Background and design: Although two cardinal skin manifestations of neurofibromatosis are cutaneous neurofibromas and cafe au lait spots, the pathogenesis of cafe au lait spots are very poorly known compared with that of cutaneous neurofibromas. Thus, the cafe au lait spots in two Japanese infants were clinically, histologically, and electron-microscopically investigated.
Observations: Some of the cafe au lait spots in the mongolian spots were surrounded by white halos. Histologically, in the cafe au lait spots, the epidermal basal cells had abundant melanin pigment, but macromelanosomes were not seen throughout the epidermis. In the white halo, the epidermal basal cells had a small amount of melanin pigment. Electron microscopically, the cafe au lait spots and their white halos had many subepidermal and intraepidermal nerves that belonged to free nerve endings. All the cutaneous nerves were mature. Some of the intraepidermal nerves had partially or completely naked axons that contacted tightly with the cytomembranes of the basal keratinocytes. Some of the axons in the subepidermal nerves showed degenerative changes only in the white halos. No ultrastructural pathologic changes were observed in the melanocytes, the epidermal keratinocytes, or melanosomes in those cells in the cafe au lait spots and their white halos; also, dermal melanocytes were absent in the both areas.
Conclusions: The increase of the cutaneous nerves and the absence of dermal melanocytes in the cafe au lait spots and their white halos may be considered as characteristic histologic cutaneous findings in infants with neurofibromatosis. However, no evidence indicates that the cutaneous nerves may participate closely in the pathogenesis of the white halos.