Journal Article

Methotrexate-associated lymphoproliferative disorders of T-cell phenotype: clinicopathological analysis of 28 cases

Kawasaki, Tomonori, Miyoshi, Hiroaki, Sato, Yasuharu, Shimada, Kazuyuki, Kohno, Kei, Yoshino, Tadashi, Nakamura, Shigeo, Suzuki, Yuka, Tsuzuki, Toyonori, Ohshima, Koichi, Yamashita, Daisuke, Tabata, Tetsuya, Satou, Akira, Takahara, Taishi

2019

Overview

Methotrexate-associated lymphoproliferative disorders are categorized as “other immunodeficiency-associated lymphoproliferative disorders in the WHO classification. Methotrexate-associated lymphoproliferative disorder is mainly a B-cell lymphoproliferative disorders or Hodgkin lymphoma type, whereas T-cell lymphoproliferative disorders are relatively rare (4–8%). Only a small number of methotrexate-associated T-cell lymphoproliferative disorders have been detailed thus far. Because of the rarity, methotrexate-associated T-cell lymphoproliferative disorder has not been well studied and its clinicopathological characteristics are unknown. A total of 28 cases of methotrexate-associated T-cell lymphoproliferative disorders were retrospectively analyzed. Histologically and immunohistochemically, they were divided into three main types: angioimmunoblastic T-cell lymphoma ( n  = 19), peripheral T-cell lymphoma, NOS ( n  = 6), and CD8 + cytotoxic T-cell lymphoma ( n  = 3). Among the 28 cases, only one CD8 + cytotoxic T-cell lymphoma case was Epstein-Barr virus-positive. The other 27 cases were negative for Epstein-Barr virus on tumor cells, but scattered Epstein-Barr virus-infected B-cells were detected in 24 cases (89%), implying the reactivation of Epstein-Barr virus caused by immunodeficient status of the patients. After the diagnosis of methotrexate-associated T-cell lymphoproliferative disorder, methotrexate was immediately withdrawn in 26 cases. Twenty (77%) cases presented with spontaneous regression. Compared to methotrexate-associated B-cell lymphoproliferative disorder, patients with methotrexate-associated T-cell lymphoproliferative disorder had a significantly higher proportion of males ( p  = 0.035) and presence of B-symptoms ( p  = 0.036), and lower proportion of Epstein-Barr virus + tumor cells ( p  < 0.001). Although the difference was not significant, the methotrexate-associated T-cell lymphoproliferative disorder also had more frequent spontaneous regression ( p  = 0.061). In conclusion, methotrexate-associated T-cell lymphoproliferative disorder was divided into three main types: angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, NOS, and CD8 + cytotoxic T-cell lymphoma. Angioimmunoblastic T-cell lymphoma was the most common type. Methotrexate-associated T-cell lymphoproliferative disorder was characterized by a high rate of spontaneous regression after methotrexate cessation. Epstein-Barr virus positivity was relatively rare in methotrexate-associated T-cell lymphoproliferative disorder, significantly less frequent than methotrexate-associated B-cell lymphoproliferative disorder, suggesting different pathogenesis.

• Publisher: Nature Publishing Group US,Elsevier Limited
• Subject: 631/67/1990/291/1621/1916 / 692/699/67/1990/291/1621/1916 / Aged / Aged, 80 and over / CD8 antigen / Cell Proliferation - drug effects / Cytotoxicity / Epstein-Barr virus / Female / Herpesvirus 4, Human - isolation & purification / Hodgkin's lymphoma / Humans / Immunoblastic Lymphadenopathy - chemically induced / Immunoblastic Lymphadenopathy - immunology / Immunoblastic Lymphadenopathy - pathology / Immunodeficiency / Immunomodulators / Immunoproliferative diseases / Immunosuppressive Agents - adverse effects / Interferon / Laboratory Medicine / Lymphatic diseases / Lymphocytes / Lymphocytes B / Lymphocytes T / Lymphoma / Lymphoma, T-Cell, Peripheral - chemically induced / Lymphoma, T-Cell, Peripheral - immunology / Lymphoma, T-Cell, Peripheral - pathology / Lymphoproliferative Disorders - chemically induced / Lymphoproliferative Disorders - immunology / Lymphoproliferative Disorders - pathology / Lymphoproliferative Disorders - virology / Male / Medicine / Medicine & Public Health / Methotrexate / Methotrexate - adverse effects / Middle Aged / Pathology / Phenotype / Phenotypes / Prognosis / Retrospective Studies / T-cell lymphoma / T-Lymphocyte Subsets - drug effects / T-Lymphocyte Subsets - immunology / T-Lymphocyte Subsets - pathology / T-Lymphocyte Subsets - virology / T-Lymphocytes, Cytotoxic - drug effects / T-Lymphocytes, Cytotoxic - immunology / T-Lymphocytes, Cytotoxic - pathology / Tumor cells