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PubMed1995

MR and cognitive testing of patients undergoing osmotic blood-brain barrier disruption with intraarterial chemotherapy.

PURPOSE: To determine whether osmotic blood-brain barrier disruption is associated with MR abnormalities or cognitive deterioration and, if so, whether the MR findings correlate with cognitive test results. METHODS: Fifteen brain tumor patients who had a complete tumor response (nine central nervous system lymphoma, three germ cell and two astrocytoma, and one primitive neuroectodermal tumor) treated with blood-brain barrier disruption procedures (318 total procedures) with intraarterial chemotherapy were included. MR images were evaluated for the development of white matter hyperintensity, vascular lesions, or atrophy. Cognitive testing was performed to assess deterioration caused by this therapy. RESULTS: In two patients white matter hyperintensity developed, in two small vascular lesions developed, and in one mild atrophy developed. One infarct was asymptomatic and the second one resulted in mild dysesthesia in one upper extremity. No patient showed diminished cognitive function on the posttherapy evaluation. CONCLUSION: In patients undergoing blood-brain barrier disruption with intraarterial chemotherapy, new abnormalities on MR imaging may develop. These patients maintain the same level of cognitive and neurologic function and MR findings do not correlate with the results of cognitive testing.

Adolescent↗
PubMed2006

Impact of high-dose busulfan plus melphalan as consolidation in metastatic Ewing tumors: a study by the Société Française des Cancers de l'Enfant.

PURPOSE: To improve the prognosis for patients with metastatic Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) using conventional chemotherapy and consolidation high-dose chemotherapy (HDCT) containing busulfan and melphalan. PATIENTS AND METHODS: Ninety-seven unselected patients with newly diagnosed metastatic ES/PNET received induction chemotherapy that included five cycles of cyclophosphamide 150 mg/m2/d for 7 days, doxorubicin 35 mg/m2/d once, followed by two cycles of ifosfamide 1.8 g/m2/d for 5 days, and etoposide 100 mg/m2/d for 5 days. Patients in complete or very good partial remission received HDCT with busulfan total dose 600 mg/m2 and melphalan 140 mg/m2 followed by autologous blood stem cells. Local therapy (surgery and/or radiation therapy) was performed before or after HDCT. RESULTS: Ninety-seven patients were enrolled from 1991 to 1999 (median age, 12.3 years; range, 0.2 to 25 years). Among them, 75 received HDCT. The 5-year event-free survival (EFS) rate for all 97 patients was 37% and the overall survival (OS) rate was 38%. The EFS after HDCT was 47%. The EFS for the 44 patients with lung-only metastases was 52%, whereas it was 36% for patients with bone metastases without bone marrow involvement. Among the 23 patients with bone marrow metastases, only one survived. The multivariate analysis for both EFS and for OS identified three independent prognostic factors: age, fever at diagnosis, and bone marrow involvement. CONCLUSION: Compared with conventional chemotherapy, HDCT may yield benefits for patients with lung-only metastases or bone metastases. These results warrant confirmation in a randomized trial and provide part of the background data for the ongoing Euro-Ewing study.

Adolescent↗
PubMed2000

Biological stability of RNA isolated from RNAlater-treated brain tumor and neuroblastoma xenografts.

BACKGROUND: Advances in molecular biological research have led to identification of prognostic factors such as Trk mRNA expression in primitive neuroectodermal tumors of the CNS and neuroblastoma. To study prospectively the importance of these prognostic factors in large groups of homogeneously treated patients, tumor specimens of good quality must be acquired, preserved, and stored at multiple institutions. Immediate freezing of tumor biopsy samples in liquid nitrogen and storage at -70 degrees C are the most commonly used method of tissue preservation for future RNA analysis. PROCEDURE: To evaluate alternative methods of preserving tissue samples for subsequent RNA analysis, we tested a new RNA stabilization solution. Using tumor tissue of two CNS tumor and one neuroblastoma human xenografts, we compared total RNA isolated from tumor tissue stored for 7 days at room temperature in stabilization solution to that of snap-frozen tissue. The quality of the RNA was studied by spectrophotometry, gel electrophoresis, RT-PCR, and gene expression profiling. RESULTS: No major differences were observed in the quality of RNA isolated from tumor samples stored at room temperature in the RNA stabilization solution compared to snap-frozen tumor samples stored at -70 degrees C. CONCLUSIONS: High-quality RNA can be prepared from tumor tissue stored at room temperature. Whenever snap freezing is not feasible, pieces of tumor tissue can be treated with RNAlater for subsequent RNA analysis. Short-term storage and shipment of well-preserved tumor tissue are clearly feasible for all institutions, thereby facilitating large multiinstitutional studies of biological prognostic factors.

