Primary Pulmonary Lymphoepithelioma-like Carcinoma Research Articles

Development of a haematological indices-based nomogram for prognostic prediction and immunotherapy response assessment in primary pulmonary lymphoepithelioma-like carcinoma patients.

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare yet aggressive malignancy. This study aims to investigate a deep learning model based on hematological indices, referred to as haematological indices-based signature (HIBS), and propose multivariable predictive models for accurate prognosis prediction and assessment of therapeutic response to immunotherapy in PPLELC. This retrospective study included 117 patients with PPLELC who received immunotherapy and were randomly divided into a training (n=82) and a validation (n=35) cohort. A total of 41 hematological features were extracted from routine laboratory tests and the least absolute shrinkage and selection operator (LASSO) algorithm were utilized to establish the HIBS. Additionally, we developed a nomogram using the HIBS and clinical characteristics through multivariate Cox regression analysis. To evaluate the nomogram's predictive performance, we used calibration curves and calculated the time-dependent area under the curve (AUC). Kaplan-Meier survival analysis was performed to estimate progression-free survival (PFS) in both cohorts. The proposed HIBS comprised 14 hematological features and showed that patients who experienced disease progression had significantly higher HIBS scores compared to those who did not progress (P<0.001). Five prognostic factors, including HIBS, tumor-node-metastasis (TNM) stage, presence of bone metastasis and the specific immunotherapy regimen, were found to be independent factors and were used to construct a nomogram, which effectively categorized PPLELC patients into a high-risk and a low-risk group, with patients in the high-risk patients demonstrating worse PFS (7.0 vs. 18.0 months, P<0.001) and lower overall response rates (22.2% vs. 52.7%, P<0.001). The nomogram showed satisfactory discrimination for PFS, with AUC values of 0.837 and 0.855 in the training and validation cohorts, respectively. The HIBS-based nomogram could effectively predict the PFS and response of patients with PPLELC regarding immunotherapy and serve as a valuable tool for clinical decision making.

Clinical significance of baseline Epstein-Barr virus DNAfor recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma.

Background: This study aimed to evaluate the clinical significance of baseline Epstein-Barr virus (EBV) DNA in recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma (PLELC). Methods: 75patients with baseline EBV DNA were included. The relationships between baseline EBV DNA and clinical characteristics, survivaland objective response rate were analyzed. Results: The baseline EBV DNA levels were related to the liver, chest wall, distant lymph node(s)or multiple sites of distant metastasis. The high baseline EBV DNA group (≥41,900copies/ml) was related to shorter progression-freeand overall survival in univariate analysis and remained significant for progression-free survival in multivariate analysis. Conclusion: The baseline EBV DNA is a valuable biomarker for predicting prognosis and reflecting tumor burden in recurrent or metastatic PLELC.

Primary pulmonary lymphoepithelioma-like carcinoma misdiagnosed as lung squamous cell carcinoma: A case report

BACKGROUND Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is an uncommon subtype of squamous cell carcinoma (SCC) of the lung, closely associated with Epstein-Barr virus (EBV) infection. The pathological features of PPLELC closely resemble those of SCC, which makes it prone to misdiagnosis. Surgical intervention constitutes the primary treatment approach for PPLELC. CASE SUMMARY This report describes a 44-year-old woman who was hospitalized for 1 mo due to left chest pain. Computed tomography revealed a mass shadow in the anterior basal segment of the left lower lobe, and a subsequent needle biopsy suggested SCC. The patient underwent radical tumor resection in the lower left lobe of the lung, and postoperative pathological examination indicated lymphoepithelial carcinoma, and the test for EBV encoded small RNA was positive. Following surgery, the patient was scheduled to receive four cycles of adjuvant chemotherapy, using the paclitaxel + carboplatin regimen, but the patient refused further treatment. CONCLUSION PPLELC is an exceptionally rare subtype of lung SCC and is prone to misdiagnosis.

Pathogenesis and therapeutic implications of EBV-associated epithelial cancers.

