Unlocking epigenetics for precision treatment of Ewing’s sarcoma

Ewing’s sarcoma(EWS)is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults.Despite the efficacy of chemoradiotherapy in some cases,the cure rate for patients with metastatic and recurrent disease remains low.Therefore,there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment.Epigenetic regulation,a crucial factor in physiological processes,plays a significant role in controlling cell proliferation,maintaining gene integrity,and regulating transcription.Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS.A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development.This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS,integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

Extraskeletal Ewing sarcoma of the stomach:A rare case report

BACKGROUND Extraskeletal Ewing sarcoma(EES)is a rare and highly malignant small round cell tumor associated with a poor clinical outcome.Ewing sarcoma(ES)involving the stomach is an uncommon presentation and can be easily confused with other small round cell tumors.We herein present a rare case of ES involving the gastric area.CASE SUMMARY We report a case of gastric ES in a 19-year-old female patient who initially presented with a complaint of a tender epigastric mass for 5 d.Contrast-enhanced abdominal computed tomography revealed a soft-tissue-density mass with a diameter of 8.5 cm between the liver and stomach;the mass was connected to the gastric antrum.Then,the mass was surgically excised completely.Upon histopathological,immunophenotype and molecular analysis,the mass was identified to be a primary gastric ES.CONCLUSION EES is an aggressive tumor with poor prognosis.Therefore,early diagnosis and timely intervention are essential for a good prognosis.It is imperative for us to raise awareness about this rare tumor.Surgical resection is still the best treatment option.

Ewing′s瘤的X线、CT和MRI影像学表现及其意义

目的 探讨Ewing′s瘤的X线、CT及MRI影像表现及其意义。资料与方法 回顾性对比分析 2 1例经穿刺及手术病理证实Ewing′s瘤的X线、CT及MRI的影像学改变。结果 管状骨骨质破坏主要表现为筛孔样、虫蚀样溶骨性破坏 ,并出现层状、葱皮样骨膜新生骨 ,放射样针状骨 ,具有一定的特征性。 13例管状骨外骨及 1例骨外Ewing′s瘤骨质破坏表现多样 ,仍以溶骨为主 ,且 2 0例骨Ewing′s瘤均伴有周围软组织肿块。结论 Ewing′s瘤在不同部位有不同的影像学表现 ,具有相对的特征性表现 ;CT及MRI在确定Ewing′s瘤软组织肿块的大小、骨皮质的破坏、骨髓腔的完整性、骨膜反应及病理性骨折优于X线平片 。

右颊部Ewing肉瘤/原始神经外胚叶肿瘤PNET1例

1病例报告患者,男,21岁,于两年前感右颊部有异物感,自行触摸有一肿物,无明显疼痛不适,肿物逐渐长大,曾于半年前切除部分肿物,近两月来肿物生长迅速,遂住院治疗。患者既往体健,无外伤史。查体：患者颈胸腹部未见异常,浅表淋巴结无肿大。

儿童外周性原始神经外胚叶肿瘤/Ewing’s肉瘤的声像图特征分析

目的分析儿童外周性原始神经外胚叶肿瘤/Ewing’s肉瘤(pPNET/EWS)的声像图特点,探讨超声对其的诊断价值。方法选取41例pPNET/EWS患儿,总结分析其声像图特征,并与病理结果进行对照分析。结果41例pPNET/EWS患儿肿瘤发生于骨组织19例,软组织22例;均呈单发巨块状,超声测量肿瘤最大径(10.10±4.48)cm;肿块形态不规则,边界清晰;20例为不均质中等回声,18例为中等偏低回声,3例为不均质低回声;28例见混杂细点状“针尖样”,24例见簇状强回声,16例见条带状强回声,19例见混杂散在小片状无回声区呈“蜂窝状”,CDFI于其内可探及短条状血流信号,19例可伴骨皮质破坏。病理显示4例见大片坏死组织。结论pPNET/EWS的声像图特征具有一定特异性,超声可用于其诊断及随访,具有较好临床应用价值。

