# From a Polymorphous Low-Grade Neuroepithelial Tumor to a Glioblastoma in an Adult Patient with FGFR3-TACC3 Fusion: A Case Report and Literature Review of the Molecular Profile

## TL;DR

This paper reports a rare case of a low-grade brain tumor progressing to glioblastoma in an adult, highlighting the molecular changes involved.

## Contribution

The study provides a detailed molecular and clinical analysis of a rare tumor progression from PLNTY to glioblastoma with FGFR3-TACC3 fusion.

## Key findings

- The tumor initially showed features of PLNTY with FGFR3-TACC3 fusion.
- At recurrence, the tumor exhibited glioblastoma features and additional molecular changes.
- The case highlights the importance of molecular profiling in understanding tumor progression.

## Abstract

Polymorphous low-grade neuroepithelial tumor (PLNTY) is a recently recognized low-grade epilepsy-associated neoplasm characterized by MAPK pathway alterations that frequently involve FGFR3, but malignant transformation has not been well documented. We report a rare adult case of PLNTY progressing to glioblastoma, highlighting the molecular evolution of the tumor. Histopathological evaluation and immunohistochemistry were performed at initial diagnosis and at recurrence, and targeted next-generation sequencing was used to assess genomic alterations, with particular focus on FGFR3 status. The primary lesion showed morphological and molecular features consistent with PLNTY, including FGFR3 alteration. At recurrence, the tumor demonstrated high-grade histological features and additional molecular changes consistent with glioblastoma, suggesting clonal evolution. This case underscores the importance of comprehensive molecular profiling in low-grade glioneuronal tumors. Further studies are needed to clarify the mechanisms driving malignant transformation and to determine whether FGFR3 alterations may represent potential therapeutic targets or biomarkers of progression.

From an epidemiological perspective, polymorphous low-grade neuroepithelial tumor (PLNTY) represents a small proportion of brain tumors encountered in epilepsy surgery series. Their rarity and relatively recent recognition likely contribute to underdiagnosis and poor prognosis. In terms of histopathological features, they are similar to oligodendrogliomas. Molecular analyses can be used to show the fusion between fibroblast growth factor receptor (FGFR3) and transforming acidic coiled coil (TACC) proteins, which most commonly results in progression towards glioblastoma (GBM). We report a case of a 62-year-old man who underwent left frontal craniotomy to remove a frontal mass. Histologically, the glial lesion consisted of elements associated with oligodendroglia-like features. Immunohistochemistry was positive for glial fibrillary acidic protein (GFAP), oligodendrocyte transcription factor 2 (OLIG2), and α-thalassemia X-linked mental retardation syndrome (ATRX) nuclear expression, but negative for isocitrate dehydrogenase 1 (IDH1) and BRAF-V600E. Next-generation sequencing showed the FGFR-TACC3 fusion, and taken together, these findings supported the final diagnosis of PLNTY. During follow-up, the patient underwent a second neurosurgery, where histological evaluation indicated a GMB. This article presents clinical and radiological data, morphology, immunohistochemistry, molecular features, and treatment to enhance the clinical and pathological understanding of PLNTY with FGFR3-TACC3 fusion for all professionals involved in medical decisions.