Epstein-Barr virus (EBV), one of the most common human viruses, has been associated with both lymphoid and epithelial cancers. Undifferentiated nasopharyngeal carcinoma (NPC), EBV associated gastric cancer (EBVaGC) and lymphoepithelioma-like carcinoma (LELC) are amongst the few common epithelial cancers that EBV has been associated with. The pathogenesis of EBV-associated NPC has been well described, however, the same cannot be said for primary pulmonary LELC (PPLELC) owing to the rarity of the cancer. In this review, we outline the pathogenesis of EBV-associated NPC and EBVaGCs and their recent advances. By drawing on similarities between NPC and PPLELC, we then also postulated the pathogenesis of PPLELC. A deeper understanding about the pathogenesis of EBV enables us to postulate the pathogenesis of other EBV associated cancers such as PPLELC.

Retracted: A Clinical Analysis and Literature Review of Six Cases with Primary Pulmonary Lymphoepithelioma-Like Carcinoma.

[This retracts the article DOI: 10.1155/2022/1086697.].

Rare cavitary lymphoepithelioma-like carcinoma of lung: clinical experience and literature review

BackgroundLymphoepithelioma-like carcinoma of the lung is a rare primary malignancy of the lung, accounting for only 0.9% of primary malignancies of the lung. Those associated with cavities are even rarer, with fewer than five cases reported in the English literature. Concurrently, the imaging findings of tumors are usually non-specific, resulting in insufficient understanding of the disease by clinicians, thus leading to misdiagnosis and delayed treatment.Case presentationA 42-year-old female presented with a right lower lung mass with cavities. First identified on chest computed tomography (CT) in 2021, the mass persisted for 1 year and subsequently enlarged on chemotherapy and routine follow-up CT. Right lower lobectomy was then performed. Postoperative pathology confirmed primary pulmonary lymphoepithelioma-like carcinoma. After 10 months of follow-up, the patient was still alive and no recurrence was observed.ConclusionsThis article aims to describe a rare case of cavitary lymphoepithelioma-like carcinoma of the lung and review it clinical and imaging characteristics reported in previous cases, which will be helpful for clinicians and imaging physicians in diagnosing this disease.

Clinicopathological characteristics and cancer-specific prognosis of primary pulmonary lymphoepithelioma-like carcinoma: a population study of the US SEER database and a Chinese hospital.

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare histological type of non-small cell lung cancer (NSCLC), which accounts for less than 1% of NSCLC. Currently, there is no well-recognized treatment guideline for PPLELC. We identified PPLELC patients from the Surveillance, Epidemiology, and End Results (SEER) dataset between 2000 and 2015 (n = 72) as well as from our medical center between 2014 and 2020 (n = 16). All diagnoses were confirmed by pathological testing, and the clinicopathological characteristics of patients were retrieved and summarized. Survival analyses were conducted using the Kaplan-Meier analysis and log-rank tests. Multivariate survival analysis was performed with the Cox regression hazards model. The median age at diagnosis of the PPLELC cohort was 64 years, ranging from 15 to 86 years. The percentages of patients with TNM stages I, II, III, and IV were 52.3%, 10.2%, 20.5%, and 17.0%, respectively. Among the 88 cases, lesion resection was performed in 69 cases (78.4%), 16 cases (18.1%) received beam radiation, and 40 cases (45.5%) underwent chemotherapy. In the SEER dataset of lung cancer, the percentage of PPLELC in the Asian race (0.528‰) was almost 10 times higher than that in the white (0.065‰) and black (0.056‰) races. Patients with TNM stage III-IV exhibited a worse prognosis than those with TNM stage I-II (p = 0.008), with a 5-year cancer-specific survival (CSS) rate of 81.8% for TNM stage I-II and 56.2% for TNM stage III-IV. Specifically, the N stage and M stage were the leading prognostic factors, not the T stage and tumor size. Moreover, patients who underwent surgery had significantly better outcomes than those who did not (p = 0.014). Additional multivariate analysis indicated that the TNM stage was an independent prognosis factor for CSS (HR, 3.31; 95% CI, 1.08-10.14). PPLELC is a rare tumor with Asian susceptibility. Although the prognosis of PPLELC is better than that of other subtypes of NSCLC, it remains unsatisfactory for advanced-stage disease. The current treatment options for PPLELC include surgical resection, chemotherapy, radiotherapy, and immune therapy. Among these options, patients with surgical resection have better survival rates in this study. However, large-scale clinical research trials will be necessary to develop effective treatment guidelines for PPLELC.

