PD-1 Expression in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Large B-cell Richter Transformation (DLBCL-RT) A Characteristic Feature of DLBCL-RT and Potential Surrogate Marker for Clonal Relatedness

被引：66

作者：

He, Rong ^{[1
]}

Ding, Wei ^{[2
]}

Viswanatha, David S. ^{[1
]}

Chen, Dong ^{[1
]}

Shi, Min ^{[1
]}

Van Dyke, Daniel ^{[3
]}

Tian, Shulan ^{[4
]}

Dao, Linda N. ^{[1
]}

Parikh, Sameer A. ^{[2
]}

Shanafelt, Tait D. ^{[2
]}

Call, Timothy G. ^{[2
]}

Ansell, Stephen M. ^{[2
]}

Leis, Jose F. ^{[5
]}

Mai, Ming ^{[1
]}

Hanson, Curtis A. ^{[1
]}

Rech, Karen L. ^{[1
]}

机构：

[1] Mayo Clin, Coll Med, Div Hematopathol, Rochester, MN 55905 USA

[2] Mayo Clin, Coll Med, Div Hematol, Rochester, MN USA

[3] Mayo Clin, Coll Med, Lab Genet & Genom, Rochester, MN USA

[4] Mayo Clin, Coll Med, Biomed Stat & Informat, Rochester, MN USA

[5] Mayo Clin, Coll Med, Div Hematol, Scottsdale, AZ USA

来源：

AMERICAN JOURNAL OF SURGICAL PATHOLOGY | 2018年 / 42卷 / 07期

关键词：

PD-1; PD-L1; chronic lymphocytic leukemia; small lymphocytic lymphoma; Richter transformation; diffuse large B-cell lymphoma; clonal relatedness; DEATH LIGAND 1; PROLIFERATION CENTERS; PROGRAMMED DEATH-1; HODGKIN LYMPHOMAS; PDL1; EXPRESSION; T-CELLS; NIVOLUMAB; PD1; CLL; PEMBROLIZUMAB;

D O I：

10.1097/PAS.0000000000001077

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and similar to 2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT. We evaluated PD-1 and PD-L1 expression by immunohistochemistry in 39 CLL/SLL, 15 DLBCL-RT, and 26 other DLBCL. In CLL/SLL, neoplastic B-cell PD-1 expression was weak and restricted to prolymphocytes/paraimmunoblasts within proliferation centers (PCs) and accentuated PCs of all sizes. Neoplastic B-cell PD-1 expression was highly prevalent and demonstrated increased intensity in DLBCL-RT, but in contrast was only rarely seen in other DLBCL (12/15 vs. 1/26; P<0.0001). An excellent correlation (90% concordance) was observed between neoplastic B-cell PD-1 immunohistochemistry positivity and molecularly defined CLL/SLL clonal relatedness in DLBCL-RT. PD-L1 expression was observed on the neoplastic B cells in rare DLBCL-RT and other DLBCL cases (1/15 vs. 1/26; P>0.05) as well as background histiocytes and dendritic cells. Overall survival of DLBCL-RT was significantly inferior to that of the other DLBCL (median, 16.9 vs. 106.1mo; P=0.002). Our findings suggest a biological continuum from prolymphocytes/paraimmunoblasts in CLL/SLL PCs to the neoplastic B-cells in DLBCL-RT. The characteristic PD-1 expression in DLBCL-RT makes it a potential surrogate marker for determining clonal relatedness to CLL/SLL, which may have important prognostic and therapeutic implications.

引用

页码：843 / 854

页数：12

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