Clinicopathological Characteristics and Lymph Node Metastasis Rates in Early Gastric Lymphoepithelioma-Like Carcinoma: Implications for Endoscopic Resection.

Background/Aims: Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of gastric cancer. We aimed to identify the clinicopathological features and rate of lymph node metastasis (LNM) to investigate the feasibility of endoscopic submucosal dissection for early gastric LELC confined to the mucosa or submucosa. Methods: We compared the clinicopathological characteristics of 116 early gastric LELC patients and 5,753 early gastric well- or moderately differentiated (WD or MD) tubular adenocarcinoma patients treated by gastrectomy. Results: Compared to WD or MD early gastric cancer (EGC) patients, early LELC patients were younger and had a higher prevalence of proximally located tumors. Despite more frequent deep submucosal invasion (86.2% vs 29.8%), lymphatic invasion was less frequent (6.0% vs 16.2%) in early LELC patients than in WD or MD EGC patients. Among tumors with deep submucosal invasion, the tumor size was smaller, lymphatic invasion was less frequent (6.0% vs 40.2%) and the rate of LNM was lower (10.0% vs 19.4%) in patients with LELC than in those with WD or MD EGC. The overall rate of LNM in early LELC patients was 8.6% (10/116). The risk of LNM in patients with mucosal, shallow submucosal invasive, or deep submucosal invasive LELC was 0% (0/6), 0% (0/10), and 10% (10/100), respectively. Conclusions: Early LELC is a distinct subtype of EGC with more frequent deep submucosal invasion but less lymphatic invasion and LNM than WD or MD EGCs. Endoscopic submucosal dissection may be considered curative for patients with early LELC confined to the mucosa or shallow submucosa, given its negligible rate of LNM.

Contrast-enhanced CT and PET-CT characteristics of primary tracheal lymphoepithelioma-like carcinoma: case series.

Background: Primary tracheal lymphoepithelioma-like carcinoma (LELC) is extremely rare, with only a few cases reported so far, and few studies have focused on the radiological features. This study aimed to investigate contrast-enhanced computed tomography (CECT) and positron emission tomography-computed tomography (PET-CT) presentations of primary tracheal LELC to improve diagnosis. Methods: A retrospective analysis was conducted on the clinical and imaging data of 13 patients with confirmed primary tracheal LELC between December 2013 and August 2022. We analyzed the radiological profiles of lesions on the CECT and PET-CT images. Results: In 92.3% (12/13) of the cases, primary tracheal LELC lesions predominantly occurred in the thoracic segment. They manifested as singular, wide-based, eccentric, irregular nodules, or exhibited mass-like thickening of the tracheal wall with invasive growth both internally and externally along the wall. The thickest dimension of the lesion ranged from 9 to 28 mm, affecting a length of 30.8±13.5 mm. Luminal stenosis was evident in all patients, with the narrowest point reaching a stenosis rate of 85%. Lesion margins were clear in 69.2% (9/13), indistinct in 23.1% (3/13), and unclear in 7.7% (1/13) of all cases. Among the patients, 92.3% (12/13) exhibited a relatively uniform density on CT plain scans, with a CT value of 44.5±7.8 Hounsfield units (HU). Enhancement scans revealed moderate to marked enhancement in 75% (9/12) of cases. In 2 cases undergoing PET-CT examination, lesion standardized uptake values (SUVs) were 4.4 and 5.1, whereas enlarged lymph node SUVs were 7.7 and 6.3, respectively. Mediastinal lymph node enlargement was observed in 8 patients (61.5%, 8/13), with a maximum short axis of 11.1±5.5 mm. After treatment, 9 out of 12 patients (75%) showed no evidence of distant metastasis upon CT re-examination. Conclusions: Early detection of primary tracheal LELC allows for curative resection and may lead to a favorable prognosis. It presents with characteristic CT findings, and the utilization of PET-CT improves diagnosis and staging.

Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma.

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC. Viral EBNA-1 and BamHI-W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results: Progression-free survival (PFS) was significantly longer in EBNA-1 high or BamHI-W high groups. A longer PFS was also observed in patients with both high plasma EBNA-1 or BamHI-W and PD-L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA-1 and BamHI-W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions: Plasma EBV DNA could be a useful and easy-to-use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.

