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PubMed1995

Toxicity and efficacy of carboplatin and etoposide in conjunction with disruption of the blood-brain tumor barrier in the treatment of intracranial neoplasms.

CARBOPLATIN AND ETOPOSIDE have been investigated in preclinical studies and a limited toxicity study in 13 patients; these studies have established carboplatin and etoposide as a tolerable combination when administered with blood-brain barrier disruption. The studies also found a predictable dose-limiting toxicity of myelosuppression. Subsequently, a broad efficacy trial of this regimen was carried out. A total of 34 patients, ranging in age from 7 to 72 years, underwent a combination chemotherapy regimen of carboplatin (200 mg/m2 administered intra-arterially) and etoposide (200 mg/m2 administered intravenously) administered with blood-brain barrier disruption on each of 2 consecutive days every 28 days. The diagnoses included glioblastoma multiforme (n = 3), malignant astrocytoma (n = 8), malignant astrocytoma-oligodendroglioma (n = 1), primitive neuroectodermal tumor (n = 4), disseminated germ cell tumor of the central nervous system (CNS) (n = 6), CNS lymphoma (n = 7), and metastatic carcinoma (n = 5). The major toxicity observed in patients treated with multiple courses of this regimen was the expected reversible myelosuppression and an unexpected, irreversible high-frequency hearing loss. Of these 34 patients, 22 had measurable disease, and 9 radiographic responses (50% or more decrease in enhancing tumors) were observed in these patients. Carboplatin and etoposide with blood-brain barrier disruption is an active regimen in the treatment of malignant astrocytomas and has shown dramatic responses in primitive neuroectodermal tumors and CNS lymphoma. Additionally, the durability of responses in patients with disseminated CNS germ cell tumors is encouraging. However, such therapy is associated with unexpected high-frequency hearing loss; even so, on the basis of the favorable responses in patients with primitive neuroectodermal tumors, germ cell tumors, and lymphomas, the study of this regimen for those tumors is being extended in a multiinstitutional trial that also includes cytoxan to further evaluate the potential enhanced drug delivery.

Adolescent↗
PubMed2002

Activation of trkA induces differentiation and inhibits the growth of JK-GMS Askin tumor cells.

Peripheral primitive neuroectodermal tumor (PNET) and Ewing's sarcoma (ES) constitute a unique group of small round cell tumors in childhood and young adults that are characterized by the same chromosomal translocation t(11;22)(q24;q12). Recently, the expression of neurotrophin receptors has been found in various human tumors including PNET/ES, but the functional significance of these receptor expressions has not been documented in PNET/ES. In the present study, we investigated the biologic effects of trkA neurotrophin receptor activation by nerve growth factor (NGF) in a newly established Askin tumor cell line, JK-GMS, which constitutively expresses a high level of trkA. The activation of trkA induced differentiation and inhibited the growth of JK-GMS cells, which was characteristically associated with down-regulation of c-myc and N-myc mRNA expression. NGF did not exert significant changes in two different PNET/ES cell lines, CADO-ES1 and RD-ES, which did not express detectable levels of trkA. The biologic effects mediated by NGF were abrogated by treatment of the cells with K-252a, and the treatment with brain-derived neurotrophic factor did not affect the biologic behavior of JK-GMS cells, indicating that the effects are trkA specific. The results observed were quite similar to those of neuroblastoma cells, another childhood tumor of neural crest origin. Overall findings strongly suggest that the trkA-mediated signaling pathway plays a crucial role in controlling the basic biologic properties of JK-GMS cells.

Adolescent↗
PubMed2003

Primary primitive peripheral neuroectodermal tumor of the prostate. Immunophenotypic and molecular study of a case.

A case of primitive peripheral neuroectodermal tumor arising in the prostate gland of a 31-year-old man and first diagnosed through a biopsy is reported. Microscopically, the tumor was made up of solid nests and sheets of small round cells, and it was difficult to distinguish the neoplasm from other small round cell tumors, such as small cell carcinoma, rhabdomyosarcoma, or malignant lymphoma. Immunohistochemically, the tumor cells showed immunoreactivity for CD99, vimentin, neuron-specific enolase, and synaptophysin. The neoplasm was excised by a radical surgical procedure preceded by chemotherapy and radiation therapy. The morphologic diagnosis of the prostatectomy specimen was complemented by molecular analysis performed on viable microdissected tissue obtained from formalin-fixed, paraffin-embedded tumor sections. Polymerase chain reaction and sequencing assessment showed the presence of EWS/FLI1 type 2 chimeric transcript, confirming the diagnosis of peripheral primitive neuroectodermal tumor. To our knowledge, this is the first description of a primary peripheral primitive neuroectodermal tumor in the prostate gland.

