以原发性脾淋巴瘤为表现的弥漫性大B细胞淋巴瘤1例并文献复习

目的：探讨原发性脾淋巴瘤（PSL）的诊断以及原发性脾弥漫性大B细胞淋巴瘤的治疗。方法：报告1例以PSL为表现的弥漫性大B细胞淋巴瘤并结合文献进行复习。结果：患者表现为左上腹疼痛,无发热、盗汗,无浅表淋巴结肿大,CT证实脾脏内有占位性病变,脾脏病理示弥漫性大B细胞淋巴瘤,外周血和骨髓检查正常,脾切除术后PET/CT未见明显与淋巴瘤相关的18F-脱氧葡萄糖摄取异常增高表现,后给予联合化疗,随访8月余仍处于完全缓解期。结论：PSL是一少见肿瘤,采取脾切除后继以CHOP±利妥昔单抗治疗原发性脾弥漫性大B细胞淋巴瘤能够达到长期生存的目的。     

以原发性脾淋巴瘤为表现的弥漫性大B细胞淋巴瘤1例并文献复习

目的:探讨原发性脾淋巴瘤(PSL)的诊断以及原发性脾弥漫性大B细胞淋巴瘤的治疗。方法:报告1例以PSL为表现的弥漫性大B细胞淋巴瘤并结合文献进行复习。结果:患者表现为左上腹疼痛,无发热、盗汗,无浅表淋巴结肿大,CT证实脾脏内有占位性病变,脾脏病理示弥漫性大B细胞淋巴瘤,外周血和骨髓检查正常,脾切除术后PET/CT未见明显与淋巴瘤相关的18F-脱氧葡萄糖摄取异常增高表现,后给予联合化疗,随访8月余仍处于完全缓解期。结论:PSL是一少见肿瘤,采取脾切除后继以CHOP±利妥昔单抗治疗原发性脾弥漫性大B细胞淋巴瘤能够达到长期生存的目的。     

孤立性原发性中枢神经系统淋巴瘤1例报告并文献复习

原发性中枢神经系统淋巴瘤（primary central nervous system lymphoma,PCNSL）是指原发于脑、软脑膜或脊髓等部位的非霍奇金淋巴瘤,发病率低,占所有颅内原发肿瘤的0．85％～2．00％。PCNSL发病急,潜伏期短,临床上非创性诊断困难,治疗棘手,缓解期短,易复发,预后较差,死亡率高。现结合1例报告,对PCNSL的诊断与鉴别诊断、治疗及预后等进行分析。     

原发性乳腺弥漫大B细胞淋巴瘤临床病理分析（附8例）

目的:探讨原发性乳腺弥漫大B细胞淋巴瘤（primary breast diffuse large B-cell lymphoma,PB-DLBCL）的临床病理特征。方法:对8例PB-DLBCL患者进行回顾性分析，观察其组织病理学形态、免疫表型、诊断及预后，并复习相关文献。结果:根据2008版和2016年修订版的WHO关于淋巴造血系统肿瘤分类标准，8例患者确诊为PB-DLBCL，均为女性，发病年龄47～76岁，中位年龄54岁，6例发生于右侧乳腺，2例发生于左侧乳腺。病例随访9～52个月，2例失访。乳酸脱氢酶（LDH）156～238 U/L，均在正常参考范围内。免疫组化CD20、CD79a均（+），Ki67约70%～90%，7例为非生发中心B细胞样型（非GCB亚型），1例为生发中心B细胞样型（GCB亚型）。8例患者EBER检测均（-）。结论:PB-DLBCL发病少见，恶性程度高，容易误诊，诊断主要依靠病理活检及免疫组织化学表型，且具有较高的增殖活性，预后较差。     

原发性乳腺弥漫性大B细胞淋巴瘤13例临床分析

目的 探讨原发性乳腺弥漫性大B细胞淋巴瘤（PB-DLBCL）的临床特征、诊断和治疗。方法 回顾性分析2010年1月至2015年11月13例PB-DLBCL患者的临床资料。13例均接受手术治疗,其中4例行乳腺癌改良根治术,1例行单侧乳腺切除术,8例行乳腺肿块切除术。结果 13例均为女性,6例发生于右乳,6例发生于左乳,1例发生于双乳。肿块大小1.5 cm～8.0 cm。术前2例诊断为乳腺纤维腺瘤,1例诊断为巨纤维瘤,10例诊断为乳腺癌。13例患者均经免疫组化检测确诊为PB-DLBCL。Ann Arbor分期：Ⅰ期10例,Ⅱ期3例。12例术后给予CHOP或R-CHOP方案化疗,1例放弃治疗。随访1个月～5年,2例复发,2例死亡,其余病例均无复发生存。结论 PB-DLBCL临床少见,多见于女性。术前检查、术中冰冻病理检查易误诊,免疫组化检查可明确诊断。治疗采用以化疗为主的综合治疗。     

弥漫性大B细胞淋巴瘤继发中枢神经系统侵犯的诊疗进展

弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）继发中枢神经系统（central nervous system,CNS）侵犯是一种严重的临床并发症,治疗方法有限,预后普遍较差。随着利妥昔单抗的广泛应用,其发生率呈降低趋势,但是脑实质受累越发多见,病理活检在诊断中则越发重要。在高危因素鉴定方面需要结合临床与分子生物学因素综合评估。以大剂量甲氨蝶呤为主的全身化疗作为主流的预防策略,其作用尚存争议。伊布替尼等新药、新疗法的治疗价值得到进一步探索。本文旨在对近年来DLBCL继发CNS侵犯的诊疗进展予以综述。      

原发性肝脏弥漫性大B细胞淋巴瘤一例并文献复习

 目的　提高对原发性肝脏淋巴瘤（PHL）的认识。方法　报道1例PHL的诊断、治疗经过并结合文献复习讨论。结果　患者经剖腹探查、免疫组织化学确诊PHL,予CTOP 方案化疗后肝脏病变组织缩小,患者发热、腹胀、腹痛等症状消失。结论　肝脏原发性弥漫性大B细胞淋巴瘤诊断困难,但只要早做病理诊断,化疗能取得部分缓解。     

中枢神经系统血管内大B细胞淋巴瘤2例

0 引言2008年版WH0造血及琳巴组织肿瘤分类中,血管内大B细胞淋巴瘤(Intravascular large B-cell lymphoma,IVLBCL)归属于弥漫性大B细胞淋巴瘤(Diffuse large B cell lymphoma,DLBCL)的独立亚型[1].该疾病非常罕见,迄今全世界近300例报道,国内报道不足10例[2-6].累及包括皮肤及中枢神经系统在内的全身各个器官,由于病变部位不一,临床表现多样,导致诊断困难或诊断延误.我们报告2例原发性中枢神经系统的IVLBCL临床病例并复习文献.     

原发性输尿管弥漫性大B细胞淋巴瘤1例

临床上原发于输尿管的淋巴瘤罕见,本科诊断1例误诊为输尿管结石的弥漫大B细胞淋巴瘤,现报道如下。患者男性,46岁,以"左腰痛2个月,加重1个月"为主诉于2011年6月30日入院。该患者于2个月前无明显诱因出现左腰部疼痛,性质呈钝痛,曾于外院就诊,行B超检查示左肾积水,左输尿管上端扩张。诊断为左输尿管结石,建议多饮水自行排出结石,未给予其他治疗。1个月前因疼痛明显加重收住本院。查体无明显阳性体征,行辅助检查。泌尿系彩超:左肾积水,左输尿管上端扩张;二维强化CT:考虑左输尿管中段占位,伴肾积水;左侧尿路逆行造影:左侧输尿管中段占位可能。于2011年7月1日行左输尿管肿瘤探查术。术中见:左输尿管中段4cm质硬肿物,输尿管与周围组织无粘连。术后病理示:符合弥漫性大B细胞性淋巴瘤,生发中心性。免疫     

甲状腺原发性乳头状癌及弥漫性大B细胞恶性淋巴瘤1例报告

甲状腺原发性非霍奇金淋巴瘤(NHL)少见,占所有NHL的2%～3%及占甲状腺恶性肿瘤的2%～8%^[1],多见于中老年女性;而甲状腺癌的发病率在全部恶性肿瘤中不足1%,在头颈恶性肿瘤中其发病率却居首位.     

