However further evidence with immunoglobulin heavy chain gene mutational signatures and immunophenotyping suggest PCNSL has germinal center origin or exposure [31,34,35,36,37] and increasingly, there is evidence PCNSL may demonstrate an overlapping state of differentiation with concurrent expression of germinal center markers such as BCL6 and activation markers such as cyclin D2 or MUM1/Interferon Regulatory Factor 4 (IRF4) [31,38]. This evidence concerns the gene IRF4 and primary central nervous system lymphoma.