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PubMed2001

Primitive neuroectodermal tumor of the lung.

Primitive neuroectodermal tumors occur most frequently in bone and soft tissue but have been reported in other locations. Primary lung primitive neuroectodermal tumors without pleural or chest wall involvement are extremely rare. We present a case with immunohistochemical and ultrastructural studies and follow-up of the patient. An 18-year-old man presented with hemoptysis. Chest radiographs revealed a right middle lobe mass, and bronchoscopy showed an endobronchial tumor. The lesion was resected by middle lobectomy. After 2 years, a local recurrence was treated by pneumonectomy. The patient died after surgery. Histologically, the tumor was composed of uniform cells with round nuclei and scanty cytoplasm arranged in cohesive lobules with occasional rosette formation. Immunohistochemically, the tumor was positive for vimentin, CD99, neuron-specific enolase, and neurofilaments. Ultrastructural study revealed neurosecretory granules and cytoplasmic processes. Our case shows the value of immunohistochemistry and electron microscopy in the diagnosis of primitive neuroectodermal tumors in unusual locations.

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↗

PubMed1999

Peripheral primitive neuroectodermal tumors of bone. A review of three cases.

The recently individualized and still incompletely understood family of peripheral neuroectodermal tumors encompasses several tumor types, of which some have a predilection for bone. Immunocytochemical studies are essential and usually provide the diagnosis. A t(11;22)(q24;q12) translocation is present in over 80% of cases. Ewing's sarcoma is now viewed as an undifferentiated form of peripheral neuroectodermal tumor, and both tumors require management with combination chemotherapy plus radiation therapy and/or surgery. Contradictory data have been reported regarding the comparative prognosis of peripheral neuroectodermal tumor and Ewing's sarcoma, indicating a need for further studies in large numbers of patients. We illustrate these points by three case-reports, two in girls diagnosed with a vertebral primary at five and nine years of age, respectively, and one in a man diagnosed with a pelvic primary at 29 years of age.

Adult↗

PubMedDate not supplied

Preliminary study of proton magnetic resonance spectroscopy in bone and soft tissue tumors: an unassigned signal at 2.0-2.1 ppm may be a possible indicator of malignant neuroectodermal tumor.

PURPOSE: To evaluate the utility of proton magnetic resonance spectroscopy in bone and soft tissue tumors, especially whether or not the N-acetyl aspartate signal (NAA) could be recognized in neurogenic tumors. MATERIALS AND METHODS: Forty-nine proton magnetic resonance spectroscopy studies were performed in 60 bone and soft tissue tumors. The patients were 28 males and 30 females. Eleven studies were incomplete, and were excluded from analysis. A point-resolved spectroscopy sequence (TR=1500 or 2000 ms, and TE=30, 60, 136, or 272 ms) was used on a 1.5-Tesla clinical MR scanner. RESULTS: An unassigned signal at about 2.0-2.1 ppm was recognized in six of 47 lesions: clear cell sarcoma (2/2), Ewing sarcoma (1/1), malignant fibrous histiocytoma (1/3), malignant schwannoma (1/1), and mucoepidermoid carcinoma (1/1). Neuroblastoma (1/1), primitive neuroectodermal tumor (1/1), and malignant melanoma (1/1) after chemotherapy or radiotherapy did not show this signal. This signal was not detected in neurofibroma (9/9), schwannoma (6/6), pheochromocytoma (2/2), or other mesenchymal tumors of non-neuroectodermal origin. CONCLUSIONS: The assigned signal at about 2.0-2.1 ppm was detected in a small percentage of bone and soft tissue tumors and could be suggestive of an untreated malignant tumor of neuroectodermal origin.

Adolescent↗

PubMed2000

A para-testicular primitive neuroectodermal tumor in an adult: a case report and literature review.

OBJECTIVE: The authors describe the salient clinical, radiologic and histopathologic features of an extremely rare para-testicular primitive neuroectodermal tumor in a 25 year-old man. INTERVENTION: Excisional biopsy of the tumor en bloc was performed. Adjuvant VAdriaC-based chemotherapy (Vincristine, Doxorubicin, and Cyclophosphamide) was given post-operatively. MAIN OUTCOME MEASURES: Histopathologic examination and immunohistochemical studies were performed on formaldehyde-fixed, paraffin-embedded tumor tissue. RESULTS: Histologic examination showed an undifferentiated small cell tumor. The tumor cells stained positively with MIC-2, a marker specific for primitive neuroectodermal tumors. The patient is 12 months post surgery and has completed adjuvant chemotherapy with no evidence of recurrent disease. CONCLUSIONS: This highly unusual, peripheral primitive neuroectodermal tumor should be considered in the differential diagnosis of undifferentiated small cell neoplasms of the genitourinary system in adults, from the kidney to the testicle. We present a patient with a PNET treated based on a Ewing's family of tumors protocol.