Animals↗
PubMed1988

Cisplatin in the treatment of recurrent childhood primary brain tumors.

Thirty-three patients were treated with intravenous (IV) cisplatin (CPDD) of whom 32 were considered evaluable. There were 14 medulloblastomas, five primitive neuroectodermal tumors (PNET), nine gliomas, three ependymomas, and one germ cell tumor. The overall response rate was 13 of 32 (41%). Eleven responses (five complete [CR], five partial [PR], one mixed [MR]) were noted in the patients with medulloblastoma. The response rate within this group was 79%. Toxicity was tolerable, although it precluded further therapy in five patients.

Adult↗
PubMed1990

A new rat brain tumor model: glioma disseminated via the cerebral spinal fluid pathways.

A rat brain tumor model has been developed with the clinical and pathological features of dissemination via the cerebral spinal fluid (CSF) pathways. A precise number of 9L gliosarcoma cells (5 x 10(2) to 5 x 10(5)) is stereotactically injected into the CSF of the lateral ventricle. The interval until the onset of neurological symptoms and then death is reproducible and dependent upon the number of cells injected. The median survival of three groups of rats receiving 5 x 10(5) cells in three different experiments was 17, 18 and 19 days respectively. For three groups receiving 5 x 10(4) cells, the median survival was 23, 24 and 25.5 days respectively and for two groups receiving 5 x 10(3) cells the median survival was 28 and 30 days respectively. The animals developed multiple tumor implants along the CSF pathways usually resulting in hydrocephalus. This tumor model was developed to simulate dissemination via CSF pathways as seen with medulloblastoma and other primitive neuroectodermal tumors of the central nervous system. It will be used to evaluate the therapeutic efficacy of intraventricularly administered anti-neoplastic drugs against small implants and malignant cells in the CSF pathways.

Animals↗
PubMed2002

PCNA and Ki-67 in central nervous system tumors: correlation with the histological type and grade.

Determination of proteins in the control of proliferation in normal cells helps a better understanding of cellular transformation and proliferation mechanisms. Measurement of proliferative activity is important in determining the tumor grade, recurrence span and malignancy. Proliferating cell nuclear antigen (PCNA) and Ki-67 are two of the nuclear markers used to demonstrate the proliferative phase of the cell cycle. In the present study, 63 central nervous system (CNS) tumors of various histologic types, diagnosed in Cukurova University Medical Faculty. Department of Pathology and graded according to WHO grading system were examined for PCNA and Ki-67 monoclonal antibodies using immunohistochemistry. Results were analyzed with statistical methods. Distribution of PCNA and Ki-67 LI (labeling index) values were determined for different tumor types. The highest PCNA and Ki-67 LI values were detected in medulloblastoma, malignant meningioma, primitive neuroectodermal tumor (PNET) and glioblastoma (GBM) groups, while pilocytic astrocytoma, meningioma, craniopharyngioma and oligodendroglioma showed the lowest values. In such tumors, the correlation between the increasing grade and PCNA and Ki-67 LI values were statistically significant. A correlation between the clinical outcome and Ki-67 and PCNA LI values was also detected. Conclusively, both markers can be used to evaluate the tumor grade and to asses the possibility of recurrence and malignancy in CNS tumors.

Astrocytoma↗
PubMed2006

Irinotecan for children with relapsed solid tumors.

Irinotecan is expected to become a new drug for childhood solid tumors. Sixteen children with relapsed solid tumors received irinotecan 180 mg/m2/day for 3 consecutive days, repeated once after 25 days off. Their original tumors were neuroblastoma in 7, rhabdomyosarcoma in 3, nephroblastoma and undifferentiated sarcoma in 2 each, and primitive neuroectodermal tumor and leiomyosarcoma in 1 each. The average age at trials was 6 years. Partial response was achieved in 5 (31.3%) (neuro-blastoma, rhabdomyosarcoma, nephroblastoma, undifferentiated sarcoma, and leiomyosarcoma), and decrease in tumor marker in the other 2. Irinotecan appears promising, and could become included in the first-line treatment.