氨磷汀联合化疗治疗Ewing肉瘤/PNET的临床观察

目的探讨氨磷汀联合化疗治疗Ewing肉瘤/PNET的疗效、不良反应和安全性。方法 32例Ewing肉瘤/PNET患者分为化疗加氨磷汀组(观察组)及单纯化疗组(对照组),观察组12例,对照组20例。行IFO-IFO-DDP-ADM化疗2周期后评价疗效、不良反应。结果观察组完全缓解(CR)及非常好的部分缓解率(VGPR)为91.6%,对照组为90.0%,两组比较差异无统计学意义(P>0.05)。比较两组各种Ⅰ度～Ⅳ度不良反应发生率,差异无统计学意义(P>0.05)。比较两组发生的Ⅳ度不良反应,观察组Ⅳ度白细胞减少为25.0%,对照组为70.0%;观察组Ⅳ度粒细胞减少25.0%,对照组为75.0%,差异均有统计学意义(P<0.05)。结论氨磷汀联合化疗治疗Ewing肉瘤/PNET不改变化疗疗效,不增加各种常见不良反应发生率;可以明显减少化疗后Ⅳ度白细胞及粒细胞减少的发生率,安全性好。

Perigastric extraskeletal Ewing's sarcoma: A case report

Ewing's sarcoma (ES) is a neoplasm of undifferentiated small round cells, which occurs in the bones and deep soft tissues of children and adolescents. We present a rare case of a 44-year-old woman with gastric ES presenting with epigastric pain and weight loss. Ultrasound and computed tomography scans indicated a solid/cystic mass in the pancreatic tail. At laparotomy, the tumor was found attached to the posterior surface of the stomach, completely free from the pancreas, with no lymphadenopathy or local metastases. The polynodal, partly pseudocystic, dark-red soft tumor was excised. Histopathology revealed an anaplastic small-round-cell tumor with strong membranous CD99 immunoexpression. Additionally, there was patchy immunostaining for S-100 protein, vimentin, protein gene product (PGP) 9.5 and neuron-specifi c enolase, and weak focal CD117 cytoplasmic immunoreactivity. The patient had no adjuvant chemotherapy; her postoperative recovery was uneventful, and she remains symptom-free, and without any sign of recurrence at 20 mo. To the best of our knowledge, this is only the third ever case of gastric ES.

肾Ewing's肉瘤/原始神经外胚层肿瘤1例

1973年Hart等首次报道了原始神经外胚层肿瘤家族（primitive neuroectodermal tumor family）,包括原始神经外胚层肿瘤（primitive neuroectodermal tumor,PNET）和Ewing’s肉瘤（Ewing’s sarcoma,ES）,是一种神经嵴衍生的罕见的高度恶性的原始肿瘤,主要由原始神经上皮产生,并且具有不同程度的分化潜能。

Ureteral Ewing’s sarcoma in an elderly woman: A case report

BACKGROUND Ewing’s sarcoma(ES)is regarded as a skeletal tumor,with few instances of extraskeletal ES.A primary ES in the ureter is extremely rare.CASE SUMMARY We report the case of a 69-year-old woman who presented with intermittent flank pain and hematuria and was found to have a mass in the left ureter.Pathology of the excised mass indicated ES.The clinical treatment and pathologic characteristics in this case,and a review of the literature describing ES in the urinary system,are presented.CONCLUSION Due to the rarity and malignancy of ES in ureter,early diagnosis and prompt surgical treatment are critical.

EWS Knockdown and Taxifolin Treatment Induced Differentiation and Removed DNA Methylation from p53 Promoter to Promote Expression of Puma and Noxa for Apoptosis in Ewing’s Sarcoma

