Download View PDF

1
Neurofibroma of the Choroid: Three Cases Report
Abstract
Purpose To review the clinical features of neurofibroma of the choroid in the Chinese
race. Design A retrospective case series design was used. Participants Two male and
one female patients diagnosed with choroidal neurofibroma in Beijing Tongren eye
center were included in this study. Methods The clinical histories were abstracted
from the patients’ medical records. Routine eye examinations including visual acuity,
intraocular pressure, slit lamp and ophthalmoscope were performed. Auxiliary
examinations included fluorescein fundus angiography (FFA), indocyaninegreen
angiography (ICGA), AB-ultrasound scan, color doppler imaging (CDI) and magnetic
resonance imaging (MRI). Local resection of the tumors was performed and the
specimens underwent pathological examinations. Main outcome measures To define
the clinical and histopathologic parameters of these rare tumors. Results The tumors
were of yellow-pink color with pigmentation on the surface. CDI showed arterial
blood signals in the tumor and MRI showed high-intensity in the T1-weighted image
and a slightly increased intensity in the T2-weighted image. FFA and ICGA
demonstrated
the
tumors
were
of
hypofluorescence
at
early stage
and
hyperfluorescence with prominent leakage at late stage. The pathological examination
confirmed the tumors were choroidal neurofibroma. After 5~10 years’ follow-up,
there were no recurrences of the tumors and the retinas were well attached.
Conclusion Choroidal neurofibroma is difficult to be diagnosed clinically and
pathological confirmation is important. These tumors can be managed conservatively
1
2
by local resection.
Key words: Neurofibroma, Choroid, Local resection
2
3
Introduction
Neurofibroma is a kind of benign neoplasm that derives from nervous tissues. It is
composed of endoneurium and perimysium cells and often occurs single. If it occurs
multiple, it is named neurofibromatosis. Though this tumor is the most common types
in the peripheral nervous system, it is rarely seen in the choroid and easy to be
misdiagnosed of choroidal melanoma.
The differentiation of the various choroidal tumors is made on clinical
examination by the typical ophthalmoscopic and fluorescein angiographic features of
each tumor. Because of the great variations in the clinical manifestations and
characteristics, diagnosis of choroidal neurofibroma may be confirmed only by
histopathological examination. We had three such patients treated with local resection
and the diagnosis was confirmed by histopathology. Here we describe the clinical
features and review the relevant literatures on this subject.
Methods
A retrospective study was performed. Three patients diagnosed of choroidal
neurofibroma were included. This study was approved by the ethic committee of
Beijing tongren hospital and conformed to the tenets of the declaration of Helsinki.
The informed consent for the study was obtained from each participate. Fine-needle
aspiration of the tumor was not performed in all the three patients. The clinical and
iconographic characteristics were described. Local resection was performed to remove
the tumors and the follow-up results were presented.
Case presentation
3
4
Case 1
A 37-year- old female was diagnosed with neurofibromatosis in 2000. There were
multiple milk coffee spots on her body. Multitude lesions were found in the spinal
canal and removed by surgery. The patient had dysmorphopsia and obfuscation in
2000, but she didn’t see the eye doctor. She had received γ-knife treatment for five
times to treat the neurofibromatosis in the brain and was found neoplasm in the left
eyeball when having brain CT scanning in 2002. She went to our clinic in 2003. The
visual acuity was 1.5 in the right eye and 0.8 in the left eye. The near vision in both
eyes was Jr1. The intraocular pressure was 14mmHg in the right eye and 12 mmHg in
the left eye. The anterior segment was normal in both eyes with slit lamp examination.
With indirect ophthalmoscopic examination, a solid neoplasm of mushroom shape
was found at the temporal part of the fundus (Fig 1A). The tumor had a slightly thin
basement with uneven pigmentation on the surface. The parenchyma of the tumor was
slightly red and the retinal vessels could be seen on the surface. The patient was
suggested to have close follow-up. When the patient revisited our clinic in 2004, the
best corrected visual acuity was 1.2 in the right eye and 0.3 in the left eye. The tumor
became larger than before and exudative retinal detachment occured. In CDI images,
the tumor showed low level echo and abundant blood signals inside, but no
excavation signs (Fig 2A). In MRI, the tumor showed high intensity in the
T1-weighted image and slight intensity in the T2-weighted image (Fig 3 A, B). FFA
showed fluorescein leaking and merging with partial fluorescence blocked at early
stage, then the leakage of fluorescein became more obvious and formed
4
5
hyperfluorescence area at late stage(Fig 4 A,B). The tumor had a size of 10×7×7mm
with A-ultrasound scanning.
Case 2
A 48-year-old female complained of blurred vision in the left eye for one week in
2001. She has no medical history. The visual acuity was 0.2 in the right eye and could
be improved to 1.0. The visual acuity was 0.02 in the left eye and the best corrected
vision was 0.3. The intraocular pressure and anterior segment were normal.
Ophthalmoscopic examination revealed a solid neoplasm of mushroom shape at the
temporal equator with retinal detachment (Fig 1B). The tumor was of orange color
with much pigment depositing on the surface. Ultrasound scan (Fig 2B), MRI (Fig 3
C, D) and FFA(Fig 4 C,D) findings were similar to case 1. The tumor had a size of 8×
5×4mm.
Case 3
A 42-year-old male complained of decreased vision acuity and dark shadow in the
right eye for five months in 1999. He had no medical history. The best corrected
visual acuity was 1.2 in the right eye and 0.2 in the left eye. The intraocular pressure
was normal in both eyes. The anterior segment was normal. A yellow-pink solid mass
located in the temporal equator in the fundus of the left eye could be found (Fig 1C).
The tumor was of hemispheroid shape with no retinal detachment. The tumor had
fairly uniform echo in the CDI and the size was of 13.7mm×5×4mm (Fig 2C). MRI
(Fig 3 E, F) and FFA (Fig 4 E, F) findings were similar to case 1 and case 2.
Treatment
5
6
Local resections of the tumors were performed in all the three patients by the same
skilled vitreoretinal surgeon. General hypotension anesthesia was adopted during the
surgery. In patient 1 and 2, endoresection was performed. Surgical procedures
involved lensectomy, vitrectomy, retinal incision peripheral to the tumor, infusion of
perfluorocarbon liquid, choroidal incision surrounding the tumor, separation of the
whole tumor body from the eye wall, floating the tumor in the pool of
perfluorocarbon liquid and extraction the tumor from the limbal incision. Subsequent
procedures included haemostasia with electric coagulation, coagulation with
endolaser to achieve retinal adhesion around the coloboma, fluid-air exchange to
reattach the retina and silicon oil injection [4].
. In patient 3, cyclectomy and choroidectomy with lamellar corneoscleral
resection was performed. The 360 degree peritomy at the limbus was performed and
the sclera around the tumor was exposed. Transillumination test was done to define
the tumor margin. A scleral slab was made from the edge of the cornea to
approximately 2~3mm from margin of the tumor. A full thickness sclera slab was
made 1mm away from the tumor. The incised sclera, iris and the ciliary body tumor
were severed from the eyeball. Then the sclera slab was covered immediately and
sutured discontinuously. The sclera graft obtained from a healthy donor was used to
strengthen the operated region. Then a closed vitrectomy was used to remove the
vitreous hemorrhage and vitreous leakage. Finally, coagulation with endolaser,
fluid-air exchange and silicon oil injection was used to reattach the retina.
6
7
The tumors were removed intact in all the three cases. There were no serious
complications during the surgeries. After 5~10 years’ follow- up, there were no tumor
recurrences or retinal detachment (Figure5A, B). The best corrected visual acuity was
light-perception in patient 1, 0.08 in patient 2 and 0.3 in patient 3.
Histopathologic findings
Grossly, all tumors were of yellow pink color with some pigmentation. Sections were
cut of 5 um thickness, and the slides were stained with H-E (hematoxylin and eosin)
and immunohistochemistry method. Monoclonal antibodies to S-100, vimetin,
HMB45 and CK were used as primary antibodies (Serotec, UK) and EnVision-HRP
(Dako, Glostrup, Denmark) used as a second antibody. Chromogen AEC (Dako) was
applied to the tissue staining, followed by counterstaining with Mayer’s haematoxylin.
The pathological findings were the same in all the three patients. In the H-E staining,
the tumors were composed of cords of amelanotic cells with slightly pleomorphic
round or oval nucleus and the mitotic figures were rare (Fig 6A).
Immunohistochemistry staining showed the tumors were positive for S-100 and
vimetin staining (Fig 6B, C), but negative for melanoma-specific antigen HMB45 and
CK staining.
Discussion
Neurofibroma is a kind of benign neoplasm that derives from epineurium,
perineurium and endoneurium and can occur at any part of the nerve endings or nerve
cord. It is commonly seen in the peripheral nervous system. In the eye, it is relatively
common seen in the orbit, but rarely seen in the choroid [1]. Except neurofibromatosis
7
8
history in one patient, the other two patients had no systemic diseases. The
confirmation of this tumor mainly depends on the pathological diagnosis. S-100,
Vimentin and GFAP are important markers for choroidal neurofibroma but the
specificity is relatively low [2].
Most choroidal neurofibroma is free of pigmentum or only contains a small
quantity of pigmentum which need to be differentiated from nonpigmented melanoma
of choroid
[3]
. While in the three cases in this study, there was inequality of
pigmentum on the surface of the tumors which also should be differentiated from
choroidal melanoma, nevus, hemangioma or even metastatic carcinoma. It is still not
clear for the origin of the pigmentum in choroidal neurofibroma, but it is regarded that
schwann cells have the ability to synthetise pigmentum[4].
In the clinical manifestation and examinations, the three cases had some
differences from classic choroidal melanoma. The tumors are of solid mushroom
shape and of yellow pink color with pigmentation on the surface which is different
from the identical brownness in choroidal melanoma. In the ultrasound scan images,
all the tumors showed low level echo and had abundant blood signals inside, but there
was no excavation sign which was different from the typical choroidal melanoma.The
FFA showed fluorescein leaking and merging with part fluorescence blocked at early
stage, then the leakage of fluorescein became more obvious and formed
hyperfluorescence area at late stage. The MRI showed short T1 signal and short T2
signal which could be intensified after enhancement. While in choroidal melanoma,
MRI showed long T1 and T2 signal. The transillumination test during the surgery
8
9
found the tumor was lucency which was also different from the choroidal melanoma.
Small intraocular neurofibroma can be followed up closely, but symptomatic
tumors should be treated promptly. There were various treatments available to the
ophthalmologists who care for patients with intraocular tumors. In practice, these
treatments are employed based on the type of tumor and conditions of the eye. In
general, treatments of intraocular tumors have trended toward ocular conservation.
The trends of treatment include observation, local resection, and radiation therapy.
Enucleation of the eyeball is typically reserved for large tumors or eyes with
untreatable glaucoma[5]. As new modalities of therapy offered lower morbidity when
compared with enucleation, more physicians and patients have opted for eye and
vision-sparing treatments. Brachytherapy is an effective way to treat some intraocular
tumors, but some severe side effects such as radiation retinopathy and optic radiation
neuropathy which would lead to vision loss should not be neglected. With the
technological development in ophthalmology, skilled ophthalmologist could perform
surgeries to remove the tumors even in some malignant cases. Because the patients
had useful vision acuity and the nature was not clear before surgery, local resection of
the tumors was performed. Local resection of the intraocular tumors was first
performed by Peyman[6] in which the resection of the whole thickness or lamellar
sclera was performed, and advanced endoresection technology was used in the recent
years[7-9]. The complications after local resection included vitreous hemorrhage,
retinal detachment, subretinal hemorrhage and cataract [10、11]. Karkhaneh[12] reported
the recurrence rate of choroidal melanoma after local resection was 15%, while
9
10
recurrence of neurofibroma after local resection was not reported. In our study, no
severe complications occurred in these three patients. Only two patients suffered from
transient ocular hypertension of 30mmHg and recovered to normal level one week
after surgery. The reason of ocular hypertension might be attributed to inflammation
and anterior chamber hyphema.
The patients were followed up from 5~10 years after surgery with retina well
attached and no tumor recurrence which demonstrated that local resection is a feasible
alternative for the chroidal neurofibroma.
10
11
Reference:
1. Shields JA. Diagnosis and Management of Orbital Tumors. Philadelphia:WB
Saunders,1989:149-169.
2. Kawahara E,Oda Y,Ooi A. Expression of glial fibrillary acidic protein(GFAP) in
peripheral nerve sheath tumors.A comparative study of immunoreactivity of
GFAP,vimentin,S-100 protein,and neurofilament in 38 schwannomas and 18
neurofibromas.Am J Surg Pathol.1988,12(2):115-120.
3. Shields JA.Shields CL.Introcular Tumors:A Text and Atlas.Philadelphia:WB
Saunders,1992:285-294.
4. Shields JA,Font RL,Eagle RC Jr, Shields CL, Gass JD. Melanotic schwannoma of
the choroid. Immunohistochemistry and electron microscopic observations.
Ophthalmology 1994, 101(5): 843-849.
5. Shields JA,Shields CL.Current management of posterior uveal melanoma.Mayo
Clin Proc.1993,68(12):1196-1200.
6. Peyman GA, Barrada A. Retinochoroidectomy ab interno. Ophthalmic Surg.
1984,15(9):749-751.
7. Damato B,Groenewald C,McGalliard J, Wong D. Endoresection of choroidal
melanoma.Br J Ophthalmol.1998,82(3):213-218.
8. Damato B,Lecuona K. Conservation of eyes with choroidal melanoma by a
multimodality approach to treatment:an andit of 1632 patients.Ophthalmology.
2004,111(5):977-983.
9. Damato B.Choroidal melanoma endoresection,dandelions and allegory-based
11
12
medicine.Br J Ophthalmol.2008,92(8):1013-1014
10. Shields JA, Shields CL, Shah P. Sivalingam V. Partial lamellar sclerouvectomy for
ciliary body and choroidal tumors.Ophthalmology.1991, 98(6):971-983.
11. Kertes PJ,Johnson JC, Peyman GA.Internal resection of posterior uveal
melanomas. Br J Ophthalmol.1998, 82(10):1147-1153.
12. Karkhaneh R,Chams H, Amoli FA. Long-time surgical outcome of posterior
choroidal melanoma treated by endoresection. Retina.2007, 27(7):908-914.
12
13
Figure legend
Fig 1. Solid choroidal neoplasms of mushroom shape could be seen in the fundus. The
tumors were of yellow pink color with pigmentation on the surface. A, patient 1; B,
patient 2; C, patient 3.
Fig 2. In CDI images, the tumors showed low level echo and abundant blood signals
inside, but there was no excavation sign. A, patient 1; B, patient 2; C, patient 3.
Fig 3. In MRI images, the tumors showed high-intensity in the T1-weighted image
and slight intensity in the T2-weighted image. A, B: patient 1; C, D: patient 2; E, F:
patient 3.
Fig 4. FFA and ICGA showed fluorescein leaking in the early stage and formed
hyperfluorescence area in the late stage. A, B: patient 1; C,D: patient 2; E,F: patient 3.
Fig 5. After 5~10 years’ follow- up, there was no tumor recurrence or retinal
detachment. A, patient 1; B, patient 3.
Fig 6. The pathological findings of the tumors. A, in the H-E staining, the tumors
were composed of cords of amelanotic cells with slightly pleomorphic round nucleus;
B, the tumors were positive for S-100 (B) and vimetin (C) staining.
13