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PubMed1994

MIC2 analysis of small cell carcinoma.

Small cell carcinomas (SCCs) and peripheral neuroectodermal tumors (PNETs) are two distinct neoplasms that show considerable histologic, immunohistochemical, and clinical overlap, but differ in their therapies and prognoses. In an attempt to further diagnostically distinguish the two, 33 SSCs were analyzed from both pulmonary and extrapulmonary sites for the MIC2 gene product, a cell surface antigen strongly and reliably expressed in PNETs and Ewing's sarcoma (ES). Two of the 33 SCCs stained positively, but the staining was less intense than that seen with PNET and ES. The remaining 31 tumors did not stain. These data indicate that, in combination with a panel of immunohistochemical stains, analysis of neuroendocrine tumors for MIC2 expression may be useful in distinguishing between small cell carcinomas of both pulmonary and extrapulmonary origins and soft tissue PNETs.

12E7 Antigen↗
PubMed2001

Flow cytometric immunophenotyping and comparison with immunocytochemistry in small round cell tumors.

OBJECTIVE: To quantitate different antigens by flow cytometric immunophenotyping (FCI) in small round cell tumors (SRCTs) and to compare the FCI technique with immunocytochemistry (IC). STUDY DESIGN: IC and FCI were performed on 24 consecutive cases of SRCT on fine needle aspiration biopsy material using a panel of antibodies--e.g., cytokeratin (CK), leukocyte common antigen (LCA), desmin, epithelial membrane antigen, neuron-specific enolase, chromogranin, retinoblastoma gene product, neuroblastoma clone (NB84a (NB), vimentin and Mic-2 gene product. IC was done by indirect immunoperoxidase and FCI by indirect immunofluorescence onflow cytometry. RESULTS: In Ewing's sarcoma, with the help of FCI, positive results were obtained in an additional 4 samples in CK, 2 samples in actin and 3 samples in desmin. Similarly, one each sample was additional positive regarding Mic-2 and vimentin by IC. In cases of neuroblastoma with the help of FCI, additional positive results were obtained in one each sample of CK, LCA and NB and two in actin. Combined use of FCI and IC helped to show chromogranin positivity in an additional two cases. Divergent differentiation was noted in four cases of Ewing's sarcoma, one neuroblastoma and two peripheral neuroectodermal tumors. CONCLUSION: FCI technique is sensitive, more objective and quantitative in comparison with manual absorbance-based microscopic detection of enzyme immunohistochemistry products. FCI may determine divergent differentiation in SRCTs.

Biomarkers, Tumor↗
PubMed1998

Vertical ramus compartment resection of the mandible for deeply invasive tumors.

PURPOSE: Vertical ramus compartment resection of the mandible is indicated in the management of pathology that originates in the ascending ramus or condyle of the mandible and invades the pterygomaxillary fossa, infratemporal space, parapharyngeal space, masseter muscle, or medial pterygoid muscle. This article describes the technique, presents a review of the relevant literature, and reports the outcome of five cases. PATIENTS AND METHODS: A retrospective review of all cases operated on by the senior author (R.A.O.) over the last 5 years at the University of Maryland was performed. The records of these cases were reviewed to identify patient sex, age, pathologic diagnosis, use of adjuvant therapy, and status after resection. RESULTS: Five surgical cases in which a vertical ramus compartment resection of the mandible was necessary were identified. The histologic diagnoses of these five cases were as follows: grade II chondrosarcoma, peripheral neuroectodermal tumor, high-grade central mucoepidermoid carcinoma, invasive squamous cell carcinoma, and odontogenic keratocyst. Four of the five patients are alive and well at follow-up of 16 to 43 months. The only death occurred in a 70-year-old man with squamous cell carcinoma that recurred intracranially by local extension. CONCLUSIONS: When indicated by local extension or tumor biology, vertical ramus compartment resection of the mandible is a viable surgical modality that allows clearance of local disease in most well-selected cases.

Adult↗
PubMed2001

Parental occupations and childhood brain tumors: results of an international case-control study.

