Intra-axial endophytic primitive neuroectodermal tumors in the pons: clinical,radiological, and immunohistochemical aspects in four children

We present the clinical findings, radiological aspects, operative results, and histopathological features of four typical primitive neuroectodermal tumors (PNET) located in the pontine region in children. All the tumors had an endophytic intra-axial growth pattern. All the children had a short history of severe neurological deficits with involvement of the cranial nerves and pyramidal tract. MRI did not reveal any common feature of malignancy. Compared to our successful experience in operations of intra-axial endophytic brainstem tumors in a total of 32 children, the outcome was poor: all 4 children died within 13 months. We conclude that PNET occurring in the pons is not as rare as was believed, and, compared to PNET in other areas the prognosis is worse.     

Atypical teratoid/rhabdoid tumor of the central nervous system: a comparative study with primitive neuroectodermal tumor/medulloblastoma

Eleven atypical teratoid/rhabdoid tumors (AT/RT) and 121 primitive neuroectodermal tumors/medulloblastomas (PNET/MB) were included in this study for evaluation of the histopathological features of AT/RT and comparison between AT/RT and PNET/MB. Histopathological studies of AT/RT showed that in addition to the commonly recognized components, i.e., rhabdoid cells, small (PNET/MB) cells, spindle cells and epithelial components, there was a previously unrecognized component, sickle-shaped embracing cells, which were present in all cases and could be useful as a histological marker of this tumor. Immunohistochemical studies showed divergent differentiation of the tumor cells and among the 16 antibodies studied, vimentin, neuron-specific enolase, epithelial membrane antigen and glial fibrillary acidic protein were most commonly reactive. The frequency of AT/RT expressed as a ratio of AT/RT to PNET/MB was 1:11 in general and increased to 1:3.8 among patients younger than 3 years old. The AT/RT patients were younger than those with PNET/MB and had a female predominance. The MIB-1 labeling index of AT/RT was significantly higher than that of PNET/MB (mean 63.9 vs 40.1), which correlated with a shorter survival in patients with AT/RT than those with PNET/MB (median survival time 15.4 months vs 156.4 months).     

Primary primitive neuroectodermal tumor of the spinal cord: case report and review of the literature.

We present the clinical, radiological, and pathological features of a primary primitive neuroectodermal tumor (PNET) that occurred in the thoracic spinal cord of a 69-year-old man. Magnetic resonance imaging (MRI) demonstrated on T1-weighted images a 2x1x5 cm isointense intraspinal mass with homogeneous contrast enhancement extending from the C7 to the Th3 level. There was no clinical or radiological evidence for the existence of an intracranial tumor. Histological examination revealed a small round cell tumor with rosette formation and immunohistochemical characteristics of a PNET. The patient is the oldest among the 20 cases with this rare spinal cord neoplasm reported so far in the literature; the previously published cases are briefly reviewed.     

High microvessel density in primitive neuroectodermal brain tumors of childhood.

Microvessel density (MVD), a measure of tumor angiogenesis, has been shown to correlate significantly with overall and progression-free survival outcomes in various cancers including astrocytic brain tumors. To assess if the MVD is an independent prognostic factor in primitive neuroectodermal tumors (PNET) of the central nervous system, formalin-fixed paraffin-embedded tumor sections of 78 children with PNET were studied by CD34 immunohistochemistry to highlight endothelial cells. Microvessel density was determined in the most active area of neovascularization according to well-established methods. While it was shown that MVD showed considerable inter-tumor variability (median 75; range 20-345 microvessels per 0.7 mm2 field), no significant associations were found between MVD and metastasis or survival outcomes. We conclude that many PNETs are highly vascular CNS tumors, indicating potent angiogenic activity. Therefore, these tumors would be good candidates for antiangiogenic strategies. However, MVD determined in the most active area of neovascularization is not a predictor of metastatic potential or survival outcomes in childhood PNET.     

Adipose tissue and smooth muscle in a primitive neuroectodermal tumor of cerebrum

We describe a case of an occipital lobe primitive neuroectodermal tumor (PNET) in a 60-year-old man with immunocytochemical evidence of neuronal, glial, smooth muscle and adipose tissue differentiation in the primary tumor and its metastases. This is the first case of PNET of cerebrum in which adipose tissue and smooth muscle has been demonstrated. The possible cells of origin for these mesenchymal elements is discussed.     

Intraspinal Ewing’s sarcoma/primitive neuroectodermal tumors

Intraspinal Ewing’s sarcoma (ES) and primitive neuroectodermal tumors (PNET) are very rare, and the characteristics and prognoses of the disease remain unclear. We present an illustrative patient with an intradural, extramedullary PNET arising within the cervical spinal canal, with clinical and radiological manifestations of leptomeningeal spread, and review the reports of a further 77 patients with intraspinal ES/PNET. Cox regression analyses showed that tumor location (extradural, intradural) (p = 0.002, RR = 4.217, 95% confidence interval [CI] 1.668-10.664) and spinal segment location (cervical, thoracic, lumbar, or sacral) (p = 0.017, RR = 2.040, 95% CI 1.133-3.673) were independent factors in the prognosis of intraspinal ES/PNET. We concluded that a peripheral PNET may originate within the spinal canal and exhibit leptomeningeal spread similar to that seen in central PNET, and that a patient with an intradural ES/PNET high in the spinal canal is more likely to have a poor prognosis.     

Primitive neuroectodermal tumors of the cauda equina in adults with no detectable primary intracranial neoplasm--three case studies

We studied three cases of primitive neuroectodermal tumors surgically removed from the cauda equina region of adults. There was no clinical or radiological evidence of cerebellar medulloblastoma, other intracranial tumor or paraspinal sympathetic neuroblastoma. Two patients died: autopsies revealed no primary intracranial neoplasm. One patient is alive 3 years after surgery with no detectable intracranial tumor. The tumors had the light and electron microscopic features of primitive neuroectodermal tumors as described earlier in the literature. In addition, in all three cases many tumor cells could be stained for cytoplasmic neurofilament antigen.     

Diagnostic pitfall in the diagnosis of mesenchymal chondrosarcoma arising in the central nervous system

Mesenchymal chondrosarcoma is a rare aggressive neoplasm typically affecting the bones of young adults. It may also arise in somatic soft tissue, the CNS and other organs. It has a characteristic biphasic histological pattern composed of highly undifferentiated small round cells and islands of well‐differentiated hyaline cartilage. We report a case of mesenchymal chondrosarcoma arising from the right tentorium cerebelli in a 21‐year‐old woman with symptoms relating to mass effect. Histological examination demonstrated a purely small round cell appearance in a specimen obtained during partial resection at an outside institution, leading to an erroneous diagnosis of Ewing sarcoma/primitive neuroectodermal tumor (PNET). The diagnosis of mesenchymal chondrosarcoma was made only after tissue obtained during a definitive complete macroscopic removal involving the regional tentorium cerebelli, transverse and sigmoid dural venous sinuses which showed a prominent cartilaginous component. We discuss the features of mesenchymal chondrosarcoma arising in the CNS, the important differential diagnoses of small round‐cell tumors within the CNS, and the differentiating features of mesenchymal chondrosarcoma from Ewing sarcoma/PNET, medulloblastoma, hemangiopericytoma, monophasic synovial sarcoma and atypical teratoid/rhabdoid tumour.     

Human central nervous system primitive neuroectodermal tumor expressing nerve growth factor receptors: CHP707m

A primitive neuroectodermal tumor (PNET) presented as a cerebral hemispheric mass in a 33-year-old man. Bone marrow metastases were discovered 11 months later. A cell line (CHP707m) was derived from these metastases. In culture, the cells showed features of neuronal differentiation, forming short neurites and synthesizing low-molecular-weight neurofilament protein. Northern blotting showed the tumor cells express nerve growth factor (NGF) receptor messenger RNA, and fluorescence-activated cell-sorting demonstrated NGF receptors on the cell surface. Western blotting showed CHP707m NGF receptors are truncated. The receptors are functional; they bind iodine 125-labeled mouse NGF with an affinity of 1.6 x 10(-9) M, and short-term treatment with NGF induces expression by the tumor cells of the proto-oncogene, c-fos. Although CHP707m is the first central nervous system PNET cell line proven to express NGF receptors, immunohistological survey of tissue sections prepared from human central nervous system PNETs showed that 13 of 35 contained NGF receptor-positive tumor cells. Thus, more than one-third of such tumors might be responsive to the effects of NGF.     

Establishment and characterization of a human primitive neuroectodermal tumor cell line from the cerebral hemisphere.

