结外ALK阳性弥漫大B细胞淋巴瘤二例

例1男性,49岁,因左侧阴囊坠胀不适10余年,偶然触及右侧睾丸肿物2个月于2014年8月就诊。阴囊彩色超声示右侧睾丸见低回声团块,边界不清,未见包膜,内部回声不均,血流丰富。盆腔CT示右侧睾丸密度略欠均,男性肿瘤标志物及碱性磷酸酶结果正常。行睾丸切除术后病理镜下观察：睾丸曲细精管结构保存,间质内肿瘤细胞弥漫性浸润,肿瘤细胞体积较大,核大,有1～3个清楚的核仁,染色质较粗,核分裂象易见（图1）。免疫组织化学：Ki-67（40%+）,CD20、CD43、CD79a、PAX-5、bcl-6、bcl-2、Mum-1、ALK （图2）、FOXP1均阳性;CD3、CD5、cyclin D、CD10、CD21、CD30、GCET1均阴性;原位杂交技术检测EBER阴性。病理诊断为非生发中心（non-GCB）型ALK阳性弥漫大B细胞淋巴瘤（DLBCL）。诊断明确后患者拒绝化疗,随访8个月后死亡。     

弥漫大B细胞淋巴瘤预后相关因素研究进展

弥漫大B细胞淋巴瘤(DLBCL)是一种最常见的侵袭性非霍奇金B细胞淋巴瘤(B-NHL),在临床表现和预后等方面具有显著的异质性,多种因素影响其预后.文章根据国内外研究进展,从临床特征及分子生物学特征两方面对影响DLBCL患者预后的因素进行综述.     

复发难治性弥漫大B细胞淋巴瘤的生物靶向治疗

含有利妥昔单抗的化疗方案能改善弥漫大B细胞淋巴瘤(DLBCL)患者的预后,然而仍有部分患者在一线应用R-CHOP方案后转为复发难治性DLBCL(RR-DLBCL),且预后不良.对DLBCL及其相关肿瘤基因表达研究证实基因水平的生物靶向治疗能改善RR-DLBCL患者的预后.目前,一些新的靶向治疗成为研究热点.文章就RR-DLBCL的生物靶向治疗进展进行综述.     

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.     

弥漫大B细胞淋巴瘤研究最新进展

弥漫大B细胞淋巴瘤(DLBCL)是成年人发生率最高的淋巴瘤亚型,是一组高度异质性的肿瘤,不同亚型有不同的生物学特征、临床表现及治疗反应,患者预后差别很大,尽管目前的标准治疗R-CHOP方案为基础的免疫化疗使DLBCL治愈率提高,但仍有约40％的患者治疗早期即出现耐药或达到缓解后复发,预后差.本文结合第59届美国血液学会(ASH)年会有关报道,对DLBCL的新分子分型、新靶点药物研发、复发难治患者治疗等的研究进展进行总结.     

原发气管弥漫大B细胞淋巴瘤一例并文献复习

目的:探讨原发气管弥漫大B细胞淋巴瘤（DLBCL）的临床特点、实验室检查、治疗及预后。方法:回顾性分析郑州大学第一附属医院收治的l例原发气管DLBCL合并干燥综合征（SS）患者的临床资料,并结合文献进行复习。结果:该患者明确诊断为DLBCL（非生发中心B细胞型）,Ⅰ期,低危组,国际预后指数（IPI）评分0分;SS。给予R-CHOP方案化疗2个周期后达到部分缓解,4个周期后达到完全缓解,共予6个周期化疗及1次局部放疗。随访24个月,患者一般情况尚可,临床无不适主诉,PET-CT未发现代谢异常细胞。结论:原发气管DLBCL非常少见,发病原因可能与SS等自身免疫性疾病有关,临床表现无特异性,易误诊,诊断主要靠病理学检查,治疗主要包括气管镜下治疗等手术治疗、联合放化疗等,预后可能与临床分期、IPI评分、肿瘤细胞来源及治疗等有关。     

弥漫大B细胞淋巴瘤治疗进展

弥漫大B细胞淋巴瘤(DLBCL)是最常见的恶性淋巴瘤.虽然R-CHOP标准治疗方案改善了DLBCL患者的整体生存,但高危患者5年总生存率仍<50%.因此DLBCL一直是研究和关注的热点,如新药的联合治疗、以嵌合抗原受体T细胞(CAR-T)和抗体治疗为代表的免疫靶向治疗、如何降低治疗的长期不良反应以及寻找新的预后生物学标志物和分型系统等.文章就第60届美国血液学会年会上DLBCL的最新进展进行概述.     

小肠弥漫大B细胞淋巴瘤颊部转移一例并文献复习

目的 提高对小肠弥漫大B细胞淋巴瘤(DLBCL)颊部转移的认识.方法 分析1例小肠DLBCL颊部转移患者的临床资料,复习相关文献并讨论其临床特征及诊疗方法.结果 患者为男性,45岁,发现小肠恶性淋巴瘤8个月,左侧面颊部肿胀1周入院.左颊部肿物活组织检查病理结果倾向恶性淋巴瘤,给予CHOPE方案化疗1个周期后左颊部肿胀消失.结论 小肠DLBCL伴颊部转移罕见,是一种高度侵袭性肿瘤,预后较差.颊部转移易被误诊为感染性疾病.组织学形态及免疫组织化学染色有助于明确诊断,手术切除后辅助化疗及放疗可能提高临床疗效.     

原发心脏弥漫大B细胞淋巴瘤一例并文献复习

目的:探讨原发心脏弥漫大B细胞淋巴瘤（DLBCL）的临床特征、诊疗及预后。方法:回顾性分析安徽医科大学第一附属医院2018年11月收治的1例原发心脏DLBCL伴房室传导阻滞患者的诊疗经过,并复习相关文献。结果:患者,女性,48岁,初期临床表现为反复活动后胸闷、气喘,后突发晕厥,行心脏肿瘤切除术+双腔起搏器植入术,术后病理提示DLBCL,予以R-CHOP方案化疗8次。随访至截稿前,患者病情处于稳定状态。结论:原发心脏DLBCL恶性程度高,病情进展迅速,临床表现缺乏特异性,多通过尸检或术后病理发现;治疗上以化疗联合放疗为主,手术辅助治疗;总体预后不佳。     

原发性脾弥漫大B细胞淋巴瘤一例并文献复习

目的 探讨原发性脾弥漫大B细胞淋巴瘤(DLBCL)的临床病理学特征及治疗策略.方法 回顾性分析1例原发性脾DLBCL患者的临床资料及病理切片,并复习相关文献.结果 患者主要表现为左上腹疼痛,无发热及浅表淋巴结肿大,CT证实脾多发占位性病变伴脾门多发肿大淋巴结.行脾、胰尾切除术,病理确诊为DLBCL,免疫分型为生发中心B细胞型.外周血和骨髓检查结果正常.脾切除术后给予联合化疗,随访1年处于完全缓解期.结论 原发性脾DLBCL罕见,患者早期无明显症状,手术探查是早期诊断的首选方法,病理学检查是诊断金标准.治疗首选脾切除术,术后辅助化疗及放疗可以提高患者生存率.     

