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Ghandour F, Anderson S, Al-Diffalha S. Epstein-Bar Virus-Positive Lymphoepithelioma-Like Intrahepatic Cholangiocarcinoma: A Case Report and Literature Review. Int J Surg Pathol 2024:10668969241297260. [PMID: 39692455 DOI: 10.1177/10668969241297260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2024]
Abstract
Intrahepatic cholangiocarcinoma is a primary liver malignancy with poor prognosis and limited treatment options. Lymphoepithelioma-like intrahepatic cholangiocarcinoma is an exceedingly rare variant of intrahepatic cholangiocarcinoma that histologically resembles nasopharyngeal carcinoma, previously known as lymphoepithelioma. It was first reported by Hsu et al in 1996 and they were able to show the presence of Epstein-Barr virus in tumor cells. Even though several risk factors for the development of intrahepatic cholangiocarcinoma have been identified, the association between Epstein-Barr virus and intrahepatic cholangiocarcinoma is relatively rare. This article aims at discussing a female patient's lymphoepithelioma-like intrahepatic cholangiocarcinoma tumor and summarizing the existing literature on Epstein-Barr virus-positiveLymphoepithelioma-like intrahepatic cholangiocarcinoma, including the clinical features, pathogenesis, diagnostic challenges, treatment approaches, prognosis, and histopathologic description.
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Affiliation(s)
- Fatme Ghandour
- Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sarah Anderson
- Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sameer Al-Diffalha
- Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA
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2
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Peng YC, Liao SH, Tsai JH, Chen PT, Chang CC, Kao JH, Liu KL. Comparison of the clinicoradiological features and outcomes of lymphoepithelioma-like cholangiocarcinoma and conventional intrahepatic cholangiocarcinoma: A propensity score matching analysis. J Formos Med Assoc 2024:S0929-6646(24)00379-6. [PMID: 39147686 DOI: 10.1016/j.jfma.2024.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 08/07/2024] [Indexed: 08/17/2024] Open
Abstract
BACKGROUND/PURPOSE Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare variant of intrahepatic cholangiocarcinoma (ICC). We aim to analyze the differences in the clinical and radiological features of LELCC and ICC. METHODS Between January 2003 and December 2019, a total of 21 patients diagnosed with LELCC were retrospectively enrolled, and 84 patients with ICC were selected through propensity score matching by sex, age, and initial cancer stage. The clinical characteristics, pathological findings, and radiological features were analyzed. The differences in overall survival (OS) between LELCC and ICC were evaluated using the Kaplan-Meier method. RESULTS The serum carbohydrate antigen 19-9 (CA 19-9) level was higher in the ICC group than in the LELCC group (77.9 vs 30.0 U/mL, p = 0.004). Non-rim arterial phase hyperenhancement (47.1% vs 13.7%, p = 0.005) and portovenous washout (35.3% vs 4.1%, p = 0.001) were more frequently observed in the LELCC group than in the ICC group. Intrahepatic duct dilatation was a distinct feature of the ICC group. The 5-year OS rates in the LELCC and ICC groups were 69.3% and 58.2%, respectively (p = 0.047). The 5-year OS of patients with stages I and II LELCC between ICC were not significantly different (90.0% vs 83.4%, p = 0.464). However, the 5-year OS of patients with stages III and IV LELCC was more favorable than that of patients with ICC (29.2% vs 23.0%, p = 0.017). CONCLUSIONS LELCC had a favorable outcome and several different clinicoradiological features compared with ICC.
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Affiliation(s)
- Yan-Chih Peng
- Department of Medical Imaging, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Sih-Han Liao
- Section of Gastroenterology, Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Jia-Huei Tsai
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Po-Ting Chen
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Chin-Chen Chang
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei City, Taiwan
| | - Kao-Lang Liu
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.
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3
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Choi JH, Thung SN. Recent Advances in Pathology of Intrahepatic Cholangiocarcinoma. Cancers (Basel) 2024; 16:1537. [PMID: 38672619 PMCID: PMC11048541 DOI: 10.3390/cancers16081537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/10/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: the small-duct type and large-duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes-inflammation and proliferation-have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.
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Affiliation(s)
- Joon Hyuk Choi
- Department of Pathology, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea
| | - Swan N. Thung
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA;
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Zheng L, Zhou N, Yang X, Wei Y, Yi C, Gou H. Clinicopathological features of a rare cancer: Intrahepatic lymphoepithelioma-like cholangiocarcinoma with Epstein-Barr virus infection. Clin Res Hepatol Gastroenterol 2023; 47:102244. [PMID: 37944749 DOI: 10.1016/j.clinre.2023.102244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/15/2023] [Accepted: 11/06/2023] [Indexed: 11/12/2023]
Abstract
PURPOSE Epstein-Barr virus-related lymphoepithelioma-like cholangiocarcinoma (EBV-LELCC), a subtype of intrahepatic cholangiocarcinoma (IHCC), is an extremely rare cancer. To date, only few cases have been reported. Therefore, more studies are needed to provide new insights into its clinicopathological characteristics and treatment. METHODS We retrospectively collected data from 16 EBV-LELCC patients admitted to our hospital between January 2013 and February 2022. We summarized their clinical characteristics and analyzed the genomic features of 5 patients by whole-exon sequencing. In addition, the Kaplan-Meier method was used to assess the prognostic differences between EBV-LELCC and EBV-negative IHCC. RESULTS A total of 16 EBV-LELCC patients aged between 35 and 70 were included in this study and were characterized by female predominance. Eight genetic mutations including KMT2C, ARID1B, BAZ1A, NPM1, POLE, PER3, TOPBP1, USP1 were identified from 5 patients. There were 11 stage I, 2 stage III and 3 stage IV patients in this study. The overall survival of stage I and stage III EBV-LELCC patients after radical surgery was significantly better than that of EBV-negative IHCC patients with matched stage (p = 0.0119). Notably, a stage IV patient treated with a variety of antitumor modalities including surgery, interventional therapy, radiotherapy, chemotherapy, targeted therapy and immunotherapy achieved long-term survival of more than seven years. CONCLUSION Altogether, EBV-LELCC presents a more favorable prognosis than IHCC. This study suggests that patients with early EBV-LELCC have a good prognosis after radical surgery, and even patients with advanced EBV-LELCC are expected to have a longer survival under appropriate and timely treatment. For such a rare cancer with unique clinicopathological features and molecular patterns, more research is needed to facilitate its diagnosis and treatment.
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Affiliation(s)
- Lingnan Zheng
- Abdominal Oncology Ward, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Nan Zhou
- Gastric Cancer Center, Division of Medical Oncology, Cancer Center, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Xi Yang
- Division of Radiotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Yuanfeng Wei
- Abdominal Oncology Ward, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Cheng Yi
- Abdominal Oncology Ward, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Hongfeng Gou
- Gastric Cancer Center, Division of Medical Oncology, Cancer Center, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
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Tang W, Huang Y, Yu S, Wang T, Yang J, Zhao Z. Potential missed opportunities for diagnosis of lymphoepithelioma-like intrahepatic cholangiocarcinoma: report of a rare case. J Int Med Res 2023; 51:3000605231210174. [PMID: 37994034 PMCID: PMC10666819 DOI: 10.1177/03000605231210174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 10/10/2023] [Indexed: 11/24/2023] Open
Abstract
Lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-ICC) is a rare distinctive variant of liver cancer with unique epidemiological and pathological characteristics, including dense lymphocyte infiltration. We herein describe a 67-year-old Chinese man with LEL-ICC. The patient had undergone endoscopic extraction of a bile duct stone 1 month prior. Contrast-enhanced abdominal computed tomography (CT) revealed a 2.5- × 2.5- × 1.5-cm low-density mass located in a covert part of the left lateral segment of the liver. Contrast-enhanced magnetic resonance imaging revealed a hyperintense lesion on T2-weighted and diffusion-weighted images of the left lateral liver, with similar size and signal characteristics in the arterial and portal venous phases. The patient subsequently underwent left lateral laparoscopic hepatectomy. The results of postoperative pathology and immunohistochemistry allowed for the definitive diagnosis. In situ hybridization using an Epstein-Barr virus-encoded RNA probe revealed extensive reactivity in the tumor cell nuclei, supporting a diagnosis of LEL-ICC. The patient was recurrence-free at 12 months postoperatively as shown by CT. A literature review indicated that in middle-aged patients with Epstein-Barr virus infection, a liver mass with a well-defined margin and a combination of hypervascularity and delayed intratumoral enhancement on CT and magnetic resonance imaging may suggest a diagnosis of LEL-ICC.
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Affiliation(s)
- Wei Tang
- Department of Radiology, Shaoxing People’s Hospital, Shaoxing, China
| | - Ya’nan Huang
- Department of Radiology, Shaoxing People’s Hospital, Shaoxing, China
| | - Shanlu Yu
- Department of Pathology, Shaoxing People’s Hospital, Shaoxing, China
| | - Ting Wang
- Department of Radiology, Shaoxing People’s Hospital, Shaoxing, China
| | - Jianfeng Yang
- Department of Radiology, Shaoxing People’s Hospital, Shaoxing, China
| | - Zhenhua Zhao
- Department of Radiology, Shaoxing People’s Hospital, Shaoxing, China
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Vij M, Veerankutty FH, Raju LP, Gowrishankar G, Rajalingam R, Jothimani D, Kaliamoorthy I, Rammohan A, Rela M. Frequent expression of PD-L1 in lymphocyte-rich hepatocellular carcinoma: A report of 4 cases. Ann Diagn Pathol 2023; 66:152172. [PMID: 37348413 DOI: 10.1016/j.anndiagpath.2023.152172] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/09/2023] [Accepted: 06/13/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND Programmed death ligand 1 (PD-L1) is an immune checkpoint inhibitor. PD-L1 binds to its receptor programmed death receptor (PD-1) expressed by immune cells and plays a key role in regulating immune responses. Engagement of PD-L1 on cancer cells and PD-1 on immune cells avoid destruction of tumour cells by immune cells. Immunostaining with PD-L1 has been suggested as a biomarker predictive of antiPD-L1 immunotherapy. Lymphocyte-rich hepatocellular carcinoma (LrHCC) is a rare histological HCC subtype which is characterised by neoplastic epithelial cells intermixed with numerous immune cells. METHODS Here in we investigated immunohistochemical PD-L1 expression in 4 cases of LrHCC. Tumour proportion score (TPS) and immune cell score was recorded. Immunophenotypic characterization of the tumour and inflammatory cells was also done. Epstein-Barr encoding region (EBER) in situ hybridization (ISH) assay as performed in all four tumours. RESULTS Expression of PD-L1 was demonstrated in tumour epithelial cells and immune cells in all four cases. Incomplete to membranous staining was demonstrated in the tumour cells. Tumour proportion score (TPS) was 1.2-20 %. Immune cells demonstrated membranous and cytoplasmic immunostaining. Immune cell score was ≥1 % to >10 %. CONCLUSION PD-L1 expression in both tumour and immune cells suggests distinct immunogenic feature and potential role of antiPD-L1 therapies in cases with inoperable disease.
