胃淋巴上皮瘤样癌一例

患者男,64岁。因呕血2h于2005年2月17日入院。临床诊断为上消化道出血。急诊手术,行胃大部切除。     

淋巴上皮样癌的光镜,电镜及免疫组织化学观察

目的：研究淋巴上皮样癌（ＬＥＬＣ）的本质特征。方法：光镜、电镜和免疫组化Ｃｙｔｏｋｅｒａｔｉｎ、ＥＭＡ、ＣＤ３、ＣＤ４５、ＣＤ２０观察６例ＬＥＬＣ癌细胞及浸润淋巴组织。结果：癌细胞含有张力微丝和桥粒样连接，Ｃｙｔｏｋｅｒａｔｉｎ阳性。浸润的淋巴细胞以Ｔ细胞为主，能直接破坏癌细胞。结论：ＬＥＬＣ是一种具有特殊组织学表现的低分化鳞癌。     

子宫颈原发性淋巴上皮瘤样癌8例临床病理分析

目的：探讨子宫颈原发性淋巴上皮瘤样癌( lymphoepithelioma-like carcinoma, LELC)的临床病理特征、组织学形态、鉴别诊断及预后。方法收集8例子宫颈原发性LELC的临床病理资料,行HE染色、免疫组化标记及原位杂交检测。结果8例子宫颈原发性LELC患者发病年龄29~67岁,平均年龄44岁,临床分期均为玉B,淋巴结均无转移。眼观：5例子宫颈肿物呈菜花状,1例呈息肉样,其余呈浸润性增厚。镜下见肿瘤由未分化的大细胞组成,散在或成片巢状、条索状分布。瘤细胞呈卵圆形或多角形,细胞核空泡状,核膜清楚,可见1个或数个突出的嗜酸性核仁,细胞界限不清,呈“合体样冶分布。瘤细胞间被丰富的淋巴细胞、浆细胞浸润。免疫表型：CK阳性率100%,p63阳性率37.5%,p16阳性率62.5%,CK5/6阳性率75%,Ki-67增殖指数10%~30%,间质淋巴细胞以CD3和CD8阳性表达为主。原位杂交检测EBER阴性,1例间质淋巴细胞弱阳性。电话随访截止2013年6月,1例死亡,其余7例均存活。结论子宫颈原发性LELC罕见,其是一种具有独特组织学形态的恶性肿瘤,临床预后较好,明确诊断依靠病理组织学和免疫组化标记。     

胃原发性淋巴上皮瘤样癌6例临床病理学观察

目的探讨胃淋巴上皮瘤样癌(lymphoepithelioma-like gastric carcinoma,LLGC)临床病理学特征、免疫表型及与EB病毒(EBV)感染的关系。方法收集6例LLGC,对其临床特征、病理学形态和免疫表型进行观察,采用原位杂交法检测EBV编码小RNA(EBER)的表达。结果 6例均为男性,发病年龄47~68岁,平均55岁,6例均累及胃体。镜检:在丰富的淋巴细胞背景中见散在的未分化癌细胞条索或细胞巢,偶尔在近黏膜表面出现发育差的腺管结构,间质内纤维组织少,见淋巴滤泡形成。瘤细胞表达CKpan、CK19、CEA及EBER,不表达CK7、CK20、CK5/6及LMP1;间质淋巴细胞表达CD3或CD20,不表达EBER。6例患者随访6~57个月,均无瘤存活。结论 LLGC是一种罕见的具有独特临床病理学特征的胃癌亚型,预后较好,与EBV感染密切相关。     

