EB病毒阴性胃淋巴上皮瘤样癌1例并文献复习.pdf

J Clin Pathol Res2023,43(8)http:/ 临床与病理杂志EB病毒阴性胃淋巴上皮瘤样癌1例并文献复习石万红1，陈新民1，李娟1，刘晓明1，徐开军2，贺琳2，孙建军1(1.云南省第三人民医院普外科，昆明 650011；2.云南省第三人民医院病理科，昆明 650011)摘要 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 cm5.5 cm1.0 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。关键词 胃淋巴上皮瘤样癌；Epstein-Barr病毒；胃癌Epstein-Barr virus-negative lymphoepithelioma-like gastric carcinoma:A case report and literature reviewSHI Wanhong1,CHEN Xinmin1,LI Juan1,LIU Xiaoming1,XU Kaijun2,HE Lin2,SUN Jianjun1(1.Department of General Surgery,Third Peoples Hospital of Yunnan Province,Kunming 650011;2.Department of Pathology,Third Peoples Hospital of Yunnan Province,Kunming 650011,China)ABSTRACT To retrospectively analyze the clinicopathological features of a patient with lymphoepithelioma-like gastric carcinoma(LELGC)and review the related pieces of literature.The patient was admitted to the hospital due to subxiphoid pain,and an initial DOI：10.11817/j.issn.2095-6959.2023.220028收稿日期(Date of reception)：2023-02-07第一作者(First author)：石万红，Email:,ORCID:0009-0004-1155-1454通信作者(Corresponding author)：孙建军，Email:,ORCID:0009-0001-6252-880XCASE ANALYSES 临床病例讨论1596EB病毒阴性胃淋巴上皮瘤样癌1例并文献复习 石万红，等gastroscopy at an external hospital revealed a huge ulcer in the gastric antrum.Contrast-enhanced CT on admission showed that the gastric wall in the gastric antrum was thickened and significantly enhanced,raising suspicion of malignancy.Consequently,a radical resection was performed.Postoperative pathology showed an ulcerative mass of 4.5 cm 5.5 cm1.0 cm in the distal stomach,which seemed to invade the deep muscle layer.Special staining results showed that Helicobacter pylori was positive.Situ hybridization results showed that Epstein-Barr virus(EBV)encoding region was negative.Immunohistochemical staining results showed that cytokeratin-Pan,epidermal growth factor receptor,P53(wild type),epithelial membrane antigen,cell adhesion molecule,and mucin(MUC)-6 were all positive;and antigen associated cell proliferation(Ki-67)was 60%positive.Lymphocyte common antigen and CD3 were partially positive;while human cellular myelocytomatosis oncogene,cyclin D1,and CD5 were weakly positive;whereas human epidermal growth factor receptor-2,D20,CD10,multiple myeloma oncogene 1,CD79a,B-cell leukemia/lymphoma(BCL)-2,BCL-6,CD56,anaplastic lymphoma kinase,paired box protein 