Rare Childhood Brain Tumor Traced Across 68 Cases in New Systematic Review

A rare childhood brain tumor that spreads like a veil across the coverings of the central nervous system has been mapped in unusual detail by a research team reporting a suspected case from Egypt alongside a systematic review of 68 previously published pediatric patients. The tumor, diffuse leptomeningeal glioneuronal tumor, or DLGNT, is so uncommon that fewer than 100 molecularly confirmed cases had been reported since the World Health Organization formally recognized it as a separate entity in the 2016 classification of central nervous system tumors. The new analysis, published in the Egyptian Journal of Neurosurgery, pooled every eligible pediatric case report and case series the authors could find, and paired that synthesis with the story of a seven-year-old girl whose illness illustrates both the tumor’s telltale imaging signature and the diagnostic traps that surround it.

The girl arrived at Ain Shams University Hospital after three months of progressive ataxia and weakness in her right leg, which had first sent her to an orthopedic clinic where a pelvic CT scan showed nothing abnormal. She then developed intermittent projectile vomiting and deteriorating vision. On examination she had bilateral Frisén grade III papilledema, reduced visual acuity, an ataxic gait, and right lower limb weakness graded 3 out of 5 on the Medical Research Council scale. Magnetic resonance imaging of the brain and spine revealed multiple tiny cystic lesions scattered along the basal cisterns, including the suprasellar, interpeduncular, and ambient cisterns, and in both cerebellar hemispheres, accompanied by prominent basal leptomeningeal enhancement and dilated ventricles consistent with communicating hydrocephalus. Spinal imaging showed small cervical and thoracic intradural cysts plus a larger cyst along the anterior right aspect of the lower thoracic cord at T11 to T12, measuring roughly 1.3 by 1.0 centimeters.

The radiological picture raised two leading possibilities: DLGNT or tuberculous meningitis. Because the hydrocephalus was symptomatic, the team placed a ventriculoperitoneal shunt, which proceeded without perioperative complications. Cerebrospinal fluid drawn during surgery showed no microbiological evidence of infection, including no evidence of tuberculosis, although the authors note that a negative cerebrospinal fluid analysis does not exclude that diagnosis. Fifteen days after surgery the child’s visual acuity had partially improved and her gait was mildly more stable, and a follow-up CT one month after shunting showed resolution of the hydrocephalus. When the family declined further invasive procedures, no biopsy, immunohistochemistry, or molecular testing could be performed. Under the 2021 WHO classification, in which DLGNT is a histologically and molecularly defined entity, the authors therefore report her as a radiologically suspected, highly probable case rather than a confirmed one, and she remains under clinical and radiological surveillance.

To place that case in context, the researchers conducted a systematic review following PRISMA 2020 guidelines, searching PubMed, Scopus, and Web of Science from database inception to November 2025 with no date restrictions. The search string covered a dozen historical names for the entity, from diffuse leptomeningeal oligodendroglioma to disseminated oligodendroglial-like leptomeningeal tumor. From 1,096 records, the removal of 493 duplicates left 603 titles and abstracts for screening; 511 were excluded, 92 full texts were sought, and after one could not be retrieved and 42 failed eligibility, 49 studies remained: 39 case reports and 10 case series, together contributing 68 eligible pediatric patients. Inclusion required diffuse or multifocal leptomeningeal involvement on MRI, diagnosis by histopathology, immunohistochemistry, or molecular analysis, and sufficient data on at least two clinical domains. The index case was deliberately kept out of the review cohort.

The pooled demographics confirm a disease of young school-age children with a male tilt. A numerical age at diagnosis was available for 67 patients, giving a mean of 7.7 plus or minus 4.6 years and a median of 7.0 years, with a range of 2 to 17. Sex was recorded for 67 patients: 40 boys and 27 girls, a ratio of 1.48 to 1. Reports came from 16 countries, with the United States contributing the most patients attributable to a single country at 18, followed by Italy with 9 and China with 7. India contributed four, and Brazil, Spain, and Turkey three each. Strikingly, no case has ever been reported from Africa, which makes the Egyptian patient, in the authors’ view, the first suspected case from the continent, a gap they attribute partly to differences in access to pediatric neurosurgery and advanced MRI that shape case recognition.

The clinical picture that emerges is dominated by symptoms of raised intracranial pressure. Among the 61 patients with a full symptom account, nausea or vomiting was the commonest complaint at 62.3 percent, followed by headache at 54.1 percent, gait disturbance or limb weakness at 41.0 percent, seizures at 36.1 percent, visual symptoms at 34.4 percent, and impaired consciousness at 31.1 percent. Most children had more than one symptom. Misdiagnosis was the rule rather than the exception: an initial working diagnosis was stated for 57 patients, and in 38 of them, 66.7 percent, it was not DLGNT. Infective or inflammatory meningitis was the leading alternative in 14 patients, and seven were investigated or treated for tuberculous meningitis before the tumor was recognized, including one child whose cerebrospinal fluid polymerase chain reaction for Mycobacterium tuberculosis was falsely positive.

