Epstein - Barr virus - associated lymphoepithelioma - like intrahepatic cholangiocarcinoma: A report of 3 cases and literature review

Abstract

Hepatic lymphoepithelioma-like carcinoma (LELC) is an extremely rare malignant tumor characterized by undifferentiated malignant epithelial cells and significant lymphatic infiltration. Hepatic LELC mainly includes lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) and lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-CC). Epstein-Barr virus (EBV) infection is considered as an important factor in LELC carcinogenesis. Since 2005, Xiangya Hospital of Central South University has treated a total of 3 patients with EBV-associated LEL-CC, which all showed liver masses by CT scans. After surgical resection, the EBV encoded RNA (EBER) and CK19 expression in all 3 patients were positive, and pathological examination confirmed EBV-associated LEL-CC. Two patients had a good postoperative prognosis, while 1 patient received relevant immunotherapy and chemotherapy after surgery. Based on the analysis of existing literature, the author believes that hepatic LELC can be included in the classification of liver tumors, which will provide new ideas for the accurate diagnosis and treatment of hepatic LELC.

Keywords: Epstein-Barr virus; hepatocellular carcinoma; lymphoepithelioma like intrahepatic cholangiocarcinoma; lymphoepithelioma-like carcinoma.

Figure 1. Preoperative CT findings and microscopic findings of the resected liver of the 48-year-old female patient with Epstein-Barr virus (EBV)-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-HCC)

According to the CT, there is a 25 mm×21 mm mass in segment 4 (A). Hematoxylin-eosin staining shows anomalous cell nests accompanied by many lymphocytes infiltrated (B and C). EBV-encoded RNA (EBER) detected by in situ hybridization (D), and CK7 (E) and CK19 (F) detected by immunohistochemical staining are positive.

Figure 2. Preoperative CT findings and microscopic findings of the resected liver of the 30-year-old female patient with Epstein-Barr virus (EBV)-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-HCC)

According to the CT, there is an approximately 36 mm×40 mm hypodense nodular in the upper right anterior lobe of the liver (A). Hematoxylin-eosin staining shows a poorly differentiated cancer with many lymphocyte infiltrations (B and C). EBV-encoded RNA (EBER) detected by in situ hybridization is positive (D). CK7 (E) is negative and CK19 (F) is positive detected by immunohistochemical staining.

Figure 3. Preoperative CT findings and microscopic findings of the resected liver of the 52-year-old female patient with Epstein-Barr virus (EBV)-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-HCC)

According to the CT, there is a 25 mm hypodense nodular lesion in the outer lobe of the left liver (A). Hematoxylin-eosin staining shows a poorly differentiated adenocarcinoma, rich in interstitial lymphocytes (B and C). EBV-encoded RNA (EBER) detected by in situ hybridization (D), and CK7 (E) and CK19 (F) detected by immunohistochemical staining are positive.

Figure 2. Effect of SS31 on anti-apoptosis evaluated by TUNEL staining at 24 h after SAH in rats

A: Temporal cortex is represented for detection. B: Immunofluorescent images show the effect of SS31 on the anti-apoptosis at 24 h induced by SAH. Fewer TUNEL-positive cells are revealed in the Sham group. The TUNEL-positive cells are obviously increased in the SAH and vehicle-treated groups. The apoptotic neurons are significantly decreased in the SAH+SS31 group. Apoptotic neurons are labeled with red, surrounding the temporal lobe, and nuclei are labeled with 4',6-diamidino-2-phenylindole (DAPI). The white arrows indicate expressions and overlaps of TUNEL and DAPI. C: Proportions of apoptotic neurons are compared among groups. Data are presented as $\overline{x}$ ± s ( n=3).