Novel classification of SMZL. Mutational analysis allows to classify SMZL in 4 clusters: PA (PI3K/AKT), DMT (DNA damage response/MAPK/Toll-like receptor), NNK (NF-kB/NOTCH/KLF2), and CBS (cytokine/BCR/spliceosome). SMZLs can be further distinguished based on transcriptome analyses of spleen sections in immune-silent, which express mostly B-associated genes, or immune-suppressive, which express also T-associated genes coding for immunomodulatory molecules.