Accepted Manuscript Ectopic Orbital Meningioma: Report of Two Cases and Literature Review Kaan Gündüz, MD Rengin Aslıhan Kurt, MD Esra Erden, MD
PII:
S0039-6257(14)00042-3
DOI:
10.1016/j.survophthal.2014.01.009
Reference:
SOP 6508
To appear in:
Survey of Ophthalmology
Received Date: 3 April 2013 Revised Date:
23 January 2014
Accepted Date: 28 January 2014
Please cite this article as: Gündüz K, Kurt RA, Erden E, Ectopic Orbital Meningioma: Report of Two Cases and Literature Review, Survey of Ophthalmology (2014), doi: 10.1016/j.survophthal.2014.01.009. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1 2 3
Ectopic Orbital Meningioma: Report of Two Cases and Literature Review
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Kaan Gündüz1, MD
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Rengin Aslıhan Kurt1, MD
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Esra Erden2, MD
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From the Department of Opthalmology1 and Department of Pathology, 2 Ankara University
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Faculty of Medicine, Ankara, Turkey
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Inquires and reprint requests to:
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Kaan Gündüz, MD, Professor of Ophthalmology
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Farilya Business Center 8/50, Ufuk Universitesi Cad, Çukurambar, Ankara, Turkey
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Phone : +90 532 633 7997
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Fax : +90-312-4272772
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E-mail: [email protected]
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Abstract Ectopic orbital meningioma is a rare orbital tumor usually affecting the medial orbit. We present two cases that occurred in a 56-year-old woman and a 28-year-old man. The tumors in both
4
patients were subtotally excised via orbitotomy surgery and were located in the superior quadrant in
5
one of our patients and in the temporal quadrant in the other. Following histopathologic diagnosis,
6
external beam radiotherapy (EBRT) was administered to one patient and intensity modulated
7
radiotherapy to the other. We identified 12 other well-documented cases of ectopic orbital
8
meningioma previously reported. Ectopic meningioma should be considered in the differential
9
diagnosis of medial as well as lateral and superior orbital tumors. The tumor is usually well-
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circumscribed but can be ill-defined in imaging studies. There are intralesional calcifications and
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sclerosis of adjacent bone in some cases. Ectopic orbital meningioma can recur after incomplete
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excision. Based on the efficacy of EBRT in optic nerve sheath meningioma, we used this treatment to
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decrease the risk of recurrence in our 2 patients and found no tumor recurrence at follow-ups of 24
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and 74 months, but one patient had severe vision loss from radiation retinopathy.
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ACCEPTED MANUSCRIPT 1 Orbital meningiomas originating from the arachnoid around the optic nerve are known as
3
primary optic nerve sheath meningiomas (ONSM). Intracranial meningiomas originating from the
4
sphenoid wing can also invade the orbit and are considered to be secondary orbital meningiomas. A
5
third group of orbital meningiomas occur apart from the optic nerve without any demonstrable
6
connection with the intracranial meninges and are classified as ectopic meningiomas.1,2,4,6,7,9,10,12,13 We
7
report two rare cases of ectopic orbital meningioma and review the literature.
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Case Reports Case 1
A 56-year-old female presented with 3 months of slowly progressive proptosis and eyelid
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swelling. She had no signs of neurofibromatosis. Best corrected visual acuity was 20/20 in both eyes.
13
There was 5 mm of proptosis OD by Hertel exophthalmometry (Fig 1a). There was no relative
14
afferent pupillary defect. Intraocular pressures were 16 mm Hg in both eyes. Anterior segment and
15
fundus examinations were unremarkable. Orbital computed tomography revealed a superiorly located
16
mass producing thinning of the overlying bone (Figs 1b,c). Orbital magnetic resonance imaging (MRI)
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showed an ill-defined mass in the right superior orbit. The tumor was isointense with respect to the
18
orbital fat and cerebral gray matter on T1-weighted images, hypointense on T2-weighted images, and
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demonstrated moderate contrast enhancement (Fig 1d,e).
The patient underwent a superonasal skin incision orbitotomy. Only a subtotal resection could
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be performed because of the friable nature of the tumor. No connections to optic nerve was detected
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during surgery but the tumor was in close approximation to the periorbita. On gross examination, it
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had a gray-yellow color. On histopathology, the tumor consisted of round-to-oval cells with indistinct
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cytoplasmic borders and vesicular nuclei. The cells seemed to form a predominantly meningothelial
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(snycytical) pattern (long arrow) and cellular arrangement reminiscent of whorling pattern (short
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arrow) (Fig 1f). Mitosis or prominent nucleoli were not observed. Hemosiderin aggregates were seen
27
within the tumor. Hypointensity on T2-weighted MR images was attributed to the presence of
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hemosiderin and blood breakdown products. On immunohistochemistry, the tumor stained negative
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for epithelial membrane antigen (EMA), HMB-45, Melanin A, S-100, glial fibrillary acidic protein
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(GFAP), and carcinoembryonic antigen (CEA). The diagnosis was ectopic intraorbital meningioma,
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despite EMA negativity. The patient underwent conventional external beam radiotherapy (EBRT [50
32
Gy]) to the right orbit. At that time, she did not have access to stereotactic fractionated radiotherapy or
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a more precise approach such as cyberknife radiosurgery. She was seen postoperatively at irregular
34
intervals. Four years after diagnosis, the right eye had radiation maculopathy and proliferative
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radiation retinopathy and underwent one intravitreal triamcinolone acetonide injection and three
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sessions of laser photocoagulation over a 10-month period. At 74 months follow-up, there was no
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tumor recurrence, and visual acuity OD was counting fingers at 2 meters.