Adult↗
PubMed2003

2-Methoxyestradiol interferes with NF kappa B transcriptional activity in primitive neuroectodermal brain tumors: implications for management.

Medulloblastoma (MB) is a primitive neuroectodermal tumor (PNET) of the central nervous system (CNS) and the most common malignant primary brain tumor in children. Currently, poor risk and recurrent MB patients are treated with cytotoxic chemotherapy alone or in combination with surgery and irradiation. In order to improve on therapeutic outcome and reduce toxicity of current treatment strategies, new and novel therapeutic agents are needed for MB patients. To that purpose, we have examined the effect of 2-methoxyestradiol (2-ME), an endogenous non-toxic estrogenic metabolite on the growth of three medulloblastoma cell lines (DAOY, D341 and D283); and two high-grade anaplastic astrocytoma/glioblastoma cell lines, U-87MG and T-98-G. We present evidence to show that 2-ME preferentially inhibits the growth of medulloblastoma cells significantly by blocking cell cycle progression predominantly in G(2)/M phase. 2-ME treatment results in phosphorylation of cdc25C without any significant alterations in the expression of cyclin B1 or p34cdc2. In addition, we observed a decrease in the levels of 14-3-3 proteins following treatment with 2-ME. Furthermore, 2-ME-mediated growth inhibition is accompanied by induction of apoptosis as evidenced by morphological alterations and DNA fragmentation analysis. Of interest is the finding that 2-ME induced apoptosis is not mediated through alterations in the expression of p53 or Bax and that transcriptional activity of NF kappa B and DNA binding activity is reduced indicating that 2-ME disrupts the NF kappa B signaling pathway. These results suggest that 2-ME may prove to be a useful therapeutic agent in the treatment of PNET brain tumors such as medulloblastoma. In addition, as 2-ME inhibits growth predominantly through G(2)/M block, it may enhance the effectiveness of radiation therapy.

2-Methoxyestradiol↗
PubMedDate not supplied

Clinical and prognostic significance of Ki-67 and proliferating cell nuclear antigen expression in childhood primitive neuroectodermal brain tumors.

The cell proliferation activity of sixteen childhood primitive neuroectodermal tumors (PNETs) was observed immunocytochemically, to determine the cell kinetics and cell proliferation activity of these relatively undifferentiated, malignant brain tumors. Two mouse anti-human monoclonal antibodies (MoABs) were employed for the detection of the nuclear antigen (Ki-67) present during proliferation in frozen sections and proliferating cell nuclear antigen (PCNA) expression in formalin fixed, paraffin embedded tissue sections. A sensitive four step, indirect, streptavidin-biotin, alkaline phosphatase (AP) conjugated, immunocytochemical experimental technique, was used. The anti-Ki-67 MoAB which binds to a special nuclear antigen, identified its expression only in proliferating cells. This nuclear antigen was detectable during the whole mitotic cycle of all malignant and fast proliferating cells, only absent between and during phases G0 (resting phase) and the first gap phase (G1). The mean labeling index (MLI) was defined as the percentage of Ki-67 and PCNA antigen positive cells of the total number counted. The MLI for the PNETs ranged between 1.4% and 11.6%, with a mean MLI of 6.2% for Ki-67; and between 3.2% and 16.8%, with a mean of 9.74% for PCNA. All observed PNETs demonstrated heterogeneous nuclear stainings, but the highest MLIs were found among the poorly differentiated classic medulloblastomas (over 30% for the Ki-67 antigen and 46% for PCNA). MLIs were low in 5/13 PNETs (under 4% for antigen Ki-67 and 9.4% for PCNA) and in this group we defined our lowest (1.4%) MLI, suggesting the presence of in vivo neuritogenesis of these undifferentiated, embryonal tumors. MLIs in 6/13 PNETs were intermediate in magnitude. The MLIs were higher in two PNETs with clear cellular differentiation towards an ependymal (10.4%) and melanocytic (8.8%) direction. Formation of astrocytes within the tumor mass did not affect the intermediate character of the MLI (7.8%). The prognosis of every intracranial tumor is obviously correlated with its proliferation activity and cell kinetics. The clinical significance of these parameters is great since they provide direct information concerning the growth characteristics of an intracranial tumor.