原发性中枢神经系统弥漫大B细胞淋巴瘤临床病理学观察

目的：观察原发性中枢系统弥漫大B细胞淋巴瘤（PCNS-DLBCL）临床病理学、影像学特点,探讨其免疫组化、基因重排检测及microRNA表达特征。方法：收集确诊的PCNS -DLBCL 25例,观察并分析影像学、病理组织学、免疫组化标记特点,并进行重链和轻链基因重排检测。对其中10例典型PCNS-DLBCL、10例颅外生发中心来源的弥漫大B细胞淋巴瘤（GC-DLBCL）和10例颅外非生发中心来源的弥漫大B细胞淋巴瘤（NGC-DLBCL）的石蜡包埋组织块微切割提取microRNA,进行芯片杂交,对三者间的差异性进行比较。结果：PCNS-DLBCL多累及两个或两个以上脑叶（10/25例）,其中额叶受累最为常见（6/25例）。所有病例均可见中心母细胞样的大淋巴细胞围绕血管呈靶环样生长。免疫组化染色结果显示,25/25例均弥漫强阳性表达CD20、CD79a,不表达CD3、CD5、CD23、CyclinD1,Ki-67阳性率在50％-90％（平均80％）,仅有3例表达CD10（占12％）,19例表达Bcl-6（占76％）,22例表达Mum-1（88％）。基因重排检测显示24/25例呈B细胞单克隆性（96％）。microRNA芯片杂交显示,与NGC-DLBCL比较,升高2倍及以上者788个microRNA或片段,下降0．5倍以下者401个microRNA或片段;与GC-DLBCL比较,升高2倍及以上者611个microR-NA或片段,下降0．5倍以下者229个microRNA或片段。结论：PCNS-DLBCL以老年男性好发,常累及多个部位,免疫组化显示大部分为活化B细胞来源,基因重排检测B细胞单克隆性高,microRNA芯片杂交显示, PCNS-DLBCL microRNA表达明显不同于颅外NGC-DLBCL和GC-DLBCL,可能存在microRNA诊断性标志物。从microRNA表达差异的数量看,PCNS-DLBCL与颅外GC-DLBCL差异较小,此与二者的预后接近相关。     

80例原发中枢神经系统弥漫大B细胞淋巴瘤的临床病理、免疫表型及EB病毒感染的研究

目的:对80例原发中枢神经系统弥漫大B细胞淋巴瘤（primary diffuse large B cell lymphoma of the central nervous system,PCNS DLBCL）进行临床病理学回顾性研究、免疫表型检测及EB病毒（Epstein-Barr virus,EBV）感染检测。旨在探讨其与预后的关系。方法:对80例PCNS DLBCL进行免疫表型检测及EB病毒检测,并进行Hans、Choi和Tally分型、统计学单因素和多因素预后分析。结果:Bcl-2、CD10、Bcl-6、Mum-1、GCET-1、BLIMP-1、FOXP-1和LMO-2的表达率分别为46.1%、8.8%、75.0%、57.5%、27.5%、11.3%、75.0%和26.3%;Ki-67指数为30%～95%,中位数为80%。Hans、Choi和Tally分型中Non-GCB型/ABC型弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）（63.9%、79.2%和90.0%）为最常见的亚型。EBV及EBER1/2-ISH的表达率均为3.8%。58.8%的患者术后未行其它治疗,其1年、2年和5年生存率分别为36.3%、16.4%和4.6%。术后是否行其它治疗、采用甲氨喋呤（methotrexate,MTX）治疗和环磷酰胺+多柔比星+长春新碱+泼尼松龙（cyclophosphamide,doxorubicin,vincristine,and prednisone,CHOP）治疗是有统计学意义的预后相关因素（P均＜0.001）。结论:80例PCNS DLBCL患者年龄较国内外报道的小;以Non-GCB型/ABC型DLBCL为主;个别病例检出EB病毒感染;术后未行其它治疗组、未采用MTX治疗组和未CHOP治疗组的预后较差。     