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Affiliation(s)
- Mukul Vij
- Department of Pathology, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India.
| | - Fadl H Veerankutty
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India
| | - Lexmi Priya Raju
- Department of Pathology, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India
| | - Gowripriya Gowrishankar
- Department of Pathology, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India.
| | - Rajesh Rajalingam
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India
| | - Dinesh Jothimani
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India.
| | - Ilankumaran Kaliamoorthy
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India.
| | - Ashwin Rammohan
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India.
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Pan YJ, Liu W, Qiu QX, Miao SL, Zeng MS, Shan Y, Lin J, Xu PJ. Prognostic value of LI-RADS category on MRI in patients with primary hepatic lymphoepithelioma-like carcinoma. Eur Radiol 2023; 33:5993-6000. [PMID: 37014407 DOI: 10.1007/s00330-023-09598-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/18/2023] [Accepted: 02/10/2023] [Indexed: 04/05/2023]
Abstract
OBJECTIVES To compare the clinical and MRI features of primary hepatic lymphoepithelioma-like carcinoma (LELC) categorized as LR-M or LR-4/5 using the Liver Imaging Reporting and Data System (LI-RADS) version 2018 and to determine the prognostic factors for recurrence-free survival (RFS). METHODS In this retrospective study, 37 patients with surgically confirmed LELC were included. Two independent observers evaluated preoperative MRI features according to the LI-RADS version 2018. Clinical and imaging features were compared between two groups. RFS and the associated factors were evaluated using Cox proportional hazards regression analysis, Kaplan-Meier analysis, and log-rank test. RESULTS In total, 37 patients (mean age, 58.5 ± 10.3 years) were evaluated. Sixteen (43.2%) LELCs were categorized as LR-M and twenty-one (56.8%) LELCs were categorized as LR-4/5. In the multivariate analysis, the LR-M category was an independent factor for RFS (HR 7.908, 95% CI 1.170-53.437; p = 0.033). RFS rates were significantly lower in patients with LR-M LELCs than in patients with LR-4/5 LELCs (5-year RFS rate, 43.8% vs.85.7%; p = 0.002). CONCLUSION The LI-RADS category was significantly associated with postsurgical prognosis of LELC, with tumor categorized as LR-M having a worse RFS than those categorized as LR-4/5. KEY POINTS • Lymphoepithelioma-like carcinoma patients categorized as LR-M have worse recurrence-free survival than those categorized as LR-4/5. • MRI-based LI-RADS categorization was an independent factor for postoperative prognosis of primary hepatic lymphoepithelioma-like carcinoma.
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Affiliation(s)
- Yi-Jun Pan
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Wei Liu
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Xuhui District, Shanghai, 200032, China
| | - Qi-Xuan Qiu
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Shou-Liang Miao
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou, 325015, Zhejiang, China
| | - Meng-Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Yan Shan
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Jiang Lin
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Peng-Ju Xu
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
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Li R, Cheng K, Li X, Chang C, Lv W, Xiaoying L, Zhang P, Yang H, Cao D. Case report: Immunotherapy plus chemotherapy and stereotactic ablative radiotherapy (ICSABR): a novel treatment combination for Epstein-Barr virus-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma. Front Pharmacol 2023; 14:1147449. [PMID: 37614316 PMCID: PMC10443589 DOI: 10.3389/fphar.2023.1147449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 07/24/2023] [Indexed: 08/25/2023] Open
Abstract
Epstein-Barr virus-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma (EBVa LEL-ICC) is a rare tumor, characterized by a rich tumor immune microenvironment (TIME). While this tumor is reportedly sensitive to immunotherapy, its response has been inconsistent. This decreased sensitivity was associated with reduced TIME abundance. We report the case of a 53-year-old woman with EBVa LEL-ICC having reduced TIME abundance. The patient presented with a liver lesion, which was detected using ultrasound. Initially, the tumor was sensitive to immunotherapy and chemotherapy (IC), but resistance developed after a short interval. Subsequently, stereotactic ablative radiotherapy (SABR) was added to the patient's treatment, which now consisted of ICSABR. Successful tumor shrinkage was achieved with the combination therapy regimen. Thus, surgery and ICSABR are effective adjuncts to the first-line IC therapy in improving the survival rate of patients with EBVa LEL-ICC. The results of this study support multidisciplinary treatment as a viable treatment strategy for EBVa LEL-ICC.
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Affiliation(s)
- Ruizhen Li
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ke Cheng
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaofen Li
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chen Chang
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wanrui Lv
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Li Xiaoying
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Pei Zhang
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Heqi Yang
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Dan Cao
- Division of Medical Oncology, State Key Laboratory of Biotherapy, Abdominal Oncology Ward, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Sam Saji A, Yang B, Hou WT, Liu X, Ren QP, Wei YF, Zhang YZ, Yang X. Combined NK-CIK and PD-1 inhibitor (nivolumab), an effective immunotherapy for treating intrahepatic lymphoepithelioma-like cholangiocarcinoma unassociated with EBV infection: Two case reports and a literature review. Front Oncol 2023; 13:1090580. [PMID: 36865802 PMCID: PMC9971717 DOI: 10.3389/fonc.2023.1090580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 01/03/2023] [Indexed: 01/31/2023] Open
Abstract
Intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC) is a very rare malignant tumor arising from the biliary epithelium. To date, there has been a lack of evidence on the radiographical features, clinicopathological features, and treatment modalities of LELCC, with less than 28 cases of LELCC without Epstein-Barr virus (EBV) infection having been reported worldwide. The treatment of LELCC remains unexplored. Here, we present two cases of patients with LELCC without EBV infection who were treated by liver resection, chemotherapy, and immunotherapy and who achieved long survival time. The patients received surgery to remove the tumors and then adjuvant chemotherapy using the GS regimen and combined immunotherapy involving natural killer-cytokine-induced killer (NK-CIK) and nivolumab were performed. Both patients had a good prognosis with a survival time of more than 100 months and 85 months.
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Affiliation(s)
- Alen Sam Saji
- Abdominal Oncology Ward, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Biao Yang
- Abdominal Oncology Ward, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China,Department of Gastroenterology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China,*Correspondence: Biao Yang, ; Xi Yang,
| | - Wan Ting Hou
- Abdominal Oncology Ward, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Xia Liu
- Abdominal Oncology Ward, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Qiu Ping Ren
- Department of Liver Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Yuan Feng Wei
- Abdominal Oncology Ward, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Yu Zu Zhang
- Abdominal Oncology Ward, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Xi Yang
- Department of Gastroenterology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China,*Correspondence: Biao Yang, ; Xi Yang,
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10
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Sapuppo E, Brunetti O, Tessitore D, Brandi G, Di Giovanni N, Fadda G, Luchini C, Martini M, Quaresmini D, Russo A, Santarpia M, Scarpa A, Scartozzi M, Tuccari G, Franchina T, Silvestris N. Rare histotypes of epithelial biliary tract tumors: A literature review. Crit Rev Oncol Hematol 2023; 181:103892. [PMID: 36481306 DOI: 10.1016/j.critrevonc.2022.103892] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/21/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
Adenocarcinoma represents the most frequent biliary tract cancer. However, other rare histotypes can be found in the biliary tract, such as cholangiolocellular carcinoma, cholangiocarcinoma with ductal plate malformation pattern, adenosquamous carcinoma, mucinous carcinoma, signet ring cell carcinoma, clear cell carcinoma, mucoepidermoid carcinoma, lymphoepithelioma-like carcinoma, and sarcomatous cholangiocarcinoma. These cancer types account for less than 10 % of all the already rare biliary tract tumors. Yet, they represent a relevant issue in everyday clinical practice, given the lack of therapeutic recommendations and the overall scarcity of data, mainly deriving from isolated small center-specific cohorts of patients.The shifts of such histotypes from the most common ones reflect genetic and molecular differences, determine changes in clinical aggressiveness, and suggest a possible variability in sensitivity to the standard treatments of biliary adenocarcinomas. The consistency and degree of these variables are still to be solidly demonstrated and investigated. Therefore, this paper aims to review the current literature concerning very infrequent and rare epithelial biliary tract cancers, focusing our attention on the clinical, molecular, and immunohistochemical features of these tumors.
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Affiliation(s)
- Elena Sapuppo
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - Oronzo Brunetti
- Medical Oncology Unit-IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, 70124 Bari, Italy
| | - Dalila Tessitore
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - Giovanni Brandi
- Haematological and Oncological Institute, Department of Experimental, Diagnostic and Specialty Medicine, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Nicola Di Giovanni
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - Guido Fadda
- Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Pathology, University of Messina, Messina, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy; ARC-Net Research Center, University and Hospital Trust of Verona, Verona, Italy
| | - Maurizio Martini
- Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Pathology, University of Messina, Messina, Italy
| | - Davide Quaresmini
- Medical Oncology Unit-IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, 70124 Bari, Italy
| | - Antonio Russo
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - Mariacarmela Santarpia
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy; ARC-Net Research Center, University and Hospital Trust of Verona, Verona, Italy
| | - Mario Scartozzi
- Azienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, Italy
| | - Giovanni Tuccari
- Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Pathology, University of Messina, Messina, Italy
| | - Tindara Franchina
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - Nicola Silvestris
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy.
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11
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Liu F, Xu Q, Regmi P, Li FY, Lin YX. Case Report: Primary lymphoepithelioma-like intrahepatic cholangiocarcinoma. Front Oncol 2023; 13:1146933. [PMID: 37197425 PMCID: PMC10183565 DOI: 10.3389/fonc.2023.1146933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 04/19/2023] [Indexed: 05/19/2023] Open
Abstract
Background Lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-ICC) is a rare variant of intrahepatic cholangiocarcinoma. Epstein-Barr virus (EBV) infection was considered to play a pivotal role in the tumorigenesis of LEL-ICC. It is difficult to diagnosis of LEL-ICC due to the lack of specific features regarding the laboratory test results and imaging findings. At present, the diagnosis of LEL-ICC mainly depends on the histopathologic and immunohistochemical examinations. In addition, the prognosis of LEL-ICC was better than classical cholangiocarcinomas. To our knowledge, only few cases of LEL-ICC have been reported in the literature. Case presentation We presented a case of a 32-year-old Chinese female with LEL-ICC. She had a 6-month history of upper abdominal pain. The magnetic resonance imaging (MRI) showed a 1.1× 1.3 cm lesion in the left lobe of liver, appearing low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. The patient underwent laparoscopic left lateral sectionectomy. The postoperative histopathologic and immunohistochemical examinations results allowed for the definitive diagnosis of LEL-ICC. The patient was free from tumor recurrence after a 28 months follow-up. Conclusion In this study, we reported a rare case of LEL-ICC associated with both HBV and EBV infection. EBV infection might play a pivotal role in the carcinogenesis of LEL-ICC, and surgical resection is still the most effective treatment at present. Further research on the etiology and treatment strategies of LEL-ICC is required.
