In the 37 brain tumor patients with POLE or POLD1 germline variants summarized in this study (references are listed in the Additional file 1: Table S6), these were pilomatricomas, fibromas, and particularly café-au-lait macules, also observed in a colorectal cancer patient with a POLE germline variant [70], and one-third of POLE-deficient individuals affected by IMAGEI syndrome without cancer [68]. This evidence concerns the gene POLD1 and Cafe-au-lait spot.