• Differential diagnosis
• EBV latency pattern
• Genome polymorphisms
• Lymphoepithelioma-like intrahepatic cholangiocarcinoma
• Treatment

• Humans
• Male
• Cholangiocarcinoma/pathology
• Cholangiocarcinoma/virology
• Female
• Middle Aged
• Bile Duct Neoplasms/pathology
• Bile Duct Neoplasms/virology
• Adult
• Epstein-Barr Virus Infections/pathology
• Epstein-Barr Virus Infections/complications
• Epstein-Barr Virus Infections/virology
• Herpesvirus 4, Human/genetics
• Aged
• Biomarkers, Tumor/analysis

• inflammation markers
• nomogram
• overall survival
• pulmonary lymphoepithelioma-like carcinoma

• frozen section
• lung pathology
• lung tumor
• lymphoepithelioma carcinoma of the lung
• lymphoepithelioma-like carcinoma
• non small cell lung cancer

• Case report
• Immune checkpoint inhibitor
• Metastasis
• Pulmonary lymphoepithelioma-like carcinoma
• Stomach neoplasm

• Epstein-Barr virus
• Gastric cancer with lymphoid stroma
• meta-analysis
• prognosis
• systematic review

• Humans
• Stomach Neoplasms/virology
• Stomach Neoplasms/pathology
• Stomach Neoplasms/mortality
• Epstein-Barr Virus Infections/complications
• Epstein-Barr Virus Infections/mortality
• Prognosis
• Herpesvirus 4, Human/isolation & purification

• Definitive chemoradiotherapy
• PLELC
• Radical surgery
• Stage III-N2

• Humans
• Lung Neoplasms/pathology
• Retrospective Studies
• Neoplasm Staging
• Carcinoma, Squamous Cell/pathology
• Chemoradiotherapy
• Nasopharyngeal Neoplasms/pathology

Lymphoepithelioma-like carcinoma (LELC), a rare and unique variant of liver cancer, can be divided into lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like intrahepatic cholangiocarcinoma. Dense lymphocytic infiltration is its characteristic pathological feature. In recent years, the number of reported cases of this type has increased each year. Studies have shown that lymphoepithelioma-like cholangiocarcinoma occurs more frequently in Asian women; LELC is associated with Epstein–Barr virus infection of liver cells of epithelial origin. Existing research shows that the prognosis of this tumour is good.

A 38-year-old female patient was hospitalized after 3 mo of abdominal pain and nausea. She had been infected with hepatitis B virus more than 10 years prior. The patient was hospitalized on January 21, 2022. Magnetic resonance imaging showed a 36 mm × 28 mm mass under the envelope of the left inner lobe of the liver. No metastasis of lymph nodes or other organs was observed. After left hemihepatectomy, biopsy and immunohistochemistry yielded a final diagnosis of lymphoepithelial hepatocellular carcinoma. After 12 mo of outpatient follow-up and chemotherapy, no tumour metastases were found on the latest computed tomography examination.

Herein, the patient was treated surgically and then followed up as an outpatient for 12 mo. This case will further expand our overall knowledge of the diagnosis and treatment of this rare tumor.

• Liver cancer
• Lymphoepithelioma-like carcinoma
• Hepatocellular carcinoma
• Epstein–Barr virus
• Literature review
• Case report

• immune checkpoint inhibitors
• lung neoplasm
• molecular targeted therapy
• preclinical model
• rare cancers

• Humans
• Immunotherapy/methods
• Lung Neoplasms/therapy
• Lung Neoplasms/drug therapy
• Antineoplastic Agents/therapeutic use
• Precision Medicine/methods
• Molecular Targeted Therapy

• NSCLC
• SEER
• cancer-specific survival
• incidence
• primary pulmonary lymphoepithelioma-like carcinoma (PPLELC)

• National Natural Science Foundation of China

• Carcinoma, Squamous Cell/drug therapy
• Humans
• Immune Checkpoint Inhibitors/adverse effects
• Lung Neoplasms/pathology
• Platinum/therapeutic use
• Programmed Cell Death 1 Receptor
• Retrospective Studies

• Lymphoepithelioma-like carcinoma
• Multicentre study
• Rare cancer
• Survival
• Treatment pattern

Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer, which mostly occurred in non-smoking Asian populations. The prognosis of this tumor is better than other lung cancers. Polymyositis, a kind of idiopathic inflammatory myopathies, may negatively affect the prognosis of patients with lung cancer as a paraneoplastic syndrome (PNPS). LELC is seldomly accompanied by PNPS, thus the treatment strategy and prognosis should be discussed.

