EB病毒阴性胃淋巴上皮瘤样癌1例并文献复习

回顾性分析1例胃淋巴上皮瘤样癌(lymphoepithelioma-like gastric carcinoma,LELGC)患者的临床病理特点并复习相关文献。本例患者因剑突下疼痛入院,外院胃镜提示胃窦部巨大溃疡,入院增强CT提示胃窦部胃壁增厚并明显强化,考虑胃窦部恶性肿瘤,行根治性手术切除。术后病理检查提示:远端胃可见一大小约为4.5 cm×5.5 cm×1.0 cm的溃疡型肿物,似侵及深肌层。特殊染色结果示幽门螺杆菌阳性。原位杂交结果示Epstein-Barr病毒(Epstein-Barr virus,EBV)编码区阴性。免疫组织化学染色示广谱细胞角蛋白、表皮生长因子受体、P53(野生型)、上皮膜抗原、细胞黏附分子、黏蛋白(mucin,MUC)-6均为阳性,细胞增殖的相关抗原Ki-67为60%阳性,淋巴细胞共同抗原和CD3均为部分阳性,人髓细胞增生原癌基因、细胞周期蛋白D1和CD5均为弱阳性,人类表皮生长因子受体-2、D20、CD10、多发性骨髓瘤癌基因1、CD79a、B细胞白血病/淋巴瘤(B-cell leukemia/lymphoma,BCL)-2、BCL-6、CD56、间变性淋巴瘤激酶、配对盒蛋白5、突触素、嗜铬粒蛋白A、CD8、波形蛋白、黑色素瘤相关抗原HMB45、黑色素A、神经特异性蛋白质S-100、SOX10、E-钙黏蛋白、尾侧型同源盒转录因子-2、MUC-5ac、MUC-2均为阴性。苏木精-伊红染色结果示:肿瘤细胞核分裂活跃,可见病理性核分裂象。通过文献复习发现,80%以上的LELGC患者与EBV感染相关,早期LELGC主要通过内镜黏膜下剥离或根治性切除术治疗,而晚期患者多采用姑息性治疗。LELGC患者过度表达程序性死亡受体配体1,这表明程序性死亡受体1/程序性死亡受体配体1抑制剂可作为LELGC的潜在治疗靶点,具有广阔的治疗前景。

胃淋巴上皮瘤样癌的研究进展

胃淋巴上皮瘤样癌(LELC)是胃癌中的一种罕见类型,预后较好。由Watanabe等在1976年以"富淋巴样间质的胃癌"首次报道,后来又有学者陆续加以报道。近年来随着分子生物学技术的发展,胃LELC的本质逐步得到认识。该文对胃淋巴上皮瘤样癌的研究进展作一综述。

胃淋巴上皮瘤样癌1例

病人,男,57岁。间断腹胀腹痛2个月。胃镜示胃窦部见2 cm×1.5 cm大小浅表溃疡,触之易出血。病理报告：黏膜重度慢性炎,另见少许异型细胞,不除外低分化腺癌。术中发现胃窦大弯侧见一大小约2.5 cm×2 cm边缘稍隆起的浅表溃疡。大小弯侧淋巴结肿大。

胃淋巴上皮瘤样癌15例临床病理分析

目的探讨胃淋巴上皮瘤样癌(LELC)的临床病理学特点。方法分析15例胃淋巴上皮瘤样癌的临床病理学特点,免疫组化法检测其免疫表型,比较其与相同分化程度和病理分期的非淋巴上皮瘤样胃腺癌的淋巴结转移率和预后。原位杂交法检测肿瘤组织中EB病毒的感染情况。结果 15例胃淋巴上皮瘤样癌均有显著的淋巴样间质,即大量淋巴细胞、浆细胞弥漫浸润,淋巴滤泡形成,癌细胞呈条索状、不规则的腺管或单个散在分布于大量淋巴细胞背景中。免疫组化:腺上皮细胞CK8/18、AE1/AE3和EMA(+),间质淋巴细胞CD20和CD3(+)。15例均无胃周围淋巴结转移,与同病理分期(T4a N0期)的非淋巴上皮瘤样胃低分化腺癌比较,差异显著(P<0.05)。3例肿瘤细胞EBER(+)。结论胃淋巴上皮瘤样癌是一种罕见类型的低分化腺癌,部分有EB病毒感染,具有特殊的临床病理学特点。

