Skip to main content


Log in

Prognostic factors in diffuse leptomeningeal glioneuronal tumor (DLGNT): a systematic review

  • Review
  • Published:
Child's Nervous System Aims and scope Submit manuscript



Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor, first described by the WHO Classification of Central Nervous System Tumors in 2016. The clinical course is variable. Most tumors have low-grade histological findings although some may have more aggressive features. The goal of this systematic review was to identify prognostic factors for poor overall survival (OS).

Material and methods

We performed a systematic review using three databases (PubMed, Google Scholar, and Embase) and the following search terms: diffuse leptomeningeal glioneuronal tumor, DLGNT, DLMGNT. Statistical analysis was performed using Statistica 13.3.


We included 34 reports in our review comprising 63 patients, published from 2016 to 2022. The median OS was 19 months (range: 12–51 months). Using multivariable Cox survival analysis, we showed that Ki-67 ≥ 7%, age > 9 years, symptoms of elevated intracranial pressure (ICP) at admission, and the presence of contrast-enhancing intraparenchymal tumor are associated with poor OS. Receiver operating characteristic (ROC) analysis identified Ki-67 ≥ 7% as a significant predictor of poor OS.


Signs or symptoms of increased ICP with imaging findings of diffuse leptomeningeal enhancement should raise suspicion for DLGNT. In our systematic review, Ki-67 ≥ 7% was the most important prognostic factor for OS in DLGNT. The presence of intraparenchymal tumor with contrast enhancement was thought to represent disease progression and, together with patient age, was associated with poor OS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

Raw data are presented in supplementary materials.


  1. Louis DN, Perry A, Reifenberger G, Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler DO, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820.

    Article  PubMed  Google Scholar 

  2. Rodriguez FJ, Perry A, Rosenblum MK, Krawitz S, Cohen KJ, Lin D, Mosier S, Lin MT, Eberhart CG, Burger PC (2012) Disseminated oligodendroglial-like leptomeningeal tumor of childhood: a distinctive clinicopathologic entity. Acta Neuropathol 124(5):627–641.

    Article  PubMed  Google Scholar 

  3. Mathews MS, Paré LS, Kuo JV, Kim RC (2009) Primary leptomeningeal oligodendrogliomatosis. J Neurooncol 94(2):275–278.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Dodgshun AJ, SantaCruz N, Hwang J, Ramkissoon SH, Malkin H, Bergthold G, Manley P, Chi S, MacGregor D, Goumnerova L et al (2016) Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation. J Neurooncol 128(2):293–302.

    Article  CAS  PubMed  Google Scholar 

  5. Rodriguez FJ, Schniederjan MJ, Nicolaides T, Tihan T, Burger PC, Perry A (2015) High rate of concurrent BRAF-KIAA1549 gene fusion and 1p deletion in disseminated oligodendroglioma-like leptomeningeal neoplasms (DOLN). Acta Neuropathol 129:609–610.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Murad MH, Sultan S, Haffar S, Bazerbachi F (2018) Methodological quality and synthesis of case series and case reports. BMJ Evidence-Based Med 23:60–63.

    Article  Google Scholar 

  7. Abongwa C, Cotter J, Tamrazi B, Dhall G, Davidson T, Margol A (2020) Primary diffuse leptomeningeal glioneuronal tumors of the central nervous system: report of three cases and review of literature. Pediatr Hematol Oncol 37(3):248–258.

    Article  PubMed  Google Scholar 

  8. Aguilera D, Castellino RC, Janss A, Schniederjan M, McNall R, MacDonald T, Mazewski C Clinical responses of patients with diffuse leptomeningeal glioneuronal tumors to chemotherapy (2018) Childs Nerv Syst 34(2):329–34.

  9. Appay R, Pages M, Colin C, Jones DTW, Varlet P, Figarella-Branger D (2020) Diffuse leptomeningeal glioneuronal tumor: a double misnomer? A report of two cases. Acta Neuropathol Commun 8(1):95

    Article  CAS  Google Scholar 

  10. Baoa Y, Hua Y, Dinga Y, Lia X, Qina L, Zhanga M, Liua G, Liu X (2019) Clinical features of diffuse leptomeningeal glioneuronal tumor with the first symptom of headache and decreased vision misdiagnosed as venous sinus thrombosis. J Neurol Res [Online] 9(3):41–47.