We report a 49-year-old female patient who was hospitalized for “symmetric limb weakness and pain for more than 2 months”. Glucocorticoid-based anti-inflammatory therapy had been performed for over 3 weeks before the patient was hospitalized, however, in vain. The result of serum autoimmune antibody showed Anti-nRNP/Sm ( +). The serum level of myoglobin, lactate dehydrogenase and creatine kinase elevated significantly. An electromyogram revealed peripheral nerves injury and myogenic damages. Imaging showed a mass in the posterior basal segment of the left lung. A percutaneous transthoracic needle biopsy was performed and the pathological result was LELC. The patient was diagnosed with pulmonary LELC accompanied by polymyositis. Positron emission tomography-computed tomography (PET-CT) showed only ipsilateral hilar and mediastinal lymph nodes metastasis. Video-assisted thoracoscopic left lower lobectomy and systematic mediastinal lymphadenectomy were performed. The postoperative pathological stage was T2N2M0, IIIA (UICC 8th), and the patient received adjuvant chemotherapy and subsequent radiotherapy. The patient was followed up for 5 months with no recurrence of tumor and the limb weakness and pain were relieved apparently after the successful comprehensive treatment of her primary tumor.

Pulmonary LELC is a rare subtype of non-small cell lung cancer seldomly accompanied by PNPS. Though polymyositis is associated with lung cancer, it is easy to ignore this relationship when a patient is diagnosed with LELC in the clinic. Surgery based comprehensive treatment of primary tumor can lead to a prospective prognosis in pulmonary LELC patients with PNPS. And successful treatment of pulmonary LELC can also improve symptoms of PNPS.

• Lung cancer
• Paraneoplastic syndrome
• Polymyositis
• Prognosis
• Pulmonary lymphoepithelioma-like carcinoma
• Treatment

• Natural Science Foundation of Guangdong Province

• Lymphoepithelioma-like carcinoma
• prognosis
• programmed death ligand-1 (PD-L1) expression
• treatment

Background: The current study analyzed resected stage I–IIIA pulmonary lymphoepithelioma-like carcinoma (LELC) cases to define the clinical characteristics, prognosis and long-term outcomes of resected LELC, with the purpose of guiding clinical management for this rare tumor.

Methods: Resected stage I–IIIA LELC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) cases from our center were enrolled. Propensity score matching (PSM) was applied to minimize the selection bias. Overall survival (OS) and disease-free survival (DFS) were compared between groups. Multivariate analyses were performed to identify the prognostic factors, and a nomogram was developed.

Results: A total of 159 LELCs, 2,757 ADCs, and 1,331 SCCs were included. LELC, dominated among younger patients and non-smokers. LELC was a poorly differentiated disease that lacked driver gene mutations and was positive for immunohistochemistry indicators of squamous cell lineage. Survival analyses revealed that OS was significantly better for LELC than for other common non-small cell lung cancers (NSCLCs) both before PSM (all P < 0.001) and after PSM (all P < 0.05). Further analyses revealed that early pathological node stage and preoperative albumin level ≥35 were identified as independent prognostic factors favoring OS and DFS.

Conclusions: LELC, dominated among younger and non-smoking populations, lacked driver gene mutations and was positive for immunohistochemistry indicators of squamous cell lineage. The survival outcome of LELC was better than other common NSCLCs.

• clinical characteristics
• lymphoepithelioma-like carcinoma
• prognosis
• stage I–IIIA
• survival

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is an extremely rare subtype of non-small cell lung cancer (NSCLC). Currently, there are no established treatment protocols due to rarity of the cancer. Thus, this study aimed to explore the molecular and clinical characteristics of PPLELC.

