Metastatic potential of small posterior uveal melanomas.

Purpose: To investigate the prevalence of aggressive traits in small posterior uveal melanomas (UM).

Methods: This retrospective, multicentre cohort study included 804 patients with small posterior UM (≤9 mm in largest basal diameter, ≤3 mm in thickness) from centres in the UK, Germany, and Sweden. Chromosomal aberrations, cytomorphology, nuclear BAP1 expression and circulating tumour cells (CTC) were analysed.

Results: Markers of poor prognosis, including monosomy 3, 8q gain, loss of BAP1 expression, and the presence of CTC, were detected in tumours as small as 3-4 mm in diameter and 1-1.5 mm in thickness. In the cytogenetically analysed subset, monosomy 3 was observed in 23% (41/175), 8q gain in 32% (23/72) and 6q aberrations in 13% (9/71); loss of nuclear BAP1 was seen in 22% (19/88); and CTC were detected in 50% (22/44). There was a strong association between tumour size and the number of clinical risk factors for lesion growth, such as subretinal fluid, orange pigment and acoustic hollowness on ultrasound, whereas these clinical features did not correlate with markers for poor prognosis. Monosomy of chromosome 3, gain of 8q, loss of 1p, gain or loss of 6q, gain or loss of 8p, loss of BAP1 expression, and cytomorphology were associated with worse survival.

Conclusion: Aggressive traits are common in small UM, including those <10 mm³ in volume. Clinical risk factors traditionally used for assessing nevus growth appear more closely related to lesion size than metastatic potential. These findings underscore the importance of identifying novel clinical markers for metastatic risk.