巨细胞心肌炎三例的组织形态学及超微结构观察及其临床治疗

Histological and ultrastructural features of giant cell myocarditis： report of 3 cases

目的探讨巨细胞心肌炎的临床、病理特征及超微结构改变，评价心脏移植及移植后免疫抑制剂的治疗效果。方法对阜外心血管病医院心脏移植的3例巨细胞心肌炎进行回顾性研究并随访。心脏离体后立即进行肉眼检查、测量和摄像记录，组织化学及免疫组织化学染色，光镜观察组织形态学表现，并对特异性蛋白进行定位标记及半定量检测，透射电镜观察超微结构特点；移植术后心内膜心肌活检评价排斥反应程度。结果3例均为男性，平均年龄42．3岁（34～47岁），患者自出现临床症状至心脏移植时间为4—9个月，均有严重的心律失常（3／3），其中2例临床诊断为扩张型心肌病。移植术后均使用免疫抑制剂治疗，1例术后4个月出现急性细胞性排异反应（2R级），治疗后消失。1例术后2周心肌中查见多核巨细胞。巨细胞心肌炎组织学以多核巨细胞肉芽肿为特征。免疫组织化学显示多核巨细胞CD68（＋）、CD11b（＋）、CD163（-），肉芽肿病灶中的淋巴细胞以CD8＋T细胞为主。电镜观察到多核巨细胞为细胞融合形成，并与淋巴细胞及含有分泌颗粒的细胞相黏附。结论巨细胞心肌炎是一种病因不明、易发猝死的罕见病。组织学呈巨细胞肉芽肿性心肌炎表现。免疫组织化学及电镜观察证实多核巨细胞系多个巨噬细胞融合而成，并参与免疫反应。心内膜心肌活检有助本病诊断。心脏移植及免疫抑制剂治疗可以显著延长患者生存时间。

Objective To identify clinical and pathological features of giant cell myocarditis. Methods Clinical presentation and follow-up data of three patients with giant cell myocarditis were collected. Gross, histopathological, immunohistological and ultrastructural findings of extransplantated hearts of the patients were documented. Results Grossly, multifocal involvement of the myocardium with variably dilated cardiac chambers were observed in all 3 cases. Histological examination revealed pronounced focal inflammatory infiltrates with multinucleated giant cells. Muhinucleated giant ceils were positive for CD68 and CD1 lb immunostains but were negative for CD163 in all cases. Transmission electron microscopy showed that the multinucleated giant cells derived from fusion of several macrophages with adherent lymphocytes and secretary cells. Clinically, the overall patient condition improved in all three cases after heart transplantation. One patient experienced acute cellular rejection （2R level） 4 months after transplantation, but recovered after treatment. One patient developed multinucleated giant cells observed in heart biopsy two weeks after transplantation. Conclusions Giant-cell myocarditis is a rare disease of adult, and cardiac transplantation could improve the clinical outcome. Multinucleated giant cell in the myocarditis lesions were derived from macrophages, likely participating in the immune response. Endomyocardial biopsy is important for the diagnosis of giant cell myocarditis.