Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 30% of malignant neoplasms in children are dysontogenetic tumors whose pathologic features resemble or recapitulate those of the developing organ or tissue of origin. Archetypes include classic neuroblastoma, Wilms' tumor, and embryonal rhabdomyosarcoma. This review traces the history of the principal types of dysontogenetic neoplasms and the primitive round cell tumors, Ewing's sarcoma, and peripheral primitive neuroectodermal tumor. Retinoblastoma, neuroblastoma, and Wilms' tumor were first described in the 19th century but with several different appellations than those we use today. Although some progress was made in the surgical management of Wilms' tumor during the 1940s and 1950s, most of these unique solid neoplasms of childhood were seen as essentially untreatable and inevitably fatal; surgery and perhaps irradiation were the principal therapeutic offerings. The folic acid analogue, aminopterin, was reported in 1948 as inducing the first complete but temporary remission in acute childhood leukemia. The chemotherapeutic era began shortly thereafter with effective chemotherapy in the management of Wilms' tumor with the introduction of dactinomycin. Pathologists were no longer restricted to being purveyors of the death sentence; they were now responsible for differentiating one type of primitive and embryonic neoplasm from another by using a variety of ancillary techniques, including tissue culture, electron microscopy, immunohistochemistry, and cytogenetics. Favorable or unfavorable morphologic types and subtypes of tumors were defined and, together with the pathologic staging, became incorporated into the therapeutic plan and prognostic assessment. During the past 40 years, these tumors progressed from being virtually treatment resistant to having an overall 5-year survival of 70% or greater. Through the cooperative efforts of pediatric hematologists/oncologists, pediatric surgeons, radiation therapists, and pathologists, the primitive and embryonic neoplasms of childhood are now viewed as some of the most treatable and curable of cancers.
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PMID:The evolution of the diagnosis and understanding of primitive and embryonic neoplasms in children: living through an epoch. 968 89

The field of molecular genetics continues to see an ever increasing number of applications to pediatric tumor analysis. Studies in pediatric tumors have identified novel genes and other genetic changes, a large number of which reflect one of the following mechanisms: (1) activation of proto-oncogenes; (2) loss of tumor suppressor genes; or (3) creation of novel fusion proteins. At least one of these mechanisms is operational in each of the following pediatric tumors: neuroblastoma, Ewing sarcoma and peripheral primitive neuroectodermal tumor (pPNET), intra-abdominal desmoplastic small-cell tumor, rhabdomyosarcoma, synovial sarcoma, and Wilms tumor. Out of this research has come not only an increased understanding of oncogenesis but also, for each of the tumors listed above, diagnostic and/or prognostic markers that can be used by the pathologist and oncologist to improve overall patient management.
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PMID:Molecular genetics in the diagnosis and prognosis of solid pediatric tumors. 968 59

Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET) are considered in the differential diagnosis of small round blue cell tumors of infancy and childhood which includes neuroblastoma, rhabdomyosarcoma and malignant lymphoma. Fine-needle aspiration diagnosis of these neoplasms can be particularly difficult when the neoplasms are composed of poorly differentiated cells or fail to produce a stroma. MIC-2 is a highly sensitive and specific marker for the PNET/ES group of neoplasms and has been studied extensively in surgical pathology. Other small blue cell neoplasms including rhabdomyosarcoma, blastemal Wilm's tumor, and lymphoblastic lymphoma have also shown positivity, but the staining reactions are usually weak and focal. The utility of this marker in the differential of small blue cell neoplasms in cytologic material has not been examined. Twenty cases of small blue cell neoplasms obtained by fine-needle aspiration (FNA) were studied. MIC-2 antibody was applied retrospectively to formalin-fixed cell block material and destained alcohol-fixed and air-dried cytologic preparations. These cases include primitive neuroectodermal tumor (five cases), Ewing's sarcoma (two cases), neuroblastoma (four cases), Wilms's tumor (four cases), lymphoblastic lymphoma (two cases), and small-cell carcinoma (three cases). The cases were judged positive when the majority of the cells showed cytoplasmic staining. Diffuse cytoplasmic staining was observed in all seven cases of PNET/ES. Staining could be seen on the destained air-dried smears (three cases), fixed smears (two cases), or the cell block material (two cases). None of the other 13 small blue cell neoplasms showed positive staining. We conclude that MIC-2 is a sensitive and specific marker for the PNET/ES group of neoplasms in specimens from formalin-fixed cell block, air-dried, and alcohol-fixed cytologic material and is useful in the differential diagnosis of small blue cell tumors.
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PMID:Diagnostic utility of MIC-2 immunocytochemical staining in the differential diagnosis of small blue cell tumors. 983 29

The term primitive neuroectodermal tumor (PNET) names a group of malignant neoplasms of presumed neural crest origin; they are composed of round small cells, and may be centrally located or outside. The former are currently seen in childhood, mostly in reference to the posterior fossa, and include medulloblastoma and neuroblastoma. Outside of the central nervous system includes peripheral neuroectodermal tumor of the bone (PNET-B, Tefft's tumor), Askin's tumor, and even Ewing's sarcoma. We describe a case in a young adult, with extremely unusual spinal localization, in which histopathological and immunohistochemical analysis were done; also, a review of some features is presented clinical-histopathological issues concerning related.
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PMID:[Spinal primitive neuroectodermal tumor]. 1032 53

Melanotic neuroectodermal tumor of infancy is a rare but well-recognized entity in pediatric pathology. However, the relationship of this tumor to other pediatric small cell tumors with neuroectodermal features (such as neuroblastoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor, and desmoplastic small round cell tumor) is undetermined. Molecular genetic studies of melanotic neuroectodermal tumor of infancy have not been reported. We studied three typical cases of melanotic neuroectodermal tumor of infancy in an attempt to link this tumor to other small cell tumors with well-characterized molecular genetic changes. Tests performed included: detection of MYCN gene amplification and deletion of 1p (all 3 cases), and presence of the t(11;22)(q24;q12) and the t(11;22)(p13;q12) translocations (2 of 3 cases). None of these tests yielded positive results. Thus, there is no genetic basis at present to link melanotic neuroectodermal tumor of infancy to neuroblastoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor, or desmoplastic small round cell tumor.
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PMID:Melanotic neuroectodermal tumor of infancy: a molecular genetic study. 1046 91

We conducted a prospective pilot study to assess the feasibility and safety of high-dose busulfan/melphalan as conditioning therapy prior to autologous PBPC transplantation in pediatric patients with high-risk solid tumors. From January 1995 to January 1999, 30 patients aged 2-21 years (median 8) were entered into the study. There were 14 females and 16 males. Diagnoses included neuroblastoma in 10 patients; Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) in 15 patients and rhabdomyosarcoma in five patients. Treatment consisted of busulfan 16 mg/kg, orally over 4 days (from days -5 to -2) in 6 hourly divided doses, and melphalan at a dose of 140 mg/m2 given by intravenous infusion over 5 min on day -1. G-CSF mobilized PBPC were used as autologous stem-cell rescue. One patient developed a single generalized convulsion during busulfan therapy. The most relevant non-hematologic toxicity was gastrointestinal, manifesting as grade 2-3 mucositis and diarrhea in 12 patients. Two patients died of procedure-related complications, one from veno-occlusive disease of liver and multiorgan failure and the other from adult respiratory distress syndrome. Probability of treatment-related mortality was 6.6 +/- 4.5%. With a median follow-up of 18 months (range, 1-48), 19 patients are alive and disease-free, the actuarial EFS at 4 years being 55 +/- 12% for the whole group. We conclude that high-dose busulfan/melphalan for autologous transplantation in children with solid tumors is feasible even in small patients. It is well-tolerated, with an acceptable transplant-related mortality and has proven antitumor activity.
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PMID:High-dose busulfan/melphalan as conditioning for autologous PBPC transplantation in pediatric patients with solid tumors. 1064 2

Small round cell tumors of childhood can be histologically ambiguous, can require tumor markers for an accurate diagnosis, and include neuroblastoma, peripheral primitive neuroectodermal tumor (pPNET), Ewing's sarcoma (ES), lymphoma, and rhabdomyosarcoma. Because the cell type of origin for ES remains controversial, characterizing gene expression in ES can provide diagnostic markers and lead to better understanding of tumor biology. We studied RNA expression of the neuronal genes protein gene product 9.5 (PGP 9.5) and tyrosine hydroxylase (TH) by Northern analysis in cell lines and tissue from small round cell tumors. PGP 9.5 showed strong expression in 17 of 17 neuroblastoma cell lines, 9 of 9 pPNET cell lines, and 11 of 11 ES cell lines. PGP 9.5 was weakly expressed in 1 of 1 alveolar rhabdomyosarcoma cell lines but not in 1 of 1 embryonal rhabdomyosarcomas, and weak expression was seen in 1 of 7 leukemia cell lines. In tumor tissue, all 12 neuroblastomas expressed PGP 9.5, as did all 7 pPNET and all 7 ES. PGP 9.5 was very weakly expressed in 6 of 9 rhabdomyosarcomas and 1 of 9 lymphomas. TH was expressed only in neuroblastomas, and no TH expression was seen in cell lines or tissue from other tumors. As high expression of PGP 9.5 was only found in neural tumors; PGP 9.5 expression by ES provides further evidence for a neural origin of this tumor, whereas TH expression is highly specific for neuroblastomas. PGP 9.5 expression should allow sensitive detection of minimal residual disease for ES and pPNET using reverse transcription-PCR, and the variability in TH and PGP 9.5 expression levels in neuroblastomas indicates that expression of both genes should be used for monitoring minimal residual disease by reverse transcription-PCR.
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PMID:Expression of protein gene product 9.5 and tyrosine hydroxylase in childhood small round cell tumors. 1069 May 38

