Ewing Sarcoma Research Articles

Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma

Ewing sarcoma (ES) poses a significant therapeutic challenge due to the difficulty in targeting its main oncodriver, EWS::FLI1. We show that pharmacological targeting of the EWS::FLI1 transcriptional complex via inhibition of P300/CBP drives a global transcriptional outcome similar to direct knockdown of EWS::FLI1, and furthermore yields prognostic risk factors for ES patient outcome. We find that EWS::FLI1 upregulates LMNB1 via repetitive GGAA motif recognition and acetylation codes in ES cells and EWS::FLI1-permissive mesenchymal stem cells, which when reversed by P300 inhibition leads to senescence of ES cells. P300-inhibited senescent ES cells can then be eliminated by senolytics targeting the PI3K signaling pathway. The vulnerability of ES cells to this combination therapy suggests an appealing synergistic strategy for future therapeutic exploration.

Case report and literature review: A young man with giant intra-abdominal Ewing sarcoma.

Extraosseous Ewing sarcoma (EES) is a rare manifestation within the Ewing sarcoma tumor family (ESFT). Its clinical manifestations lack specificity, intestinal obstruction is the main symptom but can also present with abdominal pain, gastrointestinal bleeding, and other discomforts, making it prone to misdiagnosis as intestinal mesenchymal tumor. A 29-year-old male was admitted to the hospital with intestinal obstruction symptoms and abdominal CT suggesting "left abdominal occupation." The patient was initially misdiagnosed as intestinal mesenchymal tumor, and was later definitively diagnosed as abdominal Ewing sarcoma by postoperative pathology and genetic testing. Due to the patient's surgical indication, surgical resection with exploratory laparotomy was performed and then the patient underwent systemic chemotherapy. Intraoperatively, we found a 15-cm tumor originating from the proximal jejunum, with invasion into the peritoneum, duodenum, jejunum, and colon. Finally, the pathological report revealed Ewing sarcoma. Giant abdominal Ewing sarcoma with a diameter of 15 cm is rare. Considering postoperative pathology and genetic testing, abdominal Ewing sarcoma was suspected. The patient was successfully treated using surgery.

Impaired neutrophil-mediated cell death drives Ewing's Sarcoma in the background of Down syndrome.

Ewing Sarcoma (EWS) has been reported in seven children with Down syndrome (DS). To date, a detailed assessment of this solid tumour in DS patients is yet to be made. Here, we characterise a chemo-resistant mediastinal EWS in a 2-year-old DS child, the youngest ever reported case, by exploiting sequencing approaches. The tumour showed a neuroectodermal development driven by the EWSR1-FLI1 fusion. The inherited myeloperoxidase deficiency of the patient caused failure of neutrophil-mediated cell death and promoted genomic instability. In this context, the tumour underwent genome-wide near haploidisation resulting in a massive overexpression of pro-inflammatory cytokines. Recruitment of defective neutrophils fostered rapid evolution of this EWS.

Multiple primary malignancies: sequential development of Ewing sarcoma and carcinoid tumor in a single patient

Introduction and importance: Multiple primary malignancies (MPMs) involve two or more distinct primary cancers in one individual, either simultaneously or at different times. The incidence of MPMs is rising due to advancements in cancer detection, improved survival rates, and long-term treatment effects. This case report, likely the first of its kind, highlights a rare instance of a 30-year-old female developing a carcinoid tumor 5 years after Ewing sarcoma, emphasizing the need for vigilant monitoring of cancer survivors. Case presentation: A 30-year-old female with a history of Ewing Sarcoma diagnosed 5 years prior, initially presenting with a vascular, hard mass on her right shoulder, underwent neoadjuvant chemotherapy and surgical excision. She recently presented with high-grade fever, cough, weight loss, and severe chest pain. Imaging and biopsy confirmed a high-grade carcinoid tumor. Histopathology showed positive markers for Synaptophysin, CD56, and Chromogranin, with a Ki-67 index of 30–40%. The patient passed away after one cycle of chemotherapy. Clinical discussion: Diagnosing and managing MPMs is challenging due to the complexity of distinguishing primary tumors from metastases. This case fits the Warren and Gates’ criteria for MPMs. This case confirmed Ewing sarcoma and atypical carcinoid tumor as distinct primary malignancies. Delayed diagnosis worsens outcomes, especially for aggressive atypical carcinoids. This case underscores the importance of thorough diagnostics, long-term follow-up, and improved healthcare infrastructure. Conclusion: This case report emphasizes the importance of a multidisciplinary approach, regular follow-ups, and timely detection for effective management of MPMs.