腮腺淋巴上皮瘤样癌与EB病毒感染的关系

目的：研究ＥｐｓｔｅｉｎＢａｒｒ 病毒（ＥＢＶ）与腮腺淋巴上皮瘤样癌（ｌｙｍｐｈｏｅｐｉｔｈｅｌｉｏｍａｌｉｋｅｃａｒｃｉｎｏｍａ,ＬＥＬＣ）的关系,并检测瘤细胞内ＥＢＶ 基因编码产物。方法：作者收集了中山医科大学所属病理科１９８６ 年１ 月至１９９５ 年１２ 月间３２ 例腮腺ＬＥＬＣｓ．。３２ 例ＬＥＬＣ石蜡包埋标本再次切片。采用免疫组化和原位核酸杂交法检测瘤细胞内ＥＢＶ 基因表达产物。结果：（１） 在１２５例腮腺癌中有３２ 例淋巴上皮瘤样癌,占总病例的２５－６％ （３２／１２５） 。（２）所有３２ 例腮腺ＬＥＬＣ组织中均有数量不等的ＥＢＮＡ１ 和ＥＢＥＲｓ 阳性瘤细胞。（３）２７ 例ＬＥＬＣ 组织中部分瘤细胞表达ＬＭＰ１ 。（４） 所有标本中均未见ＺＥＢＲＡ 阳性细胞。（５）３２例腮腺ＬＥＬＣ组织中ＥＡＤ、ＶＣＡ和ＭＡ的阳性表达率分别为７１－９ ％（２３／３２） 、６８－８ ％（２２／３２） 和１２－５％ （４／３２） 。结论：（１） 在鼻咽癌高发的广州地区,腮腺ＬＥＬＣ的发病率也较高。（２）腮腺ＬＥＬＣ 组织中均有ＥＢ病毒感染。（３）ＥＢ病毒在腮腺ＬＥＬＣ的感染主要为潜伏Ⅱ型,即表达ＥＢＮＡ１ 、ＥＢＥＲｓ 和ＬＭＰ１     

胃淋巴上皮瘤样癌1例并文献复习

目的 探讨胃淋巴上皮瘤样癌的临床病理学特点,诊断和鉴别诊断.方法 通过HE、免疫组化染色等方法对1例胃淋巴上皮瘤样癌进行分析,并复习文献.结果 瘤组织主要由弥漫浸润的瘤细胞和密集的淋巴细胞构成,常见淋巴滤泡形成,瘤细胞为大的卵圆形或多角形细胞,核空泡状,核仁明显,胞质丰富,呈嗜酸性.免疫表型:癌细胞CKpan(+)、EMA(+)、EB(-).结论 胃淋巴上皮瘤样癌是一种罕见的胃上皮来源恶性肿瘤,其诊断主要依靠组织病理学和免疫组化标记.     

肝细胞性淋巴上皮瘤样癌3例及文献复习

目的探讨肝细胞性淋巴上皮瘤样癌的临床病理学特点。方法通过HE、免疫组化染色对3例肝组织中肝细胞性淋巴上皮瘤样癌进行形态学观察。结果瘤细胞异型明显,呈小灶状分布,细胞呈多边形,核居中央,有一清楚核仁,细胞质丰富,嗜酸性,可见细小颗粒,易见核分裂象。肿瘤间质内见大量成熟的淋巴细胞浸润,且分散在瘤细胞之间。3例中肿瘤细胞CK7、Hepatocyte、EB（-）,CK8、AFP（＋）,而间质中淋巴细胞CIM5（＋）、小B淋巴细胞CD20（＋）、小T淋巴细胞CD45RO（＋）。结论肝细胞性淋巴上皮瘤样癌是一种少见的肝上皮源性恶性肿瘤,其诊断主要依靠组织病理学和免疫组化标记。     

唾腺粘膜相关型淋巴瘤与良性淋巴上皮病变的临床病理学

目的：探讨唾腺粘膜相关型淋巴瘤（MALT－ML）与良性淋巴上皮病变（LEL）的诊断、鉴别诊断及其发病机制。方法：手术切除标本常规石蜡切片和免疫组化ABC法标记。结果：17例唾腺MALT－ML16例为CCL细胞型，1例为淋巴浆细胞型，具有MATL－ML的共同特征，免疫组化示单克隆性，7例LEL示多克隆性。结论：Ⅰ级、Ⅱ级LEL为良性病变，Ⅲ级为交界性病变。Ⅳ级LEL即MALT－ML，因此唾腺MALT－ML与LEL密切相关。     

原发性乳腺淋巴上皮瘤样癌临床病理观察

目的观察乳腺原发性淋巴上皮瘤样癌(lymphoepithelioma-like carcinoma,LELC)的临床病理变化和免疫组化特征,以提高人们对该肿瘤的认识。方法对2例原发于乳腺的LELC的临床病理学和组织病理学特征进行观察,结合免疫表型并复习文献。结果 2例均为中年女性,临床均表现为无痛性肿块,肿瘤呈多结节状或弥漫状生长,肿瘤细胞呈卵圆形或多边形,核空泡状,核仁明显,核膜厚,间质有大量小淋巴细胞浸润。免疫表型:肿瘤细胞表达CK7、CK8/18和E-cadherin,缺乏表达ER、PR和c-erbB-2,原位分子杂交检查示EBV阴性,肿瘤细胞Ki-67增殖指数约30%。结论发生于乳腺的LELC极其少见,临床病理学特征和免疫表型与普通乳腺浸润性癌类似,病理诊断时需与乳腺发生的髓样癌和经典型霍奇金淋巴瘤进行鉴别。患者预后较好。     

