SUBMILLIMETER CHOROIDAL MELANOMA DETECTION BY ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY IN A PATIENT WITH OCULODERMAL MELANOCYTOSIS Zachary Daitch, BA, Carol L. Shields, MD, Emil A. T. Say, MD, Arman Mashayekhi, MD, Jerry A. Shields, MD
Purpose: To describe a tiny subclinical choroidal melanoma visualized only with enhanced depth imaging optical coherence tomography in a newly symptomatic patient with known oculodermal melanocytosis. Methods: Case report. Results: A 52-year-old white man with heterochromia and known oculodermal melanocytosis of the right eye, followed for 2 years without change, developed blurred vision and was referred for possible central serous chorioretinopathy. On examination, visual acuity was 20/20 in each eye. There was oculodermal melanocytosis in the right eye involving the periocular skin, episclera, iris, and choroid. On ophthalmoscopy and ocular ultrasonography, there was no appreciable mass, but subtle subfoveal fluid and perifoveal orange pigment were detected, as well as equatorial drusen. Enhanced depth imaging optical coherence tomography demonstrated a subtle optically dense focal choroidal mass measuring 4.5 mm in basal dimension and 0.7 mm in enhanced depth imaging optical coherence tomography thickness. There was choroidal vascular compression, obliteration of choroidal details, and related overlying subretinal fluid with shaggy photoreceptors, consistent with early choroidal melanoma in an eye with oculodermal melanocytosis. The patient elected early treatment considering the risk factors for growth and the risk for metastasis associated with melanoma in the setting of oculodermal melanocytosis. Plaque radiotherapy was performed with complete tumor regression clinically and by enhanced depth imaging optical coherence tomography. At 2-year follow-up, visual acuity remains 20/20, with regressed tumor and no systemic metastasis. Conclusion: Enhanced depth imaging optical coherence tomography is a useful tool in the evaluation of eyes with oculodermal melanocytosis, permitting high-resolution visualization of the choroid and detection of submillimeter early melanoma that might not be apparent with indirect ophthalmoscopy or ultrasonography. RETINAL CASES & BRIEF REPORTS 10:6–10, 2016
for those measuring 3-mm to 8-mm thickness. Furthermore, each millimeter increase in thickness added an additional 5% increase in metastatic risk. In 2014, Damato et al2 performed a prospective cohort study on the influence of tumor size on prognosis and concluded that early treatment of small melanoma prevents tumor growth, dedifferentiation, and metastatic disease in some patients, particularly those with a small tumor. Systemic
From the Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA.
E
arly detection and treatment of uveal melanoma is important in reducing risk for metastasis and prolonging patient survival. Shields et al1 found that melanoma measuring 3 mm or less at detection showed 10-year risk for metastasis at 12% compared with 26%
6
7
EDI FOR SUBCLINICAL CHOROIDAL MELANOMA
metastasis from uveal melanoma depends on tumor size at detection plus additional factors of tumor node metastasis classification, ciliary body involvement, extraocular spread, cytomorphological findings, mitotic count, closed vascular loops, and cytogenetic findings.1–4 Oculodermal melanocytosis is a benign congenital condition with increased melanocytes in the skin, episclera, uvea, orbit, meninges, palate, and eardrum.5–7 This condition occurs in less than 1% of the general population but carries a 35-fold risk for development of uveal melanoma.5,8 Our team has shown in a retrospective analysis of 7,872 eyes with melanoma that those arising from melanocytosis display double the risk for metastasis compared with those without melanocytosis, and this was further confirmed in a case-matched cohort study, when controlling for other factors.6,9 It is recommended that all eyes with oculodermal melanocytosis have lifelong monitoring for uveal melanoma. Here, we describe a patient with established ocular melanocytosis who was followed for 2 years and then developed blurred vision but without clinically or ultrasonographically visible tumor. A submillimeterpresumed early melanoma in the setting of oculodermal melanocytosis was detected only by enhanced depth imaging optical coherence tomography (EDI-OCT). Case Report A 52-year-old white man with heterochromia and established oculodermal melanocytosis of the right eye was followed for 2 years with the only clinical finding of equatorial drusen in the right eye (Figure 1). He then developed mildly symptomatic blurred vision in the right eye and was suspected to have central serous chorioretinopathy. On referral, visual acuity was 20/20 in each eye. The left eye was normal. Examination of the right eye revealed brown pigmentation of the periocular skin, sclera, iris, and choroid. The choroidal melanocytosis camouflaged the choroidal vascular details, and related circumferential equatorial drusen were noted. A subtle discrete region of subfoveal fluid and orange pigment were noted, but there was no apparent mass on indirect ophthalmoscopy or ultrasonography (Figure 1). Fluorescein angiography depicted 1 “hot spot” leak in the retinal pigment epithelium surrounded by illdefined temporal hyperfluorescence but no distinct mass (Figure 1). Indocyanine green angiography showed a distinct 4.5-mm region of hypofluorescence in the temporal parafoveal region without staining or leakage (Figure 1). Spectral domain EDI-OCT demonstrated shallow focal subfoveal fluid with “shaggy” photoreceptors in the temporal macular Supported by the Eye Tumor Research Foundation, Philadelphia, PA (Z.D., C.L.S., E.A.T.S., A.M., J.S.). The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript. C. L. Shields has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. None of the authors have any conflicting interests to disclose. Reprint requests: Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Institute, Suite 1440, 840 Walnut Street, Philadelphia, PA 19107; e-mail: [email protected]
region and a subtle shallow focally elevated choroidal mass corresponding in size to the hypofluorescent region on indocyanine green angiography (Figure 1). The mass was optically homogeneous, measuring 4.5 mm in basal dimension and 0.7 mm in thickness, and with compression of choroidal vascular structures correlating with the lack of choroidal fluorescence on indocyanine green angiography. These features were consistent with early choroidal melanoma in an eye with ocular melanocytosis (Figure 1). Management options included observation for growth, fineneedle aspiration biopsy, transpupillary thermotherapy, plaque radiotherapy, or enucleation. Considering the juxtafoveal location, thin tumor, high-risk features of subretinal fluid, orange pigment, and high-risk precursor condition, namely ocular melanocytosis, the patient elected to receive early intervention with plaque radiotherapy and declined fine-needle aspiration biopsy. Two years after the treatment, the tumor demonstrated complete regression with resolution of subretinal fluid. Enhanced depth imaging optical coherence tomography documented flattening of the choroid and retina (Figure 2). Visual acuity remained 20/20, and there was no systemic metastasis.
Discussion Oculodermal melanocytosis (nevus of Ota) is a congenital birthmark with melanocytic pigmentation of the ocular tissues and additional involvement of the periocular skin along the distribution of the first or second division of the trigeminal nerve in 19%.10 In an analysis of 33 cases, this condition was found mostly in the episclera (100%), iris (89%), trabecular meshwork (89%), choroid (100%), and less frequently, the eyelid, temporal fossa, orbit, palate, conjunctiva, lens, and optic disk.10 Melanocytosis can occur as a diffuse pigmentary condition involving the entire uvea or it can be localized to a sector of tissue.5–8,10 Diffuse melanocytosis in whites carries an estimated lifetime risk for development of melanoma at 1 in 400 cases.11 In reverse, only 3% of eyes with uveal melanoma demonstrate melanocytosis, and it was determined that the 10-year rate of metastasis was 48% compared with 24% in eyes with melanoma lacking melanocytosis.6,11 Enhanced depth imaging optical coherence tomography provides high-resolution cross-sectional analysis of the retina and choroid with relatively accurate definition of the retinochoroidal and choroidoscleral boundaries.12 This technology can resolve down 4 mm, beyond the resolution of the indirect ophthalmoscopy (50 mm) and ultrasonography (50–200 mm). In our case, the tumor was not clinically visible, and the ultrasound showed no mass, but imaging with EDI-OCT allowed for subclinical tumor detection. In addition, this case illustrates the value of EDI-OCT in following patients with ocular melanocytosis who might manifest symptomatic or asymptomatic melanoma. Shields et al13 reviewed a series of 37 eyes with small choroidal melanoma using EDI-OCT and found optical
8
RETINAL CASES & BRIEF REPORTS´ 2016 VOLUME 10 NUMBER 1
Fig. 1. A 52-year-old white man with known history of oculodermal melanocytosis of the right eye (OD). At date first seen, the fundus (A) demonstrated homogeneous choroidal melanocytosis with no sign of tumor, and (B) autofluorescence did not show orange pigment accumulation or subretinal fluid. Two years later, (C) slight orange pigment was detected in the temporal macular region, (D) confirmed as hyperautofluorescent. E. Fluorescein angiography demonstrated a focal area of leakage temporal to the fovea (arrowhead), and (F) indocyanine green angiography delineated the margins of a hypofluorescent choroidal mass (arrowheads). G. Enhanced depth imaging spectral domain optical coherence tomography showed shallow subretinal fluid with “shaggy” photoreceptors in the foveal region, and (H) the choroidal mass (arrowheads) as seen on indocyanine green angiography was appreciated, measuring 0.7 mm in thickness inferotemporal to the foveola with overlying choriocapillaris compression, consistent with a small choroidal melanoma.
