From melanin-positive to melanin-actionable: Spatial pigment phenotyping for precision melanoma phototherapy

Stockert and Blázquez-Castro have skilfully changed the perspective on melanin, turning it from a histological pigment to a possible therapeutic substrate in melanoma. However, if melanin is considered a binary and/or spatially uniform property, then translation may be restricted. The amount of pigment, its molecular structure, redox status, and intracellular localization and interactions with living tumour and immune cells could account for the ability of melanin to shield from photodynamic damage, enhance photothermal damage, or represent a photodynamic damage-resistant state. We suggest a spatial melanin phenotype, based on pigment burden, physicochemical state, cellular compartment, microenvironmental context and optical response. A combination of validated histochemistry and image analysis (digital image) with selected spectroscopic or spatial method might be a resource adaptive workflow. The hypothesis of prospective studies is whether this phenotype predicts temperature distribution, and oxidative injury, immune activation and residual viable tumour more accurately than conventional pigmentation grading. This would adjust the place of histochemistry as a tool of phototherapy selection and dosimetry that can be used for action.