Epstein-Bar病毒潜伏膜蛋白在喉癌组织中的表达

为了探讨Ｅｐｓｔｅｉｎ－Ｂａｒ病毒在喉鳞癌细胞中的表达情况，对９０例喉鳞癌组织进行了Ｅｐ－ｓｔｅｉｎ－Ｂａｒｒ病毒潜伏膜蛋白（ＥＢＶ－ＬＭＰ－１）的检测，结果显示，ＬＭＰ－１主要定位于细胞膜和细胞浆内，９０例喉鳞癌中ＬＭＰ－１阳性者４１例，阳性检出率为４５．５％，其中低分化鳞癌阳性率为４４％（１２／２７），中分化鳞癌为５２％（２５／４８），高分化鳞癌为２６．６％（４／１５）。提示，ＥＢ病毒不仅存在于低分化喉鳞癌中，也存在于高分化鳞癌中，喉癌的发生可能与ＥＢ病毒感染有关。     

EB病毒相关与不相关的肠道T细胞淋巴瘤临床病理研究

目的：探讨EB病毒相关与不相关的肠道T细胞淋巴瘤的临床病理特征、免疫分型和肿瘤细胞属性。方法：运用EBER1／2原位杂交检测EB病毒感染,采用免疫组化检测32例肠肠道原发T细胞淋巴瘤的免疫表型以及LMP－1、TIA－1、bcl-2和CD21的表达。结果：（1）27例（84．4％）为EB病毒相关淋巴瘤,其中11例（40．75）表达LMP－1。（2）32例瘤细胞均表达CD45RO,CD8＋。4例（12．5％）,CD4＋8例（25．0％）,CD56＋9例（28．1％）,17例（53．7％）为CD4－、CD8－、CD56－。TIA－1＋31例（96．9％）。无1例表达bcl2-,CD21。形态上28例为多形性中一大细胞性,单形性中等大细胞性和多形性各2例。临床上多见于青壮年男性,以腹痛、便血、发热、体重下降为主要症状,预后较差（中位生存期1．7月）。（3）EB病毒相关与相关者出现便血和发热以及CD3,CD8、CD56的表达方面差异有显著性。结论：在我国,绝大多数肠道T细胞淋巴瘤为EB病毒相关,具有特殊临床病理表现和免疫表型。其肿瘤细胞源自不同T细胞亚群（包括细胞毒性T细胞）或者NK细胞。     

肠道淋巴瘤与EB病毒相关性研究

目的：探讨EB病毒（Epstein-Barr virus,EBV)感染在肠道淋巴瘤发病中的意义。方法：采用EBV的DNA原位杂交及S－P法免疫组化技术（第一抗体为EBV、CD3、CD20、CD43、CD45、CD45RO、CD74等），观察24例肠道淋巴瘤患者（8例肠病相关T细胞淋巴瘤、16例黏膜相关淋巴组织B细胞淋巴瘤）EBV感染情况。以20例慢性结肠炎作为对照。结果：患者年龄21－92岁（平均52．8岁），男女之比为3．8：1。临床上均以腹痛、腹胀或便血就诊。组织病理学：T细胞淋巴瘤细胞多形性、核大，不规则，嗜血管性及大片坏死；B细胞淋巴瘤细胞中等大小，多呈圆形、椭圆形、胞质较少淡染，核稍大，核分裂象多见，可见“淋巴上皮病变”。24例淋巴瘤中检出（原位杂交及免疫组化）EBV－DNA 14例（检出率为58．3％），其中T细胞淋巴瘤EBV的检出率为75％，B细胞淋巴瘤EBV的检出率为50％（P＜0．01）。结论：肠道淋巴瘤的发生与EBV的感染有明显的相关性。     

Epstein-Barr virus specific salivary antibodies as related to stress caused by examinations

