Malignant Neuroectodermal Tumor Research Articles

Radiologic and clinicopathologic findings of peripheral primitive neuroectodermal tumors.

Primitive neuroectodermal tumors (PNETs) constitute a rare type of malignant neuroectodermal tumors that have chromosomal translocations identical to Ewing's sarcoma (ES), and the characteristics of this disease remain unclear. To describe the clinical, radiological, and pathological features of peripheral PNETs (pPNETs) to enhance their recognition. The clinical, imaging, and pathologic findings of 35 patients with pPNETs were retrospectively reviewed, all being confirmed by biopsy or surgical pathology. All 35 patients had preoperative computed tomography (CT) examinations; 10 patients had preoperative magnetic resonance imaging (MRI) studies. Of 35 pPNET patients, 54.3% had a primary tumor in soft tissue, the others in bone. On plain CT images, 33 lesions demonstrated heterogeneous hypodense masses with multiple lamellar lower density, and with osteolytic destruction if the tumor originated in bone. Calcification was only found in five lesions arising in soft tissue. All lesions enhanced heterogeneously with varying areas of cystic changes, and all lesions in bone and 52.6% of lesions in soft tissue showed ill-defined margins after contrast administration. On MRI, these tumors appeared in conjunction with osteolytic bone destruction and irregular soft tissue masses iso- to hypointense to skeletal muscle on T1-weighted images and showed heterogeneously high intensity on T2-weighted images. All lesions enhanced heterogeneously with cystic changes. Homer-Wright rosettes were observed in 15 lesions, and 97.1% lesions were positive for CD99 in histopathological results. pPNETs can involve any part of the body, and a large, ill-defined, aggressive soft tissue mass and heterogeneous enhancement with or without osteolytic bone destruction on CT or MR images could suggest the diagnosis.

An unusual association of malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like) and Ewing sarcoma

Very recently a new designation of “Malignant Neuroectodermal Gastrointestinal Tumor” has been proposed for an aggressive form of neuroectodermal tumor with features similar to that of Clear Cell Sarcoma of Soft Tissue, however without a melanocytic differentiation. Also known as “clear cell sarcoma-like tumors of the gastrointestinal tract”, these tumors show some features strongly suggesting an origin from a gastrointestinal neuroectodermal precursor cell unable to differentiate along the melanocytic lineage. They occur mainly in young and middle-aged adults, and have a poor prognosis with a high rate of liver and lymphnode metastases. Histologically they are composed of epithelioid or oval-to spindle cells with a sheet-like or nested pattern of growth, strongly positive for neural markers (S-100, SOX10, and vimentin) and negative for the melanocytic ones. EWSR1 gene rearrangements including EWSR1-ATF1 or EWSR1-CREB1 GENE fusions are typically assessed in these tumors. Here we report a case of malignant neuroectodermal gastrointestinal tumor which immunophenotypically unusually expressed FLI-1, occurring in a 29-year-old man with a previous medical history of Ewing sarcoma. We finally suggest that this case might be a further evidence of a link between these two entities.

Tumeur neuroectodermique primitive du nerf vague

Primitive neuroectodermal tumors are a rare type of malignant neuroectodermal tumor that is very aggressive. Cervicofacial location is rare, even exceptional. We report a case of a 4-month-old male infant, referred from the pediatric clinic for severe supralaryngeal dyspnea, a firm mass under the left mandibular angle, mobile and extended to the parotid area, painful, with a curve of the left side wall of the oropharynx. Cervical computed tomodensitometry showed a well-limited mass in the carotid area, enhanced by the contrast product. A vascularized mass, which had developed at the expense of the vagus nerve, was removed surgically. Histology found a primitive neuroectodermal tumor.

