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Published in: BMC Gastroenterology 1/2019

Open Access 01-12-2019 | Lymphoma | Case report

Methotrexate-associated lymphoproliferative disorder in the stomach and duodenum: a case report

Authors: Haruka Toyonaga, Masashi Fukushima, Naoto Shimeno, Tetsuro Inokuma

Published in: BMC Gastroenterology | Issue 1/2019

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Abstract

Background

Methotrexate-associated lymphoproliferative disorder (MTX-LPD) can present as a benign lymphoid proliferation or a malignant lymphoma in patients taking MTX. Almost 50% of MTX-LPD cases show spontaneous remission after withdrawal of MTX treatment. Studies have suggested that the hyper-immune state of rheumatoid arthritis, the immunosuppressive state associated with MTX, and the carcinogenicity of the Epstein-Barr virus might contribute to MTX-LPD development. Although most cases of MTX-LPD occur at extranodal sites, few cases of MTX-LPD affecting the stomach and duodenum have been reported. To our knowledge, no other study has reported on the endoscopic observations of dramatic withdrawal and appearance of multiple digestive tract lesions in a short period of time. Herein, we report the clinical course and imaging findings of our case, which may be useful for understanding the pathological condition of MTX-LPD.

Case presentation

We describe the case of a 70-year-old woman with MTX-LPD of the stomach and duodenum. Disease regression was temporarily achieved after cessation of MTX treatment; however, it subsequently recurred, and complete response was only achieved after six cycles of rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (R-CHOP) chemotherapy.

Conclusions

The first-choice therapy for patients taking MTX who develop suspected MTX-LPD should be the withdrawal of MTX treatment. Even after remission is achieved, patients should be kept under careful observation, and if the disease recurs, chemotherapy should be commenced promptly.
Literature
1.
go back to reference 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.PubMed 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.PubMed
2.
go back to reference 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. p. 462–4. 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. p. 462–4.
3.
go back to reference Gion Y, Iwaki N, Takata K, Takeuchi M, Nishida K, Orita Y, et al. Clinicopathological analysis of methotrexate-associated lymphoproliferative disorders: comparison of diffuse large B-cell lymphoma and classical Hodgkin lymphoma types. Cancer Sci. 2017;108:1271–80.CrossRefPubMedPubMedCentral Gion Y, Iwaki N, Takata K, Takeuchi M, Nishida K, Orita Y, et al. Clinicopathological analysis of methotrexate-associated lymphoproliferative disorders: comparison of diffuse large B-cell lymphoma and classical Hodgkin lymphoma types. Cancer Sci. 2017;108:1271–80.CrossRefPubMedPubMedCentral
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference Anderson LA, Gadalla S, Morton LM, Landgren O, Pfeiffer R, Warren JL, et al. Population-based study of autoimmune conditions and the risk of specific lymphoid malignancies. Int J Cancer. 2009;125:398.CrossRefPubMedPubMedCentral Anderson LA, Gadalla S, Morton LM, Landgren O, Pfeiffer R, Warren JL, et al. Population-based study of autoimmune conditions and the risk of specific lymphoid malignancies. Int J Cancer. 2009;125:398.CrossRefPubMedPubMedCentral
6.
go back to reference Hoshida Y, Xu JX, Fujita S, Nakamichi I, Ikeda JI, Tomita Y, et al. Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol. 2007;34:322–31.PubMed Hoshida Y, Xu JX, Fujita S, Nakamichi I, Ikeda JI, Tomita Y, et al. Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol. 2007;34:322–31.PubMed
7.
go back to reference Ichikawa A, Arakawa F, Kiyasu J, Sato K, Miyoshi H, Niino D, et al. Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: histology, Epstein–Barr virus, and clonality are important predictors of disease progression and regression. Eur J Haematol. 2013;91:20–8.CrossRefPubMed Ichikawa A, Arakawa F, Kiyasu J, Sato K, Miyoshi H, Niino D, et al. Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: histology, Epstein–Barr virus, and clonality are important predictors of disease progression and regression. Eur J Haematol. 2013;91:20–8.CrossRefPubMed
8.
go back to reference Wolfe F, Michaud K. Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients. Arthritis Rheum. 2004;50:1740–51.CrossRefPubMed Wolfe F, Michaud K. Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients. Arthritis Rheum. 2004;50:1740–51.CrossRefPubMed
9.
go back to reference Kameda T, Dobashi H, Miyatake N, Inoo M, Onishi I, Kurata N, et al. Association of higher methotrexate dose with lymphoproliferative disease onset in rheumatoid arthritis patients. Arthritis Care Res. 2014;66:1302–9.CrossRef Kameda T, Dobashi H, Miyatake N, Inoo M, Onishi I, Kurata N, et al. Association of higher methotrexate dose with lymphoproliferative disease onset in rheumatoid arthritis patients. Arthritis Care Res. 2014;66:1302–9.CrossRef
10.
go back to reference Paul CF, Ho VC, McGeown C, Christophers E, Schmidtmann B, Guillaume JC, et al. Risk of malignancies in psoriasis patients treated with cyclosporine: a 5 y cohort study. J Invest Dermatol. 2003;120:211–6.CrossRefPubMed Paul CF, Ho VC, McGeown C, Christophers E, Schmidtmann B, Guillaume JC, et al. Risk of malignancies in psoriasis patients treated with cyclosporine: a 5 y cohort study. J Invest Dermatol. 2003;120:211–6.CrossRefPubMed
11.
go back to reference Hasserjian RP, Chen S, Perkins SL, De Leval L, Kinney MC, Barry TS, et al. Immunomodulator agent-related lymphoproliferative disorders. Mod Pathol. 2009;22:1532–40.CrossRefPubMed Hasserjian RP, Chen S, Perkins SL, De Leval L, Kinney MC, Barry TS, et al. Immunomodulator agent-related lymphoproliferative disorders. Mod Pathol. 2009;22:1532–40.CrossRefPubMed
12.
go back to reference Raab-Traub N. Epstein–Barr virus in the pathogenesis of NPC. Semin Cancer Biol. 2002;12:431–41.CrossRefPubMed Raab-Traub N. Epstein–Barr virus in the pathogenesis of NPC. Semin Cancer Biol. 2002;12:431–41.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference Rizzi R, Curci P, Delia M, Rinaldi E, Chiefa A, Specchia G, et al. Spontaneous remission of “methotrexate-associated lymphoproliferative disorders” after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature. Med Oncol. 2009;26:1–9.CrossRefPubMed Rizzi R, Curci P, Delia M, Rinaldi E, Chiefa A, Specchia G, et al. Spontaneous remission of “methotrexate-associated lymphoproliferative disorders” after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature. Med Oncol. 2009;26:1–9.CrossRefPubMed
16.
go back to reference 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.CrossRef 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.CrossRef
17.
go back to reference Inui Y, Matsukoka H, Yakushijin K, Okamura A, Shimada T, Yano S, et al. Methotrexate-associated lymphoproliferative disorders: management by watchful waiting and observation of early lymphocyte recovery after methotrexate withdrawal. Leuk Lymphoma. 2015;56:3045–51.CrossRefPubMed Inui Y, Matsukoka H, Yakushijin K, Okamura A, Shimada T, Yano S, et al. Methotrexate-associated lymphoproliferative disorders: management by watchful waiting and observation of early lymphocyte recovery after methotrexate withdrawal. Leuk Lymphoma. 2015;56:3045–51.CrossRefPubMed
18.
go back to reference Yamaguchi M, Seto M, Okamoto M, Ichinohasama R, Nakamura N, Yoshino T, et al. De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients. Blood. 2002;99:815–21.CrossRefPubMed Yamaguchi M, Seto M, Okamoto M, Ichinohasama R, Nakamura N, Yoshino T, et al. De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients. Blood. 2002;99:815–21.CrossRefPubMed
19.
go back to reference Ikeda K, Nakamura T, Kinoshita T, Fujiwara M, Uose S, Someda H, et al. Methotrexate-related lymphoproliferative disorder of the stomach in a patient with rheumatoid arthritis: a case of disease regression after methotrexate cessation. Clin J Gastroenterol. 2016;9:17–21.CrossRefPubMedPubMedCentral Ikeda K, Nakamura T, Kinoshita T, Fujiwara M, Uose S, Someda H, et al. Methotrexate-related lymphoproliferative disorder of the stomach in a patient with rheumatoid arthritis: a case of disease regression after methotrexate cessation. Clin J Gastroenterol. 2016;9:17–21.CrossRefPubMedPubMedCentral
20.
go back to reference Satoh K, Yoshida N, Imaizumi K, Komatsuda A. Reversible methotrexate-associated lymphoproliferative disorder resembling advanced gastric cancer in a patient with rheumatoid arthritis. Am J Med Sci. 2009;338:334–5.CrossRefPubMed Satoh K, Yoshida N, Imaizumi K, Komatsuda A. Reversible methotrexate-associated lymphoproliferative disorder resembling advanced gastric cancer in a patient with rheumatoid arthritis. Am J Med Sci. 2009;338:334–5.CrossRefPubMed
21.
go back to reference Vetro C, Romano A, Amico I, Conticello C, Motta G, Figuera A, et al. Endoscopic features of gastro-intestinal lymphomas: from diagnosis to follow-up. World J Gastroenterol. 2014;20:12993–3005.CrossRefPubMedPubMedCentral Vetro C, Romano A, Amico I, Conticello C, Motta G, Figuera A, et al. Endoscopic features of gastro-intestinal lymphomas: from diagnosis to follow-up. World J Gastroenterol. 2014;20:12993–3005.CrossRefPubMedPubMedCentral
Metadata
Title
Methotrexate-associated lymphoproliferative disorder in the stomach and duodenum: a case report
Authors
Haruka Toyonaga
Masashi Fukushima
Naoto Shimeno
Tetsuro Inokuma
Publication date
01-12-2019

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