|Year : 2022 | Volume
| Issue : 4 | Page : 156-160
Lymphoepithelioma-like cholangiocarcinoma mimicking hepatocellular carcinoma imaging features in a young patient with Hepatitis B virus infection: A case report and literature review
Chi-Yu Lee1, Horng-Yuan Wang2, Pao-Shu Wu3, Ching-Wei Chang4
1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital; MacKay Junior College of Medicine, Nursing and Management, Taipei; MacKay Medical College, New Taipei, Taiwan
3 MacKay Junior College of Medicine, Nursing and Management; Department of Pathology, MacKay Memorial Hospital, Taipei, Taiwan
4 Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital; MacKay Junior College of Medicine, Nursing and Management; MacKay Medical College, New Taipei; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
|Date of Submission||13-May-2022|
|Date of Decision||12-Aug-2022|
|Date of Acceptance||17-Aug-2022|
|Date of Web Publication||06-Dec-2022|
Dr. Ching-Wei Chang
Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, No. 92, Sec. 2, Chung-Shan North Road, Taipei
Source of Support: None, Conflict of Interest: None
Lymphoepithelioma-like cholangiocarcinoma (LEL-CC) is a rare variant of intrahepatic cholangiocarcinoma. Only a few cases of LEL-CC have been reported, and the understanding of LEL-CC remains limited. Herein, we describe a case involving a 38-year-old Asian man with hepatitis B virus infection and LEL-CC. The patient's liver tumor was incidentally discovered during routine abdominal ultrasonography without obvious clinical signs or symptoms. Dynamic magnetic resonance imaging (MRI) revealed features of hepatocellular carcinoma and he underwent laparoscopic partial hepatectomy. Histologically, the liver tumor exhibited a lymphoepithelioma-like appearance and features of cholangiocarcinoma with Epstein–Barr virus infection.
Keywords: Epstein–Barr virus, hepatitis B virus, lymphoepithelioma-like cholangiocarcinoma
|How to cite this article:|
Lee CY, Wang HY, Wu PS, Chang CW. Lymphoepithelioma-like cholangiocarcinoma mimicking hepatocellular carcinoma imaging features in a young patient with Hepatitis B virus infection: A case report and literature review. J Cancer Res Pract 2022;9:156-60
|How to cite this URL:|
Lee CY, Wang HY, Wu PS, Chang CW. Lymphoepithelioma-like cholangiocarcinoma mimicking hepatocellular carcinoma imaging features in a young patient with Hepatitis B virus infection: A case report and literature review. J Cancer Res Pract [serial online] 2022 [cited 2023 Feb 3];9:156-60. Available from: https://www.ejcrp.org/text.asp?2022/9/4/156/362639
| Introduction|| |
Lymphoepithelioma-like carcinoma (LELC) is a rare malignancy characterized by tumors composed of undifferentiated epithelial cells with prominent lymphoid infiltration. Nasopharyngeal carcinoma is the most well-known type of LELC tumor. LELCs can also emerge at various anatomical sites, including the lungs, gastrointestinal tract, thymus, and liver. In the liver, this type of tumor is extremely rare. Hepatic LELCs have been observed in both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC), which are further designated lymphoepithelioma-like HCC and lymphoepithelioma-like cholangiocarcinoma (LEL-CC), respectively. Only a few cases of LEL-CC have been described in reports which focused on radiologic and histologic analyses. LEL-CC has similar radiologic features to HCC and IHCC, so diagnosing LEL-CC by radiologic imaging remains a challenge for physicians. Herein, we describe a rare case of LEL-CC in a 38-year-old man with HCC-like image features.