Could immune-related hepatitis rapidly progress to immune-related cirrhosis?

Immune-related hepatitis is one of the prevalent adverse events associated with immunotherapy, especially immune checkpoint inhibitors (ICIs). For patients without a history of liver disease, autoimmune disease, or alcohol consumption, it is not clear whether immune-related hepatitis could rapid progress to immune-related cirrhosis. We report the case of a 54-year-old female with stage IIIB primary pulmonary lymphoepithelioma-like carcinoma (PLELC) diagnosed with immune-related hepatitis. After 15 months, a liver biopsy demonstrated the rapid progression of liver cirrhosis although systematic corticosteroid administration. Long-term immune activation caused by ICIs may exacerbate the process of cirrhosis. Great attention should be paid to the rapid progression to liver cirrhosis of immune-related hepatitis in the clinic.

Efficacy and safety of gemcitabine and capecitabine combination for patients with previously treated advanced primary pulmonary lymphoepithelioma-like carcinoma: a retrospective single-arm cohort study.

Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of non-small cell lung cancer (NSCLC). Studies reporting on salvage treatment for pretreated PLELC are limited. Positive interactions between gemcitabine (GEM) and capecitabine (CAP) have been demonstrated in preclinical studies. In addition, the clinical benefit of the combination has been reported for other malignancies. However, the efficacy and safety of the combination for pretreated PLELC remain unclear. Therefore, we conducted this retrospective study to examine the activity and safety of gemcitabine plus capecitabine (GEM/CAP) combination for previously treated PLELC. Patients with PLELC at Sun Yat-sen University Cancer Center who received GEM combined with CAP between May 2013 and January 2021 as the second-line therapy or beyond were retrospectively enrolled. Treatment consisted of intravenous GEM (1,000 mg/m2 on days 1 and 8) and oral CAP (1,000 mg/m2 twice daily on days 1-14) every 3 weeks. Evaluation of response was performed every 2 cycles in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Safety was assessed in accordance with Common Terminology Criteria for Adverse Events version 5.0. Clinical characteristics were collected from medical records. The survival data were obtained by medical records or telephone. Follow-ups were performed until February 3rd, 2021. A total of 16 patients were enrolled in this study. There were 5, 4, 4, and 3 patients treated with GEM/CAP combination as the second-, third-, fourth-, and fifth-line settings, respectively. There were 8 patients with partial response (PR) (50.00%), 6 with stable disease (SD) (37.50%), 2 with progressive disease (PD) (12.50%), and none with complete response (CR). The objective response rate and disease control rate (DCR) were 50.00% and 87.50%, respectively. The most common hematological and nonhematological adverse events (AEs) at any grade were neutropenia (31.25%) and hand-foot syndrome (43.75%). At a median follow-up of 29.3 months with 95% confidence interval (CI) of 20.3 to 38.3 months, the median progression-free survival (PFS) was 9.3 months (95% CI: 6.5-12.1 months). The median overall survival (OS) was 41.5 months (95% CI: 3.1-79.8 months). This retrospective study demonstrated the potential clinical benefit of GEM in combination with CAP for pretreated PLELC. Future multicenter large-scale, prospective studies are warranted.

Analysis of clinical features, treatment, and prognosis of primary Xlymphoepithelioma-like carcinoma of the lung.