Camptothecin↗
PubMedDate not supplied

Canine intracranial primary neoplasia: 173 cases (1986-2003).

This study investigates the clinical and pathologic findings associated with 173 primary brain tumors in our hospital population of dogs that presented between the years 1986 and 2002. Of the 173 primary brain tumors, 78 (45%) were meningiomas, 29 (17%) were astrocytomas, 25 (14%) were oligodendrogliomas, 12 (7%) were choroid plexus tumors, and 7 (4%) were primary central nervous system lymphomas. Smaller numbers of glioblastomas (n = 5), primitive neuroectodermal tumors (n = 5), histiocytic sarcomas (n = 5), vascular hamartomas (n = 4), and unclassified gliomas (n = 3) were identified. One dog had both a meningioma and an astrocytoma. Most tumors were located within the telencephalon, and seizures were the most common clinical presenting complaint. Of 168 tumors for which a location in the brain was recorded at postmortem examination, 79 were found to involve more than 1 brain division. Other neoplasms unrelated to the primary brain tumor were identified on postmortem examination in 39 dogs (23%). Intrathoracic and intraabdominal neoplasms were present at necropsy in 13 and 24 cases, respectively. Based on the results of this study, thoracic radiographs and abdominal ultrasonography may be indicated to look for extracranial neoplasia prior to advanced imaging of the brain or intracranial surgery.

Animals↗
PubMed1986

Pediatric central nervous system tumors: a cell kinetic study with bromodeoxyuridine.

Bromodeoxyuridine (BrdU), 150 to 200 mg/m2, was administered at the time of operation to 20 pediatric patients with neuroectodermal tumors to label tumor cells in the S phase. Immunocytochemical techniques were used on excised tumor specimens to detect cells containing BrdU, and the BrdU labeling index (LI) was calculated as the number of BrdU-labeled cells divided by the total number of cells counted. Four medulloblastomas, three glioblastomas multiforme, and two highly anaplastic astrocytomas had average BrdU LIs of 13.0 +/- 3.0% (SE), 12.7 +/- 4.3%, and 14.6 +/- 6.7%, respectively. Three of nine moderately anaplastic astrocytomas had BrdU LIs of greater than 1% (average, 6.5 +/- 2.4%), whereas six had LIs of less than 1%. In two juvenile pilocytic astrocytomas, which are considered slow-growing, the BrdU LIs were unexpectedly high, averaging 6.5 +/- 1.4%. Thus pediatric medulloblastomas, glioblastomas multiforme, highly anaplastic astrocytomas, and a minority of moderately anaplastic astrocytomas had high proliferative potentials, whereas most of the moderately anaplastic astrocytomas had low proliferative potentials. Although the number of cases in this study is still too small to yield statistically significant comparisons, the results indicate that some pediatric tumors have considerably higher LIs than histologically similar adult tumors studied previously.

Adolescent↗
PubMed1990

A gene that encodes for a leukemia-associated phosphoprotein (p18) maps to chromosome bands 1p35-36.1.

The cytosolic protein p18 which is expressed in increased amounts in acute leukemia cells is variably phosphorylated as a function of growth and differentiation. Proteins with identical amino acid sequence were independently found to be highly expressed in normal brain tissue and neuroendocrine tumor cells. Here we described the mapping of the recently cloned p18 gene to chromosome 1, band p35-36.1 by Southern blot analysis of human-rodent somatic cell hybrid DNA and by chromosome in situ hybridization using a p18 genomic probe. This region of the distal short arm of chromosome 1 is a frequent site of deletions or loss of heterozygosity in tumors derived from neural crest cells, particularly neuroblastomas and melanomas. The high levels of expression of p18 in brain and neuroendocrine tumor cells, its possible role in growth regulation, and its chromosomal location in a region frequently deleted in neuroectodermal tumors suggest that this gene may be involved in common genetic events occurring in these tumors.

