Primary Ewing＇s sarcoma/primitive neuroectodermal tumor of the urogenital tract in children

Background Primary Ewing＇s sarcoma/primitive neuroectodermal tumor （ES/PNET） of urogenital tract is a rare condition with non-specific clinical presentations, which can make it difficult to diagnose. In this study, we summarize the clinical presentation, pathological features, therapeutic strategies, and prognosis of ES/PNET.

Ewing sarcoma/primitive neuroectodermal tumor of the ureter:A case report and literature review

Ewing sarcoma/primary neuroectodermal tumors are rare,invasive,and small round blue cell tumors.There are few reports of its occurrence in the urinary system.Here,we present the first middle-aged female patient whose Ewing sarcoma primary site was in the ureter.The main clinical manifestation was intermittent hematuria.She was in good health after complete surgical resection and adjuvant radiotherapy.To date,there has been no recurrence or metastasis.Accurate early diagnosis and appropriate treatment can help prolong survival.18F-fluorodeoxyglucose positron emission tomography/computed tomography is expected to be an effective means of evaluating treatment effects and detecting metastasis and recurrence.In this article,besides introducing a case of Ewing sarcoma/primitive neuroectodermal tumor of the ureter,we review the literature to discuss the current status of diagnosis and treatment.

Ewings Sarcoma-Primitive Neuroectodermal Tumour-Rare Extraosseous Presentation

Introduction: Ewings sarcoma is uncommon in extra osseous locations. They belong to Ewings family of tumours and the primitive neuroectodermal tumour is often diagnosed based on immuno histochemistry and molecular genetic studies. Discussion: A 50-year-old gentleman presented with complaints of a swelling in the right thigh. With a diagnosis of soft tissue sarcoma, the patient underwent a wide local excision of the tumour. We review literature of the small round blue cell tumour. Conclusion: Extraosseous Ewings sarcoma presenting as a thigh swelling is uncommon. The sarcoma was vimentin positive and CD99 membrane positivity.

Huge peripheral primitive neuroectodermal tumor of the small bowel mesentery at nonage:A case report and review of the literature

Extraskeletal Ewing's sarcoma/peripheral primitive neuroectodermal tumor(E-EWS/pP NET) is a rare aggressive malignant small round cell tumor. In this report, we present the case of a 15-year-old boy who suffered from acute abdominal pain accompanied by hematemesis and melena, and was eventually diagnosed with E-EWS/p PNET. To date, there have been only five reported cases of E-EWS/pP NET of the small bowel including the patient in this report. To the best of our knowledge, this is the first documentation of a pP NET of the small bowel mesentery at nonage. All these have made this report rare and significant.

Huge primitive neuroectodermal tumor of the pancreas:Report of a case and review of the literature

Primitive neuroectodermal tumor (PNET) of the pancreas is an extremely rare tumor that usually occurs in children or young adults. We report a case of a 33-year-old male patient with an 18 cm × 18 cm × 16 cm mass arising from the pancreatic body and tail with a one- day history of abdominal pain. Initial CT scan showed no signs of metastatic tumor spread. The tumor caused intrabdominal bleeding and the patient underwent primary tumor resection including partial gastrectomy, left pancreatic resection and splenectomy. Diagnosis of PNET was confi rmed by histology, immunohistochemistry and FISH analysis. All neoplastic cells were stained positive for MIC2-protein (CD99). Approximately one month after surgery, several liver metastases were observed and the patient underwent chemotherapy according to the Euro- Ewing protocol. Subsequent relaparotomy excluded any residual hepatic or extrahepatic abdominal metastases. Although PNET in the pancreas is an extremely rare entity, it should be considered in the diffential diagnosis of pancreatic masses, especially in young patients. This alarming case particularly illustrates that PNET in the pancreas although in an advanced stage can present with only a short history of mild symptoms.

