CNS tumor

Neuronal and mixed neuronal-glial tumors

Diffuse leptomeningeal glioneuronal tumor



Topic Completed: 3 August 2021

Minor changes: 3 August 2021

Copyright: 2019-2021, PathologyOutlines.com, Inc.

PubMed Search: Diffuse leptomeningeal glioneuronal tumor

Irfan Yasin, M.B.B.S.
Katherine Schwetye, M.D., Ph.D.
Page views in 2021 to date: 584
Cite this page: Yasin I, Schwetye K. Diffuse leptomeningeal glioneuronal tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumordiffuseleptglioneurtumor.html. Accessed October 15th, 2021.
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
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
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
Prognostic factors
Case reports
Treatment
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

Oligodendroglial-like appearance

Tumor adjacent parenchyma

Tumor adjacent parenchyma

Bland cytomorphology and nuclear features

Bland cytomorphology and nuclear features

S100 positive

S100 positive

Ki67 low

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).
Cytology description
  • Cerebrospinal fluid examination
Positive stains
Negative stains
Molecular / cytogenetics description
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
Board review style question #1
Common genetic alterations in the diffuse leptomeningeal glioneuronal tumor include

  1. H3F3 K27M
  2. IDH1 R132H
  3. KIAA1549-BRAF translocation and 1p deletion
  4. PTEN loss
Board review style answer #1
C. KIAA1549-BRAF translocation and 1p deletion

Comment Here

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?

  1. S100 positive, Olig2 positive, H3F3a K27M positive
  2. S100 positive, Olig2 positive, IDH R132H positive
  3. S100 negative, Olig2 positive, IDH R132H positive
  4. S100 positive, Olig2 positive, IDH R132H negative
Board review style answer #2
D. S100 positive, Olig2 positive, IDH R132H negative

Comment Here

Reference: Diffuse leptomeningeal glioneuronal tumor
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