B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma

Diffuse intrinsic pontine glioma (DIPG) is a brain cancer with a median survival of only 1 year. Lack of molecular characterization of this tumor impedes the development of novel therapies. Membrane protein B7-H3, aka CD276, involved in interactions with host defenses in certain cancers, has been shown to be over-expressed in the majority of malignant neuroectodermal tumors including adult high-grade glioma. Targeting B7-H3 with a monoclonal antibody has demonstrated safety and efficacy in the salvage treatment of stage IV childhood neuroblastoma, another neuroectodermal tumor. It thus stands to reason that B7-H3 might serve as a therapeutic target in DIPG. B7-H3 immunoreactivity was determined in DIPG and non-diffuse brainstem glioma specimens with immunohistochemistry. In addition, B7-H3 mRNA expression was evaluated with microarrays in another set of specimens. All of the nine (100 %) DIPG specimens were shown to be B7-H3 immunoreactive. In the non-diffuse brainstem glioma group, none of the eight WHO grade I specimens showed B7-H3 immunoreactivity and nine of the 24 WHO grade II specimens (37.5 %) showed B7-H3 immunoreactivity. The association between histological grade and B7-H3 immunoreactivity was statistically highly significant. B7-H3 mRNA expression was also significantly higher in DIPG samples than in normal brain and juvenile pilocytic astrocytoma (WHO grade I) specimens. In summary, B7-H3 is over-expressed in DIPG. Given the need for novel treatment in this disease, antibody-based immunotherapy against B7-H3 in DIPG warrants further investigation.

Malignant neuroectodermal tumor with melanocytic and rhabdomyoblastic differentiation

Malignant melanoma can metastasize widely and vary significantly in its histological appearance; it rarely presents as a deep-seated mass without an obvious primary site elsewhere. Malignant peripheral nerve sheath tumor (MPNST) is a high-grade sarcoma characterized by conventional and epithelioid subtypes. MPNST can demonstrate heterologous differentiation, usually in the form of osteosarcomatous, chondrosarcomatous, or rhabdomyosarcomatous differentiation. MPNST does not harbor true melanocytic differentiation, although epithelioid MPNST typically is diffusely S-100 protein positive and superficially can resemble malignant melanoma. An unusual intra-abdominal mass was recently encountered with features of both melanoma and conventional or epithelioid MPNST containing a fascicular spindle cell component, an epithelioid component with melanocytic differentiation, as well as a rhabdomyosarcomatous component. The terminology “malignant neuroectodermal tumor with melanocytic and rhabdomyoblastic differentiation” is proposed to describe this neoplasm, reflecting the unusual concomittant lines of differentiation as well as offering a possible rationale for nosologically challenging aspects of this neoplasm.

Olfactory Neuroblastoma

Olfactory neuroblastoma (ONB) is a malignant neuroectodermal tumor that typically occurs in the superior nasal cavity. It is a distinct entity with features that include nesting, low-grade stippled nuclei, and neurofibrillary stroma with formation of pseudorosettes. It has a distinctive immunoprofile that includes keratin negativity, neuroendocrine marker positivity, and S100 positive sustentacular cells, which surround the nests of tumor in a supportive manner. Although the typical clinicopathologic features leave little room for misinterpretation, the wide variability in this tumor may cause diagnostic difficulty. This includes immunophenotypic diversity or patchy staining with immunomarkers, wide spectrum of grade and histology, posttreatment changes, and occasional divergent differentiation. In addition, problems in sampling, preservation, and clinical localization may make the diagnosis more challenging. A large group of tumors may show morphologic overlap with ONB, with some mimicking low-grade tumors, whereas others mimic high-grade tumors. This differential diagnosis has important treatment and prognostic implications. Further complicating the issue is that many of the mimics themselves may show great morphologic and immunophenotypic variability. This manuscript will review the typical clinical and pathologic features of ONB, address the great variability of ONB in our experience, will focus on the differential diagnosis and report on recent findings in these tumors including molecular genetics where applicable.

