Bcl-2基因扩增和蛋白表达与原发性胃肠道弥漫大B细胞淋巴瘤临床病理特征和免疫表型的关系

背景:Bcl-2基因转录异常与结内弥漫大B细胞淋巴瘤(DLBCL)关系密切,对Bcl-2与原发性胃肠道DLBCL(PGI-DLBCL)的关系则缺乏充分研究。目的:探讨PGI-DLBCL中Bcl-2基因扩增和蛋白表达与肿瘤临床病理特征、免疫表型和预后的关系。方法:采集136例手术治疗PGI-DLBCL患者的临床资料,电话随访生存信息。以荧光原位杂交技术检测肿瘤组织Bcl-2基因扩增,免疫组化法检测Bcl-2蛋白表达,分析两者与肿瘤临床病理特征、免疫表型和预后的关系。结果:136例患者中,33例(24.3%)Bcl-2基因扩增阳性,90例(66.2%)Bcl-2蛋白表达阳性;基因扩增与肿瘤原发部位、Ann Arbor分期、血清乳酸脱氢酶水平、B症状、国际预后指数(IPI)评分相关(P0.05),蛋白表达与肿瘤原发部位和免疫表型相关(P0.05)。Bcl-2基因扩增阳性患者和免疫表型为非GCB型的Bcl-2蛋白表达阳性患者5年总生存率(OS)分别显著低于相应阴性患者(41.5%对71.5%,P0.05;54.6%对84.6%,P0.05)。Bcl-2基因扩增或蛋白表达阳性患者中,CHOP化疗的5年OS显著低于利妥昔单抗联合CHOP化疗(48.6%对80.3%,P0.05;66.4%对83.4%,P0.05)。结论:检测Bcl-2基因扩增对PGI-DLBCL的预后判断具有重要意义,检出Bcl-2基因扩增者预后较差。非GCB型PGI-DLBCL中,Bcl-2蛋白表达与预后不良相关。利妥昔单抗可提高Bcl-2基因扩增或蛋白表达阳性患者的生存率。     

原发性胃肠道弥漫大B细胞淋巴瘤的预后因素分析

目的 :探讨原发性胃肠道弥漫大B细胞淋巴瘤(PGI-DLBCL)的临床特点、免疫表型及治疗方案与预后的关系。方法:收集我院2000年4月至2014年6月诊治的91例PGI-DLBCL患者的临床资料,对其临床特征、治疗方案、免疫分型以及疗效进行回顾性分析。结果:随访时间为3~166个月,中位随访时间49个月。91例PGI-DLBCL患者中,男女比例为1.22∶1,中位年龄57(17~79)岁。Ann Arbor分期Ⅰ~Ⅱ期49例(53.8%),Ⅲ~Ⅳ期42例(46.2%);血清乳酸脱氢酶(LDH)正常者75例(82.4%),升高者16例(17.6%);国际预后指数(IPI)低/低中危患者73例(80.2%),中/中高危患者18例(19.8%);生发中心B细胞(GCB)患者22例(34.9%),非GCB(non GCB)患者41例(65.1%);采用CHOP(环磷酰胺、长春地辛、表柔比星、甲泼尼龙)方案治疗的55例(60.4%),利妥昔单抗联合CHOP方案化学治疗(化疗)36例(39.6%),5年总生存(OS)率分别为75.5%、95.7%。单因素分析结果显示IPI、Ann Arbor临床分期、LDH水平、免疫分型以及是否联合利妥昔单抗化疗对生存率有显著影响(均P     

原发于乳腺的恶性淋巴瘤8例临床分析

回顾性分析8例原发于乳腺的恶性淋巴瘤（PBL）患者的临床资料,患者均行手术、化疗或（和）放疗,中位生存期47．6个月。结果提示PBL预后与肿瘤大小、病理、临床分期及治疗方式有关。     

