Metastatic stomach lymphoepithelioma-like carcinoma and immune checkpoint inhibitor therapy:A case report

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.

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.

Favorable response of primary pulmonary lymphoepithelioma-like carcinoma to sintilimab combined with chemotherapy: A case report

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.

Lymphoepithelioma-like carcinoma of the upper urinary tract: A systematic review of case reports

BACKGROUND Lymphoepithelioma-like carcinomas(LELCs)are rare,malignant epithelial tumors,generally considered a subtype of squamous cell carcinoma.LELCs are undifferentiated and can occur in multiple tissues,although LELCs in the urinary tract are extremely rare.As such,evidence does not provide clinicians with guidelines for the best practices.Even though this is a rare disease,it is associated with high morbidity and mortality.Therefore,we must learn to differentiate LELC types and identify risk factors for early identification.AIM To develop an evidence base to guide clinicians treating primary LELCs of the upper urinary tract(UUT-LELC).METHODS We performed a systematic review of all reports on UUT-LELC from the first published case in 1998 until October 2019,according to the PRISMA.A database was then developed by extracting data from previously published reports in order to analyze interactions between clinical characteristics,pathological features,interventions and outcomes.Survival was analyzed using Kaplan–Meier estimates,which were compared using log rank tests.RESULTS A total of 28 previously published cases were identified for inclusion.The median age was 72 years with a male to female ratio of 4:3.Pure type LELCs were most common with 48.3%(n=14),followed by 37.9%(n=11)predominant LELCs and 3.4%(n=1)focal LELCs.Epstein-Barr virus testing was negative in all cases.Fourteen patients received radical nephroureterectomy(RNU)-based intervention.Twenty-three patients survived with no evidence of further metastasis,although six died before the median 18 mo follow-up point.Survival analysis suggests pure histological subtypes,and patients who receive complete tumor resection have more favorable prognoses.As always in cancer care,early identification generally increases the probability of interventional success.CONCLUSION The most effective treatment for UUT-LELC is RNU-based therapy.Since cases are few in number,case reporting must be enhanced and publishing encouraged to both save and prolong lives.

Lessons from rare tumors: Hepatic lymphoepithelioma-like carcinomas

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.

Non-Epstein-Barr virus associated lymphoepithelioma-like carcinoma of the inferior common bile duct

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.

Lymphoepithelioma-like carcinoma of the breast presenting as breast abscess

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.

Rare primary lymphoepithelioma-like carcinoma of the renal pelvis

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.

Lymphoepithelioma-Like Carcinoma of Parapharyngeal Space—A Case Report with Review of Literature

Extra-nasopharyngeal lymphoepithelioma-like carcinomas (LELC) are uncommon epithelial tumors. A few isolated case reports and series are available in literature involving the larynx, pharynx, salivary gland, lung etc., but involvement in the parapharyngeal space has not yet been reported. We aim to highlight one such case that has a clinical and radiological characteristic of a benign lesion whilst the histopathology reveals an infiltrating neoplasm. The typical clinical aggressiveness of a classical LELC of extra-nasopharyngeal lesion as described in literature is not present in our case. Also seen is an uncommon finding of abnormal branching of left external carotid artery. There is no standard treatment protocol for such a tumor;however, wide excision of this tumor in the parapharyngeal space via trans-cervical, trans-mandibular, trans-palatal approach has shown good and satisfactory tumor control of the primary site so far.

Eight-year follow-up of locally advanced lymphoepithelioma-like carcinoma at upper urinary tract: A case report

BACKGROUND Urinary tract lymphoepithelioma-like carcinoma is rarely seen.Although it is termed after lymphoepithelioma at the nasopharynx,it behaves more like high grade urothelial carcinoma by immunohistochemical features.Most published literatures focused on its rarity but few discussed results of long-term follow-ups.As no available guidelines are applicable,we postulated that principles should be similar to that of urothelial carcinoma at urinary tract.As of now,this work features the longest follow-up of this cancer at the upper urinary tract.CASE SUMMARY A 63-year-old female had a chief complaint of intermittent left flank pain for 2 mo,along with accompanying symptoms including vomiting and body weight loss,about 7 kg over 2 mo.Laboratory data showed normocytic anemia,mildly poor renal function,and hyperparathyroidism.Urine analysis showed mild hematuria.Computed tomography showed a 4.2-cm-width irregular mass over left renal pelvic and enlarged lymph node at the left renal hilum.Whole-body bone scan was negative of active bone lesions.Biopsy from ureteroscopy showed urothelial carcinoma.Specimen from laparoscopic nephroureterectomy with bladder cuff resection showed lymphoepithelioma-like carcinoma with muscular invasion(pT3).She took adjuvant chemotherapies of 2 cycles and full courses of radiation therapy.No recurrence was observed with designed investigative programs.CONCLUSION Locally advanced urinary tract lymphoepithelioma-like carcinoma could benefit from nephroureterectomy and bladder cuff excision in terms of recurrence-free survival.

