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

Prior reports described cases of lymphoproliferative diseases occur- ring after methotrexate (MTX) administration, which are called meth- otrexate-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 lym- phoproliferative disease despite the short duration of immunosuppres- sive treatment and determined the tumor doubling time. A 71 -year -old woman was diagnosed with adult -onset Still's 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, bi- weekly tocilizumab was started. After 5 months of MTX administra- tion, a solitary liver tumor measuring 37 x 32 mm 2 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 speci- mens 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 con- tinued 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.