5,synapsin,chromograin protein A,CD8,Vimentin,melanoma associated antigens HMB45,melanin A,neural specific protein S-100,sex determining region Y-box 10,E-cadherin,caudaltype homeobox transcription factor-2,MUC-5ac,MUC-2 were all negative.Hematoxylin and eosin staining results showed active tumour cell nuclear division with pathological mitotic figures.Through literature review,it is found that more than 80%of LELGC cases are associated with EBV infection.Early-stage LELGC is primarily treated with endoscopic submucosal dissection or radical resection,while advanced-stage patients mostly receive palliative treatment.LELGC patients over-express programmed death ligand 1,which indicates that programmed death receptor 1/programmed death receptor ligand 1 inhibitors can be used as potential therapeutic targets for LELGC and have broad therapeutic prospects.KEY WORDS lymphoepithelioma-like gastric carcinoma;Epstein-Barr virus;gastric cancer胃淋巴上皮瘤样癌(lymphoepithelioma-like gastric carcinoma，LELGC)是 一 种 罕 见 的 胃 癌 亚 型，Watanabe 等1在 1976 年首次对 LELGC 进行描述。LELGC占胃癌的1%4%，男性的发病率是女性的2倍，其主要特征是伴有广泛的淋巴细胞浸润2。80%的 LELGC 患 者 与 Epstein-Barr 病 毒(Epstein-Barr virus，EBV)的感染密切相关3。约60%的淋巴上皮瘤样癌患者发生在鼻咽部，同时肺、扁桃体、食道、唾液腺、胸腺、宫颈和皮肤等多个部位可能受影响1。然而，LELGC常被误诊为胃腺癌，现结合1例LELGC患者，并复习国内外相关文献对该病进行分析讨论。1 临床资料 患者，男，68岁，因剑突下疼痛3 d于2022年9月9日于云南省第三人民医院普外科就诊。外院胃镜检查结果示：胃窦部黏膜充血水肿，前壁及小弯侧、胃角可见大小约为4.0 cm4.5 cm的溃烂面，边界不规则，中央可见结节样隆起，触之易出血(图1)。图1 胃镜显示胃窦部巨大溃疡，边界不规则(白色箭头)Figure 1 Gastroscope shows a large ulcer in the gastric antrum with irregular boundaries(white arrow)1597临床与病理杂志,2023,43(8)http:/入院后行全腹部增强CT检查，结果显示：胃窦部胃壁增厚，最厚处约为1.0 cm，增强CT呈明显强化；肝胃间隙内可见大小约为1.0 cm的结节状软组织影像，增强CT呈均匀强化(图2)。初步诊断为胃窦部恶性肿瘤，排除外科手术禁忌证后于2022年9月15日在全身麻醉下行腹腔镜下胃恶性肿瘤根治术。手术切除的远端胃送病理检查。大体检查结果示：远端胃标本大小约为11.0 cm5.0 cm2.5 cm，小弯长为6.0 cm，大弯长为11.0 cm；距上切缘0.5 cm、下切缘3.0 cm；大小约为4.5 cm5.5 cm1.0 cm的溃疡型肿物，似侵及深肌层；胃小弯触及结节18枚，最大径为0.12.0 cm，胃大弯触及结节11枚，最大径为0.11.2 cm(图3)。特殊染色结果示幽门螺杆菌(Helicobacter pylori，HP)阳性。原位杂交结果示Epstein-Barr编码区(Epstein-Barr encoding region，EBER)阴性。免疫组织化学染色示广谱细胞角蛋白(cytokeratin-Pan，CK-Pan)、表皮生长因子受体(epidermal growth factor receptor，EGFR)、P53(野生 型)、上 皮 膜 抗 原(epithelial membrane antigen，EMA)、细 胞 黏 附 分 子(cell adhesion molecule，CAM)、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(lymphocytes common antigen，LCA)和CD3均为部分阳 性，人 髓 细 胞 增 生 原 癌 基 因(cellular myelocytomatosis oncogene，C-myc)、细胞周期蛋白D1(cyclin D1)和CD5均为弱阳性，人类表皮生长因子受 体-2(human epidermal