Adolescent↗
PubMedDate not supplied

Immunohistochemistry of synapsin I and synaptophysin in human nervous system and neuroendocrine tumors. Applications in diagnostic neuro-oncology.

Synapsin I is a phosphoprotein localized to the cytoplasmic surface of synaptic vesicles and is one of the best characterized neuron-specific proteins. Synaptophysin is an integral membrane glycoprotein, also located on presynaptic vesicles, which has been shown to be a useful immunohistochemical marker for neuroendocrine/neuronal differentiation in tumor diagnosis. The sensitivity and specificity of immunohistochemical staining for these two proteins in formalin-fixed, paraffin-embedded tissues was studied in a series of 67 neuroectodermal, neuroendocrine, and non-neural tumors. Intense immunoreactivity for both synapsin I and synaptophysin was observed in tumors containing well-differentiated neurons (gangliocytoma, ganglioglioma, neurocytoma). In these tumors, immunostaining was primarily concentrated along the outer surface of the cell membrane of the neuronal cells. Primitive neuroectodermal tumors (PNETs) (cerebral PNET, medulloblastoma, neuroblastoma) and most neuroendocrine tumors generally showed less intense and more variable immunoreactivity for these proteins. In most cases, immunostaining for synapsin I was sharper and often more intense than for synaptophysin. Some PNETs and neuroendocrine tumors that were immunoreactive for synapsin I did not stain for synaptophysin. We conclude that synapsin I is a reliable, sensitive immunohistochemical marker for neuronal/neuroendocrine differentiation in human neoplasms and may offer some advantages over synaptophysin when applied to formalin-fixed, paraffin-embedded tissues, particularly in the evaluation of primitive neuroectodermal tumors and neuroendocrine tumors.

Brain Neoplasms↗
PubMed1999

Clinically critical impact of molecular genetic studies in pediatric solid tumors.

BACKGROUND: Standard cytogenetic techniques are time-consuming and often not informative with solid tumors. In contrast, the reverse transcriptase-polymerase chain reaction (RT-PCR) is a readily available technique that can rapidly detect tumor-specific chromosomal rearrangements, even in small biopsy specimens. We present cases depicting the importance of including molecular diagnostic studies in the routine evaluation of pediatric solid tumors. PROCEDURE: We used RT-PCR to detect chimeric transcripts specific for major pediatric solid tumors, including peripheral primitive neuroectodermal tumor (pPNET), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round-cell tumor (DSRCT). We reviewed six recent cases in which the initial diagnosis was changed by the results of RT-PCR. RESULTS: Highly unusual or nonspecific clinical and/or histopathologic findings led to the initial diagnoses of neuroblastoma in three patients and DSRCT, leukemia, and carcinoma in one patient each. The final diagnoses after RT-PCR studies were pPNET in three patients, ARMS in two patients, and DSRCT in one patient. RT-PCR results led to early corrections in the diagnosis in two patients, but four patients received treatment not considered optimal for the neoplasms ultimately diagnosed, including three who, despite presenting with localized tumors that have a >70% cure rate with standard therapy, have died or are dying of disease. CONCLUSIONS: Molecular genetic studies on solid tumors can clarify the diagnosis in seemingly straightforward as well as in overtly problematic cases. These diagnostic distinctions are now critical as disease-specific and risk-directed therapies have emerged.

Adolescent↗
PubMed1994

Chromosome analysis of brain tumors in childhood.