OBJECTIVE: To evaluate the role of parental occupations in the etiology of childhood brain tumors (CBT). METHODS: Population-based case-control studies were conducted concurrently in seven countries under the coordination of the International Agency for Research on Cancer, gathering 1,218 cases and 2,223 controls. We report here the findings related to parental occupations during the 5-year period before the child's birth. Risk estimates related to a number of paternal and maternal occupations were obtained by unconditional logistic regression adjusted for age, sex, year of birth, and center, for all types of CBT combined and for the subgroups of astroglial, primitive neuroectodermal tumors (PNET), and other glial tumors. RESULTS: An increased risk in relation with agricultural work was seen for all CBT combined and for other glial tumors. Increased risks for all tumors and PNET were seen for paternal occupation as an electrician; the same pattern held for maternal occupation when children under 5 were selected. Paternal occupation as a driver or mechanic, and maternal work in an environment related to motor-vehicles were associated with an increased risk for all CBT and astroglial tumors. More case mothers compared to control mothers were employed in the textile industry. CONCLUSION: Our study reinforces previous findings relative to the role of parental work in agriculture, electricity, or motor-vehicle related occupations and maternal work in the textile industry. It does not confirm previous associations with work environments including aerospace, the chemical industry, or the food industry, or with maternal occupation as a hairdresser, a nurse, or a sewing machinist, and paternal occupation as a welder.

Adolescent↗
PubMed2000

In vivo assessment of the window of barrier opening after osmotic blood-brain barrier disruption in humans.

OBJECT: Osmotic blood-brain barrier (BBB) disruption induced by intraarterial infusion of mannitol is used in conjunction with chemotherapy to treat human brain tumors. The time course to barrier closure, or the so-called therapeutic window, has been examined in animals but little information is available in humans. The authors, therefore assessed the time course to barrier closure after osmotic BBB disruption in humans. METHODS: Disruption of the BBB was demonstrated using 99mTc-glucoheptonate (TcGH) single-photon emission computerized tomography (SPECT) scanning in 12 patients who were treated monthly with combination chemotherapy in conjunction with BBB disruption. The primary diagnosis was primary central nervous system lymphoma in seven patients and primitive neuroectodermal tumors in five. The TcGH (20 mCi) was injected at 1- to 480-minute intervals after osmotic BBB disruption, and patients underwent SPECT scanning after 4 hours. A total of 38 studies was performed. Good-to-excellent BBB disruption was obtained in 29 procedures and poor-to-moderate disruption was seen in the other nine studies. The TcGH indices correlated with the degree of BBB disruption as measured postprocedure on contrast-enhanced CT scans (r = 0.852). Mean baseline TcGH indices were 1.02+/-0.07. For the group of patients with good-to-excellent disruptions the mean indices at 1 minute postdisruption measured 2.19+/-0.18. After 40 minutes no significant change was noted (mean index 2.13+/-0.2). Then the indices declined more steeply and at 120 minutes after the disruption the index was 1.36+/-0.02. A very slow decline was noted between 120 and 240 minutes after mannitol infusion. At 240 minutes the barrier was still open for all good-to-excellent disruptions (index 1.33+/-0.08) but at 480 minutes the mean indices had returned to the baseline level. CONCLUSIONS: Results of these in vivo human studies indicate that the time course to closure of the disrupted BBB for low-molecular-weight complexes is longer than previously estimated. The barrier is widely open during the first 40 minutes after osmotic BBB disruption and returns to baseline levels only after 6 to 8 hours following the induction of good or excellent disruption. These findings have important clinical implications for the design of therapeutic protocols.

Adult↗
PubMed1980

Peripheral neuroepithelioma: a light and electron microscopic study.

A primitive neuroectodermal tumor of peripheral nerve origin was examined by light and electron microscopy. The lesion arose in association with the S1 nerve root of the lumbosacral plexus in a 22-year-old female. Following a surgical biopsy, the patient received systemic chemotherapy; however, approximately one-and-a-half years later, she suffered a clinical relapse with locally recurrent tumor. An excisional biopsy was performed, and pathologic examination revealed progressive neuroblastic differentiation. The ultrastructural features of neoplastic Homer-Wright rosettes will be illustrated, and the non-specificity of cytoplasmic glycogen in the evaluation of "small round cell neoplasms" will be emphasized.

Adult↗
PubMed2005

Intracranial Ewing sarcoma.

The occurrence of primary extraosseous Ewing sarcoma (EES) of the central nervous system (CNS) has only rarely been reported in the literature. It is important to distinguish this entity from the more common central primitive neuroectodermal tumor (PNET) of brain, since the management of these tumors is different from that of EES. We present the clinical, radiologic, and pathologic features of two cases of EES occurring in the brain. The diagnosis was further confirmed by detection of a rearrangement of the FLI1 and/or EWS gene loci in tumors from both patients using fluorescent in situ hybridization (FISH). Although rare, the possibility of EES should be considered particularly when tumors that arise near the meningeal surface of the brain and have the pathologic appearance of a PNET. Demonstration of t(11;22)(q24;q12) by molecular analysis essentially confirms the diagnosis and enables the oncologist to choose appropriate therapy.

Brain Neoplasms↗
PubMed1998

[Meningoradiculitis revealing an occult medulloblastoma-PNET in an adult].

Neoplastic meningitis as the presentation of occult primitive neuroectodermal tumor (PNET) is occasionally described in children. We report the case of an 64 year old-man who presented a meningo-radiculopathy with progressive injury of the cauda equina and then the ocular motor nerves, revealing an occult medulloblastoma-PNET.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Apoptosis induced by doxorubicin in neurotumor cells is divorced from drug effects on ceramide accumulation and may involve cell cycle-dependent caspase activation.

Doxorubicin (0.5 microgram/ml) induced caspase-dependent apoptosis in SH-SY5Y neuroblastoma and CHP-100 neuroepithelioma cells. The apoptotic response started to be evident approximately 15 h after drug administration and, as monitored over a 48-h period, was more pronounced in CHP-100 than in SH-SY5Y cells. In both systems, apoptosis was accompanied by elevation of intracellular ceramide levels. Ceramide accumulation was blocked by the ceramide synthase inhibitor fumonisin B(1) (25 microM); this compound, however, did not prevent drug-induced apoptosis. Untreated cells from both lines expressed negligible p53 levels; on the other hand, whereas p53 and p21(Cip1/Waf1) were rapidly up-regulated in doxorubicin-treated SH-SY5Y cells, such a response was not observed in CHP-100 cells. Doxorubicin induced a G(2)/M phase block in both cell lines, but whereas the G(1) phase was markedly depleted in CHP-100 cells, it was substantially retained in SH-SY5Y cells. In the latter system, double G(1) and G(2)/M block largely preceded cell death; however, as apoptosis underwent completion, it selectively targeted late S and G(2)/M cells. Moreover, apoptosis suppression by caspase inhibition did not result in a recovery of the G(1) cell population. These results support the notion that doxorubicin-induced apoptosis and ceramide elevation are divorced events in neuroectodermal tumors and that p53 function is at least dispensable for apoptosis completion. Indeed, as G(1) cells appear to be refractory to doxorubicin-induced apoptosis, p53 up-regulation and p21(Cip1/Waf1) expression may provide an unfavorable setting for the apoptotic action of the drug.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Successful extracorporeal membrane oxygenation in four children with malignant disease and severe Pneumocystis carinii pneumonia.

