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Zou Q, Luo K, Kang L, Huang C, Mai J, Lin Y, Liang Y. Clinical significance of baseline Epstein-Barr virus DNA for recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma. Future Oncol 2023; 19:2481-2492. [PMID: 38054449 DOI: 10.2217/fon-2023-0722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2023] Open
Abstract
Background: This study aimed to evaluate the clinical significance of baseline Epstein-Barr virus (EBV) DNA in recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma (PLELC). Methods: 75 patients with baseline EBV DNA were included. The relationships between baseline EBV DNA and clinical characteristics, survival and objective response rate were analyzed. Results: The baseline EBV DNA levels were related to the liver, chest wall, distant lymph node(s) or multiple sites of distant metastasis. The high baseline EBV DNA group (≥41,900 copies/ml) was related to shorter progression-free and overall survival in univariate analysis and remained significant for progression-free survival in multivariate analysis. Conclusion: The baseline EBV DNA is a valuable biomarker for predicting prognosis and reflecting tumor burden in recurrent or metastatic PLELC.
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Affiliation(s)
- Qihua Zou
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Kongjia Luo
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Liping Kang
- Department of Medical Oncology, Yuebei People's Hospital, Shaoguan, China
| | - Caiwen Huang
- Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences Shenzhen Center, Shenzhen, China
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Shenzhen, China
| | - Jianliang Mai
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yongbin Lin
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ying Liang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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Chen Y, Liu T, Xu Z, Dong M. Association of Epstein-Barr virus (EBV) with lung cancer: meta-analysis. Front Oncol 2023; 13:1177521. [PMID: 37860200 PMCID: PMC10582925 DOI: 10.3389/fonc.2023.1177521] [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: 03/01/2023] [Accepted: 09/13/2023] [Indexed: 10/21/2023] Open
Abstract
Objective Epstein-Barr virus (EBV) is a virus that is ubiquitous in humans. To investigate the association between EBV infection and lung cancer risk to reveal whether it is involved in the development and development of lung cancer. Although there has been discussion of EBV and lung cancer in the past. Through this study, we hope to deepen our understanding of the causes of lung cancer and provide new clues and targets for the prevention, early diagnosis and treatment of lung cancer. This study is also beneficial to the development of medical science and public health. First of all, the research results are expected to be incorporated into lung cancer prevention and treatment strategies and policies, so as to provide better treatment decisions for lung cancer patients and improve the survival rate and quality of life of patients. At the same time, communicating the research results to the public can help raise awareness of lung cancer risk factors. By encouraging healthy lifestyles and screening measures, the public can reduce their risk of lung cancer. In addition, this study also provides an important foundation for subsequent academic research and scientific exploration. It provides valuable information and inspiration for in-depth understanding of lung cancer and other related fields. Overall, this study makes an important contribution to both medical science and public health. Method By September 26, 2022, an online database was used to conduct a literature search in English. Random effects models were employed to estimate the prevalence of EBV with 95% confidence intervals (CIs). Additionally, the pooled odds ratio (OR) and 95%CI were calculated from case-control studies to determine the association between EBV and lung cancer. Results In this study of 886 patients with lung cancer, the overall prevalence of EBV infection was found to be 44.36% (95%CI: 4.08-16.9). Fourteen studies were included in the analysis, all of which used a case-control design and involved comparisons of tumors with adjacent or non-adjacent normal and non-cancerous controls. There was a significant difference in the prevalence of EBV infection in lung cancer tissues between China and other regions, with an odds ratio (OR) of 9.36 (95% confidence interval: 4.00-21.94, P<0.001, I²=73.5%). This suggests that the association between EBV infection and lung cancer cases is stronger in China than in other regions. Additionally, the prevalence of EBV infection varied across different pathological types of lung cancer, with rates of 81.08% for pulmonary lymphoepithelioma-like carcinoma (LELC),this a rare subtype of non-small cell lung cancer (NSCLC).34.78% for non-small cell lung cancer, and 21.17% for small cell lung cancer. The statistical analysis indicated that EBV infection was most significantly associated with cancer risk in LELC, while non-small cell lung cancer was more strongly associated with EBV than small cell lung cancer. Conclusion The study found that EBV infection increases the risk of lung cancer by more than four times, and this risk is associated with the pathological type, lymphatic infiltration, and degree of differentiation of the lung cancer, particularly in the rare subtype of pulmonary lymphoepithelioma in non-small cell lung cancer(NSCLC). Additionally, there are racial and regional differences in the correlation between EBV-infected lung cancer, with the Asian population showing greater susceptibility. The study used normal or abnormal tissue adjacent to the tumor as a control, which is considered a more accurate method for determining the relationship between EBV infection and lung cancer.
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Affiliation(s)
| | | | | | - Ming Dong
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China
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3
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Sha Z, Wei Y, Gao T, Luo Y, Chen J, Li T, Hu L, Niu X, Lin Z, Lv W, Pei X. Clinical observation of pulmonary lymphoepithelioma-like carcinoma. J Thorac Dis 2021; 13:5683-5690. [PMID: 34795918 PMCID: PMC8575801 DOI: 10.21037/jtd-21-1369] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/24/2021] [Indexed: 11/06/2022]
Abstract
Background Lymphoepithelioma-like carcinoma (LELC) of the lung is a rare type of non-small cell lung cancer (NSCLC), and researches of it are still not enough. Methods In this study, we retrospectively analyzed 36 patients with LELC diagnosed in the Fifth Affiliated Hospital of Sun Yat-sen University and Zhaoqing First People's Hospital from January 2014 to June 2021, to investigate the clinical manifestations, tumor markers, treatment, and prognosis of LELC. Clinical data including age, gender, smoking history, family history of cancers, Epstein-Barr virus (EBV) encoding RNA (EBER) status, gene mutations, programmed death-ligand 1 (PD-L1) expression, treatment, and prognosis. Results There was a total of 36 participants in this study, 16 males and 20 females, the median age was 57 years (37-76 years). A total of 22 cases (61.1%) were advanced (stage III and IV), and EBER was 94.4% positive. Most patients were treated with surgery, platinum chemotherapy, or radiotherapy. At the time of 31 June 2021, 33 participants had survived, and the longest survival time was 72 months. Lung LELC was more common in old participants (≥59 years) and was not associated with smoking history. Expression of PD-L1 was positive in the majority (27 cases, 75%) and participants with positive PD-L1 expression tended to have longer progression-free survival (PFS) and overall survival (OS) time than those with negative PD-L1 expression. Conclusions Pulmonary LELC usually occurs in non-smoking patients and is associated with EBV infection. Common treatments for tumors include multimodal therapy. The expression of PD-1 may be related to the prognosis of LELC, but more studies are needed to support further optimization of the treatment of LELC.
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Affiliation(s)
- Zhou Sha
- Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.,Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - Yajun Wei
- Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.,Department of Interventional Medicine, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai, China
| | - Tinghua Gao
- Department of Oncology, First People's Hospital of Zhaoqing City, Zhaoqing, China
| | - Yuanling Luo
- Department of Head and Neck Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Jiaqun Chen
- Department of Interventional Medicine, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai, China
| | - Ting Li
- Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.,Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - Liyang Hu
- Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.,Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - Xiaoli Niu
- Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Zhong Lin
- Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.,Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - Weize Lv
- Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.,Department of Interventional Medicine, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai, China
| | - Xiaofeng Pei
- Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.,Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
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Pathogenic Role of Epstein-Barr Virus in Lung Cancers. Viruses 2021; 13:v13050877. [PMID: 34064727 PMCID: PMC8151745 DOI: 10.3390/v13050877] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/27/2021] [Accepted: 05/07/2021] [Indexed: 01/02/2023] Open
Abstract
Human oncogenic viruses account for at least 12% of total cancer cases worldwide. Epstein–Barr virus (EBV) is the first identified human oncogenic virus and it alone causes ~200,000 cancer cases and ~1.8% of total cancer-related death annually. Over the past 40 years, increasing lines of evidence have supported a causal link between EBV infection and a subgroup of lung cancers (LCs). In this article, we review the current understanding of the EBV-LC association and the etiological role of EBV in lung carcinogenesis. We also discuss the clinical impact of the knowledge gained from previous research, challenges, and future directions in this field. Given the high clinical relevance of EBV-LC association, there is an urgent need for further investigation on this topic.