Animals↗
PubMed2005

The results of surgical treatment of chest wall tumors in childhood.

Chest wall tumors (CWT) are rarely seen in childhood and surgery constitutes a complementary part of the therapy. The early and late results of CWT resection and chest wall reconstruction were evaluated retrospectively. The children who underwent chest wall resection for CWT between January 1990 and November 2003 were evaluated retrospectively. Seventeen children (male/female = 12/5, mean age: 7.58 years) underwent chest wall resection for CWT. Fifteen patients underwent initial biopsy (tru-cut, n = 8 or open biopsy, n = 7) and two underwent initial resection. The diagnosis was malignant tumor in 12 (70%) and benign in 5 (30%). They were Ewing's sarcoma (ES) (n = 4), primitive neuroectodermal tumor (PNET) (n = 3), Askin's tumor (n = 1), rhabdomyosarcoma (RMS) (n = 2), neuroblastoma (n = 2), osteochondroma (n = 1), aneurysmal bone cyst (n = 2) and hamartoma (n = 2). Preoperative chemotherapy was given to most patients with malignant tumor. All patients had only local tumor at the time of resection. Thoracotomy was performed in all patients. All tumor tissues with the affected rib/ribs were resected en bloc with the adjacent tissues. The number of resected ribs was 1 (n = 6), 2 (n = 7) and 3 (n = 4). Chest wall defects were repaired primarily (n = 8) or with grafts (n = 9). Dura (n = 4), Neuro-patch (n = 3) and Goretex (n = 2) were used for closure. Wound infection and pleural fistula occurred in one patient. Patients with benign tumor were free of complaints or complications during follow up. All patients with malignant tumor received postoperative chemotherapy. Local recurrence did not occur in all patients. Five patients developed distant metastasis and two died. Scoliosis was encountered in one patient during follow-up. Since most of the CWT are malignant and not initially suitable for surgical excision, the management includes tissue diagnosis either by tru-cut or open biopsy. Determination of malignant condition should be followed by an intensive chemotherapy. Chest wall resection is planned to control local disease. Chest wall reconstruction may be needed for large defects following resection of CWT. Prosthetic materials can be used safely. Early complications of the surgery are limited. The patients should be closely followed up for late complications such as scoliosis, restrictive pulmonary disease and for the development of metastasis, which is a part of natural course of malignant CWT in children.

Adolescent↗
PubMed2005

Cyclin D1 is overexpressed in atypical teratoid/rhabdoid tumor with hSNF5/INI1 gene inactivation.

OBJECT: Although atypical teratoid/rhabdoid tumor (AT/RT) is known to generate through inactivation of the hSNF5/INI1 gene on chromosome 22q, the downstream molecular mechanism remains unclear. We histologically and molecularly reviewed our pediatric brain tumors for unrecognized AT/RTs and evaluated the role of cyclin D1, a potential molecular target of hSNF5/INI1. METHODS: We analyzed 16 tumors under three years of age: seven medulloblastomas, three anaplastic ependymomas (E IIIs), two each of supratentorial primitive neuroectodermal tumors (sPNETs) and choroid plexus carcinomas (CPCs), and one each of neuroblastoma and pineoblastoma. Immunohistochemistry for glial fibrillary acidic protein, vimentin, epithelial membrane antigen, smooth muscle actin and cyclin D1 was performed. Polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis with direct sequencing, differential PCR and microsatellite analysis were conducted for hSNF5/INI1mutation, homozygous deletion and loss of heterozygosity (LOH) on 22q, respectively. Because of the presence of rhabdoid cells and the polyimmunophenotypic features, the diagnosis was revised to AT/RT in five (31%) tumors, namely, two E IIIs and one each of medulloblastoma, CPC and pineoblastoma. Three of them harbored such hSNF5/INI1 aberrations as germline single base deletion (492/6 delC) and missense mutation (C157T) together with LOH 22q or homozygous deletion. Cyclin D1 was overexpressed in those three tumors but not in the two that lacked hSNF5/INI1 inactivation. CONCLUSION: AT/RT can be misdiagnosed as a variety of tumors, including ependymoma that potentially harbors LOH 22q. Our data indicate that cyclin D1 is a target of hSNF5/INI1in primary tumors.

Central Nervous System Neoplasms↗
PubMed2004

Recommendations for the reporting of bone tumors. Association of Directors of Anatomic and Surgical Pathology.

The diagnosis of a bone tumor is often an arduous task, even for the most experienced orthopedic pathologist. As a starting point, the classification of bone tumors is based on a histogenetic perspective encompassing the type of matrix produced (or not produced) by the tumor. In general, the surgical pathology report should include data pertinent to the treatment and prognostication of an individual patient, and the report should be delivered to the clinician in a clear, concise fashion. Reporting of most bone tumors is similar and includes such information as the type of surgery done, anatomic site, histological type and grade of the tumor (if applicable), and the adequacy of surgical margins. Special emphasis is needed for those tumors with distinct and well-established prognostic and therapeutic features such as osteosarcoma and Ewing's sarcoma/peripheral neuroectodermal tumor. Our recommendation emphasizes a standardized protocol for these sarcomas, especially in light of evidence that postchemotherapeutic tumor necrosis is of prognostic significance. It is also important to note that radiographic imaging plays a very important, often critical, role in allowing the pathologist the opportunity to reach the best final diagnosis. This is especially true when a malignant interpretation is contemplated and in subtyping lesions. We recommend close collaboration between musculoskeletal radiologists, clinicians, and pathologists when dealing with complicated neoplasms of bone.

Bone Neoplasms↗
PubMed1999

Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations.

The hSNF5/INI1 gene which encodes a member of the SWI/SNF chromatin ATP-dependent remodeling complex, is a new tumor suppressor gene localized on chromosome 22q11.2 and recently shown to be mutated in malignant rhabdoid tumors. We have searched for hSNF5/INI1 mutations in 229 tumors of various origins using a screening method based on denaturing high-performance liquid chromatography. A total of 31 homozygous deletions and 36 point alterations were identified. Point mutations were scattered along the coding sequence and included 15 nonsense, 15 frameshift, three splice site, two missense and one editing mutations. Mutations were retrieved in most rhabdoid tumors, whatever their sites of occurrence, indicating the common pathogenetic origin of these tumors. Recurrent hSNF5/INI1 alterations were also observed in choroid plexus carcinomas and in a subset of central primitive neuroectodermal tumors (cPNETs) and medulloblastomas. In contrast, hSNF5/INI1 point mutations were not detected in breast cancers, Wilms' tumors, gliomas, ependymomas, sarcomas and other tumor types, even though most analyzed cases harbored loss of heterozygosity at 22q11.2 loci. These results suggest that rhabdoid tumors, choroid plexus carcinomas and a subset of medulloblastomas and cPNETs share common pathways of oncogenesis related to hSNF5/INI1 alteration and that hSNF5/INI1 mutations define a genetically homogeneous family of highly aggressive cancers mainly occurring in young children and frequently, but not always, exhibiting a rhabdoid phenotype.

Chromatography, High Pressure Liquid↗
PubMed2003

Recent advances in pediatric renal neoplasia.

Over the past 6 years, molecular genetic studies have significantly advanced our understanding of pediatric renal neoplasms. The cellular variant of congenital mesoblastic nephroma (but not the classic variant) has been shown to bear the same t(12;15)(p13;q25) and ETV6-NTRK3 gene fusion as infantile fibrosarcoma, a tumor with which it shares morphologic and clinical features. Rhabdoid tumor of the kidney is characterized by deletion of the hSNF5/INI1 gene, which links it to other rhabdoid tumors of infancy that arise in the soft tissue and brain. Primary renal synovial sarcomas and renal primitive neuroectodermal tumors have become accepted entities, and likely comprise a subset of what had previously been termed "adult Wilms tumor." Renal carcinomas associated with Xp11.2 translocations that result in fusions involving the TFE3 transcription factor gene have been delineated, including a distinctive neoplasm that shares the identical gene fusion as alveolar soft part sarcoma. Most recently, a distinctive type of renal neoplasm with a t(6;11)(p21;q12) has been described, and the cloning of the resulting gene fusion links it to the Xp11 translocation carcinomas. Together, these last two translocation-associated tumors represent a significant proportion of pediatric renal cell carcinomas. This review highlights each of these recent advances.

