RESUMEN
RATIONALE: Hyalinizing clear cell carcinoma (HCCC) arising from a minor salivary gland is a rare malignant neoplasm. Most HCCC has been reported in the palate and tongue base, and only rarely in the nasopharynx. Here, we report a rare case of nasopharyngeal HCCC. PATIENT CONCERNS: A 44-year-old male who complained of otorrhea and aural fullness for 5 years was found to have a nasopharyngeal mass. DIAGNOSES: HCCC by fluorescence in situ hybridization analysis. INTERVENTIONS: Surgical resection plus concurrent chemotherapy and radiation therapy were administered. OUTCOMES: The patient recovered well with symptoms improved at postoperative follow-up. LESSONS: HCCC should be included in the differential diagnosis of nasopharyngeal mass. Overall, the prognosis of HCCC is positive after tumor resection and adequate management.
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Adenocarcinoma de Células Claras , Neoplasias Nasofaríngeas , Humanos , Masculino , Adulto , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/cirugía , Neoplasias Nasofaríngeas/patología , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/terapia , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/cirugía , Diagnóstico DiferencialRESUMEN
Background: IgG4-related disease (IgG4-RD) was characterized by single or multiple masses in organs, which may mimic various inflammatory and malignant diseases. Here, we summarize 4 patients with aggressive manifestations of IgG4-RD that mimic nasopharynx cancer to provide some new sights for the diagnosis of IgG4-RD. Case summary: Four patients were included in our series. The age ranged from 53 to 64 years old, and the duration of the disease ranged from 4 to 6 months. The chief complaints included headache, rhinorrhea, or diplopia. All patients had more than 10 IgG4+ plasma cells/HPF in immunohistochemistry with plasma lgG4 levels ranging from 218 mg/dL to 765 mg/dL. All of them met the diagnostic criteria of lgG4-RD. Conclusion: The described case is highly similar to the clinical manifestations of nasopharyngeal carcinoma. Although pathology is the gold standard, there are still limitations. Serological IgG4 can help confirm the diagnosis. Timely diagnosis of IgG4-RD is of great significance in preventing secondary organ damage in patients with active diseases.
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Enfermedad Relacionada con Inmunoglobulina G4 , Inmunoglobulina G , Neoplasias Nasofaríngeas , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/inmunología , Persona de Mediana Edad , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/diagnóstico , Masculino , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Diagnóstico Diferencial , Femenino , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/inmunología , Células Plasmáticas/inmunologíaRESUMEN
BACKGROUND: Nasopharyngeal amyloidoma is a rare, locally aggressive tumor that has been reported in the English literature in only 38 cases to date, most of which were in the form of case reports. The present study was aimed to summarize the characteristics of this rare tumor, with the goal of providing new insights for diagnosis and treatment. MATERIALS AND METHODS: We report three cases of nasopharyngeal amyloidoma diagnosed in our hospital following comprehensive medical examination and review the current literature on all cases of nasopharyngeal amyloidoma from PubMed. The journey of nasopharyngeal amyloidoma, including presentation, diagnostics, surgeries, and follow-up was outlined. RESULTS: None of the three patients had systemic amyloidosis. CT and nasal endoscopy showed irregular masses obstructing the nasopharyngeal cavity. Congo red staining confirmed the deposition of amyloid, and immunohistochemical analysis showed that the amyloid deposition was the AL light chain type. Through literature review, we found that nasopharyngeal amyloidoma most commonly occurred in individuals over the age of 40, patients usually had a good prognosis after complete tumor resection; however, there were still cases of recurrence, and unresected patients were at risk of progression to systemic amyloidosis. The efficacy of radiotherapy and chemotherapy was currently uncertain. CONCLUSION: Early clinical and pathological diagnosis is crucial, and surgical intervention is the primary treatment option for this disease. Although patients usually have a favorable prognosis, long-term monitoring is necessary to detect potential relapses and initiate timely intervention.
