The clinical significance of increased large cells in marginal zone lymphoma

Marginal zone lymphoma (MZL) is a primary, indolent small B-cell lymphoma. Subtypes include nodal, splenic, and those of extranodal mucosa-associated lymphoid tissue (MALT). These are slow growing and generally exhibit low rates of transformation to diffuse large B-cell lymphoma (DLBCL). At initial diagnosis, there can be an increase in large cells (LCs) that does not meet criteria for DLBCL. Prior studies have noted this finding, but the clinical significance of these LCs has not been well established. A total of 161 cases of MZL from 1994 to 2021 were evaluated, including all subtypes. There were 33 cases with increased LCs (>10 LCs per high-power field [hpf]), with the majority containing >15 LCs/hpf (28/33) and 128 cases without increased LCs. Cases with increased LCs were significantly more likely to have a Ki-67 proliferation index of ≥30% (P < .0001). Overall survival was not significantly different between the groups but progression-free survival was significantly worse in the LC group (P < .0001). MZL with increased LCs was also associated with a higher stage at diagnosis (P = .0035), was more likely to transform to DLBCL (P = .0016), and had a greater frequency of relapse (P < .0001). Subgroup analysis showed that both nodal and MALT LC groups had a worse progression-free survival and a higher rate of relapse than their standard nodal and MALT lymphoma counterparts, but only within the MALT subgroup did the LC cases present at a higher stage and have a higher rate of transformation to DLBCL than the standard cases. Although larger studies are needed for validation, these results suggest that the presence of LCs in MZL may serve as a useful prognostic indicator and potentially help guide clinical decision-making.