Adolescent↗
PubMed1986

Mural tumors with cysts in the cerebral hemispheres of children.

Thirteen infants and children with mural tumors (i.e., cysts with mural nodules) in the cerebral hemisphere are presented. The tumors comprise five benign astrocytomas, three ependymomas, two choroid plexus papillomas, one oncocytoma, one hamartoma, and one primitive neuroectodermal tumor. Computed tomography showed well-enhanced mural nodules. Cyst walls did not enhance in any but one, in which the enhancement was attributed to hemorrhage in the cyst. None of the cyst walls contained neoplastic cells. Cerebral angiography was performed in all patients, and five showed extensive vascularity in the tumor nodule. The importance of preoperative angiography is emphasized. Total extirpation of the mural nodule without excision of the cyst wall led to excellent prognosis for these patients.

Adenoma↗
PubMedDate not supplied

Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood.

In 1987, a distinctive brain tumor arising in young children was first described. This tumor contained neuroepithelial, peripheral epithelial, and mesenchymal elements, but lacked divergent tissue differentiation characteristic of malignant teratomas. It was originally designated as atypical teratoid tumor, but because of the prominent rhabdoid component, the tumor designation was modified to atypical teratoid/rhabdoid tumors (AT/RT) of infancy and childhood. AT/RTs occur most commonly in infants under 2 years of age, often have central nervous system (CNS) dissemination, do not respond to therapy, and typically are fatal within 1 year. Most are located in the cerebellum (65%), but they may arise at any CNS site. Histologically, various patterns can be present within the same tumor, but they all have a population of rhabdoid cells, and 70% contain fields typical of a primitive neuroectodermal tumor (PNET/medulloblastoma). Less frequently, malignant mesenchymal tissue and/or an epithelial component are found. Necrosis and brisk mitotic activity are common. The immunocytochemical profile is complex, but germ cell markers are consistently negative. Ultrastructural features vary and depend on the site sampled, but whorled bundles of cytoplasmic intermediate filaments are a distinctive finding in cells of the rhabdoid component. The authors report 4 AT/RTs (2 males, 2 females, age range 6 months to 4 1/2 years, 3 cerebellar, 1 cerebral). All cases showed a variety of histologic patterns with necrosis. Typical rhabdoid cells, PNET areas, undifferentiated bland large cell regions, dense connective tissue, and solid clusters of epithelial cells were present. Immunocytochemistry showed strong vimentin reactivity, whereas epithelial membrane antigen, cytokeratin, glial fibrillary acidic protein, S-100 protein, desmin, and smooth muscle actin were present to a lesser extent in most cases. Germ cell markers were negative. Ultrastructurally, many cells contained aggregates of cytoplasmic intermediate filaments, and some cells had a basal lamina on one aspect. Cells with interdigitating cytoplasmic borders were seen and rare cells had microtubules. Cytogenetic studies were normal in 2 cases. Follow-up has shown that 3 children have died of disease (< 1 year after diagnosis) and 1 child is alive with disease (18 months after diagnosis). Separation of AT/RT from PNET based on histopathologic and biologic evaluation is important, because AT/RTs are aggressive tumors with a dismal prognosis and currently there is no effective treatment. Neither clinical signs and symptoms nor radiologic features will distinguish AT/RTs from PNETs.

Brain Neoplasms↗
PubMed2001

Cerebellar liponeurocytoma. Case report and review of the literature.

Cerebellar liponeurocytoma is a rare tumor of the posterior fossa that has many morphological similarities to medulloblastoma and neurocytoma. Recently the World Health Organization working group for classification of central nervous system neoplasms adopted the term "cerebellar liponeurocytoma" to provide a unified nomenclature for a tumor variously labeled in the literature as lipomatous medulloblastoma, lipidized medulloblastoma, medullocytoma. neurolipocytoma, lipomatous glioneurocytoma, and lipidized mature neuroectodermal tumor of the cerebellum. The rarity of this tumor and paucity of pertinent information regarding its biological potential and natural history have resulted in the application of various treatment modalities. It is suggested in the available literature that these lesions have a much more favorable prognosis than typical medulloblastomas, and that adjuvant therapy for liponeurocytoma need not be as extensive as that administered for medulloblastomas.

Aged↗