A Tale of Two Myocarditides: Giant Cell Myocarditis and Sarcoidosis-A Pathologist's Review

Giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are rare but serious inflammatory heart diseases that pose significant diagnostic and therapeutic challenges. The relationship between the 2 has been debated for decades, sparked in part by a 1980 study using immunohistochemistry and electron microscopy to examine their histopathologic overlap.

To review and synthesize the historical, pathologic, clinical, and molecular understanding of GCM, explore its overlap and distinctions with CS, and outline future directions for diagnosis and treatment.

Historical literature, clinicopathologic studies, imaging studies, and molecular research including transcriptomic and proteomic analyses.

GCM is characterized by a fulminant clinical course, diffuse myocardial necrosis with multinucleated giant cells and eosinophilic infiltrate, and a predominantly CD8+ T-cell response. In contrast, CS typically presents with more indolent cardiac symptoms, well-formed nonnecrotizing granulomas with Langhans-type giant cells, and a CD4+ T-cell predominant response. GCM and CS share overlapping clinical and imaging features, and sometimes have histopathologic similarities as well. Emerging molecular data suggest transcriptional differences, but a subset of cases exhibit mixed or intermediate features, suggesting a possible disease spectrum. Advances in molecular profiling, standardized diagnostic criteria, noninvasive imaging modalities, and targeted immunosuppression may help refine diagnosis and treatment. Clarifying whether these conditions lie along a shared pathobiologic continuum remains an important goal for future research.