OJRad  Vol.4 No.4 , December 2014
Findings of 18F-Fluorodeoxyglucose Positron-Emission Tomography in Methotrexate-Related Lymphoproliferative Disorder
ABSTRACT
Introduction: The use of methotrexate (MTX) for rheumatoid arthritis (RA) is increasing. However, the immune suppression state leads to the occurrence of lymphoproliferative disorder (MTX-LPD). The purpose of this study was to describe the findings of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in MTX-LPD patients, and compare it with non-MTX-related malignant lymphoma (ML). Materials and Methods: We retrospectively reviewed 11 MTX-LPD patients (9 female, mean age 68.3 years) and 21 ML patients (7 female, mean age 60.6 years) with a histopathological diagnosis. FDG-PET imaging was performed using a standard oncology procedure. We assessed the disease distribution based on FDG-PET images and measured the maximum standardized up take values (SUVmax) for each region. Results: Mean values of SUVmax in MTX-LPD and ML were 14.6 and 17.2, respectively (p = 0.49). In MTX-LPD, 55 lesions met the Cotswold classification, consisting of 37 nodal and 18 extranodal lesions. In ML, 82 lesions were found, consisting of 68 nodal and 14 extranodal lesions. MTX-LPD showed a higher incident of the involvement in extranodal lesions throughout the whole body (p < 0.001). Conclusion: Because this disease occurs widely throughout the whole body, we need to pay attention to the less frequent sites as well when performing PET imaging in patients with MTX-LPD.

Cite this paper
Kono, A. , Kitajima, K. , Mmatsuoka, H. , Otani, K. , Itoh, T. and Sugimura, K. (2014) Findings of 18F-Fluorodeoxyglucose Positron-Emission Tomography in Methotrexate-Related Lymphoproliferative Disorder. Open Journal of Radiology, 4, 293-300. doi: 10.4236/ojrad.2014.44038.
References
[1]   Ellman, M.H., Hurwitz, H., Thomas, C. and Kozloff, M. (1991) Lymphoma Developing in a Patient with Rheumatoid Arthritis Taking Low Dose Weekly Methotrexate. The Journal of Rheumatology, 18, 1741-1743.

[2]   Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., et al. (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th Edition, IARC Press, Lyon, 439.

[3]   Georgescu, .L, Quinn, G.C., Schwartzman, S. and Paget, S.A. (1997) Lymphoma in Patients with Rheumatoid Arthritis: Association with the Disease State or Methotrexate Treatment. Seminars in Arthritis and Rheumatism, 26, 794-804.
http://dx.doi.org/10.1016/S0049-0172(97)80023-6

[4]   Menke, D.M., Griesser, H., Moder, K.G., Tefferi, A., Luthra, H.S., Cohen, M.D., et al. (2000) Lymphomas in Patients with Connective Tissue Disease. Comparison of p53 Protein Expression and Latent EBV Infection in Patients Immunosuppressed and not Immunosuppressed with Methotrexate. American Journal of Clinical Pathology, 113, 212-218.

[5]   Hoshida, Y., Xu, J.X., Fujita, S., Nakamichi, I., Ikeda, J., Tomita, Y., et al. (2007) Lymphoproliferative Disorders in Rheumatoid Arthritis: Clinicopathological Analysis of 76 Cases in Relation to Methotrexate Medication. The Journal of Rheumatology, 34, 322-331.

[6]   Minamimoto, R., Ito, K., Kubota, K., Morooka, M., Masuda-Miyata, Y., Hirai, R., et al. (2011) Clinical Role of FDG PET/CT for Methotrexate-Related Malignant Lymphoma. Clinical Nuclear Medicine, 36, 533-537.
http://dx.doi.org/10.1097/RLU.0b013e3182177296

[7]   Kostakoglu, L., Leonard, J.P., Kuji, I., Coleman, M., Vallabhajosula, S. and Goldsmith, S.J. (2002) Comparison of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography and Ga-67 Scintigraphy in Evaluation of Lymphoma. Cancer, 94, 879-888.
http://dx.doi.org/10.1002/cncr.10336

[8]   Mackie, G.C. and Pohlen, J.M. (2006) Methotrexate-Induced Pulmonary Non-Hodgkin Lymphoma. Clinical Nuclear Medicine, 31, 272-274.
http://dx.doi.org/10.1097/01.rlu.0000210690.37590.98

[9]   Nguyen, B.D., Roarke, M.C. and McCullough, A.E. (2008) Methotrexate-Induced and Epstein-Barr Virus-Associated B-Cell Lymphoma of the Spine: MR and PET/CT Imaging. Clinical Nuclear Medicine, 33, 208-210.
http://dx.doi.org/10.1097/RLU.0b013e318162db78

[10]   Jankowitz, R.C., Ganon, J., Blodgett. T., Garcia, C. and Jacobs, S. (2009) A Putative Case of Methotrexate-Related Lymphoma: Clinical Course and PET/CT Findings. Case Reports in Medicine, 2009, Article ID: 469343, 5 p.
http://dx.doi.org/10.1155/2009/469343

[11]   Lister, T.A., Crowther, D., Sutcliffe, S.B., Glatstein, E., Canellos, G.P., Young, R.C., et al. (1989) Report of a Committee Convened to Discuss the Evaluation and Staging of Patients with Hodgkin’s Disease: Cotswolds Meeting. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 7, 1630-1636.

