The Disturbance of Melanogenesis and Melanosome Transfer in the Leukoderma Lesions of Extramammary Paget’s Disease

Abstract

We frequently encounter characteristic color variation including hypopigmentation, hyperpigmentation, and erythema in extramammary Paget’s disease (EMPD) lesions. Owing to unclear hypopigmentation, the lesional border of EMPD can be poorly defined and it is likely insufficient to perform its complete resection. Although the existence of Toker’s cells and lack of lesional bFGF production have been reported to cause hypopigmentation inside of EMPD lesions, exact mechanisms of hypopigmentation in EMPD are not fully explored. We experienced three EMPD patients with obviously hypopigmented EMPD macules and histopathologically confirmed a reduced number of melanocytes on the hypopigmented macules and their loss on the erythematous plaques or nodules. An ultrastructu r al analysis on the hypopigmented lesions revealed disturbance of melanosome maturation and melanosome transfer to the adherent Pagets’ cell on the basal layer. No Paget’s cells even adhered to remaining melanocytes with dendrites contained matured melanosome and a few number of matured melanosome complex es were observed in basal keratinocytes. In the present study, we hypothesize that severe disturbance of not only melanogenesis but also melanosome transfer to surrounding Paget’s cells and basal keratinocytes may cause characteristic hypopigmentation in EMPD. Future bioanalysis would reveal molecular mechanisms for hypopigmentation in EMPD.