Histopathological Analysis Revealed Melanosome-Retaining Fibroblasts and Autophagy-Impaired Macrophages in Ashy...

Ashy dermatosis is a rare acquired dermal hyperpigmented disorder classified as a subtype of macular pigmentation of uncertain etiology. Recent studies have suggested that fibroblasts, in addition to macrophages known as melanophages, can phagocytose melanosomes under in vitro conditions. To clarify the cellular competition involved in dermal melanosome uptake, we examined 14 biopsy samples from patients with ashy dermatosis and performed histopathologic and immunohistochemical analyses. Autophagy-related markers involved in the autolysosomal degradation pathway were additionally evaluated in a subset of cases (n = 7) and compared with healthy controls. Our findings demonstrated that fibroblasts exhibited significantly greater melanosome uptake than macrophages (p = 0.0049). In the subset analysis, p62 accumulation was significantly increased in dermal macrophages from patients with ashy dermatosis compared with healthy controls (p = 0.0101), suggesting impaired autophagic degradation. These findings propose a novel pathogenic mechanism in ashy dermatosis, in which fibroblasts may contribute more substantially than macrophages to melanosome uptake while also exhibiting impaired autophagic degradation, thereby promoting persistent dermal hyperpigmentation.