肝脏原发黏膜相关淋巴组织结外边缘区淋巴瘤及肝脏假性淋巴瘤的临床病理特征北大核心CSCD

目的 探讨肝脏原发黏膜相关淋巴组织结外边缘区（MALT）淋巴瘤和肝脏假性淋巴瘤的临床病理特征、鉴别诊断.方法 收集2012年1月至2017年3月就诊于南京医科大学第一附属医院的3例肝脏原发MALT淋巴瘤和2例肝脏假性淋巴瘤患者资料,行HE和免疫组织化学EnVision法染色观察组织学形态,采用原位杂交法检测EB病毒编码小RNA,采用荧光原位杂交（FISH）技术检测MALT1基因,采用免疫球蛋白（Ig）基因重排检测技术分析克隆性基因重排情况,并复习相关文献.结果 3例MALT淋巴瘤,肿瘤结节状浸润汇管区,浸润及包绕周围肝组织并融合成结节或片状,多量小胆管陷入、散布其间伴淋巴上皮病变.瘤细胞围绕增生的淋巴滤泡,主要为中心细胞样和单核样B细胞,其中1例可见簇状上皮样组织细胞.瘤细胞CD20和PAX5阳性,不表达CD5、CD23、CD10、bcl-6及cyclin D1.2例肝脏假性淋巴瘤,病灶呈境界清楚的孤立性结节,其中1例可见部分纤维包膜.小胆管仅见于病灶周边,且缺乏淋巴上皮病变.淋巴组织增生以淋巴滤泡增生为主,缺乏明显异型性和单核样B细胞形态.免疫组织化学染色示增生的淋巴组织由B细胞和T细胞混合.Ig基因重排检测发现,3例肝脏原发MALT淋巴瘤呈单克隆性B细胞增生,而在2例假性淋巴瘤示多克隆性增生.FISH检测发现2例MALT淋巴瘤存在MALT1基因断裂.所有病例EBER原位杂交均为阴性.结论 肝脏原发MALT淋巴瘤和假性淋巴瘤均属肝脏罕见的淋巴组织增生性病变,两者具有重叠的组织学形态及免疫表型特征,互为首要鉴别诊断.综合分析组织形态、免疫表型和基因重排有助于区分两者.     

胸腺原发黏膜相关淋巴组织淋巴瘤及淋巴上皮性涎腺炎样胸腺增生的临床病理分析

目的探讨胸腺原发黏膜相关淋巴组织(mucosa associated lymphoid tissue,MALT)淋巴瘤和淋巴上皮性涎腺炎(lymphoepithelial sialadenitis,LESA)样胸腺增生的临床病理学特征、两者相关性及鉴别诊断。方法分析3例胸腺MALT淋巴瘤和1例LESA样胸腺增生的临床病理学和免疫表型特征,并复习相关文献。结果 3例胸腺MALT淋巴瘤,其中2例伴Sj9gren综合征;镜下胸腺正常结构损毁,增生的淋巴滤泡间可见肿瘤性淋巴样细胞浸润伴明显的淋巴上皮病变,以中心细胞样和单核样B细胞形态为主。瘤细胞表达CD20、PAX-5和BCL-2,其中1例伴显著浆细胞分化者Lambda轻链限制性表达。3例胸腺MALT淋巴瘤免疫球蛋白(immunoglobulin,Ig)基因检测均示单克隆性重排。LESA样胸腺增生镜下胸腺分叶状结构大体尚存,可见包含增生滤泡的丰富淋巴细胞浸润,胸腺上皮增生伴显著淋巴上皮病变,未见有单核样B细胞形态。免疫组化染色示增生淋巴组织由B和T细胞混合;Ig基因重排检测示多克隆性增生。结论 LESA样胸腺增生和胸腺MALT淋巴瘤均是胸腺少见的淋巴增生性病变,两者具有相似的组织学和免疫表型特征;结合基因重排技术详细分析两者的鉴别要点,有助于鉴别。     