[12]   Combe, B., Landewe, R., Lukas, C., Bolosiu, H.D., Breedveld, F., Dougados, M., et al. (2007) EULAR Recommendations for the Management of Early Arthritis: Report of a Task Force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Annals of the Rheumatic Diseases, 66, 34-45.
http://dx.doi.org/10.1136/ard.2005.044354

[13]   Saag, K.G., Teng, G.G., Patkar, N.M., Anuntiyo, J., Finney, C., Curtis, J.R., et al. (2008) American College of Rheumatology 2008 Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. Arthritis Care & Research, 59, 762-784.
http://dx.doi.org/10.1002/art.23721

[14]   Miyazaki, T., Fujimaki, K., Shirasugi, Y., Yoshiba, F., Ohsaka, M., Miyazaki, K., et al. (2007) Remission of Lymphoma after Withdrawal of Methotrexate in Rheumatoid Arthritis: Relationship with Type of Latent Epstein-Barr Virus Infection. American Journal of Hematology, 82, 1106-1109.
http://dx.doi.org/10.1002/ajh.21003

[15]   Salliot, C. and van der Heijde, D. (2009) Long-Term Safety of Methotrexate Monotherapy in Patients with Rheumatoid Arthritis: A Systematic Literature Research. Annals of the Rheumatic Diseases, 68, 1100-1104.
http://dx.doi.org/10.1136/ard.2008.093690

[16]   Juweid, M.E., Stroobants, S., Hoekstra, O.S., Mottaghy, F.M., Dietlein, M., Guermazi, A., et al. (2007) Use of Positron Emission Tomography for Response Assessment of Lymphoma: Consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 25, 571-578.
http://dx.doi.org/10.1200/JCO.2006.08.2305

[17]   Paes, F.M., Kalkanis, D.G., Sideras, P.A. and Serafini, A.N. (2010) FDG PET/CT of Extranodal Involvement in Non-Hodgkin Lymphoma and Hodgkin Disease. RadioGraphics, 30, 269-291.
http://dx.doi.org/10.1148/rg.301095088

[18]   Kikuchi, K., Miyazaki, Y., Tanaka, A., Shigematu, H., Kojima, M., Sakashita, H. and Kusama, K. (2010) Methotrexate-Related Epstein-Barr Virus (EBV)-Associated Lymphoproliferative Disorder—So-Called “Hodgkin-Like Lesion”—of the Oral Cavity in a Patient with Rheumatoid Arthritis. Head and Neck Pathology, 4, 305-311.
http://dx.doi.org/10.1007/s12105-010-0202-6

[19]   Bishu, S., Quigley, J.M., Schmitz, J., Bishu, S.R., Stemm, R.A., Olsasky, S.M., et al. (2007) F-18-fluoro-deoxy-glucose Positron Emission Tomography in the Assessment of Peripheral T-Cell Lymphomas. Leukemia & Lymphoma, 48, 1531-1538.
http://dx.doi.org/10.1080/10428190701344915

[20]   Schoder, H., Noy, A., Gonen, M., Weng, L., Green, D., Erdi, Y.E., et al. (2005) Intensity of 18Fluorodeoxyglucose Uptake in Positron Emission Tomography Distinguishes between Indolent and Aggressive Non-Hodgkin’s Lymphoma. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 23, 4643-4651.
http://dx.doi.org/10.1200/JCO.2005.12.072

[21]   Terasawa, T., Nihashi, T., Hotta, T. and Nagai, H. (2008) 18F-FDG PET for Posttherapy Assessment of Hodgkin’s Disease and Aggressive Non-Hodgkin’s Lymphoma: A Systematic Review. Journal of Nuclear Medicine, 49, 13-21.
http://dx.doi.org/10.2967/jnumed.107.039867

[22]   Kamel, O.W., van de Rijn, M., LeBrun, D.P., Weiss, L.M., Warnke, R.A. and Dorfman, R.F. (1994) Lymphoid Neoplasms in Patients with Rheumatoid Arthritis and Dermatomyositis: Frequency of Epstein-Barr Virus and Other Features Associated with Immunosuppression. Human Pathology, 25, 638-643.
http://dx.doi.org/10.1016/0046-8177(94)90295-X

[23]   Kamel, O.W., van de Rijn, M., Weiss, L.M., Del Zoppo, G.J., Hench, P.K., Robbins, B.A., et al. (1993) Brief Report: Reversible Lymphomas Associated with Epstein-Barr Virus Occurring during Methotrexate Therapy for Rheumatoid Arthritis and Dermatomyositis. New England Journal of Medicine, 328, 1317-1321.
http://dx.doi.org/10.1056/NEJM199305063281806

[24]   Feng, W.H., Cohen, J.I., Fischer, S., Li, L., Sneller, M., Goldbach-Mansky, R., et al. (2004) Reactivation of Latent Epstein-Barr Virus by Methotrexate: A Potential Contributor to Methotrexate-Associated Lymphomas. Journal of the National Cancer Institute, 96, 1691-1702.
http://dx.doi.org/10.1093/jnci/djh313

 
 
Top