CNS & pituitary tumors
Gliomas, glioneuronal tumors and neuronal tumors
Neuronal and mixed neuronal-glial tumors
Diffuse leptomeningeal glioneuronal tumor
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Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D.
Last author update: 3 August 2021
Last staff update: 24 September 2024
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PubMed Search: Diffuse leptomeningeal glioneuronal tumor
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Yasin I, Schwetye K. Diffuse leptomeningeal glioneuronal tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumordiffuseleptglioneurtumor.html. Accessed December 24th, 2024.
Definition / general
- Indolent, low grade neuroepithelial neoplasm that typically shows widespread leptomeningeal and superficial parenchymal CNS dissemination and oligodendroglioma-like cytology. This tumor was added provisionally to the WHO classification scheme of CNS tumors in 2016, and is no longer a provisional entity in the 2021 WHO CNS5 classification
Essential features
- Indolent, slow growing tumor with widespread and diffuse leptomeningeal involvement
- Typically affects children; rare in adults
- Presents with signs and symptoms of obstructive hydrocephalus
- Olig2 and S100 positive, monomorphic oligodendroglial-like cells in desmoplastic or myxoid matrix
- KIAA1549-BRAF fusion, 1p deletion common; 1p19q codeletion and BRAF V600E less common
- References: Acta Neuropathol 2018;136:239, Acta Neuropathol 2012;124:627
Terminology
- Abbreviations: diffuse leptomeningeal glioneuronal tumor (DLGNT)
- Other historical terms (Acta Neuropathol 2016;131:803):
- Primary leptomeningeal oligodendrogliomatosis
- Disseminated oligodendroglioma-like leptomeningeal neoplasm (DOLN)
- Disseminated oligodendroglial-like neoplasm
- Diffuse leptomeningeal neuroepithelial tumor
ICD coding
- ICD-10: C70.1 - malignant neoplasm of spinal meninges
Epidemiology
- Range: 5 months - 46 years
- Median age of diagnosis: 5 years
- M:F = 1.7:1
- Reference: Acta Neuropathol 2012;124:627
Sites
- Widespread, diffuse involvement of spinal and intracranial leptomeninges (Acta Neuropathol 2012;124:627)
- Within cranium, most common around posterior fossa, brainstem and base of brain
- May fill ventricles and spread along Virchow-Robin spaces (Acta Neuropathol 2012;124:627)
- May form cystic or solid tumor lesions in adjacent parenchyma; spinal > intracerebral
- Spread in subarachnoid space: plaque-like or multinodular pattern (Acta Neuropathol 2012;124:627)
Pathophysiology
- Unknown how tumor arises
Etiology
- Precise etiology unknown, although recurrent genetic alterations are identified (see Molecular / cytogenetics description)
Clinical features
- Often acute, presents with signs and symptoms of increased intracranial pressure (Acta Neuropathol 2012;124:627)
- Due to obstructive hydrocephalus
- Nausea, vomiting and headache
- Opisthotonos
- Encasement or irritation of spinal or cranial nerves (Acta Neuropathol 2012;124:627)
- May lead to palsies related to motor, sensory or autonomic function
- Meningeal signs
- Ataxia
- Spinal cord compression
- Rarely, seizures
Diagnosis
- Primarily made on radiologic features
- Confirmed by tissue biopsy with ancillary immunohistochemistry, cytogenetic (FISH) and molecular testing
Radiology description
- MRI shows widespread contrast enhancement and thickening along spinal cord; often extends intracranially to posterior fossa, brainstem and basal brain (J Belg Soc Radiol 2017;101:19)
- Small cystic or nodular T2 hyperintense lesions along subpial surface of spinal cord or brain
- Discrete intraparenchymal lesions, most common in spinal cord; sometimes without diffuse spread (Acta Neuropathol Commun 2020;8:95)
