Hodgkin Lymphoma in an Elderly Rheumatoid Patient on Long Term Methotrexate Therapy: A Case Report
Asian Hematology Research Journal,
Page 37-44
Abstract
Methotrexate associated lymphoproliferative disorders (MTX-LPD) are lymphomas that develop after administration of methotrexate (MTX). Here, we report a case of MTX-LPD in a 58-year-old female with rheumatoid arthritis (RA) who was on methotrexate for 10 years. She presented with complaint of cough for 1 month with no B symptoms. Chest and abdomen computed tomography showed hilar, mediastinal and abdominal lymphadenopathy. Biopsy and immunohistochemistry confirmed involvement with classical Hodgkin lymphoma. She was advised to stop methotrexate which resulted in complete regression of her lesions on PET CT within 1 month. For patients who are taking MTX for a long time, MTX associated LPD should be considered in the differential diagnosis in patients presenting with diffuse lymphadenopathy to avoid unnecessary treatment as many of these cases can be cured with discontinuation of methotrexate alone.
Keywords:
- Methotrexate
- hodgkin lymphoma
- abdominal lymphadenopathy
- computed tomography
How to Cite
Sandeep, ., Upadhyay, A., Panchal, H. P., Patel, A., Parikh, S. K., Shah, K., Jain, K., & Kokate, A. (2023). Hodgkin Lymphoma in an Elderly Rheumatoid Patient on Long Term Methotrexate Therapy: A Case Report. Asian Hematology Research Journal, 7(2), 37-44. Retrieved from https://journalahrj.com/index.php/AHRJ/article/view/30219
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Padeh S, Sharon N, Schiby G, Rechavi G, Passwell JH. Hodgkin's lymphoma in systemic onset juvenile rheumatoid arthritis after treatment with low dose methotrexate. J Rheumatol 1997;24: 2035-7
Kamel OW, van de Rijn M, Weiss LM, Del Zoppo GJ, Hench PK, Robbins BA, et al . Brief report: reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med 1993;328:1317-21.
Moseley AC, Lindsley HB, Skikne BS, Tawfik O. Reversible methotrexate associated lymphoproliferative disease evolving into Hodgkin's disease. J Rheumatol 2000;27:810-3.
Jardine DL, Colls BM. Hodgkin's disease following methotrexate therapy for rheumatoid arthritis. N Z Med J 2002;115:293-4.
Kameda T, Dobashi H, Miyatake N, Inoo M, Onishi I, Kurata N, Mitsunaka H, Kawakami K, Fukumoto T, Susaki K, et al: Association of higher methotrexate dose with lymphoprolif¬erative disease onset in rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2014;66:1302-1309.
Hoshida Y, Xu JX, Fujita S, Nakamichi I, Ikeda J, Tomita Y, Nakatsuka S, Tamaru J, Iizuka A, Takeuchi T, et al: Lymphoproliferative disorders in rheumatoid arthritis: Clinicopathological analysis of 76 cases in relation to metho-trexate medication. J Rheumatol. 2007;34:322-331.
Mokuda S, Miyazaki T, Saeki Y, Masumoto J, Kanno M and Takasugi K: Epstein-Barr virus-related MTX-LPD in rheu¬matoid arthritis patients exhibits a viral pattern of the CD64 and CD35 expression on neutrophils: Three case reports. Mod Rheumatol. 2015;25:166-168.
Tokuhira M, Watanabe R, Nemoto T, Sagawa M, Tomikawa T, Tamaru J, Itoyama S, Nagasawa H, Amano K, Kameda H, et al: Clinicopathological analyses in patients with other iatrogenic immunodeficiency-associated lymphoproliferative diseases and rheumatoid arthritis. Leuk Lymphoma. 2012;53:616-623.
Loo EY, Medeiros LJ, Aladily TN, Hoehn D, Kanagal-Shamanna R, Young KH, Lin P, Bueso-Ramos CE, Manning JT Jr., Patel K, Thomazy V, Brynes RK, Goswami M, Fayad LE, Miranda RN. Classical Hodgkin lymphoma arising in the setting of iatrogenic immunodeficiency: a clinicopathologic study of 10 cases. Am J Surg Pathol. 2013;37:1290–1297. PMID: 23774171. DOI: 10.1097/PAS.0b013e31828e6564.
Yoshifuji K, Umezawa Y, Ichikawa A, Watanabe K, Miura O, Yamamoto M. Methotrexate-associated Classical Hodgkin Lymphoma Shows Distinct Clinicopathological Features but Comparable Clinical Outcomes With Sporadic Cases. In vivo. 2019;33(5):1599-1604. DOI:10.21873/invivo.11642
Ichikawa A, Arakawa F, Kiyasu J, Sato K, Miyoshi H, Niino D, Kimura Y, Takeuchi M, Yoshida M, Ishibashi Y, et al: Methotrexate/iatrogenic lymphoproliferative disorders in rheu-matoid arthritis: Histology, Epstein-Barr virus, and clonality are important predictors of disease progression and regression. Eur J Haematol. 2013;91:20-28.
. Katsuyama T, Sada KE, Yan M, Zeggar S, Hiramatsu S, Miyawaki Y, Ohashi K, Morishita M, Watanabe H, Katsuyama E, et al: Prognostic factors of methotrexate-associated lymphop¬roliferative disorders associated with rheumatoid arthritis and plausible application of biological agents. Mod Rheumatol. 2017;27:773-777.
Niitsu N, Okamoto M, Nakamine H, Hirano M. Clinicopathologic correlations of diffuse large B-cell lymphoma in rheumatoid arthritis patients treated with methotrexate. Cancer Sci. 2010;101:1309–13.
