This fact may be explained through two alternative possibilities: (i) the second hit mutation occurred as a secondary event within a neurofibroma that had already developed polyclonally, and thus only a subpopulation of S100β+ cells is (−/−), or (ii) the tumors arose through a two-hit mechanism within a stem/progenitor cell that gave rise to most tumor cells, but the proliferating neoplastic clone stimulated the proliferation of infiltrating nonneoplastic cells such as heterozygous Schwann cells, mast cells, and fibroblasts. This evidence concerns the gene S100B and plexiform neurofibroma.