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  Table of Contents    
CASE REPORT  
Year : 2015  |  Volume : 58  |  Issue : 4  |  Page : 550-553
Lymphoepithelioma-like hepatocellular carcinoma without Epstein-Barr virus infection: A case report and a review of the literature


1 Department of Pathology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang Province, China
2 Department of Pathology, Shaoxing No. 2 Hospital, Shaoxing, Zhejiang Province, China

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Date of Web Publication4-Nov-2015
 

   Abstract 

Lymphoepithelioma-like carcinoma (LELC) of the liver is uncommon, only 20 cases have been reported in the English-language literature so far, and the majority has been identified as cholangiocarcinomas, only four cases were hepatocellular LELC. Here we described a rare case of lymphoepithelioma-like hepatocellular carcinoma (HCC). A 42-year-old Chinese female who was incidentally found to have a liver-occupying lesion during a routine medical examination. Ultrasonography revealed a 47 mm × 33 mm × 36 mm hypoechoic mass in the left lobe. Computed tomography and magnetic resonance imaging displayed a nodular lesions in the left liver lobe. The patient underwent a left-side hepatectomy. Histopathological examination of the resected specimen revealed an undifferentiated carcinoma with a dense lymphocytic infiltrate, predominantly composed of CD3(+) T cells, morphologically similar to nasopharyngeal carcinoma. Immunohistochemically, the tumor cells were positive for CK, EMA, Glypican-3 and hepatocyte, but negative for alpha-fetoprotein, CK19, CK7 and CK20. Epstein–Barr virus (EBV) in situ hybridization was negative. The final histopathological diagnosis was lymphoepithelioma-like HCC without EBV infection.

Keywords: Epstein–Barr virus, Hepatocellular carcinoma, Liver, Lymphoepithelioma-like carcinoma

How to cite this article:
Wei J, Liu Q, Wang C, Yu S. Lymphoepithelioma-like hepatocellular carcinoma without Epstein-Barr virus infection: A case report and a review of the literature. Indian J Pathol Microbiol 2015;58:550-3

How to cite this URL:
Wei J, Liu Q, Wang C, Yu S. Lymphoepithelioma-like hepatocellular carcinoma without Epstein-Barr virus infection: A case report and a review of the literature. Indian J Pathol Microbiol [serial online] 2015 [cited 2017 Nov 17];58:550-3. Available from: http://www.ijpmonline.org/text.asp?2015/58/4/550/168857



   Introduction Top


A carcinoma arising outside the nasopharynx displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma (LELC). Histologically similar carcinomas have been reported in various anatomic sites such as salivary gland, the stomach, colon, lung, uterus, bladder, and thymus. Lymphoepithelioma-like hepatocellular carcinoma (HCC) is a rare type of hepatic carcinoma with characteristic clinicopathological features. Primary LELC of the liver extremely rare, to the best of our knowledge, only twenty cases have been reported so far,[1],[2],[3],[4],[5],[6],[7],[8],[9],[10] and the majority has been identified as lymphoepithelioma-like cholangiocarcinoma,[1],[2],[3],[4],[5],[6] only four cases were hepatocellular LELC.[7],[8],[9],[10] Most of these tumors were positive for Epstein–Barr virus (EBV) on EBER in situ hybridization, but 3 cases of lymphoepithelioma-like HCC was negative.[8],[9],[10] Here we report a rare case of LELC without glandular differentiation, which immunohistochemical phenotypes were characteristic of lymphoepithelioma-like HCC rather than cholangiocarcinoma. We also present a brief review of the current literature on this extremely rare primary hepatic malignancy.


   Case Report Top


A 42-year-old Chinese female who was incidentally found to have a liver-occupying lesion during a routine medical examination. Ultrasonography revealed a 47 mm × 33 mm × 36 mm hypoechoic mass in the left lobe [Figure 1], the boundary of the mass was clear and the shape was regular. Color Doppler flow imaging showed stripped blood flow signals. Enhanced computed tomography showed a 44 mm × 34 mm low density lesions in the left liver, with clear boundary [Figure 2]a, arterial phase enhanced scan showed mild enhancement, and slightly low density during portal phase. Magnetic resonance imaging (MRI) displayed a 45 mm × 33 mm nodular lesions in the left liver lobe [Figure 2]b, T1-weighted image showed low signal, T2-weighted image showed high signal. After injection of the contrast agent, the arterial phase showed slight to mild enhancement, portal vein phase showed slightly low signal. Routine laboratory investigations were normal, including complete blood count and serum urea and electrolyte levels. The serum level of alpha-fetoprotein (AFP) was 56.3 ng/ml and was above the normal range (0-20 ng/ml), but carbohydrate antigen 19-9 and carcinoembryonic antigen were within normal ranges. Serum hepatitis viral markers were negative, also serum EBV was negative. The subsequent physical examination and whole body MRI scan was negative expect the liver. The patient underwent a left-side hepatectomy. Surgery revealed a slightly bulging mass in the left lateral lobe. The patient has been free from tumor recurrence in the 8 months since surgery.
Figure 1: B-ultrasound scan. Ultrasonography revealed a 47 mm × 33 mm × 36 mm hypoechoic mass in the left lobe

