Enhancing diagnostic precision in EBV-related HLH: a multifaceted approach using 18F-FDG PET/CT and nomogram integration.

BACKGROUND: The hyperinflammatory condition and lymphoproliferation due to Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) affect the detection of lymphomas by 18F-FDG PET/CT. We aimed to improve the diagnostic capabilities of 18F-FDG PET/CT by combining laboratory parameters. METHODS: This retrospective study involved 46 patients diagnosed with EBV-positive HLH, who underwent 18F-FDG PET/CT before beginning chemotherapy within a 4-year timeframe. These patients were categorized into two groups: EBV-associated HLH (EBV-HLH) (n = 31) and EBV-positive lymphoma-associated HLH (EBV + LA-HLH) (n = 15). We employed multivariable logistic regression and regression tree analysis to develop diagnostic models and assessed their efficacy in diagnosis and prognosis. RESULTS: A nomogram combining the SUVmax ratio, copies of plasma EBV-DNA, and IFN-γ reached 100% sensitivity and 81.8% specificity, with an AUC of 0.926 (95%CI, 0.779-0.988). Importantly, this nomogram also demonstrated predictive power for mortality in EBV-HLH patients, with a hazard ratio of 4.2 (95%CI, 1.1-16.5). The high-risk EBV-HLH patients identified by the nomogram had a similarly unfavorable prognosis as patients with lymphoma. CONCLUSIONS: The study found that while 18F-FDG PET/CT alone has limitations in differentiating between lymphoma and EBV-HLH in patients with active EBV infection, the integration of a nomogram significantly improves the diagnostic accuracy and also exhibits a strong association with prognostic outcomes.

Epstein-Barr Virus-Associated Smooth-Muscle Tumor of the Brain.

Epstein-Barr virus, a herpesvirus, has been associated with a variety of cancers, including Burkitt, Hodgkin, and non-Hodgkin lymphomas; posttransplant lymphoproliferative disorders; gastric carcinoma; and nasopharyngeal carcinoma, in both immunocompetent and immunocompromised individuals. Previous studies have established a connection between Epstein-Barr virus and the development of smooth-muscle tumors. Smooth-muscle tumors of the brain are very rare and are often misdiagnosed as meningiomas on imaging. To our knowledge, advanced imaging findings such as MR perfusion of smooth-muscle tumors of the brain have never been reported. We describe the radiologic and pathologic features of the Epstein-Barr virus-associated smooth-muscle tumors of the brain in a person with newly diagnosed advanced HIV.

Epstein-Barr virus positive gastric cancer: the pathological basis of CT findings and radiomics models prediction.

PURPOSE: To analyze the clinicopathologic information and CT imaging features of Epstein-Barr virus (EBV)-positive gastric cancer (GC) and establish CT-based radiomics models to predict the EBV status of GC. METHODS: This retrospective study included 144 GC cases, including 48 EBV-positive cases. Pathological and immunohistochemical information was collected. CT enlarged LN and morphological characteristics were also assessed. Radiomics models were constructed to predict the EBV status, including decision tree (DT), logistic regression (LR), random forest (RF), and support vector machine (SVM). RESULTS: T stage, Lauren classification, histological differentiation, nerve invasion, VEGFR2, E-cadherin, PD-L1, and Ki67 differed significantly between the EBV-positive and -negative groups (p = 0.015, 0.030, 0.006, 0.022, 0.028, 0.030, < 0.001, and < 0.001, respectively). CT enlarged LN and large ulceration differed significantly between the two groups (p = 0.019 and 0.043, respectively). The number of patients in the training and validation cohorts was 100 (with 33 EBV-positive cases) and 44 (with 15 EBV-positive cases). In the training cohort, the radiomics models using DT, LR, RF, and SVM yielded areas under the curve (AUCs) of 0.905, 0.771, 0.836, and 0.886, respectively. In the validation cohort, the diagnostic efficacy of radiomics models using the four classifiers were 0.737, 0.722, 0.751, and 0.713, respectively. CONCLUSION: A significantly higher proportion of CT enlarged LN and a significantly lower proportion of large ulceration were found in EBV-positive GC. The prediction efficiency of radiomics models with different classifiers to predict EBV status in GC was good.