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Abstract
Lymphoepithelial carcinoma of salivary glands (LECSG) is an uncommon neoplasm. This article summarizes the findings of 438 cases in a review of the literature. Concurrent lymphoepithelial lesions may suggest a primary tumor. The tumor shows a nonkeratinizing carcinoma intimately associated with a rich lymphohistiocytic infiltrate, destroying adjacent salivary gland tissue. Irrespective of race or ethnicity, the tumors usually express Epstein-Barr virus, with Epstein-Barr virus encoded small RNA (EBER) and/or latent membrane protein-1 (LMP-1), although a subset does not. There is an overall good prognosis of about 80% at 5 years.
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6
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Tang L, Chen N, He W, Zhou J, Zhang J, Lin Z, Wang Z, Hao J, Lin F. The clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma: A systematic review and meta-analysis. PLoS One 2020; 15:e0240729. [PMID: 33064745 PMCID: PMC7567369 DOI: 10.1371/journal.pone.0240729] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 10/02/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) was a sparse subtype of unclassified lung cancer. The clinicopathologic features, prognostic factors and multimodality treatment regimens of LELC remain inconclusive. We conducted this systematic review and meta-analysis to address this deficit in current knowledge. METHODS We searched PubMed, Embase, and Web of Science to filtrate studies investigating on clinical features and prognostic factors of LELC up to Sep 9th, 2020. Fixed and random effect models were generated to present the incorporated hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (CI). The quality and heterogeneity of the included studies were also evaluated carefully. RESULTS This systematic review and meta-analysis included 13 retrospective studies with a total of 1294 patients. The incidence of programmed cell death-ligand 1 (PD-L1) expression in PPLELC varied from 63.3% to 75.8%. Positive PD-L1 expression was more likely to be found in patients under 60 years old (OR = 2.16, 95%CI: 1.19-3.89, P = 0.01) and was associated with worse disease-free survival (DFS) compared with negative PD-L1 expression (HR = 2.99, 95%CI: 1.23-7.28, P = 0.02). The pooled results showed that stage was the prognostic factor for both overall survival (OS) and DFS. Moreover, a significantly better outcome of PPLELC was observed in men (HR = 0.56, 95%CI: 0.33-0.95, P = 0.03) and patients who received radiation (HR = 0.46, 95%CI: 0.22-0.96, P = 0.04). CONCLUSION PD-L1 expression was high in PPLELC patients. It was significantly associated with age under 60 and the unfavorable DFS. Stage and gender could be the prognostic factor for OS. Radiation could be the effective therapy for PPLELC.
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Affiliation(s)
- Liansha Tang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Nan Chen
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Wenbo He
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Jian Zhou
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Jinjue Zhang
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Zhangyu Lin
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Zihuai Wang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Jianqi Hao
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Feng Lin
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- * E-mail:
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Ferrara G, Nappi O. Lymphoepithelioma-Like Carcinoma of the Lung. Two Cases Diagnosed in Caucasian Patients. TUMORI JOURNAL 2018; 81:144-7. [PMID: 7778219 DOI: 10.1177/030089169508100215] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Lymphoepithelioma-like carcinoma is a non-nasopharyngeal undifferentiated carcinoma with prominent lymphoid infiltration. Ten cases arising in the lung have been reported so far; seven cases were diagnosed in Orientals, with the Epstein-Barr virus (EBV) genome demonstrated in neoplastic cells by in situ hybridization; the remaining three cases affected Caucasian patients and showed no evidence of hybridized viral genome. The present study describes two additional cases of lymphoepithelioma-like carcinoma of the lung in Caucasians, with reference to the differential diagnosis versus other thoracomediastinal malignancies. The neoplastic nuclei, blastlike in appearance, together with the immunohistochemical profile of the neoplastic cells (positivity for cytokeratins, and negativity for CD antigens, S100 protein, placental alkaline phosphatase, and neuroendocrine markers) represent the basic pathologic features of a lymphoepithelioma-like carcinoma and allow its recognition even on small bioptic fragments, in which the typical biphasic, Regaud-like morphology might be inapparent. In accordance with the previously reported cases of pulmunary lymphoepithelioma-like carcinoma in Caucasian patients, the present study found no evidence of the Epstein-Barr virus genome in neoplastic cells with in situ hybridization.
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Affiliation(s)
- G Ferrara
- Servizio di Anatomia Patologica, Azienda Ospedaliera Gaetano Rummo, Benevento, Italy
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8
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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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9
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Investigation of the relationship of Epstein-Barr virus with in situ hybridization in renal-cell carcinomas. Ann Diagn Pathol 2018; 34:45-49. [PMID: 29661727 DOI: 10.1016/j.anndiagpath.2018.01.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 12/15/2017] [Accepted: 01/13/2018] [Indexed: 01/22/2023]
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Tay CK, Chua YC, Takano A, Min Chee MY, Lim WT, Lim C, Koh MS. Primary pulmonary lymphoepithelioma-like carcinoma in Singapore. Ann Thorac Med 2018; 13:30-35. [PMID: 29387253 PMCID: PMC5772105 DOI: 10.4103/atm.atm_304_17] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of nonsmall cell lung cancer (NSCLC) predominantly reported in East Asia. We aimed to evaluate clinical characteristics, diagnosis, treatment, and prognosis of PPLELC in Singapore. METHODS Retrospective review of all patients diagnosed with PPLELC at our center between 2000 and 2014. RESULTS All 28 patients were Chinese, 67.9% were female, and the median age was 58 years (range37-76 years). Majority (89.3%) were never smokers and 53.6% asymptomatic at diagnosis. About 28.6% presented with Stage I/II disease, 25% had Stage III disease, and 46.4% had Stage IV disease. All patients with Stage I/II disease underwent lobectomy without adjuvant treatment. Four out of 7 patients with Stage III disease underwent surgery with or without adjuvant therapy while the rest received chemoradiation. Twelve out of 13 patients with Stage IV disease received chemotherapy with or without radiotherapy. At the end of 2016, survival data were available for all 28 patients. Two-year survival rates for Stage I/II, Stage III, and Stage IV disease were 100%, 85.7%, and 61.5%, respectively, while survival was 100%, 85.7%, and 9.6%, respectively, at five years. CONCLUSION The majority (46.4%) of patients presented with metastatic disease. For those with Stage I-III disease, 5-year survival for PPLELC was better than other NSCLC subtypes. Multimodality treatment including surgery could be considered in locally advanced disease. In Stage IV disease, it tended to approximate that of NSCLC.
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Affiliation(s)
- Chee Kiang Tay
- Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore
| | - Yang Chong Chua
- Division of Surgical Oncology, National Cancer Center, Singapore
| | - Angela Takano
- Department of Pathology, Singapore General Hospital, Singapore
| | - Madeline Yen Min Chee
- Faculty of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wan-Teck Lim
- Division of Medical Oncology, National Cancer Center, Singapore.,Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore
| | - Cindy Lim
- Faculty of Medicine, Duke-National University Singapore Medical School, Singapore
| | - Mariko Siyue Koh
- Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore.,Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore
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Xie M, Wu X, Wang F, Zhang J, Ben X, Zhang J, Li X. Clinical Significance of Plasma Epstein-Barr Virus DNA in Pulmonary Lymphoepithelioma-like Carcinoma (LELC) Patients. J Thorac Oncol 2017; 13:218-227. [PMID: 29191777 DOI: 10.1016/j.jtho.2017.10.031] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Revised: 10/05/2017] [Accepted: 10/26/2017] [Indexed: 02/03/2023]
Abstract
INTRODUCTION Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a histologically distinctive subtype of NSCLC and an Epstein-Barr virus (EBV)-associated epithelial neoplasm. We investigated the clinical significance of plasma concentrations of EBV DNA in patients with pulmonary LELC. METHODS Two independent sets of plasma samples from a total of 429 patients with patients with pulmonary LELC (287 initial and 142 confirmatory) were available for EBV DNA determination. Plasma samples from the patients were subjected to a real-time quantitative polymerase chain reaction before treatment and 3 months after radical resection. Cutoff points were determined for pretreatment plasma EBV DNA concentration (low <4000 copies/mL versus high ≥4000 copies/mL) on the basis of a measure of heterogeneity with the log-rank test statistic with respect to overall survival (OS). The Kaplan-Meier method and Cox regression were used to evaluate the relationship between plasma EBV DNA concentrations and clinical outcome. Among patients with advanced-stage pulmonary LELC who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in EBV DNA concentrations by using nonparametric tests. RESULTS High EBV DNA concentration was associated with shorter OS in the initial, confirmatory, and combined data sets (combined data set hazard ratio = 3.67, 95% confidence interval: 2.72-4.38, p < 0.001). These findings persisted after multivariable adjustment. Compared with low EBV DNA concentration, high EBV DNA concentration was associated with shorter OS in patients with any stage of disease. High EBV DNA concentration was also associated with shorter disease-free survival (DFS) in patients with stage I/II disease. Patients with persistently detectable plasma EBV DNA had significantly poorer OS (p < 0.001) and DFS (p < 0.001) than did patients with undetectable EBV DNA 3 months after radical resection. In patients who underwent sequential evaluation of EBV DNA, an association was identified between an increase in EBV DNA concentration and a poor response to treatment and disease progression of pulmonary LELC. CONCLUSION High baseline EBV DNA concentration is an independent poor prognostic marker in patients with pulmonary LELC. These results should be confirmed in larger prospective trials.