Axillary lesion in a young adult ends up to a peculiar diagnosis: primitive neuro-ectodermal tumor (PNET) of ulnar nerve: a rare case report

Introduction and importance: Primitive neuro-ectodermal tumor (PNET) is a highly aggressive tumor composed of small round blue cells, mostly developing in children and young adults. Being a member of Ewing’s Sarcoma Family of Tumors (ESFT); it has been discussed in two subcategories of central and peripheral PNET. PNETs of peripheral nerves are very uncommon pathologic findings, as to the best of our knowledge only 12 well-documented cases have been yet reported. Case presentation: A 30-year-old male presented with progressive paresthesia of his right hand’s little finger and painless swelling of the right axilla. Magnetic resonance (MR) neurography demonstrated a heterogeneous, high-signal, round mass within the right axilla fossa in proximity to the medial aspect of brachial plexus branches. The clinical and radiological study failed to an accurate diagnosis, thus surgical resection of the tumor was done for tissue evaluation. Histopathologic study of the lesion revealed a neoplasm comprising sheets of small, round, blue cells (Hematoxylin and Eosin stain), which immunohistochemically consisted with the diagnosis of PNET. Clinical discussion: The differential diagnosis of axillary fossa masses, focusses on peripheral nerve tumors like Schwannoma and PNET. MR neurography aids in evaluation, but tissue diagnosis remains crucial. Treatment involves surgical resection, chemotherapy, and radiotherapy tailored to individual patients. Conclusion: Although pPNET is not apparently the first differential diagnosis coming to mind when encountering a rapidly growing mass in the axillary fossa with peripheral nerve origin, its highly malignant behavior, makes it crucial to be considered in the differential diagnoses.

Metastatic site radiation therapy for Ewing sarcoma and rhabdomyosarcoma: Consensus guidelines from the National Pediatric Cancer Foundation

BackgroundDespite the urgent need for improved outcomes in patients with metastatic Ewing sarcoma (EWS) and rhabdomyosarcoma (RMS), it is unknown how to best approach metastatic site radiation therapy for these patients and whether such treatment provides a significant oncologic benefit that outweighs the toxicities. MethodsWe gathered a panel of pediatric radiation oncologists from academic hospitals to identify and discuss current controversies regarding the role of radiation in the management of metastatic EWS and RMS. The panel reviewed existing clinical data and ongoing trials to address five key questions: 1) the role of whole lung irradiation (WLI) in treating lung metastases 2) number of metastatic sites warranting radiotherapy and the radicality of such an approach; 3) radiation techniques, including stereotactic body radiation therapy (SBRT); 4) the timing of metastatic-site radiation therapy; and 5) the utility of metastatic site radiation therapy for relapsed metastatic disease. ResultsAfter a review of existing data, consensus recommendations were developed to support the decision-making process in metastatic-site irradiation with the goal of improving long-term disease control. Patients with pulmonary metastases should receive WLI. In patients with limited (<8 sites) metastatic disease, a comprehensive approach should be taken to treat all sites of metastatic disease diagnosed at presentation. SBRT should be considered as a preferred treatment technique. The timing of metastatic-site treatment should coincide with the end of systemic therapy. However, if there is a dosimetric advantage or improved compliance, concurrent treatment with the primary site may be preferred. ConclusionsA consensus guideline was established to address several critical questions regarding the role of radiation in the treatment of metastatic EWS and RMS. The study highlights the existing controversies, provides a structured approach, and underscores the need for future studies to further evaluate the therapeutic ratio of metastatic-site directed therapy.

