甲状腺原发性Burkitt淋巴瘤临床病理观察

目的甲状腺原发性Burkitt淋巴瘤非常罕见,对其临床病理特点进行探讨。方法对1例患有甲状腺Burkitt淋巴瘤的9岁男童进行详细的临床资料和病理形态学观察,并采用MaxVision法进行免疫组化染色、EBER原位杂交和c-myc基因FISH检测。结果甲状腺组织内见中等大小异型淋巴细胞弥漫浸润,可见明显"星空"现象。肿瘤细胞CD20、CD10、bcl-6、CD43和CD38(+),CD3、CD5、bcl-2和TDT均(-),Ki-67阳性率>95%。FISH检测有c-myc基因位点的染色体断裂重组。EBER分子原位杂交(-)。结论本例为原发于甲状腺的散发型Burkitt淋巴瘤,与EBV感染无关。需要与弥漫性大B细胞性淋巴瘤、结外黏膜相关淋巴组织边缘区淋巴瘤和B淋巴母细胞性淋巴瘤/白血病进行鉴别。     

171例淋巴瘤病变组织中EB病毒表达情况的分析

目的:探讨不同类型淋巴瘤与EB病毒(Epstein-Barr virus,EBV)感染的关系。方法:收集淋巴瘤组织171例,包括弥漫大B细胞淋巴瘤(DLBC)106例;结外NK/T细胞淋巴瘤,鼻型22例;霍奇金淋巴瘤(HL)19例;血管免疫母细胞性T细胞淋巴瘤(AITL)13例;黏膜相关淋巴组织B细胞淋巴瘤(MALT)11例。应用EBV Lmp-1单抗免疫组化(IHC)和生物素标记的EBER1寡核苷酸探针原位杂交(ISH)分析EBV感染与淋巴瘤的关系。结果:淋巴瘤组织中EBV Lmp-1蛋白与EBER1 mRNA总阳性率分别为11.1%(19/171)、25.7%(44/171)。其中AITL为30.8%(4/13)、61.5%(8/13);HL为47.4%(9/19)、57.9%(11/19);结外NK/T细胞淋巴瘤为22.7%(5/22)、81.8%(18/22);DLBC为0.94%(1/106)、5.7%(6/106);MALT为0(0/11)、9.1%(1/11)。结果显示EBV在DLBC及MALT中的表达率低于AITL、HL及结外NK/T细胞淋巴瘤,差异有统计学意义(P0.05);且原位杂交检测EBER1 mRNA比免疫组化检测Lmp-1蛋白更为敏感(P0.01)。结论:EBV感染与淋巴瘤有密切关系,不同类型淋巴瘤与EBV感染的关系有差异。     

不同部位和不同类型恶性淋巴瘤患者EBV感染情况分析

目的 分析不同部位和不同类型恶性淋巴瘤患者EBV感染情况.方法 收集恶性淋巴瘤标本90例,其中鼻腔/鼻咽淋巴瘤30例,肠道淋巴瘤30例,浅表淋巴结淋巴瘤30例.组织病理学诊断为非霍奇金淋巴瘤（NHL）68例,霍奇金淋巴瘤（HL）22例.应用多种抗体标记T淋巴细胞（CD3、CD45RO、CD56）和B淋巴细胞（CD20、CD79α）、免疫组化染色（Supervision二步法）.采用EBV寡核苷酸探针（EBER）确定EBV在恶性淋巴瘤细胞中的存在.结果 NHL EBV感染阳性率（42.6%）略高于霍奇金淋巴瘤EBV感染阳性率（27.3%）,但差异无显著性意义（P ＞0.05）.鼻腔及鼻咽部NHL的EBV感染阳性率（66.7%）高于肠道NHL（23.3%）和浅表淋巴结NHL（25%）（P＜0.05）.肠道T细胞淋巴瘤EBV感染阳性率（50%）高于肠道B细胞淋巴瘤EBV感染阳性率（16.7%,P＜0.05）.结论 不同类型和部位淋巴瘤患者的EBV感染率存在不同.     

