Background
The meninges have three membranes, including the dura mater, the arachnoid mater, and the pia mater, that envelop the brain and spinal cord. Meningiomas are a variety of tumours caused by arachnoid “cap” cells of meningeal arachnoid villi [
1]. Orbital meningiomas can be considered to be primary and secondary in origin [
2]. Primary orbital meningioma accounted for 5–10% of all orbital tumours and 30% of all orbital meningiomas; they were also mainly observed in adults and rarely in children [
3]. Primary orbital meningiomas originate from the arachnoid layer of the optic nerve sheath. Approximately 70% of orbital meningiomas are secondary intracranial meningiomas, usually originating at the sphenoid ridge, with orbital, intracranial, and intraluminal intrusions [
4].
A rare subset of orbital meningiomas that do not involve the optic nerve sheath or sphenoid ridge were initially considered to be “ectopic”. Ectopic orbital meningiomas are occasionally reported as single or multiple case series in the literature. However, there exists a paucity of published clinical evidence regarding the distinguishing features of ectopic orbital meningioma. Preoperative diagnosis is often difficult, which is not conducive to the establishment of surgical methods, surgical operation, and follow-up treatment success.
All cases reported in this report were admitted to the Tianjin Medical University Eye Hospital during a 217-month period. Clinical manifestations, radiographic features, and therapeutic regimens of these patients were retrospectively analysed in the following report.
Methods
Study population
The present study was approved by the Tianjin Medical University Eye Hospital Foundation Institutional Review Board (REC No.2017KY(L)L-56) and adhered to HIPAA regulations as well as the principles of the Declaration of Helsinki. The six patients included in this study were selected from 162 cases with a pathological diagnosis of orbital meningioma at Tianjin Medical University Eye Hospital during a 217-month period between August 1999 and September 2017. Patients with known optic nerve sheath meningiomas and intracranial meningiomas were excluded.
Data collection
Data were collected on patient symptoms, such as headache, nausea, vomiting, and other intracranial symptoms, and the results of regular eye examination, including (i) a visual acuity and best corrected visual acuity test using international visual chart; (ii) examination of the exophthalmos by a Hertel exophthalmometer (differences in the bilateral exophthalmos of more than 2 mm were regarded as abnormal); (iii) examination of eye movement and periorbital changes; and (iv) indirect ophthalmoscopy to check the fundus after mydriasis. All patients underwent radiographic examination, including computed tomography (CT) or magnetic resonance imaging (MRI), to identify the location of their tumour and relative location to the optic nerve, extraocular muscle, and other peripheral tissues.
Therapeutic regimen and pathological diagnosis
Surgery was the preferred therapeutic regimen. All patients underwent complete surgical resection, and surgical approaches were divided into lateral orbitotomy or anterior orbitotomy according to lesion location. All tumour specimens were sent for pathological examination. The two-step method for immunohistochemical staining was employed to detect the expression of EMA, vimentin, S-100, Ki-67 and calponin and was performed according to the manufacturer’s instructions (Shanghai Bioleaf Biotech Co, Ltd., Shanghai, China). Phosphate buffered saline (PBS) was used as the negative antibody control, and the EMA antibody for clinical pathology diagnosis was used as the positive control. Diaminobenzidine (DAB)-staining, haematoxylin staining, dehydration, transparentisation and sealing with neutral balsam were performed in that order. Positive staining presented as a tan colour in staining assessment.
Discussion
The existence of ectopic orbital meningiomas is still debated in the field of ophthalmology. Some previous cases have likely been diagnosed as central nervous system or atypical optic nerve sheath meningiomas, so ectopic orbital meningiomas may be underreported.
There is no definitive evidence as to the origin of ectopic orbital meningiomas. One theory, advanced by Craig and Cogela [
7], states that no meningeal tissue in normal orbits other than the arachnoid of the optic nerve should be observed after inspecting several autopsy specimens histologically. It was also suggested that ectopic orbital meningiomas originate from the optic nerve sheath and migrate to ectopic locations. Tan and Lim [
8] suggested that ectopic orbital meningiomas could originate from the arachnoid sheath of the cranial nerves, as opposed to the optic nerve, in orbit. Furthermore, there is no evidence that arachnoid courses with the cranial nerves into the orbit, in which cases the involved arachnoid tissue must originate outside the orbit. Another theory suggested that ectopic orbital meningiomas may originate from a regressed orbital meningocele or from meningeal tissue trapped outside the centre [
9]. Irwin Tendler et al. [
10] reported a case involving the sinus and proposed sinus enlargement as a marker of a congenital event that displaced meningeal cells. This may have caused the formation of an ectopic lesion or mechanical stress induced by the presence of an ectopic orbital tumour, thereby causing sinus asymmetry. However, obvious sinus enlargement was not observed in the present study.
In our study, we hypothesised that some ectopic meningiomas originate from meningeal cells of the OB, in which case meningeal cells could pass through the frontoethmoidal suture to the orbit. EMA and vimentin are important markers of meningioma cells, and these proteins were strongly expressed by tumour cells in all cases in the present study. However, we also found only two cases positive for calponin in tumours which were just in the location of the lateral antorbital frontoethmoidal suture. Interestingly, calponin has been reported to be strongly expressed by connective tissue cells, mesenchymal-derived cells, fibroblasts and meningeal cells from the lamina propria of the olfactory mucosa (OM) and the OB [
5,
11,
12].
To date, only 20 cases are described. Among them, 14 cases are from other studies in the literature, and the six cases presented here were treated at our hospital over the last 18 years. Among these cases, the male to female ratio and the mean age at presentation were 11:9 and 32.6 years (range 7–77 years), respectively. This is a marked difference from typical meningiomas, where females are more commonly affected, with detection occurring in the fourth or fifth decade of life. The tumour itself was observed to have little impact on vision, as most visual impairment was caused by excessive tumour growth leading to optic nerve compression (4/20, 20%). This finding differs from nerve sheath meningioma, which affects vision early in its development.
All cases presented here were identified during surgery. Remarkably, the tumours from 11 cases, including three cases in our study and eight cases in previous reports, were located in the superonasal extraconal compartment near the frontoethmoidal suture (11/20, 55%). Two cases reported in the previous literature were noted to have neither CT nor MRI data because they were diagnosed before these radiographic instruments came into use. Among the other 18 cases, radiographic features in most cases were ill-defined, heterogeneous orbital masses (15/18, 83%). MRI showed T1WI as hypointense and T2W as hyperintense fat suppression signal enhancement. Some cases of CT indicated calcium spots (4/18, 22%), and recurrence was rare with complete excision (2/20, 10%). Finally, some of the tumours were obviously separated from the optic nerve, and no evidence suggested bony hyperostosis (Table
3) [
3,
4,
8‐
10,
13‐
17].
Table 3
Results of our 6 cases and 14 cases from literature review of ectopic orbital meningioma
Sex | | | |
Male | 7 | 4 | 11 (55%) |
Female | 7 | 2 | 9 (45%) |
Range of age(years)(mean) | 7–77 (32.4) | 7–56 (33.2) | 7–77 (32.6) |
History(months) | 6–60 (22.4) | 3–72 (20.3) | 3–72 (20.8) |
History of head trauma | 2 | 2 | 4 (20%) |
Symptoms or sign | | | |
Exophthalmos | 9 | 5 | 14 (70%) |
Ptosis | 2 | 4 | 6 (30%) |
Upper eyelid edema | 3 | 6 | 9 (45%) |
Mobility restriction | 4 | 6 | 10 (50%) |
Fundus abnormality | 2 | 2 | 4 (20%) |
Tumor locations | | | |
Superonasal extraconal compartment | 8 | 3 | 11 (55%) |
Bitamporal extraconal compartment | 1 | 1 | 2 (10%) |
Intraconal compartment | 5 | 2 | 7 (35%) |
CT and MRI | | | |
Ill-defined | 9 | 4 | 13 (65%) |
Well-defined | 3 | 2 | 5 (25%) |
Calcification | 3 | 1 | 4 (20%) |
Therapeutic regimen | | | |
Complete resection | 12 | 6 | 18 (90%) |
Radiotherapy | 2 | 0 | 2 (10%) |
Histopathology | | | |
Meningothelial meningioma | 12 | 5 | 17 (85%) |
Fibrous meningioma | 2 | 0 | 2 (10%) |
Psammomatous meningioma | 0 | 1 | 1 (5%) |
Although the cases outlined here did not have a definite diagnosis before pathological testing, our study may offer ophthalmologists cues to improve the diagnostic accuracy for future patients. We found that most patients with ectopic orbital meningioma had upper eyelid oedema and eye mobility restriction through this 18-year clinical retrospective analysis, even though most of the tumours did not involve the eyelids or cause increased intraorbital pressure resulting in obstruction of the returning fluid to the lower eyelid. Such findings are not particularly common in other orbital tumours and may be related to some unknown properties of meningioma cells.
Conclusions
In summary, orbital isolate lesions, especially around the location of the frontoethmoidal suture, had accompanying upper eyelid oedema and eye mobility restriction not observed in other orbital tumours. Therefore, ectopic orbital meningioma should be considered in such cases. Ideally, further research into the origin and pathogenesis of ectopic orbital meningiomas should be conducted.
Acknowledgement
We would like to thank Professor Guoxiang Song for his advice on this manuscript.