shadowing and thinning of choriocapillaris in all cases, subretinal fluid in 92%, subretinal lipofuscin in 95%, shaggy photoreceptors in 49%, and loss of ellipsoid zone in 65%, and external limiting membrane in 43%. The authors also analyzed 51 eyes with similar-sized choroidal nevus for comparison and found optical shadowing in 94%, thinning of overlying choriocapillaris in all cases, subretinal fluid in 16%, shaggy photoreceptors in 0%, subretinal lipofuscin in 45%, and loss of ellipsoid zone in 6%, and external limiting membrane in 2%. They concluded that in addition to
established risk factors of greater tumor thickness, subretinal fluid, and orange pigment, the presence of shaggy photoreceptors (P , 0.001), loss of ellipsoid zone (P = 0.02), and loss of external limiting membrane (P = 0.008) on EDI-OCT can assist in distinguishing small choroidal melanoma from benign nevi. Further analysis using EDI-OCT for unilateral ocular melanocytosis was performed by Pellegrini et al.14 They found normal macular anatomy in all but one eye and found that eyes affected with melanocytosis had 23% greater subfoveal choroidal thickness compared with the
9
EDI FOR SUBCLINICAL CHOROIDAL MELANOMA
Fig. 2. At 6 months after the treatment with plaque radiotherapy, fundus (A) showed persistent orange pigment confirmed on fundus autofluorescence (B) without subretinal fluid and no visible choroidal mass. C. Enhanced depth imaging spectral domain optical coherence tomography through the fovea confirmed resolution of subretinal fluid and restoration of normal foveal anatomy as well as flattening and regression of (D) the small melanoma.
fellow control eye, and the affected choroid showed 51% greater perivascular interstitial tissue enwrapping Haller’s and Sattler’s layers, contributing to the increased thickness. In their series, there were no eyes with melanoma and the retinal pigment epithelium– Bruch membrane complex was smooth in all cases. In our case, EDI-OCT distinctly showed a choroidal mass with overlying subretinal fluid and shaggy photoreceptors, which is likely to represent early small choroidal melanoma in the context of oculodermal melanocytosis or an evolving choroidal nevus with high-risk features for growth and metastasis. In addition, indocyanine green angiography showed a circumscribed hypofluorescent mass corresponding to the tumor, similar to the previously described indocyanine green angiography features.15 We suggested fine-needle biopsy of the tiny mass for cytologic or cytogenetic confirmation, but the patient preferred to avoid the minimal risk for hemorrhage and visual compromise. In an analysis of cytogenetics for small choroidal melanoma (#3-mm thickness), some as thin as 1.4 mm, a sample sufficient for DNA analysis was obtained in 84% and showed high-risk monosomy 3 in 27% of cases compared with 41% for large (.8 mm) melanoma.3,16 The greater percentage of high-risk monosomy 3 in large melanoma and further calculations by Eskelin and Kivela17 that estimated metastasis occurring when the tumor is only 3 · 3 · 1.5 mm in size reinforces the concept that early detection and treatment could improve long-term survival. In ordinary circumstances, in eyes without oculodermal melanocytosis, small indeterminate choroidal melanocytic lesions are generally managed conservatively with serial observation and treated only when growth is documented. Although
observation for growth was an option in our case, the knowledge that melanoma arising from oculodermal melanocytosis has exaggerated risk for metastasis prompted early intervention before documented growth.6 Despite these risks, patients with choroidal melanocytosis who demonstrate indeterminate small choroidal melanocytic lesions should be counseled regarding observation versus early intervention. In summary, we describe a small subclinical choroidal melanoma that was best visualized with EDIOCT and allowed early detection and treatment with plaque radiotherapy. Submillimeter detection of melanoma using EDI-OCT could be particularly beneficial during screening of eyes with ocular melanocytosis. Key words: choroid, melanoma, subclinical, enhanced depth imaging, optical coherence tomography, EDI-OCT, ocular melanocytosis. References 1. Shields CL, Furuta M, Thangappan A, et al. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol 2009;127:989–998. 2. Damato BE, Heimann H, Kalirai H, Coupland SE. Age, survival predictors, and metastatic death in patients with choroidal melanoma. Tentative evidence of a therapeutic effect on survival. JAMA Ophthalmol 2014;132:605–613. 3. Shields CL, Ganguly A, Bianciotto C, et al. Prognosis of uveal melanoma in 500 cases using genetic testing of fine-needle aspiration biopsy specimens. Ophthalmology 2011;118:396–401. 4. McLean IW, Foser WD, Zimmerman LE. Uveal melanoma: location, size, cell type, and enucleation as risk factors in metastasis. Hum Pathol 1982;13:123–132. 5. Gonder JR, Shields JA, Albert DM, et al. Uveal malignant melanoma associated with ocular and oculodermal melanocytosis. Ophthalmology 1982;89:953–960.
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RETINAL CASES & BRIEF REPORTS´ 2016 VOLUME 10 NUMBER 1
6. Shields CL, Kaliki S, Livesey M, et al. Association of ocular and oculodermal melanocytosis with rate of uveal melanoma metastasis. Analysis of 7872 consecutive eyes. JAMA Ophthalmol 2013;131:993–1003. 7. Shields CL, Qureshi A, Mashayekhi A, et al. Sector (partial) oculo(dermal) melanocytosis in 89 eyes. Ophthalmology 2011;118:2474–2479. 8. Gonder JR, Ezell PC, Shields JA, Augsburger JJ. Ocular melanocytosis. A study to determine the prevalence rate of ocular melanocytosis. Ophthalmology 1982;89:950–952. 9. Mashayekhi A, Kaliki S, Walker B, et al. Metastasis from uveal melanoma associated with congenital ocular melanocytosis. A matched study. Ophthalmology 2013;120:1465–1468. 10. Gonder JR, Nichol J, Augsburger JJ, Shields JA. Ocular and oculodermal melanocytosis. Can J Ophthalmol 1985;20:176–178. 11. Singh AD, De Potter P, Fijal BA, et al. Lifetime prevalence of uveal melanoma in white patients with oculo(dermal) melanocytosis. Ophthalmology 1998;105:195–198.
12. Spaide RF, Koizumi H, Pozonni MC. Enhanced depth imaging spectral domain optical coherence tomography. Am J Ophthalmol 2008;146:496–500. 13. Shields CL, Kaliki S, Rojanaporn D, et al. Enhanced depth imaging optical coherence tomography of small choroidal melanoma: comparison with choroidal nevus. Arch Ophthalmol 2012;130:850–856. 14. Pellegrini M, Shields CL, Arepalli S, Shields JA. Choroidal melanocytosis evaluation with enhanced depth imaging optical coherence tomography. Ophthalmology 2014;121:257–261. 15. Shields CL, Shields JA, De Potter P. Patterns of indocyanine green angiography of choroidal tumors. Br J Ophthalmol 1995;79:237–245. 16. Shields CL, Materin MA, Teixeira L, et al. Small choroidal melanoma with chromosome 3 monosomy on fine-needle aspiration biopsy. Ophthalmology 2007;114:1919–1924. 17. Eskelin S, Kivela T. Uveal melanoma implications of tumor doubling times. Ophthalmology 2001;108:830–831.
Purpose: To describe a tiny subclinical choroidal melanoma visualized only with enhanced depth imaging optical coherence tomography in a newly symptomatic patient with known oculodermal melanocytosis. Methods: Case report. Results: A 52-year-old white man with heterochromia and known oculodermal melanocytosis of the right eye, followed for 2 years without change, developed blurred vision and was referred for possible central serous chorioretinopathy. On examination, visual acuity was 20/20 in each eye. There was oculodermal melanocytosis in the right eye involving the periocular skin, episclera, iris, and choroid. On ophthalmoscopy and ocular ultrasonography, there was no appreciable mass, but subtle subfoveal fluid and perifoveal orange pigment were detected, as well as equatorial drusen. Enhanced depth imaging optical coherence tomography demonstrated a subtle optically dense focal choroidal mass measuring 4.5 mm in basal dimension and 0.7 mm in enhanced depth imaging optical coherence tomography thickness. There was choroidal vascular compression, obliteration of choroidal details, and related overlying subretinal fluid with shaggy photoreceptors, consistent with early choroidal melanoma in an eye with oculodermal melanocytosis. The patient elected early treatment considering the risk factors for growth and the risk for metastasis associated with melanoma in the setting of oculodermal melanocytosis. Plaque radiotherapy was performed with complete tumor regression clinically and by enhanced depth imaging optical coherence tomography. At 2-year follow-up, visual acuity remains 20/20, with regressed tumor and no systemic metastasis. Conclusion: Enhanced depth imaging optical coherence tomography is a useful tool in the evaluation of eyes with oculodermal melanocytosis, permitting high-resolution visualization of the choroid and detection of submillimeter early melanoma that might not be apparent with indirect ophthalmoscopy or ultrasonography. RETINAL CASES & BRIEF REPORTS 10:6–10, 2016
for those measuring 3-mm to 8-mm thickness. Furthermore, each millimeter increase in thickness added an additional 5% increase in metastatic risk. In 2014, Damato et al2 performed a prospective cohort study on the influence of tumor size on prognosis and concluded that early treatment of small melanoma prevents tumor growth, dedifferentiation, and metastatic disease in some patients, particularly those with a small tumor. Systemic
From the Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA.
E
arly detection and treatment of uveal melanoma is important in reducing risk for metastasis and prolonging patient survival. Shields et al1 found that melanoma measuring 3 mm or less at detection showed 10-year risk for metastasis at 12% compared with 26%
6
7
EDI FOR SUBCLINICAL CHOROIDAL MELANOMA
metastasis from uveal melanoma depends on tumor size at detection plus additional factors of tumor node metastasis classification, ciliary body involvement, extraocular spread, cytomorphological findings, mitotic count, closed vascular loops, and cytogenetic findings.1–4 Oculodermal melanocytosis is a benign congenital condition with increased melanocytes in the skin, episclera, uvea, orbit, meninges, palate, and eardrum.5–7 This condition occurs in less than 1% of the general population but carries a 35-fold risk for development of uveal melanoma.5,8 Our team has shown in a retrospective analysis of 7,872 eyes with melanoma that those arising from melanocytosis display double the risk for metastasis compared with those without melanocytosis, and this was further confirmed in a case-matched cohort study, when controlling for other factors.6,9 It is recommended that all eyes with oculodermal melanocytosis have lifelong monitoring for uveal melanoma. Here, we describe a patient with established ocular melanocytosis who was followed for 2 years and then developed blurred vision but without clinically or ultrasonographically visible tumor. A submillimeterpresumed early melanoma in the setting of oculodermal melanocytosis was detected only by enhanced depth imaging optical coherence tomography (EDI-OCT). Case Report A 52-year-old white man with heterochromia and established oculodermal melanocytosis of the right eye was followed for 2 years with the only clinical finding of equatorial drusen in the right eye (Figure 1). He then developed mildly symptomatic blurred vision in the right eye and was suspected to have central serous chorioretinopathy. On referral, visual acuity was 20/20 in each eye. The left eye was normal. Examination of the right eye revealed brown pigmentation of the periocular skin, sclera, iris, and choroid. The choroidal melanocytosis camouflaged the choroidal vascular details, and related circumferential equatorial drusen were noted. A subtle discrete region of subfoveal fluid and orange pigment were noted, but there was no apparent mass on indirect ophthalmoscopy or ultrasonography (Figure 1). Fluorescein angiography depicted 1 “hot spot” leak in the retinal pigment epithelium surrounded by illdefined temporal hyperfluorescence but no distinct mass (Figure 1). Indocyanine green angiography showed a distinct 4.5-mm region of hypofluorescence in the temporal parafoveal region without staining or leakage (Figure 1). Spectral domain EDI-OCT demonstrated shallow focal subfoveal fluid with “shaggy” photoreceptors in the temporal macular Supported by the Eye Tumor Research Foundation, Philadelphia, PA (Z.D., C.L.S., E.A.T.S., A.M., J.S.). The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript. C. L. Shields has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. None of the authors have any conflicting interests to disclose. Reprint requests: Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Institute, Suite 1440, 840 Walnut Street, Philadelphia, PA 19107; e-mail: [email protected]
region and a subtle shallow focally elevated choroidal mass corresponding in size to the hypofluorescent region on indocyanine green angiography (Figure 1). The mass was optically homogeneous, measuring 4.5 mm in basal dimension and 0.7 mm in thickness, and with compression of choroidal vascular structures correlating with the lack of choroidal fluorescence on indocyanine green angiography. These features were consistent with early choroidal melanoma in an eye with ocular melanocytosis (Figure 1). Management options included observation for growth, fineneedle aspiration biopsy, transpupillary thermotherapy, plaque radiotherapy, or enucleation. Considering the juxtafoveal location, thin tumor, high-risk features of subretinal fluid, orange pigment, and high-risk precursor condition, namely ocular melanocytosis, the patient elected to receive early intervention with plaque radiotherapy and declined fine-needle aspiration biopsy. Two years after the treatment, the tumor demonstrated complete regression with resolution of subretinal fluid. Enhanced depth imaging optical coherence tomography documented flattening of the choroid and retina (Figure 2). Visual acuity remained 20/20, and there was no systemic metastasis.
Discussion Oculodermal melanocytosis (nevus of Ota) is a congenital birthmark with melanocytic pigmentation of the ocular tissues and additional involvement of the periocular skin along the distribution of the first or second division of the trigeminal nerve in 19%.10 In an analysis of 33 cases, this condition was found mostly in the episclera (100%), iris (89%), trabecular meshwork (89%), choroid (100%), and less frequently, the eyelid, temporal fossa, orbit, palate, conjunctiva, lens, and optic disk.10 Melanocytosis can occur as a diffuse pigmentary condition involving the entire uvea or it can be localized to a sector of tissue.5–8,10 Diffuse melanocytosis in whites carries an estimated lifetime risk for development of melanoma at 1 in 400 cases.11 In reverse, only 3% of eyes with uveal melanoma demonstrate melanocytosis, and it was determined that the 10-year rate of metastasis was 48% compared with 24% in eyes with melanoma lacking melanocytosis.6,11 Enhanced depth imaging optical coherence tomography provides high-resolution cross-sectional analysis of the retina and choroid with relatively accurate definition of the retinochoroidal and choroidoscleral boundaries.12 This technology can resolve down 4 mm, beyond the resolution of the indirect ophthalmoscopy (50 mm) and ultrasonography (50–200 mm). In our case, the tumor was not clinically visible, and the ultrasound showed no mass, but imaging with EDI-OCT allowed for subclinical tumor detection. In addition, this case illustrates the value of EDI-OCT in following patients with ocular melanocytosis who might manifest symptomatic or asymptomatic melanoma. Shields et al13 reviewed a series of 37 eyes with small choroidal melanoma using EDI-OCT and found optical
8
RETINAL CASES & BRIEF REPORTS´ 2016 VOLUME 10 NUMBER 1
Fig. 1. A 52-year-old white man with known history of oculodermal melanocytosis of the right eye (OD). At date first seen, the fundus (A) demonstrated homogeneous choroidal melanocytosis with no sign of tumor, and (B) autofluorescence did not show orange pigment accumulation or subretinal fluid. Two years later, (C) slight orange pigment was detected in the temporal macular region, (D) confirmed as hyperautofluorescent. E. Fluorescein angiography demonstrated a focal area of leakage temporal to the fovea (arrowhead), and (F) indocyanine green angiography delineated the margins of a hypofluorescent choroidal mass (arrowheads). G. Enhanced depth imaging spectral domain optical coherence tomography showed shallow subretinal fluid with “shaggy” photoreceptors in the foveal region, and (H) the choroidal mass (arrowheads) as seen on indocyanine green angiography was appreciated, measuring 0.7 mm in thickness inferotemporal to the foveola with overlying choriocapillaris compression, consistent with a small choroidal melanoma.