BACKGROUND: Toxic deaths due to intensified treatment are of increasing concern in view of the generally improved prognosis for children with malignancies. Pneumocystis carinii pneumonia (PCP) during immunosuppressive treatment in children with malignancies is a severe complication with a poor prognosis if mechanical ventilation is required. Extracorporeal membrane oxygenation (ECMO) is a recognized technique that provides temporary respiratory support for patients with intractable respiratory failure. PROCEDURE: We here report successful ECMO support in four children with PCP, secondary to chemotherapy-induced immunosuppression, in whom the respiratory situation deteriorated despite pharmacological treatment and mechanical ventilation. The duration of ECMO was 7-43 days. RESULTS: Three children with acute lymphoblastic leukemia recovered from their PCP to continue chemotherapy and are now in complete continuous remission. Their pulmonary function normalized completely during 6-12 months after ECMO therapy. One child with a primitive neuroectodermal tumor survived the PCP and was off ECMO for 11 days before succumbing to unrelated complications. CONCLUSIONS: We conclude that ECMO offers an important means of respiratory support in children with severe PCP that can also be adopted during treatment for malignant disease.

Adolescent↗
PubMed2002

Primitive neuroectodermal tumour of the mandible.

Primitive neuroectodermal tumors (PNETs) are relatively rare tumors. Tumors that once would have been diagnosed as Ewing's sarcoma are now often designated as peripheral neuroepithelioma or synonymously PNET. Herein we report the first case of PNET of the mandible in a 6-year-old female who was admitted to the hospital with a two-months history of painless, progressively enlarging lower jaw mass.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Primitive neuroectodermal tumors/medulloblastoma.

The therapy for medulloblastoma/primitive neuroectodermal tumors of the central nervous system is surgery, followed by combination chemo-radiotherapy. The radiation field is the entire craniospinal axis, which is only avoided when treating infants. The treatment is, therefore, lengthy and toxic. Less aggressive therapy is given to patients who clinically appear to have less evidence of disease. Intensive basic research has begun to identify genetic factors of the disease, but these remain far from clinical application.

Brain Neoplasms↗
PubMed2001

Aberrant hypermethylation of the major breakpoint cluster region in 17p11.2 in medulloblastomas but not supratentorial PNETs.

Deletions of 17p have been consistently reported in up to 50% of medulloblastomas (MBs), and the major breakpoint interval has been localized to chromosome segment 17p11.2. Based on several reports linking aberrant DNA methylation and chromosomal disruption, we examined the methylation pattern in this region by employing restriction landmark genomic scanning (RLGS). Several CpG islands located in the major breakpoint cluster region were identified using a bacterial artificial chromosome (BAC) contig of the breakpoint region. A long-range methylation map was established for 20 MBs and 5 supratentorial primitive neuroectodermal tumors (stPNETs). Selected CpG islands were examined using Southern and bisulfite sequencing analysis. Aberrantly hypermethylated CpG islands in 17p11. 2 were found in 33% of MBs. Interestingly, one CpG island was methylated in MBs, but not in any of the examined stPNETs. A BAC clone covering three of the methylated CpG islands was partially sequenced in the search for a potential tumor suppressor gene. None of the expressed sequence tag sequences and full-length mouse/human cDNAs that were associated with aberrant methylation showed a change in expression levels due to methylation. The potential link between chromosomal instability in 17p11.2 and hypermethylation in this region is discussed.

Adolescent↗
PubMed2005

Risk of brain tumors in children and susceptibility to organophosphorus insecticides: the potential role of paraoxonase (PON1).

Prior research suggests that childhood brain tumors (CBTs) may be associated with exposure to pesticides. Organophosphorus insecticides (OPs) target the developing nervous system, and until recently, the most common residential insecticides were chlorpyrifos and diazinon, two OPs metabolized in the body through the cytochrome P450/paraoxonase 1 (PON1) pathway. To investigate whether two common PON1 polymorphisms, C-108T and Q192R, are associated with CBT occurrence, we conducted a population-based study of 66 cases and 236 controls using DNA from neonatal screening archive specimens in Washington State, linked to interview data. The risk of CBT was nonsignificantly increased in relation to the inefficient PON1 promoter allele [per PON1(-108T) allele, relative to PON1(-108CC): odds ratio (OR) = 1.4; 95% confidence interval (CI), 1.0-2.2; p-value for trend = 0.07]. Notably, this association was strongest and statistically significant among children whose mothers reported chemical treatment of the home for pests during pregnancy or childhood (per PON1(-108T) allele: among exposed, OR = 2.6; 95% CI, 1.2-5.5; among unexposed, OR = 0.9; 95% CI, 0.5-1.6) and for primitive neuroectodermal tumors (per PON1(-108T) allele: OR = 2.4; 95% CI, 1.1-5.4). The Q192R polymorphism, which alters the structure of PON1 and influences enzyme activity in a substrate-dependent manner, was not associated with CBT risk, nor was the PON1(C-108T/Q192R) haplotype. These results are consistent with an inverse association between PON1 levels and CBT occurrence, perhaps because of PON1's ability to detoxify OPs common in children's environments. Larger studies that measure plasma PON1 levels and incorporate more accurate estimates of pesticide exposure will be required to confirm these observations.

