P060 Analysis of the clinical and molecular features of spitzoid lesions and the use of Idylla to detect gene fusions in a tertiary Irish centre

Abstract

Differentiating benign Spitz naevi (BSN), atypical Spitz tumours (AST) and spitzoid melanomas (SM) can be challenging. While the exact aetiology of these tumours is unknown, gene fusions are thought to play a role in their pathogenesis. Modern molecular based techniques such as IdyllaTM can rapidly identify gene fusions to better define management. We aimed to identify gene fusions and correlate them with clinical findings. We retrospectively examined 20 spitzoid lesions from 2021 to 2025 with traditional immunohistochemistry (IHC) for anaplastic lymphoma kinase (ALK) (D5F3), ROS1 and pan-TRK and with Idylla. Most lesions displayed benign clinical features and 12 were subsequently confirmed on histopathology as BSN. Among these, 10 were from women, whose mean age was 32 years. Seven cases showed positive staining by IHC and Idylla identified five fusions. Only two cases showed unequivocal positivity in both modalities. The remaining eight cases were composed of ASTs and SMs. Clinically, three of these presented similarly as pink papules with atypical vessels. Most (n = 5) were in women and their mean age was 34 years. IHC showed positivity in all cases and only one was positive on Idylla testing. Within this cohort, two patients in their 20s had SMs on the lower extremities with a history of sunbed use. Both cases displayed some positive staining with ALK by IHC. Overall, only three gene fusions showed unequivocal correlation on both IHC and molecular testing. Idylla identified three fusions not found on IHC. Six positive cases were found on IHC that were not identified on Idylla. The clinical and pathological diagnosis of spitzoid-spectrum lesions continues to pose a challenge for clinicians. Our data show both similarities and variation among gene fusions identified using IHC and Idylla. We are currently undertaking a prospective analysis of spitzoid lesions with additional molecular testing to further evaluate how molecular properties might inform future diagnosis and management.