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Affiliation(s)
- Mian Xie
- State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China; Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
| | - Xiaojun Wu
- Department of General Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China; Department of Corlorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Guangdong, People's Republic of China
| | - Fang Wang
- Department of General Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Jinjun Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Xiaosong Ben
- Department of Thoracic Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China
| | - Jiexia Zhang
- Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Xiaoxiang Li
- Department of Thoracic Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, People's Republic of China
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Chan JKC, Yip TTC, Tsang WYW, Seneviratne S, Poon Y, Wong CSC, Ma VWS. Lack of Evidence of Pathogenetic Role of Epstein-Barr Virus in Thymic Lymphoid Hyperplasia and Thymomas in the Chinese Population of Hong Kong. Int J Surg Pathol 2016. [DOI: 10.1177/106689699400200104] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
A previous study from Hong Kong by McGuire et al. reported frequent demonstration of Epstein-Barr virus (EBV) DNA by Southern blot analysis in thymoma, thymic lymphoepithelioma-like carcinoma, and thymic lymphoid hyperplasia. This provoca tive finding, however, could not be confirmed by studies in the Western populations using the Southern blot technique and/or polymerase chain reaction to detect EBV- DNA or in situ hybridization to detect EBV encoded RNA (EBER), raising the possibility that the association with EBV may be restricted to Asians. This study was performed to clarify this issue by using a highly sensitive localization technique for EBER on a larger series from the Asian population of Hong Kong. Paraffin sections obtained from 10 cases of thymic lymphoid hyperplasia, 42 noninvasive thymomas (including one case previously reported to be EBV positive), 11 invasive thymomas, and 9 thymic carcinomas (including 5 cases of lymphoepithelioma-like carcinoma) were studied. EBER signal was not detected in the epithelial cells in any of the cases except for two cases of lymphoepithelioma-like carcinoma. In two thymomas, a few small lympho cytes (<0.1%) were EBER positive. Failure to detect EBER was not an artifact due to RNA denaturation, because preserved mRNA could be demonstrated by oligo-dT labelling in 56 of the 72 cases. Thus, the results of this study on Hong Kong Chinese are in keeping with those reported in Caucasians, and more recently in Japanese and Taiwan Chinese, in that there is no association of EBV with thymic lymphoid hyperpla sia or thymoma, and that EBV may be demonstrated in a proportion of thymic lymph oepithelioma-like carcinomas. The positive results previously reported cannot be ex plained, because the occasional EBV-carrying lymphocytes detected in rare cases of thymoma should be insufficient to give a positive EBV result by Southern blot tech nique. Int J Surg Pathol 2(1):17-22, 1994
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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: 34] [Impact Index Per Article: 3.4] [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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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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Kolk A, Wolff KD, Smeets R, Kesting M, Hein R, Eckert AW. Melanotic and non-melanotic malignancies of the face and external ear - A review of current treatment concepts and future options. Cancer Treat Rev 2014; 40:819-37. [PMID: 24814015 DOI: 10.1016/j.ctrv.2014.04.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Revised: 04/01/2014] [Accepted: 04/05/2014] [Indexed: 12/11/2022]
Abstract
Skin has the highest incidence and variety of tumors of all organs. Its structure is of great complexity, and every component has the potential to originate a skin neoplasm (SN). Because of its exposed nature, skin is vulnerable to carcinogenic stimuli such as UV radiation. Various entities can cause SN. Nonmelanotic skin cancers (NMSC) are the most common of all cancers, with over one million cases diagnosed annually in the US. Basal cell carcinoma (BCC) accounts for approximately 80% of all NMSC, most of the remaining 20% being squamous cell carcinoma (SCC). The skin of the head and neck is the most common site for tumors, accounting for more than 80% of all NMSC. BCC, SCC, and malignant melanomas (MM) represent 85-90% of all SN. Merkel cell tumors (MCC), lymphoepithelioma-like carcinomas of the skin (LELCS), dermato-fibro-sarcomas, leiomyosarkomas, and Kaposi-sarcomas are less frequent in the facial skin region and the external ear. Based on data from the German Federal Cancer Registry (2003/2004), 140,000 people in Germany were affected by SN (100,000 BCC, 22,000 SCC, 22,000 MM). This number increases considerably if malignant precursors, such as actinic keratosis, are included. Each year, the frequency of SN diagnosis rises by 3-7%. Among all known malignant tumors, MM exhibits the highest rate of increase in incidence. In the past, SN was primarily diagnosed in people aged 50 years or older. However, recently, the risk for developing SN has shifted, and younger people are also affected. Early diagnosis is significantly correlated with prognosis. Resection of SN creates defects that must be closed with local or microvascular flaps to avoid functional disturbing scar formation and deflection of the nose, eyelids, or lips. All therapeutic strategies for SN, the current standard for adjuvant and systemic treatment, and the management of the increasing number of patients under permanent blood thinner medication are described with regard to the treatment of SN.
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Affiliation(s)
- Andreas Kolk
- Department of Oral and Cranio-Maxillofacial Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
| | - Klaus-Dietrich Wolff
- Department of Oral and Cranio-Maxillofacial Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
| | - Ralf Smeets
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Marco Kesting
- Department of Oral and Cranio-Maxillofacial Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
| | - Rüdiger Hein
- Department of Dermatology and Allergology, Technische Universität München, Munich, Germany.
| | - Alexander W Eckert
- Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Germany.
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Liu Q, Ma G, Yang H, Wen J, Li M, Yang H, Luo K, Hu Y, Fu J. Lack of epidermal growth factor receptor gene mutations in exons 19 and 21 in primary lymphoepithelioma-like carcinoma of the lung. Thorac Cancer 2014; 5:63-7. [PMID: 26766974 DOI: 10.1111/1759-7714.12060] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Accepted: 06/17/2013] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Primary lymphoepithelioma-like carcinoma (LELC) of the lung is uncommon in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) targeted therapy has been applied in advanced common NSCLC. Whether EGFR-targeted therapy is also suitable for LELC of the lung remains unclear. As we know, EGFR gene mutation is a predictive factor. Therefore, EGFR gene mutations in exons 19 and 21 in Chinese patients with LELC of the lung were investigated. METHODS Clinicopathological information was obtained by a retrospective review of the medical history recorded in the patients' charts. EGFR gene mutations in exons 19 and 21 were analyzed in 32 samples of LELC of the lung by TaqMan real-time polymerase chain reaction (RT-PCR). RESULTS Eleven (34.4%) of the patients were male and 21 (65.6%) patients female. The mean age at diagnosis was 50.9 years (range, 25-71 years). Seven (21.9%) of the patients were smokers. In situ hybridization for Epstein-Barr virus-encoded small RNAs (EBERs) showed positive signals in all 32 patients. None of the tumors had mutations in exons 19 and 21. EGFR-targeted therapy was used in three patients with advanced disease and one patient with distant recurrence. However, no obvious therapeutic effect was found. CONCLUSION These data showed that LELC of the lung, a special histological type of lung cancer, lacked EGFR gene mutations in exons 19 and 21, which suggested that there was no opportunity for EGFR-targeted therapy for patients with LELC of the lung.