423 (PB411): Characterization and evaluation of the protein kinase BUB1B as therapeutic target in ewing sarcoma

423 (PB411): Characterization and evaluation of the protein kinase BUB1B as therapeutic target in ewing sarcoma

Ewing Sarcoma in the Pediatric Population: Predictors of Survival Within the United States.

Bone and joint tumors are the third most common cause of pediatric cancer-related deaths in the United States. Although there have been improvements in survival rates among pediatric cancer patients over the past few decades, bone and joint cancers remain the exception. Considering current clinical trials involving novel targeted therapies, the establishment of updated mortality rates and predictors of survival for this cancer would be prudent. This investigation sought to determine updated 5-year survival rates and predictors of survival among pediatric Ewing sarcoma (ES) of bone treated within the United States. The National Cancer Database was retrospectively inquired for all pediatric ES cases within the most updated bone and joint public use file available in September 2022. The reported data were truncated to only include patients with reported 5-year vital (ie, survival) status. Cox proportional hazard regression was conducted on both the truncated data and the entire cohort to validate the findings. The patients were then separated into alive versus deceased cohorts, and univariate regression analysis was done followed by multivariable regression of notable variables of interest. Overall, an aggregated 5-year survival rate of 74.5% was found in the included patient cohort. Patients with localized cancer had a comparatively improved 5-year survival rate of 84.70% as opposed to those with macrometastatic disease on presentation with a survival rate of 50.4%. Patient demographic-, tumor-, and treatment-specific variables all demonstrated an effect on survival. The multivariable predictors of worse mortality were found to include older age, larger tumor size (>8 cm), macrometastatic disease on presentation, and positive surgical margins. This analysis serves to establish updated survival rates of pediatric ES treated within the United States to set standards for comparison among future studies. Continued multi-institutional and international collaboration is needed to optimize current treatment results and develop novel targeted therapies.

Characterization of Vitronectin Effect in 3D Ewing Sarcoma Models: A Digital Microscopic Analysis of Two Cell Lines.

Ewing sarcoma (ES) is an aggressive bone and soft-tissue pediatric cancer. High vitronectin (VN) expression has been associated with poor prognosis in other cancers, and we aimed to determine the utility of this extracellular matrix glycoprotein as a biomarker of aggressiveness in ES. Silk fibroin plus gelatin-tyramine hydrogels (HGs) were fabricated with and without cross-linked VN and cultivated with A673 and PDX73 ES cell lines for two and three weeks. VN secretion to culture media was assessed using ELISA. Morphometric analysis was applied for phenotypic characterization. VN release to culture media was higher in 3D models than in monolayer cultures, and intracellular, intercellular, and pericluster presence was also observed. A673-HGs showed lower density of clusters but a proportion of larger clusters than PDX73-HGs, which presented low cluster circularity. The cluster density of A673-HGs without added VN was higher than with added VN and slightly lower in the case of PDX73-HGs. Furthermore, a culture time of three weeks provided no benefits in cluster growth compared to two weeks, especially in A673-HGs. These advances in 3D modeling and digital quantification pave the way for future studies in ES and other cancers to deepen understanding about intra- and intercellular heterogeneity and anti-adhesion VN therapies.