PET/CT in a 65-Year-Old Woman With Epstein-Barr Virus-Associated Smooth Muscle Tumor After Chemotherapy for Follicular Lymphoma.

ABSTRACT: The Epstein-Barr virus-associated smooth muscle tumor (SMT) is an uncommon neoplasm. It arises mainly in 3 immunosuppression settings: HIV-associated SMT; drug-related immunosuppression in transplant recipients; and congenital immunodeficiency disorder-associated SMT. We present 18 F-FDG PET/CT findings of an adrenal Epstein-Barr virus-associated SMT in a 65-year-old woman with a history of follicular lymphoma after chemotherapy.

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

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

Unpacking the CNS Manifestations of Epstein-Barr Virus: An Imaging Perspective.

Epstein-Barr virus is a ubiquitous herpesvirus that may cause both infective (encephalitis, meningitis, and so forth) and postinfection inflammatory (such as Guillain-Barré syndrome, acute disseminated encephalomyelitis) manifestations in the CNS. Diagnosis of Epstein-Barr virus-related CNS pathologies is often complicated due to a nonspecific clinical presentation and overlap with other infectious and noninfectious causes, both clinically and on imaging. The Epstein-Barr virus is also implicated in several lymphoproliferative disorders in both immunocompromised and immunocompetent hosts. MR imaging is preferred for evaluating the extent of involvement and monitoring therapy response, given its high sensitivity and specificity, though imaging findings may be nonspecific. Herein, we review the imaging spectrum of Epstein-Barr virus-associated CNS disorders.

18F-FDG PET/CT imaging of multiple intrahepatic Epstein-Barr virus-associated smooth muscle tumors in a pediatric patient after heart transplantation.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is an exceedingly rare neoplastic disease with a predisposition in immune-compromised individuals, especially in patients with prior transplantation, human immunodeficiency virus infection, or congenital immunodeficiency. Here, we present imaging findings of EBV-SMT in multiphasic contrast-enhanced computed tomography (CT) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT in a two-and-a-half-year-old boy with prior heart transplantation.

Diffuse Large B-Cell Epstein-Barr Virus-Positive Primary CNS Lymphoma in Non-AIDS Patients: High Diagnostic Accuracy of DSC Perfusion Metrics.

BACKGROUND AND PURPOSE: Immunodeficiency-associated CNS lymphoma may occur in different clinical scenarios beyond AIDS. This subtype of CNS lymphoma is diffuse large B-cell and Epstein-Barr virus-positive. Its accurate presurgical diagnosis is often unfeasible because it appears as ring-enhancing lesions mimicking glioblastoma or metastasis. In this article, we describe clinicoradiologic features and test the performance of DSC-PWI metrics for presurgical identification. MATERIALS AND METHODS: Patients without AIDS with histologically confirmed diffuse large B-cell Epstein-Barr virus-positive primary CNS lymphoma (December 2010 to January 2022) and diagnostic MR imaging without onco-specific treatment were retrospectively studied. Clinical, demographic, and conventional imaging data were reviewed. Previously published DSC-PWI time-intensity curve analysis methodology, to presurgically identify primary CNS lymphoma, was used in this particular lymphoma subtype and compared with a prior cohort of 33 patients with Epstein-Barr virus-negative CNS lymphoma, 35 with glioblastoma, and 36 with metastasis data. Normalized curves were analyzed and compared on a point-by-point basis, and previously published classifiers were tested. The standard percentage of signal recovery and CBV values were also evaluated. RESULTS: Seven patients with Epstein-Barr virus-positive primary CNS lymphoma were included in the study. DSC-PWI normalized time-intensity curve analysis performed the best for presurgical identification of Epstein-Barr virus-positive CNS lymphoma (area under the receiver operating characteristic curve of 0.984 for glioblastoma and 0.898 for metastasis), followed by the percentage of signal recovery (0.833 and 0.873) and CBV (0.855 and 0.687). CONCLUSIONS: When a necrotic tumor is found in a potentially immunocompromised host, neuroradiologists should consider Epstein-Barr virus-positive CNS lymphoma. DSC-PWI could be very useful for presurgical characterization, with especially strong performance of normalized time-intensity curves.

