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Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that often occurs during the first year of life. More than 90% of MNTIs occur in the head and neck region, with most on the anterior part of the maxillary ridge. MNTI has also been reported in the mediastinum, thigh, foot, shoulder, and gonads. Here the authors report a rare case of MNTI of the femur in a 3-month-old child.
Primitive neuroectodermal tumors (PNETs) of the central nervous system are uncommon embryonal neoplasms, rarely occurring in adults. Differentiation into specific mesenchymal tissues, such as cartilage, bone, skeletal muscle, smooth muscle, or adipose tissue, is rare. We report a case of a 51-year-old woman with a PNET of cerebrum that showed extensive mature adipose tissue differentiation. This is the second case, to our knowledge, of PNET of cerebrum with adipose tissue elements that has been described.
The clinical, radiographic, and pathologic features of 17 patients with documented peripheral primitive neuroectodermal tumor (PNET) were evaluated in a retrospective study. The age at diagnosis ranged from 9 months to 46 years (median, 15.8 years). Primary sites of involvement were the abdomen (n = 8), extremities (n = 5), chest (n = 1), temporal bone (n = 1), maxilla (n = 1), and diploe (n = 1). At the time of diagnosis, six patients had distant metastases; all of these patients died, with an average survival of 8.8 months. Radiologic workup included standard radiographs, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy. The radiographic appearance of these tumors was not specific for differentiation of PNETs from other types of bone and soft tissue tumors. The typical appearance resembled large non-calcified, soft tissue masses with cystic or necrotic areas. Heterogeneous enhancement with intravenous contrast agents was evident on CT, as was an intermediate signal intensity on Tl-weighted images and hyperintense signal on T2-weighted and STIR sequences. After gadolinium administration, variable enhancement was seen. MRI and CT were useful in predicting resectability, in detecting distant metastases, and in the evaluation of response to treatment. Surgery was performed in all cases, either for definitive diagnosis or for therapy. All patients received combined chemotherapy and radiotherapy and five patients received autologous bone marrow transplantation. Clinical follow-up was obtained over a mean period of 3 years (range 1 day to 6 years). Prognosis was poor with a median survival of 3.4 years. Our experience in 17 patients with peripheral neuroectodermal tumors indicates that although their radiologic features are non-specific, they should be included in differential diagnosis of soft tissue tumors of aggressive behavior, especially in a young age group. CT and MRI are useful in delineating the extent and resectability of tumor and in monotoring treatment.
BACKGROUND: Recurrent non-cerebellar primitive neuroectodermal tumors (PNETs) carry a dismal prognosis when treated with conventional chemotherapy alone. XSWe tested the efficacy of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in this setting. PROCEDURE: Eligibility mandated either minimal residual disease or evidence of chemosensitivity before HDC. Conditioning consisted of carboplatin (CBDCA) (500 mg/m(2) or AUC = 7 mg/ml min using the Calvert formula) on days -8 to -6, thiotepa (300 mg/m(2)), and etoposide (250 mg/m(2)) on days -5 to -3. Irradiation was given post HDC selectively. RESULTS: Among 17 patients treated in this study, there were eight pineoblastoma(s) (pineo), seven cortical PNETs, and two arising elsewhere. Relapse was either local (nine) or metastatic to the brain (four) or spine (four). Two patients received HDC as the sole therapy for recurrence; additionally, eight underwent surgical debulking before HDC, and nine received irradiation, including six after HDC. Median age at ASCR was 3.9 years. Two patients died of toxicity (11%) and ten experienced tumor relapse (range: 23-361 days post ASCR). Five patients with cortical PNETs remain alive disease-free (median follow-up: 8.3 years); four of them received irradiation post HDC. The difference in 5-year event-free survival (EFS) between patients with pineo and other supratentorial PNETs was significant (0 vs. 62.5 +/- 17%, P = 0.0065). Both surgery at relapse and irradiation post HDC were favorable prognostic factors (P = 0.006 and 0.01, respectively). CONCLUSIONS: Patients with recurrent cortical PNETs can be cured with this strategy. Surgical debulking before, and irradiation after HDC play an important role in treatment success.
