[Polymorphous low-grade neuroepithelial tumor of the young: a molecular pathological study]

Objective: To investigate the clinical, radiologic, pathological and molecular genetic features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Methods: A retrospective analysis was performed on fourteen PLNTY cases, diagnosed at the Department of Pathology, Xuanwu Hospital, Capital Medical University, from August 2018 to December 2024. The clinical, radiologic, prognostic, histopathological, molecular genetic features, and DNA methylation clustering were analyzed. Results: Among the 14 patients (10 males, 4 females), the age range was 8-34 years, with a median age of 21 (14, 29) years. The patient's major, initial clinical symptom was epilepsy (13/14). Among 9 MRI exanimated cases, 4 showed cystic-solid abnormal signals, and 5 appeared as solid masses. Most were hypointense on T1 and hyperintense on T2. Five cases had enhancement, with no obvious diffusion restriction on DWI. Among 5 CT examined cases, 4 showed high density, and 1 showed low density. The characteristic histopathologic features of the tumor cells were oligodendroglioma-like, spindle, pleomorphic and associated with foci of calcifications. GFAP and Olig2 were expressed in tumor cells in all 14 cases (14/14). Neuronal markers (NeuN, NF) were negative in 13/13 cases. CD34 showed diffuse strong positivity in all cases (14/14). BRAF V600E was positive in 8/11 cases. Thirteen cases (13/13) harbored mitogen-activated protein kinase (MAPK) pathway alterations, including BRAF (10/13) and FGFR2/3 (3/13) gene mutations. In 7 PLNTY cases, t-SNE cluster analysis of DNA methylation profiles showed clustering with ganglioglioma, PLNTY, and pilocytic astrocytoma. Until November 2025, 13 patients have been seizure-free postoperatively, and all 14 patients showed no tumor progression or recurrence. Conclusions: PLNTY usually occurs in adolescents and is associated with epilepsy. Its diagnosis necessitates a combination of clinical, histopathological, and molecular genetic alterations. In molecular level, PLNTY exhibits alterations in the MAPK pathway; while its DNA methylation profile demonstrates diversity. Most patients achieved seizure-free outcomes postoperatively, indicating a favorable prognosis.