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.

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.

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.

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.

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.

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 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.

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 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.

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.

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.

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.

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.

Checkpoint Inhibition in the Treatment of Unresectable,Advanced Lymphoepithelioma-like Hepatocellular Carcinoma

Lymphoepithelioma-like hepatocellular carcinoma(LELHCC)is a very rare neoplasm,with distinct epidemiologic,morphologic and clinical characteristics.Molecular mechanistic insight into the pathogenesis of this carcinoma suggests a pivotal role for the host immune system in the proliferation and progression of this tumor.However,while detailed genomic profiling of these hepatic tumors have revealed an intra-tumoral inflammatory mutational signature that may predispose to immune checkpoint inhibitor efficacy,no published report has described their use in this tumor type.Unfortunately,with near 100 cases of LEL-HCC reported in the literature to date and the majority of cases confined to localized and resectable disease,current evidencebased practices in the unresectable setting are lacking,with unknown benefit of chemotherapy or immunotherapy.We report on the case of a 68 year-old man with unresectable,advanced LEL-HCC who had evidence of disease stability after starting on the immune checkpoint inhibitor nivolumab.His disease response persisted off therapy for over a year and was potentially augmented by radiotherapy at the site of local progression.For this extremely rare tumor subtype,this case highlights the potential efficacy and safety of immune checkpoint blockade in LEL-HCC and reinforces the need for more robust,large-scale analysis of patients with these rare tumors to better evaluate treatment strategies and outcomes.

Inappropriate antidiuretic hormone secretion in a patient with pulmonary lymphoepithelioma like carcinoma

Antidiuretic hormone （ADH） is produced by an area of he brain called the hypothalamus. The hormone is stored in and released by the pituitary gland. When ADH （also called vasopressin） is produced somewhere other than the hypothalamus, the condition is called syndrome of inappropriate antidiuretic hormone （SIADH）. A variety of conditions can trigger abnormal ADH production, but the main cause is cancer. It is frequently one of the first signs of lung cancer, especially small cell carcinoma, which produces ADH ectopically.l

原发性肺淋巴上皮瘤样癌的多层螺旋CT表现及诊断分析

目的探讨总结原发性肺淋巴上皮瘤样癌的多层螺旋CT(MSCT)表现,结合病理结果分析,期待提高对该病的诊断水平。方法回顾性分析经手术病理证实的19例肺淋巴上皮瘤样癌患者的MSCT表现。结果本组19例,男8例,女11例,发病部位分别为左侧肺门(2例)、双肺多发(2例)、左肺下叶(6例)、右肺上叶(2例)、右肺中叶(4例)、右肺下叶(3例)。CT示肿瘤瘤体大部分呈实性,实质部分密度尚均匀,边界模糊,CT值约30.7～65.0 HU;当瘤体最大径≤5 cm时,肿瘤周边可见长、短毛刺或浅分叶征象,部分肿瘤周边可见晕征;当瘤体最大径≥5 cm时,肿瘤瘤体边缘尚光滑,部分切面与肺组织分界清晰;增强扫描大部分病灶呈不均匀明显强化,CT值约57.8～119.2 HU,当瘤体最大径≥3 cm时,大部分肿瘤可见"血管包埋征"。结论原发性肺淋巴上皮瘤样癌影像学有一定特征性,但MSCT表现仅能提示诊断,术前确诊仍需经支气管内镜活检或经皮肺穿活检。