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare lung malignancy occurring most frequently in young non-smokers from Southeast Asia. Given its low incidence, PPLELC clinical features, treatment methods, and the factors affecting its prognosis remain elusive. To date, PPLELC data are mainly derived from clinical case reports, and no cohort studies are available. Therefore, we retrospectively analyzed a group of PPLELC cases and summarized the clinical features of patients, treatment responses, and the factors affecting patient prognosis. A total of 91 patients having primary pulmonary lymphoepithelioma-like carcinoma were recruited in this study. These included sex, age, place of birth, smoking history, pre-treatment symptoms, tumor location, tumor markers, maximum tumor diameter, treatment regimen, lymph node presence metastasis after an operation, pathological picture, immunohistochemistry, genetic findings, and tumor stage grading. We determined the overall survival (OS), progression-free survival (PFS), basic clinical characteristics, treatment option, treatment response, and recurrence pattern among the patients. In addition, we understood the influence of sex, age, tumor, nodes, and metastases (TNM) stage, tumor size, and surgery over patient prognosis. Primary pulmonary lymphoepithelioma-like carcinoma is more common among young non-smokers, with a slightly higher incidence in women than in men. The expression of Epstein-Barr virus-encoded small RNA (EBER), pancytokeratin (PCK), Cytokeratin 5/6 (CK5/6), and tumor protein 63 (P63) was positive in immunohistochemistry. Serum cytokeratin 19 fragment antigen (CYFRA21-1) and Epstein-Barr DNA (EB-DNA) could be used as markers to diagnose primary pulmonary lymphoepithelioma-like carcinoma. TNM stage and surgery were independent prognostic factors. Primary pulmonary lymphoepithelioma-like carcinoma is rare, showing a good prognosis.

PD-1/PD-L1 combined with LAG3 is associated with clinical activity of immune checkpoint inhibitors in metastatic primary pulmonary lymphoepithelioma-like carcinoma.

Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is an Epstein–Barr virus (EBV)-related, rare subtype of non-small-cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) show durable responses in advanced NSCLC. However, their effects and predictive biomarkers in PLELC remain poorly understood. We retrospectively analyzed the data of 48 metastatic PLELC patients treated with ICI. Pretreated paraffin-embedded specimens (n = 19) were stained for PD-1, PD-L1, LAG3, TIM3, CD3, CD4, CD8, CD68, FOXP3, and cytokeratin (CK) by multiple immunohistochemistry (mIHC). Next-generation sequencing was performed for 33 PLELC samples. Among patients treated with ICI monotherapy (n = 30), the objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and overall survival (mOS) were 13.3%, 80.0%, 7.7 months, and 24.9 months, respectively. Patients with PD-L1 ≥1% showed a longer PFS (8.4 vs. 2.1 months, p = 0.015) relative to those with PD-L1 <1%. Among patients treated with ICI combination therapy (n = 18), ORR, DCR, mPFS, and mOS were 27.8%, 100.0%, 10.1 months, and 19.7 months, respectively. Patients with PD-L1 ≥1% showed a significantly superior OS than those with PD-L1 <1% (NA versus 11.7 months, p = 0.001). Among the 19 mIHC patients, those with high PD-1/PD-L1 and LAG3 expression showed a longer PFS (19.0 vs. 3.9 months, p = 0.003). ICI also showed promising efficacy for treating metastatic PLELC. PD-L1 may be both predictive of ICI treatment efficacy and prognostic for survival in PLELC. PD-1/PD-L1 combined with LAG3 may serve as a predictor of ICI treatment effectiveness in PLELC. Larger and prospective trials are warranted to validate both ICI activity and predictive biomarkers in PLELC.This study was partly presented as a poster at the IASLC 20th World Conference on Lung Cancer 2019, 7–10 September 2019, Barcelona, Spain.

Polymyositis as a paraneoplastic syndrome of a patient with primary pulmonary lymphoepithelioma-like carcinoma: a case report and literature review

BackgroundPulmonary 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.Case presentationWe 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.ConclusionPulmonary 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.

A Clinical Analysis and Literature Review of Six Cases with Primary Pulmonary Lymphoepithelioma-Like Carcinoma.

Methods The clinical data of six patients with primary pulmonary lymphoepithelioma-like carcinoma treated in Zhejiang Taizhou Hospital of Taizhou Enze Medical Center (Group) from May 2014 to December 2018 were summarized and analyzed. Combined with the relevant literature, the primary pulmonary lymphoepithelioma-like carcinoma was analyzed retrospectively. Results The main manifestations of six patients were respiratory symptoms, and cough was the most common. The imaging features of six patients were mainly round-like high-density mass shadow or nodule shadow. All patients were diagnosed by pathology. Microscopically, the cancer cells were nested, with large nuclei and vacuoles and abundant lymphocyte infiltration in the tumor stroma. The positive rates of EBER, p63, CK5/6, and Ki-67 were high, and TTF-1 was negative. Five patients received surgical treatment. One patient developed brain metastasis 12 months after operation and received craniocerebral radiotherapy. The other patients did not receive radiotherapy and chemotherapy, and one patient did not receive treatment. After follow-up, four patients survived so far, the longest survival time was 82 months, one patient lost follow-up, and one patient died of lung metastasis 24 months after operation. Conclusion Primary pulmonary lymphoepitheliomatoid-like carcinoma is a rare lung malignant tumor, whose pathogenesis is related to Epstein-Barr virus infection. The clinical manifestations are nonspecific, but with unique pathological characteristics. Surgical resection is the proper treatment for early-stage patients, and comprehensive treatment with surgery as the main treatment is suitable for late-stage patients. The prognosis is good.