An Analysis of The Pattern and Frequency of Primary Malignant Bone Tumors in Nassyriah

Bone tumors are uncommon lesions and account for only 0.2% of all malignant tumors. Primary malignant bone tumors develop from bony tissue and are categorized according to their location of origin and the cell type that makes up the tumor. This research aims to report on the prevalence, geographic distribution, and comparison of malignant bone tumors in Nassyriha province. Malignant bone tumors were studied in 182 people (119 men and 63 females) between February 2021 and February 2023. Their ages varied widely (from 5 to 70), with the second decade being the most prevalent. The most common cancer was osteosarcoma, which accounted for 34.62 percent, followed by Ewing's sarcoma (24.73), chondrosarcoma (13.74), multiple myeloma (11.53), malignant giant cell tumors (8.14%), fibrosarcoma (2.74%), and 2 instances of chordoma (1.10%). None of the six instances (3.30%) could be definitively diagnosed. Primary malignant bone tumors are rising, with men being disproportionately impacted. Information gleaned from this study will be useful for both researchers and clinicians.

Mesenchymal Non-Meningothelial Tumors of the CNS: Evolving Molecular Landscape and Implications for Neuroradiologists.

The World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5) significantly revised the terminology and diagnostic criteria of "mesenchymal non-meningothelial" tumors of CNS to better align with the classification of these soft tissue tumors outside the CNS. The CNS chapter only covers the entities with distinct histological or molecular characteristics that occur exclusively or primarily in the CNS. These tumors usually arise from the meninges and are rarely intraparenchymal in origin, mainly in the supratentorial compartment. These tumors are grouped into three main categories: soft tissue, chondro-osseous, and notochordal. Soft tissue tumors, the largest group, are further divided into fibroblastic, vascular, and skeletal muscle subtypes. Notably, a new subcategory for "tumors of uncertain differentiation" has been introduced, encompassing three new histomolecular entities: FET::CREB fusion-positive, CIC-rearranged sarcoma, and primary intracranial sarcoma, DICER1-mutant. Emerging entities like dural angioleiomyomas and spindle cell neoplasms with NTRK-rearrangements have been reviewed, although not introduced in WHO CNS5. Given the often non-specific histology and immunophenotype of mesenchymal nonmeningothelial tumors of uncertain differentiation, molecular techniques have become indispensable for accurate diagnosis. This review provides a comprehensive overview of primary mesenchymal non-meningothelial CNS tumors, including their clinical, radiological, histopathological, and molecular characteristics and treatment strategies.ABBREVIATIONS: ALK: Anaplastic lymphoma kinase; ATF1: activating transcriptase factor-1; CREB: cAMP response element-binding protein; CREM: cAMP response element modulator; CIC: Capicua transcriptional receptor; EWSR1: Ewing sarcoma RNA binding protein; FUS: fused in sarcoma; NAB2: nerve growth factor-inducible protein A binding protein 2; STAT6: signal transducer and activator of transcription 6; WHO: World Health Organization WHO CNS5: World Health Organization Classification of Tumors of the Central Nervous System, fifth edition.

Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma.

Ewing sarcoma, an aggressive pediatric cancer, is driven by the EWS::FLI1 fusion protein, which disrupts gene expression by hijacking the BAF chromatin remodeling complex. Central to this mechanism is the formation of biomolecular condensates, mediated by the prion-like domains (PrLDs)of EWS and ARID1A, a core BAF subunit. ARID1A serves as a critical interface between EWS::FLI1 and the BAF complex, with its condensate-forming ability essential for the aberrant gene expression that drives tumor growth. The loss of condensate-competent ARID1A significantly impairs tumor progression, identifying it as a potential therapeutic target. However, targeting condensate formation is challenging due to the transient nature of the interactions involved, complicating the development of effective inhibitors. This work underscores the importance of further investigation into therapeutic strategies aimed at disrupting condensate formation in Ewing sarcoma and other related malignancies.

Incidence trends, overall survival, and metastasis prediction using multiple machine learning and deep learning techniques in pediatric and adolescent population with osteosarcoma and Ewing's sarcoma: nomogram and webpage.

