Primitive Neuroectodermal Neoplasms Research Articles

OPERATED PEDIATRIC POSTERIOR FOSSA TuMOURs IN BENGHAZI MEDICAL CENTER FROM 2015 TO 2016

BACKGROUND: Brain tumors in children have totally different clinical appearances, anatomical distribution, histopathological dian nosis, and clinical prognosis compared with adults. Materials and Methods: A retrospective study was conducted in the Department of Neurosurgery, Benghazi Medical Center which included all pediatric cases of posterior fossa tumor that presented or were referred to the Center and were considered for surgery from a period between the 1st Jan 2015 to 31st.Dec.2016. RESULTS: Four children, two males and two females, with the mean age of 8.75 years (4-12) were registered. The presenting symptoms were cerebellar (3), headache (2), and vomiting (2). The four cases underwent ventriculoperitoneal shunt before tumour resection surgery. Gross total resection was performed in all cases. The thirty days mortality was 25. The most common microscopic anatomy diagnosis was primitive neuroectodermal neoplasm (PNET) (4). Adjuvant therapy was planned by the oncologist according to histopathology results. CONCLUSION: Further studies should be conducted in this field for the greater understanding of the clinical presentation and management of these tumors, and judicious use of modern neurosurgical techniques should lead to more efficacious results and outcome, followed by adjuvant therapy if necessary.

Atypical adult medulloblastoma

Medulloblastomas are malignant primitive neuro-ectodermal neoplasms of childhood. In adults, clinical manifestations, imaging and prognosis can be different from that observed in children. Three adult patients with confirmed diagnoses of medulloblastoma are discussed in this report. They presented with unusually prolonged clinical courses and with imaging more suggestive of L'hermitte-Duclos disease. Medulloblastoma should be considered in all adults with posterior fossa masses despite having clinical and radiological features suggestive of a low-grade tumour. Definitive diagnosis requires histological confirmation in all cases.

Diffuse Anterior Retinoblastoma without Retinal Involvement

To present a unique case of an 8.5-year-old child with unilateral, anterior, pseudouveitis. He was found to have unilateral, invasive, small blue cell tumor of the anterior segment that was diagnosed as diffuse infiltrating retinoblastoma despite lack of retinal involvement on fundus examination or histopathologic analysis. Interventional case report. One patient. The patient was treated with topical prednisolone acetate 1% and oral prednisone with no improvement in anterior chamber reaction. The patient underwent fine-needle aspiration biopsy (FNAB) of anterior chamber fluid, the results of which were consistent with a primitive neuroectodermal neoplasm, either retinoblastoma or medulloepithelioma. Retinoblastoma was favored strongly, and the patient underwent enucleation followed by chemotherapy with vincristine, carboplatin, and etoposide, and radiation to the eye socket of 4140 cGy total was performed. The patient is alive and tumor free with follow-up of 5 years. Microscopic examination demonstrated cells similar to those seen on the FNAB infiltrating the iris stroma, trabecular meshwork, Schlemm's canal, and the inner portion of sclera in the region of the angle. No calcifications were identified. Serial sections of the entire globe were performed to determine the origin of the tumor. No retinal involvement was identified, and tumor was not seen to arise from the ciliary epithelium. Immunohistochemistry demonstrated positive staining with synaptophysin and negative staining with leukocyte common antigen and CD34. This patient represents a case of diffuse anterior retinoblastoma with lack of obvious retinal involvement. Morphologic features typical of medulloepithelioma were not found on pathologic analysis. Although the patient lacked a retinal focus, he is alive at 5 years without evidence of recurrence of tumor.

The Effects of Chemotherapy on Metastatic Testicular Germ Cell Tumors

Modern chemotherapy combined with surgery can achieve complete cure in over 90% of all patients with malignant testicular germ cell tumors. Even tumors that have already metastasized at the time of orchidectomy are curable by platinum-based multidrug treatment. Chemotherapy related changes can be seen in the residual tumor tissue in metastatic sites. In patients fully responding to chemotherapy these changes include complete necrosis of the tumor cells, and inflammatory-phagocytic response, fibrosis replacing the necrotic tumor tissue, and residual benign somatic tissue tissues in form of teratoma. Epithelial and stromal cells of these teratomas may display nuclear atypia, which is however not a reason for concern and should not be considered an indication for additional chemotherapy. Less commonly the lymph nodes contain cystic trophoblastic tumors. In contrast to metastatic classical biphasic or monophasic choriocarcinoma, cystic trophoblastic tumors portend a favorable clinical outcome. Patients with an incomplete response to chemotherapy and those with recurrences of the malignant tumor contain in metastatic sites foci composed of embryonal carcinoma cells, yolk sac carcinoma, or choriocarcinoma. The latter two subtypes of germ cell neoplasia may recur in several microscopic variant forms. Somatic forms of malignancy (also known as non-germ cell malignancies) that develop occasionally in some treated patients include most often sarcomas and tumors resembling central primitive neuroectodermal neoplasms. These secondary malignancies are usually resistant to chemotherapy. The broad spectrum of morphologic findings in the lymph nodes of patients with treated metastatic testicular germ cell tumors clearly illustrates the importance of meticulous pathologic analysis of tissue changes related to chemotherapy.