Anti-angiogenic therapy for advanced primary pulmonary lymphoepithelioma-like carcinoma: a retrospective multicenter study

PurposePrimary pulmonary lympho-epithelioma-like carcinoma (PPLELC) is a rare subtype of primary non-small cell lung cancer (NSCLC). Currently, there is still lack of research data on anti-angiogenic therapy of advanced PPLELC. The purpose of this study was to investigate the efficacy and safety of anti-angiogenic therapy combined with chemotherapy compared with traditional chemotherapy for these patients.MethodsAdvanced PPLELC patients admitted to six grade A hospitals from January 2013 to January 2021 were selected. The patients received anti-angiogenic therapy combined with chemotherapy (AT group) or chemotherapy (CT group) alone.ResultsA total of 65 patients were included in this study, including 31 patients in the AT group treated with anti-angiogenic therapy combined with chemotherapy and 34 patients in the CT group treated with chemotherapy alone. As of October 1, 2021, the median progression-free survival (PFS) in the AT group was 11.2 months [95% confidence interval (CI), 5.9–16.5]. The median PFS in the CT group was 7.0 months [95%CI, 5.1–8.9] [Hazard Ratio (HR), 0.49; 95%CI, 0.29–0.83; P = 0.008]. The 1-year PFS rates were 41.9% and 17.6%, respectively. The overall response rates (ORR) of two groups were 45.2% (95% CI, 0.27–0.64), 38.2% (95% CI, 0.21–0.56), (P = 0.571). The disease control rates (DCR) of two groups were 93.5% (95% CI, 0.84–1.03), 88.2% (95% CI, 0.77–1.00), (P = 0.756).ConclusionAmong patients with advanced PPLELC, the PFS of patients with anti-angiogenic therapy combined with chemotherapy is better than that of patients with chemotherapy alone. Anti-angiogenic therapy combined with chemotherapy is an optional treatment scheme.

The CT and PET/CT findings in primary pulmonary lymphoepithelioma-like carcinoma with pathological correlation: a study of 215 cases

To investigate the computed tomography (CT) and integrated positron-emission tomography (PET)/CT findings of primary pulmonary lymphoepithelioma-like carcinoma (PLELC). The imaging and histopathological data of 215 patients with PLELC confirmed at histopathology were analysed retrospectively. All patients underwent CT, and 70 underwent PET/CT. None of the cohort had nasopharyngeal lymphoepithelioma-like carcinoma. The PLELC was demonstrated as a solitary nodule/mass in 188 cases (188/215, 87%), multiple nodules/masses in 12 cases (12/215, 6%), lobar or segmental consolidation in 15 cases (15/215, 7%). The tumour showed a well-defined margin in 171 cases (171/215, 80%), lobular sign in 177 cases (177/215, 82%), and spicule sign in 91 cases (91/215, 42%). Most of the cases showed homogeneous density in unenhanced CT (128/215, 60%), and vascular shadows inside the tumour in the arterial stage were found in 105 cases (105/158, 66%). Involvement of the bronchus was found in 154 cases (154/215, 72%). Hilar or mediastinal lymph nodes were enlarged in 160 patients (160/215, 74%). Seventy cases demonstrated avid 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake on PET/CT. The range of maximum standardised uptake values (SUVmax) was 2.1-28.5 (14±5.93). Microscopic pathological classification of 124 resected specimens included 87 cases of the Regaud type and 37 cases of the Schmincke type. Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) was positive in all 215 cases. PLELC should be suspected when a large, lobulate, well-defined lung tumour with homogeneous density, vascular encasement, and high 18F-FDG uptake is found. Moreover, EBERs are helpful in patients with suspected PLELC.

