肝内淋巴上皮瘤样胆管细胞癌临床病理分析

Clinicopathological analysis of intrahepatic lymphoepithelioma-like cholangiocarcinoma

目的:探讨肝内淋巴上皮瘤样胆管细胞癌(intrahepatic lymphoepithelioma-like cholangiocarcinoma,LEL-ICC)的临床、病理学特征,诊断、鉴别诊断及预后。方法:收集2014年至2019年厦门大学附属中山医院诊治的7例LEL-ICC患者的临床及病理资料,采用免疫组织化学及原位杂交方法标记肿瘤细胞,分析其临床、病理形态学特征及预后等,并与其他疾病进行鉴别诊断。结果:7例LEL-ICC中4例女性、3例男性;平均年龄60.7(49~71)岁,其中1例因右上腹痛发现,余6例均于体检中发现。肝左、右叶均可发生,多单发,最大径13~45 mm,肉眼界限尚清,无包膜,切面灰白,质地中等。镜下肿瘤组织可向周围肝组织浸润性生长,一般多呈片巢状、条索状或单细胞样,可有不同程度的腺管分化。肿瘤细胞较大,立方形,胞界不清呈合体样,胞浆丰富、均质粉染或略嗜伊红,核圆形或卵圆形,呈空泡状,可见小核仁及核分裂像。间质伴大量成熟淋巴细胞、浆细胞浸润,可形成淋巴滤泡,呈多克隆性。周围肝组织呈间质性肝炎改变。肿瘤细胞免疫组织化学CK7、CK8/18、CK19阳性,可表达CEA、CD10,一般不表达Hep-Par1、Arginase-1、AFP、Glypican-3、CDX-2、CK20、Vimentin等,Ki-67阳性率为20%~30%。绝大多数病例肿瘤细胞EBER原位杂交呈阳性。平均随访45.9个月,均无复发或转移。结论:LEL-ICC多发生于中老年人,临床多无症状。其病理形态学类似鼻咽部淋巴上皮癌,但有腺体分化。其明确诊断主要依赖于病理组织学并辅以免疫组织化学、原位杂交。LEL-ICC预后好于经典型肝内胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)。需与其他组织学类型的ICC、转移性淋巴上皮瘤样癌、淋巴上皮瘤样肝细胞癌等鉴别诊断。

Objective:To discuss the clinical and pathological features,diagnosis,differential diagnosis,and prognosis of intrahepatic lymphoepithelioma-like cholangiocarcinoma(LEL-ICC).Methods:The clinical and pathological data of seven cases of LEL-ICC treated in Zhongshan Hospital,Xiamen University,from 2014 to 2019 were collected.Tumor cells were detected using immunohistochemistry and in situ hybridization,and the clinical and pathological morphological features and prognosis were analyzed.Finally,the differential diagnosis was obtained.Results:This study included seven patients with LEL-ICC(four women and three men);the mean age was 60.7(49-71)years.Only one patient had right upper-quadrant abdominal pain,while the remaining six patients underwent physical examination without obvious clinical symptoms.LEL-ICC occurred in both the left and right lobes of the liver,mostly unilaterally,with a maximum diameter of(13-45)mm.Grossly,LEL-ICC was usually circumscribed with a gray,homogeneous,firmly cut surface,without an envelope.Microscopically,the tumor tissue could grow infiltratively into the surrounding liver tissue,usually presenting as lamellar nests,streaks,or unicellular-like,with varying degrees of glandular differentiation.Tumor cells were large and cuboidal,with poorly defined cell boundaries in a syncytial pattern,abundant cytoplasm,homogeneous,pinkish or slightly eosinophilic,and vacuolated,rounded or oval nuclei,usually with a small nucleolus and few mitotic figures.The stroma was infiltrated with a large number of mature,polyclonal lymphocytes and plasma cells,and lymphoid follicle formation could be present.The surrounding liver tissue showed interstitial hepatitis changes.Tumor cells were positive for CK7,CK8/18,CK19 by immunohistochemistry,and could express CEA and CD10 but generally not express Hep-Par1,Arginase-1,AFP,Glypican-3,CDX-2,CK20,Vimentin,etc.The Ki-67 labelling index was usually 20%-30%.EBER was positive in most cases by in situ hybridization.Recurrence or metastasis was not observed with a mean follow-up of 45.9 months.Conclusions:LEL-ICC occurs mostly in middle-aged and elderly individuals and is often clinically asymptomatic.Its pathological morphology is similar to that of nasopharyngeal lymphoepithelial carcinoma but with glandular differentiation.The final diagnosis mainly depends on histopathology,immunohistochemistry and in situ hybridization.The prognosis of LEL-ICC is better than that of classical intrahepatic cholangiocarcinoma(ICC)and should be differentiated from other histological types of ICC,metastatic lymphoepithelioma-like carcinoma,and lymphoepithelioma-like hepatocellular carcinoma.