Primary pulmonary lymphoepithelioma-like carcinoma in non-endemic region: A case report and literature review.
Xie Chao,Xu Xia,Wu Bian,Yang Kun-Yu,Huang Jing
RATIONALE:Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of lung squamous cell carcinoma. In situ hybridization test for Epstein-Bar virus-encoded RNA (EBER) is generally used for distinguishing it from other lung cancers. Although plasma EBV DNA quantification has been widely used as a tumor biomarker in nasopharyngeal carcinoma (NPC), only a limiting number of studies have suggested that plasma EBV DNA quantification may be used as a tumor marker in pulmonary LELC patients. PATIENT CONCERNS:We report two female patients diagnosed as poorly differentiated squamous cell carcinoma, subsequently, their further histological examinations showed that tumor cells were EBER positive and plasma EBV DNA was detectable. DIAGNOSES:Two patients was diagnosed with advanced pulmonary LELC. INTERVENTIONS:The patients were treated with chemotherapy and chemoradiotherapy respectively. OUTCOMES:Both patients responded well to our treatment, in accordance with their decreased EBV DNA level. LESSONS:Pulmonary LELC is a rare type of lung cancer which is sensitive to chemoradiotherapy, especially in late staged patients.
Primary lymphoepithelioma-like carcinoma of the lung: report of a rare case and review of the literature.
Yener Neşe Arzu,Balikçi Ahmet,Çubuk Rahmi,Mıdı Ahmet,Örkı Alpay,Eren Topkaya Aynur
Turk patoloji dergisi
Primary lymphoepithelioma-like carcinoma of the lung is a rare type of non-small cell lung carcinoma. In this study, we aimed to present a 62-year-old smoker male with a primary lymphoepithelioma-like carcinoma of the hilar region of the left lung. The patient underwent left pneumonectomy and no adjuvant therapy was given. There were no other abnormalities on whole body PET/CT scan including the nasopharyngeal region. The patient showed seropositivity for EBV IgG but immunohistochemistry and PCR amplification studied on paraffin-embedded tissue sections of the tumor failed to show any sign of EBV infection within the tumor cells. He is alive and disease-free four months after the operation. Although primary lymphoepithelioma-like carcinoma of the lung is usually reported in young females with no history of tobacco use and the tumor cells are infected with EBV, it may rarely be seen in elderly males with a history of tobacco use and the tumor cells not infected with EBV.
About a lymphoepithelioma-like carcinoma of the lung with an endotracheal localization.
Mlika Mona,Hamdi Besma,Marghli Adel,El Mezni Faouzi
La Tunisie medicale
INTRODUCTION:Lympho-epithelioma like carcinoma is a rare lung tumour that acounts for less than 1% of non small cell lung carcinomas. It is defined as a special entity among the 2015 World Health Organization. AIM:Our aim was to describe a completely illustrated new case of lymhpo-epithelioma like carcinoma. We describe a new case diagnosed in our Department of Pathology. CASE PRESENTATION:The authors describe a case of a 22-year-old woman without a particular past medical history who presented non specific respiratory symptoms. Radiologic investigations revealed a tracheal tumor with enlarged mediastinal lumph nodes. A first biopsy was performed revealing a malignant tumor with a squamous differentiation highlighted by immunohischemistry. A surgical biopsy was performed and the final microscopic diagnosis revealed a lymphoepithelioma-like carcinoma of the lung. This diagnosis was retained after ruling out a possible metastasis of a nasopharyngeal carcinoma whose microscopic features are similar to this subtype of lung tumor. CONCLUSION:This case points out the rarity of this diagnosis, especially in a young and caucasian patient and highlights the diagnostic dilemma caused by this kind of tumor.
A multicenter analysis of genomic profiles and PD-L1 expression of primary lymphoepithelioma-like carcinoma of the lung.
Xie Zhanhong,Liu Laiyu,Lin Xinqing,Xie Xiaohong,Gu Yingying,Liu Ming,Zhang Jiexia,Ouyang Ming,Lizaso Analyn,Zhang Hua,Feng Weineng,Li Bing,Han-Zhang Han,Chen Shuyin,Li Shiyue,Zhong Nanshan,Liu Hao,Zhou Chengzhi,Qin Yinyin
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
To understand the molecular mechanism of tumorigenesis of pulmonary lymphoepithelioma-like carcinoma and explore potential therapeutic strategies, we investigated the genomic profiles and PD-L1 expression of 29 Chinese pulmonary lymphoepithelioma-like carcinoma patients at various stages. We performed capture-based targeted sequencing on tissue samples collected from 27 patients with sufficient samples using a panel consisting of 520 cancer-related genes, spanning 1.64 Mb of the human genome. We identified 184 somatic mutations in 109 genes from 26 patients. One patient had no mutations detected by this panel. Copy number variations were detected in 52% (14/27) of the patients, with a majority having advanced-stage disease (10/14). Except for the detection of ERBB2 amplification and KRAS mutation in two patients, no other classic lung cancer driver mutations were detected. Interestingly, 78% (21/27) of the patients had mutations in epigenetic regulators. Of the 184 mutations identified, 51 occurred in 29 epigenetics-related genes. Furthermore, we performed PD-L1 immunohistochemistry staining using the Dako 22C3 assay and demonstrated that 69% (20/29) of the cohort had positive PD-L1 expression, of which three patients received and benefited from a PD-1 inhibitor. In conclusion, we elucidated a distinct genomic landscape associated with pulmonary lymphoepithelioma-like carcinoma with no classic lung cancer driver mutation but an enrichment of mutations in epigenetic regulators. The detection of high PD-L1 expression and lack of any canonical druggable driver mutations raises the potential of checkpoint immunotherapy for pulmonary lymphoepithelioma-like carcinoma.
Pulmonary Lymphoepithelioma-Like Carcinoma: A Mini-Review.
Hu Yan,Ren Siying,Liu Yukang,Han Wei,Liu Wenliang
OncoTargets and therapy
Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and distinct subtype of non-small-cell lung carcinoma associated with Epstein-Barr virus (EBV) infection. We systematically reviewed the recent research that expands our knowledge about PLELC, with main focus on its genetic profile, tumor-infiltrating environment, PD-L1 expression, circulating EBV-DNA, clinical utility of 18F-FDG PET/CT, and treatment strategy. A low frequency of typical driver mutations and widespread existence of copy number variations was detected in PLELC. Persistent EBV infection may trigger intense infiltration of lymphocytes, representing enhanced tumor immunity and possibly resulting in a better prognosis. Circulating EBV-DNA in the plasma of patients with PLELC may predict disease progression and response to therapy. PLELC is 18F-FDG avid, and 18F-FDG PET may help refine palliation strategies and subsequently improve the prognosis. Most of the reported patients present at early and resectable stage, and surgical resection with curative intent is the preferred approach. There is currently no consensus on the regimen of chemotherapy for patients with advanced stages. EGFR-targeted therapies seem to have no therapeutic effect, and the clinical impact of PD-1/PD-L1 therapy is uncertain but worthy of further research.
FDG PET/CT in primary pulmonary lymphoepithelioma-like carcinoma.
Dong Aisheng,Zhang Jian,Wang Yang,Zhai Zhijun,Zuo Changjing
Clinical nuclear medicine
Primary pulmonary lymphoepithelioma-like carcinomas are extremely rare tumors with better prognosis than other types of non-small cell lung cancer. An 83-year-old man presented with cough and hemoptysis for 2 weeks. Chest CT images showed a cylinder-shaped lesion in the right upper lung. F-FDG PET/CT showed strong FDG uptake (SUVmax, 34.5) of the tumor with ipsilateral hilar lymph node metastases. Video-assisted thoracoscopic lobectomy was performed. Histopathologically, the tumor was composed of epithelial tumor cells with high proliferation index (80%) and abundant lymphoplasmacytic cells, consistent with lymphoepithelioma-like carcinoma.
Unusual presentation of pulmonary lymphoepithelioma-like carcinoma.
Oi Ryoko,Saji Hisashi,Marushima Hideki,Maeda Ichiro,Takagi Masayuki,Nakamura Haruhiko
Respirology case reports
Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare malignant tumour with histological features similar to undifferentiated nasopharyngeal carcinoma. A close association is known to exist between pulmonary LELC and Epstein-Barr virus infection in Southeast Asian countries. We report a 69-year-old man with pulmonary LELC arising from a thin-walled cavity with a smooth inner surface and characterized by an unexpectedly rapid progression.
Primary pulmonary lymphoepithelioma-like carcinoma.
Fan Ying,Li Chenghui,Qin Jing,Lu Hongyang
Medical oncology (Northwood, London, England)
Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is an extremely rare subtype of non-small-cell lung cancer (NSCLC) but differs from other NSCLC types. Most patients with PPLELC have almost no obvious clinical manifestations, and are often diagnosed in the advanced stage. Complete resection is the standard treatment for cases with early stage disease, while chemotherapy and radiotherapy are effective to some extent in late stage disease. High expression of PD-L1 in PPLELC tumor cells confers immunotherapy an important role in the treatment of PPLELC, and programmed death-1 (PD-1) inhibitors such as nivolumab and pembrolizumab may be optimal options for PPLELC patients. This review focuses on the clinical and pathologic features, treatment, and prognosis of PPLELC.
Pulmonary Lymphoepithelioma-like Carcinoma.
Sathirareuangchai Sakda,Hirata Kirk
Archives of pathology & laboratory medicine
Pulmonary lymphoepithelioma-like carcinoma is a rare type of non-small cell lung cancer. The tumor is usually discovered in young, nonsmoking Asian populations. The patients are diagnosed at an earlier stage and have a better prognosis than those with other non-small cell lung cancers. Histologically, the tumor morphology is indistinguishable from undifferentiated carcinoma of the nasopharynx. It is characterized by nests or diffuse sheets of syncytial tumor cells, which show round to oval vesicular nuclei with prominent nucleoli, along with an admixed heavy lymphocytic and plasma cell infiltrate. The presence of Epstein-Barr virus in the tumor cells is crucial for the diagnosis. The differential diagnoses include lymphoepithelioma-like carcinoma from other sites and pulmonary involvement of lymphoma. mutations and rearrangements are not commonly found in lymphoepithelioma-like carcinoma, in contrast to programmed death ligand-1 expression, which is shown in a majority of cases.
[Clinical Analysis of Primary Pulmonary Lymphoepithelioma-like Carcinoma in 8 Patients].
Zhao Hui,Chen Jianhua
Zhongguo fei ai za zhi = Chinese journal of lung cancer
BACKGROUND:Lymphoepithelioma-like carcinoma, an uncommon epithelial tumor, is mostly originated form the nasopharynx and also occurs in foregut-derived organs, such as lung, stomach, salivary gland, and thymus. Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype accounting for around 0.9% of non-small cell lung cancer (NSCLC). We aimed to evaluate clinicopathological features, treatment modalities, and prognosis of PPLELC. METHODS:In the current study, a retrospective analysis on 8 patients diagnosed with PPLELC at Hunan Cancer Hospital between October 2013 and June 2016 was conducted with respect to their clinical characteristics and outcomes, in order to deeply investigate this rare subtype of lung cancer. RESULTS:In all 8 patients, 62.5% (5/8) were female, and the median age was 51.5 years (range 41 years-64 years). The majority (87.5%) were never smokers and 50.0% were asymptomatic at diagnosis. About 37.5% presented with stage I disease, 50.0% had stage III disease and 12.5% had stage IV disease. Histologically, the tumor morphology was indistinguishable from undifferentiated carcinoma of the nasopharynx and were characterized by poorly differentiated tumor cells with large vesicular nuclei and prominent nucleoli showing syncytial growth patterns and accompanied by heavy lymphocytic infiltration. The tumor cells were presented as positive for P63 (100.0%, 6/6), CK5/6 (100.0%, 5/5), CK (100.0%, 5/5). The expression of programmed cell death ligand 1 (PD-L1) in 8 patients was detected. When membranous staining was present in ≥5% of the cells, it was defined as PD-L1 positive. The PD-L1 expression frequency was 50.0% (4/8), and the tumor proportion score (TPS) fluctuated between 20.0% and 70.0%. Epidermal growth factor receptor(EGFR) mutations were detected in 3 cases and all tested samples were wild type; moreover, ALK rearrangement was negative in 2 patients with available data. KRAS, B-raf, C-kit, HER2, VEGFR1 and VEGFR2 were detected in 1 case. The results showed that KRAS was wild type, B-raf and C-kit mutation was negative, and HER2, VEGFR1 and VEGFR2 were moderately expressed. All patients underwent surgery with or without adjuvant therapy. Among these patients, 5 patients received adjuvant chemotherapy, including 2 patients with stage Ib disease, 2 patients with stage IIIa disease and 1 patient with stage IV disease. 1 patient with stage IIIa disease received adjuvant chemotherapy and radiotherapy and 1 patient with stage IIIa disease received neoadjuvant chemotherapy. All patients survived until the deadline for follow-up. The median survival time of all LELC patients is 57 months. The 3- and 5-year overall survival (OS) rates of LELC patients were 87.5% and 50.0%, disease-free survival (DFS) rates were 87.5% and 50.0%, respectively. CONCLUSIONS:PPLELC is uncommon but distinct subtype of NSCLC with unique clinicopathologic characteristics that tends to affect young nonsmoking patients, without significant predilection for sex and with strong association with Epstein-Barr virus (EBV) infection. Histology and immunohistochemistry are the main diagnostic methods. Rare or no driver gene mutations were found in the common oncogenes such as EGFR mutations and ALK gene rearrangement, implying that the mutagenesis of these genes was not involved in the tumorigenesis of PPLELC. PD-1 and PD-L1 may be potential therapeutic targets for PPLELC. The patients are diagnosed at an earlier stage and have a better prognosis than those with other non-small cell lung cancer. No standardized treatment regimens currently exist for this rare tumor. 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. Due to its low incidence, further research is needed to determine its biological characteristics and optimal treatment options.