The primitive neuroectodermal tumors (PNET) comprise a class of malignant nervous system neoplasms that afflict children. These tumors consist of cells that are morphologically identical to the primitive neuroepithelial cells normally seen in early stages of neural embryogenesis, supporting the notion that PNET result from a disturbance in the process of normal neuronal or glial differentiation. In the central nervous system, PNET occur most commonly in the cerebellum (medulloblastomas), but only occasionally in the cerebral hemispheres. We report here the establishment and characterization of a new human cell line (PFSK) derived from a PNET from the cerebral hemisphere of a child. The growth characteristics of PFSK cells were typical of an immortalized, transformed cell line. Cytogenetic and molecular genetic studies showed that three different sublines were present. In one of these sublines, sequences from chromosome 17 had been lost during establishment in culture. Immunocytochemical studies showed that PFSK cells expressed nestin, an intermediate filament protein normally expressed by neuroepithelial stem cells during neurulation. The PFSK cells did not express antigens typically found in terminally differentiated neurons or glia, indicating that this tumor cell line might represent neuroepithelial stem cells prior to commitment to a neuronal or glial lineage.     

Insulin-induced differentiation and modulation of neuronal thread protein expression in primitive neuroectodermal tumor cells is linked to phosphorylation of insulin receptor substrate-1

Neuronal thread proteins (NTPs) are a family of developmentally regulated molecules expressed in central nervous system (CNS) neurons and primitive neuroectodermal tumor (PNET) cell lines. NTP gene expression is modulated with DNA synthesis, neuritic sprouting, and neuronal differentiation. The present study explores the mechanism of insulin modulation of NTP gene expression during neuronal differentiation using PNET cell lines of CNS origin. PNET2 cells underwent neuronal differentiation with neurite outgrowth coupled with transient up-regulation of several species of NTP. In contrast, PNET1 cells failed to differentiate in response to insulin stimulation, although insulin receptors were more abundant than in PNET2 cells. Analysis of the insulin-mediated signal transduction pathway demonstrated that the lack of insulin responsiveness in PNET1 cells was primarily caused by impaired insulin-mediated tyrosyl phosphorylation of the insulin receptor substrate-1 (IRS-1). Correspondingly, the association between phosphatidyl-inositol 3 (PI3) kinase and phosphorylated IRS-1 was reduced in PNET1 compared with PNET2 cells. In contrast, the levels of IRS-1 protein were similar in PNET1 and PNET2 cells, and expression of the insulin receptor β subunit (Irβ) and insulin-mediated tyrosyl phosphorylation of the Irβ were greater in PNET1 than PNET2 cells. The findings suggest that insulin effected neuronal differentiation and modulation of NTP gene expression in PNET cells utilizes a signal transduction cascade that requires tyrosyl phosphorylation of IRS-1.     

Multiple systemic metastases of posterior fossa - primitive neuroectodermal tumor (PF-PNET) in adult: case report

We present the case of a 30-year female patient with multiple systemic metastases of posterior fossa primitive neuroectodermal tumor (PF- PNET) and present a review concerning the usual presentation, sign and symptoms, radiological aspects, pathways of spread, genetic patterns and treatment of PF-PNET. The biological behavior of PF - PNET is analyzed taking into consideration the presence of systemic metastases.     

Primary intramedullary primitive neuroectodermal tumor (PNET) – case report and review of the literature

Spinal primitive neuroectodermal tumors (PNET) are very rare tumors, and intramedullary localization is even less common. Indeed, amongst the 23 cases of the spinal PNET described in the literature, only eight cases had an intramedullary localization. Following the WHO 2000 classification, PNETs have been considered embryonal tumors composed of undifferentiated neuroepithelial cells with a capacity of differentiation into different cellular lines, such as astrocytic, ependymal, melanotic and muscular. They have been considered to arise from a neoplastic transformation of primitive neuroepithelial cells, thereby making their presence possible in any part of the central nervous system. The optimal treatment for these malignant tumors is not yet clear, although, over the years, radiotherapy has been considered the best treatment for spinal PNETs. The described case is that of a 38-year-old man with a primary intra-extramedullary PNET, treated by laminectomy, open biopsy and chemotherapy. The patient, 18 months after the onset of his symptomatology, died without cerebral tumor involvement.     