We performed a chromosome analysis of 26 pediatric brain tumors, including 20 primitive neuroectodermal tumors (PNETs). 5 astrocytomas, and 1 immature teratoma. Specimens were treated with collagenase, placed in overnight or short-term cultures, and harvested for chromosome analysis. Numerical and/or structural abnormalities were noted in 14 of the 20 PNETs and 4 of the 5 astrocytomas. In 13 PNETs, so-called medulloblastoma in the cerebellum, an i(17q) was the most frequent structural abnormality, accounting for 30% (4/13). Double minute chromosomes (dmin) were observed in one tumor. Near-diploidy was demonstrated in three of these PNETs, hyperdiploidy in three, and near-tetraploidy in three. We could not find any correlation of these cytogenetic findings with the prognosis. In the remaining seven PNETs other than medulloblastoma, the karyotypes of five PNETs demonstrated a variety of numerical and structural abnormalities. As to the astrocytomas, losses of chromosomes 7 and 9 with dmin were observed in two, and structural abnormalities of chromosomes 1 and 17 were also observed in two tumors. In our limited cases, however, we could not find the same chromosome abnormalities that are well known in adult astrocytomas. A congenital immature teratoma showed hyperdiploidy with increased numbers of chromosomes 3, 6, and 12. We conclude that i(17q) is an important chromosome abnormality in medulloblastomas, and that the oncogenesis of pediatric astrocytomas might be different cytogenetically from that of adult astrocytomas.

Adolescent↗
PubMedDate not supplied

Neutral glycolipid composition of primary human brain tumors.

Neutral glycolipids (NGL) were isolated and quantitated in 98 primary human brain tumors; 19 low grade astrocytomas (LGA), 12 anaplastic astrocytomas (AA), 37 high grade astrocytomas (HGA), 18 oligodendroglial tumors, and 12 primitive neuroectodermal tumors (PNET). In 38 of these, the nature of the hexose in the cerebroside was determined using immunothin-layer chromatographic techniques. Galactosylceramide (GalCer) was the major ceramide monohexoside (CMH), and glucosylcerebroside never comprised more than 6% of this fraction in any tumor type. Furthermore, there was no correlation between the proportion of glucosylcerebroside and histological diagnosis. AA had the most characteristic neutral glycolipid pattern, with high levels of total lipid, total neutral glycolipid, CMH, and ceramide dihexoside (CDH) but low water contents. Consistent with this glycolipid composition is the finding that AA usually had neither ceramide trihexoside (CTH) nor globoside. Oligodendrogliomas were somewhat similar to AA in having high levels of CMH and infrequently having CTH or globoside. However, oligodendrogliomas had low water and total lipid contents. PNET had low levels of total lipid, total NGL, and CMH, but frequently contained CTH and globoside. LGA had high water contents but low levels of total lipid and CMH. HGA tended to have intermediate levels of almost all constituents analyzed, probably reflecting the pronounced cellular heterogeneity of these tumors. The frequent presence of GalCer in astrocytomas raises the possibility that some of these contain a population of cells that are related to the oligodendroglial lineage. However, the low amounts of GalCer and infrequent presence of sulfatide in PNET is consistent with their lack of differentiation toward oligodendrocytes. It will be of interest to determine if the neutral glycolipid patterns reported here will correlate with patient survival and be of prognostic significance.

Astrocytoma↗
PubMed2000

CD99 and cytokeratin-20 in small-cell and basaloid tumors of the skin.

Although it is classically a deep soft-tissue tumor of childhood, primitive neuroectodermal tumor (PNET) can occur at any age and may occasionally involve cutaneous sites. Merkel cell carcinoma (MCC) and basaloid neoplasms of cutaneous adnexa are the principal diagnostic alternatives to that tumor. The common expression of CD99 in PNET and cytokeratin-20 (CK20) in MCC suggests that these markers may be of value in this diagnostic setting, but they have not been rigorously examined in other small-cell and basaloid lesions of the skin. Accordingly, we evaluated CD99 and CK20 reactivity in formalin-fixed, paraffin-embedded sections of 30 MCC, five cutaneous metastases of pulmonary small-cell neuroendocrine carcinomas, 10 primary cutaneous adnexal carcinomas with basaloid features, 18 benign basaloid adnexal neoplasms of the skin (nine spiradenomas and nine cylindromas), and two cutaneous PNETs, using a standard immunohistologic technique and microwave-mediated epitope retrieval. Of the 30 MCC, 12 showed crisp membrane staining for CD99. Among the remaining tumors, only the two PNETs were positive for that marker. Although the majority of MCCs did not label for CD99, the pattern of reactivity in positive cases was indistinguishable from that observed in PNETs. Eighteen of 27 MCCs that were stained for CK20 were reactive for that protein, in contrast to metastatic small cell carcinomas, cutaneous PNETs, and appendageal skin tumors, which were uniformly negative for this marker. However, a subset of nine tumors, which were most consistent with MCC on clinical grounds, was CD99 positive and CK20 negative. Hence, reliance on CD99 alone as a diagnostic marker for PNET in this context cannot be recommended. Rather, careful assessment of the clinical presentation, together with extended immunophenotyping that includes other lineage markers and, when possible, cytogenetic analysis for characteristic chromosomal aberrations, remains the best means of separating MCC from PNET. Finally, the lack of CD99 reactivity in basaloid adnexal neoplasms of the skin suggests a utility in their differential diagnosis from cutaneous tumors with neuroendocrine or neuroectodermal differentiation.

12E7 Antigen↗
PubMedDate not supplied

Peripheral neuroepithelioma developing in the abdominal cavity.

Peripheral neuroepitheliomas are rare malignant tumors of presumed neural crest origin, arising outside the central and sympathetic nervous system. We present herein a case of a young man with diffuse peripheral neuroepithelioma of the abdominal cavity. Although we twice attempted a debulking procedure on this patient, and treated him with alternating VIP-CAV combined chemotherapy, his disease showed a relentless course without responding to any treatment. The development of peripheral neuroepithelioma in the abdominal cavity is an extremely rare occurrence. These rare malignant tumors, of presumed neural crest origin, arise outside the central and sympathetic nervous systems (1). Other names for this tumor are: extracranial primitive neuroectodermal tumor (PNET), Askin tumor, peripheral or adult neuroblastoma (2,3,4). We present a case of a young man with diffuse development of this tumor in the abdominal cavity.

Abdominal Neoplasms↗
PubMed2001

Antineuronal nuclei immunohistochemical staining patterns in childhood ependymomas.

NeuN, the mouse-derived monoclonal antibody to the reportedly neuron-specific nuclear protein, has been observed to react with many different types of normal, postmitotic neurons throughout the central and peripheral nervous systems. We retrospectively examined 23 surgical specimens (collected from 20 patients) originally diagnosed at our institution between 1983 and 1999 as ependymoma (9), myxopapillary ependymoma (1), anaplastic/malignant ependymoma (10), and primitive neuroectodermal tumor with ependymal differentiation (3). The ependymomas included lesions from the spine (3), cerebrum (5), and posterior fossa (15). Representative formalin-fixed, paraffin-embedded sections from each tumor were subjected to immunohistochemical staining with antibody against NeuN (Chemicon International, Inc, Temecula, CA). Five astrocytomas, four primitive neuroectodermal tumors, and normal cerebral cortex and ependyma from autopsy brains of premature newborns, term infants, and older children served as controls. Thirteen ependymal tumors had positive nuclear staining ranging from rare tumor cells to numerous groups of cells; of these, 9 were anaplastic ependymomas and had the most staining. These studies suggest that some ependymomas arise from a pluripotential neuroglial cell.

Antibodies, Monoclonal↗
PubMed1995

Ewing's sarcoma and extracranial peripheral neuroectodermal tumors.

Ewing's sarcoma and extracranial primitive neuroectodermal tumors of bone and soft tissue are small round-cell tumors that comprise a family of neoplasms distinguished by a cytogenetic marker that can be detected by reverse transcription and polymerase chain reaction. Based on molecular and immunohistochemical studies, it is generally acknowledged that this is a family of neuroectodermal tumors. Molecular methods allow accurate diagnosis with minimally invasive surgical options, provide a manner to detect minimal residual disease, and begin to shed light on the pathogenesis of these entities. Combined modality treatment regimens continue to improve the outlook for nonmetastatic Ewing's sarcoma and primitive neuroectodermal tumors patients. Patients who present with metastatic disease may benefit from intensive therapy as facilitated by peripheral stem cell and autologous bone marrow rescue programs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

[Soft tissue malignancies in childhood and adolescence. Pathology and clinical relevance based on data from the kiel pediatric tumor registry].