Study design and setting: Data from patients with PPLELC who were admitted to Zhejiang Cancer Hospital from August 2009 to September 2020 were retrospectively collected. Next-generation sequencing was performed to obtain a genomic profile and tumor mutation burden (TMB) value of patients with adequate tissue and divided them into two groups according to the expression level of PD-L1. The correlation of PD-L1 expression and the clinicopathological characteristics was evaluated by Pearson Chi-square test. Kaplan-Meier curves was applied to present the probability of survival between PD-L1 expression level and overall survival (OS). Moreover, the literature on the immunotherapy of advanced PPLELC published in PubMed between 2016 and 2020 were reviewed and the efficacy of immunotherapy were analyzed.

Results: A total of 18 patients pathologically diagnosed as PPLELC were included. After a follow-up period of 8.8–138 months, 14 patients survived, three patients died and one patient lost, the median OS was 45.3 months Seven samples (tissue-available) tested by NGS and the median TMB was 2.5 mutations/Mb. 19 somatic mutated genes were recognized and TP53 (43%) and CYLD (43%) were the two most commonly mutated genes. Only seven patients who underwent NGS were tested for PD-L1. Three patients with high PD-L1 expression (PD-L1≥ 50%) and four patients with low PD-L1 expression (PD-L1 <50%) were included. No significant correlation was observed between PD-L1 expression and clinical characteristics (age, gender, smoking status, tumor stage, lymph node metastasis) (p > 0.05) and OS (p = 1). What’s more, 10 PPLELC patients involved in previous studies and one patient received nivolumab in the current study were collected retrospectively. 4/11 (36.4%) patients achieved PR, 6/11 (54.5%) patients achieved SD, and 1/11 (9.1%) patients achieved PD and the disease control rate (DCR) was 90.9%.

Conclusions: The prognosis of PPLELC is better than that of other NSCLC, and immunotherapy may be a promising treatment to prolong the survival of advanced PPLELC patients. Whether the immunotherapy efficacy of PPLELC can be predicted by PD-L1 and TMB needs further clinical investigation. CYLD genetic alterations may participate in Epstein–Barr virus-mediated tumorigenesis in PPLELC, providing a novel therapeutic target.

• PD-L1
• PPLELC
• TMB
• clinical characteristics
• immunotherapy
• molecular characteristics

Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC). Currently, anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) has become an important treatment for NSCLC. Anti-human PD-1 monoclonal antibodies, such as nivolumab, significantly prolong the survival time of patients with advanced lung adenocarcinoma and lung squamous cell carcinoma. However, there are few reports on the therapeutic effect, drug resistance mechanism, and strategies to overcome resistance to anti-PD-1/PD-L1 treatment in advanced pulmonary LELC. We report the case of a patient with advanced pulmonary LELC harboring fibroblast growth factor receptor (FGFR)3 gene amplification that showed resistance to nivolumab. After treatment with anlotinib, a multi-targeted small-molecule tyrosine kinase inhibitor, the patient’s resistance to nivolumab was reversed. She achieved long-term disease remission with a combination of anlotinib and nivolumab treatment.

A 68-year-old woman was diagnosed with stage IVA pulmonary LELC. After multiple-line chemotherapy, her disease progressed. Since the PD-L1 expression rate of the patient was 90%, nivolumab was administered. However, the therapeutic effect of nivolumab was not ideal; the disease continued to progress, and a new cervical lymph node metastasis appeared. FGFR3 gene amplification was detected in lymph node metastasis. Based on this gene abnormality, we added anlotinib to the treatment. After two cycles of anlotinib and nivolumab, the metastatic focus of the patient was significantly reduced. The patient continued to receive this combined treatment and achieved remission for more than 15 months.

Pulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.

