title: Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem-cell phenotype.
abstract: BACKGROUND
  Multiple congenital melanocytic naevi (CMN) in one individual are caused by somatic mosaicism for NRAS mutations; however, the lineage of the mutated cells remains uncertain.
  
  
  OBJECTIVE
  To test the hypothesis that CMN may be derived from cutaneous stem cells.
  
  
  METHODS
  Sixty-six CMN samples from 44 patients were stained for immunohistochemical (IHC) markers of melanocytic differentiation (TYR, TRP1, TRP2, LEF1, MITF, cKit), pluripotency (nestin, fascin, CD133, CD20, CD34), monocyte/macrophage lineage (CD68, CD163, CD14), proliferation (Ki67) and MTOR/Wnt-signalling pathway activation (pS6, β-catenin). Semiquantitative scoring compared samples with naevus cell nesting (group 1) with those with only diffuse dermal infiltration (group 2). Transmission electron microscopy (TEM) was performed on 10 samples.
  
  
  RESULTS
  A normal melanocyte population was seen overlying many dermal CMN. Group 1 samples were significantly more likely to express melanocytic differentiation markers than group 2, and expression decreased significantly with depth. Expression of these markers was correlated with each other, and with nestin and fascin. CD20 staining was positive in a substantial proportion and was stronger superficially. Expression of β-catenin and pS6 was almost universal. Some samples expressed monocyte/macrophage markers. TEM revealed variable naevus cell morphology, striking macromelanosomes, double cilia and microvilli.
  
  
  CONCLUSIONS
  Congenital melanocytic naevi development frequently coexists with normal overlying melanocyte development, leading us to hypothesize that in these cases CMN are likely to develop from a cell present in the skin independent of, or remaining after, normal melanocytic migration. IHC and TEM findings are compatible with CMN cells being of cutaneous stem-cell origin, capable of some degree of melanocytic differentiation superficially.
authors.affiliation: Paediatric Dermatology, Great Ormond Street Hospital for Children, London, WC1N 3JH, UK. v.kinsler@ucl.ac.uk
authors.forename: V A
authors.initials: VA
authors.lastname: Kinsler
authors.forename: G
authors.initials: G
authors.lastname: Anderson
authors.forename: B
authors.initials: B
authors.lastname: Latimer
authors.forename: D
authors.initials: D
authors.lastname: Natarajan
authors.forename: E
authors.initials: E
authors.lastname: Healy
authors.forename: G E
authors.initials: GE
authors.lastname: Moore
authors.forename: N J
authors.initials: NJ
authors.lastname: Sebire
mesh_terms: D000943:Antigens, Differentiation / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019070:Cell Lineage; D006801:Humans; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D014411:Neoplastic Stem Cells / Q000000981:diagnostic imaging* / Q000378:metabolism; D009508:Nevus, Pigmented / Q000151:congenital* / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D012867:Skin / Q000166:cytology; D012878:Skin Neoplasms / Q000151:congenital* / Q000378:metabolism / Q000648:ultrastructure; D014463:Ultrasonography
chemical_list: D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor