Molecular testing prognostic of low risk in epithelioid uveal melanoma in a child

Abstract

Aims: To characterise a histologically unusual paediatric uveal melanoma by gene expression and karyotypic profiling and assess prognosis.

Methods: The tumour was studied by histopathology, karyotype analysis, single nucleotide polymorphism and gene expression profile analysis for correlation with clinical outcome.

Results: The tumour had predominantly epithelioid histology. Karyotype analysis showed none of the poor prognosis features normally associated with uveal melanoma. single nucleotide polymorphism analysis revealed no imbalance at chromosome 3. Gene expression profiling indicated low risk disease.

Conclusions: We report a child remaining relapse-free 6 years after diagnosis of a very rare uveal melanoma, with poor prognosis epithelioid histology, but gene expression profiling that accurately predicted low risk disease.

Figure 1

Radiology and histopathology (A) Axial CT orbits showed a dome-shaped hyperdense lesion in the left eye with calcification along the anterolateral margin. (B) Axial MRI of the head with gadolinium showed a T2 hypointense lesion measuring 11.6-mm width, 6.3-mm height. (C) Ultrasound showed calcified mass 6.49 mm in height. H&E stain showed tumour confined to globe (D) and predominantly epithelioid cell morphology (E) 40× (F) 60× bleached (G) 60× unbleached. (H) Tumour stained with antibody to melanocytic marker, Mart-1.

Figure 2

Gene Expression Profiling Principal Component Analysis (PCA) of the uveal melanoma against previously analysed and validated tumours. Spheres with asterisks=Class 1 gene expression signature with favourable prognosis; Black spheres=Class 2 gene expression signature with less favourable prognosis; Grey sphere=our patient’s uveal melanoma, which co-localises with the favourable-prognosis tumours with Class 1 gene expression signature. This figure is only reproduced in colour in the online version.