), and splenic MZL (SMZL) are distinct entities displaying common morphologic, immunophenotypic, and genetic characteristics. MALT lymphoma is clearly distinct from LPL, although bone marrow infiltration and IgM paraprotein are not rare. Splenic MZL and NMZL are incompletely characterized, but a plasmacytoid/plasmacytic differentiation, autoimmune manifestations, and monoclonal component are frequent in both diseases. Bone marrow involvement is constant in SMZL and present in 60% of NMZLs. Molecular IgVH gene analysis has confirmed this heterogeneity, particularly within SMZL, with mutated and unmutated cases. Further studies are needed to clarify the pathogenesis of these MZLs and their relationship with LPL.     

Immunophenotypic and cytogenetic comparison of Waldenstrom's macroglobulinemia with splenic marginal zone lymphoma

Some B-cell lymphoproliferative disorders displaying a serum monoclonal immunoglobulin (Ig) M protein could be difficult to differentiate from Waldenstrom's macroglobulinemia (WM). We report on the immunophenotypic and cytogenetic characteristics of 85 patients with WM and compare them with 29 patients with splenic marginal zone lymphoma (SMZL). For immunophenotyping, WM and SMZL constantly expressed panB-cell markers (CD19, CD20, CD22, and surface Ig). However, there were differences in the k/l ratio (1.2:1 for SMZL and 4.5:1 for WM) and in some markers such as CD22 and CD11c, which were overexpressed in patients with SMZL compared with patients with WM, whereas CD25 was more frequently positive in WM (88% vs. 44%). The CD103 antigen was always negative in WM, whereas it was positive in 40% of SMZL cases. The monoclonal antibody FMC7 was usually positive in both entities: heterogeneous in WM but homogeneous in SMZL. The combination of CD25 and CD22 could differentiate between WM and SMZL. The principal molecular abnormality in WM is 6q deletion (30% in our experience), whereas in SMZL the most common abnormalities are loss of 7q (19%) along with +3q (19%) and +5q (10%). Interestingly, the incidence of IgH rearrangement was low in WM (12%) and SMZL (10%). Immunophenotypic and molecular cytogenetic studies could help to distinguish WM from SMZL.     

Outline for Writing an Article for Current Treatment Options in Oncology: Splenic Lymphoma with Villous Lymphocytes

Two subtypes of splenic marginal zone lymphoma (SMZL) are identified in the World Health Organization (WHO) classification: SMZL without villous lymphocytes and SMZL with villous lymphocytes in the peripheral blood (SLVL). SLVL is a rare leukemic and indolent B-cell chronic lymphoproliferative disorder (B-CLPD) that we have to differentiate from hairy cell leukemia (HCL), B prolymphocytic leukemia (B-PLL) and follicular lymphoma (FL). Morphological examination associated with immunophenotyping is, in most cases, likely to distinguish these CD5 negative entities. However, the diagnosis can be difficult to make on morphological criteria, especially in patients without absolute lymphocytosis. Based on histologic, cytogenetic and molecular studies, SLVL emerges as a distinct entity. SLVL has a relatively clinical benign course but a few patients could require treatment, because of a symptomatic splenomegaly and/or a severe cytopenia. In symptomatic patients HCV negative, the frontline treatment remains questionable. Splenectomy, regarded as the most effective treatment, could be required for diagnostic purposes: however, relapse occur in 30% of cases. Fludarabine (FDR), a purine analogue and deoxycoformycin (DCF) can induce a maintained response in a substantial proportion of patients with SLVL and could be used as a first line treatment. In HCV + SLVL patients, antiviral treatment using alpha interferon and ribavirin can induce regression of SLVL.     

Establishment and characterization of the new splenic marginal zone lymphoma-derived cell line UCH1 carrying a complex rearrangement involving t(8;14) and chromosome 3

A new cell line, designated UCH1, was established from a patient with splenic marginal zone lymphoma (SMZL). UCH1 cells feature a mature B-cell phenotype, characterized by surface IgM +, kappa+, CD5-, CD10-, CD19+ and CD20+. The BCL2 and BCL6 genes retained their germ-line configurations and overexpression of cyclin D1 was not detected. UCH1 cells carry numerical and structural aberrations in chromosome 3, but these were too complex to be analyzed with the conventional G-banding method. Spectral karyotyping (SKY) and fluorescence in situ hybridization analysis clearly demonstrated the presence of a balanced translocation between chromosomes 8 and 14 [t(8;14)(q24;q32)] in the complex aberrations involving chromosome 3. The results of Southern blot analysis supported this finding by showing rearrangement of the c-myc gene in UCH1 cells. SKY analysis also identified a translocation involving chromosome band 18q21, to which BCL2 and MALT1 genes were assigned, suggesting their implication in the development or progression of SMZL.     

A Review on Splenic Diffuse Red Pulp Small B-Cell Lymphoma

Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is a rare disease, representing <1% of all non-Hodgkin lymphomas (NHL). The most common clinical manifestations include splenomegaly, lymphocytosis, and hemocytopenia. A diagnosis of SDRPL can be challenging, as it shares multiple clinical and laboratory features with splenic marginal zone lymphoma (SMZL), hairy cell leukemia (HCL), and HCL variant (HCL-v). Obtaining splenic tissue remains the gold standard for diagnosis. In the cases where splenic tissue is not available, diagnosis can be established by a review of peripheral blood and bone marrow studies. SDRPL is characterized by a diffuse involvement of the splenic red pulp by monomorphous small-to-medium sized mature B lymphocytes effacing the white pulp. The characteristic immunophenotype is positive for CD20, DBA.44 (20 to 90%), and IgG, and typically negative for CD5, CD10, CD23, cyclin D1, CD43, annexin A1, CD11c, CD25, CD123, and CD138. The Ki-67 proliferative index is characteristically low. Cyclin D3 is expressed in the majority of SDRPL in contrast with other types of small B-cell lymphomas, thus facilitating the recognition of this disease. There is no standard treatment regimen for SDRPL. Initial treatment options include splenectomy, rituximab monotherapy, or a combination of both. Chemoimmunotherapy should be considered in patients with advanced disease at baseline or progression.     

CD20阳性血管免疫母细胞性 T 细胞淋巴瘤1例及文献复习

目的:探讨CD20阳性血管免疫母细胞性T细胞淋巴瘤（angioimmunoblastic T cell lymphoma,AITL）的临床特征及预后。方法:回顾分析我院1例CD20阳性AITL患者的临床病理特征、治疗转归并复习相关文献。结果:患者男性,69岁,以水肿及腹腔积液为首发表现,CT提示全身淋巴结肿大。免疫表型:CD20阳性、CD3(+)、CD5(+)、Ki-67(+,85%),其它B细胞标记阴性,EBER原位杂交阳性,TCR基因重排及IGH单克隆性重排阳性,多种治疗方案均无效。结论:CD20阳性AITL患者的临床病理特征易与B细胞淋巴瘤混淆,病理形态学、免疫组织化学及TCR基因重排检测等可减少误诊。利妥昔单抗及其他靶向药物的应用可能提高治愈率,改善患者预后。     

Splenic marginal-zone lymphoma: a distinct clinical and pathological entity

In the World Health Organization classification system, splenic marginal-zone lymphoma (splenic MZL) is described as an indolent B-cell lymphoma, which generally presents as splenomegaly with involvement of the bone marrow and peripheral blood. Presence of disease in peripheral lymph nodes and extranodal locations is uncommon. Splenic MZL is characterised by micronodular infiltration of the spleen with marginal-zone differentiation; the immunophenotype is usually IgM+ IgD+/- cytoplasmic-Ig-/+ pan B antigens+ CD5- CD10- CD23- CD43-/+ cyclin D1-; and the most common genetic abnormalities are deletions at 7q22-7q32. Most patients with splenic MZL live for a long time but classic prognostic factors cannot distinguish between patients who are likely to have good and poor outcomes. However, immunological events, such as haemolytic anaemia and immune thrombocytopenia, or the presence of a monoclonal component, are significantly associated with shorter survival. Splenectomy is considered the first-line treatment of choice for splenic MZL; it results in only partial remission, but responses are generally sufficient for correcting cytopenia, improving quality of life, and increasing survival.     

An unusual case of indolent B-cell lymphoma with distinct chronic lymphocytic leukemia and marginal zone differentiation according to the site of involvement

The immunological profile of lymphoproliferative disorders is usually conserved whatever the involved site, thus allowing a reliable diagnosis from peripheral blood analysis, especially in small lymphocytic lymphoma/chronic lymphocytic lymphoma (SLL/CLL). Here we present a case wherein the cytology and immunophenotype of blood specimen and bone marrow argue in favor of SLL/CLL with a typical Matutes score (5/5), whereas the cyto-histology and immunophenotype of spleen specimen led to the diagnosis of splenic marginal zone B-cell lymphoma (SMZL). Moreover genomic analysis showed that the splenic cells displayed a SMZL signature. Whereas these data suggested the presence of 2 B-cell clones, the study of the mutational status of IgV_H gene in blood and spleen demonstrated the presence of a single clone, which likely developed simultaneously along two distinct ways of differentiation according to the anatomic site suggesting here the predominant role of a micro-environmental factor in cell differentiation. Although rare, this kind of event must be kept in mind as a cause of discrepancies between diagnoses from different sites.     

Splenic marginal zone lymphoma: current knowledge and future directions

Splenic marginal zone lymphoma (SMZL), along with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and nodal marginal zone lymphoma (NMZL), share a common origin from the "marginal zone." However, these three entities display different clinical characteristics, reflecting probable biological variations according to the organ and cellular origin. Within the past decade, new data have been reported regarding pathogenic mechanisms as well as therapeutic advances. Clinically, SMZL presents as an indolent and disseminated disease at diagnosis, with a specific clinical presentation that includes predominantly splenomegaly, and in half of patients, autoimmune manifestations. Establishing the diagnosis may be difficult, especially distinguishing SMZL from other low-grade lymphomas, such as small B-cell lymphomas; however, recent findings have contributed to a better characterization of the disease, and the criteria for diagnosis have been improved. Therapeutic approaches consist of splenectomy or immunochemotherapy, but there is no consensus regarding the best treatment, except when SMZL is associated with hepatitis C virus infection. In this article, we review the current knowledge on the biological findings, clinical features, and therapeutic approaches for SMZL.