CPC13 Integration of clinicopathological features and molecular testing using a gene fusion assay and next-generation sequencing in melanocytic tumours: experience of a newly established service

Abstract

Recent advances in molecular techniques have transformed our understanding of the classification and prognostication of melanocytic lesions. The current World Health Organization classification integrates molecular findings with clinical and pathological features into nine biological pathways, each representing a spectrum from benign to malignant neoplasms. Furthermore, aberrations such as copy number variations and TERT promoter mutations have been linked to more aggressive behaviour. We present our recent experience of implementing molecular testing, including a gene fusion assay and next-generation sequencing (NGS), and demonstrate its impact on the classification and risk stratification of melanocytic tumours. We present six cases illustrating how to integrate molecular findings with histopathological and immunohistochemical features. These cases highlight three points. Firstly, characterization of melanocytic lineage by association with driver aberrations, for example Reed naevus with MYO5A::NTRK3 fusion, and WNT-activated deep penetrating melanoma with mutations in NRAS and CTNNB1. Secondly, classification of melanocytic lesions with desmoplastic stroma, for example desmoplastic Spitz naevus with HRAS mutation, desmoplastic melanoma with NF1 mutation, and the recently described sclerosing melanocytoma with MAP2K1 in-frame deletions. Thirdly, the utility of NGS in risk stratification of ambiguous melanocytic tumours, including supporting the morphological impression of naevoid melanoma with abnormalities including TERT promoter mutations and high mutational burden.