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Figure 2: (a) Computed tomography (CT) and magnetic resonance imaging (MRI) findings. Enhanced CT showed a 44 mm × 34 mm low density lesions in the left liver, with clear boundary; (b) MRI displayed a 45 mm × 33 mm nodular lesions in the left liver lobe

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Pathological examination

On gross examination, the excised specimen measured 180 mm × 86 mm × 67 mm. On cut surface, revealed a slightly bulging mass, the mass was a well-demarcated but not encapsulated, yellowish, firm and soft texture mass, with focal areas of hemorrhage, measuring 46 mm × 38 mm × 36 mm [Figure 3]. Microscopically, the tumor invasived into the surrounding normal liver tissue [Figure 4]a; a dense infiltrate of mature lymphocytes insinuating between the tumor cells was observed in the background [Figure 4]b; in some areas a dense lymphoid cells admixed with a few tumor cells [Figure 4]c; the tumor cells with vesicular nuclei, prominent nucleoli, and surrounded by a dense lymphoid stroma, which are the characteristic features of LELC [Figure 4]d. No area of glandular differentiation and desmoplastic reaction was noted. Immunohistochemically, neoplastic cells were strongly reactive for Hepatocyte (HepPar 1) [Figure 5]a, Glypican-3, CK and EMA [Figure 5]b, but were negative for AFP, CK19, CK7, CK20 and CEA. Most of the lymphoid cells were positive for CD3 and CD45RO, with rare CD20 positive cells. In addition, the lymphoid stroma was composed of a mixture of CD4(+) and CD8(+) cells, with a predominance of CD8(+) T-cells. EBV in situ hybridization was negative [Figure 5]c, but in the positive control group of nasopharyngeal carcinoma EBV was positive [Figure 5]d. The final histological diagnosis was lymphoepithelioma-like HCC without EBV infection.
Figure 3: The gross appearance of the tumor (46 mm × 38 mm × 36 mm), on cut surface, revealed a slightly bulging mass, the mass was a well-demarcated but not encapsulated, yellowish, firm and soft texture mass, with focal areas of hemorrhage

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Figure 4: (a) Microscopically, the tumor invasived into the surrounding normal liver tissue; (b) A dense infiltrate of mature lymphocytes insinuating between the tumor cells was observed in the background; (c) In some areas a dense lymphoid cells admixed with a few tumor cells; (d) The tumor cells with vesicular nuclei, prominent nucleoli

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Figure 5: (a) Immunohistochemically, neoplastic cells were strongly reactive for Hepatocyte (b) And EMA (c) Epstein–Barr virus (EBV) in situ hybridization was negative, (d) But in the positive control group of nasopharyngeal carcinoma EBV was positive

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   Discussion Top


Lymphoepithelioma-like carcinoma are defined as tumors which possess histologic similarity to nasopharyngeal carcinoma. LELC of the hepatic is a rare type of hepatic malignancy that was first described by Hsu et al. in 1996.[2] To the best of our knowledge, only sixteen cases of lymphoepithelioma-like cholangiocarcinoma and four cases of lymphoepithelioma-like HCC have been reported in the liver. The previously reported cases of lymphoepithelioma-like cholangiocarcinoma are summarized in [Table 1], and lymphoepithelioma-like HCC in [Table 2].{Table 1}{Table 2}

The first lymphoepithelioma-like HCC was described in 2004 by Si et al., and the patient infected EBV and hepatitis C virus (HCV).[7] The other three cases was respectively reported by Chen et al.,[8] Nemolato et al.[9] and Shinoda et al.[10] The patient described by Chen was a liver cirrhosis patient related to HCV infection but negative EBV. The third and fourth patients were negative for hepatitis B virus, HCV and EBV, and without liver cirrhosis. The case reported here shows some differences as compared with the previous 4 cases. It is the second case of hepatocellular LELC arising in a noncirrhotic liver and without EBV and hepatitis virus infection in our patient.

The role of EBV in the tumorigenesis of LELC remains controversial at present. 10 of the 16 reported lymphoepithelioma-like cholangiocarcinoma were positive for EBV in situ hybridization, but only one of 5 cases of lymphoepithelioma-like HCC were positive for EBV, including the present case. Some reports pointed out that EBV infected ductal epithelium may undergo transformation into cholangiocarcinoma and clonal proliferation has been demonstrated in lymphoepithelioma-like cholangiocarcinoma.[1] A few reports have pointed out that LEL-HCC may be associated with hepatitis virus but serum hepatitis viral markers were negative in our patients. These tumors may originate from the peribiliary glands found around the intrahepatic bile ducts. In our case the tumor cells were positive for Hepatocyte and Glypican-3, but negative for AFP, CK19, CK7 and CK20. The morphology and immunohistochemistry indicate a hepatocytic origin rather than a biliary origin.

