B细胞特异性激活蛋白与CD20在淋巴组织增生性疾病中的表达

目的探讨B细胞特异性激活蛋白(B cell-specific activator protein, BSAP)在淋巴组织增生性疾病中表达情况及在淋巴瘤鉴别诊断中的意义.方法观察63例淋巴组织增生性疾病的组织病理学形态,按WHO新分类方案进行淋巴瘤分型,采用免疫组织化学S-P法同步检测比较BSAP和CD20的表达.结果 9例淋巴结反应性增生的B淋巴细胞,34例B细胞性淋巴瘤的瘤细胞均表达BSAP和CD20,但BSAP的中等到强阳性表达率(69.8%)高于CD20(53.5%),二者差异无显著性(P>0.05);6例霍奇金淋巴瘤H/RS瘤细胞表达阳性率为83.2%;14例T细胞淋巴瘤的肿瘤细胞均不表达BSAP.结论 BSAP表达定位于B淋巴细胞的核内,清晰易见,在B细胞性淋巴瘤表达多呈强阳性,可用于淋巴瘤的分型与鉴别诊断,是判断肿瘤为B细胞来源的又一重要辅助指标.     

C型凝集素样自然杀伤(NK)细胞受体在结外鼻型NK/T细胞淋巴瘤中表达及意义

目的 探讨C型凝集素样自然杀伤(NK)细胞受体CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中的表达及意义.方法 运用逆转录聚合酶链反应(RT-PCR)检测C型凝集素样NK细胞受体CD94和NKG2在经组织形态、免疫组织化学、EB病毒原位杂交及T细胞受体PCR克隆性重排分析确诊的21例结外鼻型NK/T细胞淋巴瘤以及对照组同部位B细胞淋巴瘤8例、淋巴结外周T细胞淋巴瘤(PTCL)10例、脾脏5例、胸腺5例和慢性炎性鼻黏膜5例组织中的表达情况并进行随访.结果 21例结外鼻型NK/T细胞淋巴瘤具有典型的形态学改变,表达CD3ε、CD56和细胞毒蛋白,TCR重排阴性,20例EB病毒阳性;RT-PCR扩增结果显示,在21例结外鼻型NK/T细胞淋巴瘤中,18例(85.7%)CD94呈阳性表达;NKG2总阳性率为95.2%(20/21),各亚基表达阳性率依次为NKG2A/2B(85.7%)、NKG2D(61.9%)、NKG2F(14.3%)、NKG2C,/2E(4.8%).对照组中PTCL和B细胞淋巴瘤均不表达CD94和NKG2,仅2例脾脏和2例慢性炎性鼻黏膜组织表达CD94,1例脾脏组织表达NKG2A/2B,1例胸腺组织表达NKG2D.CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中的表达与T细胞淋巴瘤和B细胞淋巴瘤比较,差异均有统计学意义(P均<0.01).CD94和NKG2同时表达于17例结外鼻型NK/T细胞淋巴瘤,共表达率为81.0%(17/21).结论 CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中呈特异性和顺序性表达,提示多数病例肿瘤细胞处于活化和功能NK细胞阶段.对这些分子的检测有可能成为NK细胞源性淋巴瘤诊断的重要手段.     