Hepatocyte growth factor enhances death receptor-induced apoptosis by up-regulating DR5

BackgroundHepatocyte growth factor (HGF) and its receptor c-MET are commonly expressed in malignant gliomas and embryonic neuroectodermal tumors including medulloblastoma and appear to play an important role in the growth and dissemination of these malignancies. Dependent on cell context and the involvement of specific downstream effectors, both pro- and anti-apoptotic effects of HGF have been reported.MethodsHuman medulloblastoma cells were treated with HGF for 24–72 hours followed by death receptor ligand TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) for 24 hours. Cell death was measured by MTT and Annexin-V/PI flow cytometric analysis. Changes in expression levels of targets of interest were measured by Northern blot analysis, quantitative reverse transcription-PCR, Western blot analysis as well as immunoprecipitation.ResultsIn this study, we show that HGF promotes medulloblastoma cell death induced by TRAIL. TRAIL alone triggered apoptosis in DAOY cells and death was enhanced by pre-treating the cells with HGF for 24–72 h prior to the addition of TRAIL. HGF (100 ng/ml) enhanced TRAIL (10 ng/ml) induced cell death by 36% (P < 0.001). No cell death was associated with HGF alone. Treating cells with PHA-665752, a specific c-Met receptor tyrosine kinase inhibitor, significantly abrogated the enhancement of TRAIL-induced cell death by HGF, indicating that its death promoting effect requires activation of its canonical receptor tyrosine kinase. Cell death induced by TRAIL+HGF was predominately apoptotic involving both extrinsic and intrinsic pathways as evidenced by the increased activation of caspase-3, 8, 9. Promotion of apoptosis by HGF occurred via the increased expression of the death receptor DR5 and enhanced formation of death-inducing signal complexes (DISC).ConclusionTaken together, these and previous findings indicate that HGF:c-Met pathway either promotes or inhibits medulloblastoma cell death via pathway and context specific mechanisms.

Human neural stem cells target and deliver therapeutic gene to experimental leptomeningeal medulloblastoma

Medulloblastomas are highly malignant neuroectodermal cerebellar tumors of children. One of the reasons for the difficulty for the treatment of medulloblastomas is their inherent tendency to metastasize through the cerebrospinal fluid (CSF) pathway leading to leptomeningeal dissemination. Recently, genetically modified neural stem cells (NSCs) were shown to have the capability of selectively migrating into glioma mass and delivering therapeutic agents with significant therapeutic benefits. In the present study, we applied the NSC strategy to target medulloblastomas, particularly their leptomeningeal dissemination. We used NSCs that were retrovirally transduced with the cytosine deaminase gene (CD-NSCs). In vitro studies demonstrated that CD-NSCs had sufficient migratory activity toward medulloblastoma cells and exerted a remarkable bystander effect on these cells following the application of 5-fluorocytosine (5-FC). It is noteworthy that neutralization of the hepatocyte growth factor blocked their migration In animal studies using our leptomeningeal dissemination model, CD-NSCs implanted directly into CSF space were shown to distribute diffusely within the disseminated tumor cells and could provide remarkable antitumor effect after intraperitoneal administration of 5-FC. Furthermore, CD-NSC treatment followed by 5-FC administration prolonged survival periods significantly in experimental animals. Our data suggest that the CD-NSC strategy can also be applied to target leptomeningeal dissemination of medulloblastomas.

Comprehensive cytogenetic characterization of an esthesioneuroblastoma

Esthesioneuroblastoma is a malignant neuroectodermal tumor originating from olfactory epithelial cells in the nasal vault. Due to the rarity of this tumor entity, cytogenetic data are very limited. Therefore, we performed comprehensive cytogenetic analyses of an esthesioneuroblastoma, Hyam's grade III–IV, using trypsin-Giemsa staining (GTG banding), multicolor fluorescence in situ hybridization (M-FISH), and locus-specific FISH complemented by molecular karyotyping using high-density single nucleotide polymorphism arrays. GTG banding of 25 metaphases revealed 54 structural intrachromosomal aberrations, predominantly located on 2q, 6q, 21q, and 22q, which were confirmed by FISH analysis. Interestingly, we found two novel, so far not described deletions, del(2)(q37) and del(21)(q22). Using GTG banding, locus-specific FISH, and M-FISH, we detected numeric changes of chromosomes 5, 17, 19, and 22, as well as trisomy 8 at low frequency. Applying SNP array karyotyping, we confirmed the chromosomal aberrations del(2)(q37.3), del(3)(q27.2), del(10)(q26.11), chromosomal imbalance on 17q, del(21)(q22), and revealed a number of so far unknown aberrations (gain of 2q14.3, 13q33.3, and 13q34). While the cytogenetically revealed low frequency mosaic del(6)(q22q24) was not visible using SNP array karyotyping, some of the smaller imbalances (SNP array data) could not have been detected by classic cytogenetic analysis. Therefore, our study supports the usefulness of applying complementary methods for cytogenetic analysis.

