Comprehensive Assessment of CD19 Immunohistochemical Staining in Classic Hodgkin Lymphoma

Classic Hodgkin Lymphoma (CHL) remains difficult to treat in patients with relapsed and refractory disease. The utility of immunotherapies, many of which target B-cell markers, is still under investigation. Although the neoplastic Hodgkin and Reed-Sternberg (HRS) cells are thought to lose most B-cell markers, studies have shown retention of these markers, mainly CD20, in some cases. However, the CD19 staining profile of HRS cells has not been thoroughly assessed and warrants exploration in the era of CD19-directed immunotherapies. We assessed CD19 immunohistochemical staining in 41 cases of CHL and correlated with histologic subtype, other markers, and clinical parameters. 13/41 cases (31.7%) demonstrated CD19 staining in HRS cells, with variation in staining pattern and intensity. When compared with CD19-negative cases, CD19 positivity correlated significantly with mixed-cellularity subtype (53.8% vs. 7.1%, P =0.002), CD20 (46.2% vs. 14.3%, P =0.0485), CD79a (53.8% vs. 9.1%, P =0.006), Epstein-Barr Virus (EBV) positivity (53.8% vs. 7.1%, P =0.002), and older age (median age 52 vs. 28.5 y, P =0.0006). 7/9 (77.8%) EBV+ cases demonstrated CD19 expression on HRS cells. By Kaplan-Meier analysis, CD19+ cases demonstrated worse overall survival compared with CD19- cases ( P =0.011), with EBV-, CD19- cases demonstrating the best overall survival. On the basis of these findings, CD19 expression on HRS cells should not preclude the pathologic diagnosis of CHL, particularly in the context of mixed-cellularity or EBV+ disease. In addition, older patients with mixed-cellularity and/or EBV+ disease may represent a subgroup of patients with CHL who could benefit from CD19-directed therapies.