Soft tissue malignancies in childhood and adolescence encompass a wide variety of histologically and genetically different tumor entities. In the files of the Kiel Pediatric Tumor Registry, 4,272 soft tissue malignancies were collected since 1977. Rhabdomyosarcomas are by far the most frequent sarcomas (44.6 % of the cases), followed in decreasing order of frequency by the family of Ewing tumors (peripheral primitive neuroectodermal tumors and extraosseous Ewing's sarcomas; altogether 22.3 %), malignant peripheral nerve sheath tumors (8.1 %), synovial sarcomas (5.0 %), leiomyosarcomas (3.2 %), fibrosarcomas (2.4 %), extrarenal malignant rhabdoid tumors (2.0 %), and alveolar soft tissue sarcomas (1.1 %). A further group (11.3 %) includes rare tumors, intermediate fibrohistiocytic tumors, and unclassified sarcomas. Embryonal rhabdomyosarcomas are 2.5 times more frequent than the alveolar rhabdomyosarcomas, which are prognostically unfavorable and located predominantly in the extremities and the trunk. With regard to clinical findings, histology, molecular biology and prognosis, embryonal and alveolar rhabdomyosarcomas have to be considered as two different tumor types. The family of Ewing tumors includes extraosseous Ewing's sarcoma and peripheral primitive neuroectodermal tumors (synonym: malignant peripheral neuroectodermal tumors), the former tumors without and the latter with neural differentiation. Many cases of infantile malignant peripheral nerve sheath tumors and infantile fibrosarcomas are low-grade malignancies and prognostically more favorable than their "adult" counterparts.

Adolescent↗
PubMed2006

Immunohistochemistry of primary malignant neuroepithelial tumors of the kidney: a potential source of confusion? A study of 30 cases from the National Wilms Tumor Study Pathology Center.

Ewing sarcoma/peripheral primitive neuroectodermal tumor (pPNET) is a rare primary tumor of the kidney with morphologic features similar to those of other primitive tumors. Previous studies have shown that these tumors frequently stain positively with immunostains against CD99 and FLI-1 and negatively with stains against WT-1, suggesting that these markers may be used for the distinction between Wilms tumor and pPNET. We present 30 cases of primary malignant neuroepithelial tumor with immunohistochemical profiles and reverse transcriptase polymerase chain reaction (RT-PCR) analysis and show that immunophenotypic overlap exists between Wilms tumor and pPNET. A subset of 30 neuroepithelial tumors from the National Wilms Tumor Study originally categorized as putative pPNETs of the kidney was stained with FLI-1, WT-1, and thyroid transcription factor-1. Bicolor fluorescence in situ hybridization studies were performed on 19 of the cases. Other data on these tumors were available from a previous study (Am J Surg Pathol 2001;25:133). Of 7 primary tumors that had the EWS/FLI-1 fusion transcript by RT-PCR, 6 exhibited strong immunopositivity for FLI-1. Nine that were negative by RT-PCR stained positively with the FLI-1 stain. Five fusion-negative cases stained with both FLI-1 and WT-1. Three fusion-negative cases were negative for FLI-1 but positive for WT-1. Five fusion-negative cases were negative for both FLI-1 and WT-1. Of the 30 cases, 29 were positive for CD99. Seven cases that were negative for the EWS-FLI-1 fusion by RT-PCR were positive by fluorescence in situ hybridization. All cases were negative for thyroid transcription factor-1. Reliance upon immunohistochemistry as the sole means of ancillary diagnosis in renal pPNET can lead to confusing results. We recommend molecular fusion studies for clarification of primitive renal tumors with unexpected immunophenotypic results.

Adult↗
PubMedDate not supplied

In vivo and in vitro models of medulloblastomas and other primitive neuroectodermal brain tumors of childhood.