| Case Report|| |
A 38-year-old man with type 2 diabetes mellitus, hyperlipidemia, and hepatitis B virus infection underwent routine abdominal ultrasonography at our hospital, during which a lesion was found in the S3 segment of the liver, and the lesion increased in size from 1 cm to 2.7 cm over a 1-year period. On physical examination, there was no abdominal pain, vomiting, or weight loss. The results of a liver function test panel were within normal limits. Serum levels of tumor markers, including alpha-fetoprotein, carcinoembryonic antigen, and cancer antigen 199, were not elevated. Hepatitis virus markers revealed positive hepatitis B surface antigen (854.79 IU/mL) and negative hepatitis C antibody. Magnetic resonance imaging (MRI) revealed an abnormal signal intensity of approximately 1.9 cm × 1.7 cm in the S2/3 segment of the liver, with hypersignal intensity on T2-weighted imaging (T2WI) [Figure 1]c and heavy-T2WI with fat suppression. Dynamic gadolinium-enhanced MRI showed hyposignal intensity on precontrast T1WI, early enhancement in the arterial phase [Figure 1]a, and washout in the portal venous and delayed phase [Figure 1]b. These were typical imaging characteristics of HCC. Accordingly, under the assumption of HCC diagnosis, the patient underwent laparoscopic partial hepatectomy.
|Figure 1: Magnetic resonance imaging revealing a solitary tumor, measuring 1.9 cm × 1.7 cm, in the S2/3 segment of the liver with iso-hyper signal intensity in the arterial phase (a), hyposignal intensity in the delayed phase (b), and hypersignal intensity on T2-weighted imaging (c). Macroscopic analysis of the resected specimen revealed a grayish white, firm, solitary tumor with a rough, inked green surface (d). Histopathology revealed highlighted lymphoepithelioma-like cholangiocarcinoma tumor cells with cytokeratin immunostaining (e) and positive for Epstein–Barr-encoded RNA in situ hybridization in the tumor cell nuclei (f). (×20 in [e] and ×100 in [f])|
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Grossly, a solitary tumor measure 1.7 cm in size was present in the resected liver tissue [Figure 1]d. Histopathological analysis revealed carcinoma cells in solid nests, cord, or tubule growth patterns with an indistinct intercellular border in a dense lymphoplasmacytic stroma. Immunohistochemically, the tumor cells were positive for cytokeratin (CK [AE1/AE3]) [Figure 1]e, CK7, and CK19 and negative for CK5/6, P63, HepPar-1, arginase-1, and glutamine synthetase. Epstein–Barr virus (EBV)-encoded RNA in situ hybridization was positive in the tumor cell nuclei [Figure 1]f. Collectively, these features fulfilled the criteria for the diagnosis of LEL-CC. Nasopharyngolaryngoscopy revealed no evidence of nasopharyngeal tumors, and no evidence of recurrence was found 2 years postoperatively.
| Discussion|| |
In this case report, we present a patient diagnosed with LEL-CC with similar radiologic features to HCC. In general, cholangiocarcinoma is difficult to diagnose by radiologic imaging because of its wide spectrum of radiologic appearances. Typically, mass-forming cholangiocarcinomas are hypo-to-isointense on T1WI with variable hyperintensity on T2WI depending on the proportion of fibrosis, necrosis, and mucin. Contrast-enhanced T1WI shows minimal-to-moderate thin peripheral enhancement on early images, with centripetal progression on delayed images. Lymphoepithelioma-like cholangiocarcinoma (LEL-CC) is a rare variant of IHCC, which may have an atypical radiologic pattern of mass-forming cholangiocarcinoma. According to a previous study, LEL-CC is hypointense on T1WI and hyperintense on T2WI and diffusion-weighted imaging, which is similar to mass-forming cholangiocarcinoma. Different from mass-forming cholangiocarcinoma, LEL-CC often displays early enhancement in the arterial phase and washout in the portal venous phase and delayed phase, which are typical imaging characteristics of HCC. Due to the similarity in radiologic findings between mass-forming cholangiocarcinoma, LEL-CC, and HCC, histopathology is considered mandatory to confirm the diagnosis.
With regard to the pathology, LEL-CC is composed of variable glandular differentiation with moderate amounts of syncytial, amphophilic cytoplasm, and prominent lymphoplasmacytic infiltration. In contrast to the dense lymphoplasmacytic infiltration found in LEL-CC, conventional-type cholangiocarcinoma shows little-to-scattered lymphoplasmacytic infiltration. In addition, in cholangiocarcinoma, poorly formed glands composed of cells with moderate atypia and high nuclear/cytoplasmic ratio are surrounded by dense, desmoplastic stroma. Most importantly, the conventional type of cholangiocarcinoma is negative for EBER-ISH stain.
To the best of our knowledge, 31 cases of LEL-CC,,,,,,,,,,,,,,,,,,, have been reported in the English literature. In these cases, the mean age of the patients was 53 years (range, 19–79 years), with female predominance (65.6% [21/32]), and most cases were reported in Asia (78.1% [25/32]). The LEL-CC lesions were usually solitary (87.5% [28/32]) with a tumor diameter ranging from 15 mm to 120 mm. Patients with larger tumors tended to present with abdominal discomfort or pain (31.3% [10/32]), whereas most of the smaller tumors were discovered incidentally (62.5% [20/32]). Most (93.8% [30/32]) patients underwent surgical resection. Two patients did not undergo surgical treatment due to decompensated cirrhosis and left portal vein metastasis, respectively.
Similar to nasopharyngeal carcinoma, most LELCs are strongly associated with EBV infection, as are LELCs in the digestive tract, lung, and thymus. We found a high percentage (75.0% [24/32]) of EBV-positive LEL-CC in our literature review [Table 1]. This implies that EBV may be directly involved in the carcinogenesis of LEL-CC, which may result from the immune response elicited by EBV infection. According to our review, overall survival for EBV-positive LEL-CC was not significantly different from that for EBV-negative LEL-CC (P = 0.41) [Figure 2]. We assume that the lack of statistical significance was due to the small sample size.
|Figure 2: Kaplan–Meier disease-specific survival curves for patients with and without EBV infection. EBV: Epstein–Barr virus|
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|Table 1: Demographic information, manifestations, treatment, and prognosis of reported cases of lymphoepithelioma-like cholangiocarcinoma|
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Our case had the typical characteristics of HCC in radiologic imaging, including early enhancement in the arterial phase and washout in the portal venous and delayed phase. Furthermore, our case had chronic hepatitis B, which is a known risk factor for HCC. Accordingly, HCC was first impressed according to the clinical presentation and imaging. After discussion with the patient, he chose surgical intervention other than liver mass biopsy.
In summary, LEL-CC is a rare variant of IHCC, which has both similar and different radiologic features to HCC and mass-forming cholangiocarcinoma. Diagnosing LEL-CC remains a challenge for physicians and radiologists, and so a pathological diagnosis is crucial for these cases.
This case report was approved by the Institutional Review Board of the MacKay Memorial Hospital (IRB number 22MMHIS220e).
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understood that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.
We thank Dr. Chia-Chi Tsai for the supply of surgical specimen pictures.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Manfredi R, Barbaro B, Masselli G, Vecchioli A, Marano P. Magnetic resonance imaging of cholangiocarcinoma. Semin Liver Dis 2004;24:155-64.
Ding Y, Sun Z, You W, Zhang S, Chang C, Yan S, et al
. Lymphoepithelioma-like intrahepatic cholangiocarcinoma with Epstein-Barr virus infection: Report of a rare case. Ann Transl Med 2019;7:497.
Labgaa I, Stueck A, Ward SC. Lymphoepithelioma-like carcinoma in liver. Am J Pathol 2017;187:1438-44.
Sun K, Xu S, Wei J, Wang B, Owusu-Ansah KG, Wang W, et al
. Clinicopathological features of 11 Epstein-Barr virus-associated intrahepatic cholangiocarcinoma at a single center in China. Medicine (Baltimore) 2016;95:e5069.