shadowing and thinning of choriocapillaris in all cases, subretinal fluid in 92%, subretinal lipofuscin in 95%, shaggy photoreceptors in 49%, and loss of ellipsoid zone in 65%, and external limiting membrane in 43%. The authors also analyzed 51 eyes with similar-sized choroidal nevus for comparison and found optical shadowing in 94%, thinning of overlying choriocapillaris in all cases, subretinal fluid in 16%, shaggy photoreceptors in 0%, subretinal lipofuscin in 45%, and loss of ellipsoid zone in 6%, and external limiting membrane in 2%. They concluded that in addition to
established risk factors of greater tumor thickness, subretinal fluid, and orange pigment, the presence of shaggy photoreceptors (P , 0.001), loss of ellipsoid zone (P = 0.02), and loss of external limiting membrane (P = 0.008) on EDI-OCT can assist in distinguishing small choroidal melanoma from benign nevi. Further analysis using EDI-OCT for unilateral ocular melanocytosis was performed by Pellegrini et al.14 They found normal macular anatomy in all but one eye and found that eyes affected with melanocytosis had 23% greater subfoveal choroidal thickness compared with the
9
EDI FOR SUBCLINICAL CHOROIDAL MELANOMA
Fig. 2. At 6 months after the treatment with plaque radiotherapy, fundus (A) showed persistent orange pigment confirmed on fundus autofluorescence (B) without subretinal fluid and no visible choroidal mass. C. Enhanced depth imaging spectral domain optical coherence tomography through the fovea confirmed resolution of subretinal fluid and restoration of normal foveal anatomy as well as flattening and regression of (D) the small melanoma.
fellow control eye, and the affected choroid showed 51% greater perivascular interstitial tissue enwrapping Haller’s and Sattler’s layers, contributing to the increased thickness. In their series, there were no eyes with melanoma and the retinal pigment epithelium– Bruch membrane complex was smooth in all cases. In our case, EDI-OCT distinctly showed a choroidal mass with overlying subretinal fluid and shaggy photoreceptors, which is likely to represent early small choroidal melanoma in the context of oculodermal melanocytosis or an evolving choroidal nevus with high-risk features for growth and metastasis. In addition, indocyanine green angiography showed a circumscribed hypofluorescent mass corresponding to the tumor, similar to the previously described indocyanine green angiography features.15 We suggested fine-needle biopsy of the tiny mass for cytologic or cytogenetic confirmation, but the patient preferred to avoid the minimal risk for hemorrhage and visual compromise. In an analysis of cytogenetics for small choroidal melanoma (#3-mm thickness), some as thin as 1.4 mm, a sample sufficient for DNA analysis was obtained in 84% and showed high-risk monosomy 3 in 27% of cases compared with 41% for large (.8 mm) melanoma.3,16 The greater percentage of high-risk monosomy 3 in large melanoma and further calculations by Eskelin and Kivela17 that estimated metastasis occurring when the tumor is only 3 · 3 · 1.5 mm in size reinforces the concept that early detection and treatment could improve long-term survival. In ordinary circumstances, in eyes without oculodermal melanocytosis, small indeterminate choroidal melanocytic lesions are generally managed conservatively with serial observation and treated only when growth is documented. Although