椎管内原始性神经外胚瘤(附四例报告)

目的 探讨椎管内原始性神经外胚瘤的临床特点及分型、诊断、病理特点及治疗.方法 4例经影像学、手术和病理学证实的椎管内原始性神经外胚瘤,并回顾相关文献,总结所报告病例.结果 3例显微镜下全切,1例大部切除;术后病理检查提示中枢性原始性神经外胚瘤2例,外周性原始性神经外胚瘤2例;术后3例均给予全神经轴放疗和全身化疗,1例因经济原因术后出院后未再接受其他治疗;2例随访10个月及14个月仍生存,1例随访25个月死亡,1例随访6个月后失访.结论 椎管内原始性神经外胚瘤多见于成人;病程短;预后差;应根据病理分型制定手术后放化疗方案;CD99可作为临床上区别中枢性原始性神经外胚瘤和外周性原始性神经外胚瘤的免疫组化指标.     

椎管内原始性神经外胚瘤(附四例报告)

目的 探讨椎管内原始性神经外胚瘤的临床特点及分型、诊断、病理特点及治疗.方法 4例经影像学、手术和病理学证实的椎管内原始性神经外胚瘤,并回顾相关文献,总结所报告病例.结果 3例显微镜下全切,1例大部切除;术后病理检查提示中枢性原始性神经外胚瘤2例,外周性原始性神经外胚瘤2例;术后3例均给予全神经轴放疗和全身化疗,1例因经济原因术后出院后未再接受其他治疗;2例随访10个月及14个月仍生存,1例随访25个月死亡,1例随访6个月后失访.结论 椎管内原始性神经外胚瘤多见于成人;病程短;预后差;应根据病理分型制定手术后放化疗方案;CD99可作为临床上区别中枢性原始性神经外胚瘤和外周性原始性神经外胚瘤的免疫组化指标.     

椎管内原始性神经外胚瘤(附四例报告)

目的 探讨椎管内原始性神经外胚瘤的临床特点及分型、诊断、病理特点及治疗.方法 4例经影像学、手术和病理学证实的椎管内原始性神经外胚瘤,并回顾相关文献,总结所报告病例.结果 3例显微镜下全切,1例大部切除;术后病理检查提示中枢性原始性神经外胚瘤2例,外周性原始性神经外胚瘤2例;术后3例均给予全神经轴放疗和全身化疗,1例因经济原因术后出院后未再接受其他治疗;2例随访10个月及14个月仍生存,1例随访25个月死亡,1例随访6个月后失访.结论 椎管内原始性神经外胚瘤多见于成人;病程短;预后差;应根据病理分型制定手术后放化疗方案;CD99可作为临床上区别中枢性原始性神经外胚瘤和外周性原始性神经外胚瘤的免疫组化指标.     

椎管内原始性神经外胚瘤(附四例报告)

目的 探讨椎管内原始性神经外胚瘤的临床特点及分型、诊断、病理特点及治疗.方法 4例经影像学、手术和病理学证实的椎管内原始性神经外胚瘤,并回顾相关文献,总结所报告病例.结果 3例显微镜下全切,1例大部切除;术后病理检查提示中枢性原始性神经外胚瘤2例,外周性原始性神经外胚瘤2例;术后3例均给予全神经轴放疗和全身化疗,1例因经济原因术后出院后未再接受其他治疗;2例随访10个月及14个月仍生存,1例随访25个月死亡,1例随访6个月后失访.结论 椎管内原始性神经外胚瘤多见于成人;病程短;预后差;应根据病理分型制定手术后放化疗方案;CD99可作为临床上区别中枢性原始性神经外胚瘤和外周性原始性神经外胚瘤的免疫组化指标.     

椎管内原始性神经外胚瘤(附四例报告)

目的 探讨椎管内原始性神经外胚瘤的临床特点及分型、诊断、病理特点及治疗.方法 4例经影像学、手术和病理学证实的椎管内原始性神经外胚瘤,并回顾相关文献,总结所报告病例.结果 3例显微镜下全切,1例大部切除;术后病理检查提示中枢性原始性神经外胚瘤2例,外周性原始性神经外胚瘤2例;术后3例均给予全神经轴放疗和全身化疗,1例因经济原因术后出院后未再接受其他治疗;2例随访10个月及14个月仍生存,1例随访25个月死亡,1例随访6个月后失访.结论 椎管内原始性神经外胚瘤多见于成人;病程短;预后差;应根据病理分型制定手术后放化疗方案;CD99可作为临床上区别中枢性原始性神经外胚瘤和外周性原始性神经外胚瘤的免疫组化指标.