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 rel...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.展开更多
BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare type of nonsmall-cell lung cancer.Stomach lymphoepithelioma-like carcinoma(LELC)metastasis secondary to PLELC has not been reported recently.CASE S...BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare type of nonsmall-cell lung cancer.Stomach lymphoepithelioma-like carcinoma(LELC)metastasis secondary to PLELC has not been reported recently.CASE SUMMARY A 64-year-old female was admitted to our hospital for a regular gastroscopy examination with a 6-year history of surgical resection for left PLELC.Positron emission tomography/computed tomography suggested high accumulation of 18F-fludeoxyglucose in the gastric cardia region.Upper gastrointestinal endoscopy confirmed a large mass at the stomach fundus.Immunohistochemistry(IHC)of the biopsy suggested metastatic stomach LELC.Proximal gastrectomy showed that this 6.5 cm×5.0 cm mass was located in the stomach fundus near the cardia.Histopathological examination showed a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltration.IHC demonstrated that the tumor was positive for CK(AE1/AE3),p63,p40,p53,Ki-67(70%),and EGFR(3+)and negative for CK7,CK20,Her2,and CD10.In situ hybridization analysis showed positive staining Epstein-Barr virus-encoded RNA.Tumor programmed cell death ligand 1(PD-L1)expression score was 98%,and the combined positive score was 100,with no evidence of microsatellite instability.Thus,the patient was unequivocally diagnosed with metastatic stomach LELC secondary to pulmonary LELC.After discharge,this patient underwent PD-1 inhibitor treatment(toripalimab,240 mg)every 3 wk for ten cycles,and she has had no tumor recurrence.CONCLUSION For gastric LELC metastasis,PD-1 inhibitor therapy could become a new therapeutic approach,though there is still no evidence from large data sets to support this.展开更多
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...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.展开更多
Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genet...Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.展开更多
Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression....Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.展开更多
BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases ...BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy.Controlling hyperglycemia may have important therapeutic implications for cancer patients.AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed.All patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases each.BGrelated indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively analyzed.Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor markers.The incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy,the more unfavorable the therapeutic effect of chemotherapy;the higher the level of tumor markers and inflammatory cytokines,the more adverse reactions the patient experiences.展开更多
BACKGROUND Lymphoepithelioma-like carcinoma(LELC),a rare and unique variant of liver cancer,can be divided into lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like intrahepatic cholangiocarcinom...BACKGROUND 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.CASE SUMMARY 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.CONCLUSION 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.展开更多
In this review we focus on lymphoepitheliomalike hepatocellular carcinomas(LEL-HCC) and lymphoepithelioma-like cholangiocarcinomas(LEL-ICC). Despite their rarity, these tumors are of general interest because of their ...In this review we focus on lymphoepitheliomalike hepatocellular carcinomas(LEL-HCC) and lymphoepithelioma-like cholangiocarcinomas(LEL-ICC). Despite their rarity, these tumors are of general interest because of their epidemiological and clinical features, and because they represent a distinct model of interaction between the immune systemand neoplastic cells. Approximately half of LELHCC arise in the context of chronic hepatitis C virus(HCV) infection and have been described both in Eastern and Western patients. By contrast, LEL-ICC is associated in almost all cases with Epstein-Barr virus(EBV) infection and exhibits the same epidemiological features of EBV related malignancies. Compared with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma of corresponding stage, both LEL-HCC and LEL-ICC are characterized by lower rates of recurrence after surgery and better overall survival. How this behavior is related to distinct genetic alterations and tumor microenvironment is unclear. The pathophysiological mechanisms of lymphoid infiltrations seem to be different among the two groups of tumors. In fact, LEL-HCC frequently arises in the context of inflammatory changes driven by HCV infection, and has been recognized as a variant of classical hepatocellular carcinoma. At variance, lymphocyte recruitment of LEL-ICC is similar to that described in nasopharyngeal carcinoma and gastric LEL, and possibly depends on the expression pattern of latent EBV infection.展开更多