- Obstructive hydrocephalus with associated periventricular T2 hyperintensity
Radiology images
- See Case reports
Prognostic factors
- Mostly favorable prognosis in terms of mortality (Brain Tumor Pathol 2015;32:49, Acta Neuropathol 2012;124:627)
- Indolent tumor but with significant morbidity
- Poor prognosis (Brain Tumor Pathol 2015;32:49):
- Mitotic activity (of any degree)
- Glomeruloid microvascular proliferation
- MIB1 / Ki67 labeling index ≥ 4%
Case reports
- 10 children, 2 - 14 years old; 9 patients received chemotherapy, 3 with progressive disease; 6 patient harbored genomic alterations affecting the MAPK pathway (J Neurooncol 2016;128:293)
- 4 year old boy with diffuse leptomeningeal thickening; review of imaging features (J Belg Soc Radiol 2017;101:19)
- 7 year old boy with low grade tumor versus 9 year old boy with high grade tumor (Hum Pathol 2017;70:105)
- 8 year old girl with imaging presentation mimicking tuberculous meningitis (Childs Nerv Syst 2011;27:187)
- 12 year old boy with ventriculoperitoneal shunt treated with temozolomide (Childs Nerv Syst 2020;36:459)
- 13 year old girl with predominant spinal infiltration (Childs Nerv Syst 2019;35:1609)
- 31 and 35 year old women with circumscribed intraparenchymal tumors (Acta Neuropathol Commun 2020;8:95)
- 36 year old woman with aggressive tumor (World Neurosurg 2018;114:53)
- 37 year old man with a cervical spinal cord mass (Case of the month #542)
- 7 cases with typical and less common imaging features, showing the most characteristic imaging finding is diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement (AJNR Am J Neuroradiol 2020;41:2155)
- Series of 36 patients; comprehensive description of presentation, imaging, histology, treatment and prognosis (Acta Neuropathol 2012;124:627)
Treatment
- Surgical resection, particularly for parenchymal lesions (Childs Nerv Syst 2019;35:1609)
- Symptomatic treatment for hydrocephalus (Childs Nerv Syst 2020;36:459)
- Ventriculoperitoneal shunting
- Chemotherapy (Child Neurol Open 2015;2:2329048X14567531, Childs Nerv Syst 2018;34:329)
- Temozolomide, others
- Radiotherapy in disease progression (Child Neurol Open 2015;2:2329048X14567531, Childs Nerv Syst 2018;34:329)
- Targeted therapy (Pediatr Blood Cancer 2020;67:e28478)
Gross description
- Postmortem examination confirms widespread, diffuse leptomeningeal spread in spinal and intracranial compartments (Brain Tumor Pathol 2018;35:209)
- Multifocal extension along Virchow-Robin spaces (Acta Neuropathol 2012;124:627)
- Growth along peripheral nerve roots and infiltration of basal cranial nerves and ganglia
Microscopic (histologic) description
- Low to moderate cellularity; diffuse growth or nests in leptomeninges (Brain Tumor Pathol 2015;32:49)
- Often with desmoplastic or myxoid changes
- Bland, monomorphous, oligodendroglial-like cells (Brain Tumor Pathol 2015;32:49)
- With or without perinuclear halo
- Uniform round nuclei with fine chromatin and inconspicuous nucleoli
- Some with ganglion or ganglioid cells; may be associated with neuropil
- Eosinophilic granular bodies (occasional), Rosenthal fibers (rare)
- Low mitotic activity
- Anaplasia is rare; associated with more aggressive clinical course (Brain Tumor Pathol 2015;32:49)
- Nuclear enlargement
- Atypia
- Increased mitotic activity
- Microvascular proliferation
- Necrosis
Microscopic (histologic) images
Contributed by Katherine Schwetye, M.D., Ph.D.
Oligodendroglial-like appearance
Tumor adjacent parenchyma
Bland cytomorphology and nuclear features
S100 positive
Ki67 low
These photographs were previously published in Human Pathology, Vol. 70, Schwetye KE et al., "Unusual high-grade features in
pediatric diffuse leptomeningeal glioneuronal tumor: comparison with a typical low-grade example", p.105-112 Copyright Elsevier (2017).
