Immunophenotypic and genotypic analysis of a case of primary peripheral primitive neuroectodermal tumour (pPNET) of the urinary bladder.
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Expression of Trk protein has been documented by Northern analysis in neuroblastomas with good prognosis. To localize the expression of this protein at the cellular level within individual tumors, we adapted a recently characterized pan-Trk antibody for use in formalin fixed, paraffin-embedded tissue. We have examined a group of small round blue cell tumors occurring in children, including both high and low stage neuroblastomas, to assess the presence or absence of Trk expression and its cellular localization. Positive staining for Trk protein was observed in four of four low stage (good prognosis) neuroblastomas, five of five primitive neuroectodermal tumors/Ewing's sarcoma, five of five rhabdomyosarcomas, and no lymphomas. Within the neuroblastomas, expression of Trk protein was most striking in ganglion cells, in which positive cytoplasmic staining was demonstrated regardless of tumor stage. The latter observation may lend further insight into the pathobiology of this malignant childhood tumor.
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In this report we identify two cultured human primitive neuroepithelioma cell lines that express cholecystokinin (CCK) RNA and synthesize substantial amounts of pro-CCK, but differ in their ability to process the prohormone. Seven cultured human neural tumor lines, including two primitive neuroepitheliomas and five neuroblastomas, were screened for CCK gene expression using a CCK C-terminal RIA system, a RIA specific for the carboxy-terminal extension of prepro-CCK, and RNAse protection assays specific for CCK mRNA. RNA derived from the two primitive neuroepitheliomas yielded strong hybridization signals with CCK-specific probes. The five other neuronal tumors were negative for CCK mRNA. The two primitive neuroepitheliomas also synthesized substantial quantities of material reactive in the CCK carboxy-terminal extension RIA system. One of the tumors, Sk-N-Mc, postranslationally processed the CCK prohormonal material poorly, yielding only high mol wt CCK precursors and no immunoreactive CCK. The other, SK-PN-Dw, was able to process the prohormone, producing immunoreactive CCK-like material plus a peptide that immunochemically and chromatographically resembled the intact CCK C-terminal extension peptide. These cultured tumor lines should prove useful in furthering our understanding of the regulation of the CCK gene in human neuronal cells and will also provide an in vitro system for investigation of the posttranslational processing of the CCK preprohormone. In addition, the data demonstrate that screening procedures for examining peptide hormone expression by tumors are most comprehensive when specific molecular genetic probes are employed in addition to standard peptide assay methodology. Finally, these data suggest that CCK production may be a feature of some primitive neuroepitheliomas.
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A nine-year-old horse was presented with severe exophthalmos of the right eye and a large mass in the vitreal cavity. The affected globe was enucleated and two months following surgery the horse was euthanized because of spread of the tumor into the calvarium producing compression of the brain stem and neurologic signs. Examination of tumor tissue by light and electron microscopic examination showed a mixed neoplasm of primitive neuroepithelium.
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The nervous system is the most common site for the development of solid neoplasms in children. The most frequent oncotype is the pilocytic astrocytoma, followed by the medulloblastoma. Primitive undifferentiated neuroectodermal tumors occur primarily in childhood; problems of pathogenesis of these neoplasms are discussed, as well as their relationship with central nervous system development.
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A case is reported of primary primitive neuroectodermal (neuroepithelial) tumour occurring in the right orbit of a 52-year-old man. The intraorbital extraocular location is unique for this kind of neoplasm. The malignant tumour was differentiated into primitive neuroepithelial, ependymal, and oligodendroglial cells. The neuroglia was identified by localisation of cytoplasmic glial fibrillary acidic protein. It is suggested that this primary intraorbital, extraocular, primitive neuroectodermal tumour with neuroglial differentiation is akin to the primitive neuroectodermal tumours of the neuraxis, including the cerebellar medulloblastomas, and to some peripheral nerve tumours known as malignant neuroepitheliomas, malignant ependymomas, and neuroblastomas. The ectomesenchymal remnant of the neural crest or ectopic neuroepithelium or both may have been the origin of the present tumour. Differentiation of the neuroectodermal component of the neural crest or heterotopic neuroepithelium or both would create a primitive neuroectodermal tumour with diverse neuroglial elements.
Tumors derived from the fully differentiated ciliary epithelium include adenomas and adenocarcinomas. Many such tumors in animal eyes have been reported. Medulloepitheliomas derived from the primitive medullary epithelium of the optic cup have rarely been seen in animal eyes. A teratoid variant of medulloepithelioma, recently described in human eyes, has also been seen in canine and bovine eyes. These tumors contain tissues resembling brain, cartilage, rhabdomyoblasts, and primitive mesenchyme, in addition to the poorly differentiated neuroepithelial and neuroblastic elements characteristic of malignant medulloepitheliomas.
Rats and hamsters were exposed to 1 ppm of chloromethyl methyl ether six hours per day, five days per week, throughout their lifetime. Mortality and weight gain of the exposed animals paralleled that of the control animals. Malignant tumors of the respiratory tract were found in two rats. These were a squamous cell carcinoma of the lung with blood vessel invasion and an esthesloneuroepithelioma originating in the olfactory epithelium and invading the forebrain. One hamster was found to have an adenocarcinoma of the lung and another, a squamous papilloma of the trachea. A single exposed rat had a pituitary tumor of primitive cell type that may well have been coincidental.
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