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Choroidal Nevus Transformation Into Melanoma: Analysis of 2514 Consecutive Cases

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Choroidal Nevus Transformation Into Melanoma: Analysis of 2514 Consecutive Cases CLINICAL SCIENCES Choroidal Nevus Transformation Into Melanoma Analysis of 2514 Consecutive Cases Carol L. Shields, MD; Minoru Furuta, MD; Edwina L. Berman, BS; Jonathan D. Zahler, MD; Daniel M. Hoberman, BS; Diep H. Dinh, BS; Arman Mashayekhi, MD; Jerry A. Shields, MD Objective: To determine features that are predictive of halo absence (P=.009). A mnemonic device to recall risk growth of choroidal nevi into melanoma. factors of ocular melanoma is “To find small ocular mela- noma using helpful hints,” representing thickness, fluid, Methods: This was a retrospective medical record re- symptoms, orange pigment, margin, ultrasonographic hol- view of 2514 consecutive eyes; Kaplan-Meier estimates lowness, and halo absence. The median hazard ratio for and Cox regression analyses were used. those with 1 to 2 risk factors was 3; for 3 or 4 factors, 5; for 5 to 6 factors, 9; and for all 7 factors, 21. Results: The median tumor basal diameter was 5.0 mm and thickness was 1.5 mm. Nevus growth into mela- Conclusions: In an analysis of 2514 choroidal nevi, fac- noma occurred in 2%, 9%, and 13% of eyes at 1, 5, and tors predictive of growth into melanoma included greater 10 years, respectively. Factors predictive of growth into thickness, subretinal fluid, symptoms, orange pigment, melanoma by multivariable analysis included tumor thick- margin near disc, and 2 new features: ultrasonographic ness greater than 2 mm (PϽ.001), subretinal fluid hollowness and absence of halo. (P =.002), symptoms (P =.002), orange pigment (PϽ.001), tumor margin within 3 mm of the optic disc (P=.001), ultrasonographic hollowness (PϽ.001), and Arch Ophthalmol. 2009;127(8):981-987 URING THE PAST HALF- irregularity, color variegation, and diam- century, advances in the eter larger than 6 mm, has provided ob- early detection of cutane- jective, reproducible criteria for the early ous melanoma have been diagnosis of cutaneous melanoma. Rather important for improved than diagnosing melanoma as such sim- Dsurvival of affected patients.1-3 Despite the ply because it looks like melanoma, clini- increasing incidence of cutaneous mela- cians have been guided by the well- noma, the mortality rate has gradually de- defined features of the ABCD mnemonic creased.2 In the 1950s, the estimated life- to more objectively identify early mela- time risk of a US inhabitant developing noma.1 In the 1990s, dermoscopy (epilu- invasive cutaneous melanoma was 1 in 600, minescence microscopy), autofluores- cence, and digital image analysis added CME available online at more technologically directed methods for www.jamaarchivescme.com early tumor detection, but it was realized that these tests were not universally avail- and questions on page 959 able. The most common method, clinical examination with the naked eye, has re- and that has increased to a current risk of mained the most practical one. In 2005, 1 in 62, with a projected 2010 risk of 1 in 1 further analysis identified another clini- 50. In the face of this alarming increase, the cal factor for early melanoma, evolution, 5-year survival in those with stage 1 cuta- and the ABCD mnemonic was modified to neous melanoma has improved from 50% ABCDE.1 1 in the 1950s to near 90% currently. In ophthalmology, there has been a An important factor in improved sur- Author Affiliations: Ocular similar drive toward early detection of Oncology Service, Wills Eye vival with cutaneous melanoma has been uveal melanoma. In 1995, statistically de- Institute, Thomas Jefferson the development of the ABCD mnemonic rived clinical risk factors were identified 1-3 University, Philadelphia, device in the 1980s. This mnemonic as features of early choroidal melanoma; Pennsylvania. device, representing asymmetry, border these included thickness greater than 2 (REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 8), AUG 2009 WWW.ARCHOPHTHALMOL.COM 981 ©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 mm, subretinal fluid, symptoms, orange pigment, and RESULTS margin near the optic disc.4 These features, remem- bered with the mnemonic device “To find small ocular melanoma,” were all based on routine funduscopic ex- Of the 2514 patients with choroidal nevus who were fol- amination, making their use practical and significant. The lowed up, the median patient age at referral was 62 years presence of 3 or more risk factors was associated with a (mean, 60 years; range, 4-97 years); 2487 of patients were more than 50% chance of tumor growth in 5 years.5 In white (99%), 12 were African American (Ͻ1%), 11 were our practice of ocular oncology, these risk factors have Hispanic (Ͻ1%), and 4 were Asian (Ͻ1%). Nine hun- been immensely valuable in early detection of choroidal dred thirty-one patients were male (37%) and 1583 were melanoma. In this analysis, we further investigate clini- female (63%). Medical histories revealed dysplastic ne- cal features in the detection of early choroidal mela- vus syndrome (n=20 [1%]), cutaneous melanoma (n=96 noma in a larger cohort of patients with presumed cho- [4%]), choroidal melanoma in the opposite eye (n=94 roidal nevi to further refine relevant risk factors. [4%]), conjunctival melanoma or primary acquired mela- nosis (n=10 [Ͻ1%]), neurofibromatosis (n=3 [Ͻ1%]), and ocular melanocytosis (n=94 [4%]). Patient symp- METHODS toms included decreased vision (n=135 [5%]), visual field defect (n=28 [1%]), and flashes/floaters (n=92 [4%]). A retrospective medical record review was performed on all pa- Most cases (n=2333 [93%]) had best-corrected visual acu- tients with the clinical diagnosis of choroidal nevus treated in ities (BCVAs) (by Snellen charts) of 20/20 to 20/40; 140 the Ocular Oncology Service at Wills Eye Institute between April had BCVAs of 20/50 to 20/100 (5%); 25 had BCVAs of 1974 and June 2006. Institutional review board approval was 20/200 to 20/400 (1%); 16 had BCVAs of counting fin- obtained for this retrospective study. All patients were exam- gers to hand motions (Ͻ1%); and none had BCVAs of ined by 1 of the senior authors (C.L.S. or J.A.S.) using modern light perception to no light perception. techniques of indirect ophthalmoscopy of the entire fundus and The median basal diameter of the choroidal nevi was high-resolution magnification ophthalmoscopy (Goldman or 5.0 mm (mean, 5.1 mm; range, 0.4-24 mm) and the me- 60-diopter lens with slitlamp biomicroscopy) of the nevus or dian thickness was 1.5 mm (mean, 1.6 mm; range, 0.6- macula when necessary and possible. Details of the choroidal 4.5 mm). Mean follow-up was 53 months, with a range nevus were recorded on large fundus drawings in all patients. Fundus photography was performed on patients older than 6 of 6 to 434 months. The quadrant location for the nevus years. The following clinical data were collected at initial ex- was inferior in 503 eyes (20%), temporal in 724 eyes (29%), amination: patient age, race, sex, medical history (dysplastic superior in 465 eyes (18%), nasal in 599 eyes (24%), and nevus syndrome; cutaneous, choroidal, or conjunctival mela- in the macula in 223 eyes (9%). The anteroposterior lo- noma; and neurofibromatosis), ocular melanocytosis, symp- cation to the nevus was the macula in 540 eyes (21%), toms, and best-corrected visual acuity using Snellen charts. Other macular to equator in 1752 eyes (70%), and equator to recorded data included quadrantic location of tumor epicen- ora serrata in 222 eyes (9%). The tumor was a mean of ter (inferior, temporal, superior, nasal, or macula), anteropos- 5.6 mm to the optic disc and 5.3 mm to the foveola. As- terior location of tumor epicenter (macula, macula to equator, sociated features included subretinal fluid (n=269 [11%]), or equator to ora serrata), distance of nearest tumor margin to orange pigment (n=193 [8%]), drusen (n=1356 [54%]), optic disc margin and foveola (in millimeters), largest tumor basal dimension and thickness (in millimeters), tumor color RPE atrophy (n=271 [11%]), RPE hyperplasia (n=208 (pigmented, mixed, or nonpigmented), and presence of amela- [8%]), RPE fibrous metaplasia (n=207 [8%]), RPE de- notic halo. If an eye had more than 1 nevus, then the largest tachment (n=33 [1%]), and retinal invasion (n=4 [Ͻ1%]). nevus was included in the analysis. Other related data in- Ocular ultrasonography revealed acoustic solidity in 1185 cluded subretinal fluid, orange pigment, drusen, retinal pig- eyes (64%) and hollowness in 458 eyes (25%). Other fea- ment epithelial (RPE) alterations (hyperplasia, detachment, fi- tures included a surrounding amelanotic halo in 119 eyes brosis, or atrophy), and choroidal neovascular membrane. (5%) and choroidal neovascularization in 12 (Ͻ1%). The nevus and related features were then analyzed with re- Transformation into melanoma was diagnosed in 180 gard to transformation (growth) into melanoma. Growth into eyes (7%) (Figure 1 and Figure 2). The growth mea- melanoma was defined as enlargement in the basal dimension surements and rates are listed in Table 1. The Kaplan- or thickness of at least 0.5 mm. Statistical analysis was per- formed regarding time to detection of transformation into mela- Meier estimates of time to growth are listed in Table 2. noma and features at presentation predictive of transforma- Univariable and multivariable analyses of risk factors for tion into melanoma. growth of choroidal nevus into melanoma are listed in A series of univariate Cox proportional hazards regres- Table 3 and Table 4. Through multivariable analysis, sions were used to assess the degree of relationship of all of the we found that factors predictive of growth into mela- variables at presentation to growth into melanoma. All of the noma included tumor thickness greater than 2 mm (HR, variables were analyzed as discrete variables except for patient 2.09; PϽ.001), subretinal fluid (HR, 3.16; P=.002), symp- age at presentation, tumor basal dimension, tumor thickness, toms (HR, 2.34; P=.002), orange pigment (HR, 2.75; and distance of tumor to optic disc margin and foveola, which PϽ.001), tumor margin within 3 mm of the optic disc were evaluated as continuous variables.
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