Hepatic methotrexate-associated lymphoproliferative disorders identified by multiple liver tumors: a case report and review of the literature

Abstract

Background Methotrexate, an immunosuppressant, is widely used as the standard therapeutic drug for rheumatoid arthritis. With the increasing frequency of use of methotrexate, adverse effects of methotrexate have been reported, one of which is known as methotrexate-associated lymphoproliferative disorders. The etiology of hepatic methotrexate-associated lymphoproliferative disorders remains largely unknown. To date, there have only been ten cases of hepatic methotrexate-associated lymphoproliferative disorders reported in the English literature and a case report is very rare. Case presentation An 82-year-old Japanese man with rheumatoid arthritis treated with methotrexate presented with fever. Contrast-enhanced computed tomography showed multiple hypovascular nodules in his liver, spleen, and lung, and para-aortic lesions. Endoscopic ultrasound-guided fine-needle aspiration biopsy for liver tumors was performed, and pathological results identified cluster of differentiation 20-positive lymphocytes. Discontinuance of methotrexate led to regression of the nodules and a final definitive diagnosis of methotrexate-associated lymphoproliferative disorders was made. Conclusions We review 11 reported cases of hepatic methotrexate-associated lymphoproliferative disorders including the present case. Physicians should discontinue methotrexate in patients with rheumatoid arthritis treated with methotrexate when elevated soluble interleukin-2 receptor and hypovascular lesions in contrast-enhanced computed tomography are confirmed considering the possibility of methotrexate-associated lymphoproliferative disorders.

Methotrexate-associated Lymphoproliferative Disorder in the Liver Resembling Hepatocellular Carcinoma Treated with Transarterial Chemoembolization

“…Thus far, 16 cases with MTX-LPD in the liver have been reported ( 10 , 11 , 23 ), and the duration of MTX has ranged from 24 to 120 months. Therefore, the MTX duration of 17 years in the present case is the longest yet recorded.…”

“…Regarding imaging findings, it was reported that liver tumors of MTX-LPD appeared as low-density areas on plain CT images and that most tumors were hypovascular on contrast-enhanced CT, although some showed mild ring enhancement ( 10 ). Because no typical imaging features of hepatic lymphoma have been reported, it is difficult to distinguish hepatic lymphoma from HCC or metastatic tumors based on imaging findings alone ( 11 ). Indeed, the present case showed early enhancement and wash-out in contrast-enhanced CT/MRI images, which are typical findings of HCC.…”

“…MTX-associated LPD (MTX-LPD) is found not only in lymph nodes but also several other organs such as the intestinal tract, skin, and lung ( 8 ), but its involvement in the liver is very rare, and the etiology and clinical outcome are largely unknown ( 9 ). In addition, the typical imaging features of MTX-LPD in the liver have not been defined, and its diagnosis by imaging tests is considered difficult ( 10 , 11 ).…”

Methotrexate‐associated lymphoproliferative disorder with an osteolytic vertebral lesion in an elderly patient with rheumatoid arthritis: A case report

“…Oebisu et al reported a case of MTX‐LPD with a pathological fracture of the femur, 5 and Kikuchi reported a case accompanied by a spinal lesion 6 . In addition, hepatic lesions rarely develop in patients with MTX‐LPD, with only 11 cases having been reported in the English literature to date 11 …”

“… 6 In addition, hepatic lesions rarely develop in patients with MTX‐LPD, with only 11 cases having been reported in the English literature to date. 11 …”