Children's Cancer and Leukaemia Group (CCLG): guidelines for the management of intracranial meningioma in children and young people.

Primary tumours of the meninges occur extremely rarely in children and young people (less than five new cases annually in the UK) and have remained a poorly defined group compared with the common diagnosis of meningiomas in adults. Because of the rarity in children, paediatric meningiomas are often treated according to the adult practice. This may lead to inappropriate treatment considerations since paediatric meningiomas exhibit peculiarities that distinguish them from their adult counterpart. Striking the balance between late toxicities of adjuvant radiotherapy on the growing brain versus the risk of repeated recurrences necessitating surgical interventions in young patients is of importance and will require a clinical decision making process in the paediatric neuro-oncological/neurosurgical MDT tailored to each patient's age and clinical setting. The paediatric literature is based on small, single institution retrospective studies over extensive time periods during which the imaging facilities, pathological criteria and surgical advances have led to shifts in definitions of disease making comparison of results difficult to interpret. These guidelines have been developed following a comprehensive appraisal of the literature. Primary treatment is surgical resection. Careful pathological review and multidisciplinary discussions should be undertaken before considering postoperative treatment, such as radiotherapy for histologically anaplastic or clinically aggressive, relapsing meningioma.

The Children's Cancer and Leukaemia Group guidelines for the diagnosis and management of dysembryoplastic neuroepithelial tumours.

Dysembryoplastic neuroepithelial tumours (DNETs) were incorporated into the new World Health Organization classification of brain tumours as part of the group of glioneuronal tumours in 1993. Large series of patients with DNETs and pharmaco-resistant epilepsy have been reported. DNETs are most often located in the temporal lobe, occurring in both mesial and lateral temporal locations. DNETs have also been reported in the insular cortex, brain stem, cerebellum, occipital lobe and striatum. Approximately 40% of DNETs are cystic, and solitary nodular, multinodular or diffuse forms have been recognized. Approximately 30% of DNETs are associated with subtle cortical dysplastic changes in the adjacent cortex. DNET nodules usually look like oligodendroglioma, whilst between the nodules it may be possible to recognize vertical columns of neurons surrounded by oligodendrocyte-like cells. Cytologically, oligodendroglial-like cells of DNETs are distinguished from oligodendroglioma by larger nuclei with frequent nuclear indentations and multiple, small nucleoli, whilst oligodendrogliomas consistently show nuclear roundness with one or two occasional nucleoli. Very rare cases of malignant transformation have been reported. DNETs are hypodense on CT and demonstrate decreased signal on the T1-weighted images and a hyper-intense signal on T2-weighted MRI. DNETs associated with pharmaco-resistant epilepsy should be removed early to achieve seizure freedom and prevent tumour progression. The surgical approach should be that of an extended lesionectomy, i.e. excision of the lesion and the abnormal dysplastic cortex around it. Use of MRI-based image guidance (neuronavigation) as a surgical tool to identify this area of abnormal cortex is very helpful to ensure that the extended lesionectomy includes any visibly dysplastic cortex. It is not advocated to use a stereotactic biopsy only, as this may generate an unrepresentative tissue sample consisting of an oligodendroglial component only and may lead to an incorrect diagnosis.

The acridonecarboxamide GF120918 potently reverses P-glycoprotein-mediated resistance in human sarcoma MES-Dx5 cells.

The doxorubicin-selected, P-glycoprotein (P-gp)-expressing human sarcoma cell line MES-Dx5 showed the following levels of resistance relative to the non-P-gp-expressing parental MES-SA cells in a 72 h exposure to cytotoxic drugs: etoposide twofold, doxorubicin ninefold, vinblastine tenfold, taxotere 19-fold and taxol 94-fold. GF120918 potently reversed resistance completely for all drugs. The EC50s of GF120918 to reverse resistance of MES-Dx5 cells were: etoposide 7+/-2 nM, vinblastine 19+/-3 nM, doxorubicin 21+/-6 nM, taxotere 57+/-14 nM and taxol 91+/-23 nM. MES-Dx5 cells exhibited an accumulation deficit relative to the parental MES-SA cells of 35% for [3H]-vinblastine, 20% for [3H]-taxol and [14C]-doxorubicin. The EC50 of GF120918, to reverse the accumulation deficit in MES-Dx5 cells, ranged from 37 to 64 nM for all three radiolabelled cytotoxics. [3H]-vinblastine bound saturably to membranes from MES-Dx5 cells with a KD of 7.8+/-1.4 nM and a Bmax of 5.2+/-1.6 pmol mg(-1) protein. Binding of [3H]-vinblastine to P-gp in MES-Dx5 membranes was inhibited by GF120918 (K = 5+/-1 nM), verapamil (Ki = 660+/-350 nM) and doxorubicin (Ki = 6940+/-2100 nM). Taxol, an allosteric inhibitor of [3H]-vinblastine binding to P-gp, could only displace 40% of [3H]-vinblastine (Ki = 400+/-140 nM). The novel acridonecarboxamide derivative GF120918 potently overcomes P-gp-mediated multidrug resistance in the human sarcoma cell line MES-Dx5. Detailed analysis revealed that five times higher GF120918 concentrations were needed to reverse drug resistance to taxol in the cytotoxicity assay compared to doxorubicin, vinblastine and etoposide. An explanation for this phenomenon had not been found.

Desmoplastic small round cell tumour of childhood: a report of four cases demonstrating wider clinical features and variable outcome.

Purpose. Four further cases of desmoplastic small round cell tumour with multi phenotypic differentiation are described.Subjects. Two patients were typical (male, adolescent with peritoneal tumour and, in one case, liver metastases) and did not respond well to treatment. Two other patients showed less usual features (young, female with retroperitoneal disease, both with intraspinal extension and renal tract obstruction). Both responded favourably to multi-modal treatment regimens including extensive and invasive supportive care.Results. Histologically, all tumours showed clear features of this diagnosis, namely angulated nests of small cells in a background of fibrovascular stroma. Immunohistochemistry typically showed divergent differentiation with neural, muscle and epithelial marker positivity. All four tumours stained positive for the Wilms' tumour 1 suppressor gene product. Electron microscopy showed intercellular tight junctions, cytoplasmatic intermediate filaments and absence of microvilli. Rare neurosecretory-type granules were observed.Discussion. These cases illustrate a broader spectrum of clinical presentation than previously associated with this diagnosis.