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Clinical science
Choroidal schwannoma: a case series of five patients Bertil Damato,1,2,3 Erika M Damato,1 Lazaros Konstantinidis,1 Heinrich Heimann,1 Sarah E Coupland2 1
Vitreoretinal and Ocular Oncology Service, Royal Liverpool University Hospital, Liverpool, UK 2 Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK 3 Ocular Oncology Service, University of California, San Francisco, USA Correspondence to Dr Bertil Damato, Ocular Oncology Service, University of California, San Francisco, 10 Koret Way, K327, San Francisco, CA 94143-0730, USA; [email protected] Received 26 January 2014 Revised 10 March 2014 Accepted 12 March 2014 Published Online First 23 April 2014
ABSTRACT Aim To report a case series of five patients diagnosed with choroidal schwannoma at the Liverpool Ocular Oncology Centre. Methods Patients with choroidal schwannoma were identified by searching the computerised database of the Liverpool Ocular Oncology Centre. Results The patients (3 males, 2 females) ranged in age from 15 years to 45 years. Three tumours were treated by enucleation, trans-scleral local resection, and combined bevacizumab and photodynamic therapy, respectively. Two were observed after confirmation of the diagnosis by biopsy. Conclusions Choroidal schwannoma has a variety of clinical manifestations. Associated features include hard exudates, retinal feeder vessels and serous retinal detachment. Biopsy with immunohistochemistry is required for diagnosis. Tumours not amenable to resection may respond to photodynamic therapy. INTRODUCTION Schwannoma (also known as neurilemmoma, neurinoma, neuroma) is a benign, nerve sheath tumour arising from Schwann cells, which produce myelin. It differs from neurofibroma, which arises from neoplastic, non-myelinating Schwann cells incorporating additional types of cell and structural elements. Schwannoma and neurofibroma can arise in isolation or as part of multisystem disorders; about 10% of schwannomas are associated with neurofibromatosis, schwannomatosis, multiple meningiomas, and the Carney complex (melanotic schwannoma, myxoma, spotty skin pigmentation, endocrine tumours).1 Intraocular schwannomas arise from ciliary nerves in the uvea, mostly in the ciliary body or choroid and occasionally in the iris.2–5 They are usually amelanotic or pseudo-pigmented if covered by pigment epithelium, but may rarely be pigmented.6–8 Visual loss and phthisis can occur as a result of tumour growth and serous retinal detachment. To our knowledge, malignant transformation of an intraocular schwannoma has not yet been reported. The aim of this study was to review our experience with five patients with intraocular schwannoma, to describe the clinical features, relevant histopathology and treatment options.
CASE 1 To cite: Damato B, Damato EM, Konstantinidis L, et al. Br J Ophthalmol 2014;98: 1096–1100. 1096
A 28-year-old woman was referred to us in the early 1990s with a history of blurred vision and a nasal, ciliochoroidal tumour in the left eye extending from the 7 o’clock to the 10 o’clock meridians. On examination, the visual acuity with the affected
eye was 6/12. The tumour was dome-shaped and amelanotic. The eye was enucleated on the basis of a clinical diagnosis of amelanotic melanoma. Subsequent histological examination revealed the diagnosis of schwannoma (figure 1A–C).
CASE 2 A 37-year-old woman was referred soon after 2000 with a choroidal tumour in the left eye. Her past medical history was unremarkable. The right eye was normal. On examination, the visual acuity with the left eye was 6/6. Ophthalmoscopy showed a superotemporal, pre-equatorial, choroidal tumour in the left eye. This was associated with retinal feeder vessels and adjacent hard exudates. (figure 2) On ultrasonography, the tumour measured 6.9 mm×5.8 mm×2.1 mm. The differential diagnosis included vasoproliferative tumour, adenoma, retinal angioma and amelanotic melanoma. The diagnosis of choroidal schwannoma was made on histopathological examination following trans-scleral incisional tumour biopsy. The patient was kept under observation and 11 years later the tumour remained unchanged. The patient maintained a visual acuity of 6/6.