CD56+ lymphoepithelioma-like carcinoma of the lung:A case report and literature review

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.

CK5/6-positive,P63-positive lymphoepithelioma-like hepatocellular carcinoma:A case report and literature review

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.

Lymphoepithelioma-like gastric carcinoma: A case report and review of the literature

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.

Epstein-Barr virus-associated lymphoepithelioma-like early gastric carcinomas and endoscopic submucosal dissection: Case series

Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma (LELC) is characterized by a lower lymph node (LN) metastasis rate and a higher survival rate than other forms of gastric cancer. Although current prognosis for LELC is favorable, the most common approach is radical gastrectomy involving an extensive D2 lymph node dissection. Here, we report four cases of EBV-associated early LELC that were treated by an alternative approach, endoscopic submucosal dissection (ESD). The long-term outcome of this procedure is discussed. All patients were treated by ESD en bloc, and all ESD specimens showed tumor-free lateral resection margins. None of the lesions showed lymphovascular invasion. A pathological examination of ESD specimens revealed submucosal invasion of more than 500 μm in all four cases. One patient underwent additional radical surgery post-ESD; no residual tumor or LN metastasis was noted in the surgical specimen. The other three patients did not undergo additional surgery, either because of severe comorbidity or their refusal to undergo operation, but were subjected to medical follow-up. None of the ESD-treated patients reported local recurrence or distant metastases during the 27-32 mo of follow-up after ESD.

Lymphoepithelioma-like esophageal carcinoma with macroscopic reduction

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.

Lymphoepithelioma-like cholangiocarcinoma:A mimic of hepatocellular carcinoma on imaging features

Primary lymphoepithelioma-like carcinoma in the liver is extremely rare. A few cases of lymphoepithelioma-like cholangiocarcinoma have been reported, but few radiologic features were described. We reviewed 23 cases of lymphoepithelioma-like cholangiocarcinoma reported between 1996 and 2014 and describe a rare case of a 35-year-old woman in our hospital who was diagnosed with lymphoepithelioma-like cholangiocarcinoma of the liver and was a hepatitis B carrier. The tumor(1.6 cm) in our patient appeared to be hypoechoic in sonographic images and hypodense in computed tomography(CT) images. In addition, it was homogeneous hypointense in T1-weighted magnetic resonance(MR) images(MRI) and hyperintense in T2-weighted MRI. Dynamic gadolinium-enhanced MRI showed typical image pattern of hepatocellular carcinoma(HCC). The patient underwent a laparoscopic left hepatic lobectomy, and the resected tumor consisted of well-differentiated glandular cells with extensive lymphocytic infiltration that were immunoreactive to CK(AE1/AE3), CD3, and CD20. In addition, the tumor was positive for Epstein-Barr virus-encoded RNA in situ hybridization. Finally, lymphoepithelioma-like cholangiocarcinoma was diagnosed. In previous studies, the incidence is highest among middle-aged people. Most tumors appeared to be hypodense with either hypovascular or hypervascular patterns in CT images. This case report is the first study to address sonography, CT, and MRI observations and delineate pathologic correlations. We suggest that the imaging pattern of lymphoepithelioma-like cholangiocarcinoma, either the typical cholangiocarcinoma pattern or a mimic of HCC, should be considered in the differential lists for HCC.

Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the literature

Lymphoepithelioma-like hepatocellular carcinoma(LELHCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here,a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy,the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2,CK8,CK18,CEA(polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3,CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors(GISTs).The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here,we report the clinicopathological features of our case,along with a review of the few cases present in the literature.

Lymphoepithelioma-like carcinoma of the submandibular salivary gland: a case report

Carcinoma of the salivary gland is an uncommon disease, accounting for less than 1% of all head and neck malignant neoplasm.1 Lymphoepthelioma is a malignant tumor of epithelial origin showing varying amounts of reactive lymphocytic infiltrate. Lymphoepithelioma-like carcinoma （LELC） constitutes a significant proportion of salivary gland carcinoma in Chinese and Eskimo populations and is related to Epstein-Barr virus infection. Carcinoma of the salivary gland has a propensity for early lymphatic metastasis, and thus a swelling of cervical lymph nodes is occasionally the sole initial symptom. It is very vital to consider a multimodality approach including surgery, radiotherapy and chemotherapy for the treatment in the locally advanced disease.

Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice

Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated mortality.This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease.This makes the management of patients more challenging,since physicians must take into consideration two different conditions,the chronic liver disease and the tumor.The underlying liver disease has several implications in clinical practice,because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC,obstacles in surveillance,and differences in the efficacy of the treatment against HCC.A shift in the prevalence of liver diseases has been evident over the last few years,with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance.Therefore,in an era of personalized medicine,it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.