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.     

骨原始神经外胚层肿瘤10例临床分析

目的：初步探讨骨原始神经外胚层肿瘤的临床特征及治疗原则。方法：回顾性分析10例骨原始神经外胚层肿瘤的治疗及生存情况。10例中1例行左肩关节解脱术,1例行右髋关节解脱术,2例行左大腿中段截肢术,6例行骨肿瘤切除加灭活回植加内固定术。10例患者术后均行6周期IFO＋VP-16常规化疗。结果：经手术及术后化疗,除3例生存10、14和15个月死亡外,余7例已分别生存9、12、14、16、18、22及25个月。结论：根治性手术治疗加术后早期化疗是治疗骨原始神经外胚层肿瘤的有效手段。     

血尿表现的前列腺原始神经外胚层瘤1例并文献复习

目的:探讨前列腺原始神经外胚层瘤临床表现、病理学特点、诊断标准及治疗与预后,以提高对本病的诊疗水平。方法:回顾性分析我院前列腺原始神经外胚层瘤1例及总结文献检索所得前列腺PNET病例12例的临床表现、病理结果及治疗与预后。结果:病例中最短生存期为术后一个月死于肺转移。最长生存期为随访至12个月。我院病例术后4月复查盆腔肿瘤复发。结论:外周PNET十分罕见,前列腺PNET更罕见。对于排尿困难和血尿的青年患者如诊断不明确应考虑本病可能。超声、CT、MRI可发现该疾病但无特异性,病理可诊断。早期诊断、积极治疗对预后影响大,对于晚期患者化疗效果明显。     

Melanotic primitive neuroectodermal (neuroepithelial) tumor of medulla

A 69-year-old man had a melanotic primitive neuroectodermal tumor of the medulla displaying various neuroepithelial elements including undifferentiated neuroepithelial cells forming Homer Wright's rosettes as well as neoplastic neuroglia resembling those seen in medulloblastoma. The neuroglial tumor cells were verified by demonstrating glial fibrillary acidic protein (GFAP) in the cells. These findings support the concept that the primitive neuroectodermal tumor and medulloblastoma are similar neoplasms. They have been described by such diverse names as melanotic medulloblastomas and progonomas. Review of 18 reported cases of intracranial melanotic primitive neuroectodermal tumors, including the present one, reveals that they have common pathologic features, are most frequent in the cerebellum and fourth ventricle, often metastasize widely within the neuraxis or even systemically, occur more frequently in children than adults, and strike males more often than females.     

椎管内原始神经外胚层肿瘤1例

原始神经外胚层肿瘤(primitive neuroectodermal tumor,PNET)临床少见,临床及影像学表现无特异性,极易误诊误治,为提高对本病的认识,我科近来收治1例,报道如下并结合文献复习. 1临床资料 患者,女,20岁.于1.5个月前无明显诱因出现双下肢酸软感,以右侧为甚,双下肢活动正常.当时未予注意,未行检查.近1个月来上述症状加重,出现右脚跛行,自觉右下肢无力伴双下肢麻木感,并出现腰背部疼痛,疼痛呈持续性,有针刺感,无放射他处,活动后加重.曾在我院门诊行腰部X线片检查未发现异常.     

Cerebral primitive neuroectodermal tumor in an adult,with spinal cord metastasis after 18-year dormancy

A cerebral primitive neuroectodermal tumor in a 40-year-old man recurred as a metastasis to the spinal cord after an 18-year dormant period. The metastatic tumor showed features of neuronal differentiation. The clinical course and pathologic findings are discussed.     

Supratentorial primitive neuroectodermal tumors: a Canadian pediatric brain tumor consortium report

Introduction Supratentorial primitive neuroectodermal tumors (SPNET) are rare tumors accounting for only 2.5% of childhood brain tumors. The purpose of this study was to describe the range of treatment regimens used to treat pediatric SPNET in Canada and to identify prognostic factors for overall survival in this population. Methods This study was a retrospective clinical analysis of SPNET patients treated over the last 10 years in Canada. A questionnaire was developed and distributed to all institutions in Canada who treat pediatric patients. Data were collected for patients <19 years of age who were diagnosed and treated for SPNET between 1995 and 2005. Results Data were obtained for 48 eligible patients. The stages of patients for whom complete data were provided were 80, 3, and 16% for metastatic stage M0, M1, and M2/3, respectively. The best responses to therapy included complete response in 44%, partial response in 8%, still on therapy in 2%, progressive disease in 31%, toxic death in 2%, and no therapy given in 12%. The 4-year survival was 37.7 ± 7.6%. The factors associated with an increase in survival were the use of radiation therapy and chemotherapy, and age >2 years. Overall survival was not affected by metastatic disease at diagnosis, tumor site, or degree of initial resection. Conclusions Survival is poor in SPNET patients but highest in those who received chemotherapy and radiation therapy. Further studies are needed to improve the survival of these patients.     

