PD-L1-expressing extranodal diffuse large B-cell lymphoma,NOS with and without PD-L1 3’-UTR structural variations

Immune evasion mediated by PD-L1 plays an important role in the development of B-cell malignancies. However, PD-L1 expression is infrequently observed in tumor cells of extranodal diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Other than copy number alterations, PD-L1 is aberrantly upregulated by structural variations in the 3′-UTR of PD-L1. We report four cases with PD-L1 expression on tumor cells, including two with structural variations in the 3′-UTR of PD-L1 and two without. Our report demonstrates the presence of a small number of “immune evasion-type” extranodal DLBCL, NOS cases.     

MYC/BCL2双表达大B细胞淋巴瘤中PD-L1的表达及其临床意义CSCD

目的探讨MYC/BCL2双表达大B细胞淋巴瘤(DEL)与程序性细胞死亡受体-配体1(PD-L1)mRNA、蛋白表达的相关性及其临床意义。方法收集90例弥漫大B细胞淋巴瘤(DLBCL)病例,采用免疫组织化学染色检测MYC、BCL2蛋白并分组,双标记染色法检测各组病例的肿瘤细胞或微环境细胞中PD-L1表达;实时荧光PCR技术(Real-time PCR,qPCR)检测DEL组与non-DEL组PD-L1 mRNA相对表达量;收集临床病理资料并随访,对实验数据进行统计学分析。结果90例样本中28例为DEL,肿瘤细胞和微环境中PD-L1+分别为22例和26例。DEL组肿瘤细胞和微环境中PD-L1+分别为14例和9例;肿瘤细胞和微环境细胞PD-L1蛋白表达与DEL存在相关性(P<0.05);PD-L1 mRNA相对表达量在DEL与non-DEL组间存在显著差异(P=0.012);DEL组中PD-L1+与IPI评分和B症状的出现有关(P=0.007、0.021);Kaplan-Meier显示DEL中PD-L1+、肿瘤微环境PD-L1阳性(mPD-L1+)与患者预后相关(P=0.005、0.001)。结论DEL患者PD-L1 mRNA及蛋白表达都明显上调且与患者不良预后相关,PD-L1可作为DEL患者不良预后评估的危险因素。     

Post-transplant lymphoproliferative disorders: molecular basis of disease histogenesis and pathogenesis

Post-transplant lymphoproliferative disorders (PTLD) represent a serious complication of solid organ and allogeneic bone marrow transplantation. PTLD generally display B-cell lineage derivation, involvement of extranodal sites, aggressive histology and clinical behaviour, and frequent association with EBV infection. The occurrence of IgV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC) B-cells and their descendants both in EBV-positive and EBV-negative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM-1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6(+)/MUM1(+/-)/CD138(-) profile reflect B-cells actively experiencing the GC reaction and comprise diffuse large B-cell lymphoma (DLBCL) centroblastic and Burkitt lymphoma. PTLD expressing the BCL6(-)/MUM1(+)/CD138(-) phenotype putatively derive from B-cells that have concluded the GC reaction and comprise the majority of polymorphic PTLD and a fraction of DLBCL. A third group of PTLD is reminiscent of post-GC and pre- terminally differentiated B-cells that show the BCL6(-)/MUM1(+)/CD138(+) phenotype and are morphologically represented by either polymorphic PTLD or DLBCL immunoblastic. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely Epstein-Barr virus, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of c-MYC, BCL-6, p53, DNA hypermethylation, and aberrant somatic hypermutation of proto-oncogenes.     

淋巴结外弥漫大B细胞淋巴瘤分子分型的病理学研究

目的探讨结外弥漫大B细胞淋巴瘤（diffuse large B-celll ymphoma,DLBCL）分子分型及免疫组化特点,为临床治疗和预后评估提供帮助。方法采用免疫组化法,标记88例结外原发性弥漫大B细胞淋巴瘤中CD10、bcl-6、MUM1、ki-67的表达并进行分子分型。结果88例结外DLBCL中生发中心B细胞样（GCB）36例,非生发中心B细胞样（non—GCB）52例,GCB组中ki-67的阳性表达率大于75．0％有17例,占47．2％（17／36）,non—GCB组中ki-67的阳性表达率大于75．0％有37例,占71．2％（37／52）。结论结外DLBCL以non—GCB多见。     

Diffuse large B-cell lymphoma (DLBCL) with significant intravascular invasion. Close resemblance of its clinicopathological features to intravascular large B-cell lymphoma,but not to DLBCL-not otherwise specified

Intravascular large B-cell lymphoma (IVLBCL) is defined by the World Health Organization (WHO) Classification as one type of extranodal large B-cell lymphoma and it is characterized by the selective growth of lymphoma cells within blood vessels with minimal extravascular invasion. According to the criteria, however, several reported cases of IVLBCL with significant extravascular invasion cannot be classified as IVLBCL. The purpose of the present study was to assess the clinicopathological significance of the WHO criteria for IVLBCL. We characterized clinical, histopathological, and immunohistochemical features of 11 patients with extranodal diffuse large B-cell lymphoma (DLBCL) with significant intravascular invasion (DLBCL-IV), and statistically compared their features with those of 11 patients with IVLBCL and 15 patients with extranodal DLBCL with virtually no intravascular invasion (DLBCL-noIV). When compared with the DLBCL-noIV group, the DLBCL-IV group was characterized by significantly higher rates of splenomegaly, hemophagocytosis, advanced stage disease, and CD5 expression; higher average platelet count, serum lactate dehydrogenase level, and serum ferritin level. Progression-free survival was significantly shorter in the DLBCL-IV group than the DLBCL-noIV group. In contrast, there were no significant differences in clinicopathological features between the DLBCL-IV and the IVLBCL groups. Our study suggests that DLBCL-IV should be regarded as IVLBCL-related.     

CD30在EBV阳性弥漫性大B细胞淋巴瘤中的表达及其预后意义北大核心

目的:探讨CD30在EBV阳性弥漫性大B细胞淋巴瘤(EBV-positive diffuse large B-cell lymphoma,EBV+DLBCL)中的表达及预后意义。方法:回顾性分析322例DLBCL中EBV+DLBCL与EBV-DLBCL病例临床病理参数之间的关系,以及CD30在EBV+DLBCL中的表达及预后意义。结果:CD30在EBV+DLBCL病例中的表达多于EBV-DLBCL病例(P=0.002);EBV-DLBCL中双表达的病例多于EBV+DLBCL(P=0.044);在63例EBV+DLBCL中,CD30阳性表达多见于B症状患者(P=0.015);另外有2例EBV+DLBCL病例出现BCL6基因重排。随访139例患者中,共表达CD30和EBER的患者预后较差(P=0.002);在EBV+DLBCL中,CD30阳性提示预后更差(P=0.028)。结论:CD30在EBV+DLBCL病例中具有较高的表达率,且与患者不良预后相关,进一步为靶向药物的使用提供理论依据。     

Lymphocyte-depleted classic Hodgkin lymphoma with primary extranodal disease: Two cases that highlight the combination of immunodeficiency and immune escape in the pathogenesis

Neoplastic programmed cell death ligand 1 (PD-L1) expression, activated by PD-L1 gene alterations, is strongly associated with classic Hodgkin lymphoma (CHL). This association enabled a diagnostic consensus for lymphocyte-depleted CHL (LD-CHL), a previously enigmatic disease. We describe two patients with LD-CHL and primary extranodal disease. One patient was a 92-year-old female (Case #1) with a large mass that involved the uterus combined with swollen lymph nodes in the pelvic cavity. The second patient was a 76-year-old female (Case #2) with human T-cell leukemia virus type 1 (HTLV-1) who initially exhibited massive bone marrow involvement without peripheral lymphadenopathies. Biopsies of these tumors from the cervix uteri and bone marrow, respectively, revealed lesions rich in Hodgkin and Reed-Sternberg (H-RS) cells and diminished populations of other cell populations. Immunohistochemistry demonstrated that these H-RS cells expressed CD30, BOB1, and fascin, but not CD15, CD20, PAX5, or OCT2. They also expressed PD-L1, which led to our preferred diagnosis of LD-CHL in both patients. Epstein-Barr virus was associated with LD-CHL in Case #1, but not in Case #2. Both patients were deemed too frail for treatment. They died of disease at 1 (Case #1) and 15 months (Case #2) after the diagnosis. These findings highlight the abnormal biological behavior of this immune-escape-related lymphoid neoplasm in patients with immunodeficiency due to immune senescence and HTLV1 infection.     

