Angiocentric Glioma: Report of a Rare Case Presenting with Psychosis.

Angiocentric glioma (AG), first described in 2005, was included as a distinct entity in the 2007 World Health Organization Classification of Tumors of the Central Nervous System. It is a very rare cerebrocortical tumor mainly affecting children and young adults with a history of intractable partial seizures. The histopathological features of this entity are perivascular arrangement of monomorphic, bipolar spindled cells with subpial aggregation of tumor cells and variable neuroparenchymal colonization. Of uncertain histogenesis, this is a stable/slowly growing tumor. Prognosis following total surgical resection is favorable. We describe an AG in a 16-year-old, intellectually disabled, male patient, with psychosis. This is a rare presentation with only one such case in literature. Patient's symptoms ameliorated following surgery.

Introduction

In 2005, Wang et al. described eight cases of a superficial cerebral tumor marked by an angiocentric growth pattern with features of both ependymal and astrocytic differentiation which they named “Monomorphous Angiocentric Glioma.”[1] Lellouch-Tubiana et al. described ten cases of a nearly identical tumor which they named “Angiocentric Neuroepithelial Tumor.”[2] These tumors were subsequently codified as a distinct clinicopathologic entity named angiocentric glioma (AG) in 2007 World Health Organization (WHO) Classification of Tumors of the Central Nervous System.[3] AG is a rare neoplasm, and only 71 cases are reported till date, to the best of our knowledge. It typically presents in children and young adults (mean age 17 years) with intractable partial seizures and both genders are equally affected.[3] The tumor is characterized by its typical angiocentric arrangement of monomorphic spindled cells and immunoreactivity for glial fibrillary acidic protein (GFAP), S-100, epithelial membrane antigen (EMA), and vimentin.[345] We report a case of AG which presented with psychotic symptoms that ameliorated after surgery.

Case Report

A 16-year-old boy, born of a nonconsanguineous marriage, who had delayed developmental and social milestones since birth presented with complaints of persistent bifrontal headache and vomiting since a week and an episode of generalized tonic-clonic convulsions 1½ months ago. The patient had first presented 2 years ago with irritability, fearfulness, sleep disturbances, auditory hallucinations, delusions of persecution, and suicidal attempts. While being worked up for the above, the right temporal space occupying lesion was found on magnetic resonance imaging (MRI) scan, and the patient was started on antipsychotics and anticonvulsants. The patient followed up erratically over the next 2 years and had little relief from his symptoms. Three months ago, the patient stopped all medications on his own, and he had a single episode of seizure as described above.

Recently, MRI showed a 1.7 cm × 1.2 cm solid cystic lesion, hyperintense on T1- and T2-weighted images, in the right medial temporal lobe within the parahippocampal gyrus, [Figure 1] with extensive cortical dysplasia suggestive of the right mesial temporal low-grade space occupying lesion. The patient underwent the right temporal craniotomy with total excision of the tumor.

Figure 1

Magnetic resonance imaging showing (a) solid cystic lesion, hyperintense on T1 postcontrast and (b) T2 weighted images in the right medial temporal lobe within the parahippocampal gyrus

Multiple gray-white fragmented tissue bits aggregating into 1.5 cm × 1 cm × 1 cm were received. The histopathologic examination showed small fragments of cerebral parenchyma with a diffusely permeating cortical-subcortical tumor of moderate cellularity with a fibrillary background. The tumor cells showed subpial aggregation and were arranged in sleeves around blood vessels [Figure 2a] with hyper and hypocellular areas reminiscent of a schwannoma [Figure 2b] prominent perivascular arrangement with pseudorosettes were seen [Figure 2c and d]. The tumor cells were monomorphic, elongate with spindle-shaped slender nuclei, and granular stippled chromatin [Figure 2d]. There was no evidence of necrosis, mitosis, or microvascular proliferation. The cells were immunoreactive for GFAP (clone GA 5) [Figure 2e] and S-100 (polyclonal) and were negative for synaptophysin and chromogranin. EMA (clone MC 5) showed dot positivity [Figure 2f]. All these antibodies are ready to use from Biogenex laboratory. MiB-1 labeling index was <1%. Based on the above morphology and immunohistochemistry, a diagnosis of AG was made. The adjacent normal parenchyma was not adequate to evaluate for features of cortical dysplasia.

Figure 2

(a) Angiocentric glioma showing subpial aggregates of tumor cells (H and E, ×40). (b) Hypercellular and hypocellular areas (H and E, ×100). (c and d) Prominent perivascular arrangement of tumor cells. (e) Tumor cells are expressing glial fibrillary acidic protein. (f) Dot-like ethelial membrane antigen positivity in tumor cells

At his 6 months follow-up visit to the Neurosurgery Outpatient Department, the patient was feeling well with reduction in his psychiatric symptoms and no episode of seizure after the surgery. The patient was continued on antipsychotics and anticonvulsant medications.

Discussion

AG is included in the category of “Other Gliomas” in the 2016 WHO Classification of Tumors of the Central Nervous System.[3] It is a rare low-grade glial neoplasm with distinct clinicopathological features. To the best of our knowledge, seventy-one cases of AG [Table 1] have been reported till date.[45678] They are generally associated with long-standing drug resistant epilepsy, which was seen in 63 out of 71 cases. In literature, there are only eight cases with no history of seizures. These presented with only headache in one, headache with visual disturbance in 3, headaches with decrease hearing and vision in one, and dizziness in two cases. Cranial neuropathies with gait abnormality were seen in a case with posterior midbrain tumor and psychosis with a temporal lobe tumor, as seen in the present case, is reported in only one case.[6] This case was of 13-year-old adolescent who presented with auditory and visual hallucinations, persecutory delusions, and aggression. The patient's symptoms remitted after the resection of the left temporal lobe, fusiform gyrus, uncus, amygdala, and hippocampus. Histological examination revealed AG.

Table 1

Seventy-one cases of angiocentric glioma published in literature

The present patient was intellectually disabled, and he was evaluated only when he showed symptoms suggestive of psychosis, at which time the temporal SOL was found. The psychotic symptoms, especially hallucination and delusion, can probably be explained by the location, which is medial temporal lobe, i.e., the parahippocampal gyrus. Many human and primate studies have shown that parahippocampal gyrus has a multimodal association with psychosis and its volume correlates with the severity of symptoms.[910]

Radiologically, AG is well-delineated solid, hyperintense on T2, non-enhancing cortical, or subcortical lesion and is described to form wedge-shaped lesions, which diffusely infiltrate the surface in a stemlike (stalklike) manner in the direction of the cerebral ventricle with focal enlargement of affected cortical gyrus.[3]

The characteristic histology is monomorphic, bipolar spindled cells oriented about cortical blood vessels extend lengthwise along vascular axes and as radial pseudorosettes. In addition, cells often aggregate beneath the pia-arachnoid in horizontal streams or perpendicular, strikingly palisaded arrays. Nuclei are slender, with granular chromatin stippling. Unusual histological features documented are astroblastoma-like structures, cystic regions, myxoid change, presence of abnormal neurons, and high MiB1 labeling index (6%–10%). The clinical significance of these atypical features is as yet uncertain. The main differential diagnoses on microscopy include ependymoma and pilomyxoid astrocytoma.[8] The presence of perivascular pseudorosettes and dot positivity on EMA mimics ependymal tumors; however, AG differs from ependymoma by its clinical presentation, cerebrocortical location and monomorphic spindle cells morphology with subpial aggregation and arrangement of tumor cells along the long axes of blood vessels.[37] Pilomyxoid astrocytoma usually occurs at a very young age (median 10 months) and is most often located in the hypothalamic/chiasmatic region.[3] It may histologically resemble AG due to the angiocentric arrangement of bipolar-spindled tumor cells, but it shows a prominent mucinous background and is not infiltrative.[8]

A subset of AGs is associated with malformation of cortical development/focal cortical dysplasia.[8] Cortical dysplasia was reported on MRI in the present case as well; however, the resected specimen showed very little normal cortex and cortical dysplasia could not be ascertained. Histogenesis of these tumors is unclear. Wang et al. suggested astrocytic and ependymal origin whereas Lellouch Tubiana et al. have proposed a dysembryoplastic process with origin from radial glia.[2] Prognosis following gross total resection is very good with complete cessation of seizures. A follow-up is available in 57 of 71 patients published in literature [Table 1], out of which 2 succumbed to death due to the disease. Of these 55 patients, 45 underwent a total resection and were free of symptoms without recurrence. The remaining 10 patients had stable residual disease, out of which 9 underwent partial resection, and one was not operated at all and was diagnosed on biopsy alone.[347]

This case illustrates the classical morphology of AG and is unusual for its clinical presentation.

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