儿童腹腔非霍奇金B细胞淋巴瘤的临床病理及免疫表型分析

目的 探讨儿童腹腔原发性非霍奇金B细胞淋巴瘤的临床病理、免疫表型与EBER特征及其病理诊断和鉴别诊断.方法 按WHO(2008年)淋巴瘤分类标准分析74例儿童腹腔原发性非霍奇金B细胞淋巴瘤的临床病理资料,制备组织芯片,进行免疫组织化学SP法染色,EBER原位杂交和c-myc基因荧光原位杂交,观察CD20、CD79a、CD3、CD10、bcl-6、MUM1、bcl-2、CD43、CD38和Ki-67蛋白的表达和EBER表达特征,并区分伯基特淋巴瘤(BL)、弥漫性大B细胞淋巴瘤(DLBCL)和介于BL和DLBCL之间的不能分类的B细胞淋巴瘤(DLBCL/BL)病理类型,在DLBCL中再区分其生发中心B细胞型(GCB)和非生发中心B细胞型(non-GCB)的分化特征.结果 儿童腹腔非霍奇金B细胞淋巴瘤中BL为65例(87.8%),DLBCL为4例(5.4%),DLBCL/BL为5例(6.8%).临床以腹痛、腹部包块、肠梗阻及肠套叠为主要发病症状.BL免疫组织化学表达CD20(65例)、CD79a(65例)、CD10(63例)、bcl-6(62例)、MUM1(15例)、CD43(46例)和CD38(63例);不表达CD3、bcl-2;27例(41.6%)EBER阳性;54例(93.0%)c-myc基因位点断裂.DLBCL免疫组织化学表达CD20(4例)、CD79a(4例)、CD10(3例)、bcl-6(2例)、MUM1(2例)、bcl-2(3例)、CD43(2例)、CD38(2例);不表达CD3;其中2例GCB,2例non-GCB;EBER阴性;1例c-myc基因位点断裂.DLBCL/BL免疫组织化学表达CD20(5例)、CD79a(5例)、CD10(5例)、bcl-6(4例)、MUM1(3例)、CD43(5例)、CD38(3例),不表达CD3和bcl-2;4例EBER阴性;3例c-myc基因位点断裂.结论 儿童腹腔非霍奇金B细胞淋巴瘤具有侵袭性生长的特点,以BL为主要病理类型.临床以腹痛、腹部包块、肠梗阻及肠套叠为主要发病症状,主要累及回盲部肠组织及周围系膜淋巴结,病理形态、免疫表型、EBER、c-myc基因的检测对BL、DLBC及DLBCL/BL淋巴瘤的诊断和鉴别诊断有重要作用.     

B细胞特异性激活蛋白Pax-5在淋巴瘤组织中的表达

目的探讨B细胞特异性激活蛋白(BSAP)／Pax-5在淋巴瘤的表达情况及应用价值。方法按2001年WHO关于淋巴造血组织肿瘤分类标准收集102例弥漫性大B细胞淋巴瘤(DLBCL)、3例滤泡型淋巴瘤(FL)、3例黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT淋巴瘤)、1例结节性淋巴细胞为主型的霍奇金淋巴瘤(NLPHL)、10例间变性大细胞淋巴瘤(ALCL)和10例浆细胞瘤,用免疫组织化学LSAB法同步检测比较BSAP与CD20的表达情况。结果102例DLBCL全部表达CD20,100例表达BSAP,3例FL、3例MALT淋巴瘤和1例NLPHL BSAP和CD20全部阳性表达,10例ALCL、10例浆细胞瘤BSAP和CD20全部阴性表达。BSAP与CD20的表达差异无统计学意义。结论。BSAP/Pax-5是一种新的B细胞标记,阳性信号定位于细胞核,抗BSAP抗体在常规外科病理诊断工作中的应用价值有限。     

穿孔素与颗粒酶B在鼻NK/T细胞淋巴瘤诊断中的意义

目的　检测鼻NK/T细胞淋巴瘤中的穿孔素、颗粒酶B表达分布情况 ,为临床治疗和预后判断提供依据。方法　运用免疫组化S P法检测 11例鼻NK/T细胞淋巴瘤中穿孔素、颗粒酶B的表达和分布情况 ;同时与组织芯片中其他类型淋巴瘤进行比较研究 ,10例淋巴组织反应性增生作为对照。结果　 11例鼻NK/T细胞淋巴瘤中均见穿孔素和颗粒酶B过度表达。以 6 0例淋巴瘤制成组织芯片的 4 2例B细胞淋巴瘤中见 11例少许穿孔素和 14例少许颗粒酶B阳性表达细胞散在分布于瘤细胞间 ,10例外周T细胞淋巴瘤中 8例少许表达穿孔素和 9例少许表达颗粒酶B。 2例间变性大细胞淋巴瘤见少许穿孔素和颗粒酶B阳性表达细胞。 2例霍奇金淋巴瘤阴性。NK/T细胞淋巴瘤的穿孔素和颗粒酶B表达程度与T、B淋巴瘤比较 ,差异有显著性 (P <0 0 1)。结论　穿孔素和颗粒酶B是鉴定活化的细胞毒性细胞的免疫标记物 ,可作为NK/T细胞淋巴瘤的诊断性标记物 ;其在外周T细胞淋巴瘤和B细胞淋巴瘤中的表达 ,反映了机体存在抗肿瘤的免疫反应机制。     

