Genetic findings in small melanocytic lesions

Abstract

AbstractPurpose The management of patients with small melanocytic choroidal tumour is controversial. The aim of this presentation is to inform the current debate on patient care by reporting on histological grade of malignancy and genetic type of such tumours.Methods We reviewed our database and selected patients with: a melanocytic tumour having dimensions conforming to the TNM size category 1 (i.e., ‘small’); tumour involving choroid; and clinical and/or histological features of malignancy. Patients with such a ‘small choroidal melanoma’ were excluded if not resident in the British Isles, if the tumour was not treated at our centre between 1993 and 2010 or if they had bilateral uveal melanoma.Results 3132 patients with a choroidal melanoma were identified, of which 1001 (32.2%) were ‘small’. Chromosome 3 status was known in 102 of such small choroidal melanomas. Chromosome 3 loss was detected in 40% of these. Approximately 63% of tumours with chromosome 3 loss showed chromosome 8q gain (cf. 85% of tumours of TNM size category 4). Approximately 70% (i.e., 16 tumours) of small choroidal melanomas with both these genetic abnormalities also showed epithelioid cells. Metastatic death occurred in 4 patients, all of whom had a tumour with chromosome 3 loss, chromosome 8q gain and epithelioid cells.Conclusion Our data suggest that uveal melanomas show ‘crescendo malignancy’ with cumulative genetic abnormalities ultimately resulting in a lethal ‘double‐hit’ of chromosome 3 loss and chromosome 8q gain. We hypothesize that treatment of small choroidal melanomas showing either chromosome 3 loss or chromosome 8q gain prevents such a lethal double hit and hence the onset of metastatic spread. Delayed treatment of small choroidal melanomas may therefore be dangerous. Prognostication is greatly enhanced by multivariate analysis combining TNM staging with histological grading and genetic typing also taking account of the patient’s age and sex. There would seem to be scope for greater use of biopsy so as to provide better counselling of patients and plans for systemic screening and other aspects of care.