growth factor receptor-2，HER-2)、D20、CD10、多 发 性 骨 髓 瘤 癌 基 因 1(multiple myeloma oncogene 1，MUM1)、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(anaplastic lymphoma kinase，ALK)、配对盒蛋白 5(paired box protein 5，PAX5)、突 触 素(synapsin，Syn)、嗜铬粒蛋白 A(chromogranin A，CgA)、CD8、波形蛋白(Vimentin)、黑色素瘤相关抗原HMB45、黑色素 A(melanin A，Melan A)、神经特异性蛋白质 S-100、性 别 决 定 区 Y 框 蛋 白 10(sex determining region Y-box 10 protein，SOX10)、E-钙 黏 蛋 白 (E-cadherin，E-cad)、尾 侧 型 同 源盒转录因子-2(cadualtype homeobox transcription factor-2，CDX-2)、MUC-5ac、MUC-2 均为阴性(图 4)。苏 木 精-伊 红(hematoxylin and eosin，HE)染色结果示：肿瘤细胞核分裂活跃，可见病理性核分裂象(图5)。结合HE形态及免疫组织化学染色结果，考虑淋巴上皮瘤样癌。肿瘤大小为4.5 cm5.5 cm1.0 cm，侵及固有肌层，上、下切缘未见肿瘤细胞残留，未见确定的神经侵犯及脉管癌栓，29个淋巴结(其中小弯侧18个，大弯侧11个)均未见癌转移。TNM(tumor node metastasis)分期及病理分级为T2N0M0，IB期。患者术后第8天顺利出院。图2 患者腹部增强CT检查结果Figure 2 Images of abdominal Enhanced CT scanning of the patient A:Localized thickening of gastric wall in gastric antrum on plain scan CT;B:Uniform enhancement of gastric wall in gastric antrum on enhanced CT;C:Enhancement of gastric wall in gastric antrum on delayed phase CT.CT:Computer tomography.图3 手术后大体标本：胃窦部巨大溃疡，边缘隆起且不规则(白色箭头)Figure 3 Postoperative gross specimen:A large ulcer in the gastric antrum,with prominent and irregular margins(white arrow)1598EB病毒阴性胃淋巴上皮瘤样癌1例并文献复习 石万红，等图4 组织染色(200)Figure 4 Histological staining(200)A:Special staining shows HP positive;B:In situ hybridization shows EBER negative;CO:Immunohistochemistry staining shows CK-Pan(C),EGFR(D),p53(wild-type)(E),EMA(F),CAM5.2(G),MUC-6(H)positive;Ki-67(I)60%positive;LCA(J)and CD3(K)partially positive;C-myc(L),CyclinD1(M)and CD5(N)weakly positive;CDX-2(O)negative.HP:Helicobacter pylori;EBER:Epstein-Barr virus encoding region;CK-Pan:Cytokeratin-Pan;EGFR:Epidermal growth factor receptor;EMA:Epithelial membrane antigen;CAM:Cell adhesion molecule;MUC:Mucin;Ki-67:Antigens associated cell proliferation;LCA:Lymphocyte common antigen;C-myc:Cellular myelocytomatosis oncogene;CDX-2:Cadualtype homeobox transcription factor-2.1599临床与病理杂志,2023,43(8)http:/2 讨 论 LELGC是一种罕见的胃癌亚型，国内外文献中大多以个案的方式报道。癌症基因组图谱中将LELGC分为4个分子亚型：1)EBV阳性肿瘤，表现为极强的DNA甲基化；2)微卫星不稳定型肿瘤，表现为CpG岛甲基化表型和错配修复基因MLH1启动子甲基化；3)基因组稳定型肿瘤，含有 CDH1 和RHOA突变或CLDN18-ARHGAP融合；4)染色体不稳定型肿瘤，表现为非整倍体和频繁的TP53突变4。韩国癌症中心数据5显示：2006至2017年，LELGC的发病率呈上升趋势，且男性高于女性，5年生存率达93.4%，即使晚期LELGC的预后也较其他类型胃癌预后好。越来越多的证据3,5表明超80%的LELGC都存在EBER，但在本例患者中EBER为阴性。EBV也称为人类疱疹病毒4型，是一种172 kb的双链DNA病毒，包含 80 种蛋白质和 46 种功能性小 RNA 的表达产物6。