Ewing’s sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing’s sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression using a plasmid vector encoding EWS short hairpin RNA (shRNA) to increase anti-tumor mechanisms of taxifolin (TFL), a new flavonoid, in human Ewing’s sarcoma cells in culture and animal models. Immunofluorescence microscopy and flow cytometric analysis showed high expression of EWS in human Ewing’s sarcoma SK-N-MC and RD-ES cell lines. EWS shRNA plus TFL inhibited 80% cell viability and caused the highest decreases in EWS expression at mRNA and protein levels in both cell lines. Knockdown of EWS expression induced morphological features of differentiation. EWS shRNA plus TFL caused more alterations in molecular markers of differentiation than either agent alone. EWS shRNA plus TFL caused the highest decreases in cell migration with inhibition of survival, angiogenic and invasive factors. Knockdown of EWS expression was associated with removal of DNA methylation from p53 promoter, promoting expression of p53, Puma, and Noxa. EWS shRNA plus TFL induced the highest amounts of apoptosis with activation of extrinsic and intrinsic pathways in both cell lines in culture. EWS shRNA plus TFL also inhibited growth of Ewing’s sarcoma tumors in animal models due to inhibition of differentiation inhibitors and angiogenic and invasive factors and also induction of activation of caspase-3 for apoptosis. Collectively, knockdown of EWS expression increased various anti-tumor mechanisms of TFL in human Ewing’s sarcoma in cell culture and animal models.

A Case of Ewing’s Sarcoma of the Clavicle in Adults

The Clavicle is a rare primary site for Ewing sarcoma (ES). We report one case of patient with clavicular ES under our tracking and review the related literatures on management of this rare tumor. The patient was age of 35 years and were non metastaticat presentation. The patient received chemotherapy before and after the surgery. Claviculectomy was used. The patient had good functional outcomes with no pain of the shoulder at the follow-up of ten months. In conclusion, Ewing sarcoma of clavicle is a very rare tumor and different methods of surgical treatment can be used. Clavicle often can be resected without a need of reconstruction.

A case report on retroperitoneal PNET/EWS

Primitive neuroectodermal tumor (PNET) and Ewing’s sarcoma (EWS) are small round cell tumors occurring mainly in children and adolescents, rarely in adults. It can occur in multiple tissues and organs including kidney, adrenal, bladder, liver, small intestine, colon and rectum, with a preferred location within the chest area, in the limbs and around the spine, but with rare cases of abdominal, pelvic or retroperitoneal. Here we present a case of the retroperitoneal PENT/EWS in a 38-year-old man and we discuss the clinical features, histopathological characteristics, diagnosis, treatment and prognosis.

Myometrium and Sigmoid Colon Metastatic Melanoma Simulating a Ewing Tumor: A Case Report

Malignant melanomas or lymphoma of the skin are malignant tumors of the skin and/or the mucous membranes whose uterine metastases are rare. The secondary uterine localizations, although rare, must be evoked in front of a pelvic tumoral syndrome, or diffuse metastases and a personal past history of melanoma, even after a long time of remission. In our observation, the evolution of the tumor in the pelvis extended to the muscular structures of the uterus and the sigmoid colon of a 72 year old patient, what made it an exceptional case. The diagnosis of these secondary localizations is a diagnosis of elimination, almost always post-operative, made on the histopathological and immunocytochemical study of the surgical specimen, supported by cytogenetics, even molecular biology. The treatment is based on chemotherapy.

Primary Intramedullary Ewing’s Sarcoma: A Case Report and Review of the Literature

Ewing’s sarcoma, a group of primary neuroectodermal tumor (PNET), is an uncommon rare highly malignant tumor mostly affecting the bones of male patients, and accounts for approximately 10% of the primary malignant bone tumors, and occupies the second place after osteosarcoma in children’s less than 20 years. Primary intramedullary Ewing’s sarcoma is an extremely rare condition. Here, we present a case of a 16-year-old girl with progressive weakness of lower extremities, inability to walk, progressive low back pain, bilateral leg pain, paresthesia and urinary retention. Spinal MRI showed intramedullary abnormal signal focus from T11 to L3 vertebrae with moderate heterogeneous enhancement on T1 weighted sequences. After surgery, histological examination found a lot of small round-cell tumors with a high nuclear-cytoplasmic ratio, frequent mitoses and apoptotic nuclei suggesting a diagnosis of Ewing’s sarcoma and confirmed by CD99 reactivity. She had undergone adjuvant chemotherapy and irradiation and was free of symptoms since 02 years. Within this single pure case of intramedullary Ewing’s sarcoma, perhaps the 1st in the English literature, the authors described this extremely rare uncommon localization with a brief review of the literature.

