Download The Role of High-Resolution Computed Tomography and Magnetic

The Role of High-Resolution Computed
Tomography and Magnetic Resonance
Imaging in the Evaluation of Isolated
Orbital Neurofibromas
WON CHAN PARK, MD, W. ABRAHAM WHITE, JOHN J. WOOG, MD,
JAMES A. GARRITY, MD, YOON-DUCK KIM, MD, JOHN LANE, MD,
ROBERT WITTE, MD, AND DUSICA BABOVIC-VUKSANOVIC, MD
● PURPOSE:
To analyze the imaging findings in patients
diagnosed with isolated orbital neurofibromas.
● DESIGN: Retrospective observational case series.
● METHODS: Computed tomographic (CT) and magnetic
resonance imaging (MRI) findings were reviewed in five
patients with orbital neurofibromas in the absence of
systemic neurofibromatosis in this multicenter study.
The main outcome measures were bony and soft tissue
abnormalities involving the orbit and surrounding anatomic spaces.
● RESULTS: Patient age ranged from 36 to 43 years
(mean, 41 years); three patients were men and two were
women. Duration of symptoms ranged from three to 20
years. Radiologic findings included intraconal and extraconal soft tissue masses in all patients, bony orbital
abnormalities in three patients, and intracranial extension in two patients. In addition, MRI studies in one
patient revealed the previously unreported presence of
neurofibromas involving extraocular muscle.
● CONCLUSIONS: Isolated orbital neurofibromas may
present with differing radiologic appearances. The
combined use of high-resolution CT and MRI may be
of benefit in the preoperative diagnosis of these uncommon orbital tumors. (Am J Ophthalmol 2006;
Accepted for publication Apr 18, 2006.
From the Departments of Ophthalmology (W.C.P., J.J.W., J.A.G.,
D.B.-V.) and Radiology (J.L., R.W.) and the Mayo Clinic College of
Medicine (W.A.W.), Mayo Clinic, Rochester, Minnesota; University of
Missouri–Kansas City School of Medicine, Kansas City, Missouri
(W.A.W.); and Samsung Medical Center, Sungkyunkwan University
School of Medicine, Seoul, Korea (Y.-D.K.).
Supported in part by an unrestricted grant from Research to Prevent
Blindness Inc, New York, New York.
Presented in part as a poster at the annual meeting of the American
Society of Ophthalmic Plastic Reconstructive Surgeons, Oct 23, 2004,
New Orleans, Louisiana.
Inquiries to John J. Woog, MD, Department of Ophthalmology, Mayo
Clinic, 200 First Street, SW, Rochester, MN 55905; e-mail: woog.john@
mayo.edu
456
©
2006 BY
142:456 – 463. © 2006 by Elsevier Inc. All rights
reserved.)
N
EUROFIBROMA IS A BENIGN TUMOR OF CRANIAL,
peripheral, or sympathetic nerves that may exist
as a solitary tumor or as part of neurofibromatosis
syndromes. These neoplasms may involve any area of the
body, including bone or periosteum. Plexiform neurofibromas have been thought to occur primarily in neurofibromatosis syndromes.1 Localized (otherwise known as isolated,
circumscribed, or solitary) neurofibromas are clinically
and radiologically distinct from plexiform neurofibromas
and are less frequently associated with neurofibromatosis
type I.1 Isolated orbital neurofibroma that is unassociated
with systemic neurofibromatosis is relatively rare and may
be difficult to differentiate clinically from other orbital
tumors.2 We illustrate the spectrum of high-resolution computed tomographic (CT) and magnetic resonance imaging
(MRI) findings in five patients with isolated orbital neurofibromas.
METHODS
RETROSPECTIVE REVIEW WAS PERFORMED FROM 1985
through 2003 of patients with isolated orbital neurofibromas evaluated at the participating institutions. Institutional review board approval and patient consent were
obtained and Health Insurance Portability and Accountability Act (HIPAA) requirements were observed. The
main outcome measures were clinical features and radiologic findings on high-resolution CT and MRI studies.
High-resolution CT studies were performed with a reduction in the field of view from the standard head examination of 20 to 22 cm to a field of view of 14 to 16 cm, with
a reduction in slice thickness from 5 to 10 mm to 1 to
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0002-9394/06/$32.00
doi:10.1016/j.ajo.2006.04.060
TABLE. Characteristics of Isolated Orbital Neurofibromas*
Patient
Age (y)
Gender
CT Findings
MRI Findings
1
41
F
Right proptosis, enlarged right medial rectus
muscle, homogeneous mass right
superomedial orbit.
2
42
F
3
42
M
4
36
M
Poorly defined mass involving posterior and
lateral orbit; enlarging orbital roof defect
noted on serial scans; involvement of
pterygopalatine and temporal fossa.
Extensive poorly defined mass involving
entire orbit with extension through
superior orbital fissure into cavernous
sinus and the middle cranial fossa.
—
Cystic lesion distinct from superior rectus muscle
extending into pterygopalatine fossa,
heterogeneous signal intensities within medial
and lateral rectus muscles consistent with
discrete lesions.
—
5
43
F
Enhancing, discrete mass left lacrimal sac
fossa.
—
Well-defined, cystic mass involving superior orbit,
hyperintense to aqueous humor on T2 images.
Circumscribed mass isointense to slightly
hyperintense relative to brain; expansion of
lacrimal sac fossa and nasolacrimal duct with
extension down nasolacrimal duct into inferior
meatus.
*CT ⫽ computed tomography; MRI ⫽ magnetic resonance imaging.
3 mm. High-resolution MRI studies were performed with
similar reductions in field of view and slice thickness. In
addition, scanning parameters were varied to allow threedimensional image acquisition, which allowed improved
resolution compared with two-dimensional techniques. All
MRI studies in this series were performed with a 1.5-T field
strength magnet. All patients in this series underwent
incisional or excisional biopsy or surgical debulking of
their lesions as described below.
RESULTS
FROM 1985 THROUGH 2003, WE EVALUATED FIVE PATIENTS
with isolated orbital neurofibromas. Three patients were
women and two patients were men. Ages ranged from 36
to 43 years (mean, 41 years). Medical genetic evaluation
revealed no evidence of underlying neurofibromatosis type
I. In addition, a newly developed protein truncation test3,4
performed at the University of Alabama failed to identify
the presence of a germline mutation in the neurofibroma
tumor suppressor gene in one patient with multiple neurofibromas involving one orbit.
Pertinent radiologic findings are summarized in the
Table 1 and are noted in the brief case histories below.
Patient 1: A 41-year-old woman presented with a
three-year history of increasing right-sided ocular prominence with progressive ptosis and proptosis. An initial
MRI study was reported to reveal medial and superior
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rectus muscle enlargement and was considered suggestive
of Graves disease. Her visual acuity was 20/20 in both eyes.
There was 8.5 mm of exophthalmos of the right eye.
Palpation suggested the presence of a firm mass noted in
the right superomedial orbit. Orbital CT revealed rightsided proptosis, enlarged right superior and medial rectus
muscles, and a homogeneous mass in the right superomedial orbit. This mass was isodense to muscle (Figure 1, Top
right and left). There was no bony erosion or sinus
involvement noted.
MRI revealed areas of abnormal signal intensity involving the extraocular muscles and orbit. A cystic lesion
with increased signal intensity relative to muscle was
noted distinct from the superior and medial rectus in the
superomedial orbit (Figure 1, Middle left and right, Bottom). In addition, the postgadolinium fat-suppression T1weighted image (Figure 1, Middle right) revealed discrete
masses within the medial and lateral rectus muscles themselves (arrowheads) posterior to the superomedial orbital
mass (arrow). These masses may have contributed to the
apparent muscle enlargement noted on the CT studies but
were not specifically visualized on the latter studies. MRI
also revealed subtle extension of the lesion into the
pterygopalatine fossa (Figure 1, Left).
Anterior orbitotomy with incisional biopsy was performed and a histopathologic diagnosis of neurofibroma
was made (Figure 1, Right). Medical genetics consultation
revealed no evidence of systemic neurofibromatosis.
Molecular testing for presence of a germline mutation in
the neurofibroma tumor suppressor gene was performed
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NEUROFIBROMAS
457
FIGURE 1. Right orbital neurofibroma in a 41-year-old woman. (Top left) Axial computed tomography (CT) demonstrates enlargement
of medial rectus. Muscle enlargement is relatively diffuse but appears less pronounced in area of muscle tendon. Separate mass is noted
in superomedial orbit. (Top right) Coronal CT demonstrates superomedial orbital mass that is isodense to muscle, and separate from
medial rectus. (Middle left) Axial T1-weighted magnetic resonance imaging (MRI) demonstrates lobulated appearance to mass. (Middle
right) Axial T1-weighted image with contrast and fat suppression shows peripheral rim enhancement of superomedial lesion distinguishing
it from surrounding extraocular muscles. In addition, masses are noted within medial (posterior arrow) and lateral rectus muscles.
(Bottom) Coronal T2-weighted MRI demonstrates that superomedial lesion is distinct from superior and medial rectus muscles; superior
oblique muscle is not well seen.
FIGURE 1 (Continued). (Left) Axial T2-weighted MRI demonstrates extension of mass into pterygopalatine fossa. (Right)
Hematoxylin and eosin stain reveals demonstrates spindle cell proliferation with collagenous matrix consistent with neurofibroma
(original magnification, ⴛ400).
and was negative. At one year after biopsy, the patient had
5 mm of right proptosis, and ocular motility was full. The
size of the mass was unchanged on follow-up MRI studies.
Patient 2: A 43-year-old woman was referred to our
service with a 14-year history of right proptosis. She had a
history of previous orbital debulking on three occasions at
other institutions. The first operation demonstrated a large
mass within the muscle cone that was poorly encapsulated
and was initially diagnosed as a fibrous pseudotumor.
Biopsy specimens from this procedure were not available
for review. The histologic diagnosis of neurofibroma was
not established until the second operation. The histopathology findings revealed a plexiform neurofibroma. It
should be noted that bone removal was not performed
during any of the surgical procedures. Uncorrected visual
acuity on presentation to our facility was 20/20 in both
eyes. Exophthalmometry measured 11 mm in the right eye.
She subsequently underwent further soft tissue resection
without bone removal.
CT scan performed 13 years after this procedure revealed a mass along the optic nerve and posterior to the
right globe with irregularity of the lateral rectus muscle, as
well as a new mass adjacent to the lateral rectus (Figure 2,
Top). Follow-up CT scans performed 52 months later
documented enlargement of a roof defect, with extension
into the temporal fossa and pterygopalatine fossa (Figure 2,
Middle and Bottom). CT also revealed a new nodule
displacing the right lateral rectus; however, the patient was
clinically stable, so follow-up was recommended. The most
recent visual acuity 17 years after her most recent surgery
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was 20/20 in both eyes, and 7.5 mm of exophthalmos was
noted in the right eye.
Patient 3: A 42-year-old man presented with complaint of painful bulging of the left eye for two months. His
vision was blurry, and he reported diplopia when tilting his
head to the left. His medical history included orbitotomies
in 1985, 1987, 1988, 1992, and 1993 with excision of
additional painful neurofibromas. In 1988, left frontal orbital roof removal and exenteration of left frontal sinus was
performed. In 1992, lateral orbital decompression was
done. Histopathologic findings in all procedures were
consistent with a diagnosis of plexiform neurofibromas.
Uncorrected visual acuity was 20/20 in the right eye and
20/25 in the left eye. There was 16 mm of proptosis noted
in the left eye. Neurofibroma was seen in the area of the
left caruncle.
CT scan of the orbit showed extensive neurofibroma.
The mass was noted to extend from the orbital apex,
tracking through the superior orbital fissure and into the
cavernous sinus, eventually terminating in the middle
cranial fossa (Figure 3, all panels). Involvement of Meckel
cave was also appreciated. Left superior orbitotomy with
debulking was performed with marked improvement in
the patient’s pain. Pathology again revealed plexiform
neurofibroma.
Patient 4: A 36-year-old man presented after experiencing left eye trauma. An orbital CT scan was performed
in view of his history of trauma and was reported to show
a left superior orbital mass. The actual CT scan was not
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NEUROFIBROMAS
459
FIGURE 2. Right orbital neurofibroma in a 43-year-old woman.
(Top) Coronal computed tomography (CT) (soft tissue windows) demonstrates orbital mass and superolateral roof defect.
(Middle) Follow-up CT (bone windows) reveals enlargement of
mass with increased size of orbital roof defect. (Bottom) Axial
CT shows extension of mass into pterygopalatine fossa.
FIGURE 3. Left orbital neurofibroma in a 43-year-old man. (Top)
Axial CT shows orbital apex mass extending into Meckel cave.
(Middle) Axial CT reveals marked proptosis with erosion of anterior
clinoid and widening of superior orbital fissure. (Bottom) Coronal
CT demonstrates extensive infiltration including Meckel cave.
FIGURE 4. Left orbital neurofibroma in a 36-year-old man. (Top left) T1-weighted axial MRI shows elongated mass. (Top right)
T1-weighted coronal MRI delineates well circumscribed mass extending near orbital apex. (Bottom left) T1-weighted sagittal MRI reveals
mass to be extraconal in location. (Bottom right) Axial T2-weighted MRI demonstrates predominantly cystic characteristics of mass.
available for review. He was then referred for further
evaluation. His vision was 20/20 in both eyes; 5 mm of left
exophthalmos was noted. An orbital MRI study was
obtained. A 1.8 ⫻ 1.6 ⫻ 1-cm lobulated, elongated cystic
mass was noted in the superior extraconal space of the orbit.
The mass appeared cystic on both T1- and T2-weighted
images and was hyperintense relative to the aqueous humor
on the latter image sequences. The mass displaced the globe
inferiorly and laterally (Figure 4, all panels).
The tumor was removed through a lateral orbitotomy
approach. The orbital mass originated from the frontal nerve.
The mass was removed to the superior orbital fissure posteriorly. The tissue was pinkish, hypervascular, cystic, and well
demarcated; histopathology revealed a neurofibroma.
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Patient 5: A 43-year-old woman had experienced left
epiphora for three years. She was seen at an outside
institution one year before presentation, and a left lacrimal
sac mass was noted. An orbital CT scan demonstrated an
enhancing, homogeneous discrete mass in the left lacrimal
sac fossa with expansion of the nasolacrimal duct. The
mass displaced the globe superiorly and laterally (Figure 5,
Top left and right). Incisional biopsy revealed a pigmented
neurofibroma. The patient underwent mass excision with
conjunctivodacryocystorhinostomy. Recurrence of the mass
was suspected, and an orbital MRI was obtained demonstrating a mass in the lacrimal sac and nasolacrimal duct.
In T1- and fat-suppressed T2-weighted images, the mass
showed iso- to slightly high signal intensity relative to
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FIGURE 5. Left lacrimal sac neurofibroma in a 43-year-old woman. (Top left) Axial CT with contrast shows 2 ⴛ 2-cm enhancing soft
tissue mass in lacrimal fossa with extension along nasolacrimal duct and bulging into inferior meatus. (Top right) Coronal CT with
contrast shows superior and lateral displacement of globe by nasolacrimal mass. (Bottom left) T2-weighted axial MRI demonstrates
nasolacrimal mass. Mass is associated with expansion of left lacrimal sac fossa and nasolacrimal duct and bulges into inferior meatus.
(Bottom right) Fat-suppressed T2-weighted coronal MRI demonstrates that mass is solid in nature and isointense to brain.
brain parenchyma. The mass was relatively well circumscribed. The mass expanded the left lacrimal sac fossa and
nasolacrimal duct with extension down the nasolacrimal
duct into the inferior meatus (Figure 5, Bottom left and
right). The patient was referred for further management,
and excision of the mass including nasolacrimal duct resection was performed. Histopathology revealed pigmented
neurofibroma. She underwent repeat conjunctivodacryocystorhinostomy with Jones tube insertion 31 months later.
Follow-up CT and MRI performed postoperatively showed
no evidence of a recurrent mass.
