Tertiary Lymphoid Structures Gene Signature Predicts Prognosis and Immune Infiltration Analysis in Head and Neck Squamous Cell Carcinoma.

Objectives: This study aims to assess the prognostic implications of gene signature of the tertiary lymphoid structures (TLSs) in head and neck squamous cell carcinoma (HNSCC) and scrutinize the influence of TLS on immune infiltration. Methods: Patients with HNSCC from the Cancer Genome Atlas were categorized into high/low TLS signature groups based on the predetermined TLS signature threshold. The association of the TLS signature with the immune microenvironment, driver gene mutation status, and tumor mutational load was systematically analyzed. Validation was conducted using independent datasets (GSE41613 and GSE102349). Results: Patients with a high TLS signature score exhibited better prognosis compared to those with a low TLS signature score. The group with a high TLS signature score had significantly higher immune cell subpopulations compared to the group with a low TLS signature score. Moreover, the major immune cell subpopulations and immune circulation characteristics in the tumor immune microenvironment were positively correlated with the TLS signature. Mutational differences in driver genes were observed between the TLS signature high/low groups, primarily in the cell cycle and NRF2 signaling pathways. Patients with TP53 mutations and high TLS signature scores demonstrated a better prognosis compared to those with TP53 wild-type. In the independent cohort, the relationship between TLS signatures and patient prognosis and immune infiltration was also confirmed. Additionally, immune-related biological processes and signaling pathways were activated with elevated TLS signature. Conclusion: High TLS signature is a promising independent prognostic factor for HNSCC patients. Immunological analysis indicated a correlation between TLS and immune cell infiltration in HNSCC. These findings provide a theoretical basis for future applications of TLS signature in HNSCC prognosis and immunotherapy.

A proof-of-concept study: advantages of the subxiphoid over the lateral intercostal approach.

OBJECTIVES: The study was designed to evaluate the superiority of the subxiphoid approach compared with the lateral intercostal approach during the operation and other perioperative indices. METHODS: Patients diagnosed with anterior mediastinal disease in our hospital between January 2018 and October 2019 were prospectively assigned to 2 groups; 1 group underwent the lateral intercostal approach and 1 group underwent the subxiphoid approach of video-assisted thoracoscopic surgery to resect the diseased tissue. The PaCO2, SaO2, PaO2 and circulation changes were recorded during the operation; the neutrophil-to-lymphocyte ratio and other perioperative outcomes, including clinical and surgical results, operating time, blood loss, postoperative complication and postoperative pain score were compared. RESULTS: A total of 59 patients diagnosed with an anterior mediastinal tumour or myasthenia gravis underwent a video-assisted thoracoscopic resection. Thirty-one patients were treated via the subxiphoid approach, and 28 patients were treated via the lateral intercostal approach. The PaCO2 increased significantly and the SaO2 remained stable in the subxiphoid group during the operation, whereas PaCO2 increased significantly and SaO2 decreased at the same time in the lateral intercostal group. Operations were more frequently interrupted for the hypoxia or circulation disturbance during the process of dissecting the thymus in the lateral intercostal approach. Compared with the lateral intercostal approach, patients treated via the subxiphoid approach experienced less inflammation and exhibited lower pain scores and shorter postoperative hospital stays. There were no significant differences in postoperative complications between the 2 groups. All of the patients recovered well when discharged. CONCLUSIONS: Our study results suggested that the subxiphoid approach has less of an influence on the pulmonary circulation than the lateral intercostal approach, that the whole procedure is safer and easier and that the subxiphoid approach may be the ideal choice for patients with anterior mediastinal disease.

Surgical strategy for intravenous leiomyomatosis spreading from uterine to the right atrium presenting with recurrent syncope.

Uterine leiomyoma invading internal iliac vein and consequently disseminating into the right atrium is an extremely rare condition, and surgical strategy is controversial. Here, we reported a specific case with successful surgical resection through one-stage total hysterectomy, bilateral oophorectomy, and the intracardiovascular lesion. This procedure would be an optimal choice for uterine leiomyoma invading inferior vena cava and spreading to right atrium.

Kimura's disease treated with dupilumab: A case report and literature review.

BACKGROUND: Kimura's disease (KD) is a rare chronic inflammatory disorder characterised by painless, deep subcutaneous nodules that most commonly affect the head and neck region of Asian men. Due to high relapse rates and side effects of current therapies, the treatment of KD is challenging. OBJECTIVES: To present a case of KD that was successfully treated with dupilumab and to review the literature with a focus on the evaluation of the efficacy and safety of dupilumab in KD. METHODS: A review of the available literature on the treatment of KD with dupilumab was performed and a new case was analyzed. To gain further insight into this promising therapy, literature review of 8 articles published between January 2016 and January 2024 were included in this study using the PubMed database. RESULTS: Our patient with KD was successfully treated with dupilumab 300 mg every 2 weeks, at an initial dose of 600 mg. The treatment was well tolerated. In the past, only nine patients with KD treated with dupilumab have been reported and reviewed, half of whom had failed prior treatment. All patients achieved significant efficacy after treatment with dupilumab, with no relapses during an average follow-up of 10.4 months (ranged from 4 to 16 months). CONCLUSION: Dupilumab may be an emerging alternative treatment option for KD patients. Larger randomized controlled studies are needed to confirm these findings.

Expression of Early Growth Response 3 in Skin Cancers.

OBJECTIVE: To assess the expression of early growth response 3 (EGR3) in normal skin and different types of skin tumors: cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), melanoma (MM), and cutaneous adnexal tumors containing sebaceous carcinoma (SC), trichoepithelioma (TE) and clear cell hidradenoma (CCH). BACKGROUND: EGR3, expressed in multiple organs, including skin, plays an important role in cell differentiation and tumor growth. Previous studies have shown that EGR3 suppresses tumor growth and is downregulated in various malignancies. However, its distribution in normal skin and its expression especially in skin tumors have not been studied. MATERIALS AND METHODS: Samples of normal cases (n = 4), cSCC (n = 12), BCC (n = 12), MM (n = 12), SC (n = 4), TE (n = 4), and CCH (n = 4) were collected from patients treated in our department between 2018 and 2023. Immunohistochemistry was used to investigate the expression of EGR3. The results were analyzed with the description of the staining pattern and the histochemical score. RESULTS: Immunohistochemical staining showed that EGR3 was uniquely expressed in normal skin in the granular layer and upper part of the stratum spinosum, as well as in sebaceous glands and hair follicles, but not in sweat glands. In skin cancers, BCC, SC, and TE showed positive EGR3 staining, whereas cSCC, MM, and CCH were negative. CONCLUSIONS: EGR3 has a specific expression pattern in normal skin and in skin tumors, which is important for the differential diagnosis of skin tumors, in particular for cSCC and sebaceous gland carcinoma.

Nur77 inhibition of ß-catenin expression mediates Hepatoblastoma progression and enhances cisplatin's therapeutic effect.

Hepatoblastoma (HB) is the most common malignant tumor in children under 5 years old, but its pathogenesis remains unclear. Nur77 has been reported to be an important regulator for cancer progression in various cancer types. This study found that Nur77 was downregulated in HB tumors, compared with paracancer tissue. Knockout or overexpression of Nur77 in HB tumor cell line HepG2 and HuH6 could significantly enhance or inhibit the proliferation, migration and invasion of tumor cells both in vitro and in vivo. Further studies illustrated that Nur77 regulated the proliferation of tumor cells by affecting the expression of ß-catenin. Nur77 agonist Csn-B effectively enhanced the therapeutic effect of cisplatin on HB tumors both in vitro and in vivo. This study confirms that Nur77 may act as an oncogene in HB tumors and mediate the progression of HB by inhibiting the expression of ß-catenin, which provides a new targeted therapy for the clinical treatment of HB patients; meanwhile, the combination of Nur77 agonist and cisplatin treatment may improve the chemotherapeutic efficacy of HB patients, which provides a new idea for the improvement of the clinical prognosis of HB patients.

Radiomics Features on Enhanced Computed Tomography Predict FOXP3 Expression and Clinical Prognosis in Patients with Head and Neck Squamous Cell Carcinoma.

Forkhead box P3 (FOXP3) has been identified as a novel molecular marker in various types of cancer. The present study assessed the expression of FOXP3 in patients with head and neck squamous cell carcinoma (HNSCC) and its potential as a clinical prognostic indicator, and developed a radiomics model based on enhanced computed tomography (CT) imaging. Data from 483 patients with HNSCC were downloaded from the Cancer Genome Atlas for FOXP3 prognostic analysis and enhanced CT images from 139 patients included in the Cancer Imaging Archives, which were subjected to the maximum relevance and minimum redundancy and recursive feature elimination algorithms for radiomics feature extraction and processing. Logistic regression was used to build a model for predicting FOXP3 expression. A prognostic scoring system for radiomics score (RS), FOXP3, and patient clinicopathological factors was established to predict patient survival. The area under the receiver operating characteristic (ROC) curve (AUC) and calibration curve and decision curve analysis (DCA) were used to evaluate model performance. Furthermore, the relationship between FOXP3 and the immune microenvironment, as well as the association between RS and immune checkpoint-related genes, was analyzed. Results of analysis revealed that patients with HNSCC and high FOXP3 mRNA expression exhibited better overall survival. Immune infiltration analysis revealed that FOXP3 had a positive correlation with CD4 + and CD8 + T cells and other immune cells. The 8 best radiomics features were selected to construct the radiomics model. In the FOXP3 expression prediction model, the AUC values were 0.707 and 0.702 for the training and validation sets, respectively. Additionally, the calibration curve and DCA demonstrated the positive diagnostic utility of the model. RS was correlated with immune checkpoint-related genes such as ICOS, CTLA4, and PDCD1. A predictive nomogram was established, the AUCs were 0.87, 0.787, and 0.801 at 12, 24, and 36 months, respectively, and DCA demonstrated the high clinical applicability of the nomogram. The enhanced CT radiomics model can predict expression of FOXP3 and prognosis in patients with HNSCC. As such, FOXP3 may be used as a novel prognostic marker to improve individualized clinical diagnosis and treatment decisions.

Efficacy and safety of two-stage revision for patients with culture-negative versus culture-positive periprosthetic joint infection: a single-center retrospective study.

BACKGROUND: The safety and efficacy of two-stage revision for culture-negative PJI remain controversial. This study analyzed outcomes after two-stage revision in patients with culture-negative and culture-positive periprosthetic joint infection (PJI) during follow-up lasting at least two years. METHODS: Data were retrospectively analysed patients who underwent hip or knee revision arthroplasty from January 2008 to October 2020 at our medical center. The primary outcome was the re-revision rate, while secondary outcomes were the rates of reinfection, readmission, and mortality. Patients with culture-negative or culture-positive PJI were compared in terms of these outcomes, as well as survival time without reinfection or revision surgery, based on Kaplan‒Meier analysis. RESULTS: The final analysis included 87 patients who were followed up for a mean of 72.3 months (range, 24-123 months). The mean age was 58.1 years in the culture-negative group (n = 24) and 59.1 years in the culture-positive group (n = 63). The two groups (culture-negative versus culture-positive) did not differ significantly in rates of re-revision (0.0% vs. 3.2%, p > 0.05), reinfection (4.2% vs. 3.2%, p > 0.05), readmission (8.4% vs. 8.0%, p > 0.05), or mortality (8.3% vs. 7.9%, p > 0.05). They were also similar in survival rates without infection-related complications or revision surgery at 100 months (91.5% in the culture-negative group vs. 87.9% in the culture-positive group; Mantel‒Cox log-rank χ2 = 0.251, p = 0.616). CONCLUSION: The two-stage revision proves to be a well-tolerated and effective procedure in both culture-negative and culture-positive PJI during mid to long-term follow-up.

Kirkendall effect-induced uniform stress distribution stabilizes nickel-rich layered oxide cathodes.

Nickel-rich layered oxide cathodes promise ultrahigh energy density but is plagued by the mechanical failure of the secondary particle upon (de)lithiation. Existing approaches for alleviating the structural degradation could retard pulverization, yet fail to tune the stress distribution and root out the formation of cracks. Herein, we report a unique strategy to uniformize the stress distribution in secondary particle via Kirkendall effect to stabilize the core region during electrochemical cycling. Exotic metal/metalloid oxides (such as Al2O3 or SiO2) is introduced as the heterogeneous nucleation seeds for the preferential growth of the precursor. The calcination treatment afterwards generates a dopant-rich interior structure with central Kirkendall void, due to the different diffusivity between the exotic element and nickel atom. The resulting cathode material exhibits superior structural and electrochemical reversibility, thus contributing to a high specific energy density (based on cathode) of 660 Wh kg-1 after 500 cycles with a retention rate of 86%. This study suggests that uniformizing stress distribution represents a promising pathway to tackle the structural instability facing nickel-rich layered oxide cathodes.

Atypical plaque psoriasis: a clinicopathological study of 20 cases.

BACKGROUND: Plaque psoriasis is relatively straightforward to identify. When diagnostic concerns arise in atypical cases, a biopsy is needed. It is widely accepted that the Munro microabscess and the spongiform pustule of Kogoj are diagnostic pathological features. However, the diagnostic dilemma is likely to arise in cases without these specific pathological changes and typical clinical features. This study aimed to investigate clinical and pathological clues in distinguishing atypical plaque psoriasis from its mimics. METHODS: We evaluated the clinicopathological features of 20 cases of atypical plaque psoriasis and 40 cases of psoriasis mimics as controls including pityriasis rosea (n = 10), pityriasis lichenoides chronica (n = 8), and subacute dermatitis (n = 22). RESULTS: A retrospective analysis of the clinicopathological characteristics of patients with atypical plaque psoriasis and controls was performed. Pathologically, there were significant differences between the two groups in the types of parakeratosis (P = 0.046), epidermal capture of extravasated erythrocytes (P = 0.011), focal basal liquefied degeneration (P = 0.017), types of inflammatory cells (P = 0.000), and depth of inflammation (P = 0.000). Clinically, we found the presence of scales and crusts was significantly different between the two groups. CONCLUSION: This study offers insight into the clinicopathological features of atypical plaque psoriasis. These differential diagnostic features, compared with its mimics, are proposed to assist the clinician in the diagnosis and treatment of atypical plaque psoriasis.

Quantitative Magnetic Resonance Imaging Had Greater Sensitivity in Diagnosing Chondral Lesions of the Knee: A Systematic Review and Meta-Analysis.

PURPOSE: To investigate the accuracy and reliability of magnetic resonance imaging (MRI) in identifying and grading chondral lesions and explore the optimal imaging technique to image cartilage. METHOD: A comprehensive search was conducted on Medline, Embase, and Cochrane Library. Eligible cohort studies published before August 2022 were included. The study reports used MRI to diagnose and grade cartilage lesions, with intraoperative findings as the reference standard. Summary estimates of diagnostic performance were obtained. The reliability of MRI interpretation was summarized. Subgroup analyses were performed based on assessed imaging techniques, field strength, and joint surface. RESULTS: Forty-three trials and 3,706 patients were included in the systematic review. The overall area under curve for hierarchical summarized receiver operating characteristics was 0.91 (95% confidence interval [CI] 0.88-0.93). The pooled sensitivity for quantitative MRI, 3-dimensional MRI, and 2-dimensional MRI was 0.82 (95% CI 0.64-0.92), 0.79 (95% CI 0.74-0.83), and 0.63 (95% CI 0.51-0.73), respectively. The pooled sensitivity of 3 Tesla (3T), 1.5 Tesla (1.5T), and <1.5 Tesla MRI was 0.79 (95% CI 0.72-0.85), 0.67 (95% CI 0.60-0.74), and 0.55 (95% CI 0.39-0.71), respectively. There were differences in interobserver consistency across different studies. CONCLUSIONS: In general, MRI had high specificity in discriminating normal cartilage, but its sensitivity for identifying chondral lesions is less optimal. Further analysis showed that quantitative MRI, 3D MRI, and 3T MRI demonstrate greater sensitivity compared with 2D MRI, 1.5T MRI, and <1.5 Tesla MRI. LEVEL OF EVIDENCE: Level III, systematic review of Level II-III studies.

Video assisted thorascopic assisted correction of left partial anomalous pulmonary venous connection: one case report.

INTRODUCTION: The left partial anomalous pulmonary vein connection is a rare congenital heart disease, especially with intact atrial septum. Now we reported a case of the left superior pulmonary vein drainage to left innominate vein through a vertical vein, and corrected with video assisted thoracoscopy. CASE PRESENTATION: A-59-years old man diagnosed left anomalous partial pulmonary vein connection with presentation of short breathiness and palpation, and diagnosed with computer tomography pulmonary angiography. The operation was carried out under video assisted thoracoscopy with one manipulation incision and one observational incision, the vertical vein was dissected and anastomosis with left atrial appendage. The patients recovered smoothly and postoperative CTPA showed anastomosis ostium was unobstructed. CONCLUSION: The left lateral thoracotomy and video assisted thoracoscopic surgery is a feasible for correction of left PAPVC with intact interatrial septum without using CPB.

Wearable biosensors for human sweat glucose detection based on carbon black nanoparticles.

Wearable glucose biosensors enable noninvasive glucose monitoring, thereby enhancing blood glucose management. In this work, we present a wearable biosensor based on carbon black nanoparticles (CBNPs) for glucose detection in human sweat. The biosensor consists of CBNPs, Prussian blue (PB), glucose oxidase, chitosan, and Nafion. The fabricated biosensor has a linear range of 5 µM to 1250 µM, sensitivity of 14.64 µA mM-1 cm-2, and a low detection potential (-0.05 V, vs. Ag/AgCl). The detection limit for glucose was calculated as 4.83 µM. This reusable biosensor has good selectivity and stability and exhibits a good response to glucose in real sweat. These results demonstrate the potential of our CBNP-based biosensor for monitoring blood glucose in human sweat.

Immune infiltration is associated with pan-cancer prognostic biomarker RING finger protein 187.

Cancer is associated with the highest mortality rate globally. While life-saving screening and treatments exist, better awareness is needed. RNF187, an E3 ligase regulating biological processes, belongs to the RING domain-containing E3 ligase family. RNF187 may serve as an oncogene due to abnormal expression in tumors. However, its association with immune infiltration and prognosis across various cancers remains unclear. We searched several databases including TCGA, GTE x, CCLE, TIMER, and GSEA. R software was used to evaluate RNF187 differential expression, survival, pathology stage, DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), gene co-expression analysis, mismatch repairs (MMRs), tumor microenvironment (TME), and immune cell infiltration. Clinicopathological data were collected, and immunohistochemistry was used to verify RNF187 expression in tumor tissues. RNF187 expression was up-regulated in various cancers compared to that in normal tissues and associated with poor patient outcomes. Dysregulation of RNF187 expression in multiple cancer types was strongly correlated with DNA methylation, MMR, MSI, and TMB. RNF187 could interact with different immune cells in cancers. Biomarkers associated with RNF187 may be helpful for prognosis and immunology in treating pan-cancer patients.

Preliminary study of low-pressure ionization chamber for online dose monitoring in FLASH carbon ion radiotherapy.

The FLASH effect of carbon ion therapy has recently attracted significant attention from the scientific community. However, the radiobiological mechanism of the effect and the exact therapeutic conditions are still under investigation. Therefore, the dosimetry accuracy is critical for testing hypotheses about the effect and quantifying FLASH Radiotherapy. In this paper, the FLASH ionization chamber at low-pressure was designed, and its dose rate dependence was verified with the Faraday cup. In addition, the dose response was tested under the air pressure of the ionization chamber of 10 mbar, 80 mbar and 845 mbar, respectively. The results showed that when the pressure was 10 mbar, the dose linearity was verified and calibrated at the dose rate of ∼50 Gy s-1, and the residuals were less than 2%. In conclusion, the FLASH ionization chamber is a promising instrument for online dose monitoring.

EGFR co-mutation is associated with the risk of recurrence in invasive lung adenocarcinoma with the micropapillary component.

BACKGROUND: Invasive lung adenocarcinoma (LUAD) patients with the micropapillary (MPP) component tend to have extremely poor prognosis. To optimize clinical outcomes, a better understanding of specific concurrent gene alterations and their impact on the prognosis of patients with the MPP component is necessary. METHOD: A total of 621 Chinese patients with surgically resected invasive LUAD who underwent genetic testing for lung cancer were enrolled in this retrospective study. The genomic profiling of major lung cancer-related genes based on next-generation sequencing (NGS) was carried out on formalin-fixed paraffin-embedded tumor samples. RESULT: Among 621 patients with invasive LUAD, 154 (24.8%, 154/621) had the MPP component. We found that PIK3CA (4.5% vs 1.3%), KRAS (9.1% vs 4.7%), and ROS1 (2.6% vs 0.4%) were more frequent in patients with the MPP component than those without the MPP component (P < 0.05). The co-mutation occurred in 66 patients (10.6%, 66/621), of which 19 patients with the MPP component. Most of them were EGFR co-mutations (89.5%, 17/19), including EGFR and PIK3CA, EGFR and ERBB2, and other types. Patients with the MPP component who harbored EGFR co-mutations showed significantly worse recurrence-free survival (RFS) than single EGFR mutation (median RFS 20.1 vs 30.5 months; hazard ratio [HR]: 8.008; 95% confidence interval [CI]: 1.322-48.508). CONCLUSIONS: Patients with the MPP component harbored the co-mutation of driver genes had a higher risk of recurrence after surgery, especially in patients with EGFR co-mutation. EGFR co-mutation was a significant prognostic factor for RFS in patients with the MPP component.

KPT330 promotes the sensitivity of glioblastoma to olaparib by retaining SQSTM1 in the nucleus and disrupting lysosomal function.

ABBREVIATIONS: AO: acridine orange; ATM: ATM serine/threonine kinase; CHEK1: checkpoint kinase 1; CHEK2: checkpoint kinase 2; CI: combination index; DMSO: dimethyl sulfoxide; DSBs: double-strand breaks; GBM: glioblastoma; HR: homologous recombination; H2AX: H2A.X variant histone; IHC: immunohistochemistry; LAPTM4B: lysosomal protein transmembrane 4 beta; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PARP: poly(ADP-ribose) polymerase; RAD51: RAD51 recombinase; SQSTM1: sequestosome 1; SSBs: single-strand breaks; RNF168: ring finger protein 168; XPO1: exportin 1.

Validation of the iHealth Track upper-arm blood pressure monitor KN-550BT in general population according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020).

OBJECTIVE: To validate the iHealth Track KN-550BT oscillometric upper-arm blood pressure monitor in general population according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020). METHODS: Participants were recruited and the same left-arm sequential method was used for blood pressure measurement according to the ISO 81060-2:2018+AMD1:2020. The validation results were assessed following the protocol and the Bland-Altman scatterplot was used to show the difference between the test device and reference results. RESULTS: A total of 89 qualified participants were included in the final analysis. For the validation Criterion 1, the mean ± SD of the differences between the test device and reference readings was -1.22 ±â€…5.76 mmHg and -0.08 ±â€…4.40 mmHg for systolic and diastolic blood pressure, respectively. For Criterion 2, the mean ± SD of the differences between the test device and reference readings per participant was -1.22 ±â€…5.06 mmHg and -0.08 ±â€…3.84 mmHg for systolic and diastolic blood pressure, respectively. CONCLUSION: The iHealth Track KN-550BT upper-arm blood pressure monitor passed all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020) and can be recommended for clinical use and self-measurement in general population.

Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases.

Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan-Meier method to find survival differences. All tumors in this study were negative for Epstein-Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death-ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence-to-death survival: 23 months versus 6 months); HAS patients who received anti-HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti-HER2 therapy, immunotherapy, and anti-angiogenesis therapy.