原发性肺淋巴上皮瘤样癌31例临床特点分析

Clinical characteristics of primary pulmonary lymphoepithelioma-like carcinoma:analysis of 31 cases

目的提高对原发性肺淋巴上皮瘤样癌(PPLELC)的认识。方法回顾性病例系列研究。回顾性分析2012年1月至2023年6月在广西医科大学第一附属医院就诊的31例PPLELC患者的临床资料,总结其临床特征,分析器官转移、肿瘤分期、血清肿瘤标志物、乳酸脱氢酶、清蛋白等与生存时间的相关性。结果31例患者中,男性13例(41.9%),女性18例(58.1%),年龄(50±9)岁,无吸烟史24例(77.4%),常见临床表现为咳嗽(24例,77.4%)、咳痰(19例,61.3%),7例(22.6%)患者由体检发现;24例(77.4%)血清肿瘤标志物水平升高,其余7例(22.6%)各肿瘤标志物水平正常;所有患者均为单发病灶,右中肺多见(8例,25.8%);淋巴结转移23例(74.2%)。免疫组织化学检测CK阳性率为67.7%(21/31),鳞状细胞癌标志物CK5/6、p63、p40阳性率分别为90.3%(28/31)、80.6%(25/31)、77.4%(24/31),EBER原位杂交检测阳性率85.2%(23/27)。基因检测6例表皮生长因子受体(EGFR)突变。无淋巴结转移组与淋巴结转移组中位生存时间[M(Q1,Q3)]分别为33.0个月(7.3个月,9.3个月)、19.0个月(7.0个月,27.0个月),差异有统计学意义(P<0.001)。Ⅰ~Ⅱ期与Ⅲ~Ⅳ期患者中位生存时间分别为20.0个月(12.5个月,42.0个月)、18.5个月(6.5个月,38.5个月),差异有统计学意义(P=0.002)。1例ⅠA期患者采用单纯手术治疗,随访92个月仍生存。10例采用免疫治疗,疗效较好。结论PPLELC好发于不吸烟人群,病灶多发于右中肺,易被误诊为鳞状细胞癌,EBER原位杂交检测阳性有助于诊断,淋巴结转移常见;肿瘤分期、淋巴结转移及CYFRA21-1水平与患者生存可能相关;患者可从免疫治疗中获益,抗血管生成联合化疗是一种可选的治疗方案。

Objective To improve the understanding of primary pulmonary lymphoepithelioma-like carcinoma(PPLELC).Methods A retrospective case series study was conducted.The clinical data of 31 patients with PPLELC who were admitted to the First Affiliated Hospital of Guangxi Medical University from January 2012 to June 2023 were retrospectively analyzed,and their clinical features were summarized.The correlations of organ metastasis,tumor stage,serum tumor markers,lactate dehydrogenase,and albumin with survival time were analyzed.Results Among the 31 patients,13(41.9%)were male and 18(58.1%)were female,aged(50±9)years old,with no smoking history in 24 cases(77.4%).The common clinical manifestations were cough(24 cases,77.4%)and sputum(19 cases,61.3%),and 7 patients(22.6%)were detected by physical examination;24 cases(77.4%)had elevated levels of serum tumor markers,and the rest of the 7 cases(22.6%)had normal levels of various tumor markers.All of the patients had a single lesion,with a predominance of the right middle lung(8 cases,25.8%),and 23 cases(74.2%)had lymph node metastasis.Immunohistochemical detection showed that the positive rate of CK was 67.7%(21/31),and the positive rates of squamous cell carcinoma markers CK5/6,p63 and p40 were 90.3%(28/31),80.6%(25/31)and 77.4%(24/31),respectively.The positive rate of EBER in situ hybridization detection was 85.2%(23/27).Genetic testing showed 6 cases had epidermal growth factor receptor(EGFR)mutation.The median survival time[M(Q1,Q3)]of the groups without lymph node metastasis and with lymph node metastasis was 33.0 months(7.3 months,9.3 months)and 19.0 months(7.0 months,27.0 months),and the difference was statistically significant(P<0.001).The median survival time of patients with stage Ⅰ-Ⅱ and with stage Ⅲ-Ⅳ was 20.0 months(12.5 months,42.0 months)and 18.5 months(6.5 months,38.5 months),and the difference was statistically significant(P=0.002).One stageⅠA patient was treated with surgery alone and survived at 92 months of follow-up.Ten cases were treated with immunotherapy and had a good outcome.Conclusions PPLELC is prevalent in non-smokers,the lesions are mostly in the right middle lung,and it is easily misdiagnosed as squamous cell carcinoma.The positive EBER in situ hybridization detection can help the diagnosis;lymph node metastasis is common.Tumor stage,lymph node metastasis and CYFRA21-1 level may be correlated with the survival of patients.The patients can benefit from immunotherapy,and anti-angiogenic therapy combined with chemotherapy is an optional treatment regimen.