Analysis of chromosome abnormalities by comparative genomic hybridization in malignant peripheral primitive neuroectodermal tumor of the ovary

Objective. Malignant primitive neuroectodermal tumor (PNET) originating from the ovary rather than from the central nervous system is extremely rare. The aim of this study is to demonstrate the chromosomal abnormalities in a case of peripheral primitive neuroectodermal tumor (PPNET) arising from the ovary of a girl. Methods. The 13-year-old girl underwent exploratory laparotomy because of a huge pelvic tumor in lower abdomen and pelvis. She underwent removal of ovaries, tubes, omentum, peritoneal nodules, and portion of urinary bladder. Tumor specimens were sent for pathology, short-term tissue culture, and for storage in deep freezer for laboratory studies. Immunohistochemical stainings of the tumor with antibodies against O-13 (MIC/CD99), NSE, GFAP, S-100, cytokeratin AE1/AE3, desmin, NF, and AFP were performed. Short-term cell culture of fresh tumor was done for analysis of chromosomal aberrations by the technique of comparative genomic hybridization (CGH). Names of specific genes corresponding to the losses or gains on gene map loci were identified from OMIM (Online Mendelian Inheritance in Man) of the NCBI website, www.ncbi.nlm.nih.gov. The overexpressions of N- myc and EGFR as well as underexpressions of Rb and ARHI were detected by RT-PCR analysis. The patient expired 17 months later despite of chemotherapy, repeated surgery, and radiation therapy. Result. The histopathology of the specimens revealed malignant neuroectodermal tumor, involving ovaries, tubes, bladder, omentum, and peritoneum. Immunohistochemical stainings of PPNET of the ovary showed positive reaction for O-13 (MIC2/CD99) and NSE, but negative for GFAP, S-100, cytokeratin AE1/AE3, desmin, NF, and AFP. Analysis of CGH revealed multiple chromosomal abnormalities including losses of chromosomes in 1p, 1q, 4q, 6p, 6q, 7q, 8q, 13q, and 19q; as well as gains of chromosomes in 1q, 2p, 7p, 9q, 18q, and Xq. Losses of 13q14.1–q14.2, 1p31, and 4q34–q35 indicated that Rb gene, ARHI, and FAT were deleted. Gains of 2p24.1, 1q23, and 7p12.3–p12.1 demonstrated that N- myc oncogene, FASL, GITRL, and EGFR were amplified. RT-PCR analysis showed that N- myc and EGFR were overexpressed, while Rb and ARHI were underexpressed. Conclusions. This report is the first to show multiple chromosomal aberrations in PPENT arising from the ovary. The deletions of Rb, ARHI, and FAT, as well as amplification of N- myc, FASL, GITRL, and EGFR, may be the crucial factors for tumorigenesis and the aggressive biological behavior of PPNET.