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Affiliation(s)
- Fei Liu
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Qing Xu
- Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital of Sichuan University, Chengdu, China
| | - Parbatraj Regmi
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- *Correspondence: Yi-Xin Lin, ; Fu-Yu Li,
| | - Yi-Xin Lin
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- *Correspondence: Yi-Xin Lin, ; Fu-Yu Li,
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12
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Adachi Y, Yokoo H, Hagiwara M, Takahashi H, Iwata H, Takeda T, Yamamoto T, Imai K, Yuzawa S, Tanino M, Matsuno N. Lymphoepithelioma-like cholangiocarcinoma not associated with Epstein-Barr virus or hepatitis virus: case report and literature review of 100 reported cases. Ther Adv Med Oncol 2022; 14:17588359221133169. [PMID: 36312815 PMCID: PMC9608032 DOI: 10.1177/17588359221133169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 09/29/2022] [Indexed: 11/06/2022] Open
Abstract
Lymphoepithelioma-like cholangiocarcinoma (LEL-CC) is a type of lymphoepithelioma-like carcinoma (LELC) and a rare variant of primary liver tumor. Although it is uncommon and only 100 cases have been reported thus far, the number of reports has increased in recent years. LEL-CC reportedly occurs more frequently in Asian women; Epstein-Barr virus (EBV) and hepatitis viruses are both strongly associated with tumor development. Here, we describe a 76-year-old woman who exhibited LEL-CC not associated with EBV or hepatitis virus. She was referred to our department with a 3.0-cm × 2.8-cm tumor in the left lobe of the liver. Based on computed tomography and magnetic resonance imaging findings, the tumor was preoperatively diagnosed as hepatocellular carcinoma. Thus, we performed extended left hepatectomy with caudal lobectomy. Histopathological examinations revealed columnar tumor cells with atypical nuclei that proliferated in a cord-like or glandular tubular pattern with dense lymphocytic infiltration. Immunohistochemical analysis showed negative HepPar-1 and arginase findings, indicating non-hepatocyte origin; however, the biliary-type cytokeratins CK7 and CK19 were detected. Based on these findings, the tumor was identified as LEL-CC. EBV-encoded RNA in situ hybridization findings were negative; the patient's clinical characteristics were not suggestive of hepatitis virus infection. In conclusion, we suggest that clinicians consider LEL-CC as a differential diagnosis for liver tumors in Asian women, including patients without EBV or hepatitis virus.
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Affiliation(s)
- Yuki Adachi
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Hokkaido, Japan
| | | | - Masahiro Hagiwara
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Hokkaido, Japan
| | - Hiroyuki Takahashi
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Hokkaido, Japan
| | - Hiroyoshi Iwata
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Hokkaido, Japan
| | - Tomohiro Takeda
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Hokkaido, Japan
| | - Tomohiro Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Hokkaido, Japan
| | - Koji Imai
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Hokkaido, Japan
| | - Sayaka Yuzawa
- Department of Diagnostic Pathology, Asahikawa Medical University Hospital, Hokkaido, Japan
| | - Mishie Tanino
- Department of Diagnostic Pathology, Asahikawa Medical University Hospital, Hokkaido, Japan
| | - Naoto Matsuno
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Hokkaido, Japan
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13
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Zhang X, Wang N, Wei W, Li Y. Epstein-Barr virus infection-associated cholangiocarcinoma: a report of one case and the review of literature. Virol J 2022; 19:133. [PMID: 35945590 PMCID: PMC9361612 DOI: 10.1186/s12985-022-01862-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 07/28/2022] [Indexed: 11/18/2022] Open
Abstract
The clinical data of a patient with Epstein-barr virus (EBV) associated with cholangiocarcinoma was reported in this paper: a case of a 36-year-old female presented with abdominal pain and systemic skin yellowing combined with skin itching. Laboratory studies showed increase in alanine aminotransferase 242 U/L, aspartate aminotransferase 404 U/L, r-glutamyltransferase 1516 U/L, total bilirubin 308.2 µmol/L and CA199 (101.0 U/ml). AFP (4.5 ng/ml) was normal. CT revealed multiple space-occupying lesions in the liver. PET-CT revealed liver malignant tumor and lymph node metastasis. Liver puncture pathology revealed infiltrative growth of significant heterocyst nests in the liver tissue, which was morphologically consistent with malignant tumors, considering poorly differentiated carcinoma. Pathology suggestion: combining liver puncture with morphology, immunohistochemistry, and EBV in situ hybridization results, it was consistent with EB virus-associated poorly differentiated carcinoma, therefore, consider EBV infection-associated poorly differentiated cholangiocarcinoma (CCA) (LELC morphology). The patient underwent liver transplantation in Hangzhou Shulan Hospital on June 8, 2021 successfully. After surgery, the patient orally took tacrolimus for anti-rejection, entecavir for antiviral therapy, gemcitabine 1.2 g + cis-platinum 30 mg for chemotherapy. After following up for more than 5 months post liver transplantation, the condition of the patient deteriorated. The patient subsequently died. Based on the case of our patient and the review of existing literature, when the patient's serum CA199 increased, AFP did not change significantly, and there was no previous history of hepatitis B. CT revealed a low-density mass in the liver, ring enhancement in the arterial phase, and heterogeneous enhancement of the tumor in the delayed phase. Ring enhancement of the liver lesion mass was observed on MRI. Consider the might possibility of hepatic CCA. When patients showed recurrent tonsillitis at an early age, EBV virus infection should be vigilant and oropharyngeal tissue should persist, diagnosis of EBV-associated liver cancer should be considered. In particular, EBV infection-related liver cancer is relatively rare, the clinician should improve the recognition of the disease to strive for early diagnosis and therapy.
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Affiliation(s)
- Xinchun Zhang
- Department of Radiology, Hangzhou Tianshui Wulin Street Community Health Service Centers, Hangzhou, 310006, China
| | - Ning Wang
- Department of Medical Examination Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No. 261, Huansha Road, Hangzhou, 310006, China.
| | - Wenyan Wei
- Department of Radiology, Hangzhou Tumor Hospital, Hangzhou, 310006, China
| | - Yangsheng Li
- Department of Radiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
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14
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Vij M, Puri Y, Rammohan A, G G, Rajalingam R, Kaliamoorthy I, Rela M. Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review. World J Gastrointest Oncol 2022; 14:607-627. [PMID: 35321284 PMCID: PMC8919011 DOI: 10.4251/wjgo.v14.i3.607] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 12/13/2021] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinomas are a heterogeneous group of highly aggressive cancers that may arise anywhere within the biliary tree. There is a wide geographical variation with regards to its incidence, and risk-factor associations which may include liver fluke infection, primary sclerosing cholangitis, and hepatolithiasis amongst others. These tumours are classified into intrahepatic, perihilar and distal based on their anatomical location. Morphologically, intrahepatic cholangiocarcinomas are further sub-classified into small and large duct variants. Perihilar and distal cholangiocarcinomas are usually mucin-producing tubular adenocarcinomas. Cholangiocarcinomas develop through a multistep carcinogenesis and are preceded by dysplastic and in situ lesions. While clinical characteristics and management of these tumours have been extensively elucidated in literature, their ultra-structure and tumour biology remain relatively unknown. This review focuses on the current knowledge of pathological characteristics, molecular alterations of cholangiocarcinoma, and its precursor lesions (including biliary intraepithelial neoplasia, intraductal papillary neoplasms of the bile duct, intraductal tubulopapillary neoplasms and mucinous cystic neoplasm).
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Affiliation(s)
- Mukul Vij
- Department of Pathology, Dr Rela Institute and Medical center, Chennai 600044, Tamil Nadu, India
| | - Yogesh Puri
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
| | - Ashwin Rammohan
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
| | - Gowripriya G
- Department of Pathology, Dr Rela Institute and Medical center, Chennai 600044, Tamil Nadu, India
| | - Rajesh Rajalingam
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
| | - Ilankumaran Kaliamoorthy
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
| | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
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15
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Khandakar B, Liu JR, Thung S, Li Y, Rhee H, Kagen AC, Sun-Wing Tong T, Nyun Park Y, Theise N, Ng IOL. Lymphoepithelioma-like neoplasm of the biliary tract with 'probable low malignant potential'. Histopathology 2022; 80:720-728. [PMID: 34608670 DOI: 10.1111/his.14580] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 09/23/2021] [Accepted: 10/02/2021] [Indexed: 01/06/2023]
Abstract
AIMS Lymphoepithelioma-like carcinomas (LELCs) are uncommon epithelial cancers characteristically showing two distinct components consisting of malignant epithelial cells and prominent dense lymphoid infiltrate. Hepatic LELCs consist of two types, the lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like cholangiocarcinoma (LEL-CCA), with the latter being strongly associated with Epstein-Barr virus (EBV). METHODS AND RESULTS We present a series of three cases of intrahepatic biliary EBV-associated LEL tumours in which the biliary epithelial component showed a distinctly benign appearance, instead of the usual malignant epithelial features of a typical CCA or EBV-associated LEL-CCA. In the lesions, the biliary epithelium showed interconnecting glands or cords of cells. All had a very low proliferation (Ki-67) index. Immunohistochemistry for IDH1 and TP53 performed on two cases was negative and molecular tests for EGFR and KRAS gene mutations performed on one were negative. Prognosis was very good in all three cases, with patients alive with no evidence of disease 24-62 months after surgery. Intriguingly, all three cases had co-infection of HBV and EBV. These cases are also discussed in the context of the 63 cases of LEL-CCA available in the literature, with a focus on epidemiology, clinicopathological features and potential research interests. CONCLUSIONS Based on the distinct clinicopathological features and unique survival benefits, we believe these tumours represent the benign end of the spectrum of EBV-associated lymphoepithelial biliary carcinomas. Whether these tumours require a revision of the current nomenclature to 'lymphoepithelioma-like neoplasm of the biliary tract with probable low malignant potential' will require more detailed analysis with larger case-series.