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AMERICAN JOURNAL
DISCUSSION
ISOLATED NEUROFIBROMA OF THE ORBIT IS A BENIGN,
relatively uncommon, peripheral nerve tumor representing
less than 1% of orbital tumors.5,6 Patients often present
with slowly progressive proptosis or displacement of the
globe and may not develop diplopia until the lesion is large
enough to limit ocular movement. Visual acuity is often not
affected unless the tumor compresses the optic nerve, which
can occur earlier in lesions arising in the orbital apex.7,8
OF
OPHTHALMOLOGY
SEPTEMBER 2006
A variety of radiologic patterns was noted in this series.
Encapsulated lesions were noted in three patients (patients
1, 4, and 5). MRI allowed differentiation of cystic lesions
(patient 4), solid lesions (patient 5), and mixed cystic-solid
lesions (patient 1). Both lesions with cystic components
were noted to arise from the frontal nerve.
Infiltrative lesions were noted in three patients (patients
1, 2, and 3). In patients 2 and 3, these lesions were noted
to have heterogenous enhancement patterns on highresolution CT scans. Histopathology revealed the latter
lesions to represent plexiform neurofibromas. In patient 1,
involvement of the pterygopalatine fossa was suggested on
CT and confirmed on MRI studies.
Involvement of the cavernous sinus was found in two
patients (patients 3 and 4). One of these patients also
demonstrated involvement of Meckel cave. This finding
suggests that neurofibromas may occur anywhere along the
course of the trigeminal nerve.
Involvement of the bony orbit was noted in three
patients (patients 1, 2, and 5) and was best visualized with
high-resolution CT. In patient 2, CT was also useful to
follow progression of bony erosion. In patients 1 and 5,
bony erosion was noted in conjunction with a well-circumscribed mass, whereas in patient 2, bony erosion developed in
conjunction with a poorly defined plexiform neurofibroma.
Although to our knowledge bone removal was not performed in patient 2, we do acknowledge that previous
surgery in this patient could have altered the radiologic
appearance of her lesion.
Patient 1 was initially misdiagnosed with Graves disease on
the basis of CT findings of apparently enlarged extraocular
muscles. High-resolution MRI allowed discrimination of a
neurofibroma originating within the medial rectus muscle; to
our knowledge, this is the first report of an isolated orbital
neurofibroma originating within an extraocular muscle. This
patient was also tested for a germline mutation in the
tumor-suppressor gene implicated in systemic neurofibromatosis, and no evidence of genetic anomaly was found. It has
been suggested that some neurofibromas may be related to
somatic mutations or mosaicism, producing a segmental
pattern of involvement.9 Genetic analysis of surgical specimens may reveal this to be true, but such testing was not
performed in our patients.
Patients 2 and 3 had had previous orbital surgeries
directed at these lesions, and the imaging presented was
after those procedures. No bone removal was performed in
patient 2, but patient 3 had undergone bone removal. This
likely altered the imaging appearance of neurofibromas, at
least to some extent.
This tumor may or may not require excision, depending
on the degree of symptoms and size of the tumor. It may be
possible to perform complete and curative excision of
discrete localized neurofibromas in some locations. Surgi-
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cal excision of diffuse and plexiform orbital neurofibromas
is often necessarily incomplete. This may be followed by
regrowth of the tumor with recurrent symptoms and the
need for further intervention.
In each of our cases, preoperative CT and/or MRI
studies were helpful in establishing the goals of the surgical
procedure (for example, total resection of discrete lesions
vs debulking of infiltrative lesions) and in planning the
surgical approach and minimizing to the extent possible
the risk of injury to adjacent structures.
In conclusion, radiologic presentations of isolated intraorbital neurofibromas are diverse and are similar to
those noted in the setting of systemic neurofibromatosis.10
High-resolution CT and MRI may provide complementary
information that assists in the proper diagnosis and treatment planning for patients with isolated orbital neurofibromas. CT appears to be most useful for delineating bony
involvement, while MRI is most useful for defining the
structure and relationship of neurofibromas to other soft
tissue structures within the orbit. MRI may also demonstrate subtle extension into adjacent areas such as the
pterygopalatine fossa, which may not be evident on CT.
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