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Small Choroidal Melanoma with All Eight Risk Factors for Growth

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Small Choroidal Melanoma with All Eight Risk Factors for Growth RETINAL ONCOLOGY CASE REPORTS IN OCULAR ONCOLOGY SECTION EDITOR: CAROL L. SHIELDS, MD Small Choroidal Melanoma With All Eight Risk Factors for Growth BY FELINA V. ZOLOTAREV, BA; KIRAN TURAKA, MD; AND CAROL L. SHIELDS, MD veal melanoma prognosis is A B C dependent on several factors including tumor size, location, U configuration, extraocular extension, cell type, and cytogenetic abnormalities. In general, the smaller the tumor, the better the prognosis.1 In a recent publication on 8,033 eyes with DE uveal melanoma, it was documented that increasing thickness of uveal melanoma was associated with greater risk for metastasis and ultimate death.1 Patients with uveal melanoma measuring 2.5 mm Figure 1. Features of small choroidal melanoma. A pigmented choroidal tumor thickness showed metastasis in 12% at 10 superior to the macula displays orange pigment, seen on autofluorescence (A, years as compared with 26% for those at B), hollowness on ultrasonography (C), and subretinal fluid, depicted on opti- 4.5 mm thickness.1 Hence, early detection cal coherence tomography (D, E). Note the lack of drusen or halo.These fea- of uveal melanoma is important. tures are most consistent with melanoma. The dilemma of early recognition cen- ters on the difficulty in differentiating a benign melanoma display two or three of these factors.2 In this choroidal nevus from a small malignant melanoma. Risk case presentation, we describe a small melanoma with factors for identification of small melanoma, when it all eight risk factors and discuss the importance of early might resemble choroidal nevus, have been identified detection of uveal melanoma. from several oncology centers. In an analysis of 2,514 patients with small choroidal melanocytic tumors, eight CASE REPORT important parameters were found to be predictive of A 55-year-old white woman noted photopsia for 1 year tumor growth; these include tumor Thickness of greater and slight blurred vision in the right eye. Her visual acuity than 2 mm, subretinal Fluid, Symptoms of reduced was 20/30 in her right eye and 20/20 in the left eye. The vision or photopsia, Orange pigment, tumor Margin less anterior segment was unremarkable in both eyes. The than or equal to 3 mm from the optic disc, ultrasound left fundus was normal. In the right fundus, there was a Hollowness, absence of surrounding depigmented Halo small pigmented choroidal lesion located 2.5 mm from and absence of overlying Drusen.2 These factors are the optic nerve, measuring 7.5 x 5.5 mm in basal diame- remembered by the lettering TFSOM-UHHD represent- ter and 2.3 mm in thickness without overlying drusen ing the mnemonic “To Find Small Ocular Melanoma- (Figure 1). The lesion manifested confluent overlying Using Helpful Hints Daily.”2 Most patients with small orange pigment, documented on autofluorescence, and 48 IRETINA TODAYIOCTOBER 2010 RETINAL ONCOLOGY CASE REPORTS IN OCULAR ONCOLOGY AB C Figure 2. Following treatment with plaque radiotherapy and macular-sparing thermotherapy, the choroidal melanoma regressed to 1.7 mm in thickness (A, B) and the subretinal fluid resolved (C). subtle subretinal fluid, confirmed on optical coherence thermotherapy (TTT). Fine needle aspiration biopsy for tomography (OCT). Ultrasonography demonstrated genetic testing at the time of plaque radiotherapy acoustic hollowness within the mass on B-scan and low revealed melanoma with chromosome 3 disomy. This to medium internal reflectivity on A-scan. The presence implied lower risk for metastasis than chromosome 3 of all eight risk factors in this case was strongly suggestive monosomy or other mutations.3 Following treatment, of small choroidal melanoma rather than nevus. Despite visual acuity in the left eye was 20/20 in the first year. The the small size of the tumor, it was treated with iodine-125 tumor regressed to a flat scar of 1.7 mm in thickness by 4 plaque radiotherapy and macula-sparing transpupillary months, and subretinal fluid resolved (Figure 2). TABLE 1. RELATIVE RISK FOR GROWTH OF CHOROIDAL MELANOCYTIC TUMOR INTO MELANOMA COMPARED WITH THOSE WITHOUT RISK FACTORS. Mnemonic Features Hazard Ratioa Hazard ratio Shields CL et al2 COMS4 4 if 2-2.4 mm To Thickness >2 mm 2 18 if 2.5-3 mm Find Fluid 3 NA Small Symptoms 2 NA Ocular Orange pigment 3 2 if minimal 6 if prominent Melanoma Margin ≤3 mm to disc 2 NA Using Helpful Ultrasound Hollow 3 NA Hints Halo