Structural and Pathophysiological Insights into Sialolithiasis: A Case Series Integrating Literature Review, Microscopy and Elemental Analysis

Abstract Sialolithiasis is the most common non-neoplastic disease of the salivary glands, yet its etiopathogenesis remains incompletely understood. This study aimed to describe a series of three submandibular sialolithiasis cases and propose an integrated mechanistic model of sialolith formation based on clinical, histopathological, ultrastructural, and elemental analyses. Three patients presenting with small, large, and giant submandibular sialoliths underwent surgical treatment. Clinical and imaging findings were correlated with histopathological examination, fluorescence microscopy, Scanning Electron Microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). A literature review was also performed to contextualize the findings. The cases demonstrated distinct clinical presentations, including chronic infection, gland dysfunction, and one unexpected concomitant squamous cell carcinoma. Fluorescence microscopy and SEM revealed interconnected internal canalicular structures and surface aqueduct-like channels associated with biofilm and mineralized microorganisms. EDS demonstrated a calcium phosphate–based biomineral containing an organic matrix enriched with calcium, phosphorus, oxygen, and carbon, with minor amounts of sodium, magnesium, potassium, and chlorine. ings support a dynamic biomineralization process involving heterogeneous nucleation, salivary flow, microbial biofilm, and progressive mineral deposition. Based on these observations, a hydrodynamic model is proposed to explain the asymmetric growth, multilamellar architecture, and internal canalicular network characteristic of mature sialoliths. Sialolithiasis appears to result from a multifactorial and dynamic biomineralization process regulated by the interaction between salivary composition, fluid dynamics, microbial biofilm, and ductal anatomy. This model provides new insights into disease pathogenesis and may support future diagnostic and gland-preserving therapeutic strategies. Graphical abstract Energy-dispersive X-ray spectroscopy - Jeol JEM-1400Flash Transmission Electron Microscope (TEM). Graphic 1 represents the organic portion; Graphic 2 the inorganic portion and; Graphic 3 the aqueduct systems