Saito S, Kaneko Y, Yamaoka K, Tokuhira M, Takeuchi T. Distinct patterns of lymphocyte count transition in lymphoproliferative disorder in patients with rheumatoid arthritis treated with methotrexate. Rheumatol. 2017;56: 940–6.
Hoshida Y, Xu JX, Fujita S, et al. Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol 2007;34:322–331.
Ellman MH, Hurwitz H, Thomas C, Kozloff M. Lymphoma developing in a patient with rheumatoid arthritis taking low dose weekly methotrexate. J Rheumatol. 1991;18: 1741–3.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. World Health Organization classification of Tumours of Haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press. 2017;462–4.
Gion Y, Iwaki N, Takata K, Takeuchi M, Nishida K, Orita Y, et al. Clinicopathological analysis of methotrexate- associated lymphoprolifera-tive disorders: comparison of diffuse large B-cell lymphoma and classical Hodgkin lymphoma types. Cancer Sci. 2017;108: 1271–80.
Takanashi S, Aisa Y, Ito C, Arakaki H, Osada Y, Amano Y, et al. Clinical characteristics of methotrexate-associated lymphoproliferative disorders: relationship between absolute lymphocyte count recovery and spontaneous regression. Rheumatol Int. 2017;37:1629–33.
Padeh S, Sharon N, Schiby G, Rechavi G, Passwell JH. Hodgkin's lymphoma in systemic onset juvenile rheumatoid arthritis after treatment with low dose methotrexate. J Rheumatol 1997;24: 2035-7
Kamel OW, van de Rijn M, Weiss LM, Del Zoppo GJ, Hench PK, Robbins BA, et al . Brief report: reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med 1993;328:1317-21.
Moseley AC, Lindsley HB, Skikne BS, Tawfik O. Reversible methotrexate associated lymphoproliferative disease evolving into Hodgkin's disease. J Rheumatol 2000;27:810-3.
Jardine DL, Colls BM. Hodgkin's disease following methotrexate therapy for rheumatoid arthritis. N Z Med J 2002;115:293-4.
Kameda T, Dobashi H, Miyatake N, Inoo M, Onishi I, Kurata N, Mitsunaka H, Kawakami K, Fukumoto T, Susaki K, et al: Association of higher methotrexate dose with lymphoprolif¬erative disease onset in rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2014;66:1302-1309.
Hoshida Y, Xu JX, Fujita S, Nakamichi I, Ikeda J, Tomita Y, Nakatsuka S, Tamaru J, Iizuka A, Takeuchi T, et al: Lymphoproliferative disorders in rheumatoid arthritis: Clinicopathological analysis of 76 cases in relation to metho-trexate medication. J Rheumatol. 2007;34:322-331.
Mokuda S, Miyazaki T, Saeki Y, Masumoto J, Kanno M and Takasugi K: Epstein-Barr virus-related MTX-LPD in rheu¬matoid arthritis patients exhibits a viral pattern of the CD64 and CD35 expression on neutrophils: Three case reports. Mod Rheumatol. 2015;25:166-168.
Tokuhira M, Watanabe R, Nemoto T, Sagawa M, Tomikawa T, Tamaru J, Itoyama S, Nagasawa H, Amano K, Kameda H, et al: Clinicopathological analyses in patients with other iatrogenic immunodeficiency-associated lymphoproliferative diseases and rheumatoid arthritis. Leuk Lymphoma. 2012;53:616-623.
Loo EY, Medeiros LJ, Aladily TN, Hoehn D, Kanagal-Shamanna R, Young KH, Lin P, Bueso-Ramos CE, Manning JT Jr., Patel K, Thomazy V, Brynes RK, Goswami M, Fayad LE, Miranda RN. Classical Hodgkin lymphoma arising in the setting of iatrogenic immunodeficiency: a clinicopathologic study of 10 cases. Am J Surg Pathol. 2013;37:1290–1297. PMID: 23774171. DOI: 10.1097/PAS.0b013e31828e6564.
Yoshifuji K, Umezawa Y, Ichikawa A, Watanabe K, Miura O, Yamamoto M. Methotrexate-associated Classical Hodgkin Lymphoma Shows Distinct Clinicopathological Features but Comparable Clinical Outcomes With Sporadic Cases. In vivo. 2019;33(5):1599-1604. DOI:10.21873/invivo.11642
Ichikawa A, Arakawa F, Kiyasu J, Sato K, Miyoshi H, Niino D, Kimura Y, Takeuchi M, Yoshida M, Ishibashi Y, et al: Methotrexate/iatrogenic lymphoproliferative disorders in rheu-matoid arthritis: Histology, Epstein-Barr virus, and clonality are important predictors of disease progression and regression. Eur J Haematol. 2013;91:20-28.
. Katsuyama T, Sada KE, Yan M, Zeggar S, Hiramatsu S, Miyawaki Y, Ohashi K, Morishita M, Watanabe H, Katsuyama E, et al: Prognostic factors of methotrexate-associated lymphop¬roliferative disorders associated with rheumatoid arthritis and plausible application of biological agents. Mod Rheumatol. 2017;27:773-777.
Niitsu N, Okamoto M, Nakamine H, Hirano M. Clinicopathologic correlations of diffuse large B-cell lymphoma in rheumatoid arthritis patients treated with methotrexate. Cancer Sci. 2010;101:1309–13.
Saito S, Kaneko Y, Yamaoka K, Tokuhira M, Takeuchi T. Distinct patterns of lymphocyte count transition in lymphoproliferative disorder in patients with rheumatoid arthritis treated with methotrexate. Rheumatol. 2017;56: 940–6.
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