Lymphoepithelioma-like gastric carcinoma is a rare type of gastric cancer characterized by a carcinoma with intense stromal lymphocytic infiltration. Although lymphocytic infiltration is closely associated with Epstei...Lymphoepithelioma-like gastric carcinoma is a rare type of gastric cancer characterized by a carcinoma with intense stromal lymphocytic infiltration. Although lymphocytic infiltration is closely associated with EpsteinBarr virus(EBV) infection, concomitant occurrence with differentiated adenocarcinoma is relatively rare. The clinical manifestations of lymphoepithelioma-like gastric carcinoma(including EBV-positive and-negative forms) are similar to those of gastric cancer, and the diagnosis is based on pathologic, histologic, and immunohistochemical findings. This report describes the case of a 55-year-old female patient who presented with a 10-year history of recurrent and worsening abdominal pain and melena that had been occurring for 2 mo. An ulcerative lesion was detected in the stomach by endoscopic examination, which raised suspicion of early gastric cancer. A subsequent preoperative endoscopic biopsy showed adenocarcinoma, but the postoperative pathologic, histologic, and immunohistochemical analyses of the resected specimen revealed a final diagnosis of lymphoepithelioma-like gastric carcinoma.展开更多
A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma(LEC),and some of LEC is associated with Epstein-Barr virus(EBV).All of the 13...A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma(LEC),and some of LEC is associated with Epstein-Barr virus(EBV).All of the 13 previously reported cases of LEC of the biliary system were intrahepatic in location.Herein,we describe the first case of LEC of the inferior common bile duct.A 68-year-old Japanese man,who had been previously treated for hepatocellular carcinoma using microwave coagulation therapy,was found to have tumors of the common bile duct and pancreas head.Histopathological study of the resected tumor showed solid or cohesive nests of large undifferentiated cells with irregular large vesicular nuclei and nucleoli.Around the tumor cell nests,dense lymphoplasmacytic infiltration was observed.Focal glandular differentiation(approximately 5%) was also present.These histopathological features corresponded morphologically to LEC.Immunohistochemically,the tumor cells were positive for cytokeratin(CK) 7,CK 19 and CA19-9,but negative for CK 20 and Hep Par 1.In situ hybridization for Epstein Barr virus early small RNAs disclosed no nuclear signal in tumor cells.Therefore,a diagnosis of non-EBV-associated LEC of the inferior common bile duct was made.Although the prognosis of the biliary LEC is thought to be better than that of conventional cholangiocarcinoma,the differences in prognosis between EBV-positive and-negative cases have not yet been established.Therefore,additional case studies will be needed to clarify the clinicopathological features of LEC of the biliary tract.展开更多
Esophageal lymphoepithelioma-like carcinoma(LELC) is extremely rare. We report the first case of esopha-geal LELC showing macroscopic reduction. A 67-year-old male presented with dysphagia and, by endoscopic examinati...Esophageal lymphoepithelioma-like carcinoma(LELC) is extremely rare. We report the first case of esopha-geal LELC showing macroscopic reduction. A 67-year-old male presented with dysphagia and, by endoscopic examination, was found to have a significantly raised tumor of 10 mm in diameter in the thoracic esophagus. The biopsied material showed esophageal cancer. We performed endoscopic submucosal dissection. However, the tumor became flattened, similar to a scar, in only 2 mo. Histologically, the carcinoma cells had infiltrated the submucosal layer. Prominent infiltration of T lymphoid cells that stained positive for CD8 was observed aroundthe carcinoma cells. Therefore, this lesion was consid-ered to be an LELC with poorly differentiated squamous cells. Because the margin was positive, an esophagec-tomy was performed. Carcinoma cells were detected in the neck in one lymph node. The staging was T1N0M1 b. However, the patient has been well, without adjuvant therapy or recurrence, for more than 5 years.展开更多
