Calcifications in diffuse leptomeningeal glioneuronal tumors: a case series

Abstract

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a new rare entity, typically seen in the pediatric population. Classical neuroimaging features at clinical onset include marked subarachnoid/leptomeningeal enhancement and tiny pseudo-cystic lesions along the subpial surface of the neuroaxis, frequently associated with communicating hydrocephalus. However, data on the long-term appearance of this tumor on computed tomography (CT) and magnetic resonance imaging (MRI) are still lacking. We describe a peculiar pattern of progressive leptomeningeal calcifications in three young patients with DLGNT. The calcifications, mainly located in the basal cisterns, sylvian fissures and posterior surface of the thalami, were present at clinical onset in the older subject and appeared about 2 years after clinical onset in the other two. Patients underwent different schemes of chemotherapy, variably associated with craniospinal irradiation and/or bevacizumab. In all cases, calcifications were present before starting craniospinal irradiation and/or treatment with bevacizumab. This novel peculiar pattern of progressive leptomeningeal calcifications expands the imaging phenotype of DLGNT and should be carefully sought, especially in later phases of the disease. Taking into consideration the onset, evolution, and absence of direct relationship with treatments, we hypothesize that calcifications in DLGNTs might be the effect of natural changes in the tumor and its environment.

Keywords: Diffuse leptomeningeal glioneuronal tumor (DLGNT); calcifications; case report; chemotherapy; radiotherapy.

Figure 1

Histologic features in DLGNT. The histological slides of the pathological tissue at the spinal level (Appendix 1, case 3) are obtained after fixation in formalin and inclusion in paraffin. (A) The microscopic examination shows, in the sections stained with hematoxylin-eosin (40× magnification), a moderately cellulated neoplasm consisting of elements embedded in a fibrous stroma (referable to dural tissue) that appear monomorphic, with a rounded/oval profile, with a perinuclear “oligodendroglioma-like” halo, uniform nuclei and an inconspicuous nucleolus. No mitotic figures, microvascular proliferation or necrosis are present; (B) these elements are positive on immunohistochemical characterization for Synaptophysin (×40). DLGNT, diffuse leptomeningeal glioneuronal tumors.

Figure 2

Brain and spinal MRI and CT scans of patient #1 performed at last follow-up at the age of 12.4 years. Axial T2-weighted (A-C) images show multiple small cysts scattered on the surface of the cerebellum, brainstem, mesial temporal lobes, and hypothalamus. Post-contrast T1-weighted images (D-G) reveal contrast enhancement along the surface of the spinal cord, roots of the cauda equina, and brainstem (arrowheads), and at the level of basal cisterns (arrows). Brain CT images (H-J) reveal leptomeningeal calcifications at the level of inferior cerebellar vermis (arrowhead), basal cisterns (arrows), frontal (empty arrow) and insular sulci (thick arrows). MRI, magnetic resonance imaging; CT, computed tomography.

Figure 3

Brain and spinal MRI and CT scans of patient #3 performed at last follow-up at the age of 25 years. Axial T2-weighted (A, B) and post-contrast T1-weighted (C-E) images show markedly enlarged cerebral and cerebellar subarachnoid spaces with confluent non-enhancing cystic changes, also visible along the frontal horns of the lateral ventricles (arrows). The periventricular white matter is markedly thinned with consequent enlargement of the lateral ventricles (asterisks). At this stage, there is no contrast-enhancement of the leptomeninges around the brain, but the cortex appears diffusely hypointense on both T1- and T2-weighted images. Sagittal contrast-enhanced T1-weighted image of the spine (E) demonstrates diffuse enhancement along the surface of the spinal cord and cauda equina roots, associated with marked enlargement of the subarachnoid spaces (asterisk) and bone scalloping (thick arrow) at the level of the dural cul-the-sac (this feature was not present at clinical onset); (F-I) axial SWI reveals marked hypointensities involving the cerebral and cerebellar cortex and the leptomeninges surrounding the brainstem. A faint linear hypointensity is also noted along the ventricular ependyma; (J-M) corresponding CT images show multiple coarse nodular calcifications at the level of the inferior vermis (thick arrow), hypothalamus (arrows), posterior midbrain (empty arrow) and mesial thalami (arrowheads), and along some sulci in the right frontal region (dotted arrow). MRI, magnetic resonance imaging; CT, computed tomography; SWI, susceptibility weighted imaging.

Figure 4

Head CT examinations showing the evolution of intracranial calcifications in patients with DLGNT. (A-D) patient #1: (A) CT at clinical onset (4 years of age) after ventricular shunting reveals no intracranial calcifications; (B) after 3 years, at the age of 7 years, subtle leptomeningeal calcifications appear at the level of anterior mesial frontal gyri (arrowheads), and progressively increase at subsequent CT examinations performed at 9 years (C) and at 11 years of age (D). New calcifications are visible at the level of right insula (arrows); (E-H) patient #2: (E) CT at clinical onset (2 years of age) demonstrates a communicating hydrocephalus without intracranial calcifications; (F) after 2 years, at the age of 4 years, multiple calcifications are noted at the level of basal cisterns (arrows), that progressively increase in number and size at subsequent examinations performed at 6 years (G) and 9 years (H), also involving the basal frontal and mesial temporal sulci, the cerebral convexity and hypothalamus; (I-L) patient #3: (I) CT at clinical onset (13 years of age) shows presence of calcifications along the posteromedial surface of the thalami (arrows). Follow-up CT scans performed at 15 years (J), 20 years (K) and 25 years of age (L) demonstrate increase of calcifications at the level of the leptomeninges over the posteromedial surfaces of the thalami and scattered along the cerebral convex sulci (arrowheads). Note the progressive enlargement of the lateral ventricles and subarachnoid spaces. DLGNT, diffuse leptomeningeal glioneuronal tumors; CT, computed tomography.

Figure 5

Brain and spinal MRI and CT scans of patient #2 performed at last follow-up at the age of 9 years. Axial diffusion-weighted (A), T2-weighted (B) and post-contrast T1-weighted (C) images reveal an acute ischemic infarct at the level of the left temporal cortico-subcortical region (empty arrows), in the posterior peripheral branches of the middle cerebral artery, associated with cortico-subcortical gliosis and atrophy with laminar necrosis at the level of the contralateral temporal lobe (thin arrows), resulting from the previous ischemic infarct in the right middle cerebral artery territory. There are also diffuse deep white matter signal changes, likely related to radiation-induced leukoencephalopathy. Note the enlargement of subarachnoid spaces and thickening and contrast enhancement of the dura overlying the cerebral convexity; (D) sagittal contrast-enhanced T1-weighted image of the spine demonstrates diffuse enhancement along the surface of the spinal cord as well as the roots of the cauda equina; (E-G) axial head CT images show widespread confluent calcifications at the level of basal cisterns (arrows) and hypothalamus, and along the surface of the mesial temporal, frontal, and occipital lobes, insulae and pulvinar (empty arrows). Few nodular calcifications are also scattered in the depth of fronto-temporo-parietal sulci (arrowheads). MRI, magnetic resonance imaging; CT, computed tomography.