血清外泌体miR-451a在弥漫大B细胞淋巴瘤治疗监测中的意义

目的 探索血清外泌体miR-451a在弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma, DLBCL）中的水平及其在治疗监测中的价值。方法 本研究共纳入56例DLBCL患者,56例健康对照者。收集新发DLBCL患者治疗前、化疗2~4疗程及化疗结束后血清样本,并同时收集健康人血液标本, 提取血清中的外泌体RNA,并进行实时荧光定量PCR（quantitative real time polymerase chain reaction, qRT-PCR）,用受试者工作特征（receive operator characteristic, ROC）曲线判定miR-451a的诊断效能,用各时点收集的血清样本动态分析血清外泌体miR-451a水平与化疗效果之间的关系。结果 56例DLBCL患者与56例健康对照者相比,DLBCL患者血清外泌体miR-451a水平下降（P<0.000 1）,在两组受试者间用miR-451a诊断DLBCL的曲线下面积(AUC)为0.737（95%CI0.645~0.816）。在随访到的43例DLBCL患者中,化疗后获得完全缓解或者部分缓解的患者其血清外泌体miR-451a水平较化疗前有所上升（P<0.05）,与配对的健康人水平差异无统计学意义（P>0.05）;化疗后未获得缓解的患者,其血清外泌体miR-451a水平较化疗前无明显变化（P>0.05）,且仍然低于配对的健康人水平（P<0.05）;化疗完成后在未缓解者与缓解者之间进行鉴别,血清miR-451a的AUC为0.867（95%CI0.728~0.951）。结论 血清外泌体miR-451a水平动态监测有助于DLBCL化疗过程中的疗效（是否缓解）判断。     

Hepatitis C virus in MALT-lymphoma of the ocular adnexa

ObjectiveHepatitis C virus (HCV) has been proposed as a possible etiologic factor in ocular adnexal marginal zone lymphoma (OAML). We aimed to assess the prevalence of HCV infection in patients with OAML through a systematic review and meta-analysis.MethodsElectronic databases were searched from their inception to August 2019 for studies assessing HCV seroprevalence in patients with OAML. Pooled prevalence of HCV infection was calculated with 95 % confidence interval (CI). Statistical heterogeneity among studies was quantified via the inconsistency index (I²). Funnel plot symmetry was used to assess the risk of bias across studies.ResultsNine studies with 360 patients were included. Overall pooled prevalence of HCV in OAML was 12.7 %, with low statistical heterogeneity (I² = 17.4 %) and with asymmetrical funnel plot. The studies clustered into two groups: 5 studies (3 from Italy and 2 multicenter with a major Italian contribution) showed a higher HCV prevalence in OAML (15.6 %), while the other 4 (from countries other than Italy) showed a lower prevalence (4.7 %); in both subgroups, statistical heterogeneity was null (I² = 0%) and funnel plot was symmetrical.ConclusionHCV might be a significant etiologic factor of OAML in Italy.     

原发性脑B细胞性淋巴瘤的DWI及MR多时相增强对比研究

目的:探讨和分析原发性脑B细胞性淋巴瘤MR影像特点,提高诊断的准确率.方法:将MR平扫脑内有单发肿块的71例患者,给予DWI扫描,同时分别在造影剂注射后,应用25 s、125 s和185 s三个时相进行增强扫描.根据病理资料,将所有患者分组,并测量各组ADC值、平扫时的信号强度和增强后不同时相病灶的信号强度,将所有数据进行比较分析.结果:71例中58例患者具备完整的病理资料,其中包括原发性脑B细胞性淋巴瘤12例、胶质母细胞瘤20例、肺腺癌脑转移26例.将原发性脑B细胞性淋巴瘤、胶质母细胞瘤及肺癌脑转移瘤的ADC值及平扫信号强度进行组间比较,均无统计学意义.将原发性脑B细胞性淋巴瘤三个增强时相的平均信号强度进行比较,25 s和125 s时相相关系数为1.0,有统计学差异,25 s与185 s时相及125 s与185 s时相相关系数分别为0.992、0.994,无统计学意义.原发性脑B细胞性淋巴瘤与胶质母细胞瘤有5个时相点有鉴别意义,而与肺腺癌脑转移中有11个时相点有鉴别意义.结论:应用MR多时相增强扫描,有助于鉴别原发性脑B细胞性淋巴瘤、胶质母细胞瘤及肺腺癌脑转移,而ADC值无鉴别价值.     