A congenital primitive neuroectodermal tumor associated with epithelial and glial elements is described. This soft-tissue tumor present on the right temple of a newborn boy consisted mainly of small round cells of the primitive neuroepithelial type, occasionally forming rosettes. The other components were focal glandular structures producing mucin, and aggregates of epithelioid cells bearing clear cytoplasm, both being distributed throughout the entire tumor. Additional glandular and clear cell components were strongly positive for various epithelial markers, such as carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin. Epithelioid cells were also positive for neuron-specific enolase and S100 protein. Glial differentiation was evidenced in some of the epithelioid cells by localization of cytoplasmic glial fibrillary acidic protein. These findings suggest that this tumor derives from a remnant of a neural crest, and the possibility of a special type of peripheral primitive neuroectodermal tumor is considered.
Granulocyte-colony-stimulating factor (G-CSF) is a hematopoietic cytokine that regulates the differentiation of myeloid progenitors and the function of mature neutrophils. It is produced in vitro by monocytes/macrophages, mesothelial cells, fibroblasts and endothelial cells after appropriate induction by inflammatory mediators like IL-1 and TNF. Normal as well as tumorous glial cells can also be induced to produce CSFs in vitro. However, little is yet known about the in vivo expression of G-CSF as a mediator in inflammation and malignancy within the human central nervous system. The aim of the present study was to investigate by immunostaining the expression of the G-CSF protein within non-tumorous and tumorous glial tissues, and primitive neuroectodermal tumors. Using the murine monoclonal anti-G-CSF TM 82/60 antibody, we found high G-CSF expression in astrocytoma WHO grades I and II and reactive brain tissue, low expression in astrocytoma WHO grade III, and none in glioblastoma, oligodendroglioma WHO grades II and III, and medulloblastoma. In consecutive sections of the tissue samples, G-CSF protein was localized in GFAP-positive glial cells, but not in macrophages/microglial cells, which expressed HLA-DR, detected by the antibody CR3/43. Computer-assisted microdensitometric evaluation of the intensity of immunostaining for G-CSF and statistic analysis of the data revealed significant differences between the diagnostic entities studied (p < 0.0001). We conclude that in vivo expression of G-CSF is a characteristic of reactive as well as tumorous astrocytes, with the latter losing this feature at higher degrees of dedifferentiation.
BACKGROUND: The diagnostic workup on esthesioneuroblastoma is more extensive than ever before. We have investigated whether improvements in diagnosis of sinonasal neuroectodermal tumors, including esthesioneuroblastomas (ENB), sinonasal neuroendocrine carcinomas (SNEC) and sinonasal undifferentiated carcinomas (SNUC), have had an impact on treatment and outcome. PATIENTS AND METHODS: 11 ENB, 7 SNEC and 1 SNUC in 13 men and 6 women (average age 52.9 years (range 26-82)), diagnosed between 1986 and 2001, were analyzed with regard to histopathologic and clinical diagnosis as well as outcome. Our results were compared with the available literature. RESULTS: According to the Morita classification considering endoscopy, CT and MRI scans, 2 tumors were staged D, 14 were found to be stage C, 2 were stage B and 1 was stage A. Lightmicroscopically only 4 of 19 showed higher differentiation and rosette-like structures, the others were poorly differentiated. 18 of 19 tumors were examined immunohistochemically. Neuronal markers (NSE, synaptophysin, chromogranin, S-100 and neurofilaments) were heterogeneously expressed in both ENB and NEC, only NSE stained all but 2 tumors. Coexpression of neuronal markers and cytokeratins was proven in all NEC and 5 of 11 ENB. Some tumors expressed atypical markers. Despite extensive diagnostic steps it was not possible to exclude a different histopathological diagnosis in 10 of 19 cases. CONCLUSION: For sinonasal neuroectodermal tumors no pathognomonic antigenic profiles are known. Immunohistochemical markers lack specificity and sensitivity. Nevertheless, in many sinonasal neuroectodermal tumors a panel of differentiation markers allows to specify the light-microscopic diagnosis. Until now no therapeutic consequence arises from a more extensive diagnostic workup. However, the histopathologic identification of subtypes (SNUC) and proliferation markers may help to identify patients with poor prognosis.