Growth-inhibiting effect of intratumoral recombinant human tumor necrosis factor on an experimental model of primitive neuroectodermal tumor

The effect of intratumoral administration of recombinant human tumor necrosis factor on an experimental model of primitive neuroectodermal neoplasia was studied. A clear inhibition of tumor growth was achieved by immunotherapy that consisted in intralesion injections of 100 micrograms of tumor necrosis factor daily, the first three days of each week, for a period of four weeks. At this time, tumor size was 2.21 +/- 0.66 cm2 (mean +/- standard deviation) in the treated group, versus 7.62 +/- 0.43 cm2 in the control group. These data support previous studies on the influence of tumor necrosis factor on the development of ethyl-nitrosourea-induced tumors, and suggest the potential usefulness of this cytokine in human primitive neuroectodermal neoplasms.

Development of neuroepithelial tumors of the adrenal medulla in transgenic mice expressing a mouse hypothalamic growth hormone-releasing hormone promoter-simian virus-40 T-antigen fusion gene.

Expression of the mouse GH-releasing hormone (GRH) gene is restricted to neurons within the hypothalamus and to placenta. In an attempt to generate immortalized mouse hypothalamic neurons expressing GRH, the proximal 872-nucleotide segment of the 5'-flanking region of the hypothalamic mouse GRH gene was cloned by polymerase chain reaction and ligated to a 2.7-kilobase DNA sequence encoding the simian virus-40 (SV40) T-antigen, so that regulation of SV40 T-antigen expression was dependent on sequences within the mGRH 5'-flanking region. This region contains both TATA and CAAT boxes. The mouse GRH/SV40 T-antigen fusion gene was injected into 1-cell mouse embryos, and SV40 T-antigen incorporation in the mouse genome was found in 11 of 77 live births (3 males and 8 females). Although no evidence of hypothalamic tumors was found, all mice that expressed the transgene also developed tumors originating in the adrenal medulla. Gene copy number varied from 1-20 and was inversely proportional to survival, which ranged from 7-16 weeks. Corticosterone levels were normal. The male transgenic mice were fertile, and their progeny expressed the transgene and developed similar tumors. Microscopic examination of the tumors revealed a primitive neuroectodermal neoplasm that exhibited hematogenous and lymph node metastases and contained 100 ng norepinephrine, 2.85 ng epinephrine, and 1.1 ng dopamine/mg tumor tissue. Primary culture of dispersed tumor cells released norepinephrine into the medium (180 pg/ml.24 h). Cell lines from 2 tumors were established and exhibited characteristics similar to those of mixed neuroblastoma or primitive neuroectodermal tumors. In conclusion, the proximal 872 nucleotides of the hypothalamic mouse GRH promoter contain elements directing tissue-specific expression limited to early adrenal neuroectodermal cells. Other GRH DNA sequences appear to be required for restricted expression of mouse GRH within the hypothalamus.

Neoplastic meningitis as the presentation of occult primitive neuroectodermal tumors.

Seven children and young adults initially presented with subacute meningitis and/or increased intracranial pressure. The diagnosis of neoplastic meningitis secondary to a primitive neuroectodermal neoplasm was delayed by the absence of an obvious primary tumor. The neuroradiologic appearance was that of a basimeningeal infiltrative process, complicated by communicating hydrocephalus or "pseudotumor cerebri." Myelography was important in the diagnosis of disseminated meningeal malignancy in four cases. Cerebrospinal fluid cytologic diagnosis was insensitive but ultimately confirmed in five cases. All seven patients experienced progressive disease despite neuraxis radiotherapy and intensive chemotherapy; six have died. Systemic dissemination to bone and/or peritoneum occurred in three patients while on therapy. In two, a primary parenchymal brain or spinal cord tumor could not be identified at postmortem examination. The presentation of a primitive neuroectodermal tumor as subacute meningitis without an evident primary tumor heralds an aggressive and refractory neoplasm.

Lipidized medulloblastoma in adults

We describe the clinical, imaging, histologic, immunohistochemical, and ultrastructural features as well as the DNA ploidy analysis of two primitive neuroectodermal neoplasms demonstrating prominent cytoplasmic lipid accumulation originating in the posterior fossa of adults. These two tumors most likely exemplify a variant of medulloblastoma with heavily lipidized cells and support the postulated pluripotentiality of primitive neuroectodermal neoplasms. Recognition of this entity as a phenotypic variant of medulloblastoma will militate against diagnostic confusion with other entities that may contain cells with lipoblastic or adipocytic differentiation.

