DIG (Desmoplastic Infantile Ganglioglioma) is a rare intracranial neoplasm classified as WHO grade I tumor under neuronal and mixed neuronal glial tumors (under 2007 World Health Organization brain tumor classification).It is usually considered to have a good prognosis but 40% of the cases require additional medical, radiation and/or further surgical intervention and 15% of infants and children develop leptomeningeal spread or die from DIG.We report a case of DIG presenting at 2 mo of age that showed aggressive behavior, requiring debulking at 2.5 mo age and subsequently at 10 mo age following a tumor recurrence.Chemotherapy following surgery was successful in suppressing the tumor growth for 7.5 yrs.He then presented with malignant transformation into glioblastoma.Successful debulking followed by chemotherapy was given.At 1 yr follow up, the child had moderate neurological deficits but had a subsequent rapid progression and died.Chromosome microarray analysis (CMA) using oligo array performed on the biopsy specimen obtained at 2 mo age did not show any significant abnormality.However, CMA of the glioblastoma was very abnormal showing significant genomic deletions and duplications.Genomic next generation sequencing showed a somatic single nucleotide non-synonymous variant, p.R248Q in Exon 7 of TP53 in the primary DIG and the GBM tumors.The non-synonymous variant in TP53 gene is predicted to be deleterious, altering the structure of the L2/L3 motif of the DNA binding domain tp53 protein.The TP53 gene which is a known primary site of genetic alteration that predisposes to malignant tumors provides a reason for the transformation of DIG to glioblastoma in our case.Therefore, molecular genetic testing is recommended on some DIG tumors which may provide a prognostic biological marker.

BACKGROUND: To describe therapeutic approaches in children with atypical Teratoid Rhabdoid Tumours (ATRT) in France.METHODS: Observational study including all children less than 18 years old diagnosed with ATRT in France between 2009 and 2011.RESULTS: Forty seven children were included in this retrospective study.Six patients received no curative treatment while forty-one patients had a curative project.Median age was 1.5 years (range 0-16).The disease was disseminated in 10 patients.Surgical resection was complete in 21 cases.Chemotherapy was administered in 41 children.Twenty-six patients received upfront Vincristine-Methotrexate (5g/m 2 x 3) with intra-thecal Methotrexate, which was stopped in eleven patients: in four cases the disease progressed and in seven cases the toxicities were manageable.Fifteen children received different chemotherapy courses and in four of them the diseases progressed.Eight patients underwent second-look surgery.Radiotherapy was administered in 17 patients at a median time of 19 weeks (13-44) after diagnosis.High-dose chemotherapy (HDCT) was given in 9 children and maintenance therapy in 5 children, starting at respectively 35 and 42 weeks after diagnosis.Median follow-up was 26 months (0.6-47).Median time for progression was 5 months.Two-years overall survival was 32% + /-8%.Median survival was 8 months.DISCUSSION: The survival rate of children with ATRT remains poor, the addition of VM is easily manageable but its benefit remains uncertain.The disease progressed mostly before radiotherapy.Future trials should focus on the delay of radiotherapy and the benefit of HDCT.

There is little literature to guide therapy in children and young adults with intracranial germ cell tumors. We present 17 consecutively diagnosed intracranial germ cell tumors at The Children's Hospital, Denver, from 1995 to 2001. Of 17 patients, 3 had considerable delay in diagnosis. Two with suprasellar tumors presented with dementia, blindness and pan-hypopituitarism and another with recurrent subarachnoid hemorrhage. Seven had germinoma, three were metastatic at diagnosis. Ten had non-germinomatous germ cell tumors (NGGCT), 5/10 were alpha feto-protein (AFP) positive only, one β-human chorionic growth (βHCG) factor positive only, 3 positive for AFP and βHCG, and 1 malignant teratoma. Therapy for metastatic patients consisted of chemotherapy followed by craniospinal radiation (CSI). Patients with localized disease received chemotherapy followed by focal radiation. Two patients received chemotherapy only, one because she died of sepsis while receiving chemotherapy and one because of neurologic injury incurred during surgery parents elected for no therapy. Three patients have died, one of tumor recurrence, one from a remote complication of surgery and one of sepsis. Twelve patients are alive without evidence of disease from 10 to 68 months (median 31.5 months). All five children with only AFP positivity, treated with chemotherapy and focal radiation are alive without evidence of disease at 10, 16, 22, 41 and 41 months. Thus, there is little evidence that CSI is necessary in non-metastatic germinomas and AFP positive NGGCTs when combined chemotherapy and radiation therapy is used. However, complications of delayed diagnosis, surgery and chemotherapy are important causes of mortality, with only one patient dying of tumor.