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Affiliation(s)
- Binny Khandakar
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Jun-Ru Liu
- Department of Pathology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Swan Thung
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Department of Pathology, Mount Sinai Health System, New York, New York, USA
| | - Ying Li
- Department of Radiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Hyungjin Rhee
- Department of Radiology, Research Institute of Radiological Science,, Center for Clinical Imaging Data Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Alexander C Kagen
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York, USA
| | - Tommy Sun-Wing Tong
- Department of Pathology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Young Nyun Park
- Department of Pathology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Neil Theise
- Department of Pathology, New York University School of Medicine, New York City, New York, USA
| | - Irene Oi-Lin Ng
- Department of Pathology, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
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16
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Chang CW, Lee CY, Wang HY, Wu PS. Lymphoepithelioma-like cholangiocarcinoma mimicking hepatocellular carcinoma imaging features in a young patient with Hepatitis B virus infection: A case report and literature review. JOURNAL OF CANCER RESEARCH AND PRACTICE 2022. [DOI: 10.4103/2311-3006.362639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2022] Open
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Lymphoepithelioma-like Intrahepatic Cholangiocarcinoma Is a Distinct Entity With Frequent pTERT/TP53 Mutations and Comprises 2 Subgroups Based on Epstein-Barr Virus Infection. Am J Surg Pathol 2021; 45:1409-1418. [PMID: 33859071 DOI: 10.1097/pas.0000000000001716] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The molecular characteristics of lymphoepithelioma-like intrahepatic cholangiocarcinoma (LELCC) remain elusive. We examined 27 LELCC cases through next-generation sequencing using a panel of genes commonly mutated in primary liver cancers. Alterations in BAP1, ARID1A, ARID2, and PBRM1 were detected through immunohistochemistry. Fluorescence in situ hybridization was performed to analyze FGFR2 fusions and CCND1 amplification. LELCC is histologically classified as predominantly undifferentiated or glandular. Epstein-Barr virus-encoded small RNA (EBER) expression was found in 16 LELCCs. Approximately 50% of LELCCs expressed programmed death-ligand 1 strongly. Notably, recurrent pTERT and TP53 mutations were detected in 9 (38%) and 8 (33%) tumors, respectively. Only 2 LELCCs exhibited loss of expression for PBRM1. Alterations in genes typically involved in intrahepatic cholangiocarcinoma, including IDH1, IDH2, ARID1A, ARID2, and BAP1, and FGFR2 fusions, were not identified. The 2-step clustering analysis showed 2 distinct subgroups in LELCC, which were separated by EBER expression. A meta-analysis of all reported cases (n=85) has shown that EBER+ LELCC is strongly associated with the female sex, younger age, and exhibited predominantly glandular differentiation (P=0.001, 0.012, and <0.001, respectively). Patients with EBER- LELCC were more likely to have viral hepatitis and cirrhosis (P=0.003 and 0.005, respectively). Genetic analysis demonstrated that EBER- LELCC was significantly associated with pTERT and TP53 mutations (P=0.033 and 0.008, respectively). In conclusion, LELCC is genetically distinct from intrahepatic cholangiocarcinoma. EBER- LELCC may exhibit a different pathogenesis from EBER+ LELCC. High programmed death-ligand 1 expression in LELCC has implications for potential immunotherapeutic strategies.
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18
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Clinicopathologic features, tumor immune microenvironment and genomic landscape of Epstein-Barr virus-associated intrahepatic cholangiocarcinoma. J Hepatol 2021; 74:838-849. [PMID: 33212090 DOI: 10.1016/j.jhep.2020.10.037] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 10/07/2020] [Accepted: 10/30/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about Epstein-Barr virus (EBV)-associated intrahepatic cholangiocarcinoma (EBVaICC) because of its rarity. We aimed to comprehensively investigate the clinicopathology, tumor immune microenvironment (TIME) and genomic landscape of this entity in southern China. METHODS We evaluated 303 intrahepatic cholangiocarcinomas (ICCs) using in situ hybridization for EBV. We compared clinicopathological parameters between EBVaICC and nonEBVaICC, and we analyzed EBV infection status, tumor-infiltrating lymphocytes (TILs) and genomic features of EBVaICC by immunohistochemistry, double staining, nested PCR, multiplex immunofluorescence staining, fluorescence in situ hybridization and whole-exome sequencing. RESULTS EBVaICC accounted for 6.6% of ICCs and was associated with EBV latency type I infection and clonal EBV isolates. Patients with EBVaICC were more often female and younger, with solitary tumors, higher HBV infection rates and less frequent cirrhosis; the lymphoepithelioma-like (LEL) subtype was more common in EBVaICC. EBVaICC was associated with a significantly larger TIME component than nonEBVaICC. The LEL subtype of EBVaICC - associated with a significantly increased density and proportion of CD20+ B cells and CD8+ T cells - was associated with significantly higher 2-year survival rates than conventional EBVaICC and nonEBVaICC. Both PD-1 and PD-L1 in TILs, and PD-L1 in tumor cells, were overexpressed in EBVaICC. High PD-L1 expression in tumor cells and high CD8+ TIL densities were significantly more common in EBVaICC than in nonEBVaICC. Seven genes (MUC4, DNAH1, GLI2, LIPE, MYH7, RP11-766F14.2 and WDR36) were mutated in at least 3 patients. EBVaICC had a different mutational pattern to liver fluke-associated cholangiocarcinoma and HBV-associated ICC. CONCLUSIONS EBVaICC, as a subset of ICC, has unique etiological, clinicopathological and genetic characteristics, with a significantly larger TIME component. Paradoxically, patients with EBVaICC could be candidates for immune checkpoint therapy. LAY SUMMARY Epstein-Barr virus (EBV) is associated with a subtype of intrahepatic cholangiocarcinoma, with unique clinicopathological and genetic characteristics. The tumor immune microenvironment is also different in this tumor subtype and patients with EBV-associated intrahepatic cholangiocarcinoma may respond well to immune checkpoint inhibitors.
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19
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Nogami A, Saito S, Hasegawa H, Yoneda M, Harada K, Fujikawa H. Lymphoepithelioma-like cholangiocarcinoma with Epstein-Barr virus infection treated by radiofrequency ablation. Clin J Gastroenterol 2021; 14:638-644. [PMID: 33400192 DOI: 10.1007/s12328-020-01303-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 11/18/2020] [Indexed: 01/06/2023]
Abstract
Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare intrahepatic tumor. There are usually no specific physical findings, and the tumors are often diagnosed incidentally and are frequently large-sized at diagnosis. The imaging findings of LELCC resemble those of hepatocellular carcinoma (HCC). Tumors are often found in large-sized and advanced at diagnosis, and the main treatment of the disease is surgical resection. Herein, we report treating a patient with early stage LELCC by radiofrequency ablation (RFA). We diagnosed this tumor in a 27-year-old Chinese female with a history of chronic hepatitis B (CHB). Based on the findings of blood examination, abdominal ultrasonography, and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), this tumor was diagnosed as suspected HCC. Ultrasound-guided percutaneous tumor biopsy and RFA were performed at the same time. The histopathological findings finally revealed the diagnosis of LELCC. To the best of our knowledge, this is the first report, in the English-language literature, of the treatment of LELCC by RFA; we suggest that RFA might be a candidate treatment for small-sized early stage LELCC.
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Affiliation(s)
- Asako Nogami
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, 236-0004, Japan
| | - Satoru Saito
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, 236-0004, Japan
| | - Hiromasa Hasegawa
- Hard Tissue Pathology Unit, Graduate School of Oral Medicine, Matsumoto Dental University, 1780 Hirookagohara, Shiojiri, Nagano, 399-0781, Japan
| | - Masato Yoneda
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, 236-0004, Japan
| | - Kenichi Harada
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, 920-8640, Japan
| | - Hirotoshi Fujikawa
- Division of Gastroenterology and Hepatology, Japan Community Healthcare Organization Yokohama Central Hospital, 264 Yamashita-cho, Yokohama, 231-8553, Japan.
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20
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The CT and MRI Features of Primary Intrahepatic Lymphoepithelioma-Like Cholangiocarcinoma. AJR Am J Roentgenol 2020; 216:393-402. [PMID: 33325732 DOI: 10.2214/ajr.20.22937] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE. The purpose of our study was to retrospectively characterize the CT and MRI features of primary intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC). MATERIALS AND METHODS. Eleven patients (10 women and one man; age range, 30-63 years) with 11 pathologically proven LELCCs were enrolled retrospectively from April 2016 to December 2018. Triphasic enhanced images were obtained of all patients: MR images of five patients, CT images of five patients, and both CT and MR images of one patient. The clinical data and CT and MRI findings were reviewed. RESULTS. All LELCC cases were associated with Epstein-Barr virus (EBV) infection. Eight of the 11 patients had hepatitis B virus (HBV) infection. The tumor diameter ranged from 1.1 to 8.7 cm. All tumors were well defined with a smooth or lobulated margin. A cystic area was noted in two of the 11 tumors. After the administration of contrast material, the tumors showed homogeneous (n = 7) or heterogeneous (n = 4) hypervascular arterial enhancement and gradual washout, delayed central scar or irregular enhancement (n = 9), delayed circular thin or incomplete pseudocapsule enhancement (n = 7), and homogeneous hypointensity in the hepatobiliary phase (n = 2). No cirrhosis, focal dilatation of intrahepatic ducts, or satellite nodules were detected. Lymphadenopathy were detected in four patients, appearing as hypervascular enhancement and no necrosis (even in multiple nodes > 3 cm) or as moderate peripheral enhancement and necrosis. CONCLUSION. A liver mass in a middle-aged woman with EBV and HBV infection that appears on CT and MRI to have a well-defined boundary and a combination of hypervascularity, washout, delayed intratumoral enhancement, or pseudocapsule enhancement may suggest an imaging diagnosis of primary LELCC. More cases are needed to better understand this disease.
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21
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Zhang K, Tao C, Tao Z, Wu F, An S, Wu J, Rong W. Lymphoepithelioma-like carcinoma in liver not associated with Epstein-Barr virus: a report of 3 cases and literature review. Diagn Pathol 2020; 15:115. [PMID: 32967689 PMCID: PMC7513497 DOI: 10.1186/s13000-020-01035-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 09/15/2020] [Indexed: 12/13/2022] Open
Abstract
Background Lymphoepithelioma-like carcinoma is a rare distinctive variant of liver cancer with unique epidemiological and pathological characteristics, characterized by dense lymphocyte infiltration. It can be divided into lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like intrahepatic cholangiocarcinoma. Existing research shows that the prognosis of this tumor is good. To date, only 101 cases have been reported. Case presentation The first patient was a 62-year-old Chinese man with hepatitis B virus infection who presented with a single lesion in the liver. The patient underwent surgical treatment and was discharged on the 4th day. The patient was diagnosed with combined lymphoepithelioma-like hepatocellular carcinoma and cholangiocarcinoma; he has been alive for 15 months. The second patient was a 63-year-old Chinese woman with right upper abdominal pain and hepatitis B virus infection. The imaging examination revealed a single lesion in the liver. The patient underwent surgical treatment and was discharged 1 week later. The patient was diagnosed with lymphoepithelioma-like hepatocellular carcinoma and was considered to have recurrence in the lymph nodes approximately 2 years after the operation. The patient underwent local radiotherapy; she has been alive for 60 months. The third patient was a 50-year-old Chinese man with hepatitis B virus infection who presented with a single lesion in the liver and two enlarged lymph nodes. The patient received liver puncture before surgery to indicate lymph node metastasis and experienced local recurrence after liver resection. The patient underwent chemotherapy and radiotherapy. The patient was diagnosed with lymphoepithelioma-like hepatocellular carcinoma. The patient was deceased at 24-month follow-up. Conclusions This article reports 3 cases without Epstein-Barr virus and reviews the current literature, which suggests even mixed pathological type or locally advanced cases of LELC with lymph node metastasis and postoperative recurrence should be actively treated for a longer survival period.