Imaging and laboratory findings reinforce a consistent signature. Radiological data were available for all 68 patients: leptomeningeal enhancement was present in 91.2 percent, spinal disease in 89.7 percent, hydrocephalus in 61.8 percent, multiple subpial or disseminated cysts in 54.4 percent, and a discrete parenchymal or intramedullary mass in 33.8 percent. Cerebrospinal fluid was examined in 47 patients, but individual parameters were reported inconsistently. Where quantified, protein was raised in 29 of 30 patients, pleocytosis appeared in 5 of 13 with a reported cell count, and hypoglycorrhachia in 3 of 14 with a reported glucose. Cytology identified malignant or atypical cells in 6 of 26 patients tested. Tissue was obtained in 66 of the 68 patients, and the characteristic appearance was oligodendroglia-like cells with round to oval nuclei and perinuclear haloes in a desmoplastic or myxoid stroma, often with perivascular pseudorosettes.

The molecular profile is equally distinctive. Immunohistochemistry showed OLIG2 positivity in all 29 tumors tested, S100 in 30 of 31, synaptophysin in 40 of 44, GFAP in 32 of 43, and NeuN in only 8 of 17, while IDH1 was negative in all 23 tumors examined, a finding the authors highlight as useful for ruling out IDH-mutant astrocytoma and oligodendroglioma. Molecular or cytogenetic data existed for 42 patients: loss of 1p was the commonest abnormality at 54.8 percent, and a KIAA1549::BRAF fusion was present in 42.9 percent. DNA methylation profiling, available for only six patients, matters prognostically, because prior work has reported five-year overall survival of 100 percent in methylation class 1 versus 43 percent in class 2, with class 2 more often carrying 1q gain and behaving more aggressively.

Treatment and outcomes remain stubbornly heterogeneous. Among 61 patients with treatment records, systemic chemotherapy was given to 72.1 percent, most often carboplatin with vincristine or temozolomide, and CSF diversion was performed in 70.5 percent; radiotherapy reached 24.6 percent, cytoreductive resection 23.0 percent, and targeted agents such as trametinib, vemurafenib, or bevacizumab 14.8 percent, while 15 children received no antineoplastic treatment at all. Prior cohort work cited in the review found similar progression rates across chemotherapy, targeted therapy, and radiotherapy. Vital status was known for 52 patients, of whom 34 were alive and 18 had died. Among the 46 patients with both follow-up duration and vital status, median overall survival was 72 months, with estimated survival of 83.8 percent at one year and 61.5 percent at three and five years, figures the authors stress are descriptive, resting on about two thirds of the cohort with likely informative censoring and a median follow-up of only 23.5 months.

The review’s limitations are laid out plainly: molecular data were unreported in roughly a third of cases, only English-language publications were included, creating language bias, and inconsistent cerebrospinal fluid reporting complicates comparison. The authors argue that DLGNT should be treated as a molecularly defined spectrum rather than a single prognostic entity, that early neuraxis imaging, biopsy, and integrated molecular testing should shorten a diagnostic interval currently delayed by frequent misdiagnosis as infectious meningitis, and that standardized reporting and multicenter registries are needed before comparative conclusions about this rare tumor become reliable.

Subject of Research: A systematic review of 68 pediatric diffuse leptomeningeal glioneuronal tumor cases with a radiologically suspected case report from Egypt

Article Title: Pediatric diffuse leptomeningeal glioneuronal tumor: a radiologically suspected case report and systematic review of 68 patients

Article References: Rady, A. H. A., Mohamed, A. A., Albataineh, K. O., Mahmoud, M. A., Khan, S., Ali, M. I., & Ghany, W. A. A. (2026). Pediatric diffuse leptomeningeal glioneuronal tumor: a radiologically suspected case report and systematic review of 68 patients. Egyptian Journal of Neurosurgery, 41(1), Article 171. https://doi.org/10.1186/s41984-026-00679-8

Image Credits: AI Generated

DOI: 10.1186/s41984-026-00679-8

Keywords: diffuse leptomeningeal glioneuronal tumor, DLGNT, pediatric neurosurgery, systematic review, KIAA1549::BRAF fusion, communicating hydrocephalus, leptomeningeal enhancement, misdiagnosis, WHO CNS classification, methylation classes, brain tumor, cerebrospinal fluid