Adult↗

PubMed2001

Peripheral primitive neuroectodermal tumor with neuronal and glial differentiation: report of a case arising in suprarenal region.

It is well known that embryonal neuroectodermal tumors of the central nervous system (CNS) not infrequently display varying amount of neoplastic cells acquiring glial differentiation. In contrast, glial differentiation rarely occurs in primitive neuroectodermal tumors outside the CNS being documented in less than ten cases. The author presents herein a case of peripheral primitive neuroectodermal tumor with prominent glial differentiation identified by the presence of glial fibrillary acidic protein (GFAP) arising in the right suprarenal region of a 32-year-old man, histologically indistinguishable from an ordinary neuroblastoma.

Adult↗

PubMed1989

N-myc amplification and neuronal differentiation in human primitive neuroectodermal tumors of the central nervous system.

Despite the phenotypic similarities between primitive neuroectodermal tumors of the central nervous system, childhood neuroblastoma, and peripheral neuroepithelioma, a histogenetic relationship among these neoplasms has not been shown. High levels of N-myc expression occur selectively in developing brain and in some embryonic tumors of neural origin. N-myc amplification and high levels of N-myc expression in childhood neuroblastoma have been correlated with disease stage and prognosis. To determine whether the copy number of the N-myc gene in primitive neuroectodermal tumors of the central nervous system is altered, we examined 20 primitive neuroectodermal tumors by Southern and/or slot blot hybridization to a 1-kilobase N-myc genomic DNA sequence and a 492-base pair N-myc-specific subclone as well as to a 1.1-kilobase albumin complementary DNA sequence as a control for gene copy number. Amplification of the N-myc gene was detected in two cerebellar tumors both of which exhibited neuronal differentiation by light microscopy. These tumors had not been treated previously. Of the remaining 18 tumors, eight were undifferentiated, three showed early neuroblastic, and seven focal glial differentiation. These findings suggest a possible relationship between N-myc amplification and neuronal differentiation.

Brain Neoplasms↗

PubMed1997

Expression of neurogenic basic helix-loop-helix genes in primitive neuroectodermal tumors.

The basic helix-loop-helix (bHLH) class of transcription factors plays a pivotal role in tissue-specific determination and differentiation. Moreover, dysregulated expression or loss of function of these factors contributes to leukemogenesis and solid tumor development. Neurogenesis is regulated by genes of the NEUROD/atonal and ACHAETE SCUTE families. We analyzed expression of human NEUROD1, NEUROD2, NEUROD3, and ACHAETE SCUTE 1 (HASH1) in cerebellar and cerebral primitive neuroectodermal tumors (PNETs), gliomas, and cell lines derived from a variety of neuroectodermal tumors by Northern analysis and in situ hybridization. NEUROD1 was expressed in each of the 12 medulloblastoma specimens, whereas NEUROD2 and NEUROD3/neurogenin were expressed in partly overlapping subsets of medulloblastomas. All of the tumors that presented with distant metastases expressed NEUROD3. The only other NEUROD3-positive tumor progressed early in treatment. Human ACHAETE SCUTE homologue (HASH1) was not expressed in medulloblastomas (infratentorial PNETs) but was expressed in three of five supratentorial PNETs. Neuroectodermal tumor cell lines derived from other sites (e.g., neuroblastoma and retinoblastoma) expressed NeuroD and ACHAETE SCUTE family members. No NEUROD message was detected in glial tumors or cell lines. Neurogenic bHLH transcription factor expression patterns suggest that specific family members may contribute to or reflect biological differences that arise during malignant transformation.

Brain Neoplasms↗

PubMed1997

[Mediastinal neuroectodermal tumor. Apropos of a case].

Peripheral malignant neuroectodermal tumors are rare and aggressive small-cell tumors seen predominantly in children and young adults. Mediastinal location is very uncommon. A mediastinal primitive neuroectodermal tumor was diagnosed in a 27-year-old man. Despite treatment combining surgery, radiotherapy and chemotherapy, disease recurred locally along with lungs, spinal and epidural metastases, leading to death. CT and MRI examinations show heterogeneous masses with necrosis, hemorrhage and intense enhancement after Gadolinium injection. The CT and MRI findings are not specific and the diagnosis is based on pathologic, immunohistochemical and electron microscopic features. Although uncommon, peripheral neuroectodermal tumor should be considered in the differential diagnosis of posterior mediastinal masses in children and young adults.

Adult↗

PubMed1977

Melanotic neuroectodermal tumor of infancy: its histological similarities to fetal pineal gland.

Striking similarities between the pineals of 107 fetuses and infants and a pigmented neuroectodermal tumor occurring in the right orbital and right frontal regions in a 6-month-old Puerto Rican boy were found. Both the human fetal pineal and melanotic neuroectodermal tumors of infancy are characterized by pigmented (melanin) epithelial cells, small undifferentiated cells, and a fibrovascular stroma. Our findings suggest the fetal pineal may be a normally occurring precursor of the melanotic neuroectodermal tumor of infancy, or that melanin production may be a normal capability of differentiating neuroepithelial cells.

Child, Preschool↗

PubMed1979

Malignant melanotic neuroectodermal tumor of infancy: a clinical, pathologic, ultrastructural and tissue culture study.

The melanotic neuroectodermal tumor of infancy is an uncommon neoplasm typically of early childhood which has a predilection for the head and neck region, particularly the maxilla. Except for one previous example in the literature, this tumor has consistently behaved in a benign fashion. This study documents the clinical course and pathologic findings of a tumor which began in the maxilla of a 4-month-old boy, followed by a local recurrence, metastasis to a cervical lymph node and finally, widespread dissemination and death at 18 months, 24 months and 38 months, respectively. The tumor was initially composed of nests consisting of melanin-containing cells and small dark cells. An elevated vanillylmandelic acid level was recorded during the course of the disease. At autopsy, the tumor in lymph nodes, liver, bone and soft tissues had a monotonous pattern of small dark cells similar to a conventional neuroblastoma. Previous ultrastructural studies indicate that the melanotic neuroectodermal tumor of infancy is composed of melanocytes and neuroblast-like cells. Our case provided the unique opportunity to examine in sequence the ultrastructural and in vitro characteristics of a recurring and eventually metastasizing melanotic neuroectodermal tumor. Although the neuroblast-like cells were initially difficult to identify by electron microscopy, a melanin-producing cell line and a separate nonpigmented cell line were successfully isolated from various tumor explants. Various stages of melanosome development were identified in the pigmented cells from the local recurrences and in vitro. Dibutyryl cAMP accentuated the formation of pigment and dendritic development in the melanocytes and dendrites only in the small nonpigmented cells. Electron dense granules were observed in the cultured smaller cells and also in the lymph node and soft tissue metastases. Tyrosine hydroxylase activity was demonstrated in the neuroblast-like cells. In the final biopsy and autopsy material, only the neuroblast-like cells remained and the tumor resembled a conventional neuroblastoma.

Culture Techniques↗

PubMed1983

Melanotic neuroectodermal tumor of infancy. A review of seven cases.

The melanotic neuroectodermal tumor of infancy (MNTI) is a rare, usually benign, pigmented neuroectodermal tumor which most often involves the maxilla. The authors reviewed seven cases of MNTI, with patient ages of our patients ranged from nine weeks to 18 months; six of the seven were less than six months old at initial diagnosis. Four patients were males, and all were white. One tumor each was located in the femur, the temporal bone, and the epididymis; the remaining lesions occurred in the maxilla. Three of the four maxillary tumors recurred locally; the epididymal and femoral tumors metastasized. Two of these cases had unique clinical or pathologic features. The case of the femoral tumor is remarkable in that it is the first reported one of MNTI presenting in a long bone. This tumor was aggressively malignant; within two months after its discovery, a large mass of similar tumor was formed in the pelvis, and the tumor resulted in the patient's death. To the authors' knowledge, the case of the temporal bone tumor is the first one of MNTI in which neuronal differentiation of the neuroblastic cells is convincingly demonstrated. This finding provides additional evidence in support of the neuroectodermal theory of origin of these neoplasms.

Female↗

PubMed1990

Immunophenotype profile of childhood medulloblastomas and supratentorial primitive neuroectodermal tumors using 16 monoclonal antibodies.

Immunophenotype analysis of 17 childhood medulloblastoma (MED) and supratentorial primitive neuroectodermal tumors (SPNET) was performed on frozen sections using 16 monoclonal antibodies (MoAb) with the biotin-streptavidin alkaline phosphatase immunohistochemical technique. Neuroectodermal associated antigens, reacting with MoAb UJ13/A, UJ127.11, UJ167.11, and UJ223.8 were detected on greater than 10% of the cells in 15 of 17 MED/SPNET. Thy-1 was present on 14 of 17 tumors and absent on two of three SPNET. Neuronal (NF) and glial (GFAP) differentiation markers were evaluated. NF-H was demonstrated in 15 of 17, NF-M in six of 17 and NF-L in one of 17 tumors; GFAP was positive in nine of 17 patients. In nine of 17 MED/SPNET both proteins were present within the same tumor. Common leukocyte antigen was demonstrated on greater than 50% of the cells in four of 14 tumors as were shared tumor/leukocyte markers using monoclonal antibodies Thy-1, PI153/3, UJ308. The most frequent MED immunophenotype analysis was UJ 13/A+, UJ 127.11+, UJ 167.11+, UJ223.8+, PI 153/3+, A2B5+, GFAP+, NF-H+, and CLA-, NF-M-, NF-L-, 215-, 275-, 282.1-. The authors conclude that MED and SPNET are heterogeneous for expression of 16 markers and have similar immunophenotype analysis profiles, supporting the concept of their common, neuroectodermal origin. Common leukocyte antigen on both tumor cells and leukocytes precludes identification of tumor infiltrating leukocytes using monostaining techniques.

Adolescent↗

PubMed2004

Fgf signaling induces posterior neuroectoderm independently of Bmp signaling inhibition.

Whereas according to the neural default model, neural specification is induced by extracellular inhibitors of bone morphogenetic proteins (Bmps), the role of fibroblast growth factors (Fgfs) during neural induction is heavily debated. Here, we show that, in zebrafish embryos, Bmps and Fgfs play differential roles during the induction and patterning of the anterior vs. the posterior neuroectoderm. Induction of anterior neuroectoderm, giving rise to fore- and midbrain, is accomplished by Bmp inhibition, with Fgfs playing a moderate posteriorizing/patterning role, possibly by blocking Bmp signaling at the level of Smad proteins. In contrast, in the posterior-most neuroectoderm, which is located in marginal regions of the early gastrula embryo to give rise to spinal cord and hindbrain, Fgfs play a neural-inducing rather than a neural-patterning role. This Fgf-dependent posterior neural induction takes place during late blastula and early gastrula stages, after mesoderm has been induced and cannot be blocked by Bmps or the Bmp target gene and downstream effector Delta Np63 alpha, indicating that here, Fgfs act independently of Bmp signaling inhibition.

Animals↗

PubMed1981

Common neuroectodermal antigens on human melanoma, neuroblastoma, retinoblastoma, glioblastoma and fetal brain revealed by hybridoma antibodies raised against melanoma cells.

The hybridoma system has been utilized to produce antibodies to characterize the cell surface antigens on human melanoma cells. On initial screening, two antibodies derived by the fusion of mouse myeloma cell (SP2/0-Ag14) and splenocytes from a mouse immunized with a melanoma cell line (CaCL 78-1) showed cross-reactivity with 10 melanoma cell lines and did not react with any of 4 epithelial cancer lines, or 4 normal adult fibroblast lines. However, because of reactivity with 2 neuroblastoma cell lines, additional testing with other neuroectodermal derivatives was carried out and revealed a broad cross-reactivity among melanomas, neuroblastomas, retinoblastomas and glioblastomas and against antigens shared by fetal but not adult brain. Thus, these results indicate the existence of common neuroectodermal antigens on melanoma cells. Before melanoma specificity can be claimed for, an antibody reactivity with nonmelanoma cells bearing these neuroectodermal antigen should be excluded.

Absorption↗

PubMed1986

Melanotic primitive neuroectodermal (neuroepithelial) tumor of medulla.

