Methotrexate-associated Lymphoproliferative Disorders in Patients With Rheumatoid Arthritis: Clinicopathologic Features and Prognostic Factors

Daisuke Kurita, Hiroaki Miyoshi, Ayako Ichikawa, Koji Kato, Yoshitaka Imaizumi, Ritsuko Seki, Kensaku Sato, Yuya Sasaki, Keisuke Kawamoto, Joji Shimono, Kyohei Yamada, Reiji Muto, Masahiro Kizaki, Koji Nagafuji, Jun Ichi Tamaru, Michihide Tokuhira, Koichi Ohshima

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Methotrexate (MTX) carries a risk of lymphoproliferative disorders (LPDs), but MTX-associated LPDs (MTX-LPDs) can resolve spontaneously after MTX withdrawal. However, the precise clinicopathologic features of MTX-LPD remain unclear. We aimed to investigate the clinicopathologic characteristics, outcomes, and prognostic factors for histologic types of MTX-LPD. Paraffin-embedded tissue samples of 219 patients with MTX-LPD were analyzed. In total, 30,33,106, and 26 had reactive lymphoid hyperplasia (RH), polymorphic-LPD (Poly-LPD), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphoma (CHL), respectively. The clinicopathologic features of RH, Poly-LPD, DLBCLs, and CHL were as follows: extranodal involvement: 13.8% (4/29), 36.4% (12/33), 69.5% (73/105), and 15.4% (4/26); Epstein-Barr virus encoded RNA positivity: 55.2% (16/29), 71.9% (23/32), 45.3% (48/106), and 76.9% (20/26); necrosis: 0% (0/29), 51.5% (17/33), 34.3% (36/105), and 12.0% (3/25); and Hodgkin Reed-Sternberg-like cells: 17.2% (5/29), 50% (14/28), and 19.8% (21/106). The median duration from MTX withdrawal to the time of disease regression was 10.4, 3.0, 4.2, and 2.7 months for RH, Poly-LPD, DLBCLs, and CHL. After MTX withdrawal, progression-free survival was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL (all P<0.05). Overall survival did not differ significantly between the groups. On univariate analysis, the predictive factors for progression-free survival included plasma cell infiltrate for CHL, eosinophil infiltrate, age above 70 years, and extensive necrosis for Poly-LPD, while they were Epstein-Barr virus encoded RNA positivity and International Prognostic Index risk for DLBCL on multivariate analysis. In conclusion, histologic categorization and histology-specific factors could be useful for predicting MTX-LPD progression after MTX withdrawal.

Original languageEnglish
Pages (from-to)869-884
Number of pages16
JournalAmerican Journal of Surgical Pathology
Volume43
Issue number7
DOIs
Publication statusPublished - Jul 1 2019

Fingerprint

Lymphoproliferative Disorders
Methotrexate
Rheumatoid Arthritis
Hodgkin Disease
Lymphoma, Large B-Cell, Diffuse
Pseudolymphoma
Human Herpesvirus 4
Disease-Free Survival
Necrosis
RNA
Reed-Sternberg Cells
Plasma Cells
Eosinophils
Paraffin
Histology
Multivariate Analysis
Survival

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Methotrexate-associated Lymphoproliferative Disorders in Patients With Rheumatoid Arthritis : Clinicopathologic Features and Prognostic Factors. / Kurita, Daisuke; Miyoshi, Hiroaki; Ichikawa, Ayako; Kato, Koji; Imaizumi, Yoshitaka; Seki, Ritsuko; Sato, Kensaku; Sasaki, Yuya; Kawamoto, Keisuke; Shimono, Joji; Yamada, Kyohei; Muto, Reiji; Kizaki, Masahiro; Nagafuji, Koji; Tamaru, Jun Ichi; Tokuhira, Michihide; Ohshima, Koichi.

In: American Journal of Surgical Pathology, Vol. 43, No. 7, 01.07.2019, p. 869-884.

