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Clinicopathological analysis of primary intestinal diffuse large B‐cell lymphoma: Prognostic evaluation of CD5, PD‐L1, and Epstein‐Barr virus on tumor cells
Author(s) -
Ishikawa Eri,
Kato Seiichi,
Shimada Kazuyuki,
Tanaka Tsutomu,
Suzuki Yuka,
Satou Akira,
Kohno Kei,
Sakakibara Ayako,
Yamamura Takeshi,
Nakamura Masanao,
Miyahara Ryoji,
Goto Hidemi,
Nakamura Shigeo,
Hirooka Yoshiki
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1875
Subject(s) - cd5 , diffuse large b cell lymphoma , lymphoma , tumor microenvironment , epstein–barr virus , rituximab , immune system , medicine , cancer research , virus , pathology , immunology
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.

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