Hsu HC, Chen CC, Huang GT, Lee PH. Clonal Epstein-Barr virus associated cholangiocarcinoma with lymphoepithelioma-like component. Hum Pathol 1996;27:848-50.
Vortmeyer AO, Kingma DW, Fenton RG, Curti BD, Jaffe ES, Duray PH. Hepatobiliary lymphoepithelioma-like carcinoma associated with Epstein-Barr virus. Am J Clin Pathol 1998;109:90-5.
Kim YB, Park YN, Han JY, Hong KC, Hwang TS. Biliary lymphoepithelioma-like carcinoma not associated with Epstein-Barr virus. Arch Pathol Lab Med 1999;123:441-3.
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;8:347-51.
Jeng YM, Chen CL, Hsu HC. Lymphoepithelioma-like cholangiocarcinoma: An Epstein-Barr virus-associated tumor. Am J Surg Pathol 2001;25:516-20.
Chen TC, Ng KF, Kuo T. Intrahepatic cholangiocarcinoma with lymphoepithelioma-like component. Mod Pathol 2001;14:527-32.
Szekely E. Lymphoepithelioma-like cholangiocarcinoma (LELC) not associated with Epstein-Barr virus. Am J Surg Pathol 2001;25:1464-6.
Huang Y, Tsung JS, Lin CW, Cheng TY. Intrahepatic cholangiocarcinoma with lymphoepithelioma-like carcinoma component. Ann Clin Lab Sci 2004;34:476-80.
Min HS, Shin E, Jang JJ. Carcinoma with predominant lymphoid stroma in hepatobiliary system – Report of 2 cases. Korean J Hepatol 2007;13:222-7.
Adachi S, Morimoto O, Kobayashi T. Lymphoepithelioma-like cholangiocarcinoma not associated with EBV. Pathol Int 2008;58:69-74.
Henderson-Jackson E, Nasir NA, Hakam A, Nasir A, Coppola D. Primary mixed lymphoepithelioma-like carcinoma and intra-hepatic cholangiocarcinoma: A case report and review of literature. Int J Clin Exp Pathol 2010;3:736-41.
Hur YH, Kim HH, Koh YS, Seoung JS, Cho CK. Lymphoepithelioma-like cholangiocarcinoma not associated with Epstein-Barr virus. ANZ J Surg 2011;81:652-3.
Lee W. Intrahepatic lymphoepithelioma-like cholangiocarcinoma not associated with epstein-barr virus: A case report. Case Rep Oncol 2011;4:68-73.
Chan AW, Tong JH, Sung MY, Lai PB, To KF. Epstein-Barr virus-associated lymphoepithelioma-like cholangiocarcinoma: A rare variant of intrahepatic cholangiocarcinoma with favourable outcome. Histopathology 2014;65:674-83.
Liao TC, Liu CA, Chiu NC, Yeh YC, Chiou YY. Lymphoepithelioma-like cholangiocarcinoma: A mimic of hepatocellular carcinoma on imaging features. World J Gastroenterol 2015;21:4089-95.
Aosasa S, Maejima T, Kimura A, Nishiyama K, Edo H, Shinmoto H, et al
. Intrahepatic cholangiocarcinoma with lymphoepithelioma-like carcinoma components not associated with Epstein-Barr virus: Report of a Case. Int Surg 2015;100:689-95.
Chang WH, Chen BF, Yang PS, Chu CH, Wang TE. Cholangiocarcinoma with lymphoepithelioma-like component not associated with Epstein-Barr virus. J Cancer Res Pract 2015;2:325-29.
Labgaa I, Hiotis S, Ward SC. Lymphoepithelioma-like cholangiocarcinoma: A rare finding with good outcomes. J Clin Gastroenterol 2016;50:268.
Lin A, Alpert L, Hart J, Chapman C, Pillai AA. Lymphoepithelioma-like carcinomas: A rare variant of cholangiocarcinoma. Hepatology 2020;72:353-5.
[Figure 1], [Figure 2]