Nasopharyngeal Biopsy Research Articles

Microbes translocation from oral cavity to nasopharyngeal carcinoma in patients.

The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus(EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.

One world but miles apart: great mimicry of nasopharyngeal tuberculosis with nasopharyngeal carcinoma

Nasopharyngeal tuberculosis is rare, even in endemic areas. It can be primary or secondary to pulmonary or systemic tuberculosis. Although nasopharyngeal tuberculosis represents less than 1% of all tuberculosis cases, there has been an increase in cases reported recently. The variety of presenting symptoms in nasopharyngeal tuberculosis makes it challenging to diagnose because the condition commonly mimics other pathologies. In this paper, we would like to share our experience managing three cases of rare primary nasopharyngeal tuberculosis with different backgrounds. We provide a comparison in their clinical presentations, and endoscopic and radiological features, highlighting the situations when nasopharyngeal tuberculosis needs to be considered as a differential diagnosis. A nasopharyngeal biopsy is helpful to establish the diagnosis. The patients responded well to anti-tuberculosis chemotherapy. The variation in findings proves that it is important to have a high index of suspicion in order to get an accurate early diagnosis and initiate proper treatment.

HPV18 L1 and long control region sequences variation and E6/E7 differential expression in nasopharyngeal and cervical cancers: a comparative study

BackgroundThe role of high-risk human papillomaviruses (hr-HPVs) in cervical cancer (CC) pathogenesis has long been established. Knowledge about the involvement of hr-HPVs in the etiology of nasopharyngeal cancers (NPC) was not well appreciated until the early 2000s when a clear link began to emerge. However, it is not clear whether HPV oncogenesis in the different epithelial cancers is associated with L1 gene and long-control region (LCR) sequences variation. This study aimed to investigate the HPV18 L1 gene and LCR sequences variation in cervical and nasopharyngeal biopsies, and assessed E6 and E7 genes expression level in both cancers.MethodFour-hundred and three (403) formalin-fixed paraffin-embedded tissues originating from nasopharyngeal (NPC) (279) and cervical (CC) (124) sites were collected from a pathology laboratory, Pathologist Without Borders, Accra, Ghana. Haematoxylin and eosin staining was carried out to confirm the presence of cancer on prepared biopsy sections. DNA was extracted from the confirmed cancer biopsies, followed by PCR using MY09/GP5+ /6+ primers to detect the presence of HPV and specific primers for the amplification of L1 gene and LCR. Sanger sequencing was carried out to determine HPV genotypes, and L1 and LCR sequences variant of HPV18s in CC and NPC biopsies. The HPV18 E6/E7 mRNA expression pattern in both cancers was determined using RT-qPCR.ResultsMost of the NPC (45%) and CC (55%) biopsies were HPV18 positive. Comparison of HPV18 L1 sequences obtained from cervical and nasopharyngeal cancer tissues, the L1 sequences from the NPC were highly dissimilar with a 59–100% variation among themselves, and in relation to the reference strains. However, the L1 sequences from the CC were more similar with a 91.0–100% variation among the amplified sequences. Also, the LCR sequences from CC were quite different relative to that of NPC. Results for the differential expression of E6/E7 in the two cancers showed a higher fold change in E6 expression in the CC tissues than the NPC tissues while a reverse expression pattern was found for E7 gene.ConclusionThe current study reports for the first-time variations in HPV18 L1 and LCR sequences, and differential expression of E6/E7 genes in NPC compared to CC, suggesting a possible adaptation mechanism of the virus at different cancer sites.

Nasopharyngeal masses in adults—A retrospective analysis of 255 patients to evaluate symptoms, clinical findings, and histological results

AbstractBackgroundNasopharyngeal tissue hyperplasia is generally associated with adenoids in childhood. In adults, nasopharyngeal masses are occasionally found, but data on symptoms, clinical findings, and histologic results are limited.Material and MethodsA 10‐year retrospective study was conducted, analyzing data from adult patients who underwent nasopharyngeal biopsies. The study included information on case history, preoperative suspected diagnosis, and histology type. Statistical analysis was performed.ResultsTwo hundred and fifty‐five patients were included, most of them complaining of nasal obstruction, ear pressure, and hearing loss. Biopsy revealed adenoid tissue (64.7%), solid malignancies (15.7%; dominant undifferentiated carcinoma), lymphomas (9.0%), cysts (7.8%), and other benign tumors (2.7%). Malignant neoplasms were predominantly found in male and in elderly patients (P < 0.0001). If a malignant tumor was suspected initially, histological examination confirmed this in 75% of the cases. 45% of patients with a malignant nasopharyngeal mass had a unilateral seromucous tympanum.ConclusionsPersistent nasopharyngeal masses in adults—particularly in elderly men, smokers and those with simultaneous unilateral seromucous tympanum—should undergo a histological examination.

Lumbar metastases in nasopharyngeal carcinoma (NPC) patient with uncomplete chemoradiation

Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. In Indonesia, NPC is the 4th most prevalent. Nasopharyngeal Carcinoma stage IVB as distant metastasis. The therapy in nasopharyngeal carcinoma (NPC) is Chemoradiotherapy. Concurrent chemoradiotherapy is either an established treatment modality or actively being investigated. Chemoradiotherapy have demonstrated decreased incidence of distant metastases compared with radiation only, however only if its treatment done completely. Here we present a rare case of unfinished chemoradiotherapy that caused metastases nasopharyngeal carcinoma patient. A 41-years-old consulted to ENT-HN department with main complaints of progressive cancer pain for 3 month and got worse in past 1 month. Patient also complaints for the pain at the waist, chest and headache currently. However, there was formal history of nasopharyngeal carcinoma for this patient since 2019 that had been treated with 3 cycles of chemotherapy and 26 cycles of radiotherapy. The patient was diagnosed with recurrent nasopharyngeal carcinoma post chemotherapy and radiotherapy with metastatic process. Unfortunately, the treatment underwent was not complete. A nasopharyngeal biopsy was performed and the histopathology result revealed a non-keratinizing squamous cell carcinoma nasopharynx. Lumbar CT-scan showed distant metastatic to lumbar vertebrae I-V. Nasopharyngeal carcinoma (NPC) represents a rare disease that showed as carcinoma that appears in the nasopharynx. The unfinished treatment of NPC leads to recurrent NPC and metastatic process to lumbar vertebrae I-V. Nevertheless, 20% of patients are radioresistant and experience a recurrence, which in most cases manifests with distant metastases.

Sinonasal Burkitt Lymphoma in a 2-Year-Old Child: An Uncommon Case Report.

Burkitt Lymphoma (BL) is a highly aggressive B-type non-Hodgkin lymphoma. It rarely develops at the level of the sinonasal cavities, especially in young children. We present the case of a 2-year-old boy who presented with a 2-month history of nasal obstruction, snoring, and epistaxis followed by a recent dyspnea. Examination revealed a protruding tissue mass in the left nasal cavity. Computed tomography scan showed a homogenous soft-tissue mass in the left nasal cavity extending toward the ipsilateral orbit, infratemporal fossa, nasopharynx, as well as the ethmoid and maxillary sinuses. Magnetic resonance imaging revealed a homogenous infiltrating mass with a hypo-intense signal on T2-weighted images reaching the infratemporal fossa and oropharynx. Biopsy confirmed the diagnosis of BL. The patient was referred to the clinical hematology department and received complex chemotherapy. Following chemotherapy, imaging revealed significant regression of the mass. We performed a nasopharyngeal biopsy which confirmed the absence of any persistent disease. This case report highlights a rare case of an extensive sinonasal BL emphasizing the importance of a high level of suspicion to ensure an early diagnosis and treatment.

A touch-free human-robot collaborative surgical navigation robotic system based on hand gesture recognition.

Robot-assisted minimally invasive surgery (RAMIS) has gained significant traction in clinical practice in recent years. However, most surgical robots rely on touch-based human-robot interaction (HRI), which increases the risk of bacterial diffusion. This risk is particularly concerning when surgeons must operate various equipment with their bare hands, necessitating repeated sterilization. Thus, achieving touch-free and precise manipulation with a surgical robot is challenging. To address this challenge, we propose a novel HRI interface based on gesture recognition, leveraging hand-keypoint regression and hand-shape reconstruction methods. By encoding the 21 keypoints from the recognized hand gesture, the robot can successfully perform the corresponding action according to predefined rules, which enables the robot to perform fine-tuning of surgical instruments without the need for physical contact with the surgeon. We evaluated the surgical applicability of the proposed system through both phantom and cadaver studies. In the phantom experiment, the average needle tip location error was 0.51 mm, and the mean angle error was 0.34 degrees. In the simulated nasopharyngeal carcinoma biopsy experiment, the needle insertion error was 0.16 mm, and the angle error was 0.10 degrees. These results indicate that the proposed system achieves clinically acceptable accuracy and can assist surgeons in performing contactless surgery with hand gesture interaction.

Diagnosis of nasopharyngeal carcinoma with convolutional neural network on narrowband imaging

Objective:To evaluate the diagnostic accuracy of the convolutional neural network（CNN） in diagnosing nasopharyngeal carcinoma using endoscopic narrowband imaging. Methods:A total of 834 cases with nasopharyngeal lesions were collected from the People's Hospital of Guangxi Zhuang Autonomous Region between 2014 and 2016. We trained the DenseNet201 model to classify the endoscopic images, evaluated its performance using the test dataset, and compared the results with those of two independent endoscopic experts. Results:The area under the ROC curve of the CNN in diagnosing nasopharyngeal carcinoma was 0.98. The sensitivity and specificity of the CNN were 91.90% and 94.69%, respectively. The sensitivity of the two expert-based assessment was 92.08% and 91.06%, respectively, and the specificity was 95.58% and 92.79%, respectively. There was no significant difference between the diagnostic accuracy of CNN and the expert-based assessment （P=0.282, P=0.085）. Moreover, there was no significant difference in the accuracy in discriminating early-stage and late-stage nasopharyngeal carcinoma（P=0.382）. The CNN model could rapidly distinguish nasopharyngeal carcinoma from benign lesions, with an image recognition time of 0.1 s/piece. Conclusion:The CNN model can quickly distinguish nasopharyngeal carcinoma from benign nasopharyngeal lesions, which can aid endoscopists in diagnosing nasopharyngeal lesions and reduce the rate of nasopharyngeal biopsy.

Hairy gene homolog increases nasopharyngeal carcinoma cell stemness by upregulating Bmi-1

B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is overexpressed in various cancer types. We found that Bmi-1 mRNA levels were elevated in nasopharyngeal carcinoma (NPC) cell lines. In immunohistochemical analyses, high Bmi-1 levels were observed in not only 5 of 38 non-cancerous nasopharyngeal squamous epithelial biopsies, but also in 66 of 98 NPC specimens (67.3%). High Bmi-1 levels were detected more frequently in T3-T4, N2-N3 and stage III-IV NPC biopsies than in T1-T2, N0-N1 and stage I-II NPC samples, indicating that Bmi-1 is upregulated in advanced NPC. In 5-8F and SUNE1 NPC cells, stable depletion of Bmi-1 using lentiviral RNA interference greatly suppressed cell proliferation, induced G1-phase cell cycle arrest, reduced cell stemness and suppressed cell migration and invasion. Likewise, knocking down Bmi-1 inhibited NPC cell growth in nude mice. Both chromatin immunoprecipitation and Western blotting assays demonstrated that Hairy gene homolog (HRY) upregulated Bmi-1 by binding to its promoter, thereby increasing the stemness of NPC cells. Immunohistochemistry and quantitative real-time PCR analyses revealed that HRY expression correlated positively with Bmi-1 expression in a cohort of NPC biopsies. These findings suggested that HRY promotes NPC cell stemness by upregulating Bmi-1, and that silencing Bmi-1 can suppress NPC progression.

A Rare Case of Aggressive Disseminated Nasal-Type Epstein-Barr Virus-Positive Extranodal Natural Killer/T-Cell Lymphoma with Bone Marrow Involvement.

BACKGROUND Nasal-type extranodal natural killer/T-cell lymphoma (ENKL) is an exceedingly rare and aggressive subtype of non-Hodgkin lymphoma. The malignancy has both a high morbidity and mortality and is most commonly discovered in patients with advanced stages of the disease. As a result, early detection and treatment is tantamount to improving survival and minimizing lasting effects. CASE REPORT Herein, we report a case of nasal-type ENKL in a woman with facial pain and associated nasal and eye discharge. We highlight the histopathologic features from nasopharyngeal and bone marrow biopsy, which demonstrated Epstein-Barr virus-positive biomarkers of diffuse and subtle involvement, respectively, with associated chromogenic immunohistochemical staining. We also highlight existing therapy utilizing a combination of chemotherapy with radiation, as well as consolidation therapy, and suggest the need for further research of allogeneic hematopoietic stem cell treatment and the potential of programmed death ligand 1 (PD-L1) inhibition in managing nasal-type ENKL malignancy. CONCLUSIONS Nasal-type ENKL is a rare subtype of non-Hodgkin lymphoma that is infrequently associated with bone marrow involvement. The malignancy has a poor prognosis overall and typically is discovered late in the disease course. Current treatment favors utilization of combined modality therapy. However, previous studies have been inconsistent in determining whether chemotherapy or radiation therapy can be used alone. Additionally, promising results have also been shown with chemokine modulators, including antagonistic drugs that target PD-L1, in refractory and advanced cases.

LMP1-EBV Gene Deletion Mutations and HLA Genotypes of Nasopharyngeal Cancer Patients in Vietnam.

Nasopharyngeal carcinoma (NPC) is the most common cancer among head and neck cancers in Vietnam. We aimed to identify the rate of a 30 bp deletion mutation of the LMP1-EBV gene in nasopharyngeal biopsy tissue samples, the HLA genotypes of NPC patients, and the relationship between these two targets. Patients with NPC at Can Tho Oncology Hospital from September 2014 to December 2018 were selected. A length of 30 bp of the del-LMP1-EBV gene was analyzed using a PCR technique, and the HLA genotypes in patients' blood samples were analyzed with PCR-SSO technology. HLA-B*15 gene carriers had the highest risk of 30 bp LMP1-EBV gene deletion mutation, which was found in 51 out of 70 patients (72.9%). Carriers of the HLA-B*15 allele had a 4.6-fold increased risk of a 30 bp del-LMP1-EBV gene compared with non-carriers of this allele. The initial identification of NPC was related to the 30 bp del-LMP1-EBV gene and high frequencies of the -A*02, -B*15, -DRB1*12, -DQB1*03, and -DQA1*01 HLA alleles. Our study results suggest an association of the 30 bp del-LMP1-EBV gene and the HLA-B*15 allele with NPC susceptibility.

The human oral - nasopharynx microbiome as a risk screening tool for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common head and neck cancer with a poor prognosis. There is an urgent need to develop a simple and convenient screening tool for early detection and risk screening of NPC. 139 microbial samples were collected from 40 healthy people and 39 patients with nasopharyngeal biopsy. A total of 40 and 39 oral, eight and 27 nasal cavity, nine and 16 nasopharyngeal microbial samples were collected from the two sets of individuals. A risk screening tool for NPC was established by 16S rDNA sequencing and random forest. Patients with nasopharyngeal biopsy had significantly lower nasal cavity and nasopharynx microbial diversities than healthy people. The beta diversity of the oral microbiome was significantly different between the two groups. The NPC screening tools based on nasopharyngeal and oral microbiomes have 88% and 77.2% accuracies, respectively. The nasopharyngeal biopsy patients had significantly higher Granulicatella abundance in their oral cavity and lower Pseudomonas and Acinetobacter in the nasopharynx than healthy people. This study established microbiome-based non-invasive, simple, no radiation, and low-cost NPC screening tools. Individuals at a high risk of NPC should be advised to seek further examination, which might improve the early detection of NPC and save public health costs.

Novel Genetic Variant of 30-bp Deletion: A Polymorphism of Latent Membrane Protein 1 from Vietnamese Epstein Barr Virus-Associated Nasopharyngeal Carcinoma Biopsies

Novel Genetic Variant of 30-bp Deletion: A Polymorphism of Latent Membrane Protein 1 from Vietnamese Epstein Barr Virus-Associated Nasopharyngeal Carcinoma Biopsies

Correlation of LMP-1 Expression with BCL11B in Undifferentiated Type Nasopharyngeal Carcinoma

Background: Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Asia and in Indonesia with a high incidence and mortality. The high mortality rate of patients with NPC is caused by recurrence and metastases early in the disease process, even though they have been given a combination of standard NPC therapy, namely radiotherapy and chemotherapy. Recurrences generally occur after the initial modalities of radiotherapy. Toxicity due to therapy given over a long time can also increase mortality. This study aims to determine the expression of BCL11B in undifferentiated NPC and its correlation with LMP-1 so that it can provide an overview of the nature of CSC in NPC, which is thought to cause recurrence and metastases and provide a poor prognosis in patients with NPC.
 Methods: This study was an analytical observational study using a cross-sectional approach using 30 samples from nasopharyngeal biopsy tissue diagnosed with undifferentiated NPC at the anatomical pathology installation of Dr. Saiful Anwar General Hospital, Malang, Indonesia, between 2018-2020. LMP-1 and BCL11B expression was examined using the immunohistochemical method. Data analysis was performed univariate and bivariate with the help of SPSS software. 
 Results: Statistical analysis using the Spearman correlation test between LMP-1 and BCL11B expression in undifferentiated NPC biopsy tissue showed a significant correlation (p=0.004) with a correlation coefficient of r=-0.511.
 Conclusion: The higher the expression of LMP-1, the lower the expression of BCL11B in nasopharyngeal biopsies of patients with undifferentiated.

Retrospective analysis of clinical features and prognosis of nasopharyngeal carcinoma in children and adolescents.

ObjectivesTo investigate the clinical characteristics and prognosis of nasopharyngeal carcinoma (NPC) in children and adolescents in different age groups.Materials and methodsThe clinical data of 51 patients with NPC aged ≤ 18 years who were treated in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to May 2017 were retrospectively analyzed. The patients were divided into children group (≤12 years old) and adolescent group (12–18 years old) with 12 years old as the boundary. The clinical characteristics, diagnosis, treatment, and prognosis of the children and adolescent groups were compared.ResultsThe symptoms of the first diagnosis in the children group were mainly nasal congestion (P = 0.043) and ear symptoms (P = 0.008). The diagnosis rate of nasopharyngeal biopsy in the children group was lower (P = 0.001), while the rate of diagnosis of cervical mass biopsy was significantly higher than that in the adolescent group (P = 0.009). The proportion of keratinizing squamous cell carcinoma of the children group was higher than that of the adolescent group (P = 0.006). There was no significant difference in TNM stage and risk stratification between the two groups, but the number of cases in the III-IVa children group who received induction chemotherapy + concurrent chemoradiotherapy was less than that in the adolescent group (P = 0.013). The proportion of radiotherapy in the upper and lower cervical lymph node drainage areas was lower than that in the adolescent group (P = 0.001). The percentage of recurrence and metastasis in the children group was higher than that in the adolescent group (P = 0.026).ConclusionThe diagnosis in the children group depended on endoscopic biopsy and neck mass biopsy, and the proportion of keratinizing squamous cell carcinoma was higher. The number of cases of induction chemotherapy and concurrent chemoradiotherapy in the children group was less than that in the adolescent group, and the proportion of radiotherapy in the upper and lower cervical lymph node drainage areas was lower than that in the adolescent group. Clinically, it is necessary to improve the understanding of the clinical characteristics of children with NPC and take appropriate treatment strategies.

Focal Nasopharyngeal Activity Detected on [18F]FDG PET/CT: Clinical Implications and Comparison of Metabolic Parameters for Prediction of Malignancy.

We aimed to investigate the incidence and clinical significance of incidental focal nasopharyngeal uptake on [18F]FDG PET/CT and to evaluate the diagnostic performance of various metabolic parameters to differentiate between benign and malignant nasopharyngeal lesions. A total of 63 consecutive patients with incidental focal nasopharyngeal uptake on [18F]FDG PET/CT and subsequent nasopharyngeal biopsy were retrospectively enrolled. In addition, baseline pretherapeutic [18F]FDG PET/CT images of 59 patients with newly diagnosed pathologically proven nasopharyngeal carcinoma (NPC) were reviewed. Maximum standardized uptake value (SUVmax), mean SUV (SUVmean), nasopharynx-to-palatine tonsil ratio (NPR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the nasopharyngeal lesions were determined. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the metabolic parameters. Incidental focal nasopharyngeal uptake in two patients (3.2%, 2/63) was pathologically confirmed to be NPC. All the metabolic parameters (SUVmax, SUVmean, NPR, MTV, and TLG) demonstrated significantly greater values in patients with NPC compared with patients with benign or physiological nasopharyngeal uptake (p < 0.001). Among the metabolic parameters, NPR demonstrated the greatest area under the curve of 0.992 (p < 0.05), with a sensitivity of 96.7% and a specificity of 93.4% when a cut-off of 1.1 was used. Similar results were seen in nasopharyngeal lesions without morphological abnormality. NPC is an infrequent but important cause of incidental focal nasopharyngeal uptake on [18F]FDG PET/CT. Metabolic parameters were shown to be useful to differentiate between benign and malignant nasopharyngeal lesions, and NPR showed the best diagnostic performance.

Epstein-Barr viral product-containing exosomes promote fibrosis and nasopharyngeal carcinoma progression through activation of YAP1/FAPα signaling in fibroblasts

BackgroundThe progression of nasopharyngeal carcinoma (NPC) is profoundly affected by Epstein-Barr virus (EBV) infection. However, the role of EBV in the intercommunication between NPC and surrounding stromal cells has yet to be explored.MethodsNPC biopsies were obtained for immunohistochemical (IHC) analyses. Clinical correlations between the expression of active YAP1/FAPα and the fibrotic response and between YAP1/FAPα and the density of cytotoxic CD8a+ T lymphocytes were determined. Survival times based on IHC scores were compared between groups using Kaplan-Meier survival and log-rank tests. Independent prognostic factors for metastasis/recurrence-free survival and overall survival were identified using univariate and multivariate Cox regression models. Fibroblasts were isolated from human nasopharyngeal biopsies. Exosomes were purified from culture supernatants of EBV+-positive NPC cells. The effects of EBV product-containing exosomes on fibroblast activation, fibrotic response, tumor growth, immune response, and correlations between the expression of featured genes were investigated using gel contraction assays, ELISAs, EdU incorporation assays, real-time impedance assays, RNA sequencing, immunostaining, 3D cancer spheroid coculture systems, and an NPC xenograft model.ResultsNPC patients who developed metastasis had significantly higher levels of active YAP1 and FAPα in their tumor stroma, which was further correlated with tumor fibrosis and poorer metastasis-free survival. Exosomes released from EBV+-NPC cells contained abundant FAPα protein and EBV-encoded latent membrane protein 1. Viral product-containing exosomes markedly enhanced the fibrotic response and tumor growth in a mouse xenograft model. IHC analyses of human NPC and NPC xenografts revealed positive correlations between levels of active YAP1 and FAPα, YAP1 and the fibrotic response, and FAPα and the fibrotic response. Mechanistic studies showed that treatment of fibroblasts with viral product-containing exosomes promoted the characteristics of cancer-associated fibroblasts by stimulating YAP1 signaling and the production of the immunosuppressive cytokines IL8, CCL2, and IL6. Inhibition of YAP1 activation markedly reversed these exosome-mediated protumoral effects, resulting in reduced contractility, inactivation of YAP1 signaling, and decreased production of immunosuppressive cytokines in fibroblasts. Furthermore, fibroblasts stimulated with these viral product-containing exosomes promoted NPC resistance to T cell-mediated cytotoxicity within tumor spheroids. In NPC tissues, a significant negative correlation was found between YAP1/FAPα and the density of CD8a+ T lymphocytes with a granzyme B signature.ConclusionEBV orchestrates interactions with the host and surrounding stroma by stimulating the functions of YAP1 and FAPα in fibroblasts through exosome cargos to create a more immunosuppressive, proinvasive microenvironment.

MDM2 is a useful diagnostic marker for nasopharyngeal carcinoma

BackgroundThe MDM2 gene appears to be involved in the development of nasopharyngeal carcinoma. The aim of this study was to examine MDM2 expression in a series of nasopharyngeal carcinoma biopsies to explore its potential diagnostic significance. MethodsThe study cohort consisted of 26 nasopharyngeal carcinomas, including 22 EBV positive non-keratinizing squamous cell carcinomas (NKSCC), 1 EBV negative NKSCC and 3 EBV negative keratinizing SCC. For comparison, we selected 48 oropharyngeal carcinomas, including 17 HPV positive SCC (14 non-keratinizing and 3 keratinizing) and 31 HPV negative SCCs (28 keratinizing and 3 non-keratinizing). In addition, we examined MDM2 expression in a group of 26 cervical lymph node metastases, including 5 with EBV positive nasopharyngeal NKSCC and 21 from oropharyngeal carcinoma (18 non keratinizing HPV positive, 1 keratinizing HPV positive, 1 keratinizing HPV negative and 1 non-keratinizing HPV negative). Finally, 2 bone metastases from EBV positive nasopharyngeal NKSCC were also included. A tissue microarray was constructed from formalin-fixed paraffin embedded tumor tissue specimens. Sections were immunostained for MDM2 and in situ hybridization for EBER and CISH analysis for the MDM2 gene were also conducted in all cases. ResultsOverall, MDM2 positivity was detected in 28 of 102 SCCs (27.2 %). MDM2 positivity was significantly more frequent in EBV positive NKSCC (80 %) than in oropharyngeal HPV positive NKSCC (6.1 %) and keratinizing SCCs (9.4 %) (p < 0.001, Pearson chi square). Considering only the primary tumors, 86.4 % of the nasopharyngeal carcinomas were positive, versus 13.5 % of the oropharyngeal carcinomas (p < 0.001, Pearson chi square). Considering the lymph node metastases, 3 of 5 EBV positive carcinomas with nasopharyngeal primary were positive, whereas only one of the HPV positive carcinomas was positive. Finally, both the bone metastases from EBV positive nasopharyngeal carcinoma were positive for MDM2. No amplification of the MDM2 gene was identified by in situ hybridization analysis. ConclusionsOur data indicate that MDM2 could be a valuable diagnostic marker to support the diagnosis of nasopharyngeal EBV positive NKSCC.

Expression of pepsin in nasopharyngeal carcinoma and its correlation with quality of life after radiotherapy

Objective: By analyzing the expression of pepsin in nasopharyngeal carcinoma (NPC) tissues, to investigate the correlation between laryngeal reflux (LPR) and NPC, as well as the effect of LPR on the quality of life of patients with NPC after radiotherapy. Methods: A total of 133 patients with NPC who underwent radiotherapy at the Department of Otorhinolaryngology of the Affiliated Hospital of Guizhou Medical University and the Affiliated Cancer Hospital of Guizhou Medical University from 2005 to 2019 were enrolled consecutively, including 90 males and 43 females, aged (44.32±7.47) years old. At the same period, 58 patients with chronic nasopharyngitis who underwent nasopharyngeal biopsy were selected as the control group. Immunohistochemical method was used to detect the expression of pepsin in nasopharyngeal specimens of the two groups. In addition, 188 normal individuals were selected as the normal group in the same period. NPC patients before and within 6 months after radiotherapy were inverstigated by the General Information Questionnaire and the Quality of Life Scale, and the pepsin levels in saliva of NPC patients before and after radiotherapy and the individuals in normal group were measured. SPSS 21.0 software was used for statistical analysis. Results: Pepsin expression in 133 specimens of NPC patients was strongly positive in 24 cases (18.05%), positive in 21 cases (15.79%), weakly positive in 69 cases (51.88%), and negative in 19 cases (14.29%). The specimens of control group had 10 cases of weakly positive (17.24%), 48 cases of negative (82.76%), but no strong positive or positive pepsin expression. The rate of positive pepsin expression in the NPC group was higher than that in the control group, with a statistically significant (χ2=83.15, P<0.001). The pepsin content in the saliva of NPC patients after radiotherapy ((30.31±7.82) ng/ml) was higher than that before radiotherapy ((20.47±8.21) ng/ml) and the normal group (5.11±2.13) ng/ml), and the pepsin content in saliva before radiotherapy was higher than that in the normal group, and all differences were statistically significant (all P<0.05). After radiotherapy, the five functional domains of quality of life and overall quality of life of NPC patients decreased, while the related symptom scores increased (all P<0.05). Multiple linear regression analysis showed that pepsin content in saliva was the influential factor of five functional domains of quality of life, related symptoms and overall quality of life in NPC patients after radiotherapy (all P<0.05). Conclusion: The positive rate of pepsin expression in NPC tissues is high, and the pepsin in saliva before and after radiotherapy of NPC patients is significantly higher than that in normal, suggesting that LPR may be involved in the process of NPC and affect the quality of life after radiotherapy in NPC patients.

P.116 Not everything is what it seems, look closer, think deeper: granulomatosis with polyangiitis

Background: Granulomatosis with polyangiitis (GPA) is a rare disease of unknown cause. The multitude of manifestations presents significant diagnostic challenges. This is a unique case of GPA with sinonasal, airway, skull base, petrous bones, vascular, and brain parenchyma involvement. Methods: We present a case of a 45-year-old female with a several day history of headache and left hearing loss. MRI brain demonstrated a large erosive enhancing soft process in the sinonasal cavity and nasopharynx. Results: She developed new ipsilateral rightward tongue deviation. A second MRI demonstrated disease progression. It showed posterior pharyngeal wall ulceration, involvement of the skull base foramina, petrous bones, and central bony skull erosion. It demonstrated right hemiglossal edema secondary to right hypoglossal nerve compression at the skull base. There was enhancing soft tissue partially encasing the left petrous internal carotid artery and more extensively encasing and narrowing bilateral intradural vertebral arteries with associated brainstem edema secondary to direct mass effect and new left occipital thromboembolic infarct. She underwent a nasopharyngeal biopsy which demonstrated acute inflammation on a background of GPA. Conclusions: There are no pathognomonic imaging characteristics for GPA. By recognizing the common and less-common imaging features, radiologists play a crucial role in both diagnosing and monitoring the disease activity.