CASE 3 A 33-year-old man was referred soon after 2000 with a 6-month history of reduced vision in the left eye, which was amblyopic. The right eye was healthy with a visual acuity of 6/4. The past medical history was unremarkable and the patient was otherwise well. On examination, the left eye had a visual acuity of Counting Fingers. On ophthalmoscopy, there was an amelanotic tumour involving the macula, extending to the temporal optic disc margin, measuring 4.6 mm by 6.4 mm with a thickness of 2.2 mm (figure 3A). This was associated with a localised serous retinal detachment and hard exudates. A fine needle aspiration biopsy was attempted, but was unsuccessful. The patient was discharged back to his local ophthalmologist for surveillance close to his home. The patient was referred back to our centre 4 years later, because of tumour growth and increasing exudation. On examination, the visual acuity had deteriorated to Hand Movements. The tumour now measured 7.5 mm by 6.9 mm with a thickness of 3.9 mm and had grown to obscure most of the optic disc. The exudation was much more extensive and an inferior exudative retinal detachment was observed (figure 3B). A transretinal biopsy was performed and enabled us to diagnose the tumour as being a schwannoma (figure 3C). The patient was treated with four injections of intravitreal bevacizumab at a dose of 2.5 mg in 0.1 mL over a period of 8 months. This
Damato B, et al. Br J Ophthalmol 2014;98:1096–1100. doi:10.1136/bjophthalmol-2014-304976
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Clinical science
Figure 1 Light micrograph of the left eye of patient 1 showing a large choroidal schwannoma (A). H&E stain showing spindle cells with bland nuclei and abundant cytoplasm (×40 objective) (B). Immunohistochemistry using the S-100P stain demonstrating clear cytoplasmic positivity (Alkaline phosphatase-anti alkaline phosphatase (APAAP), ×40 objective) (C).
resulted in some reduction in exudation, with crystallisation of the hard exudates and resolution of the retinal detachment. Despite this treatment, however, the tumour thickness increased from 3.9 mm to 4.2 mm. The patient was therefore treated with photodynamic therapy (six sessions over 18 months). This brought about regression of the tumour and a reduction in thickness to 1.6 mm. The eye had vision of Hand Movements 7 years after initial referral. When last reviewed, 11 years after initial referral, the patient had No Light Perception with the affected eye. The schwannoma appeared inactive but there was extensive retinal atrophy (figure 3D).
CASE 4 A 45-year-old man was referred with a 3-week history of blurred vision in the left eye, which was found to have a choroidal tumour (figure 4A). On examination, the visual acuity with the affected eye was 6/18. Ophthalmoscopy demonstrated a dome-shaped, amelanotic tumour with an inferior, serous, retinal detachment. Ultrasonography showed high internal acoustic reflectivity and the tumour measured 18 mm×18 mm basally with a thickness of 10 mm. An initial diagnosis of choroidal melanoma was made and plans were made to insert tantalum markers for proton beam radiotherapy. During the surgery,
however, the tumour was noted to transilluminate brightly and a diagnosis of choroidal schwannoma was considered. A transretinal biopsy was carried out, which confirmed this suspicion. Trans-scleral local resection was therefore performed, using a posteriorly hinged lamellar scleral flap and hypotensive anaesthesia, lowering the systolic blood pressure to approximately 50 mm Hg (figure 4B). The tumour was located in the suprachoroidal space, separating from the sclera and uvea except posteriorly, where it was adherent to choroid. Histopathological examination of the excised tumour confirmed the diagnosis of schwannoma (figure 4C,D). Postoperative recovery was uneventful and a year later the visual acuity was 6/24 with an area of choroidal atrophy temporally (figure 4E).
CASE 5 A 15-year-old boy was referred around 2005 with a choroidal tumour in the left eye. The past medical history was unremarkable and general health was good. On examination, the visual acuity was Counting Fingers with the affected eye and 6/5 with the right eye, which was healthy. Ophthalmoscopy showed an amelanotic choroidal tumour superior to and almost surrounding, the optic disc (figure 5). An inferior retinal detachment was also observed. On ultrasonography, the tumour showed a low to moderate internal acoustic reflectivity. The tumour dimensions were 12 mm×12 mm basally, with a thickness of 3.6 mm. Transretinal biopsy enabled a diagnosis of choroidal schwannoma to be made. The patient was kept under observation and remained stable with no evidence of lesion growth. He was last seen 6 years after initial referral, when the visual acuity in the affected eye was Hand Movements.