A 69-year-old man had a melanotic primitive neuroectodermal tumor of the medulla displaying various neuroepithelial elements including undifferentiated neuroepithelial cells forming Homer Wright's rosettes as well as neoplastic neuroglia resembling those seen in medulloblastoma. The neuroglial tumor cells were verified by demonstrating glial fibrillary acidic protein (GFAP) in the cells. These findings support the concept that the primitive neuroectodermal tumor and medulloblastoma are similar neoplasms. They have been described by such diverse names as melanotic medulloblastomas and progonomas. Review of 18 reported cases of intracranial melanotic primitive neuroectodermal tumors, including the present one, reveals that they have common pathologic features, are most frequent in the cerebellum and fourth ventricle, often metastasize widely within the neuraxis or even systemically, occur more frequently in children than adults, and strike males more often than females.

Aged↗

PubMed1994

Regulated expression of Wnt family members during neuroectodermal differentiation of P19 embryonal carcinoma cells: overexpression of Wnt-1 perturbs normal differentiation-specific properties.

The P19 embryonal carcinoma (EC) cell line represents a useful model system for analysis of neural development and differentiation processes that are difficult to study in mammalian embryos. Since many members of the Wnt family of signaling molecules are expressed in the developing as well as adult nervous system, we have examined expression of these genes in P19 cells. Analysis of the mRNA accumulation profiles for Wnt genes during retinoic acid (RA)-induced neural differentiation of P19 cells showed that nine Wnt family members were expressed in a regulated manner during this process. Most were induced by RA treatment, and some were also expressed in undifferentiated P19 cells. Since Wnt-1 is not expressed in undifferentiated P19 cells but is induced during neuroectodermal differentiation we have generated P19 cell lines that overexpress Wnt-1 in the absence of RA treatment, in order to address the role of Wnt-1 in P19 differentiation. In the presence of ectopic Wnt-1, expression of other endogenous Wnt genes, which serve as early differentiation markers in this system, were induced without RA, which is normally required for appearance of these gene products. Furthermore, ectopic expression of Wnt-1 resulted in a loss of SSEA-1 antigen expression, a marker of undifferentiated P19 cells. Similarly to the parental cell line, addition of RA to P19 cells overexpressing Wnt-1 induced the neuroectodermal pathway, but expression of cell type-specific markers such as MASH-1, HNK-1, and GAP-43 was diminished and the morphology of neuronal processes, stained with an antibody to neurofilament, was abnormal. These data suggest that Wnt-1 itself can induce some aspects of early neuroectodermal differentiation and, furthermore, that the correct timing of Wnt-1 expression is necessary for proper RA-induced expression of the neural phenotype.

Animals↗

PubMed1996

The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm.

Central nervous system development in Drosophila starts with the delamination from the neuroectoderm of about 30 neuroblasts (NBs) per hemisegment. Understanding the mechanisms leading to the specification of the individual NBs and their progeny requires the identification of their lineages. Here we describe 17 embryonic NB lineages derived from the ventral half of the neuroectoderm and we assign these lineages to identified medial and intermediate NBs. The lineages are composed of interneurons (NB 1-2, NB 2-1, MP2, NB 4-1, NB 5-1, NB 5-3, NB 6-1, NB 6-2, and NB 7-2), interneurons and motoneurons (NB 3-1, NB 3-2, NB 4-2, NB 5-2, NB 7-1, and NB 7-3), or interneurons, motoneurons, and glial cells (NB 1-1 and NB 2-2). NB 1-1, NB 2-2, and NB 3-1 form segment-specific lineages. Neuroectodermal progenitors forming NB 2-1, NB 5-1, and NB 7-3 divide while still in the ectoderm to give rise to an additional epidermoblast. Expression of segmentation genes is not lineal in the clones of NB 1-2 and NB 7-3 (engrailed), NB 1-1, NB 4-2, and NB 7-1 (even-skipped), and NB 7-1 (gooseberry-proximal). The timing of delamination for individual NBs as well as the number of their progeny is not strictly invariant. The 17 NBs produce about 200 neurons and only three glial cells, corresponding to about 70% of the estimated total number of neurons and 10% of the glial cells per thoracic and abdominal hemisegment. Previously identified neural cell types were linked to particular lineages and we introduce a systematic terminology for the ventral nerve cord neurons. The wild-type clones provide a foundation for the analysis of mutants, expression patterns, and experimental manipulations.

Animals↗