Histopathologic Regression as a Prognostic and Predictive Biomarker in Primary Cutaneous Melanoma

The presentation summarizes a retrospective single-center study from the University Hospital in Tübingen examining histopathologic regression in primary cutaneous melanoma. Regression, defined as partial disappearance of melanoma cells replaced by fibrosis, vascular proliferation, and immune infiltrates, has been debated as either a sign of effective anti-tumor immunity or a feature that could hide true tumor thickness and lead to understaging. The study included 1,179 melanoma patients who underwent wide excision and sentinel lymph node biopsy between 2010 and 2015, with outcomes including relapse-free survival, distant metastasis-free survival, melanoma-specific survival, and progression-free survival. Regression was seen in 18.8% of patients and was associated with superficial spreading melanoma, lower Breslow thickness, less ulceration, truncal location, and older age. Patients with regression had lower sentinel node positivity and significantly better relapse-free, distant metastasis-free, and melanoma-specific survival. In advanced disease, regression was linked to better response and progression-free survival with checkpoint blockade, but not to targeted therapy in BRAF-mutated patients. Overall, the findings suggest histopathologic regression may reflect pre-existing anti-tumor immunity and serve as a prognostic and predictive biomarker in melanoma.