CD20-negative de novo diffuse large B-cell lymphoma in HIV-negative patients: a matched case-control analysis in a single institution

Abstract

Background: HIV-negative, CD20-negative de novo diffuse large B-cell lymphoma (DLBCL) patients has rarely been reported. To elucidate the nature of this entity, we retrospectively reviewed the data of 1,456 consecutive de novo DLBCL patients who were treated at Sun Yat-Sen University Cancer Center between January 1999 and March 2011.

Methods: The pathologic characteristics of CD20-negative patients, clinical features, response to initial treatment, and outcomes of 28 patients with available clinical data (n = 21) were reviewed. Then, a matched case-control (1:3) analysis was performed to compare patients with CD20-negative and -positive DLBCL.

Results: The median age of the 28 CD20-negative DLBCL patients was 48 years, with a male-female ratio of 20:8. Seventeen of 22 (77.3%) CD20-negative DLBCL cases were of the non-germinal centre B-cell (non-GCB) subtype. High Ki67 expression (≥ 80%), an index of cell proliferation, was demonstrated in 17 of 24 (70.8%) cases. Extranodal involvement (≥ 1 site) was observed in 76.2% of the patients. Following initial therapy, 9 of 21 (42.9%) cases achieved complete remission, 4 (19%) achieved partial remission, 1 (4.8%) had stable disease, and 7 (33.3%) had disease progression. The median overall survival was 23 months. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 30.5% and 35%, respectively. A matched case-control analysis showed that patients with CD20-negative and -positive DLBCL did not exhibit a statistically significant difference with respect to the main clinical characteristics (except extranodal involvement), whereas the patients with CD20-positive DLBCL had a better survival outcome with 3-year PFS (P = 0.008) and OS (P = 0.008) rates of 52% and 74.1%, respectively.

Conclusions: This study suggests that HIV-negative, CD20-negative de novo DLBCL patients have a higher proportion of non-GCB subtype, a higher proliferation index, more frequent extranodal involvement, a poorer response, and a poorer prognosis to conventional treatment compared to patients with CD20-positive DLBCL. Further studies are warranted to investigate new target and optimal therapy of CD20-negative de novo DLBCL.

Figure 1

Typical morphology and immunophenotype of CD20-negative diffuse large B-cell lymphoma ranged from A to L. A (Hematoxylin-Eosin staining): Diffuse proliferation of large tumor cells with large nucleus, prominent nucleoli, abundant cytoplasm, and the karyokinesis were easy to be observed; B: Tumor cells were positive for CD45 (LCA); C: Tumor cells were negative for CD20; D: Tumor cells were positive for CD79a; E-F: Tumor cells were negative for CD3, CD5; G: Tumor cells were strong positive for CD30; H-I: Tumor cells were negative for CD10 and BCL-6; J: Tumor cells were positive for MUM-1; K: Tumor cells had a very high proliferation index with Ki-67 highlighting more than 90% tumor cells; L: Tumor cells were negative for EBERs ISH.

Figure 2

Progression-free survival (PFS) and overall survival (OS) of patients with CD20-negative diffuse large B-cell lymphoma (DLBCL) and CD20-positive DLBCL. (A): PFS of patients with CD20-negative DLBCL (n = 21, dotted line) and patients with CD20-positive DLBCL (n = 63, solid line). (B): OS of patients with CD20-negative DLBCL (n = 21, dotted line) and patients with CD20-positive DLBCL (n = 63, solid line).