Model of B-cell non-Hodgkin's lymphoma (NHL) histogenesis and pathogenesis.
A lymphoid follicle, constituted by the germinal center (GC) and the mantle zone (MZ), is represented together with the surrounding marginal zone (MargZ). Based on the absence or presence of IgV somatic mutations, B-cell NHL can be distinguished into two broad histogenetic categories: i) pre-GC derived NHL, lacking IgV mutations and including mantle cell lymphoma (MCL); ii) B-cell NHL derived from a cell that transited through the GC and harboring mutated IgV genes, exemplified in the figure by follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), MALT lymphoma, diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). In B-cell chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL), the presence of somatically mutated IgV genes in >50% of the cases also suggests a derivation from a GC experienced B cell.49 For each category, the arrow indicating the histogenetic origin is flanked by the genetic lesion most frequently associated with the lymphoma. In CLL/SLL, as well as in a subset of DLBCL, the relevant cancer related gene has not been identified.