膀胱原发结外黏膜相关淋巴组织边缘区淋巴瘤4例临床病理分析

目的探讨膀胱原发黏膜相关淋巴组织(mucosa-associated lymphoid tissue,MALT)边缘区淋巴瘤的临床病理学特征、诊断及鉴别诊断、治疗及预后。方法收集4例膀胱MALT淋巴瘤,行HE和免疫组化EnV ision两步法染色观察。应用原位杂交和基因重排技术检测4例膀胱MALT淋巴瘤,并复习相关文献。结果 4例膀胱MALT淋巴瘤中3例女性患者平均年龄60岁,1例男性患者44岁。所有病变均见肿瘤性淋巴样细胞弥漫或结节性浸润,以中心细胞样细胞和单核样B细胞构成为主,其中2例可见残存的增生淋巴滤泡伴滤泡殖入现象。淋巴上皮病变仅累及3例伴腺性膀胱炎患者中的腺样结构,而表面尿路上皮则缺乏。免疫表型:瘤细胞均表达CD20、Pax-5和BCL-2,未见轻链限制性反应。4例膀胱MALT淋巴瘤EBER原位杂交均阴性,其中3例免疫球蛋白基因检测提示单克隆性重排。结论膀胱MALT淋巴瘤属于罕见的膀胱原发低度恶性B细胞淋巴瘤,淋巴上皮病变的发生与腺性膀胱炎存在有关,但并非是病理诊断所必须。在膀胱镜小标本活检时,基因检测B细胞的单克隆性有助于诊断。     

胸腺黏膜相关淋巴组织结外边缘区淋巴瘤9例临床病理分析

目的探讨胸腺黏膜相关淋巴组织结外边缘区(extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, MALT)淋巴瘤的临床病理学特征、免疫表型、分子特征及鉴别诊断。方法回顾性分析9例胸腺MALT淋巴瘤的临床资料、病理学形态、免疫表型及分子遗传学特征,结合文献对其临床病理学特点进行探讨。结果 9例胸腺原发MALT淋巴瘤患者年龄35～72岁(平均50岁),男性2例,女性7例。5例患者体检发现纵隔占位,2例表现为胸痛、咳嗽及四肢面部浮肿等症状。4例患者既往伴有自身免疫性疾病。镜下肿瘤主要由小到中等的淋巴细胞样细胞构成,弥漫浸润生长,其内见大小不等的囊肿形成,囊腔内可见胆固醇结晶沉积,瘤细胞侵犯囊壁及胸腺小体而形成淋巴上皮病变。免疫表型:9例肿瘤细胞均表达B细胞标志物(CD20、CD79α、Pax-5),基因重排均显示单克隆性B细胞增生,FISH检测未见MALT1基因断裂。结论胸腺MALT淋巴瘤较少见,属于低度恶性肿瘤,多数伴有自身免疫性疾病。单一形态的瘤细胞结合免疫表型及基因重排可明确诊断,警惕漏诊或过诊。手术完整切除后密切随访即可。     

33例粘膜相关淋巴组织起源的恶性淋巴瘤临床病理观察

33例粘膜相关淋巴组织(MALT)起源的恶性淋巴瘤,具有MALT的特点,发展缓慢,局限生长,主要由滤泡中心细胞和B_2样细胞构成,可见浆化和毛细血管后微静脉壁淋巴细胞浸润。特征改变是“淋巴上皮病变”。当侵犯性生长时,可出现绣毯结构。病变早期,B_2样细胞为主时,局部治疗有效,病人预后较好。     

