Diffuse leptomeningeal glioneuronal tumor (DLGNT): a comprehensive clinical and molecular analysis

Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are rare, and optimal treatment remains undefined. We aim to comprehensively characterize their clinical and molecular features, offering granular insights into presentations and therapies to elucidate prognostic factors and therapeutic targets. Histologic, molecular, and clinical data of 30 patients with DLGNT were analyzed. Median age at diagnosis was 7.5 years (range: 0.9-20 years). Disease was localized at diagnosis in 16 patients (53.3%), predominantly in the spinal cord (14/16, 87.5%). KIAA1549::BRAF fusion occurred in 27 (96.4%) of 28 patients. DNA methylation profiling of 23 tumors classified 4 (17.4%) as DLGNT MC-1, 3 (13.0%) as DLGNT MC-2, and 16 (69.6%) as DLGNT, but not to a specific subclass. Median follow-up was 57.5 months. Most patients (90.0%) received adjuvant therapy. Chemotherapy was the first-line adjuvant therapy in 19 patients (70.4%); targeted therapy in 5 patients (18.5%), and radiotherapy in 2 patients (7.4%). Median progression-free survival (PFS) after first chemotherapy, targeted therapy, or radiotherapy was 44 (1-77) months, 18 (4-39) months, and 16.5 (9-23) months, respectively. Five-year PFS was 15.9% ± 8.0, and 5 year overall survival (OS) was 83.3% ± 8.8. Patients older than 9 years at diagnosis (p = 0.002) and those with MC-2 (p = 0.04) had worse 5 year OS. Multi-omic analysis revealed simultaneous activation of multiple signaling pathways, which may serve as potential therapeutic targets. DLGNT remains challenging to treat, with poor outcomes across modalities. Further investigation of treatment, including targeted therapies addressing activated pathways, is needed to improve patient survival.

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Publication Details

Journal
Acta Neuropathologica
Published
2025-08-11
DOI
https://doi.org/10.1007/s00401-025-02924-0
Citations
3
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
4.88

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article

Diffuse leptomeningeal glioneuronal tumor (DLGNT): a comprehensive clinical and molecular analysis

Julia Kofler, Jason Fangusaro, Daniel C. Moreira, Anthony A. High et al.
3 citations
Acta Neuropathologica
Glioma Diagnosis and Treatment
4.88
article

Diffuse leptomeningeal glioneuronal tumor (DLGNT): a comprehensive clinical and molecular analysis

Julia Kofler, Jason Fangusaro, Daniel C. Moreira, Anthony A. High, Dolly Noun, Jessica Foster, Daniel R. Boué, Jason Chiang, Haiyan Tan, Michael C. Dewan, Jessica L. Bell, Scott Coven, Trisha Larkin, Margot Lazow, Nalin Leelatian, Christopher L. Tinkle, Margit K. Mikkelsen, Giles W Robinson, Susan Spiller, Kaiwen Yu, Ibrahim A. Qaddoumi, Larissa V. Furtado, Franklin Chien, Jonathan Schwartz, Bret C. Mobley, Lindsey M. Hoffman, Ryuma Tanaka, Benjamin Posorske, Xiaoyu Li, Julia D. Berry, Adriana May, Junmin Peng, Ivanna Sheila
article en
3 citations

Abstract

Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are rare, and optimal treatment remains undefined. We aim to comprehensively characterize their clinical and molecular features, offering granular insights into presentations and therapies to elucidate prognostic factors and therapeutic targets. Histologic, molecular, and clinical data of 30 patients with DLGNT were analyzed. Median age at diagnosis was 7.5 years (range: 0.9-20 years). Disease was localized at diagnosis in 16 patients (53.3%), predominantly in the spinal cord (14/16, 87.5%). KIAA1549::BRAF fusion occurred in 27 (96.4%) of 28 patients. DNA methylation profiling of 23 tumors classified 4 (17.4%) as DLGNT MC-1, 3 (13.0%) as DLGNT MC-2, and 16 (69.6%) as DLGNT, but not to a specific subclass. Median follow-up was 57.5 months. Most patients (90.0%) received adjuvant therapy. Chemotherapy was the first-line adjuvant therapy in 19 patients (70.4%); targeted therapy in 5 patients (18.5%), and radiotherapy in 2 patients (7.4%). Median progression-free survival (PFS) after first chemotherapy, targeted therapy, or radiotherapy was 44 (1-77) months, 18 (4-39) months, and 16.5 (9-23) months, respectively. Five-year PFS was 15.9% ± 8.0, and 5 year overall survival (OS) was 83.3% ± 8.8. Patients older than 9 years at diagnosis (p = 0.002) and those with MC-2 (p = 0.04) had worse 5 year OS. Multi-omic analysis revealed simultaneous activation of multiple signaling pathways, which may serve as potential therapeutic targets. DLGNT remains challenging to treat, with poor outcomes across modalities. Further investigation of treatment, including targeted therapies addressing activated pathways, is needed to improve patient survival.

Acta NeuropathologicaVol. 150(1)
St. Jude Children's Research Hospital (US), Children's Hospital of Philadelphia (US), Emory University (US), Medical College of Wisconsin (US), Riley Hospital for Children (US), American University of Beirut Medical Center (LB), Center for Cancer and Blood Disorders (US), Instituto de Medicina Integral Professor Fernando Figueira (BR), Phoenix Children's Hospital (US), Novant Health Presbyterian Medical Center (US), University of Pittsburgh Medical Center (US), Mayo Clinic in Florida (US), The Ohio State University (US), Indiana University – Purdue University Indianapolis (US), Vanderbilt University Medical Center (US)
American Lebanese Syrian Associated Charities
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Openalex Percentile: Top 5%
Glioma Diagnosis and Treatment
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