Lymphoepithelioma-like carcinoma(LELC)is a rare,malignant epithelial tumour which can arise within the upper urinary tract.This letter adds to a previous systematic review and cumulative analysis of 28 published upper...Lymphoepithelioma-like carcinoma(LELC)is a rare,malignant epithelial tumour which can arise within the upper urinary tract.This letter adds to a previous systematic review and cumulative analysis of 28 published upper urinary tract-LELC cases which provided insight into this disease;however,the current evidence does not provide clinicians with clear guidelines due to its rarity.Therefore,the aim was to report a new case of renal pelvis LELC presented in our hospital.In this instance,we were able to report treatment experience and longterm follow-up results.This patient presented with hypertension and haemturia which initiated further investigation.While ultrasound identified an hypechoic mass,no malignant cells were detected using cytological testing.Abdominal magnetic resonance imaging identified a slightly enhanced mass in the left renal pelvis with no evidence of lymph node metastasis.Ureteroscopic tumor biopsy suggested the existence of urothelial carcinoma,hence,laparoscopic radical left nephroureterectomy with bladder cuff excision was performed.Through patientpractitioner consultations,we decided to adopt a"watch and wait"approach after radical nephroureterectomy rather than administering chemotherapy.Although,we would encourage clinicians to record and publish cases to garner insight into this type of malignant disease.展开更多
Lymphoepithelioma-like carcinoma(LELC) is a rare type of neoplasm in which only twenty cases have been reported in the breast. This type of tumor can be difficult to distinguish from other breast tumors particularly m...Lymphoepithelioma-like carcinoma(LELC) is a rare type of neoplasm in which only twenty cases have been reported in the breast. This type of tumor can be difficult to distinguish from other breast tumors particularly medullary carcinoma and lymphoma in the breast. We present a case of LELC of the breast presenting as an abscess along with a review of the literature. This is the 21 st reported case of LELC of the breast and the first case to present as an abscess. Her clinical picture could have been mistaken for other infectious or inflammatory diseases. Given the potential for favorable outcome, early detection and general knowledge of this neoplasm are essential to expedite treatment for this rare tumor type.展开更多
Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Me...Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Methods:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways.We enrolled 241 HCC patients who underwent liver transplantation from three centers.Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung metastasis.Results:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC.The expression of TNF was degraded in comparison to that in para-tumor tissues(P<0.001).The expression of key receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(P<0.001).TNF and TNFR1 showed no relationship with patients’outcomes,whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,P<0.001).Notably,elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis(hazard ratio:1.146;P<0.001).Cox regression analysis revealed that TNFR2,Hangzhou criteria,age,and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established accordingly.The nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan criteria.Conclusions:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC.展开更多
BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We ...BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We report a case of multiple synchronous lung cancers with hilar lymph node metastasis of small cell carcinoma of unknown origin in a 73-year-old man.Transbronchial lung biopsy revealed squamous cell carcinoma.Although enlargement of lymph node 12u was detected,no distant metastases were observed.The patient was preoperatively diagnosed with T1cN0M0 and underwent thoracoscopic right upper lobectomy with nodal dissection(ND2a).Based on histopathological findings,the primary lesion was squamous cell carcinoma.A microinvasive adenocarcinoma was also observed on the cranial side of the primary lesion.Tumors were detected in two resected lymph nodes(#12u and#11s).Both tumors were pathologically diagnosed as small cell carcinomas.The primary lesion of the small cell carcinoma could not be identified even by whole-body imaging;however,chemotherapy was initiated for hilar lymph node metastasis of the small cell carcinoma of unknown origin.CONCLUSION Multiple synchronous lung cancers can be accompanied by hilar lymph node metastasis of small cell carcinomas of unknown origin.展开更多
Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activiti...Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities.Olfactory receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for immunotherapy.The Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation cohorts.Results OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal programs.Compared to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related proteins.The clustering performed well in the internal and 5 external validation cohorts.Based on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment response.In addition,the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients.The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts.Conclusion Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC.ORIGs can be applied to molecularly stratify patients,and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.展开更多