经典型霍奇金淋巴瘤中CXCR5的表达及临床病理意义

目的 探讨经典型霍奇金淋巴瘤(classic Hodgkin lymphoma, CHL)中CXCR5的表达及意义。方法 采用免疫组化EnVision两步法检测33例CHL中CXCR5的表达,分析CXCR5在CHL四种亚型中的表达情况及临床病理诊断意义;同时收集10例ALK阳性间变性大细胞淋巴瘤(anaplastic large cell lymphoma, ALCL)和10例ALK阴性ALCL作为对照组,对比分析CXCR5的表达情况。结果 33例CHL中,31例CXCR5阳性(93.94%):其中结节硬化型15例(15/16,93.75%)、混合细胞型12例(12/13,92.31%)、淋巴细胞丰富型2例,淋巴细胞消减型2例。CHL中CXCR5的表达情况分别为：33例CD30阳性和PAX5弱阳性中31例阳性(93.94%);14例CD15阴性中12例阳性(85.71%);26例CD20阴性中24例阳性(92.31%);6例LMP1阴性中5例阳性;11例EBER阴性中10例阳性(90.91%)。对照组20例ALCL中,肿瘤细胞CXCR5均阴性。结论 CHL中CXCR5阳性率较高,当肿瘤...     

B细胞性非霍金奇淋巴瘤中BCL-6基因5′-非编码区突变

目的分析各种类型B细胞性非霍奇金淋巴瘤(B-NHL)中BCL-6基因5′-非编码区突变特点,探讨其在淋巴瘤发生中的作用.方法应用聚合酶链反应(PCR)、DNA直接测序方法分析135例B-NHL[包括51例弥漫性大B细胞淋巴瘤(DLBCL)、18例滤泡性淋巴瘤(FL)、18例B小淋巴细胞性淋巴瘤(SLL)、15例套细胞性淋巴瘤(MCL)、7例淋巴浆细胞性淋巴瘤(LPL)、5例Burkitt 淋巴瘤、3例B淋巴母细胞性淋巴瘤(LBL)、18例黏膜相关淋巴组织(MALT)淋巴瘤],5例T-NHL 、10例淋巴结反应性增生(LRH)、5例结节型淋巴细胞为主型霍奇金淋巴瘤(NLPHL)样本BCL-6基因5′-非编码区突变特点.结果 BCL-6基因5′-非编码区突变仅见于DLBCL(结内和结外)、FL和MALTL中,突变率分别为27.3%、20.7%、22.2%和22.2%,结内、结外DLBCL中BCL-6突变率差异无显著性(P>0.05).SLL、MCL、LPL、Burkitt 淋巴瘤、LBL、T-NHL以及NLPHL中均未见BCL-6突变(P<0.05).2例LRH的生发中心细胞可见有BCL-6突变.突变频率为0.14×10-2/bp～0.68×10-2/bp;突变类型全部为碱基替换,其中颠换略多于转换 (P>0.05).结论 BCL-6基因5′-非编码区突变可作为生发中心相关B细胞性非霍奇金淋巴瘤的分子标志,它可能在一定程度上参与B-NHL的发生、发展.     

流式细胞术在抗原异常表达淋巴瘤/白血病诊断中的应用

目的 探讨流式细胞免疫分型在抗原异常表达淋巴瘤诊断及鉴别诊断中的作用。方法 应用流式细胞术对伴有抗原异常表达的淋巴瘤3例,B淋巴细胞性白血病8例,T淋巴细胞性白血病1例及伴有淋巴细胞分化抗原表达的急性非淋巴细胞白血病17例,急性粒细胞白血病累及淋巴结1例的免疫表型进行回顾性分析,每例均作胞质CD3ε、CD79a、髓过氧化物酶(MP0)的En Vision两步法染色。结果 11例B细胞淋巴瘤／白血病胞质CD79a阳性,胞质CD3ε及MP0阴性,其中5例伴CD5表达,2例同时伴CD5及1-2项髓系分化抗原表达;1例T淋巴细胞白血病胞质CD3ε阳性,胞质CD79a及MP0阴性,伴CD13、CD33表达;18例急性非淋巴细胞白血病(包括1例急性粒细胞白血病累及淋巴结)胞质髓过氧化物酶(MP0)均阳性,胞质CD3ε及C1979a均阴性,其中8例(包括1例急性粒细胞白血病累及淋巴结)伴T细胞分化抗原表达,8例伴B细胞分化抗原表达,2例同时伴T细胞及B细胞分化抗原表达。结论流式细胞免疫分型不仅能发现淋巴瘤／白血病抗原异常的表达,而且可通过表面免疫标记及胞质CD3s、CD79a、MP0的表达来确定抗原异常表达淋巴瘤／白血病的细胞来源,对抗原异常表达淋巴瘤／白血病的诊断及鉴别诊断具有十分重要价值。     