Epstein-Barr Virus-Induced Epigenetic Pathogenesis of Viral-Associated Lymphoepithelioma-Like Carcinomas and Natural Killer/T-Cell Lymphomas.
Li Lili,Ma Brigette B Y,Chan Anthony T C,Chan Francis K L,Murray Paul,Tao Qian
Pathogens (Basel, Switzerland)
Cancer genome studies of Epstein-Barr virus (EBV)-associated tumors, including lymphoepithelioma-like carcinomas (LELC) of nasopharyngeal (NPC), gastric (EBVaGC) and lung tissues, and natural killer (NK)/T-cell lymphoma (NKTCL), reveal a unique feature of genomic alterations with fewer gene mutations detected than other common cancers. It is known now that epigenetic alterations play a critical role in the pathogenesis of EBV-associated tumors. As an oncogenic virus, EBV establishes its latent and lytic infections in B-lymphoid and epithelial cells, utilizing hijacked cellular epigenetic machinery. EBV-encoded oncoproteins modulate cellular epigenetic machinery to reprogram viral and host epigenomes, especially in the early stage of infection, using host epigenetic regulators. The genome-wide epigenetic alterations further inactivate a series of tumor suppressor genes (TSG) and disrupt key cellular signaling pathways, contributing to EBV-associated cancer initiation and progression. Profiling of genome-wide CpG methylation changes (CpG methylome) have revealed a unique epigenotype of global high-grade methylation of TSGs in EBV-associated tumors. Here, we have summarized recent advances of epigenetic alterations in EBV-associated tumors (LELCs and NKTCL), highlighting the importance of epigenetic etiology in EBV-associated tumorigenesis. Epigenetic study of these EBV-associated tumors will discover valuable biomarkers for their early detection and prognosis prediction, and also develop effective epigenetic therapeutics for these cancers.
The clinicopathological and prognostic significance of PD-L1 expression assessed by immunohistochemistry in lung cancer: a meta-analysis of 50 studies with 11,383 patients.
Translational lung cancer research
BACKGROUND:We conducted a meta-analysis to systematically evaluate the relationship between programmed death-ligand 1 (PD-L1) expression and survival in patients with lung cancer. METHODS:The electronic databases PubMed, Embase, Cochrane, and Web of Science were searched up to January 2, 2018, for articles relating to PD-L1 expression detected by immunohistochemistry (IHC) and lung cancer patient prognosis. RESULTS:Fifty studies including 11,383 patients published between 2011 and 2017 were enrolled in this meta-analysis. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) suggested that PD-L1 IHC expression was related to poor overall survival (OS) (HR =1.45, 95% CI: 1.24-1.68). In subgroup analysis categorized according to sample type, cut-off value, ethnicity and TNM stage, the pooled results demonstrated inferior survival in the PD-L1 positive group when the PD-L1 expression was detected by resection specimens (P=0.000), 5% was taken as the cutoff value (P=0.000), the patients were in early stage (I-III) (P=0.000), and the geographic setting of the study was in Asia (P=0.000). Besides, patients with high PD-L1 expression had shorter OS in NSCLC (P=0.000), ADC (P=0.000), SCC (P=0.353) and LELC (P=0.810), while no significant difference was observed in SCLC (P=0.000). The pooled odds ratios (ORs) suggested that PD-L1 expression was associated with male (P<0.001), smoker (P<0.001), poor tumor differentiation (P=0.014), large tumor size (P=0.132), positive lymph nodal metastasis (P=0.002), wild-type status (P<0.001) and mutations (P=0.393). However, age (P=0.15) and rearrangements (P=0.567) had no bearing on PD-L1 expression. CONCLUSIONS:PD-L1 expression that is associated with several clinicopathological feactures may serve as a poor prognostic biomarker for patients with lung cancer.
Pulmonary lymphoepithelioma-like carcinoma with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene.
Ose Naoko,Kawai Teruka,Ishida Daisuke,Kobori Yuko,Takeuchi Yukiyasu,Senba Hidetoshi
Respirology case reports
A pulmonary lymphoepithelioma-like carcinoma (PLELC) is similar to a lymphoepithelioma, a subtype of nasopharyngeal carcinoma and commonly associated with Epstein-Barr virus infection which is a rare tumour and classified in the group of "other and unclassified carcinoma" in the latest 2015 World Health Organization (WHO) classification. Some reports of lymphoepithelioma-like carcinoma (LELC) have noted an epidermal growth factor receptor (EGFR) mutation, whereas none have noted a mutation of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene. This is the first reported case of PLELC with ALK rearrangement. A 76-year-old woman underwent a right lower lobectomy and complicated partial resection of the upper lobe with lymph node dissection under complete thoracoscopic approach. A histopathological diagnosis of PLELC was made and the stage was classified as T1aN1(#12l) M0, pl0, G2, Ly1, V1. The results of both ALK immunohistochemistry and EML4-ALK fusion gene on fluorescence in situ hybridization (FISH) examinations were positive; however, EGFR mutational analysis results showed wild-type mutation.
Primary Pulmonary Lymphoepithelioma-like Carcinoma on FDG PET/CT.
Aktas Gul Ege,Can Nuray,Demir Selin Soyluoglu,Sarıkaya Ali
Nuclear medicine and molecular imaging
A 69-year-old male smoker was referred to F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) with the indication of a suspicious solitary pulmonary nodule. FDG PET/CT determined a 2.5 × 2-cm soft-tissue lesion (SUVmax, 16.2) with spiculated margins in the hilum of the right lung. A 1-cm diameter lymphadenopathy on the right hilum with an SUVmax of 3.2 was also determined. Transbronchial biopsy of the right hilar lymphadenopathy did not reveal any malignant features in histopathologic examination, and it was determined to be reactive. The patient underwent a right upper lobe segmentectomy, and the histopathologic evaluation revealed that the tumor was a primary lymphoepithelioma-like carcinoma (LELC) of the lung with negative Epstein-Barr virus (EBV) on in situ hybridization studies. In this case report, we mainly focus on the FDG avidity of this very rare kind of tumor comparatively with previous reports and possible explanations of discordancy in FDG avidity in relation to histopathologic characteristics.
[The Clinical Analysis of 21 Patients with Lymphoepithelioma-like Carcinoma after Operation.].
Xia Jinjing,Jiang Liyan,Zhang Jie,Miao Qian,Xin Yu,Zhong Runbo,Zhao Yizhuo,Han Baohui
Zhongguo fei ai za zhi = Chinese journal of lung cancer
BACKGROUND:Lung lymphoepithelioma-like carcinoma is a rare subtype of large cell carcinomas of the lung. The aim of this study is to retrospectively analyze the clinical characteristics, surgical methods, laboratory inspection, chemotherapy, radiotherapy and prognosis of LELC. METHODS:From 2004 to 2008, clinical data were collected from 21 patients who were treated in Shanghai Chest Hospital. The correlation between clinicopathological characteristics and prognosis was evaluated. RESULTS:Of the 21 patients, 15 patients had lobectomy; 4 patients had wedge resection; 1 patient had pneumonectomy and 1 patient had sleeve resection. 12 patients received chemotherapy and 3 patients received radiotherapy after operation. Until 2009-4-31, 4 patients died, and the median survival time (MST) was 49 months. CONCLUSIONS:Lymphoepitheliomalike carcinoma of the lung is a very rare and unique subtype of large cell carcinomas of the lung, which has a better prognosis with surgical, chemotherapy and radiotherapy.
PD-L1 expression in lung cancer and its correlation with driver mutations: a meta-analysis.
Zhang Minghui,Li Guoliang,Wang Yanbo,Wang Yan,Zhao Shu,Haihong Pu,Zhao Hongli,Wang Yan
Although many studies have addressed the prognostic value of programmed cell death-ligand 1 (PD-L1) expression in lung cancer, the results remain controversial. A systematic search of the PubMed, EMBASE, and Cochrane Library databases was performed to identify the correlation between PD-L1 expression and driver mutations and overall survival (OS). This meta-analysis enrolled a total of 11,444 patients for 47 studies, and the pooled results showed that increased PD-L1 expression was associated with poor prognosis (HR = 1.40, 95% CI: 1.19-1.65, P < 0.001). In subgroup analysis stratified according to histology types, the pooled results demonstrated that increased PD-L1 expression was an unfavorable prognostic factor for non-small cell lung cancer (NSCLC) (HR = 1.26, 95% CI: 1.05-1.52, P = 0.01) and pulmonary lymphoepithelioma-like carcinoma (LELC) (HR = 3.04, 95% CI: 1.19-7.77, P = 0.02), rather than small cell lung cancer (SCLC) (HR = 0.62, 95% CI: 0.27-1.39, P = 0.24). The pooled ORs indicated that PD-L1 expression was associated with gender, smoking status, histology, differentiation, tumour size, lymph nodal metastasis, TNM stage and EGFR mutation. However, PD-L1 expression was not correlated with ALK rearrangement and KRAS mutations.
[Pulmonary lymphoepithelioma-like carcinoma; report of a case].
Hiramatsu Yoshinori,Okagawa Takehiko
Kyobu geka. The Japanese journal of thoracic surgery
A 66-year-old male was referred to our hospital due to an abnormal chest shadow in the left lung detected on a medical examination. Chest computed tomography(CT) revealed a round mass of 40 mm in diameter in the left S10. Positron emission tomography (PET) scan showed fluorodeoxy glucose (FDG) accumulation and surgical biopsy was done. The intraoperative frozen histopathological diagnosis was mucosal associated lymphoid tissue( MALT) lymphoma or pseudoinflammatory tumor. By postoperative pathology, the mass was finally diagnosis as lymphoepithelioma-like carcinoma (LELC) of the lung, pT2aN0M0 stage I B.After a month, left lower lobectomy with mediastinal lymph node dissection was performed. The association with Epstein-Barr virus was not demonstrated by EBER in situ hybridization. The patient was well without relapse at 24 months after surgery.
Case report: lymphoepithelial-like carcinoma of the lung--a chronic disease?
Wong Joelle F S,Teo Melissa C C
World journal of surgical oncology
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.
Primary Lymphoepithelioma-like Carcinoma of the Lung in a 13 year old Girl.
Kundu Susmita,Mitra Ritabrata,Majumdar Anup,Saha Sucheta,Misra Swapnendu
Oman medical journal
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.
Multiple pulmonary nodules with high metabolic activity: Potential benefit of multiple nodule biopsies by video-assisted thoracic surgery: A case report.
Wang Jinlin,Li Shiyue,Liu Jun,Gu Yingying,Chen Ping
Experimental and therapeutic medicine
The aim of this study was to assess complex cases of multiple pulmonary nodules (PNs) with high metabolic activity that may have benefited from being managed in a manner outside the formal guidelines. The study describes the case of a patient with multiple highly metabolically-active PNs, where an original diagnosis of lung cancer metastasis was proposed. Following a failed transbronchial lung biopsy (TBLB), multiple nodule biopsies by video-assisted thoracic surgery (VATS) were performed, and a diagnosis of lymphoepithelioma-like carcinoma (LELC; stage IA) and tuberculosis was reached. This case report demonstrated that multiple nodule biopsies by VATS were effective and were able to improve the prognosis without delay.
Treatment of Lung Carcinosarcoma and Other Rare Histologic Subtypes of Non-small Cell Lung Cancer.
Yang Han,Lin Yongbin,Liang Ying
Current treatment options in oncology
OPINION STATEMENT:Lung carcinosarcoma (PCS) and other histological subtypes of non-small cell lung cancer, such as primary pulmonary lymphoma (PPL), pulmonary carcinoid (PC), and primary pulmonary lymphoepithelioma-like carcinoma (LELC), are rare. For their low incidence, the diagnosis and treatment are still controversial. Some patients only need surgery, while others may need chemotherapy, radiotherapy, or targeted therapy. In this paper, we retrospectively reviewed the literature of some rare histological subtype of NSCLC for the recent 20 years, and try to get some conclusions.
Talaromyces marneffei infection in a lung cancer patient: a rare case report.