71例原发颅内中枢神经系统DLBCL预后分析

目的 探讨原发颅内中枢神经系统弥漫性大B细胞淋巴瘤(DLBCL)的预后因素。 方法 回顾分析1991—2015年间收治的经病理和临床证实的 71例原发颅内中枢神经系统DLBCL临床资料。全组患者均进行了化疗,59例进行了放疗,化疗方案以HD-MTX (HD-MTX,66/71)为主,放疗方案以全脑放疗 ±局部推量为主。Kaplan-Meier法计算生存率,Logrank法检验和单因素预后分析,Cox模型多因素预后分析。 结果 放化疗结束时 58例CR, 10例PR,3例PD。5年生存率为43%;5年无疾病进展率为34%。单因素分析显示年龄、KPS评分、单发与多发、是否放疗、放化疗完成时评价、有无复发是影响OS的因素(P=0.000~0.047),多因素分析显示年龄、KPS评分、有无复发是影响OS的因素(P=0.000~0.022)。单因素分析化疗方案、是否放疗、总放疗剂量、全脑剂量、放化疗完成时评价、有无复发是影响PFS的因素(P=0.000~0.028);多因素分析KPS评分、有无复发是影响PFS的因素(P=0.000~0.011)。 结论 年轻、KPS评分高、无复发患者总生存更好,单发、接受放疗、放化疗后疗效好的患者可能更好;KPS评分高、放化疗后疗效好、无复发患者PFS更好,接受含HD-MTX化疗、接受放疗、总的放疗剂量和全脑剂量越高患者PFS可能更好。化疗达CR后是否还放疗及放疗靶区、剂量需进一步研究。     

A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma

Background:

Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear.

Methods:

We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP ‘group 1'' R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX ‘group 2'' dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX ‘group 3''.

Results:

Overall, 217 patients were identified (49, 125 and 43 in groups 1–3, respectively). With median follow-up of 3.4 (range 0.2–18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1–3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5–33.1%), 6.9% (3.5–13.4%) and 2.3% (0.4–15.4%) in groups 1–3, respectively (P=0.009).

Conclusions:

The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.     

Lack of benefit of central nervous system prophylaxis for diffuse large B-cell lymphoma in the rituximab era: findings from a large national database

BACKGROUND:

Little is known about the utility of central nervous system (CNS) prophylaxis for diffuse large B‐cell lymphoma (DLBCL) in the rituximab era. The objective of this study was to characterize patterns of CNS prophylaxis for patients who received combined rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) chemotherapy using the National Comprehensive Cancer Network Non‐Hodgkin Lymphoma Outcomes Database, a prospective cohort study that collects clinical and outcomes data for patients at 7 participating centers.

METHODS:

Patients who were eligible for this analysis presented with newly diagnosed DLBCL between January 2001 and July 2008, had no evidence of baseline CNS disease, and had received R‐CHOP within 180 days of diagnosis. The authors assessed incidence and covariates of prophylaxis, prophylaxis modality, and, using propensity score analysis, outcomes such as overall survival.

RESULTS:

Of 989 eligible patients, 117 received CNS prophylaxis (11.8%), most intrathecally (71.8%). Involvement of bone marrow, other high‐risk site, >1 extranodal site, higher International Prognostic Index score, and higher stage were associated individually with the receipt of prophylaxis (all P < .0001). At a median follow‐up of 2.5 years, there were 20 CNS recurrences (2% [95% confidence interval, 1.1%‐2.9%]) among all patients, and overall survival was not affected by prophylaxis.

CONCLUSIONS:

Given the overall low rate of CNS recurrence and lack of prophylaxis‐associated survival benefit, the current data called into question the practice of CNS prophylaxis in the rituximab era. Cancer 2011. © 2011 American Cancer Society.     

Prognostic significance of the aggregative perivascular growth pattern of tumor cells in primary central nervous system diffuse large B-cell lymphoma

Background

Primary central nervous system lymphomas, predominantly diffuse large B-cell lymphomas (PCNS-DLBCL), are aggressive malignancies, and no histopathological variables with independent prognostic value are currently available. The aim of this study is to determine the prognostic value of histopathological variables of PCNS-DLBCL.

Methods

Aggregative perivascular tumor cells (APVTs) and reactive perivascular T cell infiltrates (RPVIs) in tumor samples from 62 immunocompetent patients with PCNS-DLBCL were histopathologically and immunohistochemically studied. A mouse brain DLBCL model was established to confirm the special morphological features of PCNS-DLBCL. The therapy, overall response rate (ORR), and overall survival (OS) among patients were followed up.