Value of Diffusion-Weighted Imaging and Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Prediction of Treatment Outcomes in Nasopharyngeal Carcinoma.

OBJECTIVE: Magnetic resonance imaging (MRI) parameters that reflect the tumor microenvironment of nasopharyngeal carcinoma (NPC) may predict treatment response and facilitate treatment planning. This study aimed to evaluate the diffusion-weighted imaging and dynamic contrast-enhanced MRI (DCE-MRI) values for predicting the treatment outcomes in NPC patients. METHODS: Eighty-three patients with NPC underwent pretreatment MRI simulation with diffusion-weighted imaging and dynamic contrast-enhanced MRI. Average values of the apparent diffusion coefficient (ADC), Ktrans, Kep, Ve, Vp, and tumor volume of the primary tumors were measured. Other potential clinical characteristics (age, sex, staging, pathology, pretreatment Epstein-Barr virus level, and treatment type) were analyzed. Patients underwent follow-up imaging 6 months after treatment initiation. Treatment responses were assigned according to the Response Evaluation Criteria in Solid Tumors guideline (version 1.1). RESULTS: Fifty-one patients showed complete response (CR), whereas 32 patients did not (non-CR). Univariable logistic regression with variables dichotomized by optimal cutoff values showed that ADC ≥1.45 × 10 -3 mm 2 /s, Vp ≥0.14, tumor volume of ≥14.05 mL, high stage (stages III and IV), and Epstein-Barr virus level of ≥2300 copies/mL were predictors of non-CR ( P = 0.008, 0.05, 0.01, 0.009, and 0.04, respectively). The final multivariable model, consisting of a combination of ADC ≥1.45 × 10 -3 mm 2 /s, Vp ≥0.14, and high stage, could predict non-CR with a good discrimination ability (area under the receiver operating characteristic curve, 0.76 [95% confidence interval, 0.66-0.87]; sensitivity, 62.50%; specificity, 80.39%; and accuracy 73.49%). CONCLUSIONS: A multivariable prediction model using a combination of ADC ≥1.45 × 10 -3 mm 2 /s, Vp ≥0.14, and high stage can be effective for treatment response prediction in NPC patients.

Muscle Involvement Caused by Chronic Active Epstein-Barr Virus Infection on 18F-FDG PET/CT in a Pediatric Patient.

ABSTRACT: A 7-year-old girl with chronic active EBV (CAEBV) infection-associated hemophagocytic lymphohistiocytosis presented with fever. 18F-FDG PET/CT revealed heterogeneous FDG uptake in multiple muscle groups without significant abnormal activity elsewhere. On repeat FDG PET/CT scan 1 year later after therapy, the abnormal activity in muscles disappeared. Skeletal muscle involvement by CAEBV infection should be included as differential diagnosis for increased muscle activity on FDG PET/CT study.

Computed tomography radiomics to predict EBER positivity in Epstein-Barr virus-associated gastric adenocarcinomas: a retrospective study.

