Clinicopathological analysis of primary intestinal diffuse large B-cell lymphoma: Prognostic evaluation of CD5, PD-L1, and Epstein-Barr virus on tumor cells

Eri Ishikawa, Seiichi Kato, Kazuyuki Shimada, Tsutomu Tanaka, Yuka Suzuki, Akira Satou, Kei Kohno, Ayako Sakakibara, Takeshi Yamamura, Masanao Nakamura, Ryoji Miyahara, Hidemi Goto, Shigeo Nakamura, Yoshiki Hirooka

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Background: Primary 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. Methods: Tumor specimens from 62 patients consecutively diagnosed with primary iDLBCL at a single institution were analyzed. Results: Our 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. Conclusion: EBV + 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.

Original languageEnglish
Pages (from-to)6051-6063
Number of pages13
JournalCancer Medicine
Issue number12
Publication statusPublished - 12-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


Dive into the research topics of 'Clinicopathological analysis of primary intestinal diffuse large B-cell lymphoma: Prognostic evaluation of CD5, PD-L1, and Epstein-Barr virus on tumor cells'. Together they form a unique fingerprint.

Cite this