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Affiliation(s)
- Qianwen Liu
- State Key Laboratory of Oncology in South China Guangzhou, China; Department of Thoracic Surgery, Sun Yat-sen University Cancer Center Guangzhou, China
| | - Guowei Ma
- State Key Laboratory of Oncology in South China Guangzhou, China; Department of Thoracic Surgery, Sun Yat-sen University Cancer Center Guangzhou, China
| | - Haoxian Yang
- State Key Laboratory of Oncology in South China Guangzhou, China; Department of Thoracic Surgery, Sun Yat-sen University Cancer Center Guangzhou, China
| | - Jing Wen
- State Key Laboratory of Oncology in South China Guangzhou, China; Department of Thoracic Surgery, Sun Yat-sen University Cancer Center Guangzhou, China
| | - Mei Li
- State Key Laboratory of Oncology in South China Guangzhou, China; Department of Pathology, Sun Yat-sen University Cancer Center Guangzhou, China
| | - Hong Yang
- State Key Laboratory of Oncology in South China Guangzhou, China; Department of Thoracic Surgery, Sun Yat-sen University Cancer Center Guangzhou, China
| | - Kongjia Luo
- State Key Laboratory of Oncology in South China Guangzhou, China; Department of Thoracic Surgery, Sun Yat-sen University Cancer Center Guangzhou, China
| | - Yi Hu
- State Key Laboratory of Oncology in South China Guangzhou, China; Department of Thoracic Surgery, Sun Yat-sen University Cancer Center Guangzhou, China
| | - Jianhua Fu
- State Key Laboratory of Oncology in South China Guangzhou, China; Department of Thoracic Surgery, Sun Yat-sen University Cancer Center Guangzhou, China
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Wong JFS, Teo MCC. Case report: lymphoepithelial-like carcinoma of the lung--a chronic disease? World J Surg Oncol 2012; 10:91. [PMID: 22613459 PMCID: PMC3464696 DOI: 10.1186/1477-7819-10-91] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Accepted: 05/21/2012] [Indexed: 11/10/2022] Open
Abstract
This is a case of metastatic lung cancer of the lymphoepithelial-like carcinoma (LELC) variant who first presented with symptomatic brain metastasis. The patient underwent local and systemic treatment for metastatic disease with good clinical outcome. The patient was disease free for four years then she had primary lung recurrence which was surgically resected. She underwent a second course of chemotherapy with saw her through another two years of disease free period. A recurrence of the cancer was detected intra-abdominally on the seventh year of diagnosis. This was treated again with surgical resection and another course of chemotherapy.
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Affiliation(s)
- Joelle FS Wong
- Department of Surgical Oncology, National Cancer Centre, 11 Singapore General Hospital, Outram Road, Singapore, 169608, Singapore
| | - Melissa CC Teo
- Department of Surgical Oncology, National Cancer Centre, 11 Singapore General Hospital, Outram Road, Singapore, 169608, Singapore
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Huang CJ, Feng AC, Fang YF, Ku WH, Chu NM, Yu CT, Liu CC, Lee MY, Hsu LH, Tsai SYC, Shih CS, Wang CL. Multimodality treatment and long-term follow-up of the primary pulmonary lymphoepithelioma-like carcinoma. Clin Lung Cancer 2012; 13:359-62. [PMID: 22410385 DOI: 10.1016/j.cllc.2012.01.002] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2011] [Revised: 01/14/2012] [Accepted: 01/23/2012] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a very rare subtype of non-small-cell lung cancer. Most cases are reported in Southeast Asia and are associated with Epstein-Barr virus infections. Because of its rare incidence, the optimal treatment and the results of long-term follow-up are not well understood. This study is an attempt to discover the multimodality treatment results of the primary pulmonary LELC. METHODS This retrospective study enrolled 21 patients with primary pulmonary LELC treated at 2 hospitals with a multimodality approach, including surgery, chemotherapy, radiotherapy, and targeted therapy. RESULTS The median follow-up time is 5.9 years and the median survival is 6.4 years. The median overall survival for patients with stage III and with stage IV disease is 3.4 years. In early-stage primary pulmonary LELC, surgery and adjuvant chemotherapy provided good treatment outcome. Advanced primary pulmonary LELC is relatively more chemosensitive and radiosensitive. CONCLUSION Patients with primary pulmonary LELC showed better prognosis than those with other types of non-small-cell lung cancer and achieved longer survival under multimodality treatment. This disease character is similar to that of nasopharyngeal carcinoma. Accurate pathologic diagnosis is recommended before the treatment. For advanced diseases, platinum-based doublet chemotherapy can be considered the first-line treatment. Radiation dose should consider tumor location, and 5000 to 7000 cGy is frequently applied for pulmonary LELC.
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Affiliation(s)
- Chung-Jen Huang
- Division of Pulmonary Medicine and Intensive Care Medicine, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan.
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Kundu S, Mitra R, Majumdar A, Saha S, Misra S. Primary Lymphoepithelioma-like Carcinoma of the Lung in a 13 year old Girl. Oman Med J 2012; 27:e032. [PMID: 28861186 DOI: 10.5001/omj.2012.21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Lymphoepithelioma-like carcinoma, a large cell carcinoma with pronounced lymphocyte infiltration, is a rare entity mostly seen in the nasopharynx. But primary pulmonary LELC in children & adolescents is extremely rare. Here we present a 13 year old girl with chief complaint of fever, cough, shortness of breath and heaviness in the left side of chest. She underwent left upper lobectomy. Histopathological examination of the biopsy specimen confirmed it to be a case of large cell carcinoma of lung, lymphoepithelioma type, invading pleura (stage pT3N0M0) with high serum titre of anti Epstein-Barr virus IgG antibody.
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Affiliation(s)
- Susmita Kundu
- Department of Pulmonary Medicine and Radiotherapy, Institute of Postgraduate Medical Education and Research, Kolkata, 242 AJC Bose Road, Kolkata, 700020, West Bengal, India
| | - Ritabrata Mitra
- Department of Pulmonary Medicine and Radiotherapy, Institute of Postgraduate Medical Education and Research, Kolkata, 242 AJC Bose Road, Kolkata, 700020, West Bengal, India
| | - Anup Majumdar
- Department of Pulmonary Medicine and Radiotherapy, Institute of Postgraduate Medical Education and Research, Kolkata, 242 AJC Bose Road, Kolkata, 700020, West Bengal, India
| | - Sucheta Saha
- Department of Pulmonary Medicine and Radiotherapy, Institute of Postgraduate Medical Education and Research, Kolkata, 242 AJC Bose Road, Kolkata, 700020, West Bengal, India
| | - Swapnendu Misra
- Department of Pulmonary Medicine and Radiotherapy, Institute of Postgraduate Medical Education and Research, Kolkata, 242 AJC Bose Road, Kolkata, 700020, West Bengal, India
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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: 18] [Impact Index Per Article: 1.3] [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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Lountzis NI, Tyler WB, Marks VJ. Primary Cutaneous Lymphoepithelioma-Like Carcinoma Treated Using Mohs Micrographic Surgery and Zinc Chloride Fixative. Dermatol Surg 2010; 36:564-7. [DOI: 10.1111/j.1524-4725.2010.01494.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Abstract
The association of Epstein-Barr virus with pulmonary neoplasms has been restricted to lymphoepithelioma-like carcinomas in Asian patients. We have selected 19 pulmonary adenocarcinomas and squamous-cell carcinomas from 1545 pulmonary neoplasms diagnosed from 1996 to 2007 in an occidental population. All of them showed a low-power appearance confusing between an epithelial and a lymphoid neoplasm, with a dense lymphocytic infiltrate intermingled with neoplastic cells giving an image akin to lymphoepithelial complexes. Five carcinomas presented typical features of Lymphoepithelioma-like lung carcinomas; but six cases could be classified as squamous-cell carcinomas and eight as adenocarcinomas. A semiquantitative polymerase chain reaction method, Early RNA genes 1 and 2 in situ hybridization as well as Latent membrane protein immunostaining for Epstein-Barr virus DNA, RNA and protein detection methods were used in every case. None of Lymphoepithelioma-like carcinomas showed positivity for Epstein-Barr virus in any used method. Otherwise four squamous-cell carcinomas and eight adenocarcinomas (12 cases) demonstrated viral sequences in polymerase chain reaction and/or in situ hybridization analysis in neoplastic cells. Moreover two adenocarcinomas also displayed human herpesvirus 6 DNA sequences coamplification in molecular analysis. Protein immunostaining was focally positive in only three cases. We performed the same analysis in 70 more cases of conventional pulmonary squamous-cell carcinomas and adenocarcinomas that gave negative results. In conclusion, a subset of pulmonary squamous-cell carcinomas and adenocarcinomas show Epstein-Barr DNA and/or RNA sequences in neoplastic cells. This finding expands the spectra of epithelial cell common tumours Epstein-Barr virus associated.
