UNUSUAL CASE OF DIFFUSE CHOROIDAL MELANOMA MASQUERADING AS ATYPICAL CENTRAL SEROUS CHORIORETINOPATHY Adrienne W. Scott, MD,* Sharon Fekrat, MD, FACS,* Prithvi Mruthyunjaya, MD,* Thomas J. Cummings, MD,† Michael J. Cooney, MD‡
Purpose: To describe an unusual case of diffuse circumpapillary choroidal melanoma masquerading as atypical central serous chorioretinopathy, and to describe fluorescein angiographic and optical coherence tomography characteristics of this diffuse choroidal melanoma. Design: Interventional case report. Methods: A 46-year-old human immunodeficiency virus–positive man presented with an 11-month history of decreased vision and the absence of an elevated choroidal lesion. The patient failed to return for follow-up. Results: Thirteen months after his initial presentation, circumpapillary diffuse choroidal melanoma was diagnosed. The patient underwent enucleation. No extrascleral extension was present. Conclusions: Imaging characteristics on fluorescein angiography or optical coherence tomography may be of diagnostic value to aid the ophthalmologist in earlier detection of diffuse choroidal melanomas. RETINAL CASES & BRIEF REPORTS 2:280 –285, 2008
From the *Department of Ophthalmology, Albert Eye Research Institute, Duke University Eye Center, and †Department of Pathology, Duke University Medical Center, Durham, North Carolina; and ‡VitreousRetina-Macula Consultants of New York, New York Eye and Ear Infirmary, New York.
C
horoidal melanoma is the most common primary intraocular malignancy in adults.1 Diffuse melanoma is a rare variant of choroidal melanoma, representing 4 –5% of all posterior uveal melanomas.2,3 Typically, diffuse melanomas are flat or minimally elevated, and
None of the authors has a proprietary commercial interest in this study. Reprint requests: Adrienne W. Scott, MD, Duke University Eye Center, Box 3802, Durham, NC 27710; e-mail: scott127@ mc.duke.edu
Fig. 1. Left eye visual acuity measured 20/40, with serous subfoveal fluid and pigmented retinal pigment epithelial detachments in the nasal macula, and superior and inferior peripapillary retina.
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Fig. 2. Optical coherence tomography of the left eye demonstrated subretinal fluid extending under the foveal center (116 m) and mild elevation of the retinal pigment epithelium and choroid superior to the fovea (308 m).
symptoms are present long before these tumors are diagnosed.4 Early detection and treatment of diffuse choroidal melanoma is critical, as metastatic potential may be as high as 24% at 5 years.5 Diffuse choroidal melanoma may be misdiagnosed as a choroidal nevus, chronic glaucoma,3 chronic uveitis,3 episcleritis or scleritis,6 or idiopathic central serous chorioretinopathy.7,8 To our knowledge, the fluorescein pattern or optical coherence tomography (OCT) appearance of diffuse choroidal melanoma has not been described in the literature. We report an unusual case of circumpapillary diffuse choroidal melanoma that presented with the clinical picture of atypical central serous chorioretinopathy, leading to a delay in diagnosis. We also describe fluorescein angiographic and OCT characteristics of this diffuse choroidal melanoma.
Fig. 3. Fluorescein angiography of the left eye showed early, speckled hyperfluorescence with late leakage into the nasal macula and inferior and superior peripapillary retina (arrows).