Research output: Contribution to journalArticle

Kurita, D, Miyoshi, H, Ichikawa, A, Kato, K, Imaizumi, Y, Seki, R, Sato, K, Sasaki, Y, Kawamoto, K, Shimono, J, Yamada, K, Muto, R, Kizaki, M, Nagafuji, K, Tamaru, JI, Tokuhira, M & Ohshima, K 2019, 'Methotrexate-associated Lymphoproliferative Disorders in Patients With Rheumatoid Arthritis: Clinicopathologic Features and Prognostic Factors', American Journal of Surgical Pathology, vol. 43, no. 7, pp. 869-884. https://doi.org/10.1097/PAS.0000000000001271
Kurita, Daisuke ; Miyoshi, Hiroaki ; Ichikawa, Ayako ; Kato, Koji ; Imaizumi, Yoshitaka ; Seki, Ritsuko ; Sato, Kensaku ; Sasaki, Yuya ; Kawamoto, Keisuke ; Shimono, Joji ; Yamada, Kyohei ; Muto, Reiji ; Kizaki, Masahiro ; Nagafuji, Koji ; Tamaru, Jun Ichi ; Tokuhira, Michihide ; Ohshima, Koichi. / Methotrexate-associated Lymphoproliferative Disorders in Patients With Rheumatoid Arthritis : Clinicopathologic Features and Prognostic Factors. In: American Journal of Surgical Pathology. 2019 ; Vol. 43, No. 7. pp. 869-884.
@article{ab5fa25fd8314304be4bd323d8201929,
title = "Methotrexate-associated Lymphoproliferative Disorders in Patients With Rheumatoid Arthritis: Clinicopathologic Features and Prognostic Factors",
abstract = "Methotrexate (MTX) carries a risk of lymphoproliferative disorders (LPDs), but MTX-associated LPDs (MTX-LPDs) can resolve spontaneously after MTX withdrawal. However, the precise clinicopathologic features of MTX-LPD remain unclear. We aimed to investigate the clinicopathologic characteristics, outcomes, and prognostic factors for histologic types of MTX-LPD. Paraffin-embedded tissue samples of 219 patients with MTX-LPD were analyzed. In total, 30,33,106, and 26 had reactive lymphoid hyperplasia (RH), polymorphic-LPD (Poly-LPD), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphoma (CHL), respectively. The clinicopathologic features of RH, Poly-LPD, DLBCLs, and CHL were as follows: extranodal involvement: 13.8{\%} (4/29), 36.4{\%} (12/33), 69.5{\%} (73/105), and 15.4{\%} (4/26); Epstein-Barr virus encoded RNA positivity: 55.2{\%} (16/29), 71.9{\%} (23/32), 45.3{\%} (48/106), and 76.9{\%} (20/26); necrosis: 0{\%} (0/29), 51.5{\%} (17/33), 34.3{\%} (36/105), and 12.0{\%} (3/25); and Hodgkin Reed-Sternberg-like cells: 17.2{\%} (5/29), 50{\%} (14/28), and 19.8{\%} (21/106). The median duration from MTX withdrawal to the time of disease regression was 10.4, 3.0, 4.2, and 2.7 months for RH, Poly-LPD, DLBCLs, and CHL. After MTX withdrawal, progression-free survival was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL (all P<0.05). Overall survival did not differ significantly between the groups. On univariate analysis, the predictive factors for progression-free survival included plasma cell infiltrate for CHL, eosinophil infiltrate, age above 70 years, and extensive necrosis for Poly-LPD, while they were Epstein-Barr virus encoded RNA positivity and International Prognostic Index risk for DLBCL on multivariate analysis. In conclusion, histologic categorization and histology-specific factors could be useful for predicting MTX-LPD progression after MTX withdrawal.",
author = "Daisuke Kurita and Hiroaki Miyoshi and Ayako Ichikawa and Koji Kato and Yoshitaka Imaizumi and Ritsuko Seki and Kensaku Sato and Yuya Sasaki and Keisuke Kawamoto and Joji Shimono and Kyohei Yamada and Reiji Muto and Masahiro Kizaki and Koji Nagafuji and Tamaru, {Jun Ichi} and Michihide Tokuhira and Koichi Ohshima",
year = "2019",
month = "7",
day = "1",
doi = "10.1097/PAS.0000000000001271",
language = "English",
volume = "43",
pages = "869--884",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - Methotrexate-associated Lymphoproliferative Disorders in Patients With Rheumatoid Arthritis