BACKGROUND Mucoepidermoid carcinoma of the lung is a rare malignant tumor,accounting for 0.1%–0.2%of all lung malignancies.It is a primary salivary gland tumor of the lung.Surgical resection is the primary treatment ...BACKGROUND Mucoepidermoid carcinoma of the lung is a rare malignant tumor,accounting for 0.1%–0.2%of all lung malignancies.It is a primary salivary gland tumor of the lung.Surgical resection is the primary treatment for pulmonary mucoepidermoid carcinoma,for which there has been no standardized treatment strategy.This article reports a case of a young woman with pulmonary mucoepidermoid carcinoma with hemoptysis as the first symptom.CASE SUMMARY A 24-year-old female patient presented with"4 d of hemoptysis"as the chief complaint.She had no special history and denied any smoking or drinking history.Physical examination revealed that the vital signs were stable and scattered small wet rales were heard in the left lung.After admission,the lung tumor markers were checked,and no abnormalities were found.After completing the bronchoscopy,a spherical lesion was observed at the main bronchus 1.5 cm away from the protubercle,with obvious pulsation and little blood seepage on the surface,and histopathological biopsy results showed acute and chronic inflammation.She was transferred to the Department of Thoracic Surgery for surgical treatment on the 16th day after admission.After exclusion of surgical conjunctures,the patient underwent resection of the tumor in the left main bronchus with single-pore video-assisted thoracic surgery on the 19th day after admission.The postoperative histopathological biopsy results showed mucoepidermoid carcinoma of the lung.The patient and her family refused to complete genetic testing and she was discharged from the hospital on the 8th day after surgery.During the follow-up period,the patient experienced shortness of breath after feeling active and had no special discomfort.CONCLUSION We have documented a case of moderately differentiated mucoepidermoid lung cancer with hemoptysis as the first symptom to improve clinicians'understanding of the disease and provide a new dimension of thinking for its future diagnosis and treatment.展开更多
BACKGROUND There is no established treatment for primary pulmonary lymphoepithelioma-like carcinoma(LELC)until now.CASE SUMMARY In this study,the patient responded well to sintilimab combined with paclitaxel and carbo...BACKGROUND There is no established treatment for primary pulmonary lymphoepithelioma-like carcinoma(LELC)until now.CASE SUMMARY In this study,the patient responded well to sintilimab combined with paclitaxel and carboplatin,showing no obvious side effects.Meantime,the values of carbohydrate antigen 15-3(CA15-3)and carbohydrate antigen 72-4(CA72-4)gradually returned to normal.CONCLUSION Immunotherapy combined with chemotherapy in advanced-stage LELC may be more effective than immunotherapy or chemotherapy alone.CA15-3 and CA72-4 are biomarkers for evaluating therapeutic effects for LELC.展开更多
BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,a...BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.展开更多
文摘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.
基金the Zhejiang Provincial Key Project of Research and Development,No.2019C03043National Natural Science Foundation of China,No.82203452+1 种基金Health Science and Technology Plan of Zhejiang Province,No.2022RC165Clinical Research Fund of Zhejiang Medical Association,No.2021ZYC-A68.
文摘BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare type of nonsmall-cell lung cancer.Stomach lymphoepithelioma-like carcinoma(LELC)metastasis secondary to PLELC has not been reported recently.CASE SUMMARY A 64-year-old female was admitted to our hospital for a regular gastroscopy examination with a 6-year history of surgical resection for left PLELC.Positron emission tomography/computed tomography suggested high accumulation of 18F-fludeoxyglucose in the gastric cardia region.Upper gastrointestinal endoscopy confirmed a large mass at the stomach fundus.Immunohistochemistry(IHC)of the biopsy suggested metastatic stomach LELC.Proximal gastrectomy showed that this 6.5 cm×5.0 cm mass was located in the stomach fundus near the cardia.Histopathological examination showed a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltration.IHC demonstrated that the tumor was positive for CK(AE1/AE3),p63,p40,p53,Ki-67(70%),and EGFR(3+)and negative for CK7,CK20,Her2,and CD10.In situ hybridization analysis showed positive staining Epstein-Barr virus-encoded RNA.Tumor programmed cell death ligand 1(PD-L1)expression score was 98%,and the combined positive score was 100,with no evidence of microsatellite instability.Thus,the patient was unequivocally diagnosed with metastatic stomach LELC secondary to pulmonary LELC.After discharge,this patient underwent PD-1 inhibitor treatment(toripalimab,240 mg)every 3 wk for ten cycles,and she has had no tumor recurrence.CONCLUSION For gastric LELC metastasis,PD-1 inhibitor therapy could become a new therapeutic approach,though there is still no evidence from large data sets to support this.
文摘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.