内镜黏膜下剥离术诊治结直肠非霍奇金淋巴瘤3例

回顾性分析2020年6月至2022年2月于浙江大学医学院附属第一医院因结直肠黏膜下隆起性病变经超声内镜检查考虑为神经内分泌肿瘤(类癌), 后经内镜黏膜下剥离术(ESD)诊断性治疗确诊为非霍奇金淋巴瘤的3例患者临床和病理资料。通过分析术中、术后并发症和患者预后, 评估ESD作为惰性淋巴瘤治疗策略的有效性。3例患者中男2例、女1例, 年龄为55～71岁;术前均无明显临床症状;结肠镜下2例表现为乙状结肠黏膜下隆起型病变, 1例为直肠黏膜下隆起型病变;均成功实施ESD诊断性治疗;术后病理诊断为黏膜相关淋巴组织淋巴瘤2例和滤泡性淋巴瘤1例, 随访6～26个月, 均未再行内镜治疗或追加外科手术, 未行全身化学治疗。提示内镜下治疗惰性淋巴瘤具有一定潜力。     

原发性胃肠淋巴瘤p53基因与13q14染色体缺失与预后的关系

目的 探讨p53基因与13q14染色体缺失在原发性胃肠淋巴瘤(PGIL)预后判断、指导治疗中的作用.方法 采用改良的荧光标记的原位杂交(FISH)技术检测72例PGIL及30例淋巴结反应性增生患者石蜡切片中p53基因及13q14染色体缺失情况,分析其与PGIL预后的关系.结果 ① Ⅰ期～Ⅱ期患者中30.2%(16/53)有p53基因缺失,Ⅲ期～Ⅳ期患者中63.2%(12/19)有p53基因缺失(χ~2=6.397,P=0.011);②黏膜相关组织(MALT)淋巴瘤中28.6%(12/42)有p53基因缺失,非MALT淋巴瘤中53.3%(16/30)有p53基因缺失(χ~2=4.515,P=0.034);③ MALT淋巴瘤中,无基因或单基因改变者平均生存期为(39.25±22.73)个月,2种基因改变的患者平均生存期为(9.11±5.95)个月;Ⅰ期～Ⅱ期患者中,无基因或单基因改变者平均生存期为(40.33±23.18)个月,2种基因改变的患者平均生存期为(20.61±18.90)个月.④单纯 13q14 缺失与肿瘤发生部位、病理类型、临床分期以及平均生存期无关,但同时合并 p53 基因缺失则预后差.结论 p53基因缺失在非MALT淋巴瘤组及Ⅲ期～Ⅳ期患者中发生率较高.p53缺失或p53基因缺失与13q14染色体同时存在缺失的PGIL病例恶性程度高,患者平均生存期短于无基因或单基因改变者.     

乳腺原发恶性淋巴瘤的诊断及治疗方法探讨

目的探讨乳腺原发恶性淋巴瘤(PBL)的临床特点及诊断、治疗方法。方法对经病理检查证实的11例女性PBL患者的临床表现、检查及治疗方法、预后等进行分析。结果11例均经手术或穿刺活检取标本，组织学及免疫组织化学检查证实为非霍奇金氏淋巴瘤(NHL)，B细胞来源10例、T细胞来源1例，弥漫性大B细胞型占54．5％(6／11)。10例分别接受乳腺肿瘤根治术或改良根治术或肿块切除术。均辅以化疗和放射治疗。首程治疗后7例获得局部控制。全组无病生存期4～49个月(中位生存期12个月)，总生存期15～110个月(中位30个月)。结论PBL的确诊依靠病理组织学和免疫组织化学检查。治疗应包括局部手术、放射治疗和化疗的综合治疗。     