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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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Expression of Epstein–Barr-virus-encoded small nuclear RNA in nasopharyngeal carcinomas of Aegean Turkish patients. Virchows Arch 2008; 452:411-4. [DOI: 10.1007/s00428-008-0589-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2007] [Revised: 01/11/2008] [Accepted: 01/23/2008] [Indexed: 11/26/2022]
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Huang CJ, Chan KY, Lee MY, Hsu LH, Chu NM, Feng AC, Yu CT, Lin HC. Computed tomography characteristics of primary pulmonary lymphoepithelioma-like carcinoma. Br J Radiol 2007; 80:803-6. [PMID: 17875600 DOI: 10.1259/bjr/27788443] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Primary pulmonary lymphoepithelioma-like carcinoma is a very rare subtype of lung cancer. This report documents the CT features of 16 Chinese patients diagnosed with primary pulmonary lymphoepithelioma-like carcinoma from January 1999 to December 2005. A pre-treatment CT was used to assess the tumour site, size, borders, pleural and vascular involvement, and the presence of lymph node involvement. The majority of the patients were female non-smokers with centrally located tumours. Lymph node involvement and bronchial and vascular encasement were frequent. In an Epstein-Barr virus endemic area, primary pulmonary lymphoepithelioma-like carcinoma is an important differential diagnosis to consider.
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Affiliation(s)
- Chung-Jen Huang
- Division of Pulmonary Medicine and Intensive Care Medicine, Koo Foundation Sun Yat-Sen Cancer Center, Pei-Tou District, Taipei, Taiwan, Republic of China.
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Kazakov DV, Nemcova J, Mikyskova I, Michal M. Absence of Epstein-Barr Virus, Human Papillomavirus, and Simian Virus 40 in Patients of Central European Origin With Lymphoepithelioma-like Carcinoma of the Skin. Am J Dermatopathol 2007; 29:365-9. [PMID: 17667169 DOI: 10.1097/dad.0b013e31806f7fa9] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The authors report 10 cases of lymphoepithelioma-like carcinoma (LELC) of the skin and the results of a molecular biological study for HPV, EBV, and SV40 in lesional tissues. All patients originated from Central Europe. There were seven men and three women, ranging in age from 57 to 86 years. Locations included the face (n = 4), scalp (n = 2), penis (n = 2), and retroauricular area (n = 1); location was unknown for one subject. All but two patients presented with a tumor confined to the skin; in both patients with the penile carcinoma, the tumors had metastasized to an inguinal lymph node. Six patients with available follow-up included four individuals with no evidence of tumor metastasis or recurrences at 2, 3, 4, and 5 years, one patient who died with metastatic disease 7 years after diagnosis, and one patient who died of an unrelated course. Microscopically, all cases showed distinctive features of LELC characterized by variably sized and shaped nodules or syncytial sheets of epithelial cells that contained vesicular chromatic and prominent nucleoli and that were permeated and surrounded by small, well-differentiated lymphocytes and plasma cells. Because all 10 cases studied proved negative for EBV, HPV, and SV40, these viruses seem to play no causal role in LELC of the skin in patients from Central Europe.
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Affiliation(s)
- Dmitry V Kazakov
- Sikl's Department of Pathology, Charles University, Medical Faculty Hospital, Pilsen, Czech Republic.
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Abstract
Lymphoepithelioma-like carcinoma (LELC) of the lung was first reported in 1987. In the past two decades, there have been just more than 150 cases reported in the literature. This uncommon but distinct form of non-small cell lung carcinoma has a predilection for young non-smoking Asians, without gender distinction. Histologically, it is indistinguishable from undifferentiated nasopharyngeal carcinoma. The carcinogenic role of latent Epstein-Barr virus infection in causing LELC of the lung has been evident almost exclusively in Asians compared with Caucasians. Among the reported cases, more than half were in early resectable stages (I or II) and there was a tendency for peribronchovascular spread with vascular encasement in advanced diseases. In order to establish the diagnosis of LELC of the lung, both nasopharyngeal carcinoma and lymphoma have to be excluded by endoscopic biopsy (with or without magnetic resonance imaging of the nasopharynx) and immunohistochemical staining of the biopsy samples. The mainstay of treatment for early-stage disease is curative surgical resection, whereas multimodality treatment (surgery, chemotherapy, radiotherapy) has been adopted in advanced or metastatic diseases. The overall survival is more favourable in LELC of the lung compared with non-LELC type of non-small cell lung carcinoma. Future collaborative studies especially on optimizing treatment for this uncommon malignancy are clearly warranted.
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Affiliation(s)
- James C Ho
- University Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
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Tsimberidou AM, Keating MJ, Bueso-Ramos CE, Kurzrock R. Epstein-Barr virus in patients with chronic lymphocytic leukemia: a pilot study. Leuk Lymphoma 2006; 47:827-36. [PMID: 16753866 DOI: 10.1080/10428190500398856] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
The objective of this study was to assess the incidence and the clinical significance of Epstein-Barr virus (EBV) in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients with CLL/SLL who presented at The University of Texas M. D. Anderson Cancer Center over a 2-year period and had available marrow paraffin blocks were studied for evidence of EBV infection using a highly specific in-situ hybridization assay for detection of EBV encoded RNA (EBERs). Results were analysed in relation to other presenting characteristics and outcome. Thirty-two patients were examined. EBERs were detected in the bone marrow of 12 of 32 (38%) CLL/SLL marrows vs 0 of 20 normal marrows (p = 0.002). EBERs were observed in sporadic granulocytes alone or in addition to its presence in lymphocytes in nine of the 12 EBV-positive patients. EBERs were detected less frequently in patients with Rai stage 0 - 1 disease (20%) compared with Rai stage 2 - 4 (66%; p = 0.008). EBER-positive patients tended to have higher lactate dehydrogenase levels (p = 0.053). The 10-year survival rate was 22% vs 58% for patients with and without discernible EBERs (log-rank, p = 0.08). Evidence of EBV infection was found in 38% of patients with CLL/SLL. Despite the small number of patients tested, discernable EBERs were significantly more common in individuals with more advanced Rai stage and there was a trend toward shorter survival in patients in whom EBV EBERs were discerned. Larger studies are needed to determine the prognostic value and role of EBV infection in patients with CLL/SLL.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Bone Marrow Examination
- Female
- Granulocytes/virology
- Herpesvirus 4, Human
- Humans
- Incidence
- Leukemia, Lymphocytic, Chronic, B-Cell/mortality
- Leukemia, Lymphocytic, Chronic, B-Cell/pathology
- Leukemia, Lymphocytic, Chronic, B-Cell/virology
- Leukocytes/virology
- Male
- Middle Aged
- Neoplasm Staging
- Pilot Projects
- Survival Analysis
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Affiliation(s)
- Apostolia-Maria Tsimberidou
- Phase I Program and Department of Leukemia, Division of Cancer Medicine, The University of Texas M.D Anderson Cancer Center, Houston, TX, USA
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29
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Hoxworth JM, Hanks DK, Araoz PA, Elicker BM, Reddy GP, Webb WR, Leung JWT, Gotway MB. Lymphoepithelioma-like carcinoma of the lung: radiologic features of an uncommon primary pulmonary neoplasm. AJR Am J Roentgenol 2006; 186:1294-9. [PMID: 16632721 DOI: 10.2214/ajr.05.0244] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVE The purpose of this study was to review the chest radiographic, CT, and MRI appearances of primary pulmonary lymphoepithelioma-like carcinoma (LELC). CONCLUSION Primary pulmonary LELC is histopathologically identical to nasopharyngeal carcinoma. The radiographic, CT, and MRI features of primary pulmonary LELC are nonspecific, often resembling those of bronchogenic carcinoma. Primary pulmonary LELC usually presents as a poorly circumscribed, enhancing, peripheral solitary pulmonary nodule on CT; necrosis may be present and is considered a poor prognostic sign. MRI shows isointense to low-intensity signal on T1-weighted images and mildly increased signal on T2-weighted images; enhancement of abnormal tissue is typical. Most patients present with early-stage disease. Primary pulmonary LELC should be suspected in selected patients and requires differentiation from bronchogenic carcinoma and metastatic nasopharyngeal carcinoma.
