Melanocyte

  • Pigment-producing dendritic cell derived from neural crest; found in skin, hair, uveal tract of eye (choroid, iris, ciliary body), leptomeninges, and inner ear (striae vascularis of cochlea)
  • Survival/migration during embryogenesis depends on specific interactions such as c-kit activation contributing to migration and development of melanocytes and melanoblasts
  • Resides in basal layer with ratio of one melanocyte to ten basal keratinocytes (do not confuse with epidermal melanin unit where one melanocyte in contact with 36 keratinocytes)
  • Melanocytes do not form junctions with keratinocytes (hence, artifactual halo on H&E)
  • Function: production of melanin pigment with subsequent transfer to keratinocytes, absorption of UV radiation, and protection from UV-induced mutations
  • Melanin: synthesized in melanosome (specialized type of lysosome) and passes through series of stages (I–IV) before melanosome transferred to keratinocyte via phagocytosis of melanocyte tips (apocopation); melanin precursors acted upon by copper-dependent enzyme tyrosinase; two types of pigment (Figure 1.4)
    • Figure 1.4 Melanin biosynthetic pathway
      Figure 1.4 Melanin biosynthetic pathway
      Pheomelanin: red–yellow in color, synthesized in pheomelanosomes (spherical structure, microvesicular internal structure)
    • Eumelanin: brown or black in color, eumelanosome (oval-shaped, longitudinally oriented with lamellar internal structure)
  • Melanin stimulated by melanocyte-stimulating hormone (MSH), which is derived from larger precursor propiomelanocortin (POMC); POMC also a precursor for ACTH, which is why ↑ hyperpigmentation seen in Addison’s disease
  • Melanocortin-1 receptor (MC1R) controls which type of melanin is produced by melanocytes; loss of function in MC1R results in ↑ pheomelanin (red hair) and ↓ eumelanin; thus, fair skin without the more protective pigment and more prone to damage from UV radiation with subsequent ↑ risk for melanoma
  • Hair melanocytes: one melanocyte to five keratinocytes; graying caused by gradual decrease in number of follicular melanocytes
  • Chronic sun exposure results in melanocytes creating larger melanosomes
  • Racial differences NOT due to differences in number of melanocytes, but rather the size, distribution, and number of melanosomes (all races have SAME melanocyte density)
    • Dark-skinned: larger melanosomes, ↑ melanization, ↓ melanosome degradation, and melanosomes transferred as individual organelles
    • Light-skinned: smaller melanosomes and transferred as membrane-bound clusters (with 3–6 melanosomes)