B细胞非霍奇金淋巴瘤中CD40和NF-κB表达及意义

目的 探讨B细胞非霍奇金淋巴瘤(non-hodgkinlymphoma,NHL)中CD40、NF-κB的表达及意义.方法 采用免疫组化SP法检测69例B细胞NHL及22例淋巴结反应性增生组织中CD40、NF-κB的表达.B细胞NHL患者应用CHOP(环磷酰胺、阿霉素、长春新碱、地塞米松)方案治疗6～8个周期.结果 CD40和NF-κB在B细胞NHL组织中阳性率分别为72.46%(50/69)(P<0.05)和59.42%(41/69)(P<0.001).CD40在Ⅰ+Ⅱ和Ⅲ+Ⅳ期B细胞NHL中的阳性率分别为87.88%(30/33)和58.33%(20/36)(P<0.05);NF-κB在Ⅰ+Ⅱ和Ⅲ+Ⅳ期B细胞NHL中的阳性率分别为36.36%(12/33)和80.56%(29/36)(P<0.05).B细胞NHL组织中CD40与NF-κB的表达呈负相关(r=-0.443,P<0.01).结论 CD40阳性提示B细胞NHL侵袭性低,NF-κB阳性则提示B细胞NHL侵袭性高;CD40是一种提示预后良好的因子,而CD40-NF-κB信号途径对B细胞NHL预后提示的作用尚需进一步研究.     

弥漫性大B细胞淋巴瘤40例细胞病理学分析

目的 探讨细胞病理学诊断弥漫性大B细胞淋巴瘤的可行性和准确性.方法 选择40例由组织活检证实的弥漫性大B细胞淋巴瘤的细胞学病例,包括浅表淋巴结细针穿刺24例、结外包块细针穿刺6例、胸腔积液5例、腹腔积液1例、脑脊液2例、纤支镜刷片2例.对这些病例的临床特点、细胞形态和免疫细胞化学进行分析.结果 所有病例均查见较多中等偏大的淋巴样肿瘤细胞,其免疫表型为40例肿瘤细胞表达CD45(100%),39例肿瘤细胞表达CD20(97.5%),38例表达CD79α (95%),均表现为弥漫阳性,所有病例均不表达CD45RO和PCK,Ki-67增殖指数(proliferative index,PI)均值为52.1%.其中6例用细胞病理材料所作的免疫细胞化学检测中有6例表达CD45,5例表达CD20,6例表达CD79α,均不表达CD45RO和PCK,Ki-67 PI 50%～70%.40例病例中有7例(17.5%)细胞病理诊断为符合弥漫性大B细胞淋巴瘤,16例(40%)诊断为大细胞淋巴瘤,6例(15%)诊断为可疑淋巴瘤,6例(15%)误诊为低分化癌,5例(12.5%)误诊为炎性病变.结论 细胞病理虽然不是诊断弥漫性大B细胞淋巴瘤的的首选方法,但不失为一种新的尝试,仅观察细胞涂片中细胞的形态难以做出准确诊断,需要结合免疫细胞化学,流式细胞术等辅助方法来提高诊断的准确性和可靠性.     