Lymphoepithelioma-Like Intrahepatic Cholangiocarcinoma Associated with Epstein-Barr Virus and Hepatitis Virus: Case Report and a Literature Review.

Background: Lymphoepithelioma-like carcinoma of the liver is a rare primary malignancy of the liver. The identification of lymphoepithelioma-like cholangiocarcinoma is very limited as there are currently very few reports of such cases. Although previous studies have reported the lymphoepithelioma-like cholangiocarcinoma pathologic features, few studies have revealed the clinic features, imaging characteristics, and clinical course and outcomes. This study was analyzed from multiple aspects such as contrast-enhanced ultrasound, magnetic resonance imaging, and pathological characteristics, aiming to improve the comprehensive understanding of this rare subtype of disease. Case Presentation: A 43-year-old female with a history of hepatitis B for over 20 years presented with a lesion found in the right lobe of her liver. After discussion by a multidisciplinary team (MDT), malignant tumors cannot be excluded based on contrast-enhanced ultrasound and MRI. Thus, we decided to perform surgery for the patient. Postoperative pathology confirmed lymphoepithelioma-like intrahepatic cholangiocarcinoma. After 3 months of follow-up, the patient was still alive and no recurrence was observed. Conclusion: The purpose of this article is to describe a rare case of lymphoepithelioma-like intrahepatic cholangiocarcinoma and analyze its contrast-enhanced ultrasound and contrast-enhanced MRI features, which will be helpful for physicians in diagnosing this disease. From the perspective of CEUS, the wedge-shaped highly enhanced area around the lesion in the arterial phase appears to be inflammatory but looks malignant based on the extremely fast washout. The lesion showed a low signal on T1WI, a high signal on T2WI and DWI, and an abnormal perfusion shadow can be seen behind the lesion. In particular, this subtype of cholangiocarcinoma has a good prognosis, the clinician should improve the recognition of the disease to strive for early diagnosis and therapy.

Epstein-Barr virus-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma: A report of 3 cases and literature review. / Epstein-Barrç— æ¯’ç›¸å ³æ·‹å·´ä¸Šçš®ç˜¤æ ·è‚å† èƒ†ç®¡ç™Œ3ä¾‹å¹¶æ–‡çŒ®å¤ä¹ ï¼ˆè‹±æ–‡ï¼‰.

Hepatic lymphoepithelioma-like carcinoma (LELC) is an extremely rare malignant tumor characterized by undifferentiated malignant epithelial cells and significant lymphatic infiltration. Hepatic LELC mainly includes lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) and lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-CC). Epstein-Barr virus (EBV) infection is considered as an important factor in LELC carcinogenesis. Since 2005, Xiangya Hospital of Central South University has treated a total of 3 patients with EBV-associated LEL-CC, which all showed liver masses by CT scans. After surgical resection, the EBV encoded RNA (EBER) and CK19 expression in all 3 patients were positive, and pathological examination confirmed EBV-associated LEL-CC. Two patients had a good postoperative prognosis, while 1 patient received relevant immunotherapy and chemotherapy after surgery. Based on the analysis of existing literature, the author believes that hepatic LELC can be included in the classification of liver tumors, which will provide new ideas for the accurate diagnosis and treatment of hepatic LELC.

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

BACKGROUND: Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare type of non-small-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: A Case Report Utilizing Camrelizumab and Anlotinib for Prolonged Survival.

BACKGROUND: Primary Pulmonary Lymphoepithelioma-like Carcinoma (PPLELC) is a rare form of cancer for which no standard treatment has been established to date. Patients with advanced-stage PPLELC generally have a poor prognosis with overall survival of 22.7 months. CASE PRESENTATION: Here, we report a case of advanced primary pulmonary lymphoepithelioma-like carcinoma. Initially, the patient underwent a first-line (GP) and a second-line (DP) of chemotherapy, which provided temporary relief but resulted in varying degrees of myelosuppression. When the disease progressed again, we administered a third-line treatment consisting of camrelizumab combined with anlotinib. RESULT: This resulted in a progression-free survival of over 26 months without significant toxic side effects. CONCLUSION: Our findings suggest that combining camrelizumab and anlotinib could lead to a long progressionfree survival in patients with advanced PPLELC.

