Estimation of diagnostic value of chosen markers of neural differentiation in neuroblastoma group of tumors and pPNETs.

Neuroblastoma and peripheral PNETs both are typical examples of wide group of small round blue cell tumors of childhood. Matured neuroblastoma show typical clinical presentation and easy to interpret microscopic picture. Unfortunately in everyday practice much commonly appeared less differentiated neuroblastomas with difficult to predict clinical behavior and impossible to diagnose in routine stain histologic view. Peripheral PNETs are found as morphologically similar entities to some neuroblastoma subtypes but they are treated as separate CD99 positive group of tumors with different biology and clinical behavior. The aim of our study was to estimate the usefulness of neural markers expression (Neuroblastoma Marker, neurospecyfic enolase and neurofilaments) in routine separation between neuroblastoma tumors and pPNETs and between neuroblastoma subtypes according to currently used classification of those entities. We investigated 63 tumor tissue samples and found differences in expression of investigated markers between both neuroblastoma subgroups and neuroblastoma group of tumors and pPNETs.

Type 1 (11;22)(q24:q12) translocation is common in Ewing's sarcoma/peripheral neuroectodermal tumour in south Indian patients.

The Ewing's sarcoma family can present diagnostic difficulties. In the past the basis of diagnosis has been a exclusion. Identification of a specific translocation especially t(11;22) (EWS-FLI 1 fusion gene), which is seen in nearly 85 percent of Ewing's sarcoma cases can help in precise diagnosis. We have carried out a study on twenty patient samples diagnosed to have Ewing's sarcoma/peripheral neuroectodermal tumour (PNET)/small round cell malignant tumour. The study involved RT-PCR analysis for the fusion transcript, followed by sequencing to identify the specific type of fusion. Ninety percent (18/20) of the samples tested were found to be t(11;22) translocations involving EWS-FLI 1 genes. Sixty-one percent (11/18) were found to be type 1 fusion and seven were type 2 (39 percentage). This is the first study in India with quantitative information about the types of EWS-FLI 1 translocations present in Ewing's family of tumours in south Indian patients.

The neuroectodermal tumor of bone.

Four small round cell malignant tumors of bone occurring in children are described. There was no catecholamine secretion and the clinical, radiologic, and biopsy diagnosis in each was Ewing's sarcoma. Glycogen was sparse both on imprints and in tissue sections. The tumors, when extensively sampled, had areas of a lobular growth pattern and Homer Wright rosettes. The rosettes were always focal and varied in complexity from case to case; they were rudimentary in one instance and markedly fibrillar in the most obvious instance. Neuron-specific enolase was demonstrated in tissue sections and in longterm cell cultures from three of the tumors. The cultured cells put out moderately long beaded processes in serum-free medium but had no catecholamine fluorescence. Electron microscopy of the tumor rosettes and the cultured cells showed processes containing aggregates of microtubules and only one case had rare neurosecretory granules. This study suggests that some small round cell tumors of bone and soft tissue in children, which present as Ewing's sarcoma, are neuroectodermal in nature.

Sinonasal undifferentiated carcinoma. An aggressive neoplasm derived from schneiderian epithelium and distinct from olfactory neuroblastoma.

Eight cases of a highly aggressive undifferentiated carcinoma of the nasal cavity and paranasal sinuses are described. The patients, who ranged in age from 30-77 years, had multiple sinonasal symptoms, and each had involvement of the nasal cavity, maxillary antrum, and ethmoid sinus. Six tumors extended into the orbital bones, and five penetrated the cranial cavity. Five patients died of disease from 1 to 41 months after diagnosis (median: 4 months), and three are alive with tumor less than 1 year following diagnosis. Microscopically, the neoplasms formed nests, trabeculae, and sheets containing medium-sized cells with small to moderate amounts of eosinophilic cytoplasm. A high mitotic rate, tumor necrosis, and prominent vascular permeation were characteristic. Seven neoplasms were immunoreactive for cytokeratin, five for epithelial membrane antigen, and four for neuron-specific enolase. Ultrastructurally, occasional small desmosomes and rare membrane-bound, dense-core granules were observed. Sinonasal undifferentiated carcinoma is a distinctive clinicopathologic entity that must be distinguished from other, less aggressive sinonasal neoplasms.

