Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: possible refinement by measuring macrophage abundance
Abstract Background 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 th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Cardio-Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40959-023-00166-1 |
| _version_ | 1827982561923563520 |
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| author | Jesus Jimenez Nicolas Kostelecky Joshua D. Mitchell Kathleen W. Zhang Chieh-Yu Lin Daniel J. Lenihan Kory J. Lavine |
| author_facet | Jesus Jimenez Nicolas Kostelecky Joshua D. Mitchell Kathleen W. Zhang Chieh-Yu Lin Daniel J. Lenihan Kory J. Lavine |
| author_sort | Jesus Jimenez |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-04-09T22:34:53Z |
| format | Article |
| id | doaj.art-5462eb27bdc04566acb51ffc4305cb85 |
| institution | Directory Open Access Journal |
| issn | 2057-3804 |
| language | English |
| last_indexed | 2024-04-09T22:34:53Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardio-Oncology |
| spelling | doaj.art-5462eb27bdc04566acb51ffc4305cb852023-03-22T12:31:34ZengBMCCardio-Oncology2057-38042023-03-019111110.1186/s40959-023-00166-1Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: possible refinement by measuring macrophage abundanceJesus Jimenez0Nicolas Kostelecky1Joshua D. Mitchell2Kathleen W. Zhang3Chieh-Yu Lin4Daniel J. Lenihan5Kory J. Lavine6Center for Cardiovascular Research, Department of Medicine, Cardiovascular Division, Washington University School of MedicineDepartment of Pathology and Immunology, Washington University School of MedicineCardio-Oncology Center of Excellence, Department of Medicine, Cardiovascular Division, Washington University School of MedicineCardio-Oncology Center of Excellence, Department of Medicine, Cardiovascular Division, Washington University School of MedicineDepartment of Pathology and Immunology, Washington University School of MedicineCardio-Oncology Center of Excellence, Department of Medicine, Cardiovascular Division, Washington University School of MedicineCenter for Cardiovascular Research, Department of Medicine, Cardiovascular Division, Washington University School of MedicineAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s40959-023-00166-1Cardio-oncologyImmune checkpoint inhibitorsMyocarditisMacrophage |
| spellingShingle | Jesus Jimenez Nicolas Kostelecky Joshua D. Mitchell Kathleen W. Zhang Chieh-Yu Lin Daniel J. Lenihan Kory J. Lavine Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: possible refinement by measuring macrophage abundance Cardio-Oncology Cardio-oncology Immune checkpoint inhibitors Myocarditis Macrophage |
| title | Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: possible refinement by measuring macrophage abundance |
| title_full | Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: possible refinement by measuring macrophage abundance |
| title_fullStr | Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: possible refinement by measuring macrophage abundance |
| title_full_unstemmed | Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: possible refinement by measuring macrophage abundance |
| title_short | Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: possible refinement by measuring macrophage abundance |
| title_sort | clinicopathological classification of immune checkpoint inhibitor associated myocarditis possible refinement by measuring macrophage abundance |
| topic | Cardio-oncology Immune checkpoint inhibitors Myocarditis Macrophage |
| url | https://doi.org/10.1186/s40959-023-00166-1 |
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