Molecular and Clinical Characteristics of Primary Pulmonary Lymphoepithelioma-Like Carcinoma.

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.

Rhinitis may be a clinical symptom of primary pulmonary lymphoepithelioma-like carcinoma, an incidental finding during the COVID-19 pandemic.

To the Editor: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is considered to be a rare type of lung cancer and is caused by long-term Epstein–Barr virus infection with clinical symptoms similar to most lung cancers. During the COVID-19 pandemic, we treated a seemingly asymptomatic patient with PPLELC comorbidity who was admitted to the hospital for an acute attack of chronic rhinitis. The chest computed tomography (CT) scans showed an abnormal mass in the patient's lung. Based on this clinical case, we propose that there is a positive correlation between chronic Epstein–Barr virus-related rhinitis and PPLELC. In addition, we recommend that patients with rhinitis who are infected by the Epstein–Barr virus receive continuous antiviral therapy with regular monitoring of the viral concentration and CT scans. A 48-year-old non-smoking female patient, from Hunan Province (China), visited her local hospital for fear of being infected with COVID-19 as she experienced symptoms of sneezing and runny nose. The patient had a previous history of chronic rhinitis for at least 2 years. In most cases, symptoms of chronic rhinitis were mild and only presented nasal cavity secretions. Severe rhinitis is usually manifested as runny nose, nasal congestion, and difficult respiration. If these symptoms are not treated, it generally ameliorates or disappears after 5–7 days of initial symptoms. Based on measures to control the COVID-19 pandemic, all patients are required to undergo a throat swab test and chest CT scan. In addition, this patient also underwent viral detection of nasal secretions and serum as the patient showed flu-like symptoms. The Epstein–Barr virus was detected in her nasal secretions and serum. However, her chest CT scans revealed a mass in the left upper lung, which was determined to be a malignant tumor. The 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (18F-FDG PET/CT) showed a mass in the left lung lingula lobe, with a maximum area of 34 mm × 32 mm, high expression of the 18F-FDG imaging agent, and the maximum value of standardized uptake value (SUVmax) of 23.9 kBq/mL [Supplementary Digital Content, Figure 1A, https://links.lww.com/CM9/A570, indicated by the arrow 1]. The imaging agent distribution in the 18F-FDG PET/CT scan of the nose was abnormal with a maximum value of Standardized Uptake Value of 6.6 kBq/mL [Supplementary Digital Content, Figure 1A, https://links.lww.com/CM9/A570, indicated by arrow 3], which suggests a possible long-term chronic infection caused by viruses or bacteria. According to the 8th edition staging of the Union for International Cancer Control (UICC), the lung cancer of the preoperative clinical staging of T2aN1M0. The patient was subsequently admitted to the General Hospital of Central Theater Command of the People's Liberation Army for lung resection. On May 15, 2020, the patient underwent left video-assisted thoracoscopic surgery (VATS) pneumonectomy, as the intraoperative evaluation showed that the tumor had spread to both the upper and lower lobes. Postoperative pathological results indicated the presence of PPLELC in the left lung tumor [Supplementary Digital Content, Figure 1B, https://links.lww.com/CM9/A570] and confirmed metastatic carcinoma in the lymph nodes of group 11, but not in groups 5, 7, 9, and 10. Immunohistochemical analysis found panCK (+), CK5/6 (+), P40 (+), P63 (+), TTF-1 (−), CK7 (−), CD56 (−), Ki-67 (+30%), EBER (+), and PD-L1 (+80%). Postoperative genetic testing of the resected specimen for 20 common gene targets (BGI-Shenzhen [Headquarters]: Shenzhen, 518083, China) revealed no mutated genes as EGFR (Exon 18/19/20/21/T790), FGFR2, FGFR3, ROS1, RET, PIK3CA (Exon 10/12, coding exon 9/20), ALK, KRAS (Codon 12/13/61/146), NRAS (Codon 12/13/61), KIT (Exon 9/11), BRCA1, BRCA2, and ERBB2 (Exon 20/copy number amplification). PPLELC accounts for only 0.25% to 0.9% of all rare non-small cell lung cancers (NSCLC) in China,[1] and only a few cases have been reported in the literature. Most studies about PPLELC have found the Epstein–Barr virus in the serum of patients. The pathological diagnosis of PPLELC needs to meet the following two conditions: first, undifferentiated epithelial cells accompanied with a large number of lymphocyte infiltration observed on pathological sections; second, the Epstein–Barr virus detected in tumor tissues.[1–3] However, the pathologic features of PPLELC are very similar to those of nasopharyngeal carcinoma.[1,3] An untreated Epstein–Barr viral infection is the most significant risk factor for nasopharyngeal carcinoma.[4] Moreover, it has been previously demonstrated that the Epstein–Barr virus might utilize the NF-kB pathways, leading to a range of epithelial carcinomas including PPLELC and nasopharyngeal carcinoma.[4] This suggested that PPLELC and nasopharyngeal carcinoma have certain similarities, and that the Epstein–Barr virus may play a key role in both of them. PPLELC generally presented with clinical features common to other types of lung cancer, such as cough, hemoptysis, chest pain, chest tightness, and so on.[1,2] This patient was a case of PPLELC with rhinitis as the first symptom. With a history of chronic rhinitis for many years, and her rhinitis confirmed as having been caused by the Epstein–Barr virus, a potential association is inferred between rhinitis and PPLELC. On the other hand, this case happened to be discovered because of the necessity for chest CT scans of all patients seeking medical attention during the COVID-19 epidemic. It suggests that we should strengthen the management of potential lung cancer patients,[5] for example, remind patients who are at high risk for lung cancer to have a chest CT scan. If so, this patient's tumor would have been detected when at a much smaller volume and the patient's left lung lingula lobe would not have suffered from such great damage. In conclusion, patients with Epstein–Barr virus-related rhinitis should continue to be followed, because Epstein–Barr virus that has not been completely eliminated may cause PPLELC in the future. Lung cancer patients with Epstein–Barr virus-related rhinitis should be differentially diagnosed with PPLELC and metastasis of nasopharyngeal carcinoma. Declaration of patient consent Written informed consent for the publication of all clinical details and images was obtained from the patient. Conflicts of interest None.