The differential diagnosis included lymphoepithelioma-like cholangiocarcinoma, metastatic undifferentiated nasopharyngeal carcinoma, metastatic LELC from other body sites and non-Hodgkin lymphoma. In our patient, thorough physical examination and whole body MRI scan showed no extrahepatic primary tumor, supporting the primary hepatic origin of this tumor. The tumor cells were positive for Hepatocyte and Glypican-3, which is direct evidence for the diagnosis of HCC. In addition the tumor cells were negative for CK19 and CK7, also does not support the bile duct origin. Lymphomas can be easily excluded when epithelial characters are found.

Although many authors think that LELC have a better prognosis than conventional carcinoma with a less lymphocytic infiltrate.[3],[4] Given a limited number of cases reported to date and to the short follow-up periods, the clinical outcomes of the reported 20 patients with LELC of the liver were quite variable. Five patients had aggressive clinical courses with early metastasis and death, one patient alive with disease after 2 years of the surgery, only two patients had long disease-free survivals. Therefore, long-term follow-up of additional cases is very necessary to determine the disease course.

There is no consensus on standardized treatment strategy for both lymphoepithelioma-like cholangiocarcinoma and lymphoepithelioma-like HCC. Radical surgical resection is still said to be the most effective treatment. Some reports have suggested that postoperative radiation therapy and chemotherapy may be beneficial, however, the evidence has not been conclusive. Immunosuppressive therapy is likely to trigger tumor malignant progression.[7] So we must pay great attention to the use of immunosuppressive therapy.


   Conclusion Top


We report a unique case of primary EBV negative lymphoepithelioma-like HCC arising in a noncirrhotic liver. This case is the second case of non-EBV and noncirrhosis-associated lymphoepithelioma-like HCC. Further research are needed to determine the accurate causes and mechanism of hepatic LELC. Because lymphoepithelioma-like HCC is extremely rare, a regular postoperative follow-up will be important for early detection of recurrent/metastatic disease and to evaluate the efficacy of the therapeutic strategy offered.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Ortiz MR, Garijo G, Adrados M, López-Bonet E, Acero D, Bernadó L. Epstein-Barr virus-associated cholangiocarcinoma with lymphoepithelioma-like component. Int J Surg Pathol 2000;8:347-351.  Back to cited text no. 1
    
2.
Hsu HC, Chen CC, Huang GT, Lee PH. Clonal Epstein-Barr virus associated cholangiocarcinoma with lymphoepithelioma-like component. Hum Pathol 1996;27:848-50.  Back to cited text no. 2
    
3.
Jeng YM, Chen CL, Hsu HC. Lymphoepithelioma-like cholangiocarcinoma: An Epstein-Barr virus-associated tumor. Am J Surg Pathol 2001;25: 516-20.  Back to cited text no. 3
    
4.
Szekely E. Lymphoepithelioma-like cholangiocarcinoma (LELC) not associated with Epstein-Barr virus. Am J Surg Pathol 2001;25: 1464-6.  Back to cited text no. 4
[PUBMED]    
5.
Ishida M, Mori T, Shiomi H, Naka S, Tsujikawa T, Andoh A, et al. Non-Epstein-Barr virus associated lymphoepithelioma-like carcinoma of the inferior common bile duct. World J Gastrointest Oncol 2011;3:111-5.  Back to cited text no. 5
    
6.
Lee W. Intrahepatic lymphoepithelioma-like cholangiocarcinoma not associated with Epstein-Barr virus: A case report. Case Rep Oncol 2011;4:68-73.  Back to cited text no. 6
    
7.
Si MW, Thorson JA, Lauwers GY, DalCin P, Furman J. Hepatocellular lymphoepithelioma-like carcinoma associated with Epstein Barr virus: A hitherto unrecognized entity. Diagn Mol Pathol 2004;13:183-9.  Back to cited text no. 7
    
8.
Chen CJ, Jeng LB, Huang SF. Lymphoepithelioma-like hepatocellular carcinoma. Chang Gung Med J 2007;30:172-7.  Back to cited text no. 8
    
9.
Nemolato S, Fanni D, Naccarato AG, Ravarino A, Bevilacqua G, Faa G. Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature. World J Gastroenterol 2008;14:4694-6.  Back to cited text no. 9
    
10.
Shinoda M, Kadota Y, Tsujikawa H, Masugi Y, Itano O, Ueno A, et al. Lymphoepithelioma-like hepatocellular carcinoma: A case report and a review of the literature. World J Surg Oncol 2013;11:97.  Back to cited text no. 10
    

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Correspondence Address:
Jianguo Wei
Department of Pathology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, No.568 Zhongxing North Road, Shaoxing District, 312000 Shaoxing, Zhejiang Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.168857

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