Non-neural (S-100 Negative) granular cell tumor of the pericardium

Non-neural granular cell tumors (NNGCTs) are rare neoplasms with distinct histopathological and immunohistochemical features. We present the case of an asymptomatic patient in whom a pericardial mass was incidentally discovered during coronary artery bypass graft surgery. Histopathological examination revealed a lesion composed of large polygonal cells with granular eosinophilic cytoplasm, papillary-like architectural features, smooth nuclei, and a low Ki-67 proliferation index. Immunohistochemical analysis demonstrated strong positivity for CD68, while staining was negative for S-100, neuron-specific enolase (NSE), cytokeratin, CD34, α-smooth muscle actin (α-SMA), and desmin. The diagnosis was consistent with an S-100-negative non-neural granular cell tumor of the pericardium—an extremely rare entity, not previously reported in the literature to our knowledge. This case highlights the importance of considering NNGCT in the differential diagnosis of incidental pericardial masses identified on echocardiography, computed tomography, or cardiac magnetic resonance imaging.