Detection of EWS-FLI1 fusion transcripts in paraffin embedded tissues of peripheral primitive neuroectodermal tumors by nested reverse transcription polymerase chain reaction

Objective: To assess the feasibility and significance of detecting EWS-FLI1fusion transcripts in paraffin embedded tissues of peripheral primitive neuroectodermal tumors (PNETs) by nested reverse transcription polymerase chain reaction(RT-PCR). Methods: Twelve formalin-fixed and paraffin-embedded (FFPE) samples of PNET were retrieved from archive and consultation materials, together with eight cases of controlled tumor. EWS-FLI1 fusion transcripts were detected by nested RT-PCR. Home-keeping gene β-actin was used to detect the quality of mRNA. Results: β-actin mRNA was detected in 9 of the 12 tumor cases. EWS-FLI1 fusion transcripts were detected in 6 cases, among which 4 had a “type 1” fusion transcript and 2 had a “type 2” fusion transcript. None of the controlled tumor was detected the fusion gene. Conclusion: RT-PCR is a feasible method for the detection of EWS-FLI1 fusion transcripts in FFPE tissues in PNET and the result is meaningful in differential diagnosis and prognostic evaluation.

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.

Esophageal subepithelial lesion diagnosed as malignant gastrointestinal neuroectodermal tumor

A 21-year-old male visited our hospital with a complaint of aggravating dysphagia and odynophagia for a few days.Esophagogastroduodenoscopy showed huge bulging mucosa with an intact surface causing luminal narrowing at 35 cm from the incisor teeth.Endoscopic ultrasonography showed an about 35 mm sized irregular margined in-homogenous hypoechoic lesion with an obscure layer of origin.Endoscopic ultrasonography fine needle aspiration revealed spindle cell proliferation without immunoreactivity for CD117,SMA,and cytokeratin.The patient underwent excision of the subepithelial lesion at the distal esophagus.On pathologic examination of the specimen,the tumor was composed of short fascicles of oval to spindle cells with eosinophilic and clear cytoplasm and vesicular nuclei.The tumor cells were positive for S-100 and SOX10and negative for CD117,SMA,HMB-45,melan-A,cytokeratin,and CD99.The split-apart signal was detected in EWSR1 on FISH,suggesting a malignant gastrointestinal neuroectodermal tumor.At the time of writing,the patient is on radiation therapy at the operated site of esophagus and doing well,with no recurrence for three months.Malignant gastrointestinal neuroectodermal tumor is a rare gastrointestinal tumor with features of clear cell sarcoma,without melanocytic differentiation,and shows a poor prognosis.This is the first reported case of malignant gastrointestinal neuroectodermal tumor arising as subepithelial lesion in the esophagus.

Primary Vulvar Ewing Sarcoma in a 30-Year-Old Woman: A Case Report

Primary Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) are considered as Ewing sarcoma family of tumors (ESFT), characterized by chromosomal translocation t(11;22) (q24;q12) leading to a chimeric transcript EWS-FLI1 in 85% of cases. It typically involves the soft tissues of the chest wall, pelvis, paravertebral region, abdominal wall, retroperitoneal region and extremities in children, adolescents and young adults. It rarely occurs in the female genital tract. We report an extremely rare case of advanced vulvar Ewing sarcoma/PNET of the vulva confirmed by Fluorescence In Situ Hybridization (FISH) in a 30-year-old woman. The patient was treated by 6 cycles of chemotherapy followed by radiotherapy with favourable outcome.

