© Li et al.; licensee BioMed Central Ltd. 2014
Received: 5 January 2014
Accepted: 13 February 2014
Published: 20 February 2014
Meningioangiomatosis (MA) is a rare hamartomatous lesion. Only six cases of cystic MA have been reported in the literature.
We present a case of multicystic MA. A 21-year-old woman without any stigmata of neurofibromatosis type 2 presented with intractable seizures since 10 years. Brain magnetic resonance imaging revealed a well-defined, multicystic mass with heterogeneous signal intensity in the right temporal lobe. The patient underwent resection of the lesion and of the epileptogenic cortex under intraoperative electrocorticography (ECoG) assistance. Histopathological examination showed proliferation of perivascular cells that were arranged in a cuff pattern and were positive for vimentin, D2-40 and smooth muscle actin. Mutiple microcysts and enlarged perivascular spaces were present, which was similar to the structure of the arachnoid cavity. Hyalinized collagen fibers with round concentric acellular eosinophilic lamellae within areas of reactive gliosis were noted for the first time in MA. The patient was followed up without any clinical symptoms or recurrence for 2 years.
MA may originate from arachnoid and vascular tissue trapped in the cortical parenchyma during brain development, and the cysts may have resulted from the gradual accumulation of cerebrospinal fluid in the perivascular spaces of the trapped tissue. Resection of the lesion and of the epileptogenic cortex is important not only for pathological diagnosis but also for seizure control, and intraoperative ECoG assistance is recommended.
KeywordsMeningioangiomatosis Multicystic Seizure Hamartomatous lesion
Meningioangiomatosis (MA) is a rare and benign congenital disorder that involves the cortex and the overlying leptomeninges and primarily affects children and young adults . It may occur sporadically or in association with neurofibromatosis type 2 (NF2) . Approximately 120 cases of MA have been reported in the literature. Of these, only six cases were accompanied by cystic lesions [3–7]. We assess the clinical, eletrophysiological, imaging and pathological features of a case of sporadic MA with multiple microcysts, and herein, we discuss the mechanisms and treatment of this disorder.
Gross examination of the resected right temporal lobe revealed some whitish tissue that measured 5.0 cm × 2.5 cm × 1.5 cm and had medium consistency and multiple, small, fluid-filled cysts. The right hippocampus showed some whitish tissue measuring 0.8 cm × 0.5 cm × 0.5 cm.
To determine the origin of the proliferative or lesional cells, immunohistochemical examination was performed using the Ventana BenchMark XT system (Roche Ltd., Ohio, USA). Antibodies against the following antigens were used: vimentin (clone V9; Maixin, Fuzhou, China), smooth muscle actin (SMA, clone 1A4; Dako, Carpinteria, CA, USA), epithelial membrane antigen (EMA, clone E29; Maixin), cytokeratin (CK, clone AE1/AE3; Maixin), D2-40 (clone D2-40, Dako), factor VIII (Maixin), CD31 (clone JC70A, Dako), CD34 (clone QBEnd/10; Zhongshan, Peking, China), H-cald (clone H-cald, Dako), glial fibrillary acidic protein (GFAP, clone GA-5; Maixin), neurofilament (clone 2F11, Dako) and Ki-67 protein (clone MIB-1, Dako). The perivascular cells were mainly immunopositive for vimentin and D2-40, focally or weakly positive for SMA, EMA and CD34, and negative for CK, CD31, H-cald, GFAP and neurofilament (Figure 2D,E and F). The cyst walls were often immunoreactive for vimentin, D2-40 and SMA, and less frequently for CK, H-cald and CD34. Immunoreactions with CD34, CD31 and factor VIII were detected within the cytoplasm and/or the plasmalemma of the vessels in the center of the perivascular cuffs. Ki-67 staining revealed no immunoreactive nuclei in the perivascular cells. The cerebral cortex between the perivascular cell nests was immunopositive for GFAP, neurofilament and EMA. The final diagnosis was multicystic MA.
MA is a rare and benign meningovascular hamartomatous condition that usually involves the cerebral cortex in the frontal or temporal regions, with varying involvement of the overlying leptomeninges. The lesions are often associated with NF2, although the majority of cases are sporadic . Sporadic MA usually occurs as a solitary lesion in young patients and presents with a history of intractable seizures or persistent headaches [9, 10]. In contrast, NF2-associated MA more frequently involves multiple lesions and is asymptomatic . In some patients, MA may be accompanied by tumors such as meningiomas, astrocytomas and oligodendroglioma [12–14].
Summary of seven cases of cystic meningioangiomatosis
Symptoms and signs
Fedi M 
Rapidly progressing right hemiparesis and urinary incontinence
Three lesions in the left frontal cortex and subcortical white matter, a large meningioma in the foramen magnum, bilateral acoustic and right trigeminal neuromas
Small cysts within the lesions
Resection of meningioma
Died of bilateral brainstem infarction 8 months later
Wang Y 
Intractable seizures for 7 years
Cystic lesion in the left frontal lobe
Large cyst within the lesion
Seizures controlled with antiepileptic drugs for 10 months
Kobayashi H 
Intractable seizures for 3 years
A 2–3 cm mass containing small cysts in the left frontal lobe; the mass was hypointense on T1 images and isointense on T2 images
Small cysts in the periphery of the lesion
Seizures controlled with two antiepileptic drugs for 10 months
Kuchelmeister K 
Headache, forgetfulness for 10 years
Multiple cysts and a meningioma in the right frontal lobe
Septated large multiple cysts
Forgetfulness persisted; no recurrence of the lesion for 2 years after the surgery
Park MS 
Headache, generalized seizures for 5 years
Round calcified masses and eccentric cysts with edema in the left frontoparietal and right parietal lobes
Eccentric cysts in the left lesion
Total removal of the left lesion
No seizures or headaches for 15 months after the surgery
Headache, generalized seizures for 2 years
Dense round calcified cysts in the left frontal and parietal lobes
Multiple macrocysts within the lesions
Total removal of both frontal and parietal lesions
No seizures or headaches for 7 months after the surgery
Generalized complex seizures for 11 years
Lesion showing heterogeneous signals in the right temporal lobe
Multiple microcysts within the lesion
Total surgical removal
No seizures for 2 years after the surgery
The mechanisms involved in the development of MA have not yet been elucidated. MA was considered a hamartomatous proliferation of meningothelial cells, blood vessels and fibroblasts in variable proportions . However, the observation of abnormal local vascularization in some patients has led several authors to regard MA simply as a vascular malformation with an added meningothelial reaction . Furthermore, it has also been suggested that these tumors do not grow or display malignant features. Some studies have supported the opinion that MA may be related to NF2 gene mutation because of its concomitance with NF2 . In our patient, immunohistochemical examination demonstrated that the perivascular cells had originated from arachnoid cap cells. Considering the histopathological findings, the patient’s age at onset and the location of the lesion, we propose that MA is a hamartoma that results from the trapping of arachnoid and vascular tissue in the cerebral parenchyma during brain development, rather than a true neoplasm. The wide spectrum of immunohistochemical staining patterns observed in the perivascular cells in MA lesions in the cases reported in the literature and in our case suggests that MA originates from pluripotent cells. The exact mechanism underlying cyst development in MA remains controversial. It has been speculated that cysts form due to the accumulation of CSF within the lesion in a manner similar to the mechanism of cyst formation in cystic meningiomas ; however, a communication between the cysts and the subarachnoid space has not been confirmed in MA . In our patient, the proliferation of meningothelial-like cells and loose perivascular cells observed on the cortical surface may have been the early stages of the typical cystic lesion in the deep cortex and white matter, and the cystic component was attributable to the enlarged perivascular spaces. The long duration of the illness supports this hypothesis. The fact that the cysts were not connected with the vessels and that the cyst contents were similar to those of the arachnoid cavity demonstrated that the cysts had originated from arachnoid tissue. Furthermore, the same immunoresponse of the perivascular cells, microcystic walls and the arachnoid cavity wall suggests that pluripotent cells differentiate into the various cell types found in MA  and that the formation of cysts is an accompanying developmental anomaly. Mechanisms such as increased CSF pulsation, vascular ectasia, small blood vessel obstruction or abnormal arterial wall permeability may be related to the formation of enlarged perivascular spaces, in which CSF gradually accumulates, eventually resulting in the formation of microcysts and cysts. This suggests that MA originates from pluripotent arachnoidal cap cells trapped in the cerebral cortex.
Although many cases of MA have been described, presurgical diagnosis remains difficult because the wide spectrum of clinical, imaging and electrophysiological features often impedes the clinical diagnosis [13, 18, 19]. Surgical resection is important not only for seizure control but also for pathological diagnosis. Wiebe et al. reported that after surgical removal of the tumor, long-term seizures disappeared in 43% of patients, improvement occurred in 30% of patients and antiepileptic drug administration was required in more than 70% of patients . Partial removal of the tumor has been shown to improve symptoms, but total removal still seems to be more effective [8, 20]. In patients in whom postoperative seizure control was not successful, extension of the epileptic foci was found to occur with time . In our patient, ECoG revealed perilesional cortical spikes, and epileptogenic foci were present in not only the right temporal lobe but also the right hippocampus. Therefore, intraoperative or extraoperative ECoG is essential for detecting epileptogenic foci , which often exist in the adjacent cortex rather than in the lesion. In the present case, total surgical removal was achieved using intraoperative ECoG assistance, and a favorable outcome was obtained.
The present case demonstrates that MA may present as a hamartomatous lesion containing multiple microcysts in a patient with medically refractory seizures, and should be considered in the differential diagnosis of intracortical lesions, especially in young adults. It is possible that MA originates from arachnoid and vascular tissue trapped in the cortical parenchyma during brain development, and that the cysts result from gradual accumulation of CSF in the perivascular spaces that develop from the trapped tissue. Our data do not support a meningeal origin of MA, but rather suggest that pluripotent arachnoid cap cells differentiate into the various cell types found in MA. Resection of the lesion and of the epileptogenic cortex is important not only for pathological diagnosis but also for seizure control, and intraoperative ECoG assistance is recommended.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Magnetic resonance imaging
Smooth muscle actin
Epithelial membrane antigen
Glial fibrillary acidic protein
This work was funded by the National Natural Science Foundation of China (No. 81272651, to ZW). Additional funding was provided by the President Fund of the General Hospital of Jinan Military Command(to MG). The authors wish to acknowledge the professional English editing service of Elixigen Co (Huntington Beach, CA).
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