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Amiloidosis , Neoplasias Nasofaríngeas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Amiloidosis/patología , Amiloidosis/diagnóstico , Amiloidosis/metabolismo , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/cirugía , Adulto , Enfermedades Nasofaríngeas/patología , Enfermedades Nasofaríngeas/diagnóstico , Enfermedades Nasofaríngeas/metabolismo , Enfermedades Nasofaríngeas/cirugíaRESUMEN
Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.
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Biomarcadores de Tumor , ADN Tumoral Circulante , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Humanos , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Masculino , Femenino , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/sangre , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/diagnóstico , Adulto , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/diagnóstico , Estudios Longitudinales , ADN Viral/sangre , Estudios Prospectivos , Anciano , Pronóstico , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Biopsia Líquida/métodos , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicacionesRESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma arising from the nasopharyngeal mucosal lining. Diagnosis of NPC at early stage can improve the outcome of patients and facilitate reduction in cancer mortality. The most significant change between cancer cells and normal cells is the variation of cell nucleus. Therefore, accurately detecting the biochemical changes in nucleus between cancer cells and normal cells has great potential to explore diagnostic molecular markers for NPC. Highly sensitive surface-enhanced Raman scattering (SERS) could reflect the biochemical changes in the process of cell cancerization at the molecular level. However, rapid nuclear targeting SERS detection remains a challenge. RESULTS: A novel and accurate nuclear-targeting SERS detection method based on electroporation was proposed. With the assistance of electric pulses, nuclear-targeting nanoprobes were rapidly introduced into different NPC cells (including CNE1, CNE2, C666 cell lines) and normal nasopharyngeal epithelial cells (NP69 cell line), respectively. Under the action of nuclear localization signaling peptides (NLS), the nanoprobes entering cells were located to the nucleus, providing high-quality nuclear SERS signals. Hematoxylin and eosin (H&E) staining and in situ cell SERS imaging confirmed the excellent nuclear targeting performance of the nanoprobes developed in this study. The comparison of SERS signals indicated that there were subtle differences in the biochemical components between NPC cells and normal nasopharyngeal cells. Furthermore, SERS spectra combined with principal component analysis (PCA) and linear discriminant analysis (LDA) were employed to diagnose and distinguish NPC cell samples, and high sensitivity, specificity, and accuracy were obtained in the screening of NPC cells from normal nasopharyngeal epithelial cells. SIGNIFICANCE: To the best of our knowledge, this is the first study that employing nuclear-targeting SERS testing to screen nasopharyngeal carcinoma cells. Based on the electroporation technology, nanoprobes can be rapidly introduced into living cells for intracellular biochemical detection. Nuclear-targeting SERS detection can analyze the biochemical changes in the nucleus of cancer cells at the molecular level, which has great potential for early cancer screening and cytotoxicity analysis of anticancer drugs.
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Núcleo Celular , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Espectrometría Raman , Espectrometría Raman/métodos , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patología , Núcleo Celular/química , Núcleo Celular/metabolismo , Línea Celular Tumoral , Propiedades de Superficie , Nanopartículas del Metal/químicaRESUMEN
To investigate the expression of Inhibin B between various clinical stages, Chinese medicine dialectic typing, and in nasopharyngeal carcinoma (NPC) tissues and serum, and to evaluate the potential of Inhibin B as a new biomarker for NPC. Paraffin specimens of pathologically confirmed NPC tissues and paracancerous tissues were retrospectively collected, and the expression of Inhibin α (INHA) and Inhibin ßB (INHBB) was detected by SP method, and their relationship with clinicopathological indexes was analyzed; in addition, patients with NPC who had received radiotherapy were included as the study subjects, and Epstein-Barr virus DNA (EBV-DNA), INHA, and INHBB in patients were detected by using the fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and chemiluminescent immuno-sandwiching method, respectively. EBV-DNA, EBV-viral capsid antigen-immunoglobulin A (VCA IgA), INHA, and INHBB were detected in the patients, respectively, and their relationships with traditional Chinese medicine (TCM) patterns were also analyzed. The expression of INHA and INHBB in NPC tissues was lower than that in paracancerous tissues, and the expression of INHA in NPC patients was correlated with lymphatic metastasis, clinical staging, and TCM staging; the levels of EBV-DNA and VCA IgA were higher than that of healthy populations in NPC patients and were higher than that of patients with stage IIIâ +â IV than that of patients with stage Iâ +â II, and the levels of INHA and INHBB were lower than those of healthy populations and were lower than those of patients with stage IIIâ +â IV than that of patients with stage Iâ +â II. The levels of INHA and INHBB in nasopharyngeal cancer patients were lower than those in healthy people, and the levels in stage IIIâ +â IV patients were lower than those in stage Iâ +â II patients. The levels of EBV-DNA and VCA IgA in nasopharyngeal cancer patients were correlated with the Chinese medicine patterns, and had different patterns. The expression of Inhibin B may be related to the progression of NPC, and it has certain typing significance for different TCM syndromes of NPC, which is helpful for TCM typing diagnosis.
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Medicina Tradicional China , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Medicina Tradicional China/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , ADN Viral/análisis , ADN Viral/sangre , Inhibinas/sangre , Herpesvirus Humano 4/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/sangre , Estadificación de Neoplasias , Subunidades beta de Inhibinas/metabolismo , Subunidades beta de Inhibinas/sangre , Anciano , Antígenos Virales/sangre , Inmunoglobulina A/sangre , Proteínas de la CápsideRESUMEN
Purpose: This study aims to explore the prognostic values of routine pre-treatment hematological parameters in patients with nasopharyngeal carcinoma (NPC). Methods: The hematological parameters and clinical data of patients with NPC were collected from January 2012 to December 2013 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The survival statistics were obtained by regularly following-up the patients. The cut-off values for the hematological parameters were calculated using X-tile software. SPSS version 24.0 was used for the statistical analysis. The relationship between the hematological parameters and the prognosis of patients with NPC was analyzed using the Kaplan-Meier method and Cox multivariate regression. The discriminating abilities of the factors, which predict the prognosis, were evaluated by utilizing the receiver operating characteristic (ROC) area under the curve (AUC). Results: This study included 179 patients with NPC. Multivariate analysis shows that pretreatment platelet-to-lymphocyte ratio (PLR; hazard ratio; HR = 0.44, 95% CI [0.21-0.91], p = 0.029), serum albumin (ALB; HR = 2.49, 95% CI [1.17-5.30], p = 0.018), and globulin (GLO; HR = 0.44, 95% CI [0.21-0.90], p = 0.024) are independent predictors for 5-year overall survival (OS) in patients with NPC. In addition, pre-treatment PLR (HR = 0.47, 95% CI [0.25-0.90], p = 0.022) and pre-treatment GLO (HR = 0.37, 95% CI [0.19-0.72], p = 0.001) are associated with 5-year progression-free survival (PFS) in patients with NPC. Based on the results of the multivariate analysis, we proposed a new biomarker GLO-PLR, which is observably correlated with the T stage, N stage and clinical stage in patients with NPC. The OS resolving ability of the GLO-PLR evaluated by AUC is 0.714, which is better than those of GLO and PLR. The PFS resolving ability of the GLO-PLR evaluated by AUC was 0.696, which is also better than those of GLO and PLR. Conclusion: Pre-treatment PLR, ALB, and GLO are independent predictors of 5-year OS in patients with NPC, where PLR and GLO are also independent predictors of 5-year FPS. Compared with other hematological parameters, the proposed GLO-PLR is an inexpensive, effective, objective, and easy-to-measure marker for predicting the prognosis of NPC.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patología , Estudios Retrospectivos , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patología , Pronóstico , Adulto , Anciano , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Recuento de Plaquetas , Curva ROC , Estimación de Kaplan-Meier , Recuento de Linfocitos , Plaquetas/patologíaAsunto(s)
Algoritmos , Detección Precoz del Cáncer , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/genética , Detección Precoz del Cáncer/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Tamizaje Masivo/métodos , Estudios de Cohortes , Singapur/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVES: This investigation explores the clinical significance of integrating serum lactate dehydrogenase (LDH) with a multivariate model for assessing the short-term prognosis of primary nasopharyngeal carcinoma (NPC). Epstein-Barr virus (EBV) quantification is a crucial prognostic indicator in NPC cases, but not all patients with NPC test positive for EBV. Furthermore, widespread adoption of EBV-DNA quantification remains challenging due to its high cost. Consequently, it is imperative to incorporate additional convenient and cost-effective prognostic markers to comprehensively evaluate patient outcomes. METHODS: This retrospective analysis included 203 newly diagnosed NPC cases treated at the Affiliated Qingyuan Hospital of Guangzhou Medical University between January 2018 and March 2022. The dataset included personal information and clinical data, and the treatment protocols followed the CSCO guidelines. Efficacy assessments were based on the RECIST 1.1 criteria and were conducted after induction chemotherapy and one week and three months after radiotherapy. RESULTS: A noteworthy correlation emerged between baseline serum LDH levels and treatment efficacy at one week after radiotherapy (P = 0.03) and at three months after radiotherapy (P < 0.01). Additionally, a prognostic model that incorporates age (P = 0.010), LDH (P < 0.001), C-reactive protein (P = 0.010), and alkaline phosphatase (P = 0.005) demonstrated robust predictive accuracy and clinical applicability. CONCLUSION: This investigation substantiates the significant correlation between baseline serum LDH levels and NPC outcomes. Furthermore, we introduce a refined prognostic model that holds promise for informing personalized treatment strategies, thereby contributing to the advancement of the diagnosis of NPC.
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L-Lactato Deshidrogenasa , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Femenino , Masculino , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , L-Lactato Deshidrogenasa/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Pronóstico , Adulto , Anciano , Biomarcadores de Tumor/sangre , Herpesvirus Humano 4/aislamiento & purificación , Resultado del Tratamiento , Adulto Joven , Análisis Multivariante , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/sangre , Relevancia ClínicaRESUMEN
A 2-year-old Norwegian Forest cat was presented for evaluation of bilateral purulent nasal discharge and stertorous breathing. A computed tomography (CT) scan of the head revealed an intranasal mass of the left nasal cavity extending behind the tube openings and completely obstructing the nasopharynx. Rhinoscopy confirmed a pinkish, shiny mass. CT scan showed both compartments of the right middle ear filled with abnormal soft tissue attenuating material. There was no change in the bony outline of the middle ear. In the endoscopic examination, after endoscopically assisted tympanocentesis, this material in the accessible dorsolateral compartment proved to be classic polypous tissue in addition to highly viscous glue-like secretions. A secondary otitis media due to a drainage disorder was suspected.Using an endoscopic-interventional approach through the nostril, the nasopharyngeal mass was removed for histopathological examination, in order to restore the nasal airway, and to allow tube drainage. In contrast to cats with classical malignant nasal cavity masses, the cat showed several attachment points of the mass and multiple undulating elevations bilaterally in the nasopharyngeal mucosa.Cytological and histopathological examination identified the mass as a fungal granuloma in the context of a cryptococcus infection only rarely observed in Germany. Molecular genetic analysis confirmed an infection with Cryptococcus neoformans var. grubii.A single intranasal and nasopharyngeal endoscopic debridement resulted in a significant improvement of the clinical signs and a complete healing of the right middle ear (including the tympanic membrane) within 14 days, but not in a complete cure of the disease. The cat was therefore treated with oral itraconazole solution for several weeks.The case report shows that nasal cryptococcosis can also affect cats in Germany. Rhinoscopy reveals a nasopharyngeal mass with multiple attachment points, which is unusual for a neoplasia. In addition to the recommended removal of the mass, oral administration of systemic antimycotics is strongly advised.
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Enfermedades de los Gatos , Criptococosis , Animales , Gatos , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/microbiología , Enfermedades de los Gatos/patología , Criptococosis/veterinaria , Criptococosis/diagnóstico , Criptococosis/microbiología , Criptococosis/patología , Criptococosis/tratamiento farmacológico , Diagnóstico Diferencial , Neoplasias Nasofaríngeas/veterinaria , Neoplasias Nasofaríngeas/diagnóstico , Alemania , Tomografía Computarizada por Rayos X/veterinaria , Enfermedades Nasofaríngeas/veterinaria , Enfermedades Nasofaríngeas/diagnóstico , Enfermedades Nasofaríngeas/microbiología , Enfermedades Nasofaríngeas/patologíaAsunto(s)
Miositis , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Miositis/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Detección Precoz del Cáncer/métodos , Valor Predictivo de las Pruebas , Femenino , Adulto , Masculino , Persona de Mediana Edad , Edad de Inicio , Factores de RiesgoRESUMEN
Objectives: To analyze the location, discovery time and possible causes of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft carcinoma. Methods: A retrospective analysis was performed on clinical and pathological data of 15 patients misdiagnosed as branchiogenic carcinoma at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2000 and December 2020. Results: Among the 15 patients, 6 were nasopharyngeal squamous cell carcinoma, 4 tonsil squamous cell carcinoma, 2 tongue root squamous cell carcinoma, 2 hypopharyngeal squamous cell carcinoma and 1 thyroid papillary carcinoma. The median time from the diagnosis of branchial cleft carcinoma to the discovery of primary lesions was 3.58 months (0-76 months). The causes of misdiagnosis might be the lack of experience in the diagnosis and treatment of branchial cleft carcinoma, and not enough attention to comprehensive examination and close follow-up. Conclusions: Different from oropharyngeal cancer reported internationally, the proportion of misdiagnosed cases with nasopharyngeal carcinoma as the primary site in the current article is higher. As a country with a high incidence of nasopharyngeal carcinoma, the examination of nasopharynx should not be taken lightly. Most hidden cases can be found in the comprehensive examination in a short time, while a few cases need long-term follow-up. Finding the primary sites should not rely too much on imaging examination, and we cannot ignore the importance of clinical physical examination.
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Branquioma , Errores Diagnósticos , Metástasis Linfática , Neoplasias Nasofaríngeas , Neoplasias Primarias Desconocidas , Humanos , Estudios Retrospectivos , Neoplasias Primarias Desconocidas/diagnóstico , Neoplasias Primarias Desconocidas/patología , Branquioma/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Ganglios Linfáticos/patología , Cuello , Cáncer Papilar Tiroideo/diagnóstico , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patología , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/patología , Neoplasias Tonsilares/diagnóstico , Anciano , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/diagnóstico , Neoplasias Hipofaríngeas/diagnóstico , Neoplasias Hipofaríngeas/patologíaRESUMEN
Nasopharyngeal carcinoma (NPC), a malignant cancer originating from the epithelial cells of the nasopharynx, presents diagnostic challenges with current methods such as plasma Epstein-Barr virus (EBV) DNA testing showing limited efficacy. This study focused on identifying small extracellular vesicle (sEV) proteins as potential noninvasive biomarkers to enhance NPC diagnostic accuracy. We isolated sEVs from plasma and utilized 4D label-free proteomics to identify differentially expressed proteins (DEPs) among healthy controls (NC = 10), early-stage NPC (E-NPC = 10), and late-stage NPC (L-NPC = 10). Eighteen sEV proteins were identified as potential biomarkers. Subsequently, parallel reaction monitoring (PRM) proteomic analysis preliminarily confirmed sEV carbonic anhydrase 1 (CA1) as a highly promising biomarker for NPC, particularly in early-stage diagnosis (NC = 15; E-NPC = 10; L-NPC = 15). To facilitate this, we developed an automated, high-throughput and highly sensitive CA1 immune-chemiluminescence chip technology characterized by a broad linear detection range and robust controls. Further validation in an independent retrospective cohort (NC = 89; E-NPC = 39; L-NPC = 172) using this technology confirmed sEV CA1 as a reliable diagnostic biomarker for NPC (AUC = 0.9809) and E-NPC (AUC = 0.9893), independent of EBV-DNA testing. Notably, sEV CA1 exhibited superior diagnostic performance compared to EBV-DNA, with a significant incremental net reclassification improvement of 27.61 % for NPC and 72.11 % for E-NPC detection. Thus, this study identifies sEV CA1 as an innovative diagnostic biomarker for NPC and E-NPC independent of EBV-DNA. Additionally, it establishes an immune-chemiluminescence chip technology for the detection of sEV CA1 protein, paving the way for further validation and clinical application.
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Biomarcadores de Tumor , Vesículas Extracelulares , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/virología , Biomarcadores de Tumor/sangre , Vesículas Extracelulares/metabolismo , Masculino , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Femenino , Persona de Mediana Edad , Adulto , Proteómica/métodos , AncianoRESUMEN
Nasopharyngeal carcinoma (NPC) risk prediction models based on Epstein-Barr virus (EBV)-antibody testing have shown potential for screening of NPC; however, the long-term stability is unclear. Here, we investigated the kinetics of two EBV-antibody NPC risk scores within the Taiwan NPC Multiplex Family Study. Among 545 participants with multiple blood samples, we evaluated the stability of a 2-marker enzyme-linked immunosorbent assay score and 13-marker multiplex serology score using the intra-class correlation coefficient (ICC) by fitting a linear mixed model that accounted for the clustering effect of multiple measurements per subject and age. We also estimated the clustering of positive tests using Fleiss's kappa statistic. Over an average 20-year follow-up, the 2-marker score showed high stability over time, whereas the 13-marker score was more variable (p < .05). Case-control status is associated with the kinetics of the antibody response, with higher ICCs among cases. Positive tests were more likely to cluster within the same individual for the 2-marker score than the 13-marker score (p < .05). The 2-marker score had an increase in specificity from ~90% for single measurement to ~96% with repeat testing. The 13-marker score had a specificity of ~73% for a single measurement that increased to ~92% with repeat testing. Among individuals who developed NPC, none experienced score reversion. Our findings suggest that repeated testing could improve the specificity of NPC screening in high-risk NPC multiplex families. Further studies are required to determine the impact on sensitivity, establish optimal screening intervals, and generalize these findings to general population settings in high-risk regions.
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Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Taiwán/epidemiología , Herpesvirus Humano 4/inmunología , Anticuerpos Antivirales/sangre , Masculino , Femenino , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/virología , Adulto , Persona de Mediana Edad , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/epidemiología , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/epidemiología , Cinética , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Adulto Joven , Factores de Riesgo , AncianoRESUMEN
Objective: This study aimed to establish an effective prognostic model based on triglyceride and inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), to predict overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). Additionally, we aimed to explore the interaction and mediation between these biomarkers in their association with OS. Methods: A retrospective review was conducted on 259 NPC patients who had blood lipid markers, including triglyceride and total cholesterol, as well as parameters of peripheral blood cells measured before treatment. These patients were followed up for over 5 years, and randomly divided into a training set (n=155) and a validation set (n=104). The triglyceride-inflammation (TI) score was developed using the random survival forest (RSF) algorithm. Subsequently, a nomogram was created. The performance of the prognostic model was measured by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The interaction and mediation between the biomarkers were further analyzed. Bioinformatics analysis based on the GEO dataset was used to investigate the association between triglyceride metabolism and immune cell infiltration. Results: The C-index of the TI score was 0.806 in the training set, 0.759 in the validation set, and 0.808 in the entire set. The area under the curve of time-dependent ROC of TI score in predicting survival at 1, 3, and 5 years were 0.741, 0.847, and 0.871 respectively in the training set, and 0.811, 0.837, and 0.758 in the validation set, then 0.771, 0.848, and 0.862 in the entire set, suggesting that TI score had excellent performance in predicting OS in NPC patients. Patients with stage T1-T2 or M0 had significantly lower TI scores, NLR, and PLR, and higher LMR compared to those with stage T3-T3 or M1, respectively. The nomogram, which integrated age, sex, clinical stage, and TI score, demonstrated good clinical usefulness and predictive ability, as evaluated by the DCA. Significant interactions were found between triglyceride and NLR and platelet, but triglyceride did not exhibit any medicating effects in the inflammatory markers. Additionally, NPC tissues with active triglyceride synthesis exhibited high immune cell infiltration. Conclusion: The TI score based on RSF represents a potential prognostic factor for NPC patients, offering convenience and economic advantages. The interaction between triglyceride and NLR may be attributed to the effect of triglyceride metabolism on immune response.
Asunto(s)
Carcinoma Nasofaríngeo , Nomogramas , Triglicéridos , Humanos , Masculino , Femenino , Estudios Retrospectivos , Triglicéridos/sangre , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/sangre , Persona de Mediana Edad , Pronóstico , Adulto , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/sangre , Inflamación/inmunología , Inflamación/sangre , Anciano , Biomarcadores de Tumor/sangre , Curva ROC , Neutrófilos/inmunología , Neutrófilos/metabolismo , Plaquetas/metabolismo , Plaquetas/inmunología , Linfocitos/inmunología , Linfocitos/metabolismoRESUMEN
Posttransplant lymphoproliferative disorder is a life-threatening complication after solid-organ transplants. In adults, recipients of heart transplants have the highest risk, whereas renal transplant recipients have the lowest risk among all solid-organ transplants. The most common site for posttransplant lymphoproliferative disorders are gastrointestinal tract followed by the graft itself. Airway involvement in posttransplant lymphoproliferative disorder is rarely encountered. We report a case of a 26-year-old renal allograft recipient who presented to the emergency room with airway obstruction necessitating an emergency tracheostomy. Imaging revealed a left tonsillar mass extending into the nasopharynx and retropharyngeal space causing complete oropharyngeal occlusion. Endoscopic biopsy from nasopharyngeal mass showed a diffuse large B-cell lymphoma and was Ebstein-Barr virus positive. Reduction in immunosuppression and treatment with posttransplant lymphoproliferative disorder-1 risk-stratified approach resulted in complete remission.
Asunto(s)
Obstrucción de las Vías Aéreas , Inmunosupresores , Trasplante de Riñón , Linfoma de Células B Grandes Difuso , Humanos , Trasplante de Riñón/efectos adversos , Adulto , Resultado del Tratamiento , Obstrucción de las Vías Aéreas/etiología , Obstrucción de las Vías Aéreas/virología , Obstrucción de las Vías Aéreas/diagnóstico , Inmunosupresores/efectos adversos , Masculino , Linfoma de Células B Grandes Difuso/virología , Enfermedad Aguda , Biopsia , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/inmunología , Traqueostomía/efectos adversos , Inducción de Remisión , Huésped Inmunocomprometido , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/cirugía , Neoplasias Nasofaríngeas/diagnósticoRESUMEN
The study presents an analysis of the diagnostic and treatment protocol for a patient with a first episode of nasopharyngeal carcinoma who also has Sjogren's syndrome and Epstein-Barr Virus (EBV) positive cerebrospinal fluid, as detected through metagenomic next-generation sequencing (mNGS). It reviews existing literature to examine the connections between EBV and various conditions including Sjogren's syndrome, encephalitis or meningitis, and nasopharyngeal carcinoma, emphasizing the importance of EBV positive cerebrospinal fluid. The study focuses on a case from the Eighth Medical Center of the General Hospital of the People's Liberation Army, where a patient was admitted with headaches as the primary symptom on March 3, 2021. This patient had a history of Sjogren's syndrome and was later diagnosed with nasopharyngeal carcinoma. The research involved reviewing both domestic and international databases for cases related to cerebrospinal fluid EBV positive encephalitis or meningitis, and nasopharyngeal carcinoma. It aimed to aggregate data on demographics, initial symptoms, treatment methods, and patient outcomes. Findings suggest that positive cerebrospinal fluid EBV is linked to autoimmune diseases, viral encephalitis or meningitis, and nasopharyngeal carcinoma, albeit infrequently in the context of Sjogren's syndrome. Notably, EBV positive cerebrospinal fluid is commonly associated with recurrent nasopharyngeal carcinoma rather than initial episodes. The study concludes that for patients with an immune condition, exhibiting symptoms like headaches or cranial nerve issues, or in cases where nasopharyngeal carcinoma is suspected, early testing through cerebrospinal fluid mNGS or EBV DNA is recommended. This approach facilitates risk assessment, prognosis determination, and the creation of individualized treatment plans.