absent 6 NA Daily Drusen absent NA 4 a Hazard ratio (rounded) compared to eye without feature using multivariable analysis. Drusen absent was not significant in the study by Shields CL et al,2 but was significant in the study by COMS4 NA = not applicable OCTOBER 2010 IRETINA TODAYI 49 RETINAL ONCOLOGY CASE REPORTS IN OCULAR ONCOLOGY TABLE 2. RISK FOR SYSTEMIC METASTASIS AS DETERMINED BY THE SIZE OF CHOROIDAL MELANOMA AND NUMBER OF YEARS AFTER DIAGNOSIS.1 Melanoma Size (mm) Probability of Metastasis (%)1 at 3 years at 5 years at 10 years Small (0-3.0) 2 5 12 Medium (3.1-8.0) 7 14 25 Large (>8.0) 22 36 49 patients and found that metastasis at 10 years occurred Early intervention with plaque radio- in 12% of small melanoma, 26% of medium, and 49% of large melanoma1 (Table 2). In that analysis, specific therapy was employed for ocular metastatic risk based on size increase showed about 5% tumor control and minimization of increase in metastasis for each millimeter increase in 1 systemic metastatic disease. thickness. In the case presented, early intervention with plaque radiotherapy was employed for ocular tumor control DISCUSSION and minimization of systemic metastatic disease. In In the August 2009 special issue of Archives of summary, risk factors are important when evaluating a Ophthalmology on ophthalmic pathology, risk factors patient with a small melanocytic choroidal tumor as predictive of growth of small choroidal melanocytic they may allow identification of a life-threatening malig- lesions into melanoma were refined.2 The mnemonic nancy at a very early state, perhaps in time before the TFSOM-UHHD was coined to assist ophthalmologists in onset of systemic metastases.1,2 the identification of clinical factors that predict small melanoma. These factors include tumor thickness greater Support provided by the Retina Research Foundation of than 2 mm, subretinal fluid, symptoms of reduced vision the Retina Society in Capetown, South Africa (CLS), and the or photopsia, orange pigment, tumor margin less than or Eye Tumor Research Foundation, Philadelphia, PA (CLS). ■ equal to 3 mm from the optic disc, ultrasound hollow- ness, absence of surrounding depigmented halo, and Felina V. Zolotarev, BA, is a medical student at absence of overlying drusen (previously identified by the Thomas Jefferson University in Philadelphia. Collaborative Ocular Melanoma Study Group).2 The Kiran Turaka, MD, is an Ocular Oncology presence of each of these features was associated with Fellow at Wills Eye Institute, Thomas Jefferson hazard ratio (HR) of 3 for malignant transformation University. (Table 1).2 The various combinations of individual risk Carol L. Shields, MD, is the Co-Director of the factors were further evaluated for total predictive power.2 Ocular Oncology Service, Wills Eye Institute, In this case, all eight risk factors were present. These fac- Thomas Jefferson University. She is a Retina Today tors do not confirm, but strongly suggest the diagnosis of Editorial Board member. Dr. Shields can be melanoma. The greater the number of risk factors, the reached at +1 215 928 3105; fax: +1 215 928 1140; higher the risk for tumor growth, which implies malig- or via e-mail at [email protected]. nancy.2 For example, a patient with a tumor showing The authors have no financial interest on the three risk factors had a fivefold risk compared with a devices or medications in this document. tumor without risk factors, a tumor with five factors had 1. Shields CL, Furuta M, Thangappan A, et al. Metastasis of uveal melanoma millimeter-by- a ninefold risk, and one with seven factors had a 21-fold millimeter in 8033 consecutive eyes. Arch Ophthalmol. 2009;127:989-998. 2 greater risk for growth, likely representing melanoma. 2. Shields CL, Furuta M, Berman EL, et al. Choroidal nevus transformation into melanoma: analysis of 2514 consecutive cases. Arch Ophthalmol. 2009; 127:981-987. Risk for long-term metastasis is substantially less with 3. Shields CL, Materin MA, Teixeira L, et al. Small choroidal melanoma with chromosome 3 small melanoma compared to large melanoma. In the monosomy on fine needle aspiration biopsy. Ophthalmology. 2007; 114:1919-1924. 4. Melia BM, Diener-West SM, Bennett SR, Folk JC, Montague PR, Weingeist TA. same ophthalmic pathology issue, one article focused Collaborative Ocular Melanoma Study Group. Factors predictive of growth and treatment of on choroidal melanoma metastasis in more than 8,000 small choroidal melanoma: COMS report No. 5. Arch Ophthalmol. 1997; 115:1537-1544. 50 IRETINA TODAYIOCTOBER 2010.
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