Angiocentric glioma (AG) is a rare central nervous system (CNS) neoplasm that was first reported by Lellouch-Tubiana et al (1) and Wang et al (2) in 2005. AG was recognized as a distinct clinicopathologic entity by the World Health Organization (WHO) classification of CNS tumors in 2007 and was defined as ‘an epilepsy-associated, stable or slow-growing cerebral tumor primarily affecting children and young adults, histologically characterized by an angiocentric pattern of growth, monomorphous bipolar cells and features of ependymal differentiation (3,4). Since its initial description, an increasing number of cases of AG have been reported in the literature. In the 2016 WHO classification of CNS tumors (5), AG was considered as a WHO grade I tumor and was classified as ‘other gliomas’. The majority of studies on AG focus on the cytological features of the disease (6,7), while there is a lack of clinical and imaging data, as well as descriptions of the surgical treatment. The present study describes two patients with AG that received surgical treatment and provides a review of all previously reported cases to date.

A literature review of studies on AG published in English or Chinese between January 2005 and December 2019 (Fig. 7), performed using Medline, PubMed and the China National Knowledge Infrastructure database, revealed that a total of 108 cases, including the two cases of the present study, have been reported (Table SI) (1,2,6–54). Of the 108 patients with AG, 61 were male and 47 were female (male/female ratio, 1:0.77). The age at the time of admission ranged between 1.5 and 83 years (median age, 13 years) and the majority of the patients were children and young adults. A total of 90 patients (85.7%; 90/105) presented with a long history of several types of intractable seizures (symptoms in three cases were not described). Only 15 patients exhibited different symptoms. Of these 15 patients, eight had headaches, four of which had decreased vision (7,12,47), three experienced dizziness, one of which had otalgia (9,19,49), two had ataxia (11,47), two had swallowing disorders (34,37), two presented with weakness and numbness of the left side of the body (17,45) and one had strabismus (34). The majority of the AG tumors (94.4%; 102/108) were in a supratentorial location situated within/under the cerebral cortex and 81.5% (88/108) were located in a single lobe. A total of six tumors were located in the brainstem (11,34,37,47). In a total of 46 cases, the tumor was in the left brain and in 43 cases, it was in the right brain. As AG arises in a superficial location in the cerebrum, which is typically completely removed, the literature indicated that gross total resection (GTR) of this lesion is curative. A total of 64.9% (61/94) of the patients with AG underwent GTR and 27.7% (26/94) underwent subtotal resection (STR). Furthermore, 7 cases only had a biopsy (7,34,37,47). The follow-up time ranged between 0.25 and 168 months (mean, 23.5 months). Of the patients with resection, 93.1% (81/87) were free of seizures during the follow-up time and the 6 patients with seizure recurrence had all undergone STR. A total of 10 patients received adjuvant therapy including radiation or chemotherapy, of which six received STR and four had a biopsy as the lesions were located in the brainstem (6,14,34,37). Histopathological evaluation revealed that the tumors were WHO grade I, with one exception, which was WHO grade III–IV (17).

The present case study reported on two patients that were surgically treated at the Chinese PLA General Hospital (Beijing, China). The cases were similar to the ones reported in the literature, regardless of age, symptoms, tumor location and prognosis. The 8- and 16-year-old patients of the present study presented with intractable seizures and the 16-year-old patient also presented with headaches and vomiting. In the two patients, the tumor was located in the superficial cerebrum, in the left temporal lobe and in the right frontal lobe, respectively. The two patients underwent GTR. During the follow-up period of 42 and 30 months, the patients were seizure-free and did not experience any tumor recurrence.

Only a few studies have reported on the appearance of AG on CT scan (17,19). Hu et al (19) reported one case of AG that exhibited a hyperdense lesion on CT scan, which may be linked to hemorrhage and hemosiderin deposition. The 16-year-old patient in our cases showed a hypodense lesion on CT scan. The majority of AGs are similar to low-grade gliomas on MRI, i.e., hypointensity on T1-weighted imaging, hyperintensity on T2-weighted imaging, hyperintensity on FLAIR and non-enhanced on the contrast. AG tumors have a well-delineated boundary but may grow diffusely without an obvious edge. Previous studies reported that AG had a cortical rim of hypointensity on T1 and T2 around the lesion, which may be related to long-term compression by the slow-growing low-grade AG (1,14,19). The two patients in the present study also revealed similar characteristics to low-grade glioma, and a rim around the lesion was seen in the second patient.

As there is a lack of specific clinical manifestations and radiological features for AG, diagnosis still depends primarily on histopathological examination. Monomorphic, diffusely infiltrating bipolar spindled cells are commonly arranged around cortical blood vessels or neurons in concentric sleeves and pseudorosettes, which was the typical angiocentric gliomas pattern (15). Immunohistochemical staining results are generally positive for GFAP, S-100 and vimentin, and EMA has a dot-like pattern (8). Based on these findings, the main entities that were considered in the differential diagnosis were ependymoma and AG (6). The neuronal markers NeuN, Syn and chromogranin A (CgA) were usually negative. The Ki-67 proliferative index was ~1% and not >5%. This tumor type is also similar to other benign brain tumor types, including focal cortical dysplasia, ganglioglioma and certain neuroepithelial neoplasms, including pilomyxoid astrocytoma and supratentorial cortical ependymoma. Differences between AG and various easily misdiagnosed brain tumors are presented in Table I (5,55–61).

While AG has been established as a distinct tumor type, its cytogenesis remains elusive. Wang et al (2) posited that AG arises from ependymoma and astroblastoma. Lellouch-Tubiana et al (1) suggested that AG has radial glia or neuronal origin. Bandopadhayay et al (62) and Qaddoumi et al (63) observed that an myeloblastosis quaking (MYB-QKI) gene rearrangement occurred in the majority of tumors, which contributed to the tumorigenesis, and this rearrangement was specific to angiocentric gliomas. Therefore, MYB-QKI gene fusion may be a defining genetic alteration typical for AG. While mutations of isocitrate dehydrogenase-1 most commonly result in the replacement of arginine at position 132 by histidine (R132H) in WHO grade II and III diffuse gliomas and secondary glioblastomas, this was not identified in AG (20,34,43). Therefore, this may facilitate the differential diagnosis of AG from tumors with a higher potential for recurrence.

AG is a slow-growing, stable tumor and lesions in the cerebral cortex are generally benign and may be cured by surgical excision alone. Adjuvant therapy, including chemotherapy or radiation, are not typically required (45). However, angiocentric gliomas arising in structures that are not amenable to surgical resection, including the brainstem, may require stereotactic biopsies and adjuvant therapy (37). Seizure control was dependent on the degree of tumor resection. According to the present review, AG is associated with a more favorable prognosis, with low mortality and incidence of disability. In two cases of tumor recurrence (2,42), the histopathological evaluation revealed a malignant neoplasm (WHO grade III) that was ultimately fatal.

AG is a recently described rare tumor of the CNS and exhibits radiological features on MRI that usually resemble those of diffuse low-grade glioma. AG tends to be non-malignant and curable and typically has a favorable prognosis. However, certain tumors may undergo malignant transformation. Longer follow-up periods are required to accurately establish the time to recurrence, to determine whether additional treatment is required and to establish the overall survival time.