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The clinical, radiological, and surgical characteristics of anterior perforated substance glioma: a retrospective study



To explore the clinical, radiological, and surgical characteristics of anterior perforated substance (APS) gliomas.


Twenty patients with APS glioma who were treated with surgery between March 2019 and January 2022 from Tiantan hospital were retrospectively reviewed. The clinical, histological and radiological data were collected.


Twenty patients, including 7 males (55%) and 13 females (45%), with a mean age at diagnosis of 37.9 years (range, 28–53 years) underwent operative intervention for APS. Headaches and dizziness were the most common preoperative symptoms in the majority patients (14, 70%). Based on radiological features of MRI, the APS was classified into two subtypes, type A and type B. Seven patients (40%) in type A indicated a clear tumor margin, while 13 patients (60%) in type B showed an ill-defined margin. The surgical approach including frontal, temporal, and coronal frontal incisions for type A and type B tumors, respectively. Three patients in type A received total resection, while one patient in type B were total resected. Pathologically, 12 cases (60%, 12/20) were diagnosed as astrocytoma and 8 cases (20%, 8/20) were oligodendroglioma. Meanwhile, 17 cases (85%, 17/20) had MGMT promotor methylation.


In this study, we performed the first systematic research of patients with APS glioma. Most of patients with APS presented headaches and dizziness symptoms. The APS glioma was further divided into two major radiological subtypes with relevant different surgical approaches. The APS glioma in type A were more likely to receive total resection.


The anterior perforated substance (APS) is a special anatomical area. It is a small area with only 23.3 ± 3.4 mm (19–27) in the mediolateral and 12.5 ± 1.2 mm (11–14) in the anteroposterior directions [1]. Although the size is inconspicuous, it contains many important structures, such as anterior perforating arteries and lenticulostriate arteries [2]. These arteries are essential sources of blood supply for some important structures, such as the internal capsule, putamen, and caudate nucleus [3].

Glioma is the most common malignant brain tumor in the central nervous system [4]. The anatomic location of glioma influenced the progression and outcome of patients [5]. However, gliomas in APS have not been well characterized in recent research. Therefore, we conducted this study and aimed to explore the characteristics of patients with APS gliomas.


This study was a retrospective study. The study was approved by the ethics committee of Beijing Tiantan Hospital. The clinical information of 20 patients with APS glioma were collected between March 2019 and January 2022. All patients underwent surgery and were pathologically confirmed. As shown in Table 1, among the 20 patients, 11 patients were male and nine patients were female. The mean age was 37.90 ± 7.00 years old, ranging from 28 to 53 years old.

Table 1 The Clinical information of APS patients

All patients underwent magnetic resonance imaging (MRI) scanning before surgery. The MRI sequence included pre-contrast T1-weighted image(T1WI), T2-weighted image(T2WI), fluid attenuated inversion recovery (FLAIR), diffusion weighted image (DWI), and post-contrast T1WI. The MRI scanners used were SIEMENS Verio (5 cases), SIEMENS Prisma (3 cases), Philips Ingenia CX (2 cases), Philips Ingenia (4 cases), GE SIGNA Explorer (2 cases), and GE DISCOVERY MR750 (4 cases). The thickness and gap of scanning were 5.00–5.50 mm and 6.00–6.50 mm, respectively.

According to the preoperative MRI, the APS gliomas were divided into two types: type A, the tumor mainly located in the APS, showing an expansive growth pattern, while the margin was relatively clear (Fig. 1A-D); and type B, the tumor extended out of the APS, showing a diffuse growth pattern with an ill-defined margin (Fig. 2A-F).

Fig. 1
figure 1

33-year-old male patient with type A anterior perforated substance (APS) glioma. The lesion involves the right posterior part of straight gyrus, the anterior and inferior part of basal ganglia, and the medial of insula. It is low signal on T1-weighted image (T1WI) (A), high signal on T2-weighted image (T2WI) (B), low signal on diffusion weighted image (DWI) (C), and no enhancement (D)

Fig. 2
figure 2

36-year-old female patient with type B APS glioma. The lesion involves the left temporal pole, orbital gyrus, straight gyrus, paraolfactory gyrus, and paraterminal gyrus. It is low signal on T1WI (A), high signal on T2WI (B) and fluid attenuated inversion recovery (FLAIR) (C), low signal on DWI (D) and high signal on apparent diffusion coefficient (ADC) (E). On post-contrast axial image, it demonstrates patchy enhancement (F)


The clinical characteristics of the 20 patients with APS gliomas were presented in Table 1. The most common symptom was headache with or without dizziness (70%, 14/20), followed by epilepsy (30%, 6/20). Radiologically, 7 cases (35%, 7/20) were type A and 13 cases (65%, 13/20) were type B.

As shown in Table 2, total resection was performed in 3 patients (42.8%) in type A compared with 1 patient (7.6%) in type B (p = 0.101). There was a trend that APS glioma in type A was more likely to obtain total resection. Meanwhile, the molecular analysis indicated that all APS gliomas were IDH mutation and the proportion of 1p/19q codeletion was similar in two groups (p = 0.999). Besides, patients in type B were associated with MGMT promoter methylation (92.3%) and TERT promotor mutation (38.4%). In addition, all patients in type A were diagnosed as grade 2 glioma (3 astrocytoma. 3 oligodendroglioma), and nearly half of type B patients were grade 3 glioma (p = 0.031). The results indicated that type B APS gliomas were more aggressive and heterogeneous.

Table 2 The clinical and histological information of patients

In order to achieve maximum safe resection, different surgical approaches were performed. For type A glioma, surgical approaches of frontal and temporal incisions were used (Fig. 3A). After resection of the lateral orbital and the partial inferior frontal gyri, the gray tumor, olfactory nerve, and olfactory trigone could be exposed. The olfactory trigone was considered the frontal margin of surgical resection (Fig. 3B). The tumor was then removed from the lateral olfactory stria to the insula with exposure of the internal carotid artery, M1 segment of the middle carotid artery, and insula. When the outside lenticulostriate artery originating from M1 penetrating the APS was confirmed, the lateral margin of resection could be determined (Fig. 3C). The medial margin of resection may be the anterior median fissure, and the genu of the corpus callosum and A2 segment of the anterior carotid artery may be the anatomical signs. When resecting the lateral part of the tumor, the operation should be as softly as possible. We recommended to remove the tumor with aspirator one by one layer (as thick as 1 mm) and avoid using the electrocoagulation. As shown in the Fig. 3D, we can see the lenticulostriate artery penetrated the tumor during the surgery. When the posterior and superior parts of the tumor were resected, the amplification and brightness of the microscope should be adjusted. Through applying intraoperative neuro-navigation, the caudate nucleus and putamen could be identified, which showed bright and cream-colored spots under microscope (Fig. 3E). When these structures were exposed, the medial and lateral margins of the resection could be confirmed. The caudate nucleus (white spots on a gray/red background) and putamen (white stripes and dots of beige color) were the posterior and superior margins and the lateral margin of the resection (Fig. 3F). As shown in Fig. 3G, the anatomical structures of the APS could be clearly identified after the tumor resection.

Fig. 3
figure 3

The intraoperative of type A APS glioma. A, Preoperative axial T2WI showing type A APS glioma. B, Intraoperative view before resection (1. the orbital part of the inferior frontal gyrus (IFG), 2. superior temporal gyrus (STG), 3. sylvian fissure (SyF), 4. anterior sylvian point (ASyP), 5. the middle frontal gyrus). C, The lateral margin of resection (1. Olfactory tract and olfactory trigone, 2. Tumor). D, Intraoperative view of lenticulostriate artery (1. the planum polare, 2. the early branch of middle cerebral artery (MCA), 3. the M1 segment of the MCA, 4. extraparenchymatous segments of the most lateral lenticulostriate arteries (LSAs), 5. the limen insular). E, The medial and lateral margins of the resection (1. intraparenchymatous segment of the most lateral LSAs, 2. tumor in APS). F, The posterior and superior margins and the lateral margin of the resection (1. the putamen, 2. the head of the caudate nucleus, 3. The lenticulostriate veins, 4. the limen insular). G, Intraoperative view after resection (1. Internal carotid artery, 2. M1, 3. A1, 4.CN II, 5. APS, 6. superior temporal gyrus (STG), 7. the posterior part of the inferior frontal gyrus (IFG), 8. the middle frontal gyrus)

For tumors of type B, glioma invasion of frontal lobe, the surgical approach was coronal frontal incisions. The medial margin of the craniotomy was approximately 1–1.5 cm lateral to the midline. The posterior margin of the craniotomy was anterior to the coronal suture. The lateral margin of the craniotomy reached sphenoid ridge to expose the sylvian fissure. The anterior margin of the craniotomy could be performed just at the level of the skin flap exposure and be adjusted according to the size of the frontal sinus. We avoided opening the frontal sinus as much as possible.


APS is a special anatomical area, which contains many vessels [6]. Previous studies involving APS mainly focused on vascular diseases [3, 7,8,9]. Glioma, one of the most common malignant tumors in the central nervous system, can also locate in APS. However, gliomas in this area have not been well described. Our retrospective study revealed that APS gliomas differed from those in other areas in terms of clinical, radiological, and surgical characteristics.

In our study, patients with APS gliomas showed a slightly male predominance, which was in consistent with the overall population characteristics of patients with gliomas reported by Li et al. [10]. The mean age of patients with APS gliomas was 37.90 ± 7.00 years old, which was younger than 60 years old [11]. This discrepancy may be caused by the small sample size of our study; Moreover, the low tumor grade of APS gliomas in our study may play a part, as the mean age increased with the growing of glioma grade [11]. Regarding to symptoms, the most common symptom in patients with APS gliomas were headache with or without dizziness (70%, 14/20), which were different from those reported by Rasmussen et al. and IJzerman-Korevaar et al. [11, 12]. This may be a unique clinical characteristic of APS gliomas. Due to the small sample size of our study, the reliability needs to be further verified in the future.

Radiologically, APS gliomas show hypointensity on T1WI, hyperintensity on T2WI and T2 FLAIR, nonrestricted diffusion and partial enhancement on post-contrast T1WI. These radiological characteristics were not specific for gliomas. It’s worth pointing out that APS gliomas can be divided into two subtypes according to their morphological appearances on radiological images (type A, localized tumor with well-defined margins; type B, diffused tumor with ill-defined margins). This artificial classification is helpful for tumor resection and cognition of the relationship between gliomas and adjacent structures in APS.

The surgical resection of glioma in APS is a challenge for neurosurgeons due to the special anatomic characteristics. On the one hand, the determination of the depth and extent of resection is difficult. Tumor exposure and determination of the extent of resection are big challenges for APS glioma. APS is overlapped by the uncinate gyrus, olfactory trigone, optic nerve, and optic tract. Thus, it is difficult to fully expose APS. And anatomical landmarks were needed to determine the extent and depth of resection. For example, the olfactory trigone is an important landmark for determining the anterior margin of APS. Restricted by the drift of brain tissue, intraoperative navigation is not completely reliable. Therefore, gray matter identification is of great importance during surgery; On the other hand, the exposure and protection of penetrating arteries are challenging, especially the lateral lenticulostriate arteries.

Our study showed that the pathological diagnosis of all patients with APS gliomas were lower grade gliomas Furthermore, all APS gliomas possessed IDH mutations, which was higher than the general ratio of 45% in gliomas reported by Eckel-Passow et al. [13, 14]. The ratio of MGMT methylation was 85% (17/20), which means the increased sensitivity to chemotherapy and longer patient survival [14, 15]. The ratio of TERT mutations in our study was 25% (5/20), which was higher than that obtained in the study by Killela et al. [16]. The genetic status of APS gliomas provides positive information for patients because IDH mutation in gliomas has been a treatment target [17,18,19]. Patients with IDH-mutated gliomas show better prognosis [18,19,20], while patients with TERT-mutated glioma show compromised overall survival and progression-free survival [21].

Our study had some limitations. First, as a retrospective study, selective bias may exist, and the sample size was not large. Further study with more cases is needed in the future. Second, the APS patients were IDH mutation lower grade glioma with the longest follow-up nearly 4 years. Detailed information of patients with APS gliomas after surgery should be supplemented in the future. Third, except for routine MRI and DWI, more advanced imaging modalities should be performed for the tumors.

In conclusion, our study showed that gliomas in APS have different clinical, radiological, and pathological characteristics. Tumors can be divided into two types according to the radiological patterns with relevant different surgical approaches. Moreover, most APS gliomas are low-grade gliomas with a high ratio of IDH and TERT mutations and MGMT methylation. Due to the special anatomical characteristics of APS, more research is needed on gliomas in this area.

Availability of data and materials

The sequencing data, clinical, and follow-up information of patients were uploaded to the CGGA portal ( All datasets used and/or analyzed in this study are available from the corresponding author on reasonable request.



Anterior perforated substance


Diffusion weighted image


Fluid attenuated inversion recovery


Magnetic resonance imaging


T1-weighted image


T2-weighted image


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This study has received funding by the National Natural Science Foundation of China (No.81772005, No.82102764) and the collaborative innovative major special project supported by Beijing Municipal Science & Technology Commission (No. Z191100006619088).

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Conception and design: ZZ, XZC. Development of methodology: WZL. Acquisition of data: LWL, ZW. Analysis and interpretation of data: WZL. Writing, review and/or revision of the manuscript: LWL, ZW. Administrative, technical, or material support: ZZ, XZC. Study supervision: ZZ. All authors read and approved the final manuscript.

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Correspondence to Xuzhu Chen or Zhong Zhang.

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This study was approved by Capital Medical University Institutional Review Board (IRB) (KY2014-002-02). Written informed consent was obtained from the patients (or their families) for the CGGA proj.

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Not applicable.

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The authors declare no potential conflicts of interest.

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Wang, Z., Li, L., Wang, Z. et al. The clinical, radiological, and surgical characteristics of anterior perforated substance glioma: a retrospective study. Chin Neurosurg Jl 9, 36 (2023).

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