EB病毒相关的胃淋巴上皮样癌的机制研究和治疗进展

Epstein-Barr病毒(EBV)相关的胃淋巴上皮样癌(LELGC)是一种罕见的胃癌类型,其在2010年版世界卫生组织(WHO)的胃癌分型中属于髓样癌,预后较差,免疫组织化学为EBV编码的小RNA(EBER)阳性。EBV感染后,其相关基因的激活和表达打破了病毒与宿主间的平衡,并且存在抑癌基因及错配修复蛋白基因的高甲基化,这一系列免疫原性的增强使得免疫微环境趋向于促瘤方向发展。相较于传统治疗,免疫治疗为中、晚期LELGC的治疗提供了更为新颖有效的策略。

胃淋巴上皮瘤样癌1例

1临床资料患者,男性,65岁,因＂进食后上腹不适3个月＂入院。既往26年前因胃溃疡出血行胃大部切除（毕二式吻合）,术后病理为：胃溃疡伴急慢性炎症活动。查体：上腹正中20cm切口瘢痕,腹部平坦,无压痛、反跳痛及肌紧张,全腹未触及明显包块。辅助检查：血常规正常,无明显贫血,大便潜血阴性。

胃淋巴上皮瘤样癌临床病理特征、免疫表型及预后分析

目的:分析研究胃淋巴上皮样癌的临床病理特征、免疫表型以及预后质量。方法:选取2014年8月-2016年2月我校一附院医治的40例胃淋巴上皮样癌患者作为研究对象,对其临床、病理学以及影像学资料进行回顾性分析。结果:患者肿瘤最小尺寸为1.23cm×1.40cm,最大尺寸约为8.62cm×10.37cm,平均尺寸为4.96cm×5.07cm;病理组织学表现为条索状肿瘤细胞,单个或者小团形状聚集结构,大量出现淋巴细胞浸润显效,细胞核仁明显,呈空泡状;临床免疫检测结果显示,肿瘤细胞角蛋白(CK)呈阳性,细胞中CD3阳性淋巴细胞数量明显高于CD20阳性,CD8阳性淋巴细胞数量最高;所有患者术后随访1~3年,均未发现肿瘤细胞复发现象。结论:胃淋巴上皮样癌是一种罕见、病理学特征独特的胃癌亚型,预后质量较好,其临床病理特征以及免疫表型具有较好的诊断价值。

原发性胃淋巴上皮瘤样癌的临床诊治进展

原发性胃淋巴上皮瘤样癌(LELC)是胃癌中的一种罕见组织学类型,属于EB病毒相关性胃癌(EBVaGC)中的一种,占胃癌的1%~7%。其临床表现无特异性,诊断主要依靠病理组织学检查。手术治疗适用于该病,细胞程序性死亡-配体1(PD-L1)抑制剂在该病的治疗效果可能优于胃腺癌,预后可能较非胃LELC好。由于该病在世界范围内少见,目前针对胃LELC且形成广泛统一共识的诊疗方案未被提出,而它与常见的胃腺癌相比具有某些不同的疾病特点。本文根据相关文献从流行病学特征、临床诊治方法、病理学表现、预后这4个方面综述了LELC的临床诊治现况,以期为临床医生提供参考。

胃富于淋巴间质的癌的临床病理特征及EB病毒、错配修复蛋白和HER-2表达情况

目的探讨胃富于淋巴间质的癌(GCLS)的临床病理特征及EB病毒感染情况、错配修复蛋白和人表皮生长因子受体-2(HER-2)表达情况,以期深入了解这一少见类型胃癌并对其分子分型和后续治疗提供病理依据。方法收集2013年3月至2021年3月浙江大学医学院附属杭州市第一人民医院收治的8例GCLS患者的临床资料。回顾性分析其临床和病理特征,采用免疫组化方法检测4种错配修复蛋白MLH1、PMS2、MSH2和MSH6以及HER-2表达情况,原位杂交法检测EB病毒编码的小RNA(EBER)表达情况,并对HER-2染色2+以上患者进行HER-2荧光原位杂交检测。结果GCLS好发于中老年、男性、近端胃,多数患者呈膨胀性生长,少数患者可伴有腺体分化。8例中有6例EBER阳性,2例EBER阴性患者均错配修复蛋白表达缺失,为MLH1/PMS2表达缺失,1例EBER阳性患者同时HER-2过表达。结论GCLS是一种形态上相似,但是分子分型不同的少见胃癌类型,对其进行更进一步的分子分型研究有助于更好了解其发生、发展及指导治疗。