EBV表现出双重嗜性，即感染淋巴和上皮细胞特性，在健康的上皮细胞中几乎检测不到，但全世界超过95%的人口感染过该病毒。EBV与多种上皮和淋巴恶性肿瘤密切相关，包括鼻咽癌、EBV阳性胃癌和肺组织的淋巴上皮瘤样癌、鼻自然杀伤/T细胞淋巴瘤、一些Burkitt淋巴瘤和霍奇金病6。在本例患者中，EMA、CAM、CK等上皮性标志物阳性表明来源于上皮组织；LCA阳性表明来源于淋巴造血细胞，由此确诊胃淋巴上皮瘤样癌。研究7发现LELGC与HER-2、CgA和Syn无关，这与本例患者中HER-2、CgA及Syn均阴性的结果相吻合。在另一项研究8中，75%的患者钙黏蛋白17阳性表达，50%的患者肠道上皮特异性转录因子CDX2阳性表达，而本例患者CDX2阴性表达。在EBV阳性肿瘤患者唾液中存在EBV并直接感染胃黏膜上皮细胞，或者在裂解阶段再活化，使得胃黏膜组织中的 B 淋巴细胞释放 EBV 感染上皮细胞9。促红细胞生成素产生的肝细胞受体A2、整合素和非肌肉肌球蛋白重链IIA作为辅助因子，在EBV进入上皮细胞中发挥重要作用。EBV感染的淋巴细胞通过整合素1/2与上皮细胞接触，并上调CAM以增加细胞间的接触9。病毒颗粒随后通过氯氰菊酯介导的内吞途径传播，并在胃上皮细胞中建立潜在感染9。EBV阳性肿瘤的分子特征是EBV驱动DNA超甲基化、频繁的磷脂酰肌醇-4,5-二磷酸3-激酶催化亚单位 突变以及 Janus 激酶(janus kinase，JAK)2、程 序 性 死 亡 受 体 配 体(programmed death-ligand，PD-L)1和PD-L2的过度表达10。EBV阳性肿瘤患者与较高的PD-L1表达相关，且磷脂酰肌醇3激酶/蛋白激酶B通路突变更常见11。细胞毒性T淋巴细胞在面对肿瘤细胞时分泌干扰素(interferon，IFN)-；然后，IFN-与这些肿瘤细胞上的IFN-受体结合，从而刺激JAK-信号转导及转录激活因子信号通路并过表达PD-L1。活化的免疫细胞如T细胞可以表达程序性死亡受体1(programmed death 1，PD-1)，与其配体PD-L1 结合，从而导致免疫细胞凋亡和免疫抑制。PD-L1在晚期胃癌中过度表达，导致肿瘤细胞逃避免疫反应，如果PD-L1受体被阻断，T细胞就会收到抑制信号，从而无法杀死肿瘤细胞12-13。LELGC患者高表达PD-L1，这表明PD-1/PD-L1抑制剂可能是免疫疗法的一个理想靶点8。CT 发现黏膜下肿块仅占肿块型胃癌的 9.1%，LELGC最常见的CT表现是偏心性壁增厚(占67.7%)，可以看到中央溃疡和增大的淋巴结，并伴有均匀强化14。坏死在淋巴上皮瘤样癌中并不常见，而具有生发中心的淋巴滤泡和瘤内嗜酸性粒细胞在淋巴上皮癌中最常见8。在早期胃癌中，淋巴间质浸润较深，但转移较少8。18F-氟代脱氧葡萄糖正电子发射计算机体层扫描术/CT可作为评价LELGC患者远处转移或复发的有效工具15。由于LELGC较为罕见，目前美国国立综合癌症网络指南并未有系统指出其治疗方法；因此通常参考胃腺癌来治疗。由于LELGC肿瘤边界较为明确，大多数患者处于相对早期的临床阶段，内镜黏膜下图5 肿瘤细胞核分裂活跃，可见病理性核分裂象(HE染色，200)Figure 5 Tumor cell nucleus division is active and pathological mitosis is observed(HE staining,200)HE:Hematoxylin and eosin.1600EB病毒阴性胃淋巴上皮瘤样癌1例并文献复习 石万红，等剥离或根治性手术切除仍然是早期胃癌的主要治疗方法16。局部晚期患者的治疗与其他类型的胃癌类似，包括围手术期化学药物治疗和一期切除。对于无手术根治机会的转移性晚期胃癌患者的治疗，目前公认应采取以全身抗肿瘤药物治疗为主的综合治疗。在免疫或靶向治疗进入一线治疗的时代，联合化学治疗(以下简称“化疗”)序贯维持治疗已经成为临床的主要选择。对于微卫星不稳定型的晚期胃癌患者，帕博利珠单抗或帕博利珠单抗联合化疗的疗效均优于单纯化疗17。Janjigian等18研究显示双免疫治疗或免疫联合化疗均优于单纯化疗。PD-1抑制剂纳武单抗作为单一疗法已被美国食品药品监督管理局和中国国家医疗产品管理局批准用于晚期非小细胞肺癌患者的二线治疗19。另一种PD-1抑制剂帕博利珠单抗作为单一疗法已被美国食品药品监督管理局和中国国家食品药品监督管理局批准用于晚期非小细胞肺癌、复发或晚期胃癌且表达PD-L1患者的一线治疗20。对于HER-2阴性和PD-L1综合阳性评分5的胃癌患者，建议使用纳武单抗和化疗进行一线治疗。对于先前未经治疗的HER-2阳性且不可切除或转移性胃癌患者，建议使用曲妥珠单抗加帕博利珠单抗，并联合化疗。对于在一线治疗后病情进展，建议使用雷莫西尤单抗加紫杉醇。对于HER-2阳性的胃癌患者，在一线治疗后病情进展，建议使用德曲妥珠单抗21。另一项研究10中，EBV阳性胃癌的预后优于EBV阴性胃癌。综上所述，LELGC是一种罕见的胃癌病理亚型，其发生大多与EBV感染相关。与普通型胃癌相比，LELGC预后较好，且EBV阳性胃癌预后优于EBV阴性胃癌。内镜黏膜下剥离或根治性切除术是早期LELGC的主要治疗方式，而晚期患者多采用姑息性治疗。LELGC 患者过度表达 PD-L1，这表明 PD-1/PD-L1抑制剂可作为LELGC的潜在治疗靶点，在未来可能有较好的治疗前景。利益冲突声明：作者声称无任何利益冲突。参考文献1Watanabe H,Enjoji M,Imai T.Gastric carcinoma with lymphoid stroma.Its morphologic characteristics and prognostic correlationsJ.Cancer,1976,38(1):232-243.https:/doi.org/10.1002/1097-0142(197607)38:13.0.co;2-4.2Pikua A,Kwietniewska M,Rawicz-Pruszyski K,et al.The importance of Epstein-Barr virus infection in the systemic treatment of patients with gastric cancerJ.Semin Oncol,2020,47(2/3):127-137.https:/doi.org/10.1053/j.seminoncol.2020.04.001.3Guimaraes N,Bolais Monica I,Oliveira S,et al.Lymphoepithelioma-like gastric carcinoma and gastric involvement of chronic lymphocytic leukemia:two rare identities coexisting in one patientJ.J Med Cases,2022,13(1):36-39.https:/doi.org/10.14740/jmc3846.4Huang SC,Ng KF,Yeh TS,et al.Subtraction of Epstein-Barr virus and microsatellite instability genotypes from the Lauren histotypes:combined molecular and histologic subtyping with clinicopathological and prognostic significance validated in a cohort of 1,248 casesJ.Int J Cancer,2019,145(12):3218-3230.https:/doi.org/10.1002/ijc.32215.5Kim JW,Kim JH,Kim HM.Incidence and survival rates of lymphoepithelioma-like gastric carcinoma:analysis of the Korea Central Cancer Registry DatabaseJ.Scand J Gastroenterol,2021,56(10):1182-1186.https:/doi.org/10.1080/00365521.2021.1955966.6Li L,Ma BBY,Chan ATC,et al.Epstein-barr virus-induced epigenetic pathogenesis of viral-associated lymphoepithelioma-like carcinomas and natural killer/T-cell lymphomasJ.Pathogens,2018,7(3):63.https:/doi.org/10.3390/pathogens 7030063.7Ramos MFKP,Pereira MA,Dias AR,et al.Lymphoepithelioma-like gastric carcinoma:clinicopathological characteristics and infection statusJ.J Surg Res,2017,210:159-168.https:/doi.org/10.1016/j.jss.2016.11.012.8Gonzalez RS,Cates JMM,Revetta F,et al.Gastric carcinomas with lymphoid stroma:categorization and comparison with solid-type colonic carcinomasJ.Am J Clin Pathol,2017,148(6):477-484.https:/doi.org/10.1093/ajcp/aqx096.9Han S,Tay JK,Loh CJL,et al.Epstein-Barr virus epithelial cancers-a comprehensive understanding to drive novel therapiesJ.Front Immunol,2021,12:734293.https:/doi.org/10.3389/fimmu.2021.734293.10Yang J,Liu Z,Zeng B,et al.Epstein-Barr virus-associated gastric cancer:A distinct subtypeJ.Cancer Lett,2020,495:191-199.https:/doi.org/10.1016/j.canlet.2020.09.019.11Fang WL,Chen MH,Huang KH,et al.The clinicopathological features and genetic alterations in epstein-barr virus-associated