    Article  Google Scholar 

  11. Bao Y, Xiao J, Cheng Z, Qin Y, Xie D, Wu H, Guangjian L (2019) Characteristics of diffuse leptomeningeal glioneuronal tumor with first-episode headache and rapid blindness misdiagnosed as viral meningoencephalitis. J Med Cases 10(8):241–245.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Fetta A, Pruccoli J, Biasucci G, Parisi R, Toni F, Melchionda F, Cordelli DM (2022) Hemiplegic-migraine-like attacks as first manifestation of diffuse leptomeningeal glioneuronal tumor: a case report. J Pediatr Hematol Oncol. 1;44(3):e765-e769.

  13. Fiaschi P, Badaloni F, Cagetti B, Bruzzone L, Marucci G, Dellacha A, Pavanello M, Ganci G, Padolecchia R, Valsania V (2018) Disseminated oligodendroglial-like leptomeningeal tumor in the adult: case report and review of the literature. World Neurosurg 114:53–57.

    Article  PubMed  Google Scholar 

  14. Gatzert S, Durgam A, Raghuram K, Agarwal A (2019) Primary diffuse leptomeningeal oligodendrogliomatosis with an isolated 1p deletion. Br J Neurosurg 1–6.

  15. Gai D, Christie M, Gaillard F (2020) Adult diffuse leptomeningeal glioneuronal tumour with limited leptomeningeal involvement, lack of 1p deletion and BRAF V600E mutation. J Clin Neurosci 79:215–218.

    Article  CAS  PubMed  Google Scholar 

  16. Chen W, Kong Z, Fu J, Zhao D, Wang R, Ma W, Wang Y (2020) Diffuse leptomeningeal glioneuronal tumour (DLGNT) with hydrocephalus as an initial symptom: a case-based update. Childs Nerv Syst 36(3):459–468.

    Article  PubMed  Google Scholar 

  17. Cheng W, He L, Zhu J, Fan X (2022) Diffuse leptomeningeal glioneuronal tumor without KIAA1549-BRAF fusion and 1p detection: a case report and review of literature. Childs Nerv Syst 38(2):279–285.

    Article  PubMed  Google Scholar 

  18. Chiang JCH, Harreld JH, Orr BA, Sharma S, Ismail A, Segura AD, Ellison DW (2017) Low-grade spinal glioneuronal tumors with BRAF gene fusion and 1p deletion but without leptomeningeal dissemination. Acta Neuropathol 134:159–162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Igarashi K, Kawanami K, Yamaki T, Matsuda KI, Komori T, Sonoda Y (2020) [Diffuse leptomeningeal glioneuronal tumor with subarachnoid hemorrhage: a case report.] No Shinkei Geka 48(9):801–8.

  20. Kang JH, Buckley AF, Nagpal S, Fischbein N, Peters KB (2018) A diffuse leptomeningeal glioneuronal tumor without diffuse leptomeningeal involvement: detailed molecular and clinical characterization. J Neuropathol Exp Neurol 77(9):751–756.

    Article  PubMed  Google Scholar 

  21. Karlowee V, Kolakshyapati M, Amatya VJ, Takayasu T, Nosaka R, Sugiyama K, Kurisu K, Yamasaki F (2017) Diffuse leptomeningeal glioneuronal tumor (DLGNT) mimicking Whipple’s disease: a case report and literature review. Childs Nerv Syst 33(8):1411–1414.

    Article  PubMed  Google Scholar 

  22. Kurozumi K, Nakano Y, Ishida J, Tanaka T, Doi M, Hirato J, Yoshida A, Washio K, Shimada A, Kohno T, Ichimura K, Yanai H, Date I (2019) High-grade glioneuronal tumor with an ARHGEF2-NTRK1 fusion gene. Brain Tumor Pathol 36(3):121–8.

  23. Lee JK, Ko HC, Choi JG, Lee YS, Son BC (2018) A case of diffuse leptomeningeal glioneuronal tumor misdiagnosed as chronic tuberculous meningitis without brain biopsy. Case Rep Neurol Med 1391943.

  24. Manoharan N, Ajuyah P, Senapati A, Wong M, Mullins A, Rodriguez M, Doyle H, McCowage G, Lau LMS, Ekert PG, Ziegler DS (2021) Diffuse leptomeningeal glioneuronal tumour (DLGNT) in children: the emerging role of genomic analysis. Acta Neuropathol Commun 9(1):147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nambirajan A, Suri V, Kedia S, Goyal K, Malgulwar PB, Khanna G, Panda KP, Sheffali Gulati S, Ajay Garg A, Mehar Chand Sharma MC (2018) Paediatric diffuse leptomeningeal tumor with glial and neuronal differentiation harbouring chromosome 1p/19q co-deletion and H3.3 K27M mutation: unusual molecular profile and its therapeutic implications. Brain Tumor Pathol 35(3):186–91.