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Affiliation(s)
- Kai Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Changcheng Tao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zonggui Tao
- Department of Imaging, Jinan city people's hospital, Shandong First Medical University, Jinan, 271199, China
| | - Fan Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Songlin An
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
| | - Jianxiong Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Weiqi Rong
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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22
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Lin A, Alpert L, Hart J, Chapman C, Pillai AA. Lymphoepithelioma-Like Carcinomas: A Rare Variant of Cholangiocarcinoma. Hepatology 2020; 72:353-355. [PMID: 31904867 DOI: 10.1002/hep.31102] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 12/12/2019] [Indexed: 01/07/2023]
Affiliation(s)
- Austin Lin
- Department of Internal Medicine, University of Chicago Medicine, Chicago, IL
| | - Lindsay Alpert
- Department of Pathology, University of Chicago Hospitals, Chicago, IL.,Department of Pathology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL
| | - John Hart
- Department of Pathology, University of Chicago Hospitals, Chicago, IL
| | - Christopher Chapman
- Department of Internal Medicine, University of Chicago Medicine, Chicago, IL
| | - Anjana A Pillai
- Department of Internal Medicine, University of Chicago Medicine, Chicago, IL
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23
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Torbenson M, Washington K. Pathology of liver disease: advances in the last 50 years. Hum Pathol 2019; 95:78-98. [PMID: 31493428 DOI: 10.1016/j.humpath.2019.08.023] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 08/28/2019] [Indexed: 02/07/2023]
Abstract
Liver disease has been recognized in various forms for centuries. Incredible advances, however, have been made especially in the last 50 years, driven by improvements in histology, the development of immunostains, the development of high resolution imaging methods, improved biopsy and resection methods, and the emergence of the molecular era. With these tools, pathologists and their clinical and basic science colleagues moved from classifying liver disease using an observational, pattern-based approach to a refined classification of disease, one based on etiology for medical disease and tumor classification for neoplastic disease. Examples of liver specific diseases are used to illustrate these exciting advances. These impressive advances of the past provide the foundation for hope in the future, as liver pathology continues to play an important role in improving patient care through disease identification and classification and emerging roles in guiding therapy for cures.
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Affiliation(s)
- Michael Torbenson
- Department of Pathology and Laboratory Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905.
| | - Kay Washington
- C-3321 MCN, Department of Pathology, Vanderbilt University Medical Center, 1161 21(st) Avenue S, Nashville, TN 37232.
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24
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Gearty SV, Al Jurdi A, Pittman ME, Gupta R. An EBV+ lymphoepithelioma-like cholangiocarcinoma in a young woman with chronic hepatitis B. BMJ Case Rep 2019; 12:12/7/e229520. [PMID: 31289161 DOI: 10.1136/bcr-2019-229520] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Epstein-Barr virus (EBV) is implicated in the tumorigenesis of a variety of malignancies, including Burkitt's lymphoma, Hodgkin's disease and nasopharyngeal carcinoma (NPC). EBV+ lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare type of intrahepatic cholangiocarcinoma with a distinct pathology and poorly understood treatment options. Morphologically, this neoplasm resembles undifferentiated NPC, a commonly EBV+ tumour with a prominent lymphoid infiltrate. Almost all of the current literature regarding LELCC describes early stage tumours that are treated surgically and achieve good outcomes. In contrast, this report documents a late stage LELCC treated unsuccessfully with systemic chemotherapy.
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Affiliation(s)
- Sofia V Gearty
- Cornell University Joan and Sanford I Weill Medical College, New York, New York, USA
| | - Ayman Al Jurdi
- Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York, USA
| | - Meredith E Pittman
- Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York, USA
| | - Renuka Gupta
- Internal Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York, USA
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25
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Ling W, Lu C, Huang H, Qiu T, Lu Q, Huang C, Gong P, Luo Y, Chen S. Ultrasonographic findings of intrahepatic lymphoepithelioma-like cholangiocarcinoma associated with Epstein-Barr virus: Two cases report. Medicine (Baltimore) 2019; 98:e14206. [PMID: 30653176 PMCID: PMC6370147 DOI: 10.1097/md.0000000000014206] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
RATIONALE Epstein-Barr virus (EBV)-related lymphoepithelioma-like cholangiocarcinoma (LELCC) is an extremely rare primary liver tumor with nonspecific clinical manifestations. The clinicopathological features of EBV-associated LELCC have been reported in a few cases. But reports of the tumor's imaging characteristics, particularly ultrasonographic findings, are very rare. PATIENT CONCERNS The first patient was a 64-year-old man with left upper quadrant pain and no nausea and dizziness for about 3 months. The second patient was a 40-year-old man, had an incidental finding of a hepatic tumor in a routine health checkup at a local hospital. DIAGNOSES In the first patient, the abdominal ultrasound demonstrated a slightly heterogeneous hypoechoic nodule in segment 3 of the liver. The nodule was about 2.0 cm × 1.7 cm in size, with a clear margin and regular shape. Color Doppler flow imaging (CDFI) revealed no blood flow signals in this nodule. According to the clinical information and imaging features, it was difficult to determine the diagnosis of the nodule. In the second patient, gray-scale ultrasound revealed a slightly heterogeneous hypoechoic mass measuring 3.5 cm × 2.5 cm with well-defined margin and regular shape at the superior segment of the left hepatic lateral lobe. There was a blurrily hypoechoic halo around the mass. In contrast-enhanced ultrasound (CEUS), the mass was homogeneous hyperenhancement in the arterial phase. In the portal phase and late phase, the center enhancement of the mass washed out gradually, presenting hypoenhancement, Therefore, the tumor was diagnosed as malignancy. INTERVENTION Finally, a laparoscopic left hepatic lateral lobectomy was performed in the first patient. The second patient underwent a left hepatectomy with cholecystectomy. OUTCOMES The first patient has been alive without recurrence or distant metastases for 11 months since the surgery. The second patient received routine follow-up after surgery. Until now, he has been tumor-free for 32 months. LESSONS We mainly focus on the ultrasound characteristics of EBV-associated LELCC, especially its enhancement patterns on CEUS, which may provide valuable information for diagnosis of the LELCC. When a liver tumor with typical CEUS patterns of malignancy is found in middle-aged adults with EBV positive, the possibility of EBV-related LELCC should be considered.
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Affiliation(s)
- Wenwu Ling
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Department of Radiology, Mayo Clinic, Rochester, MN
| | - Changli Lu
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - He Huang
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Tingting Qiu
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Qiang Lu
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | | | - Ping Gong
- Department of Radiology, Mayo Clinic, Rochester, MN
| | - Yan Luo
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Shigao Chen
- Department of Radiology, Mayo Clinic, Rochester, MN
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26
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Very Rare Liver Neoplasm: Lymphoepithelioma-Like ( LEL) Hepatocellular Carcinoma. Case Rep Pathol 2018; 2018:2651716. [PMID: 30258661 PMCID: PMC6146624 DOI: 10.1155/2018/2651716] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Revised: 07/27/2018] [Accepted: 08/26/2018] [Indexed: 12/13/2022] Open
Abstract
A case of lymphoepithelioma-like (LEL) hepatobiliary carcinoma is reported. To date, only 89 cases of this rare neoplasm have been reported, with both hepatocellular and cholangiocellular histotype. The case reported here could be classified as LEL mixed hepatobiliary carcinoma (Hepato-Cholangio), a histotype not reported so far in the LEL variant.
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27
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Parra P, Aguilar J, López-Garrido J, Meléndez B, Merino E, Gordillo E, Roldán JP. Primary Esophageal Lymphoepithelioma. TUMORI JOURNAL 2018; 85:519-22. [PMID: 10774578 DOI: 10.1177/030089169908500619] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Lymphoepitheliomas are extremely rare outside the nasopharynx. Extranasopharyngeal lymphoepitheliomas may be located in the stomach or digestive tract, and only one single case of esophageal location has been found in our review. In many cases the tumor is related to Epstein-Barr virus infection. We report a case of undifferentiated carcinoma of the distal third of the esophagus in a 79-year-old man. Pathological examination of the esophagus revealed an undifferentiated carcinoma with lymphoid stroma (lymphoepithelioma). In situ hybridization of the neoplastic cells was negative for Epstein-Barr virus. To our knowledge, the present case is the first documented esophageal lymphoepithelioma in Western countries.
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Affiliation(s)
- P Parra
- Department of General and Digestive Surgery, Hospital Universitario Virgen de Valme, Seville, Spain
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28
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Wang L, Dong H, Ni S, Huang D, Tan C, Chang B, Sheng W. Programmed death-ligand 1 is upregulated in intrahepatic lymphoepithelioma-like cholangiocarcinoma. Oncotarget 2018; 7:69749-69759. [PMID: 27626174 PMCID: PMC5342512 DOI: 10.18632/oncotarget.11949] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 09/02/2016] [Indexed: 01/10/2023] Open
Abstract
Intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare variant of cholangiocarcinoma. Here, we report the largest single series of LELCC cases yet studied (n = 13). We retrospectively analyzed the clinical data of the 13 patients and measured the expression of programmed death-ligand 1 (PD-L1) in tumors using immunohistochemical staining. We also analyzed 15 cases of conventional intrahepatic cholangiocarcinoma (IHCC) for comparison. We found that eight patients with LELCC were infected with Epstein-Barr Virus (EBV), and EBV infection correlated with poor prognosis in LELCC. Four patients among the five (80.0%) without EBV had a history of chronic viral hepatitis B. None of the 15 cases of conventional cholangiocarcinoma were positive for EBV. PD-L1 was expressed in both the tumor cells and tumor-infiltrating immune cells in LELCC patients at higher levels than in IHCC patients (P < 0.05). These observations suggest that EBV infection may promote the development of LELCC, and that PD-L1 may be a potential therapeutic target for treatment of EBV-associated LELCC.
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Affiliation(s)
- Lei Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Hui Dong
- Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, 200438, China
| | - Shujuan Ni
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Dan Huang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Cong Tan
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Bin Chang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Weiqi Sheng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
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29
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Labgaa I, Stueck A, Ward SC. Lymphoepithelioma-Like Carcinoma in Liver. THE AMERICAN JOURNAL OF PATHOLOGY 2017; 187:1438-1444. [PMID: 28500863 DOI: 10.1016/j.ajpath.2017.02.022] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2017] [Accepted: 02/27/2017] [Indexed: 02/07/2023]
Abstract
Liver cancer, primarily encompassing hepatocellular carcinoma and intrahepatic cholangiocarcinoma, has become the second leading cause of worldwide cancer-related death during the past two decades. Lymphoepithelioma-like carcinomas (LELCs) are defined as tumors composed of undifferentiated epithelial cells with a prominent lymphoid infiltrate, and can arise in the liver as hepatocellular or cholangiocarcinoma forms. Patients with liver LELC display distinctive demographics and tumor characteristics. LELCs also appear to be associated with strikingly better outcomes compared to typical liver cancers, with 5-year survival rates of 57% to 100% versus 12% to 68%, respectively. Liver LELCs represent a unique model of immune response in liver cancer. Data on LELCs of the liver remain limited, and future comprehensive studies are needed to further elucidate this disease, which could ultimately offer precious insights for immunotherapeutic strategies in liver cancer.
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Affiliation(s)
- Ismail Labgaa
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland
| | - Ashley Stueck
- Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Stephen C Ward
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
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30
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Epstein–Barr virus (EBV) associated lymphoepithelioma-like cholangiocarcinoma with elevated EBV DNA titer and treated with systemic chemotherapy. JOURNAL OF CANCER RESEARCH AND PRACTICE 2017. [DOI: 10.1016/j.jcrpr.2016.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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31
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Intrahepatic Cholangiocarcinoma With Lymphoepithelioma-like Carcinoma Components Not Associated With Epstein-Barr Virus: Report of a Case. Int Surg 2016; 100:689-95. [PMID: 25875552 DOI: 10.9738/intsurg-d-14-00117.1] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as lymphoepithelioma-like carcinoma (LELC). Intrahepatic cholangiocarcinoma (ICC) with LELC components is rare, and most LELCs are associated with Epstein-Barr virus (EBV). We report here on a case of ICC with LELC components not associated with EBV. A 65-year-old woman was incidentally found to have a hepatic tumor in the caudate lobe. An extended right hepatectomy with lymphadenectomy was performed. Histologically, the tumor was mainly composed of large undifferentiated epithelial cells with vesicular nuclei, prominent nucleoli, indistinct cell borders, and heavy small lymphocytic infiltration, which are the characteristic features of LELC. Immunohistochemical studies revealed that the tumor cells were positive for cytokeratin 19 but were negative for glypican 3. In situ hybridization using EBV-encoded RNA was negative. Therefore, a diagnosis of ICC with LELC components not associated with EBV was made. Because there is limited information available regarding the prognosis and treatment of ICC with LELC components because of the limited number of reported cases, additional studies will be needed to clarify the clinicopathologic features of this disease.
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32
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Sun K, Xu S, Wei J, Wang B, Owusu-Ansah KG, Wang W, Wu J, Zheng S. Clinicopathological features of 11 Epstein-Barr virus-associated intrahepatic cholangiocarcinoma at a single center in China. Medicine (Baltimore) 2016; 95:e5069. [PMID: 27749575 PMCID: PMC5059078 DOI: 10.1097/md.0000000000005069] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
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.
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Affiliation(s)
| | - Shaoyan Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
- Key Laboratory of Organ Transplantation
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China
| | - Jianfeng Wei
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
- Key Laboratory of Organ Transplantation
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China
| | | | - Kwabena Gyabaah Owusu-Ansah
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
- Key Laboratory of Organ Transplantation
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China
| | - Weilin Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
- Key Laboratory of Organ Transplantation
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China
| | - Jian Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
- Key Laboratory of Organ Transplantation
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
- Key Laboratory of Organ Transplantation
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China
- Correspondence: Shusen Zheng, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou 310003, China (e-mail: )
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33
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Wiwanitkit V. Epstein-Barr Virus Infection and Opisthorchiasis: A Story of Cholangiocarcinoma in the Highly Endemic Area. IRANIAN JOURNAL OF CANCER PREVENTION 2016; 9:e3647. [PMID: 27482325 PMCID: PMC4951762 DOI: 10.17795/ijcp-3647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/25/2015] [Revised: 08/15/2015] [Accepted: 01/17/2016] [Indexed: 11/25/2022]
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34
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Solinas A, Calvisi DF. Lessons from rare tumors: Hepatic lymphoepithelioma-like carcinomas. World J Gastroenterol 2015; 21:3472-3479. [PMID: 25834311 PMCID: PMC4375568 DOI: 10.3748/wjg.v21.i12.3472] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 12/11/2014] [Accepted: 02/05/2015] [Indexed: 02/06/2023] Open
Abstract
In this review we focus on lymphoepithelioma-like hepatocellular carcinomas (LEL-HCC) and lymphoepithelioma-like cholangiocarcinomas (LEL-ICC). Despite their rarity, these tumors are of general interest because of their epidemiological and clinical features, and because they represent a distinct model of interaction between the immune system and neoplastic cells. Approximately half of LEL-HCC arise in the context of chronic hepatitis C virus (HCV) infection and have been described both in Eastern and Western patients. By contrast, LEL-ICC is associated in almost all cases with Epstein-Barr virus (EBV) infection and exhibits the same epidemiological features of EBV related malignancies. Compared with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma of corresponding stage, both LEL-HCC and LEL-ICC are characterized by lower rates of recurrence after surgery and better overall survival. How this behavior is related to distinct genetic alterations and tumor microenvironment is unclear. The pathophysiological mechanisms of lymphoid infiltrations seem to be different among the two groups of tumors. In fact, LEL-HCC frequently arises in the context of inflammatory changes driven by HCV infection, and has been recognized as a variant of classical hepatocellular carcinoma. At variance, lymphocyte recruitment of LEL-ICC is similar to that described in nasopharyngeal carcinoma and gastric LEL, and possibly depends on the expression pattern of latent EBV infection.
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35
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Patel KR, Liu TC, Vaccharajani N, Chapman WC, Brunt EM. Characterization of inflammatory (lymphoepithelioma-like) hepatocellular carcinoma: a study of 8 cases. Arch Pathol Lab Med 2014; 138:1193-202. [PMID: 25171701 DOI: 10.5858/arpa.2013-0371-oa] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
CONTEXT The World Health Organization has recently recognized lymphoepithelioma-like carcinoma, or inflammatory hepatocellular carcinoma, as a variant of hepatocellular carcinoma. OBJECTIVE To identify and characterize the inflammatory hepatocellular carcinomas in our institution from 1988 to the present. DESIGN All cases of hepatocellular carcinoma in our institution from 1988 to the present were reviewed and reclassified as lymphoepithelioma-like carcinoma and were studied in comparison to appropriately matched controls. RESULTS Among the 8 cases of lymphoepithelioma-like carcinoma identified, the male to female ratio was 1:3, the mean age was 68.5 years (range, 57-78 years), and all of the cases were seen in noncirrhotic livers. The average numbers of lymphocytes were significantly higher in the cases than in the controls. T cells were predominant, with a uniform distribution of CD4 and CD8 positive cells. Cholangiolar differentiation was seen by K19 positivity as focal in 1 case and diffuse in 2 cases. In situ hybridization for Epstein-Barr virus was negative in all of the cases. Diffuse overexpression of p16 (>75% of cells) was seen in 2 cases, both of which were negative for the presence of transcriptionally active human papilloma virus by in situ hybridization. In our series, 3 of 8 cases (37.5%) showed local recurrence, which was similar to the controls (6 of 18; 33%), P > .99. Although the rate of distant metastases was lower among the cases (12.5%) than the controls (22.2%), the difference was not statistically significant (P > .99). CONCLUSION We present the first series of 8 cases of lymphoepithelioma-like carcinoma of the liver occurring in patients without cirrhosis and with a female preponderance and the absence of Epstein-Barr virus. Although clinical outcomes were similar to those of controls in our small series, additional data may be required for confirmation.
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Affiliation(s)
- Kalyani R Patel
- From the Department of Laboratories, Seattle Children's Hospital, Seattle, Washington (Dr Patel); and the Departments of Pathology and Immunology (Drs Liu and Brunt) and Surgery (Drs Vaccharajani and Chapman), Washington University in St Louis, St Louis, Missouri
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36
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Chan AWH, Tong JHM, Sung MYM, Lai PBS, To KF. Epstein-Barr virus-associated lymphoepithelioma-like cholangiocarcinoma: a rare variant of intrahepatic cholangiocarcinoma with favourable outcome. Histopathology 2014; 65:674-83. [PMID: 24804938 DOI: 10.1111/his.12455] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Accepted: 04/30/2014] [Indexed: 01/01/2023]
Abstract
AIMS Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare variant of intrahepatic cholangiocarcinoma (IHCC). Only 16 cases have reported previously in the literature, and about 62.5% of these cases were associated with Epstein-Barr virus (EBV). METHODS AND RESULTS We present the largest series (seven cases) of LELCC with descriptions of clinical and pathological characteristics, investigations of aberrant DNA methylation and mutation analyses of EGFR and KRAS. The evaluation also included 11 cases of stage-matched conventional IHCC for comparison. RESULTS All seven patients of LELCC were female and had stage I disease. LELCC had significantly better 2- and 5-year overall survival than IHCC (100% versus 52.8%, and 100% versus 13.2%, respectively, P = 0.003). All seven LELCCs were EBV-associated and composed exclusively of adenocarcinoma with varied glandular differentiation, dense lymphoplasmacytic infiltrate, and variable expression of biliary-type cytokeratins (CK7 and CK19) and stemness markers (CD133 and EpCAM). Gene hypermethylation was more frequent in LELCC than IHCC. CRBPI (85.7% versus 9.1%, P < 0.003) and CRBPIV (85.7% versus 0%, P < 0.001) showed statistically higher methylation frequencies in LELCC than IHCC. No LELCC harboured any EGFR or KRAS mutation. CONCLUSION Epstein-Barr virus-associated LELCC is a variant of IHCC, characterized by marked female predominance, favourable overall survival and distinctively frequent DNA hypermethylation.
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Affiliation(s)
- Anthony W H Chan
- State Key Laboratory in Oncology in South China, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong
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Shinoda M, Kadota Y, Tsujikawa H, Masugi Y, Itano O, Ueno A, Mihara K, Hibi T, Abe Y, Yagi H, Kitago M, Kawachi S, Tanimoto A, Sakamoto M, Tanabe M, Kitagawa Y. Lymphoepithelioma-like hepatocellular carcinoma: a case report and a review of the literature. World J Surg Oncol 2013; 11:97. [PMID: 23642182 PMCID: PMC3654885 DOI: 10.1186/1477-7819-11-97] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2012] [Accepted: 04/08/2013] [Indexed: 12/15/2022] Open
Abstract
We report a rare case of lymphoepithelioma-like hepatocellular carcinoma. A 79-year-old Japanese man had undergone curative resection of extrahepatic bile ducts because of bile duct cancer 9 years prior. The bile duct cancer was diagnosed as mucosal adenocarcinoma, and the patient had been followed up every 6 months for the last 9 years. A recent computed tomography examination revealed a tumor, 4.2 cm in size, in the lateral segment of the liver. Based on the imaging findings, the tumor was diagnosed as hepatocellular carcinoma. Serology tests were negative for hepatitis B and C viruses. Chest and abdominal image analyses showed no evidence of metastasis, but a swollen lymph node was noted around the abdominal aorta. The patient subsequently underwent extended lateral segmentectomy and resection of the swollen lymph node. Microscopically, the tumor had the characteristic appearance of poorly differentiated hepatocellular carcinoma. Moreover, an abundant infiltration of inflammatory cells was observed in the tumor. Therefore, we diagnosed the tumor as lymphoepithelioma-like hepatocellular carcinoma. The resected para-aortic lymph node also had a carcinoma with features similar to those of the main tumor. The patient has been alive for 20 months since performance of the surgery. Since the first report of lymphoepithelioma-like hepatocellular carcinoma in 2000, only nine cases have been reported in the medical literature, and the clinicopathological features of the disease have not been well documented. Herein, we describe the clinicopathological features of this case for further understanding of the disease and review past cases in the literature.
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Affiliation(s)
- Masahiro Shinoda
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
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Ishida M, Mori T, Shiomi H, Naka S, Tsujikawa T, Andoh A, Saito Y, Kurumi Y, Kojima F, Hotta M, Tani T, Fujiyama Y, Okabe H. Non-Epstein-Barr virus associated lymphoepithelioma-like carcinoma of the inferior common bile duct. World J Gastrointest Oncol 2011; 3:111-5. [PMID: 21860687 PMCID: PMC3158861 DOI: 10.4251/wjgo.v3.i7.111] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2010] [Revised: 06/21/2011] [Accepted: 06/27/2011] [Indexed: 02/05/2023] Open
Abstract
A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma (LEC), and some of LEC is associated with Epstein-Barr virus (EBV). All of the 13 previously reported cases of LEC of the biliary system were intrahepatic in location. Herein, we describe the first case of LEC of the inferior common bile duct. A 68-year-old Japanese man, who had been previously treated for hepatocellular carcinoma using microwave coagulation therapy, was found to have tumors of the common bile duct and pancreas head. Histopathological study of the resected tumor showed solid or cohesive nests of large undifferentiated cells with irregular large vesicular nuclei and nucleoli. Around the tumor cell nests, dense lymphoplasmacytic infiltration was observed. Focal glandular differentiation (approximately 5%) was also present. These histopathological features corresponded morphologically to LEC. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7, CK 19 and CA19-9, but negative for CK 20 and Hep Par 1. In situ hybridization for Epstein Barr virus early small RNAs disclosed no nuclear signal in tumor cells. Therefore, a diagnosis of non-EBV-associated LEC of the inferior common bile duct was made. Although the prognosis of the biliary LEC is thought to be better than that of conventional cholangiocarcinoma, the differences in prognosis between EBV-positive and -negative cases have not yet been established. Therefore, additional case studies will be needed to clarify the clinicopathological features of LEC of the biliary tract.
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Affiliation(s)
- Mitsuaki Ishida
- Mitsuaki Ishida, Fumiyoshi Kojima, Machiko Hotta, Hidetoshi Okabe, Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan
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Lee W. Intrahepatic lymphoepithelioma-like cholangiocarcinoma not associated with epstein-barr virus: a case report. Case Rep Oncol 2011; 4:68-73. [PMID: 21475593 PMCID: PMC3072182 DOI: 10.1159/000324485] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Lymphoepithelioma-like cholangiocarcinomas are rare tumors and most of them are related with Epstein-Barr virus (EBV) infection. Here, a case of a patient with lymphoepithelioma-like cholangiocarcinoma not associated with EBV infection is presented. In a 79-year-old man with hepatitis B virus-associated cirrhosis, a liver mass was detected on abdominal CT. Macroscopically, the resected tumor was pale gray, rubbery and well defined. Histologically, the tumor was composed of two components: an adenocarcinoma that formed irregular small glands and a lymphoepithelioma-like carcinoma that exhibited sheets of undifferentiated epithelial cells with lymphoid stroma. Lymphoplasmacytic infiltrates were more predominant in the lymphoepithelioma-like carcinoma than in the adenocarcinoma. Both components were roughly divided, but they gradually merged. Immunohistochemically, the adenocarcinoma component was diffusely positive for AE1/AE3, cytokeratin 7, cytokeratin 19 and epithelial membrane antigen, while the lymphoepithelioma-like carcinoma component was focally positive for them. However, both components were diffusely positive for p53 protein, and in situ hybridization using EBV-encoded RNA 1 was negative in both components as well. Examination of a resected para-aortic lymph node revealed metastasis exclusively of the lymphoepithelioma-like carcinoma component.
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Affiliation(s)
- Wonae Lee
- Department of Pathology, Dankook University College of Medicine, Cheonan, Korea
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40
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Hepatocellular carcinoma with massive lymphoid infiltration: A regressing phenomenon? Pathol Res Pract 2009; 205:648-52. [DOI: 10.1016/j.prp.2009.01.001] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2008] [Revised: 12/22/2008] [Accepted: 01/06/2009] [Indexed: 02/06/2023]
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41
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Adachi S, Morimoto O, Kobayashi T. Lymphoepithelioma-like cholangiocarcinoma not associated with EBV. Pathol Int 2008; 58:69-74. [PMID: 18067645 DOI: 10.1111/j.1440-1827.2007.02192.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Reported herein is an unusual case of intrahepatic cholangiocarcinoma with lymphoepithelioma-like appearance in a 64-year-old man who was found to have an intrahepatic mass without cirrhosis. The tumor had two distinct histological patterns with dense lymphoplasmacytic infiltrate. The first was similar to nasopharyngeal undifferentiated carcinoma; the second pattern was a well-differentiated adenocarcinoma. Transition between the two components was observed in the same duct. Immunohistochemistry indicated that the tumor was immunoreactive with AE1/AE3 and cytokeratin (CK) 7, but negative for CEA and CK20. Stromal inflammatory infiltrate primarily consisted of plasma cells and lymphocytes. Immunohistochemical examination and in situ hybridization for EBV showed no integration of the virus in the tumor cells. Intrahepatic lymphoepithelioma-like carcinoma is rare, and most are associated with EBV. Only three cases were not associated with EBV. The authors would like to add one more example of the tumors not associated with EBV.
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Affiliation(s)
- Shiro Adachi
- Department of Pathology, City Hospital of Ikeda, Ikeda, Osaka, Japan.
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42
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Si MW, Thorson JA, Lauwers GY, DalCin P, Furman J. Hepatocellular lymphoepithelioma-like carcinoma associated with epstein barr virus: a hitherto unrecognized entity. ACTA ACUST UNITED AC 2005; 13:183-9. [PMID: 15322431 DOI: 10.1097/01.pas.0000124336.90615.8d] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Lymphoepithelioma-like carcinoma (LELC) is an undifferentiated carcinoma with a dense lymphoid stroma. It has been reported in diverse organs and shows variable association with Epstein-Barr virus (EBV). Only a few EBV positive cases have been observed in the hepatobiliary system, all of which were considered to be cholangiocarcinomas. We report a unique case of hepatocellular LELC arising in a cirrhotic liver with EBV demonstrated in the tumor cells. METHODS AND RESULTS A 39-year-old Hispanic female underwent an orthotopic liver transplant for end stage liver disease secondary to chronic hepatitis C. A high-grade hepatocellular carcinoma with a dense lymphocytic infiltrate was found in the explant as well as in a portal lymph node. Three months posttransplant, the patient developed numerous hepatic nodules with enlarged periaortic and portacaval lymph nodes. Biopsy of the hepatic nodules showed a recurrent hepatocellular carcinoma devoid of a dense lymphocytic infiltrate. Both the primary and recurrent tumors were positive for EBV by molecular studies. The patient eventually expired from liver failure over a 6-week period. CONCLUSION This case represents the first report of EBV-positive hepatocellular LELC. It is particularly interesting given the precipitous clinical outcome, which was possibly related to immunosuppresive therapy.
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MESH Headings
- Adult
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/virology
- Carcinoma, Squamous Cell/genetics
- Carcinoma, Squamous Cell/pathology
- Carcinoma, Squamous Cell/virology
- Chromosomes, Human, Pair 11/genetics
- Epstein-Barr Virus Infections/complications
- Epstein-Barr Virus Infections/pathology
- Female
- Gene Dosage
- Herpesvirus 4, Human/isolation & purification
- Humans
- Immunohistochemistry
- In Situ Hybridization, Fluorescence
- Liver Cirrhosis/virology
- Liver Neoplasms/genetics
- Liver Neoplasms/pathology
- Liver Neoplasms/virology
- Liver Transplantation
- Lymphatic Metastasis/pathology
- Polymerase Chain Reaction
- Tumor Virus Infections/complications
- Tumor Virus Infections/pathology
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Affiliation(s)
- Michael W Si
- Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA
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44
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Kekis PB, Murtin C, Künzli BM, Kappler A, Buchholz B, Büchler MW, Zimmermann A, Friess H. Epstein-Barr virus-associated lymphoepithelial carcinoma in the pancreas. Pancreas 2004; 28:98-102. [PMID: 14707738 DOI: 10.1097/00006676-200401000-00016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Lymphoepithelial carcinoma is a relatively common malignancy in the nasopharyngeal region, but it rarely occurs at other sites. We report a lymphoepithelial carcinoma in the pancreas of a 65-year-old male patient operated on for a gastric stump carcinoma 7 years previously. The solitary tumor in the pancreas presented as a circumscribed lesion and measured 5.5 cm in diameter. The tumor was densely infiltrated by lymphocytes, and the neoplastic cells fulfilled all criteria for a lymphoepithelial carcinoma. Several peripancreatic lymph node metastases were observed. Marked reactivity for Epstein-Barr virus (EBV) early RNA (EBER) was detected in the majority of tumor cells using in situ hybridization. Nuclear EBER signals were also detected in the previously operated gastric stump adenocarcinoma, which also exhibited focal lymphocytic infiltration but otherwise displayed a histology different from lymphoepithelial carcinoma and did not show local recurrence. Even though an unusually late metastasis of the gastric carcinoma cannot be ruled out, we favor the hypothesis that this patient developed an EBV-related pancreatic lymphoepithelial carcinoma as a second primary tumor, based on the considerable delay of this tumor manifestation, the unusual site, the pathologic presentation, the exclusively peripancreatic nodal spread, and the different histology of the lesion.
