Diffuse leptomeningeal glioneuronal tumor

Last revised by Jane McEniery on 13 Sep 2022

Diffuse leptomeningeal glioneuronal tumor (previously known as disseminated oligodendroglial-like leptomeningeal tumor of childhood) is a rare and only recently described tumor of the central nervous system. It typically presents with hydrocephalus secondary to prominent leptomeningeal enhancement, often without a readily identifiable parenchymal component.

These tumors are most commonly encountered in children and adolescents, with the vast majority of reported cases in individuals less than 18 years of age 2,5. Occasionally they are encountered in young to middle-aged adults 5. There appears to be a moderate male predilection 5

Clinical presentation is dominated by hydrocephalus due to the pronounced accumulation of tumor within the subarachnoid space. Occasionally, patients may present with focal neurological symptoms, including cranial nerve impairment, ataxia and spinal cord compression, or with seizures 3,5

These tumors histologically are composed of intense desmoplastic fibrous response admixed with cells with perinuclear halos and cytoplasmic swelling similar to oligodendroglial cells. They have round to oval nuclei with finely granular dispersed chromatin and inconspicuous nucleoli 1,5.

This morphology, combined with common chromosome arm 1p deletions, sometimes with co-deletion of 19q, accounts for its prior name including the term "oligodendroglial-like" (see 1p19q codeletion). In contrast to oligodendrogliomas, diffuse leptomeningeal glioneuronal tumors do not have IDH mutations 2,5

Other markers identified include 2,3,5,6:

  • KIAA1549-BRAF fusion (common) 
  • OLIG2 (patchy immunoreactivity) 
  • MAP2 (diffuse immunoreactivity) 
  • S-100 (diffuse immunoreactivity) 
  • GFAP (patchy immunoreactivity) seen in less than 50% of cases
  • synaptophysin  (diffuse immunoreactivity)  seen in over two-thirds of cases

Negative for neurofilament and EMA, and no IDH mutations 1,2,5

Most of these tumors have a low-grade histological appearance, with commensurately low mitotic index (<1%) 1 and behave fairly indolently. Some tumors, however, do demonstrate anaplastic histologic features including increased mitotic rate, and even microvascular proliferation and these have, not surprisingly, had a more aggressive clinical course 3,5

They have not been formally assigned a grade in the 5th edition (2021) of WHO classification of CNS tumors although it does comment on most low-grade tumors being similar to other WHO grade 2 tumors, and those with high-grade features being similar to WHO grade 3 5.

Imaging is ideally carried out with MRI, although CT will demonstrate many of the same features, within its limitations. 

The dominant finding is of thick nodular leptomeningeal enhancement, particularly around the basal cisterns, and extending over the surface of the brain and spinal cord 1

A further finding, which is believed to be fairly specific for this entity, is the presence of numerous small subpial cysts (high T2, low T1, FLAIR attenuating) located over the surface of the inferior parts of the cerebral hemispheres (temporal lobes, inferior frontal lobes), posterior fossa (cerebellum and brainstem) and spinal cord 5. It is thought that perhaps these represent dilatation of the perivascular spaces (Virchow-Robin spaces) 1.

Importantly, often, no definitely dominant primary parenchymal mass identified 1. In many patients, however, discrete intraparenchymal lesions can be identified, most frequently in the spinal cord 5

Although diffuse leptomeningeal glioneuronal tumors demonstrate fairly indolent growth, morbidity is quite prominent due to profound hydrocephalus 2. To complicate matters further, the entity has only relatively recently been described and the literature is confusing; it is unclear if all reported cases are, in fact, of the same entity. Survival varies widely, reported in some instances to be quite low, with an average survival of only 22 months 3, whereas other series have long follow-up 4,5

The differential is essentially that of leptomeningeal enhancement, with the florid nature of enhancement particularly reminiscent of tuberculous leptomeningitis. Causes of leptomeningeal enhancement to particularly consider include: 

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