Epstein-Barr virus (EBV) is prevalent in 90% of the population. After primary infection it remains in a latent state and the majority of the virus carriers are asymptomatic during their life. Among the immunocompromized patients such as organ and bone marrow transplant recipients, individuals lacking T cell immunity, and patients treated with corticosteroid, cancer, and AIDS patients EBV primary infection and reactivation can cause life threatening diseases. Immunosupression may occur also during stressful events, which induce corticosteroid release and thus activate EBV. The effect of examination stress on EBV reactivation among female students was studied by detecting the values of EBV specific IgG and IgA salivary antibodies. Sequential saliva samples were obtained from first year female students before, during, and after two important examinations. EBV specific IgG and IgA salivary antibodies were tested by enzyme-linked immunosorbent assay (ELISA). Hepatitis A virus (HAV) salivary antibodies served as a non-latent virus control. A statistically significant increase in the values of EBV specific IgG and IgA antibodies was detected in samples collected during the examinations, as compared to the samples collected two months before and one month after the exams (P < 0.05). HAV antibody levels did not change significantly between the four time points. The menstrual cycle had no significant effect on the results. No significant symptoms were reported during the whole study. These results indicate that among female students who endure stress during academic examinations, a significant increase in EBV specific IgG and IgA salivary antibody values could be detected. EBV reactivation should be confirmed by measuring salivary EBV DNA or infectious virus.     

Epstein-Barr virus immune response in high-risk nasopharyngeal carcinoma families in Greenland

Undifferentiated nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV) infection. Presence of EBV IgA antibodies is rare among healthy individuals and is used as a marker of nasopharyngeal carcinoma in high-incidence populations. Reasons for EBV IgA seropositivity are unknown, but high EBV IgA levels have been found among unaffected close family members and spouses to nasopharyngeal carcinoma patients in Chinese populations. In Greenland, a nasopharyngeal carcinoma-high-incidence area, we compared EBV serology and viral load in high-risk nasopharyngeal carcinoma family members (N = 20) and controls without nasopharyngeal carcinoma-affected relatives (N = 90). There was no significant difference in EBV viral loads between relatives and controls, and EBV was detected in plasma in 5.0% of relatives and 11.4% of controls. There was no significant difference in EBV serology, but the seroprevalence of EBV viral capsid antigen (VCA) IgA was high in both relatives (25.0%) and controls (20.5%). Compared with anti-VCA IgA-negative, anti-VCA IgA-positive individuals had significantly higher EBV viral loads in peripheral blood mononuclear cells (PBMCs) (P < 0.01). The very high prevalence of anti-VCA IgA indicates that this antibody is unsuitable for nasopharyngeal carcinoma screening among Inuits.     

鼻咽刷片细胞学检查和EB病毒检测在鼻咽癌诊断中的意义

目的：探讨鼻咽细胞学检查结合DNA核型判断和细胞EB病毒检测在可疑鼻咽癌病人筛查中的作用。方法：分别对66例可疑鼻咽癌就诊病人作鼻咽刷片细胞学诊断和应用CAS200图像分析仪测定涂片细胞DNA含量,细胞学癌阳性病例同时作EB病毒编码RNA（EBERs)原位杂交。结果：与组织学诊断相比,细胞学诊断和DNA非二倍体诊断癌的敏感性分别为66％和55％,两者结合判断不能提高敏感性,并且假阴性率高;细胞学癌阳性病例的癌细胞核EBERs阳性率92．1％,其中6例DNA二部体核型病例均呈EBERs阳性,可诊断为鼻咽癌。结论：鼻咽细胞学检查结合DNA核型判断不能提高可凝鼻咽癌病人的诊断率,不适用于鼻咽癌筛查。细胞涂片的EB病毒原位杂交方法,在鼻咽癌可疑病人的诊断和鉴别诊断上具有重大实用价值,在鼻咽癌筛查的作用有待进一步研究。     

Detection of Epstein-Barr virus antigens and DNA in major and minor salivary glands using immunocytochemistry and polymerase chain reaction: possible relationship with Sjogren's syndrome.