DISCUSSION
Figure 2 Superotemporal, choroidal schwannoma in the left eye of patient 2, showing an amelanotic tumour with large feeder vessels (arrow) and hard exudates.
Choroidal schwannoma is a rare benign tumour, which may be mistaken for an amelanotic choroidal melanoma on clinical assessment. Our findings highlight the diagnostic value of tumour biopsy and provide preliminary evidence indicating a potential role for bevacizumab and photodynamic therapy in the treatment of this disease. To our knowledge, these treatment modalities have not been used previously in this condition. Case 1 is typical in that the patient was enucleated with a mistaken diagnosis of melanoma. The absence of tumour pigmentation is not diagnostic; for example, melanoma, leiomyoma and other tumours can be amelanotic while schwannoma can be deeply pigmented. We have encountered similar, smooth, dome-shaped amelanotic uveal tumours in our practice, which have been treated, and which proved histologically to be melanoma, leiomyoma or suprachoroidal adenoma.
Damato B, et al. Br J Ophthalmol 2014;98:1096–1100. doi:10.1136/bjophthalmol-2014-304976
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Clinical science
Figure 3 Left fundus of patient 3 with a choroidal schwannoma at the temporal disc margin (A). Fundus appearance, 4 years later, when the tumour had grown (B). Light microscopy demonstrating an Antoni B-like growth pattern spindle cells, confirming the diagnosis of schwannoma (H&E stain, ×40 objective) (C). Fundus appearance after intravitreal bevacizumab and photodynamic therapy (D).
Case 2 showed a slight resemblance to retinal haemangioblastoma, in view of the presence of feeder vessels and hard exudates; however, such retinal angiomas tend to be pink or red and not white/yellow as in this case. Case 3 is instructive because it demonstrates the apparent benefits of bevacizumab and photodynamic therapy. The bevacizumab injection was immediately followed by resolution of the retinal detachment and cessation of the exudation. Anti-VEGF (vascular endothelial growth factor) therapy has been demonstrated in animal models to be of benefit in treating tumours associated with neurofibromatosis 1.9 The photodynamic therapy induced significant tumour shrinkage, although it was not possible to eradicate the lesion entirely. The aim of treatment in this case was to conserve the eye and this objective was achieved. Case 4 is interesting because it was treated by trans-scleral local resection. This has been reported by other authors.10–12 Because the tumour had not invaded the sclera, it separated from the deep scleral lamella, which could therefore not be used as a ‘handle’. The tumour was soft and friable, which precluded the use of forceps, making it necessary for it to be levered out with a retractor and to be held between two 1098
sponge cells. It may have been possible to glue the tumour to the deep scleral lamella, as achieved previously with melanomas that detached from the sclera. As with other benign, suprachoroidal tumours, there was an area of adhesion between the tumour and the choroid, making it necessary to decide whether to leave a tiny fragment behind, as was done in this case, or to perform a partial choroidectomy, with the associated risk of creating a retinal tear. Fortunately, rhegmatogenous retinal detachment did not develop even though the patient had previously undergone transretinal tumour biopsy with a 25-gauge vitreous cutter. In all our cases schwannoma was an isolated tumour with no association with any multisystem disorder. In this series, a diagnosis was enabled by tumour biopsy in cases 2, 3, 4 and 5. Light microscopy usually reveals a tumour composed of spindle cells with bland nuclei.13 Two main growth patterns are seen: first, Antoni A tissue, in which there is a dense accumulation of elongated cells, often with nuclear palisading (so-called Verocay bodies, as seen in case 4) and, second, Antoni B tissue, where cells are less densely arranged in a loose myxoid matrix, within which xanthoma cells may be present. The pathological variants of schwannoma include: (a)
Damato B, et al. Br J Ophthalmol 2014;98:1096–1100. doi:10.1136/bjophthalmol-2014-304976
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Clinical science
Figure 4 Amelanotic choroidal tumour in the left eye of patient 4 (A). Intraoperative photograph showing the tumour located suprachoroidally (B). Histological examination of the excised tumour demonstrates Antoni A (C) (negative MelanA stain showing Verocay body, as well as some areas of siderin deposits following haemorrhage) and Antoni B growth patterns (D) (H&E stain, ×40 objective). Postoperative photograph showing an area of surgical coloboma where the tumour had previously been located (E).