The objective of this study was to analyze the incidence and overall survival (OS) of osteosarcoma (OSC) and Ewing's sarcoma (EWS) in a pediatric and adolescent population, employing machine learning (ML) and deep learning (DL) models to predict the likelihood of metastasis. Involving 2465 OSC and 1373 EWS patients aged 0-19 years, from 2004 to 2020. ML techniques-Lasso, Ridge Regression, Elastic Net, and Random Forest-were used alongside a deep learning model based on TensorFlow and Keras, to construct predictive models for metastasis. These models were optimized using grid search with cross-validation and evaluated on their performance metrics, including AUC, sensitivity, and accuracy. The variables' importance in metastasis prediction was determined using SHAP values. Statistical analysis was performed using R software, and an online nomogram was developed for clinical use. The age-adjusted incidence of OSC and EWS from 2004 to 2020 showed a significant uptrend. The deep learning model, iterated 50 times, outperformed the Random Forest model in both loss and accuracy stabilization. The nomogram created demonstrated accurate survival predictions, as evidenced by its calibration curves and the distinction between high and low-risk groups. The increasing trend in age-adjusted incidence of OSC and EWS highlights the need for continued research and improved therapeutic strategies in this domain. The study employed ML and DL models to predict distant metastasis in pediatric and adolescent patients with OSC and EWS, providing a valuable tool for prognosis. The online nomogram developed as a part of this research enhances the models' clinical utility, offering an accessible means for clinicians to predict survival outcomes effectively.

A phenome-wide association study of polygenic scores for selected childhood cancer: Results from the UK Biobank

The aim of this study was to scan phenotypes in adulthood associated with polygenic risk scores (PRS) for childhood cancers with well-articulated genetic architectures: acute lymphoblastic leukemia (ALL), Ewing sarcoma, and neuroblastoma to examine genetic pleiotropy. Furthermore, we aimed to determine which single nucleotide polymorphisms (SNPs) could drive associations. Per-SNP summary statistics were extracted for PRS calculation. Participants with white British ancestry were exclusively included for analyses. SNPs were queried from the UK biobank genotype imputation data. Records from the cancer registry, death registry, and inpatient diagnoses were abstracted for phenome-wide scans. Firth logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) alongside corresponding p-values, adjusting for age at recruitment and sex. A total of 244,332 unrelated white British participants were included. We observed a significant association between ALL-PRS and ALL (OR: 1.20e+24, 95% CI: 9.08e+14-1.60e+33). In addition, we observed a significant association between high-risk neuroblastoma PRS and nonrheumatic aortic valve disorders (OR: 43.9, 95% CI: 7.42-260). There were no significant phenotype associations with Ewing sarcoma and neuroblastoma PRS. Regarding individual SNPs, rs17607816 increased the risk of ALL (OR: 6.40, 95% CI: 3.26-12.57). For high-risk neuroblastoma, rs80059929 elevated the risk of atrioventricular block (OR: 3.04, 95% CI: 1.85-4.99). Our findings suggest that individuals with genetic susceptibility to ALL may face a lifelong risk for developing ALL, along with a genetic pleiotropic association between high-risk neuroblastoma and circulatory diseases.

ENL mutation and AML: a new model that reveals oncogenic condensate's function in leukemogenesis.

Precise regulation of gene expression is essential for proper development and the maintenance of homeostasis in organisms. Studies have shown that some transcriptional regulatory proteins influence gene expression through the formation of dynamic, locally concentrated assemblies known as condensates, while dysregulation of transcriptional condensates was associated with several cancers, such as Ewing sarcoma and AML [Wang Y etal. (2023) Nat Chem Biol 19, 1223-1234; Chandra B etal. (2022) Cancer Discov 12, 1152-1169]. Mutations in the histone acetylation "reader" eleven-nineteen-leukemia (ENL) have been shown to form discrete condensates at endogenous genomic targets, but it remains unclear how ENL mutations drive tumorigenesis and whether it is correlated with their condensate formation property. Liu etal. now show, using a conditional knock-in mouse model, that ENL YEATS domain mutation is a bona fide oncogenic driver for AML. This mutant ENL forms condensates in hematopoietic stem/progenitor cells at the genomic loci of key leukemogenic genes, including Meis1 and Hoxa cluster genes, and disrupting condensate formation via mutagenesis impairs its chromatin and oncogenic function. Furthermore, they show that small-molecule inhibition of the acetyl-binding activity displaces ENL mutant condensates from oncogenic target loci, and this inhibitor significantly impairs the onset and progression of AML driven by mutant ENL in vivo.

