Han Qianqian, Li Lin, Li Ziyao, Yang Mei, Lei Song, Su Yanyan, Xu Huan
Department of Pathology, West China Hospital of Sichuan University, Chengdu 610041, China.
Department of Pathology, West China Hospital of Sichuan University, Chengdu 610041, China.
Pathol Res Pract. 2025 Feb;266:155824. doi: 10.1016/j.prp.2025.155824. Epub 2025 Jan 27.
Anti-vascular endothelial growth factor-associated thrombotic microangiopathy (aVEGF-TMA) was recently discovered in patients with malignant tumors. Four aVEGF-TMA patients diagnosed by renal biopsy between 2018 and 2022 were identified, and all were females aged 30-62 years (mean age, 47 years). Two patients with malignant gastrointestinal stromal tumors who received sunitinib were analyzed. One patient was treated with bevacizumab plus regorafenib, which has never been reported before. Another patient had lung adenocarcinoma with multiple metastasis and was treated with bevacizumab. Proteinuria was often the first symptom, and the mean onset time was 23.25 months (7-36 months). Renal function was decreased in all patients, and nephrotic syndrome, hematuria, hypertension and anemia were present in some patients. Microscopically, both bevacizumab-TMAs and sunitinib-TMAs presented thrombi within dilated capillaries, mesangiolysis, double counters of the glomerular basement membrane and effaced or fused foot processes. Glomerulosclerosis and endothelial cell injury occurred in only some patients. Positive IgM deposits were observed in all aVEGF-TMAs, but IgA and C3 deposits were observed only in bevacizumab-TMAs. CD34 expression was absent around dilated capillaries containing thrombi, and immunostaining for fibrin/fibrinogen was positive; however, CD61 staining was negative in all patients. Thus, fibrin thrombi were suggested to be present in aVEGF-TMA. The mean follow-up time after renal biopsy was 19.5 months (range 14-32 months). One patient continued sunitinib treatment and eventually progressed to permanent dialysis, but tumor progression was controlled. The other three patients developed drug resistance, two patients discontinued aVEGF medication, and proteinuria decreased significantly. Notably, one patient recovered 14 months after withdrawal. The other patient who continued bevacizumab treatment had persistent proteinuria, and the tumor still progressed. In summary, renal function needs to be monitored in patients with malignant tumors who are receiving aVEGF drug treatment, especially females. Timely termination of related aVEGF administration after comprehensive assessment could alleviate their clinical symptoms. DATA AVAILABILITY: Data are available from the corresponding Author upon reasonable request.
抗血管内皮生长因子相关血栓性微血管病（aVEGF-TMA）最近在恶性肿瘤患者中被发现。我们确定了2018年至2022年间经肾活检诊断的4例aVEGF-TMA患者，均为30 - 62岁的女性（平均年龄47岁）。分析了2例接受舒尼替尼治疗的恶性胃肠道间质瘤患者。1例患者接受了贝伐单抗联合瑞戈非尼治疗，此前从未有过相关报道。另1例患有多发转移肺腺癌的患者接受了贝伐单抗治疗。蛋白尿通常是首发症状，平均发病时间为23.25个月（7 - 36个月）。所有患者肾功能均下降，部分患者出现肾病综合征、血尿、高血压和贫血。显微镜下，贝伐单抗-TMA和舒尼替尼-TMA均表现为扩张毛细血管内血栓形成、系膜溶解、肾小球基底膜双轨征以及足突消失或融合。仅部分患者出现肾小球硬化和内皮细胞损伤。所有aVEGF-TMA均观察到IgM沉积阳性，但仅在贝伐单抗-TMA中观察到IgA和C3沉积。含血栓的扩张毛细血管周围CD34表达缺失，纤维蛋白/纤维蛋白原免疫染色阳性；然而，所有患者CD61染色均为阴性。因此，提示aVEGF-TMA中存在纤维蛋白血栓。肾活检后的平均随访时间为19.5个月（范围14 - 32个月）。1例患者继续舒尼替尼治疗，最终进展为永久性透析，但肿瘤进展得到控制。其他3例患者出现耐药，2例患者停用aVEGF药物，蛋白尿显著下降。值得注意的是，1例患者停药14个月后恢复。另1例继续接受贝伐单抗治疗的患者蛋白尿持续存在，肿瘤仍进展。总之，接受aVEGF药物治疗的恶性肿瘤患者，尤其是女性，需要监测肾功能。综合评估后及时停用相关aVEGF药物可缓解其临床症状。数据可用性：合理请求下可向相应作者获取数据。