p53基因突变与EB病毒相关性鼻咽部T细胞淋巴瘤

目的：了解Ｐ５３基因突变与埃伯斯坦－巴尔病毒相关性鼻咽部Ｔ细胞淋巴瘤的关系。方法;应用免疫组织化学方法,原位杂交（ＩＳＨ）,ＰＣＲ－ＳＳＣＰ对２６例确诊为鼻咽部Ｔ细胞淋巴瘤的病例进行Ｐ５３蛋白及基因的检测。结果：ＥＢＶ编码的小ＲＮＡ探讨（ＥＢＥＲ）１７／２６例阳性;Ｐ５３蛋白１３／２６例阳性;对其中１２例进行Ｐ５３外显子５,７,８的ＰＣＲ－ＳＳＣＰ检测,发现Ｐ５３突变７／１２例阳性,ＥＢＶ阳性组５     

The prognostic significance of EBV DNA load and EBER status in diagnostic specimens from diffuse large B‐cell lymphoma patients

Epstein–Barr virus (EBV)‐encoded small RNA in situ hybridization (EBER‐ISH) is a widely accepted method to evaluate EBV involvement in diffuse large B‐cell lymphoma (DLBCL), although little is known regarding associations between EBV DNA load and the EBER status and whether EBV DNA load data provide additional clinical information. In this study, we quantified EBV DNA load in diagnostic specimens from DLBCL patients diagnosed at our hospital to evaluate clinical implications of EBV DNA load in diagnostic specimens as contrasted with EBER‐ISH. Among 140 DLBCL patients without underlying immunodeficiency, 51 were evaluable for both EBER and EBV DNA load, 83 for EBER only and one for EBV DNA load only. The median EBV DNA load was 708 copies/µg. Although EBV DNA load was significantly higher for EBER‐positive patients than for EBER‐negative patients (p < 0.001), EBV DNA was detected in up to 72% of EBER‐negative patients. Progression‐free survival and overall survival were significantly worse for patients with EBV DNA load above 700 copies/µg than for those with EBV DNA load below 700 copies/µg (p = 0.009 and p = 0.003); they were also significantly worse for EBER‐positive patients than for EBER‐negative patients (p < 0.001 and p = 0.001). Even among EBER‐negative patients, higher EBV DNA load conferred worse progression‐free survival and overall survival (p = 0.041 and p = 0.013). These findings indicate that EBV DNA load in diagnostic specimens is not a simple surrogate for the EBER status and may be a potential biomarker associated with EBV involvement and prognosis in DLBCL. Copyright © 2015 John Wiley & Sons, Ltd.     

初诊伴自身免疫性溶血性贫血的侵袭性非霍奇金淋巴瘤特征分析

  目的  探讨首发伴自身免疫性溶血性贫血（autoimmune hemolytic anemia,AIHA）的侵袭性非霍奇金淋巴瘤（non-Hodgkin's lymphoma,NHL）的临床及实验室特征。  方法  收集2013年9月至2016年7月苏州大学附属第二医院收治的6例首发伴AIHA的侵袭性NHL患者的临床资料,分析患者的发病情况、疾病进展、治疗及预后相关因素。  结果  2013年9月至2016年7月苏州大学附属第二医院收治初发侵袭性NHL 155例,起病伴AIHA为6例（3.9%）,其中男性3例,女性3例;中位年龄67（62~74）岁。首发症状包括:全身多发淋巴结肿大5例、发热3例、多发骨破坏并骨痛1例,均表现血红蛋白进行性下降。6例患者病理类型分别为:弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）3例,其中1例Bcl-2（+）Bcl-6（+）c-myc（+）三表达,1例CD5阳性;1例外周T细胞淋巴瘤-非特指型（peripheral T-cell lymphoma-not otherwise specified,PTCL-NOS）;2例血管免疫母细胞性T细胞淋巴瘤（angioimmunoblastic T-cell lymphoma,AITCL）。色素原位杂交（chromogenic in situ hybridization,CISH）法检测石蜡组织EB病毒基因（Epstein-Barr virus-mRNA,EBV-mRNA）（EBER）的表达:所检测5例均阳性。6例ECOG评分3~4分,Ann-Arbor分期均为Ⅲ~Ⅳ期,IPI评分4~5分,均为高危组。淋巴瘤病理确诊时中位血红蛋白56（34~79）g/L、中位网织红细胞比例6.7（0.2~21.0）%;6例患者Coombs试验均阳性:6例抗C3阳性（1:64~1:2048）、4例抗IgG阳性（±~1:16）;检测3例血浆EBV-DNA拷贝数均增高。6例患者中:1例AITCL确诊后放弃治疗;其余5例应用CHOP样方案±利妥昔单抗联合化疗2~8个疗程（4例化疗间歇期加强的松治疗）,其中2例DLBCL持续完全缓解（complete response,CR）,总生存时间（overall survival,OS）分别为20、14个月,另1例DLBCL及1例PTCL-NOS经2个疗程化疗后骨髓抑制期继发严重肺部感染、心功能衰竭死亡,OS分别为1.5、2个月,1例AITCL化疗4个疗程后疾病快速进展死亡,OS为4.5个月。  结论  侵袭性NHL首发伴AIHA多见于老年患者,EBV感染率高,溶血进展快、程度严重,化疗耐受性差,总体预后差,早期死亡率高。早期诊断及有效化疗可能改善预后。      