Diagnostic Strategies and Treatment for Ewing’s Sarcoma

Ewing’s sarcoma is an enigmatic malignancy of progenitor cell origin, driven by transcription factor oncogenic fusions. About 85% of ESFT cases harbor the t(11;22) translocation and express the fusion protein EWS-FLI. Both bone marrow-derived human Mesenchymal stem cells and Neural crest stem cells are permissive for EWS-FLI1 expression that initiates transition to ESFT-like cellular phenotype. Diagnosis of Ewing’s tumor is based on pathologic and molecular findings. The hypoxia enhances the malignancy of ESFT invasive capacity. An ALDHhigh subpopulation of Ewing’s sarcoma cells, capable of self-renewal, tumor initiation and resistant to chemotherapy in vitro, are not resistant to YK-4-279. Intensive high-dose chemotherapy followed by stem-cell reconstitution was used for ESFT patients in second remission. Plerixafor in combination with G-CSF is an effective enhance stem cell mobilization regimen for stem cell collection with lowest success rate in patients with neuroblastoma. The ESFT-derived antigens EZH2(666) and CHM1(319) are suitable targets for protective allo-restricted human CD8(+) T-cell responses against non-immunogenic ESFT. Primitive neuroectodermal features and MSC origin are both compatible with G(D2) aberrant expression and explore G(D2) immune targeting in ESFT.

Peripheral Primary Neuroectodermal Tumour of the Ileum: A Case Report and Review of the Literature

Background: Ewing’s Sarcoma (ES)/peripheral Primitive Neuroectodermal Tumor (pPNET) is a rare aggressive malignant small round cell tumour. Most of them arise in bony sites, and they represent the second commonest primary osseous malignancy in adolescence and young adults. The localization of the small bowel is very rare, to our knowledge only 35 cases of ES/pPNET of the small bowel have been reported in the literature. Case Presentation: We report a case of pPNET of the ileum in a 26-year-old female, presented abdominal pain with a transit disorder. The clinical examination was unremarkable. The histological and immunohistochemical study confirmed the diagnosis of peripheral primary neuroectodermal tumours. The patient was treated by tumor resection followed by adjuvant chemotherapy. The evolution was good, without recurrence with a follow-up of 12 months. Conclusion: PNET of the ileum is very rare. We report this case to enrich the database of this rare clinical entity and to improve the management of patients with PNET of the ileum.

EWING’S SARCOMA CAN EXPRESS BONE MORPHOGENETIC PROTEIN

Paraffin sections from 6 cases of Ewing's sarcoma were immunostained by ABC method using BMP -McAb for investigating the existence of BMP in Ewing' s sarcoma. All cases were positive. The result was coincided with human tumor transplants in athymic nude mouse by Bauer. It is shown that Ewing' s sarcoma can express BMP. So we support the hypothesis that Ewing' s sarcoma originates from primitive multipotential cells and can pluripotentially differentiate.

A Case of Ewing’s Sarcoma Arising in the Cervical Spine with an Elevation of Serum ProGRP

We experienced a case of small, round-cell malignant neoplasm diagnosed by touch smear cytology and histopathology when an open biopsy was performed in a 50-year-old Japanese woman. She was suspected of having a cervical spine tumor after surgery for cervical spine foraminal stenosis. After consent, the cervical spine tumor histologically diagnosed by an open biopsy was confirmed to be Ewing sarcoma (EWS) by genetic testing. EWS belongs to a group of small, round-cell tumors that are morphologically similar and often difficult to differentiate. After the open biopsy, the present patient received radiotherapy, and her plasma level of Pro-Gastrin-Releasing-Peptide was decreased (217.2 pg/ml before surgery to 30.3 pg/ml;reference value: 0 - 80 pg/ml). We herein report the process for making the final diagnosis by focusing on the intraoperative cytology, histopathology, and immunohistochemical findings. Our diagnosis was validated by karyotyping and a fluorescence in-situ hybridization analysis.

Molecular detection of EWS-Ets fusion transcripts and their clinicopathologic significance in Ewing’s sarcoma/peripheral primitive neuroectodermal tumor

Background Ewing＇s sarcoma/peripheral primitive neuroectodermal tumor （ES/pPNET） is often difficuh to distinguish from other small round cell tumors. The EWS-Ets gene fusions that result from chromosomal translocations in this tumor provide potential molecular diagnostic markers. To apply these molecular markers to commonly available archival materials, we evaluated the feasibility of detecting EWS-Ets including EWS-Flil and EWS-ERG fusion transcripts in paraffin-embedded tissues and its diagnostic value for detecting ES/pPNET. Methods Thirteen paraffin-embedded samples of ES/pPNETs were retrieved from archives. Thirteen cases of other tumors with small round cell features （including rhabdomyosarcoma, neuroblastoma, lymphoma, small ceil carcinoma, and desmoplastic small round cell tumor ） were used as negative controls. β-actin and β2- microglobulin were used as internal controls. A nested reverse transcriptase-polymerase chain reaction （RT- PCR）-based assay was performed to detect the EWS-Flil and EWS-ERG fusion transcripts. Results β-aetin and β2-mieroglobulin were detected in 10/13 and 13/13 ES/pPNETs, respectively. EWS- Flil fusion transcripts were detected in 11 of 13 （85%） ES/pPNETs. Three chimeric transcripts, all EWS-Flil, were detected in ES/pPNET samples. Among 11 EWS-Flil-positive cases, 7 eases had a type Ⅰ fusion transcript involving fusion of EWS exon 7 with Flil exon 6, 2 eases had a type Ⅱ fusion transcript involving EWS exon 7 with Flil exon 5, and 2 eases expressed fusion transcripts involving EWS exon 7 and Flil exon 8. Type Ⅰ EWS- Flil fusion predominated over other types. Fusion types could not be distinguished in the remaining 2 eases. Thirteen negative controls did not show detectable chimeric messages. There was a significant relationship between EWS-Flil fusion transcripts and CD99 expression. Conclusions Molecular detection of EWS-Flil fusion transcripts in formalin-fixed paraffin-embedded material by nested RT-PCR is feasible and is useful for the diagnosis and differential diagnosis of ES/pPNETs.

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。

EWS易位分离探针荧光原位杂交和免疫组织化学抗体(FLI-1和CD99)在尤文肉瘤/原始神经外胚层肿瘤诊断中的价值

目的:评价EWS易位分离探针荧光原位杂交(fluorescence in situ hybridization,FISH)与免疫组化抗体CD99、FLI-1对尤文肉瘤/原始神经外胚层肿瘤(Ewing’s sarcoma/primitive neuroectodermal tumor,EWS/PNET)的诊断价值。方法:收集35例EWS/PNET和其他小圆细胞肿瘤24例,应用FISH检测EWS基因易位、免疫组化抗体CD99和FLI-1的表达,进行对比研究,评价各自及联合应用的诊断价值。结果:FISH检测在EWS/PNET的敏感性、特异性、阳性预期值和阴性预期值分别为93.8%(30/32)、81.8%(18/22)、88.2%(30/34)和90%(18/20);CD99分别为100%(35/35)、58.3%(14/24)、77.8%(35/45)和100%(14/14);FLI-1分别为71.4%(25/35)、62.5%(15/24)、73.5%(25/34)和60%(15/25)。不同指标两两联合应用敏感性、特异性和阳性预期值、阴性预期值为:CD99+FLI-1分别为71.4%(25/35)、75%(18/24)、80.6%(25/31)和64.3%(18/28);FLI-1+FISH分别为68.7%(22/32)、86.4%(19/22)、88%(22/25)和65.5%(19/29),CD99+FISH分别为93.8%(30/32)、95.5%(21/22)、96.8%(30/31)和91.3%(21/23)。结论:应用EWS基因易位分离探针FISH检测染色体易位,是辅助诊断EWS/PNET非常敏感和特异的分子指标,与CD99联合应用诊断价值最大。在缺乏FISH结果的情况下,FLI-1和CD99联合应用能够提高诊断的特异性。

