Supplementary Material for: 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 six 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 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 vacuole, leading to the diagnosis of epithelioid hemangioendothelioma (EHE) of the liver. The patient got well four weeks after the endoscopic biliary drainage. CTs showed marked regression of the EHE lesions three months after biliary drainage and complete regression in 12 months. The patient further developed Hodgkin lymphoma in the para-aortic lymph nodes in 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 at least for 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.

一名71岁男性因轻度发热及腹部隐痛就诊于我院。该患者因类风湿关节炎接受甲氨蝶呤（methotrexate, MTX）治疗已逾六年，入院后因肝功能快速恶化停用该药。计算机断层扫描（Computed tomography, CT）显示多发肝脏病灶伴延迟强化，高度提示为胆管癌。除PIVKA-II水平轻度升高（45 mAU/ml，参考范围0~40 mAU/ml）外，其余肿瘤标志物水平均正常。我们对最大病灶实施活检，并同期行内镜下胆道引流术，分别以明确肝脏病灶的定性诊断及治疗黄疸。病理学检查可见呈肉瘤样生长的圆形、多边形及梭形上皮样异型细胞；异型细胞表达CD31、CD34、波形蛋白（vimentin）及TFE3，部分细胞内可见胞内空泡，据此确诊为肝脏上皮样血管内皮瘤（epithelioid hemangioendothelioma, EHE）。内镜下胆道引流术后4周，患者病情好转；术后3个月复查CT显示肝脏上皮样血管内皮瘤病灶显著消退，术后12个月病灶完全消失。术后23个月，患者于主动脉旁淋巴结出现霍奇金淋巴瘤，目前正在接受恶性淋巴瘤化疗。截至肝脏上皮样血管内皮瘤病灶完全消退后的至少16个月，我们未在肝脏或远处脏器中检出任何上皮样血管内皮瘤病灶。临床医师应警惕上皮样血管内皮瘤的自发消退现象，并进一步探究甲氨蝶呤停药与上皮样血管内皮瘤消退之间的相关性。