schwanomma with degenerative change (‘ancient schwannoma’); (b) plexiform schwannoma; (c) epithelioid schwannoma; and (d) melanotic schwannoma. Prominent blood vessels are typical and may be significant enough to simulate a vascular neoplasm. This feature may be relevant in understanding reasons for significant exudation in some cases and for the response to anti-VEGF therapy. Features on electron microscopy include spindle cells with long interdigitating tapering processes consistent with Schwann cell origin. Long-spaced collagen (‘Luse bodies’) are also present.13 In the pigmented and melanocytic variants, numerous melanin granules are seen. In the melanocytic variant, features of melanogenesis can be observed (melanosomes in varying stages of melanisation, fine cytoplasmic filaments and micropinocytotic vesicles). Immunohistochemically, the spindle cells of schwannomas are
positive for S-100P and vimentin.13 With the exception of the melanocytic and pigmented variants, they are usually negative for the melanocytic markers, MelanA and HMB45. Although the vast majority of schwannomas are benign, malignant transformations in non-ocular sites have been described. In conclusion, we confirm the role of diagnostic biopsy prior to enucleating or irradiating an eye with a smooth, amelanotic tumour and emphasise that this should be considered when diagnostic uncertainty occurs. Immunohistochemistry is required to distinguish schwannoma from other spindle-cell tumours. Optimal therapy is with local resection; however, if the tumour is unresectable, there is potentially a role for attempting photodynamic therapy and perhaps intraocular bevacizumab to induce tumour regression, and resolution of retinal exudates and detachment.
Damato B, et al. Br J Ophthalmol 2014;98:1096–1100. doi:10.1136/bjophthalmol-2014-304976
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Clinical science Competing interests None. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1 2
3 4 5 6 7
8 9
Figure 5 Superior, juxtapapillary choroidal schwannoma (arrows) in the left eye of patient 5, with an inferior retinal detachment.
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Contributors BD conceived and supervised the study. EMD, LK and BD were involved in the preparation of the manuscript. EMD and LK participated in the collection of data. SEC prepared all histomicrographs. SEC, HH and BD revised the manuscript for important intellectual content. All authors read and approved the final manuscript.
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12 13
Espiard S, Bertherat J. Carney complex. Front Horm Res 2013;41:50–62. Shields JA, Sanborn GE, Kurz GH, et al. Benign peripheral nerve tumor of the choroid: a clinicopathologic correlation and review of the literature. Ophthalmology 1981;88:1322–1329. Lee SH, Hong JS, Choi JH, et al. Choroidal schwannoma. Acta Ophthalmol Scand 2005;83:754–756. Kim IT, Chang SD. Ciliary body schwannoma. Acta Ophthalmol Scand 1999;77:462–466. Mawas J. Schwannomas of the iris (gliomas of the terminal ciliary nerves). Bull Soc Ophtalmol 1962;62:31–41. Smith PA, Damato BE, Ko MK, et al. Anterior uveal neurilemmoma--a rare neoplasm simulating malignant melanoma. Br J Ophthalmol 1987;71:34–40. Shields JA, Font RL, Eagle RC, et al. Melanotic schwannoma of the choroid. Immunohistochemistry and electron microscopic observations. Ophthalmology 1994;101:843–849. Saavedra E, Singh AD, Sears JE, et al. Plexiform pigmented schwannoma of the uvea. Surv Ophthalmol 2006;51:162–168. Wong HK, Lahdenranta J, Kamoun WS, et al. Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors. Cancer Res 2010;70:3483–3493. Cho YJ, Won JB, Byeon SH, et al. A choroidal schwannoma confirmed by surgical excision. Korean J Ophthalmol 2009;23:49–52. Huang Y, Wei W. Choroidal schwannoma presenting as nonpigmented intraocular mass. J Clin Oncol 2012;30:e315–317. Kuchle M, Holbach L, Schlotzer-Schrehardt U, et al. Schwannoma of the ciliary body treated by block excision. Br J Ophthalmol 1994;78:397–400. Matsuo T, Notohara K. Choroidal schwannoma: immunohistochemical and electron-microscopic study. Ophthalmologica 2000;214:156–160.
Damato B, et al. Br J Ophthalmol 2014;98:1096–1100. doi:10.1136/bjophthalmol-2014-304976
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Choroidal schwannoma: a case series of five patients Bertil Damato, Erika M Damato, Lazaros Konstantinidis, Heinrich Heimann and Sarah E Coupland Br J Ophthalmol 2014 98: 1096-1100 originally published online April 23, 2014
doi: 10.1136/bjophthalmol-2014-304976 Updated information and services can be found at: http://bjo.bmj.com/content/98/8/1096
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Clinical science
Choroidal schwannoma: a case series of five patients Bertil Damato,1,2,3 Erika M Damato,1 Lazaros Konstantinidis,1 Heinrich Heimann,1 Sarah E Coupland2 1
Vitreoretinal and Ocular Oncology Service, Royal Liverpool University Hospital, Liverpool, UK 2 Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK 3 Ocular Oncology Service, University of California, San Francisco, USA Correspondence to Dr Bertil Damato, Ocular Oncology Service, University of California, San Francisco, 10 Koret Way, K327, San Francisco, CA 94143-0730, USA; [email protected] Received 26 January 2014 Revised 10 March 2014 Accepted 12 March 2014 Published Online First 23 April 2014
ABSTRACT Aim To report a case series of five patients diagnosed with choroidal schwannoma at the Liverpool Ocular Oncology Centre. Methods Patients with choroidal schwannoma were identified by searching the computerised database of the Liverpool Ocular Oncology Centre. Results The patients (3 males, 2 females) ranged in age from 15 years to 45 years. Three tumours were treated by enucleation, trans-scleral local resection, and combined bevacizumab and photodynamic therapy, respectively. Two were observed after confirmation of the diagnosis by biopsy. Conclusions Choroidal schwannoma has a variety of clinical manifestations. Associated features include hard exudates, retinal feeder vessels and serous retinal detachment. Biopsy with immunohistochemistry is required for diagnosis. Tumours not amenable to resection may respond to photodynamic therapy. INTRODUCTION Schwannoma (also known as neurilemmoma, neurinoma, neuroma) is a benign, nerve sheath tumour arising from Schwann cells, which produce myelin. It differs from neurofibroma, which arises from neoplastic, non-myelinating Schwann cells incorporating additional types of cell and structural elements. Schwannoma and neurofibroma can arise in isolation or as part of multisystem disorders; about 10% of schwannomas are associated with neurofibromatosis, schwannomatosis, multiple meningiomas, and the Carney complex (melanotic schwannoma, myxoma, spotty skin pigmentation, endocrine tumours).1 Intraocular schwannomas arise from ciliary nerves in the uvea, mostly in the ciliary body or choroid and occasionally in the iris.2–5 They are usually amelanotic or pseudo-pigmented if covered by pigment epithelium, but may rarely be pigmented.6–8 Visual loss and phthisis can occur as a result of tumour growth and serous retinal detachment. To our knowledge, malignant transformation of an intraocular schwannoma has not yet been reported. The aim of this study was to review our experience with five patients with intraocular schwannoma, to describe the clinical features, relevant histopathology and treatment options.
CASE 1 To cite: Damato B, Damato EM, Konstantinidis L, et al. Br J Ophthalmol 2014;98: 1096–1100. 1096
A 28-year-old woman was referred to us in the early 1990s with a history of blurred vision and a nasal, ciliochoroidal tumour in the left eye extending from the 7 o’clock to the 10 o’clock meridians. On examination, the visual acuity with the affected
eye was 6/12. The tumour was dome-shaped and amelanotic. The eye was enucleated on the basis of a clinical diagnosis of amelanotic melanoma. Subsequent histological examination revealed the diagnosis of schwannoma (figure 1A–C).
CASE 2 A 37-year-old woman was referred soon after 2000 with a choroidal tumour in the left eye. Her past medical history was unremarkable. The right eye was normal. On examination, the visual acuity with the left eye was 6/6. Ophthalmoscopy showed a superotemporal, pre-equatorial, choroidal tumour in the left eye. This was associated with retinal feeder vessels and adjacent hard exudates. (figure 2) On ultrasonography, the tumour measured 6.9 mm×5.8 mm×2.1 mm. The differential diagnosis included vasoproliferative tumour, adenoma, retinal angioma and amelanotic melanoma. The diagnosis of choroidal schwannoma was made on histopathological examination following trans-scleral incisional tumour biopsy. The patient was kept under observation and 11 years later the tumour remained unchanged. The patient maintained a visual acuity of 6/6.
CASE 3 A 33-year-old man was referred soon after 2000 with a 6-month history of reduced vision in the left eye, which was amblyopic. The right eye was healthy with a visual acuity of 6/4. The past medical history was unremarkable and the patient was otherwise well. On examination, the left eye had a visual acuity of Counting Fingers. On ophthalmoscopy, there was an amelanotic tumour involving the macula, extending to the temporal optic disc margin, measuring 4.6 mm by 6.4 mm with a thickness of 2.2 mm (figure 3A). This was associated with a localised serous retinal detachment and hard exudates. A fine needle aspiration biopsy was attempted, but was unsuccessful. The patient was discharged back to his local ophthalmologist for surveillance close to his home. The patient was referred back to our centre 4 years later, because of tumour growth and increasing exudation. On examination, the visual acuity had deteriorated to Hand Movements. The tumour now measured 7.5 mm by 6.9 mm with a thickness of 3.9 mm and had grown to obscure most of the optic disc. The exudation was much more extensive and an inferior exudative retinal detachment was observed (figure 3B). A transretinal biopsy was performed and enabled us to diagnose the tumour as being a schwannoma (figure 3C). The patient was treated with four injections of intravitreal bevacizumab at a dose of 2.5 mg in 0.1 mL over a period of 8 months. This
Damato B, et al. Br J Ophthalmol 2014;98:1096–1100. doi:10.1136/bjophthalmol-2014-304976
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Clinical science
Figure 1 Light micrograph of the left eye of patient 1 showing a large choroidal schwannoma (A). H&E stain showing spindle cells with bland nuclei and abundant cytoplasm (×40 objective) (B). Immunohistochemistry using the S-100P stain demonstrating clear cytoplasmic positivity (Alkaline phosphatase-anti alkaline phosphatase (APAAP), ×40 objective) (C).
resulted in some reduction in exudation, with crystallisation of the hard exudates and resolution of the retinal detachment. Despite this treatment, however, the tumour thickness increased from 3.9 mm to 4.2 mm. The patient was therefore treated with photodynamic therapy (six sessions over 18 months). This brought about regression of the tumour and a reduction in thickness to 1.6 mm. The eye had vision of Hand Movements 7 years after initial referral. When last reviewed, 11 years after initial referral, the patient had No Light Perception with the affected eye. The schwannoma appeared inactive but there was extensive retinal atrophy (figure 3D).
CASE 4 A 45-year-old man was referred with a 3-week history of blurred vision in the left eye, which was found to have a choroidal tumour (figure 4A). On examination, the visual acuity with the affected eye was 6/18. Ophthalmoscopy demonstrated a dome-shaped, amelanotic tumour with an inferior, serous, retinal detachment. Ultrasonography showed high internal acoustic reflectivity and the tumour measured 18 mm×18 mm basally with a thickness of 10 mm. An initial diagnosis of choroidal melanoma was made and plans were made to insert tantalum markers for proton beam radiotherapy. During the surgery,
however, the tumour was noted to transilluminate brightly and a diagnosis of choroidal schwannoma was considered. A transretinal biopsy was carried out, which confirmed this suspicion. Trans-scleral local resection was therefore performed, using a posteriorly hinged lamellar scleral flap and hypotensive anaesthesia, lowering the systolic blood pressure to approximately 50 mm Hg (figure 4B). The tumour was located in the suprachoroidal space, separating from the sclera and uvea except posteriorly, where it was adherent to choroid. Histopathological examination of the excised tumour confirmed the diagnosis of schwannoma (figure 4C,D). Postoperative recovery was uneventful and a year later the visual acuity was 6/24 with an area of choroidal atrophy temporally (figure 4E).
