Jimenez Jesus, Kostelecky Nicolas, Mitchell Joshua D, Zhang Kathleen W, Lin Chieh-Yu, Lenihan Daniel J, Lavine Kory J
Center for Cardiovascular Research, Department of Medicine, Cardiovascular Division, Washington University School of Medicine, 660 South Euclid Campus, Box 8086, St. Louis, MO, 63110, USA.
Cardio-Oncology Center of Excellence, Department of Medicine, Cardiovascular Division, Washington University School of Medicine, 660 South Euclid Campus, Box 8086, St. Louis, MO, 63110, USA.
Cardiooncology. 2023 Mar 13;9(1):14. doi: 10.1186/s40959-023-00166-1.
Immune checkpoint inhibitor (ICI) myocarditis is associated with high morbidity and mortality. While endomyocardial biopsy (EMB) is considered a gold standard for diagnosis, the sensitivity of EMB is not well defined. Additionally, the pathological features that correlate with the clinical diagnosis of ICI-associated myocarditis remain incompletely understood.
We retrospectively identified and reviewed the clinicopathological features of 26 patients with suspected ICI-associated myocarditis based on institutional major and minor criteria. Seventeen of these patients underwent EMB, and the histopathological features were assessed by routine hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for CD68, a macrophage marker.
Only 2/17 EMBs obtained from patients with suspected ICI myocarditis satisfied the Dallas criteria. Supplemental IHC staining and quantification of CD68 macrophages identified an additional 7 patients with pathological features of myocardial inflammation (> 50 CD68 cells/HPF). Macrophage abundance positively correlated with serum Troponin I (P = 0.010) and NT-proBNP (N-terminal pro-brain natriuretic peptide, P = 0.047) concentration. Inclusion of CD68 IHC could have potentially changed the certainty of the diagnosis of ICI-associated myocarditis to definite in 6/17 cases.
While the Dallas criteria can identify a subset of ICI-associated myocarditis patients, quantification of macrophage abundance may expand the diagnostic role of EMB. Failure to meet the traditional Dallas Criteria should not exclude the diagnosis of myocarditis.
免疫检查点抑制剂（ICI）相关性心肌炎具有较高的发病率和死亡率。虽然心内膜心肌活检（EMB）被认为是诊断的金标准，但EMB的敏感性尚未明确界定。此外，与ICI相关性心肌炎临床诊断相关的病理特征仍未完全明确。
我们根据机构的主要和次要标准，回顾性地确定并审查了26例疑似ICI相关性心肌炎患者的临床病理特征。其中17例患者接受了EMB，并通过常规苏木精和伊红（H&E）染色以及针对巨噬细胞标志物CD68的免疫组织化学（IHC）染色评估组织病理学特征。
从疑似ICI心肌炎患者中获得的17份EMB中，只有2份符合达拉斯标准。补充的IHC染色和CD68巨噬细胞定量分析又发现了7例具有心肌炎症病理特征（>50个CD68细胞/HPF）的患者。巨噬细胞丰度与血清肌钙蛋白I（P = 0.010）和NT-proBNP（N末端脑钠肽前体，P = 0.047）浓度呈正相关。纳入CD68 IHC可能会使17例中的6例ICI相关性心肌炎诊断的确定性变为明确。
虽然达拉斯标准可以识别一部分ICI相关性心肌炎患者，但巨噬细胞丰度的定量分析可能会扩大EMB的诊断作用。未达到传统达拉斯标准不应排除心肌炎的诊断。