宫颈淋巴瘤样病变与宫颈淋巴瘤的鉴别

目的探讨宫颈淋巴瘤样病变和宫颈淋巴瘤的临床病理特点及免疫球蛋白重链（IgH）基因重排在两者鉴别诊断上的价值。方法对10例宫颈淋巴瘤样病变和16例宫颈淋巴瘤进行临床资料分析和组织病理学观察,以免疫组织化学（EnVision法）检测B、T淋巴细胞标记物和免疫球蛋白轻链（κ,λ）的表达,并应用半套式聚合酶链反应方法检测了4例淋巴瘤样病变和4例淋巴瘤中IgH基因重排的情况。结果宫颈淋巴瘤样病变患者年龄24—54岁（中位年龄43岁）,临床多表现为宫颈糜烂或息肉,镜下观察可见表浅分布的、局灶或弥漫性免疫母细胞样大细胞浸润,伴淋巴细胞转化成熟现象和多型性炎性细胞浸润（多量成熟浆细胞、嗜酸性粒细胞、中性粒细胞）。宫颈淋巴瘤患者年龄28—78岁（中位年龄58岁）,临床表现为宫颈肿块或弥漫性宫颈肥大,镜下观察示12例弥漫性大B细胞淋巴瘤和4例滤泡性淋巴瘤,二者组织学形态分别以弥漫分布、形态单一的肿瘤性大淋巴细胞浸润和肿瘤性滤泡形成为特点,病灶中少有多型性炎性细胞浸润,也不出现淋巴细胞转化成熟现象。宫颈淋巴瘤样病变中,免疫母细胞样大细胞κ和λ染色结果欠满意。4例宫颈淋巴瘤病例和2例宫颈淋巴瘤样病变中检出单克隆性IgH基因重排。结论宫颈淋巴瘤样病变和淋巴瘤主要依据不同的临床和病理形态特点相互区分。IgH基因重排检测对于二者鉴别有帮助,但需注意部分良性病变也有单克隆性淋巴细胞增生。     

骨髓活检组织淋巴瘤的病理诊断和分型

目的 探讨组织形态改变、免疫组织化学、基因重排在淋巴瘤骨髓侵犯的病理诊断和分型中的作用。材料与方法 对62例甲醛固定、石蜡包埋的骨髓活检组织,分别做了组织学、EnVision法观察和免疫球蛋白重链(IgH)基因和TCRγ基因重排检测。结果 慢性淋巴细胞性白血病／小淋巴细胞淋巴瘤(CLL／SLL)的异型淋巴细胞呈小梁间结节状或散在分布,有时可见假滤泡结构。滤泡型淋巴瘤(FCL)表现为结节性小梁旁或小梁间的浸润,结节内小淋巴样细胞松散聚集。淋巴浆细胞性淋巴瘤(LPL)主要为小梁间弥散浸润,在小而圆的淋巴细胞间可见散在数量不等的浆细胞样淋巴细胞。边缘区淋巴瘤(MZL)则见模糊的或界限不清的小梁间或小梁旁结节,一些细胞胞质透明。套细胞性淋巴瘤(MCL)异型细胞小到中等大小,缺乏副免疫母细胞和假滤泡。毛细胞性淋巴瘤(HCL)瘤细胞胞膜多清晰,胞质丰富透明,常形成荷包蛋样表现。霍奇金病可见大核瘤细胞,核仁明显。T-非霍奇金淋巴瘤(NHL)浸润骨髓主要为小梁间间质性散在或弥漫分布,胞质多透明,核有芋艿样或脑回状改变,DLBL造血细胞间体积大的瘤细胞散在或弥漫分布。CD3对T细胞来源、CD20和CD79对B细胞来源淋巴瘤有鉴别诊断价值,cyclin D1和(SD5阳性对MCL具有诊断性价值,bcl-2和CD10阳性则对FCL具有诊断性意义,而CLL／SLL除了(SD20和CD79阳性外,也可CD5和CD23阳性。HCL的瘤细胞CD25强阳性。CD15、CD30和Fascin也适用于骨髓霍奇金病的诊断。骨髓中CLL／SLL,LPL,MZL及DLBL的IgH重排率(80％、60％、66．7％、70％)及T—NHL的TCRγ重排率(66．7％)较高。结论 综合组织形态改变、免疫组织化学和IgH／TCRγ重排检测,有助于淋巴瘤骨髓侵犯的诊断和分型,有助于发现骨髓中为数不多的淋巴瘤细胞。     