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

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

Cervical lymphoepithelioma-like carcinoma with deficient mismatch repair and loss of SMARCA4/BRG1: a case report and five related cases.

BACKGROUND: We encountered a cervical lymphoepithelial carcinoma (LEC) possessing a predominantly solid architecture with deficient mismatch repair (dMMR) and loss of expression of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex subunit. This is the first case report of LEC with dMMR and loss of SWI/SNF complex subunit. CASE PRESENTATION: A 34-year-old woman presented at our hospital with menstrual irregularities and abnormal vaginal bleeding. Magnetic resonance imaging revealed an exophytic mass in the posterior uterine cervix. Biopsy specimens confirmed squamous cell carcinoma with a 2018 International Federation of Gynecology and Obstetrics (FIGO) uterine cervical cancer stage of IB2. In a subsequent conization specimen, the tumor appeared exophytic. Microscopically, the tumor cells formed a predominant solid architecture. Abundant lymphocytic infiltration was observed. The pathological diagnosis indicated human papillomavirus (HPV)-associated squamous cell carcinoma with LEC pattern and pT1b2. Immunohistochemically, high programmed death-ligand 1 (PD-L1) expression, dMMR, and loss of the switch/sucrose non-fermentable family-related, matrix-associated, actin-dependent regulator of chromatin subfamily member 4 (SMARCA4)/BRG1, an SWI/SNF complex subunit, were observed. The patient underwent a radical hysterectomy and is alive without disease one year and five months later. Our analysis of five additional LEC cases revealed a consistent association with high-risk HPV and elevated PD-L1 expression. In addition to the present case, another patient exhibited dMMR. The SWI/SNF complex was retained except in the present case. The prognosis was favorable in all cases. CONCLUSIONS: This unique case of LEC with dMMR suggests a distinct clinical entity with potential immunotherapy implications. Analysis of the other five LEC cases revealed that LEC was immune hot, and immune checkpoint inhibitors may be effective. The two dMMR cases showed loss of MLH1 and PMS2 expressions, and prominently high tumor PD-L1 expression. In those cases, dMMR might have contributed to the morphological characteristics of LEC.

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.

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

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

Clinicopathological features of a rare cancer: Intrahepatic lymphoepithelioma-like cholangiocarcinoma with Epstein-Barr virus infection.

PURPOSE: Epstein-Barr virus-related lymphoepithelioma-like cholangiocarcinoma (EBV-LELCC), a subtype of intrahepatic cholangiocarcinoma (IHCC), is an extremely rare cancer. To date, only few cases have been reported. Therefore, more studies are needed to provide new insights into its clinicopathological characteristics and treatment. METHODS: We retrospectively collected data from 16 EBV-LELCC patients admitted to our hospital between January 2013 and February 2022. We summarized their clinical characteristics and analyzed the genomic features of 5 patients by whole-exon sequencing. In addition, the Kaplan-Meier method was used to assess the prognostic differences between EBV-LELCC and EBV-negative IHCC. RESULTS: A total of 16 EBV-LELCC patients aged between 35 and 70 were included in this study and were characterized by female predominance. Eight genetic mutations including KMT2C, ARID1B, BAZ1A, NPM1, POLE, PER3, TOPBP1, USP1 were identified from 5 patients. There were 11 stage I, 2 stage III and 3 stage IV patients in this study. The overall survival of stage I and stage III EBV-LELCC patients after radical surgery was significantly better than that of EBV-negative IHCC patients with matched stage (p = 0.0119). Notably, a stage IV patient treated with a variety of antitumor modalities including surgery, interventional therapy, radiotherapy, chemotherapy, targeted therapy and immunotherapy achieved long-term survival of more than seven years. CONCLUSION: Altogether, EBV-LELCC presents a more favorable prognosis than IHCC. This study suggests that patients with early EBV-LELCC have a good prognosis after radical surgery, and even patients with advanced EBV-LELCC are expected to have a longer survival under appropriate and timely treatment. For such a rare cancer with unique clinicopathological features and molecular patterns, more research is needed to facilitate its diagnosis and treatment.

