Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: possible refinement by measuring macrophage abundance.
Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: possible refinement by measuring macrophage abundance.
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DOI：
10.1186/s40959-023-00166-1
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发表时间：
2023-03-13
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免疫检查点抑制剂（ICI）心肌炎与高发病率和死亡率相关。虽然肌内膜活检（EMB）被认为是诊断的金标准，但EMB的敏感性尚未明确。此外，与ICI相关性心肌炎临床诊断相关的病理学特征仍不完全清楚。我们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，这些患者是基于机构的主要和次要标准。其中17例患者接受了EMB，并通过常规苏木精和伊红（H&E）染色和免疫组化（IHC）染色的巨噬细胞标记物CD 68来评估组织病理学特征。从疑似ICI心肌炎患者中获得的17个EMB中只有2个符合达拉斯标准。CD 68+巨噬细胞的补充IHC染色和定量鉴定了另外7名具有心肌炎症病理特征的患者（> 50个CD 68+细胞/HPF）。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CD 68 IHC可能会改变ICI相关心肌炎诊断的确定性，从而在6/17例病例中确定。虽然达拉斯标准可以识别ICI相关心肌炎患者的一个子集，但巨噬细胞丰度的定量可能会扩大EMB的诊断作用。不符合传统的达拉斯标准不应排除心肌炎的诊断。
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.