Molecular and clinical characteristics of primary pulmonary lymphoepithelioma-like carcinoma.

e20541 Background: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is an extremely rare subtype of non-small cell lung cancer (NSCLC) and there are no established treatment protocols due to its rarity. At present there are only limited studies about the molecular and clinical characteristics of PPLELC and the results are often inconsistent. Methods: The study collected patients with PPLELC who were admitted to Zhejiang Cancer Hospital from 2009 to 2020 retrospectively. Next-generation sequencing (NGS) was performed to obtain a more comprehensive mutation profile of PPLELE, tumor mutation burden (TMB) level and the expression of programmed cell death 1 ligand 1(PD-L1) was detected for 7 patients. In addition, we review the studies concerning the immunotherapy of advanced PPLELC. Results: 18 patients diagnosed as PPLELC pathologically were collected. 71.4% (5/7) patients expressed PD-L1 (≥ 1%) and the median TMB was 2.5 mutations/Mb. TP53 (43%) and CYLD (43%) were the two most common mutations and other variants included LRIG1 (14%), PTPRT (14%), PPP2R2A (14%). 15 patients survived, 3 patients died and 1 patient was lost after a followed up time for 8.8 to 138 months. A total of 11 cases of advanced PPLELC patients who received immunotherapy were analyzed retrospectively 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 time of advanced PPLELC.Whether the immunotherapy efficacy of PPLELC can be predict by PD-L1 and TMB is worthy of further clinical research. CYLD genetic alterations may participate in Epstein-Barr virus (EBV) -mediated tumorigenesis in PPLELC and expected to provide a new therapeutic target.

Immune Checkpoint Blockade Therapy May Be a Feasible Option for Primary Pulmonary Lymphoepithelioma-like Carcinoma.