骨外Ewing肉瘤/外周原始神经外胚叶肿瘤的临床病理分析

目的探讨骨外Ew ing肉瘤/外周原始神经外胚叶肿瘤的临床病理特征及诊断、鉴别诊断依据。方法18例骨外E-w ing肉瘤/外周原始神经外胚叶肿瘤行常规病理检查及免疫组化染色,其中2例进行电镜检查。结果光镜显示肿瘤组织主要由小圆形或卵圆形细胞组成,免疫组化染色显示肿瘤细胞膜CD99强阳性,电镜显示肿瘤细胞质内有神经内分泌颗粒。结论骨外Ew ing肉瘤/外周原始神经外胚叶肿瘤的诊断依赖病理特征,并需要与其他小细胞恶性肿瘤进行鉴别。

RT-PCR法检测外周原始神经外胚叶瘤石蜡包埋组织中EWS-FLI1融合基因

目的 研究嵌套式逆转录-聚合酶链反应(nestedRT- PCR)方法检测外周原始神经外胚叶瘤石蜡包埋组织中EWS -FLI1融合基因的可行性和临床意义。方法 收集12例外周原始神经外胚叶瘤及8例对照肿瘤标本,均为福尔马林固定石蜡包埋组织。EWS -FLI1融合基因检测方法采用嵌套式RT- PCR法。看家基因β-actin为内参照。结果 9例标本检测到β-actin片断, 6例检测到EWS FLI1融合基因表达,其中,“1型”4例,“2型”2例。8例对照肿瘤中未检测到EWS- FLI1基因。结论 在外周原始神经外胚叶瘤石蜡包埋组织中,用嵌套式RT- PCR检测EWS- FLI1融合基因是可行的方法,检测结果对肿瘤鉴别诊断和预后判断有意义。

16例口腔颌面部Ewing肉瘤/原始神经外胚层瘤的临床、影像学及病理分析

目的分析和总结口腔颌面部Ewing肉瘤/原始神经外胚层瘤（primitive neuroectodermal tumors,PNET）的临床、影像学及病理特征,提高对口腔颌面部Ewing肉瘤/PNET的认识和诊治水平。方法对16例口腔颌面部Ewing肉瘤/PNET患者的临床及影像学特点、肿瘤的大体和镜下特征、免疫组织化学、治疗和预后进行观察与分析。结果 16例口腔颌面部Ewing肉瘤/PNET中,PNET13例,Ewing肉瘤3例。发病年龄5个月~48岁,平均20.9岁,男性14例,占87.5%;CT、MRI均表现为侵袭性的生长方式,HE染色镜下表现为小圆细胞肿瘤,CD99、NSE表达均阳性。随访15例,其中12例术后3~17个月死亡,尚存3例病人随访6~10月至今。结论 Ewing肉瘤/PNET是一组罕见的高度恶性的小圆细胞肿瘤,具有恶性程度高、易复发、预后差等特点。影像学可提示肿瘤的恶性性质,最终的肿瘤类型依靠病理HE染色镜下和免疫组织化学的特点决定。治疗以手术切除为主,结合术后放化疗。

RT-PCR法检测EWS-FLI1融合基因诊断尤文肉瘤/外周原始神经外胚层瘤

目的探讨尤文肉瘤/外周原始神经外胚层瘤(EWS/pPNET)石蜡包埋组织中EWS-FLI1融合基因表达的临床病理意义。方法采用免疫组化对1例纵隔尤文肉瘤/外周原始神经外胚层瘤进行观察,应用反转录-聚合酶链反应(RT-PCR)检测融合基因EWS-FLI1的表达。结果肿瘤由小圆细胞、卵圆形细胞及短梭形细胞构成,巢状、片状或列兵样排列,间质显著增生,未见典型菊形团结构。免疫组化显示CK、EMA和CD99弥漫强(+)。RT-PCR检测出EWS-FLIl融合基因的表达。结论EWS/pPNET与促结缔组织增生性小圆细胞肿瘤(DSRCT)具有重叠的形态学和免疫组化特点,石蜡包埋组织中检测EWS-FLI1融合基因的表达可作为诊断EWS/pPNET的可靠指标。