Role of the Aspartyl-Asparaginyl-β-Hydroxylase Gene in Neuroblastoma Cell Motility

Aspartyl (asparaginyl) β-hydroxylase (AAH) is overexpressed in various malignant neoplasms, and high levels of immunoreactivity mainly occur in infiltrating or metastasized tumors. In addition, AAH is abundantly expressed in normally invasive placental trophoblastic cells. These observations led to the hypothesis that AAH may have a role in motility and aggressive behavior of tumor cells. The present study demonstrates that AAH is overexpressed in primary human malignant neuroectodermal tumors, including medulloblastomas and neuroblastomas, and that AAH expression is at a low level or undetectable in the normal mature brain. In the Sy5y neuroblastoma cell line, endogenous expression of the ∼86-kd AAH protein was demonstrated by Western blot analysis, and immunoreactivity predominantly localized to the cell surface by immunocytochemical staining and FACS analysis. Sy5y cells that were stably transfected with the human AAH cDNA had increased levels of proliferating cell nuclear antigen and Bcl-2, and reduced levels of p21/Waf1 and p16. In addition, increased AAH expression enhanced Sy5y cell motility, whereas antisense oligodeoxynucleotide inhibition of AAH significantly reduced Sy5y cell motility and increased the levels of p21/Waf1 and p16. The findings suggest that AAH overexpression contributes to the malignant phenotype of neuroectodermal tumor cells by increasing motility and enhancing proliferation, survival, and cell cycle progression. Because AAH expression is at a low level or undetectable in normal brain, the AAH gene may be a target for treating primitive neuroectodermal tumors.

Antitumoral effect of irinotecan (CPT-11) on an experimental model of malignant neuroectodermal tumor.

Irinotecan (CPT-11) is a topoisomerase I inhibitor with antitumor activity on a wide variety of neoplasms in several preclinical studies, but it showed poor efficacy in patients with nervous system tumors. We have carried out an experimental study in order to evaluate the effect of CPT-11 on the growth of a subcutaneously implanted malignant neuroectodermal tumor, after administration by different routes. The results showed that CPT-11 administration by intraperitoneal injections (at dose 10 mg/kg, 5 days per week, for 2 weeks, followed by 7-days rest period--one course--to a total of two courses) had no significant antitumor effect. Nevertheless, continuous infusion by intraperitoneal osmotic minipump over 28 days (at an infusion rate of 4.4 microg/h) showed a significant delay in tumor growth in 4 weeks of the implantation. The best antitumor effects were observed after CPT-11 intratumoral administration (at dose of 5 mg/kg, 5 days per week, for 2 weeks, followed by 7-days rest period, to a total of three courses) reaching tumor regression in the treated animals. These results suggest the utility of CPT-11, by means of intralesional administration, on malignant tumors of the nervous system.

Benign epithelioid schwannoma.

Benign schwannoma (neurilemoma) has various morphologic patterns that may cause problems in differential diagnosis. Although an epithelioid variant of malignant schwannoma simulating carcinoma and melanoma is well recognized, a benign counterpart has not yet been defined. In the current study, we describe five cases of benign epithelioid schwannoma that were in the subcutis (four cases) and the neck of the urinary bladder (one case). The tumors occurred in adults 28-73 years of age, were 1-4.5 cm in diameter, were well circumscribed and cellular, and were composed of epithelioid cells arranged in cords and nests. The benign nature of the lesions was evident by a constellation of features, including small size, sharp circumscription, bland morphology, low proliferative activity (four of five had < or =1% Ki67 immunostaining), and a benign clinical course after either marginal or intralesional excision. All cases had some features of classic schwannoma light microscopically and a high degree of Schwann cell differentiation both ultrastructurally and immunohistochemically. The recognition of benign epithelioid schwannoma is important because it may be misinterpreted as a malignant neuroectodermal, mesenchymal, epithelioid, or melanocytic tumor.

THE COMBINED USE OF THE DECISION TREE TECHNIQUE AND THE COMPUTER-ASSISTED MICROSCOPE ANALYSIS OF FEULGEN-STAINED NUCLEI AS AN AID FOR ASTROCYTIC TUMOR AGGRESSIVENESS CHARACTERIZATION