Guidance for Circumflex Scapular Artery Flap Utilization in Pediatric Reconstruction.

The circumflex scapular artery (CSA) flap system, consisting of scapular, parascapular, and chimeric flaps, is useful for pediatric reconstruction in many anatomical locations. The objectives of this case series are to offer insights into our decision-making process for selecting the CSA flap in particular pediatric reconstructive cases and to establish a framework for choosing a scapular or parascapular skin paddle. We also aim to emphasize important technical considerations of CSA flap utilization in pediatric patients. Pediatric reconstruction with CSA flaps performed at our institution between 2006-2022 was retrospectively reviewed. Patient demographics, indications, flap characteristics, complications, and operative data were abstracted. Functional donor site morbidity was assessed through postoperative physical examinations. Unpaired t test analyzed scapular versus parascapular flap size. Eleven CSA flaps were successfully performed in 10 patients (6 scapular and 5 parascapular flaps). Patient ages ranged from 2 to 17 years. Scapular fasciocutaneous free flaps (n = 4) were performed in patients' ages 2-5 years for hand and forearm scar contractures. Two pedicled scapular flaps were performed for a single patient for bilateral axillary hidradenitis suppurativa. The 5 parascapular flaps were performed in patients' ages 2-14 years for calcaneus and forearm avulsion wounds and reconstruction after resection of hidradenitis suppurativa, nevus sebaceous, and Ewing sarcoma. In the sarcoma resection case, a chimeric flap with latissimus dorsi was employed. Average flap size was 101.6 ± 87.3 cm2 (range: 18-300 cm2). Parascapular flaps were significantly larger than scapular flaps (156.60 ± 105.84 cm2 vs 55.83 ± 26.97 cm2, P = 0.0495). Overall, 3 complications occurred (27.3% of cases) including venous congestion (n = 2) and wound dehiscence (n = 1). There were no reported cases of compromised shoulder function at 1.9 ± 2.5-year follow-up. The successful reconstruction rate for scapular, parascapular, and chimeric flaps was 100%. The CSA flap treated a wide variety of indications demonstrating the flap's attributes: large vessel caliber, wide arc of rotation, reliable vascular anatomy, minimal donor site morbidity, and ability to incorporate bone and muscle. Our cases also highlight important pediatric considerations such as vascular mismatch and limited scapular bone stock. We recommend selection of the parascapular over the scapular flap with reconstruction of larger, complex defects given its ability to be harvested with a large skin paddle.

Is Information About Musculoskeletal Malignancies From Large Language Models or Web Resources at a Suitable Reading Level for Patients?