Chemotherapy for medulloblastomas and primitive neuroectodermal tumors

Summary In the past two decades, chemotherapy has proven to be an increasingly more effective modality in the treatment of medulloblastoma. Current evidence suggests that chemotherapy be included as part of standard treatment for all patients with high-risk medulloblastoma. Ongoing multi-centre trials are determining whether chemotherapy should be added to reduced dose radiotherapy as a substitute therapy for standard-dose radiotherapy. The major randomized and non-randomized chemotherapy trials for newly diagnosed patients with medulloblastoma or for patients at recurrence are presented. It is hoped that the addition of chemotherapy will eventually lead to improved survival rates as well as the reduction in the craniospinal radiotherapy dose for patients with medulloblastoma.     

Cytogenetic confirmation of a gastrointestinal stromal tumor and ewing sarcoma/primitive neuroectodermal tumor in a single patient

We report a rare case in which two tumor entities, a gastrointestinal stromal tumor (GIST) and Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), with distinct cytogenetic features occurred in a single patient. The patient was a 72-year-old woman. The first tumor was a submucosal gastric tumor and was diagnosed as a low-risk group GIST based on morphological characteristics and the results of an immunohistochemical analysis for c-kit and CD34. Further cytogenetic analysis revealed that this tumor had a point mutation (D842V substitution) in exon 18 of the platelet-derived growth factor receptor alpha gene. The second tumor was found more than 4 years after the appearance of the first tumor. ES/PNET was highly suspected both morphologically and immunohistochemically, and the diagnosis was confirmed by the detection of an EWS rearrangement using a fluorescence in situ hybridization technique. Although the cytogenetic correlations of these two tumors are unclear, accurate histologic recognition is of clinical importance because the treatments for these two tumors differ.     

A supratentorial primitive neuroectodermal tumor in an adult: a case report and review of the literature

Supratentorial primitive neuroectodermal tumors (sPNET) occurring in adults are rare. Only 56 such cases have been previously reported. This report documents a 56-year-old male who presented with the chief complaint of right facial palsy. Magnetic resonance imaging (MRI) revealed left frontal and bilateral periventricular lesions. Surgery was performed for the frontal mass, which was histologically diagnosed to be sPNET. An immunohistochemistry assay for CD99, and a fluorescence in situ hybridization (FISH) assay for t(11;22) translocation revealed this PNET to be a central PNET. This case was the first case to detect a central PNET using both immunohistochemistry and the FISH assay in adult sPNET. Though radiation therapy was performed, an MRI performed 2.5 months after the surgery revealed a regrowth of the tumor. The patient died 5 months after surgery. This case report is accompanied by a review of 57 cases of adult sPNET.     

原始神经外胚层肿瘤化疗相关因素的研究

目的评价原始神经外胚层肿瘤患者化疗的客观疗效,分析影响预后的因素。方法总结2000年3月～2008年9月我院收治的23例接受化疗的原始神经外胚层肿瘤患者的临床特点及化疗效果,用COX生存模型回顾性分析年龄、性别、是否手术、是否放疗、是否有远处转移、CD99的表达强度及是否接受新辅助化疗对其生存预后的影响。结果23例患者中女性11例,男性12例,中位年龄27岁,化疗后CR0例,PR11例,客观有效率55％,有效率与CD99表达强度不相关（P=0．843）,中位生存期为12个月。年龄（P=0．024）、远处转移（P=0．032）和放疗（P=0．044）对死亡风险有显著性影响,CD99表达强度在模型中P值为0．067。结论本组研究中原始神经外胚层肿瘤患者男女比例相当,多为年轻患者,化疗有效率较高,但生存期不长。接受放疗、年龄小、无远处转移、CD99表达强度低的患者死亡的风险小,CD99表达强度越高死亡的风险越大。     

Cytogenetic and histopathologic studies of congenital supratentorial primitive neuroectodermal tumors: A case report

Primitive neuroectodermal tumors (PNET) represent about 25% of primary central nervous system tumors in childhood, but congenital PNETs are rare. Cytogenetic studies and studies on molecular pathology have identified several genetic alterations in medulloblastoma, but molecular investigations on supratentorial PNETs are infrequent. We present a male newborn with a large congenital PNET of the right cerebral hemisphere and the molecular analysis of the tumor. Tumor tissue was investigated by routine histology and immunohistochemistry. Fluorescence in-situ hybridization was carried out on native tumor tissue to investigate deletions on chromosome 17p and to analyze c-Myc or N-Myc amplifications. Histologic examination revealed a primitive neuroectodermal tumor with massive extension covering almost the entire right hemisphere. Genetic analysis of the native tumor tissue of our patient excluded a deletion of chromosome 17p. An amplification of the c-Myc or N-Myc oncogene was absent using fluorescence in-situ hybridization. Despite unremarkable genetic analysis in our case prognosis was poor, suggesting that there are additional, yet unknown constitutional genetic aberrations in the pathogenesis of congenital supratentorial PNET.     