  26. Peer S, Murumkar V, Kulanthaivelu K, Prasad C, Rao S, Santosh V (2021) Diffuse leptomeningeal glioneuronal tumor with high-grade features masquerading as tubercular meningitis—a case report. Egyptian J Radiol Nuc Med 52(1):146.

    Article  Google Scholar 

  27. Peerboccus M, Beltran-Marin M, Sariban E, Fontanges Q, Ziereisen F (2017) Disseminated oligodendroglial-like leptomeningeal tumor of childhood: a distinctive entity revised and correlated with pathology. J Belg Soc Radiol 101(1):19.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Perez-Vega C, Akinduro OO, Cheek BJ, Beier AD (2021) Spinal cord diffuse leptomeningeal glioneuronal tumor presenting without leptomeningeal dissemination. Pediatr Neurosurg 9:1–6.

    Article  Google Scholar 

  29. Sasaki S, Hirose T, Sumihito Nobusawa S, Myojin T, Morita K, Nakai T, Hirato J, Ohbayashi C (2017) Anaplastic diffuse leptomeningeal glioneuronal tumor associated with H3 K27M mutation. Human Pathol: Case Rep 17:200296.

    Article  Google Scholar 

  30. Sáez-Alegre M, Saceda Gutiérrez JM, Utrilla Contreras C, Aracil Santos FJ, García-Feijoo P, Carceller Benito F (2021) Diffuse leptomeningeal glioneuronal tumour: where to biopsy? Case report and literature review. Childs Nerv Syst 37(7):2405–2408.

    Article  PubMed  Google Scholar 

  31. Schwetye KE, Kansagra AP, McEachern J, Schmidt RE, Gauvain K, Dahiya S (2017) Unusual high-grade features in pediatric diffuse leptomeningeal glioneuronal tumor: comparison with a typical low-grade example. Hum Pathol 70:105–112.

    Article  PubMed  Google Scholar 

  32. Sarkinaite M, Devyziene I, Makstiene J, Matukevicius A, Gleizniene R (2022) Diffuse leptomeningeal glioneuronal tumour with 9-year follow-up: case report and review of the literature. Diagnostics (Basel). 28;12(2):342.

  33. Teoh S, Hofer M, Kerr R, Warner N, Kueker W, Rothwell PM (2019) Zamboni G (2019) Disseminated leptomeningeal tumour mimicking a subarachnoid haemorrhage. Neuroradiol J 32(1):53–56.

    Article  PubMed  Google Scholar 

  34. Tiwari N, Tamrazi B, Robison N, Krieger M, Ji J, Tian D (2019) Unusual radiological and histological presentation of a diffuse leptomeningeal glioneuronal tumor (DLGNT) in a 13-year-old girl. Childs Nerv Syst 35(9):1609–1614.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Tu JH, Wang LM, Liu L, Han HW, Fu YJ, Piao YS, Lu DH, Teng LH (2021) [Clinicopathological features of diffuse leptomeningeal glioneuronal tumor]. Zhonghua Bing Li Xue Za Zhi. 8;50(8):876–881.

  36. Valiakhmetova A, Papusha L, Druy A, Yasko L, Ektova A, Karachunsky A, Maschan A, Hwang EI, Novichkova G, Packer RJ (2020) Pediatric diffuse leptomeningeal glioneuronal tumor: two clinical cases of successful targeted therapy. Pediatr Blood Cancer 67(12):e28478.

    Article  PubMed  Google Scholar 

  37. Wei J, Huang XR, Wang Q, Qiu OP (2018) Diffuse leptomeningeal glioneuronal tumor. Chinese J Contemp Neurol Neurosurg 18(17).

  38. Xiao J, Gao L, Zhang M, Wang X, Xuan J, Liu G, Bao Y (2019) Clinical features of diffuse leptomeningeal glioneuronal tumor with rapid blindness misdiagnosed as NMOSD and literature review. SN Compre Clinic Med 1(6):434–441.

    Article  Google Scholar 

  39. Xu H, Chen F, Zhu H, Luo L, Zhang R (2020) Diffuse leptomeningeal glioneuronal tumor in a Chinese adult: a novel case report and review of literature. Acta Neurol Belg 120(2):247–256.