基金supported by the Major Program of National Natural Science Foundation of China (No. 91959205)National Natural Science Foundation of China (No. 82141117)+3 种基金The Capital’s Funds for Health Improvement and Research (CFH) (No. 2022-2-1023)Beijing Xisike Clinical Oncology Research Foundation Ypierrefabre (No. 202101-0099)Beijing Municipal Administration of Hospitals Incubating Program (No. PX2020045)Science Foundation of Peking University Cancer Hospital (No. 2020-4)。
文摘Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.
文摘Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.
基金Supported by Chronic Disease Management Center for Thoracic Tumor,The Affiliated Hospital of Medical School of Ningbo University,No.2021MGZX-07Natural Science Foundation of Ningbo,No.2019A610238.
文摘BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy.Controlling hyperglycemia may have important therapeutic implications for cancer patients.AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed.All patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases each.BGrelated indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively analyzed.Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor markers.The incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy,the more unfavorable the therapeutic effect of chemotherapy;the higher the level of tumor markers and inflammatory cytokines,the more adverse reactions the patient experiences.
基金Supported by Zhongshan Bureau of Science and Technology,No.2017B1044and No.2017SYF04.
文摘BACKGROUND 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.CASE SUMMARY 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.CONCLUSION 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.
文摘In this review we focus on lymphoepitheliomalike hepatocellular carcinomas(LEL-HCC) and lymphoepithelioma-like cholangiocarcinomas(LEL-ICC). Despite their rarity, these tumors are of general interest because of their epidemiological and clinical features, and because they represent a distinct model of interaction between the immune systemand neoplastic cells. Approximately half of LELHCC arise in the context of chronic hepatitis C virus(HCV) infection and have been described both in Eastern and Western patients. By contrast, LEL-ICC is associated in almost all cases with Epstein-Barr virus(EBV) infection and exhibits the same epidemiological features of EBV related malignancies. Compared with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma of corresponding stage, both LEL-HCC and LEL-ICC are characterized by lower rates of recurrence after surgery and better overall survival. How this behavior is related to distinct genetic alterations and tumor microenvironment is unclear. The pathophysiological mechanisms of lymphoid infiltrations seem to be different among the two groups of tumors. In fact, LEL-HCC frequently arises in the context of inflammatory changes driven by HCV infection, and has been recognized as a variant of classical hepatocellular carcinoma. At variance, lymphocyte recruitment of LEL-ICC is similar to that described in nasopharyngeal carcinoma and gastric LEL, and possibly depends on the expression pattern of latent EBV infection.
文摘Lymphoepithelioma-like gastric carcinoma is a rare type of gastric cancer characterized by a carcinoma with intense stromal lymphocytic infiltration. Although lymphocytic infiltration is closely associated with EpsteinBarr virus(EBV) infection, concomitant occurrence with differentiated adenocarcinoma is relatively rare. The clinical manifestations of lymphoepithelioma-like gastric carcinoma(including EBV-positive and-negative forms) are similar to those of gastric cancer, and the diagnosis is based on pathologic, histologic, and immunohistochemical findings. This report describes the case of a 55-year-old female patient who presented with a 10-year history of recurrent and worsening abdominal pain and melena that had been occurring for 2 mo. An ulcerative lesion was detected in the stomach by endoscopic examination, which raised suspicion of early gastric cancer. A subsequent preoperative endoscopic biopsy showed adenocarcinoma, but the postoperative pathologic, histologic, and immunohistochemical analyses of the resected specimen revealed a final diagnosis of lymphoepithelioma-like gastric carcinoma.
文摘A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma(LEC),and some of LEC is associated with Epstein-Barr virus(EBV).All of the 13 previously reported cases of LEC of the biliary system were intrahepatic in location.Herein,we describe the first case of LEC of the inferior common bile duct.A 68-year-old Japanese man,who had been previously treated for hepatocellular carcinoma using microwave coagulation therapy,was found to have tumors of the common bile duct and pancreas head.Histopathological study of the resected tumor showed solid or cohesive nests of large undifferentiated cells with irregular large vesicular nuclei and nucleoli.Around the tumor cell nests,dense lymphoplasmacytic infiltration was observed.Focal glandular differentiation(approximately 5%) was also present.These histopathological features corresponded morphologically to LEC.Immunohistochemically,the tumor cells were positive for cytokeratin(CK) 7,CK 19 and CA19-9,but negative for CK 20 and Hep Par 1.In situ hybridization for Epstein Barr virus early small RNAs disclosed no nuclear signal in tumor cells.Therefore,a diagnosis of non-EBV-associated LEC of the inferior common bile duct was made.Although the prognosis of the biliary LEC is thought to be better than that of conventional cholangiocarcinoma,the differences in prognosis between EBV-positive and-negative cases have not yet been established.Therefore,additional case studies will be needed to clarify the clinicopathological features of LEC of the biliary tract.