CASE 5 A 15-year-old boy was referred around 2005 with a choroidal tumour in the left eye. The past medical history was unremarkable and general health was good. On examination, the visual acuity was Counting Fingers with the affected eye and 6/5 with the right eye, which was healthy. Ophthalmoscopy showed an amelanotic choroidal tumour superior to and almost surrounding, the optic disc (figure 5). An inferior retinal detachment was also observed. On ultrasonography, the tumour showed a low to moderate internal acoustic reflectivity. The tumour dimensions were 12 mm×12 mm basally, with a thickness of 3.6 mm. Transretinal biopsy enabled a diagnosis of choroidal schwannoma to be made. The patient was kept under observation and remained stable with no evidence of lesion growth. He was last seen 6 years after initial referral, when the visual acuity in the affected eye was Hand Movements.
DISCUSSION
Figure 2 Superotemporal, choroidal schwannoma in the left eye of patient 2, showing an amelanotic tumour with large feeder vessels (arrow) and hard exudates.
Choroidal schwannoma is a rare benign tumour, which may be mistaken for an amelanotic choroidal melanoma on clinical assessment. Our findings highlight the diagnostic value of tumour biopsy and provide preliminary evidence indicating a potential role for bevacizumab and photodynamic therapy in the treatment of this disease. To our knowledge, these treatment modalities have not been used previously in this condition. Case 1 is typical in that the patient was enucleated with a mistaken diagnosis of melanoma. The absence of tumour pigmentation is not diagnostic; for example, melanoma, leiomyoma and other tumours can be amelanotic while schwannoma can be deeply pigmented. We have encountered similar, smooth, dome-shaped amelanotic uveal tumours in our practice, which have been treated, and which proved histologically to be melanoma, leiomyoma or suprachoroidal adenoma.
Damato B, et al. Br J Ophthalmol 2014;98:1096–1100. doi:10.1136/bjophthalmol-2014-304976
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Clinical science
Figure 3 Left fundus of patient 3 with a choroidal schwannoma at the temporal disc margin (A). Fundus appearance, 4 years later, when the tumour had grown (B). Light microscopy demonstrating an Antoni B-like growth pattern spindle cells, confirming the diagnosis of schwannoma (H&E stain, ×40 objective) (C). Fundus appearance after intravitreal bevacizumab and photodynamic therapy (D).
Case 2 showed a slight resemblance to retinal haemangioblastoma, in view of the presence of feeder vessels and hard exudates; however, such retinal angiomas tend to be pink or red and not white/yellow as in this case. Case 3 is instructive because it demonstrates the apparent benefits of bevacizumab and photodynamic therapy. The bevacizumab injection was immediately followed by resolution of the retinal detachment and cessation of the exudation. Anti-VEGF (vascular endothelial growth factor) therapy has been demonstrated in animal models to be of benefit in treating tumours associated with neurofibromatosis 1.9 The photodynamic therapy induced significant tumour shrinkage, although it was not possible to eradicate the lesion entirely. The aim of treatment in this case was to conserve the eye and this objective was achieved. Case 4 is interesting because it was treated by trans-scleral local resection. This has been reported by other authors.10–12 Because the tumour had not invaded the sclera, it separated from the deep scleral lamella, which could therefore not be used as a ‘handle’. The tumour was soft and friable, which precluded the use of forceps, making it necessary for it to be levered out with a retractor and to be held between two 1098
sponge cells. It may have been possible to glue the tumour to the deep scleral lamella, as achieved previously with melanomas that detached from the sclera. As with other benign, suprachoroidal tumours, there was an area of adhesion between the tumour and the choroid, making it necessary to decide whether to leave a tiny fragment behind, as was done in this case, or to perform a partial choroidectomy, with the associated risk of creating a retinal tear. Fortunately, rhegmatogenous retinal detachment did not develop even though the patient had previously undergone transretinal tumour biopsy with a 25-gauge vitreous cutter. In all our cases schwannoma was an isolated tumour with no association with any multisystem disorder. In this series, a diagnosis was enabled by tumour biopsy in cases 2, 3, 4 and 5. Light microscopy usually reveals a tumour composed of spindle cells with bland nuclei.13 Two main growth patterns are seen: first, Antoni A tissue, in which there is a dense accumulation of elongated cells, often with nuclear palisading (so-called Verocay bodies, as seen in case 4) and, second, Antoni B tissue, where cells are less densely arranged in a loose myxoid matrix, within which xanthoma cells may be present. The pathological variants of schwannoma include: (a)