    Article  PubMed  Google Scholar 

  40. Yamasaki T, Sakai N, Shinmura K, Kawaji H, Koizumi S, Samashima T, Namba H (2018) Anaplastic changes of diffuse leptomeningeal glioneuronal tumor with polar spongioblastoma pattern. Brain Tumor Pathol 35(4):209–216.

    Article  PubMed  Google Scholar 

  41. Lee DW, Lee KH, Kim J, Keam B (2016) Molecular targeted therapies for the treatment of leptomeningeal carcinomatosis: current evidence and future directions. Int J Mol Sci 17(7):1074.

    Article  CAS  PubMed Central  Google Scholar 

  42. Forshew T, Tatevossian RG, Lawson AR, Ma J, Neale G, Ogunkolade BW, Jones TA, Aarum J, Dalton J, Bailey S et al (2019) Activation of the ERK/ MAPK pathway: a signature genetic defect in posterior fossa pilocytic astrocytomas. J Pathol 218:172–181.

    Article  CAS  Google Scholar 

  43. Jeuken JW, Wesseling P (2010) MAPK pathway activation through BRAF gene fusion in pilocytic astrocytomas; a novel oncogenic fusion gene with diagnostic, prognostic, and therapeutic potential. J Pathol 222:324–328.

    Article  CAS  PubMed  Google Scholar 

  44. Jones DT, Gronych J, Lichter P, Witt O, Pfister SM (2012) MAPK pathway activation in pilocytic astrocytoma. Cell Mol Life Sci 69:1799–1811.

    Article  CAS  PubMed  Google Scholar 

  45. Kieran MW, Geoerger B, Dunkel IJ, Broniscer A, Hargrave D, Hingorani P, Aerts I, Bertozzi AI, Cohen KJ, Hummel TR (2019) A phase I and pharmacokinetic study of oral dabrafenib in children and adolescent patients with recurrent or refractory BRAF V600 mutation-positive solid tumors. Clin Cancer Res 25:7294–7302.

    Article  CAS  PubMed  Google Scholar 

  46. Kim KB, Kefford R, Pavlick AC, Infante JR, Ribas A, Sosman JA, Fecher LA, Millward M, McArthur GA, Hwu P et al (2013) Phase II study of the MEK1/ MEK2 inhibitor trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor. J Clin Oncol 31:482–489.

    Article  CAS  PubMed  Google Scholar 

  47. Tiwari S, Yadav T, Pamnani J, Mathew JM, Elhence P, Praneeth K, Vedant D, Khera PS, Garg P, Vyas V (2020) Diffuse leptomeningeal glioneuronal tumor: a unique leptomeningeal tumor entity. World Neurosurg 135:297–300.

    Article  PubMed  Google Scholar 

  48. Yüksel MF, Bektaş Ö, Fitöz ÖS, Akıncı Göktaş Ö, Şahin S, Teber S (2021) A cytology negative rare tumor with the presentation of pseudotumor cerebri clinical symptoms: diffuse leptomeningeal glioneuronal tumor. Iran J Ped Hematol Oncol 11(2):142–147.

    Article  Google Scholar 

  49. Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I et al (2013) Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat Genet 45:602–612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Deng MY, Sill M, Chiang J, Schittenhelm J, Ebinger M, Schuhmann MU, Monoranu CM, Milde T, Wittmann A, Hartmann C et al (2018) (2018) Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features. Acta Neuropathol 136:239–253.

    Article  CAS  PubMed  Google Scholar 

Download references


This work was financially supported by the Polish National Agency for Academic Exchange (the Walczak Programme).

Author information

Authors and Affiliations



Conceptualization, K.W.; methodology, K.W., M.G.B., D.D.G.; analysis, K.W., M.G.B.; investigation, K.W., M.G.B., D.D.G.; writing—original draft preparation, K.W., M.G.B; writing—review and editing, K.W., D.D.G., J.R.C, M.L.L.; project administration, K.W.; supervision, K.W., M.L.L., J.R.C. All authors reviewed the manuscript.

Corresponding author

Correspondence to Karol Wiśniewski.

Ethics declarations

Ethics approval

This article does not contain any studies involving human participants or animals performed by any of the authors; thus, no formal consent is required for this type of study.

Consent for publication

All authors approved the article.

Conflict of interest

The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 41 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wiśniewski, K., Brandel, M.G., Gonda, D.D. et al. Prognostic factors in diffuse leptomeningeal glioneuronal tumor (DLGNT): a systematic review. Childs Nerv Syst 38, 1663–1673 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: