Epithelioid Hemangioendothelioma of the Liver Showing Spontaneous Complete Regression after the Cessation of Methotrexate Intake

A 71-year-old man with slight fever and dull abdominal pain was referred to our hospital. He had been receiving methotrexate (MTX) to treat his rheumatoid arthritis for more than 6 years but stopped taking MTX after admission due to the rapid aggravation of his liver function. Computed tomography (CT) showed multiple liver lesions with late enhancement, highly suggesting them to be cholangiocarcinomas. Tumor marker levels were normal except for a slightly elevated PIVKA-II level, i.e., 45 mAU/mL (range 0–40 mAU/mL). We did a biopsy to the largest lesion and endoscopic biliary drainage to make a definitive diagnosis of the hepatic lesions and treat jaundice, respectively. Pathological study showed round, polygonal, and spindle-shaped epithelial atypical cells growing in a sarcomatoid fashion. Atypical cells were positive for CD31, CD34, vimentin, and TFE3, and some of them had intracellular vacuoles, leading to the diagnosis of epithelioid hemangioendothelioma (EHE) of the liver. The patient got well 4 weeks after the endoscopic biliary drainage. CTs showed marked regression of the EHE lesions 3 months after biliary drainage and complete regression in 12 months. The patient further developed Hodgkin lymphoma in the para-aortic lymph nodes 23 months after the biliary drainage and is now under chemotherapy for the malignant lymphoma. We, however, have not detected any EHE lesions in the liver or distant organs for at least 16 months after the confirmation of complete regression of the EHE lesions. Oncologists should note the spontaneous regression of the EHE and investigate the correlation between MTX cessation and EHE regression.