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Affiliation(s)
- Joseph M Hoxworth
- Department of Radiology, University of California, San Francisco, 505 Parnassus Avenue, Room M-391, Box 0628, San Francisco, CA 94110, USA
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30
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Fenniche S, Zidi Y, Tekaya NB, Ammar FB, Yaacoub K, Mokni M, Mokhtar I, Osman AB, Zitouna MM, Haouet S. Lymphoepithelioma-Like Carcinoma of the Skin in a Tunisian Patient. Am J Dermatopathol 2006; 28:40-4. [PMID: 16456324 DOI: 10.1097/01.dad.0000175530.42615.94] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Lymphoepithelioma-like carcinoma of the skin (LELCs) is a rare cutaneous neoplasm with histologic features resembling lymphoepitheliomatous tumors of the nasopharynx. The association of lymphoepitheliomas with Epstein-Barr Virus (EBV) at some extracutaneous sites is well documented. In contrast, the presence of EBV in LELCs has never been shown in either Caucasians or Asian patients. We present the first case of LELCs in a Tunisian patient, a 78-year-old woman who presented with a nodule of the right cheek of 2 months' duration. The patient underwent surgical excision and there was no evidence of local recurrence 6 months later. Histologically, the entire dermis was occupied by lobules composed of atypical epithelial cells surrounded by a dense lymphoplasmacytic infiltrate. Immunohistochemical examination showed that the epithelial tumor cells were positive for cytokeratin and epithelial membrane antigen. In situ hybridization investigations for the presence of EBV-encoded RNA showed negative results. Our findings suggest that LELCs is not related to EBV among North African patients.
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Affiliation(s)
- Samy Fenniche
- Dermatology Department, Habib Thameur Hospital, Tunis, Tunisia.
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31
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Kurose A, Ichinohasama R, Kanno H, Kobayashi T, Ishida M, Nishinari N, Sawai T. Lymphoepithelioma-like carcinoma of the breast. Report of a case with the first electron microscopic study and review of the literature. Virchows Arch 2005; 447:653-9. [PMID: 15947950 DOI: 10.1007/s00428-004-1195-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2004] [Accepted: 12/06/2004] [Indexed: 12/17/2022]
Abstract
Lymphoepithelioma-like carcinoma (LELC) is a tumor which occurs outside the nasopharynx and has morphological features identical to nasopharyngeal lymphoepithelioma. LELC of the breast (LELC-B) is uncommon, and its resemblance to medullary carcinoma of the breast (MC-B) obscures distinction between these two tumors. We report a case of LELC-B occurring in a 47-year-old woman. The tumor consisted of multinodules without circumscription. The tumor cells mainly exhibited loose clusters being permeated by numerous lymphocytes. The tumor cell clusters showed inconspicuous margins, which were far from syncytial patterns. The epithelial nature of the tumor cells was demonstrated by positivity for epithelial membrane antigen, AE1/AE3 and CAM5.2. Furthermore, glandular differentiation of the tumor cells was confirmed using electron microscopy for the first time. Epstein-Barr virus (EBV) was not detected using either in situ hybridization or polymerase chain reaction. These findings, together with former reports of LELC-B, suggest that the distinction between LELC-B and MC-B depends on whether circumscription and syncytial growth patterns exist. The other findings, including absence of EBV and immunohistochemical aspects of the tumor cells, are not considered different thus far. Although the prognosis of LELC-B is thought to be favorable, which is also similar to MC-B, distant metastasis was detected in the present case. To confirm the clinicopathological entity of these two tumors, it is important to recognize the difference between LELC-B and MC-B.
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Affiliation(s)
- Akira Kurose
- Department of Pathology, Iwate Medical University, Morioka, 020-8505 Iwate, Japan.
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32
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Viguer JM, Jiménez-Heffernan JA, López-Ferrer P, Banaclocha M, Vicandi B. Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma. Diagn Cytopathol 2005; 32:233-7. [PMID: 15754369 DOI: 10.1002/dc.20216] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Cytological features of nasopharyngeal carcinoma (NPC) were reviewed in an attempt to select cytological criteria that permit a specific recognition of metastases. For this purpose, 54 fine-needle aspiration (FNA) procedures from 43 patients with NPC were analyzed. Thirty-two (59.3%) procedures were performed before the histological diagnosis. In 25 (46.3%) procedures, smears showed many neoplastic single cells, clusters, and abundant lymphoid cells (mixed pattern). A dissociated (single cell) pattern consisting of individual neoplastic and lymphoid cells was seen in 18 (33.3%) cases. Finally, 11 (20.4%) cases showed cohesive epithelial clusters (cohesive pattern) without relevant cellular dissociation or lymphoid cells. Squamous-cell differentiation was seen in three of these cases. Most single neoplastic cells presented as large, pleomorphic naked nuclei. Other interesting findings were granulomas (n = 3), prominent eosinophilic infiltrates (n = 4), and suppurative changes (n = 5). In most smears with mixed and dissociated patterns, a nasopharyngeal origin could be suggested. On the contrary, those smears with a cohesive pattern were indistinguishable from other head and neck carcinomas. The presence (on cervical lymph nodes) of a dissociated or mixed (single cells and groups) architectural pattern of large, anaplastic cells and naked nuclei accompanied by an abundant lymphoid component is highly suggestive of undifferentiated NPC. Cytology offers a rapid diagnosis, establishes the necessity of a complete cavum examination, and helps in avoiding unnecessary and harmful biopsies.
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Affiliation(s)
- José M Viguer
- Department of Pathology, University Hospital La Paz, and Faculty of Medicine, Universidad Autonoma, Madrid
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33
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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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34
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Kobayashi M, Ito M, Sano K, Honda T, Nakayama J. Pulmonary lymphoepithelioma-like carcinoma: predominant infiltration of tumor-associated cytotoxic T lymphocytes might represent the enhanced tumor immunity. Intern Med 2004; 43:323-6. [PMID: 15168777 DOI: 10.2169/internalmedicine.43.323] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Lymphoepithelioma-like carcinoma (LELC) of the lung is an undifferentiated carcinoma with prominent lymphoid stroma. We encountered a case of synchronous primary lung cancers of LELC and papillary adenocarcinoma in a 67-year-old Japanese woman. By in situ hybridization, Epstein-Barr virus (EBV) genome was detected in malignant epithelial cells of LELC but not in the papillary adenocarcinoma. Tumor-infiltrating lymphocytes in LELC were predominantly CD8+ and T cell intracytoplasmic antigen (TIA-1)+ cytotoxic T cells with closely associated with HLA-DR-positive LELC cells by double immunostaining. These data indicate that the exaggerated lymphoid infiltration in and around the EBV-infected carcinoma cells may represent the enhanced tumor immunity, suggesting a better prognostic indicator.
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Affiliation(s)
- Motohiro Kobayashi
- Department of Pathology, Shinshu University School of Medicine, Matsumoto
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35
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Abstract
A case of primary lymphoepithelioma of the esophagus is presented in an Arabic female patient. This very rare Epstein-Barr virus infection-related malignancy has previously been reported only in patients from Japan. The tumor exhibited classic histologic and immunohistochemical features of lymphoepithelioma, and was successfully treated with neoadjuvant chemotherapy and irradiation followed by surgical resection.
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Affiliation(s)
- Freddy Angulo-Pernett
- Department of Thoracic and Cardiovascular Surgery, Section of Thoracic Molecular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
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36
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Jen KY, Cheng J, Li J, Wu L, Li Y, Yu S, Lin H, Chen Z, Gurtsevitch V, Saku T. Mutational events in LMP1 gene of Epstein-Barr virus in salivary gland lymphoepithelial carcinomas. Int J Cancer 2003; 105:654-60. [PMID: 12740914 DOI: 10.1002/ijc.11100] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
It is still unknown what kinds of roles Epstein-Barr virus (EBV) infection that are highly specific to salivary gland lymphoepithelial carcinomas (LECs) play in their tumorigenesis. To clarify the significance of EBV in LECs, we paid particular attention to the LMP1 gene, which is responsible for triggering several pathways for activating transcription factors. Sixty-one cases of EBV positive LECs confirmed by PCR and in-situ hybridization were collected from various areas of the world and studied immunohistochemically for latent membrane protein-1. Furthermore, PCR for the LMP1 carboxyl (C)-terminus region was performed, and the PCR products were sequenced for detection of other mutational events. LMP1 gene products were immunohistochemically demonstrated in 51% of the cases, while PCR amplification of the LMP1 gene was successful in 41 cases (67%). Among them, a 30 bp deletion in the C-terminus of the LMP1 gene, which had been shown to be characteristic to EBV in Chinese nasopharyngeal carcinomas, was found in 20 cases (32%). Most of them were from Guangzhou, Chengdu and Taiwan, while most of the cases from Shanghai and other areas exhibited no 30 bp deletion. In addition, several point mutations including codon 338 of LMP1 were commonly shared by the cases with or without the 30 bp deletion. These results indicate that there are 2 major genomic variations of EBV infecting salivary gland LECs. The frequent mutational events in the C-terminus in addition to the 30 bp deletion also seem to be critical for the pathogenesis because such mutational events may possibly promote cellular proliferation.
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Affiliation(s)
- Kai Yu Jen
- Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan
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37
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Hayakawa H, Shirai M, Uchiyama H, Imokawa S, Suda T, Chida K, Muro H. Lack of evidence for a role of Epstein-Barr virus in the increase of lung cancer in idiopathic pulmonary fibrosis. Respir Med 2003; 97:281-4. [PMID: 12645836 DOI: 10.1053/rmed.2003.1398] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Idiopathic pulmonary fibrosis (IPF) is known as an independent risk factor for lung cancer. Because Epstein-Barr virus (EBV) may be involved in the genesis of IPF as well as certain malignancies, we investigated whether EBV contributes to the increased incidence of lung cancer in IPF The formalin-fixed and paraffin-embedded lung sections were prepared from 22 lung cancer patients with IPF and 22 lung cancer patients without IPF All ofthe IPF patients pathologically showed usual interstitial pneumonia. In situ hybridization for EBV-encoded small non-polyadenylated RNAs failed to show positive signals in the cancer tissues of either IPF or non-IPF patients. This study did not provide evidence for an etiologic role of EBV in the development of lung cancer in IPF.
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Affiliation(s)
- H Hayakawa
- Department of Internal Medicine, National Tenryu Hospital, Hamakita, Japan.
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38
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Middeldorp JM, Brink AATP, van den Brule AJC, Meijer CJLM. Pathogenic roles for Epstein-Barr virus (EBV) gene products in EBV-associated proliferative disorders. Crit Rev Oncol Hematol 2003; 45:1-36. [PMID: 12482570 DOI: 10.1016/s1040-8428(02)00078-1] [Citation(s) in RCA: 131] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Epstein-Barr virus (EBV) is associated with a still growing spectrum of clinical disorders, ranging from acute and chronic inflammatory diseases to lymphoid and epithelial malignancies. Based on a combination of in vitro and in vivo findings, EBV is thought to contribute in the pathogenesis of these diseases. The different EBV gene expression patterns in the various disorders, suggest different EBV-mediated pathogenic mechanisms. In the following pages, an overview of the biology of EBV-infection is given and functional aspects of EBV-proteins are discussed and their putative role in the various EBV-associated disorders is described. EBV gene expression patterns and possible pathogenic mechanisms are discussed. In addition, expression of the cellular genes upregulated by EBV in vitro is discussed, and a comparison with the in vivo situation is made.
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Affiliation(s)
- Jaap M Middeldorp
- Department of Pathology, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
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39
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Kim I, Park ER, Park SH, Lin Z, Kim YS. Characteristics of Epstein-Barr virus isolated from the malignant lymphomas in Korea. J Med Virol 2002; 67:59-66. [PMID: 11920819 DOI: 10.1002/jmv.2193] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Epstein-Barr virus (EBV) is a common herpes virus linked to a variety of human neoplasms. In this study, the EBV detection was identified with the paraffin-embedded tissues from 62 non-Hodgkin's lymphomas, 20 Hodgkin's lymphomas, and 48 non-neoplastic tonsils, using PCR for EBNA-1 and EBER-1 mRNA in situ hybridization for EBER-1 mRNA. The isolates were analyzed for type 1/2, variants C/D and F/f, and LMP-1 30 bp deletion. EBV was isolated in 31 of 48 (66%) non-neoplastic tonsils, 24 of 42 (57%) B cell lymphomas, in 15 of 20 (75%) T cell lymphomas, and 17 of 20 (85%) Hodgkin's lymphomas. These viruses were classified as type 1 for 81% of non-neoplastic tonsils, 95% of B cell lymphomas, 93% of T cell lymphomas, and 73% of Hodgkin's diseases. Both type 1 and 2 viruses were isolated in one non-neoplastic tonsil and 3 Hodgkin's diseases. Type C virus was predominant in non-neoplastic tonsils (77%) and B cell lymphomas (75%), while type D virus was common in T cell lymphomas (71%) and Hodgkin's diseases (73%) (P < 0.05). Majority of the viruses detected in non-neoplastic tonsils (93%) and malignant lymphomas (91%) were "F" prototype. LMP-1 30 bp deletion was found in high frequency in both non-neoplastic tonsils (92%) and malignant lymphomas (86%). In conclusion, most of EBV found in Korea was type 1, and "DF" genotype was more frequent in T cell lymphomas and Hodgkin's diseases than in non-neoplastic tonsils and B cell lymphomas. LMP-1 30 bp deletion did not seem to be associated with malignant lymphomas.
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Affiliation(s)
- Insun Kim
- Department of Pathology, Korea University Medical College, Seoul, Korea.
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40
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Abstract
This article reviews current concepts in pathologic classification of lung cancer based on 1999 World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC) classification. Preinvasive lesions including squamous dysplasia/carcinoma in situ, atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia are discussed in addition to current concepts of bronchioloalveolar carcinoma and neuroendocrine tumors.
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Affiliation(s)
- William D Travis
- Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington, D.C., USA
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41
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Cervantes G, Rodríguez AA, Leal AG. Squamous cell carcinoma of the conjunctiva: clinicopathological features in 287 cases. CANADIAN JOURNAL OF OPHTHALMOLOGY 2002; 37:14-9; discussion 19-20. [PMID: 11865953 DOI: 10.1016/s0008-4182(02)80093-x] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Squamous cell carcinoma is the most frequently encountered malignant tumour of the conjunctiva. The objective of this study was to describe the clinicopathological features of patients with squamous cell carcinoma of the conjunctiva seen at a large ophthalmologic hospital in Mexico City. METHODS We reviewed the clinical and pathological files of all patients with documented squamous cell carcinoma of the conjunctiva seen at the hospital between 1957 and 1996. RESULTS A total of 287 cases (286 patients) were reviewed. The mean age of the patients was 60.4 (range 12 to 99) years; 55% were male. The clinical diagnosis was accurate in 41% of cases. Typical keratinized squamous cell carcinoma of the conjunctiva accounted for 98% of the lesions, and there were small numbers of histologic variants: lymphoepithelioma-like carcinoma (three cases), spindle cell carcinoma (two cases) and mucoepidermoid carcinoma (one case). Evidence of local extension of the tumour was found in 150 patients (52%), with the cornea being most frequently involved (108 cases [38%]). Regional metastasis was found in two patients, to a submandibular lymph node in one and to a preauricular lymph node in the other. The most common form of treatment was local resection (258 cases [90%]). The mean length of follow-up was 7.7 (range 2 to 24) months. The recurrence rate was 5.2%. INTERPRETATION We report a large series of patients with squamous cell carcinoma of the conjunctiva. The incidence of local extension was high. Three cases of lymphoepithelioma-like carcinoma, a variant not previously reported in the conjunctiva, were encountered and were confirmed by immunohistochemical reactions.