To elucidate a relationship between neuronal anaplasia, tumor proliferation, and ganglioside contents, we quantified gangliosides by HPTLC in tumors of neuroepithelial tissues at different grade, i. e. peripheral primitive neuroectodermal tumor (PPNET, grade IV), ependymoma (EPEN, grade III), neuroblastoma (NB, grade IV), and dysembryoplastic neuroepithelial tumor (DNT, grade I). PPNET, the most undifferentiated tumor examined had lowest concentration of total lipid-bound sialic acid. GM3 was the major ganglioside in all undifferentiated tumors (46-72.7% of total lipid-bound sialic acid). GD3 was an another component in PPNET and EPEN (7.2-17.3%). Concentration of a complex gangliosides GM1 was decreased in all tumor tissues and those of GT1a, GD1b and GT1b were decreased in tumors of high grade. The results suggest that the composition of gangliosides could be of considerable value in refining the classification of neuroepithelial tumors in infancy and childhood.
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PMID:Ganglioside patterns in neuroepithelial tumors of childhood. 1081 5

Twelve cases of neuroblastoma (NB) (7 boys and 5 girls) and 4 cases of primitive peripheral neuroectodermal tumor (PNET) (3 boys and 1 girl) were investigated for the presence of apoptosis and retinoic acid receptor (RAR) by immunhistochemical method. The apoptotic index in NB was zero or 1% in 8 children and relatively low (2-4.8%) in the other 4 cases, while it was higher (4.1-10.5%) in PNET. The RAR index determined by immunoperoxidase reaction in NB was zero or 3% in 5 cases and 9-34% in 7 children. RAR index in PNET was 16-68% in all the 4 cases. Good correlation (r = .47 according to Pearson-Bravis) was found between the number of RAR and spontaneous apoptosis. These results suggest that the RAR index in untreated NB and PNET shows great individual variation since its determination is necessary for the evaluation of the efficacy of retinoic acid treatment.
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PMID:Spontaneous apoptosis and retinoic acid receptor incidence in neuroblastomas and peripheral neuroectodermal tumors. 1084 30

In the present study, DNA flow cytometry (FCM) and immunocytochemistry (ICC) with a selected panel of antibodies were performed on 51 cases of malignant tumors which were referred for fine-needle aspiration biopsy (FNAB) to our Department of Cytology for the last 2 yr. Twelve cases were diagnosed as neuroblastoma, 16 as Ewing's sarcoma, 2 as retinoblastoma, 5 as non-Hodgkin's lymphoma (NHL), 5 as rhabdomyosarcoma, 2 as peripheral neuroectodermal tumors (PNETs), and 8 as Wilms' tumor. Eleven of 12 neuroblastomas were diploid by FCM, and 1 was aneuploid, with an S-phase fraction (SPF) of 8.3%. Neuron-specific enolase (NSE) was negative in 3 and positive in 8 cases of neuroblastoma, whereas neuroblastoma marker was positive in 3/11. Sixteen of 17 Ewing's sarcomas were diploid, and 1 showed tetraploid aneuploidy, with an SPF of 10.06%. Eight of 13 Ewing's sarcomas were positive for Mic-2 gene product (Ewing's marker). All 5 NHL were positive for leukocyte-common antigen (LCA). Three of 5 rhabdomyosarcomas were diploid, and 2 cases showed aneuploidy. Rhabdomyosarcoma showed muscle-specific actin positivity in 4 and desmin positivity in 3 cases. All 3 cases of PNET were diploid and positive for the Mic-2 gene product, whereas NSE and vimentin were positive in 2 cases. Both cases of retinoblastoma were diploid. Immunostaining was noncontributory in 1 case, and the other showed positivity for the retinoblastoma gene product, NSE, and chromogranin. Seven of 8 Wilms' tumors were diploid, and 1 showed aneuploid, with an SPF of 11.13%. Seven of 8 Wilms' tumors were positive for cytokeratin (CK), 5 were positive for NSE, 6 were positive for epithelial membrane antigen (EMA), and 5 were positive for vimentin. FNAB diagnosis of malignant round-cell tumors is difficult only by light microscopy. Due to the availability of specific markers for subgrouping tumors, ICC has proved to be more useful these days, while DNA FCM has little diagnostic value, as most of them are diploid. Further ancillary studies, e.g., electron microscopy, image analysis, and other molecular investigations, are required to further categorize these tumors more precisely for better clinical management of these cases.
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PMID:Role of immunocytochemistry and DNA flow cytometry in the fine-needle aspiration diagnosis of malignant small round-cell tumors. 1128 17


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