TY - JOUR
T1 - Clinicopathological analysis of primary intestinal diffuse large B-cell lymphoma
T2 - Prognostic evaluation of CD5, PD-L1, and Epstein-Barr virus on tumor cells
AU - Ishikawa, Eri
AU - Kato, Seiichi
AU - Shimada, Kazuyuki
AU - Tanaka, Tsutomu
AU - Suzuki, Yuka
AU - Satou, Akira
AU - Kohno, Kei
AU - Sakakibara, Ayako
AU - Yamamura, Takeshi
AU - Nakamura, Masanao
AU - Miyahara, Ryoji
AU - Goto, Hidemi
AU - Nakamura, Shigeo
AU - Hirooka, Yoshiki
N1 - Funding Information:
The authors thank Y. Katayama, Y. Inagaki, K. Matsubara, and K. Kito for technical assistance and the following collaborators for providing patient clinical data and specimens: Anjo Kosei Hospital, Chukyo Hospital, Ekisaikai Hospital, Ishikawa Prefectural Central Hospital, Japanese Red Cross Society Nagano Hospital, Kagawa University Hospital, Kanazawa City Hospital, Kanazawa University Hospital, Koseiren Takaoka Hospital, Matsunami General Hospital, Nagoya City East Medical Center, Shizuoka Saiseikai General Hospital, Toukatsu Hospital, Tokai Central Hospital, Toyohashi Municipal Hospital, Toyota Memorial Hospital, University Hospital Kyoto Prefectural University of Medicine, and University of Fukui Hospital.
Publisher Copyright:
© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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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U2 - 10.1002/cam4.1875
DO - 10.1002/cam4.1875
M3 - Article
C2 - 30449068
AN - SCOPUS:85056781509
VL - 7
SP - 6051
EP - 6063
JO - Cancer Medicine
JF - Cancer Medicine
SN - 2045-7634
IS - 12
ER -