眼结膜黏膜相关淋巴组织边缘带B细胞淋巴瘤临床病理分析

目的 探讨眼结膜黏膜相关淋巴组织边缘带B细胞淋巴瘤(marginal zone B cell lymphoma of mucosa-associated lymphoid tissue)(简称为MALT淋巴瘤)的临床病理特征、治疗及预后.方法 对15例眼结膜MALT淋巴瘤患者的临床病理资料进行回顾性分析及随访,复查和完善HE及免疫组化染色切片,4例进行Ig基因重排克隆性分析.结果 (1)15例患者中,男性5例,女性10例,中位年龄42岁,病史平均20个月.(2)病理形态:黏膜下大量密集淋巴样细胞弥漫浸润,并有模糊淋巴滤泡样结节.浸润细胞多为小～中等大小的淋巴样细胞及单核样B细胞.(3)免疫表型:浸润细胞CD20、CD79a、BCL-2均(+),CD3、CD5、CD10、Cyclin D1、TdT均(-).(4)Ig基因克隆性分析:4例均呈单克隆.(5)随访:随访时间2～35个月,截止随访日期,所有患者均生存,且病变无复发.结论 眼结膜MALT淋巴瘤好发于中年女性,结膜红肿突起为主要特征,镜下以小细胞样边缘带B细胞为主,具有典型MALT淋巴瘤的免疫表型和惰性临床经过,预后良好.     

甲状腺显著浆细胞分化黏膜相关淋巴组织结外边缘区淋巴瘤的临床病理观察

目的 探讨原发性甲状腺罕见的具有显著浆细胞分化的黏膜相关淋巴组织结外边缘区(extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, MALT)淋巴瘤的临床病理特征、诊断与鉴别诊断。方法 收集1例MALT淋巴瘤的临床资料，采用免疫组化EnVision两步法进行检测，应用荧光探针PCR-毛细管电泳测序法检测MYD88 L265基因突变，并复习相关文献。结果 淋巴瘤侵犯甲状腺组织，肿瘤细胞为中～大的淋巴细胞，胞质丰富、嗜酸性，核偏位，大小不一，可见淋巴上皮病变，核分裂象少见，伴显著浆细胞分化。免疫表型：瘤细胞不表达CD20、PAX5,表达CD38、MUM1、BOB1、CD79a等浆细胞标志物，Ki-67增殖指数20%～30%,MYD88 L265基因野生型。结论 甲状腺伴显著浆细胞分化的MALT淋巴瘤临床罕见，与良性淋巴组织增生和其他淋巴瘤鉴别困难，需进行综合判断。     

肺原发性黏膜相关淋巴组织结外边缘区淋巴瘤5例临床病理分析

目的 探讨肺原发性黏膜相关淋巴组织结外边缘区(primary pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, MALT)淋巴瘤的临床病理学特征、诊断及鉴别诊断、治疗及预后。方法 回顾性分析5例肺原发性MALT淋巴瘤的临床病理学特征、免疫表型、治疗及预后等,并复习相关文献。结果 5例患者年龄42～59岁,中位年龄47岁,无相关肺部症状;CT示片状团块或斑片状高密度影。5例镜下形态相似,瘤细胞弥漫浸润肺组织,形如单核细胞样细胞和小淋巴细胞,其间散在分布少许免疫母细胞及中心母细胞样细胞,可见淋巴上皮病变,CD20、CD79a均呈阳性,CD3、CD5、Cyclin D1、CD10、BCL-6和CD30均阴性,Ki-67增殖指数为3%～20%。5例均行胸腔镜下肺叶或肺结节切除术,术后恢复良好,未见复发及淋巴结累及。结论 肺原发性MALT淋巴瘤于惰性淋巴瘤,临床易误诊,患者预后良好,诊断依赖于病理检查。     

Mucosa-associated lymphoid tissue of the thymus hyperplasia vs lymphoma.

In the thymus, the relationship between lymphofollicular hyperplasia and mucosa-associated lymphoid tissue (MALT)-type lymphoma is uncertain. We analyzed 14 cases with a diagnosis of thymic follicular hyperplasia in patients with connective tissue disease (n = 2), myasthenia gravis (n = 11), or both (n = 1). In 11 cases, well-defined reactive lymphoid follicles were surrounded by a continuous layer of medullary epithelial cells. A polyclonal rearrangement of the immunoglobulin heavy chain gene (IgH) was observed. In 3 cases, ill-defined lymphoid follicles with sheets of centrocytic-like B cells disrupting the medullary cytokeratin epithelial network were observed on certain sections. These cells expressed the phenotypic features of memory B cells with CD20, CD79a, and bcl-2 positivity and CD5, CD10, CD23, and bcl-6 negativity, and a monoclonal rearrangement of the IgH gene was detected. Appropriate sampling, cytokeratin staining, and molecular analyses may help to identify early MALT-type lymphoma developing in the setting of thymic lymphofollicular hyperplasia.     

富于T细胞/组织细胞的B细胞淋巴瘤病理形态、免疫表型及鉴别诊断

目的 探讨富于T细胞／组织细胞的B细胞淋巴瘤（TCRBCL）的组织学特点、免疫表型及鉴别诊断。方法 根据WHO淋巴瘤新分类（2001）回顾性研究245例霍奇金淋巴瘤,发现8例TCRBCL;另有5例会诊病例及3例外检诊断病例,共16例;应用免疫组织化学SP方法检测瘤细胞及背景细胞的免疫表型,所用抗体包括CD20、CD79a、CD3、CD8、CD45RO、CDl0、bcl-6、CD21、CD35、CD57、T细胞限制性细胞内抗原（TIA）-1、CD15、CD30、上皮膜抗原（EMA）、细胞周期蛋白（cyclin）D1、CD68、潜伏膜抗原（LMP）-1;4例行原位杂交检测EBER;4例应用聚合酶链反应技术检测瘤细胞IgH基因重排。结果 16例TCRBCL,男8例,女8例,男女比为1：1。年龄10～68岁,平均年龄40．3岁,中位年龄46．5岁。主要表现为淋巴结肿大,伴发热及肝脾肿大。临床分期Ⅱ期3例,Ⅲ期10例,Ⅳ期3例。组织学上见少数非典型性大细胞散在分布于小淋巴细胞和组织细胞背景中。免疫组织化学显示大细胞呈CD20、CD79a、EMA阳性,CD15、CD30阴性;背景小淋巴细胞呈CD3、CD45RO阳性,其中CD8、TIA-1阳性细胞多于CD57阳性细胞;组织细胞呈CD68阳性。CD21、CD35均为阴性反应。所检测的4例均为EBER1／2阴性,4例行IgH基因重排检测均可见单克隆条带。结论 TCRBCL有着独特的组织学和免疫表型特征,诊断应结合形态学和免疫表型特征。鉴别诊断包括霍奇金淋巴瘤、反应性淋巴组织增生、淋巴瘤样肉芽肿病等。     

B淋巴细胞增生性疑难病例中IgH基因克隆性重排的分析

目的 探讨IgH基因克隆性重排对B淋巴细胞增生性疑难病变的辅助诊断价值.方法 检测77例B淋巴细胞增生性疑难病例中IgH基因的克隆性重排情况,均采用BIOMED-2系统IgH克隆性试剂盒中FR1、FR2、FR3三组家族引物进行PCR及聚丙烯酰胺凝胶电泳,硝酸银染色后观察,并对照最终病理诊断进行分析.结果 77例病变的最终病理诊断:B淋巴细胞反应性增生12例,不能排除B淋巴细胞不典型增生或淋巴瘤20例,B细胞性淋巴瘤45例.三组中FR1、FR2和FR3至少有一个为阳性的比值分别为2/12、11/20(55%)和36/45(80%).B细胞性淋巴瘤中,FR1、FR2和FR3的阳性率分别为60%(27/45)、60%(27/45)、56%(25/45),其类型有边缘区B细胞性淋巴瘤20例(其中黏膜相关淋巴组织型结外边缘区淋巴瘤18例,结内边缘区淋巴瘤2例),弥漫性大B细胞淋巴瘤7例,滤泡性淋巴瘤7例,套细胞性淋巴瘤1例,Burkitt淋巴瘤1例,浆细胞瘤4例,不能分型5例.FR1、FR2和FR3三者检测均为阴性但仍诊断为淋巴瘤9例(20%),其中1例后来出现肝脏B细胞淋巴瘤.对IgH基因重排阳性的B淋巴细胞反应性增生和不典型增生14例的随访结果,4例重新取活检后诊断为B细胞性淋巴瘤,其中3例IgH基因重排检测为阳性.结论 联合检测IgH基因FR1、FR2和FR3克隆性重排对B淋巴细胞增生性疑难病变诊断有重要的辅助价值;对形态改变和免疫表型诊断淋巴瘤依据不足而基因重排阳性者,重取活检或随访有一定价值;对阴性病例有必要补充IgH基因重排及IgK和IgL基因重排的检测以提高检测敏感性.     