弥漫大B细胞淋巴瘤组织bcl-6蛋白表达及基因重排

目的探讨弥漫大B细胞淋巴瘤(DLBCL)中bcl-6和CD10蛋白表达以及基因重排的特点及其临床病理意义。方法应用免疫组织化学EnVision法分析51例DLBCL(22例为淋巴结内,29例为淋巴结外)和10例淋巴结反应性增生石蜡组织中bcl-6蛋白表达,并与CD10的表达作比较分析;应用断裂分离探针及间期核荧光原位杂交(FISH)技术检测32例淋巴结内DLBCL(22例为石蜡组织,10例为新鲜组织)和5例淋巴结反应性增生石蜡组织中bcl-6基因的重排。结果(1)淋巴结内、外DLBCL和淋巴结反应性增生中bcl-6蛋白均呈细胞核表达,阳性率分别为72.7%(16/22)、75.9%(22/29)、100.0%(10/10);CD10的阳性率分别为40.9%(9/22)、41.4%(12/29)、100.0%(10/10),所有CD10阳性肿瘤均共同表达bcl-6蛋白。(2)40.9%(9/22)的淋巴结内DLBCL和41.4%(12/29)的淋巴结外DLBCL为两蛋白共同阳性表达;将之与两蛋白均不表达的DLBCL(27.3%,6/22和24.1%,7/29)相比,前者(Ⅰ或Ⅱ期)的临床分期低于后者(Ⅲ或Ⅳ期,P<0.05)。(3)淋巴结内DLBCL样本中bcl6基因重排阳性率为28.1%(9/32),其中石蜡组织样本阳性率为27.3%(6/22),新鲜组织样本阳性率为30.0%(3/10),P>0.05。5例淋巴结反应性增生样本中均未检测到bcl-6基因重排,与DLBCL相比P<0.05。结论(1)在DLBCL中bcl6有较高的阳性表达率,bcl-6和CD10蛋白的联合检测可以协助DLBCL的诊断和鉴别诊断;bcl6和CD10共同阳性的DLBCL可能具有更好的预后。(2)bcl-6基因重排可能参与了部分DLBCL的发生,并可作为DLBCL诊断的参考指标。     

Expression of B-cell markers in classical hodgkin lymphoma: a tissue microarray analysis of 330 cases.

Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma arise from B-lymphocytes. However, classical markers of the B-cell phenotype, such as CD20, are present only in about 25% of the cases. The aim of the present study was to assess expression of the B-cell-related antigens CD20, CD79a, and CD138 in classical Hodgkin lymphoma using a tissue microarray consisting of 330 classical Hodgkin lymphoma cases. Expression of CD15, CD20, CD30, CD79a, CD138, and latent membrane protein 1 of Epstein-Barr virus was assessed by immunohistochemistry, and the methodology was validated by direct comparison of CD20 expression on the tissue microarray cores with corresponding large sections. The influence of the number of arrayed sample cores on the obtained expression levels of CD20 was analyzed by comparing the results from single, duplicate, and triplicate cores. Two-hundred fifty-three (77%) of the 330 cases were morphologically representative. CD20 was expressed in 84 cases (33%), CD79a in 26 (10%), and CD138 in 2 (1%), respectively. CD20 and CD79a were co-expressed in 16 cases (P <.005), and expression of CD20 correlated inversely with CD15 (P <.01). Comparing the tissue microarray results with those from conventional sections for expression of CD20 yielded a concordance of 94% (63/67). Examining one, two, and three cores from individual cases revealed positivity for CD20 at 24% (61/253), 32% (82/253), and 33% (84/253), respectively. We conclude that B-cell markers are expressed in 38% of classical Hodgkin lymphoma in the following rank order: CD20>CD79a>CD138. The use of two cores per tissue sample renders the tissue microarray technology effectively representative and thus very useful for high-throughput evaluation of heterogeneously expressed markers in classical Hodgkin lymphoma.     

Expression of c-FLIP in classic and nodular lymphocyte-predominant Hodgkin lymphoma.