gastric cancer patients after curative surgeryJ.Cancers(Basel),2020,12(6):1517.https:/doi.org/10.3390/cancers 12061517.12Jin X,Liu Z,Yang D,et al.Recent progress and future perspectives of immunotherapy in advanced gastric cancerJ.Front Immunol,2022,13:948647.https:/doi.org/10.3389/fimmu.2022.948647.13Zhao Q,Cao L,Guan L,et al.Immunotherapy for gastric cancer:dilemmas and prospectJ.Brief Funct Genomics,2019,18(2):107-112.https:/doi.org/10.1093/bfgp/ely019.1601临床与病理杂志,2023,43(8)http:/14Kim C,Kim HJ,Son da H,et al.Computed tomography findings for a gastric lymphoepithelioma-like carcinoma:How often does it present as a submucosal mass?J.Eur Radiol,2016,26(9):3077-3085.https:/doi.org/10.1007/s00330-015-4122-4.15Park S,Lee D,Lee KM,et al.Clinical usefulness of F-18 FDG PET in lymphoepithelioma-like gastric carcinomaJ.Eur J Radiol,2017,94:160-166.https:/doi.org/10.1016/j.ejrad.2017.06.022.16Xu Q,Du J,Liu B.Lymphoepithelioma-like gastric carcinoma located in the lesser curvature of the gastric body:A case report and review of the literatureJ.Mol Clin Oncol,2016,4(3):405-408.https:/doi.org/10.3892/mco.2015.717.17Shitara K,van Cutsem E,Bang YJ,et al.Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line,advanced gastric cancer:the KEYNOTE-062 phase 3 randomized clinical trialJ.JAMA Oncol,2020,6(10):1571-1580.https:/doi.org/10.1001/jamaoncol.2020.3370.18Janjigian YY,Shitara K,Moehler M,et al.First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric,gastro-oesophageal junction,and oesophageal adenocarcinoma(CheckMate 649):a randomised,open-label,phase 3 trialJ.Lancet,2021,398(10294):27-40.https:/doi.org/10.1016/S0140-6736(21)00797-2.19Cui Q,Wu H,Zeng W,et al.Comprehensive genomic profiling and PD-L1 expression of primary lymphoepithelioma-like carcinoma of the stomach and parotid glandJ.Ann Transl Med,2022,10(1):13.https:/doi.org/10.21037/atm-21-5908.20Seeneevassen L,Bessde E,Mgraud F,et al.Gastric cancer:advances in carcinogenesis research and new therapeutic strategiesJ.Int J Mol Sci,2021,22(7):3418.https:/doi.org/10.3390/ijms22073418.21Shah MA,Kennedy EB,Alarcon-Rozas AE,et al.Immunotherapy and targeted therapy for advanced gastroesophageal cancer:ASCO guidelineJ.J Clin Oncol,2023,41(7):1470-1491.https:/doi.org/10.1200/JCO.22.02331.（本文编辑 宋柳、郭征）本文引用：石万红,陈新民,李娟,刘晓明,徐开军,贺琳,孙建军.EB病毒阴性胃淋巴上皮瘤样癌1例并文献复习J.临床与病理杂志,2023,43(8):1596-1602.DOI: