gms | German Medical Science

Objective: Pediatric glioblastomas (PGBM) accounts for less than 3% of all primary CNS tumors among children with an incidence between 4,5 and 8,8%. The classification of brain tumors based so far on histology and has been fundamentally changed by molecular data. The histological appearance of these tumors is malignant, but molecularly there are distinct entities with divergent biology and different prognosis. We here report5 cases that were initially diagnosed as pGBM whose diagnosis changed significantly after molecular analysis.

Methods: Five children were included, aged between 7 and 17 years. The neuropathology of case 1 was a mesencephalic GBM WHO IV (central view: anaplastic astrocytoma III), case 2 a GBM WHO IV of the right cerebellar peduncle, case 3 a left frontal GBM with giant cells WHO IV and case 4 a right parieto-occipital anaplastic astrocytoma III. Case 5 was a (insert location) left frontal GBM IV. Case 1, 2 and 5 were incompletely resected, case 3 and 4 were completely resected. All cases were treated by chemo- and /radiotherapy after surgery.

Results: Diagnoses and/or prognoses changed significantly after molecular profiling: case 1, 2 and 4 were reclassified as low grade gliomas, and case 3 as a pleomorphic malignant glioma with germline alteration and case 5 unchanged GBM WHO IV. DNA sequencing revealed important molecular alterations in 3 cases: a TP53 mutation (tumor and germline) in the pleomorphic malignant glioma (case 3), a BRAF V 600E mutation in case 4 (pilocytic astrocytoma), and an IDH1 mutation in case 5. Follow up revealed stable disease or complete remission, respectively, over 7 years in case 1, 2 and 4, a complete remission over 2,5 years in case 3, and a stable disease over 2 years in case 5.

Conclusion: PGBMs are distinct from adult GBMs and molecular analysis can identify miss-classified low grade tumors, underlying cancer predisposition syndromes, and molecular subgroups with better prognosis. All these factors significantly impact patient management, by either informing first-line treatment specialized follow up screening or patient information about prognosis. In conclusion molecular diagnostics, from the appropriate collection of material in the OR, specialized shipment, to availability of molecular diagnostics in neuropathology.