Lin Fanhai,Qiu Ye,Zeng Wen,Liang Yi,Zhang Jianquan
BMC infectious diseases
BACKGROUND:Talaromyces marneffei is an invasive, and thermal dimorphic pathogenic fungus, whose infection is life threatening in human. Although immunocompromised patients, such as patients with human immunodeficiency virus infection and recipients of organ transplant, are susceptible hosts, infections have been recently reported in people with normal immune function. Patients with cancer may also be susceptible hosts but no case of T. marneffei infection has been reported in patients with lung cancer. In this case, we describe T. marneffei infection coexisting with primary pulmonary lymphoepithelioma-like carcinoma (LELC) in an HIV-negative patient. CASE PRESENTATION:A 50-year-old, previously healthy female presented with a 1-month history of cough and fever. CT scans showed a mass in the left lower lung, left pleural thickening, pleural effusion, and multiple swollen lymph nodes throughout the body. Based on the pathology of the left lung lesion, she was diagnosed with left primary pulmonary LELC complicated with T. marneffei. She received both anti-tumor and anti-fungal treatments. A subsequent CT re-examination demonstrated that the mass was absorbed remarkably after treatment. Follow up showed no tumor progression and no relapse of T. marneffei infection. CONCLUSION:This case suggested that clinicians should pay more attention to the potential hosts of T. marneffei infection, especially those with lung cancer. Early diagnosis and treatment can improve the prognosis of T. marneffei infection coexisting with lung cancer.
The clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma: A systematic review and meta-analysis.
Tang Liansha,Chen Nan,He Wenbo,Zhou Jian,Zhang Jinjue,Lin Zhangyu,Wang Zihuai,Hao Jianqi,Lin Feng
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.
PD-L1 is highly expressed in lung lymphoepithelioma-like carcinoma: A potential rationale for immunotherapy.
Chang Yih-Leong,Yang Ching-Yao,Lin Mong-Wei,Wu Chen-Tu,Yang Pan-Chyr
Lung cancer (Amsterdam, Netherlands)
OBJECTIVES:Programmed cell death-ligand 1 (PD-L1) and driver mutations are found in non-small cell lung cancers (NSCLCs) and may be suitable targets for specific therapies, but their roles in lymphoepithelioma-like carcinoma (LELC) of the lung are unclear. MATERIALS AND METHODS:Sixty-six patients with pulmonary LELCs were investigated. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Tumors with moderate-to-strong membrane staining in ≥5% of tumor cells were positive for PD-L1 overexpression. The presence of driver mutations in the genes for epidermal growth factor receptor (EGFR), KRAS, and BRAF were examined by direct sequencing. Anaplastic lymphoma kinase (ALK) and ROS1 levels were determined by immunohistochemistry. Correlations of PD-L1 expression and driver mutations with clinicopathologic parameters were analyzed. RESULTS:The overall frequency of PD-L1 overexpression and EGFR mutation was 75.8% and 12.1%, respectively. No KRAS, BRAF, ALK or ROS1 aberrations could be detected. PD-L1 expression was not associated with driver mutations. Multivariate analysis revealed that smoking and advanced stage were independent risk factors for poor overall survival, whereas PD-L1 positivity was not significantly associated with patient outcome. CONCLUSION:There are high PD-L1 expression and infrequent driver mutations in LELCs compared with conventional NSCLCs. The high expression of PD-L1 in EBV and inflammation associated LELC may provide a rationale for immunotherapy in this subtype of lung cancer.
Collision of lymphoepithelioma-like carcinoma and adenocarcinoma of the lung: a case report.
Chan Jammy Kin Iong,Tai Wai Meng,Wen Jian Ming
The clinical respiratory journal
We report a rare case of collision of lymphoepithelioma-like carcinoma (LELC) and adenocarcinoma (AC) in the lung. A 59-year-old woman had a history of fever and cough. A mass was found by X-ray in the left upper lung. Magnetic resonance imaging (MRI) shows a dumbbell-like mass in the fore and tongue segment of the left upper lung with irregular spiculate margin. Positron emission tomography/computed tomography (PET/CT) (18F-FDG) shows strong concentration of radioactivity (SUVmax 6.9-12.3 cm) in the lung mass only. The patient subsequently underwent resection of left upper lung and associated hilar lymph nodes. Histological examination revealed it was a collision carcinoma comprising LELC and AC. The hilar lymph nodes were tumuor free. The immunoreactions, Epstein-Barr early RNA in situ hybridization and molecular analyses, such as EGFR mutation, c-Met, anaplastic lymphoma kinase were different in both tumuor components, indicating they derived from different cell origin. This rare case was discussed.
Plasma Epstein-Barr Virus-Deoxyribonucleic Acid Copy Number Predicts Disease Progression in Stage I-III Pulmonary Lymphoepithelioma-Like Carcinoma.
Li Qi-Wen,Qiu Bo,Hu Wan-Ming,Guo Su-Ping,Wu Ying-Jia,Zhu Yu-Jia,Hu Nan,Ai Xin-Lei,Chen Nai-Bin,Guo Jin-Yu,Hu Yong-Hong,Liu Meng-Zhong,Zeng Mu-Sheng,Liu Hui
Frontiers in oncology
To investigate the predictive values of plasma Epstein-Barr Virus (EBV)- deoxyribonucleic acid (DNA) copy number on disease progression and survival in stage I-III pulmonary lymphoepithelioma-like carcinoma (LELC). Patients with pathologically confirmed, initially diagnosed or locally recurrent stage I-III pulmonary LELC, who received locally radical treatment and had plasma EBV-DNA results, were retrospectively reviewed. Risk factors of progression-free survival (PFS) and overall survival (OS) were assessed, including the predictive value of pre- and post-treatment EBV-DNA levels. The EBV-DNA change during follow-up was analyzed to determine its association with tumor progression and survival. A total of 102 patients were included in analysis. Eighty-eight patients had initially-diagnosed and 14 had locally recurrent disease. There were 33 patients treated with radical surgery, 55 with definite radiotherapy and 14 with both. EBV-DNA was tested pre-treatment ( = 66), post-treatment ( = 93) and/or during follow-up ( = 58). Forty-one patients had complete EBV-DNA results of all three time points. The overall 2-year PFS and OS were 66.3 and 96.0%, respectively. Pre-treatment EBV-DNA copy number > 10,000 copies/mL was a risk factor of PFS (2-year PFS, > 10,000 vs. ≤ 10,000 copies/mL, 37.2 vs. 75.1%, = 0.007). Positive post-treatment EBV-DNA also indicated a worse PFS in univariable (2-year PFS, > 0 vs. 0 copy/mL, 25.6 vs. 76.8%, < 0.001) and multivariable analysis (HR = 3.44, 95% CI, 1.52-7.78; = 0.003). In the follow-up set, an increasing EBV-DNA exceeding 1,000 copies/mL strongly predicted disease progression within 3 months, with a specificity of 97.5% (95% CI: 86.8-99.6%) and was associated with impaired OS (2-year OS, > 1,000 vs. ≤ 1,000 copies/mL, 72.9 vs. 100%, < 0.001). Regular testing of EBV-DNA is suggested for pulmonary LELC to predict disease progression. If EBV-DNA copy number was increasing and beyond 1,000 copies/mL during follow-up, intensive radiologic evaluations are recommended.
Lymphoepithelioma-like carcinoma of the lung: an unusual case and literature review.
Huang Yuan-Chun,Hsueh Ching,Ho Shang-Yun,Liao Chiung-Ying
Case reports in pulmonology
We described a case of lymphoepithelioma-like carcinoma (LELC) of the lung of a 65-year-old man with initial symptoms of intermittent chest pain and mild shortness of breath for 2 weeks. A right-lung mass was noted on chest computed tomography (CT) scan and was proved histopathologically as LELC of lung after video-assisted thorascopic lobectomy. He was successfully treated with lobectomy with postoperative adjuvant chemotherapy and is alive without signs of recurrence for 36 months after the diagnosis. It is important for clinicians, pathologists, and radiologists to understand the clinical, pathological, and radiological presentations of this neoplasm to avoid improper clinical decision making and misdiagnosis.
Distinct Molecular Landscape of Epstein-Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing.
Chau Shuk-Ling,Tong Joanna Hung-Man,Chow Chit,Kwan Johnny Sheung-Him,Lung Raymond Wai-Ming,Chung Lau-Ying,Tin Edith Ka-Yee,Wong Shela Shu-Yan,Cheung Alvin Ho-Kwan,Lau Rainbow Wing-Hung,Ng Calvin Sze-Hang,Mok Tony Shu-Kam,Lo Kwok-Wai,To Ka-Fai
Pulmonary lymphoepithelioma-like carcinoma (LELC) is a subtype of non-small cell lung cancer (NSCLC) characterized by marked lymphocytic infiltration and association with Epstein-Barr virus (EBV). The molecular basis underlying the disease remains unclear. We sought to study the molecular landscape by multiple approaches including whole genomic sequencing, capture-based targeted sequencing, fluorescent in situ hybridization and immunohistochemistry. Tumor cells from 57 EBV-positive pulmonary LELCs were isolated by careful microdissection prior to genomic sequencing. Integrated analysis revealed a distinct genomic landscape of low mutation rate (11%), low incidence of known drivers in the RTK/RAS/RAF (11%) and PI3K/AKT/mTOR pathways (7%), but enriched for loss-of-function mutations in multiple negative regulators of the NF-κB pathway. High level programmed cell death ligand-1 (PD-L1) expression was shown with 47% and 79% of the cases showing positive PD-L1 immunoreactivity at ≥50% and ≥1% tumor proportion score, respectively. Subsets of the patients with actionable fibroblast growth factor receptor 3 ( aberrations (4%) and mismatch repair deficiency (4%) were potentially eligible for precision medicine. Pulmonary LELC showed a distinct genomic landscape, different from major NSCLC subtypes but resembled that of EBV-associated nasopharyngeal carcinoma. Our work facilitated the understanding of molecular basis underlying pulmonary LELC to explore potential therapeutic options.
Epstein-Barr Virus-Associated Pulmonary Carcinoma: Proposing an Alternative Term and Expanding the Histologic Spectrum of Lymphoepithelioma-like Carcinoma of the Lung.
Yeh Yi-Chen,Kao Hua-Lin,Lee Kang-Lung,Wu Mei-Han,Ho Hsiang-Ling,Chou Teh-Ying
The American journal of surgical pathology
Lymphoepithelioma-like carcinoma (LELC) of the lung is a rare Epstein-Barr virus (EBV)-associated carcinoma. It is histologically characterized by a syncytial growth pattern with marked lymphocytic infiltration that is indistinguishable from the histology observed in undifferentiated nasopharyngeal carcinomas. However, it has been noted that LELC can display nonclassic morphology and lack significant lymphocytic infiltration. In this study, we conducted a comprehensive clinicopathologic analysis of 61 patients with pulmonary LELC and performed automatic quantification of the lymphocytic infiltrate using the IHC Profiler software. We demonstrated that pulmonary LELCs have a morphologically continuous spectrum, ranging from classic poorly differentiated tumors with intense lymphocytic infiltration to nonclassic morphology with little lymphocytic infiltration. These EBV-associated tumors represent a distinct entity and usually occur in female and nonsmoking patients. Tumors with low lymphocytic infiltration can closely resemble nonkeratinizing squamous cell carcinoma and tend to be larger in size, have higher maximum standardized uptake values on radiography, and exhibit shorter times to recurrence than those with high lymphocytic infiltration. Through detailed pathologic examination, we observed several distinct morphologic features in pulmonary LELCs, including granulomatous inflammation, focal keratinization, spread through alveolar spaces, and lepidic spreading pattern. We also found that patients with tumors exhibiting granulomatous inflammation have favorable outcomes; however, spread through alveolar spaces did not significantly correlate with prognosis. As many of these "LELCs" do not resemble undifferentiated nasopharyngeal carcinoma or lymphoepithelioma, we propose using an alternative term, EBV-associated pulmonary carcinoma, to encompass the entire morphologic spectrum of this distinct disease entity.
Unique p53 and epidermal growth factor receptor gene mutation status in 46 pulmonary lymphoepithelioma-like carcinomas.
Chang Yih-Leong,Wu Chen-Tu,Shih Jin-Yuan,Lee Yung-Chie
p53 and epidermal growth factor receptor (EGFR) are common genes involved in the pathogenesis of lung cancer, but their roles in lymphoepithelioma-like carcinomas (LELC) are unclear. In this study, we investigate the roles of p53 and EGFR in LELC carcinogenesis. Forty-six pulmonary LELCs were identified to evaluate p53 and EGFR aberrations. p53 mutations were identified in three patients, which all occurred in exon 8. EGFR mutations were detected in 8 of 46 cases with a majority of exon 21 mutations but without L858R. The other cases harbored mutations in exons 20 and 18. Only one case gained a deletion in exon 19. Notably, EGFR mutation was more commonly observed in patients with tumor size ≤ 3 cm (P = 0.014). In addition, there was a trend of more common EGFR overexpression in female (22/30) than in male patients (7/16, P = 0.061). However, there was no correlation between p53/EGFR mutations and protein expressions, suggesting the presence of complex mechanisms. p53 and EGFR mutations are uncommon in LELCs, indicating that these genes are not the important events in carcinogenesis for this tumor subtype. The EGFR mutation in 35% patients with LELC tumors <3 cm in size suggests the potential benefits to EGFR tyrosine kinase inhibitors of inoperable LELCs.
Coexisting TIF1γ-positive Primary Pulmonary Lymphoepithelioma-like Carcinoma and Anti-TIF1γ Antibody-positive Dermatomyositis.
Nakanishi Yu,Yamaguchi Kakuhiro,Yoshida Yusuke,Sakamoto Shinjiro,Horimasu Yasushi,Masuda Takeshi,Nakashima Taku,Miyamoto Shintarou,Iwamoto Hiroshi,Hirata Shintaro,Fujitaka Kazunori,Hamada Hironobu,Sugiyama Eiji,Hattori Noboru
Internal medicine (Tokyo, Japan)
Anti-transcriptional intermediary factor 1γ (anti-TIF1γ) antibody-positive dermatomyositis (DM) is strongly associated with cancer, although the mechanism of action is still unclear. We herein describe the first known case of an 80-year-old woman diagnosed with TIF1γ-positive primary pulmonary lymphoepithelioma-like carcinoma (LELC) coexisting with anti-TIF1γ antibody-positive DM. The diagnosis of LELC can only be made by a surgical lung biopsy, and not by a computed tomography-guided biopsy, because of heavy lymphocytic infiltration. This instructive case reaffirmed the importance of active screening for malignancy in patients with anti-TIF1γ antibody-positive DM. Interestingly, the results also suggested that the strong relationship which exists between anti-TIF1γ antibody-positive DM and cancer is potentially caused by tumor-derived TIF1γ.
Successful treatment with carboplatin and pemetrexed for multiple lymph node metastases of lymphoepithelioma-like carcinoma from an unknown primary site.
Yasuda Yuichiro,Tobino Kazunori,Ko Yuki,Asaji Mina,Yamaji Yoshikazu,Tsuruno Kosuke,Miyajima Hiroyuki,Mukasa Yosuke,Ebi Noriyuki
Internal medicine (Tokyo, Japan)
We herein report the case of an 80-year-old Japanese man with multiple lymph node metastases of lymphoepithelioma-like carcinoma (LELC) from an unknown primary site. The patient was admitted to our hospital due to hoarseness and left supraclavicular lymphadenopathy. Contrast-enhanced whole-body computed tomography revealed mediastinal, left supraclavicular, and left axillary lymphadenopathy. A left supraclavicular lymph node biopsy was performed and the specimen was consequently diagnosed as exhibting LELC. The patient's Eastern Cooperative Oncology Group performance status was 0, therefore he was started on chemotherapy with carboplatin and pemetrexed. His lymph nodes responded well to four cycles of chemotherapy without any intolerable adverse effect.
Unusual presentation of lymphoepithelioma-like carcinoma of lung as a thin-walled cavity.
Hsieh Min-Shu,Wu Chen-Tu,Chang Yih-Leong
The Annals of thoracic surgery
Most thin-walled cavities in the lung are benign lesions, but a few cases of lung cancer can have this unusual pattern. All previously reported cases were adenocarcinomas. Here we report a case of lymphoepithelioma-like carcinoma (LELC) of the lung presenting as a thin-walled cavity with a smooth inner surface. LELC is more commonly seen in Southeast Asia, including Taiwan, and its gross picture is usually a solid mass with a round, circumscribed border, which is indistinguishable from other non-small cell lung cancers. Asymmetric thickness of the cystic wall and lymphadenopathy are important features in the diagnosis and the selection of treatment.
An Elevated Peripheral Blood Monocyte-to-Lymphocyte Ratio Predicts Poor Prognosis in Patients with Primary Pulmonary Lymphoepithelioma-Like Carcinoma.
Wang Liang,Long Wen,Li Peng-fei,Lin Yong-bin,Liang Ying
Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer. In this study, we retrospectively reviewed the data from 74 consecutive patients with pulmonary LELC and investigated the prognostic value of pretreatment monocyte-to-lymphocyte ratio (MLR). The cut-off value determined by ROC curve for MLR was 0.262. According to this cut-off value, 36 (48.6%) patients had lower MLR value (<0.262) at diagnosis. There was no significant correlation between MLR level and gender, age, smoking history, stage, and lactate dehydrogenase (LDH) level. The 2-year, 5-year, and 10-year OS rate were 86%, 72%, and 61%, respectively; the 2-year, 5-year, and 10-year PFS rate were 71%, 63%, and 49%, respectively. In univariate analysis, advanced stage, elevated LDH level, and higher MLR value (> = 0.262) were significantly associated with poor OS and PFS. In a multivariate Cox regression model that included stage, LDH and MLR level, all of these three factors were found to be independent prognostic factors for both PFS and OS. In patients who received radical surgery, MLR level remained significantly correlated with OS and PFS. In conclusion, we firstly demonstrated that pretreatment MLR can be used as a useful independent prognostic marker in patients with pulmonary LELC, and might guide us to optimize the treatment strategies. However, due to the relatively rarity of this disease and the limitation of a retrospective study, further prospective studies performed in multicenter are necessary to validate the prognostic value of MLR in pulmonary LELC.
[Imaging features of primary pulmonary lymphoepithelioma-like carcinoma: report of 10 cases and literature review].
Gong Yan,Chen Wei-guo,Ye Hua-xiu,Zheng Tong,Zhang Ling
Nan fang yi ke da xue xue bao = Journal of Southern Medical University
OBJECTIVE:To study the imaging features of primary pulmonary lymphoepitheliom-like carcinoma (LELC). METHODS:Ten cases of primary pulmonary LELC were confirmed by surgery and pathology. The findings in clinical pathology, X-ray and CT were retrospectively analyzed and the related references were reviewed. RESULTS:The clinical manifestations included coughing (5 cases), hemoptysis (2 cases), chest distress (4 cases), thoracodynia (3 cases), and fever (2 cases), with 3 cases being asymptomatic. Radiographically, primary pulmonary LELC appeared mainly as peripheral nodules or masses. The maximum diameter of the lesion was 2.3 to 12.4 cm. The lesions were slightly lobulated in 7 cases and spiky on the edge in 3 cases. Pleura retraction was shown in 3 cases. CT contrast scanning revealed light or significant enhancement in 5 cases. CONCLUSION:Primary pulmonary LELC has some characteristic imaging features, but X-ray and CT only are not sufficient for a definite diagnosis, which still relies on bronchoscopic biopsy and percutaneous pulmonary puncture biopsy.
Cytopathologic features and differential diagnostic considerations of primary lymphoepithelioma-like carcinoma of the lung.
Hayashi Toshitetsu,Haba Reiji,Tanizawa Junko,Katsuki Naomi,Kadota Kyuichi,Miyai Yumi,Bando Kenji,Shibuya Shinsuke,Nakano Masayuki,Kushida Yoshio
Primary lymphoepithelioma-like carcinoma (LELC) of the lung is an extremely rare disease that occurs more commonly in Asians, and is composed of undifferentiated carcinoma with prominent lymphoid stroma. LELC is reported to be closely associated with Epstein-Barr virus (EBV) infection. A case is presented here in which bronchial brushing smears in a 70-year-old man, revealed large clusters of neoplastic cells with scant cytoplasm. The nuclei were large, hyperchromatic, of irregular contour and with prominent nucleoli. Also identified were prominent intratumoral lymphoid infiltration and brisk mitotic figures. We detected EBV-coded small RNA in situ hybridization in smears. A cytologic diagnosis of a LELC was suggested. Further evaluation and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Cords or nests of large neoplastic cells with enlarged nuclei and prominent nucleoli with marked lymphoid infiltration and lymphoid stroma were identified on H&E sections. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for CK(AE1/AE3), CK5/6, CK34βE12, Napsin A and Bcl-2 but were negative for CK7, CK14, CK20, EMA, TTF-1, chromogranin A, synaptophysin and CD56. The proliferative index with MIB-1 was around 60%, and the p53 positive cells around 20%. The diagnosis of primary LELC of the lung was confirmed based on cytopathologic, histopathologic, immunohistochemical and EBER results, and a detailed systemic examination to exclude possible extrapulmonary (nasopharyngeal) origin. We report the cytopathological features of LELC of the lung and demonstrate here for the first time the positivity of the EBER with RNA-ISH method in smears with emphasis on differential diagnostic considerations.
Positive expression of programmed death ligand-1 correlates with superior outcomes and might be a therapeutic target in primary pulmonary lymphoepithelioma-like carcinoma.
Jiang Li,Wang Liang,Li Peng-Fei,Zhang Xin-Ke,Chen Jie-Wei,Qiu Hui-Juan,Wu Xiao-Dong,Zhang Bei
OncoTargets and therapy
BACKGROUND:Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of non-small cell lung cancer (NSCLC), and no effective treatments have been defined for advanced disease. Programmed cell death-ligand 1 (PD-L1) is expressed in a group of cancers that may be suitable targets for specific immunotherapy. METHODS:This study investigated the expression and clinical value of PD-L1 in pulmonary LELC. Seventy-nine patients with pulmonary LELC were investigated. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Correlations of PD-L1 expression with clinicopathologic parameters and outcomes were analyzed. RESULTS:Fifty patients (63.3%) were PD-L1 positive. The 3-year and 5-year progression-free survival (PFS) rate was 76.0% and 68.0%, respectively, and the 3-year and 5-year overall survival (OS) rate was 88.0% and 79.0%, respectively. Kaplan-Meier analysis revealed that patients with positive PD-L1 expression had longer PFS and OS than those with negative PD-L1 expression (P=0.019 and P=0.042, respectively). In a multivariate Cox regression model including age, tumor size, stage, and PD-L1 expression status, the latter three factors were found to be independent predictors of PFS (P=0.023, P=0.000, and P=0.009, respectively), but only stage was found to be an independent factor for OS (P=0.007), and PD-L1 expression status showed a trend to be independently correlated with OS (P=0.080). CONCLUSION:Our results showed that a large proportion of patients with pulmonary LELC had positive expression of PD-L1, supporting the potential use of anti-PD-1/PD-L1-targeted therapies in this distinct type of NSCLC.
Pulmonary lymphoepithelioma-like carcinoma with rapid progression.
Tanaka Satona,Chen Fengshi,Date Hiroshi
General thoracic and cardiovascular surgery
Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare entity, commonly associated in East Asia with Epstein-Barr virus (EBV) infection. A 71-year-old woman underwent partial resection of the left lower lobe for a 17-mm nodule and was subsequently diagnosed with pulmonary LELC. Six months postoperatively, chest computed tomography (CT) showed lymphadenopathy in the left hilum and a 16-mm nodule in the S6 segment of the left lower lobe that had been difficult to point out (3 mm in size) at the initial surgery. She underwent a second surgical resection because of rapid progression-a clinical course at variance with the generally good prognosis for pulmonary LELC. At admission, the EBV deoxyribonucleic acid (DNA) blood level was 40 copies/μg. The EBV DNA was undetectable after the second surgery.
Prognostic Value and Clinical Impact of Pretreatment FDG PET in Pulmonary Lymphoepithelioma-Like Carcinoma.
Su Tzu-Pei,Ho Kung-Chu,Wang Chih-Wei,Lin Chun-Yu,Liu Chien-Ying,Yang Cheng-Ta,Yen Tzu-Chen
Clinical nuclear medicine
PURPOSE:Compared with other forms of non-small cell lung cancer, pulmonary lymphoepithelioma-like carcinoma (LELC) is rarer and portends better outcomes. We sought to investigate the prognostic role and clinical impact of pretreatment F-FDG PET in pulmonary LELC. METHODS:A total of 71 patients with pulmonary LELC were identified through a retrospective review of clinical records. Of them, 41 underwent F-FDG PET for primary staging. Outcomes were assessed using the Kaplan-Meier method and Cox regression models with a forward stepwise selection procedure. Staging changes served as the main outcome measure for assessing the impact of F-FDG PET. For the purpose of analyses, all patients were restaged according the American Joint Committee on Cancer Staging Manual eighth edition. RESULTS:Stage and pretreatment F-FDG PET were significantly independent predictors of overall survival (OS) on multivariate analysis. Five-year OS rates for patients with stages I-II, III-IVA, and IVB were 92.3%, 70.4%, and 20.0%, respectively. The use of F-FDG PET for staging purposes was associated with a better OS (P = 0.003). Specifically, the 5-year OS rates for patients who were staged with and without F-FDG PET were 85.4% and 49.7%, respectively (P = 0.012). F-FDG PET resulted in a disease upstage in 28.6% of patients with CT-defined stages III-IVA; of them, 14.3% were upstaged to IVB disease. CONCLUSIONS:The American Joint Committee on Cancer eighth edition stage and pretreatment F-FDG PET were independent prognostic factors for OS in patients with pulmonary LELC. F-FDG PET imaging resulted in a better disease staging with a corresponding optimization of therapeutic interventions, which ultimately improved survival outcomes.
Primary pulmonary lymphoepithelioma-like carcinoma initially diagnosed as squamous metaplasia: A case report and literature review.
Liang Yasha,Shen Cheng,Che Guowei,Luo Fengming
A mass was detected in the middle lobe of the right lung of a 58-year-old female. The patient did not present any symptoms and was a nonsmoker. Diagnostic evaluation revealed squamous metaplasia in the middle lobe of the right lung. During surgery, a tumor was identified, which was diagnosed as a lymphoepithelioma-like carcinoma (LELC). LELCs have been mainly reported in the Asian population and are associated with the Epstein-Barr virus (EBVs), while they are not associated with smoking. Squamous metaplasia, which is the basis of squamous cell carcinoma, differs from LELC in the therapeutic methods used and the prognostic evaluation. Squamous metaplasia requires regular follow-up in out-patient clinics, while pulmonary LELC is treated by surgery and chemotherapy. Therefore, distinguishing between LELCs and other nonmalignant or premalignant conditions is essential.
A Case of Primary Pulmonary Lymphoepithelioma-like Carcinoma Misdiagnosed as Adenocarcinoma.
Jeong Jae Seok,Kim So Ri,Park Seung Yong,Chung Myoung Ja,Lee Yong Chul
Tuberculosis and respiratory diseases
Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with a more favorable prognosis compared with that of other types of non-small cell lung cancers. Herein, we describe an interesting case of primary pulmonary LELC confirmed postoperatively, which had been initially diagnosed as poorly differentiated adenocarcinoma. We suggest that despite the rarity of pulmonary LELC, it should be included as one of the differential diagnoses for lung malignancies. Physicians should consider taking a larger biopsy, especially when histologic examination shows undifferentiated nature.
Computed tomography characteristics of primary pulmonary lymphoepithelioma-like carcinoma in 41 patients.
Ma Huali,Wu Yaopan,Lin Yongbin,Cai Qingqing,Ma Guowei,Liang Ying
European journal of radiology
PURPOSE:To assess the computed tomography (CT) findings of primary pulmonary lymphoepithelioma-like carcinoma (LELC). MATERIALS AND METHODS:Clinical information and CT findings of 41 patients with pulmonary LELC were reviewed. CT images of 2 or 5mm thickness were obtained with a pre-treatment CT and were jointly evaluated by two radiologists. RESULTS:Thirty central tumors and 11 peripheral tumors with diameters ranging from 1.0 to 8.7cm (mean, 4.1±1.9cm) were identified. Central tumors appeared to be larger than peripheral tumors (P=0.017). Tumors occurred more frequently in right middle lobe (31.7%) and left lower lobe (29.3%). CT findings of patients with early stage were similar to those observed in patients with advanced stage except that lymphadenopathy was significantly more common in patients with advanced stage. CT findings of pulmonary LELC consisted of well defined border (63.4%), lobulation (78.0%), vascular or bronchial encasement (43.9%), obstructive pneumonia (41.5%), pleural effusion (12.2%) and calcification (4.9%). On contrast-enhanced CT scans, inhomogeneously enhanced tumors were significantly larger than homogeneously enhanced tumors (P<0.001). Lymphadenopathy was seen in 28 patients, and lymph nodes with homogeneous enhancement were observed in 24/28 patients. Enlarged lymph nodes were more frequently occurred in peribronchial or hilar nodes (53.7%), subcrinal nodes (39.0%), right lower paratracheal nodes (31.7%) and right upper paratracheal nodes (22.0%). CONCLUSION:Pulmonary LELC usually appeared as a large, central, well defined and lobulated tumor with vascular or bronchial encasement and obstructive pneumonia. Calcification was rare in pulmonary LELC. Lymphadenopathy was common, usually with homogeneous enhancement.
Clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma.
Jiang Wen-Yang,Wang Rui,Pan Xu-Feng,Shen Yu-Zhou,Chen Tian-Xiang,Yang Yun-Hai,Shao Jin-Cheng,Zhu Lei,Han Bao-Hui,Yang Jun,Zhao Heng
Journal of thoracic disease
BACKGROUND:Lymphoepithelioma-like carcinoma (LELC) is a rare form of non-small cell lung carcinoma. The current study focused on its clinicopathological features and potential factors influencing the prognosis. METHODS:The statistical analysis was based on the clinicopathological records and the prognosis of 43 LELC patients, analyzed by Kaplan-Meier method, Log-rank test, and COX regression analysis. RESULTS:The patients' average age was 57.35±9.22 years, 86.05% of them were non-smokers and 53.49% were women. The average tumor diameter was 3.24±1.57 cm. The 2- and 5-year overall survival (OS) rates of LELC patients were 90% and 74%, respectively; the disease-free survival (DFS) rates were 87% and 47%, respectively. The patients with large tumor, accompanied with lymph nodes metastasis or at the advanced stage had the worst OS, and the patients with lymph nodes metastasis or at the advanced stage had the worst DFS. Univariate analysis indicated that T and N grading and TNM stage influenced the OS, and N grading and TNM stage influenced the DFS; the independent factors affecting OS or DFS were not identified by multivariate analysis. CONCLUSIONS:LELC commonly occurred in senior non-smoking women. In summary, the prognosis of LELC was satisfactory.
Primary lymphoepithelioma-like carcinoma of the lung: distinct computed tomography features and associated clinical outcomes.
Mo Yunxian,Shen Jingxian,Zhang Yun,Zheng Lie,Gao Fei,Liu Lizhi,Xie Chuanmiao
Journal of thoracic imaging
PURPOSE:The aim of the study was to describe the clinical and computed tomography (CT) findings of primary lymphoepithelioma-like carcinoma (LELC) of the lung. MATERIALS AND METHODS:The clinical data and CT findings of 35 patients with histologically proven primary LELC of the lung were retrospectively reviewed. The clinical data included age, sex, smoking history, signs and symptoms, tumor location, tumor size, stage, Epstein-Barr virus (EBV)-encoded small nuclear RNA status, treatment, and outcomes. Pretreatment CT scans of the thorax were used to access the tumor site, size, contour, density, vascular and/or bronchial involvement, relationship with pleura, and lymphadenopathy. RESULTS:The distinct clinical features of primary lung LELC include no significant predilection for sex, minimal association with a history of smoking, strong association with EBV in Asians, and a predilection for early or locally advanced stage of the disease. Most patients received complete resection and/or chemotherapy and radiotherapy. The 2- and 5-year overall survival rates for all patients were 81% and 51%, respectively. The common CT findings of primary lung LELC include peripheral nodules that have direct contact with the adjacent pleural surface, with a lesion density that is homogenous and sometimes heterogenous. CONCLUSIONS:Radiologists should consider the diagnosis of LELC when encountering solitary peripheral pulmonary nodules that have direct contact with the pleural surface in EBV endemic areas, and an EBV-encoded small nuclear RNA test should be performed on histologic specimens of patients meeting these clinical criteria.
The genomic landscape of Epstein-Barr virus-associated pulmonary lymphoepithelioma-like carcinoma.
Hong Shaodong,Liu Dongbing,Luo Shuzhen,Fang Wenfeng,Zhan Jianhua,Fu Sha,Zhang Yaxiong,Wu Xuan,Zhou Huaqiang,Chen Xi,Chen Gang,Zhang Zhonghan,Zheng Qiufan,Li Xiaobo,Chen Jinghao,Liu Xingmin,Lei Mengyue,Ye Chen,Wang Jian,Yang Huanming,Xu Xun,Zhu Shida,Yang Yunpeng,Zhao Yuanyuan,Zhou Ningning,Zhao Hongyun,Huang Yan,Zhang Lanjun,Wu Kui,Zhang Li
Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare and distinct subtype of primary lung cancer characterized by Epstein-Barr virus (EBV) infection. Herein, we reported the mutational landscape of pulmonary LELC using whole-exome sequencing, targeted deep sequencing and single-nucleotide polymorphism arrays. We identify a low degree of somatic mutation but widespread existence of copy number variations. We reveal predominant signature 2 mutations and frequent loss of type I interferon genes that are involved in the host-virus counteraction. Integrated analysis shows enrichment of genetic lesions affecting several critical pathways, including NF-κB, JAK/STAT, and cell cycle. Notably, multi-dimensional comparison unveils that pulmonary LELC resemble NPC but are clearly different from other lung cancers, natural killer/T-cell lymphoma or EBV-related gastric cancer in terms of genetic features. In all, our study illustrates a distinct genomic landscape of pulmonary LELC and provides a road map to facilitate genome-guided personalized treatment.
Tracheal Lymphoepithelioma-Like Carcinoma on FDG PET/CT.
Shao Dan,Ding Wenshuang,Wang Siyun,Liang Jiawei,Wang Shuxia
Clinical nuclear medicine
Lymphoepithelioma-like carcinoma (LELC) in the trachea is an extremely rare disease. We present a case of a 64-year-old man with FDG-avid tracheal LELC on F-FDG PET/CT. Despite its rarity, LELC in the trachea should be considered as one of the possibilities in patients with a hypermetabolic mass in the trachea. If LELC in the trachea is suspected, F-FDG PET/CT is a useful tool for initial staging.
Metastatic lymphoepithelioma-like carcinoma of the lung treated with nivolumab: a case report and focused review of literature.
Kim Chul,Rajan Arun,DeBrito Pedro A,Giaccone Giuseppe
Translational lung cancer research
In recent years, significant advances have been made in cancer immunotherapy. Here, we present the first report of a patient with lymphoepithelioma-like carcinoma (LELC) of the lung, an Epstein-Barr virus (EBV)-associated lung cancer, who was treated with nivolumab, a fully human IgG4 anti-PD-1 monoclonal antibody. We also carry out a focused review to identify and examine studies of LELC of the lung in the literature. This case report highlights the need to further assess the role of immune checkpoint inhibitors in LELC of the lung.
PD-L1 is remarkably over-expressed in EBV-associated pulmonary lymphoepithelioma-like carcinoma and related to poor disease-free survival.
Fang Wenfeng,Hong Shaodong,Chen Nan,He Xiaobo,Zhan Jianhua,Qin Tao,Zhou Ting,Hu Zhihuang,Ma Yuxiang,Zhao Yuanyuan,Tian Ying,Yang Yunpeng,Xue Cong,Tang Yanna,Huang Yan,Zhao Hongyun,Zhang Li
BACKGROUD:Programmed cell death-ligand 1 (PD-L1) and driver mutations are commonly seen in non-small-cell lung cancer (NSCLC). However, the prevelance of PD-L1 over-expression and its prognostic value in Epstein-Barr virus (EBV) associated pulmonary lymphoepithelioma-like carcinoma (LELC) remains poorly understood. METHODS:A total of 214 NSCLC patients and 113 surgically treated pulmonary LELC patients were included. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Correlations between PD-L1 expression and clinicopathological features as well as survival outcomes were analyzed. RESULTS:The frequency of PD-L1 over-expression in NSCLC was 51.4%. No significant association was observed between common driver mutations and PD-L1 over-expression. Remakably, the positive rate of PD-L1 in pulmonary LELC was 74.3%. High PD-L1 expression was associated with impaired disease-free survival (DFS) compared with low PD-L1 expression (p = 0.008). Multivariate analysis shows that PD-L1 expression level, N stage and M stage were independent prognostic factors for DFS. N stage and M stage but not PD-L1 expression level were significantly associated with overall survival (OS). CONCLUSIONS:PD-L1 over-expression was not related to common driver mutations in NSCLC. Pulmonary LELC have remarkably high incidence of PD-L1 expression. PD-L1 was a negative prognostic factor for DFS in surgically resected pulmonary LELC. These findings may provide a rationale for immunotarget therapy in this virus-associated lung cancer.
Primary pulmonary lymphoepithelioma-like carcinoma accompanied by hypertrophic pulmonary osteoarthropathy in a non-epidemic region: a case report and literature review.
Zhu Ning,Lin Shanhong,Xu Ning,Chen Lei,Piao Zhenghua,Cao Chao
The Journal of international medical research
Pulmonary lymphatic epithelioma-like carcinoma (LELC) is a rare and unique subtype, accounting for 0.9% of all lung cancers. To date, just over 200 cases have been reported worldwide. The Epstein-Barr virus plays a role in the pathogenesis of LELC. Most patients are from East Asia, especially southeastern China. Chest computed tomography mainly shows a single lump or nodule around the lung. In this article, we report a 49-year-old male patient from a non-epidemic area who was hospitalized for "intermittent blood in his phlegm for more than 4 months". Imaging revealed two nodules in the left lower lobe of his lung. Transbronchial lung biopsy was performed on one of the nodules, and he was diagnosed with primary LELC. Single-photon emission computed tomography revealed that he had hypertrophic pulmonary osteoarthropathy, which is a rare symptom of paraneoplastic syndrome. Because the preoperative evaluation considered early-stage disease, video-assisted thoracoscopic surgery for the left lower lobe and mediastinal lymph node dissection were performed. Both lesions were eventually diagnosed as LELC. Fortunately, lymph node metastasis did not occur, and he did not receive other postoperative treatments. He was followed up for 1 year, and no recurrence was found.
Primary pulmonary lymphoepithelioma-like carcinoma: fifty-two patients with long-term follow-up.
Liang Ying,Wang Liang,Zhu Yujia,Lin Yongbin,Liu Hui,Rao Huilan,Xu Guangchuan,Rong Tiehua
BACKGROUND:Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare kind of cancer. METHODS:In this study, the authors evaluated 52 patients with pulmonary LELC who had long-term follow-up. Clinical characteristics, tumor markers, epidermal growth factor receptor (EGFR) mutation status, treatments, and outcomes were analyzed. RESULTS:Pulmonary LELC mostly affected young, nonsmoking patients. Most patients were in early or locally advanced stages and received multimodality treatment. Serum levels of neuron-specific enolase and cytokeratin 19 fragment 21-1 were elevated in 11 of 20 patients and 10 of 16 patients, respectively. Mutational analysis of EGFR was done in 11 patients, and all were wild type. The median overall survival (OS) for all the patients was not reached, and the 2-year and 5-year OS rate was 88% and 62%, respectively. The patients with early tumor stage, normal serum lactate dehydrogenase level, normal serum albumin level, without lymph node metastasis, and those who underwent complete resection had significantly better OS (P < .05); and the serum albumin level was an independent prognostic factor in a Cox regression model (P = .005). For all patients who underwent complete resection, whether or not they received adjuvant chemotherapy did not affect OS (P > .05); whereas, for patients with stage IIIA disease who underwent complete resection, adjuvant chemotherapy was correlated with a significantly better prognosis (P < .05). CONCLUSIONS:Pulmonary LELC obviously is a distinct entity of lung cancer that has a better prognosis, because patients with LELC can receive multimodality treatment, and LELC has biologic behavior similar to that of nasopharyngeal carcinoma. The current results indicated that future collaborative efforts are needed to determine the optimal treatment methods for this uncommon malignancy.
Lack of epidermal growth factor receptor gene mutations in exons 19 and 21 in primary lymphoepithelioma-like carcinoma of the lung.
Liu Qianwen,Ma Guowei,Yang Haoxian,Wen Jing,Li Mei,Yang Hong,Luo Kongjia,Hu Yi,Fu Jianhua
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.
Case report: mutation analysis of primary pulmonary lymphoepithelioma-like carcinoma via whole-exome sequencing.
Xuan Hong,Zhengjun Chai,Yang Han,Guohan Chen
BACKGROUND:Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare tumor subtype accounting for around 0.9% of lung cancers. At present, research on LELC mainly focuses on pathological diagnosis, while the molecular mutation landscape is still unclear. CASE PRESENTATION:A 72-year-old female presented a productive cough for three weeks followed by severe symptoms for another week. Respiratory sounds were weak and coarser in the right lung field. F-FDG PET-CTA showed a hypermetabolic mass in the upper lobe of the right lung as well as the enlargement of right hilar and subcarinal lymph nodes. Hematoxylin-eosin staining and immunohistochemistry staining of the biopsy established the diagnosis of primary pulmonary LELC. After thoracoscopic-assisted radical resection of right lung cancer and middle lobe of right lung, the patient's vital signs were stable without apparent productive cough, chest pain, chest tightness and other subjective discomforts. Furtherwhole exome sequencing of the patient's tumor tissue and leukocytes (served as a germline mutation control) revealed 613 somatic gene mutations, and of which mutations in PRIM2, KCNB1, CDH1, and ATRX were most likely related to the LELC pathogenesis. The recurrence of gene mutations from various cancers database and a tumor mutation burden (TMB) of 18.7 mutations/mb were revealed as well. CONCLUSION:Our findings have illustrated the genomic profile of a primary pulmonary LELC case and provided a positive biomarker that immune checkpoint blockade is potentially effective for this patient in further treatment.
Multimodality treatment and long-term follow-up of the primary pulmonary lymphoepithelioma-like carcinoma.
Huang Chung-Jen,Feng An-Chen,Fang Yueh-Fu,Ku Wen-Hui,Chu Nei-Min,Yu Chih-Teng,Liu Chia-Chuan,Lee Ming-Yuan,Hsu Li-Han,Tsai Stella Y C,Shih Chih-Shiun,Wang Chih-Liang
Clinical lung cancer
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.
First-line platinum-based chemotherapy and survival outcomes in locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma.
Lin Zuan,Fu Sha,Zhou Yixin,Zhang Xuanye,Chen Chen,He Li-Na,Li Haifeng,Wang Yuhong,Chen Tao,Zhang Li,Hong Shaodong
Lung cancer (Amsterdam, Netherlands)
OBJECTIVES:Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of primary lung cancer. Due to the lack of prospective studies, the optimal first-line chemotherapy regimens and survival outcomes remain unclear. MATERIALS AND METHODS:This real-world, retrospective study enrolled consecutive patients with unresectable pulmonary LELC. The survival outcomes, prognosis, and comparative efficacy of different chemotherapy regimens were investigated. RESULTS:In total, 127 patients were included in the analyses. The first-line chemotherapy regimens included gemcitabine plus platinum (GP, n = 19 [15.0%]), taxanes plus platinum (TP, n = 70 [55.1%]) and pemetrexed plus platinum (AP, n = 38 [30.0%]). 25 (19.7%) patients underwent palliative thoracic radiotherapy. 60 (47.2%) patients had detectable baseline Epstein-Barr virus (EBV) DNA. For the entire cohort, objective response was obtained in 41 patients (32.3%). Median progression-free survival (PFS) and overall survival (OS) were 7.7 months (95% CI, 6.6-8.8) and 36.7 months (95% CI, 30.9-42.5), respectively. Among the three chemotherapy regimens, GP achieved the highest response rate (GP, 63.2% vs. TP, 30.0% vs. AP, 21.1%; p = 0.005). Median PFS in the GP group (8.8 months) was also significantly longer than that in the TP group (7.9 months) and AP group (6.4 months) (p = 0.031). In the multivariate model, cycles of first-line chemotherapy (p < 0.001), palliative thoracic radiotherapy (p < 0.001), and chemotherapy regimens (p = 0.031) remained independent prognostic factors for PFS; while cycles of first-line chemotherapy (p = 0.002), baseline EBV DNA (p = 0.033) and palliative thoracic radiotherapy (p = 0.041) were significantly associated with OS. CONCLUSION:Gemcitabine-based chemotherapy and palliative thoracic radiotherapy are active in pulmonary LELC. These data provide added evidence for the similarity between pulmonary LELC and nasopharyngeal carcinoma in endemic area. Randomized controlled studies are needed to further define the standard-of-care for patients with advanced pulmonary LELC.
Metabolic tumor volume predicts overall survival in patients with primary pulmonary lymphoepithelioma-like carcinoma.
Lin Chun-Yu,Chang Yu-Chuan,Wang I-Ting,Hsieh Meng-Heng,Wang Chih-Wei,Lin Shu-Min,Wu Ching-Yang,Fang Yueh-Fu
Pretreatment tumor metabolic burden, measured using fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (F-FDG PET/CT), has been demonstrated to predict outcomes in various types of malignancies. Additionally, Epstein-Barr virus (EBV) serum titer is associated with stages of pulmonary lymphoepithelioma-like carcinoma (LELC). The present study aimed to investigate the prognostic value of the functional parameters of F-FDG PET/CT in pulmonary LELC and their association with serum EBV DNA. The present retrospective study analyzed data from 71 patients with pulmonary LELC; among these, 32 patients with pulmonary LELC underwent pretreatment F-FDG PET/CT staging between January 2008 and December 2016. EBV viral load and functional parameters of F-FDG PET/CT were used for survival analysis. Multivariate analysis identified tumor stage IV as a significant predictor of poor progression-free survival [hazard ratio (HR), 4.85; P=0.049], whereas elevated total metabolic tumor volume (MTV ≥72.6 ml) independently predicted worse overall survival (OS; HR, 12.59; P=0.024). Pretreatment serum EBV DNA titer was significantly positively associated with total MTV (P=0.0337) and total lesion glycolysis (TLG; P=0.0093), but could not predict outcomes. Total MTV was an independent predictor of OS, and may guide clinical management for pulmonary LELC.
Thorough survey and analysis of pulmonary lymphoepithelioma-like carcinoma in Macau and multimodality treatment for advanced disease.
Zhou Na,Lin Yi,Peng Xianghong,Wang Yingyi,Wang Yuzhou
Lung cancer (Amsterdam, Netherlands)
OBJECTIVE:Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer. The clinical course and prognosis of advanced LELC are largely unknown. Few reports have discussed multimodality treatment for LELC. MATERIALS AND METHODS:This retrospective study identified records from 2007 to 2018 of pulmonary LELCs and other lung cancer subtypes from hospital information systems and collected demographic, treatment, and survival data. RESULTS:In this cohort of 69 LELCs (median age: 55.4), more female, non-smokers, and fewer right upper lobe tumors (4.3%) were observed in the LELC subgroup compared with others. The median overall survival (OS) of LELCs was 40 months, superior to other subtypes (p < 0.05), except adenocarcinoma (p = 0.062). Patients with early stage disease and primary tumor resection tended to have better OS in univariate analysis, but surgery was the independent predictor in multivariate analysis (0.042). The median OS of 52 advanced LELCs was 22.7 months. Platinum-based chemotherapy and radiotherapy with curative purpose were independent predictors for OS of advanced LELCs (p = 0.004 and 0.003, respectively). For patients who received multimodality treatment in advanced setting, the median line of treatments was two. The overall response and disease-control rates were 61.8% and 80.6%, respectively. There were no differences in response or survival between patients receiving taxane-combined and non-taxane-combined chemotherapy. However, patients treated with radiotherapy in upfront settings had significantly favorable response and progression-free survival compared with those without. One case with PD-L1 positivity had pembrolizumab in the 4 line and achieved tumor shrinkage and stable disease for 12 months. CONCLUSION:Patients who underwent radical resection of primary tumors had better prognoses. Patients with advanced LELC could achieve satisfactory survival by receiving multimodality treatment, including platinum-based chemotherapy and/or radiotherapy. Immune checkpoint inhibitors may be part of future therapies. A well-organized clinical trial should be performed to determine the optimal treatment regimen.
Overcoming resistance to anti-PD-1 immunotherapy in lymphoepithelioma-like carcinoma: A case report and review of the literature.
Tang Zhengwu,Fang Rui,Tong Guihui,Liu Peng,Ou Zhu'an,Tang Yong
Lung cancer (Amsterdam, Netherlands)
OBJECTIVES:Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of non-small-cell lung cancer with no established treatment protocols. Immunotherapy is rarely used as a second-line choice in patients with advanced LELC, and more cases of this condition should be presented. MATERIALS AND METHODS:We present a patient with advanced primary pulmonary LELC overcoming the resistance to second-line anti-programmed death-1 (PD-1) immunotherapy. We also review the literature to summarize the current immunotherapy landscape of this rare disorder. RESULTS AND CONCLUSION:The LELC patient progressed after first-line chemotherapy, was treated by immunotherapy alone and progressed again. To overcome the developed resistance to immunotherapy, chemotherapy with nedaplatin plus paclitaxel in addition to nivolumab was administered and a progression-free survival (PFS) of 5 months was achieved. It was also observed that the blood levels of neuron-specific enolase may act as an efficacy biomarker in LELC. Patients with this rare disorder resistant to anti-PD-1 immunotherapy might benefit from therapy based on PD-1 inhibition; this is a future avenue of research.
Clinicopathological and prognostic analyses of 86 resected pulmonary lymphoepithelioma-like carcinomas.
Chen Jiafei,Gu Chang,Chen Xiaojian,Dai Chenyang,Zhao Shengnan,Xie Huikang,Fei Ke,Chen Chang
Journal of surgical oncology
BACKGROUND:Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of primary lung cancer. The present study aims at investigating clinicopathological features and prognostic characteristics of the resected pulmonary LELC. METHODS:Patients with resected pulmonary LELC were identified in our hospital from December 2008 to December 2018. Data of these patients were retrospectively reviewed, clinicopathological features and prognostic characteristics were analyzed subsequently. RESULTS:In total, 86 patients were enrolled in the study, including 39 (45.3%) males and 47 (54.7%) females. Most of the serum tumor markers were normal. Immunohistochemical staining result showed frequent differentiation traits of epithelial tissue such. Positive PD-L1 (15 of 19, 78.9%) and PD-1 (13 of 17, 76.5%) were also common, but cancer-related genetic mutation was scarce (1 of 47, 2.1%). Survival analyses demonstrated that the N stage (p = .011) and extent of resection (p = .023) were identified as independent predictive factors for overall survival. CONCLUSIONS:Pulmonary LELC is a distinctive subtype of lung cancer with several exclusive traits, such as the trend to happen among nonsmoking young people, epithelial origin of tumor differentiation, frequent expression of the immune checkpoint, and scarce presence of driver mutation. In addition, pulmonary LELC was apt to get a favorable outcome, especially in cases diagnosed and treated in the early stage.
Detection of rearrangement of anaplastic lymphoma kinase (ALK) and mutation of epidermal growth factor receptor (EGFR) in primary pulmonary lymphoepithelioma-like carcinoma.
Wang Liang,Lin Yongbin,Cai Qingqing,Long Hao,Zhang Yu,Rong Tiehua,Ma Guowei,Liang Ying
Journal of thoracic disease
BACKGROUND:Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a distinct rare subtype of lung cancer. The prevalence of anaplastic lymphoma kinase (ALK) rearrangement and epidermal growth factor receptor (EGFR) mutation in primary pulmonary LELC had not been thoroughly investigated. METHODS:We investigated a cohort of 42 patients with primary pulmonary LELC and genotyped for ALK rearrangement and EGFR mutation. ALK rearrangement was detected by fluorescence in situ hybridization (FISH). EGFR mutational analysis of exons 18 through 21 was analyzed by TaqMan real-time polymerase chain reaction (PCR). RESULTS:Epstein-Barr virus-encoded RNAs (EBERs) showed positive signals in all 42 patients. By immunohistochemistry staining, all patients demonstrated positive expression of CK5/6 and P63, but almost all patients were negative for TTF-1 (34/34, 100%) or CK7 (34/35, 97.1%). None of the 42 patients had ALK rearrangement. Of 42 patients tested, only one patient (2.4%) harbored L858R mutation and gefitinib was applied to this case, however no objective response was observed and the progression free survival (PFS) time was only 1 month. CONCLUSIONS:Primary pulmonary LELC is a unique histological subtype of lung cancer. ALK rearrangement and EGFR mutation are lack and they may not be the oncogenic driver gene in pulmonary LELC. Future efforts should be made to explore other oncogenic driver gene to guide targeted therapy in this rare disease to determine the optimal treatment.
Surgical treatment for primary pulmonary lymphoepithelioma-like carcinoma.
Lin Zhichao,Situ Dongrong,Chang Xiangzhen,Liang Wenhua,Zhao Meiling,Cai Chengjie,Liu Yang,He Jianxing
Interactive cardiovascular and thoracic surgery
OBJECTIVES:Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare but unique subtype of non-small-cell lung cancer (NSCLC). Our study aimed to evaluate clinicopathological characteristics and the value of surgical treatment for LELC and explore the relevant prognostic factors in a relatively large cohort. METHODS:We retrospectively reviewed the medical records of 39 lung LELC patients who underwent pulmonary resection with curative intent between January 2009 and December 2013. The clinical and pathological characteristics, survival data and relevant prognostic factors were analysed. RESULTS:The median age of lung LELC patients was 47 years (36-81), and 32 of 39 patients were non-smokers (82.1%). Positive expression of P63 and CK5/6 was shown in all the tested LELC specimens. In situ hybridization of Epstein-Bar virus-encoded RNA (EBER) was performed in 36 patients and all of them were positive. However, epidermal growth factor receptor (EGFR) mutational analysis was done in 19 patients and all of them were wild-type. The median follow-up time was 26.0 months in our cohort, and 6-, 12-, 24- and 36-month recurrence-free survival (RFS) rates were 92, 82, 73 and 73%, respectively. Patients with positive lymph nodes experienced significantly worse postoperative RFS than those with negative ones (P = 0.002). Multivariate survival analysis confirmed that only lymph node involvement [RR 0.051; 95% confidence interval, 0.003-0.991, P = 0.049] was an independent prognostic factor. CONCLUSIONS:Primary lung LELC is closely associated with Epstein-Bar virus infection but not involved in EGFR mutation pathway. Radical surgery could achieve a good outcome for resectable pulmonary LELC, and regional lymph node status is a vital prognostic factor.
Response of advanced stage recurrent lymphoepithelioma-like carcinoma to nivolumab.
Kumar Vivek,Dave Vishangi,Harris Jonathan,Huang Yiwu
Lymphoepithelioma-like carcinoma (LELC) of lung is a rare tumor that is mostly reported in south-east Asian countries. The surgical removal is curative in the early stages but there is no consensus on the choice of chemotherapy for the treatment of advanced stage tumors. Most of the data on chemotherapy are based on small case series and retrospective studies. As per available data, this tumor responds to chemotherapy initially but recurrences are common. The use of conventional chemotherapy in recurrent tumors leads to cumulative toxicities in the long term. Due to lack of actionable mutations, targeted therapies are also not very useful. Immune check point inhibitors immune checkpoint inhibitors have shown survival benefit in patients with advanced stage non-small-cell and small cell carcinoma with better side effect profile than conventional chemotherapy. The role of immune checkpoint inhibitors in LELC is unknown. Though several studies have reported high expression of programmed cell death-1 (PD-1)/or its -ligand (PD-L1) in LELC providing a rationale for trial of these agents, the actual benefit of these agents in LELC has not been reported so far. In this case series, we report two cases of advanced stage LELC that progressed despite multiple lines of chemotherapy but responded favorably to a PD-1 inhibitor, nivolumab.
Correlation and prognostic significance of PD-L1 and P53 expression in resected primary pulmonary lymphoepithelioma-like carcinoma.
Yu Xiang-Yang,Zhang Xue-Wen,Wang Fang,Lin Yong-Bin,Wang Wei-Dong,Chen Yong-Qiang,Zhang Lan-Jun,Cai Ling
Journal of thoracic disease
BACKGROUND:Aberrant expression of programmed cell death-ligand 1 (PD-L1) and protein 53 (P53) has been observed in various malignancies, and recently, the mechanism of PD-L1 regulation by P53 has been elucidated. We aimed to explore possible correlations between PD-L1 and P53 expression and the prognosis of patients with resected pulmonary lymphoepithelioma-like carcinoma (LELC). METHODS:A total of 67 consecutive patients with primary pulmonary LELC who underwent radical resection from January 2003 to December 2014 were enrolled in our study. Membranous PD-L1 and nuclear P53 expression were detected by immunohistochemical staining (IHC). RESULTS:Positive expression of PD-L1 in tumor cells (TCs), PD-L1 in tumor-infiltrating lymphocytes (TILs) and P53 was investigated in 44 patients (65.7%), 37 patients (55.2%), and 34 patients (50.7%), respectively. Using univariate and multivariable analysis, both PD-L1 (+) in TCs and P53 (+) were observed to be significantly independent prognostic factors associated with longer disease-free survival (DFS, P=0.037 and 0.039, respectively), along with early stage LELC (P=0.037), but had no association with overall survival (OS) (P>0.05). In the P53 (+) group, the rate of patients with PD-L1 (+) in TCs was significantly higher than in the P53 (-) group (85.3% 45.5%, P=0.001). In addition, among the 45 patients who underwent adjuvant chemotherapy, DFS was significantly longer in patients with either PD-L1 (+) in TCs or P53 (+) (P=0.036 and 0.044, respectively). CONCLUSIONS:PD-L1 and P53 may be potential therapeutic targets for primary pulmonary LELC. PD-L1 (+) in TCs and P53 (+) were reliable predictors for longer DFS and benefits from adjuvant therapy in resected cases. Routine detection of these two indices in lung LELC may be warranted.
Primary lymphoepithelioma-like carcinoma of the lung: An unusual cancer and clinical outcomes of 14 patients.
Lin Lan,Lin Tingyan,Zeng Bangwei
Advanced lung cancer is considered to exhibit a poor prognosis; however, the pulmonary lymphoepithelioma-like carcinoma (LELC), a rare subtype of non-small cell lung cancer (NSCLC), exhibits an improved prognosis, compared with non-LELC. The present study aimed at investigating the clinical manifestation, imaging characteristics, pathology, tumor markers, treatment and prognosis of primary LELC of the lung. A total of 14 patients with pulmonary LELC were confirmed by surgery and pathology. Clinical data of those patients were retrospectively reviewed including age, sex, smoking history, symptoms, computed tomography (CT) results, Epstein-Barr virus-encoded RNA (EBER) status, treatment and outcomes. In the present study, there were 7 males and 7 females who ranged in age between 22 and 64 years (mean, 51.21±11.37 years) and who all were from eastern China. The tumor-node-metastasis stage ranged between stages I and IV, with 71.43% of the patients at advanced stage (stages III and IV). The results of the present study identified 100% positive expression of EBER. Tumors located centrally were of significantly increased size, compared with peripheral tumors (P<0.05), and lymphadenopathy was more common in patients with advanced stage (P<0.05). The majority of patients were treated with surgery, platinum-based chemotherapy or radiotherapy. At time of writing, 12 patients were alive and the longest survival time was 60 months. Pulmonary LELC typically affected young patients and was not associated with smoking history; however, pulmonary LELC was associated with Epstein-Barr virus infection in the Asian population. The majority of patients were in early or locally advanced stages and exhibit an improved prognosis compared with other types of NSCLC. Pulmonary LELC was sensitive to chemotherapy and surgery, with postoperative chemotherapy-based multimodality treatment recommended.
Primary Pulmonary Lymphoepithelioma-Like Carcinoma Response Favorably To Nivolumab: A Case Report.
OncoTargets and therapy
OBJECTIVES:Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of non-small cell lung cancer (NSCLC). No clinical trials have been performed, and no course of treatment for LELC has been established because of it's rarity. This study presents a patient with primary pulmonary LELC, who was treated with nivolumab, and responded favorably. MATERIALS AND METHODS:A patient with primary pulmonary LELC was treated using nivolumab. RESULT:The patient responded well to immunotherapy with nivolumab. After five cycles of the nivolumab, the size of the tumor and the lesions of the liver became smaller. A blood test showed that CYFRA21-1 and NSE had dramatically decreased from before, especially the CYFRA21-1. CONCLUSION:EBV-positive pulmonary LELC with high expression of PD-L1 may derive a benefit from PD-1/PD-L1 blockade.
Treatment outcomes of patients with different subtypes of large cell carcinoma of the lung.
Sun Yung-Han,Lin Shih-Wei,Hsieh Chih-Cheng,Yeh Yi-Chen,Tu Cheng-Che,Chen Kuan-Jeng
The Annals of thoracic surgery
BACKGROUND:Although large cell neuroendocrine carcinoma (LCNEC) and lymphoepithelioma-like carcinoma (LELC) are the variants of large cell carcinoma (LCC) of lung, there are few studies comparing them. The aim of this study was to compare the clinical characteristic and treatment outcomes of LCNEC, LELC, and classic LCC. METHODS:Patients with LCNEC, LELC, or classic LCC were identified in a prospectively collected database, and their data were analyzed. RESULTS:A total of 46 patients with classic LCC, 30 with LCNEC, and 18 with LELC, who received surgical resection with curative intent, were identified and included in the analysis. Patients with LELC were younger, and the frequency of nonsmokers was greater than in patients with classic LCC or LCNEC. In patients with LCNEC or LELC, most lesions were located on the left side. There were 5 surgical deaths, and the median follow-up time of the surviving patients was 44.1 months. The 5-year disease free survival among the three subgroups was similar (p = 0.601), but patients with LELC had a significantly better overall survival than the other two subgroups (LELC vs classic LCC, p = 0.009; LELC vs LCNEC, p = 0.002). Multivariate analysis showed tumor location site, tumor stage, and LELC were independent prognostic factors of overall survival. CONCLUSIONS:The clinical manifestations and treatment outcomes of LCNEC, LELC, and classic LCC are different. LCNEC has a poor survival, and survival is not different than that of classic LCC. LELC is associated with younger age and a higher frequency of nonsmokers, and the treatment outcomes are better than those of other subtypes.
Advanced primary pulmonary lymphoepithelioma-like carcinoma: clinical manifestations, treatment, and outcome.
Lin Chun-Yu,Chen Ying-Jen,Hsieh Meng-Heng,Wang Chih-Wei,Fang Yueh-Fu
Journal of thoracic disease
BACKGROUND:Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with better clinical outcomes than other lung cancers. However, reports on advanced LELC characteristics and prognosis are lacking. METHODS:This retrospective study included adults diagnosed with advanced LELC (at least stage IIIA) between January 2003 and December 2015. Clinical characteristics, treatment modalities, and outcomes were recorded. RESULTS:Study population comprised 23 patients with a mean age of 63.7±10.6 years. The Eastern Cooperative Oncology Group status on diagnosis was 0 in five patients and 1 in the others. Most patients received multimodality treatment and all received cisplatin-based chemotherapy. Median follow-up duration was 28.8 months. The median progression free survival (PFS) was 14.6 months in patients received palliative chemotherapy. There were nine (39.1%) deaths. The median overall survival (OS) was not achieved. Until July 31, 2016, median OS was 54.1 months for stage IIIB and 27.6 months for stage IV. There was no significant difference in OS among all stages. No prognostic factors were found. CONCLUSIONS:Advanced LELC responded well to cisplatin-based chemotherapy and/or radiotherapy. Main tumor resection is probably beneficial for advanced LELC. Long-term survival is possible for advanced LELC after multimodality treatment.
Utility of 18F-FDG PET/CT in the assessment of lymphoepithelioma-like carcinoma.
Chan Hiu Yan,Tsoi Adelina,Wong Maria Pik,Ho James C M,Lee Elaine Yuen Phin
Nuclear medicine communications
Lymphoepithelioma-like carcinoma (LELC) is a rare Epstein-Barr virus (EBV)-related disease, which commonly originates from the lung and is associated with more favourable treatment outcomes compared with other non-LELC thoracic carcinomas. Radiological assessment utilizing fluorine-18 fluorodeoxyglucose PET combined with computed tomography (F-FDG PET/CT) is important for initial disease staging to tailor the treatment strategy, evaluation of treatment response and detection of disease recurrence. The aim of this article was to highlight the utility of F-FDG PET/CT in different stages of disease evaluation of LELC. We reviewed seven patients with histologically proven LELC who underwent F-FDG PET/CT for disease evaluation. We described the F-FDG-avidity of LELC (ranged from maximum standardized uptake value 7.6 to maximum standardized uptake value 14.5 in our series) and highlighted the clinical values of F-FDG PET/CT in different stages of disease evaluation. F-FDG PET/CT enables accurate evaluation of the primary tumour, its relationship with the surrounding structures and accurate staging. It is also useful in treatment response assessment to monitor the efficacy of the treatment and to decide upon treatment strategy. Given the F-FDG-avidity of LELC, F-FDG PET/CT is advantageous in detecting tumour recurrence of LELC. LELC is a rare disease entity associated with EBV and is more prevalent in Asia, where EBV is endemic. LELC is an F-FDG-avid tumour. Although the features on F-FDG PET/CT are not specific, F-FDG PET/CT provides valuable information for disease management of LELC.
Pulmonary lymphoepithelioma-like carcinoma: a Surveillance, Epidemiology, and End Results database analysis.
He Jiaxi,Shen Jianfei,Pan Hui,Huang Jun,Liang Wenhua,He Jianxing
Journal of thoracic disease
BACKGROUND:Pulmonary lymphoepithelioma-like carcinoma (LELC) is one of the rare histological non-small cell lung cancers. Only a few case reports have been published. The knowledge of its characteristics and prognosis in western population is limited. Based on the data of the Surveillance, Epidemiology, and End Results database (SEER), an analysis was performed to fill the gap of our knowledge. METHODS:Characteristics, treatment and outcomes of all pulmonary LELC patients was extracted both from the SEER database from 1973 to 2011 using SEER*Stat 8.2.1 statistical analysis was performed using SPSS 16.0 and GraphPad Prism 5. RESULTS:A total of 62 patients with pulmonary LELC are identified and analyzed. The median age at diagnosis is 65. Among them, the majority was male (64.4%). Early stage patients account for the largest proportion (67.8%). The median survival of all LELC patients is 107 months [95% confidence interval (CI), 67-147]. The 1, 3 and 5 years survival rates of LELC are 85.6%, 74.5% and 55.2%. In the comparisons incorporating with other types of large cell lung cancer (LCC), adenocarcinoma (AD) and squamous cell lung cancer (SQ), the overall survival (OS) of LELC is superior to others. Most of the early stage (localized and regional) LELC patients (37/45, 82.2%) received surgical resection as the primary treatment. Patients older than 65 years predicted a worse prognosis. CONCLUSIONS:Pulmonary LELC is a rare pathological type of lung cancer. In this cohort, most LELC cases were male and in early stage. Majority of early stage LELC patients have received surgical resection. Patients older than 65 years had worse survival. Unfortunately, no other prognostic factor has been identified in our study. In addition, we observed that LELC had an ideal prognosis comparing to other types of LCC, AD and SQ. In order to understand pulmonary LELC more thoroughly, more cases are required.
Partial absence of PD-1 expression by tumor-infiltrating EBV-specific CD8 T cells in EBV-driven lymphoepithelioma-like carcinoma.
Clinical & translational immunology
OBJECTIVES:Lymphoepithelioma-like carcinoma (LELC) is an uncommon lung cancer, typically observed in young, non-smoking Asian populations. LELC is associated with Epstein-Barr virus (EBV) infection of lung tumor cells of epithelial origin, suggesting a carcinogenic role of EBV as observed in nasopharyngeal carcinoma (NPC). Here, we studied the antigen specificity and phenotype of EBV-specific CD8 T cells in blood and tumor of one LELC patient positive for EBV infection in lung tumor cells. METHODS:Using multiplex MHC class I tetramers, mass cytometry and mRNA sequencing, we studied EBV-specific CD8 T cells at the transcriptomic and phenotypic levels in blood and tumor tissues of the LELC patient. RESULTS:Lymphoepithelioma-like carcinoma lung tumor cells were positive for EBV infection. In both blood and tumor tissues, we detected two populations of EBV-specific CD8 T cells targeting the EBV lytic cycle proteins: BRLF1 and BMLF1. Transcriptomic analyses of these two populations in the tumor, which can be considered as tumor-specific, revealed their distinct exhausted profile and polyclonal TCR repertoire. High-dimensional phenotypical analysis revealed the distinct phenotype of these cells between blood and tumor tissues. In tumor tissue, EBV-specific CD8 TILs were phenotypically heterogeneous, but consistently expressed CD39. Unexpectedly, although the LELC tumor cells expressed abundant PD-L1, these tumor-specific CD8 tumor-infiltrating lymphocytes (TILs) mostly did not express PD-1. CONCLUSION:Epstein-Barr virus-specific CD8 TILs in EBV-driven tumor are heterogeneous and partially lack PD-1 expression, suggesting that anti-PD1/PD-L1 immunotherapy may not be an appropriate strategy for disinhibiting EBV-specific cells in the treatment of LELC patients.
CD56+ lymphoepithelioma-like carcinoma of the lung: A case report and literature review.
Yang Lin,Liang Hua,Liu Li,Guo Lei,Ying Jian-Ming,Shi Su-Sheng,Hu Xing-Sheng
World journal of clinical cases
BACKGROUND:Lymphoepithelioma-like carcinoma (LELC) is a non-keratinizing carcinoma with rich lymphocytic infiltration, which primarily originates from the nasopharynx. Primary lung LELC is a type of lung cancer with a relatively low incidence. Herein, we report a rare case of lung LELC with expression of CD56. We also performed a literature review to summarize the epidemiological, clinical, and prognostic features of this disease. CASE SUMMARY:A 51-year-old man was admitted to Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College due to cough and chest pain lasting > 2 mo and 1 wk, respectively. Positron emission tomography-computed tomography and magnetic resonance imaging examinations revealed the presence of a mass in the right upper lobe with enlargement of lymph nodes and multiple bone metastases. According to the results of bronchoscopy and cervical lymph node biopsy, a diagnosis of lung LELC with CD56-positive staining (CD56 lung LELC) was made. In the literature, 458 cases of lung LELC have been reported. However, only one other case of CD56 lung LELC has been reported thus far. CONCLUSION:The mechanism and potential role of CD56 expression in CD56 lung LELC require further investigation.
Computed tomography-based differentiation of primary pulmonary lymphoepithelioma-like carcinoma and small-cell lung cancer.
Lee Kang-Lung,Wu Mei-Han,Jhang Ying-Yu,Chen Chun-Ku,Yen Yi-Chen,Chen Yi-Chun
Journal of the Chinese Medical Association : JCMA
BACKGROUND:Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of lung cancer. Both small-cell lung cancer (SCLC) and LELC often manifest as a centrally located tumor with lymphadenopathy. This retrospective study investigated and compared the initial computed tomography (CT) features and subsequent survival outcomes of LELC and SCLC. METHODS:A total of 50 patients with a confirmed diagnosis of LELC were enrolled and matched at a ratio of 1:1 with patients with SCLC according to the tumor stage. Utilizing a consensus approach, two radiologists reviewed pretreatment CT images. Survival outcomes were analyzed. RESULTS:Well-defined tumors were significantly more common in the LELC group (LELC: 42% vs SCLC: 24%, p = 0.005). Based on the comparisons of the primary tumor with the muscles, LELC tumors exhibited a significantly higher percentage of attenuation on contrast-enhanced CT scans (21.6% ± 29% vs -14.2% ± 37%, p < 0.001). The prevalence of vascular or bronchial encasement (18% vs 40%, p = 0.028), background emphysematous changes (10% vs 60%, p < 0.001), and tumors located in upper lobes (18% vs 64%, p < 0.001) was significantly lower in the LELC group. Female gender (70% vs 12%, p < 0.001), younger age (57.6 ± 12.0 years vs 68.0 ± 11.0 years, p < 0.001), and without a history of smoking (16% vs 88%, p < 0.001) were factors more commonly found in the LELC group. The patients with LELC had a better prognosis with significantly longer median survival than did the patients with SCLC (23.4 months vs 17.3 months, p = 0.01). CONCLUSION:Because SCLC demonstrated a more aggressive disease progression, differentiating LELC from SCLC is crucial. In Epstein-Barr virus-endemic areas, the diagnosis of LELC should be considered when approaching a patient with the above-mentioned CT and clinical features.
[Lymphoepithelioma-like carcinoma（ LELC） of the lung].
Inoue Takashi,Inaba Hirohisa,Atsuta Kouji,Shimojima Reiko,Shintani Tsunehiro,Miyabe Rika,Kobayashi Hideaki,Shiraishi Kou,Nakayama Takamori,Mori Shunji,Isobe Kiyoshi,Kasahara Masao
Kyobu geka. The Japanese journal of thoracic surgery
A 77-year-old woman was admitted to our hospital with abnormal chest shadow detected on a medical checkup. Chest computed tomography(CT)showed a well-defined tumor in the upper lobe of the right lung. On positron emission tomography by fluorodeoxyglucose(FDG),the tumor revealed to be positive. We performed right upper lobectomy with hilar and mediastinal lymph node dissection. The histopathological diagnosis was lymphoepithelioma-like carcinoma (LELC). In the past 25-years, 41 cases have been reported in Japan. The average age is 64 years old, including 25 male cases and 16 female cases. Among these cases, more than half were in the early resectable stage.
Primary pulmonary lymphoepithelioma-like carcinoma: a rare type of lung cancer with a favorable outcome in comparison to squamous carcinoma.
Chen Bojiang,Chen Xuping,Zhou Ping,Yang Lan,Ren Jing,Yang Xiaodong,Li Weimin
BACKGROUND:Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare tumor and often misdiagnosed as squamous carcinoma. In the current study, clinical characteristics and outcome of primary pulmonary LELC were systematically compared with pulmonary squamous carcinoma. METHODS:Forty-two cases of primary pulmonary LELC and 134 squamous carcinomas were enrolled retrospectively. Characteristic and prognosis difference between the two groups was compared, and the independent prognostic factor for pulmonary LELC was identified as well. RESULTS:In comparison to squamous carcinoma, pulmonary LELC was more common in women with a younger median age and less smokers. LELC seemed to be smaller in diameter on computed tomography (CT) scans than squamous carcinoma, with scarce spiculation and vascular convergence signs. Epstein-Bar virus-encoded RNA (EBER) by in-situ hybridization was detected in 33 LELC cases, among whom 27 ones were positive in serum EBV-DNA examination. LELC patients presented a much longer median progression-free survival (PFS) than squamous carcinoma. Positive serum EBV-DNA, distant lymph node invasion, advanced clinical stage and receiving radiotherapy were correlated with the shorter PFS in LELC patients. However, only positive serum EBV-DNA was the independent PFS predictor. CONCLUSION:Pulmonary LELC looks like distinct from squamous carcinoma. Middle-aged women and nonsmokers are comparatively predominated. CT features of pulmonary LELC are relatively less-malignant. Correspondently, the progression of pulmonary LELC is seemingly favorable than squamous carcinoma and the positive serum EBV-DNA appears to be the predictor of PFS.
Immunotherapy for LELC: Case Report and a Focused Review.
Darrason Marie,Martin Antoine,Soussan Michael,Chouahnia Kader,Pailler Marie-Christine,Boudabous Hanene,Brillet Pierre-Yves,Bousquet Guilhem,Zelek Laurent,Duchemann Boris
Clinical lung cancer
Lymphoepithelioma-like carcinoma of the lung (LELC) is a rare, Epstein-Barr virus-associated tumor. LELC occurs mostly in young, Asian nonsmokers. A few hundred cases have been reported, mostly from retrospective Asian studies. Optimal treatment has not been clearly established. Treatment options are based on surgery for early stage and on cisplatin-based chemotherapy as first-line therapy for metastatic disease. Prognosis may seem better than for other types of non-small-cell lung cancer, but it remains poor in advanced disease, with a median survival of 24 months, and new treatments options are still warranted. Immunotherapies are now key players in the treatment of non-small-cell lung cancer. However, few data are available for this rare histologic subgroup. We have reviewed the available data on LELC with a focus on the first few cases reported with a response to a programmed cell death 1 inhibitor.
Clinical Significance of Plasma Epstein-Barr Virus DNA in Pulmonary Lymphoepithelioma-like Carcinoma (LELC) Patients.
Xie Mian,Wu Xiaojun,Wang Fang,Zhang Jinjun,Ben Xiaosong,Zhang Jiexia,Li Xiaoxiang
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
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.