The relationship between primary gastric B-cell lymphoma and immunoglobulin heavy chain (IgH) gene rearrangement--a histopathological study of primary gastric lymphomas

The aim of this study was to review our primary gastric lymphoma cases according to the new WHO classifications and to investigate the histopathological features of B-cell lymphomas. In addition, B-cell monoclonality was analyzed for immunoglobulin heavy chain (IgH) gene rearrangement using the polymerase chain reaction at the site of the lymphoma lesion, transitional lesion, and the non-lymphoma lesion. Specimens resected from 31 primary gastric lymphomas were examined. There were 28 cases (90.3%) of B-cell lymphoma and three cases (9.7%) of T-cell lymphoma. The B-cell lymphomas were classified as low-grade mucosa-associated lymphoid tissue (MALT) lymphoma (LGML) (9%), high-grade MALT lymphoma (HGML) (42%), and diffuse large B-cell lymphoma (DLBCL) (29%). Histopathologically, lymphoepithelial lesions (LEL) were higher in LGML (100%) than in DLBCL (22%), with statistical significance (p < 0.05). A monoclonal pattern of IgH rearrangement was detected in LGML (50.0%), HGML (60.0%), and DLBCL (80.6%), with a statistically significant difference between LGML and DLBCL (p < 0.01). The IgH monoclonal pattern may reflect the gross appearance of lymphoma or the lymphoma infiltration depth. Superficial spreading and shallow growth in LGML may correspond to an oligoclonal pattern, and mass-forming and deep invasive growth in DLBCL may correspond to a more monoclonal pattern.     

The application of antigen receptor gene rearrangement of BIOMED-2 in the pathologic diagnosis of 348 cases with non-Hodgkin lymphoma in a single institution in Southwest of China

ObjectiveTo explore the clinical value of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangement in the diagnosis of non-Hodgkin lymphoma.MethodsUsing the standardized BIOMED-2 multiplex PCR strategy to detect IgH, IgK and TCR in 272 cases of mature B-cell lymphoma, 55 cases of mature T-cell lymphoma, 21 cases of extranodal NK/ T-cell lymphoma, nasal type, and 20 cases of lymphoid tissue reactive hyperplasia.ResultsAmong all mature B-cell lymphomas, the sensitivity of Ig gene rearrangement was 91.18% (248/272), IgH and IgK gene rearrangement was 76.47% (208/272) and 75.00% (204/272), respectively, meanwhile the sensitivity of TCRγ rearrangement was 3.68% (10/272). In the 55 cases of mature T-cell lymphoma, the sensitivity of the detection of TCRγ was 76.36% (44/55), at the same time the sensitivity of Ig gene rearrangement was 14.55% (8/55), IgH and IgK gene rearrangement was 7.27% (4/55) and 12.73% (7/55), respectively. In 21 cases of extranodal NK/T cell lymphoma, nasal type, and 20 cases of reactive lymphoid hyperplasia, no gene rearrangement was found in the samples of IgH, IgK and TCR. The sensitivity of gene rearrangement in Ig/TCR in B and T-cell lymphoma was significantly different from that in the control group (P < 0.05).ConclusionThe Ig/TCR gene rearrangement of BIOMED-2 multiplex PCR strategy has important auxiliary value in the diagnosis of B/T-cell non-Hodgkin lymphoma respectively, however, a few B-cell lymphomas may company TCR gene rearrangement as well as a few T-cell lymphomas may accompany Ig gene rearrangement, it must be comprehensively judged with the combination of morphology, immunohistochemistry and clinical features.     

Pityriasis lichenoides: a clonal T-cell lymphoproliferative disorder

Pityriasis lichenoides (PL) is a papulosquamous disorder often considered a form of reactive dermatosis and classified with small plaque parapsoriasis (digitate dermatosis). However, some patients with PL have developed large plaque parapsoriasis (LPP) and mycosis fungoides (MF), and lymphoid atypia and T-cell clonality have been reported in lesions of PL. We set out to explore the possibility that PL is a form of T-cell dyscrasia. Cases were selected by natural language search from an outpatient dermatopathology database; 35 cases were reviewed and clinicians and patients were contacted. Hematoxylin and eosin-stained sections were examined and immunophenotyping was carried out on paraffin-embedded, formalin-fixed tissue using antibodies to CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD30, and CD56. In paraffin-embedded tissue, T-cell receptor (TCR)-gamma chain rearrangement was sought through polymerase chain reaction single stranded conformational polymorphism analysis. There were 14 males and 21 females with a mean age of 40 years held clinically to have PL chronica (PLC) (28 cases) and/or PL et varioliformis acuta (PLEVA) (7 cases). Five patients developed large atrophic poikilodermatous and/or annular plaques compatible with MF and/or LPP in a background of typical PLC. All biopsies showed tropism of lymphocytes to an epidermis manifesting psoriasiform hyperplasia, dyskeratosis, parakeratosis, and intraepithelial collections of Langerhans' cells and lymphocytes mimicking Pautrier's microabascesses. Epidermal atrophy, dermal fibroplasia, poikilodermatous alterations, and a dominance of intraepidermal cerebriform cells were seen only in patients with chronic persistent disease (i.e., PLC) and in some cases corresponded with clinical progression to MF. All cases had a T cell-dominant infiltrate, with a CD7 deletion in 21 of 32 biopsies examined; the CD7-negative cells were typically the largest and most atypical forms, often in a cohesive array within the upper layers of the epidermis. In 17 biopsies in which a CD4 stain was satisfactory for evaluation, 50% or more of the intraepidermal population was CD4 positive in 8 biopsies, whereas in 11 biopsies 50% or more of the dermal infiltrate was CD4 positive. The CD4-positive cells frequently had a cerebriform nuclear morphology and were CD7 negative. Most cases had an admixture of CD8-positive lymphocytes in excess of 40% or more of the intraepidermal and/or dermal infiltrate; it was the dominant intraepidermal infiltrate in 10 cases. The CD8-positive cells, typically small, round, and CD7 positive, showed a directed pattern of migration into acrosyringia and suprapapillary plates, with satellitosis around CD4-positive/CD8-negative/CD7-negative atypical lymphocytes. CD56 positivity was seen among the intraepidermal lymphoid cells and roughly paralleled the CD8 profile. In general, CD8-positive lymphocytes dominated in cases of PLEVA, whereas CD4-positive lymphocytes were very conspicuous and composed the dominant intraepidermal populace only in those biopsies of progressive PL/PLC. Clonality was shown in 25 of 27 biopsies in which amplifiable DNA was obtained. Intraepithelial atypical lymphocytes, phenotypic abnormalities, and TCR-gamma rearrangements suggest that PLC and PLEVA are a form of T-cell dyscrasia. Lesions may follow a recalcitrant course characteristic of MF and premycotic disorders such as LPP. The aberrant phenotype cell is similar to that defining MF: a CD4-positive T lymphocyte with a CD5 and CD7 deletion. Directed epidermal migration seen in biopsies procured from incipient lesions along with occasional temporal association to viral or drug exposure suggests that an abnormal immune response to an antigenic trigger may be the inciting event.     

B细胞非霍奇金淋巴瘤IgH基因重排检测及凝胶扫描技术应用的初步研究

目的 采用凝胶扫描技术,力求对采用聚合酶链反应(PCR)检测非霍奇金淋巴瘤(NHL)抗原受体基因重排结果分析时建立量化标准,以利于临床医师应用时客观判断,并为其筛选随访病例提供依据。方法用PCR对96例B-NHL分别采用IgH FR3A及FR2A检测IgH基因克隆性重排。65例经IgH FR3APCR已证实为IgH基因克隆性重排B-NHL及8例良性病变淋巴组织和5例正常人外周血单核细胞,IgH FR3APcR产物8％变性聚丙烯酰胺凝胶电泳银染后图像行凝胶扫描,绘制曲线并计算h1／h2比值。结果(1)采用FR3A引物,克隆性IgH基因重排在96例B-NHL中检测率为68％,采用FR2A引物,检测率为61％,结合FR3A、FR2A引物,总检测率为83％。(2)凝胶扫描曲线示65例B-NHL的h1／h2均＞3,而5例正常人外周血单核细胞曲线均表现为钟型,8例良性病变淋巴组织h1／h2比值均＜1．5。结论非霍奇金淋巴瘤抗原受体基因重排检测的凝胶扫描分析曲线中,h1／h2峰高比值至少＞3可提示为IgH基因克隆性苇排,＜1．5可能提示IgH基因多克隆重排。比值介于1．5和3之间,提示有随访意义。联合FR3A,FR2A引物,可提高B-NHL IgH基因克隆性重排的检测率。     

De novo CD5-positive and Richter's syndrome-associated diffuse large B cell lymphomas are genotypically distinct.

