Molecular Profiling at the MIS Borderline: Boon or Bane for Melanoma Diagnosis?

In this presentation, Dr. Sharon Bajaj from Memorial Sloan Kettering Cancer Center discusses the complexities of diagnosing borderline melanoma lesions using molecular profiling technologies. While many melanocytic tumors are identifiable as benign or malignant, the diagnosis of borderline lesions remains challenging, particularly with the rise of dermoscopy and an increased focus on subclinical melanomas. The ideal molecular test for melanoma diagnosis would combine diagnostic and prognostic capabilities, yet developing such tests is hindered by inter-rater variability and the nature of excised borderline lesions, which complicates understanding their biological history. Dr. Bajaj covers two promising tools: the Pigmented Lesion Assay (PLA) and immunohistochemistry with PRAME. The PLA, a non-invasive test that extracts RNA from lesions to identify melanoma-associated genes, shows high negative predictive values but is best used in high-risk populations due to significant variability in test performance. PRAME, on the other hand, is an accessible immunohistochemical marker that can improve sensitivity for identifying melanoma in situ compared to other tests but also raises concerns about overdiagnosis. Finally, she notes that the 23-gene assay for gene expression profiling was not specifically designed for borderline cases and has limited data supporting its use in this context. Overall, molecular profiling may enhance early disease detection but may also lead to overdiagnoses and questions regarding clinical relevance. Dr. Bajaj emphasizes the need for careful consideration in employing these tests to ensure they contribute positively to patient outcomes.