Adult Low-Grade Glioma With MEF2D::NTRK1 Fusion: A Case Report and Literature Review.

Abstract

Low-grade glioma (LGG) is a malignancy that is rare in adult central nervous system (CNS). Clinical management decisions are increasingly guided by molecular alterations rather than the histological subtype alone. Neurotrophic tropomyosin receptor kinase 1 (NTRK1) is constitutively activated in multiple tumor types. TRK inhibitors, targeting NTRK fusion proteins, have exhibited notable therapeutic efficacy in some NTRK gene fusion tumors. NTRK fusions with diverse partners have been reported in CNS tumors. Nevertheless, MEF2D::NTRK1 fusion cases were only reported in high-grade glioneuronal neoplasms and infantile-type hemispheric glioma. We report a 33-year-old patient with LGG morphological features, but presented a diffuse invasive growth pattern involving the corpus callosum, the third ventricle, the entire anterior cranial base and the suprasellar cistern. Histology showed oligodendrocyte-like cells within an abundant mucinous matrix, with scattered astrocytes and no dense collagen, Rosenthal fibers or glomeruloid microvascular. The nucleoli were inconspicuous and mitotic figure was rare. Next-generation sequencing (NGS) showed it harbored a MEF2D::NTRK1 fusion and 22q loss with no additional mutations identified. DNA methylation clustered with pilocytic astrocytoma (PA) and diffuse leptomeningeal glioneuronal tumor (DLGNT). However, according to the tumor's growth pattern, morphological features, and molecular characteristics, it does not match to PA or DLGNS. This report provides a comprehensive description of the clinical, radiographic, histopathological, immunohistochemical, and molecular characteristics of MEF2D::NTRK1 fused LGG with the aim of enhancing the clinical and pathological understanding of MEF2D::NTRK1 fused LGG. Patient in this case had benefited from NTRK-targeted therapeutic intervention.