Abstracts

Rationale:
Low-grade epilepsy-associated neuroepithelial tumors (LEAT) were the second most common histopathological diagnosis in epilepsy surgery. LEAT includes low-grade gliomas (LGGs) and low-grade glioneuronal tumors (LGNTs), present an important group of central nervous system (CNS) neoplasm in children and young adults. Genotype-pathological correlation is not evident in LEAT. The inconsistent genotype-pathological correlation partly stems from the difficulty in pathological diagnosis of LEAT.  If, only a part of the tumor obtained at surgery, pathological diagnosis is more difficult because LEAT has polymorphous pathohistological features. The above issue motivated us to investigate the correlation of genotypes to neuroimaging findings in LEAT. Imaging study is advantageous in that it captures the entire picture of tissue characteristics. To date, no studies have been conducted to investigate the association between neuroimaging and genotype in LEAT. This study aimed to evaluate the association between neuroimaging and DNA mutation pattern of LEAT. We included only patients with drug-resistant epilepsy to this study because epilepsy is the essential phenotype associated with treatment decisions in patients with LEAT.
Method:
Cases were identified retrospectively from the neuropathology database at the National Center Hospital, National Center of Neurology and Psychiatry. Surgical treatment was performed after a comprehensive pre-surgical evaluation of epilepsy including MRI and long-term video-EEG monitoring in all cases. Inclusion criteria were as follows: (1) who exhibited histopathologically confirmed low-grade neuroepithelial tumor: (2) who agreed in writing to participate in this study  :(3) sufficient amount of tumor tissue could be available. :(4) the tumor genotype was identified. :(5) preoperative T2-weighted, FLAIR and T1-weighted images were available. :(6) myelination was complete on imagings. One patient with coexisting white matter disease was excluded. Finally, a total of 41 cases (male: 21, female: 20) were included. Mean age was 13.5 (1-34) years old. DNA was extracted either from frozen tissue or formalin-fixed paraffin-embedded (FFPE) tissue. All samples were analyzed with Multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS). FGFR1-TKD duplication, KIAA1549-BRAF fusion and NF1 mutation were confirmed with the sanger sequence. Pre-operative neuroimaging studies were reviewed independently by three experienced neuroradiologists.
Results:
Genotypes of our study subjects included 27 cases with BRAF V600E mutation, 6 cases with FGFR1-TKD duplication, 2 cases with FGFR1 point mutation, and the remaining 6 cases had other different genotypes, respectively. Two types of neuroimaging patterns were identified in BRAF V600E mutant LEAT (n = 27). One type was characterized by a wedge- or band-shaped high-intensity lesion on T2WI, FLAIR or DIR (double inversion recovery) with indistinct tumor border (n=25). Another was a well-defined, round-shaped mass (n=2). The cases with both FGFR1-TKD duplication and FGFR1 point mutation showed the same neuroimaging pattern (n = 8). The tumor showed exophytic growth and its intensity was  very high on T2WI and  heterogeneous on FLAIR with hyperintensity rim, and it extended along the white matter tract. Those neuroimaging features were found in none of the remaining 6 cases.
Conclusion:
The specific neuroimaging patterns of BRAF V600E mutant and FGFR1 mutant  LEAT were revealed.
Funding:
:Japan Agency for Medical Research and Development, 18059168