胃淋巴上皮瘤样癌误诊分析

目的:探讨胃淋巴上皮样瘤样癌误诊原因。方法:对本院发现四例胃淋巴上皮样癌做回顾性分析。结果:胃镜检查与术后病理免疫组化有差异。结论:胃淋巴上皮瘤样癌特殊病理特点易致误诊。

原发性胃淋巴上皮瘤样癌的临床及免疫学特征分析

目的比较原发性胃淋巴上皮瘤样癌(gastric lymphoepithelioma-like carcinoma, GLELC)和胃腺癌的临床特征,分析GLELC组织免疫学指标变化。方法原发性GLELC患者18例为GLELC组,同期诊治胃腺癌患者28例为胃腺癌组。比较2组临床资料及手术切除组织中程序性死亡受体-1(programmed cell death-1, PD-1)、程序性死亡受体配体-1(programmed cell death ligand-1, PD-L1)表达情况;比较GLELC组癌组织CD3^(+)、CD4^(+)、CD8^(+)、CD20^(+)细胞比率。结果 GLELC组TNM分期Ⅰ~Ⅱ期比率(77.78%)高于胃腺癌组(35.71%)(P<0.05),Ⅱ、Ⅲ期者肿瘤直径[(5.00±2.10)cm、(7.50±0.91)cm]大于胃腺癌组[(2.80±1.30)、(5.46±2.89)cm](P<0.05),淋巴结转移比率(38.89%)低于胃腺癌组(71.43%)(P<0.05),PD-L1阳性表达率(88.89%)高于胃腺癌组(21.43%)(P<0.05),PD-1阳性表达率(22.22%)与胃腺癌组(17.86%)比较差异无统计学意义(P>0.05)。GLELC组癌组织中CD3^(+)T淋巴细胞比率[(76.39±4.13)%]高于CD20^(+)B淋巴细胞比率[(18.06±3.49)%](t=45.762,P<0.001),CD8^(+)T淋巴细胞比率[48.89±6.54)%]高于CD4^(+)T淋巴细胞比率[(27.50±3.54)%](t=12.202,P<0.001)。结论与胃腺癌相比,原发性GLELC肿瘤分期较低,肿瘤直径较大,淋巴结转移较少,癌组织PD-L1呈高表达,且淋巴细胞浸润以CD3^(+)、CD8^(+)T淋巴细胞为主。

胃淋巴上皮瘤样癌6例的临床病理特征

目的探讨胃淋巴上皮瘤样癌(LELGC)的临床病理特征。方法回顾性分析手术切除的6例LELGC患者的临床资料。结果患者的主要临床症状是上腹部不适。1例行胃镜下胃黏膜剥除术后追加胃癌根治术。1例合并腺癌,3例发生淋巴结转移,1例脉管内见癌栓。4例EB病毒编码的小RNA阳性。术后随访1～22个月,6例患者均存活。结论 LELGC临床少见,其发病可能与EB病毒感染有关,治疗方法以手术切除为主,预后较好。

Vascular Endothelial Growth Factor C Expression in Gastric Carcinoma and Its Relationship with Lymph Node Metastasis

Objective: To study the expression of vascular endothelial growth factor C (VEGF-C) in gastric carcinoma and its relationship with lymph node metastasis. Methods: The expression of VEGF-C mRNA in 5 gastric carcinoma cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR). Simultaneously, the expression of VEGF-C protein in gastric carcinoma tissues, which were obtained from 63 patients who underwent radical gastrectomy, was detected by immunohistochemistry. Results: Three of the 5 gastric carcinoma cell lines, MKN-45, SGC-7901 and AGS, expressed VEGF-C mRNA. VEGF-C protein was expressed in 52.4% (33/63) of patients. VEGF-C protein expression was more frequently found in tumors with lymph node metastasis than in those without (P<0.01). VEGF-C protein expression was also closely related to lymphatic invasion (P<0.01) and TNM stage (P<0.01). However, there was no significant correlation between VEGF-C expression and the age, gender, tumor size, tumor location, Lauren classification, depth of invasion, and vascular invasion. Conclusion: The expression of VEGF-C is closely related to lymph node metastasis of gastric carcinoma, and lymphangiogenesis might be a new target for treatment of gastric carcinoma.

