Angiocentric Glioma

Abstract

Angiocentric glioma has recently been described as a novel epilepsy associated tumor with distinct clinico-pathologic features. We report the clinical and pathologic findings in 8 additional cases of this rare tumor type and extend its characterization by genomic profiling. Almost all patients had a history of long-standing drug-resistant epilepsy. Cortico-subcortical tumors were located in the temporal and parietal lobes. Seizures began at 3 to 14 years of age and surgery was performed at 6 to 70 years. Histologically, the tumors were characterized by diffuse growth and prominent perivascular tumor cell arrangements with features of astrocytic/ependymal differentiation, but lacking neoplastic neuronal features. Necrosis and vascular proliferation were not observed and mitoses were sparse or absent. MIB-1 proliferation indices ranged from <1% to 5%. Immunohistochemically, all cases stained positively for glial fibrillary acidic protein, vimentin, protein S100B, variably for podoplanin, and showed epithelial membrane antigen-positive cytoplasmic dots. Electron microscopy showed ependymal characteristics in 2 of 3 cases investigated. An analysis of genomic imbalances by chromosomal comparative genomic hybridization revealed loss of chromosomal bands 6q24 to q25 as the only alteration in 1 of 8 cases. In 1 of 3 cases, a high-resolution screen by array-comparative genomic hybridization identified a copy number gain of 2 adjacent clones from chromosomal band 11p11.2 containing the protein-tyrosine phosphatase receptor type J (PTPRJ) gene. All patients are seizure free and without evidence of tumor recurrence at follow-up times ranging from 1/2 to 6.9 years. Our findings support 2 previous reports proposing that angiocentric glioma is a novel glial tumor entity of low-grade malignancy.

Angiocentric Glioma-Like Tumor of the Midbrain

“…In all previous reports of angiocentric glioma, tumors were located in the cerebral hemispheres, and the vast majority of patients presented with seizures [1,2,3,4,6]. We describe the unique case of a 5-year-old girl who presented with several cranial neuropathies and mild gait disturbance.…”

“…Angiocentric glioma was first added to the WHO tumor classification in 2007 based upon 4 previous reports describing 26 patients in total [1,2,3,4,5]. All previously reported cases occurred in children or young adults, and almost all patients presented with seizures.…”

“…Imaging findings include hyperintensity on T 2 -weighted and FLAIR MRI sequences without contrast enhancement [3]. Histologically, tumors are composed of bipolar spindle cells arranged around blood vessels in concentric sleeves and pseudorosettes [2,3,4]. Angiocentric gliomas have been classified as WHO grade I based upon their indolent clinical behavior, absent mitoses, and low MIB-1 proliferative index [4,5,7].…”

“…Histologically, tumors are composed of bipolar spindle cells arranged around blood vessels in concentric sleeves and pseudorosettes [2,3,4]. Angiocentric gliomas have been classified as WHO grade I based upon their indolent clinical behavior, absent mitoses, and low MIB-1 proliferative index [4,5,7]. Immunohistochemical staining is typically positive for GFAP, S100, vimentin, and a ‘dot-like’ pattern for EMA [4].…”

“…These authors also noted ependymoma-like characteristics, and postulated a derivation of this curious lesion from bipolar radial glia that spans the embryonic neuroepithelium and that may exhibit ependymoglial traits or be capable of spawning ependymocytes. Based upon these reports and an additional 8 examples analyzed by Preusser et al [4], the 2007 World Health Organization (WHO) classification system designated this new pathological entity under the term ‘angiocentric glioma’ [5]. …”