Clinicopathological features of 11 Epstein–Barr virus-associated intrahepatic cholangiocarcinoma at a single center in China

Abstract

To date, only 20 cases of Epstein–Barr virus (EBV)-associated intrahepatic cholangiocarcinomas (IHCCs) have been reported in the literature.Pathology records of IHCC from January 1, 2007 to December 31, 2013 were retrieved from our hospital. Clinical information related to EBV-associated IHCC were also obtained, including gender, age at initial diagnosis, tumor size, tumor–node–metastasis stage, and follow-up duration. Surgically resected stage-matched EBV-negative IHCCs with full follow-up were selected for comparison. All liver specimens were fixed in 10% neutral-buffered formalin and paraffin-embedded tissue blocks containing cholangiocarcinoma and nonneoplastic liver tissue. Hematoxylin and eosin-stained sections were present in all cases.Among 329 primary IHCC patients, intranuclear expression of EBV was only found in 11 patients (3.3%), with an age range of 30 to 67 years (mean, 53.2 years; median, 54 years). The group consisted of 4 male and 7 female patients (M:F ratio 1:1.8). Histopathological analysis showed 1 case (9.1%) belonged to the typical lymphoepithelioma-like carcinoma (LELC), primarily composed of undifferentiated tumor cells intimately admixed with abundant lymphoplasmacytic cells. Two cases (18.2%) belonged to the conventional-type IHCCs, showing irregularly shaped neoplastic glands and scattered lymphoplasmacytic infiltration. The remaining 8 cases (72.7%) belonged to the lymphoepithelioma-like cholangiocarcinomas (LELCCs), showing varied glandular differentiation and dense lymphoplasmacytic infiltration. The overall survival of EBV-positive IHCCs was not significantly different from that of EBV-negative IHCCs (P = 0.512).Our data demonstrate that EBV-associated IHCC is very rare and may be subclassified into 3 different pathological types including LELC, conventional-type IHCC and LELCC on the basis of the tumor cellular differentiation, and host cellular immune responses in the tumors. The etiological, clinical, pathological, and molecular features are needed to be future studied by multicentric efforts in recruiting more EBV-associated IHCC patients.

Lymphoepithelioma-like cholangiocarcinoma in middle-aged woman with Epstein-Barr Virus infection: a case report and review of the literature

“…The size of LELCC tumors ranged from 1.2 to 7.3 cm in diameter (mean, 3. 3 cm) [12,18].Clinical symptoms were nonspecifific, usually found incidentally or abdominal fullness and abdominal pain [10]. In our study,EBV were positive in situ hybridization and HBV and HCV were both negative in a Chinese middle-aged woman, Clinical information was similar to previous reports.…”

“…Epidemiology and clinical characteristics: EBV-associated ICC is very rare and can be divided into 3 types: LELC, conventional-type ICC and LELCC on the basis of the tumor cellular differentiation, and host cellular immune responses in the tumors [12].Indicating that LELCC, which was first reported by Jeng et al [13] in 2001, is a rare variant of ICC. Literature reported, EBER in situ hybridisation was positive in 70% of LELCC cases, while conventional cholangiocarcinomas are not associated with EBV infection [13] According to previous studies, 26 cases of LELCC was analyzed, found that 73.1% (19 of 26) patients were EBV-positive [1,8].These results suggested that LELCC is highly associated with Epstein-Barr virus (EBV) infection [14] and EBV infection might promote the development of LELCC.…”

“…The published literatures reported that majority of LELCC patients were discovered in the Asian countries [11,13,16]. LELCC with EBV infection tends to occur in middle-aged women with a female:male ratio of more than 3:1, the range of age was 19 to 71 years (mean age, 53.39 years) [8][9][10][11][12]. No preference in the tumor location was found between the left and the right hepatic lobe [17].…”

The tumour microenvironment and immune milieu of cholangiocarcinoma

“…EBERs were positive in almost all cases, latency membrane proteins-1 and -2 (LMP1 and LMP2) were negative in eight tested samples, and LMP-related gene showed a 30 bp deletion in two tested cases. 137,138 Thus, similar to nasopharyngeal carcinoma, the expression of EBV-related antigens and tumour genetics might drive the lymphocyte recruitment. Expression of PD-L1 has been studied in LEL-CCA and compared with iCCA, showing a much higher rate in LEL-CCA in both tumour and tumour-infiltrating cells, though the latter were not specifically phenotyped.…”

Surgical treatment for metastasis from lymphoepithelioma-like cholangiocarcinoma in the liver

“…Further studies were required to investigate the relation between EBV and LEL-CC. [ 4 ] We observed that the average followed month of EBV positive and negative was, respectively, 42.4 months and 20.4 months, which may show that EBV infection can be protective aspect for LEL-CC. The case we reported was positive for EBV, and the patient had 3 years survival after the first surgery.…”