The mononuclear Hodgkin’s cells alongside the prominent presence of large, bi- or multinucleated Reed-Sternberg (HRS) cells, which account for less than 2% of the total tumor bulk, display a constitutive pattern of activated signaling pathways due to EBV infection, microenvironment interaction and gene mutations that drive to activation of among others, NF-κB (nuclear factor kappa B), JAK/STAT3 (Janus Kinase/Signal transducer and activator of transcription factor 3), and PI3K/Akt (Phosphoinositide 3-kinase/RACα serine/threonine protein kinase) pathways (6). Here, AKT1 is linked to Epstein-Barr virus infection.