Cytogenetic and pathologic aspects of Ewing's sarcoma and neuroectodermal tumors

Diagnostic classification of poorly differentiated, round cell, primitive neuroectodermal neoplasms, including Ewing's sarcoma, peripheral neuroepithelioma, Askin's tumor, and esthesioneuroblastoma, is challenging to the surgical pathologist using conventional histopathologic approaches because of very similar and overlapping morphologic and cytologic features. Furthermore, distinguishing these noeplasms from neuroblastoma, embryonal rhabdomyosarcoma, small cell osteogenic sarcoma, and non-Hodgkin's lymphoma can be difficult. This paper describes and reviews the cytogenetic and molecular genetic changes in these tumors and demonstrates how the ability to detect these changes has enabled a greater understanding of the histogenesis, classification, diagnosis, and prognosis of these neoplasms.

Primitive neuroectodermal (neuroepithelial) tumour of soft tissue of the neck in a child: demonstration of neuronal and neuroglial differentiation

A 4-year-old girl had a pathologically proven primitive neuroectodermal (neuroepithelial) tumour of soft tissue in the left posterolateral aspect of the neck. The neoplasm consisted of primitive neuroepithelial cells forming Homer Wright rosettes, mature ganglion cells and astrocytes. Astroglia were identified by localization of cytoplasmic glial fibrillary acidic protein (GFAP). Striking similarity is noted between the current tumour and those found in the central nervous system, including cerebellar medulloblastomas. The diverse cellular elements of the present primitive neuroectodermal neoplasm suggest an origin of the tumour from the neuroectodermal component of an ectomesenchymal remnant of the neural crest. Differentiation of the neuroectodermal component of the neural crest into primitive neuroepithelial cells could result in the occurrence of a primitive neuroectodermal neoplasm which may further differentiate into neurons and neuroglia.

Contribution of electron microscopy of cell cultures to the classification of three round cell sarcomas in children.

We have studied three round cell sarcomas from pediatric patients in tissue culture to compare the electron microscopic morphology of cells in culture to cells from original biopsy specimens. None of the original tumors displayed distinctive features by light microscopy that would allow classification of a specific tumor type, and electron microscopy was not helpful in identifying specific morphologic features that would allow further classification of tumor types. However, electron microscopy of cells in culture from the three neoplasms revealed distinctive morphologic features that did allow further classification of all three tumors. Cells from an inguinal lymph node, which were cultured in soft agar tumor colony-forming assay, revealed Z-bands and actin and myosin filaments indicative of a rhabdomyosarcomatous nature for the tumor. Cells from 5-day, 10-day, and 4-month cultures of a bone marrow metastasis of a second tumor revealed features of skeletal muscle in the young cultures and neuroblasts in the older culture, suggesting a primitive neuroectodermal neoplasm. Cultured cells from the third tumor, a neoplasm of the calf in an infant, displayed large lakes of glycogen, typical of cells of Ewing's sarcoma, which were not present in the cells examined from the original lesion. Ultrastructural studies of cells in culture have the potential to add morphologic data that may be useful to further define and classify a neoplasm, as illustrated in the 3 cases reported here.

Electron microscopic findings in primitive neuroectodermal tumors of the cerebrum

The fine structure of 3 primitive neuroectodermal neoplasms of the cerebral hemispheres was studied. The predominant tumor cells were undifferentiated cells with prominent nuclei and scanty cytoplasm containing few organelles. Ultrastructural evidence suggesting differentiation into ependymal, neuronal and possibly astrocytic elements was also present. This study suggests that the cell of origin of this tumor is a primitive multipotential cell of the cerebrum.

Ultrastructure of primitive neuroectodermal neoplasms of the central nervous system

Ultrastructure of primitive neuroectodermal neoplasms of the central nervous system

Ultrastructure of primitive neuroectodermal neoplasms of the central nervous system

The ultrastructure of one spinal and five cerebral neoplasms diagnosed by light microscopy as primitive neuroectodermal tumors supports a cell population consisting largely of poorly differentiated neuroepithelial cells. The most unique ultrastructure feature was the presence of annulate lamellae in four of the six cases. Glial cells in the neoplasm were not unequivocally of neoplastic origin and were possible reactive. There was no evidence of neuroblastic or neuronal elements, although there was frequently focal early neuroblastic differentiation by light microscopy. Although we have seen neoplasms which are clearly neuroblastic, these particular tumors are not purely neuroblastic and should not be classified as neuroblastomas.