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Case 2 A 27-year-old man presented with slowly progressive proptosis of the left eye over 6 months
4
(Fig 2a). He did not have neurofibromatosis. Visual acuity was 20/20 in both eyes. There was 12 mm
5
of proptosis on the left side. The motility of the left eye was limited on elevation and abduction.
6
Conjunctival edema and injection were present over the lateral rectus muscle insertion in the left eye.
7
Both fundi were normal. Orbital MRI showed a well-defined tumor laterally in the orbit. The tumor
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was hypointense on T1-weighted images, hyperintense on T2-weighted images, and demonstrated
9
moderate contrast enhancement (Fig 2 b,c). Orbital CT revealed no connection to the bony orbit,
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ruling out a sphenoid wing meningioma, as well as no intracranial involvement.
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The patient underwent anterior orbitotomy via a superolateral skin crease approach. About 70% of the total tumor mass was excised (Fig 2d). There were no connections to the optic nerve. The
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tumor was in close proximity, but distinct from, the periosteum and had a yellow-gray color on gross
14
examination. Microscopically, it consisted of cells forming whorls (arrow) with no mitosis or
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prominent nucleoli (Fig 2e). Tumor cells stained positive with EMA, consistent with the diagnosis of
16
meningothelial meningioma. One month after surgery, the patient underwent intensity modulated
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radiotherapy to the left orbit (50 Gy). At 24 months follow-up, VA was 20/20, and there was 2 mm of
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residual proptosis OS.
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Farah et al in 1999 concluded that only 5 published cases of orbital ectopic meningioma had
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sufficient clinical, radiologic, and histopathologic evidence to support this diagnosis.4 Many cases of
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ectopic orbital meningiomas were reported in the pre-MRI era and the anatomic localization in the
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orbit was based on intraoperative findings. Furthermore, not everyone is convinced of the existence of
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ectopic orbital meningiomas. Some cases of ectopic orbital meningiomas might have previously been
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classified as central nervous system meningiomas with predominant orbital involvement or as atypical
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optic nerve sheath meningiomas; therefore, ectopic orbital meningioma is probably an underreported
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entity.
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Our literature search yielded 10 papers detailing 12 well-documented ectopic or extradural
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orbital meningiomas including 5 cases reported by Farah et al. 1,2,4,6,7,9,10,12,13 Table 1 summarizes
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patient demographics, tumor location, treatment, follow-up, complications, tumor connection to optic
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nerve and periorbita, and histopathologic classification in 14 cases with ectopic orbital meningioma.
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Age ranged from 7 to 66 years, with a mean of 28.9 years. Ten patients were males and 4 were
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females. Ectopic orbital meningioma occurs in both children and adults with a male predominance.
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Twelve cases had CT/MRI studies done and 2 cases were reported before these neuroimaging
36
modalities came into use. Table 2 summarizes the imaging features (tumor margins, calcification in
37
the tumor, hyperosteosis/sclerosis of adjacent bone and asymmetry of orbital sinuses) in 14 cases with
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ACCEPTED MANUSCRIPT ectopic orbital meningioma [1-9]. The tumor had a medial location in 5 (35.7%) cases, superonasal in
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4 (28.6%) cases, lateral in 2 (14.3%) cases, superior in 2 (14.3%) cases, and inferonasal in one (7.1%)
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case. Ten out of 14 (71.4%) cases with ectopic orbital meningioma summarized in this review had
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superonasal, medial, or inferonasal tumors; however, 4 of 14 (28.6%) cases had superior and lateral
5
orbital involvement [1,8,9]. The tumor was in the superior orbit in one of our patients and laterally in
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the other. Ectopic orbital meningioma usually occurs in medial orbital quadrants; however, it should
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also be considered in the differential diagnosis of orbital tumors with a superior and lateral location.
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Ectopic orbital meningioma had a well-circumscribed appearance in 8 (57.1%) cases, an ill-
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defined appearance in 3 (21.4%) cases and there was no information concerning the margins in 3 (21.4%) cases (Table 2). Calcification was present in 3 (21.4%) cases, absent in 9 (64.3%) cases, and
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there was no information in 2 (14.3%) cases. Hyperosteosis/sclerosis of adjacent bone was present in 3
12
(21.4%) cases, absent in 10 (71.4%) cases, and there was no data concerning this feature in one case.
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Asymmetry of orbital sinuses was present in 4 (28.6%) cases, absent in 3 (21.4%) cases with no
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information about this finding in the remaining 7 (50.0%) cases. Ectopic orbital meningioma usually
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appears as a well-circumscribed lesion but it can also be ill-defined. Calcification in the lesion and
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hyperosteosis/sclerosis of adjacent bone may be seen. Asymmetry of orbital sinuses is also observed
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but the significance of this is unknown.4
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An ectopic meningioma located in the lateral orbital quadrant may be mistaken for a sphenoid wing meningioma. Sphenoid wing meningioma is usually hypointense to isointense on T1-weighted
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images and can be more hyperintense with greater degrees of osseous invasion. On T2-weighted
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images, sphenoid wing meningioma with osseous invasion is usually hypointense. On the other hand,
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an ectopic orbital meningioma is hyperintense on T2-weighted images as in our case 2. The
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hyperintensity on T2-weighted images is as a distinguishing feature of ectopic orbital meningiomas
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and effectively rules out sphenoid wing meningioma with osseous involvement.3
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There were no data concerning connection of the tumor to the optic nerve and/or periorbita in 5 of 14 (35.7%) cases. Connection to the periorbita was present in 5 of 9 (55.6%) cases where this
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feature was specifically addressed. On the other hand, there was no connection to the optic nerve in 9
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cases where the presence or absence of this feature was mentioned. Histopathologic examination
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revealed that 12 of 14 tumors (85.7%) had meningothelial meningioma and 2 of 14 (14.3%) had
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fibroblastic meningioma.