This study has investigated the presence of Epstein-Barr virus (EBV) in parotid (n = 12), submandibular (n = 15), and minor salivary glands (n = 25) using immunohistochemical methods for detection of EBV-encoded antigens and the polymerase chain reaction (PCR) for detection of viral DNA. Major salivary glands were from patients without connective tissue disease. Labial glands were from patients with primary Sjogren's syndrome (n = 10), rheumatoid arthritis (n = 8), or from normal individuals (n = 7). None of the glands exhibited specific reactivity for lytic (EA-D, EA-R, VCA) or latent (EBNA-2, LMP) viral antigens. Antibodies to EA-D, when used at 20-50 times their optimal concentration, gave lumenal staining of ducts and acini of all the specimens tested (n = 14), irrespective of the presence (n = 8) or absence (n = 6) of EBV-DNA by PCR. Ductal immunoreactivity for the EBV/C3d (CR2, CD21) receptor was found in 40 per cent of specimens. PCR detected EBV-DNA in 64 per cent submandibular, 46 per cent parotid, and 80 per cent of minor glands. There were no significant differences in the detection of EBV-DNA between specimen/patient groups. Only type A EBV was detected by strain typing PCR. These results indicate that EBV (type A), undetected immunocytochemically, is commonly present at low copy numbers within salivary glands irrespective of a clinical diagnosis of Sjogren's syndrome.     

环孢素A对稳定EBV诱发淋巴瘤模型的作用和意义

目的：观察环孢素A（CSA）对hu-PBL/SCID嵌合体小鼠发生移植物和抗宿主反应（GVHR）的抑制作用，建立稳定的EBV诱发淋巴瘤动物模型，方法：从健康成人新鲜外周血中分离出淋巴细胞，将之移植到SCID小鼠腹腔中，实验感染EB病毒，腹腔注射CSA，并采用ELISA检测小鼠血清中人sIL-2R水平。结果：环孢素A组（14只）无1只小鼠因GVHR而死亡，而其余3组共39只小鼠有15只因GVHR而死亡，中位生存时间为17d，死亡率分别为55．56％（5／9例）、30．43％（7／23例）、42．86％（37．7例），与环孢素A组比较差异有显著性意义。环孢素A组在不同时间sIL-2R含量较稳定，而实验感染组sIL-2R水平有逐渐升高趋势，环孢素A组与实验感染组同一时间比较15d和22d时sIL-2R水平有显著性差异。后者明显高于前者，渡过急性GVHR期而存活的38只SCID小鼠中，共有24只形成肿瘤。结论：CSA可显著抑制hu-PBL/SCID嵌合体小鼠GVHR的发生，对稳定建立EWBV诱发淋巴瘤动物模型具有的实际意义。     

抗凋亡基因bcl—2在EB病毒相关性鼻咽癌中的表达

目的：探讨抗凋亡基因ｂｃｌ－２与鼻咽癌发生及与ＥＢ病毒感染的关系。方法：应用ＰＣＲ技术和免疫组化ＳＰ法检测４６例鼻咽癌组织中ＥＢ病毒ＤＮＡ和抗凋亡基因ｂｃｌ－２的表达。结果：３７例ＥＢ病毒ＤＮＡ阳性病例中３１例出现ｂｃｌ－２表达８３．８％，９例ＥＢ病毒ＤＮＡ阴性病例吸７例ｂｃｌ－２阳性反应，两组间无明显差异。结论：ｂｃｌ－２基因在鼻咽癌中的异常高表达与ＥＢ病毒的感染无明显关系。     

Gastric carcinoma with osteoclast‐like giant cells. Lymphoepithelioma‐like carcinoma with Epstein–Barr virus infection is the predominant type

Osteoclast‐like giant cells (OGC) are rare in gastric carcinomas. Histopathological study of seven gastric carcinomas with OGC demonstrated three distinct types: lymphoepithelioma‐like carcinoma (LELC), non‐LELC, and giant cell tumor (GCT) types. LELC is a poorly differentiated adenocarcinoma with prominent lymphoid stroma. The LELC type (n= 4) showed similar histology to LELC of the stomach, except that they were accompanied by OGC and granulomatous reaction. Epstein‐Barr virus (EBV) infection was demonstrated by EBV‐encoded RNA (EBER) in situ hybridization (ISH) in all the neoplastic cells. The non‐LELC type (n= 2) consisted of EBV‐negative carcinoma cells with inflammatory infiltrates. OGC and granulomas were frequently observed in the glandular lumens with accumulated mucus. The GCT type (n= 1) was a neuroendocrine carcinoma, containing many OGC with metaplastic bone formation, which showed typical morphological features of OGC in GCT of the bone. In all three types, OGC expressed CD68, but not cytokeratin, indicating that OGC had a reactive histiocytic lineage. Both LELC and non‐LELC types are included in the differential diagnosis of isolated granulomatous gastritis, and EBER‐ISH was useful for the identification of LELC type. Both LELC and no‐LELC types were also suggested to have better prognoses, but the behavior of the GCT type needs to be further characterized.