January 2022 – Cardiovascular Pathology

A 45-year-old previously healthy man presents with rapidly progressive paroxysmal nocturnal dyspnea, orthopnea, and lower extremity edema. Echocardiogram reveals left ventricular dilation and an ejection fraction of 30%. Endomyocardial biopsy is performed for diagnostic purposes. Histologic sections of the myocardium are shown below. Ziehl Neelsen, PAS, and GMS stains are performed and are negative for organisms.

Figure 1: H&E 100x original magnification
Figure 2: H&E 200x original magnification
Figure 3: H&E 400x original magnification

Based on the history and photomicrographs, which of the following is the correct diagnosis?

  • Cardiac sarcoidosis
  • Fungal infection/myocarditis
  • Giant cell myocarditis
  • Eosinophilic myocarditis

The correct answer is ...

Giant cell myocarditis.

Giant cell myocarditis (GCM) is a rapidly progressive idiopathic disease that most often affects healthy young to middle-aged adults. Patients with GCM typically present with acute-onset congestive heart failure. GCM is characterized by a poor prognosis, with a median time from symptom onset to death or cardiac transplant of three months (1). The pathogenesis of GCM is thought to be autoimmune in nature. Proposed mechanisms include degranulation of eosinophils resulting in cardiomyocyte damage, as well as T lymphocyte-mediated immune dysregulation (1). 

Histopathologically, GCM is characterized by an extensive mixed inflammatory infiltrate with widespread myocyte damage. This infiltrate predominantly consists of macrophages, eosinophils, and lymphocytes. In addition, GCM displays multinucleated giant cells scattered throughout the myocardium, but lacks well-formed granulomas. Early in the disease, there is prominent cardiomyocyte necrosis with surrounding inflammatory cells. In later stages of the disease, giant cells become more rare, and reparative fibrosis dominates the histologic picture (2).

The differential diagnosis for GCM includes other types of granulomatous myocarditis, such as mycobacterial myocarditis, fungal myocarditis, and Chagas disease. These infectious etiologies more often affect immunocompromised patients. Microscopically, fungal myocarditis displays prominent neutrophilic inflammatory infiltrates and granulomas, and would be positive for organisms on PAS or GMS histochemical stains. 

The differential also includes cardiac sarcoidosis, which more commonly presents clinically with heart block and arrhythmias, and histopathologically with well-formed, GMS-negative epithelioid granulomas (3). Compared to the eosinophil-rich inflammatory infiltrate of GCM, cardiac sarcoidosis contains fewer eosinophils. Moreover, while both GCM and eosinophilic myocarditis can have prominent eosinophilic inflammation, eosinophilic myocarditis generally lacks abundant giant cells within the inflammatory milieu. 


  1. Ghaly M, Schiliro D, Stepczynski J. Giant Cell Myocarditis: A Time Sensitive Distant Diagnosis. Cureus. 2020;12(1):e6712. Published 2020 Jan 20. doi:10.7759/cureus.6712
  2. Leone O, Pieroni M, Rapezzi C, Olivotto I. The spectrum of myocarditis: from pathology to the clinics. Virchows Arch. 2019 Sep;475(3):279-301. doi: 10.1007/s00428-019-02615-8. Epub 2019 Jul 11. PMID: 31297595.
  3. Okura Y, Dec G, Hare JM, et al. A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis. Journal of the American College of Cardiology. 2003;41(2):322-329. doi:10.1016/s0735-1097(02)02715-8.

Allison Kerper, M.D.

Resident, Anatomic and Clinical Pathology
Mayo Clinic

Melanie Bois, M.D.

Consultant, Anatomic Pathology
Mayo Clinic
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.