Metastatic disease is a major problem in the management of the most frequent childhood brain tumors, in ependymoma and primitive neuroectodermal tumors (PNET). Today, contrast enhanced craniospinal MRI and careful analysis of craniospinal fluid are a prerequisite for correct staging of both tumors and imply therapeutic consequences. So far metastatic spread of medulloblastoma and some ependymomas is prevented by conventional chemotherapy and radiotherapy. However, some forms of diffuse metastatic dissemination in medulloblastoma are resistant to conventional therapeutic regimens and require new experimental strategies.
PURPOSE: To document the late radiographic change following hyperfractionated craniospinal radiotherapy for primitive neuroectodermal tumor. METHODS AND MATERIALS: We reviewed long-term MRI scans on 21 patients with standard risk and high risk primitive neuroectodermal tumor treated with hyperfractionated radiotherapy following surgical resection. High risk patients also received adjuvant chemotherapy. Long-term scans were defined as scan obtained at least 1 year from diagnosis. Clinical follow-up data was available on all patients. RESULTS: Twelve of 21 patients had MRI evidence of necrosis, telangiectasia, white matter changes, basal ganglia change, or cerebral atrophy consistent with radiation injury. No patient required treatment for the radiographic change. CONCLUSIONS: Slightly over half of the patients had evidence of long-term radiation effect following craniospinal axis radiotherapy. However, no patient had frank clinical symptoms related to the radiographic findings.
Thirty-five selected intracranial tumors qualifying as primitive neuroectodermal tumors (PNETs) were investigated; these included medulloblastomas, cerebral neuroblastomas, pinealoblastomas, retinoblastomas, polar spongioblastomas, ependymoblastomas. For control purposes 11 tumors, including glioblastomas (small cell, spongioblastic variants), one anaplastic astrocytoma (astroblastic component), anaplastic oligo-astrocytomas, gangliogliomas, one primary melanoblastoma, and one pineal germinoma, were also studied. Six neuronal markers, i.e., synaptophysin, chromogranin A, neuron-specific enolase (NSE), neurofilament protein (NFP) (160 kDa, 200 kDa, 70 and 200 kDa), and six other markers (glial fibrillary acidic protein, S-100 protein, vimentin, myoglobin, desmin, cytokeratin) were investigated immunohistochemically. A certain recapitulation of the ontogenetic development of neuronal differentiation in PNETs is given by the fact that chromogranin A immunoreactivity can regularly be seen already in poorly differentiated neurons and synaptophysin in well-differentiated ones. Immunostaining for NFPs showed different results depending on the subunit investigated. NSE reaction gave different results even within the single tumor groups. This study is, to the best of our knowledge, the first attempt to evaluate and compare, by combined morphological and immunohistochemical methods, PNETs without and with different stages of cellular differentiation with the stepwise differentiation of the human embryonic neuroectoderm.
A case of melanotic neuroectodermal tumor of infancy occurring in the mandible is described. The patient was a 1-month-old boy with a rapidly growing tumor of the mandible. Computed tomography showed 2 well-defined osteolytic lesions in the right mandible. Histopathologic diagnosis of a biopsy specimen was melanotic neuroectodermal tumor of infancy. The tumor was excised with removal of the surrounding bone, but 1(1/2) months later it recurred, and segmental mandibulectomy and reconstruction of the defect with a titanium miniplate was performed. Retrospectively, evidence of recurrence was noted on computed tomography taken on the tenth postoperative day. The recurrence was caused by incomplete removal of the tumor. Histopathologically, the tumor cells of the recurrent lesion were dispersed extensively in the bone marrow, and bone remodeling was active. The surgical procedure may have stimulated tumor cell proliferation and reactive bone formation. The patient was followed for 2 years with no evidence of recurrence or metastasis.
A case of melanotic neuroectodermal tumor of infancy arising from the transverse sinus is presented. The tumor was located on the outer surface of the dura and extended extracranially through the occipitomastoid suture. Two cell populations were observed: pigmented melanocyte-like cells and small neuroblast-like cells. Ultrastructural analysis revealed epithelial tumor cells and melanosomes at various stages. Expression of melanotransferrin messenger RNA transcripts within the tumor tissue was observed using a reverse transcriptase-polymerase chain reaction method in addition to immunohistological studies. The positive expression of melanotransferrin confirmed that this melanotic neuroectodermal tumor was derived from neural crest cells.
