Case Report
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 6, 2019; 7(21): 3553-3561
Published online Nov 6, 2019. doi: 10.12998/wjcc.v7.i21.3553
Methotrexate-related lymphoproliferative disorders in the liver: Case presentation and mini-review
Takeshi Mizusawa, Kenya Kamimura, Hiroki Sato, Takeshi Suda, Hiroyuki Fukunari, Go Hasegawa, Osamu Shibata, Shinichi Morita, Akira Sakamaki, Junji Yokoyama, Yu Saito, Yoshihisa Hori, Yuduru Maruyama, Fumitoshi Yoshimine, Takahiro Hoshi, Shinichi Morita, Tsutomu Kanefuji, Masaaki Kobayashi, Shuji Terai
Takeshi Mizusawa, Yu Saito, Yoshihisa Hori, Yuduru Maruyama, Fumitoshi Yoshimine, Department of Internal Medicine, Niigata Prefectural Tokamachi Hospital, Tokamachi, Niigata 948-0065, Japan
Takeshi Mizusawa, Kenya Kamimura, Hiroki Sato, Osamu Shibata, Shinichi Morita, Akira Sakamaki, Junji Yokoyama, Shinichi Morita, Shuji Terai, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
Takeshi Suda, Shinichi Morita, Takahiro Hoshi, Shinichi Morita, Tsutomu Kanefuji, Masaaki Kobayashi, Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine Niigata University Hospital, Minami Uonuma, Niigata 949-7302, Japan
Hiroyuki Fukunari, Department of Surgery, Niigata Prefectural Tokamachi Hospital, Tokamachi, Niigata 948-0065, Japan
Go Hasegawa, Department of Pathology, Uonuma Institute of Community Medicine Niigata University Hospital, Minami Uonuma, Niigata 949-7302, Japan
Yuduru Maruyama, Department of Internal Medicine, Tokamachi Central Clinic, Tokamachi, Niigata 948-0065, Japan
Masaaki Kobayashi, Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata 951-8566, Japan
Author contributions: Mizusawa T, Kamimura K and Terai S wrote the manuscript; Sato H, Suda T, Fukunari H, Hasegawa G, Shibata O, Moriata S, Sakamaki A and Yokoyama J collected data for review; Saito Y, Hori Y, Maruyama Y, Yoshimine F, Hoshi T, Morita S, Kanefuji T and Kobayashi M treated patients; all authors read and approved the final version of the manuscript.
Informed consent statement: Informed written consent was obtained from the patient.
Conflict-of-interest statement: The authors declare that they have no current financial arrangement or affiliation with any organization that may have a direct influence on their work.
CARE Checklist (2016) statement: The authors revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article which was selected by an in house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Kenya Kamimura, MD, PhD, Lecturer, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1–757 Asahimachi–dori, Chuo–ku, Niigata 951-8510, Japan. kenya–k@med.niigata–u.ac.jp
Telephone: +81-25-2272207 Fax: +81-25-2270776
Received: February 12, 2019
Peer-review started: February 15, 2019
First decision: May 31, 2019
Revised: June 19, 2019
Accepted: July 27, 2019
Article in press: July 27, 2019
Published online: November 6, 2019
Processing time: 269 Days and 19.5 Hours
Abstract
BACKGROUND

Immunosuppression is effective in treating a number of diseases, but adverse effects such as bone marrow suppression, infection, and oncogenesis are of concern. Methotrexate is a key immunosuppressant used to treat rheumatoid arthritis. Although it is effective for many patients, various side effects have been reported, one of the most serious being methotrexate-related lymphoproliferative disorder. While this may occur in various organs, liver involvement is rare. Information on these liver lesions, including clinical characteristics, course, and imaging studies, has not been summarized to date.

CASE SUMMARY

We present a case of 70-year-old woman presented with a 2-wk history of fever and abdominal pain. She had had rheumatoid arthritis for 5 years and was being treated with medication including methotrexate. Contrast-enhanced computed tomography revealed multiple low density tumors in the liver and the histological analyses showed significant proliferation of lymphocytes in masses that were positive on immunohistochemical staining for CD3, CD4, CD8, and CD79a but negative for CD20 and CD56. Staining for Epstein-Barr virus-encoded RNA was negative. And based on these findings, the liver tumors were diagnosed as Methotrexate-related lymphoproliferative disorders. A time-dependent disappearance of the liver tumors after stopping methotrexate supported the diagnoses.

CONCLUSION

The information obtained from our case and a review of 9 additional cases reported thus far assist physicians who may face the challenge of diagnosing and managing this disorder.

Keywords: Arthritis; Rheumatoid; Methotrexate; Malignant lymphoma; Case report

Core tip: Methotrexate-related lymphoproliferative disorder is a severe adverse event of immunosuppression in the treatment of rheumatoid arthritis. Even if the methotrexate is discontinued leading to resolution of the side effect, the disorder may recur. Decisions based on the patient’s disease status in regard to stopping or continuing administration of methotrexate are challenging. Methotrexate-related lymphoproliferative disorder has rarely caused tumors in the liver. Therefore, little information has been reported on clinical findings, imaging characteristics, and treatment of this entity. To promote early diagnosis and appropriate treatment, we report a new case with multiple imaging studies and summarized previously reported cases.