Aryldialkylphosphatase↗
PubMed1995

Infarction of the territory supplied by the contralateral superior cerebellar artery in a case of descending transtentorial herniation.

Infarction of the territory supplied by the contralateral superior cerebellar artery in cases of descending transtentorial herniation has not been reported. The authors experienced a primitive neuroectodermal tumor in a patient whose consciousness deteriorated transiently due to descending transtentorial herniation. On the magnetic resonance imaging taken 8 days after the herniation, lesions thought to be infarction of territories supplied by the ipsilateral posterior cerebral artery and the contralateral superior cerebellar artery were noted. The possible mechanism of this peculiar pattern of infarction is discussed.

Arteries↗
PubMed2006

Laparoscopic removal of extraosseous Ewing's sarcoma of the kidney in a pediatric patient.

In the pediatric population, to the best of our knowledge, only 2 cases of renal extraosseous Ewing's sarcoma/primitive neuroectodermal tumor (EES/PNET) have been published. We report the initial case of renal EES/PNET occurring in a 10-year-old girl treated by a laparoscopic radical nephrectomy. The regimen used is the first documented use of neoadjuvant chemotherapy prior to laparoscopic radical nephrectomy for PNET. This approach obviated the need for a large incision and a prolonged postsurgical recovery. The minimally invasive nature of the laparoscopic procedure allowed for a rapid convalescence and resumption of her chemotherapy regimen within 14 days of the surgery.

Child↗
PubMed1997

Central neurocytoma: one associated with a fourth ventricular PNET/medulloblastoma and the second mixed with adipose tissue.

We report two cases of central neurocytoma; one located in the right lateral ventricle and associated with a distinctly separate primitive neuroectodermal tumor (PNET)/medulloblastoma of the fourth ventricle, and the other admixed with fat cells and arising from the left lateral and third ventricles with extension into the corpus callosum. We discuss that concurrent occurrences of PNET and adipose tissue are not fortuitous events, but an evidence that neurocytomas and PNETs originate in the residual germinal pool from common progenitor cell rests recapitulating features of developing neurons and with a potential for mesenchymal differentiation.

Adipose Tissue↗
PubMed1998

Computed tomography in the diagnosis of maxillofacial mass lesions in younger children.

OBJECTIVE: To evaluate the CT findings of maxillofacial mass lesions in younger children and to discuss the effectiveness of CT in their differential diagnosis. PATIENTS AND METHODS: CT findings of 17 patients (age range, 0 years 5 months to 3 years 3 months) with histopathologically proven maxillofacial mass lesions were retrospectively evaluated. About two-thirds (11/17) comprised congenital lesions or more common lesions in infancy or younger children. RESULTS: Hemangiomas, dermoid cysts and ranulas in this age group presented characteristic CT findings in common with those occurring in adults. Two invasive lesions (melanotic neuroectodermal tumor and aggressive fibromatosis) had irregular margins and the latter also showed aggressive bone destruction. Two angiomas had irregular margins. A fibrosarcoma showed expansile bone destruction but had a regular margin. CONCLUSION: CT was useful in demonstrating the extent of maxillofacial mass lesions in children and for surgical treatment planning. Although some invasive lesions could be correctly diagnosed on the basis of CT, its diagnostic value in differentiating malignant from benign maxillofacial lesions in younger children was limited.

Ameloblastoma↗