Malignant progression of a pleomorphic xanthoastrocytoma in a child.

Pleomorphic xanthoastrocytoma (PXA) is a recently recognized rare cerebral neoplasm that predominantly affects young patients. We report on the case of a 3-year-old boy who presented with a 2-week history of headaches and seizures. Radiological investigation revealed a lesion in the right parietal-occipital lobe. The lesion was excised and histology disclosed the presence of a PXA with anaplastic features. 1 year later follow-up magnetic resonance imaging (MRI) revealed tumor relapse. An MRI of the spine was also performed and demonstrated leptomeningeal dissemination. The patient underwent a second operation. Histology revealed that the presence of a malignant PXA with anaplastic features. The patient received radiotherapy and 9 months later on follow-up MRI a new tumor recurrence was noted. A third craniotomy was performed and the tumor removed. Histological examination revealed dedifferentiation to glioblastoma multiforme. The patient was referred to the oncology department and received chemotherapy with temozolamide. 8 months later the patient was stable without tumor recurrence. PXAs require close follow-up because of their unpredictable biological behaviour.

[Surgical treatment of grade 5 arteriovenous malformation in a girl]. / Tratamiento quirúrgico de malformaciones arteriovenosas grado V en una niña.

We report on a case of a 12-year-old girl that was admitted under our care complaining of headache for over a month which was accompanied by vomiting and diplopia over the last 10 days. On neurological examination a right upper limb tremor and cervical rigidity were noted. CT and MRI scan was performed and revealed a giant left frontotemporal lesion. The lesion was heterogenous with calcifications and hemosidirin, surrounded by brain swelling and causing midline shift. There was little enhancement after gadolinium administration. The last finding led us to consider the presence of a vascular abnormality as a possible diagnosis. The patient was operated upon via a left fronto-temporal craniotomy. We managed to excise the lesion totally. Histopathology revealed the presence of an AVM. Postoperatively the patient was neurologically intact but a subcutaneous collection of CSF was noted that was successfully treated by drainage. Although surgical treatment of deeply seated giant AVM's in the dominant hemisphere of speech and motor-sensory area have a relative high proportion of postoperative neurological deficit, careful surgical intervention can produce excellent outcome.

Histone deacetylase inhibitors in APL and beyond.

In recent years the study of chemical modifications to chromatin and their effects on cellular processes has become increasingly important in the field of cancer research. Disruptions to the normal epigenetic pattern of the cell can serve as biomarkers and are important determinants of cancer progression. Accordingly, drugs that inhibit the enzymes responsible for modulating these epigenetic markers, in particular histone deacetylases, are the focus of intense research and development. In this chapter we provide an overview of class I and II histone deacetylases as well as a guide to the diverse types of histone deacetylase inhibitors and their activities in the context of APL. We also discuss the rationale for the use of histone deacetylase inhibitors in combination therapy for the treatment of cancer and the current status of clinical trials.

MicroRNA expression profiles in pediatric dysembryoplastic neuroepithelial tumors.

Among noncoding RNAs, microRNAs (miRNAs) have been most extensively studied, and their biology has repeatedly been proven critical for central nervous system pathological conditions. The diagnostic value of several miRNAs was appraised in pediatric dysembryoplastic neuroepithelial tumors (DNETs) using miRNA microarrays and receiving operating characteristic curves analyses. Overall, five pediatric DNETs were studied. As controls, 17 samples were used: the FirstChoice Human Brain Reference RNA and 16 samples from deceased children who underwent autopsy and were not present with any brain malignancy. The miRNA extraction was carried out using the mirVANA miRNA Isolation Kit, while the experimental approach included miRNA microarrays covering 1211 miRNAs. Quantitative real-time polymerase chain reaction was performed to validate the expression profiles of miR-1909* and miR-3138 in all samples initially screened with miRNA microarrays. Our findings indicated that miR-3138 might act as a tumor suppressor gene when down-regulated and miR-1909* as a putative oncogenic molecule when up-regulated in pediatric DNETs compared to the control cohort. Subsequently, both miRNA signatures might serve as putative diagnostic biomarkers for pediatric DNETs.

Epidemiology of pediatric brain tumors in Greece (1991-2008). Experience from the Agia Sofia Children's Hospital.

BACKGROUND: We set out to determine the epidemiology of pediatric brain tumors in a single Greek institute. METHODS: We reviewed all cases of brain tumors in children, under the age of 15 years, that were treated surgically in the Neurosurgical Department of Children's Hospital "Agia Sofia", between January 1991 and December 2008. RESULTS: From January 1991 through December 2008, we encountered 335 cases of pediatric brain tumors. The mean age was 7.2 years and there was a slight male predominance. Astrocytomas made up the largest component, with pilocytic astrocytomas accounting for 25.6% of all tumors. The second most common entity was medulloblastoma, accounting for 18% of all tumors, whereas ependymomas were the third most frequent tumor. There was an increase in the total number of brain tumors during the last decade. Furthermore, examining low-grade astrocytoma, medulloblastoma and ependymoma trends over the last 2 decades, we found a trend for a decrease of low-grade astrocytomas and an increase of the more aggressive medulloblastomas and ependymomas. CONCLUSION: This study presents the first epidemiological data of pediatric brain tumors in Greece. Astrocytomas were the most common tumor followed by medulloblastomas and ependymomas. Furthermore, a trend for an increase of malignant tumors over the last decade has been observed.

Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors.

Raf/MEK/ERK and phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) cascades are key signalling pathways interacting with each other to regulate cell growth and tumourigenesis. We have previously shown B-Raf and Akt overexpression and/or overactivation in pituitary adenomas. The aim of this study is to assess the expression of their downstream components (MEK1/2, ERK1/2, mTOR, TSC2, p70S6K) and effectors (c-MYC and CYCLIN D1). We studied tissue from 16 non-functioning pituitary adenomas (NFPAs), six GH-omas, six prolactinomas and six ACTH-omas, all collected at transsphenoidal surgery; 16 normal autopsy pituitaries were used as controls. The expression of phospho and total protein was assessed with western immunoblotting, and the mRNA expression with quantitative RT-PCR. The expression of pSer217/221 MEK1/2 and pThr183 ERK1/2 (but not total MEK1/2 or ERK1/2) was significantly higher in all tumour subtypes in comparison to normal pituitaries. There was no difference in the expression of phosphorylated/total mTOR, TSC2 or p70S6K between pituitary adenomas and controls. Neither c-MYC phosphorylation at Ser 62 nor total c-MYC was changed in the tumours. However, c-MYC phosphorylation at Thr58/Ser62 (a response target for Akt) was decreased in all tumour types. CYCLIN D1 expression was higher only in NFPAs. The mRNA expression of MEK1, MEK2, ERK1, ERK2, c-MYC and CCND1 was similar in all groups. Our data indicate that in pituitary adenomas both the Raf/MEK/ERK and PI3K/Akt/mTOR pathways are upregulated in their initial cascade, implicating a pro-proliferative signal derangement upstream to their point of convergence. However, we speculate that other processes, such as senescence, attenuate the changes downstream in these benign tumours.

Primary cystic midline lesions of the brain in childhood.

It is known that primary cystic lesions of the midline of the brain in infants and children are not rare. In some cases these cystic lesions are considered to be the main cause in the production of hydrocephalus. The use of CT-scan tomography and CT scan metrizamide cisternography helped us to reveal some unsuspected cases of them. Our operative approach of these cystic lesions of the midline of the brain is described.

Action of intermediate doses of methotrexate on dihydrofolate reductase in malignant diseases.

This report describes the effect of intermediate methotrexate (MTX) doses on dihydrofolate reductase (DHFR) activity in vivo in the leukocytes of 16 children with malignant diseases. The authors used a cytochemical technique, and the enzyme was studied in intact cells. The treatment protocols included MTX 500 mg-2 g/m2 weekly with leucovorin rescue. The above doses of MTX partially inhibit DHFR. The reduction of enzyme activity was observed in leukocytes within 24 h after MTX infusion, and it was more obvious in the polymorphonucleas and the monocytes. Complete inhibition of enzyme activity was not observed. These results do not agree with those of previous reports using biochemical techniques, which showed that small amounts of MTX inhibit DHFR activity. Even the large doses of MTX used in this study do not completely inhibit enzyme activity. It would be worthwhile to test the effect of even larger doses of MTX to find out if DHFR activity is inhibited.

Familial medulloblastoma.

Medulloblastomas account for 20% of all primary brain tumors. The vast majority of them are sporadic. Familial medulloblastoma is very rare--only a few cases have been reported worldwide. Most were observed in siblings of the same sex. The affected children presented at various ages and all of them have died, usually within the first 2 years following diagnosis. The authors describe a case of familial medulloblastoma with unusual characteristics: Two siblings of different sex and a second-degree relative have presented at exactly the same age of 18 months. The histologic pattern was the same in all patients, that of desmoplastic medulloblastoma. All patients are alive and remain in remission 12, 5, and 11 years, respectively, after diagnosis. The genetics and the pathogenesis of the disease remain obscure.