Asunto(s)
Herpesvirus Humano 4 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/líquido cefalorraquídeo , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/virología , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/líquido cefalorraquídeo , Herpesvirus Humano 4/aislamiento & purificación , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/líquido cefalorraquídeo , Infecciones por Virus de Epstein-Barr/líquido cefalorraquídeo , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
BACKGROUND: Screening with anti-Epstein-Barr virus (EBV) serology and endoscopy decreased nasopharyngeal carcinoma (NPC) mortality in Guangdong in a randomized trial. We conducted a secondary analysis of this trial using local incidence and cost data to optimize screening programs, hypothesizing that screening could be cost-effective in southern China. METHODS: Screening costs and life-years after NPC diagnosis were obtained from the Guangdong trial's intent-to-screen population (men and women aged 30-69). Seropositive subjects were rescreened annually for 5 years. Thereafter, we evaluated 12 screening strategies in Guangdong and Guangxi using a validated model. Strategies used combinations of serology, nasopharyngeal swab PCR (NP PCR), endoscopy, and MRI from trial subcohorts. Incidence data and costs were obtained from local cancer registries and the provincial healthcare system. RESULTS: In the intent-to-screen population, screening with serology and endoscopy was cost-effective (¥42,366/life-year, 0.52 GDP per capita). Screening for 5 to 15 years between ages 35 and 59 years met a willingness-to-pay threshold of 1.5 GDP/quality-adjusted life-years in all modeled populations. Despite doubling costs, adding MRI could be cost-effective via improved sensitivity. NP PCR triage reduced endoscopy/MRI referrals by 37%. One-lifetime screen could reduce NPC mortality by approximately 20%. CONCLUSIONS: EBV-based serologic screening for NPC is likely to be cost-effective in southern China. Among seropositive subjects, the preferred strategies use endoscopy alone or selective endoscopy triaged by MRI with or without NP PCR. These data may aid the design of screening programs in this region. IMPACT: These findings support population-based screening in southern China by defining the target population, cost-effectiveness, and optimized screening approach.
Asunto(s)
Análisis Costo-Beneficio , Detección Precoz del Cáncer , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Femenino , Persona de Mediana Edad , China/epidemiología , Masculino , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/economía , Adulto , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/economía , Neoplasias Nasofaríngeas/virología , Detección Precoz del Cáncer/economía , Detección Precoz del Cáncer/métodos , Anciano , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Tamizaje Masivo/economía , Tamizaje Masivo/métodosRESUMEN
OBJECTIVES: Current guidelines recommend universal PET/CT screening for metastases staging in newly diagnosed nasopharyngeal carcinoma (NPC) despite the low rate of synchronous distant metastasis (SDM). The study aims to achieve individualized screening recommendations of NPC based on the risk of SDM. METHODS AND MATERIALS: 18 pre-treatment peripheral blood indicators was retrospectively collected from 2271 primary NPC patients. A peripheral blood risk score (PBRS) was constructed by indicators associated with SDM on least absolute shrinkage and selection operator (LASSO) regression. The PBRS-based distant metastases (PBDM) model was developed from features selected by logistic regression analyses in the training cohort and then validated in the validation cohort. Receiver operator characteristic curve analysis, calibration curves, and decision curve analysis were applied to evaluate PBDM model performance. RESULTS: Pre-treatment Epstein-Barr viral DNA copy number, percentage of total lymphocytes, serum lactate dehydrogenase level, and monocyte-to-lymphocyte ratio were most strongly associated with SDM in NPC and used to construct the PBRS. Sex (male), T stage (T3-4), N stage (N2-3), and PBRS (≥1.076) were identified as independent risk factors for SDM and applied in the PBDM model, which showed good performance. Through the model, patients in the training cohort were stratified into low-, medium-, and high-risk groups. Individualized screening recommendations were then developed for patients with differing risk levels. CONCLUSION: The PBDM model offers individualized recommendations for applying PET/CT for metastases staging in NPC, allowing more targeted screening of patients with greater risk of SDM compared with current recommendations.