Angiotropic large B-cell lymphoma with clinical features resembling subacute combined degeneration of the cord

Angiotropic large cell lymphoma is a rare neoplastic disorder associated with a high mortality. The hallmark of the disease is lymphoid proliferation confined to the intravascular compartment without local tissue or vessel wall infiltration [1]. This feature is so striking that the disease was originally thought to arise from endothelial tissue and early cases were described as malignant angioendotheliomatosis. However, application of immunohistochemical methods for detection of lymphoid markers such as the CD45 and CD20 cell surface markers has confirmed its lymphoid origin, usually of B-cell lineage [2]. Clinical manifestations of the disease are protean and are due to multifocal medium and small vessel occlusion by tumour cells [3]. Characteristic sites of involvement are skin and central nervous system and although an ante-mortem diagnosis can be made from a biopsy specimen, it is often unsuspected [4]. We present a case of angiotropic large B-cell lymphoma in a 74-year-old man who presented with urinary symptoms and had a neurological picture resembling subacute combined degeneration of the cord.     

Inactivation of p16 INK4a /CDKN2A gene may be a diagnostic feature of large B cell lymphoma leg type among cutaneous B cell lymphomas

The World Health Organization-European Organization for Research and Treatment of Cancer has individualized three main categories among the primary cutaneous B cell lymphoma (PCBCL): leg-type primary cutaneous large B cell lymphoma (PCLBCL leg type), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous marginal zone lymphoma (PCMZL). The genetic features of 21 PCBCL cases (six PCLBCL leg type four PCFCL large cells, seven PCFCL small cells, and four PCMZL) were investigated by comparative genomic hybridization (CGH array). Fluorescent in situ hybridization (FISH) analysis was performed to confirm CGH array data and to detect lymphoma-associated gene rearrangements. p14 ( ARF )/p16 ( INK4a ) CDKN2A gene quantification, methylation analysis, and immunohistochemical detection were also performed. CGH array showed a higher number of recurrent genetic imbalances in PCLBCL leg type (mean 62) than in PCFCL large cells (mean 34). PCFCL small cells and PCMZL exhibited fewer chromosomal alterations (mean 24 and 9). FISH analysis provided concordant results with CGH array data in 97% (98 of 101) assays and demonstrated a t(8;14)(q24;q32) in two of six PCLBCL leg type. Recurrent deletions in 9p21 (p14 ( ARF )/p16 ( INK4a ) CDKN2A) were a constant finding in PCLBCL leg type (six of six). Conversely, PCFCL large cells exhibited recurrent 1p36 deletions (four of four) without deletion in 9p21 (zero of four). The diagnostic and prognostic impact of the p16 ( INK4a ) CDKN2A gene status in PCBCL should therefore be confirmed on a larger series.     

胃T细胞淋巴瘤临床病理观察

目的 探讨胃T细胞淋巴瘤的临床病理学特点.方法 收集7例胃T细胞淋巴瘤病例标本,对其进行了临床病理分析、免疫组织化学检测、EBER原位杂交检测及T细胞受体(TCR)基因重排检测.结果 7例病例中6例为男性,1例为女性,平均发病年龄为45岁.6例可获得资料的病例中,1例有长期腹泻史,5例有低蛋白血症.组织学上,7例标本中,有5例表现为肿瘤细胞体积较大而不一致,2例表现为大小一致的中等细胞.1例病例可见肿瘤细胞浸润腺上皮.所有病例的肿瘤组织均不表达CD20及CD79a.7例病例中,各有6例表达CD3及T细胞胞质内抗原,各有4例表达CD5、βF-1及CD30,有3例表达CDM,各有1例病例表达CD8、CD56、问变性淋巴瘤激酶及粒酶B.7例病例肿瘤细胞EBER原位杂交检测均为阴性且都存在TCR基因克隆性重排.结论 胃T细胞淋巴瘤是一种少见的恶性淋巴瘤,具有独特的临床病理特点.     

