免疫治疗相关心肌炎临床及病理特征观察  

Clinicopathological features of immune checkpoint inhibitor induced myocarditis

作　　者：熊焰[1] 李东[1] 邸吉廷 郭翠艳[2] 贺鹏康[3] 赵凯[4] Xiong Yan;Li Dong;Di Jiting;Guo Cuiyan;He Pengkang;Zhao Kai(Department of Pathology,Peking University First Hospital,Beijing 100034,China;Department of Respiratory and Critical Care Medicine,Peking University First Hospital,Beijing 100034,China;Department of Cardiology,Peking University First Hospital,Beijing 100034,China;Department of Radiology,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院病理科,北京100034 [2]北京大学第一医院呼吸和危重症医学科,北京100034 [3]北京大学第一医院心血管内科,北京100034 [4]北京大学第一医院医学影像科,北京100034

出　　处：《中华病理学杂志》2023年第3期268-273,共6页Chinese Journal of Pathology

摘　　要：目的:探讨免疫检测点抑制剂(immune checkpoint inhibitor,ICI)诱导心肌炎的临床病理学特点和可能的发病机制,以提高对该类新型心肌炎的认识。方法:于北京大学第一医院2020—2022年因ICI治疗不良反应就诊的病例中,筛选出经心肌活检确诊为ICI诱导心肌炎2例。收集患者临床资料、组织形态学特点、心肌细胞PD-L1表达、炎性细胞分类进行分析,并复习相关文献。结果:例1男,64岁,患胃印戒细胞癌。例2男,56岁,患肺鳞状细胞癌。2例均在接受PD-1抑制剂治疗期间发生急性心肌炎,病情进展迅速,例2病情比例1更危急。心肌活检,2例均可见心肌坏死,多量炎性细胞浸润,但纤维化不明显,符合心肌炎Dallas标准。例1和例2中,变性、坏死心肌占标本总面积的百分比分别为10%和30%,最密集区炎性细胞计数分别为150个/HPF和350个/HPF。CD20阳性细胞,例1为5个/HPF,例2为0个/HPF。CD3阳性细胞,例1为60个/HPF,例2为100个/HPF。CD8阳性细胞,例1为50个/HPF,例2为90个/HPF。CD68阳性细胞,例1为70个/HPF,例2为200个/HPF。PD-L1阳性心肌细胞均集中于炎症区,例1占全部心肌细胞约8%,例2约30%。结论:ICI诱导心肌炎,发病急、症状重、进展快。其组织形态符合心肌炎Dallas标准;病灶内心肌细胞表达PD-L1,浸润炎性细胞由CD8阳性T淋巴细胞和巨噬细胞组成,巨噬细胞数量明显超过淋巴细胞。综合上述病理学特点,并结合临床用药史,即可诊断ICI诱导心肌炎。心肌损伤的严重程度与PD-L1阳性心肌细胞的百分比、CD8阳性淋巴细胞和巨噬细胞的密度呈正相关。Objective To investigate the clinicopathological characteristics and possible pathogenesis of immune checkpoint inhibitor(ICI)induced myocarditis,and to improve understanding of this new type of myocarditis.Methods Two cases of ICI induced myocarditis with endomyocardial biopsy available for review were selected from the cases with immune-related adverse events treated by ICI in Peking University First Hospital,Beijing,China from 2020 to 2022.The clinical data,histomorphological characteristics,PD-L1 expression of cardiomyocytes,and classification of inflammatory cells in two cases of ICI-induced myocarditis were analyzed.Relevant literature was reviewed.Results Case 1 was a 64-year-old male diagnosed with gastric signet ring cell carcinoma.Case 2 was a 56-year-old male ad diagnosed with lung squamous cell carcinoma.Both patients developed acute myocarditis during PD-1 inhibitor treatment,and the disease progressed rapidly.Case 2 was more serious than case 1.Endomyocardial biopsy showed definite cardiomyocytic injury and prominent inflammatory infiltration in both cases,which met the full Dallas criteria for myocarditis.The degenerated and necrotic cardiomyocytes accounted for about 10%of the tissues in case 1 and 30%in case 2,respectively.In case 1,the inflammatory cells counted in the densest area were about 150/HPF,comprised of CD20+cells(about 5/HPF),CD3+cells(about 60/HPF),CD8+cells(about 50/HPF)and CD68+cells(about 70/HPF).In case 2,the inflammatory cells counted in the densest area were about 350/HPF,comprised of CD20+cells(0/HPF),CD3+cells(about 100/HPF),CD8+cells(about 90/HPF)and CD68+cells(about 200/HPF).In both cases,PD-L1+cardiomyocytes aggregated in the inflammatory lesions,and the percentage was about 8%and 30%in case 1 and case 2,respectively.Conclusions ICI-induced myocarditis is frequently acute onset,severe symptoms,and rapid progression.The histological morphology meets the full Dallas criteria for myocarditis.Expression of PD-L1 in cardiomyocytes can be detected in the inflammatory lesions.The

关 键 词：心肌炎 药物副反应报告系统 肿瘤治疗方案 免疫检测点抑制剂 

分 类 号：R542.21[医药卫生—心血管疾病]