BACKGROUND: The relevance of Epstein-Barr virus (EBV) in gastric carcinoma has been represented by the existence of EBV-encoded small RNA (EBER) in the tumor cells and has prognostic significance in gastric cancer, while gastric adenocarcinoma represents the most frequently occurring gastric malignancy. PURPOSE: To observe the capacity of radiomic features extracted from contrast-enhanced computed tomography (CE-CT) images to differentiate EBER-positive gastric adenocarcinoma from EBER-negative ones. MATERIAL AND METHODS: A total of 54 patients with gastric adenocarcinoma (EBER-positive: 27, EBER-negative: 27) were retrospectively examined. Radiomic imaging features were extracted from all regions of interest (ROI) delineated by two experienced radiologists on late arterial phase CT images. We distinguished related radiomic features through the two-tailed t test and applied them to construct a decision tree model to evaluate whether EBER in situ hybridization positive had appeared. RESULTS: Nine radiomics features were significantly related to EBER in situ hybridization status (P < 0.05), four of which were used to build the decision tree through backward elimination: Correlation_ AllDirection_offset7, Correlation_ angle135_offset7, RunLengthNonuniformity_ AllDirection_offset1_SD, and HighGreyLevelRunEmphasis_ AllDiretion_offset1_SD. The decision tree model consisted of seven decision nodes and six terminal nodes, three of which demonstrated positive EBER in situ hybridization. The specificity, sensitivity, and accuracy of the model were 84%, 80%, and 81.7%, respectively. The area under the curve of the decision tree model was 0.87. CONCLUSION: Radiomics based on CE-CT could be applied to predict EBER in situ hybridization status preoperatively in patients with gastric adenocarcinoma.

Two Cases of Epstein-Barr Virus-Positive Mucocutaneous Ulcer Mimicking Head and Neck Cancers in 18F-FDG PET/CT.

ABSTRACT: Epstein-Barr virus-positive mucocutaneous ulcer is a newly recognized clinicopathological entity among mature B-cell neoplasms according to the 2016 revision of the World Health Organization diagnostic criteria. Here, we present FDG PET/CT images of 2 Epstein-Barr virus-positive mucocutaneous ulcer cases. Both cases shown in the images mimicked head and neck cancers, which are similar to carcinomas of the tonsil and gingiva, respectively, and both lesions showed intense FDG uptake on PET scan.

Case Report: Splenic Infarction in Infectious Mononucleosis due to Epstein-Barr Virus Infection.

Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and IM is a clinical syndrome typically characterized by fever, pharyngitis, and cervical lymph node enlargement. We describe the case of a 19-year-old man with IM complicated by splenic infarction. The patient visited our hospital because of upper abdominal pain without a fever and sore throat. Abdominal computed tomography revealed a low-density area in the spleen, which indicated splenic infarction. The next day, he developed a fever. After diminishing abdominal pain and fever, he developed pharyngitis accompanied by fever. Acute EBV infection was confirmed by serological tests. The patient was successfully managed with no specific therapy. Splenic infarction is a rare complication of IM and this case showed that splenic infarction can precede a fever and pharyngitis.

Novel EBV LMP1 C-terminal domain binding affibody molecules as potential agents for in vivo molecular imaging diagnosis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) latent infection and is common in Southern China and Southeast Asia. The viral latent membrane proteins LMP1 and LMP2 are persistently expressed in NPC tissues; the cytoplasmic domain of LMP1 (LMP1 C-terminal) and LMP2A (LMP2A N-terminal) proteins is essential for maintenance of latency and can alter host cell signaling to facilitate tumor growth and progression. Thus, targeting LMP1 or LMP2 oncoprotein has been an increasing interest for diagnosis and targeted therapy of NPC. Affibody molecules, a new class of small-affinity engineered scaffold proteins, have demonstrated high potential for therapeutics, diagnostics, and biotechnological applications. More recently, radiolabelled HER2-specific affibody molecules have demonstrated to be useful in imaging of HER2 expressing tumor. In this study, we report three novel EBV LMP1 C-terminal (EBV LMP1-C) domain affibody molecules (ZLMP1-C15, ZLMP1-C114, and ZLMP1-C277) were selected by biopanning from a random-peptide displayed phage library and used for molecular imaging in tumor-bearing nude mice. Surface plasmon resonance (SPR), indirect immunofluorescence, and immunohistochemistry (IHC) clearly showed that all three selected affibody molecules have high affinity and specificity in binding to EBV LMP1 protein. Moreover, in vivo tumor imaging revealed that Dylight-755-labeled affibody molecules accumulated rapidly in tumor site after injection (1 h) and then were continuously maintained for 24 h in EBV-positive NPC xenograft mice model. In conclusion, our findings highlight the potential use of ZLMP1-C affibody molecules as tumor-specific molecular imaging agents of EBV-associated NPC.Key points• We screened three novel affibody molecules (ZLMP1-C15, ZLMP1-C114, and ZLMP1-C277) targeting EBV LMP1-C terminal domain• ZLMP1-C recognize the recombinant and native LMP1-C with high affinity and specificity• ZLMP1-C can be used for molecular imaging.