Case Report A 46-year-old, red-haired white man was referred with an 11-month history of blurred central vision in the left eye. He had been given the diagnosis of atypical chronic central serous chorioretinopathy (CSR) by an outside ophthalmologist. He had hypertension and human immunodeficiency virus (HIV) positive status (undetectable viral load and CD4⫹count of 700 cells/mm3). Medications included Trizivir and atenolol. Past ocular history was negative for prior surgery, lasers, or trauma. Visual acuity measured 20/25 in the right eye and 20/40 in the left eye. Intraocular pressure was 16 mmHg in each eye, and there was no afferent pupillary defect. Slit-lamp examination was unremarkable without vitreous cell in either eye. Ophthalmoscopy of the right eye revealed a normal fundus. Ophthalmoscopy of the left eye demonstrated subtle macular pigment changes and serous subfoveal fluid with pigmented retinal pigment epithelial (RPE) detachments in the nasal macula and superior and inferior peripapillary retina (Figure 1). OCT of the left eye showed an area of low-lying subretinal fluid extending under the foveal center (Figure 2). Fluorescein angiog-
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Fig. 4. Color fundus photograph of the left eye 2 years after initial presentation shows a choroidal lesion superior to the optic nerve (white arrow) accompanied by a newly evident lesion inferonasal to the optic nerve (black arrow).
raphy demonstrated early, speckled hyperfluorescence with late leakage in the nasal macula and superior and inferior peripapillary retina of the left eye (Figure 3). The differential diagnosis included atypical central serous chorioretinopathy, occult choroidal neovascularization (CNV), choroidal nevus, and malignant melanoma. Two months later, the left eye visual acuity remained 20/40. A flat choroidal nevus was noted superior to the optic nerve. Observation with standardized echography was recommended. The patient failed to return for follow-up until 13 months later. While his general health remained good with stable CD4⫹cell count and viral load, the visual acuity had deteriorated to 20/100 in the left eye. A choroidal lesion was evident inferonasal to the optic nerve (Figure 4). OCT of the left eye showed RPE elevation, peripapillary subretinal fluid, and cystoid macular edema (Figure 5). Fluorescein angiography showed increased leakage (Figure 6). B-scan ultrasonography showed a 6 ⫻ 8 ⫻ 2 mm peripapillary lesion with low to medium
reflectivity (Figure 7). It became apparent that the newly evident inferonasal choroidal lesion, the lesion superior to the optic nerve (previously thought to be a flat choroidal nevus), and the subtle macular pigment changes were all components of a circumpapillary, diffuse melanoma. The patient underwent uncomplicated enucleation of his left eye approximately 2 years after the initial onset of his visual complaints. Histopathology demonstrated a mixed cell choroidal melanoma (containing spindle and epithelioid elements) without extraocular extension (Figure 8). Systemic work-up was negative for metastases. He remains disease-free 2 years after enucleation.
Discussion Diffuse choroidal melanoma is described as a flat tumor with a tumor thickness measuring less than 20% of basal tumor diameter and carries a poorer prognosis
Fig. 5. Optical coherence tomography of the left eye 2 years after initial presentation shows an increase in subretinal fluid in the papillomacular bundle with intraretinal fluid. Retinal pigment epithelium/ choroidal elevation is present. Foveal thickness measured 210 m.
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Fig. 6. Fluorescein angiography of the left eye 2 years after initial presentation shows decreased macular leakage. There is a new area of speckled hyperfluorescence from the inferior lesion (white arrow).
than other uveal melanomas.2,3,5 Shields and colleagues reviewed 111 eyes with diffuse choroidal melanoma.5 Tumor characteristics predisposing to metastasis in the multivariate analysis included tumor basal dimension of greater than 18 mm, poorly defined tumor margins, and optic nerve invasion. There is no fluorescein angiographic pattern that is pathognomonic for choroidal melanoma. Choroidal melanomas can have varied fluorescein angiographic patterns.7 Our patient’s diffuse choroidal melanoma demonstrated multiple noncontiguous foci of speckled
Fig. 7. Ultrasonography shows an elevated lesion superior to the optic nerve with low to medium reflectivity. The lesion measured 6.6 ⫻ 7.7 ⫻ 2.1 mm.
hyperfluorescence with late leakage on fluorescein angiography corresponding to the multiple areas of mildly elevated choroidal lesions. OCT is a newer diagnostic imaging tool that can be used to provide high resolution cross-sectional information about retinal and RPE architecture. Not much information is available regarding the characteristics of choroidal melanoma on OCT. While OCT cannot provide in vivo information on choroidal tumors, secondary changes of the retina and RPE can be observed. Muscat and colleagues observed a higher in-
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Fig. 8. Histopathology demonstrates a mixed cell type choroidal melanoma. Hematoxylin and eosin staining of the enucleated specimen shows melanoma cells indenting the optic nerve (black arrows). Intraretinal cysts (white arrow) and subretinal fluid (star) are present.
cidence of serous retinal detachment, cystoid retinal degeneration, and abnormal retinal structure more often in eyes with choroidal melanoma than in eyes with choroidal nevi.9 Subretinal fluid is a welldocumented risk factor in choroidal tumor growth.10 Over a 2-year period, serial OCT studies in our patient demonstrated an increasingly broad area of low-lying subretinal fluid within the papillomacular bundle. While this finding may not be specific to the diffuse variant of choroidal melanoma, these characteristics certainly correlate with the broad, diffuse nature of this tumor. Plaque radiotherapy has been successfully used in the treatment of diffuse choroidal melanoma. Shields and colleagues reported equivalent survival rates between patients treated with plaque radiotherapy compared to those treated with enucleation.5 A randomized, prospective trial to compare survival rates in the differing treatments of this neoplasm would be difficult given its rarity.5 Had it been our patient’s preference to attempt to preserve the eye, notched plaque radiotherapy could have been considered.
The initial presentation of an 11-month history of blurry vision in the absence of an elevated choroidal lesion made prompt diagnosis of diffuse choroidal melanoma difficult. Upon retrospective review of our patient’s fundus photographs, the subtle macular pigmentary changes, the lesion described as a nevus noted superior to the optic nerve, and the inferonasal lesion evident after the patient returned after being lost to follow-up were all components of a diffuse choroidal melanoma. Fortunately, the delay in diagnosis of this diffuse choroidal melanoma did not result in extrascleral extension, and the patient remains free of tumor metastasis 2 years after enucleation. Imaging characteristics on fluorescein angiography or OCT may be of diagnostic value to aid the ophthalmologist in earlier detection of diffuse choroidal melanomas. References 1. 2.
Singh AD, Topham A. Incidence of uveal melanoma in the United States: 1973–1997. Ophthalmol 2003;110:956–961. Reese AB, Howard GM. Flat uveal melanomas. Am J Ophthalmol 1967;64:1021–1028.
DIFFUSE CHOROIDAL MELANOMA MASQUERADING AS ATYPICAL CSC 3.
4.
5.
6.
Font RL, Spaulding AG, Zimmerman LE. Diffuse malignant melanoma of the uveal tract: a clinicopathologic report of 54 cases. Trans Am Acad Ophthalmol Otolaryngol 1968;72:877–895. Biswas J, Raghavendra R, Ratra V, Krishnakumar S, Gopal L, Shanmugam MP. Diffuse malignant melanoma of the choroids simulating metastatic tumour in the choroid. Indian J Ophthalmol 2000;48:137–140. Shields CL, Shields JA, De Potter P, Tardio D, Barrett J. Diffuse choroidal melanoma: clinical features predictive of metastasis. Arch Ophthalmol 1996;114:956–963. Yap EY, Robertson DM, Buettner H. Scleritis as an initial manifestation of choroidal malignant melanoma. Ophthalmology 1992;99:1693–1697.
7.
8. 9.
10.
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Shields JA, Shields CL. Choroidal nevus. In: Shields JA, Shields CL. Intraocular Tumors: A Text and Atlas. Philadelphia: WB Saunders; 1992. Gass JDM. Differential Diagnosis of Intraocular Tumors. St Louis: C.V. Mosby; 1974. Muscat S, Parks S, Kemp E, Keating D. Secondary retinal changes associated with choroidal nevi and melanomas documented by optical coherence tomography. Br J Ophthalmol 2004;88:120–124. Shields CL, Cater J, Shields JA, Singh AD, Santos MC, Carvalho C. Combination of clinical factors predictive of growth of small choroidal melanocytic tumours. Arch Ophthalmol 2000;118:360–364.