Recent advances in understanding the basic biology of the neoplastic cells that populate childhood primitive neuroectodermal tumors (PNET) of the central nervous system (CNS) underline several unique properties of these common pediatric brain neoplasms. For example, studies of posterior fossa cerebellar medulloblastomas (MB), a prototypical group of brain tumors that comprise the largest class of PNET, suggest that the molecular phenotype of subpopulations of neoplastic cells in MB partially recapitulates stages in the acquisition of the neuronal phenotype by normal developing human CNS progenitor cells. However, as reviewed here, it appears that the neoplastic cells in MB exhibit one or more molecular defects in the sequence of normal maturational events that enable CNS progenitor cells to exit the cell cycle, become committed to the neuronal lineage, and undergo terminal differentiation into fully mature, permanently postmitotic CNS neurons. Indeed, since PNET emerge almost exclusively in early childhood, the induction of PNET may result from genetic lesions that arise in developing CNS progenitor cells thereby preventing these neural precursors from executing normal programs of lineage commitment and differentiation in the CNS. Clarification of how lineage commitment and maturation in PNET comprised of neuron-like tumor cells deviate from normal CNS development may clarify how oncogenes and tumor suppressor genes exert their effects in a cell type specific manner at different stages in the normal maturation of CNS cells. Recently, a number of potentially effective in vitro and in vivo model systems of PNET have been developed. Since these model systems could facilitate efforts to elucidate mechanisms of neoplastic transformation and tumor progression in the CNS, we review the potential utility of several recently described in vitro (e.g., MB cell lines) and in vivo (e.g., transgenic mice) experimental systems as models of authentic childhood CNS neoplasms.

Animals↗
PubMed2006

Successful treatment of primitive neuroectodermal tumor-associated microangiopathy with multiple bone metastases.

We report here a 16-year-old male with primitive neuroectodermal tumor (PNET)-associated probable microangiopathy with multiple bone metastases. Laboratory findings excluded the possibility of amegakaryocytic or immune thrombocytopenia and/or disseminated intravascular coagulation. He was first treated with plasma-exchange (PE), followed by platelet transfusions, steroid pulse therapy and combined chemotherapy. PE and steroid pulse therapy reduced his plasma CRP level. Combined chemotherapy drastically increased his platelet count until it had almost normalized without further transfusion. The plasma level of von Willebrand factor-cleaving protease (ADAMTS13) activity measured before PE was not severely deficient (48% of normal) and an unusually large von Willebrand factor multimer (UL-VWFM) was detected. We consider that this therapeutic strategy has the following benefits: (1) reduction of plasma levels of factors that are harmful to both platelet activation and endothelial cell injury; and (2) the safe transfusion of platelet concentrate in thrombotic microangiopathy. This strategy should be confirmed in further cases.

Adolescent↗
PubMedDate not supplied

Primary intracranial peripheral primitive neuroectodermal tumor/Ewing's sarcoma presenting with acute intracerebral hemorrhage.

OBJECTIVE: To report two cases of intracerebral hemorrhage due to primary intracranial peripheral primitive neuroectodermal tumor (pPNET)/Ewing's sarcoma (ES) and review of related literatures. MATERIAL: Two cases of 17-year-old patients presented with acute increased intracranial pressure one of which also had left hemiparesis. METHOD: On neuroimaging studies, the first patient had an intraparenchymal hematoma with a size of 4 cm at the right fronto-parietal junction adjacent to tumor infiltrating the superior sagittal sinus. The second patient had a large left temporal tumor with intraventricular hemorrhage. Both patients underwent craniotomy with complete removal of tumor and hematoma. RESULTS: Pathological examination in both cases revealed numerous small round tumor cells with stippled chromatin pattern and scanty cytoplasm. Tumor cells strongly expressed CD99. Vimentin immunoreactivity was observed. The final diagnosis of pPNET/ES was rendered. There was no evidence of extracranial disease in both cases. Both patients were doing well without evidence of recurrent disease at 12 and 24-month follow-up respectively. CONCLUSIONS: Peripheral primitive neuroectodermal tumor (pPNET)/Ewing's sarcoma (ES) is a malignant small round cell tumor, commonly arising in soft tissue of the trunk and lower extremity. Those occurring in the intracranium are rare, and most patients present with progressively increased intracranial pressure and/or cranial nerve deficit. The occurrence of intracerebral hemorrhage due to primary intracranial pPNET/ES is exceedingly rare. The role of adjuvant therapy in this condition is yet to be investigated.

Acute Disease↗