INTRODUCTION: The neuroectodermal tumor of bone constitutes a recently isolated neoplasm, which morphologically resembles the peripheral neuroepithelioma of soft tissue. The diagnosis is made by excluding readily classified small round cell neoplasms and then demonstrating the neural origin of the tumor by means of ultrastructural or immunocytochemical studies. CLINICAL CASE: We report a case of a primary neuroectodermal tumor (PNET) with atypical findings (primary cervical location, massive vertebral body infiltration and isolated neurological symptomatology). Total tumor removal was achieved by means of a one-stage three-level laminectomy (partial C5, total C6-C7), C6 somatectomy, and combined anterior and posterior cervical spinal instrumentation and fusion. CONCLUSIONS: Our case presents three peculiar features: 1) isolated myelopathic symptomatology (first case described); 2) primary isolated massive vertebral cervical involvement with intraspinal epidural extension (first case described); 3) one-stage tumor resection, fusion and instrumentation. Since radiation therapy causes tumor shrinkage but is not curative, radical removal is mandatory even with complex instrumentation procedures.
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.
The hypothesis that tumor growth depends on neovascularization has been broadly used in oncology research. TNP-470 is a fumagillin synthetic analog that is isolated from Aspergillus fumigatus, and experimental studies suggested that it shows antitumor effect mediated by its strong antiangiogenic effect. Because limited experience exists about the antitumoral effect of TNP-470 in cerebral tumors, we have carried out a study in order to evaluate the effect of TNP-470 on tumor growth and the vascular area in an experimental malignant neuroectodermic tumor growing in the subcutaneous space of immunocompetent Wistar rats. Our results showed a significant tumor growth inhibition in animals treated with TNP-470 when compared to those in the control group (intratumoral injections were administered in 30 mg/kg dose, three times a week on alternate days during four consecutive weeks). Since the quantitative analysis of tumor vascular parameters--number of microvessels and total intratumor vascular area--in the experimental groups did not show significant statistical differences, we conclude that TNP-470 has a significant antitumor effect on our neuroectodermic tumor, but this effect is mediated by other antineoplastic mechanisms that are independent of its previously described angiostatic capacity.
A case is presented of a primitive neuroectodermal tumor located in the left frontal cerebrum, which demonstrated electron microscopic and immunocytochemical evidence of rhabdomyoblastic differentiation. Within the group of supratentorial primitive neuroectodermal tumors, only medulloepithelioma has previously been shown to manifest "divergent" differentiation. In several respects our case is analogous to infratentorial "medullomyoblastoma."
PURPOSE: To report an orbital, intraconal, primitive neuroectodermal tumor (PNET) in a 5-year-old child with microphthalmia since birth. METHODS: Orbitotomy was performed and a large, polycystic, retroscleral, intraconal tumor was removed and subsequent histological, immunohistochemical and electron-microscopic analyses of the excised mass were performed. RESULTS: The tumor showed characteristic features of peripheral primitive neuroectodermal tumor including pseudorosettes, positive immunohistochemical reactions for the MIC2 gene and synaptophysin and ultrastructural finding of neurosecretory granules. CONCLUSION: This case is the first reported intraconal PNET of the orbit, and the first orbital case that expresses the MIC2 gene. In spite of the aggressive malignant features of peripheral PNET, the orbital variety seems to be the least aggressive since most of the reported patients are still alive.
Two monospecific human antibodies (anti-OFA-I-1 and anti-OFA-I-2) produced in vitro by lymphoblast cell lines originating from melanoma patients have been shown previously to recognize cell surface antigens (OFA-I-1 and OFA-I-2) on human tumors and fetal brain: OFA-I-1 is expressed on a variety of human tumors, while OFA-I-2 has been detected only on tumors of neuroectodermal origin. Evidence presented in this report suggests that the two antigens expressed by a cultured human melanoma cell line (M14) are chemically distinct and that OFA-I-2 is a cell surface glycolipid, ganglioside GD2: GalNAc beta 1 leads to 4 NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3 Gal beta 1 leads to 4Glc-ceramide.