209例慢性B淋巴细胞增殖性疾病临床特征及预后分析

目的:探讨慢性B淋巴细胞增殖性疾病(B-CLPD)的临床特征、鉴别诊断、治疗方式与预后转归的相关性。方法:回顾性研究209例B-CLPD患者的临床特征、实验室及影像学检查资料,分析患者初诊时疾病状态、诊断方式、治疗方案与生存预后的关系。结果:209例患者男女比例约2.67∶1.00,中位年龄59(17~86)岁,中位随访时间33(2~331)个月,慢性淋巴细胞白血病/小淋巴细胞淋巴瘤化疗患者完全缓解率(CR)、部分缓解率(PR)、总体有效率(ORR)分别为59.7%、14.5%、74.2%,滤泡性淋巴瘤化疗患者CR、PR、ORR分别为54.5%、18.2%、72.7%,套细胞淋巴瘤化疗患者CR、PR、ORR分别为46.7%、26.7%、73.3%,边缘区淋巴瘤化疗患者CR、PR、ORR分别为57.1%、21.4%、78.6%,淋巴浆细胞淋巴瘤/华氏巨球蛋白血症化疗患者CR、PR、ORR分别为75.0%、8.3%、83.3%,以骨髓检查或淋巴结/原发病灶检查确诊的患者生存期无显著差异。多因素生存分析显示,血清乳酸脱氢酶、红细胞沉降率水平升高为预后不良的独立影响因素。淋巴瘤联合利妥昔单抗化疗组(67例)较未联合化疗组(16例)5年累积生存率明显改善(53.9%∶33.3%,P0.05)。结论:流式细胞检测显示单克隆性B淋巴细胞增生通常提示B-CLPD。血乳酸脱氢酶、红细胞沉降率升高为预后不良因素。骨髓检查或淋巴结/原发病灶检查确诊不影响患者预后。联合应用利妥昔单抗能显著改善患者生存。     

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.     

核转录因子-κB在原发性胃肠道弥漫性大B细胞淋巴瘤中的表达及临床意义

目的:探讨原发性胃肠道弥漫性大B细胞淋巴瘤(PGI-DLBCL)中核转录因子κB(NF-κB)的表达及临床意义.方法:采用免疫组织化学方法检测PGI-DLBCL患者中CD10、Bcl-6、Mum-1、NF-κB p65的表达,结合临床随访资料,分析NF-κB p65与PGI-DLBCL免疫分型、临床生物学行为及预后的关...     

非何杰金淋巴瘤放射免疫治疗的进展

非何杰金淋巴瘤(NHL)是一组具有高度生物学异质性和病理学多样化表现特征的恶性肿瘤.虽经传统的放射治疗和化学治疗可使患者缓解、生存期延长,然而对难治性和复发患者的治疗效果却难以令人满意。大剂量致死性化疗辅以自身骨髓移植虽然使这部份患者长期无病生存率达到20～25%,但大多数患者仍死于 NHL 本身或治疗相关的并发症.八十年代以来,单克隆抗体(MAb)的广     

What is CD4+CD56+ malignancy and how should it be treated?

CD4+CD56+ malignancy is a rare neoplasm with a typical clinical pattern, an aggressive course and high early relapse rate despite good initial response to chemotherapy. In this review, the impact of different therapeutic approaches on clinical outcome has been studied. We evaluated 91 published cases and our own six patients in terms of clinical features, immunophenotype/cytogenetics and treatment outcome. Treatment was divided into four groups: (A) chemotherapy less intensive than CHOP; (B) CHOP and CHOP-like regimens; (C) therapy for acute leukemia; (D) allogeneic/autologous stem cell transplantation. The median overall survival was only 13 months for all patients. Patients with skin-restricted disease showed no difference in the overall survival from patients with advanced disease (17 and 12 months, respectively). Age >/=60 years was a negative prognostic factor. Age-adjusted analysis revealed improved survival after high-dose chemo/radiotherapy followed by allogeneic stem cell transplantation when performed in first complete remission. This therapeutic approach should be recommended for eligible patients with CD4+CD56+ malignancy. For older patients the best treatment option is still unknown.     