弥漫大B细胞淋巴瘤中B7-H1临床表达水平分析

目的 对弥漫大B细胞淋巴瘤(DLBCL)中B7-H1的表达水平进行分析.方法 收集DLBCL患者病理活检或手术切除的肿瘤组织标本50例,另收集瘤周正常淋巴组织标本50例作为对照.采用Western Blot法检测B7-H1在瘤周正常淋巴组织与DLBCL肿瘤组织中的表达水平;采用流式细胞仪检测瘤周正常淋巴组织与DLBCL肿瘤组织中B7-H1和调节性T细胞(Treg)的表达水平.结果 Western Blot检测结果显示,B7-H1在DLBCL肿瘤组织与瘤周正常淋巴组织中均有表达,与瘤周正常淋巴组织比较,DLBCL肿瘤组织中B7-H1的表达水平较高.HLA-DR+CD14+巨噬细胞在DLBCL肿瘤组织中表达B7-H1的比例较瘤周正常淋巴组织高(P﹤0.05).与瘤周正常淋巴组织相比较,DLBCL肿瘤组织中(包括IPI值≥2分与IPI值﹤2分)pDC、Treg、mDC与调节性T细胞(CD4+/CD8+)的比例较高(P﹤0.05).结论 B7-H1在DLBCL患者的淋巴组织中呈高表达,提示B7-H1与淋巴瘤细胞的免疫逃逸有关,从而造成了DLBCL细胞免疫平衡的失调.     

Primary Diffuse Large B-Cell Lymphoma of the Urinary Bladder: Update on a Rare Disease and Potential Diagnostic Pitfalls

Diffuse large B-cell lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma. Globally, DLBCL is an aggressive disease, requiring an accurate diagnosis and prompt treatment. The diagnosis is often made on biopsy samples of a nodal mass, however, approximately 40% of DLBCL cases arise at extranodal sites. The most common extranodal site is the gastrointestinal tract, however any extranodal area may be primarily involved. Primary urinary bladder lymphoma represents only 0.2% of extranodal non-Hodgkin lymphomas, whereas secondary involvement of the urinary bladder by a systemic lymphoma is a more common event. Despite being rare, DLBCL is considered to represent the predominant primary urinary bladder lymphoma. The majority of cases reported in the bladder belong to the DLBCL, NOS group, and there are only rare cases of EBV-positive DLBCL, NOS. In this review, we summarize the current knowledge on DLBCL primarily occurring in the urinary bladder, with the aim of increasing clinician and pathologist awareness on this aggressive lymphoma rarely arising in the urinary bladder. Additionally, we focus on those entities which should be taken into consideration in the differential diagnosis, highlighting potential diagnostic pitfalls.     

非特指EBV阳性弥漫大B细胞淋巴瘤的研究进展

EB病毒(Epstein-Barr virus,EBV)感染人体后,可长期潜伏于静息记忆性或幼稚B淋巴细胞中。随着免疫系统的衰老,EBV感染者发生EBV相关恶性肿瘤的风险明显增加。非特指EBV阳性弥漫大B细胞淋巴瘤(EBV positivediffuse large B-cell lymphoma, not otherwise specified,EBV⁺DLBCL-NOS)是指发生在无已知免疫缺陷疾病或淋巴瘤病史,且肿瘤细胞核表达EBV编码RNA(EBV encoded RNA,EBER)的大B细胞淋巴瘤。流行病学研究显示,EBV⁺DLBCL-NOS主要流行于亚洲及拉丁美洲,多数患者年龄超过50岁。临床上,与EBV阴性DLBCL(EBV negative DLBCL,EBV-DLBCL)患者相比,EBV⁺DLBCL-NOS患者的临床病程更具侵袭性,初诊患者的临床分期多为晚期,且结外受累率可超过80%。老年患者通常较年轻患者的预后更差。尽管包括利妥昔单抗的免疫化疗方案可显著提高EBV-DLBCL患者的预后,EBV     

Age cutoff for Epstein-Barr virus-positive diffuse large B-cell lymphoma–is it necessary?

Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly (EBV+ DLBCL-e) is a molecularly distinct variant of DLBCL, characterized by a monoclonal B-cell proliferation that occurs in patients >50 years of age without a history or clinicopathologic evidence of immunodeficiency. However, patients with EBV+ DLBCL younger than 50-years-old also exist in Western countries. We evaluated the clinicopathologic, immunophenotypic and genetic features in Cacausian patients with EBV+ DLBCL who are ≤50 years of age and compared this patient group to patients who are >50 years. In patients who are ≤50 years, less frequent expression of BCL6 and a trend of more frequent expression of CD30 and pSTAT3 were found in patients with EBV+ DLBCL. In patients who are >50 years, common expression of CD30, p50, pSTAT3 and less frequent expression of BCL6 were observed. Older patients also more commonly had a poor performance status (ECOG≥2). Comparing EBV+ DLBCL patients in ≤50 years versus >50 years, both groups had similar clinicopathologic, immunophenotypic and genetic features. Gene expression profiling, microRNA profiling and treatment outcome of the younger patients with EBV+ DLBCL was not distinctive from tumors in older patients. Based on our data, we suggest that the arbitrary age cutoff for EBV+ DLBCL is unnecessary and should be eliminated in the WHO lymphoma classification scheme.     

171例淋巴瘤病变组织中EB病毒表达情况的分析

目的:探讨不同类型淋巴瘤与EB病毒(Epstein-Barr virus,EBV)感染的关系。方法:收集淋巴瘤组织171例,包括弥漫大B细胞淋巴瘤(DLBC)106例;结外NK/T细胞淋巴瘤,鼻型22例;霍奇金淋巴瘤(HL)19例;血管免疫母细胞性T细胞淋巴瘤(AITL)13例;黏膜相关淋巴组织B细胞淋巴瘤(MALT)11例。应用EBV Lmp-1单抗免疫组化(IHC)和生物素标记的EBER1寡核苷酸探针原位杂交(ISH)分析EBV感染与淋巴瘤的关系。结果:淋巴瘤组织中EBV Lmp-1蛋白与EBER1 mRNA总阳性率分别为11.1%(19/171)、25.7%(44/171)。其中AITL为30.8%(4/13)、61.5%(8/13);HL为47.4%(9/19)、57.9%(11/19);结外NK/T细胞淋巴瘤为22.7%(5/22)、81.8%(18/22);DLBC为0.94%(1/106)、5.7%(6/106);MALT为0(0/11)、9.1%(1/11)。结果显示EBV在DLBC及MALT中的表达率低于AITL、HL及结外NK/T细胞淋巴瘤,差异有统计学意义(P0.05);且原位杂交检测EBER1 mRNA比免疫组化检测Lmp-1蛋白更为敏感(P0.01)。结论:EBV感染与淋巴瘤有密切关系,不同类型淋巴瘤与EBV感染的关系有差异。     

Hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus-positive diffuse large B-cell lymphoma,NOS of bone marrow-liver-spleen type: an autopsy case report

Lymphoma-associated hemophagocytic lymphohistiocytosis (HLH) has a significantly poor prognosis among secondary HLH. We describe the rare case of a 74-year-old female with secondary HLH presenting with a rapidly fatal course. Post-mortem examination revealed Epstein-Barr virus (EBV) -positive diffuse large B-cell lymphoma (DLBCL). We were unable to make a definite antemortem diagnosis because the patient did not exhibit lymphadenopathy and bone marrow biopsy demonstrated hemophagocytosis without evidence of lymphoma. She died of multiple organ failure on the twelfth day of hospitalization despite a temporary response to steroids. Autopsy revealed diffuse lymphoma cell infiltration of the bone marrow, liver and spleen, suggesting “bone marrow-liver-spleen” (BLS)-type large B-cell lymphoma (LBCL). BLS-type LBCL is a rare and clinically aggressive lymphoma, usually associated with fever, cytopenia and HLH. The disease has a high mortality rate due to the delay in diagnosis and a highly aggressive clinical course. Further studies are required to improve our understanding of this rare extranodal DLBCL.     

Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma: Is It Different between Over and Under 50 Years of Age?

Background: Epstein–Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly is an entity introduced in the latest WHO classification of lymphoid tumors and defined in patients older than 50 years without prior lymphoma or immunodeficiency. However, recently it has also been seen in patients under 50. There is thus debate as to whether these are separate entities. Materials and Methods: In this retrospective study, we analyzed de novo DLBCL admitted to our institute over a period of two years. Clinical data included age, sex, nodal and extranodal presentation. The results of an immunohistochemistry (IHC) panel were also reviewed. IHC findings were mainly used to sub-classify DLBCL as germinal center vs. non germinal center types. IHC for identification of LMP-1 (latent membrane protein) and in situ hybridization for detection of EBV- encoded RNA (EBER) was performed. EBV prevalence, clinical data and IHC findings were compared between patients under and over 50 years of age. Results: Out of 95 DLBCL, 11.6% were EBV positive (7.5% and 14.5% in the young and old groups). We did not find any significant differences in IHC subclasses and clinical data between EBV positive DLBCL (EBVDLBCL) of young and old groups. Conclusions: EBVDLBCL are not exclusive to patients older than 50 years. With regard to clinical data as well as IHC subclasses, no differences were evident between EBVDLBCL of young and old groups. Our suggestion is to eliminate any cut off age for EBVDLBCL.     

Predicting treatment response of patients with extranodal natural killer/T-cell lymphoma based on levels of PD-L1 mRNA and soluble PD-L1

Appropriate biomarkers may help predict patient response to treatment for extranodal natural killer/T-cell lymphoma (ENKTL), a subtype of non-Hodgkin's lymphoma in China. Programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) have been investigated in various tumors. However, few studies have addressed expression of PD-1/PD-L1 in peripheral blood of ENKTL patients. To identify novel peripheral blood biomarkers for diagnosis and treatment of ENKTL, we retrospectively examined 89 healthy volunteers, 49 patients with ENKTL and 74 patients with diffuse large B-cell lymphoma treated at West China Hospital from September 2017 to September 2018. Both patient groups showed significantly higher expression of PD-1 and PD-L1 on CD4+ T cells, higher levels of PD-L1 mRNA in peripheral blood mononuclear cells (PBMCs) and higher levels of soluble PD-L1 in plasma than healthy volunteers (P < .05). In ENKTL patients, levels of PD-L1 mRNA and soluble PD-L1 were related to disease stage, level of lactate dehydrogenase, lymphocyte count, and copies of Epstein-Barr genome in blood. Levels of PD-L1 mRNA and soluble PD-L1 were similar between healthy volunteers and ENKTL patients who showed complete remission after treatment, and uni- and multivariate analyses identified soluble PD-L1 as a predictor of treatment response in ENKTL patients. Our results suggest that the levels of PD-L1 mRNA in PBMCs and soluble PD-L1 in plasma are useful for ENKTL staging and prediction of treatment response.     

EB病毒阳性老年人弥漫大B细胞淋巴瘤二例并文献复习

 目的　分析我国老年人EB病毒（EBV）阳性弥漫大B细胞淋巴瘤（DLBCL）的临床特点,提高对该病的认识。方法　报道2例老年人EBV阳性DLBCL患者临床、实验室资料及治疗经过。结果　老年人EBV阳性DLBCL高发年龄70～79岁,患者主要表现为全身淋巴结肿大,可伴结外器官受累,可出现巨脾和免疫性溶血性贫血,多伴有发热、体质量减轻等B症状,病理表现为多形性大细胞浸润,伴不同程度的反应性细胞,特别是T细胞增殖。结论　老年EBV阳性DLBCL患者肿瘤细胞CD20或CD79a阳性,EBV 编码的小RNA（EBER）阳性。疾病进展快,对标准化疗反应差。利妥昔单抗对CD20阳性病例短期有效,但疗效有限。患者的生存期短。死亡原因主要是感染所致的呼吸衰竭。     