原始神经外胚层瘤预后相关因素分析

目的：探讨各临床因素、治疗对原始神经外胚层瘤（primitive neuroecto dermal tumor，PNET）预后的影响。方法：回顾性分析2004—12—06—2012—10—25苏州大学附属第一医院收治的46例PNET患者临床资料，其中男28例，女18例，男女比例为1．56：1；年龄6～84岁，中位年龄37岁；肿瘤原发部位位于非中线部位为21例，位于中线部位或盆腔为25例；46例患者中Ⅰ～Ⅱ期患者14例（30．4％），Ⅲ期14例（30．4％），Ⅳ期18例（39．1％）。29例患者初诊时LDH值〈225U／L，17例≥225U／L。12例行根治术＋化疗／放疗，16例行单纯根治术，4例行姑息术，14例放疗／化疗。采用Ka—plan-Meier法进行单因素生存分析，Log—rank法检验差异显著性，Cox回归模型进行多因素分析，偏相关进行相关性分析。结果：全组中位生存期为10个月（2～50个月），1、3年生存率分别为48．0％和11．0％。单因素分析显示，肿瘤原发部位、分期、初诊时LDH值和治疗方式可以影响全组患者的总生存期；多因素分析显示，原发部位、分期、初诊时LDH值和治疗方式是影响患者生存的独立预后因素。偏相关分析显示，Ki-67表达强度与生存时间呈负相关。结论：原发部位在盆腔或中线位、分期晓和初诊时LDH值≥225U／L是PNET患者预后不良的主要因素，采用综合治疗可延长PNET患者的生存时间。     

Congenital peripheral primitive neuroectodermal tumor: A case treated successfully with multimodality treatment

Neonatal tumors comprise less than two percent of childhood malignancies. Most are solid tumors, most common histologies being teratoma and neuroblastoma. We encountered a child who was detected to have a right arm mass on antenatal sonogram, which was diagnosed to be a primitive neuroectodermal tumor involving the triceps on fine needle aspiration cytology performed in the post-natal period. The child was successfully treated with multimodality treatment consisting of surgery, chemotherapy and radiotherapy. We also discuss briefly the problems associated with therapy in neonatal period. A review of all cases reported to have congenital Ewing’s sarcoma family of tumors is presented. Novel therapies are needed to improve efficacy and decrease the devastating side effects of treatment in this age group.     

Long-term relapse-free survival with supratentorial primitive neuroectodermal tumor in an adult: a case report

Summary Objective In adults, supratentorial primitive neuroectodermal tumor (sPNET) is a very rare undifferentiated embryoblastic neoplasm. Prognosis is worse in comparison to infratentorial medulloblastoma. Older age appears to be prognostically favorable. At present, 5-year survival rates remain below 50% in all age groups. Survival longer than 15 years in an adult has only been reported once so far. Case report In 1987, a 33-year-old-male patient presented with seizures following a six-month’s history of dizziness. CT- and MRI-scans revealed a right occipital tumor with moderate contrast enhancement. The tumor was completely removed. The original histological diagnosis was that of an undifferentiated sarcoma, malignant hemangioendothelioma, grade III. The patient was treated by CyVADIC chemotherapy and conventional radiation therapy (60 Gy). Admission for another reason in 2003 led to a re-evaluation of the original diagnosis. Microscopy revealed a malignant, highly cellular, poorly differentiated tumor with a desmoplastic component. Up to 20% of tumor nuclei were labeled for Ki-67. Almost all cells were stained for neuron specific enolase and NGF-Rp75, with neuronal and glial markers being present to a variable extent. According to these findings, the diagnosis was changed to a sPNET (WHO IV°). Other tumor entities were excluded by immunohistochemistry. Conclusions Although the prognosis of sPNET is reported to be poor, a small fraction with a rather benign biological and clinical behavior exists. Parameters determining long-term-survival in sPNET are not yet known. Whenever possible, complete surgical resection should be attempted followed by postoperative radiotherapy. The value of chemotherapy is an issue of continuous investigation. Supratentorial primitive neuroectodermal tumor is a very rare and highly malignant neoplasm in adults, carrying a poor prognosis. Complete surgical resection followed by radiotherapy proved to be essential for the outcome. We report the case of long-term survival at more than 17 years in an adult patient treated by surgery, postoperative radiation and chemotherapy.     