Serum CD 4 4 Variant 6 as an Indicator of Tumor Burden and Metastasis in Patients with Gastric Car cinoma

Objective: To study the expression of CD44 correlation with the ability ofmetastasis of tumor cells in gastric carcinoma, to find the correlation of the concentration ofsoluble CD 44 Variant 6 (sCD44v6) and the histologic expression of CD44 Variant 6 (CD44v6) in tumorswith the clinico- pathologic features, and to make serum concentration of the CD44v6 and theexpression of CD44v6 may be useful an indicator as an early diagnosis, invasion, metastasis, andprognosis. Methods: Serum samples were obtained from 70 patients with primary gastric carcinomabefore surgery and 20 patients after surgery. Serum levels of CD44v6 were determined with aquantitative- enzyme- link-immuno- adsorbent assay. The expression of CD44v6 in tumors was examinedby immuno-histo-chemical staining. Results: Both the serum concentration of CD44v6 and itsexpression in tumors were positively related to the depth of invasion of the tumor, lymph nodemetastasis, clinical stage, and diffuse type gastric carcinoma, but not to the tumor size. The serumlevel of CD44v6 in patients with gastric cancer was significantly higher than that in control. Theserum concentration of CD44v6 was markedly lowered after curative surgery (F<0. 001), and the serumlevel of CD44v6 was higher in patients with gastric cancer with CD44v6 positive tumor cells than inthose with CD44v6 negative tumor cells. The serum level of CD44v6 was a prognostic indicator inpatients with diffuse type gastric carcinoma, as was the histological expression of CD44v6.Conclusion: CD44v6 of gastric cancer and serum concentration of CD44v6 seems to be correlated to theprogression of diffuse type gastric carcinoma metas- tasis and clinical stage. An elevated level ofsCD44v6 may serve as an indicator of lymph node metastasis (especially early metastasis) and badprognosis in pa tients with gastric carcinoma.

Factors related to lymph node metastasis and surgical strategy used to treat early gastric carcinoma

AIM:The prognosis of early gastric carcinoma (EGC) is generally excellent after surgery. The presence or absence of lymph node metastasis in EGC is an important prognostic factor. The survival and recurrence rates of node-negative EGC are much better than those of node-positive EGC. This study examined the factors related to lymph node metastasis in EGC to determine the appropriate treatment for EGC.METHODS: We investigated 748 patients with EGC who underwent surgery between January 1985 and December 1999 at the Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Hospital. Several clinicopathologic factors were investigated to analyze their relationship to lymph node metastasis: age, sex, tumor location, tumor size, gross type, histologic type, depth of invasion, extent of lymph node dissection, type of operation,and DNA ploidy.RESULTS:Lymph node metastases were found in 75 patients (10.0%). Univariate analysis showed that male sex, tumor size larger than 2.0cm, submucosal invasion of tumor, histologic differentiation, and DNA ploidy pattern were risk factors for regional lymph node metastasis in EGC patients. However, a multivariate analysis showed that three risk factors were associated with lymph node metastasis:large tumor size, undifferentiated histologic type and submucosal invasion. No statistical relationship was found for age, sex, tumor location, gross type, or DNA ploidy in multivariate analysis. The 5-year survival rate was 94.2% for those without lymph node metastasis and 87.3% for those with lymph node metastasis, and the difference was significant (P<0.05).CONCLUSION: In patients with EGC, the survival rate of patients with positive lymph nodes is significantly worse than that of patients with no lymph node metastasis. Therefore,a standard D2 lymphadenectomy should be performed in patients at high risk of lymph node metastasis: large tumor size, undifferentiated histologic type and submucosal invasion.

Expression of E-cadherin in gastric carcinoma and its correlation with lymph node micrometastasis

AIM: To examine the expression of E-cadherin in the primary tumor and to evaluate its relationship with lymph node micrometastasis (LNM).METHODS: The authors studied 850 lymph nodes resected from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy using reverse transcription polymerase chain reaction (RT-PCR) assay in addition to H&E staining. Cytokeratin-20 (CK-20)gene marker was used in this assay. The level of E-cadherin expression in the primary tumor was examined by immunochemical technique (EliVisionTM plus).RESULTS: LNM was detected in 77 (12.5%) lymph nodes of 14 patients (46.7%) with gastric carcinoma. The incidence of LNM was significantly higher in the diffuse type (12 of 19 cases, 63.2%) than in the intestinal type of gastric carcinoma (2 of 11 cases, 18.2%, P = 0.026). The incidence of LNM also increased in accordance with the depth of tumor invasion. The loss of expression of E cadherin in primary tumors was found in 14 (46.7) of 30 tumors. The absence of E-cadherin expression was significantly associated with the Lauren classification (P = 0.026), lymph node metastasis (P = 0.011), the grade of differentiation (P = 0.004) and the lymphatic invasion (P = 0.001). Expression of E-cadherin was negative in 10 (71.4%) of the 14 patients with LNM, and in 4 (25%) of the 16 patients without LNM (P = 0.026). CONCLUSION: The current results indicate that the RT PCR assay is useful for the detection of LNM and can significantly increase the detection rate of lymph node metastasis in patients with gastric carcinoma. The Laurenclassification and depth of tumor invasion are significantlyassociated with lymph node micrometastases. Our findings also indicate that E-cadherin may play an important role in determining the growth type and differentiation of gastric carcinoma. The loss of E-cadherin expression may contribute to LNM.

Prognostic impact of dissected lymph node count on patients with node-negative gastric cancer

AIM:To investigate the long-term effect of the number of resected lymph nodes (LNs) on the prognosis of patients with node-negative gastric cancer.METHODS: Clinical data of 211 patients with gastric cancer, without nodal involvement, were analyzed retrospectively after D2 radical operation. We analyzed the relationship between the number of resected LNs with the 5-year survival, the recurrence rate and the post-operative complication rate.RESULTS: The 5-year survival of the entire cohort was 82.2%. The total number of dissected LNs was one of the independent prognostic factors. Among patients with comparable depth of invasion, the larger the number of resected LNs, the better the survival (P<0.05). A cut-point analysis provided the possibility to detect a significant survival difference among subgroups. Patients had a better long-term survival outcomes with LN counts ≥15 for pT1-2, ≥20 for pT3-4, and ≥15 for the entire cohort. The overall recurrence rate was 29.4% within 5 years after surgery. There was a statistically significant, negative correlation between the number of resected LNs and the recurrence rate (P>0.01). The post-operative complication rate was 10.9% and was not signif icantly correlated with the number of dissected LNs (P>0.05).CONCLUSION: For node-negative gastric cancer, sufficient number of dissected LNs is recommended during D2 lymphadenectomy, to improve the long-term survival and reduce the recurrence. Suitable increments of the dissected LN count would not increase the post-operative complication rate.

Significance of Survivin and PTEN expression in full lymph node-examined gastric cancer

AIM： To study the relationship between Survivin and PTEN expression and lymph node metastasis, depth of invasion and prognosis of gastric cancer patients in China.METHODS： Specimens of gastric cancer tissue were collected from the Affiliated Hospital of Jianghan University. All the 140 patients had complete examination data. All lymph nodes were found by the fat-clearing method. The interrupted serial 4-micron sections, routine hematoxylin and eosin staining and immunohistochemical methods were used to detect the lymph node metastases. Gastric cancer tissue microarray was performed to test the expression of Survivin and PTEN （17A） in gastric cancer by immunohistochemical method. All data were processed using X^2 test, Fisher＇s exact test, Kaplan-Meyer Log-rank method and Cox multivariate analysis （SPSS 12.0 software）.RESULTS： One hundred and eighteen specimens were used in our tissue microarray （utilization rate was 82.4%）. A total of 7580 lymph nodes were found. Metastases were found in 90 specimens and 1618 lymph nodes were detected. The positive rate of Survivin and PTEN expression was 52.5% （62/118） and 76.2% （90/118）, respectively. A highly positive correlation was found between Survivin and PTEN expression （X^2=4.17, P=0.04）. Survivin expression was positively correlated with UICC N stage （X^2=8.69, P=0.03） and histological classification （X^2=4.41, P=0.04） by X^2 tests. PTEN expression was positively correlated with depth of invasion （P=0.02） and histological classification （X^2=5.47, P=0.02）. But Survivin and PTEN expressions were not related with prognosis of gastric cancer patients. A significant correlation between lymph node metastasis and prognosis was demonstrated by Cox multivariate analysis （X^2=4.85, P=0.028）.CONCLUSION： Survivin is positively correlated with PTEN expression in gastric cancer and is a molecular marker of lymph node metastasis while PTEN expression is a molecular marker of advanced gastric cancer. UICC N stage is the most important prognostic factor of gastric cancer in China.