A systematic and thus objective method is proposed to characterize astrocytic tumor aggressiveness. This method relies upon the combined use of a specific decisional algorithm (the decision tree) and 23 parameters which include 15 morphonuclear parameters describing the geometric, densitometric, and textural features of a cell nucleus, and 8 parameters describing the various levels of nuclear DNA content. These 23 parameters were objectively quantified by means of the digital cell image analysis of Feulgen-stained nuclei. This methodology was used to investigate whether it could be applied as a diagnostic tool. The biological model chosen included 12 cell lines adapted to grow in vitro and stemming from 4 astrocytomas (weakly malignant astrocytic tumors) and 6 glioblastomas (highly malignant ones). The 2 additional cell lines were from two medulloblastomas (MED) (2 highly malignant primitive neuro-ectodermal tumors). The results demonstrate unambiguously that it is actually possible to distinguish between low-grade and high-grade tumors on the basis of these parameters, which describe their morphonuclear features and the amount of their nuclear content. However, a clear-cut distinction between these different types of tumors can only be attained when a specific technique is used. In the present case this was the decision tree technique. We were not able to distinguish between these various histopathological groups when we used conventional statistical methods including the one-way-variance analysis of data or the carrying out of the X(2) test.

A Monoclonal Antibody to a Cytoskeletal Protein Selectively Recognizing Malignant Neuroectodermal Tumors

Fusion of myeloma (P3X63-Ag 8.653) cells with spleen cells from BALB/c mice immunized with human neuroblastoma (SK-N-SH) cells yielded a hybridoma clone, referred to as 3XB7, with a unique pattern of reactivity to malignant neuroectodermal tumors except gliomas of low-grade malignancy. Indirect immunofluorescence staining under different conditions and Western blot analysis indicate that the 3XB7 MAb recognizes an intracellular cytoskeletal protein of M(r) 52K. Immunohistochemical studies with cryostat and paraffin-embedded sections from tumor biopsies revealed that the 3XB7 MAb specifically recognizes malignant neuroectodermal tumors and reacts negatively with other epithelial and mesenchymal tumors, e.g., carcinomas, lymphomas, and sarcomas as well as with normal adult and fetal brain tissues. Negative reaction was also observed with other small round cell tumors of childhood. Thus the 3XB7 antigen can be used for diagnosis of all stages of neuroblastomas, and its specific expression in gliomas with high-grade malignancy (grades III and IV) confer on it additional prognostic value.

Malignant neuroectodermal tumour of the chest wall (Askin tumour): CT and MR findings in eight patients

Malignant neuroectodermal tumour of the chest wall (Askin tumour) is an uncommon malignant neoplasm affecting young adults. We retrospectively reviewed the clinical and pathological information and radiologic studies in our archives on eight cases of this tumour. All cases were pathologically proven. Plain films, CT scans and radionuclide images were available in all cases. MR images were also available in two patients. Although rare, Askin tumour should be included in the differential diagnosis when a chest wall or thoracic paraspinal mass is identified in a young individual.

Tumor induction by ras and myc oncogenes in fetal and neonatal brain: modulating effects of developmental stage and retroviral dose.

Introduction into fetal rat brain cells of a replication-defective retroviral vector harboring v-Ha-ras and v-gag-myc rapidly causes the induction of highly malignant undifferentiated neuroectodermal tumors following transplantation into the brains of syngeneic hosts [Wiestler, et al. (1992) Cancer Res. 52: 3760-3767]. In the present study, we have investigated the modulating effect of the developmental stage of neural target cells and of the dose of the retroviral vector used in the grafting experiments. Exposure of fetal cells from embryonic day (E)12 or E14 produced a 100% incidence of malignant neuroectodermal tumors which led to the death of recipient animals after a median latency period of 32 days. A 100-fold reduction of the virus dose from 2.062 x 10(6) to 2.062 x 10(4) focus-forming units/ml resulted in a lower tumor incidence of 25%. Of six neural grafts exposed to v-Ha-ras and v-myc at E16, only one showed evidence of tumorigenesis (low-grade astrocytoma and hemangioma). All other transplants were morphologically normal for observation periods of 26 weeks, indicating a marked loss of transforming activity of ras and myc in more advanced stages of brain development. In retrovirus-exposed donor cells which caused the development of neural tumors in recipient rats, malignant transformation was also evident during culture in vitro, usually after 9-12 days. Oncogene complementation was also studied in the newborn rat brain. After microinjection of the retroviral vector into the brain at postnatal day (P)0, P1 and P3, 5 out of 20 animals (25%) developed a total of seven brain tumors. Histopathologically, three of these neoplasms were malignant neuroectodermal tumors which, in contrast to those induced in fetal brain transplants showed evidence of focal glial and/or neuronal differentiation. In addition, we observed one oligodendroglioma, two hemangiomas and a malignant hemangioendothelioma. These data indicate that neural precursor cells and endothelia of the rat brain represent the major target cells for the complementary action of ras and myc and that the use of target cells from later developmental stages (E16 and postnatal) leads to the induction of both primitive and more differentiated neoplasms.