CT and multimodal imaging findings of primary orbital Ewing＇s sarcoma involving the middle cranial fossa： a case report

This report details the CT and MR imaging findings of a primary orbital Ewing＇s sarcoma case involving the middle cranial fossa in a 13-year old boy. CT showed an ill-circumscribed homogeneous soft-tissue density mass with needle-like bone reaction. On MRI, the mass showed homogeneous iso-intensity on T1WI, heterogeneous hyper- intensity on T2WI, and marked homogeneous enhancement. Meanwhile, the mass was hyper-intense on DWI, and ADC alue was 575x10-6 mm2/s. The mass showed as high rCBV and rCBF, prolonged MTT based on DCS- PWI, and wash-out pattern of TIC derived from the DCE-MRI. Our case suggests that functional MRI modalities, including DWI, DSC-PWI or DCE-MR, could provide additional information for differential diagnoses. Both CT and MRI should be performed and comprehensively analyzed for limiting differential diagnoses, determining lesion extension and facilitating operative approach.

Primary extraosseous Ewing's sarcoma of the lung in a 36-year-old female patient:clinical,imaging,and pathologic findings

Primary extraosseous Ewing's sarcoma is a very rare clinical entity. In the report, we present the case of a 36year-old female patient who underwent resection of lung mass and was diagnosed as having Ewing's sarcoma by pathological examination. The clinical, imaging, and pathologic features of the case are described and discussed.

Anesthesia and perioperative management for giant adrenal Ewing’s sarcoma with inferior vena cava and right atrium tumor thrombus:A case report

BACKGROUND Ewing’s sarcoma of the adrenal gland with inferior vena cava(IVC)and right atrium thrombus is extremely rare.Here,we report a case of giant adrenal Ewing’s sarcoma with IVC and right atrium tumor thrombus and summarize the anesthesia and perioperative management.CASE SUMMARY A young female was admitted to the Department of Urology with intermittent pain under the right costal arch for four months.Enhanced abdominal computed tomography revealed a large retroperitoneal mass(22 cm in diameter),which may have originated from the right adrenal gland and was closely related to the liver.Transthoracic echocardiography showed a strong echogenic filling measuring 70 mm extended from the IVC into the right atrium and ventricle.After preoperative preparation with cardiopulmonary bypass,sufficient blood products,transesophageal echocardiography and multiple monitoring,tumor and thrombus resection by IVC exploration and right atriotomy were successfully performed by a multidisciplinary team.Intraoperative hemodynamic stability was the major concern of anesthesiologists and the status of tumor thrombus and pulmonary embolism were monitored continuously.During transfer of the patient to the intensive care unit(ICU),cardiac arrest occurred without external stimulus.Cardiopulmonary resuscitation was performed immediately and cardiac function was restored after 1 min.In the ICU,extracorporeal membrane oxygenation(ECMO)and continuous renal replacement therapy(CRRT)were provided to maintain cardiac,liver and kidney function.Histopathologic examination confirmed the diagnosis of Ewing’s sarcoma.After postoperative treatments and rehabilitation,the patient was discharged from the urology ward.CONCLUSION An adrenal Ewing’s sarcoma with IVC and right atrium thrombus is extremely rare,and its anesthesia and perioperative management have not been reported.Thus,this report provides significant insights in the perioperative management of patients with adrenal Ewing’s sarcoma and IVC tumor thrombus.Intraoperative circulation fluctuations and sudden cardiovascular events are the major challenges during surgery.In addition,postoperative treatments including ECMO and CRRT provide essential support in critically ill patients.Moreover,this case report also highlights the importance of multidisciplinary cooperation during treatment of the disease.