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Jeng YM, Sung MT, Fang CL, Huang HY, Mao TL, Cheng W, Hsiao CH. Sinonasal undifferentiated carcinoma and nasopharyngeal-type undifferentiated carcinoma: two clinically, biologically, and histopathologically distinct entities. Am J Surg Pathol 2002; 26:371-6. [PMID: 11859210 DOI: 10.1097/00000478-200203000-00012] [Citation(s) in RCA: 86] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Sinonasal undifferentiated carcinoma (SNUC) is a rare aggressive neoplasm arising in the nasal cavity and paranasal sinuses. Primary sinonasal nasopharyngeal-type undifferentiated carcinoma (PSNPC) is an even rarer tumor that has not been adequately reported. Both tumors have been reported to be associated with Epstein-Barr virus (EBV). We studied the clinicopathologic features and EBV status of 36 SNUC and 13 PSNPC patients from Taiwan, an EBV endemic area. The median age of SNUC patients was 53 years (range 20-76 years), with a male/female ratio of approximately 2:1. Five patients had histories of previous nasopharyngeal carcinoma treated with irradiation 6-26 years earlier. The most common locations were nasal cavity and ethmoid sinus. Orbital and intracranial invasion and distant metastasis were frequent findings. The median survival was 10 months. All 36 tumors were negative for EBER-1 by in situ hybridization. The median age of PSNPC patients was 58 years (range 36-75 years), with a male/female ratio of approximately 2:1. The most common location is nasal cavity. Eight patients achieved disease-free survival. Eight tumors had the morphology of lymphoepithelioma, whereas significant inflammatory infiltrate was not detected in the other five tumors. All 13 tumors were positive for EBER-1 by in situ hybridization. Because of the difference in the relation with EBV, prognosis, and response to radiotherapy, SNUC and PSNPC should be considered as two entirely different entities. The most important criteria for PSNPC are vesicular nuclei, syncytial pattern, spindle cells, and absence of necrosis.
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Affiliation(s)
- Yung-Ming Jeng
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
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46
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Szekely E. Lymphoepithelioma-like cholangiocarcinoma (LELC) not associated with Epstein-Barr virus. Am J Surg Pathol 2001; 25:1464-6. [PMID: 11684969 DOI: 10.1097/00000478-200111000-00023] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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47
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Kijima Y, Hokita S, Takao S, Baba M, Natsugoe S, Yoshinaka H, Aridome K, Otsuji T, Itoh T, Tokunaga M, Eizuru Y, Aikou T. Epstein-Barr virus involvement is mainly restricted to lymphoepithelial type of gastric carcinoma among various epithelial neoplasms. J Med Virol 2001; 64:513-8. [PMID: 11468737 DOI: 10.1002/jmv.1079] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
To demonstrate the association of Epstein-Barr virus (EBV) with primary epithelial neoplasms in the south part of Kyushu, Japan, 761 carcinomas consisting of 75 lung, 61 breast, 107 esophagus, 102 colon, 58 pancreas, 45 thyroid, and 313 gastric cancers were examined by EBER-1 in situ hybridization. EBER-1 was detected in 23 cases (7.3%) out of 313 gastric carcinomas, while none of the other carcinomas was positive for EBER-1. Twenty-eight (9.4%) out of 313 gastric carcinomas were differentiated poorly to moderately carcinomas with prominent lymphoid cell infiltration, similar to so-called lymphoepithelioma-like carcinoma, and 19 cases (67.9%) were positive for EBER-1. Although two (2.6%) and 11(10.3%) out of 75 lung and 107 esophagus carcinomas were so-called lymphoepithelioma-like carcinomas, respectively, but EBER-1 was not detected in other epithelial neoplasms that originated from the lung, esophagus, breast, colon, pancreas, and thyroid in the south of Kyushu, Japan. As a result, EBV was associated with only some gastric carcinomas but not with other epithelial neoplasms originating from the lung, esophagus, breast, colon, pancreas, and thyroid in southern Japan.
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Affiliation(s)
- Y Kijima
- The First Department of Surgery, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
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48
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Castro CY, Ostrowski ML, Barrios R, Green LK, Popper HH, Powell S, Cagle PT, Ro JY. Relationship between Epstein-Barr virus and lymphoepithelioma-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature. Hum Pathol 2001; 32:863-72. [PMID: 11521232 DOI: 10.1053/hupa.2001.26457] [Citation(s) in RCA: 99] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Lymphoepithelioma-like carcinoma (LELC) is a rare form of lung cancer, usually encountered in Chinese patients. Similar to nasopharyngeal carcinoma, LELC of the lung is strongly associated with Epstein-Barr virus (EBV) infection in Asian patients, but there is controversy over whether an association exists in patients from Western countries. To determine whether such a relationship exists, we retrospectively studied 6 cases of primary LELC of the lung, all of which were in Western patients. There were 4 men and 2 women, ranging in age from 49 to 75 years. The tumors ranged from 1 to 4.5 cm in diameter. Four patients had stage I disease, 1 had stage IIb disease, and 1 had stage IIIa disease. All patients are alive without evidence of disease with a follow-up of 18 to 30 months. Formalin-fixed, paraffin-embedded tissue was stained with hematoxylin-eosin for routine evaluation and immunostained for keratin and leukocyte common antigen (LCA). LCA staining was performed to exclude large-cell lymphoma. Immunoperoxidase staining (1:500 clone CS1-4; Dako, Carpinteria, CA) and in situ hybridization were performed to detect EBV. Tumors consisted of solid nests of undifferentiated tumor cells in a syncytial arrangement surrounded by heavy lymphoplasmacytic infiltrate. Tumor cells stained positively for keratin but negative for LCA. All 6 cases were negative for EBV, suggesting no association between EBV and LELC in the Western population.
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Affiliation(s)
- C Y Castro
- Division of Pathology, the University of Texas M.D. Anderson Cancer Center, Baylor College of Medicine, Houston, TX, USA
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Abstract
We present two cases of intrahepatic cholangiocarcinoma with lymphoepithelioma-like component. The patients included one woman and one man, aged 67 and 41 years, respectively. They presented with right upper quadrant pain and epigastralgia. Histologically, both tumors showed two distinct histological patterns with dense lymphoplasma cell infiltration. The first pattern was a well to moderately differentiated adenocarcinoma; the second component showed a feature similar to lymphoepithelioma-like carcinoma. Granulomatous reaction was noted in one case. Immunohistochemical study revealed that both tumors were immunoreactive with AE1/AE3, cytokeratin 7, and cytokeratin 19 but negative for carcinoembryonic antigen and cytokeratin 20. The stromal lymphocytes were composed of predominantly CD3(+) T cells. In situ hybridization for Epstein-Barr virus (EBV)-encoded RNA (EBER) showed positive nuclear signal in tumor cells but not in inflammatory cells in one case. The presence or absence of EBV genome was confirmed by polymerase chain reaction of LMP-1 gene in both cases. The LMP-1 gene also had a 30-bp deletion in Exon 3 as compared with the products from B95-8 cells. We further sequenced the PCR product and confirmed a 30-bp deletion between Nucleotide (nt) 168,282 and nt 168,253 corresponding to the B95-8 sequence. The clinical significance of 30-bp deletion in Exon 3 of the LMP-1 gene in lymphoepithelioma-like carcinoma of the liver warrants further investigation.
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MESH Headings
- Adaptor Proteins, Signal Transducing
- Aged
- Bile Duct Neoplasms/chemistry
- Bile Duct Neoplasms/genetics
- Bile Duct Neoplasms/pathology
- Bile Duct Neoplasms/virology
- Bile Ducts, Intrahepatic/pathology
- Biomarkers, Tumor/analysis
- Carcinoma, Squamous Cell/chemistry
- Carcinoma, Squamous Cell/genetics
- Carcinoma, Squamous Cell/pathology
- Carcinoma, Squamous Cell/virology
- Carrier Proteins/analysis
- Carrier Proteins/genetics
- Cholangiocarcinoma/chemistry
- Cholangiocarcinoma/genetics
- Cholangiocarcinoma/pathology
- Cholangiocarcinoma/virology
- Cytoskeletal Proteins
- DNA, Neoplasm/analysis
- Female
- Gene Deletion
- Herpesvirus 4, Human/genetics
- Herpesvirus 4, Human/isolation & purification
- Humans
- Immunoenzyme Techniques
- In Situ Hybridization
- Intracellular Signaling Peptides and Proteins
- LIM Domain Proteins
- Male
- Middle Aged
- Neoplasm Proteins/analysis
- Polymerase Chain Reaction
- RNA, Viral/analysis
- RNA-Binding Proteins/analysis
- Ribosomal Proteins
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Affiliation(s)
- T C Chen
- Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Kwei San, Tao Yuan, Taiwan.
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50
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Oga A, Sadamitu D, Hattori Y, Nakamura Y, Kohno M, Kawauchi S, Sasaki K. Imported malaria in a Japanese male: an autopsy report. Pathol Int 2001; 51:371-5. [PMID: 11422795 DOI: 10.1046/j.1440-1827.2001.01206.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Fatal cases of malaria are rare in Japan. We report a case of a 47-year-old Japanese man with Plasmodium falciparum malaria. The patient was examined because of fever and headache after a trip to Africa. He was diagnosed with malaria. Chemotherapy begun on day three decreased the percentage of infected red blood cells (RBC) from 25% to 2%, but the patient fell into coma on the same day. The patient was considered brain dead for 3 days before he died, and he was autopsied on day nine. Brain hemispheres were preserved and swollen with meningeal congestion. The ventral area of the pons and medulla oblongata were softened, and the tonsils of the cerebellum were softened and herniated. The spleen was blackish, enlarged and showed a small infarction. The liver was yellowish and enlarged. Many infected RBC were seen in the capillaries of the brain and malaria pigments were seen in the spleen and liver. DNA of P. falciparum was detected by polymerase chain reaction from paraffin-embedded brain materials, however, the DNA could not be detected in other organs. Besides malaria, the patient had latent primary thyroid cancer, which was a small and invasive papillary carcinoma.
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Affiliation(s)
- A Oga
- Department of Pathology, Yamaguchi University School of Medicine, Yamaguchi, Japan.
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