Primary cerebral neuroblastoma (neurocytoma) in adults

Summary We report a case of a third ventricular neuroblastoma (neurocytoma) in a 66 year old man. A stereotactic needly biopsy was performed to obtain a tissue diagnosis and was followed by total resection. We elected not to give radiation or chemotherapy and to follow the patient closely with serial CT scans. Presently, 48 months postoperatively, the patient is free of tumor by head CT scan and able to live independently. We reviewed the literature of primary cerebral neuroblastomas/neurocytomas occurring in adults (15 years of age) and found 32 cases. Our patient is the oldest of this group with a mean age of 32 ± 14 years (S.D.). The location of the 33 neoplasms was intraventricular in 17 cases (52%) and intraparenchymal in 16 cases. The male to female ratio was 2: 1. Of the 17 patients having a minimal follow-up period of 5 months (mean 51 months), five developed recurrences after 5 to 144 months (mean 50 months) compared to 12 patients without recurrence after a 6- to 72-month follow-up period (mean 52 months). Recurrences occurred statistically significantly more often in parenchymal neuroblastomas/neurocytomas than in intraventricular tumor locations.     

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。     

Human neuroblastoma cells and 13-cis-retinoic acid

Summary To a limited extent, we corroborated a previous report of human neuroblastoma sensitivity to 13-cis-retinoic acid. Seven cultured human neuroblastoma, two primitive neuroectodermal tumor, and one melanoma cell line were exposed to 0.001 to 10.0 º M 13-cis-retinoic acid for six to fourteen days. The neuroblastoma cell line, SK-N-DZ, was the only cell line lysed by all concentrations of 13-cis-retinoic acid. The other cell lines were refractory to concentrations as high as 10 µM. Increased cell process formation was observed in three neuroblastoma, SK-N-SH, SK-N-BE, SK-N-LE, and one melanoma cell line. We conclude that sensitivity to 13-cis-retinoic acid is unevenly distributed among histogenetically similar tumors from different patients.     

Primitive neuroectodermal tumours of the cerebrum

Summary Eighteen cases of cerebral tumour composed partly or totally of primitive embryonal cells are reported. These lesions comprise 2.8% of all primary cerebral hemisphere tumours in the histopathology files of The Royal Marsden Hospital between 1971 and 1980 inclusive. Most exhibited some degree of differentiation towards neuronal or glial elements and, as more than one type of differentiation was often present in the same lesion, we agree with others that the term primitive neuroectodermal tumour (PNET) is more appropriate to describe these lesions than terms based on histogenesis. The extent of the primitive component varied, but usually accounted for more than 80% of the tumour. Although the tumours bear some similarities to posterior fossa medulloblastomas, they exhibit important differences in histology, immunohistology, natural history and response to treatment. Nearly all PNETs examined expressed some glial fibrillary acidic (GFAP) both in primitive areas and zones of astrocytic differentiation. GFAP staining may thus be of value in distinguishing PNETs from undifferentiated non-neurogenic tumours. Of 14 patients referred for radiotherapy, the survival rate at 3 years was 29% (\414) and 5 years 25% (\312). Patients with tumours in which at least 90% of the tissue was undifferentiated exhibited an extremely poor prognosis with none of 9 patients still alive at 3 years in contrast to 3 of 5 patients (60%) with tumours showing less than 90% undifferentiation. Radical tumour removal, where feasible, followed by irradiation of the whole cerebrospinal axis is recommended. Adjuvant chemotherapy with such agents as CCNU and Vincristine may be of value: the 3 long term survivors in the present series (7–11 years), including one who presented disseminated intracranial disease, received such adjuvant treatment.     

Differentiation of a primitive neuroectodermal tumor into a benign ganglioglioma

We describe a case of cerebellar neuroblastoma with histologic documentation of maturation into a ganglioglioma sixteen months later. Only chemotherapy was administered following the initial surgery and the child is well and disease-free three years following her final surgical procedure. The outcome of this patient supports previous hypotheses that the cerebellar neuroblastoma may be a less malignant tumor than its other primitive neuroectodermal posterior fossa counterparts. Furthermore, this case suggests a role for second-look surgery in the management of selected pediatric brain tumors.     

Hypoalbuminaemia is an Independent Predictor of Poor Outcome in Metastatic Ewing's Sarcoma Family of Tumours: A Single Institutional Experience of 150 Cases Treated with Uniform Chemotherapy Protocol

AimsData on metastatic Ewing's sarcoma family of tumours (ESFT) with uniform chemotherapy protocol are minimal.Materials and methodsThis was a single institutional patient review of patients treated between June 2003 and November 2011 and evaluated on an intent-to-treat analysis. All patients received uniform chemotherapy: neoadjuvant chemotherapy (NACT), surgery and/or radiotherapy as local treatment followed by adjuvant chemotherapy. Local treatment was offered if the patient achieved a complete response and/or a partial response at both the primary and the metastatic site.ResultsIn total, 150/374 (40%) ESFT patients were metastatic, with a median age of 15 years (range: 2–50); a tumour diameter of 10 cm (range: 1.8–26). Most common metastatic sites were lung only (53; 35%), bone only (35; 23%) and combined bone/lung (25; 17%). Twenty patients underwent surgery; 55 patients received radical radiotherapy after NACT. After a median follow-up of 26.1 months (range: 1.6–101.6), 5 year event-free survival (EFS), overall survival and local control rate (LCR) were 9.1 ± 3.3%, 16.9 ± 5.2% and 31.8 ± 7.9%, respectively. Univariate analysis showed serum albumin ≤3.4 g/dl (P < 0.001) to predict inferior EFS. Tumour size >8 cm (P = 0.05), haemoglobin ≤10 g/dl (P = 0.04), hypoalbuminaemia (P = 0.003) and radical radiotherapy as local treatment (P = 0.03) predicted inferior overall survival. No factor significantly predicted LCR, although age ≤15 years (P = 0.08) and radical radiotherapy as local treatment (P = 0.09) had a trend towards inferior LCR. Hypoalbuminaemia was the only prognostic factor to predict EFS on multivariate analysis.ConclusionThis was the largest study of metastatic ESFT from Asia and identified a unique prognostic factor. In view of dismal prognosis with conventional chemotherapy in metastatic ESFT with hypoalbuminaemia, palliative intent therapy may be a potential therapeutic alternative for this subgroup of patients, especially in resource-challenged situations.     

