Low-grade spinal glioneuronal tumors with BRAF gene fusion and 1p deletion but without leptomeningeal dissemination

Excerpt

Concurrent KIAA1549-BRAF fusion and chromosome 1p deletion with or without concomitant chromosome 19q loss are recurrent molecular alterations in the diffuse leptomeningeal glioneuronal tumor (DLGNT) [6, 7, 10], in which widespread leptomeningeal dissemination is a diagnostic feature [1, 6, 10]. We have reviewed five spinal cord tumors (Table 1) that show the morphologic and molecular genetic characteristics of DLGNT, but in which radiographically apparent leptomeningeal dissemination was not identified at presentation. At the initial review, we sought to understand the relationship between these tumors and DLGNT by undertaking immunohistochemical analyses with a panel of neural markers: GFAP, OLIG2, and synaptophysin, and with antibodies to the BRAF V600E, histone H3.1/H3.3 K27 M, and IDH1 R132H mutant proteins. Duplication of chromosome 7q34 (a surrogate marker for the presence of KIAA1549-BRAF fusion) and deletion of chromosome arms 1p and 19q were examined by interphase fluorescence in situ hybridization (iFISH). The presence of KIAA1549-BRAF fusion transcripts was also tested by reverse transcription polymerase chain reaction (RT-PCR). We collected relevant clinical information and follow-up radiologic studies to characterize the tumors’ clinical behavior and tendency for leptomeningeal dissemination. …