Purpose: To describe an unusual case of diffuse circumpapillary choroidal melanoma masquerading as atypical central serous chorioretinopathy, and to describe fluorescein angiographic and optical coherence tomography characteristics of this diffuse choroidal melanoma. Design: Interventional case report. Methods: A 46-year-old human immunodeficiency virus–positive man presented with an 11-month history of decreased vision and the absence of an elevated choroidal lesion. The patient failed to return for follow-up. Results: Thirteen months after his initial presentation, circumpapillary diffuse choroidal melanoma was diagnosed. The patient underwent enucleation. No extrascleral extension was present. Conclusions: Imaging characteristics on fluorescein angiography or optical coherence tomography may be of diagnostic value to aid the ophthalmologist in earlier detection of diffuse choroidal melanomas. RETINAL CASES & BRIEF REPORTS 2:280 –285, 2008
From the *Department of Ophthalmology, Albert Eye Research Institute, Duke University Eye Center, and †Department of Pathology, Duke University Medical Center, Durham, North Carolina; and ‡VitreousRetina-Macula Consultants of New York, New York Eye and Ear Infirmary, New York.
C
horoidal melanoma is the most common primary intraocular malignancy in adults.1 Diffuse melanoma is a rare variant of choroidal melanoma, representing 4 –5% of all posterior uveal melanomas.2,3 Typically, diffuse melanomas are flat or minimally elevated, and
None of the authors has a proprietary commercial interest in this study. Reprint requests: Adrienne W. Scott, MD, Duke University Eye Center, Box 3802, Durham, NC 27710; e-mail: scott127@ mc.duke.edu
Fig. 1. Left eye visual acuity measured 20/40, with serous subfoveal fluid and pigmented retinal pigment epithelial detachments in the nasal macula, and superior and inferior peripapillary retina.
280
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DIFFUSE CHOROIDAL MELANOMA MASQUERADING AS ATYPICAL CSC
Fig. 2. Optical coherence tomography of the left eye demonstrated subretinal fluid extending under the foveal center (116 m) and mild elevation of the retinal pigment epithelium and choroid superior to the fovea (308 m).
symptoms are present long before these tumors are diagnosed.4 Early detection and treatment of diffuse choroidal melanoma is critical, as metastatic potential may be as high as 24% at 5 years.5 Diffuse choroidal melanoma may be misdiagnosed as a choroidal nevus, chronic glaucoma,3 chronic uveitis,3 episcleritis or scleritis,6 or idiopathic central serous chorioretinopathy.7,8 To our knowledge, the fluorescein pattern or optical coherence tomography (OCT) appearance of diffuse choroidal melanoma has not been described in the literature. We report an unusual case of circumpapillary diffuse choroidal melanoma that presented with the clinical picture of atypical central serous chorioretinopathy, leading to a delay in diagnosis. We also describe fluorescein angiographic and OCT characteristics of this diffuse choroidal melanoma.
Fig. 3. Fluorescein angiography of the left eye showed early, speckled hyperfluorescence with late leakage into the nasal macula and inferior and superior peripapillary retina (arrows).
Case Report A 46-year-old, red-haired white man was referred with an 11-month history of blurred central vision in the left eye. He had been given the diagnosis of atypical chronic central serous chorioretinopathy (CSR) by an outside ophthalmologist. He had hypertension and human immunodeficiency virus (HIV) positive status (undetectable viral load and CD4⫹count of 700 cells/mm3). Medications included Trizivir and atenolol. Past ocular history was negative for prior surgery, lasers, or trauma. Visual acuity measured 20/25 in the right eye and 20/40 in the left eye. Intraocular pressure was 16 mmHg in each eye, and there was no afferent pupillary defect. Slit-lamp examination was unremarkable without vitreous cell in either eye. Ophthalmoscopy of the right eye revealed a normal fundus. Ophthalmoscopy of the left eye demonstrated subtle macular pigment changes and serous subfoveal fluid with pigmented retinal pigment epithelial (RPE) detachments in the nasal macula and superior and inferior peripapillary retina (Figure 1). OCT of the left eye showed an area of low-lying subretinal fluid extending under the foveal center (Figure 2). Fluorescein angiog-
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Fig. 4. Color fundus photograph of the left eye 2 years after initial presentation shows a choroidal lesion superior to the optic nerve (white arrow) accompanied by a newly evident lesion inferonasal to the optic nerve (black arrow).
raphy demonstrated early, speckled hyperfluorescence with late leakage in the nasal macula and superior and inferior peripapillary retina of the left eye (Figure 3). The differential diagnosis included atypical central serous chorioretinopathy, occult choroidal neovascularization (CNV), choroidal nevus, and malignant melanoma. Two months later, the left eye visual acuity remained 20/40. A flat choroidal nevus was noted superior to the optic nerve. Observation with standardized echography was recommended. The patient failed to return for follow-up until 13 months later. While his general health remained good with stable CD4⫹cell count and viral load, the visual acuity had deteriorated to 20/100 in the left eye. A choroidal lesion was evident inferonasal to the optic nerve (Figure 4). OCT of the left eye showed RPE elevation, peripapillary subretinal fluid, and cystoid macular edema (Figure 5). Fluorescein angiography showed increased leakage (Figure 6). B-scan ultrasonography showed a 6 ⫻ 8 ⫻ 2 mm peripapillary lesion with low to medium
reflectivity (Figure 7). It became apparent that the newly evident inferonasal choroidal lesion, the lesion superior to the optic nerve (previously thought to be a flat choroidal nevus), and the subtle macular pigment changes were all components of a circumpapillary, diffuse melanoma. The patient underwent uncomplicated enucleation of his left eye approximately 2 years after the initial onset of his visual complaints. Histopathology demonstrated a mixed cell choroidal melanoma (containing spindle and epithelioid elements) without extraocular extension (Figure 8). Systemic work-up was negative for metastases. He remains disease-free 2 years after enucleation.
Discussion Diffuse choroidal melanoma is described as a flat tumor with a tumor thickness measuring less than 20% of basal tumor diameter and carries a poorer prognosis
Fig. 5. Optical coherence tomography of the left eye 2 years after initial presentation shows an increase in subretinal fluid in the papillomacular bundle with intraretinal fluid. Retinal pigment epithelium/ choroidal elevation is present. Foveal thickness measured 210 m.
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Fig. 6. Fluorescein angiography of the left eye 2 years after initial presentation shows decreased macular leakage. There is a new area of speckled hyperfluorescence from the inferior lesion (white arrow).
than other uveal melanomas.2,3,5 Shields and colleagues reviewed 111 eyes with diffuse choroidal melanoma.5 Tumor characteristics predisposing to metastasis in the multivariate analysis included tumor basal dimension of greater than 18 mm, poorly defined tumor margins, and optic nerve invasion. There is no fluorescein angiographic pattern that is pathognomonic for choroidal melanoma. Choroidal melanomas can have varied fluorescein angiographic patterns.7 Our patient’s diffuse choroidal melanoma demonstrated multiple noncontiguous foci of speckled
Fig. 7. Ultrasonography shows an elevated lesion superior to the optic nerve with low to medium reflectivity. The lesion measured 6.6 ⫻ 7.7 ⫻ 2.1 mm.
hyperfluorescence with late leakage on fluorescein angiography corresponding to the multiple areas of mildly elevated choroidal lesions. OCT is a newer diagnostic imaging tool that can be used to provide high resolution cross-sectional information about retinal and RPE architecture. Not much information is available regarding the characteristics of choroidal melanoma on OCT. While OCT cannot provide in vivo information on choroidal tumors, secondary changes of the retina and RPE can be observed. Muscat and colleagues observed a higher in-
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Fig. 8. Histopathology demonstrates a mixed cell type choroidal melanoma. Hematoxylin and eosin staining of the enucleated specimen shows melanoma cells indenting the optic nerve (black arrows). Intraretinal cysts (white arrow) and subretinal fluid (star) are present.
cidence of serous retinal detachment, cystoid retinal degeneration, and abnormal retinal structure more often in eyes with choroidal melanoma than in eyes with choroidal nevi.9 Subretinal fluid is a welldocumented risk factor in choroidal tumor growth.10 Over a 2-year period, serial OCT studies in our patient demonstrated an increasingly broad area of low-lying subretinal fluid within the papillomacular bundle. While this finding may not be specific to the diffuse variant of choroidal melanoma, these characteristics certainly correlate with the broad, diffuse nature of this tumor. Plaque radiotherapy has been successfully used in the treatment of diffuse choroidal melanoma. Shields and colleagues reported equivalent survival rates between patients treated with plaque radiotherapy compared to those treated with enucleation.5 A randomized, prospective trial to compare survival rates in the differing treatments of this neoplasm would be difficult given its rarity.5 Had it been our patient’s preference to attempt to preserve the eye, notched plaque radiotherapy could have been considered.
The initial presentation of an 11-month history of blurry vision in the absence of an elevated choroidal lesion made prompt diagnosis of diffuse choroidal melanoma difficult. Upon retrospective review of our patient’s fundus photographs, the subtle macular pigmentary changes, the lesion described as a nevus noted superior to the optic nerve, and the inferonasal lesion evident after the patient returned after being lost to follow-up were all components of a diffuse choroidal melanoma. Fortunately, the delay in diagnosis of this diffuse choroidal melanoma did not result in extrascleral extension, and the patient remains free of tumor metastasis 2 years after enucleation. Imaging characteristics on fluorescein angiography or OCT may be of diagnostic value to aid the ophthalmologist in earlier detection of diffuse choroidal melanomas. References 1. 2.
Singh AD, Topham A. Incidence of uveal melanoma in the United States: 1973–1997. Ophthalmol 2003;110:956–961. Reese AB, Howard GM. Flat uveal melanomas. Am J Ophthalmol 1967;64:1021–1028.
DIFFUSE CHOROIDAL MELANOMA MASQUERADING AS ATYPICAL CSC 3.
4.
5.
6.
Font RL, Spaulding AG, Zimmerman LE. Diffuse malignant melanoma of the uveal tract: a clinicopathologic report of 54 cases. Trans Am Acad Ophthalmol Otolaryngol 1968;72:877–895. Biswas J, Raghavendra R, Ratra V, Krishnakumar S, Gopal L, Shanmugam MP. Diffuse malignant melanoma of the choroids simulating metastatic tumour in the choroid. Indian J Ophthalmol 2000;48:137–140. Shields CL, Shields JA, De Potter P, Tardio D, Barrett J. Diffuse choroidal melanoma: clinical features predictive of metastasis. Arch Ophthalmol 1996;114:956–963. Yap EY, Robertson DM, Buettner H. Scleritis as an initial manifestation of choroidal malignant melanoma. Ophthalmology 1992;99:1693–1697.
7.
8. 9.
10.
285
Shields JA, Shields CL. Choroidal nevus. In: Shields JA, Shields CL. Intraocular Tumors: A Text and Atlas. Philadelphia: WB Saunders; 1992. Gass JDM. Differential Diagnosis of Intraocular Tumors. St Louis: C.V. Mosby; 1974. Muscat S, Parks S, Kemp E, Keating D. Secondary retinal changes associated with choroidal nevi and melanomas documented by optical coherence tomography. Br J Ophthalmol 2004;88:120–124. Shields CL, Cater J, Shields JA, Singh AD, Santos MC, Carvalho C. Combination of clinical factors predictive of growth of small choroidal melanocytic tumours. Arch Ophthalmol 2000;118:360–364.