干扰素诱导淋巴瘤细胞凋亡实验及临床研究

目的：分析梯度浓度的干扰素(IFN-α)对Burkitt淋巴瘤细胞株Daudi和T细胞淋巴瘤细胞株Jurkut及15例难治性淋巴瘤患者的直接作用。方法：以MTT法测定梯度浓度的IFN-α对两种淋巴瘤细胞株Daudi、Jurkat增殖作用的影响，以DNA末端标记法，流式细胞术，电镜观察测定IFN-α对淋巴瘤细胞的凋亡诱导作用，并采用瘤内注射IFN-α联合化疗治疗15例耐药的难治性淋巴瘤。结果：低浓度亚IFN-α对DaudiJurkat细胞增殖无明显抑制作用，高浓度IFN(10000U／ml)可显著抑制两种细胞增殖，且有时间相关性。高浓度的IFN-α可诱导淋巴瘤细胞凋亡。15例患者CR5例，PR7例，有效率80％，无明显毒副作用。结论：IFN-α可抑制淋巴瘤细胞增殖，诱导凋亡，有显著时间，剂量依赖性。局部应用IFN-α联合化疗是治疗难治性淋巴瘤的有效方法之一。     

Biomarkers of lymphoma in Sjögren’s syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: Results of a multicenter study

ObjectivesTo define the biomarkers associated with lymphoproliferation in primary Sjögren’s syndrome (pSS) by distinguishing in separate groups the two best-recognized non-malignant prelymphomatous conditions in pSS, i.e., salivary gland swelling and cryoglobulinemic vasculitis (CV).MethodsA multicenter study was conducted in 5 centres. Patients fulfilled the following criteria: (1) positive AECG criteria for pSS, (2) serum cryoglobulins evaluated, and (3) lack of hepatitis C virus infection. Four groups were distinguished and analysed by multinomial analyses: (1) B-cell non-Hodgkin's lymphoma (NHL), (2) CV without lymphoma, (3) salivary swelling without NHL (SW), and (4) pSS patients without NHL or prelymphomatous conditions.ResultsSix hundred and sixty-one patients were studied. Group 1/NHL comprised 40/661 (6.1%) patients, Group 2/CV 17/661 (2.6%), Group 3/SW 180/661 (27.2%), and Group 4/pSS controls 424/661 (64.1%).Low C4 [relative-risk ratio (RRR) 8.3], cryoglobulins (RRR 6.8), anti-La antibodies (RRR 5.2), and leukopenia (RRR 3.3) were the variables distinguishing Group 1/NHL from Group 4/Controls. As concerns the subset of patients with prelymphomatous conditions, the absence of these biomarkers provided a negative predictive value for lymphoma of 98% in patients with salivary swelling (Group 3/SW). Additional follow-up studies in patients with SW confirmed the high risk of lymphoma when at least 2/4 biomarkers were positive.ConclusionsLymphoma-associated biomarkers were defined in a multicentre series of well-characterized patients with pSS, by dissecting the cohort in the pSS-associated prelymphomatous conditions. Notably, it was demonstrated for the first time that among the pSS patients with salivary swelling, only those with positive biomarkers present an increased risk of lymphoma evolution.     

A Comparison of the Conditioning Regimens BEAM and FEAM for Autologous Hematopoietic Stem Cell Transplantation in Lymphoma: An Observational Study on 1038 Patients From Fondazione Italiana Linfomi

BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM =?607, FEAM =?431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM?=?2011 versus FEAM?=?2013, P?<?.001), Sorror score ≥3 (BEAM?=?15% versus FEAM?=?10%, P?=?.017), and radiotherapy use (BEAM?=?18% versus FEAM?=?10%, P?<?.001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM?=?31% versus FEAM?=?44%, P?<?.001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM?=?.1 versus FEAM?=?.19, P?<?.001). Response status at day 100 post-ASCT (overall response: BEAM?=?91% versus FEAM?=?88%, P?=?.42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P?=?.04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply.