Several genetic studies on HS have thus focused mainly on Notch signaling alterations with a particular emphasis on the GSC; indeed, loss-of-function pathogenic variants in NCSTN, PSEN1, and PSENEN explain a subset of familial HS cases [13], leading it to be considered a single-gene disorders with an autosomal dominant inheritance pattern [9]. Here, NCSTN is linked to histiocytic sarcoma.