Abstract
BackgroundPrimary intestinal diffuse large B‐cell lymphoma (iDLBCL) is rare. In this study, we investigated the clinicopathological features of this disease to further understand the prognostic value of CD5, programmed cell death ligand 1 (PD‐L1), and Epstein‐Barr virus (EBV) on tumor cells.MethodsTumor specimens from 62 patients consecutively diagnosed with primary iDLBCL at a single institution were analyzed.ResultsOur series consisted of EBV‐positive (EBV+) iDLBCL (n = 10), de novo CD5+ iDLBCL (n = 4), and DLBCL, not otherwise specified (DLBCL‐NOS; n = 48). Notably, seven of 10 EBV+ cases had treated lymphoma‐associated (n = 4) or iatrogenic immunodeficiency (n = 3). Two of 10 EBV+ cases expressed PD‐L1 on tumor cells, whereas the remaining eight were positive for PD‐L1 on microenvironment immune cells. Only one DLBCL‐NOS case had neoplastic PD‐L1 expression with a giant cell‐rich appearance. Both EBV‐harboring and PD‐L1 expression on tumor cells, but not CD5, were associated with worse overall survival (OS) in iDLBCL patients receiving rituximab‐containing chemotherapy (P = 0.0354, P = 0.0092, and P = 0.1097, respectively). Multivariate analysis identified PD‐L1 positivity on tumor cells (P = 0.0106), PD‐L1 negativity on microenvironment immune cells (P = 0.0193), and EBV positivity (P = 0.0324) as poor independent prognostic factors for OS. Among iDLBCL cases without any EBV association, CD5 positivity, or neoplastic PD‐L1 expression, high PD‐L1 expression (≥40%) on microenvironment immune cells predicted an extremely favorable outcome.ConclusionEBV+ iDLBCL mainly comprised immunodeficiency‐associated patients, which may highlight the specificity of the intestine. PD‐L1 expression on tumor cells or microenvironment immune cells was found to have an opposite prognostic impact in iDLBCL.
Highlights
The remaining eight Epstein‐Barr virus (EBV)+ cases were positive for programmed cell death ligand 1 (PD‐L1) on microenvironment immune cells, with a higher rate than in EBV− intestinal diffuse large B‐cell lymphoma (iDLBCL) (100% vs 65%, P = 0.090)
The present study aimed to clarify the prognostic significance of EBV, CD5, and programmed cell death (PD)‐L1 expression associated with
Multivariate analysis of nodal and extranodal diffuse large B‐cell lymphoma (DLBCL) revealed that patients with small intestinal involvement had worse overall survival (OS) in the rituximab era.[5]
Summary
The gastrointestinal tract is the most common (34%‐44%) extranodal site of involvement in diffuse large B‐cell lymphoma (DLBCL).[1,2] Small and large intestinal lymphoma behave differently than gastric lymphoma, with comparatively lower survival and account for approximately 25% of gastrointestinal DLBCL cases.[3,4] DLBCL patients with small intestine involvement have significantly worse overall survival (OS) and often require a combination of chemotherapy and surgery due to increased complication rates and decreased survival.[5,6]. EBV+ DLBCL affects extranodal sites in approximately two‐thirds of elderly immunocompetent patients.[9] We previously reported that EBER positivity is associated with an adverse outcome in patients with primary gastric DLBCL.[14] the issue of tumor cells harboring EBV has not been addressed in primary intestinal DLBCL (iDLBCL) due to diagnostic difficulties. Large cohort studies have shown a higher incidence of extranodal disease including central nervous system (CNS) involvement and adverse outcome in patients with CD5+ DLBCL.[26,27] involvement of the gastrointestinal tract has been reported to occur less frequently in CD5+ DLBCL than CD5− DLBCL.[28] the prognostic significance of CD5 positivity in primary iDLBCL has not been well analyzed. We investigated 62 cases of primary iDLBCL to further understand the clinicopathological features and biological properties of this rare disease by surveying the association of EBV and the expression of CD5 and PD‐L1
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