• FGFR3
• anlotinib
• anti-PD-1 resistance
• nivolumab
• pulmonary lymphoepithelioma-like carcinoma

• immune checkpoint inhibitors
• immunotherapy
• lung cancer
• primary pulmonary lymphoepithelioma-like carcinoma
• treatment

Lymphoepithelioma-like carcinoma (LELC) is a rare malignant tumor of the lung. It is related to EB virus infection. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are rarely found in this disease, while high level programmed cell death ligand 1 (PD-L1) expression is observed. Here a series of patients with advanced LELC treated with immunotherapy were summarized.

This retrospective, observational study was conducted in patients who were pathologically confirmed, metastatic or recurrent LELC patients. Patients were prescribed with either chemotherapy or immunotherapy, according to treating physicians’ discretion.

A total of 27 patients were included in our study, 10 with immunotherapy (ICI group) and 17 with chemotherapy (Chemo group). The objective response rates (ORR) of the two groups were 80.0% and 70.5% (p=0.678), and disease control rates (DCR) were 100% and 88.2% (p=0.516). However, the response depth was better in the ICI group. Although the cohort of patients in the ICI group was in a disadvantageous state (both up-front and salvage), the progression-free survival (PFS) was much longer (15.0 and 7.9 m, p=0.005). The 1-year PFS rate in the ICI group was also much higher (40% and 5.9%, p=0.047).

This study implicated the high efficiency of ICI therapy in this disease.

• ICIs
• PD-L1
• immunotherapy
• lymphoepithelioma-like carcinoma

• computed tomography
• diagnosis
• pulmonary lymphoepithelioma-like carcinoma

• Female
• Humans
• Lung/pathology
• Lung/surgery
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/pathology
• Lung Neoplasms/surgery
• Middle Aged
• Tomography, X-Ray Computed

• driver mutation
• immune checkpoint
• lung cancer

• B7-H1 Antigen/metabolism
• Disease-Free Survival
• Female
• Humans
• Lung Neoplasms/diagnosis
• Lung Neoplasms/pathology
• Lymphoma/diagnosis
• Lymphoma/pathology
• Male
• Middle Aged
• Prognosis
• Publication Bias

• Sichuan Province Science and Technology Support Program

Lymphoepithelioma-like carcinoma is a rare distinctive variant of liver cancer with unique epidemiological and pathological characteristics, characterized by dense lymphocyte infiltration. It can be divided into lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like intrahepatic cholangiocarcinoma. Existing research shows that the prognosis of this tumor is good. To date, only 101 cases have been reported.

The first patient was a 62-year-old Chinese man with hepatitis B virus infection who presented with a single lesion in the liver. The patient underwent surgical treatment and was discharged on the 4th day. The patient was diagnosed with combined lymphoepithelioma-like hepatocellular carcinoma and cholangiocarcinoma; he has been alive for 15 months. The second patient was a 63-year-old Chinese woman with right upper abdominal pain and hepatitis B virus infection. The imaging examination revealed a single lesion in the liver. The patient underwent surgical treatment and was discharged 1 week later. The patient was diagnosed with lymphoepithelioma-like hepatocellular carcinoma and was considered to have recurrence in the lymph nodes approximately 2 years after the operation. The patient underwent local radiotherapy; she has been alive for 60 months. The third patient was a 50-year-old Chinese man with hepatitis B virus infection who presented with a single lesion in the liver and two enlarged lymph nodes. The patient received liver puncture before surgery to indicate lymph node metastasis and experienced local recurrence after liver resection. The patient underwent chemotherapy and radiotherapy. The patient was diagnosed with lymphoepithelioma-like hepatocellular carcinoma. The patient was deceased at 24-month follow-up.

This article reports 3 cases without Epstein-Barr virus and reviews the current literature, which suggests even mixed pathological type or locally advanced cases of LELC with lymph node metastasis and postoperative recurrence should be actively treated for a longer survival period.

• Case report
• Hepatocellular carcinoma
• Liver Cancer
• Lymphoepithelioma-like carcinoma

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.

• EBV infection
• PD-L1 expression
• genetic profile
• pulmonary lymphoepithelioma-like carcinoma
• treatment strategy
• tumor inflammatory microenvironment

• Giant saddle area
• Lymphoid epithelial carcinoma
• Radiotherapy