ALK-positive diffuse large B-cell lymphoma: report of three cases

Diffuse large B-cell lymphoma positive for anaplastic lymphoma kinase (ALK(+) DLBCL) is a rare variant of diffuse large B-cell lymphoma, with characteristic morphological, immunohistochemical and cytogenetic features. Only 34 cases of ALK-positive diffuse large B-cell lymphoma have so far been reported in the literature. We examined three new cases, which showed similar characteristics to previously reported cases, but with peculiar nuclear-membrane staining for ALK protein in one patient and a 5'-ALK gene deletion in another. All of them had stage IV disease at initial presentation, with poor outcomes. The tumour cells showed immunoblastic/plasmablastic histology and were positive for ALK and Oct2, but negative for CD3, CD20, CD79a, CD30 and PAX5. The staining pattern of ALK protein was cytoplasmic in two patients and associated with the nuclear membrane in one patient. Fluorescence in situ hybridization (FISH) analysis using the ALK break-apart probe revealed ALK gene rearrangements in all three patients, with a 5'-ALK gene deletion in one patient. These three cases suggest that different types of cytogenetic aberrations may involve the ALK gene in ALK-positive diffuse large B-cell lymphoma leading to peculiar immunohistochemical staining patterns.     

具有微绒毛特征的CD30阳性弥漫大B细胞淋巴瘤一例临床病理特征

目的 讨论具有微绒毛特征的CD30+弥漫大B细胞淋巴瘤的临床、病理特征,提高对该病的认识与诊断水平.方法 对1例76岁女性的颈部肿大的淋巴结进行组织学、免疫组织化学、EBER原位杂交和电子显微镜观察,并复习相关文献.结果 组织病理学示,淋巴结正常结构消失,形态单一的、胞质丰富的异型细胞呈片状增生,部分区域可见异型细胞淋巴窦内生长模式.免疫组织化学示,异型细胞CD20+、CD79a+、PAX-5+、CD10+、bcl-6+、MUM-1+,40％肿瘤细胞CD30+,80％肿瘤细胞Ki-67+,肿瘤细胞不表达CK、CD3、CD5、CD15、CD56、EMA、bcl-2.电子显微镜观察,瘤细胞体积大,胞质丰富,瘤细胞表面大量微绒毛,微绒毛长短不一,粗细较均匀,少数有分枝.结论 微绒毛淋巴瘤是一类具有独特形态学改变、免疫组织化学表型和超微结构的淋巴瘤.     

21例原发乳腺弥漫大B细胞淋巴瘤的临床分析

  目的  探讨原发乳腺弥漫大B细胞淋巴瘤（primary breast diffuse large B cell lymphoma,PB-DLBCL）的临床特征、治疗方案及预后因素。  方法  回顾性分析2010年1月至2018年1月郑州大学第一附属医院收治的21例PB-DLBCL患者的临床病理资料。所有患者均为女性,中位年龄为49（21~77）岁,均接受化疗,其中17例接受CHOP方案,4例接受EPOCH方案。8例接受化疗序贯放疗,13例接受单纯化疗。采用Kaplan-Meier法及Cox回归模型进行多因素分析。  结果  21例患者无痛性肿块为主要表现。5年总生存率（overall survival,OS）和无进展生存率（progressione-free survival,PFS）分别为74%和66%。EPOCH方案与CHOP方案之间在复发或进展上的差异无统计学意义（P=0.603）。行预防性鞘内注射的患者无中枢神经系统复发,未行鞘内注射患者有2例中枢神经系统复发,差异无统计学意义（P=0.232）。单因素及多因素分析结果均显示,β2微球蛋白（HR=0.431,95%CI为0.432~ 0.967,P=0.044）和放疗（HR=0.495,95%CI为1.073~2.508,P=0.002）与PB-DLBCL的OS均相关。  结论  PB-DLBCL好发于女性,多累及单侧乳腺,主要表现为无痛性肿块。β2微球蛋白水平为不良的预后因素。化疗联合放疗可显著提高患者的生存期。鞘内注射对于预防中枢神经系统淋巴瘤的复发可能具有意义。      

慢性淋巴细胞白血病/小B细胞淋巴瘤继发急性髓系白血病一例并文献复习

目的 提高对慢性淋巴细胞白血病/小B细胞淋巴瘤(CLL/SLL)继发髓系肿瘤的认识.方法 报道1例CLL/SLL继发急性髓系白血病患者,并对该病的发生率、危险因素及可能的机制进行文献复习.结果 CLL/SLL继发髓系肿瘤患者大多数伴有染色体异常,对接受以氟达拉滨为基础联合化疗的患者出现造血不良特征或血细胞减少应加强评估.结论 CLL/SLL继发髓系肿瘤少见,预后差,临床医师对具有危险因素的患者应提高警惕,争取早诊断、早干预.     

血管免疫母细胞性T细胞淋巴瘤并发EB病毒阳性弥漫大B细胞淋巴瘤二例并文献复习

目的:探讨血管免疫母细胞性T细胞淋巴瘤（AITL）并发EB病毒（EBV）阳性弥漫大B细胞淋巴瘤（DLBCL）患者的临床病理特征、治疗及预后。方法:回顾性分析解放军总医院第五医学中心2例AITL并发EBV阳性DLBCL患者的临床资料,并进行文献复习。结果:例1为混合淋巴瘤（CL）患者,以低热伴全身浅表淋巴结肿大起病,右侧腋窝肿物活组织检查示AITL并发EBV阳性DLBCL,予以8个周期化疗后达不确定的完全缓解;后续应用西达本胺维持治疗,仍生存中。例2为不一致性淋巴瘤（DL）患者,以皮下结节起病,后出现浅表淋巴结进行性肿大;皮下结节病理检查诊断为DLBCL,右腹股沟淋巴结病理检查诊断为AITL;接受7个周期化疗,因合并噬血细胞综合征而死亡。结论:AITL合并EBV阳性DLBCL罕见,临床症状主要以AITL的表现为主,存在T细胞及B细胞免疫表型特征,预后差,治疗方案主要依据预后较差的淋巴瘤进行选择。     

三氧化二砷及维甲酸治疗复发难治急性单核细胞白血病二例并文献复习

目的 观察三氧化二砷（As2O3）及维甲酸（RA）单独或联合应用治疗复发难治性急性单核细胞白血病（AML-M5）的效果.方法 报道2例经As2O3及RA治疗的复发难治性AML-M5患者,例1患者骨髓移植后复发,应用As2O3联合RA治疗;例2患者诱导化疗失败后,分别应用As2O3和RA治疗.结果 2例患者治疗后均获得完全缓解,例1完全缓解8个月后复发,例2完全缓解7个月后复发,继续应用As2O3获完全缓解1个月后再次复发.结论 As2O3及RA单独或联合应用治疗复发难治性AML-M5效果较好.     

Therapy-related acute promyelocytic leukemia: a report on 16 cases.

PURPOSE: To analyze the type of prior tumor and treatment in therapy-related acute promyelocytic leukemia (tAPL) that occurs after chemotherapy and/or radiotherapy (RT), and the hematologic characteristics and outcome of tAPL. PATIENTS AND METHODS: Sixteen patients with tAPL who were gathered during a 10-year period (1982 to 1991) in seven hematologic centers were analyzed retrospectively. RESULTS: There were 13 women and three men. The median age was 46 years (range, 12 to 82). Prior tumor was breast carcinoma in 10 cases, another solid tumor in three cases, and lymphoma in three cases. Two patients had received RT alone, and 14 had received chemotherapy (with RT in 11 cases). Prior chemotherapeutic agents generally included a combination of cyclophosphamide (used for limited periods), fluorouracil (5-FU), vinca alkaloids, and doxorubicin, mitoxantrone, or etoposide (VP16). By contrast, alkylating agents other than cyclophosphamide had been used in only two patients. Median interval between onset of treatment for the prior tumor and diagnosis of APL was 25 months. No patient had a known preleukemic phase. Hematologic and cytogenetic characteristics of the cases of tAPL were identical to those of the usual de novo APL, which included the presence of t(15; 17) in nine of the 10 patients tested. Two patients had early death. Seven patients were treated with intensive chemotherapy, and six achieved complete remission (CR). Three of them subsequently relapsed. Seven patients were treated with all-trans-retinoic acid (ATRA), and four achieved CR through the differentiation of blasts into mature granulocytes. None has relapsed so far. CONCLUSIONS: Our findings suggest that tAPL is not exceptional, and usually has several features in common with other types of therapy-related AML with specific karyotype (ie, t(8;21),t(9;11), inv(16)): solid tumor rather than hematologic malignancy as primary tumor, short interval of development, absence of known preleukemic phase, prior chemotherapy with a combination of several drugs that often included an agent that targets topoisomerase II (doxorubicin or mitoxantrone, but less often VP16). Hematologic characteristics and response to therapy (intensive chemotherapy or ATRA) in tAPL do not seem to differ from those of de novo APL.     

Donor-derived diffuse large B-cell lymphoma after haploidentical stem cell transplantation for acute myeloid leukemia

We report a case of donor-derived diffuse large B-cell lymphoma (DLBCL), which developed 5 years after stem cell transplantation from a human leukocyte antigen (HLA)-haploidentical donor for acute myeloid leukemia (AML). A 51-year-old male was diagnosed with AML with variant KMT2A translocation involving t(6;11)(q13;q23). After 12 cycles of azacitidine treatment, fluorescence in situ hybridization (FISH) for KMT2A split signal indicated that 94% of his bone marrow (BM) cells were positive. He underwent peripheral blood stem cell transplantation (PBSCT) from his HLA-haploidentical son. The preconditioning regimen consisted of fludarabine, busulfan, melphalan, and antithymocyte globulin (ATG). The graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and short-term methotrexate. On day 28, KMT2A FISH analysis indicated that he had achieved a complete response (CR). He continued to receive tacrolimus for the limited type of cutaneous chronic GVHD. Five years after the transplantation, positron emission tomography/computed tomography (PET/CT) showed an abdominal tumor. The tumor was diagnosed as DLBCL without Epstein-Barr virus. BM aspiration revealed the infiltration of lymphoma cells with t(8;14)(q24;q32). Chimerism analysis showed that both the peripheral blood (PB) and abdominal lymphoma cells were of donor origin. After 4 cycles of salvage chemotherapy, PET/CT showed that a CR had been achieved. He underwent a second PBSCT from an HLA-identical unrelated donor. The preconditioning regimen and GVHD prophylaxis were the same as those for the first PBSCT without ATG. The patient’s PB revealed complete second donor-type chimerism, and the patient has maintained a CR since the second transplantation.     

9例原发睾丸弥漫大B细胞淋巴瘤临床特点及预后分析

目的 探讨原发睾丸弥漫大B细胞淋巴瘤(primary testicular diffuse large B-cell lymphoma,PTDLBCL)的临床床特征、治疗及预后.方法 回顾性分析我院2013年1月至2016年12月确诊的9例PTDLBCL患者的临床资料.结果 9例患者中位发病年龄为64岁(50～72岁),以右侧睾丸受累为主;Ann Arbor分期以早期为主,其中Ⅰ期6例,Ⅲ期1例,Ⅳ期2例;细胞来源以非生发中心来源为主,非生发中心B细胞来源7例,生发中心B细胞来源2例;肿瘤增殖指数Ki-67偏高,Ki-67中位数为80％.治疗以手术加术后辅助化疗为主,其中单纯手术治疗1例,手术联合CHOP方案为主的化疗8例.获完全缓解6例,部分缓解2例,疾病进展1例.随访时间5～34个月,存活6例,死亡3例.结论 原发睾丸弥漫大B细胞淋巴瘤是一组罕见的疾病,复发风险高,一线治疗方案推荐患侧睾丸根治性切除术后联合R-CHOP方案化疗,同时对对侧睾丸及受累野进行放疗及预防性甲氨蝶呤鞘内化疗.