observation for growth was an option in our case, the knowledge that melanoma arising from oculodermal melanocytosis has exaggerated risk for metastasis prompted early intervention before documented growth.6 Despite these risks, patients with choroidal melanocytosis who demonstrate indeterminate small choroidal melanocytic lesions should be counseled regarding observation versus early intervention. In summary, we describe a small subclinical choroidal melanoma that was best visualized with EDIOCT and allowed early detection and treatment with plaque radiotherapy. Submillimeter detection of melanoma using EDI-OCT could be particularly beneficial during screening of eyes with ocular melanocytosis. Key words: choroid, melanoma, subclinical, enhanced depth imaging, optical coherence tomography, EDI-OCT, ocular melanocytosis. References 1. Shields CL, Furuta M, Thangappan A, et al. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol 2009;127:989–998. 2. Damato BE, Heimann H, Kalirai H, Coupland SE. Age, survival predictors, and metastatic death in patients with choroidal melanoma. Tentative evidence of a therapeutic effect on survival. JAMA Ophthalmol 2014;132:605–613. 3. Shields CL, Ganguly A, Bianciotto C, et al. Prognosis of uveal melanoma in 500 cases using genetic testing of fine-needle aspiration biopsy specimens. Ophthalmology 2011;118:396–401. 4. McLean IW, Foser WD, Zimmerman LE. Uveal melanoma: location, size, cell type, and enucleation as risk factors in metastasis. Hum Pathol 1982;13:123–132. 5. Gonder JR, Shields JA, Albert DM, et al. Uveal malignant melanoma associated with ocular and oculodermal melanocytosis. Ophthalmology 1982;89:953–960.
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RETINAL CASES & BRIEF REPORTS´ 2016 VOLUME 10 NUMBER 1
6. Shields CL, Kaliki S, Livesey M, et al. Association of ocular and oculodermal melanocytosis with rate of uveal melanoma metastasis. Analysis of 7872 consecutive eyes. JAMA Ophthalmol 2013;131:993–1003. 7. Shields CL, Qureshi A, Mashayekhi A, et al. Sector (partial) oculo(dermal) melanocytosis in 89 eyes. Ophthalmology 2011;118:2474–2479. 8. Gonder JR, Ezell PC, Shields JA, Augsburger JJ. Ocular melanocytosis. A study to determine the prevalence rate of ocular melanocytosis. Ophthalmology 1982;89:950–952. 9. Mashayekhi A, Kaliki S, Walker B, et al. Metastasis from uveal melanoma associated with congenital ocular melanocytosis. A matched study. Ophthalmology 2013;120:1465–1468. 10. Gonder JR, Nichol J, Augsburger JJ, Shields JA. Ocular and oculodermal melanocytosis. Can J Ophthalmol 1985;20:176–178. 11. Singh AD, De Potter P, Fijal BA, et al. Lifetime prevalence of uveal melanoma in white patients with oculo(dermal) melanocytosis. Ophthalmology 1998;105:195–198.
12. Spaide RF, Koizumi H, Pozonni MC. Enhanced depth imaging spectral domain optical coherence tomography. Am J Ophthalmol 2008;146:496–500. 13. Shields CL, Kaliki S, Rojanaporn D, et al. Enhanced depth imaging optical coherence tomography of small choroidal melanoma: comparison with choroidal nevus. Arch Ophthalmol 2012;130:850–856. 14. Pellegrini M, Shields CL, Arepalli S, Shields JA. Choroidal melanocytosis evaluation with enhanced depth imaging optical coherence tomography. Ophthalmology 2014;121:257–261. 15. Shields CL, Shields JA, De Potter P. Patterns of indocyanine green angiography of choroidal tumors. Br J Ophthalmol 1995;79:237–245. 16. Shields CL, Materin MA, Teixeira L, et al. Small choroidal melanoma with chromosome 3 monosomy on fine-needle aspiration biopsy. Ophthalmology 2007;114:1919–1924. 17. Eskelin S, Kivela T. Uveal melanoma implications of tumor doubling times. Ophthalmology 2001;108:830–831.
