Incidence and tumour location of iris melanoma in Denmark: a nationwide cohort study (1943-2021)

Iris melanoma differs from posterior uveal melanoma in clinical behaviour and location. Situated anteriorly, it is directly exposed to ultraviolet radiation (UVR), unlike posterior melanomas shielded by the lens. However, epidemiological patterns and UVR's role in iris melanoma development remain poorly understood. Therefore, we investigated long-term incidence trends of iris melanoma in Denmark, focusing particularly on tumour location in relation to sun exposure.

We conducted a nationwide retrospective cohort study of patients diagnosed with iris melanoma in Denmark from 1943 to 2021. Population-based data were obtained from national registries and institutional records, with tumours classified by anatomical location as inferior, superior or mixed.

We included 405 patients. Disease-specific mortality was 3% (12 patients), mainly in American Joint Committee on Cancer c-subcategories with secondary glaucoma and extensive anterior chamber angle involvement. Over the study period, the age-standardised incidence increased substantially. Inferiorly located tumours constituted 58% during 1943-1962 and 84% during 2003-2021 (p<0.001), with age-standardised incidence increasing from 0.15 per 100 000 in 1943-1954 to 0.97 per 100 000 in 2010-2014. Superior melanomas demonstrated non-significant increases over time. Age-period-cohort analysis revealed effects of both age and calendar period. The age effect demonstrated a sharp increase after age 65 years for both inferior and superior tumours while the calendar period effect showed increases only for inferior iris melanomas.

Iris melanoma incidence increased significantly over the 79-year study period, primarily driven by inferior iris tumours most exposed to the sun. These findings support the hypothesis that UVR plays a pathogenic role in iris melanoma development.