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Affiliation(s)
- Guadalupe Cervantes
- Department of Ophthalmology, Asociación para evitar la ceguera en México, Hospital Dr. Luis Sánchez Bulnes, Mexico City, DF.
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42
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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: 58] [Impact Index Per Article: 2.4] [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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43
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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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44
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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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Han AJ, Xiong M, Gu YY, Lin SX, Xiong M. Lymphoepithelioma-like carcinoma of the lung with a better prognosis. A clinicopathologic study of 32 cases. Am J Clin Pathol 2001; 115:841-50. [PMID: 11392880 DOI: 10.1309/buan-bgfw-69u9-c3h8] [Citation(s) in RCA: 101] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
The purpose of our study was to clarify the prognosis of lymphoepithelioma-like carcinoma (LELC) of the lung, which is rare. We analyzed the clinicopathologic features of 32 cases of pulmonary LELC and compared the cases with 84 cases of pulmonary non-LELC with available long-term follow-up information. The results show that LELC of the lung as a distinct entity has a better prognosis than non-LELC. We found a significant difference in the survival rates between patients with LELC and patients with non-LELC in stage II and stages III and IV, respectively. Tumor recurrence and necrosis (5% or more of tumor) are associated with a poor prognosis. It seems that the histologic typing (Regaud type and Schmincke type) of pulmonary LELC is of no clinical value.
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Affiliation(s)
- A J Han
- Dept of Pathology, Sun Yat-sen University of Medical Sciences, 74, Zhongshan Road 2, Guangzhou, 510089, People's Republic of China
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Naidoo P, Chetty R. Lymphoepithelioma-like carcinoma of the breast with associated sclerosing lymphocytic lobulitis. Arch Pathol Lab Med 2001; 125:669-72. [PMID: 11300942 DOI: 10.5858/2001-125-0669-llcotb] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The purpose of this article is to highlight an unusual form of breast carcinoma and discuss its differential diagnosis. A 50-year-old woman underwent wide local excision of a breast lump. Microscopic examination revealed features of a lymphoepithelioma-like carcinoma. Individual tumor cells were present within an abundant lymphoid stroma. Immunohistochemistry revealed the epithelial nature of the cells and excluded a diagnosis of lymphoma. In addition, surrounding nontumorous breast tissue displayed the histologic features of sclerosing lymphocytic lobulitis or lymphocytic mastopathy. This is the second report of a lymphoepithelioma-like carcinoma of the breast, but to the best of our knowledge, it is the first description of coexistent sclerosing lymphocytic lobulitis.
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Affiliation(s)
- P Naidoo
- Division of Anatomical Pathology, School of Pathology and Laboratory Medicine, University of Natal, Durban, South Africa
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Jeng YM, Chen CL, Hsu HC. Lymphoepithelioma-like cholangiocarcinoma: an Epstein-Barr virus-associated tumor. Am J Surg Pathol 2001; 25:516-20. [PMID: 11257627 DOI: 10.1097/00000478-200104000-00012] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Epstein-Barr virus (EBV) has been linked to carcinomas of several body sites, especially of the nasopharynx, salivary gland, lung, and stomach. We present five cases of lymphoepithelioma-like cholangiocarcinoma, including one that had been previously reported. Two patients were men and three were women. Their ages ranged from 42 to 66 years. Histologically, all five tumors were composed of variable proportions of undifferentiated epithelial cells and glandular components in a lymphocyte-rich stroma. EBV was detected in all five tumors by in situ hybridization for EBER-1 in both lymphoepithelioma-like carcinoma (LELC) and glandular parts, but not in 36 cases of cholangiocarcinoma without the LELC component. Taken together, these observations indicate that lymphoepithelioma-like cholangiocarcinoma is strongly linked to EBV. The LELC type of cholangiocarcinoma, like LELC of other body sites, may be more common in areas with endemic EBV infection.
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Affiliation(s)
- Y M Jeng
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
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Dadmanesh F, Peterse JL, Sapino A, Fonelli A, Eusebi V. Lymphoepithelioma-like carcinoma of the breast: lack of evidence of Epstein-Barr virus infection. Histopathology 2001; 38:54-61. [PMID: 11135047 DOI: 10.1046/j.1365-2559.2001.01055.x] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
AIMS Six cases of lymphoepithelioma-like carcinomas of the breast were studied in order to better define the morphology of this type of breast tumour and to see if these neoplastic lesions are related to Epstein-Barr virus (EBV) infection by analogy with histologically similar tumours located in other organs. METHODS AND RESULTS The cases were studied with immunohistochemistry using several antibodies and with in-situ hybridization method employing different types of nucleotides in four cases. The cases presented the distinctive morphology of the lymphoepithelioma-like carcinomas as seen in other organs. Specifically Rigaud and Schminke's patterns of growth were observed. In addition, at the edge of the neoplastic lesions, a lymphoepithelial lobulitis was seen. In-situ hybridization failed to reveal any positivity for EBV genome. CONCLUSION Lymphoepithelioma-like carcinoma is a specific type of breast tumour, but its relation to EBV has yet to be proven. The differential diagnosis with medullary carcinoma is discussed.
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Affiliation(s)
- F Dadmanesh
- Department of Anatomical Pathology, Vancouver Hospital and Health Sciences Center, B.C. Cancer Agency, University of British Columbia, Vancouver, Canada
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Ho JC, Lam WK, Ooi GC, Lam B, Tsang KW. Chemoradiotherapy for advanced lymphoepithelioma-like carcinoma of the lung. Respir Med 2000; 94:943-7. [PMID: 11059946 DOI: 10.1053/rmed.2000.0856] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Lymphoepithelioma-like carcinoma (LELC) of the lung, an Epstein-Barr virus-associated undifferentiated carcinoma, is a rare entity of pulmonary malignancy. It tends to affect young non-smoking Asians and is often resectable. However, little is known of the treatment of the even rarer locally advanced or metastatic cases. We report our experience of three Chinese patients with advanced LELC of the lung who were treated with combination-chemotherapy (5-fluorouracil, leucovorin, and cisplatin) and radiotherapy. The encouraging response of these patients supports the use of this regime in other patients.
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Affiliation(s)
- J C Ho
- University Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China
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Han AJ, Xiong M, Zong YS. Association of Epstein-Barr virus with lymphoepithelioma-like carcinoma of the lung in southern China. Am J Clin Pathol 2000; 114:220-6. [PMID: 10941337 DOI: 10.1309/148k-nd54-6njx-na61] [Citation(s) in RCA: 77] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Having reviewed the data on 3,663 consecutive cases of primary lung carcinoma in southern China, we found that 32 cases could meet the criteria for lymphoepithelioma-like carcinoma (LELC) of the lung. To study the relationship between pulmonary LELC and Epstein-Barr virus (EBV) infection, we used in situ hybridization and immunohistochemistry techniques to detect the EBV-encoded small nonpolyadenylated RNA (EBER), latent membrane protein 1 (LMP1), and viral capsid antigen (VCA) in 32 cases of LELC and 19 cases of non-LELC lung carcinoma. Of the 32 cases, 30 (94%) showed EBER positivity. Of the 30 EBER-positive pulmonary LELC cases, 16 and 7 expressed LMP1 and VCA, respectively. In contrast with LELC, none of the 19 cases of non-LELC lung carcinoma showed EBER-, LMP1-, or VCA-positive signals in carcinoma cells. The results demonstrate that there is a close relationship between EBV infection and pulmonary LELC. EBV infection may have an essential role in the tumorigenesis of pulmonary LELC. EBV latent infection is the main status in pulmonary LELC except for individual EBV entering into a lytic cycle.
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Affiliation(s)
- A J Han
- Department of Pathology, Sun Yat-sen University of Medical Sciences, Guangzhou, Peoples' Republic of China
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