Upregulated expression of CD30 protein in sclerosing angiomatoid nodular transformation (SANT): studies of additional 4 cases and analyses of 6 cases previously published cases

Sclerosing angiomatoid nodular transformation (SANT) of spleen is a benign lesion with a distinct morphological and immunohisochemical characteristics. Only Weinred I et al (Virchow Arch 451: 73-9, 2007) reported 6 cases of SANT expressing CD30, of which positive for EBV by in situ hybridization (EBER). 4 cases of SANT were added to investigate the clinicopathological features and focused on the expression of CD30 and EBER combined with the previously published literature. Histologically, individual angiomatoid nodules were sharply delineated by fibrocollagenous stroma with numerous vascular lumens and surrounded by a different population of spindle and ovoid cells. Angiomatoid nodules of all of the 4 cases heterogeneously expressed CD34, CD8, CD68 and diffusely demonstrated CD31 and CD30, but none were positive for EBER. We added these cases with reviewed literature to emphasize and verify the fact that upregulated expression of CD30 in SANT is quite common, which should be taken into consideration when making differential diagnosis.     

Evidence for the association of Epstein‐Barr Virus in breast cancer in Indian patients using in‐situ hybridization technique

Epstein‐Barr Virus (EBV) is etiologically linked to Burkitt lymphoma (BL), nasopharyngeal carcinoma, post‐transplant lymphomas, Hodgkin disease, and possibly other tumors. However, the association of oncogenic EBV with breast carcinoma (BC) is still controversial and a matter of debate. We aimed to study the presence of EBV genome in BC cases in Indian patients and its association with the clinicopathological features. The formalin fixed paraffin embedded tissues from 83 women with primary invasive BC were studied for the presence of EBV by in‐situ hybridization (ISH) technique for Epstein‐Barr Virus Encoded RNA (EBER) with appropriate controls. Correlation of EBER‐ISH positivity with clinicopathological features was performed using Fisher exact test and P<.05 was considered as significant. Eighty‐three BC cases were comprised of 47 (56.5%) triple negative breast cancers (TNBC), 17 (20.5%) hormone positive and 19 (22.9%) HER2 positive cases. Of 83 cases, 25 cases (30.1%) were positive for EBER‐ISH test. The positivity was restricted to the tumor cells and not seen in the surrounding breast lobules. EBER‐ISH positivity was statistically associated with larger tumor size (52.6% in >5 cm tumors vs 19.3% in ≤5 cm; P=.014) and with TNBCs (21/47 [44.7%] in TNBCs vs 4/36 [11.1%] in non‐TNBCs; P=.001). A possible causal association of EBV in BC cases in Indian patients is suggested by high frequency of EBER‐ISH positivity noted in our study. This might have therapeutic significance because of the possible role of EBV specific cytotoxic T cells in targeting EBV associated tumor cells and can be considered as a potential targeted therapy. To the best of our knowledge, this is the first study from India to address this issue using EBER‐ISH technique.     

浆母细胞淋巴瘤1例报告及文献回顾

目的:探讨浆母细胞淋巴瘤（plasmablastic lymphoma,PBL）的临床病理特征及预后。方法:对1例鼻腔浆母细胞淋巴瘤进行光镜、免疫组化及原位杂交检测,并回顾分析63例文献报告病例。结果:肿瘤组织由中等或大细胞弥漫增生组成,胞浆少,嗜碱性,部分细胞胞浆嗜酸性伴核偏位,核圆形或卵圆形,核仁较明显,核分裂象易见,可见凋亡及肿瘤性坏死;免疫组化:瘤细胞CD79a、CD138、Plasma cell弥漫强（+）,Ki-67（约90%+）,LCA、CD20（-）;原位杂交:EBER（-）。结论:PBL在诊断标准、鉴别诊断及治疗方面仍存在争议,尚需积累更多病例进一步探讨。