Epstein‐Barr virus‐positive diffuse large B‐cell lymphoma association is not only restricted to elderly patients

Diffuse large B‐cell lymphoma (DLBCL), the most common group of malignant lymphomas, account for 30% of adult non‐Hodgkin lymphomas. The 2008 World Health Organization (WHO) classification included a new entity, Epstein‐Barr virus (EBV)+ DLBCL of the elderly, affecting patients aged 50 years or older. However, some reports of younger EBV+ DLBCL cases, without evidence of underlying immunosuppression, can be found. The role of EBV in tumor microenvironment composition in DLBCL is still not well understood. Our aim was to assess EBV presence and latency pattern as well as tumor T‐cell population in an adult DLBCL series of Argentina. The study was conducted on biopsies from 75 DLBCL patients. EBERs expression was performed by in situ hybridization, while EBV gene expression was analyzed using real‐time polymerase chain reaction. LMP1, LMP2A, EBNA2, EBNA3A, CD4, CD8 and Foxp3 expression was assessed by immunohistochemistry. Nine percent of cases showed EBV expression, with similar frequency among patients younger than 50 years and 50 years or older (13% and 8%, respectively). T‐cell subsets were not altered by EBV presence. Latency type II was the most frequently observed, together with lytic gene expression in EBV+ DLBCL, with ≥20% of EBERs+ cells. These findings suggest that EBV+ DLBCL in our series was similar to the previously described in Asia and Latin‐America, displaying latency II or III expression profile and no age‐specific characteristics. Finally, EBV+ DLBCL may be an entity that is not only restricted to patients who are older than 50 years of age, in consequence the age cutoff revision may be a current goal.     

Expression and clinical value of programmed cell death-ligand 1(PD-L1)in diffuse large B cell lymphoma:a retrospective study

Background: The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis. Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical (IHC) assay. The expression of anaplastic lymphoma kinase (ALK), CD5, CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein–Barr virus (EBV)-encoded RNAs (EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan–Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis. Results: Of the 204 patients, 100 (49.0%) were PD-L1-positive in tumor cells and 44 (21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like (GCB) subtype than in the GCB subtype (P = 0.02 and P = 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment (P = 0.03). PD-L1 expression in tumor micro-environment was negatively correlated with C-Myc expression (r = ? 0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival (OS) rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells (P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS (P < 0.01). Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expres-sion in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.     

原发乳腺弥漫大B细胞淋巴瘤的诊断与治疗进展

原发乳腺淋巴瘤(PBL)是一种少见的结外淋巴瘤亚型,具有独特的特点.最主要的病理类型为弥漫大B细胞淋巴瘤(DLBCL),其他病理类型比较罕见.文章将以原发乳腺DLBCL为主,阐述其疾病定义、分期,并探讨全身性化疗、局部巩固放疗及利妥昔单抗靶向治疗的地位.     

Sequential development of peripheral t-cell lymphoma post immunochemotherapy of diffuse large B cell lymphoma

Reports of sequential occurrence of two or more types of lymphoma are rare, especially when they involve different cell lineages. Herein, we report a rare case of sequential development of peripheral t-cell lymphoma following treatment of diffuse large B cell lymphoma. In a 73-year-old Chinese male patient, diffuse large B-cell lymphoma (DLBCL) was diagnosed in September 2011 based on the result of a tongue biopsy. Afterwards, he received rituximab combined with chemotherapy and local radiotherapy. Though he achieved completed remission, he had a new symptom of one enlarged left inguinal lymph node in November of 2015. A new biopsy was then performed. Immunohistochemistry and polymerase chain reaction (PCR) for gene rearrangements proved monoclonal T-cell lymphoma. We didn't detect EBV infection in either of two biopsies, nor any evidence of immune dysfunction complications. Sequential development of B-cell and T-cell malignancy in this patient maybe an example of treatment-related secondary lymphoma.