# Diffuse Leptomeningeal Glioneuronal Tumor: A Systematic Review Highlighting Molecular Heterogeneity and Survival Outcome

## TL;DR

This paper reviews a rare brain tumor in children and young adults, finding that surgery may improve survival and that genetic changes are common but not predictive of outcomes.

## Contribution

The study systematically reviews clinical and molecular data of DLGNT cases to clarify features and outcomes, emphasizing the need for standardized molecular profiling.

## Key findings

- Surgical resection was associated with significantly longer overall survival compared to biopsy alone.
- BRAF alterations, including KIAA1549::BRAF fusion, were frequently observed but did not predict survival outcomes.
- Median overall survival was 89 months and median progression-free survival was 30 months across 75 patients.

## Abstract

Diffuse leptomeningeal glioneuronal tumor is a very rare brain tumor that mainly affects children and young adults and often spreads along the brain and spinal cord. Because it is uncommon and difficult to diagnose, treatment strategies vary widely and clinical outcomes remain unpredictable. To address this, we reviewed all published cases reported since this tumor was first defined to summarize clinical features, genetic findings, treatments, and survival outcomes. We found that hydrocephalus and spinal involvement were common, and that surgery was associated with longer survival in selected patients. Genetic alterations affecting tumor growth–related pathways were also frequently observed. This summary of current evidence may help clinicians recognize this tumor earlier and consider appropriate management strategies.

Background/Objectives: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare central nervous system neoplasm characterized by leptomeningeal dissemination and heterogeneous clinical and molecular features. Owing to its rarity, the prognostic relevance of clinical, radiological, and molecular factors remains poorly defined. This systematic review aimed to comprehensively summarize the clinicopathological characteristics, molecular landscape, treatment strategies, and survival outcomes of patients with DLGNT. Methods: A systematic literature search was conducted in PubMed, Embase, Scopus, and Google Scholar to identify published cases of DLGNT. Studies reporting individual patient data were included. Clinical, molecular, treatment, and survival data were pooled. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan–Meier method, with subgroup analyses according to clinical and molecular variables. Results: Seventy-five patients were included. Most patients were pediatric, and spinal leptomeningeal dissemination and hydrocephalus were frequent. BRAF alterations, most commonly KIAA1549::BRAF fusion, were frequently identified, although no molecular marker predicted survival. The median OS was 89 months, and the median PFS was 30 months. Surgical resection was associated with significantly longer OS compared with biopsy only, while a trend toward longer PFS was observed. Survival outcomes did not differ significantly according to age group, BRAF status, chemotherapy, or radiotherapy. Conclusions: DLGNT is a rare and heterogeneous tumor with variable presentation and prolonged survival in selected patients. Although surgical resection may be associated with improved survival, interpretation is limited by selection bias. No single molecular alteration reliably predicts prognosis, highlighting the need for prospective multicenter studies with standardized molecular profiling.