<scp>E</scp>pstein–<scp>B</scp>arr virus‐associated lymphoepithelioma‐like cholangiocarcinoma: a rare variant of intrahepatic cholangiocarcinoma with favourable outcome

Chan, Anthony W.H.; Tong, Joanna H.M.; Sung, Mandy Y M; Lai, Paul Bs; To, Ka‐Fai

doi:10.1111/his.12455

Cited by 61 publications

(88 citation statements)

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“…1 Although a small subset of HCC may express CK19, CD133, and/or EpCAM, LEL-CC does not demonstrate any hepatocellular differentiation evident by typical histology and negative immunoreactivity to hepatic markers (HepPar-1 and Arginase-1). However, a few differential diagnoses, including LEL-CC, metastatic LELC from other sites, and lymphoma, may need to be considered.…”

Section: Discussionmentioning

confidence: 85%

“…Firstly, EBV has been shown to be associated with many LELCs. 1 Is there any association between LEL-HCC and EBV? 18 Pulmonary and gastric LELCs in Asian populations show strong associations with EBV.…”

Section: Discussionmentioning

confidence: 99%

“…1 In contrast, LEL-HCC has not been well characterized yet. The tumors, which develop outside of the nasopharynx and exhibit the morphology of lymphoepithelioma, are designated as lymphoepithelioma-like carcinomas (LELCs).…”

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confidence: 99%

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Lymphoepithelioma-like Hepatocellular Carcinoma

Chan¹,

Tong²,

Pan³

et al. 2015

American Journal of Surgical Pathology

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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.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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Lymphoepithelioma-like Hepatocellular Carcinoma

Chan¹,

Tong²,

Pan³

et al. 2015

American Journal of Surgical Pathology

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“…LEL‐HCC was defined as HCC with abundant TILs (>100 in a ×400 high‐power‐field). The possibility of LEL‐cholangiocarcinoma was excluded by using the morphology (in absence of mucin production, glandular differentiation or specific morphological features of combined hepatocellular‐cholangiocarcinoma of both classical type and subtypes with stem‐cell features), the immunoreactivity towards markers of hepatocellular differentiation, and the absence of EBER‐ISH . Clinicopathological characteristics are summarized in supplementary material, Table S1.…”

Section: Methodsmentioning

confidence: 99%

Genomic landscape of lymphoepithelioma‐like hepatocellular carcinoma

Chan¹,

Zhang²,

Chong

et al. 2019

The Journal of Pathology

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Lymphoepithelioma‐like hepatocellular carcinoma (LEL‐HCC) is a distinct variant of HCC that is characterized by dense tumor‐infiltrating lymphocytes (TILs). Patients with LEL‐HCC also show better clinical outcomes compared to conventional HCC (c‐HCC), which is commonly presented with low TIL. Emerging evidence has begun to highlight tumor‐intrinsic genetic abnormalities in the tumor–host immune interfaces. However, genome‐wide characterization of LEL‐HCC remains largely unexplored. Here, we defined the genomic landscape of 12 LEL‐HCC using whole‐exome sequencing, and further underpinned those genetic alterations related to an immune active microenvironment by comparing findings to 15 c‐HCC that were sequenced in parallel. Overall, the mutational load between LEL‐HCC and c‐HCC was similar. Interestingly, SNV incidences of specific genes (CTNNB1, AXIN1, NOTCH1, and NOTCH2) were significantly higher in c‐HCC than LEL‐HCC, suggesting a plausible link between activated Wnt/β‐catenin and Notch signaling pathways and immune avoidance. Marked focal amplification of chromosome 11q13.3 was prevalent in LEL‐HCC. Using The Cancer Genome Atlas dataset, we further established oncogenes expressed from chromosome 11q13.3 (CCND1, FGF19, and FGF4) to be strongly associated with the immune checkpoint signature (CD274, PDCD1, BTLA, CTLA4, HAVCR2, IDO1, and LAG3). Our results have illustrated for the first time the somatic landscape of LEL‐HCC, and highlighted molecular alterations that could be exploited in combinatory therapy with checkpoint inhibitors in targeting HCC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…Studies have postulated that certain Chineserelated human leukocyte antigen profiles conferred genetic susceptibility leading to reduced efficiency in activating the host immune response to EBV infection. 29 Childhood consumption of salted fish has also been shown to be related to an increased risk of NPC in southern Chinese people. 1…”

Section: Discussionmentioning

confidence: 99%

Coexistence of Two Epstein-Barr Virus–associated Malignancies: Lymphoepithelioma-like Cholangiocarcinoma in a Patient with a History of Undifferentiated Nasopharyngeal Carcinoma

Tai¹,

Ngan²,

Ting³

2015

Hong Kong J Radiol

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Undifferentiated nasopharyngeal carcinoma is particularly common in Southern China and is consistently associated with Epstein-Barr virus. In contrast, lymphoepithelioma-like carcinoma of the bile duct is a rare disease and not always associated with Epstein-Barr virus. We report the first case of coexisting Epstein-Barr virus-associated nasopharyngeal carcinoma and lymphoepithelioma-like carcinoma of the bile duct in aChinese patient. 中文摘要兩種Epstein-Barr病毒相關惡性腫瘤並存：一名有未分化鼻咽癌病史的病人併發淋巴上皮瘤樣膽管癌戴燕萍、顏繼昌、丁信顯未分化鼻咽癌在南中國地區特別常見，發病通常與Epstein-Barr病毒相關。相反，淋巴上皮瘤樣膽管癌是一種罕見疾病，且不一定與Epstein-Barr病毒相關。本文報告首個併發Epstein-Barr病毒相關性鼻咽癌和淋巴上皮瘤樣膽管癌的華籍病例。

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Epstein–Barr virus‐associated lymphoepithelioma‐like cholangiocarcinoma: a rare variant of intrahepatic cholangiocarcinoma with favourable outcome

Abstract: Epstein-Barr virus-associated LELCC is a variant of IHCC, characterized by marked female predominance, favourable overall survival and distinctively frequent DNA hypermethylation.

Cited by 61 publications

References 32 publications

Lymphoepithelioma-like Hepatocellular Carcinoma

Lymphoepithelioma-like Hepatocellular Carcinoma

Genomic landscape of lymphoepithelioma‐like hepatocellular carcinoma

Coexistence of Two Epstein-Barr Virus–associated Malignancies: Lymphoepithelioma-like Cholangiocarcinoma in a Patient with a History of Undifferentiated Nasopharyngeal Carcinoma

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