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small cell lung cancer (NSCLC) for which there is currently no recognized treatment. Recently, favorable immune checkpoint blockade responses have been observed in PPLELC. This study aimed to review the effects of this regimen in patients with advanced PPLELC. PPLELC patients treated with immune checkpoint inhibitors at West China Hospital between January 2008 and December 2019 were retrospectively identified. Demographic parameters and antitumor treatment details were retrieved and reviewed. Among 128 patients diagnosed with PPLELC, 5 who received immune checkpoint inhibitors at advanced stages were included in the analysis. All of these patients were female nonsmokers with a median age of 55.6 (range 53-58) years at diagnosis. Their median PD-L1 expression was 40% (range, 30-80%). Although the patients underwent surgeries, chemotherapy and radiotherapy, all the treatments failed. Immune checkpoint inhibitors were administered palliatively, and three patients responded favorably, with the best overall response being partial remission (PR). Thus, immune checkpoint inhibitors may be a promising treatment for advanced PPLELC, and large clinical trials are warranted to obtain more evidence regarding this regimen.

MA01.08 Gemcitabine Plus Capecitabine in Patients With Primary Pulmonary Lymphoepithelioma-Like Carcinoma Previously Treated With Chemotherapy

Primary pulmonary lymphoepithelioma-like carcinoma(PLELC) is a rare and unique pathological subtype of NSCLC. It was found as an Epstein-Barr virus(EBV)-associated epithelial neoplasm. Histologically, PLELC presented as an undifferentiated carcinoma with lymphocytic infiltration, similar to an undifferentiated nasopharyngeal carcinoma(NPC). Because of low incidence of PLELC, the evidence-based treatment guideline was limited. Currently, the treatment strategy of PLELC was following the guidance of NSCLC and platinum-based chemotherapy was the most common first-line regimen. Few studies about salvage chemotherapy in advanced PLELC were reported. Gemcitabine(Gem) was reported to be an active agent in squamous cell NSCLC and also NPC. Ho reported capecitabine (Cap) for pretreated PLELC had promising activity and good tolerability in a small cohort. The combination of gemcitabine/ capecitabine(Gem/Cap) showed active efficacy and favorable toxicity profile in various cancers. Therefore, we conducted this retrospective study to examine the activity and safety of Gem/Cap combination in previously treated advanced PLELC. Patients with histologically confirmed PLELC seen at Sun Yat-Sen University Cancer Center between May 2013 to December 2019 were identified. Sixteen patients treated with Gem/Cap in the second-line setting or beyond were included in this analysis. Treatment consisted of i.v. gemcitabine (1000 mg/m2 on days 1 and 8) and oral capecitabine (1000 mg/m2 twice daily on days 1–14) every 3 weeks. Characteristics of the patients were shown in Table 1 . There were 5(31.3%) patients who had received one prior chemotherapy regimen while the remaining patients received 2–4 prior chemotherapy regimens. Four patients had ever received gemcitabine/ platinum or gemcitabine/docetaxel as prior chemotherapy, but no patient had ever exposed to Gem/Cap regimen. As of the last follow-up, 16 patients received a total of 89 (median: 5.5, range: 2-12) cycles of Gem/Cap therapy. All patients were evaluable for response. There were 0 CR, 8 (50.0%) PR, 6 (37.5%) SD and 2 (12.5%) patients with PD after at least 2 cycles. The ORR was 50% and DCR was 87.5%. At a median follow-up of 15.9 months, the median PFS was 8.8 months (95% CI: 5.6 -12.0 months). The median OS was not reach at the time of data cut-off. All patients were evaluated for toxicity. The most common AE at any grade was neutropenia (31.25%). The grade 3-4 neutropenia was 6.25%. There was no treatment-related death.Table 1Patients' characteristicsVariableDataMedian age (range), years46(35-65)GenderMale8(50.00%)Female8(50.00%)WHO Performance Status09(56.25%)17(43.75%)History of smokingYes6(37.50%)No10(62.50%)Number of prior chemotherapy15 (31.25%)25 (31.25%)33 (18.75%)43 (18.75%)Cycles of Gemcitabine/Capcitabine combinationMedian5.5Range2-12 Open table in a new tab This retrospective study has shown good efficacy and well tolerability of gemcitabine plus capecitabine combination as salvage chemotherapy in PLELC patients previously treated with chemotherapy.