Objective: To analyze the pathological features and their influence on the clinical outcome of non-nasopharyngeal EBV-associated carcinomas. Methods: One hundred and twenty cases of non-nasopharyngeal EBV-associated carcinoma confirmed by in situ hybridization were identified at Zhejiang Cancer Hospital from January 1, 2006 to May 1, 2018, and the clinicopathological data were collected and analyzed using Kaplan-Meier survival analysis, Cox univariate and multivariate analysis. Results: One hundred and twenty cases were involved in the study; the male to female ratio was 1∶1; patients' age range was 24 to 89 years (median 50 years). The primary sites were large parotid glands (62 cases), lung(26 cases), stomach(15 cases), and others (oral, oropharynx, larynx, cervix, liver; totally 17cases). Non-nasopharyngeal EBV-associated cancer could be divided into two histological types according to the amount of interstitial lymphocytes: type Ⅰ was "lymphoepithelial-like carcinoma" and rich in stromal lymphocytes; type Ⅱ lacked lymphocytic infiltration. Ninety-eight primary tumor samples could be classified morphologically: 43 cases were as type Ⅰ and 55 cases as typeⅡ; the distribution of type Ⅰ was 57.4% (27/47) in large parotid glands, 20.8% (5/24) in lung, 4/13 in stomach, and 7/14 in other sites. Complete treatment and survival data were obtained for 114 patients. According to the TNM staging criteria of WHO, 52 patients were at early stages (Ⅰ-Ⅱ) and 62 were at advanced stages (Ⅲ-Ⅳ); 102 patients underwent surgery. Seventy-four patients received adjuvant chemotherapy before or after surgery, and 52 patients received local radiotherapy. Kaplan-Meier survival analysis showed that patients with type Ⅱ EBV-associated carcinoma had a worse prognosis than patients with type Ⅰtumors (P=0.010 2). In addition, vascular invasion(P=0.021 8),neural recidivism(P=0.000 1),advanced stage(P=0.017 1),lymph node metastasis (P=0.005 0) and chemotherapy (P=0.013 2) were poor prognostic factors; female patients had better survival than male (P=0.028 4). Cox multivariate regression analysis found that lymph node metastasis (95%CI: 1.489-13.830, P=0.007 6) and neural recidivism (95%CI: 1.228-6.544, P=0.014 7) were independent adverse prognostic factors. Cox multivariate regression analysis after stratification by site revealed that radiotherapy was a preferable prognostic factor for EBV-associated carcinoma of the large salivary glands (95%CI: 0.003-0.569, P=0.016 8). Conclusion: EBV associated carcinoma can be divided into two types, for which type Ⅰ was with abundant interstitial lymphocytes and type Ⅱ was lack of interstitial lymphocytes. TypeⅡ EBV-associated carcinoma has a worse prognosis than type Ⅰ. Radiation therapy can prolong the survival time of patients with primary EBV-associated carcinoma of large salivary glands.
目的： 探讨非鼻咽部EB病毒（EBV）相关性癌的临床病理学特征及其与预后的关系。 方法： 收集浙江省肿瘤医院2006年1月1日至2018年5月1日期间120例发生在非鼻咽部的经原位杂交证实的EBV相关性癌患者的病理及临床资料，对其进行形态学分型，并对相关数据进行生存分析、Cox多因素回归分析。 结果： 男性60例，女性60例，男女比例为1∶1，发病年龄24~89岁，中位年龄50岁。原发部位按发病率高低依次为大涎腺62例、肺26例、胃15例、其他少见部位（口腔、口咽、喉部、宫颈、肝脏）共17例。按间质淋巴细胞的多寡可以大致分为两种组织学类型：Ⅰ型为间质富于淋巴细胞间质的"淋巴上皮样癌（LELC）"，Ⅱ型为间质缺乏淋巴细胞间质的上皮性癌。可以进行形态学分型的原发肿瘤样本共98例，Ⅰ型43例，Ⅱ型55例；各部位Ⅰ型EBV相关性癌所占比例依次为：大涎腺57.4%（27/47）、肺20.8%（5/24）、胃（4/13），其他少见部位（7/14）。114例患者具有完整的临床治疗信息及生存数据，按照WHO各系统TNM分期标准评价，早期（Ⅰ~Ⅱ）患者52例，进展期（Ⅲ~Ⅳ）患者62例；102例患者接受了手术，74例患者接受术前或术后的辅助化疗，52例患者接受了局部放疗。生存分析发现Ⅱ型患者预后较Ⅰ型预后差（P=0.010 2），脉管瘤栓（P=0.021 8）、神经累犯（P=0.000 1）、进展期（P=0.017 1）、淋巴结转移（P=0.005 0）、化疗（P=0.013 2）均为不良预后因素；女性患者生存率优于男性（P=0.028 4）。Cox多因素回归分析发现，淋巴结转移（95%CI：1.489~13.830，P=0.007 6）和神经累犯（95%CI：1.228~6.544，P=0.014 7）为独立的预后不良因素。按部位分层后做Cox多因素回归分析发现，放射治疗是大涎腺EBV相关性癌的良好预后因素（95%CI：0.003~0.569，P=0.016 8）。 结论： EBV相关性癌可分为间质富于淋巴细胞的Ⅰ型及间质缺乏淋巴细胞的Ⅱ型。Ⅱ型EBV相关性癌较Ⅰ型预后差。放射治疗可以延长涎腺原发的EBV相关性癌患者的生存时间。.
Keywords: Herpesvirus 4, human; Pathology, clinical; Prognosis.