Damato B, et al. Br J Ophthalmol 2014;98:1096–1100. doi:10.1136/bjophthalmol-2014-304976
Downloaded from http://bjo.bmj.com/ on June 11, 2015 - Published by group.bmj.com
Clinical science
Figure 4 Amelanotic choroidal tumour in the left eye of patient 4 (A). Intraoperative photograph showing the tumour located suprachoroidally (B). Histological examination of the excised tumour demonstrates Antoni A (C) (negative MelanA stain showing Verocay body, as well as some areas of siderin deposits following haemorrhage) and Antoni B growth patterns (D) (H&E stain, ×40 objective). Postoperative photograph showing an area of surgical coloboma where the tumour had previously been located (E).
schwanomma with degenerative change (‘ancient schwannoma’); (b) plexiform schwannoma; (c) epithelioid schwannoma; and (d) melanotic schwannoma. Prominent blood vessels are typical and may be significant enough to simulate a vascular neoplasm. This feature may be relevant in understanding reasons for significant exudation in some cases and for the response to anti-VEGF therapy. Features on electron microscopy include spindle cells with long interdigitating tapering processes consistent with Schwann cell origin. Long-spaced collagen (‘Luse bodies’) are also present.13 In the pigmented and melanocytic variants, numerous melanin granules are seen. In the melanocytic variant, features of melanogenesis can be observed (melanosomes in varying stages of melanisation, fine cytoplasmic filaments and micropinocytotic vesicles). Immunohistochemically, the spindle cells of schwannomas are
positive for S-100P and vimentin.13 With the exception of the melanocytic and pigmented variants, they are usually negative for the melanocytic markers, MelanA and HMB45. Although the vast majority of schwannomas are benign, malignant transformations in non-ocular sites have been described. In conclusion, we confirm the role of diagnostic biopsy prior to enucleating or irradiating an eye with a smooth, amelanotic tumour and emphasise that this should be considered when diagnostic uncertainty occurs. Immunohistochemistry is required to distinguish schwannoma from other spindle-cell tumours. Optimal therapy is with local resection; however, if the tumour is unresectable, there is potentially a role for attempting photodynamic therapy and perhaps intraocular bevacizumab to induce tumour regression, and resolution of retinal exudates and detachment.
Damato B, et al. Br J Ophthalmol 2014;98:1096–1100. doi:10.1136/bjophthalmol-2014-304976
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Clinical science Competing interests None. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
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Figure 5 Superior, juxtapapillary choroidal schwannoma (arrows) in the left eye of patient 5, with an inferior retinal detachment.
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Contributors BD conceived and supervised the study. EMD, LK and BD were involved in the preparation of the manuscript. EMD and LK participated in the collection of data. SEC prepared all histomicrographs. SEC, HH and BD revised the manuscript for important intellectual content. All authors read and approved the final manuscript.
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Damato B, et al. Br J Ophthalmol 2014;98:1096–1100. doi:10.1136/bjophthalmol-2014-304976
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Choroidal schwannoma: a case series of five patients Bertil Damato, Erika M Damato, Lazaros Konstantinidis, Heinrich Heimann and Sarah E Coupland Br J Ophthalmol 2014 98: 1096-1100 originally published online April 23, 2014
doi: 10.1136/bjophthalmol-2014-304976 Updated information and services can be found at: http://bjo.bmj.com/content/98/8/1096
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