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

CONTEXT.—: 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.

OBJECTIVE.—: 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.

DATA SOURCES.—: Historical literature, clinicopathologic studies, imaging studies, and molecular research including transcriptomic and proteomic analyses.

CONCLUSIONS.—: 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.