Effect of lymph node micrometastases on prognosis of gastric carcinoma

AIM： To evaluate the relationship between lymph node micrometastases and prognosis of patients with gastric carcinoma and to evaluate the significance of the new assessment of nodal status in determining the pN categories in the 5th edition of the UICC TNM classification.METHODS： A total of 850 lymph nodes from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy were assessed by reverse transcription polymerase chain reaction assay in addition to histologic examination. Cytokeratin-20 gene marker was used in this assay.RESULTS： Routine examination by HE staining confirmed metastasis in 233 lymph nodes from 20 patients. All these 233 lymph nodes were oltokeratin-20 positive. Moreover, lymph node micrometastases were detected in an additional 67 lymph nodes in 12 of these 20 patients. Lymph node micrometastases were also detected in t0 lymph nodes from 2 of 10 patients who had no obvious metastases identified by HE staining. Totally, lymph node micrometastases were identified by the reverse transcription polymerase chain reaction assay in 77 （12.5%） lymph nodes from 14 （46.7%） patients with gastric carcinoma. Of 27 patients who underwent curative resection, 7 （25.9%） were up-staged （from Ⅰ B stage to Ⅱ stage in 1 patient, from IB stage to ⅢA stage in 1 patient, from Ⅱ stage to ⅢA stage in 1 patient, from ⅢA stage to ⅢB stage in 1 patient, from ⅢA stage to Ⅳ stage in 1 patient, from ⅢB stage to Ⅳ stage in 2 patients）. In a median follow-up of 32 （range 8-36） too, Kaplan-Meier survival analysis showed significant improvements in median survival （22.86 ± 3.17 mo, 95% CI： 16.64-29.08 mo vs 18.00 ± 7.4 mo, 95% CI： 3.33-32.67 mo） of patients with negative lymph node micrometastases over patients with positive lymph node micrometastases （log-rank, P 〈 0.05）.CONCLUSION： Lymph node micrometastases have a significant impact on the current staging system of gastric carcinoma, and are significant risk factors for prognosis of patients with gastric carcinoma.

Distribution of solitary Iymph nodes in primary gastric cancer:A retrospective study and clinical implications

AIM： To investigate the distribution pathway of metastatic lymph nodes in gastric carcinoma as a foundation for rational lymphadenectomy. METHODS： We investigated 173 cases with solitary or single station metastatic lymph nodes （LN） from among 2476 gastric carcinoma patients. The location of metastatic LN, histological type and growth patterns were analyzed retrospectively. RESULTS： Of 88 solitary node metastases cases, 65 were limited to perigastric nodes （N1）, while 23 showed skipping metastasis. Among 8 tumors in the upper third stomach, 3 involved right paracardial LN （station number： No.1）, and one in the greater curvature was found in No.1. In the 28 middle third stomach tumors, 10 were found in LN of the lesser curvature （No.3） and 6 in LN of the left gastric artery （No.7）; 5 of the 20 cases on the lesser curvature spread to No.7, while 2 of the 8 on the greater curvature metastasized to LN of the spleen hilum （No.10）. Of 52 lower third stomach tumors, 13 involved in No.3 and 19 were detected in inferior pyloric LN （No.6）; 9 of the 29 cases along the lesser curvature were involved in No.6. CONCLUSION： Transversal and skipping metastases of sentinel lymph nodes （SLN） are notable, and rational lymphadenectomy should, therefore, be performed.