Immunohistochemical CD20-negative change in B-cell non-Hodgkin lymphomas after rituximab-containing therapy

CD20^- change after rituximab-containing therapy is considered one of the main reasons of rituximab resistance of B-cell non-Hodgkin lymphomas (B-NHLs). However, the clinicopathological characteristics of B-NHL with CD20^- change are not entirely understood. In this study, 252 B-NHL patients who were CD20⁺ at initial diagnosis, whose diseases relapsed or were refractory after rituximab-containing therapy, and who were re-biopsied between 2000 and 2018, were included. The median number of rituximab administration was 11 (range, 1-48). Completely negative (cCD20^-) and partially negative (pCD20^-) change of CD20 was observed in 49 (20%) and 16 (6%) cases, respectively. Among cCD20^- and pCD20^- cases, 74% and 62% of the cases changed to CD20^- at the second relapse or later, respectively. Overall survival was significantly shorter in cCD20^- follicular lymphoma (FL) cases than in CD20⁺ FL cases. Seven histopathological patterns, such as CD20^- change without histological change, histological transformation (HT) to CD20^- diffuse large B-cell lymphoma, and proliferation of plasmablastic/plasmacytoid tumor cells, were associated with CD20^- change. HT occurred more frequently in FLs with CD20^- change than in FLs continuously expressing CD20 (P < 0.0001), regardless of the timing of HT. Nine out of 25 cases (36%) showed regain or heterogeneous regain of CD20 expression. In conclusion, 20% and 6% of the 252 B-NHL cases show cCD20^- and pCD20^- changes with 7 histological patterns after rituximab-containing therapy. Because changes in morphology and CD20 expression after rituximab-containing therapy vary, and recovery of CD20 expression is not rare, careful follow-up and re-biopsy in B-NHL patients are recommended.