Contributed by P.J. Cimino, M.D., Ph.D. (Case #542)
Cytology description
- Cerebrospinal fluid examination
- Increased protein levels
- Reactive lymphocytosis (rare feature)
- Typically negative for tumor cells (Childs Nerv Syst 2018;34:329)
Positive stains
- S100, Olig2, MAP2, synaptophysin (70%), GFAP (focal, in 50%)
- Ki67 ~1.5% (median)
Negative stains
- NeuN, neurofilaments, EMA and IDH1 R132H
Molecular / cytogenetics description
- KIAA1549-BRAF fusion protein is most frequent (60 - 70%) (Acta Neuropathol 2012;124:627, Acta Neuropathol 2015;129:609)
- Chromosome 1p deletion (50 - 100%, varies by series) (Acta Neuropathol 2012;124:627, Acta Neuropathol 2015;129:609)
- DNA methylation profiling identifies 2 distinct classes of diffuse leptomeningeal glioneuronal tumor (Acta Neuropathol 2018;136:239)
- Chromosome 1p / 19q codeletion differs by methylation defined groups (47% versus 15%) (Acta Neuropathol 2018;136:239)
- Other reported alterations: TRIM33-RAF1, NTRK1/2/3 fusions, CDKN2A/B homozygous deletion, TERT C228T, C228A, ATRX point mutation, BCOR frameshift alteration, BRAF V600E (Acta Neuropathol 2018;136:239)
- Negative for IDH1 R132, IDH R172, H3F3A K27 alterations (Acta Neuropathol 2018;136:239)
Sample pathology report
- Spine, leptomeninges, biopsy:
- Diffuse leptomeningeal glioneuronal tumor (see comment)
- Comment: Hematoxylin and eosin examination of the biopsy material shows a moderately cellular, neoplastic proliferation within the leptomeninges with associated desmoplastic and myxoid change. The cells show relatively monomorphic, bland morphology, round nuclei with perinuclear haloes (reminiscent of an oligodendroglial-like appearance) and inconspicuous nucleoli. Mitotic activity is not identified. Necrosis is not identified. Immunohistochemical stains demonstrate reactivity for S100 and Olig2. Ki67 shows a low (< 2%) index of proliferation. FISH studies confirm the KIAA1549-BRAF rearrangement and deletion of chromosome 1p. Taken together, the radiologic, histomorphologic, immunohistochemical and cytogenetic features support a diagnosis of diffuse leptomeningeal glioneuronal tumor.
Differential diagnosis
- Pilocytic astrocytoma:
- Typically intraparenchymal tumor without primary leptomeningeal spread
- More predominant Rosenthal fibers
- Glomeruloid microvascular proliferation does not alone confer worse prognosis
- Oligodendroglioma:
- Diffusely infiltrative glial tumor
- Typically intraparenchymal
- IDH1 / IDH2 mutations as a requisite feature for diagnosis
- Macrophage rich reactive / inflammatory process:
- CD68 positive macrophages
- Tumors metastatic to the leptomeninges:
- Clinical history, more likely adults
Additional references
Board review style question #1
Common genetic alterations in the diffuse leptomeningeal glioneuronal tumor include
- H3F3 K27M
- IDH1 R132H
- KIAA1549-BRAF translocation and 1p deletion
- PTEN loss
Board review style answer #1
C. KIAA1549-BRAF translocation and 1p deletion
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Reference: Diffuse leptomeningeal glioneuronal tumor
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Reference: Diffuse leptomeningeal glioneuronal tumor
Board review style question #2
Based on the image shown above in conjunction with MRI findings of an enhancing, spinal leptomeningeal process without a distinctive intraparenchymal lesion in a 5 year old boy, what is the expected pattern of immunoreactivity?
- S100 positive, Olig2 positive, H3F3a K27M positive
- S100 positive, Olig2 positive, IDH R132H positive
- S100 negative, Olig2 positive, IDH R132H positive
- S100 positive, Olig2 positive, IDH R132H negative
Board review style answer #2
D. S100 positive, Olig2 positive, IDH R132H negative
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