Peripheral primitive neuroectodermal tumour and extra-osseous Ewing's sarcoma; a histological, immunohistochemical and DNA flow cytometric study.

Although peripheral primitive neuroectodermal tumour (pPNET) and extra-osseous Ewing's sarcoma (EES) are thought to be closely related neoplasms, their clinical behaviour differs considerably. To determine the clinical relevance of the Schmidt classification scheme for differentiating pPNET and EES, 20 tumour specimens of poorly differentiated round cell tumours were evaluated. In addition, the diagnostic value of several neural markers and the prognostic value of quantitative morphological variables (DNA ploidy, S-phase fraction, and the mitotic activity) were assessed. Homer-Wright rosettes were present in 9 tumours. Neuron specific enolase (NSE) was expressed in 11 tumours, 8 of which expressed a second neural marker (CD57, S100, or neurofilament). According to the Schmidt classification, 11 pPNET and 5 EES were distinguished. HBA-71 was exclusively expressed in pPNET and EES. The remaining tumours were classified as sarcoma not otherwise specified (n = 2), rhabdomyosarcoma (n = 1), and desmoplastic tumour with divergent differentiation (n = 1). EES611 patients fared significantly better than the pPNET patients (100% versus 42% 5-year survival). Neither DNA ploidy nor S-phase fraction assessed in 12 evaluative histograms (9 pPNET and 3 EES), nor mitotic activity yielded information of additional prognostic value. On the basis of this study and the Schmidt classification scheme, it can be concluded that if the diagnosis of EES and pPNET is based on light microscopy (Homer-Wright rosettes) and/or immunohistochemistry (at least two neural markers, i.e. NSE, S-100, CD57, and neurofilament), the classification provides important clinical information. Furthermore, positivity for HBA-71 is helpful in differentiating pPNET and EES from all other small round cell tumours.

Embryonal central neuroepithelial tumors and their differentiating potential. A cytogenetic view of a complex neuro-oncological problem.

The embryonal central nervous system (CNS) neoplasms are reviewed with special reference to their differentiating potential and in the light of current neuro-oncogenetic concepts partly derived from the experimental induction of neural tumors. The conceptual (and, occasionally, practical) distinction between adult-type and embryonal CNS tumors raises a complex problem, because neoplastic transformation essentially involves replicating stem cells in tissues of renewal and because in the human brain such cells are found mostly in the course of CNS development. A cytogenetic scheme is therefore needed to serve as a frame of reference for a classification of embryonal CNS tumors that will account for the different histological entities documented so far and for the range and the restrictions of their differentiating capabilities. Most embryonal CNS tumors can be fitted into such a scheme. The cerebral medulloepithelioma, the cerebral and cerebellar neuroblastomas, the primitive polar spongioblastoma, and the ependymoblastoma show characteristic morphological features and a correspondingly distinctive cellular differentiating potential. The differentiating capabilities of the cerebellar medulloblastoma, the pineoblastoma, and the retinoblastoma are also distinctive, and are apparently determined by the cytogenesis of the area of the CNS in which the tumors originate. The indiscriminate application of a simplistic concept that would include all the so-called "primitive neuroectodermal tumors" into a single neuroepithelial tumor entity is unlikely to bring further understanding to the problem.

Peripheral and central primitive neuroectodermal tumors. A nosologic concept seeking a consensus.

The term primitive neuroectodermal tumor is widely used in the literature for a group of small, round-cell tumors in the central and sympathetic nervous systems and soft tissues as well as a specific diagnostic term for individual neoplasms; however, the contention that these various clinicopathologic entities (neuroblastoma, medulloblastoma, and peripheral neuroepithelioma) are histogenetically related is an unproved hypothesis. Morphologic, cytogenetic, immunohistochemical, biochemical, and in vitro studies have established phenotypic similarities among these putatively related neoplasms whether they originate in the brain, adrenal gland, or soft tissues. Because one tumor resembles another in terms of its phenotypic expression, that does not necessarily imply a common histogenesis. This point has been made by previous investigators. The purpose of this review is to evaluate and discuss the present status of our understanding and some of the controversial aspects of this enigmatic category of neoplasms, mainly occurring in children, known as the primitive neuroectodermal tumors.

Ewing tumor: tumor biology and clinical applications.

The Ewing tumor family includes classical Ewing's sarcoma of bone and soft tissues, peripheral primitive neuroectodermal tumors (pPNET), Askin tumor, and other less frequent variants. This group of tumors is defined by the consistent presence of chromosomal translocations resulting in gene fusions between EWS gene and a member of the ETS family of transcription factors, mainly FLI1 and ERG. Analogous fusions are seen in other solid developmental tumors, like desmoplastic small round cell tumor. These fusions, which are consistently present and tumor-specific, control transcription of several target genes, largely unknown but critical to cell proliferation and differentiation. Therefore, gene fusions are useful to diagnose and classify small round cell tumors, have prognostic significance, are probably useful to detect micrometastasis and monitor minimal residual disease, and are potential therapeutic targets. Secondary molecular alterations, which include mutations of cell cycle regulatory genes, are not tumor-specific but are related to progression and may have prognostic value. The Ewing tumor family represents a paradigm of the application of the knowledge of biology of neoplasia to the clinical management of patients.

Immunohistochemical demonstration of Wilms tumour gene product WT1 in a canine "neuroepithelioma" providing evidence for its classification as an extrarenal nephroblastoma.

An intradural extramedullary tumour, surgically removed from the spinal canal of a young dog with paraplegia, had the histological appearance of a nephroblastoma. Subsequent necropsy revealed no evidence of a renal primary tumour or of any other tumour. Similar tumours of the spinal canal have been described previously under a variety of names, in particular neuroepithelioma. With an antibody to the human Wilms tumour (nephroblastoma) gene product WT1, labelling of glomeruloid bodies, similar to glomerular podocytes in human fetal kidney, was demonstrated in the tumour. This finding strengthened the suggestion that it was a nephroblastoma.

[Immunohistochemical identification of olfactory esthesioneuromas. Apropos of 16 cases]. / Identification immunohistochimique des esthésioneuromes olfactifs. A propos de 16 observations.

We report anatomoclinical and immunohistochemical analysis of sixteen cases of esthesioneuroblastomas. Microscopic study confirm difficulty of diagnostic for this tumors. Results of S 100 protein reaction for Schwann cells identification, NSE and HNK1 reaction for nervous cells and KL1 reaction for epithelial cells drawn from olfactory mucosa, allow definition of immunologic ENO profile. Pattern immunologic criteria are defined by S 100, NSE or/and HNK1, and eventually KL1 positive reactions permit differential diagnosis with other nervous tumors or undifferentiated carcinomas of nasal fossa. Histo-prognostic patterns are defined by S 100 reactivity distributed in neoplastic cells and cytoplasmic process of cells, to form a continuous network in well differentiated ENO and discontinuous network in undifferentiated forms of ENBO. These results confirm histogenesis of this tumor derived from olfactory mucosa and emphasized only two distinct types: neuro epithelial tumors corresponding to ENEO and cases of ENBO and nervous tumors grouping ENCO and any cases of ENBO.

[Embryonal neuroepithelial tumors of the cerebral hemispheres]. / Embrional'nye neiroépitelial'nye opukholi bol'shikh polusharii golovnogo mozga.

33 embryonal neuroepithelial tumours of the cerebral hemispheres were examined light- and electron-microscopically, immunohistochemically. 4 types of tumours were distinguished: neuroblastoma, neuroepithelioma, ependymoblastoma and choroid carcinoma. Each type was characterised by its own pathohistological, immunohistochemical and ultrastructural features. Our results and literature data prove immunophenotypic and ultrastructural heterogeneity of embryonal neuroepithelial tumors of the cerebral hemispheres, in spite of some similarities in their pathohistological features.

[Olfactory neuroblastoma. A clinical and morphological study]. / Neuroblastoma olfatorio. Estudio clínico y morfológico.

A clinical and morphological study about neuroblastoma with olfactory differentiation are made. This study includes: TAC, vanimil mandelic acid urine determination, optic microscope, immunohistochemical technique, neuropeptidal, in situ hybridization, DNA analysis by flow cytometry and electronic microscope.