Correlation between immunophenotypic diversity and clinical features in B-cell lymphoblastic lymphoma

Lymphoblastic lymphoma (LBL) is a highly malignant subtype of non-Hodgkin's lymphoma (NHL) and generally carries a T-cell phenotype with mediastinum or central nervous system (CNS) involvement. However, only a small proportion of LBL exhibit a B-cell phenotype (B-LBL), and these frequently present at the head and neck without mediastinum or CNS involvement. Three immunological subgroups may exist. The most predominant CD10-positive pre-B-cell type, corresponding to a precursor B-cell neoplasm, frequently involves the head and neck. The second, CD10-negative or mature B-cell type, defined by the absence of CD10 or presence of surface membrane immunoglobulins combined with expression of CD19 or CD20, often involves the mediastinum. The final group is a CD5-positive B-cell type corresponding to a blastic variant of mantle cell lymphoma (MCL). Its clinical course is less aggressive, patients are often older, and nodal lesions are more frequent than extranodal involvement. Thus, B-LBL is immunologically diverse, but its biological behavior correlates with the immunophenotype.     

A prospective study on antibody response to repeated vaccinations with pneumococcal capsular polysaccharide in splenectomized individuals with special reference to Hodgkin's lymphoma

BACKGROUND: Splenectomy is accompanied by a life-long risk of overwhelming postsplenectomy infection (OPSI), mainly caused by polysaccharide (PS) encapsulated bacteria such as Streptococcus pneumoniae. Despite extensive prophylactic efforts the mortality and morbidity rates remain high. The present study was based on a strategy with a predefined vaccination algorithm including repeated 23-valent pneumococcal vaccinations and monitoring of pneumococcal antibody levels. The antibody levels of splenectomized Hodgkin's lymphoma (HL) patients were compared with those patients splenectomized due to immune-mediated cytopenias [autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP)] and also individuals who were splenectomized because of trauma (TRAUMA). METHODS: A total of 311 splenectomized individuals were included in this prospective study (208 HL; 15 AIHA; 60 ITP; 28 TRAUMA). Depending on their individual anti-PS antibody levels measured by enzyme-linked immunosorbent assay technique the patients were revaccinated with 23-valent pneumococcal PS vaccine up to four times in accordance with the predefined algorithm. For each vaccination occasion, serum was collected at vaccination, after 1 month +/- 2 weeks (peak), and after 1 year +/- 6 months (follow-up). Patient files, a national population-based database, and microbiological databases were checked for 124 HL patients to identify OPSI. RESULTS: A significant response was recorded on primary vaccination as well as on two revaccination occasions for HL, AIHA/ITP, as well as TRAUMA patients. None of the variables age, gender, or time elapsed between splenectomy and first pneumococcal vaccination was found to be associated with mean PS antibody levels at prevaccination, peak or follow-up. No severe adverse events were reported. Amongst 124 clinically monitored HL patients, 10 OPSI were recorded in seven patients during the study period. One of these patients, a middle-aged female, died as a result of fulminant pneumococcal bacteraemia, which was her third OPSI during a 7-year period. CONCLUSIONS: A significant response to pneumococcal PS vaccination was found in all three groups (HL, AIHA/ITP and TRAUMA) of splenectomized patients. Importantly, both primary and repeated vaccinations were safe. Until further knowledge is gained regarding the protective concentration of serotype-specific antibody concentrations we believe that the value of vaccination and frequent revaccination (every 1-5 years) in combination with education of patients and health care professionals and clinical monitoring is beneficial for these patients at risk for OPSI.     

Impaired PI3K/Akt signal pathway and hepatocellular injury in high-fat fed rats

AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this membrane.RESULTS:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P < 0.01),deformed mitochondria (9.0% ± 4.3% vs 83.0% ± 10.9%,P < 0.05),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P < 0.05). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis.     