T2 - Clinicopathologic Features and Prognostic Factors

AU - Kurita, Daisuke

AU - Miyoshi, Hiroaki

AU - Ichikawa, Ayako

AU - Kato, Koji

AU - Imaizumi, Yoshitaka

AU - Seki, Ritsuko

AU - Sato, Kensaku

AU - Sasaki, Yuya

AU - Kawamoto, Keisuke

AU - Shimono, Joji

AU - Yamada, Kyohei

AU - Muto, Reiji

AU - Kizaki, Masahiro

AU - Nagafuji, Koji

AU - Tamaru, Jun Ichi

AU - Tokuhira, Michihide

AU - Ohshima, Koichi

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Methotrexate (MTX) carries a risk of lymphoproliferative disorders (LPDs), but MTX-associated LPDs (MTX-LPDs) can resolve spontaneously after MTX withdrawal. However, the precise clinicopathologic features of MTX-LPD remain unclear. We aimed to investigate the clinicopathologic characteristics, outcomes, and prognostic factors for histologic types of MTX-LPD. Paraffin-embedded tissue samples of 219 patients with MTX-LPD were analyzed. In total, 30,33,106, and 26 had reactive lymphoid hyperplasia (RH), polymorphic-LPD (Poly-LPD), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphoma (CHL), respectively. The clinicopathologic features of RH, Poly-LPD, DLBCLs, and CHL were as follows: extranodal involvement: 13.8% (4/29), 36.4% (12/33), 69.5% (73/105), and 15.4% (4/26); Epstein-Barr virus encoded RNA positivity: 55.2% (16/29), 71.9% (23/32), 45.3% (48/106), and 76.9% (20/26); necrosis: 0% (0/29), 51.5% (17/33), 34.3% (36/105), and 12.0% (3/25); and Hodgkin Reed-Sternberg-like cells: 17.2% (5/29), 50% (14/28), and 19.8% (21/106). The median duration from MTX withdrawal to the time of disease regression was 10.4, 3.0, 4.2, and 2.7 months for RH, Poly-LPD, DLBCLs, and CHL. After MTX withdrawal, progression-free survival was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL (all P<0.05). Overall survival did not differ significantly between the groups. On univariate analysis, the predictive factors for progression-free survival included plasma cell infiltrate for CHL, eosinophil infiltrate, age above 70 years, and extensive necrosis for Poly-LPD, while they were Epstein-Barr virus encoded RNA positivity and International Prognostic Index risk for DLBCL on multivariate analysis. In conclusion, histologic categorization and histology-specific factors could be useful for predicting MTX-LPD progression after MTX withdrawal.

AB - Methotrexate (MTX) carries a risk of lymphoproliferative disorders (LPDs), but MTX-associated LPDs (MTX-LPDs) can resolve spontaneously after MTX withdrawal. However, the precise clinicopathologic features of MTX-LPD remain unclear. We aimed to investigate the clinicopathologic characteristics, outcomes, and prognostic factors for histologic types of MTX-LPD. Paraffin-embedded tissue samples of 219 patients with MTX-LPD were analyzed. In total, 30,33,106, and 26 had reactive lymphoid hyperplasia (RH), polymorphic-LPD (Poly-LPD), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphoma (CHL), respectively. The clinicopathologic features of RH, Poly-LPD, DLBCLs, and CHL were as follows: extranodal involvement: 13.8% (4/29), 36.4% (12/33), 69.5% (73/105), and 15.4% (4/26); Epstein-Barr virus encoded RNA positivity: 55.2% (16/29), 71.9% (23/32), 45.3% (48/106), and 76.9% (20/26); necrosis: 0% (0/29), 51.5% (17/33), 34.3% (36/105), and 12.0% (3/25); and Hodgkin Reed-Sternberg-like cells: 17.2% (5/29), 50% (14/28), and 19.8% (21/106). The median duration from MTX withdrawal to the time of disease regression was 10.4, 3.0, 4.2, and 2.7 months for RH, Poly-LPD, DLBCLs, and CHL. After MTX withdrawal, progression-free survival was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL (all P<0.05). Overall survival did not differ significantly between the groups. On univariate analysis, the predictive factors for progression-free survival included plasma cell infiltrate for CHL, eosinophil infiltrate, age above 70 years, and extensive necrosis for Poly-LPD, while they were Epstein-Barr virus encoded RNA positivity and International Prognostic Index risk for DLBCL on multivariate analysis. In conclusion, histologic categorization and histology-specific factors could be useful for predicting MTX-LPD progression after MTX withdrawal.

UR - http://www.scopus.com/inward/record.url?scp=85067872490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067872490&partnerID=8YFLogxK

U2 - 10.1097/PAS.0000000000001271

DO - 10.1097/PAS.0000000000001271

M3 - Article

C2 - 31116708

AN - SCOPUS:85067872490

VL - 43

SP - 869

EP - 884

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

IS - 7

ER -