Next-generation sequencing of a large uveal melanoma with whole genome doubling and a PBRM1 mutation

PURPOSE: To report a large uveal melanoma with extra-scleral extension which underwent spontaneous infarction and its unique molecular signature profile. OBSERVATIONS: An 81-year-old female presented with a blind, painful eye. Intraocular pressure was 48 mm Hg. There was a large subconjunctival melanotic mass overlying a choroidal melanoma with anterior extension involving the ciliary body and the iridocorneal angle and iris. Ultrasonography confirmed a dome-shaped anterior cilio-choroidal mass with extra-scleral extension. The patient underwent enucleation and pathologic evaluation confirmed cilio-choroidal melanoma. The posterior half of the tumor involving the ciliary body and the extra-scleral component were spontaneously infarcted and were composed of large melanophages. Next-generation sequencing demonstrated a splice site mutation in PBRM1 and whole-genome doubling in addition to a GNAQ hotspot mutation, chromosome 3 loss and 8q gain. CONCLUSIONS AND IMPORTANCE: This case of a large, auto-infarcted uveal melanoma demonstrates a PBRM1 mutation and whole-genome doubling.