Rapid deterioration of intravascular large B-cell lymphoma with mass formation in the trigeminal nerve and multiple organ infiltration: An autopsy case report

Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoma characterized by the selective growth of lymphoma cells within the lumen of vessels. We describe the case of a 69-year-old male who presented with marked pain in the left facial region. Gadolinium-enhanced magnetic resonance imaging revealed a swollen left trigeminal nerve (TN) and positron emission tomography/computed tomography demonstrated fluorodeoxyglucose-only uptake at the same site. The patient had high serum lactate dehydrogenase and soluble interleukin-2 receptor levels. As random skin biopsy and bone marrow biopsy detected no abnormal pathogenesis, open biopsy of the TN was performed, revealing diffuse large B-cell lymphoma (DLBCL). However, ground glass opacities rapidly developed in both lung fields with severe respiratory failure. The patient died of progressive disease before the initiation of chemotherapy. Postmortem examination revealed widespread lymphoma cells in the lumen of vessels in multiple organs, including the lungs, excluding the bone marrow and skin. Lymphoma cells formed a mass in the TN and left lumbar plexus. A diagnosis of IVLBCL was made based on the postmortem pathological analysis. DLBCL of abnormal sites, such as the peripheral nervous system, should be considered in cases of IVLBCL as a differential diagnosis.     

A sporadic case of CTLA4 haploinsufficiency manifesting as Epstein–Barr virus-positive diffuse large B-cell lymphoma

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is a coinhibitory receptor that plays an essential role in maintaining immune system homeostasis by suppressing T-cell activation. We report a sporadic case of CTLA4 haploinsufficiency in a patient with Epstein–Barr virus-positive diffuse large B-cell lymphoma and subsequent benign lymphadenopathy. A missense mutation in exon 2 of the CTLA4 gene (c.251T>C, p.V84A) was found in the patient’s peripheral blood and buccal cell DNA, but not in her parents’ DNA. CTLA4 expression decreased in the peripheral regulatory T cells upon stimulation, whereas CTLA4 and PD-1-positive T cell subsets increased, possibly to compensate for the defective CTLA4 function. This case suggests that some adult lymphoma patients with no remarkable medical history have primary immune disorder. As immune-targeted therapies are now widely used for the treatment of malignancies, it is increasingly important to recognize the underlying primary immune disorders to properly manage the disease and avoid unexpected complications of immunotherapies.     

外周T细胞淋巴瘤合并自身免疫性溶血性贫血的临床特点分析

背景与目的:与自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)相关的淋巴瘤病理学类型多见于惰性B细胞淋巴瘤,而很少见于弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)及外周T细胞淋巴瘤(peripheral T-cell lympho...     

骨原发性恶性淋巴瘤影像学诊断与组织病理对照研究

目的 探讨骨原发恶性淋巴瘤(PLB)的影像学表现特点.方法 回顾性分析经手术或穿刺活检病理学证实的PLB 9例,其中男6例,女3例,年龄9～60岁,中位年龄26.5岁.9例中X线平片检查8例、CT检查5例、MRI检查7例.其中2例行X线平片和MR检查,2例CT和MR检查,4例具有X线、CT和MR资料.2例为穿刺活检证实;7例行手术切除和病理学检查证实,全部病例均做了常规的组织切片HE染色和免疫组化检查.结果 病灶位于骨盆4例、额骨1例、枕骨斜坡1例、脊柱1例、股骨上端2例.影像学表现:X线表现,病变骨组织外形基本正常4例,内部可见斑点状、大小不等的虫蚀状骨质破坏;4例表现为病变骨质轻度～中度膨胀性改变,局部骨质呈明显溶骨性破坏:CT表现骨髓腔内和骨皮质上可见大小不等的溶骨性破坏,病变骨质周围围绕明显的软组织肿块;MR表现病变区骨髓腔内及周围软组织肿块在T2WI上呈不均匀中度～明显高信号,T1WI上呈均匀等信号.增强扫描后骨髓腔内病灶和周围软组织肿块在CT和MRI上均呈中度～明显强化.病理结果B细胞型5例、T细胞型4例.结论 影像学上PLB以斑点状或渗透性溶骨性破坏为主,病变骨质外形可正常或呈膨胀性改变,伴有明显的周围软组织肿块,中块以病骨为中心生长并有明显强化为其特征.     

Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma

In this study, we aimed to investigate how homologous recombinant (HR)-related genomic instability is involved in ionizing radiation (IR)-induced thymic lymphoma in mice. We divided five-week-old Rosa26 Direct Repeat-GFP (RaDR-GFP) transgenic mice into non-IR control and IR groups and exposed the mice in the IR group to a 7.2 Gy dose of γ-rays, delivered in 1.8 Gy fractions, once a week for four weeks. We then estimated mouse survival and recorded their body, thymus, and spleen weights. The frequency of HR events in the chromosomes of the thymus, bone marrow, and spleen cells and the phenotype of thymic lymphoma cells were analyzed using fluorescence-activated cell sorting (FACS). We found that most mice in the IR group developed thymic lymphoma, their survival rate decreasing to 20% after 180 days of IR exposure, whereas no mice died in the non-IR control group until day 400. The thymus and spleen weighed significantly more in the IR-4-month group than that in the non-IR group; however, we observed no significant differences between the body weights of the control and IR mice. FACS analysis indicated that the frequency of HR events significantly increased at two and four months after the last IR dose in the bone marrow and thymus cells, but not in the spleen cells of RaDR-GFP transgenic mice, suggesting that recombinant cells accumulated in the thymus upon IR exposure. This suggests that IR induces genome instability, revealed as increased HR, that drives the development of thymic lymphoma. Additionally, phenotypic analysis of lymphoma cells showed an increase in the CD4^-/CD8⁺ (CD8SP) cell population and a decrease in the CD4⁺/CD8^- (CD4SP) cell population in the IR-4-month group compared to that in the non-IR group, indicating that IR induces an aberrant cell phenotype characteristic of lymphoma. In conclusion, we observed a significant increase in HR events and abnormal phenotype in thymic lymphoma cells at two and four months after IR exposure in both the thymus and bone marrow tissues, suggesting that genomic instability is involved in the early stages of thymic lymphomagenesis. Our study indicates that HR-visualizing RaDR-GFP transgenic mice can help explore the links between the molecular mechanisms of genome instability and IR-induced tumorigenesis.     

初发表现为不典型结节的A型淋巴瘤样丘疹病1例报道

本文报告1例49岁男性淋巴瘤样丘疹病患者,皮损广泛发作且多种形态,表现为小核桃大小结节和红色小花生米大小水肿性丘疹,但无瘙痒,病程9年,再发2周.曾在第一次皮损发作时进行过5次局部注射"得宝松"(复方倍他米松注射液)和光化学疗法照光治疗;本次就诊未进行处理,皮损能自行减轻.局限性或无症状的泛发性皮损建议采取观望策略,但...     

利妥昔单抗对儿童高分期成熟B细胞非霍奇金淋巴瘤的疗效研究

目的探讨儿童高分期、成熟B细胞非霍奇金淋巴瘤标准化疗联合利妥昔单抗治疗的的有效性和安全性。方法收治儿童非霍奇金淋巴瘤62例,为St.Jude分期Ⅲ～Ⅳ的患者,35例采用法国儿童肿瘤协会系列研究(lymphomes malins B,LMB)89方案,27例采用LMB89联合利妥昔单抗治疗方案,分析两组患儿的临床资料特征、治疗效果,Kaplan-Meier方法进行生存分析。结果原发部位、病理诊断、临床分期、乳酸脱氢酶≥2ULN者和骨髓和(或)中枢神经受累等参数两组相比均无统计学差异(P>0.05)。治疗后,LMB89组中有5例继发感染,LMB89+利妥昔单抗组为8例,差异无统计学意义(P>0.05)。两组发生肿瘤溶解综合征的患儿例数分别为4例和2例,差异无统计学意义(P>0.05)。LMB89组在化疗过程中出现肝功能受损1例,肠穿孔1例。LMB89+利妥昔单抗组出现肝功能受损1例,两组化疗出现并发症总数相比无统计学意义(P>0.05)。LMB89组5年无事件生存率为68.8%,5年总生存率为62.9%,LMB89+利妥昔单抗组5年的无事件生存率为92.6%,5年总...