Different molecular pathways are believed to be involved in the pathogenesis of classic Hodgkin lymphoma as opposed to non-Hodgkin lymphoma. Antiapoptotic mechanisms have been proposed for classic Hodgkin lymphoma, including expression of the cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP), which plays a critical role in resistance to CD95/Fas-mediated apoptosis. In this study, we compare the expression of c-FLIP in the neoplastic cells of classic Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma cases. Sixteen cases of classic Hodgkin lymphoma and 19 cases of nodular lymphocyte-predominant Hodgkin lymphoma were reviewed. Of 16 classic Hodgkin lymphoma cases, 13 cases (81%) were c-FLIP-positive, compared with 6 of 19 (32%) nodular lymphocyte-predominant Hodgkin lymphoma cases. Strong cytoplasmic staining was seen in 7 of 13 c-FLIP-positive classic Hodgkin lymphoma cases, in contrast with only 2 of 6 c-FLIP-positive nodular lymphocyte-predominant Hodgkin lymphoma cases. The 2 cases of nodular lymphocyte-predominant Hodgkin lymphoma with strong c-FLIP expression were associated with transformation to large B-cell lymphoma. An additional 15 cases of diffuse large B-cell lymphoma were studied for c-FLIP expression. All but 1 were c-FLIP-positive. In conclusion, we detected c-FLIP in a significantly lower proportion of nodular lymphocyte-predominant Hodgkin lymphoma cases compared with classic Hodgkin lymphoma cases. Therefore, c-FLIP expression may not be the major mechanism of pathogenesis in nodular lymphocyte-predominant Hodgkin lymphoma. However, strong c-FLIP expression in nodular lymphocyte-predominant Hodgkin lymphoma was associated with transformation to large B-cell lymphoma in 2 cases. c-FLIP expression is not limited to Hodgkin lymphoma, because the majority of diffuse large B-cell lymphoma cases tested were strongly c-FLIP-positive.     

经典型霍奇金淋巴瘤组织中脆性三联组氨酸蛋白表达的意义

目的探讨脆性三联组氨酸（FHIT）蛋白在经典型霍奇金淋巴瘤（CHL）组织中的表达及其意义。方法对33例确诊的CHL组织采用免疫组织化学EnVision法检测其抑癌基因蛋白FHIT、造血系统肿瘤干细胞标记CDl33／AC133、CD34、B细胞标记CD20、T细胞标记CD3和癌基因蛋白c-erbB-2表达状况。结果90．9％（30／33）CHL组织中FHIT蛋白表达阳性,表达定位于肿瘤细胞的胞质、胞核和胞膜;对照组正常B、T淋巴细胞和B、T细胞淋巴瘤FHIT蛋白表达均为阴性;单核细胞、组织细胞以及树突状组织细胞均表达阳性。CDl33／ACl33、CD34、CD3、c-erbB-2表达均为阴性．2例CD20阳性。结论FHIT蛋白检测可作为诊断CHL的一个辅助指标。     

Programmed death 1 expression in variant immunoarchitectural patterns of nodular lymphocyte predominant Hodgkin lymphoma: comparison with CD57 and lymphomas in the differential diagnosis

Recent studies have exploited an antibody directed against programmed death 1 expressed by follicular helper T-cells in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma. We had previously described clinically relevant, variant immunoarchitectural patterns of nodular lymphocyte predominant Hodgkin lymphoma and, in this study, sought to address the diagnostic utility of programmed death 1 in comparison with CD57 in variant nodular lymphocyte predominant Hodgkin lymphoma. Immunohistologic staining for programmed death 1 was carried out on biopsies of 67 patients with variant nodular lymphocyte predominant Hodgkin lymphoma. Thirty-four additional cases of nodular lymphocyte predominant Hodgkin lymphoma with associated diffuse areas, de novo T-cell and histiocyte-rich large B-cell lymphoma, and lymphocyte-rich classic Hodgkin lymphoma were also studied. Our results show that programmed death 1 positivity was found in the majority of nodular lymphocyte predominant Hodgkin lymphoma cases with a classic nodular architecture (87%) as compared with 50% for CD57 and was particularly helpful in identifying extranodular large atypical cells. Nodular lymphocyte predominant Hodgkin lymphoma with diffuse areas showed a gradual decrease in programmed death 1 reactivity from nodular to diffuse areas, although a significant proportion (40%-50%) of cases retained programmed death 1 positivity also in diffuse areas. In addition, T-cell and histiocyte-rich large B-cell lymphoma and lymphocyte-rich classic Hodgkin lymphoma displayed programmed death 1 positivity in a significant subset of cases (33%-40%). In conclusion, our study supports the utility of programmed death 1 in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma and shows greater sensitivity of staining of programmed death 1 as compared with CD57 across all variants of nodular lymphocyte predominant Hodgkin lymphoma. Loss of programmed death 1 reactivity did not correlate with diffuse areas, progression, or the ability to differentiate nodular lymphocyte predominant Hodgkin lymphoma from T-cell and histiocyte-rich large B-cell lymphoma. These findings suggest the need for continued vigilance in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma and its immunoarchitectural variants as well as related lymphomas in their differential diagnosis.