Uveal melanoma clinical presentation and outcomes have been shown to vary by race.31-34 In a study of race and uveal melanoma in 8100 patients, Caucasian patients were noted to present at an older age than Hispanic, Asian and African American patients (58, 48, 44 and 52 years; p<0.001), with smaller tumor basal dimension (11, 12, 12, 13 mm, p<0.001) and smaller tumor thickness (5.4, 7.1, 6.5, 7.5 mm, p<0.001).33 Although no significant difference was demonstrated in the 8100 patients in terms of melanoma-related metastasis or death based on race, the relative risk for metastasis, compared with Caucasians, was 0.31 for African Americans, 0.73 for Hispanics and 1.42 for Asians.33 An analysis of the Surveillance, Epidemiology and End Results (SEER) registries from 2004 to 2014 in 4130 patients with uveal melanoma revealed that non-white patients (compared to white patients) were more likely to be diagnosed with uveal melanoma at a younger age (<55 years old) (48% vs 33%, p<0.001) and receive management of primary enucleation (OR, 1.45 95% CI, 1.12-1.88).32 Disease-specific survival did not vary significantly by race in that SEER analysis.32 Using race as a variable can be problematic given that race is a social category and self-identified and not a biological category and race can change over time and vary across societies.36,37 FST could be a more objective alternative to race to estimate a patient’s skin tone and evaluate whether skin tone has an influence on uveal melanoma features and outcomes.
Cutaneous melanoma has been shown in multiple studies to present at a more advanced stage and to have worse outcomes in patients with darker FST.10-17 Determining whether this is due to skin color or socio-demographic status has been problematic.11 A recent study of 135 patients with cutaneous melanoma from Malta showed that patients with FST I and II were more likely to have invasive disease than those with FST III and IV.3 Conjunctival melanoma incidence has been increasing over time in the white populations of Europe and the United States.38,39 In Finland, the annual age-adjusted incidence increased from 0.4 to 0.8 per million white inhabitants between 1967 and 2000.38 In the United States, the age-adjusted incidence rate for white men increased 295% between 1973 and 199939. The incidence and outcomes of conjunctival melanoma based on race have not been well studied because of the rarity of this malignancy. However, a recent study of conjunctival melanoma outcomes based on FST in 540 patients confirmed that this tumor is far more common in patients with lower FST, but FST was not associated with various outcomes including vision loss, tumor recurrence, exenteration metastasis or death.18
In this report, we describe the relationship of FST and uveal melanoma clinical features and outcomes. We have shown that patients with darker skin tone are less likely to be classified racially as white, present at a younger age, and are more likely to have ocular melanocytosis and worse visual acuity at presentation. Patients with darker skin tone are less likely to have high risk tumor cytogenetics based on TCGA classification. Furthermore, we have documented that FST is a predictor of melanoma-related metastasis as well as TCGA group and that patients with darker skin tone may be less likely to develop melanoma-related metastasis than those with lighter skin tone.
It is well established that light iris color is associated with increased risk of iris melanocytic lesions and uveal melanoma.20,40 The association between iris color and uveal melanoma could be independent of skin tone or it could actually represent an accurate surrogate for FST. A recent Dutch study of 412 patients with uveal melanoma and 5951 control patients showed that patients with light iris colors of green/hazel (Odds Ratio=3.64) or blue/grey (Odds ratio=1.38) demonstrated higher crude risk of uveal melanoma than those with brown irides.19 Furthermore, the biology of uveal melanoma in eyes with different iris colors can differ, with chromosome 3 and 8 aberrations imparting a greater influence with reduction in patient survival with light irides compared to brown irides.30
There are several limitations to this study, beginning with its retrospective nature. Despite the retrospective nature of the data collection, the FST had been charted at date first seen prospectively over 15 years. The ideal method of FST collection has been described with observation of skin tone in non-sun-exposed skin, such as the buttocks or inner arm6. As this is often not practical in an ophthalmology clinic, facial skin, particularly in the sub-brow, minimally-sun-exposed area, was assessed as a surrogate which could be less accurate than purely non-sun-exposed skin. Another limitation is that outcomes for metastasis and death were per report by the patient, family, or physician, following systemic monitoring on a twice-yearly basis with liver and lung imaging. Data collection ended with the patient last visit or office correspondence to avoid missing metastatic or death events. However, there could have been some overlooked metastatic events. Patients, families, and physicians may have been less likely to report death events than metastatic events which could explain why no firm conclusions can be drawn on this outcome’s relationship with FST. Due to a limited number of patients being followed-up for 6 years or greater, the 10-year outcome data needs to be interpreted with caution.
In conclusion, we present novel observations on the relationship between skin tone using Fitzpatrick Skin Type (FST) and clinical features, genetic outcomes, and metastatic risk of uveal melanoma. In this large cohort of 854 consecutive patients, we have shown that FST I patients are at increased risk for uveal melanoma metastasis and high-risk TCGA tumor cytogenetic classification.