Adult primary pulmonary primitive neuroectodermal tumor: Molecular features and translational opportunities

Primitive neuroectodermal tumors (PNET) arising directly from the lung are very rare but particularly aggressive neoplasms. We report a case of a 31-y-old man with primary pulmonary neuroectodermal tumor. We review the clinical as well as pathological features. As typical for these tumors, the diagnosis was initially delayed in our patient and prognosis was poor despite aggressive surgical resection, postoperative chemotherapy and local irradiation. Recent biological insights have revealed unique chromosomal translocations crucial to the pathogenesis of these tumors, most notably the EWS-FLI-1 translocation. We provide an overview of the molecular features of the Ewing Sarcoma Family of Tumors (ESFT) including PNET and their potential implications for therapeutic targeting.     

Growth-inhibiting effect of intratumoral recombinant human tumor necrosis factor on an experimental model of primitive neuroectodermal tumor

The effect of intratumoral administration of recombinant human tumor necrosis factor on an experimental model of primitive neuroectodermal neoplasia was studied. A clear inhibition of tumor growth was achieved by immunotherapy that consisted in intralesion injections of 100 g of tumor necrosis factor daily, the first three days of each week, for a period of four weeks. At this time, tumor size was 2.21 ± 0.66 cm² (mean ±standard deviation) in the treated group, versus 7.62 ± 0.43 cm² in the control group. These data support previous studies on the influence of tumor necrosis factor on the development of ethyl-nitrosourea-induced tumors, and suggest the potential usefulness of this cytokine in human primitive neuroectodermal neoplasms.     

CT、MRI检查在外周原始神经外胚层肿瘤诊治中的作用

目的：通过对影像学和病理学的分析，旨在提高对外周神经外胚层肿瘤(pPNET)的认识。方法：回顾性分析有完整影像和病理资料的6例pPNET。结果：软组织pPNET的CT表现为大的、边界不清的软组织肿块，密度不均匀伴坏死囊变，不伴钙化，增强后呈不均匀强化。骨pPNET主要表现为较大的溶骨性骨质破坏伴软组织肿块，无新生骨、瘤骨，增强后不均匀强化。MRI在SE序列T1W表现为等肌肉信号，T2W表现为不均匀高信号，增强后强化不均匀，可见类似包膜和分隔样改变。结论：pPNET的影像学表现没有明显特征性。CT和MRI的作用主要用于描述肿瘤内部结构、侵犯范围以及与周围组织、血管神经的关系，同时可以提供肿瘤远处转移的信息，对临床手术可切除性与评价疗效有着非常重要的意义。     

A patient tumor-derived orthotopic xenograft mouse model replicating the group 3 supratentorial primitive neuroectodermal tumor in children

Background

Supratentorial primitive neuroectodermal tumor (sPNET) is a malignant brain tumor with poor prognosis. New model systems that replicate sPNET''s molecular subtype(s) and maintain cancer stem cell (CSC) pool are needed.

Methods

A fresh surgical specimen of a pediatric sPNET was directly injected into the right cerebrum of Rag2/SCID mice. The xenograft tumors were serially sub-transplanted in mouse brains, characterized histopathologically, and subclassified into molecular subtype through qRT-PCR and immunohistochemical analysis. CSCs were identified through flow cytometric profiling of putative CSC markers (CD133, CD15, CD24, CD44, and CD117), functional examination of neurosphere forming efficiency in vitro, and tumor formation capacity in vivo. To establish a neurosphere line, neurospheres were propagated in serum-free medium.

Results

Formation of intracerebral xenograft tumors was confirmed in 4 of the 5 mice injected with the patient tumor. These xenograft tumors were sub-transplanted in vivo 5 times. They replicated the histopathological features of the original patient tumor and expressed the molecular markers (TWIST1 and FOXJ1) of group 3 sPNET. CD133⁺ and CD15⁺ cells were found to have strong neurosphere-forming efficiency in vitro and potent tumor-forming capacity (with as few as 100 cells) in vivo. A neurosphere line BXD-2664PNET-NS was established that preserved stem cell features and expressed group 3 markers.

Conclusion

We have established a group 3 sPNET xenograft mouse model (IC-2664PNET) with matching neurosphere line (BXD-2664PNET-NS) and identified CD133⁺ and CD15⁺ cells as the major CSC subpopulations. This novel model system should facilitate biological studies and preclinical drug screenings for childhood sPNET.