Primitive Neuroectodermal Tumor Arising in an Ovarian Mature Cystic Teratoma

The occurrence of a malignant neuroectodermal tumor in a mature cystic teratoma is extremely rare. Five cases of ovarian primitive neuroectodermal tumors (PNET) or neuroepitheliomas have been reported. In two, the tumor was adjacent to foci of a mature teratomatous element. We present the immunohistochemical profile and electron microscopic study of an ovarian mature cystic teratoma with PNET or malignant neuroepithelioma. The transition between the mature neural elements and the malignant PNET presents a model for monodermic neuroepithelial differentiation and explains the histogenesis of this unusual tumor.

Proliferating cell nuclear antigen immunoreactivity in human central nervous system neoplasms.

Formalin-fixed, paraffin-embedded surgical specimens from 140 primary human central nervous system tumors, including 51 meningiomas, 26 astrocytomas, 26 anaplastic astrocytomas, 9 glioblastomas, 1 gliosarcoma, 8 oligodendrogliomas, 5 ependymomas, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were immunostained using a streptavidin/peroxidase method and the PC10 monoclonal antibody, which recognizes an epitope on the proliferating cell nuclear antigen (PCNA). The following PCNA labeling index (LI) mean values were found for the above neoplasms: meningiomas, 3.80 +/- 7.35%; astrocytomas, 0.65 +/- 1.03%; anaplastic astrocytomas, 8.46 +/- 7.95%; glioblastomas, 10.26 +/- 11.21; gliosarcoma, 46.34%; oligodendrogliomas, 2.31 +/- 3.59%; ependymomas, 1.12 +/- 2.10%; medulloblastomas, 23.91 +/- 11.95%; and paragangliomas, 2.07 +/- 1.86%. Collectively, our findings indicate that while benign central nervous system tumors generally have low PCNA LI values, consistent over-expression of PCNA epitopes was noted in some examples, especially in a number of meningiomas. Among the malignant neuroectodermal tumors, medulloblastomas were found to have the highest PCNA LI values, corresponding to their histological grade of malignancy, and malignant glial tumors generally displayed significantly higher PCNA LI values, than their benign counterparts. Although in our study mean PCNA LI values seemed to reflect histological grading, large discrepancies were noted in all tumor groups. Our data, therefore, suggest than PCNA immunoreactivity can not be considered reliable for predicting the prognosis of the disease in individual cases.

Malignant Primitive Neuroectodermal Tumor Presenting as a Scalp Nodule

We report a case of a 20-year-old woman who presented with a 3-year history of a stable cystic nodule on the scalp. Light microscopy of the excised nodule demonstrated a malignant small round cell undifferentiated neoplasm. Immunohistochemical studies suggested a neural crest origin, while ultrastructural examination revealed characteristics of schwannian differentiation. Both of these special techniques were essential in establishing the diagnosis of a malignant epithelioid schwannoma of superficial tissue (neurotropic melanoma, desmoplastic melanoma). We discuss the differential diagnoses and describe the immunohistochemical and ultrastructural characteristics of this tumor. This case illustrates the difficulty of diagnosing this rare malignant tumor, which masqueraded as a benign-appearing scalp lesion.