原发性中枢神经系统淋巴瘤18例临床分析

目的探讨原发性中枢神经系统淋巴瘤(PCNSL)的诊断及治疗措施。方法回顾性分析18例PCNSL的临床、影像学特征及治疗效果。结果18例患者均经手术病理确诊;15例患者行手术治疗和(或)术后放疗和(或)常规CHOP方案化疗,生存期为3~18个月;3例患者手术确诊后使用大剂量甲氨蝶呤(MTX)为主的方案化疗及鞘内注射药物等治疗,生存期均大于36个月。结论PCNSL临床症状及影像学无特征性,诊断困难,易误诊;手术治疗、术后放疗及常规CHOP方案化疗的疗效欠佳,采用易通过血脑屏障药物治疗可取得一定的疗效。     

Clinical analysis and prognostic significance of lymphoma-associated hemophagocytosis in peripheral T cell lymphoma

This study aims to retrospectively analyze the clinical characteristics, treatments, and prognosis of aggressive peripheral T cell lymphoma (PTCL) patients with a lymphoma-associated hemophagocytosis syndrome (LAHS). We compared the clinical features and the overall survival (OS) rates of 159 PTCL patients with and without LAHS as well as the treatment outcomes of these patients with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or intensive chemotherapy regimens. We observed that in 23 % (36/159) patients PTCL was associated with LAHS. Different subtypes of PTCL in LAHS patients were diagnosed and peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) was the main subtype (78 %). The median survival rates of the LAHS and non-LAHS groups were 3 and 16 months, respectively. The elevated rates of serum β2-microglobulin, ferritin, fasting triglycerides, and hypofibrinogen levels were higher in the LAHS group, so were bone marrow involvement, liver dysfunction, hepatosplenomegaly, and B symptoms. Three patients who were treated with a plasma exchange had a longer survival time. There was no statistically significant difference in the OS rates between the intensive chemotherapy and CHOP regimen groups (P?>?0.05). PTCL patients with LAHS had a poorer prognosis. Awareness of the clinical symptoms and laboratory findings are crucial in order to diagnose LAHS in an early stage and repeated biopsies of multiple bone marrows from different locations in those patients without enlargement of superficial lymph nodes are necessary to improve the diagnosis. Intensive chemotherapy due to its severe toxicity was not obviously advantageous for the OS rate compared to the CHOP regimen.     

细支气管肺泡癌77例临床分析

目的 探讨细支气管肺泡癌的临床症状、诊断、误诊、病理类型、影像学特点、治疗方案及预后.方法 回顾性分析解放军总医院2003年1月至2007年12月期间住院治疗的经病理证实的77例细支气管肺泡癌病例.结果本 组病例占我院同期住院治疗的原发性支气管肺癌患者的4.6%(77/1 665),男女比例为1.66:1;对53例资料完整病例进行统计学分析,中位生存期47.4个月;吸烟、治疗方案的组间生存曲线差异有显著意义(P<0.05).结论 细支气管肺泡癌患者临床表现多样.缺乏特征,咳大量泡沫样痰的症状并不多见.再加上影像学上的多样性.易被溟诊;对细支气管肺泡癌的治疗应采用手术为主,结合化疗、放疗、分子靶向治疗的综合治疗方式;对晚期不能手术的患者采用先化疗后分子靶向治疗的续贯疗法可取得较好的疗效.     

腹膜假黏液瘤的临床病理特征和预后分析

目的 探讨腹膜假黏液瘤的临床病理特点和预后。方法 回顾我院33例腹膜假黏液瘤患者的临床资料,对病理组织重新阅片和分型,对随访资料进行生存分析。结果 33例患者中男女之比为1：2,平均年龄50岁,发病至确诊中位间期为12个月,误诊率高达84．8％。腹胀、腹部包块、腹围增大为主要临床表现。肠道肿瘤标志物、影像学和腹腔穿刺等辅助检查常有阳性发现。减瘤手术为主要的治疗方法,化疗是主要的辅助疗法。病理分型中良性66．7％,交界性21．2％,恶性12．1％。中位生存期为70个月。病理类型和化疗对生存时间具有影响。结论 腹膜假黏液瘤具有独特的临床病理特点,肠道肿瘤标志物、影像学和腹腔穿刺对诊断具有提示意义,目前的治疗方法有待于完善,病理类型和化疗是预后的影响因素,应对其加强认识以降低误诊率。     

Lack of prognostic significance of the germinal-center phenotype in diffuse large B-cell lymphoma patients treated with CHOP-like chemotherapy with and without rituximab

The influence of the germinal-center B-cell (GCB) and the non-GCB phenotypes of diffuse large B-cell lymphoma (DLBCL) on the outcome of 92 patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like chemotherapy, with or without rituximab was determined in this study. The differentiation between the GCB and non-GCB types was arrived at by immunohistochemistry using previously published criteria. Thirty-nine patients had the GCB and 53 had the non-GCB type of DLBCL. Forty-nine patients were treated with rituximab and chemotherapy; 43 were treated with chemotherapy alone. The GCB and non-GCB group did not differ in their international prognostic index factors and score, presence of bulky disease, or frequency of rituximab treatment. Median follow-up of the surviving patients was carried out for 37 months. There was no difference between the GCB and non-GCB groups in both overall response rates (67 vs. 70%, respectively) and estimated rates of 3-year event-free (46 vs. 49%, respectively) and overall (54 vs. 56%, respectively) survival. In addition, no differences of the outcomes were observed between the subgroups treated with or without rituximab. The patients of this study with immunohistochemically determined GCB-type DLBCL did not have an improved prognosis, irrespective of whether they had received rituximab or not.     

A new prognostic model identifies patients aged 80 years and older with diffuse large B‐cell lymphoma who may benefit from curative treatment: A multicenter,retrospective analysis by the Spanish GELTAMO group

The means of optimally managing very elderly patients with diffuse large B‐cell lymphoma (DLBCL) has not been established. We retrospectively analyzed 252 patients aged 80‐100 years, diagnosed with DLBCL or grade 3B follicular lymphoma, treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze the influence of the type of treatment and comorbidity scales on progression‐free survival (PFS) and overall survival (OS). One hundred sixty‐three patients (63%) were treated with chemotherapy that included anthracyclines and/or rituximab, whereas 15% received no chemotherapeutic treatment. With a median follow‐up of 44 months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis restricted to the 205 patients treated with any kind of chemotherapy, comorbidity scales did not influence the choice of treatment type significantly. Independent factors associated with better PFS and OS were: age < 86 years, cumulative illness rating scale (CIRS) score < 6, intermediate risk (1‐2) R‐IPI, and treatment with R‐CHOP at full or reduced doses. We developed a prognostic model based on the multivariate analysis of the 108 patients treated with R‐CHOP‐like: median OS was 45 vs. 12 months (P = .001), respectively, for patients with 0‐1 vs. 2‐3 risk factors (age > 85 years, R‐IPI 3‐5 or CIRS > 5). In conclusion, treatment with R‐CHOP‐like is associated with good survival in a significant proportion of patients. We have developed a simple prognostic model that may aid the selection patients who could benefit from a curative treatment, although it needs to be validated in larger series.     

Mad2 overexpression is associated with high cell proliferation and reduced disease-free survival in primary gastrointestinal diffuse large B-cell lymphoma

Objectives: Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) is a rare hematological malignancy with limited results on carcinogenesis and clinical characteristics. The aims of the current study were to examine mitotic arrest deficiency protein 2 (Mad2) expressions in PGI-DLBCL, and assess its association with Ki-67 expression, Helicobacter pylori (H. pylori) infection, BCL-6 gene rearrangement, and clinicopathological variables.

Methods: Cancer tissues from 38 PGI-DLBCL patients were examined for Mad2, Ki-67, and H. pylori expression by immunohistochemistry, using normal gastrointestinal tissues and nodal DLBCL as controls. BCL-6 gene translocation was analyzed by fluorescence in situ hybridization (FISH), and Mad2 expression status was evaluated along with clinicopathological characteristics.