CT 在小儿神经母细胞瘤诊断和随访中的应用

目的：评价 CT 检查在小儿神经母细胞瘤的诊断及治疗后随访中的临床应用价值。方法：回顾性分析23例经病理证实为神经母细胞瘤患儿的临床资料及 CT 表现特征。结果：23例神经母细胞瘤中来源于肾上腺13例,腹膜后7例,纵隔3例;15例肿瘤形态不规整,5例肿瘤呈椭圆形或类圆形,3例呈分叶状;肿瘤内部多呈混杂密度,20例瘤体内伴多发钙化灶,15例内伴囊性坏死低密度区,增强扫描后,17例瘤体呈明显强化,4例呈轻中度强化,2例未见明显强化;11例瘤体包绕大血管;CT 正确诊断20例,诊断准确率为87.0%。结论：CT 检查是诊断小儿神经母细胞瘤及治疗后随访观察的重要检查方法。     

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.     

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.     

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.     

The use of paediatric chemotherapy protocols at full dose is both a rational and feasible treatment strategy in adults with Ewing's family tumours

Background: Ewing's sarcoma and primitive neuroectodermal tumour (ES/PNET) are rare, limiting opportunities for therapy studies in adults. Chemotherapy regimens adapted from paediatric studies are often used for adults but concerns about poor outcome and treatment toxicity may adversely affect drug dose intensity. We present our experience using a paediatric protocol at full dose.Patients and methods: Records of 34 patients with ES/PNET who received the IVAD chemotherapy regimens were reviewed. Received drug dose intensity, toxicity and survival data were collected.Results: Received dose intensity in 30 evaluable patients was 0.92 compared to the standard IVAD schedule. Myelosuppression was the major toxicity, 83% of patients experienced grade 4 neutropenia. There was no major renal or cardiac toxicity. In patients without metastases at presentation, five-year overall survival was 63% and progression free survival was 39%. Tumour burden at presentation was statistically significantly associated with survival (P = 0.002). The five-year survival rate of 80% in patients presenting with low volume non metastatic disease was equivalent to published paediatric series.Conclusions: Although the IVAD chemotherapy regimens are myelotoxic in adults, they can be given safely. We recommend that adults with ES/PNET should be included in current multicentre, multidisciplinary treatment studies directed at children.     

肾脏原始神经外胚叶肿瘤一例报告并文献复习

原始神经外胚叶肿瘤(primitive neuroectodermal tumor,PNET)发源于神经嵴胚胎残留组织,具有多向分化潜能,且临床上较原始的恶性小圆细胞肿瘤少见,多分布于颅内、四肢、胸壁及中轴软组织[1-2]。Celli等[3]1975年首次报道PNET,大部分发病于儿童和青年人,>70%的患者发病于20岁之前,女性多见。     

Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours

The genes encoding Caspase-9 and DFF45 have both recently been mapped to chromosome region 1p36.2, that is a region alleged to involve one or several tumour suppressor genes in neuroblastoma tumours. This study presents an update contig of the 'Smallest Region of Overlap of deletions' in Scandinavian neuroblastoma tumours and suggests that DFF45 is localized in the region. The genomic organization of the human DFF45 gene, deduced by in-silico comparisons of DNA sequences, is described for the first time in this paper. In the present study 44 primary tumours were screened for mutation by analysis of the genomic sequences of the genes. In two out of the 44 tumours this detected in the DFFA gene one rare allele variant that caused a non-polar to a polar amino acid exchange in a preserved hydrophobic patch of DFF45. One case was hemizygous due to deletion of the more common allele of this polymorphism. Out of 194 normal control alleles only one was found to carry this variant allele, so in respect of it, no healthy control individual out of 97 was homozygous. Moreover, our RT-PCR expression studies showed that DFF45 is preferably expressed in low-stage neuroblastoma tumours and to a lesser degree in high-stage neuroblastomas. We conclude that although coding mutations of Caspase-9 and DFF45 are infrequent in neuroblastoma tumours, our discovery of a rare allele in two neuroblastoma cases should be taken to warrant further studies of the role of DFF45 in neuroblastoma genetics.     

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.     

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.     

增强CT在小儿神经母细胞瘤化疗监测方面的价值

目的:评价CT增强检查在小儿神经母细胞瘤化疗监测中的作用。方法:搜集经病理证实、临床影像资料完整的小儿神经母细胞瘤患者44例,男26例,女18例,年龄2个月到7岁,平均3.15岁。分为术前组(10例)和术后组(34例)。所有患者化疗前后均行增强CT检查,对比分析化疗前后的CT图像。结果:CT增强检查可以清晰显示原发肿瘤的体积及肿块内钙化的变化,了解肿瘤推挤临近器官或包绕大血管的情况;帮助判断原发肿瘤部位有无复发、残留;明确有无远处转移及其变化。结论:无论是手术前还是手术后化疗,CT增强扫描均是帮助评价小儿神经母细胞瘤化疗疗效的重要手段。