文摘Esophageal lymphoepithelioma-like carcinoma(LELC) is extremely rare. We report the first case of esopha-geal LELC showing macroscopic reduction. A 67-year-old male presented with dysphagia and, by endoscopic examination, was found to have a significantly raised tumor of 10 mm in diameter in the thoracic esophagus. The biopsied material showed esophageal cancer. We performed endoscopic submucosal dissection. However, the tumor became flattened, similar to a scar, in only 2 mo. Histologically, the carcinoma cells had infiltrated the submucosal layer. Prominent infiltration of T lymphoid cells that stained positive for CD8 was observed aroundthe carcinoma cells. Therefore, this lesion was consid-ered to be an LELC with poorly differentiated squamous cells. Because the margin was positive, an esophagec-tomy was performed. Carcinoma cells were detected in the neck in one lymph node. The staging was T1N0M1 b. However, the patient has been well, without adjuvant therapy or recurrence, for more than 5 years.
基金Supported by the Capital Clinical Characteristics Applications Research Program,No.Z171100001017201the Beijing Hospital Clinical Research 121Project,No. BJ-2018-090.
文摘Lymphoepithelioma-like carcinoma(LELC)is a rare,malignant epithelial tumour which can arise within the upper urinary tract.This letter adds to a previous systematic review and cumulative analysis of 28 published upper urinary tract-LELC cases which provided insight into this disease;however,the current evidence does not provide clinicians with clear guidelines due to its rarity.Therefore,the aim was to report a new case of renal pelvis LELC presented in our hospital.In this instance,we were able to report treatment experience and longterm follow-up results.This patient presented with hypertension and haemturia which initiated further investigation.While ultrasound identified an hypechoic mass,no malignant cells were detected using cytological testing.Abdominal magnetic resonance imaging identified a slightly enhanced mass in the left renal pelvis with no evidence of lymph node metastasis.Ureteroscopic tumor biopsy suggested the existence of urothelial carcinoma,hence,laparoscopic radical left nephroureterectomy with bladder cuff excision was performed.Through patientpractitioner consultations,we decided to adopt a"watch and wait"approach after radical nephroureterectomy rather than administering chemotherapy.Although,we would encourage clinicians to record and publish cases to garner insight into this type of malignant disease.
文摘Lymphoepithelioma-like carcinoma(LELC) is a rare type of neoplasm in which only twenty cases have been reported in the breast. This type of tumor can be difficult to distinguish from other breast tumors particularly medullary carcinoma and lymphoma in the breast. We present a case of LELC of the breast presenting as an abscess along with a review of the literature. This is the 21 st reported case of LELC of the breast and the first case to present as an abscess. Her clinical picture could have been mistaken for other infectious or inflammatory diseases. Given the potential for favorable outcome, early detection and general knowledge of this neoplasm are essential to expedite treatment for this rare tumor type.
基金the National Key Research and Development Program of China(No.2021YFA1100500)the Major Research Plan of the National Natural Science Foundation of China(No.92159202)+2 种基金the Key Research&Development Plan of Zhejiang Province(No.2019C03050),the Key Research&Development Plan of Zhejiang Province(No.2021C03118)National S&T Major Project(No.2017ZX10203205)the Health Science&Technology Plan of Zhejiang Province(No.2022RC060)。
文摘Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Methods:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways.We enrolled 241 HCC patients who underwent liver transplantation from three centers.Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung metastasis.Results:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC.The expression of TNF was degraded in comparison to that in para-tumor tissues(P<0.001).The expression of key receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(P<0.001).TNF and TNFR1 showed no relationship with patients’outcomes,whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,P<0.001).Notably,elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis(hazard ratio:1.146;P<0.001).Cox regression analysis revealed that TNFR2,Hangzhou criteria,age,and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established accordingly.The nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan criteria.Conclusions:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC.
