Desmoplastic infantile astrocytoma/ganglioglioma with rare BRAF V600D mutation. Issue 6 (10th November 2016) - Greer, Ashley
Abstract: Background: Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile gangliogliomas (DIGs) are rare, massive, cystic and solid tumors of infants usually found in superficial cerebral hemispheres. They manifest prominent desmoplastic stroma, admixed neoplastic astrocytes, primitive‐appearing small cells, and additional neoplastic ganglion cells in the case of DIGs. While v‐Raf murine sarcoma viral oncogene homolog B ( BRAF ) mutation is found in up to 50% of pediatric gangliogliomas, two recent studies found that it was rare in DIA/DIGs; we sought to assess BRAF status in DIA/DIGs from our institution. Procedure: Departmental files from 2000 to 2016 were reviewed to identify cases. Clinical, neuroimaging, histological, and immunohistochemistry (IHC) features were assessed; the latter included IHC for astrocytic and neuronal markers and BRAF VE1. BRAF mutational assessment by Sanger and next‐generation sequencing was attempted in all cases. Results: All six identified cases (four males–two females; three DIA–three DIG) occurred in children <1‐year old, were large, cerebral‐hemispheric, cystic and solid, and enhancing tumors. Only one case, a DIG with prominent aggregates of neoplastic ganglion cells, showed either BRAF VE1 IHC positivity or mutation by Sanger and next‐generation sequencing (rare c. 1799_1800delinsAT; p. V600D). Four of six archival cases were BRAF VE1 IHC negative, but failed mutational sequencing. Conclusion: Five of six classic DIA/DIGs were negative for BRAF mutation; previous series have identified BRAF mutation in two of 18 and one of 14 cases, although all were the more common BRAF V600E. We were unable to find other examples of glial tumors in public databases with this rare BRAF V600D mutation. Identification of BRAF mutational opens the possibility of BRAF‐targeted therapies for the subset of DIA/DIG that clinically progress postresection.