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

Rong He, Wei D Ding, David S. Viswanatha, Dong Chen, Min Shi, Daniel Van Dyke, Shulan Tian, Linda N. Dao, Sameer A Parikh, Tait D. Shanafelt, Timothy G. Call, Stephen Maxted Ansell, Jose F. Leis, Ming Mai, Curtis A. Hanson, Karen L. Rech

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼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. 106.1 mo; 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.

Original languageEnglish (US)
Pages (from-to)843-854
Number of pages12
JournalAmerican Journal of Surgical Pathology
Volume42
Issue number7
DOIs
StatePublished - Jan 1 2018

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
B-Lymphocytes
Biomarkers
Immunotherapy
Neoplasms
Cell Death
Histiocytes
Lymphoma, Large B-Cell, Diffuse
Dendritic Cells
Immunity
Lymphoma
Immunohistochemistry

Keywords

  • chronic lymphocytic leukemia
  • clonal relatedness
  • diffuse large B-cell lymphoma
  • PD-1
  • PD-L1
  • small lymphocytic lymphoma, Richter transformation

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

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. / He, Rong; Ding, Wei D; Viswanatha, David S.; Chen, Dong; Shi, Min; Van Dyke, Daniel; Tian, Shulan; Dao, Linda N.; Parikh, Sameer A; Shanafelt, Tait D.; Call, Timothy G.; Ansell, Stephen Maxted; Leis, Jose F.; Mai, Ming; Hanson, Curtis A.; Rech, Karen L.

In: American Journal of Surgical Pathology, Vol. 42, No. 7, 01.01.2018, p. 843-854.

Research output: Contribution to journalArticle

He, Rong ; Ding, Wei D ; Viswanatha, David S. ; Chen, Dong ; Shi, Min ; Van Dyke, Daniel ; Tian, Shulan ; Dao, Linda N. ; Parikh, Sameer A ; Shanafelt, Tait D. ; Call, Timothy G. ; Ansell, Stephen Maxted ; Leis, Jose F. ; Mai, Ming ; Hanson, Curtis A. ; Rech, Karen L. / 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. In: American Journal of Surgical Pathology. 2018 ; Vol. 42, No. 7. pp. 843-854.
@article{a3d208c2f5d74047be65f86c2224a562,
title = "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",
abstract = "Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼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. 106.1 mo; 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.",
keywords = "chronic lymphocytic leukemia, clonal relatedness, diffuse large B-cell lymphoma, PD-1, PD-L1, small lymphocytic lymphoma, Richter transformation",
author = "Rong He and Ding, {Wei D} and Viswanatha, {David S.} and Dong Chen and Min Shi and {Van Dyke}, Daniel and Shulan Tian and Dao, {Linda N.} and Parikh, {Sameer A} and Shanafelt, {Tait D.} and Call, {Timothy G.} and Ansell, {Stephen Maxted} and Leis, {Jose F.} and Ming Mai and Hanson, {Curtis A.} and Rech, {Karen L.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1097/PAS.0000000000001077",
language = "English (US)",
volume = "42",
pages = "843--854",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - PD-1 Expression in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Large B-cell Richter Transformation (DLBCL-RT)

T2 - A Characteristic Feature of DLBCL-RT and Potential Surrogate Marker for Clonal Relatedness

AU - He, Rong

AU - Ding, Wei D

AU - Viswanatha, David S.

AU - Chen, Dong

AU - Shi, Min

AU - Van Dyke, Daniel

AU - Tian, Shulan

AU - Dao, Linda N.

AU - Parikh, Sameer A

AU - Shanafelt, Tait D.

AU - Call, Timothy G.

AU - Ansell, Stephen Maxted

AU - Leis, Jose F.

AU - Mai, Ming

AU - Hanson, Curtis A.

AU - Rech, Karen L.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼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. 106.1 mo; 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.

AB - Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼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. 106.1 mo; 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.

KW - chronic lymphocytic leukemia

KW - clonal relatedness

KW - diffuse large B-cell lymphoma

KW - PD-1

KW - PD-L1

KW - small lymphocytic lymphoma, Richter transformation

UR - http://www.scopus.com/inward/record.url?scp=85048756744&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048756744&partnerID=8YFLogxK

U2 - 10.1097/PAS.0000000000001077

DO - 10.1097/PAS.0000000000001077

M3 - Article

C2 - 29762141

AN - SCOPUS:85048756744

VL - 42

SP - 843

EP - 854

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

IS - 7

ER -