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Lymphoepithelioma-like Hepatocellular Carcinoma: An Uncommon Variant of Hepatocellular Carcinoma With Favorable Outcome.

淋巴上皮样肝细胞癌:一种预后较好的肝细胞癌少见亚型

Chan AW,Tong JH,Pan Y,Chan SL,Wong GL,Wong VW,Lai PB,To KF

Abstract

Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is an uncommon variant of HCC with only 22 cases reported in the literature. To better determine the incidence, clinicopathologic features, prognostic significance, and molecular pathogenesis of LEL-HCC, we presented the largest series of LEL-HCC from a 9-year retrospective cohort of patients with HCC undergoing surgical resection. LEL-HCC was identified in 20 patients (4.9%). Compared with patients having HCC without significant tumor-infiltrating lymphocyte (TIL), patients with LEL-HCC had a relatively lower frequency of male sex (P=0.022), tended to present at early-stage disease (80.0% vs. 56.3% as AJCC stage I, P=0.037; 100% vs. 77.3% as BCLC stage 0/A, P=0.010), and all harbored a solitary tumor only (P=0.006). There was no significant difference in the age at presentation, underlying chronic liver disease, cirrhotic background, serum α-fetoprotein level, tumor size, histologic grade, and frequencies of vascular invasion. Most of the TILs in LEL-HCC were cytotoxic T lymphocytes. None of the LEL-HCCs was associated with Epstein-Barr virus. LEL-HCC was associated with better overall (5-y survival: 94.1% vs. 63.9%; P=0.007) and progression-free (5-y survival: 87.8% vs. 46.6%; P=0.002) survivals compared with HCC without significant TIL. The multivariate analysis revealed that LEL-HCC was an independent prognostic factor for overall and progression-free survivals. The adjusted hazard ratio of cancer death and tumor progression for LEL-HCC was 0.12 (P=0.037) and 0.14 (P=0.002), respectively. LEL-HCC did not differ in frequencies of microsatellite instability, BRAF mutation, and DNA hypermethylation. In brief, LEL-HCC is a distinct uncommon variant of HCC characterized by dense cytotoxic T-cell infiltration and favorable prognosis.

摘要

淋巴上皮样肝细胞肝癌(LEL-HCC)是肝癌的少见变异型,文献仅有22例报道。为更好的认识其发病率、临床病理特征、预后意义及分子发病机理,我们研究了一个目前最大的LEL-HCC病例组,该病例组得自一个因肝癌而做外科切除的9年回顾性研究病例群。LEL-HCC有20例(4.9%)。相比无显著淋巴细胞浸润的肝癌来说,LEL-HCC中男性发病率较低(p=0.022)、疾病分期较早(AJCCI期:80%vs56.3%,p=0.037;BCLC0/A期:100%vs77.3%,p=0.010)、仅有单一结节(P=0.006)。而在患者年龄、基础性肝疾病、硬化性背景、血清AFP水平、肿瘤大小、组织学分级及血管浸润比例等方面两者没有显著差异。LEL-HCC中的大部分浸润性淋巴细胞为细胞毒性T淋巴细胞。没有发现LEL-HCC与EB病毒相关。相比无显著淋巴细胞浸润的肝癌,LEL—HCC具有较好的总体存活率(5年存活率:94.1%vs63.9%;p=0.007)及无疾病进展存活率(5年存活率:87.8%vs46.6%;p=0.002)。多变量分析表明LEL-HCC是肝癌总体及无疾病进展存活率的独立预后因子。LEL-HCC的死亡及进展校正风险比分别为0.12(p=0.037)及0.14(p=0.002)。LEL-HCC在微卫星不稳定、BRAF突变和DNA过甲基化的发生频率上无差异。总之,LEL-HCC是一种独特的少见肝细胞癌变异亚型,其显著特点是有致密的细胞毒性T细胞浸润及预后较好。

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