Patients and caregivers may experience immense distress when receiving the diagnosis of a primary musculoskeletal malignancy and subsequently turn to internet resources for more information. It is not clear whether these resources, including Google and ChatGPT, offer patients information that is readable, a measure of how easy text is to understand. Since many patients turn to Google and artificial intelligence resources for healthcare information, we thought it was important to ascertain whether the information they find is readable and easy to understand. The objective of this study was to compare readability of Google search results and ChatGPT answers to frequently asked questions and assess whether these sources meet NIH recommendations for readability. (1) What is the readability of ChatGPT-3.5 as a source of patient information for the three most common primary bone malignancies compared with top online resources from Google search? (2) Do ChatGPT-3.5 responses and online resources meet NIH readability guidelines for patient education materials? This was a cross-sectional analysis of the 12 most common online questions about osteosarcoma, chondrosarcoma, and Ewing sarcoma. To be consistent with other studies of similar design that utilized national society frequently asked questions lists, questions were selected from the American Cancer Society and categorized based on content, including diagnosis, treatment, and recovery and prognosis. Google was queried using all 36 questions, and top responses were recorded. Author types, such as hospital systems, national health organizations, or independent researchers, were recorded. ChatGPT-3.5 was provided each question in independent queries without further prompting. Responses were assessed with validated reading indices to determine readability by grade level. An independent t-test was performed with significance set at p < 0.05. Google (n = 36) and ChatGPT-3.5 (n = 36) answers were recorded, 12 for each of the three cancer types. Reading grade levels based on mean readability scores were 11.0 ± 2.9 and 16.1 ± 3.6, respectively. This corresponds to the eleventh grade reading level for Google and a fourth-year undergraduate student level for ChatGPT-3.5. Google answers were more readable across all individual indices, without differences in word count. No difference in readability was present across author type, question category, or cancer type. Of 72 total responses across both search modalities, none met NIH readability criteria at the sixth-grade level. Google material was presented at a high school reading level, whereas ChatGPT-3.5 was at an undergraduate reading level. The readability of both resources was inadequate based on NIH recommendations. Improving readability is crucial for better patient understanding during cancer treatment. Physicians should assess patients' needs, offer them tailored materials, and guide them to reliable resources to prevent reliance on online information that is hard to understand. Level III, prognostic study.

Ewing Sarcoma of Temporal bone Presentation as Chronic Otitis Media: A rare Clinical Confusion

Ewing Sarcoma of Temporal bone Presentation as Chronic Otitis Media: A rare Clinical Confusion

Identification of ENO‐1 positive extracellular vesicles as a circulating biomarker for monitoring of Ewing sarcoma

AbstractThe lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug‐resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell‐derived extracellular vesicles identified 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO‐1 were identified on extracellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma‐derived extracellular vesicles but also Ewing sarcoma cells demonstrated proteomic expression of CD99 and ENO‐1 on their surface membranes. ENO‐1+CD63+ extracellular vesicle detection was reduced after tumor resection while both CD99+CD63+ and ENO‐1+CD63+ extracellular vesicles were detected in serum from Ewing sarcoma‐bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO‐1+CD81+ extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P &lt; 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO‐1+CD81+ extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma.

Primary Ewing Sarcoma of Kidney in an Adult: An Oddball

Ewing sarcoma (ES) is a malignant bone and soft-tissue tumor derived from neuroectoderm. It occurs, mostly, in pediatric adolescentswith the histopathological features of invasiveness. The occurrence of ES of the kidney is rare, comprising only 1% of all renal tumorswhich are limited to case reports and small case series. Herein, we report a case of a 44-year-old male patient, presenting with the rightflank pain and hematuria. Computed tomography scan demonstrated a right midpolar exophytic renal mass with intraluminal right renalvein and inferior vena cava (IVC) thrombus without visceral metastasis suggesting the diagnosis of renal cell carcinoma (T3BN0M0).The patient underwent the right radical nephrectomy with IVC thrombectomy. In view of the aggressiveness of the tumor, the patientreceived adjuvant chemotherapy (i.e., four cycles of vincristine, adriamycin, and cyclophosphamide alternating every 3 weeks with fourcycles of ifosphamide and etoposide). The patient had near-complete resolution of the tumor with no thrombus seen in the follow-upscan. We could not complete six cycles of chemotherapy which were planned initially due to recurrent cytopenias. Six months postchemotherapy,the patient is clinically and radiologically disease-free and is in close follow-up. We are reporting this case to highlightthe rarity of this entity and its challenging clinicopathological diagnosis when presenting as a renal tumor.