Results

APVT was present in 54 (87%) of the 62 cases, whereas RPVI was present in 20 (32%). Patients with APVT-positive lesions exhibited significantly worse OS, with intermediate to high International Extranodal Lymphoma Study Group (IELSG) scores, compared with patients with RPVI-positive lesions. Among cases of APVT-positive lymphoma, the semiquantitative score of immunostaining of X-box–binding protein (XBP1) and CD44 demonstrated prognostic significance. Multivariate analysis confirmed independent associations between APVT and XBP1 and between CD44 staining and survival.

Conclusions

The presence of APVT and staining of XBP1 and CD44 are independently associated with survival among patients with PCNS-DLBCL. These features could be routinely assessed in histopathological and immunohistochemical specimens.     

Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high‐risk patients with diffuse large B‐cell lymphoma

BACKGROUND:

The outcome of patients with systemic diffuse large B‐cell lymphoma (DLBCL) had improved over the past decade with the addition of monoclonal antibody therapy. Unfortunately, approximately 5% of these patients still developed a secondary central nervous system (CNS) recurrence followed invariably by rapid death. This rate is substantially increased in patients with certain high‐risk features. Although prophylaxis against CNS recurrence with either intrathecal or intravenous methotrexate is commonly used for such patients, to the authors' knowledge, there is no standard of care. Retrospectively evaluated was the role of high‐dose systemic methotrexate combined with standard cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (R‐CHOP) chemotherapy to decrease CNS recurrence in high‐risk patients.

METHODS:

A total of 65 patients with DLBCL and CNS risk factors were identified at the study institution between 2000 and 2008 who received intravenous methotrexate as CNS prophylaxis concurrent with standard systemic therapy with curative intent. CNS recurrence rate, progression‐free survival, and overall survival were calculated.

RESULTS:

Patients received a median of 3 cycles of methotrexate at a dose of 3.5 gm/m² with leucovorin rescue. The complete response rate was 86%, with 6% partial responses. At a median follow‐up of 33 months, there were only 2 CNS recurrences (3%) in this high‐risk population. The 3‐year progression‐free and overall survival rates were 76% and 78%, respectively. Complications associated with methotrexate therapy included transient renal dysfunction in 7 patients and a delay in systemic chemotherapy in 8 patients.

CONCLUSIONS:

Intravenous methotrexate can be safely administered concurrently with R‐CHOP and is associated with a low risk of CNS recurrence in high‐risk patients. Cancer 2010. © 2010 American Cancer Society.     

原发性中枢神经系统淋巴瘤的临床特征及预后分析

目的:探讨原发性中枢神经系统淋巴瘤（primary central nervous system lymphoma,PCNSL）患者的临床病理和分子学特征及预后影响因素。方法:收集2013年03月至2021年05月山西省人民医院35例PCNSL患者的临床资料及组织标本,总结其临床病理特征并应用二代测序技术检测淋巴瘤相关基因,分析年龄、病灶部位、乳酸脱氢酶（lactate dehydrogenase,LDH）、免疫组化等指标对预后的影响,比较不同基因突变组及治疗方案之间的总生存（overall survival,OS）差异。结果:最常见的基因突变为MYD88（66.7%,12/18）,IGLL5、PIM1（38.9%,7/18）;PIM1突变组、IGLL5突变组OS差于未突变组,差异均有统计学意义（P=0.019和0.021）;多因素Cox回归分析显示LDH、不同的治疗方案是PCNSL患者独立的预后影响因素（P=0.007和0.002）;接受大剂量甲氨蝶呤（methotrexate,MTX）、利妥昔单抗（rituximab,R）治疗组OS明显优于未接受组,差异均有统计学意义（P=0.005和＜0.001）;使用布鲁顿酪氨酸激酶抑制剂（broughton tyrosine kinase inhibitor,BTKi）组与未接受组相比,有生存获益的趋势,但未显示出统计学差异。结论:血清LDH升高与不良预后显著相关,PIM1及IGLL5突变患者生存较差,含MTX、R治疗方案可改善患者生存。