文摘BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We report a case of multiple synchronous lung cancers with hilar lymph node metastasis of small cell carcinoma of unknown origin in a 73-year-old man.Transbronchial lung biopsy revealed squamous cell carcinoma.Although enlargement of lymph node 12u was detected,no distant metastases were observed.The patient was preoperatively diagnosed with T1cN0M0 and underwent thoracoscopic right upper lobectomy with nodal dissection(ND2a).Based on histopathological findings,the primary lesion was squamous cell carcinoma.A microinvasive adenocarcinoma was also observed on the cranial side of the primary lesion.Tumors were detected in two resected lymph nodes(#12u and#11s).Both tumors were pathologically diagnosed as small cell carcinomas.The primary lesion of the small cell carcinoma could not be identified even by whole-body imaging;however,chemotherapy was initiated for hilar lymph node metastasis of the small cell carcinoma of unknown origin.CONCLUSION Multiple synchronous lung cancers can be accompanied by hilar lymph node metastasis of small cell carcinomas of unknown origin.
基金the Wuhan University Medical Faculty Innovation Seed Fund Cultivation Project(No.TFZZ2018025)the Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province(No.CXPJJH12000001-2020313)the National Natural Science Foundation of China(No.81670123 and No.81670144).
文摘Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities.Olfactory receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for immunotherapy.The Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation cohorts.Results OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal programs.Compared to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related proteins.The clustering performed well in the internal and 5 external validation cohorts.Based on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment response.In addition,the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients.The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts.Conclusion Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC.ORIGs can be applied to molecularly stratify patients,and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.
文摘BACKGROUND Mucoepidermoid carcinoma of the lung is a rare malignant tumor,accounting for 0.1%–0.2%of all lung malignancies.It is a primary salivary gland tumor of the lung.Surgical resection is the primary treatment for pulmonary mucoepidermoid carcinoma,for which there has been no standardized treatment strategy.This article reports a case of a young woman with pulmonary mucoepidermoid carcinoma with hemoptysis as the first symptom.CASE SUMMARY A 24-year-old female patient presented with"4 d of hemoptysis"as the chief complaint.She had no special history and denied any smoking or drinking history.Physical examination revealed that the vital signs were stable and scattered small wet rales were heard in the left lung.After admission,the lung tumor markers were checked,and no abnormalities were found.After completing the bronchoscopy,a spherical lesion was observed at the main bronchus 1.5 cm away from the protubercle,with obvious pulsation and little blood seepage on the surface,and histopathological biopsy results showed acute and chronic inflammation.She was transferred to the Department of Thoracic Surgery for surgical treatment on the 16th day after admission.After exclusion of surgical conjunctures,the patient underwent resection of the tumor in the left main bronchus with single-pore video-assisted thoracic surgery on the 19th day after admission.The postoperative histopathological biopsy results showed mucoepidermoid carcinoma of the lung.The patient and her family refused to complete genetic testing and she was discharged from the hospital on the 8th day after surgery.During the follow-up period,the patient experienced shortness of breath after feeling active and had no special discomfort.CONCLUSION We have documented a case of moderately differentiated mucoepidermoid lung cancer with hemoptysis as the first symptom to improve clinicians'understanding of the disease and provide a new dimension of thinking for its future diagnosis and treatment.
文摘BACKGROUND There is no established treatment for primary pulmonary lymphoepithelioma-like carcinoma(LELC)until now.CASE SUMMARY In this study,the patient responded well to sintilimab combined with paclitaxel and carboplatin,showing no obvious side effects.Meantime,the values of carbohydrate antigen 15-3(CA15-3)and carbohydrate antigen 72-4(CA72-4)gradually returned to normal.CONCLUSION Immunotherapy combined with chemotherapy in advanced-stage LELC may be more effective than immunotherapy or chemotherapy alone.CA15-3 and CA72-4 are biomarkers for evaluating therapeutic effects for LELC.
文摘BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.