Potential missed opportunities for diagnosis of lymphoepithelioma-like intrahepatic cholangiocarcinoma: report of a rare case.

Lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-ICC) is a rare distinctive variant of liver cancer with unique epidemiological and pathological characteristics, including dense lymphocyte infiltration. We herein describe a 67-year-old Chinese man with LEL-ICC. The patient had undergone endoscopic extraction of a bile duct stone 1 month prior. Contrast-enhanced abdominal computed tomography (CT) revealed a 2.5- × 2.5- × 1.5-cm low-density mass located in a covert part of the left lateral segment of the liver. Contrast-enhanced magnetic resonance imaging revealed a hyperintense lesion on T2-weighted and diffusion-weighted images of the left lateral liver, with similar size and signal characteristics in the arterial and portal venous phases. The patient subsequently underwent left lateral laparoscopic hepatectomy. The results of postoperative pathology and immunohistochemistry allowed for the definitive diagnosis. In situ hybridization using an Epstein-Barr virus-encoded RNA probe revealed extensive reactivity in the tumor cell nuclei, supporting a diagnosis of LEL-ICC. The patient was recurrence-free at 12 months postoperatively as shown by CT. A literature review indicated that in middle-aged patients with Epstein-Barr virus infection, a liver mass with a well-defined margin and a combination of hypervascularity and delayed intratumoral enhancement on CT and magnetic resonance imaging may suggest a diagnosis of LEL-ICC.

Pathogenesis and therapeutic implications of EBV-associated epithelial cancers.

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

Comparison of first-line immunotherapy efficacy between advanced lung squamous cell carcinoma and pulmonary lymphoepithelioma-like carcinoma: A propensity score matching multicenter study.

Background: Compared with other lung squamous cell carcinomas (LUSC), pulmonary lymphoepithelioma-like carcinoma (pLELC) is closely associated with Epstein-Barr virus (EBV) infections with a unique molecular profile and immune microenvironment. This study was thus established to compare the treatment response and effectiveness of immunotherapy between pLELC and LUSC. Material and Methods: We enrolled 31 patients with pLELC and 116 with LUSC receiving first-line immunotherapy at three centers in China and compared the treatment response and effectiveness of immunotherapy. Propensity score matching (PSM) was used to balance the differences in baseline data between the two groups. Results: Before PSM, progression-free survival and overall survival were longer in the pLELC group than in the LUSC group (progression-free survival: hazard ratio (HR), 1.67, 95% CI: 1.05-2.63, P = 0.028; overall survival: HR, 1.90, 95% CI: 1.06-3.40, P = 0.028). This remained unchanged after PSM (progression-free survival: HR, 1.79, 95% CI: 1.02-3.15, P = 0.044; overall survival: HR, 2.20; 95% CI: 1.10-4.37, P = 0.022). Conclusion: pLELC showed a clinically meaningful survival benefit compared with traditional LUSC following immunotherapy. Subsequent studies should consider the role of the EBV in the tumor immune microenvironment of pLELC.

Perspectives for immunotherapy of EBV-associated GLELC: A relatively "hot" tumor microenvironment.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric lymphoepithelioma-like carcinoma (EBVaGLELC) represents a small number of gastric cancer (GC), and research on tumor microenvironment (TME) and treatment strategy are still lacking. AIMS: Here, we aim to elucidate the immune features of this rare disease and further help to develop more effective treatment options. MATERIALS & METHODS: A retrospective analysis was conducted between 2019 to 2022 in West China Hospital to reveal the immunological characteristics of EBV-positive GLELC. The difference of immune cell subset and tumor vascular structure between gastric denocarcinoma (GAC) and EBVaGLELC will be pointed out. DISCUSSION: 13 patients with GELEC and 8 patients with GAC were retrospectively studied. The heterogeneity of the immune cell profile was then confirmed through multiplexed immunofluorescence staining (mIF), which revealed a higher proportion of CD3+ T cells, CD8+ T cells, and Treg cells in the EBV-associated GLELC group. Such a distinct TME may provide therapeutic advantages, and patients with this rare subtype of GC could be good candidates for immune checkpoint inhibitors (ICIs). Angiogenesis in EBV-positive GLELC may be less intense than that in gastric adenocarcinoma (GAC), a feature that might decrease their susceptibility to antiangiogenic therapy. Furthermore, we reported a 52-year-old male with advanced EBV-positive GLELC who showed a favorable response to the combined therapy with . A repeat evaluation showed sustained partial response (PR), and the progression-free survival (PFS) was more than 34 months until now. CONCLUSION: Compared with GAC, EBVaGLELC revealed higher T cell infiltration and less intense of angiogenesis. It displays relatively "hot" TME that may provide the rationality to treat with immunotherapy in EBV-related GLELC.

Clinicopathological characteristics and molecular analysis of lymphocyte-rich hepatocellular carcinoma.

Lymphocyte-rich hepatocellular carcinoma (LR-HCC), a newly proposed subtype of HCC, is characterized with abundant lymphocyte infiltration in the tumor. LR-HCC has a relatively good prognosis and is quite rare (<1% of all HCC). We examined LR-HCC clinicopathological and molecular characteristics by analyzing 451 surgically resected HCC cases without any prior treatment history at our hospital between 2012 and 2021. Clinicopathological features of LR-HCC and other HCCs (non-LR-HCC) were compared. Neoplastic and nonneoplastic hepatocytes from LR-HCC (n = 4) were collected with a laser microdissection system; RNA was extracted, followed by microarray analysis to examine lymphocytic infiltration-related molecular targets. Immunohistochemical staining of identified molecular target was performed in LR-HCC and non-LR-HCC. CD3, CD20, and CD8 immunostaining was also performed in LR-HCCs. There were 28 cases of LR-HCC (6%). No statistically significant differences were found in clinicopathological features, except for gross type, between LR-HCC and non-LR-HCC cases. The LR-HCC 5-year survival rate was >90%. Microarray analysis revealed high CCL20 expression in LR-HCC cases; immunohistochemical study showed significantly higher CCL20 expression in LR-HCC (P < 0.01) than in non-LR-HCC. CCR6, the only CCL20 receptor, was observed in infiltrating lymphocytes and HCC cells in LR-HCC. There were significantly more CD3-positive cells than CD20-positive cells (P < 0.0001) in tumor-infiltrating lymphocytes, most of which were CD8-positive T cells. In conclusion, there were no significant differences in clinicopathological characteristics between LR-HCC and non-LR-HCC, except for gross and LR microscopic features. CCL20 expression in LR-HCC may contribute to infiltration of large numbers of CD8-positive lymphocytes.

The MR Imaging of Primary Intrahepatic Lymphoepithelioma-like Cholangiocarcinoma: A Diagnostic Challenge.

PURPOSE: To characterize the magnetic resonance imaging features of primary intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC). MATERIALS AND METHODS: Thirty-four patients with 38 histologically confirmed LELCCs were enrolled retrospectively from January 2014 to August 2022. We evaluated the clinical features, histologic findings, and imaging manifestations on dynamic enhanced MRI. RESULTS: 74% (25/34) of the cases were associated with EBV infection. Moreover, patients infected with EBV exhibited a lower level of Ki-67 proliferation. The serum CA199 level was elevated in 10 patients. The median tumor diameter was 2.8 cm (range, 1.1-8.7 cm). Most tumors were well-defined with a smooth or lobulated margin and showed peripheral hyperintensity and central hypointensity on T2-weighted imaging (T2WI). T2 hyperintense foci were recognized in 8 patients. In the dynamic enhanced MRI, 21 tumors demonstrated Type A enhancement pattern (rim enhancement), 10 demonstrated Type B (rapid wash-in and wash-out), and seven demonstrated Type C (rapid wash-in without wash-out). Capsular enhancement in PVP or DP was found in 22 tumors. A few patients had satellite lesions, portal vein thrombosis, bile duct dilatation, and distal metastasis. Lymph node metastases were discovered pathologically in 11 patients. CONCLUSIONS: MRI findings of LELCC vary and are non-specific. While a majority of LELCCs exhibit typical features of intrahepatic cholangiocarcinoma (iCCA), unique findings like T2 hyperintense foci or capsular enhancement could suggest LELCC. EBV infection and elevated tumor markers can aid in differentiation. However, given the mimics of some cases of liver hypervascular lesions, histological examination remains essential for definitive diagnosis.