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The pathogenesis of ectopic orbital meningioma is not clear. These tumors can arise from
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congenitally dislocated nests of meningothelial cells or regressed orbital meningoceles located within
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the orbit.2 Ectopic intraorbital meningiomas may be associated with penetrating trauma to the orbit,
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which serves to dislodge meningeal tissues within the orbit that later serve as a nidus for the
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development of meningiomas.4,6 Neither of our cases had a history of trauma.
36 37
Some ectopic orbital meningiomas are amenable to complete surgical excision.1,2,413 Six of 14 (42.9%) cases with ectopic orbital meningioma had residual/recurrent tumors after primary surgery.
Gündüz/Ectopic meningioma/6
ACCEPTED MANUSCRIPT Four of these 6 cases (66.7%) underwent secondary surgery and 2 (33.3%) received EBRT. The
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follow-up ranged from 0 to 74 months. The tumors in our cases had a friable structure that made
3
complete surgical excision impossible. Therefore, they could only be excised in a subtotal fashion. A
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previous study found that incompletely resected spheno-orbital meningiomas have a high recurrence
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rate of about 33%.5 The decision to use postoperative external-beam radiotherapy (EBRT) in our cases
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was based on recurrence risk and on the efficacy of this modality in the treatment of ONSMs.12
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Considering the high risk of recurrrence, we employed early EBRT. Other treatment options include
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second surgery or late EBRT if the tumor recurs.
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One study reported the rate of radiation retinopathy to be only about 12% after conventional or stereotactic fractionated radiotherapy for progressive ONSMs.13 Although one of our patients
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developed radiation retinopathy and vision loss after EBRT, we considered that this adjunctive
12
treatment, even for a relatively benign pathology such as meningioma, was justified to prevent
13
recurrent tumor, which would threaten vision and possibly require multiple surgeries. Although
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targetted radiation treatment was attempted, a radiation treatment error could not be ruled out as the
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cause of this visually destructive vasculopathy.
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Method of Literature Search
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We made a literature search of the pubmed database using the key word combinations “orbit, ectopic, meningioma” and “orbit, extradural, meningioma”. We took into consideration only the
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articles published in English and German. Some of the articles were discarded because they did not
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really fit into the description of ectopic orbital meningioma although they came up under the above
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mentioned key words. The reference list of these articles were checked for further references. We
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realize that we may have missed other ectopic orbital meningioma cases because the publishing
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journal or book is not indexed on pubmed and because of search strategy/key word errors. Although
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our list may not be complete, we nevertheless made a significant effort to put together a reasonable
26
number of well-documented ectopic orbital meningioma cases to help us understand the presentation,
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clinical features and treatment of these lesions better.
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References 1. Arai H, Sato K, Matsumoto T. Free-lying ectopic meningioma within the orbit. Br J Neurosurg 1997;11:560-563. 2. Decock CE, Kataria S, Breusegem CM, Van Den Broecke CM, Claerhout IJ. Ectopic
5
meningioma anterior to the lacrimal gland fossa. Ophthal Plast Reconstr Surg 2009;25:57-59.
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doi: 10.1097/IOP.0b013e3181936811.
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3. DePotter P, Shields CL, Shields JA. Optic nerve and meningeal tumors. In: MRI of the Eye
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and Orbit. DePotter P, Shields CL, Shields JA, eds. Philadelphia: JB Lippincott, 1995:193-211.
9 10
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4. Farah SE, Konrad H, Huang DT, Geist CE. Ectopic orbital meningioma: a case report and review. Ophthal Plast Reconstr Surg 1999;15:463-466.
5. Heufelder MJ, Sterker I, Trantakis C, Schneider JP, Meixensberger J, Hemprich A, Frerich B.
12
Reconstructive and ophthalmologic outcomes following resection of spheno-orbital
13
meningiomas. Ophthal Plast Reconstr Surg 2009;25:223-226. doi:
14
10.1097/IOP.0b013e3181a1f345
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6. Johnson TE, Weatherhead RG, Nasr AM, Siqueira EB. Ectopic (extradural) meningioma of
16
the orbit: a report of two cases in children. J Pediatr Ophthalmol Strabismus 1993;30:43-47.
17
7. Pushker N, Shrey D, Kashyap S, Sen S, Khurana S, Sharma S. Ectopic meningioma of the
18
orbit. Int Ophthalmol 2013 Jan 21. [Epub ahead of print]
19
8. Saeed P, Blank L, Selva D, Wolbers JG, Nowak PJ, Geskus RB, et al. Primary radiotherapy
20
in progressive optic nerve sheath meningiomas: a long-term follow-up study. Br J Ophthalmol
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2010;94:564-568. doi: 10.1136/bjo.2009.166793.
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9. Spraul CW, Gareis O, Lang GK. Primary extradural intraorbital meningioma: A case
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presentation and review of the literature. Klin Monatsbl Augenheilkd 1996;209:322-327.
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10. Tan KK, Lim ASM. Primary extradural intraorbital meningioma in a chinese girl. Br J
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Ophthalmol 1965;49:377-380.
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11. Turbin RE, Thompson CR, Kennerdell JS, Cockerham KP, Kupersmith MJ. A long-term
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visual outcome comparison in patients with optic nerve sheath meningioma managed with
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observation, surgery, radiotherapy, or surgery and radiotherapy. Ophthalmology 2002;109:890-
29
899; discussion 899-900.
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12. Wolter JR, Benz SC. Ectopic meningioma of the superior orbital rim. Arch Ophthalmol
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1976;94:1920-1922.
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13. Yokoyama T, Nishizawa S, Sugiyama K, Yokota N, Ohta S, Uemura K, et al. Skull Base
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Surgery 1999;9:47-50.
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ACCEPTED MANUSCRIPT Legend
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Fig 1a. Facial photograph demonstrates right proptosis in 56 year-old woman.
3
Fig 1b. Axial computed tomography shows a superiorly located orbital mass on the right side.
4
Fig 1c. Coronal computed tomography shows a superiorly located orbital mass producing thinning of
5
the overlying bone on the right side.
6
Fig 1d. T1W contrast enhanced orbital MRI reveals an ill-defined in the right superior orbit with
7
marked contrast enhancement.
8
Fig 1e. The tumor is hypointense with respect to orbital fat and cerebral gray matter on T2 weighted
9
images. This hypointensity on T1W images is due to the accumulation of blood breakdown products in
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the tumor.
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Fig 1f. Histopathologic examination shows that the tumor consists of round to oval cells
12
with indistinct cytoplasmic borders and vesicular nuclei. Mitosis or prominent nucleoli
13
are not observed The tumor cells seemed to form a predominantly meningothelial
14
(snycytical) pattern (arrow) and cellular arrangement reminiscent of whorling pattern
15
(arrowhead). (Hematoxylin-eosin x 200). The histopathologic findings were consistent
16
with the diagnosis of orbital meningothelial meningioma. Scale bar 250 µm
17
Fig 2a. Facial photograph shows left proptosis in 27 year-old man.
18
Fig 2b. T1W axial orbital MRI reveals a well-defined orbital mass occupying the entire
19
lateral orbit. The tumor is isointense to the cerebral gray matter.
20
Fig 2c. T2W coronal orbital MRI shows that the orbital mass defined above is
21
hyperintense with respect to the cerebral gray matter.
22
Fig 2d. Gross photograph of the excised tumor piece. The tumor could only be excised in
23
a subtotal fashion.
24
Fig 2e. Histopathologic examination demonstrates that the tumor is composed of cells
25
with indistinct cytoplasmic borders forming whorls (arrow). Mitosis and prominent
26
nucleoli are not present. (Hematoxylin-eosin x 40) The histopathologic findings and
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EMA positivity supported the diagnosis of orbital meningothelial meningioma. Scale bar
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1000 µm
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Tables
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Table 1. Patient demographics, tumor location, treatment, follow-up, complications, tumor connection
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to optic nerve and periorbita, and histopathologic classification in 14 cases with ectopic orbital
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meningioma.
34
Table 2. Imaging features (tumor margins, calcification in the tumor, hyperosteosis/sclerosis
35
of adjacent bone and asymmetry of orbital sinuses) in 14 cases with ectopic orbital
36
meningioma.
ACCEPTED MANUSCRIPT
Table 1. Patient demographics, tumor location, treatment, follow-up, complications, tumor connection to optic nerve and periorbita, and histopathologic classification in 14 cases with ectopic orbital meningioma CT/ MRI
Orbital location
Primary surgery
Secondary treatment
Orbitotomy
Recurrent/ residual tumor None
None
Follow -up (mos) 0
1
Tan
1965
9/F
Not done
Medial
2
Wolter
1976
33/M
3
Johnson
1993
10/M
Not done CT
Supero medial Medial
Orbitotomy
None
None
3
Orbitotomy
Residual
Craniotomy
12
4
Johnson
1993
7/M
CT
Medial
Orbitotomy
Residual
Medial Supero medial Medial Infero medial
Orbitotomy Craniotomy
None None
External ethmoidectomy None None
5 6
Spraul Arai
1996 1997
30/M 27/F
MRI MRI
7 8
Farah Yokoyama
1999 1999
53/M 7/M
CT MRI
Orbitotomy Cranitomy
None None
9 10 11
Decock Pushker Pushker
2009 2013 2013
66/M 30/F 40/M
MRI CT CT
Orbitotomy Orbitotomy Orbitotomy
None Recurrence Recurrence
12
Pushker
2013
9/M
CT
13
Gündüz
2013
56/F
MRI
14
Gündüz
2013
27/M
Lateral Superior Supero medial Supero medial Superior
Orbitotomy Orbitotomy
Complications
Tumor connection to optic nerve N/A
Tumor connection to periorbita Present
Histopathologic classification
Absent
Absent
Meningothelial
Absent
N/A
Meningothelial
4
Frozen globe, ptosis None
Absent
N/A
Meningothelial
18 1
None None
N/A Absent
N/A Absent
Fibroblastic Fibroblastic
None None
42 0
Absent Absent
Present Absent
Meningothelial Meningothelial
None Orbitotomy Orbitotomy
15 18 24
None Optic atrophy, no light perception None None None
Absent N/A N/A
Absent N/A N/A
Meningothelial Meningothelial Meningothelial
None
None
3
None
N/A
Present
Meningothelial
Residual
EBRT
74
Radiation retinopathy None
Absent
Present
Meningothelial
Present
Meningothelial
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Age/sex
SC
Year
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Case no
Wound infection, muscle paresis None
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MRI, Lateral Orbitotomy Residual EBRT 24 Absent CT M: Male, F: Female, CT: Computed tomography, MRI: Magnetic resonance imaging, EBRT: External beam radiation therapy, mos: months, N/A: data not available in the article
Meningothelial
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Present N/A Present Present N/A N/A Present N/A Absent N/A N/A N/A Absent Absent
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Asymmetry of orbital sinuses
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N/A N/A Present Absent Absent Absent Present Absent Present Absent Absent Absent Absent Absent
Hyperosteosis/ sclerosis of adjacent bone N/A Present Absent Absent Absent Absent Absent Absent Absent Present Absent Present Absent Absent
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1 Tan N/A 2 Wolter N/A 3 Johnson Ill-defined 4 Johnson Well-defined 5 Spraul Well-defined 6 Arai Well-defined 7 Farah Well-defined 8 Yokoyama Well-defined 9 Decock N/A 10 Pushker Ill-defined 11 Pushker Well-defined 12 Pushker Ill-defined 13 Gündüz Well-defined 14 Gündüz Well-defined N/A: data not available in the article
Calcification in the tumor
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Tumor Margins
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Author
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Case no
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ACCEPTED MANUSCRIPT
PII:
S0039-6257(14)00042-3
DOI:
10.1016/j.survophthal.2014.01.009
Reference:
SOP 6508
To appear in:
Survey of Ophthalmology
Received Date: 3 April 2013 Revised Date:
23 January 2014
Accepted Date: 28 January 2014
Please cite this article as: Gündüz K, Kurt RA, Erden E, Ectopic Orbital Meningioma: Report of Two Cases and Literature Review, Survey of Ophthalmology (2014), doi: 10.1016/j.survophthal.2014.01.009. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1 2 3
Ectopic Orbital Meningioma: Report of Two Cases and Literature Review
4 5
Kaan Gündüz1, MD
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Rengin Aslıhan Kurt1, MD
7
Esra Erden2, MD
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SC
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From the Department of Opthalmology1 and Department of Pathology, 2 Ankara University
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Faculty of Medicine, Ankara, Turkey
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Inquires and reprint requests to:
24
Kaan Gündüz, MD, Professor of Ophthalmology
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Farilya Business Center 8/50, Ufuk Universitesi Cad, Çukurambar, Ankara, Turkey
26
Phone : +90 532 633 7997
27
Fax : +90-312-4272772
28
E-mail: [email protected]
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Gündüz/Ectopic meningioma/2
ACCEPTED MANUSCRIPT 1 2
Abstract Ectopic orbital meningioma is a rare orbital tumor usually affecting the medial orbit. We present two cases that occurred in a 56-year-old woman and a 28-year-old man. The tumors in both
4
patients were subtotally excised via orbitotomy surgery and were located in the superior quadrant in
5
one of our patients and in the temporal quadrant in the other. Following histopathologic diagnosis,
6
external beam radiotherapy (EBRT) was administered to one patient and intensity modulated
7
radiotherapy to the other. We identified 12 other well-documented cases of ectopic orbital
8
meningioma previously reported. Ectopic meningioma should be considered in the differential
9
diagnosis of medial as well as lateral and superior orbital tumors. The tumor is usually well-
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3
circumscribed but can be ill-defined in imaging studies. There are intralesional calcifications and
11
sclerosis of adjacent bone in some cases. Ectopic orbital meningioma can recur after incomplete
12
excision. Based on the efficacy of EBRT in optic nerve sheath meningioma, we used this treatment to
13
decrease the risk of recurrence in our 2 patients and found no tumor recurrence at follow-ups of 24
14
and 74 months, but one patient had severe vision loss from radiation retinopathy.
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Gündüz/Ectopic meningioma/3
ACCEPTED MANUSCRIPT 1 Orbital meningiomas originating from the arachnoid around the optic nerve are known as
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primary optic nerve sheath meningiomas (ONSM). Intracranial meningiomas originating from the
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sphenoid wing can also invade the orbit and are considered to be secondary orbital meningiomas. A
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third group of orbital meningiomas occur apart from the optic nerve without any demonstrable
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connection with the intracranial meninges and are classified as ectopic meningiomas.1,2,4,6,7,9,10,12,13 We
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report two rare cases of ectopic orbital meningioma and review the literature.
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Case Reports Case 1
A 56-year-old female presented with 3 months of slowly progressive proptosis and eyelid
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swelling. She had no signs of neurofibromatosis. Best corrected visual acuity was 20/20 in both eyes.
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There was 5 mm of proptosis OD by Hertel exophthalmometry (Fig 1a). There was no relative
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afferent pupillary defect. Intraocular pressures were 16 mm Hg in both eyes. Anterior segment and
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fundus examinations were unremarkable. Orbital computed tomography revealed a superiorly located
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mass producing thinning of the overlying bone (Figs 1b,c). Orbital magnetic resonance imaging (MRI)
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showed an ill-defined mass in the right superior orbit. The tumor was isointense with respect to the
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orbital fat and cerebral gray matter on T1-weighted images, hypointense on T2-weighted images, and
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demonstrated moderate contrast enhancement (Fig 1d,e).
The patient underwent a superonasal skin incision orbitotomy. Only a subtotal resection could
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be performed because of the friable nature of the tumor. No connections to optic nerve was detected
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during surgery but the tumor was in close approximation to the periorbita. On gross examination, it
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had a gray-yellow color. On histopathology, the tumor consisted of round-to-oval cells with indistinct
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cytoplasmic borders and vesicular nuclei. The cells seemed to form a predominantly meningothelial
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(snycytical) pattern (long arrow) and cellular arrangement reminiscent of whorling pattern (short
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arrow) (Fig 1f). Mitosis or prominent nucleoli were not observed. Hemosiderin aggregates were seen
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within the tumor. Hypointensity on T2-weighted MR images was attributed to the presence of
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hemosiderin and blood breakdown products. On immunohistochemistry, the tumor stained negative
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for epithelial membrane antigen (EMA), HMB-45, Melanin A, S-100, glial fibrillary acidic protein
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(GFAP), and carcinoembryonic antigen (CEA). The diagnosis was ectopic intraorbital meningioma,
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despite EMA negativity. The patient underwent conventional external beam radiotherapy (EBRT [50
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Gy]) to the right orbit. At that time, she did not have access to stereotactic fractionated radiotherapy or
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a more precise approach such as cyberknife radiosurgery. She was seen postoperatively at irregular
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intervals. Four years after diagnosis, the right eye had radiation maculopathy and proliferative
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radiation retinopathy and underwent one intravitreal triamcinolone acetonide injection and three
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sessions of laser photocoagulation over a 10-month period. At 74 months follow-up, there was no
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tumor recurrence, and visual acuity OD was counting fingers at 2 meters.
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Case 2 A 27-year-old man presented with slowly progressive proptosis of the left eye over 6 months
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(Fig 2a). He did not have neurofibromatosis. Visual acuity was 20/20 in both eyes. There was 12 mm
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of proptosis on the left side. The motility of the left eye was limited on elevation and abduction.
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Conjunctival edema and injection were present over the lateral rectus muscle insertion in the left eye.
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Both fundi were normal. Orbital MRI showed a well-defined tumor laterally in the orbit. The tumor
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was hypointense on T1-weighted images, hyperintense on T2-weighted images, and demonstrated
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moderate contrast enhancement (Fig 2 b,c). Orbital CT revealed no connection to the bony orbit,
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ruling out a sphenoid wing meningioma, as well as no intracranial involvement.
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The patient underwent anterior orbitotomy via a superolateral skin crease approach. About 70% of the total tumor mass was excised (Fig 2d). There were no connections to the optic nerve. The
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tumor was in close proximity, but distinct from, the periosteum and had a yellow-gray color on gross
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examination. Microscopically, it consisted of cells forming whorls (arrow) with no mitosis or
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prominent nucleoli (Fig 2e). Tumor cells stained positive with EMA, consistent with the diagnosis of
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meningothelial meningioma. One month after surgery, the patient underwent intensity modulated
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radiotherapy to the left orbit (50 Gy). At 24 months follow-up, VA was 20/20, and there was 2 mm of
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residual proptosis OS.
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19 Discussion
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Farah et al in 1999 concluded that only 5 published cases of orbital ectopic meningioma had
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sufficient clinical, radiologic, and histopathologic evidence to support this diagnosis.4 Many cases of
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ectopic orbital meningiomas were reported in the pre-MRI era and the anatomic localization in the
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orbit was based on intraoperative findings. Furthermore, not everyone is convinced of the existence of
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ectopic orbital meningiomas. Some cases of ectopic orbital meningiomas might have previously been
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classified as central nervous system meningiomas with predominant orbital involvement or as atypical
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optic nerve sheath meningiomas; therefore, ectopic orbital meningioma is probably an underreported
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entity.
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Our literature search yielded 10 papers detailing 12 well-documented ectopic or extradural
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orbital meningiomas including 5 cases reported by Farah et al. 1,2,4,6,7,9,10,12,13 Table 1 summarizes
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patient demographics, tumor location, treatment, follow-up, complications, tumor connection to optic
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nerve and periorbita, and histopathologic classification in 14 cases with ectopic orbital meningioma.
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Age ranged from 7 to 66 years, with a mean of 28.9 years. Ten patients were males and 4 were
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females. Ectopic orbital meningioma occurs in both children and adults with a male predominance.
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Twelve cases had CT/MRI studies done and 2 cases were reported before these neuroimaging
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modalities came into use. Table 2 summarizes the imaging features (tumor margins, calcification in
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the tumor, hyperosteosis/sclerosis of adjacent bone and asymmetry of orbital sinuses) in 14 cases with
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ACCEPTED MANUSCRIPT ectopic orbital meningioma [1-9]. The tumor had a medial location in 5 (35.7%) cases, superonasal in
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4 (28.6%) cases, lateral in 2 (14.3%) cases, superior in 2 (14.3%) cases, and inferonasal in one (7.1%)
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case. Ten out of 14 (71.4%) cases with ectopic orbital meningioma summarized in this review had
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superonasal, medial, or inferonasal tumors; however, 4 of 14 (28.6%) cases had superior and lateral
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orbital involvement [1,8,9]. The tumor was in the superior orbit in one of our patients and laterally in
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the other. Ectopic orbital meningioma usually occurs in medial orbital quadrants; however, it should
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also be considered in the differential diagnosis of orbital tumors with a superior and lateral location.
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Ectopic orbital meningioma had a well-circumscribed appearance in 8 (57.1%) cases, an ill-
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defined appearance in 3 (21.4%) cases and there was no information concerning the margins in 3 (21.4%) cases (Table 2). Calcification was present in 3 (21.4%) cases, absent in 9 (64.3%) cases, and
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there was no information in 2 (14.3%) cases. Hyperosteosis/sclerosis of adjacent bone was present in 3
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(21.4%) cases, absent in 10 (71.4%) cases, and there was no data concerning this feature in one case.
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Asymmetry of orbital sinuses was present in 4 (28.6%) cases, absent in 3 (21.4%) cases with no
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information about this finding in the remaining 7 (50.0%) cases. Ectopic orbital meningioma usually
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appears as a well-circumscribed lesion but it can also be ill-defined. Calcification in the lesion and
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hyperosteosis/sclerosis of adjacent bone may be seen. Asymmetry of orbital sinuses is also observed
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but the significance of this is unknown.4
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An ectopic meningioma located in the lateral orbital quadrant may be mistaken for a sphenoid wing meningioma. Sphenoid wing meningioma is usually hypointense to isointense on T1-weighted
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images and can be more hyperintense with greater degrees of osseous invasion. On T2-weighted
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images, sphenoid wing meningioma with osseous invasion is usually hypointense. On the other hand,
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an ectopic orbital meningioma is hyperintense on T2-weighted images as in our case 2. The
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hyperintensity on T2-weighted images is as a distinguishing feature of ectopic orbital meningiomas
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and effectively rules out sphenoid wing meningioma with osseous involvement.3
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There were no data concerning connection of the tumor to the optic nerve and/or periorbita in 5 of 14 (35.7%) cases. Connection to the periorbita was present in 5 of 9 (55.6%) cases where this
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feature was specifically addressed. On the other hand, there was no connection to the optic nerve in 9
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cases where the presence or absence of this feature was mentioned. Histopathologic examination
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revealed that 12 of 14 tumors (85.7%) had meningothelial meningioma and 2 of 14 (14.3%) had
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fibroblastic meningioma.
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The pathogenesis of ectopic orbital meningioma is not clear. These tumors can arise from
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congenitally dislocated nests of meningothelial cells or regressed orbital meningoceles located within
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the orbit.2 Ectopic intraorbital meningiomas may be associated with penetrating trauma to the orbit,
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which serves to dislodge meningeal tissues within the orbit that later serve as a nidus for the
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development of meningiomas.4,6 Neither of our cases had a history of trauma.
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Some ectopic orbital meningiomas are amenable to complete surgical excision.1,2,413 Six of 14 (42.9%) cases with ectopic orbital meningioma had residual/recurrent tumors after primary surgery.
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follow-up ranged from 0 to 74 months. The tumors in our cases had a friable structure that made
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complete surgical excision impossible. Therefore, they could only be excised in a subtotal fashion. A
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previous study found that incompletely resected spheno-orbital meningiomas have a high recurrence
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rate of about 33%.5 The decision to use postoperative external-beam radiotherapy (EBRT) in our cases
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was based on recurrence risk and on the efficacy of this modality in the treatment of ONSMs.12
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Considering the high risk of recurrrence, we employed early EBRT. Other treatment options include
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second surgery or late EBRT if the tumor recurs.
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One study reported the rate of radiation retinopathy to be only about 12% after conventional or stereotactic fractionated radiotherapy for progressive ONSMs.13 Although one of our patients
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developed radiation retinopathy and vision loss after EBRT, we considered that this adjunctive
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treatment, even for a relatively benign pathology such as meningioma, was justified to prevent
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recurrent tumor, which would threaten vision and possibly require multiple surgeries. Although
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targetted radiation treatment was attempted, a radiation treatment error could not be ruled out as the
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cause of this visually destructive vasculopathy.
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Method of Literature Search
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We made a literature search of the pubmed database using the key word combinations “orbit, ectopic, meningioma” and “orbit, extradural, meningioma”. We took into consideration only the
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articles published in English and German. Some of the articles were discarded because they did not
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really fit into the description of ectopic orbital meningioma although they came up under the above
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mentioned key words. The reference list of these articles were checked for further references. We
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realize that we may have missed other ectopic orbital meningioma cases because the publishing
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journal or book is not indexed on pubmed and because of search strategy/key word errors. Although
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our list may not be complete, we nevertheless made a significant effort to put together a reasonable
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number of well-documented ectopic orbital meningioma cases to help us understand the presentation,
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clinical features and treatment of these lesions better.
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References 1. Arai H, Sato K, Matsumoto T. Free-lying ectopic meningioma within the orbit. Br J Neurosurg 1997;11:560-563. 2. Decock CE, Kataria S, Breusegem CM, Van Den Broecke CM, Claerhout IJ. Ectopic
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meningioma anterior to the lacrimal gland fossa. Ophthal Plast Reconstr Surg 2009;25:57-59.
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doi: 10.1097/IOP.0b013e3181936811.
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3. DePotter P, Shields CL, Shields JA. Optic nerve and meningeal tumors. In: MRI of the Eye
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and Orbit. DePotter P, Shields CL, Shields JA, eds. Philadelphia: JB Lippincott, 1995:193-211.
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4. Farah SE, Konrad H, Huang DT, Geist CE. Ectopic orbital meningioma: a case report and review. Ophthal Plast Reconstr Surg 1999;15:463-466.
5. Heufelder MJ, Sterker I, Trantakis C, Schneider JP, Meixensberger J, Hemprich A, Frerich B.
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Reconstructive and ophthalmologic outcomes following resection of spheno-orbital
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meningiomas. Ophthal Plast Reconstr Surg 2009;25:223-226. doi:
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10.1097/IOP.0b013e3181a1f345
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6. Johnson TE, Weatherhead RG, Nasr AM, Siqueira EB. Ectopic (extradural) meningioma of
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the orbit: a report of two cases in children. J Pediatr Ophthalmol Strabismus 1993;30:43-47.
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7. Pushker N, Shrey D, Kashyap S, Sen S, Khurana S, Sharma S. Ectopic meningioma of the
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orbit. Int Ophthalmol 2013 Jan 21. [Epub ahead of print]
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8. Saeed P, Blank L, Selva D, Wolbers JG, Nowak PJ, Geskus RB, et al. Primary radiotherapy
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in progressive optic nerve sheath meningiomas: a long-term follow-up study. Br J Ophthalmol
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2010;94:564-568. doi: 10.1136/bjo.2009.166793.
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9. Spraul CW, Gareis O, Lang GK. Primary extradural intraorbital meningioma: A case
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presentation and review of the literature. Klin Monatsbl Augenheilkd 1996;209:322-327.
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10. Tan KK, Lim ASM. Primary extradural intraorbital meningioma in a chinese girl. Br J
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Ophthalmol 1965;49:377-380.
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11. Turbin RE, Thompson CR, Kennerdell JS, Cockerham KP, Kupersmith MJ. A long-term
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visual outcome comparison in patients with optic nerve sheath meningioma managed with
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observation, surgery, radiotherapy, or surgery and radiotherapy. Ophthalmology 2002;109:890-
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899; discussion 899-900.
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12. Wolter JR, Benz SC. Ectopic meningioma of the superior orbital rim. Arch Ophthalmol
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1976;94:1920-1922.
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13. Yokoyama T, Nishizawa S, Sugiyama K, Yokota N, Ohta S, Uemura K, et al. Skull Base
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Surgery 1999;9:47-50.
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ACCEPTED MANUSCRIPT Legend
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Fig 1a. Facial photograph demonstrates right proptosis in 56 year-old woman.
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Fig 1b. Axial computed tomography shows a superiorly located orbital mass on the right side.
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Fig 1c. Coronal computed tomography shows a superiorly located orbital mass producing thinning of
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the overlying bone on the right side.
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Fig 1d. T1W contrast enhanced orbital MRI reveals an ill-defined in the right superior orbit with
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marked contrast enhancement.
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Fig 1e. The tumor is hypointense with respect to orbital fat and cerebral gray matter on T2 weighted
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images. This hypointensity on T1W images is due to the accumulation of blood breakdown products in
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the tumor.
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Fig 1f. Histopathologic examination shows that the tumor consists of round to oval cells
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with indistinct cytoplasmic borders and vesicular nuclei. Mitosis or prominent nucleoli
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are not observed The tumor cells seemed to form a predominantly meningothelial
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(snycytical) pattern (arrow) and cellular arrangement reminiscent of whorling pattern
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(arrowhead). (Hematoxylin-eosin x 200). The histopathologic findings were consistent
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with the diagnosis of orbital meningothelial meningioma. Scale bar 250 µm
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Fig 2a. Facial photograph shows left proptosis in 27 year-old man.
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Fig 2b. T1W axial orbital MRI reveals a well-defined orbital mass occupying the entire
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lateral orbit. The tumor is isointense to the cerebral gray matter.
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Fig 2c. T2W coronal orbital MRI shows that the orbital mass defined above is
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hyperintense with respect to the cerebral gray matter.
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Fig 2d. Gross photograph of the excised tumor piece. The tumor could only be excised in
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a subtotal fashion.
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Fig 2e. Histopathologic examination demonstrates that the tumor is composed of cells
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with indistinct cytoplasmic borders forming whorls (arrow). Mitosis and prominent
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nucleoli are not present. (Hematoxylin-eosin x 40) The histopathologic findings and
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EMA positivity supported the diagnosis of orbital meningothelial meningioma. Scale bar
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1000 µm
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Tables
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Table 1. Patient demographics, tumor location, treatment, follow-up, complications, tumor connection
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to optic nerve and periorbita, and histopathologic classification in 14 cases with ectopic orbital
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meningioma.
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Table 2. Imaging features (tumor margins, calcification in the tumor, hyperosteosis/sclerosis
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of adjacent bone and asymmetry of orbital sinuses) in 14 cases with ectopic orbital
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meningioma.
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Table 1. Patient demographics, tumor location, treatment, follow-up, complications, tumor connection to optic nerve and periorbita, and histopathologic classification in 14 cases with ectopic orbital meningioma CT/ MRI
Orbital location
Primary surgery
Secondary treatment
Orbitotomy
Recurrent/ residual tumor None
None
Follow -up (mos) 0
1
Tan
1965
9/F
Not done
Medial
2
Wolter
1976
33/M
3
Johnson
1993
10/M
Not done CT
Supero medial Medial
Orbitotomy
None
None
3
Orbitotomy
Residual
Craniotomy
12
4
Johnson
1993
7/M
CT
Medial
Orbitotomy
Residual
Medial Supero medial Medial Infero medial
Orbitotomy Craniotomy
None None
External ethmoidectomy None None
5 6
Spraul Arai
1996 1997
30/M 27/F
MRI MRI
7 8
Farah Yokoyama
1999 1999
53/M 7/M
CT MRI
Orbitotomy Cranitomy
None None
9 10 11
Decock Pushker Pushker
2009 2013 2013
66/M 30/F 40/M
MRI CT CT
Orbitotomy Orbitotomy Orbitotomy
None Recurrence Recurrence
12
Pushker
2013
9/M
CT
13
Gündüz
2013
56/F
MRI
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Gündüz
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27/M
Lateral Superior Supero medial Supero medial Superior
Orbitotomy Orbitotomy
Complications
Tumor connection to optic nerve N/A
Tumor connection to periorbita Present
Histopathologic classification
Absent
Absent
Meningothelial
Absent
N/A
Meningothelial
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Frozen globe, ptosis None
Absent
N/A
Meningothelial
18 1
None None
N/A Absent
N/A Absent
Fibroblastic Fibroblastic
None None
42 0
Absent Absent
Present Absent
Meningothelial Meningothelial
None Orbitotomy Orbitotomy
15 18 24
None Optic atrophy, no light perception None None None
Absent N/A N/A
Absent N/A N/A
Meningothelial Meningothelial Meningothelial
None
None
3
None
N/A
Present
Meningothelial
Residual
EBRT
74
Radiation retinopathy None
Absent
Present
Meningothelial
Present
Meningothelial
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Year
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Case no
Wound infection, muscle paresis None
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MRI, Lateral Orbitotomy Residual EBRT 24 Absent CT M: Male, F: Female, CT: Computed tomography, MRI: Magnetic resonance imaging, EBRT: External beam radiation therapy, mos: months, N/A: data not available in the article
Meningothelial
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Present N/A Present Present N/A N/A Present N/A Absent N/A N/A N/A Absent Absent
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Asymmetry of orbital sinuses
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N/A N/A Present Absent Absent Absent Present Absent Present Absent Absent Absent Absent Absent
Hyperosteosis/ sclerosis of adjacent bone N/A Present Absent Absent Absent Absent Absent Absent Absent Present Absent Present Absent Absent
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1 Tan N/A 2 Wolter N/A 3 Johnson Ill-defined 4 Johnson Well-defined 5 Spraul Well-defined 6 Arai Well-defined 7 Farah Well-defined 8 Yokoyama Well-defined 9 Decock N/A 10 Pushker Ill-defined 11 Pushker Well-defined 12 Pushker Ill-defined 13 Gündüz Well-defined 14 Gündüz Well-defined N/A: data not available in the article
Calcification in the tumor
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Tumor Margins
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