Primary Hepatic Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders After Methotrexate Therapy

Yasuki Hatayama, Harutoshi Sugiyama, Daisuke Murakami, Hirotaka Oura, Yukiko Shima, Miho Shirato, Takayoshi Nishino, Tadao Nakazawa, Kenichi Suehiro, Makoto Arai


Prior reports described cases of lymphoproliferative diseases occurring after methotrexate (MTX) administration, which are called methotrexate-associated lymphoproliferative disorders (MTX-LPDs). It has become clear that these lymphoproliferative diseases also occur following treatment with other immunosuppressive drugs, and they have been termed as other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs). In most of these cases, the duration of immunosuppressive drugs is very long, on the order of years. In the present study, we evaluated the development of lymphoproliferative disease despite the short duration of immunosuppressive treatment and determined the tumor doubling time. A 71-year-old woman was diagnosed with adult-onset Stills disease. The patient was administered prednisone 30 mg per day starting on February 25, 2022 and MTX 6 mg per week starting 2 weeks later. Because she was a hepatitis B virus (HBV) carrier, nucleic acid analog therapy was also started to prevent HBV activation. Eight weeks later, biweekly tocilizumab was started. After 5 months of MTX administration, a solitary liver tumor measuring 37 32 mm2 was detected. Three months later, repeat computed tomography revealed that the liver tumor had grown rapidly to 7 cm in diameter. We considered the possibility of OIIA-LPDs and stopped MTX therapy. Biopsy specimens of the liver tumor exhibited lymphocyte proliferation, which was consistent with OIIA-LPDs. The doubling time for tumor growth was 33 days. Despite withdrawing MTX for 6 weeks, the tumor continued to grow, and thus, the patient was referred to the hematology unit. In previously reported cases of MTX-LPDs of hepatic origin, the average duration of MTX administration was 7.3 (2 - 13) years. This report describes a primary hepatic OIIA-LPDs-associated tumor that rapidly increased in size after an extremely short period of MTX administration.

J Med Cases. 2023;14(8):282-288


Methotrexate; Hepatic lymphoma; Methotrexate-associated lymphoproliferative disorders; Tumor doubling time

Full Text: HTML PDF

Browse  Journals  


Journal of Clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics


World Journal of Oncology

Gastroenterology Research

Journal of Hematology


Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity


Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research


Journal of Neurology Research

International Journal of Clinical Pediatrics



Journal of Medical Cases, monthly, ISSN 1923-4155 (print), 1923-4163 (online), published by Elmer Press Inc.                     
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)

This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website:   editorial contact:
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.

Disclaimer: The views and opinions expressed in the published articles are those of the authors and do not necessarily reflect the views or opinions of the editors and Elmer Press Inc. This website is provided for medical research and informational purposes only and does not constitute any medical advice or professional services. The information provided in this journal should not be used for diagnosis and treatment, those seeking medical advice should always consult with a licensed physician.