TCGA-TCIA-Based CT Radiomics Study for Noninvasively Predicting Epstein-Barr Virus Status in Gastric Cancer.

OBJECTIVE. The purpose of this study was to investigate the value of TCGA-TCIA (The Cancer Genome Atlas and The Cancer Imaging Archive)-based CT radiomics for noninvasive prediction of Epstein-Barr virus (EBV) status in gastric cancer (GC). MATERIALS AND METHODS. A total of 133 patients with pathologically confirmed GC (94 in the training cohort and 39 in the validation cohort) who were identified from the TCGA-TCIA public data repository and two hospitals were retrospectively enrolled in the study. Two-dimensional and 3D radiomics features were extracted to construct corresponding radiomics signatures. Then, 2D and 3D nomograms were built by combining radiomics signatures and clinical information on the basis of multivariable analysis. Their performance and clinical practicability were determined, validated, and compared with respect to discrimination, calibration, reclassification, and time spent on tumor segmentation. RESULTS. Both 2D and 3D nomograms were robust and showed good calibration. The AUCs of the 2D and 3D nomograms showed no significant difference in the training cohort (0.919 vs 0.945, respectively; p = .41) or validation cohort (0.939 vs 0.955, respectively; p = .71). The net reclassification index showed that the 3D nomogram revealed no significant improvement in risk reclassification when compared with the 2D nomogram in the training cohort (net reclassification index, 0.68%; p = .14) and the validation cohort (net reclassification index, 6.06%; p = .08). Of note, the time spent on 3D segmentation (median, 907 seconds) was higher than that spent on 2D segmentation (median, 129 seconds). CONCLUSION. The 2D and 3D radiomics nomograms might have the potential to be used as effective tools for prediction of EBV in GC. When time spent on segmentation is considered, the 2D nomogram is more highly recommended for clinical application.

Epstein-Barr virus infection in a woman with aquaporin-4 seropositive neuromyelitis optica.

Neuromyelitis optica spectrum disorders (NMOSD) are characterised by pathological antibodies to aquaporin-4 water channels of astrocytes, resulting in severe brain and spinal cord injury. Serological evidence suggests that Epstein-Barr virus (EBV) reactivation may contribute to their pathogenesis. We describe an unusual case of a woman with fever, rash and headache preceding an Aquaporin-4 antibody positive longitudinally extensive transverse myelitis. EBV was detected in her cerebrospinal fluid by polymerase chain reaction assay. This case highlights the potential role of EBV in the pathogenesis of NMOSD.

Paraneoplastic Neurologic Symptoms in a Pediatric Patient with Hodgkin Lymphoma.

Neurological paraneoplastic syndromes are exceedingly rare, and often difficult to recognize clinically. Paraneoplastic achalasia is a condition characterized by new-onset dysphagia that is unrelated to tumor burden, most often due to the development of auto-immune antibodies targeting esophageal tissue. Due to the rarity of this condition, diagnosis is often delayed, leading to increased time to treatment. Here we report a case of a rare paraneoplastic achalasia in a female child with EBV + Hodgkin lymphoma (HL), review literature describing paraneoplastic achalasia, and discuss treatment strategies for improving clinical outcome in these patients.