Diffuse large B cell lymphomas (DLBLs) represent a heterogeneous collection of aggressive non-Hodgkin's lymphomas that can arise either de novo or as a result of transformation from chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphomas, or lymphomas of mucosa-associated lymphoid tissue. A small percentage of DLBLs express the CD5 antigen. The majority of these cases have evolved from a pre-existing low grade non-Hodgkin's lymphoma (Richter's syndrome). However, we identified and characterized nine CD5-positive DLBLs in which the patients did not have a previous history or concomitant evidence of chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, or mucosa-associated lymphoid tissue-associated non-Hodgkin's lymphoma, suggesting that they arose de novo. All nine cases expressed CD20 and monotypic immunoglobulin, all eight cases examined expressed CD19, CD22 and CD43, eight of the nine cases expressed HLA-DR, and two of eight cases expressed CD11c. None of the cases expressed CD3, CD10, CD11b, CD21, CD23 or CD30. CD5 expression by these cells was found to be identical to that of CD5-positive B cell chronic lymphocytic leukemia by quantitative polymerase chain reaction analysis of CD5 mRNA. These nine de novo CD5-positive DLBLs exhibited clonal immunoglobulin heavy and light chain gene rearrangements but lacked integration of the Epstein-Barr virus genome and structural alterations of the bcl-1, bcl-2, c-myc, H-ras, K-ras, and N-ras proto-oncogenes and the p53 tumor suppressor gene. However, bcl-6 proto-oncogene rearrangement, which is involved in chromosome band 3q27 aberrations, was found in four cases (44.4%). This is comparable with the frequency of bcl-6 gene rearrangement in CD5-negative DLBL. In contrast, bcl-6 gene rearrangement was absent in six cases of DLBL associated with Richter's syndrome. These findings suggest that de novo CD5-positive DLBLs are genotypically similar to CD5-negative DLBLs and may be pathogenetically distinct from the DLBLs associated with Richter's syndrome.     

HIV-associated lymphoepithelial cysts and lesions: morphological and immunohistochemical study of the lymphoid cells

Aims : To determine the morphology, immunophenotype and bcl-2 protein status of intraepithelial lymphocytes in HIV-positive lymphoepithelial lesions.  

Methods and results

Seventeen cases (from adults and children) of HIV-associated parotid and lung lymphoid lesions were examined. In addition, three lymphoepithelial cysts from HIV-negative patients were studied in parallel. Immunohistochemistry was performed on paraffin embedded tissue with the following antibodies: CD20, CD79a, CD3, CD4, CD8, bcl-2, CAM5.2, AE1/3, MIB1, kappa/lambda light chains and EBV-LMP-1. Heavy chain rearrangement was sought by polymerase chain reaction (PCR) in four of the cases. The lymphocytes participating in lymphoepithelial lesions of HIV-positive patients had the morphology of centrocyte-like cells with occasional cells resembling centroblasts. The majority of these cells were of B-cell lineage, but occasional intraepithelial T-cells (CD8 positive, CD4 negative) were also present. T-cells also formed a significant component of the infiltrative lymphoid cells outside the lymphoepithelial lesions. These were mainly CD8 positive, but very occasional CD4-positive T-cells were also noted. None of the cases showed light chain restriction and the four cases did not demonstrate heavy chain rearrangement by molecular biology. The interesting finding was the absence of bcl-2 expression by the intraepithelial lymphocytes. In contrast, the intraepithelial lymphocytes seen in the non-HIV setting were strongly bcl-2 positive. The majority of these were B-cells, and very occasional CD8 and CD4 positive T-cells formed the intraepithelial population.  

Conclusion

It is postulated that this finding is due to the HIV causing down-regulation of bcl-2 protein.