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

In her presentation, Sharon Bajaj discusses the implications of molecular profiling for diagnosing melanoma, particularly at the borderline of melanoma in situ (MIS). Despite rising melanoma incidence since 1975, there has been no corresponding decrease in invasive melanoma cases, suggesting a problem of overdiagnosis, where non-threatening cases may be unnecessarily identified. Factors contributing to this issue include heightened detection pressures due to advanced imaging technologies like dermoscopy, increased biopsy incentives in the healthcare system, and evolving pathology interpretations over time, termed "pathologic drift." She highlights how molecular profiling, such as the pigmented lesion assay (PLA) and immunohistochemistry (e.g., PRAME), plays a role in diagnosing borderline lesions. While these tests have potential benefits, they can also contribute to mislabeling benign conditions as malignant, exacerbating overdiagnosis. Bajaj cautions against using these tests indiscriminately in low-prevalence populations, as they could lead to unnecessary biopsies without proven mortality benefits. She advocates for further studies to validate the clinical relevance of molecular profiling in melanoma diagnosis and the need for precise risk stratification to prevent the harms of overdiagnosis. Additionally, she refers to ongoing research aimed at identifying molecular markers that could distinguish benign lesions from those likely to become invasive, underscoring the complexity of developing such tools amidst existing diagnostic challenges.