Papillary fibroelastomas (PFEs) are benign endocardial tumors that now represent the most commonly diagnosed primary cardiac tumor, surpassing myxomas in frequency owing to advances in echocardiography and other imaging modalities [1,2]. Although typically small (<1 cm) and valvular in origin, PFEs are clinically significant due to their established association with embolic events, including transient ischemic attack, stroke, myocardial infarction, and pulmonary embolism [[1], [2], [3], [4], [5], [6]]. Histologically, PFEs are composed of avascular branching fronds covered by a single layer of endothelium overlying a fibroelastic and mucopolysaccharide-containing core. Most arise on the aortic or mitral valves, but they may develop anywhere along the endocardium. Their etiology remains uncertain, with proposed mechanisms including reactive proliferation after endothelial injury, organized thrombus, hamartomatous processes, and true neoplasia [2,[7], [8], [9]]. Associations with prior valve disease, instrumentation, and altered intracardiac flow patterns suggest a role for mechanical stress or endothelial injury in their pathogenesis [10].

Existing literature focuses primarily on small, valve-based PFEs, with limited characterization of larger lesions (≥1 cm) [2,4,5,11]. The clinicopathologic features, recurrence potential, and stromal composition of these large PFEs remain poorly understood. Moreover, a stromal spindle or stellate-shaped cell component in PFEs has been noted sporadically in prior reports, but has not been systematically quantified or correlated with anatomic location [4,[11], [12], [13], [14]]. Since the stromal spindle cells in PFEs may express S100, it has been proposed that they are related to dendritic cells [2,14]. Alternatively, it has been suggested that these cells may be fibroblastic in nature [4,13].

This study characterizes the clinical, histopathologic, and immunohistochemical features of large PFEs, with an emphasis on the S100+ spindle cell component, particularly its variation by anatomic site and potential relationship to cardiac valvular interstitial cells. Our findings broaden the morphologic and phenotypic spectrum of PFEs.