NCSTN and histiocytic sarcoma: Conflicting findings concerning Notch signaling pathway involvement have also been reported; for example, PIK3R3 (Phosphoinositide-3-Kinase Regulatory Subunit 3) and AKT3 (AKT Serine/Threonine Kinase 3), two downstream signaling pathway components of NCSTN and Notch, have been found markedly overexpressed both in lesional and perilesional skin of HS patients when compared to control [64]; the levels of these proteins, in addition to NCSTN and Notch, were significantly higher in patients with mild disease when compared to those with moderate and severe HS.