Abstracts

Rationale: Low-grade epilepsy-associated neuroepithelial tumors (LEAT) 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 classic pathological diagnosis of LEAT. To resolve above issues, we investigated the association of genotypes with neuroimaging features in LEAT. To date, no studies have been conducted to investigate the association between neuroimaging and genotype in LEAT. Furthermore, we validate the association between neuroimaging and genotypes by modern pathological evaluation.

Methods: Patients were identified retrospectively from the neuropathology database. Surgical treatment was performed after a comprehensive pre-surgical evaluation of epilepsy including MRI and long-term video-EEG monitoring in all cases. 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 formalinfixed paraffin-embedded (FFPE) tissue. All samples were analyzed with Multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS). Pre-operative neuroimaging studies were reviewed independently by three neuroradiologists. Histopathological diagnoses were determined by three neuropathologists. Diffuse glioneuronal tumor (d-GNT) was further divided into the following two subcategories according to the result of the immunohistochemistry with the anti-BRAF V600E antibody (VE1); dGNT-VE1+ and dGNT-VE1-.

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. The imaging features were classified into four groups: Group 1, focal cortical dysplasia (FCD)-like tumors; Group 2, ganglioglioma-like tumors; Group 3, DNT-like tumors; and Group 4, other tumors. The neuroimaging features of Group 1 FCD-like and Group 2 ganglioglioma-like tumors were associated with BRAF V600E mutation, and Group 3 DNT-like tumors were associated with FGFR1 mutation with 100% sensitivity and specificity. Group 4 tumors were associated with various genetic mutations which were different from those in Groups 1 to 3. The histopathological diagnoses in Group 1 were diffuse glioneuronal tumor (dGNT)-VE1+ (n = 24) and pleomorphic xthantoastrocytoma (n = 1). Two cases in Group 2 were dGNT-VE1+ (n = 1) and ganglioglioma (n = 1). The histopathological diagnoses in Group 3 were low-grade diffuse glioma with myxoid degeneration (n = 6) carrying FGFR1-TKD duplication and rosette-forming glioneuronal tumor (n = 2) having FGFR1 point mutations.

Conclusions: We found genotype-specific neuroimaging features with BRAF V600E or FGFR1 mutations, which were also associated with histopathology. These findings may help establishing accurate diagnoses and appropriate classification of LEAT as well as optimal patient care.

Funding: Please list any funding that was received in support of this abstract.: This study was supported by a grant from the Japan Agency for Medical Research and Development (no. JP20ek0109374).