Results: Mad2 expression was increased in PGI-DLBCL patients when compared with controls. The expression of Mad2 was 51.55?±?22.88% in PGI-DLBCL, which was higher than reactive lymph node (28.77?±?10.89%) and lymphoid nodule in normal gastrointestinal tissue (26.41?±?11.30%) (P?=?0.002), while it was comparable to nodal DLBCL (57.23?±?20.79%) (P?=?0.358). Mad2 overexpression had a positive correlation with Ki-67 proliferation index (r?=?0.55, P?=?0.01) in PGI-DLBCL, and patients with BCL-6 gene rearrangement had lower Mad2 expression (P?=?0.032) than patients with intact BCL-6, while no relation was found between Mad2 expression and H. pylori infection. PGI-DLBCL patients with higher Mad2 expression had lower estimated disease-free survival (DFS) (17.10% vs. 53.00%) (P?=?0.049). However, no correlation was found between Mad2 expression levels and overall survival (OS) (P?=?0.443).

Conclusions: Aberrant Mad2 expression was associated with cell proliferation and genetic instability, which may contribute to the carcinogenesis of PGI-DLBCL. Mad2 overexpression indicated a poor DFS and may be a potential biomarker for estimating prognosis for PGI-DLBCL patients.     

Primary colonic lymphoma: an analysis of 74 cases with localized large-cell lymphoma

Background: Surgical resection is considered a crucial treatment in patients with primary colonic lymphoma, but combining surgery with chemotherapy has provided additional therapeutic benefits in some studies. To further explore the optimal therapeutic approach in different clinical scenarios, we reviewed cases with localized large‐cell lymphoma and analyzed the factors related to the outcomes. Patients and methods: The 74 cases diagnosed between February 1979 and October 2010 were retrospectively reviewed for clinical features, laboratory findings, and pathological diagnosis. The outcomes were correlated with their demographics and different treatment modalities. Results: Of the 74 cases, only the patients who had complete tumor resection had significantly improved progression‐free survival (PFS). The patients treated with resection and chemotherapy had better overall survival (OS) and PFS than those treated with resection alone. The OS and PFS of the patients who were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy without surgery were similar to those of patients treated with CHOP and resection, but the patients treated with resection followed by cyclophosphamide, vincristine, and prednisone (COP) chemotherapy had significantly better OS and PFS than the patients treated with COP chemotherapy alone. For patients with diffuse large B‐cell lymphoma (DLBCL), rituximab‐based chemotherapy with or without resection had similar OS and PFS. Conclusions: We conclude that chemotherapy alone provides similar therapeutic effect compared with surgery and chemotherapy and that surgical resection can be spared if an endoscopic diagnosis could be made.     

急性红白血病55例染色体特征和预后分析

目的探讨急性红白血病（M6）染色体特征和预后因素。方法回顾性分析55例患者染色体核型特征,采用病例对照方法,分为原发组和骨髓增生异常综合征（MDS）转化组;染色体核型异常组和正常组,并分析各组异基因造血干细胞移植（all-HSCT）治疗和（或）化疗疗效及生存预后因素。结果45例经染色体检查,18例正常,染色体异常检出率为60．0％（27／45）,其中复杂异常17例,简单异常10例,10例可见亚二倍体或超二倍体明显增多,18．5％（5／27）5号染色体受累,25．9％（7／27）7号或8号染色体受累。55例患者完全缓解（CR）率63．6％;MDS转化组CR率（42．8％）显著低于原发组（85．2％）,P〈0．05;染色体核型异常组CR率（37．0％）显著低于正常组（83．3％）,P〈0．01。生存预后因素：随访中位时间30（3—79）个月,染色体核型异常组和MDS转化M6患者生存期（OS）和无病生存期（DFS）,移植治疗者较化疗者显著延长（P〈0．01）。16例患者行all-HSCT治疗,其中9例为染色体核型异常MDS转化M6患者,4例为未缓解患者;移植后11例DFS 28个月,2年生存率68．7％（11／16）。结论染色体核型异常和（或）MDS转化M6患者常规化疗疗效差、生存期短,预后差,all-HSCT治疗显著延长生存期,改善预后,染色体核型异常和（或）MDS转化M6患者,宜早期all-HSCT治疗。