Resection with limb salvage in an Asian male adolescent withEwing’s sarcoma: A case report

BACKGROUNDEwing’s sarcoma is a highly malignant primary bone tumor that commonly affectschildren. For young patients, multidisciplinary treatment and limb salvage arerecommended, and surgical plans considering the growth potential and boneactivity after tumor resection are essential.CASE SUMMARYAn 11-year-old Asian boy had a 1-mo history of a right-sided limping gait.Imaging revealed a proximal tumor with bone destruction and physealinvolvement over the right femoral neck. He was diagnosed with stage IV(T1N0M1aG3) Ewing’s sarcoma with bilateral lung metastases. Neoadjuvantchemotherapy decreased the tumor size and confined it to the metaphysealregion. The patient underwent four stages of surgery: wide tumor excision plusreconstruction with vascular fibular bone graft plus internal fixation;repeat openreduction and internal fixation;femoral lengthening with orthosis after physealmaturity;and orthosis removal and bone elongation (approximately 6 cm).Following surgery, he could walk without discomfort and had almost equal-sizedbilateral femoral heads, indicating physis preservation. The surgery wassuccessful, and normal femoral head growth was achieved after completeremission. The patient was able to resume normal activities with equal length ofthe bilateral lower limbs.CONCLUSIONTumor treatment and reconstruction following resection are important in skeletally immature patients with Ewing’s sarcoma to improve quality of life.

Primary extraskeletal Ewing’s sarcoma of the lumbar nerve root:A case report

BACKGROUND Ewing’s sarcoma(ES)is a highly aggressive bone malignancy.Extraskeletal ES(EES)originating in the spinal canal is extremely rare.Herein,we report on a rare case of EES with a primary lumbar spinal nerve root including the complete diagnosis and treatment.CASE SUMMARY A young female patient presented with a complaint of right lower limb pain for 1 mo.Magnetic resonance imaging(MRI)revealed an 11 mm×14 mm×31 mm mass in the lumbar epidural region extending at the fifth lumbar spine(L5)level toward the right L5 neural foramen.Our initial diagnosis was an epidural schwannoma.The patient underwent total laminectomy,tumor resection and pedicle screw internal fixation and the L5 root tumor was found to have been completely removed intraoperatively.Histopathological examination of the lesion showed a typical ES with a large number of small,round cells.Immunohistochemistry analysis indicated positive CD99 and S100.After surgery,the patient received chemotherapy and radiotherapy with a 1 year of follow-up and no recurrent tumors or new lesions were found upon spine MRI and positron emission tomography/computed tomography reexamination.CONCLUSION Clinically,ES outside the bone should be considered when nerve root tumors are encountered inside and outside the spinal canal and the diagnosis should be determined by pathological biopsy.After surgical resection,chemotherapy and radiotherapy should be performed.After treatment,active follow-up and regular review should be completed.

Long-Term Results of Ewing’s Sarcoma—In a Single Institution

Purpose: This study analyzed oncological and functional outcomes of treatment for Ewing’s sarcoma, as well as its significant risk factors through long-term follow up. Objective and Method: Between September 1990 and April 2009, 20 cases that were diagnosed and treated as Ewing’s sarcoma in Kosin University Gospel Hospital were entered onto the study. Mean follow-up period was 45.4 (12 - 108) months. There were 7 cases of male and 13 cases of female, and mean age was 19.9 (5 - 48) years old. Retrospective review was done about treatment outcomes, complications, and significant risk factors. Results: In terms of oncologic results, there were 9 cases of CDF (continuous disease free), 1 case of NED (no evidence of disease), 4 cases of AWD (alive with disease), 5 cases of DOD (dead of disease), and 1 case of DWOD (dead with other disease). Five-year overall survival rate of all the patients was 70.0% and event-free survival rate was 50.0%. The mean MSTS (Musculoskeletal Tumor Society) score was 15.9 (53%) points at last follow-up. Among prognostic factors of age at diagnosis, Enneking stage, size of tumor, site of primary lesion, and distant metastasis, 5-year survival rate of groups without metastasis were 90.9%, nevertheless 44.4% in other group with the metastasis showing statistical significance (p = 0.020). Postoperative complications were 3 cases of infection, each 2 cases of ankylosis and metal failure, and each 1 case of leg length discrepancy, periprosthetic fracture, and local recurrence. Conclusion: Five-year survival rate of this study was similar to that of multicenter studies in America and Europe. Among the prognostic factors, distant metastasis was proven to be most significant. Enneking stage, size of tumor and site of primary lesion are also important and could be statistically significant if with more cases.